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WASHINGTON--People with diabetes and depression who take antidepressants may have a lower risk of death and of serious diabetes complications, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

People with diabetes face a higher risk of depression, which makes them more likely to die or develop diabetes complications including heart and kidney disease, stroke, eye, and foot problems. Depression makes diabetes complications worse due to stress, body weight changes, and lack of exercise.

"People with depression and diabetes have poorer health outcomes than those with diabetes alone, and regular antidepressant treatment could lower their risk of complications," said study author Shi-Heng Wang, Ph.D., of the China Medical University in Taichung, Taiwan.

"People who adhere to their antidepressants have better diabetes outcomes and quality of life than those with poor adherence," said study author Chi-Shin Wu, M.D., Ph.D., of the National Taiwan University Hospital in Taipei, Taiwan.

The researchers conducted a nationwide retrospective cohort study of 36,276 patients with depression and diabetes to determine if antidepressants could improve diabetes outcomes. They found regular antidepressant treatment was associated with a lower risk of death and heart disease.

Other authors of the study include: Le-Yin Hsu of the National Taiwan University in Taipei, Taiwan; and Yi-Jiun Pan of the China Medical University in Taichung, Taiwan.

The manuscript received funding from the Ministry of Science and Technology, the China Medical University, and the Ministry of Health and Welfare.

The manuscript, "Associations Between Antidepressant Use and Advanced Diabetes Outcomes in Patients with Depression and Diabetes Mellitus," was published online, ahead of print.

Researchers at Johns Hopkins Bloomberg School of Public Health have shown in a brain organoid study that exposure to a common pesticide synergizes with a frequent autism-linked gene mutation.

The results represent one of the clearest pieces of evidence yet that genetic and environmental factors may be able to combine to disturb neurodevelopment. Researchers suspect that genetic and environmental factors might contribute to the increased prevalence of autism spectrum disorder, a developmental disorder characterized by cognitive function, social, and communication impairments.

The study's use of brain organoids also points the way towards quicker, less expensive, and more human-relevant experimentation in this field when compared to traditional animal studies.

The brain organoid model, developed by the Bloomberg School researchers, consists of balls of cells that are differentiated from human stem cell cultures and mimic the developing human brain. The researchers found in the study that chlorpyrifos, a common pesticide alleged to contribute to developmental neurotoxicity and autism risk, dramatically reduces levels of the protein CHD8 in the organoids. CHD8 is a regulator of gene activity important in brain development. Mutations in its gene, which reduce CHD8 activity, are among the strongest of the 100-plus genetic risk factors for autism that have so far been identified.

The study, which appears online July 14 in Environmental Health Perspectives, is the first to show in a human model that an environmental risk factor can amplify the effect of genetic risk factor for autism.

"This is a step forward in showing an interplay between genetics and environment and its potential role for autism spectrum disorder," says study lead Lena Smirnova, PhD, a research associate in the Department of Environmental Health and Engineering at the Bloomberg School.

Clinically rare as recently as 40 years ago, autism spectrum disorder now occurs in roughly two percent of live births, according to the Centers for Disease Control and Prevention.

"The increase in autism diagnoses in recent decades is hard to explain--there couldn't have been a population-wide genetic change in such a short time, but we also haven't been able to find an environmental exposure that sufficiently accounts for it," says study co-author Thomas Hartung, MD, PhD, professor and Doerenkamp-Zbinden Chair in the Bloomberg School's Department of Environmental Health and Engineering. Hartung is also director of the Center for Alternatives to Animal Testing at the Bloomberg School. "To me, the best explanation involves a combination of genetic and environment factors," says Hartung.

How environmental factors and genetic susceptibilities interact to increase risk for autism spectrum disorder remains mostly unknown, in part because these interactions have been difficult to study. Traditional experiments with laboratory animals are expensive and, especially for disorders involving the brain and cognition, of limited relevance to humans.

Advances in stem cell methods in the past decades have allowed researchers to use human skin cells that can be transformed first into stem cells and then into almost any cell type and studied in the lab. In recent years, scientists have expanded beyond simple lab-dish cell cultures to make cultures of three-dimensional organoids that better represent the complexity of human organs.

For their study, the researchers used brain organoids to model the effects of a CHD8 gene disruption combined with exposure to chlorpyrifos. A group led by co-author Herbert Lachman, MD, professor at Albert Einstein College of Medicine, engineered the cells that make up the organoids to lack one of the two normal copies of the CHD8 gene. This modeled a substantial, but less-than-total, weakening of the CHD8 gene's activity, similar to that seen in people who have CHD8 mutations and autism. The researchers then examined the additional effect of exposure to chlorpyrifos, which is still widely used on agricultural produce in the U.S. and abroad.

"High-dose, short-term experimental exposures do not reflect the real-life situation, but they give us a starting point to identify genetic variants that might make individuals more susceptible to toxicants," says Smirnova. "Now we can explore how other genes and potentially toxic substances interact."

The researchers found that the brain organoids with just one copy of the CHD8 gene had only two-thirds the normal level of CHD8 protein in their cells, but that chlorpyrifos exposure drove CHD8 levels much lower, turning a moderate scarcity into a severe one. The exposure demonstrated clearly how an environmental factor can worsen the effect of a genetic one, likely worsening disease progression and symptoms.

As part of their study, the researchers compiled a list of molecules in blood, urine, and brain tissue that prior studies have shown to be different in autism spectrum patients. They found that levels of several of these apparent autism biomarkers were also significantly altered in the organoids by CHD8 deficiency or chlorpyrifos exposure, and moreso by both.

"In this sense, we showed that changes in these organoids reflect changes seen in autism patients," Smirnova says.

The findings, according to the researchers, pave the way for further studies of gene-environment interactions in disease using human-derived organoids.

"The use of three-dimensional, human-derived, brain-like models like the one in this study is a good way forward for studying the interplay of genetic and environmental factors in autism and other neurodevelopmental disorders," Hartung says.

Researchers examined the role of primary care physicians and other clinicians in delivering vaccinations in the United States. They used two main datasets to create an in-depth analysis of services delivered to Medicare patients, followed by analysis of the Agency for Healthcare Research and Quality's 2017 Medical Expenditure Panel Survey (MEPS) to determine where patients are getting vaccinated and by whom. In the 2017 Medicare Part B Fee-For-Service, primary care physicians provided the largest share of services for vaccinations (46%), followed by mass immunizers (45%), then nurse practitioners/physician assistants (5%). The MEPS showed that primary care physicians provided a majority of clinical visits for vaccination (54%). Primary care physicians have played a crucial role in vaccination delivery to the U.S. population, including the elderly. They are well positioned to help with administering COVID-19 vaccinations. They are also equipped to provide clinical guidance to help patients interpret results from COVID-19 testing and immunity determinations and can answer vaccine questions.

