case study on human health and disease

Health Case Studies

(29 reviews)

Glynda Rees, British Columbia Institute of Technology

Rob Kruger, British Columbia Institute of Technology

Janet Morrison, British Columbia Institute of Technology

Publisher: BCcampus

Language: English

Formats Available

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Reviewed by Jessica Sellars, Medical assistant office instructor, Blue Mountain Community College on 10/11/23

Comprehensiveness rating: 5 see less

This is a book of compiled and very well organized patient case studies. The author has broken it up by disease patient was experiencing and even the healthcare roles that took place in this patients care. There is a well thought out direction and plan. There is an appendix to refer to as well if you are needing to find something specific quickly. I have been looking for something like this to help my students have a base to do their project on. This is the most comprehensive version I have found on the subject.

Content Accuracy rating: 5

This is a book compiled of medical case studies. It is very accurate and can be used to learn from great care and mistakes.

Relevance/Longevity rating: 5

This material is very relevant in this context. It also has plenty of individual case studies to utilize in many ways in all sorts of medical courses. This is a very useful textbook and it will continue to be useful for a very long time as you can still learn from each study even if medicine changes through out the years.

Clarity rating: 5

The author put a lot of thought into the ease of accessibility and reading level of the target audience. There is even a "how to use this resource" section which could be extremely useful to students.

Consistency rating: 5

The text follows a very consistent format throughout the book.

Modularity rating: 5

Each case study is individual broken up and in a group of similar case studies. This makes it extremely easy to utilize.

Organization/Structure/Flow rating: 5

The book is very organized and the appendix is through. It flows seamlessly through each case study.

Interface rating: 5

I had no issues navigating this book, It was clearly labeled and very easy to move around in.

Grammatical Errors rating: 5

I did not catch any grammar errors as I was going through the book

Cultural Relevance rating: 5

This is a challenging question for any medical textbook. It is very culturally relevant to those in medical or medical office degrees.

I have been looking for something like this for years. I am so happy to have finally found it.

Reviewed by Cindy Sun, Assistant Professor, Marshall University on 1/7/23

Interestingly, this is not a case of ‘you get what you pay for’. Instead, not only are the case studies organized in a fashion for ease of use through a detailed table of contents, the authors have included more support for both faculty and students. For faculty, the introduction section titled ‘How to use this resource’ and individual notes to educators before each case study contain application tips. An appendix overview lists key elements as issues / concepts, scenario context, and healthcare roles for each case study. For students, learning objectives are presented at the beginning of each case study to provide a framework of expectations.

The content is presented accurately and realistic.

The case studies read similar to ‘A Day In the Life of…’ with detailed intraprofessional communications similar to what would be overheard in patient care areas. The authors present not only the view of the patient care nurse, but also weave interprofessional vantage points through each case study by including patient interaction with individual professionals such as radiology, physician, etc.

In addition to objective assessment findings, the authors integrate standard orders for each diagnosis including medications, treatments, and tests allowing the student to incorporate pathophysiology components to their assessments.

Each case study is arranged in the same framework for consistency and ease of use.

This compilation of eight healthcare case studies focusing on new onset and exacerbation of prevalent diagnoses, such as heart failure, deep vein thrombosis, cancer, and chronic obstructive pulmonary disease advancing to pneumonia.

Each case study has a photo of the ‘patient’. Simple as this may seem, it gives an immediate mental image for the student to focus.

Interface rating: 4

As noted by previous reviewers, most of the links do not connect active web pages. This may be due to the multiple options for accessing this resource (pdf download, pdf electronic, web view, etc.).

Grammatical Errors rating: 4

A minor weakness that faculty will probably need to address prior to use is regarding specific term usages differences between Commonwealth countries and United States, such as lung sound descriptors as ‘quiet’ in place of ‘diminished’ and ‘puffers’ in place of ‘inhalers’.

The authors have provided a multicultural, multigenerational approach in selection of patient characteristics representing a snapshot of today’s patient population. Additionally, one case study focusing on heart failure is about a middle-aged adult, contrasting to the average aged patient the students would normally see during clinical rotations. This option provides opportunities for students to expand their knowledge on risk factors extending beyond age.

This resource is applicable to nursing students learning to care for patients with the specific disease processes presented in each case study or for the leadership students focusing on intraprofessional communication. Educators can assign as a supplement to clinical experiences or as an in-class application of knowledge.

Reviewed by Stephanie Sideras, Assistant Professor, University of Portland on 8/15/22

The eight case studies included in this text addressed high frequency health alterations that all nurses need to be able to manage competently. While diabetes was not highlighted directly, it was included as a potential comorbidity. The five overarching learning objectives pulled from the Institute of Medicine core competencies will clearly resonate with any faculty familiar with Quality and Safety Education for Nurses curriculum.

The presentation of symptoms, treatments and management of the health alterations was accurate. Dialogue between the the interprofessional team was realistic. At times the formatting of lab results was confusing as they reflected reference ranges specific to the Canadian healthcare system but these occurrences were minimal and could be easily adapted.

The focus for learning from these case studies was communication - patient centered communication and interprofessional team communication. Specific details, such as drug dosing, was minimized, which increases longevity and allows for easy individualization of the case data.

While some vocabulary was specific to the Canadian healthcare system, overall the narrative was extremely engaging and easy to follow. Subjective case data from patient or provider were formatted in italics and identified as 'thoughts'. Objective and behavioral case data were smoothly integrated into the narrative.

The consistency of formatting across the eight cases was remarkable. Specific learning objectives are identified for each case and these remain consistent across the range of cases, varying only in the focus for the goals for each different health alterations. Each case begins with presentation of essential patient background and the progress across the trajectory of illness as the patient moves from location to location encountering different healthcare professionals. Many of the characters (the triage nurse in the Emergency Department, the phlebotomist) are consistent across the case situations. These consistencies facilitate both application of a variety of teaching methods and student engagement with the situated learning approach.

Case data is presented by location and begins with the patient's first encounter with the healthcare system. This allows for an examination of how specific trajectories of illness are manifested and how care management needs to be prioritized at different stages. This approach supports discussions of care transitions and the complexity of the associated interprofessional communication.

The text is well organized. The case that has two levels of complexity is clearly identified

The internal links between the table of contents and case specific locations work consistently. In the EPUB and the Digital PDF the external hyperlinks are inconsistently valid.

The grammatical errors were minimal and did not detract from readability

Cultural diversity is present across the cases in factors including race, ethnicity, socioeconomic status, family dynamics and sexual orientation.

The level of detail included in these cases supports a teaching approach to address all three spectrums of learning - knowledge, skills and attitudes - necessary for the development of competent practice. I also appreciate the inclusion of specific assessment instruments that would facilitate a discussion of evidence based practice. I will enjoy using these case to promote clinical reasoning discussions of data that is noticed and interpreted with the resulting prioritizes that are set followed by reflections that result from learner choices.

Reviewed by Chris Roman, Associate Professor, Butler University on 5/19/22

It would be extremely difficult for a book of clinical cases to comprehensively cover all of medicine, and this text does not try. Rather, it provides cases related to common medical problems and introduces them in a way that allows for various... read more

Comprehensiveness rating: 4 see less

The narrative form of the cases is less subject to issues of accuracy than a more content-based book would be. That said, the cases are realistic and reasonable, avoiding being too mundane or too extreme.

These cases are narrative and do not include many specific mentions of drugs, dosages, or other aspects of clinical care that may grow/evolve as guidelines change. For this reason, the cases should be “evergreen” and can be modified to suit different types of learners.

Clarity rating: 4

The text is written in very accessible language and avoids heavy use of technical language. Depending on the level of learner, this might even be too simplistic and omit some details that would be needed for physicians, pharmacists, and others to make nuanced care decisions.

The format is very consistent with clear labeling at transition points.

The authors point out in the introductory materials that this text is designed to be used in a modular fashion. Further, they have built in opportunities to customize each cases, such as giving dates of birth at “19xx” to allow for adjustments based on instructional objectives, etc.

The organization is very easy to follow.

I did not identify any issues in navigating the text.

The text contains no grammatical errors, though the language is a little stiff/unrealistic in some cases.

Cases involve patients and members of the care team that are of varying ages, genders, and racial/ethnic backgrounds

Reviewed by Trina Larery, Assistant Professor, Pittsburg State University on 4/5/22

The book covers common scenarios, providing allied health students insight into common health issues. The information in the book is thorough and easily modified if needed to include other scenarios not listed. The material was easy to understand... read more

Content Accuracy rating: 4

The treatments were explained and rationales were given, which can be very helpful to facilitate effective learning for a nursing student or novice nurse. The case studies were accurate in explanation. The DVT case study incorrectly identifies the location of the clot in the popliteal artery instead of in the vein.

The content is relevant to a variety of different types of health care providers and due to the general nature of the cases, will remain relevant over time. Updates should be made annually to the hyperlinks and to assure current standard of practice is still being met.

Clear, simple and easy to read.

Consistent with healthcare terminology and framework throughout all eight case studies.

The text is modular. Cases can be used individually within a unit on the given disease process or relevant sections of a case could be used to illustrate a specific point providing great flexibility. The appendix is helpful in locating content specific to a certain diagnosis or a certain type of health care provider.

The book is well organized, presenting in a logical clear fashion. The appendix allows the student to move about the case study without difficulty.

The interface is easy and simple to navigate. Some links to external sources might need to be updated regularly since those links are subject to change based on current guidelines. A few hyperlinks had "page not found".

Few grammatical errors were noted in text.

The case studies include people of different ethnicities, socioeconomic status, ages, and genders to make this a very useful book.

I enjoyed reading the text. It was interesting and relevant to today's nursing student. There are roughly 25 broken online links or "pages not found", care needs to be taken to update at least annually and assure links are valid and utilizing the most up to date information.

Reviewed by Benjamin Silverberg, Associate Professor/Clinician, West Virginia University on 3/24/22

Comprehensiveness rating: 3 see less

The appendix reviews the "key roles" and medical venues found in all 8 cases, but is fairly spartan on medical content. The table of contents at the beginning only lists the cases and locations of care. It can be a little tricky to figure out what is going on where, especially since each case is largely conversation-based. Since this presents 8 cases (really 7 with one being expanded upon), there are many medical topics (and venues) that are not included. It's impossible to include every kind of situation, but I'd love to see inclusion of sexual health, renal pathology, substance abuse, etc.

Though there are differences in how care can be delivered based on personal style, changing guidelines, available supplies, etc, the medical accuracy seems to be high. I did not detect bias or industry influence.

Relevance/Longevity rating: 4

Medications are generally listed as generics, with at least current dosing recommendations. The text gives a picture of what care looks like currently, but will be a little challenging to update based on new guidelines (ie, it can be hard to find the exact page in which a medication is dosed/prescribed). Even if the text were to be a little out of date, an instructor can use that to point out what has changed (and why).

Clear text, usually with definitions of medical slang or higher-tier vocabulary. Minimal jargon and there are instances where the "characters" are sorting out the meaning as well, making it accessible for new learners, too.

Overall, the style is consistent between cases - largely broken up into scenes and driven by conversation rather than descriptions of what is happening.

There are 8 (well, again, 7) cases which can be reviewed in any order. Case #2 builds upon #1, which is intentional and a good idea, though personally I would have preferred one case to have different possible outcomes or even a recurrence of illness. Each scene within a case is reasonably short.

Organization/Structure/Flow rating: 4

These cases are modular and don't really build on concepts throughout. As previously stated, case #2 builds upon #1, but beyond that, there is no progression. (To be sure, the authors suggest using case #1 for newer learners and #2 for more advanced ones.) The text would benefit from thematic grouping, a longer introduction and debriefing for each case (there are learning objectives but no real context in medical education nor questions to reflect on what was just read), and progressively-increasing difficulty in medical complexity, ethics, etc.

I used the PDF version and had no interface issues. There are minimal photographs and charts. Some words are marked in blue but those did not seem to be hyperlinked anywhere.

No noticeable errors in grammar, spelling, or formatting were noted.

I appreciate that some diversity of age and ethnicity were offered, but this could be improved. There were Canadian Indian and First Nations patients, for example, as well as other characters with implied diversity, but there didn't seem to be any mention of gender diverse or non-heterosexual people, or disabilities. The cases tried to paint family scenes (the first patient's dog was fairly prominently mentioned) to humanize them. Including more cases would allow for more opportunities to include sex/gender minorities, (hidden) disabilities, etc.

The text (originally from 2017) could use an update. It could be used in conjunction with other Open Texts, as a compliment to other coursework, or purely by itself. The focus is meant to be on improving communication, but there are only 3 short pages at the beginning of the text considering those issues (which are really just learning objectives). In addition to adding more cases and further diversity, I personally would love to see more discussion before and after the case to guide readers (and/or instructors). I also wonder if some of the ambiguity could be improved by suggesting possible health outcomes - this kind of counterfactual comparison isn't possible in real life and could be really interesting in a text. Addition of comprehension/discussion questions would also be worthwhile.

Reviewed by Danielle Peterson, Assistant Professor, University of Saint Francis on 12/31/21

This text provides readers with 8 case studies which include both chronic and acute healthcare issues. Although not comprehensive in regard to types of healthcare conditions, it provides a thorough look at the communication between healthcare workers in acute hospital settings. The cases are primarily set in the inpatient hospital setting, so the bulk of the clinical information is basic emergency care and inpatient protocol: vitals, breathing, medication management, etc. The text provides a table of contents at opening of the text and a handy appendix at the conclusion of the text that outlines each case’s issue(s), scenario, and healthcare roles. No index or glossary present.

Although easy to update, it should be noted that the cases are taking place in a Canadian healthcare system. Terms may be unfamiliar to some students including “province,” “operating theatre,” “physio/physiotherapy,” and “porter.” Units of measurement used include Celsius and meters. Also, the issue of managed care, health insurance coverage, and length of stay is missing for American students. These are primary issues that dictate much of the healthcare system in the US and a primary job function of social workers, nurse case managers, and medical professionals in general. However, instructors that wish to add this to the case studies could do so easily.

The focus of this text is on healthcare communication which makes it less likely to become obsolete. Much of the clinical information is stable healthcare practice that has been standard of care for quite some time. Nevertheless, given the nature of text, updates would be easy to make. Hyperlinks should be updated to the most relevant and trustworthy sources and checked frequently for effectiveness.

The spacing that was used to note change of speaker made for ease of reading. Although unembellished and plain, I expect students to find this format easy to digest and interesting, especially since the script is appropriately balanced with ‘human’ qualities like the current TV shows and songs, the use of humor, and nonverbal cues.

A welcome characteristic of this text is its consistency. Each case is presented in a similar fashion and the roles of the healthcare team are ‘played’ by the same character in each of the scenarios. This allows students to see how healthcare providers prioritize cases and juggle the needs of multiple patients at once. Across scenarios, there was inconsistency in when clinical terms were hyperlinked.

The text is easily divisible into smaller reading sections. However, since the nature of the text is script-narrative format, if significant reorganization occurs, one will need to make sure that the communication of the script still makes sense.

The text is straightforward and presented in a consistent fashion: learning objectives, case history, a script of what happened before the patient enters the healthcare setting, and a script of what happens once the patient arrives at the healthcare setting. The authors use the term, “ideal interactions,” and I would agree that these cases are in large part, ‘best case scenarios.’ Due to this, the case studies are well organized, clear, logical, and predictable. However, depending on the level of student, instructors may want to introduce complications that are typical in the hospital setting.

The interface is pleasing and straightforward. With exception to the case summary and learning objectives, the cases are in narrative, script format. Each case study supplies a photo of the ‘patient’ and one of the case studies includes a link to a 3-minute video that introduces the reader to the patient/case. One of the highlights of this text is the use of hyperlinks to various clinical practices (ABG, vital signs, transfer of patient). Unfortunately, a majority of the links are broken. However, since this is an open text, instructors can update the links to their preference.

Although not free from grammatical errors, those that were noticed were minimal and did not detract from reading.

Cultural Relevance rating: 4

Cultural diversity is visible throughout the patients used in the case studies and includes factors such as age, race, socioeconomic status, family dynamics, and sexual orientation. A moderate level of diversity is noted in the healthcare team with some stereotypes: social workers being female, doctors primarily male.

As a social work instructor, I was grateful to find a text that incorporates this important healthcare role. I would have liked to have seen more content related to advance directives, mediating decision making between the patient and care team, emotional and practical support related to initial diagnosis and discharge planning, and provision of support to colleagues, all typical roles of a medical social worker. I also found it interesting that even though social work was included in multiple scenarios, the role was only introduced on the learning objectives page for the oncology case.

Reviewed by Crystal Wynn, Associate Professor, Virginia State University on 7/21/21

The text covers a variety of chronic diseases within the cases; however, not all of the common disease states were included within the text. More chronic diseases need to be included such as diabetes, cancer, and renal failure. Not all allied health care team members are represented within the case study. Key terms appear throughout the case study textbook and readers are able to click on a hyperlink which directs them to the definition and an explanation of the key term.

Content is accurate, error-free and unbiased.

The content is up-to-date, but not in a way that will quickly make the text obsolete within a short period of time. The text is written and/or arranged in such a way that necessary updates will be relatively easy and straightforward to implement.

The text is written in lucid, accessible prose, and provides adequate context for any jargon/technical terminology used

The text is internally consistent in terms of terminology and framework.

The text is easily and readily divisible into smaller reading sections that can be assigned at different points within the course. Each case can be divided into a chronic disease state unit, which will allow the reader to focus on one section at a time.

Organization/Structure/Flow rating: 3

The topics in the text are presented in a logical manner. Each case provides an excessive amount of language that provides a description of the case. The cases in this text reads more like a novel versus a clinical textbook. The learning objectives listed within each case should be in the form of questions or activities that could be provided as resources for instructors and teachers.

Interface rating: 3

There are several hyperlinks embedded within the textbook that are not functional.

The text contains no grammatical errors.

Cultural Relevance rating: 3

The text is not culturally insensitive or offensive in any way. More examples of cultural inclusiveness is needed throughout the textbook. The cases should be indicative of individuals from a variety of races and ethnicities.

Reviewed by Rebecca Hillary, Biology Instructor, Portland Community College on 6/15/21

This textbook consists of a collection of clinical case studies that can be applicable to a wide range of learning environments from supplementing an undergraduate Anatomy and Physiology Course, to including as part of a Medical or other health care program. I read the textbook in E-reader format and this includes hyperlinks that bring the students to subsequent clinical study if the book is being used in a clinical classroom. This book is significantly more comprehensive in its approach from other case studies I have read because it provides a bird’s eye view of the many clinicians, technicians, and hospital staff working with one patient. The book also provides real time measurements for patients that change as they travel throughout the hospital until time of discharge.

Each case gave an accurate sense of the chaos that would be present in an emergency situation and show how the conditions affect the practitioners as well as the patients. The reader gets an accurate big picture--a feel for each practitioner’s point of view as well as the point of view of the patient and the patient’s family as the clock ticks down and the patients are subjected to a number of procedures. The clinical information contained in this textbook is all in hyperlinks containing references to clinical skills open text sources or medical websites. I did find one broken link on an external medical resource.

The diseases presented are relevant and will remain so. Some of the links are directly related to the Canadian Medical system so they may not be applicable to those living in other regions. Clinical links may change over time but the text itself will remain relevant.

Each case study clearly presents clinical data as is it recorded in real time.

Each case study provides the point of view of several practitioners and the patient over several days. While each of the case studies covers different pathology they all follow this same format, several points of view and data points, over a number of days.

The case studies are divided by days and this was easy to navigate as a reader. It would be easy to assign one case study per body system in an Anatomy and Physiology course, or to divide them up into small segments for small in class teaching moments.

The topics are presented in an organized way showing clinical data over time and each case presents a large number of view points. For example, in the first case study, the patient is experiencing difficulty breathing. We follow her through several days from her entrance to the emergency room. We meet her X Ray Technicians, Doctor, Nurses, Medical Assistant, Porter, Physiotherapist, Respiratory therapist, and the Lab Technicians running her tests during her stay. Each practitioner paints the overall clinical picture to the reader.

I found the text easy to navigate. There were not any figures included in the text, only clinical data organized in charts. The figures were all accessible via hyperlink. Some figures within the textbook illustrating patient scans could have been helpful but I did not have trouble navigating the links to visualize the scans.

I did not see any grammatical errors in the text.

The patients in the text are a variety of ages and have a variety of family arrangements but there is not much diversity among the patients. Our seven patients in the eight case studies are mostly white and all cis gendered.

Some of the case studies, for example the heart failure study, show clinical data before and after drug treatments so the students can get a feel for mechanism in physiological action. I also liked that the case studies included diet and lifestyle advice for the patients rather than solely emphasizing these pharmacological interventions. Overall, I enjoyed reading through these case studies and I plan to utilize them in my Anatomy and Physiology courses.

Reviewed by Richard Tarpey, Assistant Professor, Middle Tennessee State University on 5/11/21

As a case study book, there is no index or glossary. However, medical and technical terms provide a useful link to definitions and explanations that will prove useful to students unfamiliar with the terms. The information provided is appropriate for entry-level health care students. The book includes important health problems, but I would like to see coverage of at least one more chronic/lifestyle issue such as diabetes. The book covers adult issues only.

Content is accurate without bias

The content of the book is relevant and up-to-date. It addresses conditions that are prevalent in today's population among adults. There are no pediatric cases, but this does not significantly detract from the usefulness of the text. The format of the book lends to easy updating of data or information.

The book is written with clarity and is easy to read. The writing style is accessible and technical terminology is explained with links to more information.

Consistency is present. Lack of consistency is typically a problem with case study texts, but this book is consistent with presentation, format, and terminology throughout each of the eight cases.

The book has high modularity. Each of the case studies can be used independently from the others providing flexibility. Additionally, each case study can be partitioned for specific learning objectives based on the learning objectives of the course or module.

The book is well organized, presenting students conceptually with differing patient flow patterns through a hospital. The patient information provided at the beginning of each case is a wonderful mechanism for providing personal context for the students as they consider the issues. Many case studies focus on the problem and the organization without students getting a patient's perspective. The patient perspective is well represented in these cases.

The navigation through the cases is good. There are some terminology and procedure hyperlinks within the cases that do not work when accessed. This is troubling if you intend to use the text for entry-level health care students since many of these links are critical for a full understanding of the case.

There are some non-US variants of spelling and a few grammatical errors, but these do not detract from the content of the messages of each case.

The book is inclusive of differing backgrounds and perspectives. No insensitive or offensive references were found.

I like this text for its application flexibility. The book is useful for non-clinical healthcare management students to introduce various healthcare-related concepts and terminology. The content is also helpful for the identification of healthcare administration managerial issues for students to consider. The book has many applications.

Reviewed by Paula Baldwin, Associate Professor/Communication Studies, Western Oregon University on 5/10/21

The different case studies fall on a range, from crisis care to chronic illness care. read more

The different case studies fall on a range, from crisis care to chronic illness care.

The contents seems to be written as they occurred to represent the most complete picture of each medical event's occurence.

These case studies are from the Canadian medical system, but that does not interfere with it's applicability.

It is written for a medical audience, so the terminology is mostly formal and technical.

Some cases are shorter than others and some go in more depth, but it is not problematic.

The eight separate case studies is the perfect size for a class in the quarter system. You could combine this with other texts, videos or learning modalities, or use it alone.

As this is a case studies book, there is not a need for a logical progression in presentation of topics.

No problems in terms of interface.

I have not seen any grammatical errors.

I did not see anything that was culturally insensitive.

I used this in a Health Communication class and it has been extraordinarily successful. My studies are analyzing the messaging for the good, the bad, and the questionable. The case studies are widely varied and it gives the class insights into hospital experiences, both front and back stage, that they would not normally be able to examine. I believe that because it is based real-life medical incidents, my students are finding the material highly engaging.

Reviewed by Marlena Isaac, Instructor, Aiken Technical College on 4/23/21

This text is great to walk through patient care with entry level healthcare students. The students are able to take in the information, digest it, then provide suggestions to how they would facilitate patient healing. Then when they are faced with... read more

The case studies provided accurate information that relates to the named disease.

It is relevant to health care studies and the development of critical thinking.

Cases are straightforward with great clinical information.

Clinical information is provided concisely.

Appropriate for clinical case study.

Presented to facilitate information gathering.

Takes a while to navigate in the browser.

Cultural Relevance rating: 1

Text lacks adequate representation of minorities.

Reviewed by Kim Garcia, Lecturer III, University of Texas Rio Grande Valley on 11/16/20

The book has 8 case studies, so obviously does not cover the whole of medicine, but the cases provided are descriptive and well developed. Cases are presented at different levels of difficulty, making the cases appropriate for students at different levels of clinical knowledge. The human element of both patient and health care provider is well captured. The cases are presented with a focus on interprofessional interaction and collaboration, more so than teaching medical content.

Content is accurate and un-biased. No errors noted. Most diagnostic and treatment information is general so it will remain relevant over time. The content of these cases is more appropriate for teaching interprofessional collaboration and less so for teaching the medical care for each diagnosis.

The content is relevant to a variety of different types of health care providers (nurses, radiologic technicians, medical laboratory personnel, etc) and due to the general nature of the cases, will remain relevant over time.

Easy to read. Clear headings are provided for sections of each case study and these section headings clearly tell when time has passed or setting has changed. Enough description is provided to help set the scene for each part of the case. Much of the text is written in the form of dialogue involving patient, family and health care providers, making it easy to adapt for role play. Medical jargon is limited and links for medical terms are provided to other resources that expound on medical terms used.

The text is consistent in structure of each case. Learning objectives are provided. Cases generally start with the patient at home and move with the patient through admission, testing and treatment, using a variety of healthcare services and encountering a variety of personnel.

The text is modular. Cases could be used individually within a unit on the given disease process or relevant sections of a case could be used to illustrate a specific point. The appendix is helpful in locating content specific to a certain diagnosis or a certain type of health care provider.

Each case follows a patient in a logical, chronologic fashion. A clear table of contents and appendix are provided which allows the user to quickly locate desired content. It would be helpful if the items in the table of contents and appendix were linked to the corresponding section of the text.

The hyperlinks to content outside this book work, however using the back arrow on your browser returns you to the front page of the book instead of to the point at which you left the text. I would prefer it if the hyperlinks opened in a new window or tab so closing that window or tab would leave you back where you left the text.

No grammatical errors were noted.

The text is culturally inclusive and appropriate. Characters, both patients and care givers are of a variety of races, ethnicities, ages and backgrounds.

I enjoyed reading the cases and reviewing this text. I can think of several ways in which I will use this content.

Reviewed by Raihan Khan, Instructor/Assistant Professor, James Madison University on 11/3/20

The book contains several important health issues, however still missing some chronic health issues that the students should learn before they join the workforce, such as diabetes-related health issues suffered by the patients. read more

The health information contained in the textbook is mostly accurate.

I think the book is written focusing on the current culture and health issues faced by the patients. To keep the book relevant in the future, the contexts especially the culture/lifestyle/health care modalities, etc. would need to be updated regularly.

The language is pretty simple, clear, and easy to read.

There is no complaint about consistency. One of the main issues of writing a book, consistency was well managed by the authors.

The book is easy to explore based on how easy the setup is. Students can browse to the specific section that they want to read without much hassle of finding the correct information.

The organization is simple but effective. The authors organized the book based on what can happen in a patient's life and what possible scenarios students should learn about the disease. From that perspective, the book does a good job.

The interface is easy and simple to navigate. Some links to external sources might need to be updated regularly since those links are subject to change that is beyond the author's control. It's frustrating for the reader when the external link shows no information.

The book is free of any major language and grammatical errors.

The book might do a little better in cultural competency. e.g. Last name Singh is mainly for Sikh people. In the text Harj and Priya Singh are Muslim. the authors can consult colleagues who are more familiar with those cultures and revise some cultural aspects of the cases mentioned in the book.

The book is a nice addition to the open textbook world. Hope to see more health issues covered by the book.

Reviewed by Ryan Sheryl, Assistant Professor, California State University, Dominguez Hills on 7/16/20

This text contains 8 medical case studies that reflect best practices at the time of publication. The text identifies 5 overarching learning objectives: interprofessional collaboration, client centered care, evidence-based practice, quality improvement, and informatics. While the case studies do not cover all medical conditions or bodily systems, the book is thorough in conveying details of various patients and medical team members in a hospital environment. Rather than an index or glossary at the end of the text, it contains links to outside websites for more information on medical tests and terms referenced in the cases.

