Preclinical obesity curriculum: audit, implementation, and evaluation.

BACKGROUND: This study aimed to (1) evaluate the current status of obesity education at Case Western Reserve University School of Medicine (CWRU) (2), introduce a comprehensive first-year curriculum on obesity, and (3) assess the impact of the curriculum on self-reported attitudes and knowledge regarding obesity among first-year medical students. METHODS: The preclinical curriculum at CWRU was reviewed to determine the degree of coverage of Obesity Medicine Education Collaborative (OMEC) competencies for healthcare professionals, and recommendations were provided for revising the curriculum to better adhere to these evidence-based competencies. A survey on obesity attitudes and knowledge was given before and after the implementation of the new curriculum to measure intervention-related changes. Changes in obesity attitudes and knowledge were compared (1) before and after the intervention for the class of 2025 and (2) after the intervention for the class of 2025 to a historical cohort that did not receive the intervention. RESULTS: Among the 27 competencies examined in the audit, 55% were unmet and 41% were partially met. Of 186 first-year medical students (M1s), 29 (16%) completed the baseline survey and 26 (14%) completed the post-intervention survey. Following the intervention, there was a notable improvement in attitudes and knowledge regarding obesity. Specifically, there was a significant decrease in the belief that obesity is caused by poor personal choices, and knowledge of obesity in fourteen out of fifteen areas showed significant improvement from pre- to post-intervention. Additionally, obesity attitudes and knowledge were significantly better post-intervention when compared to the historical cohort. CONCLUSIONS: The improvements made to the preclinical curriculum through this project improved obesity attitudes and knowledge among first-year medical students. This method provides a practical approach for evaluating and enhancing obesity education in medical school curricula.

Obesity preclinical elective: a qualitative thematic analysis of student feedback.

BACKGROUND: Education about the prevalent chronic disease of obesity is still minimal and variable in medical school curricula. In a student-led effort with faculty support, the authors designed and implemented an obesity medicine elective at Case Western Reserve University School of Medicine (CWRU). The 10-week elective, taught by seven physicians and one dietitian, was offered in January 2023 to medical students and included: weekly lectures, an interactive session with a patient, shadowing in obesity medicine practices, attendance at a distance-learning intensive behavioral lifestyle program, student presentations, and a final written reflection. The purpose of this study was to analyze the elective reflections and identify themes about the elective's value and areas to improve. METHODS: The authors analyzed reflections from the 20 medical students that completed the elective via qualitative thematic analysis. The analysis was performed using the Braun and Clarke six-phase framework: (1) become familiar with the data, (2) generate initial codes, (3) search for themes, (4) review themes, (5) define themes, and (6) write-up. RESULTS: The themes identified were improved: (1) understanding of obesity as a chronic disease, (2) knowledge about treatment options for obesity (3) confidence in compassionate obesity counseling skills, and (4) skills to confront weight bias. Theme (5) consisted of highlights (hearing from experts, practicing evidence-based medicine, and interacting with patients), and areas to improve (session length, presentation format, more peer-to-peer interaction, and more diverse patient interactions). CONCLUSIONS: Medical student assessments of a new obesity medicine elective described improved attitudes, knowledge, and skills to address obesity and obesity bias. Students were very satisfied and contributed ideas for improvements. This elective structure and evaluation method is a feasible model to provide medical students with meaningful experiences related to obesity.

Team-Based Learning Intervention to Improve Obesity Education in Medical School.

Introduction: Obesity is a multifactorial chronic disease and a major contributor to numerous health conditions. Despite the high prevalence, costs, and health effects of obesity, physicians are largely unprepared to treat it. Most medical students and residents lack sufficient training in obesity and obesity management. Methods: We evaluated a two-part team-based learning seminar (TBL) on obesity pathogenesis and treatment for first-year medical students at Case Western Reserve University School of Medicine (CWRU SOM). A questionnaire on attitudes toward obesity and self-perceived knowledge of obesity was administered before and after the TBL, utilizing Likert scales. Results: Of 183 medical students who attended both TBLs, 155 (85%) completed the baseline questionnaire, and 127 (69%) completed the postintervention questionnaire. Confidence in treating obesity increased significantly from preintervention (M = 2.7, SD = 1.0) to postintervention (M = 3.7, SD = 0.8). The attitude that obesity is caused by poor personal choices decreased significantly from preintervention (M = 2.8, SD = 0.9) to postintervention (M = 2.1, SD = 0.9). Self-perceived knowledge of obesity in all nine areas-epidemiology, energy homeostasis, etiologies, nutrition, physical activity, behavior, pharmacology, surgery, and language-increased significantly. Discussion: Despite obesity being one of the most prevalent health concerns, obesity education in medical school is scant. This TBL resulted in improved attitudes toward obesity and self-perceived knowledge of obesity among first-year medical students at CWRU SOM and offers a practical mechanism to introduce more obesity education into undergraduate medical curricula.

Investigating Alcohol Behavior and Physiology Using Drosophila melanogaster.

Drosophila melanogaster, the fruit fly, is one of the most versatile models for biomedical studies due to the economical husbandry, rapid generation time, and the array of tools for spatial and temporal gene manipulation. The relatively short lifespan of Drosophila (60-80 days) and the high degree of molecular conservation across species make Drosophila ideal to study the complexities of aging. Alcohol is the most abused drug worldwide and alcohol use disorders represent a significant public health problem and economic burden to individuals and society. Stereotypical alcohol-induced behaviors and the underlying molecular mechanisms are conserved from flies to humans making Drosophila a practical model for investigating the development of alcohol-induced behaviors and alcohol pathologies. Here, we outline how to assemble an efficient and controlled alcohol vapor delivery system, the FlyBar, and review paradigms and protocols for the assessment of alcohol-induced behaviors and physiology in Drosophila including the loss-of-righting reflex, sedation, tolerance, alcohol metabolism, and gut permeability.