Primary Care Poised to Provide Clinical Guidance, Answers About COVID-19 Testing, Vaccine Administration

Researchers examined the role of primary care physicians and other clinicians in delivering vaccinations in the United States. They used two main datasets to create an in-depth analysis of services delivered to Medicare patients, followed by analysis of the Agency for Healthcare Research and Quality's 2017 Medical Expenditure Panel Survey (MEPS) to determine where patients are getting vaccinated and by whom. In the 2017 Medicare Part B Fee-For-Service, primary care physicians provided the largest share of services for vaccinations (46%), followed by mass immunizers (45%), then nurse practitioners/physician assistants (5%). The MEPS showed that primary care physicians provided a majority of clinical visits for vaccination (54%). Primary care physicians have played a crucial role in vaccination delivery to the U.S. population, including the elderly. They are well positioned to help with administering COVID-19 vaccinations. They are also equipped to provide clinical guidance to help patients interpret results from COVID-19 testing and immunity determinations and can answer vaccine questions.

Primary Care's Historic Role in Vaccination and Potential Role in COVID-19 Immunization Programs

Elizabeth Wilkinson, BA, et al

The Robert Graham Center for Policy Studies in Family Medicine and Primary Care, Washington, D.C.

https://www.annfammed.org/content/19/4/351

Medication or Exercise? What's Most Effective for Older Adults With Mild to Moderate Depression?

Depression is the most frequently diagnosed psychiatric disorder among older adults, with 8% to 16% of older patients presenting with clinically significant depressive symptoms. Researchers in Spain conducted a randomized clinical trial of 347 older adults with mild to moderate depression, comparing the effectiveness of physical exercise and antidepressants as treatment methods. Study participants were assigned to either a group engaged in supervised physical exercise or a group that received antidepressant treatment by their general practitioners. Depressive symptoms were not significantly different after one month between the two groups. However, after three and six months, the number of people who showed improvement was significantly higher in the antidepressant group. The authors note that the number of participants who withdrew from the study was higher in the physical activity group, while more adverse side-effects were reported in the group treated with antidepressants. Authors felt the advanced age of participants and the health problems and/or functional limitations common to older adults may have negatively influenced adherence to a six-month physical activity program.

Effectiveness of Physical Exercise in Older Adults With Mild to Moderate Depression

Jesús López-Torres Hidalgo, MD, et al

University of Castile-La Mancha and Albecete Zone VIII Health Center, Albacete, Spain

https://www.annfammed.org/content/19/4/302

Community Health Workers Can Play a Role in Identifying Health-Related Social Needs in Patients

Addressing patients' health-related social needs, like housing and food security, is integral to patient care. Federally Qualified Health Centers are leaders in screening for and addressing patients' health-related social needs. However, screening practices vary. This variation is relatively unexplored, particularly with regards to organizational and state policy influences. Study authors conducted in-person, qualitative interviews at Michigan FQHCs to examine how screening approaches vary in the context of statewide social needs screening initiatives and structural factors. They identified four themes: 1) Statewide initiatives and local leadership drove variation in screening practices. 2) Community health workers played an integral role in identifying patients' needs and their roles often shifted from "screener" to "implementer." 3) Social needs screening data was variably integrated into electronic health records and infrequently used for population health management and 4) Sites experienced barriers to social needs screening that limited their perceived impact and sustainability. FQHCs placed value on the role of community health workers, on sustainable initiatives and on funding to support continued social needs screening in primary care settings, according to the study. Determining the optimal approaches to screening is important to advancing community health.

Implementation of Health-Related Social Needs Screening at Michigan Health Centers: A Qualitative Study

Margaret Greenwood-Ericksen, MD, MSc, et al

Department of Emergency Medicine, University of New Mexico, Albuquerque, New Mexico

https://www.annfammed.org/content/19/4/310

Lessons from Primary Care and Behavioral Health Integration Should Inform Health Care Practices to Identify and Address Patients' Social, Economic Needs

Although interest is accelerating around addressing patients' social and economic needs, effective and sustainable strategies for integrating social care practices into health care delivery have not yet been identified. This paper synthesizes learnings from primary care and behavioral health care integration and translates them into organizing principles with the goal of advancing social care integration practices to improve the health of patients and communities.

Applying Lessons From Behavioral Health Integration to Social Care Integration in Primary Care

Theresa J. Hoeft, PhD, et al

Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle

https://www.annfammed.org/content/19/4/356

Researchers, Policy Makers, Health Care Systems and Payers All Play a Part in Meeting Patient Social Care Needs

Drs. Alicia Cohen and Emilia De Marchis provide commentary on three articles in this issue of Annals of Family Medicine, specifically Greenwood-Ericksen et al's research on Michigan's Federally Qualified Health Centers; Hoeft et al's special report about translating lessons learned from behavioral health integration into the social care realm; and Fessler et al's narrative about how they as medical students stepped away from their medical clerkships to act as community volunteers for people experiencing homelessness during the COVID-19 pandemic. All three articles serve as a timely call to action, reminding those in health care that work remains to meet the needs of patients, particularly in screening for and intervening on identified social risks. The urgency of this work has only been heightened by the pandemic as patients face new or intensified socio-economic hardships. Cohen and De Marchis write that collaboration is needed among researchers, policy makers, payers and health care systems to assist in identifying evidence-based practices for social needs integration. This includes improved training and education for all clinical care team members about social risk and social care activities, best practice guidelines, evidence-based interventions, and sustainable funding streams. Social risk data can also more broadly aid advocacy and policy efforts to expand community-based resources, efforts to address health inequities, and population health-level interventions. Cohen and De Marchis note that greater flexibility in using Center for Medicare & Medicaid dollars and the new 2021 Evaluation and Management coding guidelines for social determinants may help with more consistent funding for social care activities. "The path ahead requires working together and sharing learnings to advance our common goal of achieving health equity and wellness--for patients and the health care workforce alike," they write.

Building an Evidence Base for Integration of Social Care Into Health Care: Our Collective Path Ahead

Alicia J. Cohen, MD, MSc, FAAFP, Center of Innovation in Long Term Services and Supports, VA Providence Healthcare System; Departments of Family Medicine and Health Services, Policy, and Practice, Brown University, Providence, Rhode

Island. Department of Family Medicine, University of Michigan, Ann Arbor, Michigan.

Emilia H. De Marchis, MD, MAS, Department of Family & Community Medicine, University of California, San Francisco

https://www.annfammed.org/content/19/4/290

Medical Students Hang Up White Coats, Stethoscopes to Serve Unhoused Communities During COVID-19 Pandemic

Four University of Michigan Medical School students write about being removed from their clinical clerkships and returning to the community to support their neighbors experiencing homelessness during the COVID-19 pandemic. The students made brown bag lunches for people experiencing homelesness and also worked as community volunteers for temporary shelters. "Though formal education was stalled, we reconnected with the initial desire that led us to pursue medical education in the first place and developed key skills in communication, relating to others, and compassion that we believe will enable us to become better physicians in the future," they write.

Sandwiches, 6 Feet Apart: Reflections on Community (and Medical School) During COVID-19

M. Margaret Fessler, BA, et al

University of Michigan Medical School, Ann Arbor, Michigan

https://www.annfammed.org/content/19/4/368

Today's Health Care Requires Understanding of Social Determinants to Address Increasingly Complex Patient Needs

The authors use a patient story to illustrate their experiences as family physicians who care for patients with complex health care needs that go beyond just physical symptoms or a single morbidity. Justesen et al write that they care for patients with increased medical complexity, which may include both medical and mental health diagnoses and are often combined with substance abuse disorders and low socioeconomic status. Their experiences highlight the importance of addressing social determinants of health, which permeate the context of health and health care. Factors such as financial challenges, limited transportation, food insecurity and low health literacy have a profound influence on health. Family physicians are in a unique position to treat patients appropriately and efficiently by embracing the complexities of the patients they encounter. By doing so, family physicians can help improve health outcomes and manage health care costs in patient populations that increasingly present with complex health needs.