The content provided is reflective of best practices in patient care, interdisciplinary collaboration, and communication at the time of publication. It is specifically accurate for the context of hospitals in Canada. The links provided throughout the text have the potential to supplement with up-to-date descriptions and definitions, however, many of them are broken (see notes in Interface section).

The content of the case studies reflects the increasingly complex landscape of healthcare, including a variety of conditions, ages, and personal situations of the clients and care providers. The text will require frequent updating due to the rapidly changing landscape of society and best practices in client care. For example, a future version may include inclusive practices with transgender clients, or address ways medical racism implicitly impacts client care (see notes in Cultural Relevance section).

The text is written clearly and presents thorough, realistic details about working and being treated in an acute hospital context.

The text is very straightforward. It is consistent in its structure and flow. It uses consistent terminology and follows a structured framework throughout.

Being a series of 8 separate case studies, this text is easily and readily divisible into smaller sections. The text was designed to be taken apart and used piece by piece in order to serve various learning contexts. The parts of each case study can also be used independently of each other to facilitate problem solving.

The topics in the case studies are presented clearly. The structure of each of the case studies proceeds in a similar fashion. All of the cases are set within the same hospital so the hospital personnel and service providers reappear across the cases, giving a textured portrayal of the experiences of the various service providers. The cases can be used individually, or one service provider can be studied across the various studies.

The text is very straightforward, without complex charts or images that could become distorted. Many of the embedded links are broken and require updating. The links that do work are a very useful way to define and expand upon medical terms used in the case studies.

Grammatical errors are minimal and do not distract from the flow of the text. In one instance the last name Singh is spelled Sing, and one patient named Fred in the text is referred to as Frank in the appendix.

The cases all show examples of health care personnel providing compassionate, client-centered care, and there is no overt discrimination portrayed. Two of the clients are in same-sex marriages and these are shown positively. It is notable, however, that the two cases presenting people of color contain more negative characteristics than the other six cases portraying Caucasian people. The people of color are the only two examples of clients who smoke regularly. In addition, the Indian client drinks and is overweight, while the First Nations client is the only one in the text to have a terminal diagnosis. The Indian client is identified as being Punjabi and attending a mosque, although there are only 2% Muslims in the Punjab province of India. Also, the last name Singh generally indicates a person who is a Hindu or Sikh, not Muslim.

Reviewed by Monica LeJeune, RN Instructor, LSUE on 4/24/20

Has comprehensive unfolding case studies that guide the reader to recognize and manage the scenario presented. Assists in critical thinking process. read more

Has comprehensive unfolding case studies that guide the reader to recognize and manage the scenario presented. Assists in critical thinking process.

Accurately presents health scenarios with real life assessment techniques and patient outcomes.

Relevant to nursing practice.

Clearly written and easily understood.

Consistent with healthcare terminology and framework

Has a good reading flow.

Topics presented in logical fashion

Easy to read.

No grammatical errors noted.

Text is not culturally insensitive or offensive.

Good book to have to teach nursing students.

Reviewed by april jarrell, associate professor, J. Sargeant Reynolds Community College on 1/7/20

The text is a great case study tool that is appropriate for nursing school instructors to use in aiding students to learn the nursing process. read more

The text is a great case study tool that is appropriate for nursing school instructors to use in aiding students to learn the nursing process.

The content is accurate and evidence based. There is no bias noted

The content in the text is relevant, up to date for nursing students. It will be easy to update content as needed because the framework allows for addition to the content.

The text is clear and easy to understand.

Framework and terminology is consistent throughout the text; the case study is a continual and takes the student on a journey with the patient. Great for learning!

The case studies can be easily divided into smaller sections to allow for discussions, and weekly studies.

The text and content progress in a logical, clear fashion allowing for progression of learning.

No interface issues noted with this text.

No grammatical errors noted in the text.

No racial or culture insensitivity were noted in the text.

I would recommend this text be used in nursing schools. The use of case studies are helpful for students to learn and practice the nursing process.

Reviewed by Lisa Underwood, Practical Nursing Instructor, NTCC on 12/3/19

The text provides eight comprehensive case studies that showcase the different viewpoints of the many roles involved in patient care. It encompasses the most common seen diagnoses seen across healthcare today. Each case study comes with its own set of learning objectives that can be tweaked to fit several allied health courses. Although the case studies are designed around the Canadian Healthcare System, they are quite easily adaptable to fit most any modern, developed healthcare system.

Content Accuracy rating: 3

Overall, the text is quite accurate. There is one significant error that needs to be addressed. It is located in the DVT case study. In the study, a popliteal artery clot is mislabeled as a DVT. DVTs are located in veins, not in arteries. That said, the case study on the whole is quite good. This case study could be used as a learning tool in the classroom for discussion purposes or as a way to test student understanding of DVTs, on example might be, "Can they spot the error?"

At this time, all of the case studies within the text are current. Healthcare is an ever evolving field that rests on the best evidence based practice. Keeping that in mind, educators can easily adapt the studies as the newest evidence emerges and changes practice in healthcare.

All of the case studies are well written and easy to understand. The text includes several hyperlinks and it also highlights certain medical terminology to prompt readers as a way to enhance their learning experience.

Across the text, the language, style, and format of the case studies are completely consistent.

The text is divided into eight separate case studies. Each case study may be used independently of the others. All case studies are further broken down as the focus patient passes through each aspect of their healthcare system. The text's modularity makes it possible to use a case study as individual work, group projects, class discussions, homework or in a simulation lab.

The case studies and the diagnoses that they cover are presented in such a way that educators and allied health students can easily follow and comprehend.

The book in itself is free of any image distortion and it prints nicely. The text is offered in a variety of digital formats. As noted in the above reviews, some of the hyperlinks have navigational issues. When the reader attempts to access them, a "page not found" message is received.

There were minimal grammatical errors. Some of which may be traced back to the differences in our spelling.

The text is culturally relevant in that it includes patients from many different backgrounds and ethnicities. This allows educators and students to explore cultural relevance and sensitivity needs across all areas in healthcare. I do not believe that the text was in any way insensitive or offensive to the reader.

By using the case studies, it may be possible to have an open dialogue about the differences noted in healthcare systems. Students will have the ability to compare and contrast the Canadian healthcare system with their own. I also firmly believe that by using these case studies, students can improve their critical thinking skills. These case studies help them to "put it all together".

Reviewed by Melanie McGrath, Associate Professor, TRAILS on 11/29/19

The text covered some of the most common conditions seen by healthcare providers in a hospital setting, which forms a solid general base for the discussions based on each case. read more

The text covered some of the most common conditions seen by healthcare providers in a hospital setting, which forms a solid general base for the discussions based on each case.

I saw no areas of inaccuracy

As in all healthcare texts, treatments and/or tests will change frequently. However, everything is currently up-to-date thus it should be a good reference for several years.

Each case is written so that any level of healthcare student would understand. Hyperlinks in the text is also very helpful.

All of the cases are written in a similar fashion.

Although not structured as a typical text, each case is easily assigned as a stand-alone.

Each case is organized clearly in an appropriate manner.

I did not see any issues.

I did not see any grammatical errors

The text seemed appropriately inclusive. There are no pediatric cases and no cases of intellectually-impaired patients, but those types of cases introduce more advanced problem-solving which perhaps exceed the scope of the text. May be a good addition to the text.

I found this text to be an excellent resource for healthcare students in a variety of fields. It would be best utilized in inter professional courses to help guide discussion.

Reviewed by Lynne Umbarger, Clinical Assistant Professor, Occupational Therapy, Emory and Henry College on 11/26/19

While the book does not cover every scenario, the ones in the book are quite common and troublesome for inexperienced allied health students. The information in the book is thorough enough, and I have found the cases easy to modify for educational purposes. The material was easily understood by the students but challenging enough for classroom discussion. There are no mentions in the book about occupational therapy, but it is easy enough to add a couple words and make inclusion simple.

Very nice lab values are provided in the case study, making it more realistic for students.

These case studies focus on commonly encountered diagnoses for allied health and nursing students. They are comprehensive, realistic, and easily understood. The only difference is that the hospital in one case allows the patient's dog to visit in the room (highly unusual in US hospitals).

The material is easily understood by allied health students. The cases have links to additional learning materials for concepts that may be less familiar or should be explored further in a particular health field.

The language used in the book is consistent between cases. The framework is the same with each case which makes it easier to locate areas that would be of interest to a particular allied health profession.

The case studies are comprehensive but well-organized. They are short enough to be useful for class discussion or a full-blown assignment. The students seem to understand the material and have not expressed that any concepts or details were missing.

Each case is set up like the other cases. There are learning objectives at the beginning of each case to facilitate using the case, and it is easy enough to pull out material to develop useful activities and assignments.

There is a quick chart in the Appendix to allow the reader to determine the professions involved in each case as well as the pertinent settings and diagnoses for each case study. The contents are easy to access even while reading the book.

As a person who attends carefully to grammar, I found no errors in all of the material I read in this book.

There are a greater number of people of different ethnicities, socioeconomic status, ages, and genders to make this a very useful book. With each case, I could easily picture the person in the case. This book appears to be Canadian and more inclusive than most American books.

I was able to use this book the first time I accessed it to develop a classroom activity for first-year occupational therapy students and a more comprehensive activity for second-year students. I really appreciate the links to a multitude of terminology and medical lab values/issues for each case. I will keep using this book.

Reviewed by Cindy Krentz, Assistant Professor, Metropolitan State University of Denver on 6/15/19

The book covers eight case studies of common inpatient or emergency department scenarios. I appreciated that they had written out the learning objectives. I liked that the patient was described before the case was started, giving some understanding of the patient's background. I think it could benefit from having a glossary. I liked how the authors included the vital signs in an easily readable bar. I would have liked to see the labs also highlighted like this. I also felt that it would have been good written in a 'what would you do next?' type of case study.

The book is very accurate in language, what tests would be prudent to run and in the day in the life of the hospital in all cases. One inaccuracy is that the authors called a popliteal artery clot a DVT. The rest of the DVT case study was great, though, but the one mistake should be changed.

The book is up to date for now, but as tests become obsolete and new equipment is routinely used, the book ( like any other health textbook) will need to be updated. It would be easy to change, however. All that would have to happen is that the authors go in and change out the test to whatever newer, evidence-based test is being utilized.

The text is written clearly and easy to understand from a student's perspective. There is not too much technical jargon, and it is pretty universal when used- for example DVT for Deep Vein Thrombosis.

The book is consistent in language and how it is broken down into case studies. The same format is used for highlighting vital signs throughout the different case studies. It's great that the reader does not have to read the book in a linear fashion. Each case study can be read without needing to read the others.

The text is broken down into eight case studies, and within the case studies is broken down into days. It is consistent and shows how the patient can pass through the different hospital departments (from the ER to the unit, to surgery, to home) in a realistic manner. The instructor could use one or more of the case studies as (s)he sees fit.

The topics are eight different case studies- and are presented very clearly and organized well. Each one is broken down into how the patient goes through the system. The text is easy to follow and logical.

The interface has some problems with the highlighted blue links. Some of them did not work and I got a 'page not found' message. That can be frustrating for the reader. I'm wondering if a glossary could be utilized (instead of the links) to explain what some of these links are supposed to explain.

I found two or three typos, I don't think they were grammatical errors. In one case I think the Canadian spelling and the United States spelling of the word are just different.

This is a very culturally competent book. In today's world, however, one more type of background that would merit delving into is the trans-gender, GLBTQI person. I was glad that there were no stereotypes.

I enjoyed reading the text. It was interesting and relevant to today's nursing student. Since we are becoming more interprofessional, I liked that we saw what the phlebotomist and other ancillary personnel (mostly different technicians) did. I think that it could become even more interdisciplinary so colleges and universities could have more interprofessional education- courses or simulations- with the addition of the nurse using social work, nutrition, or other professional health care majors.

Reviewed by Catherine J. Grott, Interim Director, Health Administration Program, TRAILS on 5/5/19

The book is comprehensive but is specifically written for healthcare workers practicing in Canada. The title of the book should reflect this. read more

The book is comprehensive but is specifically written for healthcare workers practicing in Canada. The title of the book should reflect this.

The book is accurate, however it has numerous broken online links.

Relevance/Longevity rating: 3

The content is very relevant, but some links are out-dated. For example, WHO Guidelines for Safe Surgery 2009 (p. 186) should be updated.

The book is written in clear and concise language. The side stories about the healthcare workers make the text interesting.

The book is consistent in terms of terminology and framework. Some terms that are emphasized in one case study are not emphasized (with online links) in the other case studies. All of the case studies should have the same words linked to online definitions.

Modularity rating: 3

The book can easily be parsed out if necessary. However, the way the case studies have been written, it's evident that different authors contributed singularly to each case study.

The organization and flow are good.

Interface rating: 1

There are numerous broken online links and "pages not found."

The grammar and punctuation are correct. There are two errors detected: p. 120 a space between the word "heart" and the comma; also a period is needed after Dr (p. 113).

I'm not quite sure that the social worker (p. 119) should comment that the patient and partner are "very normal people."

There are roughly 25 broken online links or "pages not found." The BC & Canadian Guidelines (p. 198) could also include a link to US guidelines to make the text more universal . The basilar crackles (p. 166) is very good. Text could be used compare US and Canadian healthcare. Text could be enhanced to teach "soft skills" and interdepartmental communication skills in healthcare.

Reviewed by Lindsey Henry, Practical Nursing Instructor, Fletcher on 5/1/19

I really appreciated how in the introduction, five learning objectives were identified for students. These objectives are paramount in nursing care and they are each spelled out for the learner. Each Case study also has its own learning... read more

As a seasoned nurse, I believe that the content regarding pathophysiology and treatments used in the case studies were accurate. I really appreciated how many of the treatments were also explained and rationales were given, which can be very helpful to facilitate effective learning for a nursing student or novice nurse.

The case studies are up to date and correlate with the current time period. They are easily understood.

I really loved how several important medical terms, including specific treatments were highlighted to alert the reader. Many interventions performed were also explained further, which is great to enhance learning for the nursing student or novice nurse. Also, with each scenario, a background and history of the patient is depicted, as well as the perspectives of the patient, patients family member, and the primary nurse. This really helps to give the reader a full picture of the day in the life of a nurse or a patient, and also better facilitates the learning process of the reader.

These case studies are consistent. They begin with report, the patient background or updates on subsequent days, and follow the patients all the way through discharge. Once again, I really appreciate how this book describes most if not all aspects of patient care on a day to day basis.

Each case study is separated into days. While they can be divided to be assigned at different points within the course, they also build on each other. They show trends in vital signs, what happens when a patient deteriorates, what happens when they get better and go home. Showing the entire process from ER admit to discharge is really helpful to enhance the students learning experience.

The topics are all presented very similarly and very clearly. The way that the scenarios are explained could even be understood by a non-nursing student as well. The case studies are very clear and very thorough.

The book is very easy to navigate, prints well on paper, and is not distorted or confusing.

I did not see any grammatical errors.

Each case study involves a different type of patient. These differences include race, gender, sexual orientation and medical backgrounds. I do not feel the text was offensive to the reader.

I teach practical nursing students and after reading this book, I am looking forward to implementing it in my classroom. Great read for nursing students!

Reviewed by Leah Jolly, Instructor, Clinical Coordinator, Oregon Institute of Technology on 4/10/19

Good variety of cases and pathologies covered. read more

Good variety of cases and pathologies covered.

Content Accuracy rating: 2

Some examples and scenarios are not completely accurate. For example in the DVT case, the sonographer found thrombus in the "popliteal artery", which according to the book indicated presence of DVT. However in DVT, thrombus is located in the vein, not the artery. The patient would also have much different symptoms if located in the artery. Perhaps some of these inaccuracies are just typos, but in real-life situations this simple mistake can make a world of difference in the patient's course of treatment and outcomes.

Good examples of interprofessional collaboration. If only it worked this way on an every day basis!

Clear and easy to read for those with knowledge of medical terminology.

Good consistency overall.

Broken up well.

Topics are clear and logical.

Would be nice to simply click through to the next page, rather than going through the table of contents each time.

Minor typos/grammatical errors.

No offensive or insensitive materials observed.

Reviewed by Alex Sargsyan, Doctor of Nursing Practice/Assistant Professor , East Tennessee State University on 10/8/18

Because of the case study character of the book it does not have index or glossary. However it has summary for each health case study outlining key elements discussed in each case study. read more

Because of the case study character of the book it does not have index or glossary. However it has summary for each health case study outlining key elements discussed in each case study.

Overall the book is accurately depicting the clinical environment. There are numerous references to external sites. While most of them are correct, some of them are not working. For example Homan’s test link is not working "404 error"

Book is relevant in its current version and can be used in undergraduate and graduate classes. That said, the longevity of the book may be limited because of the character of the clinical education. Clinical guidelines change constantly and it may require a major update of the content.

Cases are written very clearly and have realistic description of an inpatient setting.

The book is easy to read and consistent in the language in all eight cases.

The cases are very well written. Each case is subdivided into logical segments. The segments reflect different setting where the patient is being seen. There is a flow and transition between the settings.

Book has eight distinct cases. This is a great format for a book that presents distinct clinical issues. This will allow the students to have immersive experiences and gain better understanding of the healthcare environment.

Book is offered in many different formats. Besides the issues with the links mentioned above, overall navigation of the book content is very smooth.

Book is very well written and has no grammatical errors.

Book is culturally relevant. Patients in the case studies come different cultures and represent diverse ethnicities.

Reviewed by Justin Berry, Physical Therapist Assistant Program Director, Northland Community and Technical College, East Grand Forks, MN on 8/2/18

This text provides eight patient case studies from a variety of diagnoses, which can be utilized by healthcare students from multiple disciplines. The cases are comprehensive and can be helpful for students to determine professional roles, interprofessional roles, when to initiate communication with other healthcare practitioners due to a change in patient status, and treatment ideas. Some additional patient information, such as lab values, would have been beneficial to include.

Case study information is accurate and unbiased.

Content is up to date. The case studies are written in a way so that they will not be obsolete soon, even with changes in healthcare.

The case studies are well written, and can be utilized for a variety of classroom assignments, discussions, and projects. Some additional lab value information for each patient would have been a nice addition.

The case studies are consistently organized to make it easy for the reader to determine the framework.

The text is broken up into eight different case studies for various patient diagnoses. This design makes it highly modular, and would be easy to assign at different points of a course.

The flow of the topics are presented consistently in a logical manner. Each case study follows a patient chronologically, making it easy to determine changes in patient status and treatment options.

The text is free of interface issues, with no distortion of images or charts.

The text is not culturally insensitive or offensive in any way. Patients are represented from a variety of races, ethnicities, and backgrounds

This book would be a good addition for many different health programs.

Reviewed by Ann Bell-Pfeifer, Instructor/Program Director, Minnesota State Community and Technical College on 5/21/18

The book gives a comprehensive overview of many types of cases for patient conditions. Emergency Room patients may arrive with COPD, heart failure, sepsis, pneumonia, or as motor vehicle accident victims. It is directed towards nurses, medical laboratory technologists, medical radiology technologists, and respiratory therapists and their roles in caring for patients. Most of the overview is accurate. One suggestion is to provide an embedded radiologist interpretation of the exams which are performed which lead to the patients diagnosis.

Overall the book is accurate. Would like to see updates related to the addition of direct radiography technology which is commonly used in the hospital setting.

Many aspects of medicine will remain constant. The case studies seem fairly accurate and may be relevant for up to 3 years. Since technology changes so quickly in medicine, the CT and x-ray components may need minor updates within a few years.

The book clarity is excellent.

The case stories are consistent with each scenario. It is easy to follow the structure and learn from the content.

The book is quite modular. It is easy to break it up into cases and utilize them individually and sequentially.

The cases are listed by disease process and follow a logical flow through each condition. They are easy to follow as they have the same format from the beginning to the end of each case.

The interface seems seamless. Hyperlinks are inserted which provide descriptions and references to medical procedures and in depth definitions.

The book is free of most grammatical errors. There is a place where a few words do not fit the sentence structure and could be a typo.

The book included all types of relationships and ethnic backgrounds. One type which could be added is a transgender patient.

I think the book was quite useful for a variety of health care professionals. The authors did an excellent job of integrating patient cases which could be applied to the health care setting. The stories seemed real and relevant. This book could be used to teach health care professionals about integrated care within the emergency department.

Reviewed by Shelley Wolfe, Assistant Professor, Winona State University on 5/21/18

This text is comprised of comprehensive, detailed case studies that provide the reader with multiple character views throughout a patient’s encounter with the health care system. The Table of Contents accurately reflected the content. It should be noted that the authors include a statement that conveys that this text is not like traditional textbooks and is not meant to be read in a linear fashion. This allows the educator more flexibility to use the text as a supplement to enhance learning opportunities.

The content of the text appears accurate and unbiased. The “five overarching learning objectives” provide a clear aim of the text and the educator is able to glean how these objectives are captured into each of the case studies. While written for the Canadian healthcare system, this text is easily adaptable to the American healthcare system.

Overall, the content is up-to-date and the case studies provide a variety of uses that promote longevity of the text. However, not all of the blue font links (if using the digital PDF version) were still in working order. I encountered links that led to error pages or outdated “page not found” websites. While the links can be helpful, continued maintenance of these links could prove time-consuming.

I found the text easy to read and understand. I enjoyed that the viewpoints of all the different roles (patient, nurse, lab personnel, etc.) were articulated well and allowed the reader to connect and gain appreciation of the entire healthcare team. Medical jargon was noted to be appropriate for the intended audience of this text.

The terminology and organization of this text is consistent.

The text is divided into 8 case studies that follow a similar organizational structure. The case studies can further be divided to focus on individual learning objectives. For example, the case studies could be looked at as a whole for discussing communication or could be broken down into segments to focus on disease risk factors.

The case studies in this text follow a similar organizational structure and are consistent in their presentation. The flow of individual case studies is excellent and sets the reader on a clear path. As noted previously, this text is not meant to be read in a linear fashion.

This text is available in many different forms. I chose to review the text in the digital PDF version in order to use the embedded links. I did not encounter significant interface issues and did not find any images or features that would distract or confuse a reader.

No significant grammatical errors were noted.

The case studies in this text included patients and healthcare workers from a variety of backgrounds. Educators and students will benefit from expanding the case studies to include discussions and other learning opportunities to help develop culturally-sensitive healthcare providers.

I found the case studies to be very detailed, yet written in a way in which they could be used in various manners. The authors note a variety of ways in which the case studies could be employed with students; however, I feel the authors could also include that the case studies could be used as a basis for simulated clinical experiences. The case studies in this text would be an excellent tool for developing interprofessional communication and collaboration skills in a variety healthcare students.

Reviewed by Darline Foltz, Assistant Professor, University of Cincinnati - Clermont College on 3/27/18

This book covers all areas listed in the Table of Contents. In addition to the detailed patient case studies, there is a helpful section of "How to Use this Resource". I would like to note that this resource "aligns with the open textbooks... read more

The book appears to be accurate. Although one of the learning outcomes is as follows: "Demonstrate an understanding of the Canadian healthcare delivery system.", I did not find anything that is ONLY specific to the Canadian healthcare delivery system other than some of the terminology, i.e. "porter" instead of "transporter" and a few french words. I found this to make the book more interesting for students rather than deter from it. These are patient case studies that are relevant in any country.

The content is up-to-date. Changes in medical science may occur, i.e. a different test, to treat a diagnosis that is included in one or more of the case studies, however, it would be easy and straightforward to implement these changes.

This book is written in lucid, accessible prose. The technical/medical terminology that is used is appropriate for medical and allied health professionals. Something that would improve this text would to provide a glossary of terms for the terms in blue font.

This book is consistent with current medical terminology

This text is easily divided into each of the 6 case studies. The case studies can be used singly according to the body system being addressed or studied.

Because this text is a collection of case studies, flow doesn't pertain, however the organization and structure of the case studies are excellent as they are clear and easy to read.

There are no distractions in this text that would distract or confuse the reader.

I did not identify any grammatical errors.

This text is not culturally insensitive or offensive in any way and uses patients and healthcare workers that are of a variety of races, ethnicities and backgrounds.

I believe that this text would not only be useful to students enrolled in healthcare professions involved in direct patient care but would also be useful to students in supporting healthcare disciplines such as health information technology and management, medical billing and coding, etc.

Introduction

Case Study #1: Chronic Obstructive Pulmonary Disease (COPD)

Learning Objectives
Patient: Erin Johns
Emergency Room

Case Study #2: Pneumonia

Day 0: Emergency Room
Day 1: Emergency Room
Day 1: Medical Ward
Day 2: Medical Ward
Day 3: Medical Ward
Day 4: Medical Ward

Case Study #3: Unstable Angina (UA)

Patient: Harj Singh

Case Study #4: Heart Failure (HF)

Patient: Meryl Smith
In the Supermarket
Day 0: Medical Ward

Case Study #5: Motor Vehicle Collision (MVC)

Patient: Aaron Knoll
Crash Scene
Operating Room
Post Anaesthesia Care Unit (PACU)
Surgical Ward

Case Study #6: Sepsis

Patient: George Thomas
Sleepy Hollow Care Facility

Case Study #7: Colon Cancer

Patient: Fred Johnson
Two Months Ago
Pre-Surgery Admission

Case Study #8: Deep Vein Thrombosis (DVT)

Patient: Jamie Douglas

Appendix: Overview About the Authors

Ancillary Material

About the book.

Health Case Studies is composed of eight separate health case studies. Each case study includes the patient narrative or story that models the best practice (at the time of publishing) in healthcare settings. Associated with each case is a set of specific learning objectives to support learning and facilitate educational strategies and evaluation.

The case studies can be used online in a learning management system, in a classroom discussion, in a printed course pack or as part of a textbook created by the instructor. This flexibility is intentional and allows the educator to choose how best to convey the concepts presented in each case to the learner.

Because these case studies were primarily developed for an electronic healthcare system, they are based predominantly in an acute healthcare setting. Educators can augment each case study to include primary healthcare settings, outpatient clinics, assisted living environments, and other contexts as relevant.

About the Contributors

Glynda Rees teaches at the British Columbia Institute of Technology (BCIT) in Vancouver, British Columbia. She completed her MSN at the University of British Columbia with a focus on education and health informatics, and her BSN at the University of Cape Town in South Africa. Glynda has many years of national and international clinical experience in critical care units in South Africa, the UK, and the USA. Her teaching background has focused on clinical education, problem-based learning, clinical techniques, and pharmacology.

Glynda‘s interests include the integration of health informatics in undergraduate education, open accessible education, and the impact of educational technologies on nursing students’ clinical judgment and decision making at the point of care to improve patient safety and quality of care.

Faculty member in the critical care nursing program at the British Columbia Institute of Technology (BCIT) since 2003, Rob has been a critical care nurse for over 25 years with 17 years practicing in a quaternary care intensive care unit. Rob is an experienced educator and supports student learning in the classroom, online, and in clinical areas. Rob’s Master of Education from Simon Fraser University is in educational technology and learning design. He is passionate about using technology to support learning for both faculty and students.

Part of Rob’s faculty position is dedicated to providing high fidelity simulation support for BCIT’s nursing specialties program along with championing innovative teaching and best practices for educational technology. He has championed the use of digital publishing and was the tech lead for Critical Care Nursing’s iPad Project which resulted in over 40 multi-touch interactive textbooks being created using Apple and other technologies.

Rob has successfully completed a number of specialist certifications in computer and network technologies. In 2015, he was awarded Apple Distinguished Educator for his innovation and passionate use of technology to support learning. In the past five years, he has presented and published abstracts on virtual simulation, high fidelity simulation, creating engaging classroom environments, and what the future holds for healthcare and education.

Janet Morrison is the Program Head of Occupational Health Nursing at the British Columbia Institute of Technology (BCIT) in Burnaby, British Columbia. She completed a PhD at Simon Fraser University, Faculty of Communication, Art and Technology, with a focus on health information technology. Her dissertation examined the effects of telehealth implementation in an occupational health nursing service. She has an MA in Adult Education from St. Francis Xavier University and an MA in Library and Information Studies from the University of British Columbia.

Janet’s research interests concern the intended and unintended impacts of health information technologies on healthcare students, faculty, and the healthcare workforce.

She is currently working with BCIT colleagues to study how an educational clinical information system can foster healthcare students’ perceptions of interprofessional roles.

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2020 Research Highlights — Human Health Advances

Disease prevention, diagnosis, and treatment .

With NIH support, scientists across the United States and around the world conduct wide-ranging research to discover ways to enhance health, lengthen life, and reduce illness and disability. Groundbreaking NIH-funded research often receives top scientific honors. In 2020, these honors included one of NIH’s own scientists and another NIH-supported scientist who received Nobel Prizes . Here’s just a small sample of the NIH-supported research accomplishments in 2020.

