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Physician burnout and suicide are a growing public health concern, with 1 in 15 physicians experiencing suicidal ideation. Studies consistently show that physicians are more likely than non-physicians to experience work-related stressors prior to suicide. Still, the exact nature of these stressors was unknown.
To better understand and characterize the job stressors that contribute to physician suicide, researchers at UC San Diego Health reviewed the death investigation narratives from 200 physician suicides collected by a national database between 2003 and 2018. Using natural language processing and thematic analysis — tools for extracting and interpreting data from the reports — the team was able to identify the main issues contributing to physician job stress and suicide.
The study, published June 29, 2022 in Suicide and Life-Threatening Behavior, found six overarching themes in the reports. These included an incapacity to work due to deterioration of physical health, substance use that was jeopardizing employment, the interaction between mental health and work-related issues, relationship conflicts affecting work, legal problems and increased financial stress.
“We often overlook the physical health of our health care workers, but poor health can lead to difficulty performing tasks at work, which then leads to job stress and mental health issues,” said corresponding author Kristen Kim, MD, a resident physician in psychiatry at UC San Diego Health.
The authors outlined several short- and long-term solutions for health care systems to consider.
In the short-term, they stressed the need to improve physicians’ access to primary care services, minimize their scheduling challenges, and address their concerns about confidentiality. Kim encouraged health care workers to utilize resources like the UC San Diego Healer Education Assessment and Referral (HEAR) program, which provides access to confidential mental health counseling and was recently endorsed by the U.S. Surgeon General’s Advisory on Health Worker Burnout.
In the long-term, the authors called for broader structural and cultural changes to address workplace stress and poor physician self-care.
“The unspoken culture of medicine encourages self-sacrifice, deferred needs and delayed rewards,” said Kim. “We always want to put our patients first, but healers cannot optimally heal unless they themselves are first whole.”
The authors highlighted the importance of cultivating a sense of safety and community among physicians. They also suggested that health care systems and medical schools provide additional personal finance education and legal support.
“There is a lot of work to be done,” said Kim, “but identifying and acknowledging the problem is always the first step towards a solution, and that’s exactly what we’re doing.”
Co-authors include: Gordon Y. Ye, Nicholas Kos, Sidney Zisook and Judy E. Davidson at UC San Diego, as well as Angela Maria Haddad at Universidad Autónoma de Guadalajara.
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Materials provided by University of California – San Diego. Original written by Nicole Mlynaryk. Note: Content may be edited for style and length.

Exposure to the air pollution known as fine particulate matter (PM2.5) is associated with an increased risk of having a cluster of multiple chronic diseases, according to a new study published this week in the open-access journal PLOS Global Public Health by Kai Hu of University of St. Andrews, UK, and colleagues.
Previous studies have provided abundant evidence on the association between air pollution and individual chronic diseases. Although chronic diseases tend to cluster due to shared biological or environmental risk factors, there has been a limited understanding of how air pollution might promote the accumulation of multiple chronic diseases.
In the new study, the researchers used data on 19,098 respondents of the China Health and Retirement Longitudinal Study (CHARLS) surveys from 2011 to 2015, as well as historical satellite data on PM2.5 exposure over 15 years. Participants were people aged 45 to 85 from 125 cities across China.
When the team modeled the associations between self-reported chronic disease diagnosis and PM2.5 exposure, the data revealed four distinct groups of multimorbidity, with patients sorting into respiratory, musculoskeletal, cardio-metabolic, or healthy clusters. The analysis showed that a 1µg/m3 increase in cumulative exposure to PM2.5 over 15 years was associated with a 2.4 percent (95% CI 1.02-1.03) increased chance of belonging to the respiratory cluster, a 1.5 percent (95% CI 1.01-1.02) increased chance of belonging to the musculoskeletal cluster, and a 3.3 percent (95% CI 1.03-1.04) increased chance of belonging to the cardio-metabolic cluster. However, the models also showed a U-shaped association, with both lower and higher PM2.5 exposure associated with increased multimorbidity. The increased multimorbidity at the low end of the spectrum may be due to differences in rural-urban living and economic development, the authors hypothesized.
The results are limited by the fact that only 4 years of health data were available, but the authors concluded that current PM2.5 levels are harmful to human health among the majority of Chinese adults, and that for most low and middle income countries, efforts to reduce PM2.5 would likely be associated with a substantial reduction in the burden of multiple diseases.
