Impact of the COVID-19 pandemic on internal medicine training in the United States: results from a national survey.

BACKGROUND: Internal medicine (IM) residency is a notoriously challenging time generally characterized by long work hours and adjustment to new roles and responsibilities. The COVID-19 pandemic has led to multiple emergent adjustments in training schedules to accommodate increasing needs in patient care. The physician training period, in itself, has been consistently shown to be associated with vulnerability with respect to mental well-being. The impact of the COVID-19 pandemic on the experience of IM trainees is not well established. OBJECTIVE: Characterize the impact of the COVID-19 pandemic on trainee clinical education, finances, and well-being. METHODS: We developed a survey composed of 25 multiple choice questions, 6 of which had an optional short-answer component. The survey was distributed by the American College of Physicians (ACP) to 23,289 IM residents and subspecialty fellows. We received 1,128 complete surveys and an additional 269 partially completed surveys. RESULTS: The majority of respondents reported a disruption in their clinical schedule (76%) and a decrease in both didactic conferences (71%) and protected time for education (56%). A majority of respondents (81%) reported an impact on their well-being with an increase in their level of burnout and 41% of respondents reported a decrease in level of direct supervision. Despite these changes, the majority of trainee respondents (78%) felt well prepared for clinical practice after graduation. CONCLUSIONS: These results outline the vulnerable position of internal medicine physicians in training. Preserving educational experiences, adequate supervision, and humane work hours are essential in protecting trainees from mental illness and burnout during global emergencies.

Antiracist Structural Intervention at the Emory University Institutional Review Board.

Although racial and ethnic categories are social constructs without inherent biologic or genetic meaning, race and ethnicity impact health outcomes through racism. The use of racial categories in biomedical research often misattributes the cause of health inequities to genetic and inherent biological differences rather than to racism. Improving research practices around race and ethnicity is an urgent priority and requires education as well as structural change. We describe an evidence-based intervention for an institutional review board (IRB). Our IRB now requires all biomedical study protocols to define racial and ethnic classifications they plan to use, to state whether they are describing or explaining differences between groups, and to provide justification for any use of racial or ethnic group variables as covariates. This antiracist IRB intervention is an example of how research institutions can help ensure the scientific validity of studies and avoid the unscientific reification of race and ethnicity as inherently biological or genetic concepts.

HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men.

Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.

Health Justice Standards in Graduate Medical Education: Moving from Performative to Concrete Change.

BACKGROUND: Inadequate support for underrepresented-in-medicine physicians, lack of physician knowledge about structural drivers of health, and biased patient care and research widen US health disparities. Despite stating the importance of health equity and diversity, national physician education organizations have not yet prioritized these goals. AIM: To develop a comprehensive set of Health Justice Standards within our residency program to address structural drivers of inequity. SETTING: The J. Willis Hurst Internal Medicine Residency Program of Emory University is an academic internal medicine residency program located in Atlanta, Georgia. PARTICIPANTS: This initiative was led by the resident-founded Churchwell Diversity and Inclusion Collective, modified by Emory IM leadership, and presented to Emory IM residents. PROGRAM DESCRIPTION: We used an iterative process to develop and implement these Standards and shared our progress with our coresidents to evaluate impact. PROGRAM EVALUATION: In the year since their development, we have made demonstrable progress in each domain. Presentation of our work significantly correlated with increased resident interest in advocacy (p<0.001). DISCUSSION: A visionary, actionable health justice framework can be used to generate changes in residency programs' policies and should be developed on a national level.

Condomless receptive anal intercourse is associated with markers of mucosal inflammation in a cohort of men who have sex with men in Atlanta, Georgia.

INTRODUCTION: We previously showed that the rectal mucosal immune environment among men who have sex with men (MSM) engaging in condomless receptive anal intercourse (CRAI) is immunologically distinct from that of men who do not engage in anal intercourse (AI). Here, we further examined these differences with quantitative immunohistochemistry to better understand the geographic distribution of immune markers of interest. METHODS: We enrolled a cohort of MSM engaging in CRAI (n = 41) and men who do not engage in AI (n = 21) between October 2013 and April 2015. Participants were healthy, HIV-negative men aged 18-45 from the metro Atlanta area. We performed rectal mucosal sampling via rigid sigmoidoscopy during two study visits separated by a median of nine weeks and timed with sexual activity for MSM engaging in CRAI. We used standardized, automated immunohistochemistry and quantitative image analysis to investigate the rectal mucosal distribution of neutrophils (MPO), IL-17-producing cells (IL-17) and Tregs (FOXP3) in the lamina propria, and cellular proliferation (Ki67) and adherens junction protein (E-cadherin) in the epithelium. We examined associations between biomarker expression and the rectal mucosal microbiota composition by 16s rRNA sequencing. RESULTS: Relative to the colonic crypt base, IL-17, FOXP3, and MPO expression increased towards the rectal lumen, while Ki67 decreased and E-cadherin was more uniformly distributed. Throughout the rectal mucosa distribution examined, MSM engaging in CRAI had higher mean lamina propria MPO expression (p = 0.04) and epithelial Ki67 (p = 0.04) compared to controls. There were no significant differences in IL-17, FOXP3 or E-cadherin expression. We found no significant associations of the five biomarkers with the global rectal microbiota composition or the individual taxa examined. CONCLUSIONS: Understanding the mucosal distribution of inflammatory mediators can enhance our knowledge of the earliest events in HIV transmission. Neutrophil enrichment and crypt epithelial cell proliferation likely represent sub-clinical inflammation in response to CRAI in the rectal mucosa of MSM, which could increase the risk for HIV acquisition. However, the contributory role of the microbiota in mucosal inflammation among MSM remains unclear. HIV prevention may be enhanced by interventions that reduce inflammation or capitalize on the presence of specific inflammatory mechanisms during HIV exposure.