Full 2020 NIH Research Highlights List

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COVID-19 vaccines and treatments

Since first appearing in China late last year, COVID-19 has become an ongoing global pandemic. NIH researchers quickly began testing potential treatments to help reduce the severity of the disease. Remdesivir, a broad-spectrum antiviral treatment, showed early promise . Results from the completed trial in October showed that it shortened recovery time for patients hospitalized with COVID-19 . NIH research was also instrumental in determining which treatments, such as hydroxychloroquine , were ultimately not effective. Meanwhile, NIH researchers began developing vaccine candidates to protect against the disease. The first COVID-19 vaccine candidate tested in people , co-developed by NIH and the biotech company Moderna, Inc., triggered an immune response against the virus without serious side effects. An analysis in November found the vaccine was safe and well-tolerated, with a vaccine efficacy rate of 94.5% . The FDA approved it for emergency use in December. NIH also launched the Rapid Acceleration of Diagnostics (RADx SM ) initiative to speed innovation in COVID-19 testing. An NIH-funded COVID-19 home test was the first to receive over-the-counter authorization from the FDA.

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Physician listens to senior patient’s heart

Comparing heart disease treatments

People with moderate to severe but stable heart disease may undergo invasive procedures, such as bypass surgery and stenting, or manage their condition with medication and lifestyle changes alone. A study showed that invasive procedures may offer better symptom relief and quality of life for some patients with chest pain. But for those who didn't have any symptoms, it was safe to begin treatment with non-invasive approaches. The findings may change clinical practice and official guidelines for treating patients.

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Doctor in consultation with male patient

Combining tests more accurately diagnoses prostate cancer

The type of biopsy traditionally used to diagnose prostate cancer takes systematically spaced tissue samples from the prostate gland. This method isn’t targeted and can lead to uncertainty about whether a man has aggressive prostate cancer. Researchers found that adding MRI-targeted biopsies to the traditional prostate biopsy created a more accurate diagnosis and prediction of the course of prostate cancer. The approach is poised to help reduce both overtreatment and undertreatment of the disease.

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Early detection of Alzheimer’s disease

Having a simple blood test to detect Alzheimer’s disease before symptoms develop would aid the study of treatments to slow or stop its progression. Studies found that a protein called ptau181, which can be measured in the blood, was as good as invasive or expensive tests at diagnosing Alzheimer’s early . Another protein, called ptau217, was even better at predicting who would later develop the disease . A type of brain imaging could also play a role in tracking disease development. These approaches could help identify people to participate in trials of early treatments or preventive strategies.

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Number of steps per day more important than step intensity

Walking is an easy way for many inactive people to ease into better health. A goal of 10,000 steps a day is common. A study found that adults who took at least 8,000 steps a day had a reduced risk of death over the following decade than those who only walked 4,000 steps a day. Step intensity (number of steps per minute) didn’t influence the risk of death, suggesting that the total number of steps per day is more important than intensity.

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Photos of elbow with eczema before treatment and without eczema afterward

Harnessing the health benefits of bacteria

Some types of bacteria cause disease, but others can help protect human health. A strain of bacteria called Lactobacillus crispatus was used as a treatment to prevent recurring bacterial vaginosis . In another study, treatment with the bacterium Roseomonas mucosa, taken from healthy human skin, improved eczema in children . These findings show the potential of harnessing the healthy human microbiome to prevent or treat disease.

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Multifocal contact lenses slow myopia progression in children

Myopia, also called nearsightedness, is a common vision problem, where close objects can be seen clearly but objects farther away appear blurry. In the U.S., myopia typically begins in childhood. Researchers found that children who wore certain multifocal contact lenses had slower progression of their myopia, or nearsightedness, over three years. The findings support using multifocal contacts to treat myopia in children, which could also help prevent other vision problems later in life.

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Biomarkers predict recovery from brain injury

More than a million people in the U.S. experience a mild traumatic brain injury, or concussion, every year. Researchers found that military veterans with higher blood levels of a protein released by injured neurons were more likely to report long-term symptoms. More study is needed to confirm whether this could be used to predict who is at risk of long-term health problems after concussion. Two blood proteins were linked to the time needed by college athletes to return to play following a concussion. These biomarkers may help doctors predict which athletes need additional time to recover.

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Case Studies: Diseases

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Aging (including Alzheimer's disease)

C Rundel, Genes, aging, and the future of longevity. Engineering & Science LXV #4, 12/02, p 36. A delightful essay on some issues of aging, written by a Caltech undergraduate as part of a science writing class -- and then published in the Caltech magazine. The article is available online at http://eands.caltech.edu/articles/LXV4/longevity.html . The article discusses some genes that are known to affect aging in simple model organisms, and even a drug which seems to extend the life of fruit flies.

An intriguing result has recently been published: A team at Scripps Research Institute (La Jolla, California) has engineered mice to have a slightly lower core body temperature (by about 0.5 degree Celsius). These mice lived longer (by about 15%) than the "normal" mice. How did they lower the body temperature? By engineering the mice to make a heat-producing protein (uncoupling protein) in the hypothalamus -- where the body senses and regulates its temperature. The cooler mice ate and exercised normally, had somewhat higher weight (since they were producing less heat from the same food) -- and lived longer. Interestingly, one effect of severe caloric restriction, which is known to increase lifespan, is lowering the body temperature. So this work may give us one more piece of a complex puzzle. Its practical significance for now is purely speculative: there is no known way to reduce human body temperature, and of course we know nothing about what the side effects might be. The paper is B Conti et al, Transgenic mice with a reduced core body temperature have an increased life span. Science 314:825, 11/3/06. The paper is accompanied by a "perspective" article: C B Saper, Biomedicine: Life, the universe, and body temperature. Science 314:773, 11/3/06. These are online at http://www.sciencemag.org/content/314/5800/773.summary (perspective, probably the best place to start) and http://www.sciencemag.org/content/314/5800/825.abstract (article).

SAGE KE, the Science of Aging Knowledge Environment Archive Site, from Science magazine. "From October 2001 to June 2006, Science's SAGE KE provided news, reviews, commentaries, disease case studies, databases, and other resources pertaining to aging-related research. Although SAGE KE has now ceased publication, we invite you to search and browse the article content on this archive site." http://sageke.sciencemag.org/ .

Nature web focus sites on aging:

http://www.nature.com/nm/focus/alzheimer/index.html . Alzheimer's disease. (June 2006)
http://www.nature.com/nature/focus/s...nce/index.html . Senescence: Cells, ageing and cancer. (August 2005)
http://www.nature.com/nature/focus/l...pan/index.html . Determining lifespan. (September 2003)

Book. Stephen S Hall, Merchants of Immortality - Chasing the dream of human life extension. Houghton Mifflin, 2003. ISBN 0-618-09524-1. Available in Berkeley Public Library. For more about this book, see the listing of it under Cloning and stem cells . The "aging" parts of the book largely deal with telomerase, a fascinating scientific topic which probably is not a key limiting factor in human aging. In fact, much of the book deals with the hype surrounding telomerase -- and attempts to commercialize telomerase technologies.

Book. Lenny Guarente, Ageless Quest - One scientist's search for genes that prolong youth. Cold Spring Harbor Lab Press, 2003. ISBN 0-87969-652-4. Available in UC Berkeley Library. Guarente is a biologist at MIT. In this short book, he talks about finding a gene that extends the life of simple yeast -- and of worms. The question, then, is whether it is relevant to aging in higher organisms, including humans. He discusses evidence that it may be, though conclusive evidence is not yet available. This story is a good testimonial to the importance of basic research -- how studying simple model systems leads to insights that guide work in more complex systems. It is also a good story of how scientists develop and pursue leads -- some of which work out and some of which do not; that is how science works. It is an optimistic book -- perhaps too optimistic, since the gap between what has been shown and what is needed is still quite large. Enjoy the story, and Guarante's enthusiasm. But be careful to distinguish what turns out to work from the exciting discussions of what might be.

Anthrax vaccine immunization program. One place where the anthrax vaccine is actually used with high frequency is in the US military. This is their site about the vaccine and the program. Be alert for bias (as with any source!), but there is actually a lot of good info here. www.anthrax.osd.mil.

Researchers, including a group from UC Berkeley, have explored the tricks that the anthrax bacteria use to get the iron they need for growth. They found that these bacteria make two chemicals designed to steal iron from their host; such chemicals are generically called siderophores. One of these is attacked by the human immune system; however, the other -- the more novel one -- evades it, and actually succeeds in supplying iron to the bacteria. They suggest that this novel siderophore might be a good target for anti-anthrax drugs, or simply a marker for detection of this pathogen. The work was featured in the student newspaper, December 8, 2006: Researchers Find Possible Way to Block Anthrax, http://archive.dailycal.org/article/22576/_i_science_technology_i_br_researchers_find_possib . It was also discussed in a nice article in the student publication BSR: N Keith, Double Trouble - Anthrax has two tricks for stealing iron. Berkeley Science Review, Issue 12, p 15, Spring 2007. BSR is free online; this item is at sciencereview.berkeley.edu/ar...ticle=briefs_5. The work was published as R J Abergel et al, Anthrax pathogen evades the mammalian immune system through stealth siderophore production. PNAS 103:18499, 12/5/06. Online at http://www.pnas.org/content/103/49/18499.abstract . This work is also briefly noted on my Intro Chem Internet Resources page under solutions .

Book. For some interesting history, see the listing for Thomas D Brock, Robert Koch - A Life in Medicine and Bacteriology (1988) on my page Books: Suggestions for general reading . One major story is the first clear elucidation of the life cycle of a pathogenic bacterium -- anthrax. Those interested in bacteria, especially as agents of disease, will enjoy this fascinating tale of the origins of modern medical microbiology.

Antibiotics

Bacterial 'battle for survival' leads to new antibiotic -- Holds promise for treating stomach ulcers. A press release from MIT, Feb 2008, on a new approach for discovering new antibiotics. Briefly, they force bacteria not known to make antibiotics to compete with other bacteria. One possible response is for them to develop the ability to make antibiotics. This should be considered interesting lab work at this point. The potential of the new antibiotics is unknown. web.mit.edu/newsoffice/2008/a...tics-0226.html.

Alliance for the Prudent Use of Antibiotics. www.tufts.edu/med/apua/. This site has "an agenda" -- trying to reduce "inappropriate" use of antibiotics. A particular concern is the use of vast amounts of antibiotics with farm animals, sometimes with minimal justification. The site also contains a lot of general information about antibiotics, aimed at the consumer and at doctors.

A local angle. The July 24, 2003, issue of the Berkeleyan (a campus newspaper for staff) published part of an interview with science writer and UCB journalism professor Michael Pollan on the subject of antibiotics in beef farming, with a focus on McDonald's announcement of favoring suppliers that use less antibiotics. The article title is Prof has a beef with McDonald's antibiotics announcement. The entire interview is online at http://www.berkeley.edu/news/media/releases/2003/07/01_pollan.shtml . Very readable, with a useful general overview of why antibiotics are used in commercial production of animals. Pollan also expresses reservations about how significant the policy announcement will be.

The DNA double helix has become a popular icon, known well beyond the circles of those who know anything about biology. And of course, some artists are attracted to social issues. Thus it should not be surprising that DNA and genes and genomes and related issues have become the subject of artistic efforts.

John Sulston was the head of the British lab working on the human genome. Provocatively and/or appropriately, artist Marc Quinn did a "portrait" of Sulston -- using his DNA. For a news article on this, which includes the "portrait", see http://www.guardian.co.uk/culture/2001/sep/22/art . If you have access to Nature, see Martin Kemp's article about the portrait in the October 25, 2001, issue (413:778). (The printed article and the online PDF file contain the "portrait"; however the online HTML file does not.) This article is part of Nature's regular series, Science and Culture; art historian Kemp is a regular contributor.

Sulston shared the 2002 Nobel prize for his work on development in the worm Caenorhabditis elegans. In the course of that work, he played a key role in discovering the phenomenon of programmed cell death, now called apoptosis. http://www.nobelprize.org/nobel_priz...aureates/2002/ .

England issued a coin to commemorate the 50th anniversary of the DNA structure (which was developed at Cambridge Univ in England); it shows a DNA double helix on one side. (The other side shows the Queen, who coincidentally is celebrating her 50th anniversary as monarch.) For pictures of the coin, plus some information: http://www.taxfreegold.co.uk/2003two...dsdnagold.html .

Also see L Gamwell, Science in culture: Art after DNA. Nature 422:817, 4/24/03. http://www.nature.com/nature/journal...l/422817a.html . The subtitle notes "The double helix has inspired scientists and artists alike."

Bio-inspiration (biomimetics)

Book. Peter Forbes, The Gecko's Foot - Bio-inspiration: Engineering new materials from nature. Norton, 2005. The lotus leaf is easily rinsed clean; the gecko can climb a glass wall. Why? And, can we make use of the principles that Nature has used to achieve these remarkable accomplishments? Those are just two of the topics in this delightful book -- one of which is reflected in its title. The theme is bio-inspiration (sometimes called biomimetics), in which we look to Nature for an idea about how to do something. The hook-and-loop fastener, popularly known by the tradename Velcro, is an example of old, but the field has now taken on an identity that reflects a more focused effort to discover and exploit what Nature has already learned. Forbes emphasizes work at the "nano" level, where recent advances in instrumentation, such as the scanning electron microscope (SEM), helped us unlock Nature's secrets. Commercial importance? Well, products based on the self-cleaning lotus leaf and the sticky gecko foot are on the market. They are not yet big successes; perhaps that will take time, or perhaps there is less here of commercial importance than we would like to believe. In any case, the book is delightful biology, delightfully presented. It is suited for the scientific novice, but even biologists are likely to find it rewarding. This book is listed on my Book suggestions page, and as further reading for Intro Chem Ch 15, re intermolecular forces, and for Organic/Biochem Ch 15, re spider silk. In fact, it was reading this book that prompted me to start this BITN section.

From the University of Reading:

Centre for Biomimetics. www.reading.ac.uk/biomim/home.htm.
BIONIS: The Biomimetics Network for Industrial Sustainability. www.reading.ac.uk/bionis/.

From University of California, Berkeley

Biomimetic Millisystems Lab. "The goal of the Biomimetic Millisystems Lab is to harness features of animal manipulation, locomotion, sensing, actuation, mechanics, dynamics, and control strategies to radically improve millirobot capabilities. Research in the lab ranges from fundamental understanding of mechanical principles to novel fabrication techniques to system integration of autonomous millirobots. The lab works closely with biologists to develop models of function which can be tested on engineered and natural systems. The lab's current research is centered on fly-size flapping flight, and all-terrain crawling using nanostructured adhesives." The "Current Research Projects" listed in January 2008 include: Micromechanical Flying Insect, Biologically Inspired Synthetic Gecko Adhesives, Millirobot Rapid Prototyping, Micro-Robots and Microassembly. http://robotics.eecs.berkeley.edu/~ronf/Biomimetics.html . This page is from Ronald Fearing, in EECS (Electrical engineering and computer science). However, a glance at the people shows that this is a collaboration that also includes the Departments of Integrative Biology and Chemical Engineering.
CIBER. The Center for Interdisciplinary Bio-inspiration in Education & Research. A new center at Berkeley, headed by Dr Robert Full, of Integrative Biology. http://ciber.berkeley.edu . From "Objectives": CIBER "will innovate methods to extract principles in biology that inspire novel design in engineering and train the next generation of scientists and engineers to collaborate in mutually beneficial relationships. ... Biologists working with engineers, computer scientists and mathematicians are discovering general principles of nature from the level of molecules to behavior at an ever-increasing pace. Now more than ever before, nature can instruct us on how to best use new materials and manufacturing processes discovered by engineers, because these human technologies have more of the characteristics of life. This effort will require unprecedented integration among disciplines that include biology, psychology, engineering, physics, chemistry, computer science and mathematics." Choose Publications & Journals for good information on the work going on.

* Robot Flea Circus - Berkeley engineers build bionic bugs, by Tracy Powell. Berkeley Science Review, Fall 2007, p 22. Studying insect locomotion leads to ideas for designing robots. sciencereview.berkeley.edu/ar...cle=bionicbugs. * News story in the Daily Cal, the student newspaper, February 12, 2008. Mimicking the geckos' ability to defy gravity - From geckos to humans to robots: new adhesive tape makes the vertical horizontal. http://archive.dailycal.org/article/100353/mimicking_the_geckos_ability_to_defy_gravity . * News release: Engineers create gecko-inspired high-friction micro-fibers, August 2006. http://www.berkeley.edu/news/media/releases/2006/08/22_microfiber.shtml . As you read the item, note that they are not making synthetic gecko feet, but rather using some of what they learned about gecko feet to help them design a new material.

'Gecko foot' band-aids could promote healing. A news story in New Scientist, February 19, 2008, about the development of a new type of adhesive tape, which may be suitable for not only band-aids but also sutures. It is based in part on the structure of the gecko foot. Importantly, the work does not simply mimic the gecko foot, but builds on it, to develop a material suitable for the intended use. The story is online at http://www.newscientist.com/article/dn13347 . The work referred to is published as: A Mahdavi et al, A biodegradable and biocompatible gecko-inspired tissue adhesive. PNAS 105:2307, 2/19/08. There is a link to the article at the end of the news story.

Posts on my Musings pages on biomimetics include... * New, April 18, 2011. Why don't woodpeckers get headaches? Designing better shock absorbers (April 18, 2011) . * New, February 27, 2011. Robots should learn to crawl first, then walk (February 27, 2011) . * Added December 15, 2010. Armor (February 5, 2010) .

Brain (autism, schizophrenia)

There is evidence to suggest that infection of the mother during pregnancy may increase the chances of some brain diseases, including autism and schizophrenia. The effects seem to be due not to the infectious agent per se, but to the host response. Now, work with a mouse model system points to one specific component, the cytokine IL-6, as promoting the brain mis-development. Remember, this is with mice; the work generates some leads that must be followed up to see if they are relevant to humans. A press release about this work: "Researchers discover link between schizophrenia, autism and maternal flu", Oct 1, 2007: media.caltech.edu/press_releases/13039. The paper is: S E P Smith et al, Maternal immune activation alters fetal brain development through interleukin-6. Journal of Neuroscience, 27:10695-10702, 10/3/07.

Some general educational resources...

New, November 29, 2010. Inside Cancer. Educational materials, for the general public. Sections include: hallmarks, causes and prevention, diagnosis and treatment, pathways. Some materials are specifically for teachers. www.insidecancer.org. This is from the Dolan DNA Learning Center, Cold Spring Harbor Laboratory: http://www.dnalc.org/websites/ . Other parts of the Dolan DNA Learning Center are referred to under BITN Resources: DNA and the genome and Molecular Biology Internet Resources: Methods .

Understanding Cancer. A series of informational web pages for the general public, from the National Cancer Institute. www.cancer.gov/cancertopics/U...standingCancer. Also in Spanish.

Cancer Quest, a broad informational resource, largely organized as a tutorial, from G Orloff, Emory Univ. Topics range from the basic underlying biology to clinical issues. Special pages offer guidance to patients, educators, students, and health professionals. http://www.cancerquest.org . Also available in Chinese, Italian, Russian, Spanish.

Personalized cancer vaccine made in plants. This work deals with a cancer of the immune system, called follicular B cell lymphoma. An important characteristic of this cancer is that each case expresses a unique antigen, reflecting its development from a single immune system cell. The goal is to make a vaccine that targets this particular antigen. Here, they show that they can do this in a plant system -- which is both faster and cheaper than animal systems previously tried. The resulting vaccines do elicit an immune response in [most of] the patients, though no therapeutic benefit was seen in this small early study. The work is of note both for the special approach of making a personalized vaccine, and for the broader issue of making vaccines in plants. News story, from Stanford: Plants can be factories making vaccine to treat cancer, July 23, 2008. http://news.stanford.edu/news/2008/july23/med-plants-072308.html . The paper: A A McCormick et al, Plant-produced idiotype vaccines for the treatment of non-Hodgkin's lymphoma: Safety and immunogenicity in a phase I clinical study. PNAS 105:10131, 7/22/08. Free online: http://www.pnas.org/content/105/29/10131 .

Drug targeting. A group from UC Berkeley and San Francisco reported making a new drug delivery system. The active drug is attached to a large molecule called a dendrimer. Because the blood system in tumors tends to be leaky, the large drug complex is taken up by the tumor selectively, and then hydrolyzed. They report promising results in a mouse model system. Both the article and the story about it discuss some of the logic of the system. There is a good news story about the work in BSR, a student publication: N Parghi, Right on target - Reducing chemotherapy's collateral damage. Berkeley Science Review, issue 12, p 12, Spring 2007. Free online: sciencereview.berkeley.edu/ar...ticle=briefs_3. The paper: C C Lee et al, A single dose of doxorubicin-functionalized bow-tie dendrimer cures mice bearing C-26 colon carcinomas. PNAS 103:16649, 11/7/06. Free online: http://www.pnas.org/content/103/45/16649 .

Irreversible electroporation. UC Berkeley scientists, led by B Rubinsky, are working on a new approach to treating solid tumors. A new paper is on the use of the method with pigs, the first large animal tests. The method is a variation of the common electroporation used in laboratory work to make transient membrane pores that can allow uptake of drugs or even DNA. The key difference is that the conditions are chosen so that the pores do not quickly reseal; thus the cells "leak to death". In this method, the electrical pulse is delivered directly to tumor cells, in a surgical procedure. News story, "A breakthrough treatment for tumors? New medical technique uses electrical pulses to punch holes in target cell membrane." February 14, 2007. Online: http://www.berkeley.edu/news/berkele...reatment.shtml .

The Carcinogenic Potency Database (CPDB). A database of carcinogens, based on testing in animals. From Lois Swirsky Gold, Bruce Ames, and colleagues at UC Berkeley. potency.berkeley.edu/.

Book. J Michael Bishop, How to win the Nobel prize - An unexpected life in science. Harvard Univ Press, 2003. ISBN 0-674-00880-4. Bishop is a local story -- long time scientist at UCSF, now Chancellor there. Bishop's work on cellular genes that become cancer genes earned the Nobel Prize for him and his UCSF colleague Harold Varmus. (And a few days after the Nobel announcement he was at Candlestick Park for the World Series game that did not happen.) The book is based on a series of lectures, and has the informal breezy style of talks for a general audience. It is more generally about the nature of science, and about baseball, music and the human Michael Bishop, than about cancer in particular. One chapter does indeed give a good, not-too-technical introduction to the nature of cancer -- and his own contributions. The final chapter is about the future of science, and its role in society. All-in-all, a fairly light but interesting read.

J Diamond, The double puzzle of diabetes. Nature 423:599, 6/5/03. Feature. Nature's blurb for this article: "Why is the prevalence of type 2 diabetes now exploding in most populations, but not in Europeans? The genetic and evolutionary consequences of geographical differences in food history may provide the answer." The article gives an overview of the types of diabetes, and their incidence. The main purpose is to propose an explanation of why diabetes is not rampant among Europeans. As you read this, remember that he is proposing a hypothesis -- and some tests of it; be careful about remembering his "answer" as if it were true. Reading the article for its background information can be good. Online at http://www.nature.com/nature/journal...l/423599a.html .

Ebola and Marburg

Ebola and Marburg are related viruses. Ebola has been observed to emerge "from the jungle" from time to time. A major -- and important -- mystery is where is it "hiding". That is, what is the "reservoir" (likely an animal) from which the virus emerges? Now there is evidence that bats may be the culprit.; the bats carrying the virus show no symptoms. It is important to emphasize that this is a new finding, subject to further work. Even if correct, it only shows that the bats are a part of the story; there may be more to it. The article is: E M Leroy et al, Fruit bats as reservoirs of Ebola virus. Nature 438:575, 12/1/05. The abstract is at http://www.nature.com/nature/journal...s/438575a.html . Here are two news stories on this finding: http://www.innovations-report.com/ht...ort-53574.html and http://news.bbc.co.uk/2/hi/health/4484494.stm .

Now there is a report of Marburg virus being detected in bats. The work is published: J S Towner et al, Marburg virus infection detected in a common African bat. PLoS ONE 2(8):e764, 8/22/07. There is a news story, August 2007: Scientists detect presence of Marburg virus in African fruit bats, at: http://www.eurekalert.org/pub_releas...-sdp082107.php . This has a link to the article, which is freely available.

Progress with efforts to control Ebola, Marburg viruses. Microbe 1:217, 5/06. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at forms.asm.org/microbe/index.asp?bid=42381. Discusses both vaccines and drugs.

Emerging diseases (general)

In the Spring of 2003, as I started to put together a BITN web site, one dominant news story was a new illness, called SARS (severe acute respiratory syndrome). Our fears of SARS are enhanced by our ignorance. And that is not just the ignorance of the general public, but also the ignorance of the medical and scientific communities. SARS is a new disease. At least at the start, we do not know what causes it, how it is transmitted, how to contain or treat it -- even how to diagnose or define it, or what its risks are. Of course, over time, answers to some of these questions are developed. It is actually quite amazing how fast some of the answers come in. On the other hand, not all the answers we hear are correct. (For example, three different organisms were quickly "identified" as the cause of SARS. Obviously, two of those were likely to be incorrect.)

By mid-summer, we may have the disease under control. Yet, we still have little idea how the disease started -- and if/when it may return.

SARS is an example of an emerging disease -- a new disease. Other diseases that have emerged over the last 30 years include Legionnaire's diseases, AIDS , toxic shock syndrome, Ebola , West Nile Virus -- and perhaps a new strain of Influenza each year. Both SARS and the broader topic raise lots of questions about how we deal with a disease that has emerged, and how we might predict or prevent new emerging diseases.

M E J Woolhouse, Where Do Emerging Pathogens Come from? Microbe 1:511, 11/06. microbemagazine.org/index.php...gens-come-from. A discussion of the factors involved in the emergence of new diseases.

J L Fox, Cats with MRSA, elephants with TB are parts of a "microbial storm". Microbe 3:451, 10/08. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at microbemagazine.org/images/st...1008000448.pdf (scroll down to page 4 of the file for this item -- or just look for the elephants). "Emerging diseases" is a two-way street. Diseases may pass from humans to other animals, too. This news story discusses some examples and concerns.

The following sites track emerging diseases

Center for Infectious Disease Research and Policy (Univ Minnesota). http://www.cidrap.umn.edu . I list specific CIDRAP sections on my pages for Influenza (Bird flu) and Prions (BSE, CJD, etc) . Other topic areas here include: Bioterrorism, Biosecurity (e.g., food), Food safety (foodborne illnesses, irradiation), and a miscellaneous section that includes SARS, West Nile, Monkeypox, Chemical Terrorism. Useful for the general audience.
Healthmap, a "Global disease alert map", presents disease reports by country. You can click on a map or chose from a list of countries. http://www.healthmap.org/ . From J Brownstein, Harvard Medical School. Also in Arabic, Chinese, French, Portuguese, Russian, Spanish. Caution: loads very slowly.
ProMED-mail is aimed at medical professionals, informing them about emerging diseases; it is one of the major primary sources underlying the sites listed above. Includes announcements and maps of outbreaks, as well as general information. From the International Society for Infectious Diseases. http://www.promedmail.org . Parts of the site are also available in Chinese, Japanese, Portuguese, Russian, Spanish.
US government sites with information on emerging diseases:
CDC. www.cdc.gov/ncidod/diseases/e...ease_sites.htm.
NIH. http://www.niaid.nih.gov/topics/emerging/ .
Book. See the listing for Dorothy H Crawford, Deadly Companions - How microbes shaped our history (2007) on my page Books: Suggestions for general reading . This book is about the relationship between microbes and man. It starts with a discussion of SARS, and discusses many emergences of the past. Good perspective.
Added April 9, 2011. One health (November 15, 2010) .
Added March 12, 2011. Both ways (November 18, 2008) . ge

Ethical and social issues

As noted in the introductory materials, I intend the main emphasis here to be the scientific issues. Of course, other issues are important parts of the overall story. Some of the topic-specific resources listed include ethical and social issues. But occasionally, I may want to list a site that focuses on these matters.

Bloodlines: Technology Hits Home. The web site http://www.pbs.org/bloodlines/ was written to accompany a PBS show. It broadly deals with issues arising from reproductive and genetic technologies, and includes interactive questions which you can try to evaluate for yourself.

