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Introduction Atrial fibrillation (AF) is the most common arrhythmia, with an estimated prevalence between 1–4%. On the other hand, obesity continued to be a prevalent health issue worldwide. Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis (ISTH) recommended avoiding the use of DOACs in patients with a BMI >40 or weight >120 kg because of limited clinical data in these patients. In this meta-analysis, we aimed to evaluate the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. Method We performed a comprehensive literature search using multiple databases from database inception through January 2021, for all the studies that evaluated the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. The primary outcome of interest was stroke or systemic embolism (SSE) rate. The secondary outcome was major bleeding (MB). All meta-analyses were conducted using a random-effect model. Results A total of 10 studies including 89,494 morbidly obese patients (BMI >40 or weight >120 kg) with non-valvular AF on oral anticoagulation therapy (45427 on DOACs vs. 44067 on warfarin) were included in the final analysis. One included study was a randomized controlled trial (RCT), another study was a post hoc analysis of an RCT and the rest were retrospective cohort studies. The mean follow-up period was 1.8 years (range 8 months to 3.1 years). The SSE rate was significantly lower in DOACs group compared to warfarin group (odds ratio (OR): 0.71; 95% confidence interval (CI): 0.62, 0.81; p Conclusions Our meta-analysis demonstrated that DOACs are effective and safe when compared to warfarin in morbidly obese patients. However, more large scale randomized clinical trials are needed to further evaluate the efficacy and safety of DOACs compared to warfarin in this cohort of patients. Funding Acknowledgement Type of funding sources: None. Stroke and systemic embolism eventsMajor bleeding events

UNSTRUCTURED We feel that the current COVID-19 crisis has created great uncertainty and anxiety among medical students. With medical school classes initially being conducted on the web and the approaching season of “the Match” (a uniform system by which residency candidates and residency programs in the United States simultaneously “match” with the aid of a computer algorithm to fill first-year and second-year postgraduate training positions accredited by the Accreditation Council for Graduate Medical Education), the situation did not seem to be improving. The National Resident Matching Program made an official announcement on May 26, 2020, that candidates would not be required to take or pass the United States Medical Licensing Examination Step 2 Clinical Skills (CS) examination to participate in the Match. On January 26, 2021, formal discontinuation of Step 2 CS was announced; for this reason, we have provided our perspective of possible alternative solutions to the Step 2 CS examination. A successful alternative model can be implemented in future residency match seasons as well.

We feel that the current COVID-19 crisis has created great uncertainty and anxiety among medical students. With medical school classes initially being conducted on the web and the approaching season of “the Match” (a uniform system by which residency candidates and residency programs in the United States simultaneously “match” with the aid of a computer algorithm to fill first-year and second-year postgraduate training positions accredited by the Accreditation Council for Graduate Medical Education), the situation did not seem to be improving. The National Resident Matching Program made an official announcement on May 26, 2020, that candidates would not be required to take or pass the United States Medical Licensing Examination Step 2 Clinical Skills (CS) examination to participate in the Match. On January 26, 2021, formal discontinuation of Step 2 CS was announced; for this reason, we have provided our perspective of possible alternative solutions to the Step 2 CS examination. A successful alternative model can be implemented in future residency match seasons as well.

