Practical and customizable study strategies for clerkship year success.

The transition from a pre-clerkship curriculum to the clerkship year presents a need to re-examine and modify study strategies for clinical subject examinations and ultimately the United States Medical License Examination STEP 2 Clinical Knowledge. Efficient and effective learning are keys in balancing the significantly increased responsibility of patient care and decreased time for examination preparation. We describe several customizable study approaches, advice on selecting resources, and methods for applying the educational framework of deliberate practice and corrective feedback to learning during a medical student's clerkship years. These strategies focus on intentional and outcome-driven self-assessments to identify and patch knowledge gaps tailored to the clerkship year that will empower learners.

Le passage du programme de préexternat à l'année d'externat exige que les étudiants revoient leurs stratégies d'étude pour les examens de matières cliniques et, à terme, pour l'examen STEP 2 Clinical Knowledge du United States Medical License Examination. Un apprentissage efficace et efficient est essentiel pour trouver un équilibre entre l'importante augmentation des responsabilités de soins aux patients et la diminution du temps consacré à la préparation des examens.Nous proposons aux étudiants en médecine plusieurs approches d'étude personnalisables, ainsi que des conseils sur la sélection de ressources et méthodes pour appliquer le modèle éducatif de la pratique délibérée et de la rétroaction corrective à leur apprentissage pendant les années d'externat. Ces stratégies, adaptées à l'année d'externat, sont focalisées sur l'autoévaluation intentionnelle et axée sur les résultats pour repérer et combler les lacunes en matière de connaissances. Elles aideront les apprenants à se sentir en confiance de leurs moyens.

Effect of a High-Fat Meal on Single-Dose Rencofilstat (CRV431) Oral Bioavailability in Healthy Human Subjects.

Rencofilstat (RCF) is a novel cyclophilin inhibitor under development for the treatment of nonalcoholic steatohepatitis and hepatocellular carcinoma. This phase 1, randomized, open-label study in healthy participants assessed the relative bioavailability of a single dose of RCF 225-mg soft gelatin capsules in both fasted and high-fat conditions. Forty-four participants were enrolled to either the fasted (n = 24) or the high-fat fed (n = 20) arm. Noncompartmental pharmacokinetics were evaluated following a single 225-mg oral dose. Administration of RCF with a high-fat meal led to increases in maximum concentration, area under the concentration-time curve (AUC) from time 0 to 24 hours, and AUC from time 0 to infinity fed-to-fasted geometric mean ratios of 102.2%, 114.5%, and 132.9%, respectively. All AUC geometric mean ratios were outside of the 80% to 125% range, suggesting that a high-fat meal can increase the extent of RCF exposure. Time to maximum concentration increased from 1.5 to 1.8 hours in the fasted and high-fat groups, respectively, suggesting slightly delayed absorption. High fat intake may delay gastric emptying while increasing the absorption and bioavailability of RCF. No treatment-emergent adverse events were observed in the fasted group, and 1 treatment-emergent adverse event occurred in the high-fat meal group. The differences in observed whole-blood concentrations are unlikely to have clinically relevant effects given the wide therapeutic index of RCF demonstrated in previous phase 1 studies.

Rencofilstat, a cyclophilin inhibitor: A phase 2a, multicenter, single-blind, placebo-controlled study in F2/F3 NASH.

Rencofilstat (RCF) demonstrated antifibrotic effects in preclinical models and was safe and well tolerated in Phase 1 studies. The aim of this Phase 2a study was safety, tolerability, pharmacokinetics, and exploration of efficacy biomarkers in subjects with nonalcoholic steatohepatitis (NASH). This Phase 2a, multicenter, single-blind, placebo-controlled study randomized 49 presumed F2/F3 subjects to RCF 75 mg once daily (QD), RCF 225 mg QD, or placebo for 28 days. Primary safety and tolerability endpoints were explored using descriptive statistics with post hoc analyses comparing active to placebo groups. Pharmacokinetics were evaluated using population pharmacokinetics methods. Efficacy was explored using biomarkers, transcriptomics, and lipidomics. RCF was safe and well tolerated, with no safety signals identified. The most frequently reported treatment-emergent adverse events were constipation, diarrhea, back pain, dizziness, and headache. No clinically significant changes in laboratory parameters were observed, and RCF pharmacokinetics were unchanged in subjects with NASH. Alanine transaminase (ALT) reduction was greater in active subjects than in placebo groups. Nonparametric analysis suggested that ALT reductions were statistically different in the 225-mg cohort compared with matching placebo: -16.3 ± 25.5% versus -0.7 ± 13.4%, respectively. ProC3 and C6M reduction was statistically significant in groups having baseline ProC3 > 15.0 ng/ml. RCF was safe and well tolerated after 28 days in subjects with presumed F2/F3 NASH. Presence of NASH did not alter its pharmacokinetics. Reductions in ALT, ProC3, and C6M suggest direct antifibrotic effects with longer treatment duration. Reductions in key collagen genes support a mechanism of action via suppression and/or regression of collagen deposition. Conclusion: These results support advancement of rencofilstat into a larger and longer Phase 2b study.