Bioethics Web. "BioethicsWeb is a gateway to evaluated, high quality Internet resources relating to biomedical ethics, including ethical, social, legal and public policy questions arising from advances in medicine and biology, issues relating to the conduct of biomedical research and approaches to bioethics." Subtopics include: Biomedicine, Clinical practice, Environment/agriculture/foods, Ethics: theory and concepts, Research conduct, Society/policy/law, and more.

aidsinfo.nih.gov. A broad source of HIV information, from NIH. It includes a section on vaccine trials, as well as drug treatments and other research areas.

The 2008 Nobel prize in Physiology or Medicine was awarded to Harald zur Hausen, "for his discovery of human papilloma viruses causing cervical cancer" and Francoise Barre-Sinoussi and Luc Montagnier, "for their discovery of human immunodeficiency virus". See the Nobel site: http://www.nobelprize.org/nobel_priz...aureates/2008/ . This item is listed on this page for HIV and HPV .

Hormone replacement therapy

A major and continuing news story for 2002-3 was based on some long term studies of the use of replacement hormones by post-menopausal women. The results were not at all what had been commonly expected. One important general point from the story is the problem of knowing what long term effects of a treatment are, especially the smaller effects -- without doing long term studies with large numbers of patients. Lots of info, with regular updates, is available at the home page for the Women's Health Initiative: http://www.whi.org . "The Women's Health Initiative (WHI) is a long-term national health study that focuses on strategies for preventing heart disease, breast and colorectal cancer and fracture in postmenopausal women. This 15-year project involves over 161,000 women ages 50-79, and is one of the most definitive, far reaching programs of research on women's health ever undertaken in the U.S. The purpose of this site is to provide WHI participants [and] others interested in the WHI findings a way of obtaining information about research results directly from the study."

And now, after five more years of data, the advice changes again. It is more detailed, more nuanced. This is common, and emphasizes that we must be cautious about over-interpreting any data set. News story, June 21, 2007, from Brigham and Women's Hospital and Harvard Medical School: "Estrogen Therapy and Coronary Artery Calcification. Women aged 50-59 who took estrogen show a reduced risk of coronary plaque buildup." www.brighamandwomens.org/abou...b=0&PageID=272.

For an introduction to the use of testosterone supplements in men, see a page from the US National Institute on Aging: Frequently Asked Questions About Testosterone and the IOM Report, 11/12/03. www.nia.nih.gov/NewsAndEvents...eIOMReport.htm.

HPV (Human papillomavirus)

A new vaccine was announced recently. It is widely known by its trade name, Gardasil. It acts to prevent infection by some strains of the human papillomavirus, which cause cervical cancer and genital warts. The vaccine itself is indeed a product of modern biotechnology: it contains only viral proteins (produced in yeast), with no viral genome; thus it cannot grow at all. Here are some materials from the CDC about this vaccine: * "Questions and Answers about HPV Vaccine Safety". www.cdc.gov/vaccinesafety/Vac.../hpv_faqs.html * A more technical report: "Quadrivalent Human Papillomavirus Vaccine -- Recommendations of the Advisory Committee on Immunization Practices (ACIP)", by L E Markowitz et al, dated March 23, 2007. It provides background about the type of virus and its effects, and the nature of the vaccine. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm

Notes... There are many strains of HPV. Only some of them cause cancer or warts. The vaccine is effective against four of these strains. Data so far suggests that the vaccine is extremely effective against those four strains, but it is important to realize that strains other than those in the vaccine are responsible for some cancer. One might be confused by hearing that the virus is "100%" effective or "70%" effective. The former number refers to the apparent effectiveness against the strains included in the vaccine; the latter number refers to the overall effectiveness against cervical cancer, given that the current vaccine works against only some of the relevant strains. Long term issues about this new vaccine are, of course, not known. For example, how long is it effective?

The May 10, 2007, issue of the New England Journal of Medicine contains several articles on this new vaccine -- with more data and perspectives. I suggest that readers start with two editorials, with differing views. Both are freely available online.

L R Baden et al, Human papillomavirus vaccine - opportunity and challenge. N Engl J Med 356:1990, 5/10/07. http://www.nejm.org/doi/full/10.1056/NEJMe078088
G F Sawaya & K Smith-McCune, HPV vaccination - more answers, more questions. N Engl J Med 356:1991, 5/10/07. http://www.nejm.org/doi/full/10.1056/NEJMe078060

Here is another approach to making an HPV vaccine. This one seeks to treat a person who is infected; it is thus a therapeutic vaccine. It targets a protein that is part of the viral life cycle in an infected cell -- and which is actually responsible for causing and maintaining cancer. This vaccine is still in testing. News story: Experimental HPV Vaccine Helps in Treating Mice with Cervical Cancer, Microbe 3:318, 7/08. Free online: microbemagazine.org/images/st...0708000314.pdf. Scroll down to page 5 of the file for this item.

The main emphasis with HPV and cancer has been cervical cancer. However, there is increasing evidence that these viruses, probably the same strains, may cause other cancers. Here is one news story on this: HPV-Linked Oral Cancer In Men Increasing, Feb 4, 2008. http://www.medicalnewstoday.com/articles/96053.php .

The traditional method of screening for cervical cancer is the pap smear, which looks for abnormal cells; in poor countries, little or no screening may be done. A new study suggests that it might be better to screen for the virus that causes the cancer. Their extensive testing shows that the test for the viral DNA is more effective than the pap smear. They argue that it is also likely to become inexpensive enough to be practical -- and worthwhile -- in poorer countries. A news story on this work: DNA Test Outperforms Pap Smear; April 6, 2009. www.nytimes.com/2009/04/07/he...virus.html.The paper is: R Sankaranarayanan et al, HPV Screening for Cervical Cancer in Rural India. N Engl J Med 360:1385, April 2, 2009. Freely available at http://www.nejm.org/doi/full/10.1056/NEJMoa0808516 . The article is accompanied by an editorial: M Schiffman & S Wacholder, From India to the World - A Better Way to Prevent Cervical Cancer. N Engl J Med 360:1453, April 2, 2009. Freely available at http://www.nejm.org/doi/full/10.1056/NEJMe0901167 . The editorial is a good overview of many issues surrounding cervical cancer.

Malaria is one of the world's great killers. Recent years have seen the analysis of the genome of both the malaria parasite itself and its mosquito vector. Nature has posted a "web focus" on the diverse aspects of this disease, 2008. http://www.nature.com/nature/focus/malaria/index.html

A UC Berkeley group led by Jay Keasling is working on production of artemisinin, a new type of anti-malarial drug, in microbes (bacteria and yeast).

Here is a campus news story on the funding of this project by the Gates Foundation: "QB3 + Gates' millions = a cure? Helped by Microsoft's founder, Jay Keasling and his industry partners hope to create an inexpensive treatment for malaria". January 12, 2005. http://www.berkeley.edu/news/berkele...keasling.shtml .
A status report -- a news story, June 4, 2008. "Synthetic yeast to brew up vital malaria drug." http://www.newscientist.com/article/...aria-drug.html .
This group of items is also listed for Organic/Biochemistry Internet resources: Alkenes . It is also noted in the Synthetic biology section of this page.

Malaria Vaccine Initiative (MVI). http://malariavaccine.org/ . For a short news story on malaria vaccines, including the role of the MVI: Money, Technology, and Fresh Ideas Converge on Malaria. Microbe 3:9, 1/08. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at forms.asm.org/microbe/index.asp?bid=55316.

In some ways measles would seem to be a good target for eradication. It occurs only in humans, so there is no need to worry about animal reservoirs. A good vaccine is available. Yet measles remains a major killer. One key reason is that the virus is highly infectious, thus a very high level of population immunity is needed to block its transmission. The following article is a good readable discussion of the issues of measles, its vaccine, and the difficulty of eradicating this disease. D E Griffin & W J Moss, Can We Eradicate Measles? Microbe 1:409, 9/06. It is at microbemagazine.org/images/st...0906000409.pdf.

Whatever happened to polio?. A history site from the Smithsonian Institution, posted to coincide with the 50th anniversary of the first polio vaccine. http://americanhistory.si.edu/polio/ . Includes information on the current effort to eradicate polio.

A report from the Institute of Medicine (IOM)... K Stratton et al, Immunization safety review: SV40 Contamination of Polio Vaccine and Cancer, October 2002. http://www.nap.edu/catalog.php?record_id=10534 . Some early batches of the original polio vaccine (the Salk vaccine, with killed virus) were later found to be contaminated with the virus SV40 (which was not killed by the treatment used to kill the poliovirus). SV40 may be a cancer-causing virus. So, inadvertently, we have been running a big test on whether it causes cancer in humans. A long enough time has passed that it is rather clear there is no big problem. Some data has suggested increases in certain very rare cancers. This report analyzes what is known. One of the frustrations, inherent in an accidental test, is that the data is not kept very well. This is an interesting story, but I do suggest you read it for the message about how things should be done, and not try to make SV40 into a big problem.

Nature web focus: http://www.nature.com/nature/focus/polio/index.html . End of polio - the final assault. (September 2004)

Protein Folding -- and diseases

This topic was suggested by a student. It was stimulated in part by the Sept 8, 2003, issue of The Scientist, including a feature article by P Hunter, Protein Folding: Theory meets disease, p 24: http://classic.the-scientist.com/art...display/14060/ . It is also related to the topic Prions (BSE, CJD, etc.) .

There are several issues here. The general topic of how proteins fold has long fascinated -- and frustrated -- biologists. But the topic has taken on greater significance with the increasing recognition of how relevant the protein folding problem is to disease. In fact, a good place to start with the Hunter article, listed above, is the side-bar on p 25, "Miss a fold, prompt a disease." Many cases are now known where we realize that the main effect of a mutation that causes a disease is to interfere with protein folding. For example, the major mutation found in cystic fibrosis is of this type. Once/if the mutant protein manages to fold, it works fine, but the mutation greatly slows the folding process.

Another type of folding-disease connection is illustrated by the prions. Although our understanding of prions is still incomplete, it seems that the prion proteins have two stable forms. One is the normal form of the protein, in your cells, and the other form causes disease. See the Prions (BSE, CJD, etc.) page for more.

A classic experiment in the history of studying protein folding was done by Christian Anfinsen, around 1960. Anfinsen showed that a protein could fold up properly in vitro, without any external source of "information" on how to fold. This established the paradigm that the 3D shape of a protein follows from its amino acid sequence. Although there are some nuances, this still underlies our modern understanding of protein folding. Anfinsen shared the 1972 Nobel prize for Chemistry "for his work on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation". See the Nobel site: http://www.nobelprize.org/nobel_priz...aureates/1972/ .

RNAi (RNA interference or silencing)

Natural small RNA molecules act as gene regulators. Similarly, synthetic small RNA molecules may be useful to biologists to probe gene function -- and may be useful as therapeutic agents. This is a new field. Particularly with regard to actual therapeutic use, there is much promise but little information. Two articles in the March 29, 2004, issue of The Scientist provide a good introduction and overview. The articles are A Adams, RNAi inches toward the clinic (p 32), and A Constans, Concocting a knock-out punch for HIV-1 (p 28). http://classic.the-scientist.com/art...display/14559/ & http://classic.the-scientist.com/art...display/14552/ .

The Scientist for Sept 13, 2004 (Vol 18 #17) has the feature topic of RNAi, with multiple articles: classic.the-scientist.com/2004/9/13/. Again, an excellent introduction and overview.

The idea of using an inhibitory RNA as a therapeutic is simple enough, but there are many technical hurdles. Here is a report of targeting an siRNA (small interfering RNA) to the brain -- by using a protein from rabies virus. Rabies infects the nervous system, and the scientists exploit one part of that virus to deliver the therapeutic RNA across the blood brain barrier. The therapeutic RNA attached to the rabies virus delivery system protects the mice from an experimental viral infection of the brain. Press release, from NIH, June 17, 2007: Blood-Brain Barrier Breached by New Therapeutic Strategy. http://www.niaid.nih.gov/news/newsre...inbarrier.aspx . The work was published: P Kumar et al, Transvascular delivery of small interfering RNA to the central nervous system . Nature 448:39, 7/5/07. Accompanying news story: E M Cantin & J J Rossi, Molecular medicine: Entry granted. Nature 448:33, 7/5/07.

The 2006 Nobel prize for physiology or medicine was awarded to Andrew Z Fire and Craig C Mello for their discovery of "RNA interference - gene silencing by double-stranded RNA". http://www.nobelprize.org/nobel_priz...aureates/2006/ .

See the BITN page Prions (BSE, CJD, etc): Treatment for a paper on the possible use of RNAi to treat a prion disease.

See the BITN page Agricultural biotechnology (GM foods): Recent items for a paper on the use of RNAi, targeted to the seeds, to reduce production of a toxic chemical in cotton seeds.

Nature has a web focus site on this topic. Of particular interest may be a set of animations of how the process works: www.nature.com/focus/rnai/ani...ons/index.html.

SARS (Severe acute respiratory syndrome)

See Emerging diseases section, above, for perspective.

The web site of the US Centers for Disease Control (CDC) is a good site to keep abreast of SARS -- and of course of other diseases. The CDC SARS page: www.cdc.gov/ncidod/sars/

The CDC site has links to all local and state public health departments, and also includes travel advisories.

Nature magazine's "web focus" on SARS: http://www.nature.com/nature/focus/sars/index.html . This set seems to be freely available.

In July, Nature published a "news feature" called "SARS - What have we learned?" It is in the form of a series of questions, with answers, about various aspects of the SARS story. Among the questions... Was the fuss overblown? Are we prepared for the next viral threat? Where did the SARS virus come from? What about a vaccine? Very readable overview and update. Nature 424:123, 7/10/03; also available at the top of their web focus page, listed above.

A free online SARS "textbook", maintained by B S Kamps & C Hoffmann: http://www.sarsreference.com . Also available in Chinese, French, Greek, Italian, Portuguese, Romanian, Spanish, Vietnamese.

www.bt.cdc.gov/agent/smallpox/index.asp. The site provides a wide range of information, including much history. Some materials are also available here in Spanish.

Sudden Oak Death

http://www.suddenoakdeath.org . A range of information, both for the consumer and the scientist. The site is from UC Berkeley.

Sudden larch death (SLD) is due to the same pathogen. Some information on the spread of SLD in Europe is included at this site. Just search on larch.

Synthetic biology

A nice overview of the field of synthetic biology. M Stone, Life redesigned to suit the engineering crowd. Microbe 1:566, 12/06. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at forms.asm.org/microbe/index.asp?bid=47155 (HTML) or forms.asm.org/ASM/files/ccLib...1206000566.pdf (PDF).

Craig Venter, of genome sequencing fame, plans to make new organisms. One key step along the way was to take a small bacterium, and determine how many of its -- already small -- gene set are really needed. This sets the stage for making artificial genomes -- and then for designing new organisms to do specific tasks. News has been coming fast and furious from the Venter lab; I list some of the news coverage and some of their own press releases below.

Good news stories: * Venter Institute team builds M. genitalium genome from scratch (Microbe magazine, April 2008). microbemagazine.org/images/st...0408000162.pdf. * Countdown to a synthetic lifeform (7/11/07). http://www.newscientist.com/article/mg19526114.000 . * Genetic engineers who don't just tinker (7/8/07). http://www.nytimes.com/2007/07/08/we...ew/08wade.html . * Tycoon's team finds fewest number of genes needed for life (6/8/07). http://www.guardian.co.uk/science/20...etics.research . Press releases from the J Craig Venter Institute: * First Self-Replicating Synthetic Bacterial Cell (5/20/10). www.jcvi.org/cms/press/press-...te-researcher/. Since the terms "synthetic" or "artificial" cells are ambiguous and subject to hype, we should be clear what is accomplished here. They made a synthetic genome; that is, they assembled a new genome without using any natural DNA. They then transplanted this into an existing cell, and the new genome "took over". In this case, the synthetic genome is (substantially) identical to a known genome. That is, this work is proof of principle that a new genome can be made and used. * Synthetic bacterial genome (1/24/08). www.jcvi.org/cms/research/pro...press-release/. * JCVI scientists publish first bacterial genome transplantation changing one species to another (6/28/07). www.jcvi.org/cms/press/press-...es-to-another/.

Jay Keasling's work, at UC Berkeley, to develop a cheaper way to make the anti-malarial drug artemisinin is noted in the Malaria section of this page. The work involves making major changes in the metabolic capabilities of the microbes, and is considered synthetic biology.

TGN1412: The clinical trial disaster

March 2006. The news media carried a story of a clinical trial gone terribly wrong. Within an hour or so of receiving a drug, all recipients were seriously ill. What happened? Was there some mix-up -- perhaps the wrong drug used? Was the trial not properly planned or executed? Or was this just "one of those things" -- showing why we start with a small test in humans? So far, the evidence suggests that the last possibility is correct. Everything seems to have been done properly. However, given the severe result in this case, people are questioning whether "properly" was good enough. Was there reason to have been more cautious in this case -- more cautious than just following standard procedure? Perhaps -- and people are debating this. The drug was of a new type, one about which we know little, and about which some are very concerned -- despite the good data from animal tests. It is clear that even a simple precaution, of giving the drug to one patient at a time, and watching them for an hour or two, would have been much better in this case.

As to the nature of the drug, it is hard to describe briefly. But a simple start would be that it was designed to stimulate the immune system -- and the problem is that it did so inappropriately in the human subjects.

The analysis of the incident is still in progress. However, some information is now appearing in the literature, so it seems appropriate to share that here. I do encourage people to be cautious in reaching conclusions at this point.

The New England Journal of Medicine published three articles in the September 7 issue on this topic. In the order listed below: one is a perspective (an overview discussion of the topic), one is the main scientific report, and one is a commentary. All are freely available online. For most people, the first item listed below -- the perspective -- may be the best place to start. * A H Sharpe & A K Abbas, Perspective: T-Cell Costimulation � Biology, Therapeutic Potential, and Challenges. New England Journal of Medicine 355:973, 9/7/06. http://www.nejm.org/doi/full/10.1056/NEJMp068087 . * G Suntharalingam et al, Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412. New England Journal of Medicine 355:1018, 9/7/06. http://www.nejm.org/doi/full/10.1056/NEJMoa063842 . * J M Drazen, Commentary: Volunteers at Risk. New England Journal of Medicine 355:1060, 9/7/06. http://www.nejm.org/doi/full/10.1056/NEJMe068175 .

There is also a government report on the incident. I might cynically comment that it reads like a government report. Nevertheless, browsing it may be useful, at least as a guide to the questions that get raised. The final report (December 2006) is at www.dh.gov.uk/en/Publications...ance/DH_063117. (The link to the preliminary version of the report at the end of the Drazen article listed above is now a dead link.)

Vaccines (general)

A general comment and caution... Vaccines seem to be the subject of many controversies. But be particularly careful with any arguments that appear to make criticism of vaccines in general. The diseases against which we have vaccines are diverse, and the vaccines are diverse. Most real vaccine issues are specific to a particular vaccine or type of vaccine. This section is mainly for sources about vaccines in general, or sources with info about many vaccines. Also see sections for individual diseases for info about specific vaccines. For example, the sections on Anthrax , Ebola , HIV (AIDS) , HPV (Human papillomavirus) , Malaria , Measles , Polio , Smallpox , and West Nile Virus contain info on vaccines for those diseases. An item listed under Cancer deals with making personalized vaccines in plants.

Added September 21, 2011. VIOLIN -- the Vaccine Investigation and Online Information Network. A broad-based vaccine resource, from the University of Michigan Medical School... http://www.violinet.org .

Added September 8, 2011. A report from the Institute of Medicine (IOM)... Adverse Effects of Vaccines: Evidence and Causality, August 25, 2011. www.iom.edu/Reports/2011/Adve...Causality.aspx. The report addresses numerous possible side effects of vaccines, and tries to analyze whether evidence supports a causal relationship between vaccine and effect. You can download a pdf file of a "Report Brief", or read the report online.

Making a wimpy virus. One approach to making vaccines is to use an attenuated strain of the infectious agent -- one that can induce an immune response, but not cause disease. Scientists at Stony Brook have developed a new approach to making an attenuated virus for use in a vaccine. They re-code the virus so that it uses codons that are poorly translated. They made a few hundred changes in the poliovirus genome, each one making it harder for the genome to function. The result was a virus that seemed to work well as a vaccine strain in mouse tests. A nice feature of this approach is that it would seem to be of general applicability, though of course it needs to be tested in each case. Press release, summarizing the story: "SBU Team Designs Customized "Wimpy" Polioviruses, A Method That Could Be A New Path To Vaccines. Reported in Science, the 'Save' Computer-driven Method Creates a Weakened Synthetic Virus"; June 26, 2008. commcgi.cc.stonybrook.edu/am2...Vaccines.shtml. The paper is: J R Coleman et al, Virus attenuation by genome-scale changes in codon pair bias. Science 320:1784, 6/27/08.

Thimerosal in vaccines. Thimerosal is an organic mercury compound, used as a preservative -- including in vaccines. As with any mercury compound, it is toxic. Of course, the fact that it is toxic is why it is used as a preservative. The intent is that it is more toxic to bacteria and fungi than to humans. The available information suggests that the risks from exposure to mercury from thimerosal are quite small. (Exposures from eating fish and from coal-fired power plants are likely to be larger.) As a precaution -- in the US and Europe -- thimerosal is now rarely used in vaccines intended for children; the common Influenza vaccine is the one prominent exception. Note points of uncertainty, especially regarding children (which is why extra precautions are taken with children), but also note that there is really no data suggesting any problem with thimerosal as used in vaccines. * This FDA web page is a good overview of the use of thimerosal. It should serve as a good framework for further discussion. http://www.fda.gov/BiologicsBloodVac...fety/UCM096228 . * A new study shows that ethyl mercury, the form of mercury from thimerosal, is eliminated from the body much faster than methyl mercury. (Methyl mercury is a more common toxic form of mercury, and has been used as a frame of reference for discussing thimerosal in the absence of more direct information.) Children getting many vaccines containing thimerosal (in Argentina) do not show elevated blood level of mercury. A press release from the University of Rochester accompanying publication of this work: Babies Excrete Vaccine-Mercury Quicker than Originally Thought, January 30, 2008. http://www.urmc.rochester.edu/news/s...ex.cfm?id=1848 . The paper is M E Pichichero et al, Mercury Levels in Newborns and Infants After Receipt of Thimerosal-Containing Vaccines. Pediatrics 121:e208-e214, 2/08. It is freely available at http://pediatrics.aappublications.or.../e208.abstract . * I have posted a page showing the chemical structure of thimerosal and some related compounds, including aspirin: thimerosal . * This topic is also listed under Introductory Chemistry Internet Resources: Thimerosal and Introduction to Organic and Biochemistry Internet Resources: Alcohols, ethers, sulfur compounds .

Growing vaccines in plants. Oral, Plant-Based Vaccine against Shiga Toxin Effective in Mice. A news story about this new approach, in Microbe 1:311, 7/06. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at forms.asm.org/microbe/index.asp?bid=43695.

The article this news story refers to is S X Wen et al, A plant-based oral vaccine to protect against systemic intoxication by Shiga toxin type. PNAS 103:7082, May 2, 2006. Online at http://www.pnas.org/content/103/18/7082.abstract .

National Network for Immunization Information (NNii). An excellent general resource on immunizations. Articles address individual vaccines, and some of the news stories you may hear about them (see Immunization Issues). http://www.immunizationinfo.org/ . From their introduction: "The mission of the National Network for Immunization Information (NNii) is to provide the public, health professionals, policy makers, and the media with up-to-date, scientifically valid information related to immunization to help them understand the issues and to make informed decisions. The National Network for Immunization Information (NNii) is an affiliation of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, the American Academy of Pediatrics, the American Nurses Association, the American Academy of Family Physicians, the National Association of Pediatric Nurse Practitioners, the American College of Obstetricians and Gynecologists and the University of Texas Medical Branch."

Financing Vaccines in the 21st Century: Assuring Access and Availability, a report from the Institute of Medicine, August 2003. This report discusses policy issues regarding vaccines. The economics of vaccine production are complex, and in some cases not very good. What role should the government play is assuring vaccine availability even when "ordinary economics" might seem to argue otherwise? www.iom.edu/Reports/2003/Fina...ilability.aspx. As with all IOM reports, you can read it online, or purchase it; a short summary is also available online.

The Jordan Report: Accelerated Development of Vaccines, from the NIAID (National Institute of Allergy and Infectious Diseases). 2007. The purpose of the Jordan Report is "to inform policy-makers, researchers and the public about recent accomplishments and future trends in vaccine research." http://www.niaid.nih.gov/topics/hivaids/research/vaccines/reports/Pages/default.aspx ; the report is listed near the top, under "Vaccines Reports and Articles - General Reports".

A report from the Institute of Medicine (IOM)... K Stratton et al, Immunization safety review: Multiple immunizations and immune dysfunction, February 2002. http://www.nap.edu/catalog.php?record_id=10306 . A short summary is that they found no evidence of vaccine-induced problems, but they also note areas where the evidence is insufficient to reach a conclusion and further study is needed.

West Nile Virus

The Contra Costa Mosquito & Vector Control District (CCMVCD) has a short flier, which it distributes to all county residents, about West Nile Virus. It is written, of course, for the general public, and contains a range of useful information -- about the disease, the virus, and prevention measures. They also have a website, with much useful information: http://www.ccmvcd.dst.ca.us . See menu bar at left for items about West Nile Virus.

California West Nile Virus (and dead bird surveillance) web site, from the state Department of Health Services: http://westnile.ca.gov .

Yellow Fever Virus-based West Nile vaccine edges others protecting horses. Microbe 3:11, 1/08. A news story on vaccine development. A similar West Nile vaccine for humans is under development. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at: forms.asm.org/microbe/index.asp?bid=55322.

Some scientists now suggest that the West Nile Virus has "settled in" in North America, and probably peaked. That is, they suggest it is likely to stay, but at the generally low levels now observed. Their view is not entirely accepted at this point. A brief summary, West Nile Virus Settled in, but Perhaps No Longer Expanding in the U.S., is in Microbe (Vol 2, p 167, April 2007); it refers to the primary publication. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at: forms.asm.org/microbe/index.asp?bid=49483.

The impact of consanguinity on human health and disease with an emphasis on rare diseases

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Published: 07 December 2022
Volume 1 , article number 2 , ( 2022 )

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G. Temaj 1 ,
N. Nuhii 2 &
J. A. Sayer ORCID: orcid.org/0000-0003-1881-3782 3

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Consanguinity increases the likelihood of the inheritance of homozygous pathogenic alleles which may predispose to rare autosomal recessive disorders. Here we discuss the role of consanguinity in informing inherited disease with a focus on rare diseases.

We reviewed the literature concerning the impact of consanguinity on human diseases and chose examples to illustrate the most important themes.

Consanguinity rates vary hugely between different populations influencing the prevalence of rare autosomal recessive diseases. Some founder genetic variants leading to human disease are specific for a single country, or a specific ethnic or geographic group while others are shared more widely. Inherited diseases of known molecular genetic etiology are characterized by their genotype and phenotype but many exhibit marked heterogeneity which may be population dependent. Increased rates of consanguinity are associated with rare autosomal recessive inherited diseases and can lead to more than one human genetic disease in affected individuals leading to complex and overlapping phenotypes. Next-generation sequencing strategies allow new insights into these cases. In contrast, the impact of consanguinity on malignancies and common multifactorial diseases is less predictable and needs further exploration.

Conclusions

High rates of consanguinity remain prevalent in certain populations and lead to an increased burden of rare autosomal recessive inherited diseases. Strategies to reduce consanguinity are needed to reduce these disease consequences and will require global improvements in education, social, and economic conditions.

Autozygosity-driven genetic diagnosis in consanguineous families from Italy and the Greater Middle East

Flavia Palombo, Claudio Graziano, … Marco Seri

Genomics of rare genetic diseases—experiences from India

The GUaRDIAN Consortium, Sridhar Sivasubbu & Vinod Scaria

The prevalence, genetic complexity and population-specific founder effects of human autosomal recessive disorders

Qingyang Xiao & Volker M. Lauschke

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Introduction

The term consanguinity literally means “shared blood.” Consanguineous marriage is defined as a marriage between individuals who are closely related and is associated with an increased risk of autosomal recessive genetic diseases in the offspring of these parents [ 4 ]. More than 1.2 billion of the current population in the world are reported to practice consanguineous marriage. Consanguinity is often observed in poorly educated populations [ 22 ], and improving education allows greater independence and enables more informed life decisions. Consanguineous marriages are known to be practiced for many generations in many communities all around the world [ 18 ]. The most common form of consanguinity is between first cousin marriages. In this scenario, spouses share 1/8th of their genes inherited from their ancestors and their progeny are typically homozygous for 1/16th of all loci [ 19 ]. The prevalence of consanguinity varies from country to country (Fig. 1 ) and is shown to be influenced by multiple different factors such as religion, ethnicity, demography, geography (rural or urban areas), education, and economic factors [ 19 ]. Consanguineous marriages account for less than 20% to more than 50% of all marriages in Arab countries (Table 1 ), which span the region from North Africa to the Middle East and western Asia [ 12 ].

