The long-term impact of team-based learning on medical students' team performance scores and on their peer evaluation scores.

BACKGROUND: The Faculty of Medicine at the American University of Beirut implemented a new medical curriculum, which included 90 team-based learning (TBL) sessions in years 1 and 2 of medical school. METHODS: A validated team performance scale (TPS) and peer evaluation of communication skills, professionalism and personal development were collected at different time points during the two years. Grades on the individual and group readiness assurance tests and an evaluation form were collected after every TBL session. RESULTS: Students generally positively evaluated most TBL sessions as promoters of critical thinking and appreciated the self-learning experience, though they preferred and had better individual grades on those that entailed preparation of didactic lectures. There was a sustained and cumulative improvement in teamwork skills over time. Similar improvement was noted with peer evaluations of communication skills, professionalism, and personal development over time. CONCLUSIONS: This is the first report about such a longitudinal follow-up of medical students who were exposed to a large number of TBL sessions over two years. The results support the suggestion that TBL improves medical students' team dynamics and their perceived self-learning, problem solving and communication skills, as well as their professionalism and personal development.

Podocyturia: an earlier biomarker of cardiovascular outcomes.

Urinary podocin and nephrin mRNAs (podocyturia), as candidate biomarkers of endothelial/podocyte injury, were measured by quantitative PCR in Type II diabetics with normal albumin excretion rates (AER) at baseline, at 3-4 years, and at 7 years. Development of cardiovascular disease (CVD) was collected as outcome. Visit 1 podocyturia was significantly higher in subjects who subsequently developed CVD versus those who did not. Visit 1 AER terciles exhibited similar time to CVD, in contrast with stepwise and substantial increases in CVD events predicted by Visit 1 podocyturia terciles. Covariate-adjusted hazard ratios were highest for podocin, intermediate for nephrin mRNAs, and lowest for AER. Podocyturia was also measured in patients with and without significant coronary obstruction, and in 480 normoalbuminuric subjects at the enrolment visit to the Multi-Ethnic Study of Atherosclerosis (MESA). Podocyturia > 3 × 106 copies was associated with presence of obstructive coronary artery disease. In the MESA population, Visit 1 podocyturia was significantly higher in men, subjects with elevated BMI, and those with Type II DM. Conclusions: Podocyturia may be an earlier predictor of cardiovascular events than moderate albuminuria; it is significantly higher in patients with obstructive coronary artery disease, and in subjects with established risk factors for CVD.

A 5-year survey of biopsy proven kidney diseases in Lebanon: significant variation in prevalence of primary glomerular diseases by age, population structure and consanguinity.

BACKGROUND: Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years' detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon. METHODS: Records of renal biopsies analysed at the American University of Beirut Medical Center, Hotel Dieu de France Hospital and the Institut National de Pathologie from January 2003 till December 2007 were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Religious affiliation and parents' consanguinity were recorded when feasible. RESULTS: The mean age at renal biopsy was 36.76 ± 20 years (range 1-84). The most common diagnosis was mesangioproliferative glomerulonephritis (GN; 20%), followed by focal segmental glomerulosclerosis (13.2%). While there were no differences in age, gender or indications for biopsy among different religious affiliations, mesangioproliferative GN was significantly more frequent among Muslims (P = 0.039) and offspring of consanguineous unions (P = 0.036). On the other hand, focal segmental glomerulosclerosis was most prevalent in Christians (P < 0.001). CONCLUSIONS: Variation in the distribution of diagnoses between Muslim and Christian groups likely reflects differences in population structure and ancestry. In particular, the increased prevalence of mesangioproliferative GN among offspring of consanguineous unions in Muslims suggests a recessive genetic component to this disease which may be identified via homozygosity mapping. These findings have important implications for formulating renal health policies and designing research studies in this population.

Regionalizing healthcare: a vision for transforming Lebanon into a regional academic hub.

