Uniquely human CHRFAM7A gene increases the hematopoietic stem cell reservoir in mice and amplifies their inflammatory response.

A subset of genes in the human genome are uniquely human and not found in other species. One example is CHRFAM7A, a dominant-negative inhibitor of the antiinflammatory α7 nicotinic acetylcholine receptor (α7nAChR/CHRNA7) that is also a neurotransmitter receptor linked to cognitive function, mental health, and neurodegenerative disease. Here we show that CHRFAM7A blocks ligand binding to both mouse and human α7nAChR, and hypothesized that CHRFAM7A-transgenic mice would allow us to study its biological significance in a tractable animal model of human inflammatory disease, namely SIRS, the systemic inflammatory response syndrome that accompanies severe injury and sepsis. We found that CHRFAM7A increased the hematopoietic stem cell (HSC) reservoir in bone marrow and biased HSC differentiation to the monocyte lineage in vitro. We also observed that while the HSC reservoir was depleted in SIRS, HSCs were spared in CHRFAM7A-transgenic mice and that these mice also had increased immune cell mobilization, myeloid cell differentiation, and a shift to inflammatory monocytes from granulocytes in their inflamed lungs. Together, the findings point to a pathophysiological inflammatory consequence to the emergence of CHRFAM7A in the human genome. To this end, it is interesting to speculate that human genes like CHRFAM7A can account for discrepancies between the effectiveness of drugs like α7nAChR agonists in animal models and human clinical trials for inflammatory and neurodegenerative disease. The findings also support the hypothesis that uniquely human genes may be contributing to underrecognized human-specific differences in resiliency/susceptibility to complications of injury, infection, and inflammation, not to mention the onset of neurodegenerative disease

Medical students in distress: a mixed methods approach to understanding the impact of debt on well-being

BackgroundNearly three in four U.S. medical students graduate with debt in six-figure dollar amounts which impairs students emotionally and academically and impacts their career choices and lives long after graduation. Schools have yet to develop systems-level solutions to address the impact of debt on students' well-being. The objectives of this study were to identify students at highest risk for debt-related stress, define the impact on medical students' well-being, and to identify opportunities for intervention.MethodsThis was a mixed methods, cross-sectional study that used quantitative survey analysis and human-centered design (HCD). We performed a secondary analysis on a national multi-institutional survey on medical student wellbeing, including univariate and multivariate logistic regression, a comparison of logistic regression models with interaction terms, and analysis of free text responses. We also conducted semi-structured interviews with a sample of medical student respondents and non-student stakeholders to develop insights and design opportunities.ResultsIndependent risk factors for high debt-related stress included pre-clinical year (OR 1.75), underrepresented minority (OR 1.40), debt 20-100 K (OR 4.85), debt >100K (OR 13.22), private school (OR 1.45), West Coast region (OR 1.57), and consideration of a leave of absence for wellbeing (OR 1.48). Mental health resource utilization (p = 0.968) and counselors (p = 0.640) were not protective factors against debt-related stress. HCD analysis produced 6 key insights providing additional context to the quantitative findings, and associated opportunities for intervention.ConclusionsWe used an innovative combination of quantitative survey analysis and in-depth HCD exploration to develop a multi-dimensional understanding of debt-related stress among medical students. This approach allowed us to identify significant risk factors impacting medical students experiencing debt-related stress, while providing context through stakeholder voices to identify opportunities for system-level solutions

Modulating the Biologic Activity of Mesenteric Lymph After Traumatic Shock Decreases Systemic Inflammation and End Organ Injury_Minimal Data Set

Minimal Data Set to accompany manuscript entitled, "Modulating the Biologic Activity of Mesenteric Lymph After Traumatic Shock Decreases Systemic Inflammation and End Organ Injury"

Medical students in distress: The impact of gender, race, debt, and disability.

BackgroundIn 2012, over half of US medical students experienced burnout and depression. Since that time, there have been many changes to student demographics, school resources and awareness of burnout in the medical field altogether. New tools are also available to screen for student distress, a condition that correlates with low mental quality-of-life, suicidal ideation and serious thoughts of dropping out. Despite increased attention on wellbeing and improved screening methods, no large-scale studies have evaluated student distress in the modern era of medical education. The objective of this study was to determine the current prevalence of medical student distress and contributing risk factors.MethodsStudent wellbeing from a national cohort of US medical students was measured with an electronic survey in a prospective, observational survey study from 2019-2020. Medical student distress was defined as a Medical Student Wellbeing Index (MS-WBI) of ≥4. Demographic details including age, race, gender, marital status, disability, desired specialty, and debt burden were evaluated in a multivariate logistic regression model to determine possible risk factors for the development of distress.ResultsA total of 3,162 students responded to the survey, representing 110 unique medical schools. Of these respondents, 52.9% met criteria for distress and 22% had either taken or considered taking a leave of absence for personal wellbeing. Independent risk factors for distress included involvement in the clinical phase of medical school (OR 1.37); non-male gender (OR 1.6); debt burden >$20,000 (OR 1.37), >$100,000 (OR 1.81), and >$300,000 (OR 1.96); and disability status (OR 1.84).ConclusionsMedical student wellbeing remains poor in the modern era of medical education despite increased attention to wellbeing and increased availability of wellbeing resources. Disability status is a novel risk factor for distress identified in this study. The persistence of previously identified risk factors such as non-male gender, debt burden and clinical phase of school suggest that efforts to curb medical student distress have been inadequate to date

Medical students in distress: The impact of gender, race, debt, and disability

Background In 2012, over half of US medical students experienced burnout and depression. Since that time, there have been many changes to student demographics, school resources and awareness of burnout in the medical field altogether. New tools are also available to screen for student distress, a condition that correlates with low mental quality-of-life, suicidal ideation and serious thoughts of dropping out. Despite increased attention on wellbeing and improved screening methods, no large-scale studies have evaluated student distress in the modern era of medical education. The objective of this study was to determine the current prevalence of medical student distress and contributing risk factors. Methods Student wellbeing from a national cohort of US medical students was measured with an electronic survey in a prospective, observational survey study from 2019–2020. Medical student distress was defined as a Medical Student Wellbeing Index (MS-WBI) of ≥4. Demographic details including age, race, gender, marital status, disability, desired specialty, and debt burden were evaluated in a multivariate logistic regression model to determine possible risk factors for the development of distress. Results A total of 3,162 students responded to the survey, representing 110 unique medical schools. Of these respondents, 52.9% met criteria for distress and 22% had either taken or considered taking a leave of absence for personal wellbeing. Independent risk factors for distress included involvement in the clinical phase of medical school (OR 1.37); non-male gender (OR 1.6); debt burden &gt;20,000 (OR 1.37), >100,000 (OR 1.81), and &gt;$300,000 (OR 1.96); and disability status (OR 1.84). Conclusions Medical student wellbeing remains poor in the modern era of medical education despite increased attention to wellbeing and increased availability of wellbeing resources. Disability status is a novel risk factor for distress identified in this study. The persistence of previously identified risk factors such as non-male gender, debt burden and clinical phase of school suggest that efforts to curb medical student distress have been inadequate to date. </jats:sec