World map showing consanguineous marriages. Consanguineous marriages are defined here as second-degree cousins or closer, and frequency is shown in percentage (%). Image adapted from https://commons.m.wikimedia.org/wiki/File:Global_prevalence_of_consanguinity.svg and licensed under the Creative Commons Share Alike 3.0 unported

Consanguinity, unsurprisingly, has been identified as a risk for congenital malformation and major developmental medical conditions. These malformations include diverse phenotypes such as polydactyly, spinocerebellar degeneration, neural tube defects, anencephaly, and encephalocele [ 38 ]. Here, we discuss the global distribution of consanguinity and the impact of consanguinity on a wide variety of different diseases using examples of acute lymphoblastic leukemia, breast cancer, obesity, and rare genetic diseases to illustrate key messages. We also show how modern genetic sequencing techniques can inform the genetics of consanguinity with the identification of novel disease alleles, hypomorphic alleles, and founder alleles.

Global distribution of consanguinity

Recent data indicate that approximately 10.4% of the total population in the world is reported to be married to biological relatives [ 12 ]. In North Africa, West Asia, and South India, marriages to biological relatives are culturally favored and constitute 20–50% of all marriages [ 47 ]. In Qatar, it is reported that the rate of consanguinity is approximately 54% [ 8 ]. In Saudi Arabia, the rate is between 29.7 and 56% [ 47 , 48 ]. In Libya, the interfamilial marriage rate was 37.6% in the city of Bengazi [ 1 ], and a study in Mauritania estimated a consanguinity rate of 47.2% [ 21 ]. In Pakistan, the rate of consanguineous rate is reported to be over 60% of marriages [ 43 ].

In European countries, South America, and Australia, the interfamily marriage rate is in comparison low [ 25 ]. In North America and Australia, the interfamily marriage is approximately 1%; in Europe, it is approximately 1.5% but depends on local geography and social conditions [ 27 ].

Consanguinity and rates of childhood malformations

The rates of early childhood malformations have been correlated with rates of consanguinity [ 19 ]. In addition, consanguineous marriage is shown to have a higher level of reproductive loss, risk of abortion, and neonatal or postnatal death [ 38 ]. However, in consanguineous populations overall there may be selection against severe recessive diseases. Many recessive genetic diseases are not compatible with life and reproduction, leading to a counter-selection of these pathogenic variants in the populations with ancient practices of consanguinity.

Consanguinity and incidence of cancer

Many studies from different research groups have indicated that rates of consanguinity have little or no effect on the incidence of cancers. Bener et al. [ 10 ] showed that although the rate of consanguinity in Qatar was high, it had no effect on the incidence of cancers overall [ 10 ]. However, at a tissue-specific level, an increase in risk for leukemia and lymphoma and colorectal and prostate cancer was shown while a reduction in breast, skin, thyroid, and female genital cancers was noted [ 10 ].

Breast cancer is the most common type of cancer in adult females. The majority of cases are sporadic, but 5–10% are reported to be inherited, with pathogenic variants in BRCA1 and BRCA2 accounting for the majority of these cases. In family genetic studies in Morocco, using next-generation sequencing (NGS) technologies, four heterozygous pathogenic variant genotypes were found: BRCA1 c.212insA and c.3453delT and BRCA2 c.1310_1313delAAGA and c.723insG [ 23 ]. The BRCA1 c.3453delT allele was novel and is likely to be a local founder allele, prompting better characterization of population-specific alleles. In studies from Arabian countries, consanguinity has been shown to be protective against breast cancer [ 9 , 15 , 28 ] and this may be in part due to the fact that BRCA1/BRCA2 deleterious variants are lethal in their homozygous state and are outbred from the population. There may also be an increased carrier rate of protective alleles, which may have an increased effect if present homozygously [ 11 ].

In contrast, much rarer oncogene pathogenic variants may be revealed in consanguineous populations. Ripperger et al. reported a case with constitutional mismatch repair deficiency caused by a novel MSH6 pathogenic variant leading to a T-cell lymphoma and colonic adenocarcinoma [ 37 ]. The constitutional mismatch repair deficiency syndrome (CMMRD), is an example of a rare recessive inherited cancer syndrome with a broad tumor spectrum including hematological malignancies, brain tumors, and colon cancer in childhood and adolescence. Baris et al. found a consanguineous Bedouin family, a homozygous MSH6 pathogenic variant (c.3603_3606delAGTG) [ 6 ].

Consanguinity and obesity

Obesity is known to be a risk factor for many different diseases including cardiovascular disease, insulin resistance, and type 2 diabetes mellitus. Polymorphisms in the ACE gene have been implicated in different metabolic disorders, including obesity. A recent study investigated genetic associations in the offspring of first cousins and found an association of the ACE II polymorphism with obesity in the Saudi population [ 4 ]. Also, Alharbi et al. noted that while screening for obesity in children from consanguineous parents they noted that adolescents and adults were more prone (three times more likely) to develop obesity [ 3 ]. The exact molecular mechanisms have not been explored but metabolic pathways that regulate obesity are influenced by genetic background [ 45 ], as well as environmental factors [ 42 ]. In outbred populations, only 2–5% of obesity is secondary to monogenic disorders. Interestingly, in a Pakistani inbred population pathogenic variants in monogenic genes LEP , LEPR , and MC4R were able to explain 30% of severe childhood obesity. The genetics of common obesity is more complex but studies have shown that genes associated with monogenic causes of obesity ( LEPR , POMC , MC4R , BDNF , SH2B1 , and PCSK1 ) [ 29 , 31 , 41 , 49 ] are enriched for more common alleles in obese patients from the general population. Therefore, variants in the same genes are having different penetrance and consanguineous populations may be enriched for both rare and common genetic variants contributing to an overall increase in obesity [ 40 ].

Consanguinity and rare genetic diseases

Rare diseases are by definition those that affect a minor proportion of the population. A prevalence of <0.05% is considered to be a rare disease by the European Union, while in the USA, a disorder affecting fewer than 200,000 people is considered rare (roughly 0.086%). Rare autosomal recessive disorders are known to be increased with consanguineous parents [ 33 ]. Cockayne syndrome (CS) is a rare autosomal recessive genetic disease caused by pathogenic variants in ERCC6 or ERCC8 . CS is characterized by psychomotor retardation, cerebral atrophy, microcephaly, mental retardation, sensorineural hearing loss, premature aging, kyphosis, ankyloses, and optic atrophy [ 51 ]. In a Tunisian patient from a consanguineous family, a novel homozygous variant in ERCC6 (c.3156dup; p.Arg1053Thr*8) was identified [ 51 ]. Similarly, in a consanguineous family from Jordan with a severe CS phenotype a novel frameshift ERCC6 variant (c.2911_2915del5Ins9; p.Lys971Tyrfs*14)) was found. Such findings of a rare disease diagnosis with novel pathogenic homozygous alleles in inbred populations are frequent. Studying rare diseases in families allows numerous other opportunities for genetic discoveries. Modern NGS, such as targeted panel sequencing, whole exome sequencing, and whole genome sequencing offers huge potential for molecular genetic diagnostics in these families [ 44 ]. What is interesting is that homozygous alleles predicted to be benign, such as synonymous changes within coding regions can be given disease pathogenicity if the variant is rare, segregates with disease phenotype, and is investigated at the transcriptomic level. An interesting example of such a finding is the identification of a synonymous NPHP3 allele in a consanguineous Omani family with a ciliopathy syndrome phenotype (hepatorenal fibrocystic kidney and liver disease) [ 32 ]. The NPHP3 variant (c.2805C>T; p.Gly935Gly) was initially filtered out as it was predicted to be non-pathogenic. However, the allele was exceedingly rare, within a large region of homozygosity by descent, and predicted to be pathogenic by in silico splicing tools. The allele was segregated with the disease phenotype and the identical allele was found in 4 other cases with similar phenotypes. Finally, abnormal splicing secondary to this allele was shown using RT-PCR [ 32 ]. As NGS sequencing moves from exomes to genomes there will be opportunities to identify and determine the pathogenicity of rare deep intronic alleles that may be driving rare disease phenotype. An example of this is the identification of a deep intronic allele in PKHD1 (c.8798–459C>A) leading to an antenatal presentation of ARPKD in two fetuses in a consanguineous Chinese family [ 14 ]. Consanguineous populations allow these genetic studies to be driven forward.

Founder alleles may also be identified by studying specific genetic disorders within specific inbred populations. An example is the identification of a GBA c.1246G>A; p.Gly377Ser homozygous missense variant in patients with Gaucher’s disease from Northeastern Brazil. The original population from Portugal was of Sephardic Jewish extraction and settled in this location in the 1700s. The combination of this founder allele and high rates of consanguinity contributed to a high prevalence of Gaucher’s disease in this population [ 13 ]. Other such examples are seen in other inbred populations, including the identification of a founder allele in AGL , leading to Glycogen storage disease type IIIa in Inuit populations [ 39 ].

Awareness of rare disease alleles within specific populations is now growing and premarital genetic screening for such alleles is becoming more frequent. Ashkenazi Jews have an exceptionally high carrier frequency for a range of genetic disorders named “Jewish Genetic Disorders” which include the lysosomal storage disorder Tay Sachs disease [ 5 ]. Carrier screening for these disorders is now recommended and allows informed decisions about marriage and reproduction to be taken. A recent report performed carrier screening of forty disease-causing variants in individuals from Syrian and Iranian Jewish ancestry and compared these to Ashkenazi Jewish carrier frequency rates [ 52 ]. Over 8% of the study population were carriers for at least one pathogenic variant, supporting the importance of premarital genetic screening in order to reduce the incidence of autosomal recessive disease. Such screening programs need to be adopted by other at-risk populations. In a Saudi Arabian population, the carrier frequency of variants in 35 genes associated with the most prevalent disorders was recently performed [ 2 ]. As an example, an allele, in MPL (c.317C>T; p.Pro106Leu) which causes thrombocytopenia was seen in 2.46% of the population compared to 0.01% in the gnomAD database. There are clearly issues regarding economic ethical and social implications for such screening programs and compliance of genetic screening programs can be low [ 46 ].

Within consanguineous families, the occurrence of more than one rare genetic disorder is also more frequently seen [ 24 ]. There are numerous reports of more than one rare homozygous disease-causing variant giving a combination of disease phenotypes. For example, a Chinese patient had both Wilson disease and retinitis pigmentosa and homozygous pathogenic variants were identified in ATP7B and CNGA1 accounting for the two phenotypes respectively [ 50 ]. Where concurrent inherited genetic disorders lead to overlapping phenotypes there can be diagnostic confusion. Perrault syndrome is a disorder characterized by primary ovarian insufficiency in females and sensorineural deafness in males and females. Whole exome sequencing in a consanguineous family with six deaf individuals, with the proband also having primary ovarian insufficiency, identified a pathogenic variant in CLDN14 which explained the sensorineural deafness phenotype and a SGO2 homozygous pathogenic variant explaining the concurrent ovarian insufficient [ 20 ]. Both deafness and primary ovarian insufficiency are genetically heterogeneous, and the variants were likely acting independently to produce a blended phenotype suggestive of Perrault syndrome. Caution therefore needs to be taken when researchers widen phenotypic spectra of monogenic disorders in consanguineous individuals without excluding a second homozygous disease-causing allele contributing to the disease phenotype.

A further pitfall of the investigation of a rare disease in consanguineous families is the transmission of two alleles (in heterozygous or homozygous state) within the same gene within the same family in such a way that it mimics autosomal dominant inheritance patterns. A consanguineous family of 13 individuals with variable features of Alport syndrome (including hematuria, proteinuria, and kidney failure) appeared to have a male-to-male transmission of disease pattern suggesting autosomal dominant inheritance. Genetic analysis however showed a mixture of homozygous and compound heterozygous alleles producing this pseudo-dominant transmission pattern [ 30 ]. This case is a good example of how assuming identity by descent in consanguineous families can be misleading.

NGS approaches in consanguineous families are a useful way of identifying homozygous hypomorphic alleles. In autosomal recessive diseases, these alleles typically give milder phenotypes when homozygous and more severe disease phenotypes when in trans with a heterozygous deleterious allele. Such variants have been reported in TMEM67 leading to more limited liver and kidney phenotypes rather than the embryonic lethal Meckel syndrome [ 34 ]. Homozygous hypomorph alleles in autosomal dominant diseases can be identified also, which provide exceptional cases for studying disease pathogenicity, such as the identification of a homozygous UMOD allele in a Pakistani family. These families allow a direct comparison of heterozygote and homozygote allele carriers in order to unravel gene dosage effects [ 16 ].

Whole exome and whole genome sequencing to investigate consanguineous families

With the advent of affordable NGS approaches, the use of whole exome and whole genome sequencing for the investigation of rare diseases and cancers is rapidly becoming the first line. Individual families or large cohorts of families with shared phenotypes are subject to exome or genome sequencing and results yield high diagnostic rates, add to the number of disease-causing alleles, and inform global genetics projects. Some care does need to be given before assigning pathogenicity to genetic variants in rare diseases. An example of this was the identification of a homozygous variant in CCDC28B as a potential novel genetic cause of Joubert syndrome [ 36 ]. However, further analysis of this variant showed that it was not ultra-rare and had been seen in its homozygous state in control samples from a wide range of ethnicities [ 7 ]. A similar example was the initially reported findings of a homozygous c.428delG variant in KIAA0586 in patients with Joubert syndrome. However, careful segregation and RNA studies, alongside population frequency data demonstrated that this allele on its own was not pathogenic [ 35 ].

In countries with limited resources, singleton whole exome sequencing has been advocated as a first-tier diagnostic test to limit costs [ 26 ]. This approach may be suitable to detect known alleles in known genes, but without segregation of alleles some caution, given the examples above, needs to be given to using this approach for gene discovery in consanguineous families, where homozygous alleles may be numerous and rare but not necessarily pathogenic.

Consanguinity and education

There are numerous reports correlating poor levels of education and consanguinity [ 17 ]. Women with low levels of education are more likely to be in a consanguineous marriage. Improving the education of women will allow more informed decisions based on the huge evidence base of the adverse health effects on their children resulting from a consanguineous marriage. However, there is also evidence that deep-rooted social and cultural beliefs and personal preferences outweigh improvements in education [ 17 ]. The modern advent of genetic screening and awareness of certain risk alleles within specific inbred populations allows opportunities for positive health care interventions such as premarital screening to reduce risks of inherited diseases.

The effects of consanguinity on health and disease are being increasingly recognized. We have used examples from cancer diseases, obesity, and rare inherited diseases to define how the effects of consanguinity need to be carefully considered. NGS approaches in consanguineous families with both common and rare disease has allowed many new gene disease discoveries. Such technologies make it much more accessible to investigate consanguineous families for inherited diseases and predisposition to other disorders such as cancers. It is important to increase knowledge and public awareness regarding the risks of consanguinity and worldwide education programs may help with this. Patients, families, and their physicians should actively engage into research on the relationship between consanguinity and disease through a multidisciplinary approach.

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analyszed during the current study.

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JAS is supported by Kidney Research UK and the Northern Counties Kidney Research Fund.

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Temaj, G., Nuhii, N. & Sayer, J.A. The impact of consanguinity on human health and disease with an emphasis on rare diseases. J Rare Dis 1 , 2 (2022). https://doi.org/10.1007/s44162-022-00004-5

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Published: 31 March 2021

Plant health and its effects on food safety and security in a One Health framework: four case studies

David M. Rizzo 1 ,
Maureen Lichtveld 2 ,
Jonna A. K. Mazet 3 ,
Eri Togami 3 &
Sally A. Miller ORCID: orcid.org/0000-0001-9611-0535 4

One Health Outlook volume 3 , Article number: 6 ( 2021 ) Cite this article

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Although healthy plants are vital to human and animal health, plant health is often overlooked in the One Health literature. Plants provide over 80% of the food consumed by humans and are the primary source of nutrition for livestock. However, plant diseases and pests often threaten the availability and safety of plants for human and animal consumption. Global yield losses of important staple crops can range up to 30% and hundreds of billions of dollars in lost food production. To demonstrate the complex interrelationships between plants and public health, we present four case studies on plant health issues directly tied to food safety and/or security, and how a One Health approach influences the perception and mitigation of these issues. Plant pathogens affect food availability and consequently food security through reductions in yield and plant mortality as shown through the first case study of banana Xanthomonas wilt in East and Central Africa. Case studies 2, 3 and 4 highlight ways in which the safety of plant-based foods can also be compromised. Case study 2 describes the role of mycotoxin-producing plant-colonizing fungi in human and animal disease and examines lessons learned from outbreaks of aflatoxicosis in Kenya. Plants may also serve as vectors of human pathogens as seen in case study 3, with an example of Escherichia coli (E. coli) contamination of lettuce in North America. Finally, case study 4 focuses on the use of pesticides in Suriname, a complex issue intimately tied to food security though protection of crops from diseases and pests, while also a food safety issue through misuse. These cases from around the world in low to high income countries point to the need for interdisciplinary teams to solve complex plant health problems. Through these case studies, we examine challenges and opportunities moving forward for mitigating negative public health consequences and ensuring health equity. Advances in surveillance technology and functional and streamlined workflow, from data collection, analyses, risk assessment, reporting, and information sharing are needed to improve the response to emergence and spread of plant-related pathogens and pests. Our case studies point to the importance of collaboration in responses to plant health issues that may become public health emergencies and the value of the One Health approach in ensuring food safety and food security for the global population.

Background: plant health as part of one health

Although plant health is currently part of the definition of One Health [ 1 ], plants have typically not been well integrated into discussions of One Health approaches [ 2 , 3 ]. However, plant health is vital to sustain human and animal health and a critical component of the complex interactions among the environment, humans, and animals. Recognizing the key role of plants in public health, the United Nations declared the year 2020 to be the International Year of Plant Health (IYPH) [ 4 , 5 ]. The overarching purpose of the IYPH was to raise awareness of plant health and its effects on society [ 4 ]. Maintaining plant health has important consequences for human and animal health as an important driver of food security and safety, as a source of livelihoods in plant-based agriculture, as a source of pharmaceuticals, and as part of healthy environments [ 3 , 6 , 7 , 8 , 9 ].

Plants provide over 80% of the food consumed by humans and are the primary source of nutrition for livestock [ 5 ]. Food security—the state of having reliable access to sufficient, safe, affordable, and nutritious food at all times—is necessary to have healthy and productive societies [ 7 , 10 ]. Food security is also a crucial aspect of One Health and is a pillar of the United Nations Sustainable Development Goals (SDGs) [ 11 , 12 ]. The UN definition of food security identified four key pillars: 1) availability, 2) access (both economic and socio-cultural), 3) utilization, including food preparation and safety, and 4) lastly the stability of these three pillars [ 13 ]. Food security thus reflects a complex value chain of production, food processing and distribution, and food access, beginning with plant health in the field. Employing a One Health approach to ensure the safety and continuity of this value chain will result in the protection and advancement of public health.

Plant diseases and pests influence the availability and safety of plants for human and animal consumption, reduce crop yield and detrimentally affect quality [ 9 , 14 ]. Measures to prevent or treat diseases, including application of pesticides, may adversely impact the health of agricultural workers and consumers, as well as drive the development of antimicrobial and antifungal resistance in pathogens [ 15 , 16 ]. In addition, food plants may serve as carriers of human pathogens and harmful microbial-based toxins. For example, foodborne illnesses pose a serious global burden on human health, reportedly affecting 600 million people or 33 million Disability Adjusted Life Years (DALYs) in a single year [ 17 ]. Although international food standards, such as the Codex Alimentarius, are implemented to protect consumers’ health and fair trade, foodborne illnesses continue to affect high-, middle-, and low-income countries around the world [ 17 , 18 ]. Plants are important origins of foodborne outbreaks, including fresh vegetables and fruits irrigated with, washed with, or exposed to water and soil contaminated with pathogens of animal or human origin. More than half (51%) of outbreak-associated illnesses in the US were traced to plant-foods over a 10-year period, higher than any other food commodity, such as meat, fish, and dairy products [ 19 ]. Additionally, antibiotic resistant bacteria and resistance genes originating from animal feces can also contaminate fresh produce and pose health risks for humans [ 20 ]. Therefore, a key aspect of food security is timely and effective management of plant pathogens and pests and other microbes associated with plants that can cause foodborne illnesses, often disproportionately impacting the most vulnerable and health disparate populations locally and globally.

The emergence of new variants of pathogens and pests, as well as the expansion of the geographic range of known ones, can cause significant disruption in food production and pose a burden on the global economy. Global yield losses of important staple crops to pathogens and pests can range up to 30% with estimated costs to the global economy due to lost food production in the hundreds of billions of dollars [ 7 ]. Effective pest and disease management approaches, including pesticide management strategies, are required to successfully prevent and mitigate these issues. Recognition of and action to address the need for quantification of crop losses and their impact on humans, plants, animals, and land use are critically important [ 2 , 10 , 21 ]. Traditional surveillance strategies are often expensive and associated with a delay in problem recognition and access to actionable data. The lack of time-sensitive responses to foodborne outbreaks negatively impacts public health and the food service industry.

To show the complex interrelationships between plants and public health, and to demonstrate the value of the One Health approach, we review four cases studies. One study shows the relationship between plant health and food security. Two case studies involving a naturally-occurring pathogen (one plant-based and one animal-based) show the relationship between plant food safety and human health. The final case study involving a man-made toxin represents a study of both food security and food safety. Through these case studies, we examine challenges and opportunities moving forward for mitigating negative public health consequences and ensuring health equity.

Case studies

Case study 1: plant pathogens and food availability: banana xanthomonas wilt in east and central africa, 2001-present (fig. 1 ; fig. 2 -1).

Based on currently available data, up to 30% of global staple food crops are lost annually due to plant pests, including diseases, insects, and weeds, but excluding abiotic factors such as drought, excessive water, or poor soils [ 7 ]. When diseases severely affect staple crops in low income or under-resourced regions of the world, food availability is threatened, potentially resulting in malnutrition and population-based famine in severe cases. In addition, loss of income from cash crops sold by small commercial farms can have a cascading effect, exacerbating poverty among populations who depend upon farmers to purchase goods and services from the rural non-farm sector.

Rotting banana fruit caused by the bacterial phytopathogen Xanthomonas campestris pathovar musacearum in Uganda. The disease (banana Xanthomonas wilt) also causes wilting and death of banana plants and significant reductions in availability of this staple food in East and Central Africa (source S. Miller)

Case studies and linkages to One Health as discussed in the text. The studies illustrate different examples of the interconnectedness of plant, animal and human health, and the negative consequences of plant health problems to public health

Bananas ( Musa spp.), including dessert banana, plantain, and cooking banana, comprise the eighth most important food crop in the world and the fourth most important in low- and middle-income countries in terms of gross production value [ 22 ]. Bananas are a staple crop and important source of protein, starch, vitamins, and minerals in East and Central Africa, ranging from 20% of household food consumption each day in Uganda to 80% in Rwanda [ 23 ]. Bananas historically had been among the least expensive of the staple crops to produce [ 24 ]. They have multiple uses in crop production systems, such as cycling carbon and soil nutrients, preventing soil erosion, and providing shade for understory crops [ 23 ]. Additionally, bananas are a source of food for livestock and used for the production of goods such as baskets, carpets, and shoes [ 23 ].

Banana Xanthomonas wilt (BXW) is an invasive bacterial disease first observed in Uganda in 2001, where it developed into a severe epidemic within 4 years of emergence and spread to the Democratic Republic of the Congo, Rwanda, Kenya, Tanzania, and later to Burundi [ 22 ]. BXW is caused by Xanthomonas campestris pathovar musacearum , a gram-negative rod-shaped bacterium that enters the plant through wounds or natural openings, colonizes the plant’s vascular system, and causes wilting, fruit rotting, and plant death [ 22 ]. The disease is spread by planting infected banana pseudostems, by various insects that visit the male flowers, by wind-driven rain, and by using contaminated cutting tools [ 22 ].

During the peak of the 2000–2010 epidemic in heavily affected areas of Tanzania, Burundi, and Rwanda, there were significant harmful effects on food production, availability, and subsequently, household consumption practices [ 25 ]. For example, the production of banana beer and juice declined approximately 60%, and the number of banana bunches sold and consumed declined 35 and 25% respectively, compared to pre-BXW levels. Importantly, the BXW epidemic greatly affected the availability of bananas, because the price of banana bunches increased by 46% compared to pre-BXW levels. As a result of reduced banana availability and higher prices, households coped by eating fewer meals than usual, eating smaller meals than needed, or substituting bananas with other available food items, such as maize, cassava, or sweet potatoes. Increased food prices have a disproportionate influence on low income households, often already struggling to meet basic needs. Loss of bananas from cropping systems may also result in damage to the environment (soil erosion) and reduced crop productivity (loss of shade) [ 26 ]. Long-term impacts of BXW epidemics on human nutrition and health, poverty, the environment and cultural practices in East and Central Africa have not yet been determined.

There are no effective antibiotics or other pharmaceutical treatments available for BXW. However, the disease can be managed by adoption of specific farming practices, including removing the male flower buds to reduce insect transmission of the pathogen, removing or burning affected plant pseudostems, decontaminating farm tools after each use, and using disease-free planting materials [ 26 ]. The cost and complexity of these disease management practices pose barriers to adoption by farmers [ 27 ]. Deployment of BXW-resistant varieties would be a significant step forward in managing this disease locally and reducing its spread. However, banana breeding is extremely slow and difficult, and sources of resistance to BXW have not been found in cultivated banana. Musa balbisiana is the only known source of resistance but is not preferred for breeding due to genome configuration differences [ 28 ]. Genetically engineered (GE) bananas resistant to BXW have been developed and tested extensively in field trials [ 22 , 29 ]. In Uganda, which has been particularly hard-hit by BXW, it has been estimated that adoption of GE bananas could benefit farmers by $15 million and consumers by $10 million annually and could result in 55,000 people escaping poverty each year. BXW-resistant GE banana varieties may be available for distribution by 2023, if an appropriate biosafety regulatory system is in place. However, for Uganda and other countries affected by BXW, political considerations based on public perceptions of GMO foods may delay or even stop the implementation of the necessary regulatory systems [ 30 ]. In the meantime, increased adoption of BXW cultural management practices can be better facilitated by effective training programs such as farmer field schools and refining disease management strategies into more feasible and easy-to-implement recommendations. These include limiting removal of BXW-affected plants to dry periods when the disease is least likely to spread, covering cut plant stems with soil and sterilizing tools in fire pits within banana fields [ 26 ]. Furthermore, leveraging advances in technology to track transmission patterns by using innovative citizen science strategies as well as collaboration between scientists and farmers to improve training, can accelerate progress toward prevention of BXW. Specifically, citizen science and information communication technologies can accelerate the identification of new outbreaks, information sharing can enable rapid decision making among farmers, and enhanced connectivity among stakeholders can create networks for collective action [ 31 ].

Case study 2: food safety and mycotoxins: aflatoxicosis outbreak in Kenya, 2004–2005 (Fig. 2 -2)

Aflatoxin B 1 is a type of mycotoxin produced by Aspergillus flavus and A. parasiticus [ 32 ]. Mycotoxins, which are small molecular-weight fungal metabolites, are produced on a wide array of food plants and are toxic to animals and humans [ 33 ]. Aflatoxins can contaminate human foods such as cereals, roots, nuts, and pulses under favorable conditions such as high temperatures, high humidity, and drought stress, which lead to plant colonization by the A. flavus and A. parasiticus molds [ 32 ]. In 2004–2005, aflatoxin contamination of maize—a major staple food in Kenya—was found to be the cause of a severe outbreak of acute liver disease in eastern Kenya, resulting in 317 cases, including 125 deaths [ 33 ]. The primary risk factor for aflatoxicosis in this event was the consumption of homegrown maize, followed by storage of wet grain in the home [ 33 ]. Aflatoxin B 1 concentrations in stored maize in affected households were up to 50 times the limit prescribed for food in Kenya [ 33 ]. Chronic aflatoxin B 1 contamination is a risk factor for acute liver damage, which may lead to chronic illnesses including liver cancer and immune system suppression [ 32 ].