BACKGROUND: Lebanon suffers from a large scale emigration of physicians coupled with an oversaturation of the physician job market. Lebanon is currently witnessing an expansion of its medical education capacity with the establishment of new private medical schools, raising the fears of a worsening market oversaturation. DISCUSSION: The neighboring Arabian Gulf countries are suffering from a serious shortage of clinicians and academicians. In spite of their enormous investments in educational, clinical and research collaborative initiatives with some of the most renowned North American medical schools and institutions, their ability to recruit and retain highly qualified clinicians and academicians remains a major challenge. Lebanese universities have the opportunity to establish triangular collaborations with the Gulf regional medical centers and their North American partners. They could achieve this goal by tapping into the globalized and high quality Lebanese physician workforce and consequently regionalize healthcare delivery in the Middle East. SUMMARY: By recruiting its globalized and high quality physician workforce to establish collaborations with the Gulf regional, Lebanon could become a regional "academic hub".

Effect of Targeted Curricular Reform on the Learning Environment, Student Empathy, and Hidden Curriculum in a Medical School: A 7-Year Longitudinal Study.

OBJECTIVE: The American University of Beirut Faculty of Medicine follows the American model of medical education. In 2013-2014, a carefully designed new curriculum replaced the previous, largely traditional curriculum, and aimed to improve student wellbeing, upgrade the learning environment, enhance student empathy, and counter the negative influences of the hidden curriculum. This longitudinal study assessed the effectiveness of the new curriculum in those domains over a period of 7 years. METHODS: Three cohorts of medical students anonymously filled a paper-based survey at the end of years 1, 2, 3, and 4 of the 4-year curriculum. These included the Class of 2016, the last batch of students who followed the old curriculum, and 2 cohorts that followed the new curriculum (Class of 2017 and Class of 2019). The perceived learning environment was assessed by the Dundee Ready Education Environment Measurement survey; the student's empathy was assessed by the Jefferson Scale of Physician Empathy-Student version; and the hidden curriculum was examined using a locally developed survey. RESULTS: The scores on the learning environment survey were significantly higher among the cohorts following the new curriculum relative to those following the old curriculum. Similar significant results appeared when looking at each of the subscales for the learning environment. The students' empathy scores were also significantly higher in both cohorts of the new curriculum when compared with the old curriculum. Nevertheless, there was a significant decrease in empathy in both third and fourth years relative to second year. The new curriculum also improved aspects of the students' perceptions and responses to the hidden curriculum. CONCLUSION: In conclusion, a well-planned and well-researched curricular intervention, based on sound educational theories, practices, and standards can indeed transform the learning environment, as well as the attitudes, values, and experiences of medical students.

Modulation of COX-2 expression by statins in human monocytic cells.

Macrophage cyclooxygenase-2 (COX-2) plays an important role in prostaglandin E2 and thromboxane A2 production. Statins are inhibitors of HMG CoA (3-Hydroxy-3-methylglutaryl coenzyme A) reductases and cholesterol synthesis, which block the expression of several inflammatory proteins independent of their capacity to lower endogenous cholesterol. In the present study, we investigated the effect of simvastatin and mevastatin on COX-2 induction in human monocytic cell line U937 and analyzed the underlying mechanisms. Pretreatment of U937 cells with simvastatin or mevastatin for 24 h resulted in a significant reduction in the lipopolysaccharide (LPS)-dependent induction of prostaglandin E2, thromboxane A2 synthesis, and COX-2 expression. Mevalonate, the direct metabolite of HMG CoA reductase, and farnesyl pyrophosphate and geranylgeranyl-pyrophosphate, intermediates of the mevalonate pathway, significantly reversed the inhibitory effect of statins on COX-2. An inhibitor of geranylgeranyl transferases, GGTI-286 mimicked the effect of statins on COX-2 expression. Cytonecrotic factor-1 increased LPS-dependent expression of COX-2. Treatment of cells with NSC 23766, an inhibitor of Rac, which we demonstrated to block Rac 2 activation, resulted in an inhibition of the LPS-dependent expression of COX-2. Whereas no effect was obtained with RhoA/C blocker, C3 exoenzyme. Gel retardation experiments and NFkappaB-p65 transcription factor assay showed that simvastatin and NSC 23766 decrease significantly NF-kappaB complex formation. In macrophages, the antiinflammatory effects of statins are mediated in part through the inhibition of COX-2 and prostanoids. Rac GTPase protein is identified as one of the targets of statins in this regulation.

