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Abstract Background Higher level of care (HLOC) treatment for eating disorders (EDs) is sometimes necessary, but research is lacking on whether HLOCs are actually more effective than less structured, lower levels of care. The purpose of the current study was to compare outcomes for patients with EDs at low weights who entered 24/7 care (inpatient and residential) to those entering non-24/7 care (partial hospitalization programming and intensive outpatient programming). Methods Participants were 1104 adults with body mass indices (BMI) between 14 and 17 receiving treatment for an ED at a large multisite treatment facility offering HLOCs between August 2019 and February 2024. The Eating Disorder Examination-Questionnaire (EDE-Q), assessing ED psychopathology, was completed at admission and discharge. Weight was taken throughout treatment. Results In unadjusted analyses, there was a significant difference between those receiving 24/7 care (3.79) versus non-24/7 care (2.17) in BMI increase during treatment. In adjusted analyses controlling for ED diagnosis, length of stay, and admission BMI, results remained the same. Weight gain per week was significantly greater for patients in 24/7 care. Changes in ED psychopathology, as measured by the EDE-Q, were not significantly associated with 24/7 care. Conclusions The current study suggests that patients with EDs at low BMIs gain more weight at a faster rate when participating in 24/7 care compared to non-24/7 care. Entering treatment at an appropriate level may result in shorter overall lengths of stay and may increase the chances of a positive long-term outcome.

Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene. The Col7a1 gene codes for collagen type VII protein, a major component of anchoring fibrils. Mutations of the Col7a1 gene can cause aberrant collagen type VII formation, causing an associated lack or absence of anchoring fibrils. This presents clinically as chronic blistering, scarring, and fibrosis, often leading to the development of cutaneous squamous cell carcinoma. Patients also experience persistent pain and pruritus. Pain management and supportive bandaging remain the primary treatment options. The pathology of recessive dystrophic epidermolysis bullosa was first described in the 1980s, and there has since been a multitude of encouraging treatment options developed. However, in vivo research has been hindered by inadequate models of the disease. The various mouse models in existence possess longevity and surface area constraints, or do not adequately model a normal human disease state. In this paper, we describe a novel rat model of recessive dystrophic epidermolysis bullosa that offers an alternative to previous murine models. An 8-base pair deletion was induced in the Col7a1 gene of Lewis rats, which was subsequently found to cause a premature stop codon downstream. Homozygous mutants presented with a fragile and chronically blistered phenotype postnatally. Further histological analysis revealed subepidermal clefting and the absence of anchoring fibrils. The generation of this novel model offers researchers an easily maintained organism that possesses a larger surface area for experimental topical and transfused therapies to be tested, which may provide great utility in the future study of this debilitating disease.

Abstract A recent article in the Journal of Eating Disorders (10:23, 2022) proposed criteria for “terminal anorexia” with a cited goal of improving access to end-of-life care (Gaudiani et al. in J Eat Disord 10(1):23, 2022). The authors presented three cases in which patients received end-of-life care, including the prescription of medical assistance in dying (MAID), also known as physician-assisted suicide (PAS). The proposed criteria lack the evidence base for adoption and do not acknowledge the compelling evidence that exists surrounding possible prolonged timelines to recovery for some individuals and the nuances of assessing capacity in this population.