The toxicity, morbidity, and potentially lethal effects of aflatoxin, as observed in the Kenya outbreak, highlight the significance of aflatoxin as an important public health challenge. Humans are exposed to aflatoxins through contaminated food crops or by consuming products from animals that have been exposed to contaminated feed. Aflatoxin contamination threatens the health and wellbeing of already vulnerable populations, such as children and individuals with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections [ 32 ]. Children are especially susceptible to aflatoxins and can suffer short- and long-term effects such as malnutrition and stunting [ 32 ]. Additionally, chronic exposure to aflatoxins disproportionately affects low-resourced populations, with an estimated 5 billion people in low- and middle-income countries (LMICs) at risk of chronic exposure to aflatoxins [ 34 ].

Chronic exposure to aflatoxins has detrimental effects on animal health and can cause growth inhibition and immune suppression [ 32 ]. Consequently, health risks to animals and humans alike and compounding impacts on livelihoods result when aflatoxicosis is not prevented. Limited availability of food, lack of regulatory systems for monitoring and controlling aflatoxin, and environmental conditions that favor fungal development in crops are some of the common factors that increase the likelihood of aflatoxin poisoning [ 32 ]. Therefore, preventing and mitigating aflatoxin poisoning requires employing a One Health approach to protect human, plant, and animal health.

Ultimately, prevention and mitigation of aflatoxin contamination of food and feed, particularly in LMICs that often lack the expertise and infrastructure to effectively prevent and interdict aflatoxin contamination, require multi-pronged, economically-feasible, integrated approaches supported by private and public sector entities. For example, the appropriate and recommended use of irrigation and insecticides during the pre-harvest period and hand sorting of grains and effective rodent control during the post-harvest period could mitigate risks of aflatoxin contamination. Increasing awareness of the burden of aflatoxin exposure on public health is critical to encourage implementation of these strategies. In response to the deadly 2004–2005 outbreak in Kenya, Kenyan government agencies investigated the cause and established the National Food Safety Coordinating Committee in 2006, active at the policy level and coordinating mycotoxin testing in food and feed, inspection, enforcement, education, and program monitoring and evaluation [ 35 ]. A holistic, coordinated approach including plant, animal, and public health research and practice is necessary to address the gaps in knowledge, technology and education to prevent aflatoxicosis. These include insufficient documentation of human exposure, lack of measurements of economic impacts of aflatoxin contamination throughout various value chains and analyses of long-term impacts of aflatoxin mitigation approaches, inadequate sampling of grains on smallholder farms and storage facilities, lack of consumer awareness of the attributes associated with aflatoxin contamination and absence of economic incentives for the production and/or marketing of low-aflatoxin grain [ 35 , 36 ].

Case study 3: human pathogens associated with plants and food safety: E. coli O157:H7 outbreak caused by romaine lettuce in the United States and Canada, 2018–2019 (Fig. 2 -3)

Between October 2018 and January 2019, a foodborne outbreak of Shiga-toxin producing E.coli O157:H7 (STEC) resulted in 91 illnesses and 35 hospitalizations, including four cases of hemolytic uremic syndrome (HUS) but no deaths, in multiple areas of the United States (US) and Canada [ 37 , 38 ]. Fortunately, the outbreak was detected in its early stages by US and Canadian surveillance systems, including FoodNet and PulseNet, and on November 1, 2018 the US Food and Drug Administration (FDA), CDC, Canadian Food Inspection Agency (CFIA), and Public Health Agency of Canada initiated a multi-agency outbreak investigation. On November 20, FDA issued a public health advisory warning to consumers not to eat romaine lettuce until further notice, a bold and atypical advisory against a type of produce without identifying its farm of origin. In Canada, CFIA advised industry not to import, distribute, or sell romaine lettuce during the investigation. Ultimately, trace back of suspected food ingredients, field visits, and laboratory testing, including whole-genome sequencing, determined that the cause of the outbreak was in fact romaine lettuce produced on a farm in Santa Barbara, California, whose irrigation system was implicated as the contamination source for E. coli O157:H7. Genetic characterization of the pathogens revealed that the DNA footprints of the E. coli strains in this outbreak were genetically closely linked among cases, as well as related to a previous E. coli outbreak that affected the US and Canada in December 2017 [ 37 , 38 , 39 ]. By early January 2019, despite its extensive geographical spread, the outbreak was contained and declared over within 11 to 14 weeks since the recognition of illness in the initial cases in both the US and Canada.

By employing One Health approaches to food surveillance, public health, and animal health, and taking rapid actions as demonstrated during this outbreak, public health officials will be better able to understand the source of foodborne illnesses, rapidly enabling and informing prevention and mitigation measures for future outbreaks. It is important to consider that the intestinal tracts of healthy ruminant animals are reservoirs of E. coli O157:H7, and cattle feces are believed to be a major source for human illness [ 40 ]. Shedding of E. coli O157:H7 by cattle is influenced by seasonality, food production strategies, and life stage of cattle. In addition, the pathogen can persist in the environment, such as in water troughs, in animal feces that are not removed expeditiously, and on feedlots [ 41 ]. In this outbreak, there was no conclusive evidence that the water was contaminated from domestic ruminant feces. However, the final investigation highlighted that ruminant intestinal tracts are well-established reservoirs for E. coli O157:H7. Wildlife and humans can also be sources of bacterial contamination of the food supply, and investigators noted “evidence of extensive wild animal activity, including waterfowl, rodents, coyotes, etc., and animal burrows near the contaminated reservoir sediment,” likely warranting intensive exploration in future outbreaks, including water supplies. In California, this and other foodborne outbreaks have highlighted the importance of complying with, and accelerated the implementation of, local and national produce safety practices, such as the Produce Safety Rule under the Food Safety Modernization Act of the FDA which came into effect in 2016 [ 42 , 43 ]. Farmers are required to reduce the likelihood of direct or indirect contamination of produce with wildlife fecal material through soil, water, vehicles, and other means of transmission and have taken an active role in preventing foodborne illnesses as integral stakeholders for protecting public health.

The successful rapid containment of this large-scale STEC outbreak can be attributed to early detection of the event through robust surveillance systems, swift multi-agency coordination with an employment of the One Health approach, use of whole genome sequencing for E. coli characterization, and timely and appropriate issuance of a broad public health advisory. Plant, environmental, animal, and human health experts will likely continue to be challenged by the burden of foodborne illnesses, which should be addressed by continuing to coordinate multi-agency prevention, detection, response, and containment strategies; incorporating state-of-the art technologies to identify pathogens; and balancing the benefits of protecting the health of populations with the economic cost of issuing prompt public safety advisories.

Case study 4: pesticide use in plant-based agriculture and food security and safety in Suriname, 2010–2015 (Fig. 2 –4; Fig. 3 )

Suriname, a middle-income country located on the northeastern coast of South America, has one of the highest pesticide use rates per area crop land in the Caribbean (8.8 kg/ha). Pesticides are intended for preventing, destroying, repelling, or mitigating any pest [ 44 ]. They can be classified according to the target organism (most commonly: insecticides, herbicides, and fungicides), or molecular structure (such as insecticides categorized as organophosphates, carbamates, organochlorines, pyrethroids, and neonicotinoids). The term pesticide in this case study will refer to chemical pesticides that are used for agricultural purposes.

Manual application of pesticides (center) with potential exposure of workers during manual crop maintenance operations in Southeast Asia (Source: S. Miller)

Agriculture is a developing sector in Suriname, which contributes approximately 9% to the Gross Domestic Product (GDP) and employs 17% of the population [ 45 , 46 ]. Screening data from the Dutch Food and Consumer Product Safety Authority (NVWA) from 2010 to 2015 consistently showed pesticide residues in crops imported from Suriname [ 47 ]. The Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH) is examining the association of pesticide exposure to birth outcomes in 1000 mother/child dyads [ 48 ]. CCREOH’s preliminary environmental assessment showed pesticide residues in Surinamese produce, including the insecticides endosulfan and lindane in the leafy vegetable Xanthosoma brasiliense (tannia). According to an interviewer-assisted dietary survey, which was administered to assess dietary exposure to pesticides in Surinamese women (including 696 pregnant women), women living in non-urban districts and less educated women were more likely to have a higher tannia intake rate compared to those living in urban districts and women who received higher levels of education [ 47 ]. This disparity in exposure to tannia illustrates how pesticide use can have inequitable consequences for food safety based on region and education level.

Pesticides play an important role in food security by protecting crops from pests and diseases, leading to improved productivity. However, the misuse of pesticides may lead to residues in produce, potentially compromising food safety [ 49 ]. In addition, the use of banned pesticides continues to be a problem in low-income countries. Due to financial constraints and lack of policy and enforcement, less favorable (older, more toxic and environmentally persistent) pesticides are being used in these countries [ 50 ].

Chronic low-level pesticide exposures, such as through diet, are harmful to human health and have been associated with depression and neurodegenerative disease in adults [ 51 , 52 ]. Furthermore, exposure during gestation and the early postnatal period has been associated with a lower birth weight, decreased gestational age, and neuro-developmental toxicity that can lead to motor- and neurocognitive developmental delays in children [ 53 , 54 ]. In addition, the presence of pesticide residues in plants and the environment has been linked to the emergence of antimicrobial resistant organisms [ 15 ]. Recently, the use of triazole fungicides in certain horticultural systems in Europe has been linked to the emergence of azole-resistant environmental isolates of Aspergillus fumigatus and subsequent fatal human aspergillosis cases [ 55 ]. Especially in the case of Suriname, the greenest country in the world with biodiverse and unique flora and fauna, it is important to consider the possible negative consequences of pesticides on wildlife, such as loss of species and declines in diversity [ 56 , 57 , 58 ].

Appropriate use of pesticides is important for safeguarding food security, food safety, and health equity. While pesticide use is highly regulated in high income countries, there is an urgent need in LMICs to formulate policies on pesticide residues in plants and the environment, such as monitoring and reporting levels of pesticide residues. In Suriname, the development and implementation of national pesticide policies are limited, and the country does not monitor pesticide residues in crops. Although there is currently no policy on the emergence and spread of resistance in plant pathogens associated with pesticides, guidance exists for developing comprehensive action plans to address these potential threats.

Training farmers to use pesticides correctly and screening pesticide residues in crops are pivotal to reducing human risk of pesticide exposure. In addition, approaches to reduce the use of pesticides should be implemented. A well-known strategy is Integrated Pest Management (IPM), which prioritizes the use and integration of multiple cultural, biological, and host resistance strategies, while reducing pesticide use, to manage pests and diseases of plants and animals [ 59 ]. IPM is geared toward improving economic benefits of production systems and reducing human health risks and adverse environmental effects of pesticide use. Ultimately, implementation of IPM, development and enforcement of international recommendations and national policies, and equipping of farmers with the knowledge and means to use pesticides appropriately will minimize pesticide residues in food and the environment and enable economically sustainable food production while reducing adverse health effects in people.

Conclusions

Threats to plant health pose challenges to population health, productivity, and prosperity across the globe. Efforts to protect plants from emerging and endemic pathogens and pests help to not only increase food security and safety to ensure healthy lives, but also to alleviate poverty, promote equity, confront the impact of climate change, protect the environment, boost economic development, and strengthen global partnerships. Establishing a much closer partnership among advocates for One Health, including experts in sustainable agriculture, and public health practitioners will lead to promoting a safe, sustainable, and nutritious diet for families worldwide.

The case studies presented above demonstrate how management practices aimed at reducing crop losses and ensuring food safety would benefit from employment of a One Health approach. Outbreaks of emerging pathogens can be mitigated by mobilizing experts and resources from all arms of One Health to elevate integrated research and development in human, animal, and plant health. For example, protecting bananas from the harmful effects of banana Xanthomonas wilt and alleviating the shortage of food caused by the disease involves a framework that highlights the interaction and interdependence of physical and socio-cultural factors across all levels of a health problem [ 60 ]. This involves effective integrated training on individual and organizational levels; collaboration with plant, environmental, and animal health specialists on the interpersonal level; and implementation of feasible policies on the community and society levels. Similar approaches can be utilized in ensuring food safety, as evidenced in the cases of aflatoxicosis, E. coli , and pesticide use. The 2004 case of aflatoxicosis in Kenya resulted in an intervention on the societal and policy levels with positive effects observed by individuals, communities and organizations. Suriname’s case of pesticide use and safety concerns exhibits a need for societal policy interventions that lead to positive cascading effects on the economy and other parts of society.

The relationship between plant health and human health is especially important in public health and illustrates a need for research specifically focused on the direct and indirect effects of compromised plant health to human populations. Research and development that allows for inclusion of multiple potential causes for public health concern, including plant diseases and pests that endanger human and animal health and wellbeing, is vital for holistically preventing and mitigating the effects of public health threats. To successfully and effectively protect plant health and address food security, there will need to be a stronger regulatory framework, effective surveillance and monitoring systems, feasible disease management practices, and effective training of food production professionals in protecting plant, animal, environmental, and human health. Our case studies also point to the importance of interagency coordination in facilitating rapid responses to public health emergencies, benefits of technological advances that facilitate data sharing, and the value of the One Health approach in ensuring food safety and food security for the global population.

Availability of data and materials

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Abbreviations

Banana Xanthomonas wilt

Caribbean consortium for research in environmental and occupational health

Canadian Food Inspection Agency

Gross domestic product

Hepatitis C virus

Hemolytic uremic syndrome

Integrated pest management

International year of plant health

Low- and middle-income countries

Sustainable development goals

Shiga-toxin producing E. coli

United Nations

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Acknowledgements

We are thankful for the intellectual input from members and staff of the One Health Action Collaborative and the Forum on Microbial Threats of the National Academies of Sciences, Engineering, and Medicine. Special thanks to Chris Braden, Gail Hansen, James Hughes, Ayano Ogawa, Edith Amponsah, Mary Wilson, and Firoz Abdoel Wahid for their contributions to this paper. We also thank NASEM for financial support of this effort.

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DMR and SAM led the conceptualization of the manuscript. DMR wrote the introduction and conclusion sections, SAM wrote case studies 1 and 2, JM and ET wrote case study 3, and ML wrote case study 4. All authors contributed to manuscript editing and read and approved the final manuscript.

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Rizzo, D.M., Lichtveld, M., Mazet, J.A.K. et al. Plant health and its effects on food safety and security in a One Health framework: four case studies. One Health Outlook 3 , 6 (2021). https://doi.org/10.1186/s42522-021-00038-7

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Meta-analysis of the human upper respiratory tract microbiome reveals robust taxonomic associations with health and disease

Nick Quinn-Bohmann ORCID: orcid.org/0009-0001-5358-7322 1 , 2 ,
Jose A. Freixas-Coutin 3 ,
Jin Seo 3 ,
Ruth Simmons ORCID: orcid.org/0000-0002-9303-639X 4 ,
Christian Diener ORCID: orcid.org/0000-0002-7476-0868 1 &
Sean M. Gibbons ORCID: orcid.org/0000-0002-8724-7916 1 , 2 , 5 , 6 , 7

BMC Biology volume 22 , Article number: 93 ( 2024 ) Cite this article

Metrics details

The human upper respiratory tract (URT) microbiome, like the gut microbiome, varies across individuals and between health and disease states. However, study-to-study heterogeneity in reported case–control results has made the identification of consistent and generalizable URT-disease associations difficult.

In order to address this issue, we assembled 26 independent 16S rRNA gene amplicon sequencing data sets from case–control URT studies, with approximately 2–3 studies per respiratory condition and ten distinct conditions covering common chronic and acute respiratory diseases. We leveraged the healthy control data across studies to investigate URT associations with age, sex, and geographic location, in order to isolate these associations from health and disease states.

Conclusions

We found several robust genus-level associations, across multiple independent studies, with either health or disease status. We identified disease associations specific to a particular respiratory condition and associations general to all conditions. Ultimately, we reveal robust associations between the URT microbiome, health, and disease, which hold across multiple studies and can help guide follow-up work on potential URT microbiome diagnostics and therapeutics.

The human respiratory system is a complex structure, divided into the upper respiratory tract (URT) and the lower respiratory tract (LRT), and is primarily responsible for the exchange of oxygen and carbon dioxide with the atmosphere [ 1 ]. The upper respiratory tract, with an approximate surface area of 70 m 2 , is known to harbor a diverse microbial community [ 2 ]. Beginning at birth, colonization by microbes occurs through constant exposure to the surrounding environment via aspiration, inhalation, and direct contact [ 2 , 3 , 4 ]. A quasi-stable community develops over time, typically consisting of genera such as Corynebacterium and Dolosigranulum in young healthy children [ 5 ] and Corynebacterium and Staphylococcus in healthy adults [ 6 ] . The URT, consisting of the nares, nasal passages, mouth, sinuses, pharynx, and larynx, is the section of the respiratory tract most exposed to the environment and harbors the highest bacterial density [ 2 ]. Upsetting the balance of the URT microbiome may lead to opportunistic pathogen invasion and serious respiratory tract-related disease and infection [ 7 , 8 ]. Chronic respiratory diseases represent the largest disease burden worldwide, affecting over half a billion people in 2017 [ 9 ]. Pneumonia, an infection of the lungs, is a leading cause of mortality across the world, responsible for an estimated 3.2 million deaths in 2015 [ 10 ]. The likelihood of being infected by the influenza virus, another common respiratory pathogen that has caused recurrent epidemics over the past century, has been shown to be partially dependent on the composition of the URT microbiome [ 7 , 11 ]. Additional respiratory conditions, such as RSV, rhinosinusitis, and recurrent respiratory allergies, have all been linked with the disruption of the URT microbiome [ 12 , 13 , 14 ].

Maintaining a diverse commensal microbiome can be protective against the invasion of opportunistic pathogens [ 2 , 15 ]. Commensal bacteria can help to saturate metabolic niche space, preventing invasion and engraftment of potential pathogens [ 8 ]. Additionally, commensals have been shown to directly suppress viral infections through the activation of host immune responses [ 16 ]. Early exposure to certain commensal microbes can even lead to long-term immunomodulation, preventing autoimmune diseases and promoting tolerance to allergens [ 17 , 18 ]. Overall, the symbiotic relationship between the URT microbiome and the host appears critical for the maintenance of human health [ 2 , 19 ].

As with the gut microbiome, variability exists in the microbial composition of these URT communities across individuals. In addition to inter-individual heterogeneity and disease status, URT microbiome profiles may be shaped by other covariates known to impact community structure, such as age [ 1 , 7 ], and possibly others such as technical variation (e.g., sequencing methodologies), demographics, geographic location, and sex, although these associations are not well defined. Certain keystone or core taxa are well known to have a generally positive association with health, including the genera Dolosigranulum and Corynebacterium [ 20 , 21 , 22 ]. The sinonasal area is predominantly colonized by Corynebacterium and Staphylococcus [ 23 , 24 ], whereas the throat and tonsil areas are mostly colonized by Streptococcus , Fusobacterium , and Prevotella [ 25 , 26 ]. Certain species in the genera Streptococcus , Haemophilus , and Pseudomonas have been linked to negative health outcomes and disease [ 1 , 20 , 27 , 28 , 29 ]. However, respiratory illnesses are often polymicrobial, caused or facilitated by the presence of multiple organisms [ 30 ]. Identifying consistent signatures of URT health and disease has been hampered by the variability in reported results from individual case–control studies.

Here, we conducted a meta-analysis of the composition of the URT microbiome across health and disease states to identify consistent patterns that persist across independent studies in demographically and geographically divergent cohorts within and across multiple respiratory conditions. Using 16S rRNA amplicon sequencing data collected from the nasopharynx or the oropharynx across cases and controls from 26 independent studies representing 10 respiratory diseases and conditions, we observe robust associations between the relative abundance of specific genera and disease status. The diseases, conditions, or set of conditions included in the meta-analysis are as follows: asthma [ 31 , 32 , 33 ], chronic obstructive pulmonary disease (COPD) [ 34 ], COVID-19 [ 35 , 36 , 37 ], influenza [ 38 , 39 , 40 ], pneumonia [ 41 , 42 , 43 ], respiratory allergies [ 44 , 45 ], rhinosinusitis [ 46 , 47 , 48 ], respiratory syncytial virus (RSV, includes a range of conditions caused by the human respiratory syncytial virus) [ 49 , 50 , 51 ], respiratory tract infection (RTI, defined as a viral or bacterial infection of the upper or lower respiratory tract, including bronchitis) [ 52 , 53 , 54 ], and tonsillitis [ 55 , 56 ]. Knowledge of these consistent within- or across-disease associations may help guide the development of diagnostic tools and therapeutic interventions aimed at prevention or treatment of respiratory conditions.

Assembling case–control studies for a URT meta-analysis

To investigate the associations between the composition of the URT microbiome and disease susceptibility, we analyzed data collected from 26 independent case–control studies including 4706 total samples (study inclusion criteria outlined in the “ Methods ” section). Studies included in this meta-analysis had, at a minimum, publicly available 16S rRNA amplicon sequencing data and associated metadata on disease status, URT sampling site, sequencing method, and 16S rRNA hypervariable region used for amplicon sequencing. Unfortunately, additional metadata, such as age, gender, and other demographic data, were not uniformly available across all studies. Four studies included samples from both the nasopharynx and oropharynx; these samples were analyzed separately. For each study, raw data in FASTQ format were downloaded and processed through the same bioinformatic pipeline, defined in the “ Methods ” section below. All analyses were conducted at the genus level, given the phylogenetic resolution of partial 16S rRNA amplicon sequencing [ 57 ]. Details on each study included in this meta-analysis can be found in Additional file 1 : Table 1.

Alpha- and beta-diversity analyses show community-wide impacts of disease conditions

We compared URT microbiome alpha-diversity (Shannon index and Chao1 index) between disease cases and healthy controls at a per-study level. Prior to calculating diversity metrics, rarefaction to a sampling depth of 2000 reads was conducted. After rarefaction, 4536 samples remained, representing a loss of 170 samples. Due to the large compositional differences observed between the nasopharynx and oropharynx [ 40 ], diversity was investigated separately between these environments (Fig. 1 A, B). Across 20 studies sampling the nasopharynx, 7 showed significant differences in alpha-diversity as measured by the Shannon Index between cases and controls, spanning asthma, influenza, RSV, RTI, and respiratory allergies (two-tailed independent Student’s t -test, p < 0.05). All but one (Wen et al., Influenza) of these significant relationships showed significantly higher alpha-diversity in healthy vs unhealthy samples (Fig. 1 A). Across 10 studies sampling the oropharynx, four significant differences were observed between healthy and disease groups, for asthma, influenza, pneumonia, and RTI (two-tailed independent Student’s t -test, p < 0.05). Again, all but one (Wen et al., Influenza) showed significantly higher alpha-diversity in healthy vs unhealthy samples (Fig. 1 B). Similar relationships were observed when examining taxonomic richness (Chao1 index). Among studies sampling the nasopharyngeal microbiome, 10 of 20 showed significant differences between cases and controls, including six that were also significantly enriched in the same direction in the Shannon index (Fig. 1 C, two-tailed independent Student’s t -test, p < 0.05). For oropharyngeal samples, 8 of 10 studies showed significant enrichment between cases and controls (Fig. 1 D, two-tailed independent Student’s t -test, p < 0.05). It has not been well established whether or not alpha-diversity of the URT microbiome is associated with disease [ 58 ]. These results indicate that changes in alpha-diversity of the URT microbiome during respiratory disease are disease-specific, not wholly consistent across studies, and lean toward an overall decline in diversity in the disease state.

Alpha-diversity between disease cases and healthy controls for each respiratory condition. Alpha-diversity (Shannon Index or Chao1 index) is shown between cases and controls for each study. Shannon diversity for both samples from the nasopharynx ( N = 3223) ( A ) and the oropharynx ( N = 1313) ( B ) was calculated, as well as Chao1 richness for the nasopharynx ( N = 3223) ( C ) and the oropharynx ( N = 1313) ( D ). Significant differences between cases and controls were determined by independent Student’s t -test, two-tailed p -value * = p < 0.05, ** = p < 0.01, *** = p < 0.001

We calculated Bray–Curtis distances at the genus level, to investigate beta-diversity patterns across studies (Fig. 2 ). For these analyses, all samples from all studies were pooled after rarefaction, including samples from both URT sampling sites. Analysis by PERMANOVA showed significant differences in beta-diversity between samples collected from two different URT sites, the nasopharynx and the oropharynx (Fig. 2 A, PERMANOVA p < 0.05). This is consistent with findings that the nasopharyngeal and oropharyngeal microbiomes are compositionally distinct [ 59 ]. Additionally, a significant difference was observed between samples taken from different continents, which pushes against prior assertions that the URT microbiome is generally consistent across geographic regions [ 60 ] (Fig. 2 C, PERMANOVA p < 0.05). As expected, significant differences were observed in Bray–Curtis dissimilarity in cases relative to controls, as well as between disease conditions (Fig. 2 B, D, PERMANOVA p < 0.05). Finally, significant differences in beta-diversity were observed between sequencing methods, and 16S rRNA hypervariable region used for amplicon sequencing (Fig. 2 E, F, PERMANOVA p < 0.05). These results indicated that any further analysis would necessarily require consideration of these confounding variables.

Principal coordinate analysis (PCoA) plots of genus-level Bray–Curtis distances along the first two principal coordinatess across all samples. Within subplots, each point represents a single sample ( N = 4536). Beta-diversity was significantly associated with disease status ( A ), URT sampling site ( B ), geographic region ( C ), disease type ( D ), sequencing method ( E ), and 16S rRNA hypervariable region used for amplicon sequencing ( F ). Significant differences in beta-diversity were observed for all six parameters, as determined by PERMANOVA, p < 0.001 in all cases

Covariates are significantly associated with URT microbiome composition

Next, we aimed to examine the influence of geographic regions on taxonomic composition in healthy URT samples. Using metadata on geographic regions available for all studies, multiple regression was run for each genus to estimate the effect of geographic region (Europe, N. America, S. America, Africa, Asia, or Oceania) on centered log-ratio transformed relative abundance data, correcting for URT sampling site, sequencing method, and hypervariable region. Ninety-eight genera showed significant association with at least one geographic region (Fig. 3 , multiple regression, FDR-corrected p -value < 0.05). FDR-corrected p -values and mean relative abundances of each taxon per geographic region can be found in the supplementary material (Additional file 1 : Table 2).

Significant differences in centered log-ratio (CLR) relative abundance of prevalent taxa between geographic regions and ages across healthy control samples. Heatmaps show significant taxonomic associations with geographic location and age in healthy controls. In both, mean CLR-transformed relative abundance is shown via color encoding, with red indicating higher CLR abundance and blue indicating lower CLR abundance. A Taxa displaying significant associations with geographic location in healthy controls are shown in each column ( N = 2387). Each row represents one study, with the URT sampling site annotated (NP = nasopharynx, OP = oropharynx). Geographic region per study is shown via the color bar to the left of the heatmap. Significance was determined by multiple regression, correcting for URT sampling site, sequencing method, and 16S hypervariable region, with FDR-corrected two-tailed p -value < 0.05. B Taxa significantly associated with age are shown, for samples with available metadata for age ( N = 554). Significance was determined by ANCOVA, treating age as a continuous variable, correcting for geographic region, URT sampling site, sequencing method, and 16S hypervariable region, with FDR-corrected two-tailed p -value < 0.05

To investigate how relative abundances of URT genera vary with age in healthy populations, ANCOVA analyses controlling for URT sampling site, geographic region, sequencing method, and 16S rRNA hypervariable region and treating age as a continuous variable were conducted. Overall, 45 genera were significantly associated with age (ANCOVA, FDR-corrected p -value < 0.05), based on ANCOVA containing a squared term for age to uncover potential non-linear relationships. Samples were grouped into age quantiles, in order to visualize mean CLR-transformed relative abundance across age groups for genera that showed significant associations (Fig. 3 ). FDR-corrected p -values associated with age and age^2, as well as mean relative abundances of each taxon per age quantile can be found in the supplementary material (Additional file 1 : Table 3). Using a multiple regression framework similar to the age analysis (i.e., with the same set of covariates), with sex as a categorical independent variable, no genera were found to be significantly associated with sex.

