Recent Updates on Predicting Conversion in Youth at Clinical High Risk for Psychosis.

PURPOSE OF REVIEW: This review highlights recent advances in the prediction and treatment of psychotic conversion. Over the past 25 years, research into the prodromal phase of psychotic illness has expanded with the promise of early identification of individuals at clinical high risk (CHR) for psychosis who are likely to convert to psychosis. RECENT FINDINGS: Meta-analyses highlight conversion rates between 20 and 30% within 2-3 years using existing clinical criteria while research into more specific risk factors, biomarkers, and refinement of psychosis risk calculators has exploded, improving our ability to predict psychotic conversion with greater accuracy. Recent studies highlight risk factors and biomarkers likely to contribute to earlier identification and provide insight into neurodevelopmental abnormalities, CHR subtypes, and interventions that can target specific risk profiles linked to neural mechanisms. Ongoing initiatives that assess longer-term (> 5-10 years) outcome of CHR participants can provide valuable information about predictors of later conversion and diagnostic outcomes while large-scale international biomarker studies provide hope for precision intervention that will alter the course of early psychosis globally.

Medical student's perception of the COVID-19 pandemic effect on their education and well-being: a cross-sectional survey in the United States.

BACKGROUND: The effects of drastic curricular changes necessitated by the COVID-19 pandemic on medical students' education and wellbeing have remained largely unstudied. Out study aimed to characterize how medical students were affected by the pandemic, specifically how limitations introduced by the pandemic may have affected the quality, delivery, and experience of medical education. METHODS: Three hundred students from 5 U.S. allopathic medical schools were surveyed to determine students' perceptions about their quality of medical education, professional development, and mental health during the COVID-19 pandemic (October 2020-December 2020). RESULTS: A large majority of students report that while lecture-based learning has not been significantly affected by the pandemic, small-group and clinical learning have greatly declined in quality. Students also reported higher levels of depression, anxiety, and uncertainty with regards to their futures as physicians. CONCLUSIONS: The COVID-19 pandemic has greatly affected the medical student education and wellbeing. Although medical schools have implemented measures to continue to train medical students as effectively as they can, further strategies must be devised to ensure the well-being of students in the present and for future national emergencies.

Associations between childhood ethnoracial minority density, cortical thickness, and social engagement among minority youth at clinical high-risk for psychosis.

An ethnoracial minority density (EMD) effect in studies of psychotic spectrum disorders has been observed, whereby the risk of psychosis in ethnoracial minority group individuals is inversely related to the proportion of minorities in their area of residence. The authors investigated the relationships among area-level EMD during childhood, cortical thickness (CT), and social engagement (SE) in clinical high risk for psychosis (CHR-P) youth. Data were collected as part of the North American Prodrome Longitudinal Study. Participants included 244 ethnoracial minoritized (predominantly Hispanic, Asian and Black) CHR-P youth and ethnoracial minoritized healthy controls. Among youth at CHR-P (n = 164), lower levels of EMD during childhood were associated with reduced CT in the right fusiform gyrus (adjusted ß = 0.54; 95% CI 0.17 to 0.91) and right insula (adjusted ß = 0.40; 95% CI 0.05 to 0.74). The associations between EMD and CT were significantly moderated by SE: among youth with lower SE (SE at or below the median, n = 122), lower levels of EMD were significantly associated with reduced right fusiform gyrus CT (adjusted ß = 0.72; 95% CI 0.29 to 1.14) and reduced right insula CT (adjusted ß = 0.57; 95% CI 0.18 to 0.97). However, among those with greater SE (n = 42), the associations between EMD and right insula and fusiform gyrus CT were not significant. We found evidence that lower levels of ethnic density during childhood were associated with reduced cortical thickness in regional brain regions, but this association may be buffered by greater levels of social engagement.

Nonalcoholic Steatohepatitis and HCC in a Hyperphagic Mouse Accelerated by Western Diet.

BACKGROUND & AIMS: How benign liver steatosis progresses to nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC) remains elusive. NASH progression entails diverse pathogenic mechanisms and relies on complex cross-talk between multiple tissues such as the gut, adipose tissues, liver, and the brain. Using a hyperphagic mouse fed with a Western diet (WD), we aimed to elucidate the cross-talk and kinetics of hepatic and extrahepatic alterations during NASH-HCC progression, as well as regression. METHODS: Hyperphagic mice lacking a functional Alms1 gene (Foz/Foz) and wild-type littermates were fed WD or standard chow for 12 weeks for NASH/fibrosis and for 24 weeks for HCC development. NASH regression was modeled by switching back to normal chow after NASH development. RESULTS: Foz+WD mice were steatotic within 1 to 2 weeks, developed NASH by 4 weeks, and grade 3 fibrosis by 12 weeks, accompanied by chronic kidney injury. Foz+WD mice that continued on WD progressed to cirrhosis and HCC within 24 weeks and had reduced survival as a result of cardiac dysfunction. However, NASH mice that were switched to normal chow showed NASH regression, improved survival, and did not develop HCC. Transcriptomic and histologic analyses of Foz/Foz NASH liver showed strong concordance with human NASH. NASH was preceded by an early disruption of gut barrier, microbial dysbiosis, lipopolysaccharide leakage, and intestinal inflammation. This led to acute-phase liver inflammation in Foz+WD mice, characterized by neutrophil infiltration and increased levels of several chemokines/cytokines. The liver cytokine/chemokine profile evolved as NASH progressed, with subsequent predominance by monocyte recruitment. CONCLUSIONS: The Foz+WD model closely mimics the pathobiology and gene signature of human NASH with fibrosis and subsequent HCC. Foz+WD mice provide a robust and relevant preclinical model of NASH, NASH-associated HCC, chronic kidney injury, and heart failure.