AbstractIntroduction:While previous studies have described career outcomes of physician-scientist trainees after graduation, trainee perceptions of research-intensive career pathways remain unclear. This study sought to identify the perceived interests, factors, and challenges associated with academic and research careers among predoctoral MD trainees, MD trainees with research-intense (>50%) career intentions (MD-RI), and MD-PhD trainees.Methods:A 70-question survey was administered to 16,418 trainees at 32 academic medical centers from September 2012 to December 2014. MD vs. MD-RI (>50% research intentions) vs. MD-PhD trainee responses were compared by chi-square tests. Multivariate logistic regression analyses were performed to identify variables associated with academic and research career intentions.Results:There were 4433 respondents (27% response rate), including 2625 MD (64%), 653 MD-RI (15%), and 856 MD-PhD (21%) trainees. MD-PhDs were most interested in pursuing academia (85.8%), followed by MD-RIs (57.3%) and MDs (31.2%). Translational research was the primary career intention for MD-PhD trainees (42.9%). Clinical duties were the primary career intention for MD-RIs (51.9%) and MDs (84.2%). While 39.8% of MD-PhD respondents identified opportunities for research as the most important career selection factor, only 12.9% of MD-RI and 0.5% of MD respondents shared this perspective. Interest in basic research, translational research, clinical research, education, and the ability to identify a mentor were each independently associated with academic career intentions by multivariate regression.Conclusions:Predoctoral MD, MD-RI, and MD-PhD trainees are unique cohorts with different perceptions and interests toward academic and research careers. Understanding these differences may help to guide efforts to mentor the next generation of physician-scientists.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease caused by a trinucleotide CAG repeat. SCA7 predominantly causes a loss of photoreceptors in the retina and Purkinje cells of the cerebellum. Severe infantile-onset SCA7 also causes renal and cardiac irregularities. Previous reports have shown that SCA7 results in increased susceptibility to DNA damage. Since DNA damage can lead to accumulation of senescent cells, we hypothesized that SCA7 causes an accumulation of senescent cells over the course of disease. A 140-CAG repeat SCA7 mouse model was evaluated for signs of disease-specific involvement in the kidney, heart, and cerebellum, tissues that are commonly affected in the infantile form. We found evidence of significant renal abnormality that coincided with an accumulation of senescent cells in the kidneys of SCA7140Q/5Q mice, based on histology findings in addition to RT-qPCR for the cell cycle inhibitors p16Ink4a and p21Cip1 and senescence-associated ß-galactosidase (SA-ßgal) staining, respectively. The Purkinje layer in the cerebellum of SCA7140Q/5Q mice also displayed SA-ßgal+ cells. These novel findings offer evidence that senescent cells accumulate in affected tissues and may possibly contribute to SCA7's specific phenotype.

Progressive immune deficiency of aging is characterized by severe thymic atrophy, contracted T cell repertoire, and poor immune function. p63 is critical for the proliferative potential of embryonic and adult stem cells, as well as thymic epithelial cells (TECs). Because p63 null mice experience rapid post-natal lethality due to epidermal and limb morphogenesis defects, studies to define a role for p63 expression in TEC biology focused on embryonic thymus development and in vitro experiments. Since post-natal thymic stromal development and function differs from that of the embryo, we assessed the impact of lineage-restricted p63 loss on pre- and post-natal murine TEC function by generating mice with a loss of p63 function targeted to TEC, termed p63TECko mice. In adult p63TECko mice, severe thymic hypoplasia was observed with a lack in a discernable segregation into medullary and cortical compartments and peripheral T cell lymphopenia. This profound thymic defect was seen in both neonatal as well as embryonic p63TECko mice. In addition to TECs, p63 also plays in important role in the development of stratified epithelium of the skin; lack of p63 results in defects in skin epidermal stratification and differentiation. Interestingly, all adult p63TECko mice lacked hair follicles despite having normal p63 expression in the skin. Together our results show a critical role of TEC p63 in thymic development and maintenance and show that p63 expression is critical for hair follicle formation.

Abstract Background Prior studies have described the career paths of physician-scientist candidates after graduation, but the factors that influence career choices at the candidate stage remain unclear. Additionally, previous work has focused on MD/PhDs, despite many physician-scientists being MDs. This study sought to identify career sector intentions, important factors in career selection, and experienced and predicted obstacles to career success that influence the career choices of MD candidates, MD candidates with research-intense career intentions (MD-RI), and MD/PhD candidates. Methods A 70-question survey was administered to students at 5 academic medical centers with Medical Scientist Training Programs (MSTPs) and Clinical and Translational Science Awards (CTSA) from the NIH. Data were analyzed using bivariate or multivariate analyses. Results More MD/PhD and MD-RI candidates anticipated or had experienced obstacles related to balancing academic and family responsibilities and to balancing clinical, research, and education responsibilities, whereas more MD candidates indicated experienced and predicted obstacles related to loan repayment. MD/PhD candidates expressed higher interest in basic and translational research compared to MD-RI candidates, who indicated more interest in clinical research. Overall, MD-RI candidates displayed a profile distinct from both MD/PhD and MD candidates. Conclusions MD/PhD and MD-RI candidates experience obstacles that influence their intentions to pursue academic medical careers from the earliest training stage, obstacles which differ from those of their MD peers. The differences between the aspirations of and challenges facing MD, MD-RI and MD/PhD candidates present opportunities for training programs to target curricula and support services to ensure the career development of successful physician-scientists.

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 protein. Exogenous type VII collagen did not alter LH3 expression in cultured RDEB keratinocytes and we show that RDEB patients receiving bone marrow transplantation who demonstrate significant increase in type VII collagen do not show increased levels of LH3 at the basement membrane. Our data report a direct link between LH3 and endogenous type VII collagen expression concluding that reduction of LH3 at the basement membrane in patients with RDEB will likely have significant implications for disease progression and therapeutic intervention.