The authors add: “Both lower and higher historical PM2.5 exposure is associated with faster multimorbidity accumulation. However, higher exposure to PM2.5 is associated with a higher risk of developing cardio-metabolic and respiratory multimorbidity (dominated by lung disease), whereas lower PM2.5 exposure is associated with a higher likelihood of musculoskeletal multimorbidity.”
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Carbon monoxide is best known as a potentially deadly gas. However, in small doses it also has beneficial qualities: It has been shown to reduce inflammation and can help stimulate tissue regeneration.
A team of researchers led by MIT, Brigham and Women’s Hospital, the University of Iowa, and Beth Israel Deaconess Medical Center has now devised a novel way to deliver carbon monoxide to the body while bypassing its potentially hazardous effects. Inspired by techniques used in molecular gastronomy, they were able to incorporate carbon monoxide into stable foams that can be delivered to the digestive tract.
In a study of mice, the researchers showed that these foams reduced inflammation of the colon and helped to reverse acute liver failure caused by acetaminophen overdose. The new technique, described today in a Science Translational Medicine paper, could also be used to deliver other therapeutic gases, the researchers say.
“The ability to deliver a gas opens up whole new opportunities of how we think of therapeutics. We generally don’t think of a gas as a therapeutic that you would take orally (or that could be administered rectally), so this offers an exciting new way to think about how we can help patients,” says Giovanni Traverso, the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital.
Traverso and Leo Otterbein, a professor of surgery at Harvard Medical School and Beth Israel Deaconess Medical Center, are the senior authors of the paper. The lead authors are James Byrne, a physician-scientist and radiation oncologist at the University of Iowa (formerly a resident in the Mass General Brigham/Dana Farber Radiation Oncology Program), and a research affiliate at MIT’s Koch Institute for Integrative Cancer Research; David Gallo, a researcher at Beth Israel Deaconess; and Hannah Boyce, a research engineer at Brigham and Women’s.
Delivery by foam
Since the late 1990s, Otterbein has been studying the therapeutic effects of low doses of carbon monoxide. The gas has been shown to impart beneficial effects in preventing rejection of transplanted organs, reducing tumor growth, and modulating inflammation and acute tissue injury.

The Universidad Carlos III de Madrid (UC3M) is conducting research that analyses antibiotic resistance patterns with the aim of finding trends that can help decide which treatment to apply to each type of patient and stop the spread of bacteria. This study, recently published in the scientific journal Nature Communications, has been carried out together with the University of Exeter, the University of Birmingham (both in the United Kingdom) and the Westmead Hospital in Sydney (Australia).
In order to observe a bacterial pathogen’s resistance to an antibiotic in clinical environments, a measure called MIC (Minimum Inhibitory Concentration) is used, which is the minimum concentration of antibiotic capable of inhibiting bacterial growth. The greater the MIC of a bacterium against an antibiotic, the greater its resistance.
However, most public databases only contain the frequency of resistant pathogens, which is aggregated data calculated from MIC measurements and predefined resistance thresholds. “For example, for a given pathogen, the antibiotic resistance threshold may be 4: if a bacterium has an MIC of 16, it is considered resistant and is counted when calculating the resistance frequency,” says Pablo Catalán, lecturer and researcher in the UC3M Mathematics Department and author of the study. In this regard, the resistance reports that are carried out nationally and by organisations such as the WHO are prepared using this aggregated resistance frequency data.
To conduct this research, the team has analysed a database which is ground-breaking, as it contains raw data on antibiotic resistance. This database, called ATLAS, is managed by Pfizer and has been public since 2018. The working group led by UC3M has compared the information of 600,000 patients from over 70 countries and has used machine learning methods (a type of artificial intelligence technique) to extract resistance evolution patterns.
By analysing this data, the research team has discovered that there are resistance evolution patterns that can be detected when using the raw data (MIC), but which are undetectable using the aggregated data. “A clear example of this is a pathogen whose MIC is slowly increasing over time, but below the resistance threshold. Using this frequency data we wouldn’t be able to say anything, since the resistance frequency remains constant. However, by using MIC data we can detect such a case and be on alert. In the paper, we discuss several clinically relevant cases which have these characteristics. Furthermore, we are the first team to describe this database in depth,” says Catalán.
