Citations

Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B , which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo in both mouse and ferret models, including leading to abnormal gyration in the ferret model. Tmem161b localizes non-exclusively to the primary cilium, and scanning electron microscopy revealed shortened, dysmorphic, and ballooned ventricular zone cilia in the Tmem161b null mouse, suggesting that the Shh-related phenotypes may reflect ciliary dysfunction. Our data identify TMEM161B as a regulator of cerebral cortical gyration, as involved in primary ciliary structure, as a regulator of Shh signaling, and further implicate Shh signaling in human gyral development.

BACKGROUND: Promotions in academic medicine are frequently based on number of publications and leadership positions held. While prior study has established women publish less than men, many evaluations are limited to individual specialties and do not evaluate involvement with educational activities. OBJECTIVE: To compare gender differences in academic output, intramural leadership positions, and educational leadership positions of academic physicians. METHODS: The curriculum vitae and de-identified demographic data of all permanent physicians employed at a multi-site academic medical center were reviewed from April to May 2020. Multivariable logistic and Poisson regressions evaluated leadership positions and number of publications. RESULTS: Of 3,359 physicians in the demographic database, 32.3% (n = 1,087) were women and 72.5% were white (n = 2,510). Of the 3,015 physicians in the curriculum vitae database, 32% (n = 962) were women. Women were more likely (p < 0.001) to be assistant professor (54% vs. 42.7%) and less likely to be associate (18.1% vs. 20.3%) or full professor (14.6% vs. 29.1%). Women assistant professors published 22% fewer articles (ratio estimate = 0.78, p < 0.001), associate professors 18% less (coefficient = 0.82, p < 0.001), and full professors 23% less (coefficient = 0.77, p < 0.001). Fewer women were program directors for residencies (1.6% vs. 2.9%, p = 0.02) or fellowships (5.4% vs. 7.4%, p = 0.04), and held fewer division or department leadership positions (OR 0.8, 95% CI as [0.6, 1.0], p = 0.03). CONCLUSION: Women physicians do not outperform men across any education, leadership, or publication category. A cultural shift is needed to redefine traditional metrics for leadership appointments if academic medicine hopes to achieve equity.

Objective: To assess the timing, duration, methodology, and content of human trafficking (HT) curricula in U.S. medical schools. Methods: An anonymous, cross-sectional survey was sent through email and phone to administrators of 199 U.S. allopathic and osteopathic medical schools. A supplementary survey was sent to students and faculty through email listservs and social media links. Data collection occurred from April to October 2020 and findings were analyzed through SAS software. All study measures were approved by the institutional review board. Results: Administrators were from 22 states and 34 schools ( n = 51/199 schools; response rate: 25.6%) and n = 41 responded to all questions. Of these, 32% (13/41) self-identified as deans, 34.1% (14/41) as faculty, and 29.3% (12/41) as other administrators. Less than half (41.5%, n = 17/41) reported an HT curriculum. There was a wide range in length (average = 3 hours) and when present was almost always mandatory ( n = 51, 88.2%). Few curricula mentioned labor (23.5%) or organ (5.9%) trafficking, or at-risk populations such as lesbian, gay, bisexual, trans, queer, and intersex (LGBTQI) members (13.7%), foreign nationals (7.8%), victims of political conflict (3.9%), and indigenous peoples (2.0%). Students and staff ( n = 242) were from 34 states and 83 schools, and n = 36 (27.5%) reported a curriculum. Less than half (44.4%) felt the length (average 4.1 hours) was sufficient. Conclusions: Less than half of respondents reported an HT curriculum. It is unclear how well this curriculum prepares students to treat victim-survivors of HT. Future work is necessary to incorporate effective education on HT for trainees and evaluate patient outcomes after curricular implementation.

Abstract Purpose: The purpose of this study was to evaluate the feasibility and specimen quality of lymph node biopsies prepared through a novel automated system for automated fixation, drying and staining compared to standard slide preparation method. Methods: We performed a prospective, single-center study of patients undergoing endobronchial ultrasound. Samples were split into conventional standard of care (SOC) slide preparation and preparation using the device (ASP). Pathologists compared the SOC slides to the slides prepared by the automated system and assessed the following metrics: nuclear and cytoplasmic quality, presence of debris/artifact, staining quality, creation of a monolayer, and ease of adequacy/diagnosis assessment. A score between 1 (lowest quality) and 3 (highest quality) was assigned to the above metrics. Results: 60 patients were recruited. One to three lymph nodes were sampled for each patient with a total of 73 samples collected. The mean scores of each assessment category showed no statistical difference between the two preparation techniques except for improved monolayer creation in the ASP samples. All samples showed diagnostic equivalency between the automated slides and conventional slides except for one which was reported to be suspicious on the ASP sample and atypical on the SOC. Conclusion: Study results suggest that slides prepared by the automated system are of adequate quality for adequacy assessment with diagnostic concordance when compared to SOC slides.