Pelvic Organ Prolapse Stage and the Relationship to Genital Hiatus and Perineal Body Measurements.

OBJECTIVES: This study aimed to describe the relationship between genital hiatus (GH) and perineal body (PB) measurements with increasing pelvic organ prolapse (POP) stage in a large cohort of women referred to Urogynecology clinic for pelvic floor disorders. METHODS: Retrospective chart review of all new patients seen in an academic Urogynecology clinic between January 2007 and September 2011 was performed. Data were extracted from a standardized intake form. All patients underwent a Pelvic Organ Prolapse Quantification (POPQ) examination. Descriptive statistics compared the study population. Analysis of variance was used to compare GH and PB measurements by prolapse stage. Fisher least significant differences were used for post hoc comparisons of means between prolapse stages. Pearson correlations were used to evaluate the associations between GH and PB measurements and patient characteristics. RESULTS: A total of 1595 women with POPQ examinations comprised the study population. The mean age was 55.3 ± 14.8 years with a body mass index of 30.3 ± 7.6 kg/m, most women were parous (90%), 40% were Hispanic, and 33% had undergone prior hysterectomy for indications exclusive of POP. Women with any prior prolapse repair were excluded, 6.5% had a prior incontinence procedure. Perineal body measurements were slightly larger for stage 2 POP, but overall did not vary across other prolapse stages (all P > 0.05). In contrast, GH measurements increased through stage 3 POP, GH measurements decreased for stage 4 POP. CONCLUSIONS: Mean PB measurements did not demonstrate large changes over prolapse stage, whereas GH measurements increased through stage 3 POP. Genital hiatus serves as an important marker for underlying pelvic muscle damage.

Complement-dependent modulation of antitumor immunity following radiation therapy.

Complement is traditionally thought of as a proinflammatory effector mechanism of antitumor immunity. However, complement is also important for effective clearance of apoptotic cells, which can be an anti-inflammatory and tolerogenic process. We show that localized fractionated radiation therapy (RT) of subcutaneous murine lymphoma results in tumor cell apoptosis and local complement activation. Cotreatment of mice with tumor-targeted complement inhibition markedly improved therapeutic outcome of RT, an effect linked to early increases in apoptotic cell numbers and increased inflammation. Improved outcome was dependent on an early neutrophil influx and was characterized by increased numbers of mature dendritic cells and the subsequent modulation of T cell immunity. Appropriate complement inhibition may be a promising strategy to enhance a mainstay of treatment for cancer.

Release of nonmuscle myosin II from the cytosolic domain of tumor necrosis factor receptor 2 is required for target gene expression.

Tumor necrosis factor-α (TNF-α) elicits its biological activities through activation of TNF receptor 1 (TNFR1, also known as p55) and TNFR2 (also known as p75). The activities of both receptors are required for the TNF-α-induced proinflammatory response. The adaptor protein TNFR-associated factor 2 (TRAF2) is critical for either p55- or p75-mediated activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, as well as for target gene expression. We identified nonmuscle myosin II (myosin) as a binding partner of p75. TNF-α-dependent signaling by p75 and induction of target gene expression persisted substantially longer in cells deficient in myosin regulatory light chain (MRLC; a component of myosin) than in cells replete in myosin. In resting endothelial cells, myosin was bound constitutively to the intracellular region of p75, a region that overlaps with the TRAF2-binding domain, and TNF-α caused the rapid dissociation of myosin from p75. At early time points after exposure to TNF-α, p75 activated Rho-associated kinase 1 (ROCK1). Inhibition of ROCK1 activity blocked TNF-α-dependent phosphorylation of MRLC and the dissociation of myosin from p75. ROCK1-dependent release of myosin was necessary for the TNF-α-dependent recruitment of TRAF2 to p75 and for p75-specific activation of NF-κB and MAPK signaling. Thus, our findings have revealed a previously uncharacterized, noncanonical regulatory function of myosin in cytokine signaling.

Activation of p53 with Nutlin-3a radiosensitizes lung cancer cells via enhancing radiation-induced premature senescence.

Radiotherapy is routinely used for the treatment of lung cancer. However, the mechanisms underlying ionizing radiation (IR)-induced senescence and its role in lung cancer treatment are poorly understood. Here, we show that IR suppresses the proliferation of human non-small cell lung cancer (NSCLC) cells via an apoptosis-independent mechanism. Further investigations reveal that the anticancer effect of irradiation correlates well with IR-induced premature senescence, as evidenced by increased senescence-associated ß-glactosidase (SA-ß-gal) staining, decreased BrdU incorporation and elevated expression of p16(INK4a) (p16) in irradiated NSCLC cells. Mechanistic studies indicate that the induction of senescence is associated with activation of the p53-p21 pathway, and that inhibition of p53 transcriptional activity by PFT-α attenuates IR-induced tumor cell killing and senescence. Gain-of-function assays demonstrate that restoration of p53 expression sensitizes H1299 cells to irradiation, whereas knockdown of p53 expression by siRNA inhibits IR-induced senescence in H460 cells. Furthermore, treatment with Nutlin-3a, a small molecule inhibitor of MDM2, enhances IR-induced tumor cell killing and senescence by stabilizing the activation of the p53-p21 signaling pathway. Taken together, these findings demonstrate for the first time that pharmacological activation of p53 by Nutlin-3a can sensitize lung cancer cells to radiation therapy via promoting IR-induced premature senescence.