Revisiting the Merits of a Mandatory Large Group Classroom Learning Format: an MD-MBA Perspective

The role of classroom learning in medical education is rapidly changing. To promote active learning and reduce student stress, medical schools have adopted policies such as pass/fail curriculums and recorded lectures. These policies along with the rising importance of the USMLE (United States Medical Licensing Examination) exams have made asynchronous learning popular to the detriment of classroom learning. In contrast to this model, modern day business schools employ mandatory large group classes with assigned seating and cold-calling. Despite similar student demographics, medical and business schools have adopted vastly different approaches to the classroom. When examining the classroom dynamic at business schools with mandatory classes, it is evident that there’s an abundance of engaging discourse and peer learning objectives that medical schools share. Mandatory classes leverage the network effect just like social media forums such as Facebook and Twitter. That is, the value of a classroom discussion increases when more students are present to participate. At a time when students are savvy consumers of knowledge, the classroom is competing against an explosion of study aids dedicated to USMLE preparation. Certainly, the purpose of medical school is not solely about the efficient transfer of knowledge – but to train authentic, competent, and complete physicians. To accomplish this, we must promote the inimitable and deeply personal interactions amongst faculty and students. When viewed through this lens, mandatory classes might just be a way for medical schools to leverage their competitive advantage in educating the complete physician

Management of Urinoma Formation After Laparoscopic Cryoablation of Renal Cyst

Aim: To describe the presentation and management of a urinoma developing as a complication of laparoscopic cryoablation of a Bosniak III renal cyst. Case: A 74-year-old woman presented with acute onset of severe left lower abdominal pain 1 day after a laparoscopic cryoablation of a 3 cm multilobular left cystic renal mass. CT revealed a perinephric fluid collection adjacent to the lower pole of the left kidney with active urinary extravasation seen on retrograde pyelogram, confirming the presence of an urinoma. A retrograde ureteral stent was placed with complete resolution of symptoms and the patient was discharged on the first postoperative day. Follow-up CT scans 2 weeks and 2 months after the procedure showed significant reduction of urinoma size, and retrograde pyelogram 5 months after showed resolution of urinoma. Conclusion: Although often discussed as a possible complication, to our knowledge there are no published case reports in the literature regarding the formation of a urinoma after laparoscopic cryoablation. Furthermore, no data exist on the management of a urinoma after laparoscopic cryoablation. We propose that ureteral stenting is a reasonable approach to the management of this condition

Measuring change in health status of older adults at the population level: The transition probability model

BACKGROUND: The current demographic transition will lead to increasing demands on health services. However, debate exists as to the role age plays relative to co-morbidity in terms of health services utilization. While age has been identified as a critical factor in health services utilization, health services utilization is not simply an outcome of ill health, nor is it an inevitable outcome of aging. Most data on health service utilization studies assess utilization at one point in time, and does not examine transitions in health service utilization. We sought to measure health services utilization and to investigate patterns in the transition of levels of utilization and outcomes associated with different levels of utilization. METHODS: We conducted a population-based retrospective cohort study of all Ontario residents aged 65+ eligible for public healthcare coverage from January 1998-December 2006. The main outcome measure was total number of utilization events. The total is computed by summing, on a per annum basis, the number of family physician visits, specialist visits, Emergency Department visits, drug claims, lab claims, X-rays, CT scans, MRI scans, and inpatient admissions. Three categories of utilization were created: low, moderate, and high. RESULTS: There is heterogeneity in health services utilization across the late lifespan. Utilization increased consistently in the 9-year study period. The probability of remaining at the high utilization category when the person was in the high category the previous year was more than 0.70 for both males and females and for all age groups. Overall healthcare utilization increases more rapidly among the high users compared to the low users. There was negligible probability for moving from high to low utilization category. Probability of death increased exponentially as age increased. Older adults in the low utilization category had the lowest probability of death. The number of male nonagenarians increased more rapidly than female nonagenarians. CONCLUSION: There are measurable and identifiable differences in the patterns of health services utilization among older adults. This data will permit clinicians and policy makers to tailor interventions appropriate to the risk class of patients