Within-study Random Forest Classifiers show how predictive URT microbiome profiles are in distinguishing cases from controls across disease types

Random forest classifiers were constructed on a per-study basis using genus-level URT relative abundance data, with fivefold cross-validation. The capacity of these classifiers to correctly discriminate cases from controls was assessed by calculating the area under the receiver-operating characteristic (AUROC, Fig. 4 ) from the results of cross-validation testing. Generally, moderate classification accuracy was observed, with an average per-study AUROC of 0.71. Higher AUROC values were observed for some disease conditions, such as influenza and pneumonia. Others showed less capacity to discriminate cases from controls, such as asthma and RTI. No strong correlation was observed between study sample count ( N ) and AUROC (Pearson correlation r = − 0.059, p = 0.75), nor between the URT sampling site and AUROC (two-tailed Student’s independent t -test, t = − 0.76, p = 0.45). These results indicate that URT composition contains information that can be leveraged to predict case versus control status, but that the predictive capacity can vary substantially across diseases.

Area under the receiver-operating characteristic (AUROC) for classifying case versus control status from the URT microbiome profile across studies. AUROC values are shown for each study and sampling site ( N = 30 data sets, 4706 samples), based on random-forest classifiers constructed using fivefold cross-validation for data from each study, separately. Values less than 0.5 are not shown. Sample count for each study is shown (range = 12–1021). Per-study disease type is shown via color encoding. Shaded background indicates the URT sampling site of each study (nasopharynx = pink; oropharynx = blue)

URT microbiomes show distinct taxonomic associations across studies and disease states

We next investigated whether we could identify robust taxonomic patterns of URT microbiome disruption across disease conditions. We conducted logistic regression on a per-study basis, in order to avoid cross-study comparisons due to sparsity in available covariates, with disease status as the dependent variable, iterating through separate regressions for each genus (significant genera defined as those with FDR-corrected p < 0.05). Studies spanning 8 disease types showed significant enrichment in at least one taxon (Fig. 5 ). COPD, COVID-19, and asthma were the three respiratory conditions that showed no significant taxonomic enrichments in health or disease (all FDR-corrected p > 0.05). Several consistent enrichments, where a taxon showed significant enrichment in the same direction in at least two studies within a disease, were observed (Fig. 5 ; designated by black boxes drawn around cells in the heatmap). For instance, Pseudomonas was consistently enriched in cases of influenza, while Veillonella was consistently enriched in cases of influenza, pneumonia, and RSV. Overall consistent cross-disease associations with health or disease status were defined as those genera that showed significant enrichments in the same direction in at least three more studies across all diseases than in the opposing direction ( N same_direction − N opposite_direction ≥ 3). Following this heuristic , Corynebacterium , Veillonella , Fusobacterium , Rothia , and Gemella were all associated with health, although Corynebacterium , and Veillonella each showed enrichment in cases in one study. Pseudomonas and Acinetobacter were consistently associated with disease (Fig. 5 ). Influenza and pneumonia showed the largest number of significant enrichments among all the disease conditions analyzed. Streptococcus had the highest mean relative abundance of taxa with significant associations, at 17.2% ± 0.3%, followed by Corynebacterium , Staphylococcus , Dolosigranulum , Haemophilis , and Prevotella , all with mean relative abundances over 5% (Fig. 5 ). Effect sizes and FDR-corrected p values were recorded for each genus-disease pair (Additional file 1 : Table 4).

Within-study case vs. control logistic regression results at the genus-level. A Per-study taxonomic enrichment in cases is denoted in red, and enrichment in controls is denoted in blue ( N = 30 data sets, 4706 samples). Blank/gray spaces indicate no significant association. Only taxa with at least one significant association are shown. Significant associations are defined as having FDR-corrected two-tailed p -value < 0.05. Black boxes are shown around consistent enrichments within a disease, in which taxa are enriched in the same direction in at least two studies within a disease. Overall disease associations are shown in the last heatmap row, in which enrichment in the same direction in three or more studies than in the opposite direction ( N same_direction − N opposite_direction ≥ 3) are considered across-disease significant. B Mean relative abundance across all samples of each taxon shown in A . C Prevalence across all samples for each taxon shown in A

The results of this meta-analysis were consistent with prior findings regarding the composition of the URT microbiome in health and disease [ 1 ] and revealed novel compositional patterns within and across diseases and between healthy individuals across age and geography. They also underscore the importance of recognizing different types of dysbioses in the URT microbiome that can potentially contribute to disease.

URT microbiome samples showed a trend toward lower alpha-diversity in disease cases, as opposed to healthy controls, in at least one study representing asthma, RTI, influenza, respiratory allergies, RSV, and pneumonia (Fig. 2 A, B ). Previous studies have reported similar signatures in cases of bacterial or viral infection [ 61 , 62 ]. Influenza was the sole respiratory condition in which one study showed significantly higher alpha-diversity in disease cases, aligning with previous findings that alpha-diversity patterns vary depending on the disease context [ 43 ]. However, this finding will need further validation, as prior reports have found no association between URT alpha-diversity and susceptibility to influenza infection, and another study in this analysis showed an association in the opposite direction from what we report (likely due to methodological differences across analyses) [ 7 , 63 ].

Bray–Curtis dissimilarity between URT communities was associated with multiple covariates: case–control status, sampling site (nasopharynx or oropharynx), disease type, geographic region, sequencing method, and 16S rRNA hypervariable region used for amplicon sequencing (Fig. 2 ). Concordantly, prior work has shown significant beta-diversity differences between health and disease states [ 61 ] and separation between nasopharyngeal and oropharyngeal samples, with the oropharynx harboring a more diverse microbial population than the nasopharynx [ 40 ] (Fig. 2 ). The significant beta-diversity differences reported here between samples from distinct geographic regions were novel. Prior work has asserted a lack of geographic signal in the URT microbiome [ 60 ]. However, it is intuitive that variation in the surrounding environment could give rise to variation in URT composition (Fig. 2 ). Technical differences in sequencing methodology were significantly associated with beta-diversity, as one might expect (Fig. 2 ). These results underscore the need to account for relevant covariates when looking for associations between URT composition and diseases that are independent of these potentially confounding factors.

We next looked into how the covariates age, sex, and geographic location shaped the taxonomic composition of the URT microbiome in healthy individuals across studies, in order to identify and isolate these signals from health and disease associations, and further indicate which covariates should be considered in future analyses (Fig. 4 ). Relative abundances of several taxa ( N = 98) were observed to show significant associations with geography. Corynebacterium , a known health-associated taxon, showed higher mean relative abundance in samples from North America (12.0%), South America (15.2%), and Oceania (12.9%) than in samples from Africa (5.0%), Asia (4.2%), or Europe (8.6%). Conversely, Streptococcus showed much higher mean relative abundance in samples collected in Africa (35%) than in any other geographic region. Other taxa that show significant association with geographic region include Gemella, Pseudomonas, Rothia , and Veillonella , all of which show significant associations with health or disease via case–control analysis. Due to these significant differences in taxonomic composition, it is imperative to account for geographic location in the construction of diagnostic or therapeutic tools. Two keystone taxa, Dolosigranulum and Moraxella , were enriched in children as compared to adults, which was previously reported (Fig. 4 ) [ 5 ]. Additionally, we saw an increase in the health-associated taxon Veillonella in adults, when compared to children (Fig. 4 ). Due to the breadth of associations observed with age, and the purported inhibition of pathogenic invasion by some of these age-associated genera [ 2 ], we suggest that age should be included as a covariate when analyzing URT microbiome data, whenever possible. However, when age metadata are unavailable, we hope that the list of taxa provided here can be used to identify associations that may be driven by variation in age, rather than by disease. Sex showed no associations.

We ran case–control logistic regression analyses separately within each study and URT sampling site, to avoid pooling data across samples with very different demographic, biological, and methodological characteristics, similar to the approach taken in a prior meta-analysis of human gut microbiomes [ 64 ]. Robust taxonomic enrichments associated with case–control status were observed within 11 out of the 26 studies included in the meta-analysis (Fig. 5 ), including two studies that contained both nasopharyngeal and oropharyngeal samples. Studies from 7 of the 10 respiratory conditions included showed significant enrichment of at least one genus. Asthma, COPD, and COVID-19 were the three diseases that showed no significant URT genus-level associations, although previous URT studies have shown a microbial association with these diseases, such as with Rothia in COVID-19 patients [ 65 , 66 , 67 ].

Several consistent signatures were observed across studies within a disease. For instance, Veillonella was significantly enriched in controls for at least two independent studies within both pneumonia and RSV, and across OP and NP samples in the same study for influenza (Fig. 5 ). Two studies included in the meta-analysis, one in influenza and one in RSV, similarly report Veillonella enrichment in cases as compared to controls [ 49 , 62 ]. Conversely, Pseudomonas was significantly enriched in cases across two independent studies for influenza. This association was also reported in two influenza studies included in the meta-analysis [ 39 , 40 ]. Prevotella showed six significant enrichments across studies, but interestingly showed very inconsistent associations, with enrichment in controls in four studies and enrichment in cases in two. Here we see an example of putative dysbiosis taking many forms, and the health or disease associations of many taxa showing strong context-specificity. Across diseases, significant signatures were observed for several keystone taxa that were enriched in healthy individuals [ 2 ], like Corynebacterium, Veillonella , Fusobacterium , Rothia , and Gemella . Of these, Corynebacterium has been previously identified as a core taxon, putatively associated with health [ 1 ]. Additionally, these are largely abundant/prevalent taxa, with mean relative abundance above 5% for Corynebacterium , specifically (Fig. 5 ) . Conversely, a few genera known to harbor opportunistic pathogen species, including Pseudomonas and Acinetobacter , showed multiple associations with diseases. Acinetobacter baumannii and Pseudomonas aeruginosa are both known to cause disease in humans [ 27 , 28 , 29 , 68 ]. Understanding which taxa are strongly related to health or disease, and in which contexts, will further aid the development of effective microbial diagnostics and therapeutics.

There were several limitations to our study that are important to highlight. First, there were differences in amplicon sequencing methodologies across the 26 studies included in this analysis, which introduced substantial technical biases. For example, not all studies had paired-end reads available, so we elected to use only forward reads for all studies to mitigate potential bias. Using longer, merged reads for some studies and not others would impact the efficiency of taxonomic annotation across studies (i.e., even for studies with the same variable region sequenced). Furthermore, there are often a large number of paired-end reads that fail to merge, which can lead to a substantial drop in sequencing depth in a given sample, which is another layer of bias. Additionally, samples across studies showed differences in sequencing depth. To account for this, we elected to rarefy the data to normalize sampling depth across samples. While other options exist, the current consensus in the field is that rarefaction is still optimal for comparing point estimates of alpha- and beta-diversity across samples [ 69 ].

First, while we controlled for these technical variables in our statistical testing whenever possible, incomplete metadata on these differences across studies can skew the final results. Second, many studies were missing pertinent demographic metadata, such as sex or age, which limited our statistical power by preventing us from correcting for these covariates in regressions that pooled data across all studies. It was not possible to determine whether geographic region-related trends were consistent across age groups, due to age metadata not being available for a majority of samples. Third, some studies have nearly 100-fold more samples than others, which can skew regression results if samples were pooled across studies that differed substantially in cohort size. For these reasons, the case versus control genus enrichment analyses were conducted on a per-study basis, to avoid introducing these myriad biases into the regressions. Significant case–control hits from within-study regressions that were consistent across studies provided strong support for disease-specific associations that are independent of the aforementioned limitations.

Overall, these findings point to different flavors of dysbiosis that distinguish different disease states in the URT. In some cases, the disease state is characterized by a loss of putatively beneficial commensals, such as Veillonella in influenza, pneumonia, and RSV, and in other cases, it is characterized by the gain of putatively pathogenic taxa such as Pseudomonas in influenza, which mirrors what has been found across diseases in the human gut microbiome [ 64 ]. Future work should leverage these results to help guide the development of diagnostics and therapeutics for the URT.

Systematic review of relevant studies

A systematic review was conducted using two main search engines (PubMed and Embase) to retrieve all relevant publications describing microbiome sequencing in the human upper respiratory tract. A PRISMA flow chart (Additional file 2 : Fig. S1) shows how the publications were screened, identified as relevant, and finally selected based on inclusion and exclusion criteria. Briefly, a total of 153,586 reports were identified using relevant keywords such as “microbiome,” “16S rRNA,” “URT,” “oropharynx,” “nasopharynx,” and “larynx.” Of these, 37,083 were classified as conference abstracts, conference papers, short surveys, and book chapters and therefore were excluded from the analysis. Additional exclusion criteria included 16S rRNA studies from non-human URT, which filtered out 115,883 manuscripts, leaving only 620 manuscripts. Of these 620 manuscripts, a very strict and manual pre-selection was conducted to eliminate those with irrelevant topics or disease conditions, such as studies that involved interventions or those without healthy patient controls, as well as studies with unavailable sequencing data, incomplete metadata, or duplicate manuscripts that referred to the same clinical study. This pre-selection step reduced the number of manuscripts by approximately 90%, leaving only 68 manuscripts. The final selection step was conducted manually to ensure the public availability of well-curated metadata and corresponding raw sequencing data files. This step also excluded studies from overrepresented disease conditions, so that no more than 3 studies were selected per disease condition. At the end, a total of 26 peer-reviewed publications survived all inclusion and exclusion criteria, yielding a total of 10 URT-related conditions (asthma, chronic obstructive pulmonary disease, COVID-19, influenza, pneumonia, respiratory allergies, rhinosinusitis, RSV, respiratory tract infection, tonsillitis) with 1–3 studies per condition representing a total of 4,706 samples.

16S rRNA amplicon sequencing URT cohorts

All phylogenetic and read count data used in this study consisted of 16S rRNA gene amplicon sequencing data, with multiple hypervariable regions sequenced across studies, spanning the V1 to V7 regions. A full list of the 26 data sets analyzed in this study, along with links to SRA accession numbers and accompanying metadata, can be found in Additional file 1 : Table 1. The studies contained between 12 and 1021 subjects and varied in age from birth to 97 years old (in studies where age metadata was available), with more representation of young individuals. Studies were conducted in all six inhabited continents, with more representation from Europe and North America. 16S rRNA amplicon sequencing data consisting of FASTQ files, along with associated metadata, were downloaded from the NCBI SRA. While some studies included paired-end sequencing reads, only forward reads were used to maintain better analytical consistency across all studies and to avoid biases in the efficiency of taxonomic assignment between studies. Following data collection, all FASTQ data were imported into QIIME2 version 2022.8.3 [ 70 ] for further processing and analysis. Data were imported through the construction of a single-end Phred33v2 FASTQ manifest for each dataset. Following import, quality control and filtering in the QIIME2 DADA2 (v1.12.1) [ 71 ] plug-in removed chimeric sequences, trimmed left ends of all sequences by 10 bp to remove primers, truncated sequences uniformly at 200 bp, and identified amplicon sequence variants (ASVs). In total 623,507,314 reads were filtered, with 134,649,099 removed for poor quality or chimerism.

Data preprocessing and taxonomic classification

The Silva high-quality rRNA gene database version 138 was used to assign taxonomy to ASVs [ 72 ]. The full-length 16S rRNA classifier was used due to heterogeneity in the hypervariable region used for sequencing between studies. Mean classification at the genus level was 86.0% (Additional file 1 : Table 5; Additional file 2 : Fig. S2). At the species level, classification was unsuccessful, with a mean classification of 13.9%. As a result, all subsequent analyses were conducted at the genus level by binning ASV counts together based on their genus-level annotations. All subsequent data analysis was managed using pandas (v1.4.4) in Python (v3.8.13).

Alpha-diversity analyses

To investigate alpha-diversity, QIIME2 artifacts containing sequences for each study were merged into a single dataframe. Prior to calculation, algorithmic filtering removed any taxa with fewer than two reads per study, and any taxa present in less than 5% of samples across a study. This merged data frame was converted into a QIIME2 artifact and rarefied using the qiime feature-table rarefy function to a sampling depth of 2000. Alpha-diversity was calculated in QIIME2 via the alpha function within the diversity plugin. Shannon entropy and Chao1 index were used to estimate alpha-diversity for all samples included in the meta-analysis. Shannon entropy and Chao1 index for cases and controls within each disease were plotted and significant differences across groups were tested using two-tailed independent Student’s t -test ( p < 0.05) in SciPy (v1.8.1).

Beta-diversity analyses

To estimate beta-diversity, the filtered and rarefied genus count table constructed previously was used to construct a Bray–Curtis dissimilarity matrix using the beta function in the QIIME2 diversity plugin. Subsequently, principal coordinate analysis (PCoA) was used to analyze and visualize overall beta-diversity in scikit-bio version 0.5.7. Significant differences in beta-diversity were observed along multiple axes, including case vs. control status, disease type, geographic location, URT sampling site, sequencing method, and 16S rRNA hypervariable region as determined by PERMANOVA, using the adonis function within the diversity plugin for QIIME2.

URT compositional patterns across geographic regions

A genus-level abundance matrix was constructed using only healthy control samples, and taxa with fewer than two reads per study or those present in fewer than 5% of samples across a study were removed. To examine the association between geographic location and centered log-ratio (CLR) transformed relative abundance of common taxa, multiple regression was used to determine significant enrichments of taxa in each geographic region while correcting for URT sampling site, sequencing method, and 16S rRNA hypervariable region using the formula “clr ~ region + v_region + sequencing + URT” in statsmodels (v0.13.5) [ 73 ]. For the purpose of these analyses, the continents in which studies took place were used as the geographic regions, as too many countries were represented to have appropriate statistical power at smaller geographic scales. As sex and age metadata were not available for 61.5% of the studies, these covariates were not accounted for in this analysis. Multiple comparison correction for p -values was done using the Benjamini–Hochberg method for adjusting the false discovery rate (FDR) [ 74 ], using statsmodels (v0.14.1). Per-study mean CLR-transformed relative abundance of taxa identified to be significantly enriched in at least one geographic region (multiple regression, FDR-corrected p < 0.05) were added to a clustered heatmap, with color encoding the average CLR-transformed relative abundances in each context. Columns containing average CLR-transformed relative abundances were clustered via an agglomerative clustering algorithm using clustermap in seaborn (v0.12.2).

URT microbiome-age associations

Associations between age and CLR-transformed relative abundances was analyzed via ANCOVA in statsmodels. Using 10 studies for which age metadata was available, ANCOVA was conducted using the following formula “clr ~ age + age 2 + variable_region + sequencing + URT_site + region” that was used to determine significant associations with age, accounting for URT sampling site, geographic region, sequencing method, and 16S rRNA hypervariable region. The square term for age was included to determine if non-linear relationships existed between CLR and age. The p -values were corrected for multiple comparisons via the Benjamini–Hochberg FDR correction as previously described. Samples were split into quantiles by age for visualization. Significantly associated taxa (FDR-corrected p < 0.05) were added to a heatmap with color encoding the average CLR-transformed relative abundances.

URT microbiome associations with sex

Associations between sex and genus-level CLR abundances were determined via multiple regression. Using the 10 studies for which sex metadata was available, multiple regression were conducted using the following formula: “clr ~ sex + variable_region + sequencing + URT_site + region” in statsmodels. The resulting p -values were corrected for multiple comparisons via the Benjamini–Hochberg FDR correction. After correction, no taxa showed a significant association with sex.

Supervised classification of cases and control

Random forest classifiers were constructed for each study to classify cases and controls within each study using scikit-learn (v0.24.1) [ 74 , 75 ]. Classifiers were constructed with fivefold cross-validation, using the scikit-learn StratifiedKFold function to shuffle data. The RandomForestClassifier function within scikit-learn was used to construct classifiers with n_estimators = 100. Area under the curve of the receiver-operating characteristic was calculated using the results of cross-validation testing, using the cross_val_predict and roc_auc_score functions in scikit-learn .

URT microbiome-disease associations

To investigate the association between genera in the URT microbiome and disease, sample read counts were normalized using a CLR transformation, as above. Logistic regressions used case–control status as the dependent variable and CLR-transformed abundance as the independent variable, following the formula “case_control_status ~ clr” in statsmodels. Regressions were run separately within each study and sampling site. By running separate analyses within each study and sampling site, key confounders like geographic location, sampling site, 16S rRNA hypervariable region, and sequencing method were constant within a given regression analysis. Mean relative abundance of each taxon within a given study and sampling site found to be significant was calculated for visualizations. P -values were FDR-corrected as described above. Significance was assigned to any association with an FDR-corrected p -value less than 0.05. Results were plotted in a binary heatmap, with significant health-associated genera designated as blue and disease-associated genera designated as red. Heatmaps were constructed using seaborn.

Availability of data and materials

All data generated or analyzed during this study are included in this published article, its supplementary information files, and publicly available repositories. Additional supplementary data can be found in Additional file 1 : Tables 1–5. All original data are available on the NCBI SRA under accession codes provided in Additional file 1 : Table 1, with the exception of one study for which data is not publicly available. All intermediate data files for this analysis are available at Zenodo under DOI: 10.5281/zenodo.10962515. Analysis code can be found at the following GitHub repository: https://github.com/Gibbons-Lab/2023_URTmetaanalysis .

Abbreviations

Upper respiratory tract

Nasopharynx

Respiratory tract infection

Respiratory syncytial virus

Chronic obstructive pulmonary disease

Coronavirus disease 2019

Amplicon sequence variant

False detection rates

Centered log-ratio

Area under the receiver-operating characteristic

Principal coordinate analysis

Analysis of covariance

National Center for Biotechnology Information Sequence Read Archive

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Chiu C-Y, Chan Y-L, Tsai M-H, Wang C-J, Chiang M-H, Chiu C-C, et al. Cross-talk between airway and gut microbiome links to IgE responses to house dust mites in childhood airway allergies. Sci Rep. 2020;10:13449.

Marazzato M, Zicari AM, Aleandri M, Conte AL, Longhi C, Vitanza L, et al. 16S metagenomics reveals dysbiosis of nasal core microbiota in children with chronic nasal inflammation: role of adenoid hypertrophy and allergic rhinitis. Front Cell Infect Microbiol. 2020;10:458. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA554533 (2019)

De Boeck I, Wittouck S, Martens K, Claes J, Jorissen M, Steelant B, et al. Anterior nares diversity and pathobionts represent sinus microbiome in chronic rhinosinusitis. mSphere. 2019;4. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJEB30316 (2019), https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJEB23057 (2017)

Gan W, Yang F, Tang Y, Zhou D, Qing D, Hu J, et al. The difference in nasal bacterial microbiome diversity between chronic rhinosinusitis patients with polyps and a control population. Int Forum Allergy Rhinol. 2019;9:582–92. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA493980 (2018)

Vickery TW, Armstrong M, Kofonow JM, Robertson CE, Kroehl ME, Reisdorph NA, et al. Specialized pro-resolving mediator lipidome and 16S rRNA bacterial microbiome data associated with human chronic rhinosinusitis. Data Brief. 2021;36:107023. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA678776 (2020)

Edouard S, Million M, Bachar D, Dubourg G, Michelle C, Ninove L, et al. The nasopharyngeal microbiota in patients with viral respiratory tract infections is enriched in bacterial pathogens. Eur J Clin Microbiol Infect Dis. 2018;37:1725–33. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJEB14780 (2018)

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Sande CJ, Njunge JM, Mwongeli Ngoi J, Mutunga MN, Chege T, Gicheru ET, et al. Airway response to respiratory syncytial virus has incidental antibacterial effects. Nat Commun. 2019;10:2218. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJEB28053 (2018)

Man WH, van Houten MA, Mérelle ME, Vlieger AM, Chu MLJN, Jansen NJG, et al. Bacterial and viral respiratory tract microbiota and host characteristics in children with lower respiratory tract infections: a matched case-control study. Lancet Respir Med. 2019;7:417–26. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA428382 (2018)

Teo SM, Mok D, Pham K, Kusel M, Serralha M, Troy N, et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe. 2015;17:704–15. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA275918 (2015)

van den Munckhof EHA, Hafkamp HC, de Kluijver J, Kuijper EJ, de Koning MNC, Quint WGV, et al. Nasal microbiota dominated by Moraxella spp. is associated with respiratory health in the elderly population: a case control study. Respir Res. 2020;21:181. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA596902 (2019)

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Acknowledgements

Thanks to members of the Gibbons Lab for helpful comments on this work.

This work was funded by a research grant from Reckitt Health US LLC, by a Washington Research Foundation Distinguished Investigator Award, and by startup funds from the Institute for Systems Biology.

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Contributions

N.Q.B., S.M.G., and C.D. conceptualized the study. N.Q.B. ran the analyses, interpreted the results, and authored the first draft of the manuscript. S.M.G., C.D., and J.F.C. provided resources for the work and supervised the work. J.F.C. conducted the study selection for inclusion in the analysis. J.S. and R.S. provided support with the interpretation of results. All authors read and approved the final manuscript.

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This work was funded, in part, by Reckitt Health US LLC and co-authored by Reckitt employees: JFC, JS, and RS. The authors report no other competing interests.

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Supplementary Information

Additional file 1: table s1..

Studies Inclusion. Table S2. Taxonomic Classification Percentage. Table S3. Enrichment associated with geographic region in healthy controls. Table S4. Enrichment associated with age in healthy controls. Table S5. Results from case v. control logistic regression.

Additional file 2: Fig. S1.

Prisma Flowchart for Study Inclusion, An original search returned 153,586 studies. Filtering out conference abstracts, conference papers, short surveys and book chapters left 116,503 peer-reviewed publications. Additional screening removed 115,883 publications by screening for keywords “16S rRNA” and “human” and “upper respiratory” or “nasopharynx” or “oropharynx” or “larynx”, leaving 620 publications. Another phase of screening removed 552 publications for irrelevance (e.g., intervention studies or studies that lacked healthy controls), lack of sequencing data, unavailable, incomplete data/metadata, and duplicate studies reporting on the same cohort, leaving 68 publications. Of these, 42 were excluded due to overrepresentation of disease conditions in the final cohort, or problems with accessing the raw data and metadata. In the end, 26 publications remained, with 1-3 studies per disease. Fig. S2. Mean classification percentage for each study at each taxonomic level. Classification remained at or above 60% for all studies through the genus level. At the species level, a significant drop in classification percentage was observed.

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Quinn-Bohmann, N., Freixas-Coutin, J.A., Seo, J. et al. Meta-analysis of the human upper respiratory tract microbiome reveals robust taxonomic associations with health and disease. BMC Biol 22 , 93 (2024). https://doi.org/10.1186/s12915-024-01887-0

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DOI : https://doi.org/10.1186/s12915-024-01887-0

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Global Burden of Disease Study 2021 Estimates: Implications for Health Policy and Research

This editorial article, published by The Lancet , outlines the health policy and research implications of the newest iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), GBD 2021. Published in 2024, GBD 2021 estimates include data on the global disease burden for 371 diseases and injuries between 1990 and 2021 and represent the first estimates published since the onset of the COVID-19 pandemic. GBD 2021 provides a comprehensive assessment of the burden of emerging diseases at the global, regional, and country levels and explores how data varies by location and over time.

Led by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, GBD is a global effort with researchers from over 150 countries and territories. IHME and other partnering organizations have developed numerous resources to disseminate and visualize the findings of the GBD studies, data visualizations and interactives , country profiles , policy reports , research articles , infographics , and the GBD Results Tool , which allows users to search GBD data.

Ward ZJ, Goldie SG. Global Burden of Disease Study 2021 Estimates: Implications for Health Policy and Research. The Lancet 2024. DOI: https://doi.org/10.1016/S0140-6736(24)00812-2 .

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CBSE 12th Standard Biology Subject Human Health and Disease Case Study Questions 2021

By QB365 on 21 May, 2021

QB365 Provides the updated CASE Study Questions for Class 12 Biology, and also provide the detail solution for each and every case study questions . Case study questions are latest updated question pattern from NCERT, QB365 will helps to get more marks in Exams

QB365 - Question Bank Software

12th Standard CBSE

Final Semester - June 2015

Case Study Questions

Your classmate complains of cough and headache to the doctor. The doctor confirms that he is suffering from pneumonia and not just common cold. (a) How did the doctor arrive at this conclusion? (b) Write the binomials of the causative organisms of pneumonia. (c) What is common about the transmission of the two diseases, common cold and pneumonia?

Read the following and answer any four questions from (i) to (v) given below : X and Yare communicable diseases whereas Wand Z are non-communicable diseases. X is transmitted through vectors whereas Y is transmitted through droplet infection. W is caused due to a hormone deficiency whereas Z is a degenerative disease. Based on the above information, answer the following questions. (i) Identify W, X, Y and Z.

(ii) Select the correct statement.

(iii) If X and Y both are usual diseases then which of the following holds true?

(iv) If X and Y both are bacterial diseases then select the correct match from the following.

(v) Assertion: Communicable diseases could be contagious or non-contagious. Reason: Diseases that spread through vectors are non-contagious disease.