Physician assessment of stroke risk in hypertensive patients in the Middle East and Africa: results of the action survey.

OBJECTIVES: In the absence of reliable, contemporary national data, the ACTION survey was designed to: a) provide preliminary data on stroke risk in the MEA (Middle East and Africa); b) describe the contribution of specific cardiovascular risk factors; 3) assess blood pressure (BP) control. DESIGN AND PATIENTS: This was a multi-center observational study in nine countries in the MEA region. From 2003 to 2005, 562 physicians from a variety of specialties recorded observations of cardiovascular risk factors in 4,747 hypertensive patients, aged 54-80 years. The 10-year absolute stroke risk was calculated using a scoring system based on the Framingham Heart Study observations, and comparisons made with an age-matched cohort. RESULTS: The mean 10-year stroke risk was estimated at 22.7% and was significantly higher for men (25.4%) than for women (19.5%) (P < .001) and for diabetics (28.2%) than for non-diabetics (19.4%) (P < .001). Compared with an age-matched Framingham cohort, the estimated stroke risk in our population was almost double, and was significantly higher for females (212%) than for males (192%) (P < .001). Hypertension, diabetes, left ventricular hypertrophy, and smoking were major contributing risk factors, as were physical inactivity and elevated cholesterol. Blood pressure was controlled in only 18% of the population and in 12% of diabetics. CONCLUSION: Physicians of all specialties were willing to participate in stroke risk assessment. The risk of stroke in hypertensive patients in the MEA region is high, and is higher than would be predicted using Framingham data, particularly for females. Hypertension appears to be poorly controlled in more than 80% of hypertensive patients in the MEA region.

Effect of salt intake on beat-to-beat blood pressure nonlinear dynamics and entropy in salt-sensitive versus salt-protected rats.

Blood pressure exhibits substantial short- and long-term variability (BPV). We assessed the hypothesis that the complexity of beat-to-beat BPV will be differentially altered in salt-sensitive hypertensive Dahl rats (SS) versus rats protected from salt-induced hypertension (SSBN13) maintained on high-salt versus low-salt diet. Beat-to-beat systolic and diastolic BP series from nine SS and six SSBN13 rats (http://www.physionet.org) were analyzed following 9 weeks on low salt and repeated after 2 weeks on high salt. BP complexity was quantified by detrended fluctuation analysis (DFA), short- and long-range scaling exponents (αS and αL), sample entropy (SampEn), and traditional standard deviation (SD) and coefficient of variation (CV(%)). Mean systolic and diastolic BP increased on high-salt diet (P < 0.01) particularly for SS rats. SD and CV(%) were similar across groups irrespective of diet. Salt-sensitive and -protected rats exhibited similar complexity indices on low-salt diet. On high salt, (1) SS rats showed increased scaling exponents or smoother, systolic (P = 0.007 [αL]) and diastolic (P = 0.008 [αL]) BP series; (2) salt-protected rats showed lower SampEn (less complex) systolic and diastolic BP (P = 0.046); and (3) compared to protected SSBN13 rats, SS showed higher αL for systolic (P = 0.01) and diastolic (P = 0.005) BP Hypertensive SS rats are more susceptible to high salt with a greater rise in mean BP and reduced complexity. Comparable mean pressures in sensitive and protective rats when on low-salt diet coupled with similar BPV dynamics suggest a protective role of low-salt intake in hypertensive rats. This effect likely reflects better coupling of biologic oscillators.

Isoprostanes and the kidney.

Isoprostanes are not mere bystanders of oxidative injury, but possess potent biological activity and may thus contribute to the pathophysiology of various disorders associated with an increase in free radical formation. 15-F2t-IsoP (8-iso-prostaglandin F2) and 15-E2t-IsoP (8-iso-prostaglandin E2), two of the most abundant isoprostanes, are potent vasoconstrictors in various vascular beds, including the kidney. Since their discovery, numerous studies have aimed to define the receptors through which isoprostanes exert their effects. Whether the thromboxane receptor and/or other prostaglandin receptors mediate the actions of isoprostanes, or whether these compounds interact with their own unique receptors, remains to be clarified. Regardless of their exact mode of action, isoprostanes are being implicated in the pathophysiology of a variety of diseases, and their discovery might give rise to novel therapies for these diseases. Here we describe early studies that defined the vasoactive properties of isoprostanes in the kidney, and subsequent discoveries relating to their renal actions and pathophysiologic significance.