Michelle's Story: The Complexity of Patient Care in a Family Medicine Residency Clinic

Kathryn Justesen, MD, et al

Department of Family Medicine and Community Health, University of Minnesota Medical School, Minneapolis, Minnesota

https://www.annfammed.org/content/19/4/362

Minority Physicians Experience More Diversity, Less Burnout in Family Medicine Practice

More than 40% of physicians in the United States reported at least one symptom of burnout, which is particularly high among family physicians. This study examined a nationally-representative sample of family physicians to determine whether physician race-ethnicity was associated with burnout among a nationally-representative sample of family physicians. Of the 3,0916 physicians studied, 450 (15%) were from racial-ethnic groups underrepresented in medicine (UIM), which include Blacks/African Americans, Hispanics/Latinos, American Indians and Pacific Islanders who together comprise 30-35% of the general population yet account for only 12.4% of family physicians. The study findings support the researchers' hypothesis that UIMs were significantly less likely than their non-UIM counterparts to report emotional exhaustion and depersonalization. This may be attributed to practicing in more racially-diverse counties and being less likely to practice obstetrics, both of which partially mediated the protective effect of UIM status on depersonalization. The mediating effect of working in more racially and ethnically diverse counties is consistent with evidence of the beneficial effect of cultural diversity on health outcomes for minorities and better overall self-rated health among adults. Understanding the attributes of UIMs that may prevent burnout may also provide insights for developing a more resilient physician workforce.

Lower Likelihood of Burnout Among Family Physicians From Underrepresented Racial-Ethnic Groups

Montgomery Douglas, MD, et al

Department of Family Medicine, University of Connecticut School of Medicine, Farmington, Connecticut

https://www.annfammed.org/content/19/4/342

Primary Health Care Practice Characteristics Make Little Impact on Unplanned Hospital Admissions

Given the aging world population, there is international interest in helping older people live longer and healthier lives. Avoiding unplanned hospital admissions is an important aspect of care for older people. Palapar et al focused on the way primary care practice characteristics influence outcomes such as unplanned hospitalizations, function and well-being. They investigated the variability in older people's outcomes by primary care physician and practice characteristics in New Zealand and the Netherlands. Findings revealed that none of the physician or practice characteristics were significantly associated with rates of unplanned admissions in the New Zealand sample. In contrast, in the Netherlands sample, researchers found higher rates of admissions in large practices and practices staffed with a practice nurse who typically works in the primary care setting with general practitioners. Practice nurses are common in primary care practices in New Zealand but are relatively new and only in a portion of practices in the Netherlands, the authors note. It is unclear if these associations are causal or if the increase in hospitalizations represent higher or lower quality care. Considering these findings, the authors conclude that the central focus of international health policies on reducing hospital overuse should approach primary health care structural reform carefully.

Primary Care Variation in Rates of Unplanned Hospitalizations, Functional Ability, and Quality of Life of Older People

Leah Palapar, MD, PhD, et al

Department of General Practice and Primary Health Care, School of Population Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

https://www.annfammed.org/content/19/4/318

Chinese Medical Insurance Achieves "Remarkable" Success in Decreasing Diabetes Medication Usage, Costs

Approximately 642 million people are expected to be diagnosed with diabetes by 2040, with Asians representing more than 55% of cases. Researchers conducted the first large-scale study since the implementation of medical insurance in China to evaluate the complexity and cost of drug therapy for Asian people with diabetes. They used available treatment records from Beijing's medical insurance bureau from 2016 to 2018 and looked at five outcomes, including: 1) quantity of outpatient medications, 2) number of co-morbidities diagnosed, 3) estimated annual cost of the outpatient drug regimen, 4) drug therapy strategies for diabetic patients and 5) the most commonly prescribed drug class in the patient cohort. They found that over three years, there was a gradual decrease of almost 9% decrease in the average quantity of diabetes medications. The mean usage of both anti-glycemic and non-antiglycemic drugs decreased by 3.6% and 12.8%, respectively. Researchers found an 18.39% decrease in estimated annual medication costs. The decrease in medical costs could be due to rational use of medications, leading to a decrease in the usage of medications over the three years. This is especially true for what the authors call the needless use of most types of insulin. This could have indirectly led to decreased costs. China's health insurance appears to have achieved "remarkable" success. The study authors advise that therapeutic drugs should be selected with caution according to the diet and lifestyle of each individual.

Changes in Direct Medical Cost and Medications for Managing Diabetes in Beijing, China, from 2016 to 2018: Electronic Insurance Data Analysis

Lixin Guo, MD, et al

Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China

https://www.annfammed.org/content/19/4/332

Early Perceptions of COVID-19 in Pennsylvania

A survey conducted in March 2020 reports that early concern for COVID-19 outmatched concern for influenza, but respondents may have been less focused on their perceived likelihood of contracting COVID-19 and more concerned with its severe impact on their health. Additionally, when the Centers for Disease Control and Prevention began advising social distancing recommendations in the early months of the pandemic, a majority of adults surveyed believed in the effectiveness of social distancing and intended to follow CDC guidelines. Health agency websites like the CDC were the most frequently identified as "trusted sources" for COVID-19 information, as opposed to substantial distrust in COVID-19 information from mass media and politicians. The study, conducted by researchers at Penn State University, was completed by almost 6,000 adults enrolled in a central Pennsylvania health care system in late March 2020. It suggests that knowledge about COVID-19 and adherence to behavioral recommendations was generally high.

Knowledge, Perceptions, and Preferred Information Sources Related to COVID-19 Among Central Pennsylvania Adults Early in the Pandemic: A Mixed Methods Cross-Sectional Survey

Lauren Jodi Van Scoy, MD, Department of Medicine, Pennsylvania State University.

Robert P. Lennon, MD, JD, et al

Departments of Medicine, Humanities, Public Health Sciences and Qualitative and Mixed Methods Core, Pennsylvania State University, State College, Pennsylvania

https://www.annfammed.org/content/19/4/293

Choosing the Right Communication Tool at the Right Time Ensures Patients Have Full Access to Health Care

Kumara Raja Sundar, MD, a family physician at Kaiser Permanente of Washington, uses two media synchronicity theory principles - conveyance and convergence - as a framework for choosing the right medium of care for his patients. In this essay, Sundar discusses how operating within this framework changed his own practice and decision making during the COVID-19 pandemic, particularly with the use of telemedicine versus in-person clinic visits. The theory of conveyance focuses on transmitting and processing diverse information to understand a situation. It requires time to analyze data, create patterns and make conclusions. Convergence focuses on discussing pre-processed information to achieve a mutual understanding of it. It often requires a rapid exchange of information to allow immediate feedback to test and verify each person's knowledge. Sundar writes that patients benefit from telehealth's convenience when they have access to the right technology but that they must have access to all care options. "We must guide patients towards the right care medium for them and in the correct order and use all of our tools efficiently and effectively," he adds. "It is the only way we will be able to achieve our mission of healing."