Read the following and answer any four questions from (i) to (v) given below : Priya was 4 years old when she contracted chicken pox. It took her around 15 days to recover completely. Now Priya is 5 years old so her mother got her vaccinated few days back for DPT (5th dose) as per immunisation program. Recently she was playing with her friend in the park when her friend accidently fell on iron pipe and badly bruised her knee. She was taken to the hospital where doctor gave her ATS injection and painkillers. Based on the above information, answer the following questions. (i) Select the correct statement.

(ii) Which of the following do you think is an example of natural passive immunity?

(iii) Which of the following is true for active immunity?

(iv) Select the incorrect match.

(v) Assertion: A person recovered from measles develops an active immunity against this infection. Reason: In active immunity, person's own cells develop antibodies in response to infection.

*****************************************

Cbse 12th standard biology subject human health and disease case study questions 2021 answer keys.

(a) In pneumonia, the lung alveoli become filled with a fluid leading to severe problems in breathing, whereas in common cold, only the nose and respiratory passage are affected, but not the lungs. (b) Pneumonia is caused by (i) Streptococcus pneumoniae (ii) Haemophilus influenzae. (c) Both common cold and pneumonia spread by the droplets/aerosols released by the infected person during coughing and sneezing.

(a) Macrophage. (b) RNA (Ribonucleic acid). (c) Reverse transcriptase.

(a) It is consumed by (i) inhalation and (ii) oral ingestion. (b) Marijuana, Hashish, Ganja, Charas.

(i) (b) : X is a communicable disease that is transmitted through vectors. It could be malaria, chikungunya, etc. Y is communicable disease that is transmitted through droplet infection. It could be rhinitis, diphtheria, pertussis, etc. W is a non-communicable disease like diabetes that is caused by deficiency of insulin hormone. Z is a non-communicable degenerative disease like Alzheimer's disease. (ii) (c) : Sleeping sickness is caused by Trypanosoma. Diphtheria is caused by Corynebacterium diphtheriae. In myocardial infarction a large portion of heart muscle is deprived of blood due to coronary thrombosis and patient develops heart attack. (iii) (b) (iv) (a) : Leprosy is a bacterial infection that spreads through prolonged contact with the infected person. Whooping cough spreads through droplet infection. Botulism spreads through faecal oral route. (v) (b)

(i) (d) : In active immunity, person's own cells produce antibodies in response to infection or vaccination. A person who has recovered from an infection develops natural active immunity whereas artificial active immunity is the resistance induced by vaccines. When ready-made antibodies are directly injected into a person to protect the body against foreign agents, it is called passive immunity. (ii) (b) (iii) (c) : Active immunity provides relief only after long period. It is long lasting. (iv) (c) : Administration of antidiphtheric serum in a patient provides artificial passive immunity. (v) (a)

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Translational Research and Health Equity: Gene Therapies for Sickle Cell Disease as a Case Study

Affiliations.

1 Dalton Tomlin Professor of Medical Ethics and Health Policy in the Center for Medical Ethics and Health Policy at the Baylor College of Medicine.
2 Assistant professor in the Division of Hematology/Oncology in the Department of Pediatrics at Baylor College of Medicine and the codirector of the Sickle Cell and Thalassemia Program at Texas Children's Hospital.
PMID: 38629220
DOI: 10.1002/eahr.500211

In August of 2023, the National Academies of Science, Engineering, and Medicine published a timely report titled "Toward Equitable Innovation in Health and Medicine: A Framework." Here, we review some of the key contributions of the report, focusing on two dimensions of equity: input equity and deployment equity. We then use the example of new gene therapies to treat sickle cell disease (SCD) as a case study of input and deployment equity in translational research. The SCD case study illustrates the need for a kind of translational bioethics with deep understanding of lived experiences and clinical realities as well as a high degree of economic and policy sophistication.

Keywords: gene therapy; health equity; human subjects research; sickle cell disease; translational bioethics; translational research; translational science.

Publication types

Anemia, Sickle Cell* / genetics
Anemia, Sickle Cell* / therapy
Health Equity*
Translational Research, Biomedical
Translational Science, Biomedical

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Case Study Questions Class 12 Biology Human Health and Disease

Case study questions class 12 biology chapter 8 human health and disease.

CBSE Class 12 Case Study Questions Biology Human Health and Disease. Term 2 Important Case Study Questions for Class 12 Board Exam Students. Here we have arranged some Important Case Base Questions for students who are searching for Paragraph Based Questions Human Health and Disease.

At Case Study Questions there will given a Paragraph. In where some Important Questions will made on that respective Case Based Study. There will various types of marks will given 1 marks, 2 marks, 3 marks, 4 marks.

CBSE Case Study Questions Class 12 Biology Human Health and Disease

Case study 1:.

Our mind and mental state can affect our health. Of course, health is affected by- (i) genetic disorders – deficiencies with which a child is born and deficiencies/defects which the child inherits from parents from birth; (ii) infections and (iii) life style including food and water we take, rest and exercise we give to our bodies, habits that we have or lack etc. When the functioning of one or more organs or systems of the body is adversely affected, characterised by appearance of various signs and symptoms, we say that we are not healthy, i.e., we have a disease. Diseases can be broadly grouped into infectious and non-infectious.

Diseases which are easily transmitted from one person to another, are called infectious diseases. Infectious diseases are very common and every one of us suffers from these at some time or other. Some of the infectious diseases like AIDS are fatal. Among non-infectious diseases, cancer is the major cause of death. Drug and alcohol abuse also affect our health adversely.

Que. 1) Which of the following thing mainly affects health?

(a) Life style

(b) Education

(d) Both (a) and (b)

Que. 2) When the child is born with some deficiencies then it is ……………………………………………………………………… .

(a) Heart disease

(b) Genetic disorder

(d) Infections

Que. 3) If a person’s organ or organ system is affected then the symptoms will appear. And the person can say ……………………………………………………………… .

(a) I am healthy.

(b) I am in good state.

(d) I am resting.

Que. 4) Define the term ‘Infectious disease’ and write an example.

Que. 5) Identify ‘B’

Que. 1) (d) Both (a) and (b)

Que. 2) (b) Genetic disorder

Que. 3) (c) I am unhealthy.

Que. 4) Answer: Transmission of the diseases from one person to another is called as Infectious diseases. AIDs is an example of infectious disease.

Case Study 2:

A wide range of organisms belonging to bacteria, viruses, fungi, protozoans, helminths, etc., could cause diseases in man. Such disease causing organisms are called pathogens. Most parasites are therefore pathogens as they cause harm to the host by living in (or on) them. The pathogens can enter our body by various means, multiply and interfere with normal vital activities, resulting in morphological and functional damage. Pathogens have to adapt to life within the environment of the host. For example, the pathogens that enter the gut must know a way of surviving in the stomach at low pH and resisting the various digestive enzymes. A few representative members from different groups of pathogenic organisms are discussed here along with the diseases caused by them. Preventive and control measures against these diseases in general, are also briefly described. Salmonella typhi is a pathogenic bacterium which causes typhoid fever in human beings. These pathogens generally enter the small intestine through food and water contaminated with them and migrate to other organs through blood. Sustained high fever (39° to 40°C), weakness, stomach pain, constipation, headache and loss of appetite are some of the common symptoms of this disease. Intestinal perforation and death may occur in severe cases.

Typhoid fever could be confirmed Widal test : A classic case in medicine, that of Mary Mallon nicknamed Typhoid Mary, is worth mentioning here. She was a cook by profession and was a typhoid carrier who continued to spread typhoid for several years through the food she prepared.

Que. 1) In a classic case, who was spreading typhoid by cooking?

(a) Mary Mallon

(b) Typhoid Cook

(d) Mary Classic

Que. 2) Which of the following is a pathogenic bacterium?

(a) Plasmodium vivax

(b) Salmonella typhi

(d) Aedes Aegypti

Que. 3) The organisms like viruses, helminths, protozoa and bacteria which are responsible for causing disease in man are known as ……………………………………………………………………………………… .

(a) Non-Infectious

(b) Enzymes

(d) Pathogens

Que. 4) Write the name of pathogenic bacteria that causes typhoid and its symptoms.

Que. 5) Why most of parasites are pathogens?

Que. 1)(a) Mary Mallon.

Que. 2) (b) Salmonella typhi .

Que. 3) (d) Pathogens.

Que. 4) Answer: A pathogenic bacterium that causes typhoid fever in humans is Salmonella typhi . Salmonella typhi causes typhoid by entering small intestine. The common symptoms of typhoid disease are weakness, high fever, and loss of appetite, constipation, and headache.

Que. 5) Parasites live in or on the host and causes harm to the host. Hence, most of parasites are pathogens.

Case Study 3:

Bacteria like Streptococcus pneumoniae and Haemophilus influenzae are responsible for the disease pneumonia in humans which infects the alveoli (air filled sacs) of the lungs. As a result of the infection, the alveoli get filled with fluid leading to severe problems in respiration. The symptoms of pneumonia include fever, chills, cough and headache. In severe cases, the lips and finger nails may turn gray to bluish in colour. A healthy person acquires the infection by inhaling the droplets/aerosols released by an infected person or even by sharing glasses and utensils with an infected person. Dysentery, plague, diphtheria, etc., are some of the other bacterial diseases in man. Many viruses also cause diseases in human beings. Rhino viruses represent one such group of viruses which cause one of the most infectious human ailments – the common cold. They infect the nose and respiratory passage but not the lungs.

The common cold is characterised by nasal congestion and discharge, sore throat, hoarseness, cough, headache, tiredness, etc., which usually last for 3-7 days. Droplets resulting from cough or sneezes of an infected person are either inhaled directly or transmitted through contaminated objects such as pens, books, cups, doorknobs, computer keyboard or mouse, etc., and cause infection in a healthy person.

Que. 1) Which organ in the humans get affected by pneumonia disease?

(a) Stomach

(d) Bladder

Que. 2) Rhino virus can infect ………………………………………………………………………… in the humans.

Que. 3) By which of the following reason, an healthy person can acquire pneumonia disease?

(a) By exhaling droplets of non-infected person.

(b) By headache or leg pain.

(d) By inhaling droplets of infected person.

Que. 4) How long does common cold last?

Que. 5) Write any two symptoms of common cold and pneumonia.

Que. 1)(c) Lungs

Que. 2) (b) Nose

Que. 3) (d) By inhaling droplets of infected person.

Que. 4) Answer: Common cold usually last for three to Seven days.

Que. 5) Answer: Common cold manly infects respiratory passage and pneumonia mainly infects alveoli. Symptoms of common cold are sore throat, cough and headache etc., and symptoms of pneumonia are fever, cough and chills etc. Fingers and lips turn gray to bluish colour in severe cases.

Case Study 4:

Ascaris, the common round worm and Wuchereria, the filarial worm, are some of the helminths which are known to be pathogenic to man. Ascaris, an intestinal parasite causes ascariasis. Symptoms of these disease include internal bleeding, muscular pain, fever, anemia and blockage of the intestinal passage. The eggs of the parasite are excreted along with the faeces of infected persons which contaminate soil, water, plants, etc. A healthy person acquires this infection through contaminated water, vegetables, fruits, etc. Wuchereria (W. bancrofti and W. malayi), the filarial worms cause a slowly developing chronic inflammation of the organs in which they live for many years, usually the lymphatic vessels of the lower limbs and the disease is called elephantiasis or filariasis. The genital organs are also often affected, resulting in gross deformities. The pathogens are transmitted to a healthy person through the bite by the female mosquito vectors.

Many fungi belonging to the genera Microsporum, Trichophyton and Epidermophyton are responsible for ringworms which is one of the most common infectious diseases in man. Appearance of dry, scaly lesions on various parts of the body such as skin, nails and scalp are the main symptoms of the disease.

Que. 1) If a person is having dry and scaly lesions on various parts of the body, then the person is infected by …………………………………………………………………. Disease.

(a) Ringworm

(b) Roundworm

(d) Earthworm

Que. 2) A healthy person can have infection of Ascaris through ………………………………………………………………………………… .

(a) Moisture

(b) Mosquito

(d) Contaminated food and water

Que. 3) The disease filariasis can transmit to a healthy person through ……………………………………………………………………………… .

(a) Through fungi

(b) Through round worm

(d) Through ringworms

Que. 4) Name any two genera of the fungi which are responsible for causing ringworms.

Que. 5) Give an example of filarial worm and round worm.

Que. 1)(a) Ringworm.

Que. 2) (d) Contaminated food and water

Que. 3) (c) Through female mosquito bite.

Que. 4) Answer: Epidermophyton and Microsporum are the two genera of fungi which are responsible for causing ringworms.

Que. 5) Answer: Example of filarial worm is Wuchereria and an example of round worm is Ascaris.

Case Study 5:

Every day we are exposed to large number of infectious agents. However, only a few of these exposures result in disease. Why? This is due to the fact that the body is able to defend itself from most of these foreign agents. This overall ability of the host to fight the disease-causing organisms, conferred by the immune system is called immunity.

Immunity is of two types: (i) Innate immunity and (ii) Acquired immunity. Innate Immunity Innate immunity is non-specific type of defence, that is present at the time of birth. This is accomplished by providing different types of barriers to the entry of the foreign agents into our body. Innate immunity consist of four types of barriers. These are — (i) Physical barriers: Skin on our body is the main barrier which prevents entry of the micro-organisms. Mucus coating of the epithelium lining the respiratory, gastrointestinal and urogenital tracts also help in trapping microbes entering our body. (ii) Physiological barriers: Acid in the stomach, saliva in the mouth, tears from eyes–all prevent microbial growth. (iii) Cellular barriers: Certain types of leukocytes (WBC) of our body like polymorpho-nuclear leukocytes (PMNL-neutrophils) and monocytes and natural killer (type of lymphocytes) in the blood as well as macrophages in tissues can phagocytose and destroy microbes. (iv)Cytokine barriers: Virus-infected cells secrete proteins called interferons which protect non-infected cells from further viral infection.

Que. 1) A skin barrier that protects our body from entering micro-organisms is a …………………………………………………………….. barrier.

(a) Cellular barrier

(b) Physical barrier

(d) Both (a) and (c)

Que. 2) A non-specific type of defence is also known as ……………………………………………………………………………… .

(a) Innate immunity

(b) Acquired immunity

Que. 3) When the host is able to fight against disease-casing organisms, then the ability is known as …………………………………………………………………………… .

(a) Microbial growth

(b) Immunity

(d) Interferons

Que. 4) What is meant by cellular barriers?

Que. 5) Which type of barrier include interferons that protects non-infected cells from further viral infection?

Que. 1)(b) Physical barrier.

Que. 2) (a) Innate immunity.

Que. 3) (b) Immunity.

Que. 4) Answer: An Innate immunity which has specific types of leukocytes (Like monocytes, polymorpho-nuclear leukocytes,and natural killer macrophages in tissue and in the blood) that can phagocytose and destroy microbes in our body, this is known as Cellular barriers.

Que. 5) Answer: Cytokine is a type of barrier which include interferons to protect non-infected cells from further viral infection.

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Unit 8: Human Health and Disease

About this unit.

Learn about the human immune system and some common diseases we suffer from. This unit is aligned to the Class 12 NCERT curriculum.

Common Diseases in Human Beings

Infectious and non-infectious diseases (Opens a modal)
Manifestation & treatment of infectious diseases (Opens a modal)
Common diseases in humans (Opens a modal)
What is pneumonia? (Opens a modal)
The basics of malaria (Opens a modal)
What is malaria? (Opens a modal)
Malaria and Plasmodium life cycle 4 questions Practice

Types of Immunity and the Immune System

The immune system review (Opens a modal)
Types of immune responses: Innate and adaptive, humoral vs. cell-mediated (Opens a modal)
Active & Passive immunity (Opens a modal)
Adaptive immunity (Opens a modal)
Self vs. non-self immunity (Opens a modal)
What is allergic rhinitis? (Opens a modal)
Allergies (what causes them?) (Opens a modal)
The lymphatic system's role in immunity (Opens a modal)
Lymphoid organs review (Opens a modal)
Active and passive immunity 4 questions Practice
Acquired immunity 4 questions Practice
Antibodies and acquired immunity 4 questions Practice
Vaccination and immunisation 4 questions Practice
The immune system 4 questions Practice
Allergies 4 questions Practice

HIV and AIDS

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Addiction and Dependence

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Wildfire smoke contributes to thousands of deaths each year in the U.S.

Alejandra Borunda

Wildfire smoke covered huge swaths of the U.S. in 2023, including places like New York City, where it has historically been uncommon. New research shows the health costs of breathing in wildfire smoke can be high. David Dee Delgado/Getty Images hide caption

New research shows that the health consequences of wildfire smoke exposure stretch well beyond the smoky days themselves, contributing to nearly 16,000 deaths each year across the U.S., according to a National Bureau of Economic Research (NBER) analysis released in April. The analysis warns that number could grow to nearly 30,000 deaths a year by the middle of the century as human-driven climate change increases the likelihood of large, intense, smoke-spewing wildfires in the Western U.S. and beyond.

"This really points to the urgency of the problem," says Minhao Qiu, a researcher at Stanford University and the lead author. "Based on our results, this should be one of the policy priorities, or the climate policy priority, of the U.S., to figure out how to reduce this number."

Another analysis , led by researchers from Yale University, finds that the human death toll every year from wildfire smoke could already be near 30,000 people in the U.S. Deaths from cardiovascular disease, respiratory problems, kidney disease, and mental health issues all rise in the days and weeks after smoke exposure.

Together, the studies point to an underappreciated threat to public health, says Yiqun Ma, a researcher at Yale and an author of the second study.

"It's a call to action," she says—outlining the real, and significant, human stakes of failing to rein in further human-caused climate change.

How bad is smoke for health?

Wildfire smoke is rarely listed as a cause of death on people's death certificates. But research has shown that tiny particles present in smoke worsen many different health problems. These particles penetrate deep into people's lungs and can cross into the bloodstream or even into the brain. Repeated exposures, or high-concentration exposures, can supercharge other health problems, from heart and kidney disease to hastening the onset of dementia symptoms. In some cases, the stress from wildfire smoke is so great that some people die.

Because the harm from wildfire smoke can accumulate and isn't always immediately obvious, the long-term risks from wildfire smoke exposure have gone underappreciated.

"It's not obvious, necessarily, if you're looking at any individual case," says Sam Heft-Neal, an environmental economist at Stanford and an author of the NBER study. Stepping back and looking at the data statistically makes the picture much clearer, he says: smoke is a big problem that is contributing to thousands of deaths already in the U.S.

Physician and researcher Juan Aguilera, now at the University of Texas School of Public Health in El Paso, has studied the impacts of air pollution on his patients' health. He had just moved to the San Francisco Bay Area in 2020 when the smoke descended. "The 2020 wildfires brought a lot of perspective to people living in the Bay Area," he says.

Aguilera and colleagues sampled people's blood before and during the smoke event. They found markers of stressed immune systems and inflammation , signs that people were heavily impacted during the smoke. "As scientists, we do understand that things like chronic inflammation, chronic stress, lead to chronic conditions that are often related to mortality," he says.

The exact mechanisms by which smoke impacts people's health are still being unraveled. Some evidence suggests that wildfire smoke is more harmful than other tiny particles, like pollution from fossil fuel combustion or fine dust. It's likely more harmful smoke is produced when wildfires burn through urban areas, where everything from houses full of insulation to car batteries, and metal are torched.

Aguilera compares the risk of inhaling wildfire smoke to smoking cigarettes. "Being in a wildfire-prone area, it seems something equivalent to smoking like one pack a day, or 10 packs a week," says Aguilera.

Big problems, big impacts

Despite the growing understanding of the health risks from wildfire smoke, the costs have not been factored into most policy decisions, says Susan Anenberg, a public health and pollution expert at George Washington University.

The new research adds to a body of work "showing that wildfire smoke is one of the largest public health consequences of climate change," Anenberg says.

By 2050, the overall annual economic cost credited to lives lost from wildfire smoke could reach $240 billion, according to the NBER analysis. That is larger than previous estimates of all climate-related damages combined—including direct costs related to wildfire and tropical cyclone damages.

"Our estimates of the damages of climate change are undercounting the true effects," Anenberg says.

The NBER analysis used a suite of different computer models, trained on fire observations from 2000 to 2021, to figure out the relationship between fire activity and how much smoke was produced. The researchers then linked that smoke to weather patterns, letting them see how the smoke spread and drifted into different parts of the U.S. at various times. They linked those maps of smoke pollution to county-level death records across the country from 2006 to 2019 to see how deaths changed when the overall exposure to wildfire smoke went up or down.

In years like 2020, some northern California counties were exposed to double their normal pollution load for the year. In conditions like those, the total number of deaths increased by almost 6%. But even small increases in smoke exposure averaged out over the year, push mortality up. "Our findings are consistent with a host of recent work suggesting there is no safe level of air pollution exposure," the study authors write.

Those same models also let them look further into a climate-changed future. Even with aggressive climate action in coming decades, wildfire activity is forecast to grow—and with it, smoke exposure. By the middle of the century, models suggest people across the U.S. will likely experience two to three times as much smoke as they did before 2020. Smoke-related deaths could rise by at least 8,000 people every year. With less aggressive climate action, the number of deaths could be even higher.

"Not to be an alarmist, but the results are staggering," says Aguilera. "They paint a difficult picture for years to come."

The Yale study, led by Ma, uses a similar strategy to estimate the impact of smoke on deaths across the country. But the researchers also looked at the recorded causes of death. Even at very low concentrations, smoke was associated with a higher frequency of deaths related to heart disease. They also saw upticks in the number of deaths related to mental health, endocrine problems, and even diabetes.

Despite AI advancements, human oversight remains essential

Study reveals its limitations in medical coding.

State-of-the-art artificial intelligence systems known as large language models (LLMs) are poor medical coders, according to researchers at the Icahn School of Medicine at Mount Sinai. Their study, published in the April 19 online issue of NEJM AI , emphasizes the necessity for refinement and validation of these technologies before considering clinical implementation.

The study extracted a list of more than 27,000 unique diagnosis and procedure codes from 12 months of routine care in the Mount Sinai Health System, while excluding identifiable patient data. Using the description for each code, the researchers prompted models from OpenAI, Google, and Meta to output the most accurate medical codes. The generated codes were compared with the original codes and errors were analyzed for any patterns.

The investigators reported that all of the studied large language models, including GPT-4, GPT-3.5, Gemini-pro, and Llama-2-70b, showed limited accuracy (below 50 percent) in reproducing the original medical codes, highlighting a significant gap in their usefulness for medical coding. GPT-4 demonstrated the best performance, with the highest exact match rates for ICD-9-CM (45.9 percent), ICD-10-CM (33.9 percent), and CPT codes (49.8 percent).

GPT-4 also produced the highest proportion of incorrectly generated codes that still conveyed the correct meaning. For example, when given the ICD-9-CM description "nodular prostate without urinary obstruction," GPT-4 generated a code for "nodular prostate," showcasing its comparatively nuanced understanding of medical terminology. However, even considering these technically correct codes, an unacceptably large number of errors remained.

The next best-performing model, GPT-3.5, had the greatest tendency toward being vague. It had the highest proportion of incorrectly generated codes that were accurate but more general in nature compared to the precise codes. In this case, when provided with the ICD-9-CM description "unspecified adverse effect of anesthesia," GPT-3.5 generated a code for "other specified adverse effects, not elsewhere classified."

"Our findings underscore the critical need for rigorous evaluation and refinement before deploying AI technologies in sensitive operational areas like medical coding," says study corresponding author Ali Soroush, MD, MS, Assistant Professor of Data-Driven and Digital Medicine (D3M), and Medicine (Gastroenterology), at Icahn Mount Sinai. "While AI holds great potential, it must be approached with caution and ongoing development to ensure its reliability and efficacy in health care."

One potential application for these models in the health care industry, say the investigators, is automating the assignment of medical codes for reimbursement and research purposes based on clinical text.

"Previous studies indicate that newer large language models struggle with numerical tasks. However, the extent of their accuracy in assigning medical codes from clinical text had not been thoroughly investigated across different models," says co-senior author Eyal Klang, MD, Director of the D3M's Generative AI Research Program. "Therefore, our aim was to assess whether these models could effectively perform the fundamental task of matching a medical code to its corresponding official text description."

The study authors proposed that integrating LLMs with expert knowledge could automate medical code extraction, potentially enhancing billing accuracy and reducing administrative costs in health care.

"This study sheds light on the current capabilities and challenges of AI in health care, emphasizing the need for careful consideration and additional refinement prior to widespread adoption," says co-senior author Girish Nadkarni, MD, MPH, Irene and Dr. Arthur M. Fishberg Professor of Medicine at Icahn Mount Sinai, Director of The Charles Bronfman Institute of Personalized Medicine, and System Chief of D3M.

The researchers caution that the study's artificial task may not fully represent real-world scenarios where LLM performance could be worse.

Next, the research team plans to develop tailored LLM tools for accurate medical data extraction and billing code assignment, aiming to improve quality and efficiency in health care operations.

The study is titled "Generative Large Language Models are Poor Medical Coders: A Benchmarking Analysis of Medical Code Querying."

The remaining authors on the paper, all with Icahn Mount Sinai except where indicated, are: Benjamin S. Glicksberg, PhD; Eyal Zimlichman, MD (Sheba Medical Center and Tel Aviv University, Israel); Yiftach Barash, (Tel Aviv University and Sheba Medical Center, Israel); Robert Freeman, RN, MSN, NE-BC; and Alexander W. Charney, MD, PhD.

This research was supported by the AGA Research Foundation's 2023 AGA-Amgen Fellowship to-Faculty Transition Award AGA2023-32-06 and an NIH UL1TR004419 award.

The researchers affirm that the study was conducted without the use of any Protected Health Information ("PHI").

Today's Healthcare
Medical Topics
Personalized Medicine
Diseases and Conditions
Computer Modeling
Computers and Internet
Genetic code
Mathematical model
Stem cell treatments
Artificial intelligence
Personalized medicine
Computer vision

Story Source:

Materials provided by The Mount Sinai Hospital / Mount Sinai School of Medicine . Note: Content may be edited for style and length.

Journal Reference :

Ali Soroush, Benjamin S. Glicksberg, Eyal Zimlichman, Yiftach Barash, Robert Freeman, Alexander W. Charney, Girish N Nadkarni, Eyal Klang. Large Language Models Are Poor Medical Coders — Benchmarking of Medical Code Querying . NEJM AI , 2024; DOI: 10.1056/AIdbp2300040

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Comparing heart disease treatments

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Combining tests more accurately diagnoses prostate cancer

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Early detection of Alzheimer’s disease

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Number of steps per day more important than step intensity

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Harnessing the health benefits of bacteria

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Multifocal contact lenses slow myopia progression in children

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Case Studies: Diseases

Aging (including Alzheimer's disease)

Antibiotics

Bio-inspiration (biomimetics)

Brain (autism, schizophrenia)

Ebola and Marburg

Emerging diseases (general)

The following sites track emerging diseases

Ethical and social issues

Hormone replacement therapy

HPV (Human papillomavirus)

Protein Folding -- and diseases

RNAi (RNA interference or silencing)

SARS (Severe acute respiratory syndrome)

Sudden Oak Death

Synthetic biology

TGN1412: The clinical trial disaster

Vaccines (general)

West Nile Virus

The impact of consanguinity on human health and disease with an emphasis on rare diseases

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Autozygosity-driven genetic diagnosis in consanguineous families from Italy and the Greater Middle East

Genomics of rare genetic diseases—experiences from India

The prevalence, genetic complexity and population-specific founder effects of human autosomal recessive disorders

Introduction

Global distribution of consanguinity

Consanguinity and rates of childhood malformations

Consanguinity and incidence of cancer

Consanguinity and obesity

Consanguinity and rare genetic diseases

Whole exome and whole genome sequencing to investigate consanguineous families

Consanguinity and education

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Plant health and its effects on food safety and security in a One Health framework: four case studies

Background: plant health as part of one health

Case studies

Case study 2: food safety and mycotoxins: aflatoxicosis outbreak in Kenya, 2004–2005 (Fig. 2 -2)

Case study 3: human pathogens associated with plants and food safety: E. coli O157:H7 outbreak caused by romaine lettuce in the United States and Canada, 2018–2019 (Fig. 2 -3)

Case study 4: pesticide use in plant-based agriculture and food security and safety in Suriname, 2010–2015 (Fig. 2 –4; Fig. 3 )

Conclusions

Availability of data and materials

Abbreviations