Cytokine imbalance in acute coronary syndrome.

The excessive mortality of coronary heart disease is attributed primarily to rupture and thrombotic transformation of the atherosclerotic plaque. Inflammation plays a critical role in plaque destabilization and vulnerability. Inflammation is not confined to the culprit segment but is convincingly widespread in the coronary and remote vascular beds. Systemic inflammatory, thrombotic and hemodynamic factors are relevant to the pathological and clinical outcome. In addition to their fundamental role in thrombosis, there is ample evidence that platelets contribute significantly to promoting plaque inflammation. A new paradigm of unbalanced cytokine-mediated inflammation is emerging, providing diagnostic and therapeutic opportunity for intervention. Amplifying intrinsic anti-inflammatory mechanisms constitutes attractive avenues for future investigation.

Molecular pharmacology of isoprostanes in vascular smooth muscle.

Isoprostanes are marker of lipid peroxidation and are produced after free-radical attack of membrane lipids. In addition, they are biologically active and are essentially vaso- and broncho-constrictor. Their smooth muscle constrictor actions are closely linked to the activation of the thromboxane A(2) receptor, but also involve a distinct receptor not yet identified. The response of vascular smooth muscle to isoprostanes is subclass-specific (F-series versus E-series isoprostanes) and cell- and species-related. In this review, we will address the vascular actions of isoprostanes and their possible role in vascular physiology and pathophysiology.

Inhibition of 5-lipoxygenase activating protein decreases proteinuria in diabetic rats.

BACKGROUND: The binding of 5-lipoxygenase (5-LO) to the 5-LO activating protein (FLAP) is a prerequisite for subsequent formation of leukotrienes (LT) from arachidonic acid. We have shown that FLAP antagonist administration decreased proteinuria in glomerulonephritic patients. In this follow-up study, we assessed the role for FLAP in a rat model of streptozotocin-induced diabetic nephropathy. METHODS: Diabetic rats were treated for 4 weeks with FLAP (BAY X-1005, 200 mg/kg) or 5-LO (Zileuton, 80 mg/Kg) antagonists. Proteinuria, renal function and LT production was assessed. We also determined protein permeability of cultured glomerular endothelial cells (which possess no 5-LO) by measuring their permeability to radiolabeled albumin with and without FLAP antagonists. RESULTS: FLAP mRNA levels increased dramatically in glomeruli from diabetic animals compared to controls. Inhibition of FLAP (but not inhibition of 5-LO) reduced proteinuria, with no effect on estimated glomerular filtration rate. Interestingly, diabetes-induced rises in urinary excretion and glomerular production of leukotrienes were not modified by the inhibitors. Increased FLAP expression in glomerular endothelial cells in culture was associated with an increase in albumin permeability, and this increase was abolished by FLAP antagonists. On the other hand, addition of LTA(4) led to increases in leukotriene formation and in permeability. This increase in permeability was also reduced by co-incubation with FLAP antagonists, whereas the increase in leukotriene synthesis was not modified. CONCLUSIONS: These results suggest a role for FLAP other than the activation of 5-LO, possibly in protein handling, and point to FLAP antagonists as anti-proteinuric agents.

Increased 5-lipoxygenase activating protein in immune-mediated experimental nephritis.