International audience; The influence of cell confluence on the β-adrenoceptor (β-AR)/cAMP/phosphodiesterase (PDE) pathway was investigated in cultured rat aortic smooth muscle cells (RASMCs).Cells were plated either at low density (LD: 3.103 cells/cm2) or high density (HD: 3.104 cells/cm2) corresponding to non-confluent or confluent cells, respectively, on the day of experiment.β-AR-stimulated cAMP was monitored in real-time using the fluorescence resonance energy transfer (FRET)-based cAMP sensor, Epac2-camps. A brief application (15 s) of the β-AR agonist isoprenaline (Iso) induced a typical transient FRET signal, reflecting cAMP production followed by its rapid degradation. The amplitude of this response, which increased with the concentration of Iso (10 or 100 nM), was higher in HD than in LD cells, whatever the Iso concentration used. However, activation of adenylyl cyclase by L-858051 (100 µM) induced a similar saturating response in both LD and HD cells. A β1-AR antagonist (CGP 20712A, 100 nM) reduced the Iso (100 nM) response in HD but not LD cells, whereas a β2-AR antagonist (ICI 118,551, 5 nM) reduced this response in HD cells and almost abolished it in LD cells. Competitive [125I]-ICYP binding experiments with betaxolol, a β-AR ligand, identified two binding sites in HD cells, corresponding to β1- and β2-ARs with a proportion of 11% and 89%, respectively, but only one binding site in LD cells, corresponding to β2-ARs. Total cAMP-PDE activity (assessed by a radioenzymatic assay) was increased in HD cells compared to LD cells. This increase was associated with a rise in mRNA expression of five cAMP-PDEs subtypes (PDE1A, 3A, 4A, 4B and 7B) in HD cells, and a decrease in basal [cAMP]i (assessed by an EIA assay). PDE4 inhibition with Ro-20-1724 (10 µM) strongly prolonged the Iso response in LD and HD cells, whereas PDE3 inhibition with cilostamide (1 µM) slightly prolonged Iso response only in LD cells. Interestingly, inhibition of PDE4 unmasked an effect of PDE3 in HD cells. Our results show that in cultured RASMCs, the β-AR/cAMP/PDE signalling pathway is substantially modulated by the cell density. In HD cells, Iso response involves both β1- and β2-AR stimulation and is mainly controlled by PDE4, PDE3 being recruited only after PDE4 inhibition. In LD cells, Iso response involves only β2-AR stimulation and is controlled by PDE4 and to a lower degree by PDE3. This low density state is associated with an absence of membrane expression of the β1-AR, a lower cAMP-PDE activity and a higher basal [cAMP]i. This study highlights the critical role of the cellular environment in controlling the vascular β-AR signalling.

This study aimed at evaluating the cognitive levels of the questions following the reading texts of Master Class textbook. A checklist based on Bloom’s Taxonomy was the instrument used to categorize the cognitive levels of these questions. The researchers used proper statistics to rank the cognitive levels of the comprehension questions. The results showed that the author of Master Class emphasized the cognitive level of Comprehension having 52% of the questions, which was much more than the expected frequency, while wrote only 3.7% and 6% of the questions on the cognitive levels of Knowledge and Application respectively. The frequency of questions on the cognitive levels of Evaluation and Analysis were much closer to the expected frequencies. The results indicated that about 40% of the textbook’s questions emphasized higher-order thinking skills, which goes with the requirements of the revised curriculum. Evaluating and choosing a good textbook that goes with the goals of the curriculum is recommended. Such a study would shed light upon the role of textbooks in developing cognitive skills among Arab students.

Objectifs Des etudes cliniques rapportent l’utilisation d’ondes de choc de faible intensite (Li-ESWT) appliquees sur la verge pour traiter la dysfonction erectile (DE). Le mecanisme d’action de cette therapeutique innovante reste inconnu. Nous avons evalue l’efficacite des Li-ESWT dans le contexte experimental de la DE associee au diabete utilisant le rat diabetique Goto-Kakizaki (GK) et son controle normoglycemique Wistar pour preciser le mecanisme d’action des Li-ESWT. Methodes Certains rats GK ( n = 24) ont recu 2 series de traitements bi-hebdomadaires par Li-ESWT (Omnispec ED1000, Medispec), separees de 3 semaines sans traitement. Ce protocole de traitement par Li-ESWT reproduisait exactement le protocole humain. Parmi ces rats GK, certains ont egalement recu 0,3 mg/kg iv de sildenafil au moment de l’evaluation de la fonction erectile, 4 semaines apres la derniere seance par Li-ESWT, en mesurant la pression intracaverneuse lors de stimulations electriques du nerf caverneux. La reactivite en bain d’organes isoles des corps caverneux (CC) issus des memes rats a ete egalement mesuree afin d’explorer le role eventuel de la voie NO/cGMP. Resultats La fonction erectile des rats diabetiques GK est significativement diminuee en comparaison des rats controles Wistar et associee a une diminution des relaxations endothelium-dependantes, -independantes et nitrergiques des corps caverneux. Les Li-ESWT ont significativement ameliore la fonction erectile des rats diabetiques GK. De plus, le sildenafil a augmente significativement l’effet pro-erectile du traitement par Li-ESWT. Cependant, la relaxation des CC n’a pas ete amelioree par Li-ESWT, qu’elle soit endothelium-dependante, -independante ou nitrergique. Conclusion Li-ESWT ameliore la fonction erectile des rats diabetiques de type II GK. Le sildenafil associe aux Li-ESWT ameliore encore ces reponses. L’effet therapeutique des Li-ESWT est independant de la voie du NO/cGMP. D’autres etudes sont necessaires pour comprendre le mecanisme d’action des Li-ESWT.