Virtual Care: Choosing the Right Tool, At the Right Time

Kumara Raja Sundar, MD

Kaiser Permanente of Washington, Burien, Washington

https://www.annfammed.org/content/19/4/365

Innovations in Primary Care

Innovations in Primary Care are brief one-page articles that describe novel innovations from health care's front lines. In this issue:

A Novel Adaptation to the Extension for Community Healthcare Outcomes (ECHO) Model--To better meet the need for up-to-date information about COVID-19, ECHO Colorado connects experts in academic medicine with community primary care counterparts. The addition of a research team primarily composed of medical students and family medicine residents allowed for a dynamic, experiential learning opportunity.

Allison Costello, MD, MBA, et al

University of Colorado Family Medicine Residency, Denver, Colorado

https://www.annfammed.org/content/19/4/371

Annals of Family Medicine is a peer-reviewed, indexed research journal that provides a cross-disciplinary forum for new, evidence-based information affecting the primary care disciplines. Launched in May 2003, Annals is sponsored by seven family medical organizations, including the American Academy of Family Physicians, the American Board of Family Medicine, the Society of Teachers of Family Medicine, the Association of Departments of Family Medicine, the Association of Family Medicine Residency Directors, the North American Primary Care Research Group, and The College of Family Physicians of Canada. Annals is published six times each year and contains original research from the clinical, biomedical, social and health services areas, as well as contributions on methodology and theory, selected reviews, essays and editorials. Complete editorial content and interactive discussion groups for each published article can be accessed free of charge on the journal's website, http://www.AnnFamMed.org.

A survey conducted in March 2020 reports that early concern for COVID-19 outmatched concern for influenza, but respondents may have been less focused on their perceived likelihood of contracting COVID-19 and more concerned with its severe impact on their health. Additionally, when the Centers for Disease Control and Prevention began advising social distancing recommendations in the early months of the pandemic, a majority of adults surveyed believed in the effectiveness of social distancing and intended to follow CDC guidelines. Health agency websites like the CDC were the most frequently identified as "trusted sources" for COVID-19 information, as opposed to substantial distrust in COVID-19 information from mass media and politicians. The study, conducted by researchers at Penn State University, was completed by almost 6,000 adults enrolled in a central Pennsylvania health care system in late March 2020. It suggests that knowledge about COVID-19 and adherence to behavioral recommendations was generally high.

Knowledge, Perceptions, and Preferred Information Sources Related to COVID-19 Among Central Pennsylvania Adults Early in the Pandemic: A Mixed Methods Cross-Sectional Survey

Lauren Jodi Van Scoy, MD, Department of Medicine, Pennsylvania State University.

Robert P. Lennon, MD, JD, et al

Departments of Medicine, Humanities, Public Health Sciences and Qualitative and Mixed Methods Core, Pennsylvania State University, State College, Pennsylvania

https://www.annfammed.org/content/19/4/293

HOUSTON - The University of Texas MD Anderson Cancer Center's Research Highlights provides a glimpse into recently published studies in basic, translational and clinical cancer research from MD Anderson experts. Current advances include a promising combination therapy for acute myeloid leukemia, understanding mechanisms driving resistance to PARP inhibitors, a therapeutic neoantigen vaccine to treat lung cancer, a novel treatment for triple-negative breast cancer and a new understanding of how telomeres may drive inflammatory bowel disease.

Combination therapy shows promise in mouse models of acute myeloid leukemia

Acute myeloid leukemia (AML) is a cancer that develops in the bone marrow. It is frequently treated with venetoclax, a drug that targets the protein Bcl-2 in combination with a hypomethylating agent, but often, patients develop resistance to venetoclax and then relapse. A research team led by Bing Carter, Ph.D. and Michael Andreeff, M.D, Ph.D., examined the effectiveness of combination therapy with venetoclax and SNDX-50469, a drug that inhibits another protein, menin, which is critical for a certain subset of AML cases. In their mouse model leukemia study, venetoclax alone showed no activity against the disease, but the combination showed strong anti-leukemia activity and prolonged mouse survival. Further investigation is needed to understand the combination's mechanism of action, its appropriate dosage and its clinical effectiveness for patients. Learn more in Blood.

Identifying mechanism of resistance to PARP inhibitors

Cancer cells with mutations in certain pathways may be hypersensitive to targeted therapies against related pathways - a concept known as synthetic lethality. An example is poly ADP-ribose polymerase (PARP) inhibitors, which target DNA repair and are effective in cancers with mutations in other DNA repair genes, such as BRCA1/2. Unfortunately, cancers often develop resistance to PARP inhibitors. To identify these mechanisms of resistance, Mengfan Tang, Ph.D., and Junjie Chen, Ph.D., systematically knocked out more than 18,000 genes using CRISPR/Cas9 gene editing in cells with BRCA2 loss. They identified several genes that, when lost, led to improved survival of BRCA2-deficient cells, even when treated with PARP inhibitors. In particular, they identified loss of cyclin C (CCNC) as critical to survival of the cells, suggesting a novel therapeutic target to overcome PARP inhibitor resistance. Learn more in Nucleic Acids Research.

Therapeutic vaccine targets mutant proteins in lung cancer

Neoantigens are mutant proteins, resulting from genetic alterations in cancer cells, that can be recognized by the immune system as abnormal. MD Anderson researchers have developed therapeutic vaccines containing small neoantigen fragments, or peptides, found in a given patient's tumor. The personalized vaccine is designed to prime the immune system to recognize and attack the tumor. A Phase I clinical trial, led by Fenge Li, M.D., Ph.D., and Gregory Lizée, Ph.D., evaluated these vaccines in patients with non-small cell lung cancer that had progressed with conventional therapies. There were minimal side effects and seven of 24 patients on the study had clinical responses - including one complete response. All responding patients had EGFR mutations, and immune monitoring suggested responses were made against several shared EGFR neoantigens. The results suggest that personalized neoantigen vaccines are safe, feasible and potentially beneficial for patients with advanced lung cancer. Learn more in the Journal for ImmunoTherapy of Cancer.

JNK signaling axis drives triple-negative breast cancer aggressiveness

Triple-negative breast cancer (TNBC) is an aggressive disease that makes up roughly 10% to 15% of breast cancer diagnoses. Because TNBCs have a poor prognosis, understanding the mechanisms that drive tumor growth and progression and finding new treatment targets are major areas of focus in breast cancer research. A team led by Naoto Ueno, M.D., Ph.D., and Takashi Semba, M.D., Ph.D., showed that the JNK/C-JUN/CCL2 signaling axis in TNBC contributes to the formation of an immunosuppressive tumor microenvironment (TME), which plays a critical role in tumor progression. The team confirmed that JNK-regulated CCL2, secreted by tumor-associated macrophages, recruits tumor-infiltrating regulatory T cells to form an immunosuppressive TME that promotes TNBC aggressiveness. The trial's findings offer novel therapeutic strategies for TNBC by demonstrating that the immunosuppressive TME can be reversed using JNK inhibitors. A combination therapy of JNK inhibitors and immune checkpoint blockade may be effective in overcoming TNBC tumor progression. Learn more in Journal of the National Cancer Institute.