BACKGROUND: The binding of 5-lipoxygenase (5-LO) to 5-LO activating protein (FLAP) is a prerequisite for subsequent formation of leukotrienes from arachidonic acid. METHODS: We investigated the localization of FLAP in a rat model of accelerated anti-glomerular basement membrane nephritis and protein expression in cultured rat glomerular endothelial cells. RESULTS: As expected, 5-LO staining was intense and localized exclusively to perinuclear region and inside the nucleus of leukocytes and macrophages. In these cells, FLAP immunoreactivity co-localized with that of 5-LO, and was restricted to nuclear envelope. Surprisingly, intense nuclear and cytoplasmic staining for FLAP was also observed in glomerular endothelial cells in early experimental glomerulonephritis. Although 5-LO and FLAP mRNA were detected in cultured rat glomerular endothelial cells by RT-PCR, Western blot revealed only FLAP and no 5-LO protein. FLAP protein was regulated in glomerular endothelial cells by the proinflammatory cytokine, interferon-gamma, in a dose-dependent manner. CONCLUSION: The unexpected discovery of FLAP in glomerular endothelial cells in this model of glomerulonephritis, coupled with our demonstration that oral FLAP antagonist therapy reduces proteinuria in human glomerulonephritis and animal models of diabetes, provides further impetus to examine the role of this pro-inflammatory protein in glomerular immune injury.

Crowd-funded micro-grants for genomics and "big data": an actionable idea connecting small (artisan) science, infrastructure science, and citizen philanthropy.

Biomedical science in the 21(st) century is embedded in, and draws from, a digital commons and "Big Data" created by high-throughput Omics technologies such as genomics. Classic Edisonian metaphors of science and scientists (i.e., "the lone genius" or other narrow definitions of expertise) are ill equipped to harness the vast promises of the 21(st) century digital commons. Moreover, in medicine and life sciences, experts often under-appreciate the important contributions made by citizen scholars and lead users of innovations to design innovative products and co-create new knowledge. We believe there are a large number of users waiting to be mobilized so as to engage with Big Data as citizen scientists-only if some funding were available. Yet many of these scholars may not meet the meta-criteria used to judge expertise, such as a track record in obtaining large research grants or a traditional academic curriculum vitae. This innovation research article describes a novel idea and action framework: micro-grants, each worth $1000, for genomics and Big Data. Though a relatively small amount at first glance, this far exceeds the annual income of the "bottom one billion"-the 1.4 billion people living below the extreme poverty level defined by the World Bank ($1.25/day). We describe two types of micro-grants. Type 1 micro-grants can be awarded through established funding agencies and philanthropies that create micro-granting programs to fund a broad and highly diverse array of small artisan labs and citizen scholars to connect genomics and Big Data with new models of discovery such as open user innovation. Type 2 micro-grants can be funded by existing or new science observatories and citizen think tanks through crowd-funding mechanisms described herein. Type 2 micro-grants would also facilitate global health diplomacy by co-creating crowd-funded micro-granting programs across nation-states in regions facing political and financial instability, while sharing similar disease burdens, therapeutics, and diagnostic needs. We report the creation of ten Type 2 micro-grants for citizen science and artisan labs to be administered by the nonprofit Data-Enabled Life Sciences Alliance International (DELSA Global, Seattle). Our hope is that these micro-grants will spur novel forms of disruptive innovation and genomics translation by artisan scientists and citizen scholars alike. We conclude with a neglected voice from the global health frontlines, the American University of Iraq in Sulaimani, and suggest that many similar global regions are now poised for micro-grant enabled collective innovation to harness the 21(st) century digital commons.

Measuring filtration function in clinical practice.

PURPOSE OF REVIEW: The global prevalence of chronic kidney disease is increasing, as are its complications. Central to the diagnosis, evaluation and management of chronic kidney disease is the estimation of glomerular filtration rate. This article summarizes the various equations used to estimate filtration function and the performance of each in clinical practice. RECENT FINDINGS: During the past year the prediction equations to estimate glomerular filtration rate, especially the Modification of Diet in Renal Disease Study equation, continued to receive much interest. Many studies have compared the performance of the Modification of Diet in Renal Disease Study equation and the Cockcroft-Gault equation. The performance of these equations in various patient populations, such as patients with advanced heart failure, diabetic patients, renal transplantation patients, and the healthy general population, has been extensively studied. Overall, the Modification of Diet in Renal Disease Study equation has had an acceptable validity and has outperformed the Cockcroft-Gault equation in the various populations, but with some limitations that the physician should account for in clinical practice. SUMMARY: The use of the prediction equations to estimate glomerular filtration rate, especially the Modification of Diet in Renal Disease Study equation, should be implemented more frequently in clinical practice. An ever increasing number of studies has validated its use in different patient populations.