Schizophrenia risk from complex variation of complement component 4.

Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

Large multiallelic copy number variations in humans.

Thousands of genomic segments appear to be present in widely varying copy numbers in different human genomes. We developed ways to use increasingly abundant whole-genome sequence data to identify the copy numbers, alleles and haplotypes present at most large multiallelic CNVs (mCNVs). We analyzed 849 genomes sequenced by the 1000 Genomes Project to identify most large (>5-kb) mCNVs, including 3,878 duplications, of which 1,356 appear to have 3 or more segregating alleles. We find that mCNVs give rise to most human variation in gene dosage-seven times the combined contribution of deletions and biallelic duplications-and that this variation in gene dosage generates abundant variation in gene expression. We describe 'runaway duplication haplotypes' in which genes, including HPR and ORM1, have mutated to high copy number on specific haplotypes. We also describe partially successful initial strategies for analyzing mCNVs via imputation and provide an initial data resource to support such analyses.

Fine-scale genetic assessment of sex-specific dispersal patterns in a multilevel primate society.

Like humans, hamadryas baboons (Papio hamadryas) are unusual among primates in having a multilevel social system and stable pair bonds, and are thus a useful model for the evolution of human sociality. While the kinship structure and sex-biased dispersal patterns that underlie human social organization have been extensively elucidated, the impact of these factors on the social system of hamadryas baboons is currently unclear. Here we use genetic analysis of individuals to elucidate the patterns of male and female dispersal across multiple levels of society in a wild population of hamadryas baboons. We characterized 244 members of five hamadryas bands at Filoha, Ethiopia by genotyping one Y-linked and 23 autosomal microsatellite loci and sequencing part of the mitochondrial hypervariable control region I. We found both male and female dispersal to be limited at the level of the band, with more movement of females than males among bands. By integrating long-term behavioral data for Band 1, we also found evidence for male and female philopatry at the clan level. We speculate that male philopatry at the clan level and female dispersal across one-male units and clans may enable both kin-based cooperation among males and the maintenance of kin bonds among females after dispersal. This would mean that, as in humans, kin bonds within both sexes are a core feature of the hamadryas social system, thus contributing to our understanding of the evolution of social organization in humans.

Genetic variation of genes involved in dihydrotestosterone metabolism and the risk of prostate cancer.

PURPOSE: Dihydrotestosterone (DHT) is an important factor in prostate cancer (PCA) genesis and disease progression. Given PCA's strong genetic component, we evaluated the possibility that variation in genes involved in DHT metabolism influence PCA risk. EXPERIMENTAL DESIGN: We investigated copy number variants (CNV) and single nucleotide polymorphisms (SNP). We explored associations between CNV of uridine diphospho-glucuronosyltransferase (UGT) genes from the 2B subclass, given their prostate specificity and/or involvement in steroid metabolism and PCA risk. We also investigated associations between SNPs in genes (HSD3B1, SRD5A1/2, and AKR1C2) involved in the conversion of testosterone to DHT, and in DHT metabolism and PCA risk. The population consisted of 426 men (205 controls and 221 cases) who underwent prostate-specific antigen screening as part of a PCA early detection program in Tyrol, Austria. RESULTS: No association between CNV in UGT2B17 and UGT2B28 and PCA risk was identified. Men carrying the AA genotype at SNP rs6428830 (HSD3B1) had an odds ratio (OR) of 2.0 [95% confidence intervals (95% CI), 1.1-4.1] compared with men with GG, and men with AG or GG versus AA in rs1691053 (SRD5A1) had an OR of 1.8 (95% CI, 1.04-3.13). Individuals carrying both risk alleles had an OR of 3.1 (95% CI, 1.4-6.7) when compared with men carrying neither (P = 0.005). Controls with the AA genotype on rs7594951 (SRD5A2) tended toward higher serum DHT levels (P = 0.03). CONCLUSIONS: This is the first study to implicate the 5alpha-reductase isoform 1 (SRD5A1) and PCA risk, supporting the rationale of blocking enzymatic activity of both isoforms of 5alpha-reductase for PCA chemoprevention.