This study makes it possible to design antibiotic treatments that are more effective in controlling infections and curbing the rise of resistance which causes many clinical problems. “The research uses mathematical ideas to find new ways of extracting antibiotic resistance patterns from 6.5 million data points,” concludes the research author.
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A new study led by Lerner Research Institute and the Center for Young-Onset Colorectal Cancer at Cleveland Clinic has identified geographic patterns of high and low mortality rates of young-onset colorectal cancer (yoCRC) in the United States, according to a research letter published in Gastroenterology. The findings will contribute to improved understanding of the underlying drivers of yoCRC mortality and may help to guide policy discussions surrounding screening guidelines and region-specific interventions.
“Incidence and mortality of yoCRC, defined as colorectal cancer occurring in individuals under the age of 50, have been steadily increasing since the mid-1990’s, but we still do not understand why,” said the study’s senior author Stephanie Schmit, PhD, MPH, Vice Chair of the Genomic Medicine Institute. “With this study, we aimed to establish where yoCRC mortality rates were higher or lower than expected, known as hot and cold spots, in order to pinpoint regions in the country warranting further investigation and to understand the factors contributing to this increasing burden.”
In this study, the researchers utilized colorectal cancer-specific mortality data from 3,036 U.S. counties between 1999 and 2019. The geospatial clustering models were adjusted for yoCRC risk factors and prognostic indicators, including age, sex, race/ethnicity, obesity, smoking, alcohol consumption and socioeconomic conditions. They specifically assessed two broad age-at-diagnosis categories of younger than 50 and older than 50 as well as four stratified categories of younger than 35, 35 to 49, 50 to 64 and older than 65.
Notably, they discovered new mortality hot spots in the Midwest/northeastern Great Lakes region, which constitutes the first reporting of yoCRC mortality hot spots in these areas, in addition to cold spots in western/southwestern counties that have lower risk of yoCRC death. They also found mortality hot spots in southern and Appalachian counties in the younger than 50 category that were consistent with previous studies. However, they determined that hot spots among those ages 35 to 49 more closely followed southern patterns seen in average-onset CRC while hot spots in those younger than age 35 did not, which suggests that deaths among the youngest yoCRC patients may be driven by a distinct set of factors.
“While we recognize that unmeasured factors, such as access to care and related treatment disparities, may be influencing our study results, our findings may initiate new research examining yoCRC mortality-related factors specific to region and age, such as healthcare system accessibility or diet, and provide an impetus to target interventions in particular regions,” said R. Blake Buchalter, PhD, MPH, the study’s first author.
Dr. Buchalter is a postdoctoral fellow in Dr. Schmit’s lab and the lab of Jesse Schold, PhD, in the Department of Quantitative Health Sciences. His fellowship is supported by the Computational Genomic Epidemiology of Cancer (CoGEC) National Cancer Institute-funded T32 Training Program at Case Western Reserve University.
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A new oral treatment for ulcerative colitis that focuses on reducing inflammation in gut microbiota has been developed by researchers in the Institute for Biomedical Sciences at Georgia State University, according to a new study.
In the study published in the journal Pharmaceutics, the researchers took a two-step approach to fighting ulcerative colitis. First, they reduced inflammation in gut microbiota from a mouse with an anti-inflammatory drug candidate delivered by lipid nanoparticles. Then, they orally administered the end products of these treated microbiota to the same mouse, resulting in a new, effective way to prevent ulcerative colitis.
The findings report the nano formulation, M13/nLNP, shifted the inflamed microbiota composition toward being non-inflamed. This altered microbiota composition induced significant changes in the chemical profiles of secreted metabolites (end products of metabolic reactions), and when these metabolites were orally administered to mice, they established strong protection against the formation of chronic inflammation.
Ulcerative colitis is a form of chronic inflammatory bowel disease (IBD) that affects more than five million patients worldwide. Studies have shown that irregular gut microbiota composition is associated with the progression of ulcerative colitis. Altering the composition of gut microbiota is an effective approach to treating a variety of chronic diseases, including ulcerative colitis. However, current methods such as fecal microbiota transplants pose a risk of serious infections because they involve the transmission of drug-resistant organisms.
