Collaborative Approach Toward Transplant Candidacy for Obese Patients with End-Stage Renal Disease.

BACKGROUND: An elevated BMI is a major cause of transplant preclusion for patients with end-stage renal disease (ESRD). This phenomenon exacerbates existing socioeconomic and racial disparities and increases the economic burden of maintaining patients on dialysis. Metabolic bariatric surgery (MBS) in such patients is not widely available. Our center created a collaborative program to undergo weight loss surgery before obtaining a kidney transplant. STUDY DESIGN: We studied the outcomes of these patients after MBS and transplant surgery. One hundred eighty-three patients with ESRD were referred to the bariatric team by the transplant team between January 2019 and June 2023. Of these, 36 patients underwent MBS (20 underwent Roux-en-Y gastric bypass and 16 underwent sleeve gastrectomy), and 10 underwent subsequent transplantation, with another 15 currently waitlisted. Both surgical teams shared resources, including dieticians, social workers, and a common database, for easy transition between teams. RESULTS: The mean starting BMI for all referrals was 46.4 kg/m 2 and was 33.9 kg/m 2 at the time of transplant. The average number of hypertension medications decreased from 2 (range 2 to 4) presurgery to 1 (range 1 to 3) postsurgery. Similarly, hemoglobin A1C levels improved, with preoperative averages at 6.2 (range 5.4 to 7.6) and postoperative levels at 5.2 (range 4.6 to 5.8) All transplants are currently functioning, with a median creatinine of 1.5 (1.2 to 1.6) mg/dL (glomerular filtration rate 46 [36.3 to 71]). CONCLUSIONS: A collaborative approach between bariatric and transplant surgery teams offers a pathway toward transplant for obese ESRD patients and potentially alleviates existing healthcare disparities. ESRD patients who undergo MBS have unique complications to be aware of. The improvement in comorbidities may lead to superior posttransplant outcomes.

The neural basis of smile authenticity judgments and the potential modulatory role of the oxytocin receptor gene (OXTR).

Accurate perception of genuine vs. posed smiles is crucial for successful social navigation in humans. While people vary in their ability to assess the authenticity of smiles, little is known about the specific biological mechanisms underlying this variation. We investigated the neural substrates of smile authenticity judgments using functional magnetic resonance imaging (fMRI). We also tested a preliminary hypothesis that a common polymorphism in the oxytocin receptor gene (OXTR) rs53576 would modulate the behavioral and neural indices of accurate smile authenticity judgments. A total of 185 healthy adult participants (Neuroimaging arm: N = 44, Behavioral arm: N = 141) determined the authenticity of dynamic facial expressions of genuine and posed smiles either with or without fMRI scanning. Correctly identified genuine vs. posed smiles activated brain areas involved with reward processing, facial mimicry, and mentalizing. Activation within the inferior frontal gyrus and dorsomedial prefrontal cortex correlated with individual differences in sensitivity (d') and response criterion (C), respectively. Our exploratory genetic analysis revealed that rs53576 G homozygotes in the neuroimaging arm had a stronger tendency to judge posed smiles as genuine than did A allele carriers and showed decreased activation in the medial prefrontal cortex when viewing genuine vs. posed smiles. Yet, OXTR rs53576 did not modulate task performance in the behavioral arm, which calls for further studies to evaluate the legitimacy of this result. Our findings extend previous literature on the biological foundations of smile authenticity judgments, particularly emphasizing the involvement of brain regions implicated in reward, facial mimicry, and mentalizing.

Blood levels of T-Cell Receptor Excision Circles (TRECs) provide an index of exposure to traumatic stress in mice and humans.

Exposure to stress triggers biological changes throughout the body. Accumulating evidence indicates that alterations in immune system function are associated with the development of stress-associated illnesses such as major depressive disorder and post-traumatic stress disorder, increasing interest in identifying immune markers that provide insight into mental health. Recombination events during T-cell receptor rearrangement and T-cell maturation in the thymus produce circular DNA fragments called T-cell receptor excision circles (TRECs) that can be utilized as indicators of thymic function and numbers of newly emigrating T-cells. Given data suggesting that stress affects thymus function, we examined whether blood levels of TRECs might serve as a quantitative peripheral index of cumulative stress exposure and its physiological correlates. We hypothesized that chronic stress exposure would compromise thymus function and produce corresponding decreases in levels of TRECs. In male mice, exposure to chronic social defeat stress (CSDS) produced thymic involution, adrenal hypertrophy, and decreased levels of TRECs in blood. Extending these studies to humans revealed robust inverse correlations between levels of circulating TRECs and childhood emotional and physical abuse. Cell-type specific analyses also revealed associations between TREC levels and blood cell composition, as well as cell-type specific methylation changes in CD4T + and CD8T + cells. Additionally, TREC levels correlated with epigenetic age acceleration, a common biomarker of stress exposure. Our findings demonstrate alignment between findings in mice and humans and suggest that blood-borne TRECs are a translationally-relevant biomarker that correlates with, and provides insight into, the cumulative physiological and immune-related impacts of stress exposure in mammals.