This paper is a theoretical investigation of a method of scanning a beam of an antenna consisting of a fixed reflector and an array of elements illuminating the reflector by appropriately controlling the phase and amplitude of the signal radiating from each element. For the purpose of determining the feasibility of such a systems the two-dimensional problem is explored where a specific antenna geometry and an element radiation pattern are assumed. It was found that although the system exhibits similar performance to a system with a single radiating element when radiating a beam on axis, it could be scanned some eight beamwidths off axis without significant deterioration in characteristics. Interestingly, it was discovered that there is a separation (about 0.7\lambda in this case) between the feed elements where the sidelobes become dramatically high, analogous to grating lobes in a phased array.

International audience; Reactive oxygen species production is necessary to induce cell death following hypoxia/reoxygenation but the effect of reactive oxygen species produced during hypoxia on mitochondrial permeability transition pore (mPTP) opening and cell death is not established. Here we designed a model of hypoxia/reoxygenation in isolated cardiomyocytes measuring simultaneously reactive oxygen species production, mPTP opening and cell death in order (i) to establish a causal relationship between them, and (ii) to investigate the roles of various reactive oxygen species in mPTP opening. The percentage of cardiomyocytes exhibiting mPTP opening during reoxygenation increased with the duration of hypoxia. Antioxidants increased the time to mPTP opening when present during hypoxia but not at reoxygenation. This was associated with a drop in hydroxyl radical and hydrogen peroxide during hypoxia and the first minutes of reoxygenation. The increase in time to mPTP opening was accompanied by an improvement in cell viability reflected by maintenance of superoxide production at reoxygenation. Cyclosporin A delayed both the time to mPTP opening and cell death despite maintenance of reactive oxygen species production during hypoxia. These findings demonstrate that reactive oxygen species production precedes mPTP opening and that reactive oxygen species produced during hypoxia, particularly hydroxyl radicals and hydrogen peroxide, are necessary to induce mPTP opening which depends on hypoxia duration.

International audience; Myocardial ischemia-reperfusion injury is a major cause of morbidity and mortality in developed countries. To date, the only treatment of complete ischemia is to restore blood flow; thus the search for new cardioprotective approaches is absolutely necessary to reduce the mortality associated with myocardial ischemia. Ischemia has long been considered to result in necrotic tissue damage but the reduction in oxygen supply can also lead to apoptosis. Therefore, in the last few years, mitochondria have become the subject of growing interest in myocardial ischemia-reperfusion since they are strongly involved in the regulation of the apoptotic process. Indeed, during ischemia-reperfusion, pathological signals converge in the mitochondria to induce permeabilization of the mitochondrial membrane. Two classes of mechanisms, which are not mutually exclusive, emerged to explain mitochondrial membrane permeabilization. The first occurs via a non-specific channel known as the mitochondrial permeability transition pore (mPTP) in the inner and the outer membranes causing disruption of the impermeability of the inner membrane, and ultimately complete inhibition of mitochondrial function. The second mechanism, involving only the outer membrane, induces the release of cell death effectors. Thus, drugs able to block or to limit mitochondrial membrane permeabilization may be cytoprotective during ischemia-reperfusion. The objective of this review is to examine the pharmacological strategies capable of inhibiting mitochondrial membrane permeabilization induced by myocardial ischemia-reperfusion.

International audience; Myocardial ischemia-reperfusion injury is a major cause of morbidity and mortality in developed countries. To date, the only treatment of complete ischemia is to restore blood flow; thus the search for new cardioprotective approaches is absolutely necessary to reduce the mortality associated with myocardial ischemia. Ischemia has long been considered to result in necrotic tissue damage but the reduction in oxygen supply can also lead to apoptosis. Therefore, in the last few years, mitochondria have become the subject of growing interest in myocardial ischemia-reperfusion since they are strongly involved in the regulation of the apoptotic process. Indeed, during ischemia-reperfusion, pathological signals converge in the mitochondria to induce permeabilization of the mitochondrial membrane. Two classes of mechanisms, which are not mutually exclusive, emerged to explain mitochondrial membrane permeabilization. The first occurs via a non-specific channel known as the mitochondrial permeability transition pore (mPTP) in the inner and the outer membranes causing disruption of the impermeability of the inner membrane, and ultimately complete inhibition of mitochondrial function. The second mechanism, involving only the outer membrane, induces the release of cell death effectors. Thus, drugs able to block or to limit mitochondrial membrane permeabilization may be cytoprotective during ischemia-reperfusion. The objective of this review is to examine the pharmacological strategies capable of inhibiting mitochondrial membrane permeabilization induced by myocardial ischemia-reperfusion.