Dompep-a general method for predicting modular domain-mediated protein-protein interactions

Protein-protein interactions (PPIs) are frequently mediated by the binding of a modular domain in one protein to a short, linear peptide motif in its partner. The advent of proteomic methods such as peptide and protein arrays has led to the accumulation of a wealth of interaction data for modular interaction domains. Although several computational programs have been developed to predict modular domain-mediated PPI events, they are often restricted to a given domain type. We describe DomPep, a method that can potentially be used to predict PPIs mediated by any modular domains. DomPep combines proteomic data with sequence information to achieve high accuracy and high coverage in PPI prediction. Proteomic binding data were employed to determine a simple yet novel parameter Ligand-Binding Similarity which, in turn, is used to calibrate Domain Sequence Identity and Position-Weighted-Matrix distance, two parameters that are used in constructing prediction models. Moreover, DomPep can be used to predict PPIs for both domains with experimental binding data and those without. Using the PDZ and SH2 domain families as test cases, we show that DomPep can predict PPIs with accuracies superior to existing methods. To evaluate DomPep as a discovery tool, we deployed DomPep to identify interactions mediated by three human PDZ domains. Subsequent in-solution binding assays validated the high accuracy of DomPep in predicting authentic PPIs at the proteome scale. Because DomPep makes use of only interaction data and the primary sequence of a domain, it can be readily expanded to include other types of modular domains. © 2011 Li et al

Numb regulates cell–cell adhesion and polarity in response to tyrosine kinase signalling

Epithelial-mesenchymal transition (EMT), which can be caused by aberrant tyrosine kinase signalling, marks epithelial tumour progression and metastasis, yet the underlying molecular mechanism is not fully understood. Here, we report that Numb interacts with E-cadherin (E-cad) through its phosphotyrosine-binding domain (PTB) and thereby regulates the localization of E-cad to the lateral domain of epithelial cell–cell junction. Moreover, Numb engages the polarity complex Par3–aPKC–Par6 by binding to Par3 in polarized Madin-Darby canine kidney cells. Intriguingly, after Src activation or hepatocyte growth factor (HGF) treatment, Numb decouples from E-cad and Par3 and associates preferably with aPKC–Par6. Binding of Numb to aPKC is necessary for sequestering the latter in the cytosol during HGF-induced EMT. Knockdown of Numb by small hairpin RNA caused a basolateral-to-apicolateral translocation of E-cad and β-catenin accompanied by elevated actin polymerization, accumulation of Par3 and aPKC in the nucleus, an enhanced sensitivity to HGF-induced cell scattering, a decrease in cell–cell adhesion, and an increase in cell migration. Our work identifies Numb as an important regulator of epithelial polarity and cell–cell adhesion and a sensor of HGF signalling or Src activity during EMT

A C. elegans Model of Nicotine-Dependent Behavior: Regulation by TRP-Family Channels

Nicotine, the primary addictive substance in tobacco, induces profound behavioral responses in mammals, but the underlying genetic mechanisms are not well understood. Here we develop a C. elegans model of nicotine-dependent behavior. We show that worms exhibit behavioral responses to nicotine that parallel those observed in mammals, including acute response, tolerance, withdrawal, and sensitization. These nicotine responses require nicotinic acetylcholine receptor (nAChR) family genes that are known to mediate nicotine dependence in mammals, suggesting functional conservation of nAChRs in nicotine responses. Importantly, we find that mutant worms lacking TRPC (transient receptor potential canonical) channels are defective in their response to nicotine and that such a defect can be rescued by a human TRPC channel, revealing an unexpected role for TRPC channels in regulating nicotine-dependent behavior. Thus, C. elegans can be used to characterize known genes as well as to identify new genes regulating nicotine responses