Advancing treatment options for inflammatory bowel disease

The ends of chromosomes contain long sequences of repetitive DNA, called telomeres, designed to protect the integrity of genetic information and prevent aging. Research led by Deepavali Chakravarti, Ph.D., and Ronald DePinho, M.D., previously found that telomere disruption can cause increased inflammation by activating a cellular cascade, leading to increased production of the pro-inflammatory factor IL-18. In a new study, the researchers demonstrated for the first time that this telomere-IL-18 circuit also is relevant to the development of inflammatory bowel disease (IBD). In the study, therapeutically restoring telomeres or blocking the pathways downstream of disrupted telomeres was able to reduce IL-18 production. This points to possible therapeutic strategies for treating patients with IBD who currently have limited effective therapeutic options. Learn more in Proceedings of the National Academy of Sciences.

Drs. Alicia Cohen and Emilia De Marchis provide commentary on three articles in this issue of Annals of Family Medicine, specifically Greenwood-Ericksen et al's research on Michigan's Federally Qualified Health Centers; Hoeft et al's special report about translating lessons learned from behavioral health integration into the social care realm; and Fessler et al's narrative about how they as medical students stepped away from their medical clerkships to act as community volunteers for people experiencing homelessness during the COVID-19 pandemic. All three articles serve as a timely call to action, reminding those in health care that work remains to meet the needs of patients, particularly in screening for and intervening on identified social risks. The urgency of this work has only been heightened by the pandemic as patients face new or intensified socio-economic hardships. Cohen and De Marchis write that collaboration is needed among researchers, policy makers, payers and health care systems to assist in identifying evidence-based practices for social needs integration. This includes improved training and education for all clinical care team members about social risk and social care activities, best practice guidelines, evidence-based interventions, and sustainable funding streams. Social risk data can also more broadly aid advocacy and policy efforts to expand community-based resources, efforts to address health inequities, and population health-level interventions. Cohen and De Marchis note that greater flexibility in using Center for Medicare & Medicaid dollars and the new 2021 Evaluation and Management coding guidelines for social determinants may help with more consistent funding for social care activities. "The path ahead requires working together and sharing learnings to advance our common goal of achieving health equity and wellness--for patients and the health care workforce alike," they write.

A new paper in the Journal of the National Cancer Institute, published by Oxford University Press, indicates that disruptions in health care due to the COVID 19 pandemic may increase breast cancer deaths.

In March 2020 public health measures prohibited most elective procedures, including mammography, due to hospital capacity and limited personal protective equipment. This reduced mammograms up to 80%. Breast cancer patients also experienced treatment delays and reductions in planned or expected chemotherapy treatments.

Researchers here used three independently-developed breast cancer simulation models from the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network to predict the effect of COVID-19-related interruptions on breast cancer mortality due to health care delivery disruptions in the first 6 months of the pandemic.

The models predicted that the cumulative number of excess breast cancer deaths due to the COVID-19 pandemic's impact on screening, diagnosis, and chemotherapy treatment could reach 2,487 by 2030.

By 2030, the models project 950 additional breast cancer deaths related to reduced screening; 1,314 associated with delayed diagnosis of symptomatic cases, and 151 due to reduced chemotherapy use in women with early stage breast cancer. This corresponds to a 0.52% increase in breast cancer deaths between 2020 and 2030.

"There were many reports on the short-term impact of COVID-19 on breast cancer control activities," said Oguzhan Alagoz, the lead author of the study. "We found that the rapid adaptations of healthcare facilities to devise strategies to resume breast cancer screening, diagnosis, and treatment services within a six-month period greatly mitigated the potential impact on breast cancer mortality. Facilities should prioritize screening women who missed their routine mammography exam during the pandemic to reduce the impact of pandemic on mortality."

DALLAS, July 14, 2021 -- Heart failure hospitalizations and costs related to methamphetamine use jumped sharply over a decade in California, according to new research published today in Circulation: Cardiovascular Quality and Outcomes, an American Heart Association journal.

"Our study results should bring urgent attention to this insidious yet rapidly growing form of severe heart failure - methamphetamine-related heart failure, which is taking the lives of young people, straining health care resources and threatening to spread like wildfire in California, the West and to the rest of the nation," said lead author Susan X. Zhao, M.D., a cardiologist at Santa Clara Valley Medical Center in San Jose, California. "California is seeing a resurgence of methamphetamine use, and the problem has been made drastically worse in recent years by the increase in purer, more potent methamphetamine throughout our communities."

Heart failure is a chronic condition in which the heart becomes too weak to properly pump blood. Signs of heart failure include fatigue, shortness of breath and heart palpitations. According to the American Heart Association's Heart Disease and Stroke Statistics--2021 Update, an estimated 6 million American adults ages 20 and older have heart failure based on 2015-2018 data. The condition is most prevalent among people ages 60 and older.

Methamphetamine, also known as meth, is an addictive stimulant that can affect the cardiovascular system by triggering blood vessel spasms and life-threatening spikes in blood pressure. It can also increase plaque in the arteries and rewire the heart's electrical system. Prolonged methamphetamine use has been associated with a severe form of dilated cardiomyopathy, a condition in which the weakened heart muscle becomes enlarged and cannot pump adequate blood. According to the 2017 U.S. National Survey on Drug Use and Health, 1.6 million people reported using methamphetamines, and the average age of new methamphetamines users was 23.

This study is a retrospective review of California hospital data including more than one million patients discharged between 2008 and 2018 with a diagnosis of heart failure. During that 11-year period, researchers noted:

42,565 (4%) of the patients had been diagnosed with methamphetamine-related heart failure - also known as MethHF - compared with 990,511 (96%) diagnosed with heart failure unrelated to methamphetamine use.

Hospitalizations for methamphetamine-related heart failure rose 585%, while heart failure hospitalizations unrelated to methamphetamine use declined 6%.

94% of methamphetamine-related heart failure patients were under age 65, with more than half being between ages 35 and 54.

79% of methamphetamine-related heart failure patients were men, and nearly half of methamphetamine-related heart failure patients were white adults.

Methamphetamine-related heart failure patients were also more likely to consume alcohol and use tobacco and other illicit drugs. They were more likely to be homeless compared with other heart failure patients, as well.

People with methamphetamine-related heart failure had fewer pre-existing cardiovascular conditions such as atrial fibrillation or Type 2 diabetes, though, more had high blood pressure (33%) compared to heart failure patients who did not use methamphetamines (30%).

Researchers found that the financial toll of methamphetamine-related heart failure is also significant: hospital stays were several days longer than those of other heart failure patients, and they had more procedures performed, leading to significantly higher health care costs. Hospitalization costs for methamphetamine-related heart failure in California rose 840%, from $41.5 million in 2008 to $390.2 million in 2018, compared with an 82% increase in costs for all heart failure-related hospitalizations, which rose from $3.5 billion to $6.3 billion.