In this study, the researchers developed an organism-free strategy in which gut microbiota were altered in test tubes, and then microbiota-secreted metabolites were transferred back to the host. By collecting feces from mice with chronic ulcerative colitis, the researchers determined that a natural lipid nanoparticle-encapsulated drug candidate modified the composition of inflamed gut microbiota, which were cultured outside of the host, and the secreted metabolites.
“Our study demonstrates that modifying microbiota outside of the host using M13/nLNP effectively reshaped the microbial secreted metabolites,” said Dr. Didier Merlin, a Distinguished University Professor in the Institute for Biomedical Sciences at Georgia State and a senior research career scientist at Atlanta Veterans Affairs Medical Center. “Oral transfer of these metabolites might be an effective and safe therapeutic approach for preventing chronic ulcerative colitis.”
A limitation of the study is that alteration of the microbiota composition could be affected by the accumulation of secreted metabolites. A dynamic flowing device must be developed to continuously eliminate the secreted metabolites from the medium so the metabolites themselves will not affect how the drug formulation changes the composition of cultured microbiota. In addition, other key factors, such as the drug concentration, culture time and anaerobic gas composition, can be further optimized.
“Our strategy to tackle the progression of ulcerative colitis might offer an alternative and complementary approach for better managing this disease,” said Dr. Chunhua Yang, a research assistant professor at the Institute for Biomedical Sciences at Georgia State. “Although this study demonstrates the anti-inflammatory effects of metabolites modified outside of the organism, further investigations are required to characterize the specific bacteria that contribute to the anti-inflammatory metabolites and to identify anti-inflammatory metabolite structures.”
Co-authors of the study include Chunhua Yang (first author) and Didier Merlin of the Institute for Biomedical Sciences at Georgia State and the Atlanta Veterans Affairs Medical Center; Junsik Sung and Dingpei Long of the Institute for Biomedical Sciences at Georgia State; and Zahra Alghoul of the Institute for Biomedical Sciences and Department of Chemistry at Georgia State.
The study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, the Department of Veterans Affairs and the Crohn’s and Colitis Foundation.
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In a pilot project exploring ways to monitor COVID-19, University at Buffalo scientists hunted for pharmaceuticals and viral RNA simultaneously in wastewater in Western New York.
The results of their study, published on May 18 in the journal Environmental Science & Technology Letters, suggest that measuring the concentrations of medicines in wastewater could add another layer to disease-monitoring efforts.
“Wastewater-based disease surveillance is being done worldwide through monitoring of viral RNA,” says lead scientist Diana Aga, PhD, director of the UB RENEW Institute and Henry M. Woodburn Professor of Chemistry in the UB College of Arts and Sciences. “The potential of complementing existing efforts with detection of pharmaceuticals is exciting. There are a lot of opportunities here, though more research is needed.”
One interesting discovery in the new study involves acetaminophen, a pain reliever and fever reducer that serves as an active ingredient in over-the-counter medicines such as Tylenol, Theraflu and other brands.
At all four wastewater treatment plants included in the project, the research found that acetaminophen concentrations in wastewater spiked before other measures of COVID-19 in the community in early 2021, including concentrations of COVID-19 viral RNA in wastewater and the estimated number of confirmed COVID-19 cases.
For example, at the Bird Island Wastewater Treatment Plant, which serves Buffalo and some surrounding suburbs, acetaminophen levels in wastewater spiked about two weeks earlier than levels of SARS-CoV-2 RNA in wastewater. The spike in viral RNA, in turn, preceded the spike in the estimated number of confirmed cases of COVID-19 by about a week, scientists say.

Researchers at Indiana University School of Medicine are learning more about how special regulatory T cells can impact the immune system’s response and how those cells could be manipulated for potential treatments for food allergies and autoimmune diseases.
In a study recently published in Science Immunology, researchers focused on regulatory T cells, or Treg cells, that regulate immune responses in the body and keep the immune system in order while fighting pathogens. In some cases, the immune system becomes overly responsive, leading to autoimmune diseases, such as Type 1 diabetes or lupus, food allergies or other issues. Researchers were able to identify the differences in isoforms that control Treg cells and how that affects the body’s immune function.
“There is a particular gene that controls this regulatory group of T cells, which controls immune response,” said Baohua Zhou, PhD, lead author of the study and associate professor of pediatrics for IU School of Medicine Department of Pediatrics. “Treg cells can help maintain the right balance to help the immune system not respond too strongly or too weakly.”