A C. elegans Model of Nicotine-Dependent Behavior: Regulation by TRP-Family Channels

Nicotine, the primary addictive substance in tobacco, induces profound behavioral responses in mammals, but the underlying genetic mechanisms are not well understood. Here we develop a C. elegans model of nicotine-dependent behavior. We show that worms exhibit behavioral responses to nicotine that parallel those observed in mammals, including acute response, tolerance, withdrawal, and sensitization. These nicotine responses require nicotinic acetylcholine receptor (nAChR) family genes that are known to mediate nicotine dependence in mammals, suggesting functional conservation of nAChRs in nicotine responses. Importantly, we find that mutant worms lacking TRPC (transient receptor potential canonical) channels are defective in their response to nicotine and that such a defect can be rescued by a human TRPC channel, revealing an unexpected role for TRPC channels in regulating nicotine-dependent behavior. Thus, C. elegans can be used to characterize known genes as well as to identify new genes regulating nicotine responses

Cardiovascular Risk Factors Are Associated With Future Cancer

BACKGROUND The extent to which co-occurrence of cardiovascular disease (CVD) and cancer is due to shared risk factors or other mechanisms is unknown. OBJECTIVES This study investigated the association of standard CVD risk factors, CVD biomarkers, pre-existing CVD, and ideal cardiovascular (CV) health metrics with the development of future cancer. METHODS This study prospectively followed Framingham Heart Study and PREVEND (Prevention of Renal and Vascular End-Stage Disease) study participants free of cancer at baseline and ascertained histology-proven cancer. This study assessed the association of baseline CV risk factors, 10-year atherosclerotic (ASCVD) risk score, established CVD biomarkers, prevalent CVD, and the American Heart Association (AHA) Life's Simple 7 CV health score with incident cancer using multivariable Cox models. Analyses of interim CVD events with incident cancer used time-dependent covariates. RESULTS Among 20,305 participants (mean age 50 +/- 14 years; 54% women), 2,548 incident cancer cases occurred over a median follow-up of 15.0 years (quartile 1 to 3: 13.3 to 15.0 years). Traditional CVD risk factors, including age, sex, and smoking status, were independently associated with cancer (p < 0.001 for all). Estimated 10-year ASCVD risk was also associated with future cancer (hazard ratio [HR]: 1.16 per 5% increase in risk; 95% confidence interval [CI] 1.14 to 1.17; p < 0.001). The study found that natriuretic peptides (tertile 3 vs. tertite 1; HR: 1.40; 95% 0:1.03 to 1.91; p 0.035) were associated with incident cancer but not high-sensitivity troponin (p 0.47). Prevalent CVD and the development of interim CV events were not associated with higher risk of subsequent cancer. However, ideal CV health was associated with tower future cancer risk (HR: 0.95 per 1-point increase in the AHA health score; 95% CI: 0.92 to 0.99; p = 0.009). CONCLUSIONS CVD risk, as captured by traditional CVD risk factors, 10-year ASCVD risk score, and natriuretic peptide concentrations are associated with increased risk of future cancer. Conversely, a heart healthy lifestyle is associated with a lower risk of future cancer. These data suggest that the association between CVD and future cancer is attributable to shared risk factors. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Cardiovascular disease related circulating biomarkers and cancer incidence and mortality:is there an association?

Aims Recent studies suggest an association between cardiovascular disease (CVD) and cancer incidence/mortality, but the pathophysiological mechanisms underlying these associations are unclear. We aimed to examine biomarkers previously associated with CVD and study their association with incident cancer and cancer-related death in a prospective cohort study. Methods and results We used a proteomic platform to measure 71 cardiovascular biomarkers among 5032 participants in the Framingham Heart Study who were free of cancer at baseline. We used multivariable-adjusted Cox models to examine the association of circulating protein biomarkers with risk of cancer incidence and mortality. To account for multiple testing, we set a 2-sided false discovery rat