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Objective While medical student wellness has been a subject of recent study and discussion, current efforts may fail to address possible underlying, harmful cognitive distortions regarding academic performance. The authors sought to examine dysfunctional thoughts (maladaptive perfectionism, impostor phenomenon) and negative feelings (shame, embarrassment, inadequacy) that may contribute to poor mental health in pre-clinical medical students. Methods A survey was administered to first-year medical students at Saint Louis University that included assessments for maladaptive perfectionism, impostor phenomenon, depression, and anxiety, as well as questions about feelings of shame, embarrassment, inadequacy, comparison, and self-worth. Results A total of 169 students (93%) participated. Students who met criteria for maladaptive perfectionism were significantly more likely to report greater feelings of shame/embarrassment and inadequacy ( P  < 0.001) than their peers who did not; similar associations were observed in students who reported high/intense levels of impostor phenomenon ( P  < 0.001). Furthermore, students who reported feelings of shame/embarrassment or inadequacy were significantly more likely to report moderate/severe levels of depression symptoms ( P  < 0.001) and moderate/high levels of anxiety symptoms ( P  = 0.001) relative to students who did not report these negative feelings. Conclusions These preliminary data support a model for how negative thoughts may lead to negative emotions, and depression and anxiety in medical students. The authors propose strategies for preventive interventions in medical school beginning in orientation. Further research is needed to develop targeted interventions to promote student mental health through reduction of cognitive distortions and negative feelings of shame, embarrassment, and inadequacy.

L. (family: Polygonaceae), named Hongcao in China, is a Traditional Chinese Medicinal and has long been used for rheumatic arthralgia and rheumatoid arthritis. However, no pharmacological and mechanism study to confirm these clinic effects have been published. In this investigation, the anti-inflammatory, analgesic effects and representative active ingredient compounds of have been studied. Dried small pieces of the stems and leaves of were decocted with water and partitioned successively to obtain ethyl acetate and ethyl ether extract of (POEa and POEe). Chemical compositions of them were analyzed by UPLC-Q-Exactive HRMS. Anti-inflammatory and analgesic effects of POEa and POEe were evaluated using xylene induced ear edema, carrageenan induced paw edema, Freunds' complete adjuvant induced arthritis, and formaldehyde induced pain in rat. Their mechanisms of anti-inflammatory and analgesic effects were also studied via assays of TNF-α, IL-1β, IL-6, and PGE2 in serum. UPLC-Q-Exactive HRMS analysis showed that POEa and POEe mainly contained flavonoids including orientin, isoorientin, vitexin, luteolin, and quercetin. Furthermore, anti-inflammatory effects of POEa and POEe were evident in xylene induced ear edema. The paw edema in Freund's complete adjuvant and carrageenan were significantly ( < 0.05, 0.01) inhibited by POEa (5, 7.5 g/kg). POEe (7.5 g/kg) was significantly ( < 0.05, 0.01) inhibited Freunds' complete adjuvant induced paw edema and cotton pellet induced granuloma formation. Similarly, POEe significantly ( < 0.05, 0.01) inhibited the pain sensation in acetic acid induced writhing test. POEa (5, 7.5 g/kg) significantly ( < 0.05, 0.01) inhibited formaldehyde induced pain in both phases. POEa (7.5 g/kg) markedly ( < 0.05) prolonged the latency period of hot plate test after 30 and 60 min. The concentrations of TNF-α, IL-1β, IL-6, and PGE2 were significantly ( < 0.01) decreased by POEa (3.75, 5 g/kg). POEa and POEe have anti-inflammatory and analgesic effects, which was mainly relevant to the presence of flavonoids, including orientin, isoorientin, vitexin, luteolin, and quercetin. The mechanism of anti-inflammatory and analgesic effects of POEa may be to decrease the concentrations of TNF-α, IL-1β, IL-6, and PGE2 in serum.

Pregnancy and parturition are intricately regulated to ensure successful reproductive outcomes. However, the factors that control gestational length in humans and other anthropoid primates remain poorly defined. Here, we show the endogenous retroviral long terminal repeat transposon-like human element 1B (THE1B) selectively controls placental expression of corticotropin-releasing hormone (CRH) that, in turn, influences gestational length and birth timing. Placental expression of CRH and subsequently prolonged gestational length were found in two independent strains of transgenic mice carrying a 180-kb human bacterial artificial chromosome (BAC) DNA that contained the full length of CRH and extended flanking regions, including THE1B. Restricted deletion of THE1B silenced placental CRH expression and normalized birth timing in these transgenic lines. Furthermore, we revealed an interaction at the 5' insertion site of THE1B with distal-less homeobox 3 (DLX3), a transcription factor expressed in placenta. Together, these findings suggest that retroviral insertion of THE1B into the anthropoid primate genome may have initiated expression of CRH in placental syncytiotrophoblasts via DLX3 and that this placental CRH is sufficient to alter the timing of birth.

This randomized, noninferiority trial compared ketamine with electroconvulsive therapy in treatment-resistant depression. Ketamine was noninferior to ECT for treatment-resistant depression without psychosis.

Acute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. Here, we show that mice deficient in the double-stranded DNA sensor AIM2 are protected from both subtotal body irradiation-induced gastrointestinal syndrome and total body irradiation-induced hematopoietic failure. AIM2 mediates the caspase-1-dependent death of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks caused by ionizing radiation and chemotherapeutic agents. Mechanistically, we found that AIM2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death. Our results suggest that AIM2 may be a new therapeutic target for ionizing radiation exposure.

Physician-scientists are critical members of the biomedical workforce. The combination of rigorous scientific training and clinical skills uniquely positions them to bridge clinical needs with investigational pursuits by identifying important clinical questions that drive basic discoveries and translating those into therapeutics that improve patient outcomes. The impact of physician-scientists on biomedical science has been profound. Here, Permar describes innovative strategies implemented at three academic medical centers in the US that are working to fill the physician-scientist pipeline.

The retina is a widely profiled tissue in multiple species by single-cell RNA sequencing studies. However, integrative research of the retina across species is lacking. Here, we construct the first single-cell atlas of the human and porcine ocular compartments and study inter-species differences in the retina. In addition to that, we identify putative adult stem cells present in the iris tissue. We also create a disease map of genes involved in eye disorders across compartments of the eye. Furthermore, we probe the regulons of different cell populations, which include transcription factors and receptor-ligand interactions and reveal unique directional signalling between ocular cell types. In addition, we study conservation of regulons across vertebrates and zebrafish to identify common core factors. Here, we show perturbation of KLF7 gene expression during retinal ganglion cells differentiation and conclude that it plays a significant role in the maturation of retinal ganglion cells. A comprehensive analysis of the ocular networks among various tissues is necessary to understand eye physiology in health and disease. Here the authors present a multi-species single-cell transcriptomic atlas consisting of cells of the cornea, iris, ciliary body, neural retina, retinal pigmented epithelium, and choroid.

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods 1 . Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations. A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.