Enhanced endogenous oxytocin signaling in the brain modulates neural responses to social misalignment and promotes conformity in humans: A multi-locus genetic profile approach.

The neuropeptide oxytocin (OT) is known to promote social conformity. However, the specific neurocognitive mechanisms underlying OT-induced conformity remain unclear. We aimed to address this gap by examining how genetic variation in the oxytocin receptor gene (OXTR) is linked with behavioral conformity and its underlying neural systems. Specifically, we utilized the genotype-tissue expression database (GTEx) to create a novel multi-locus genetic profile score (MPS) that reflects the level of OXTR expression in the human brain. A total of 194 participants (Neuroimaging N = 50, Behavioral N = 144) performed a novel conformity task in which they viewed a series of word pairs depicting various moral values and virtues widely recognized in the United States. In each trial, participants indicated the relative importance of these words and subsequently learned about the majority opinion. Participants later rated the same word pairs a second time. Changes in participants' ratings between the first and second sessions were measured and analyzed with respect to social feedback, blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals, and OXTR MPS. We found that participants adjusted their ratings in accordance with the majority opinions. Social misalignment between self and others activated brain areas such as the striatum and the posterior medial frontal cortex (pMFC). However, unlike most findings from previous studies, activation in the pMFC during the inconsistent social feedback negatively, rather than positively, predicted behavioral conformity. Notably, those with higher OXTR MPS had reduced pMFC activation in the face of social misalignment, which led to greater conformity. Our findings suggest that OT may promote conformity by dampening the conflict-related signals in the pMFC. They also show that OXTR MPS may be useful for studying the effect of genes on highly complex human social traits, such as conformity.

The National Longitudinal Study of Young Life Scientists: Career differentiation among a diverse group of biomedical PhD students.

Young biomedical PhD scientists are needed in a wide variety of careers. Many recent efforts have been focused on revising training approaches to help them choose and prepare for different careers. However, very little is known about how biomedical PhD students decide on and "differentiate" into careers, which limits the development of new training models. This knowledge gap also severely limits efforts to increase the representation of women and some racial/ethnic groups in academic research careers. Previous studies have used cross-sectional surveys of career interests and ratings, and have not been designed to identify career intentions. They also are limited by single-time data and response bias, having typically asked participants to recount decisions made years in the past. This report draws on annual, in-depth interviews with 147 biomedical PhD students from the start of the PhD to graduation. Qualitative content analysis methods were used to fully understand scientific development and career intentions over time. Longitudinal analysis reveals a striking level of fluidity and complexity in career intentions over time. Contrary to previous studies and the dominant narrative, data do not show generalized shifts away from academic careers. In addition to those who are consistent in this intention from the start, nearly as many students shift toward research academic careers as away from them, and only modest differences exist by gender and race/ethnicity. Thus, the dominant narrative misses the high fraction of individuals who acquire or sustain their intention to purse an academic research career during training. Efforts to increase diversity in academia must capitalize on and support those who are still considering and evolve toward an academic career. Efforts to revise research training should incorporate knowledge of the tremendous fluidity in when and how career differentiation occurs.

A new approach to mentoring for research careers: the National Research Mentoring Network.

BACKGROUND AND PURPOSE: Effective mentorship is critical to the success of early stage investigators, and has been linked to enhanced mentee productivity, self-efficacy, and career satisfaction. The mission of the National Research Mentoring Network (NRMN) is to provide all trainees across the biomedical, behavioral, clinical, and social sciences with evidence-based mentorship and professional development programming that emphasizes the benefits and challenges of diversity, inclusivity, and culture within mentoring relationships, and more broadly the research workforce. The purpose of this paper is to describe the structure and activities of NRMN. KEY HIGHLIGHTS: NRMN serves as a national training hub for mentors and mentees striving to improve their relationships by better aligning expectations, promoting professional development, maintaining effective communication, addressing equity and inclusion, assessing understanding, fostering independence, and cultivating ethical behavior. Training is offered in-person at institutions, regional training, or national meetings, as well as via synchronous and asynchronous platforms; the growing training demand is being met by a cadre of NRMN Master Facilitators. NRMN offers career stage-focused coaching models for grant writing, and other professional development programs. NRMN partners with diverse stakeholders from the NIH-sponsored Diversity Program Consortium (DPC), as well as organizations outside the DPC to work synergistically towards common diversity goals. NRMN offers a virtual portal to the Network and all NRMN program offerings for mentees and mentors across career development stages. NRMNet provides access to a wide array of mentoring experiences and resources including MyNRMN, Guided Virtual Mentorship Program, news, training calendar, videos, and workshops. National scale and sustainability are being addressed by NRMN "Coaches-in-Training" offerings for more senior researchers to implement coaching models across the nation. "Shark Tanks" provide intensive review and coaching for early career health disparities investigators, focusing on grant writing for graduate students, postdoctoral trainees, and junior faculty. IMPLICATIONS: Partners from diverse perspectives are building the national capacity and sparking the institutional changes necessary to truly diversify and transform the biomedical research workforce. NRMN works to leverage resources towards the goals of sustainability, scalability, and expanded reach.