"Treating patients with methamphetamine-related heart failure is consuming resources and burdening the health care system," Zhao said. "Many patients present late in the course of illness with limited options available to them. Proactive, preventative public health outreach and education are needed to stem the influx of methamphetamine-related heart failure at its source."

Zhao said while methamphetamine-related heart failure may be seen as a "working class white men's disease", the demographics are shifting and diversifying, among people from different racial and ethnic groups and women, too. Methamphetamine-related heart failure is also spreading from urban areas to rural communities.

"The methamphetamine epidemic is often overshadowed by the surge in opioid-related death and illnesses," she said. "The long-term health consequences associated with methamphetamine use require recognition from the public as well as the clinical communities. This study was intended more as a public health alarm: the urgency of methamphetamine use disorder cannot be overstated."

An accompanying editorial by Uri Elkayam, M.D., and Pavan Reddy, M.D., commented that the inattention to methamphetamine-related heart failure may be due in part to a lower risk of immediate death caused by methamphetamine overdose as compared to opioids. However, they note methamphetamines are "equally dangerous and costly to society but more insidious in nature, its effects potentially causing decades of mental and physical debilitation before ending in premature death."

According to the editorial, "The rising prevalence of MethHF should ring alarm bells but also signals an opportunity. "Until recently, MethHF was highlighted only in the form of isolated case reports but is now seen regularly in high usage areas. Though this study makes strides in underscoring the potential societal impact of this protracted illness, prospective data from larger cohorts may help clarify questions left unanswered by the current study. Importantly, we do not know which risk factors predispose to the development of MethHF, which prognostic factors may predict cardiac recovery or which medical therapies may benefit patients. Additional understanding may simultaneously benefit the patient and alleviate spiraling healthcare costs."

Zhao and colleagues plan to work with public health agencies to develop a statewide awareness campaign in California and to examine national data to determine if it reflects what's happening at the state level, she added.

This study is limited in that it is a retrospective review of hospital discharge data based on a standardized coding system that may be susceptible to biases and confounding factors, including that certain groups of patients may be asked about drug habits more than other groups.

HOUSTON - A phase II study led by researchers from The University of Texas MD Anderson Cancer Center found that treatment with atezolizumab and bevacizumab was well-tolerated and resulted in a 40% objective response rate in patients with advanced malignant peritoneal mesothelioma, a rare cancer in the lining of the abdomen. Responses occurred in patients regardless of PD-L1 expression status and tumor mutation burden.

Trial results indicated that the combination was safe and effective in patients with disease progression or intolerance to previous chemotherapy treatment. The study, led by Kanwal Raghav, M.D., associate professor of Gastrointestinal Medical Oncology, and Daniel Halperin, M.D., assistant professor of Gastrointestinal Medical Oncology, was published today in Cancer Discovery.

Malignant peritoneal mesothelioma (MPeM) is known as a rare but aggressive disease with historically poor survival and limited treatment options. Because symptoms most often go unnoticed, peritoneal cancer is usually diagnosed at a late stage. If left untreated, life expectancy is often less than a year.

"There is a grave unmet need for patients with peritoneal mesothelioma," Raghav said. "This study establishes a much-needed treatment option and represents an effort to encourage research for this rare disease."

One of the first trials for MPeM patients

Researchers estimate that 300-500 Americans are diagnosed with MPeM each year. MPeM usually follows the same treatment as pleural mesothelioma, a cancer of the lung lining, although there are significant differences between the diseases. MPeM is far rarer, understudied, has a weaker association with asbestos exposure, affects women more frequently, occurs at a younger age and is diagnosed more often at an advanced stage.

Treatment strategies are varied, but usually include optimal cytoreductive surgery, hypothermic intraoperative peritoneal perfusion with chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC). Patients with MPeM usually are treated following the recommendations for malignant pleural mesothelioma and most studies on chemotherapy drugs have been done for pleural mesothelioma, often excluding MPeM patients.

The National Comprehensive Cancer Network (NCCN) recommends first-line platinum chemotherapy for both mesotheliomas, but after disease progression there is no established treatment strategy or any Food and Drug Administration-approved treatments for advanced MPeM.

This single-center study is a multicohort basket trial for evaluation of atezolizumab and bevacizumab in a variety of advanced cancers. Atezolizumab is a type of immunotherapy drug called an immune checkpoint inhibitor that targets PD-L1, while bevacizumab is a targeted therapy that slows the growth of new blood vessels by inhibiting vascular endothelial growth factor (VEGF). This publication reports data for the 20 patients in the MPeM cohort. The median age was 63 years, 60% of participants were women and 75% self-reported that they had not been exposed to asbestos. Trial participants were 80% white, 10% Hispanic, 5% Black and 5% other.

Prior to enrolling in this clinical trial, patients who received standard of care chemotherapy progressed to next treatment at 8.3 months compared to 17.6 months with atezolizumab and bevacizumab on the study. The median response duration was 12.8 months.

Progression-free and overall survival at one year were 61% and 85%, respectively. The treatment was well-tolerated, with the most common events being hypertension and anemia.

"Patients treated on this regimen surpassed outcomes expected with conventional therapies," Raghav said. "This data shows that this is a reasonable treatment option and reiterates the importance of clinical trials for rare cancers to extend patient survival."

Biomarker analysis

Integration of biopsies before and during treatment established the practicability and the value of a translationally motivated approach in rare cancers. Using the biopsies, the researchers demonstrated that the clinical activity seen with this treatment combination did not correlate with clinically established biomarkers of response to immune checkpoint inhibition in other tumors.

The biomarker analysis determined that epithelial-mesenchymal transition (EMT) gene expression, which is a cancer state associated with a more aggressive biology, correlated with aggressive disease, treatment resistance and poorer response rates.

To define a tumor environment predictive of response to this drug treatment, researchers examined pre-treatment immune cell subsets using 15 available patient samples. They found that VEGF inhibition improves the effectiveness of immune checkpoint inhibitors by adapting the immunosuppressive tumor environment.

"I am very encouraged by the responses to this treatment, and I am hopeful that with additional research this will provide a better treatment option for these patients," Raghav said. "I am thankful for the patients who are willing to participate in clinical trials and help further our knowledge of rare cancers."

Additional trials with larger numbers of patients are needed to validate these study results, determine if this drug combination could be given as frontline treatment or improve surgical outcomes for these patients.

Vaccine skepticism among young adults may stall efforts to achieve herd immunity - a threshold in which approximately 80 percent of a population is vaccinated against the coronavirus.

A study by UC San Francisco researchers found that about one in four unvaccinated people aged 18 to 25 said that they "probably will not" or "definitely will not" get the COVID-19 vaccination, despite the fact that this demographic has been found to be more likely than other age-groups to transmit coronavirus, jeopardizing the health of older unvaccinated adults and facilitating the rise of virulent vaccine variants.

The researchers analyzed March 2021 data from the Household Pulse Survey, an online nationally representative sample of the population conducted by the U.S. Census Bureau in collaboration with the National Center for Health Statistics and other agencies.

Among the 5,082 respondents, 83 percent reported that they had not been vaccinated, 10 percent said they definitely will not get the vaccine, and 14 percent said they probably will not. The study appears July 14, 2021, in the Journal of Adolescent Health.