INTRODUCTION: Access to care is a predictor of health outcomes for the aged female population. The purpose of this study was to evaluate the accessibility of obstetrician–gynecologists (ob-gyns) and gynecologic oncologists to the U.S. Medicare population, over time and by state. METHODS: The supply of ob-gyns and gynecologic oncologists was extracted from the Physician and Other Supplier Public Use File (POSPUF) database of Medicare Part B claims submitted to the U.S. Centers for Medicare and Medicaid Services. This supply was compared to the number of providers normalized by the number of Original Medicare beneficiaries; values reported are providers per 100,000 beneficiaries by state from 2012 to 2019, obtained from the Kaiser Family Foundation. RESULTS: In 2019, the average number of ob-gyns per 100,000 beneficiaries across all states was 67.2 (standard deviation [SD] ±19.3), and ranged from 157.01 (District of Columbia) to 45.39 (Wyoming). The average number of gynecologic oncologists was 2.48 (SD±1.18), and ranged from 6.60 (District of Columbia) to 0.83 (Mississippi). From 2012 to 2019, the average absolute difference in number of ob-gyns across all states was −7.71±8.59 and ranged from+15.74 (Connecticut) to −37.32 (Alaska). For gynecologic oncologists, this difference was+0.10±1.04 and ranged from+5.22 (District of Columbia) to −1.84 (South Dakota). CONCLUSION: There is wide geographic variation in the accessibility and growth rate of ob-gyns and GYNONCs for the Medicare population. This provides insight into areas of the country where the supply of ob-gyns and gynecologic oncologists may not meet current and future demand.

PURPOSE: Contemporary breast cancer surgery often requires hospital stays of 1 day or less, presenting challenges to delivery of high-quality care. Without sufficient time for proper education and guidance, patients may delay seeking care, experience anxiety, or seek unnecessary care, leading to poorer outcomes and increased costs. To address this, we evaluated the feasibility of a planning-, outcomes-, and analytics-based mobile health application called Manage My Surgery (MMS) for patients undergoing elective breast cancer surgery. METHODS: Patients undergoing breast cancer surgery at an academic health center were invited to use MMS. Those who used the application received pre- and postoperative surveys, which recorded and reported patient satisfaction and outcomes related to the application. RESULTS: Thirty-three female patients undergoing elective breast cancer surgery used MMS. The median age was 58 years. Nineteen patients underwent lumpectomy, and 14 underwent mastectomy. Users logged on to the application an average of 3.5 times. The median number of questions viewed was 12 (range 2-35). Of 17 patients who completed the feedback survey, 100% said that MMS was helpful during preparation for surgery, 82.3% said that MMS was helpful postoperatively, and 94.1% would recommend MMS to others. Preliminary data on patient-reported outcomes collected by MMS suggest improvements in anxiety and depression over time. CONCLUSION: Implementation of a digital care navigation tool in breast cancer surgery patients is feasible. Patients found the tool helpful in both the pre- and postoperative period. Additional ongoing work will focus on patients' self-management skills, long-term outcomes, and health system costs.

AbstractBiallelic loss‐of‐function variants in the thrombospondin‐type laminin G domain and epilepsy‐associated repeats (TSPEAR) gene have recently been associated with ectodermal dysplasia and hearing loss. The first reports describing a TSPEAR disease association identified this gene is a cause of nonsyndromic hearing loss, but subsequent reports involving additional affected families have questioned this evidence and suggested a stronger association with ectodermal dysplasia. To clarify genotype–phenotype associations for TSPEAR variants, we characterized 13 individuals with biallelic TSPEAR variants. Individuals underwent either exome sequencing or panel‐based genetic testing. Nearly all of these newly reported individuals (11/13) have phenotypes that include tooth agenesis or ectodermal dysplasia, while three newly reported individuals have hearing loss. Of the individuals displaying hearing loss, all have additional variants in other hearing‐loss‐associated genes, specifically TMPRSS3, GJB2, and GJB6, that present competing candidates for their hearing loss phenotype. When presented alongside previous reports, the overall evidence supports the association of TSPEAR variants with ectodermal dysplasia and tooth agenesis features but creates significant doubt as to whether TSPEAR variants are a monogenic cause of hearing loss. Further functional evidence is needed to evaluate this phenotypic association.