Sleep and gynecological cancer outcomes: opportunities to improve quality of life and survival.

Sleep is important for immune function, metabolic function and physical repair. Sleep is more commonly disrupted in women compared with men and is disrupted by surgery, chemotherapy, and cancer itself, making gynecological oncology patients at higher risk of insomnia and sleep disruption. Insomnia and sleep disruption are linked to increased pain, poorer quality of life, depression, and anxiety which can all negatively affect patient outcomes. A number of environmental, behavioral, and pharmacological interventions have been investigated to improve patient sleep and aid in the recovery process. It is vital to understand and address patient sleep quality in order to give patients the highest quality care and improve outcomes.

The Relationship Between COVID-19 Related Stress and Medication Adherence Among High-Risk Adults During the Acceleration Phase of the US Outbreak.

PURPOSE: To assess the relationship between stress regarding COVID-19 and medication adherence. PATIENTS AND METHODS: Older adults with ≥1 chronic condition(s) were recruited from 4 active, federally funded studies in Chicago to participate in a longitudinal telephone survey. Participants self-reported stress regarding COVID-19 in the last week. Adherence was measured via the ASK-12 survey. RESULTS: Most participants reported feeling stressed "some of the time" (54.0%), while 18.2% felt stressed "most" or "all of the time" and 27.8% "never" felt stressed. In bivariate analyses, participants who reported being stressed "most" or "all of the time" had worse medication adherence than participants who reported being stressed "some of the time" or "never" (p < 0.001). In multivariable analyses, participants who reported feeling stressed "most" or "all of the time" had worse adherence than those who "never" felt stressed (Adjusted Least Square Mean (Standard Error): 21.3 (0.6) vs 19.7 (0.6), p=0.01). CONCLUSION: Stress due to COVID-19 has significantly impacted medication adherence, which has negative implications for the course of both COVID-19 and comorbid conditions. Healthcare providers should be aware of the potential impact of COVID-19 on patients' mental and physical well-being and consider ways to routinely assess patient experiences.

Reflections on Study Strategy Modifications Using Cognitive Load Theory and Dual Processing Theory in the First Year of Medical School.

Navigating the beginning of medical school can be challenging for students. The new learning environment and the increased volume and complexity of information presented within a short period of time demand more efficient and effective study strategies. We describe the experience and perspective of a first-year medical student, as well as the adjustment of study strategies based on the application of cognitive load theory and dual processing theory. We provide practical approaches that promote intentional and individualized studying planning and better knowledge retention, which may also improve the wellbeing of the new medical students.

Preparation for the United States Medical Licensing Examinations in the Face of COVID-19.

The COVID-19 pandemic has led to the canceling and rescheduling of the United States Medical Licensing Examination (USMLE) examinations due to the nationwide closure of the Prometric testing centers, which poses a significant challenge to medical students. The rescheduling of a high-stakes board examination leads to significant stress and potential burnout. Students may need guidance to decrease anxiety and reframe their study plan while maintaining their knowledge. Here, we combined board examination coaching tips with specific worked examples to describe how to prevent burnout, give recommendations for scheduling, and suggest practical approaches to USMLE and other high-stakes examinations.

Proteomic Architecture of Human Coronary and Aortic Atherosclerosis.

BACKGOUND: The inability to detect premature atherosclerosis significantly hinders implementation of personalized therapy to prevent coronary heart disease. A comprehensive understanding of arterial protein networks and how they change in early atherosclerosis could identify new biomarkers for disease detection and improved therapeutic targets. METHODS: Here we describe the human arterial proteome and proteomic features strongly associated with early atherosclerosis based on mass spectrometry analysis of coronary artery and aortic specimens from 100 autopsied young adults (200 arterial specimens). Convex analysis of mixtures, differential dependent network modeling, and bioinformatic analyses defined the composition, network rewiring, and likely regulatory features of the protein networks associated with early atherosclerosis and how they vary across 2 anatomic distributions. RESULTS: The data document significant differences in mitochondrial protein abundance between coronary and aortic samples (coronary>>aortic), and between atherosclerotic and normal tissues (atherosclerotic<

The function of cathepsins B, D, and X in atherosclerosis.

Cathepsins are proteolytic enzymes typically located within the lysosomes of macrophages. Once released, they can enhance the inflammatory process in atherosclerosis. Cathepsin X aids in the migration of T-lymphocytes and the release of cytokines. Cathepsin D modifies low-density lipoprotein to promote its uptake by macrophages and its subsequent foam cell formation. Furthermore, cathepsin D regulates apoptosis. Cathepsin B degrades the extracellular matrix within the arterial intima. Together, they increase plaque vulnerability. This evidence suggests that cathepsins play an important role in the pathogenesis of atherosclerosis.