While data from the Centers for Disease Control and Prevention (CDC) show that very few 18 to 29-year-olds die of COVID relative to older adults, this age group accounts for more than 20 percent of all COVID cases to date. Furthermore, previous research by lead author Sally Adams, PhD, RN, of the UCSF National Adolescent and Young Adult Health Information Center, found that as many as one in three young adults is at risk of severe COVID.

'Long COVID' May Impact Young Adults even with Mild Symptoms

"Young adults who have had COVID, regardless of symptoms, may be vulnerable to long-term complications and debilitating symptoms that may include respiratory difficulties, loss of smell and brain fog, often referred to as 'long COVID.' Estimates range from 10 to 50 percent for long COVID symptoms, which is a serious concern for young adults given their high infection rates and low vaccination rates," Adams said.

"Prompt vaccinations could help limit the further development of virulent variants and infection rates among the vulnerable and unvaccinated," she added.

Among the unvaccinated respondents who said they would definitely not or probably not get the vaccine, more than half said they were concerned about possible side effects. Half said they planned to wait and see if the vaccine was safe and may get it later. Also, within this group, a third said that they do not trust the vaccine, compared to fewer than one in 10 of those who said that they probably would get vaccinated.

The recent spate of heart inflammation cases in teens and young adults following the Pfizer and Moderna vaccines may have amplified many people's fears, said senior author Charles Irwin Jr., MD, director of the Division of Adolescent and Young Adult Medicine at UCSF Benioff Children's Hospitals.

"It's important to note that the rate of heart inflammation in young people who have been vaccinated is only slightly higher than in young people who have not been vaccinated. In most cases, symptoms are mild and resolve with minimal treatment," said Irwin. "As a result, the majority of providers support the CDC and other advisory bodies that continue to recommend the vaccine for everyone age 12 or older."

The researchers recommend that young adults' concerns about vaccine safety and side effects are addressed via public education campaigns. "Education and public health messaging encouraging young adult vaccination is needed, ideally harnessing social media and key influencers," Irwin said, "including clinicians who have a key role in reducing vaccine hesitancy in youth and adult patients."

Unlike other population-level stressful events such as natural disasters, COVID-19 has not resulted in a net increase in smoking, according to a new study from the International Tobacco Control (ITC) Project, at the University of Waterloo.

The researchers also found that although nearly half of smokers reported that COVID-19 made them think about quitting, the vast majority of smokers did not change their smoking habits during the early phase of the COVID-19 pandemic.

Led by Shannon Gravely, research assistant professor with the ITC Project, the study surveyed 6,870 smokers and vapers in four high-income countries--Australia, Canada, England, and the United States--during the first global wave of COVID-19 between April and June 2020. The team examined the association between COVID-19 and thoughts about quitting smoking, changes in smoking, and factors related to positive changes such as attempting to quit or reducing smoking.

Only 1.1 per cent of smokers in the four countries attempted to quit and 14.2 per cent reduced smoking, but this was offset by the 14.6 per cent who increased smoking, with 70.2 per cent reported no change.

"It is important to note that population-level stressful events, such as 9/11 and natural disasters, have often led to increased smoking," said Geoffrey Fong, professor of psychology at Waterloo and principal investigator of the ITC Project. "So, our findings that there was no net increase in smoking in response to COVID-19 may actually represent a positive result for public health."

The study found that those who thought about quitting smoking because of COVID-19 were predominantly females, ethnic minorities, those with financial stress, current vapers, less dependent smokers, those with greater concern about personal susceptibility of infection, and those who believe COVID-19 is more severe for smokers.

According to Fong, who was a co-author of the study, this latter finding may be the key to why the COVID-19 pandemic has not led to significant increases in smoking, compared to past tragedies.

"Unlike other population stressors such as earthquakes, which are unrelated to smoking, COVID-19 severity is indeed linked to smoking," Fong said. "Public health officials have mentioned the link as yet another reason for smokers to quit, and over 80 per cent of smokers across the four countries believed that smoking made COVID-19 more severe. And this led to the lack of an increase in smoking, unlike what we have seen after other tragedies."

Before Millennials were over laugh-cry emojis, they were the most used emojis across the world, according to researchers at USC. The emoji was more popular than smiley faces say researchers who categorized millions of tweets across 30 countries and evaluated over 1700 emojis. Their study, "An empirical study of emoji usage on Twitter in linguistic and national contexts" was published in Online Social Networks and Media.

Mayank Kejriwal, a research assistant professor in the Department of Industrial and Systems Engineering, and a research lead at the USC Information Sciences Institute who is the lead author on the paper, says approximately 100 emojis are used most often.

The most important take away? Emojis represent the human condition and that we are more alike than different. Universal emotions dominated, says Kejriwal. Less popular are the tribalism and differences demonstrated by showing flags.

While the term emoji comes from Japanese language, greatest use of emojis on Twitter came from the English-speaking world, Spanish speaking nations and Arabic speakers.

The countries most likely to use emojis outside the US? The Philippines, Brazil and India.
Most prominent emoji out of the Middle East? Representations of love--the heart.

Across the world, coastal cities tend to use emojis more than inland areas.

Contextually, in Brazil, tweets about family were mostly likely accompanied by hearts, in the US, there were few tweets about family that were accompanied by emojis.

A new method of DNA testing on cocoa beans could revolutionise the chocolate industry, offering consumers greater reassurance about the origins and ethics of their beloved confectionery, and giving the global cocoa industry a precision tool to help end slavery and child labour.

Researchers from the University of Bath, University of the West of England, and Surrey Business School have proven a low-cost method which compares DNA in chocolate products to the cocoa when it is farmed. This means cocoa can be reliably traced back from an individual chocolate bar to the specific farms which cultivated the cocoa in it, a major advance on current fairtrading, certification and sustainability practices.

"This has the potential to revolutionise sustainability in a market rife with environmental destruction and human misery in that firms will now be able to buy from a specific set of known farms which have approved labour and environmental standards and to prove that their chocolate is made with that cocoa," said Michael Rogerson, researcher at the University of Bath School of Management.

"And activists, NGOs, and governments, will be able to prove that the chocolate bar you buy in your local supermarket contains cocoa grown on farms which abuse the environment or employ child or forced labour. We know consumers care about this - but they need accurate, reliable information to make ethical choices," Rogerson said.

Rogerson said the research team had developed a method where the DNA sampling would cost around £5 per farm, putting this well within the reach of the $78 billion cocoa supply industry, and government and NGO foreign aid budgets.

"It would cost a tiny fraction of the industry's revenues to build such a database in Ghana and Ivory Coast, which is the source of more than 70% of the world's cocoa production. There are an estimated 2.2 million child labourers working on farms in West Africa and reports suggest the problems are worsening despite promises made by large chocolate producers," he said.

Rogerson said the research team's interviews of chocolate and cocoa industry stakeholders along the whole supply chain revealed a certain 'fatalism' about the child labour issue and a sense it was too great a problem to tackle.

The interviews also showed third-party ethical certification and labelling was regarded primarily as a marketing ploy, easily understood by consumers, considered desirable, but ultimately in need of improvement to be meaningful.