The human gene FOXP3 produces two major isoforms through alternative splicing — a longer isoform and a shorter isoform. The two isoforms are naturally expressed in humans, but their differences in controlling regulatory T cell phenotype and functionality has been unclear. In this study, researchers showed patients expressing only the shorter isoform fail to maintain self-tolerance and develop issues like immunodeficiency, polyendocrinopathy and enteropathy X-linked (IPEX) syndrome. They uncovered different functions of the FOXP3 isoforms to regulate Treg cells and immune homeostasis.
“Now that we know the different functions of the isoforms, we hope to study how to change them, which could lead to new treatments for autoimmune diseases and allergies,” Zhou said. “We could also potentially manipulate them to keep the body from responding improperly to diseases like cancer. If T reg cells are suppressing the antitumor response, can we change that?”
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Materials provided by Indiana University School of Medicine. Original written by Christina Griffiths. Note: Content may be edited for style and length.

Mitochondria are the power plants of cells, and they contain their own genetic material and RNA molecules. Scientists from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now discovered that certain modifications in mitochondrial RNA boost the invasive spread of cancer cells by supporting protein synthesis in mitochondria. They have established that a specific gene expression signature correlating with high levels of mitochondrial RNA modifications is associated with metastasis and poor prognosis in patients with head and neck cancer. When the researchers blocked the responsible RNA modifying enzyme in cancer cells, the number of metastases was reduced. Certain antibiotics that suppress protein synthesis in mitochondria were also able to prevent the invasive spread of cancer cells in laboratory experiments. The results have now been published in the journal Nature.
Cancer cells in aggressive tumours invade the surrounding tissue in an attempt to form a new tumour in other organs. During this journey, cancer cells have to survive unfavourable conditions such as shortage of oxygen or shortage in nutrients. To overcome these stress factors, cancer cells adapt their energy production accordingly. The molecular mechanisms allowing this flexibility were poorly understood until now. “However, we suspected that this metabolic plasticity must be a key to the successful spread of the cancer cells,” says Michaela Frye; cell biologist at the German Cancer Research Center.
Mitochondria are tiny, membrane-enveloped structures known as the powerhouse of every cell in our body. For energy production, they use the so-called respiratory chain present in the mitochondrial membrane. Because mitochondria contain their own genetic material, they themselves produce key components of the respiratory chain.
The production of components of the respiratory chain is tightly regulated by a specific machinery in the mitochondria — with implications for the metastatic spread of cancer cells, as Michael Frye and her team have now discovered and published in the journal Nature. tRNA molecules are part of this machinery and are responsible for providing the individual amino acid building blocks during protein assembly. The research team identified the deposition of molecular modifications on mitochondrial tRNAs as the control mechanism to support production of proteins during metastasis.
RNA modifications regulate mitochondrial function and drive metastasis
Cancer cell invasion is a very energy consuming process. The team in Heidelberg discovered that a specific chemical modification found in mitochondrial tRNA, known as “m5C” (5-methylcytosine), is required for metastasis development. The m5C modification cranks up protein synthesis in the mitochondria. This enhances the production of components of the respiratory chain. As a result, the cell increases its pool of energy to fuel demanding cellular processes such as cancer cell dissemination from the tumour.

Scientists have shown it is possible to reverse a key process that allows pancreatic cancer cells to grow and spread around the body.
These findings, published in Nature,show that a protein called GREM1 is key to regulating the type of cells found in pancreatic cancer — and manipulating its levels can both fuel and reverse the ability of these cells to change into a more aggressive subtype.
The researchers believe this fundamental discovery could ultimately pave the way for new pancreatic cancer treatments.
Researchers from The Institute of Cancer Research, London, studied pancreatic cancer with the gene that makes the GREM1 protein switched off in mice, and in pancreatic ‘mini-tumours’, which are also known as organoids.
Switching off GREM1 caused the tumour cells to rapidly change shape and develop new properties that help them invade new tissues and migrate around the body. Within just 10 days, all the tumour cells changed their identity into a dangerous, invasive cell type.
Switching off the gene also made tumours in mice more likely to spread. The researchers studied a mouse model of pancreatic ductal adenocarcinoma (PDAC) — the most common and aggressive form of the disease. Around 90 per cent of mice without functioning GREM1 developed tumours which had spread to their liver, compared to 15 per cent of mice where GREM1 was working normally.