"What we are offering industry is a way to break out of that fatalism, and consumers the reassurance that when they pick an 'ethical' product that it is genuinely ethical. We could also see third-party certifiers like Fairtrade or the Rainforest Alliance strengthening their offering and credibility with this," he said.

Rogerson said the difficulty of tracing cocoa from farms to the end product was at the heart of the issue. The majority of the world's cocoa is collected by small-scale traders and taken to larger trading facilities, where vast quantities are traded on international markets. Tracing beans back to the farm of origin is a challenge due to the number of different parties aggregating and mixing crops early in the supply chain. He said current certification systems, while laudable in their intent, were not addressing the core issues.

"And this is not a new issue. During our research we found reports that in 1905 Cadbury investigated claims of abuses on cocoa plantations on the islands of São Tomé and Príncipe, in Central Africa. The industry has known of the problems for over 100 years, and not yet found a viable solution to trace cocoa through supply chains, perhaps until now," he said

Biomarkers - biochemical 'barcodes' extracted from plant DNA - offer a way to resolve this issue, Rogerson said.

Biomarkers are unique indicators of a plant and the particular environment in which it plant is grown. Biomarkers in cocoa beans are sufficiently hardy that they can survive the industrial processes used in chocolate making, allowing for the identification of individual cocoa farm beans from a mixture of different origins in final products.

Biomarkers are produced by isolating DNA at cocoa farms, enabling the creation of a database of those markers specific to each farm. Further biomarkers can be taken from the location of cocoa fermentation as these also have unique signatures. Once a database has been created with sufficient samples, chocolate bought anywhere in the world can be traced back to farms of origin. This enables a chocolate producer, or even a customer given access to the right technology, to know precisely where the cocoa in their chocolate comes from.

Rogerson said the solution had been proven in a small pilot study but the approach would need operationalization at scale, something the chocolate industry could accomplish, given the will or incentive to act.

"If the method can be scaled effectively there can be no excuses for continued abuses within chocolate supply chains. Claims that farms are too widespread or remote, or that the trading of cocoa through various intermediaries makes it impossible to trace become suddenly empty. I would like the chocolate industry and governments to honestly face this ethical challenge - we have developed a tool they can deploy in that fight," he said.

Notes to editors

* For further information please contact Tony Roddam at the University of Bath press office on +44 7971 500460 or press@bath.ac.uk

The University of Bath is one of the UK's leading universities both in terms of research and our reputation for excellence in teaching, learning and graduate prospects.

The University is rated Gold in the Teaching Excellence Framework (TEF), the Government's assessment of teaching quality in universities, meaning its teaching is of the highest quality in the UK.

In the Research Excellence Framework (REF) 2014 research assessment 87 per cent of our research was defined as 'world-leading' or 'internationally excellent'. From developing fuel efficient cars of the future, to identifying infectious diseases more quickly, or working to improve the lives of female farmers in West Africa, research from Bath is making a difference around the world. Find out more: http://www.bath.ac.uk/research/

Well established as a nurturing environment for enterprising minds, Bath is ranked highly in all national league tables. We are ranked 6th in the UK by The Guardian University Guide 2021, and 9th in The Times & Sunday Times Good University Guide 2021 and 10th in the Complete University Guide 2021. Our sports offering was rated as being in the world's top 10 in the QS World University Rankings by Subject in 2021.

Irritable bowel syndrome (IBS) is, unfortunately, a common gastrointestinal disorder. Affecting between 10 to 15% of the global population, IBS negatively impacts the lives of those who have it by frequently causing a variety of symptoms, including abdominal pain, bloating, and bouts of diarrhea or constipation. Despite the high worldwide prevalence of IBS, gastroenterologists still haven't pinpointed its causes, as there seems to be no obvious structural or biochemical abnormalities associated with the disorder. In a similar vein, there is still much debate on effective diagnostic criteria and treatment options.

Considering it has been hard for scientists and doctors to reach a consensus on best practices regarding IBS, it's important that all the latest information that has been gathered on this disorder is made available in a practical format. That's why a pair of Chinese scientists recently published a review article in the Chinese Medical Journal summarizing the findings of IBS studies carried out in China. This review was made available online on June 1, 2021 and was published in Volume 134 Issue 12 of the journal on June 20, 2021.

This work addresses a particular gap in the global literature on IBS, as main-author Dr. Jin-Song Lui from Huazhong Science and Technology University, China, explains: "Though China has the largest IBS-afflicted population, IBS studies in China are not well known worldwide because most publications are in the Chinese language. Therefore, we found it necessary to review and introduce the Chinese literature to a wider audience to promote the research and management of IBS." The researchers collected post-2010 articles published on IBS in China and condensed them into a review covering three distinct aspects: epidemiology, diagnosis, and management.

The epidemiology section summarizes the findings of studies on how IBS affects subpopulations differently. In China, according to a previous review, the global prevalence of the disorder ranges from 5 to 10% depending on the diagnostic criteria used. However, current studies have updated their criteria according to more recent western guidelines, throwing results revealing that, for example, prevalence can be as high as 33% among young adults. Several risks factors are recognized in Chinese literature on IBS, including acute gastrointestinal infection, alcohol intake, being female, and anxiety or depression. In addition, adults 39 to 59 years old seem to be at greater risk. Remarkably, notorious regional differences were found in the prevalence of IBS within China.

As for diagnosis, the so-called Rome criteria are the most commonly used. These criteria are of western origin and have been modified four times, with Rome III and Rome IV criteria being the most used today. According to Chinese experts, Rome III criteria are more appropriate to diagnose IBS in China because Rome IV criteria are more restrictive in their definitions, requiring there to be abdominal pain instead of only discomfort to even consider the presence of the disorder. The review article also covers other gastrointestinal diseases that have overlapping symptoms with IBS, as well the most commonly investigated biomarkers to diagnose and manage IBS. On this last point, the authors highlight fecal calprotectin, blood erythrocyte sedimentation, small intestinal bacterial overgrowth, and blood levels of intestinal fatty acid-binding proteins as promising biomarkers. Still, more research is needed to validate their use both clinically and scientifically.

In terms of IBS management in China, a variety of strategies have been studied. Certain types of foods have been found to be associated with the disorder; mainly cold foods, spicy foods, raw foods, greasy foods, and dairy products excluding yogurt. Further studies should help clarify what type of diet would be best suited to combat IBS or alleviate symptoms. The review article goes over various types of treatments and their success so far. The antibiotic rifaximin is the most used because gastrointestinal infections play an important role in diarrhea-predominant IBS, which is the most common among Chinese patients. There is some limited evidence hinting at the potential of certain antispasmodics and secretagogues (substances that promote secretions), whereas treatment with probiotics or fecal microbiota transplants have been particularly effective in improving symptoms without adverse effects. Finally, 'tongxieyaofang,' a plant-based traditional Chinese medicine, has also shown potential as effective treatment in a few studies.

Overall, this review will help Chinese IBS studies reach a wider audience, which in turn shall contribute to the development of better practices. "Our article will enable scientists to cross reference Chinese findings on IBS with those published worldwide. We hope this will inspire future research in IBS," concludes Dr. Lui.