Exercise promotes learning and memory formation. These effects depend on increases in hippocampal BDNF, a growth factor associated with cognitive improvement and the alleviation of depression symptoms. Identifying molecules that are produced during exercise and that mediate hippocampal Bdnf expression will allow us to harness the therapeutic potential of exercise. Here, we report that an endogenous molecule produced during exercise in male mice induces the Mus musculus Bdnf gene and promotes learning and memory formation. The metabolite lactate, which is released during exercise by the muscles, crosses the blood-brain barrier and induces Bdnf expression and TRKB signaling in the hippocampus. Indeed, we find that lactate-dependent increases in BDNF are associated with improved spatial learning and memory retention. The action of lactate is dependent on the activation of the Sirtuin1 deacetylase. SIRT1 increases the levels of the transcriptional coactivator PGC1a and the secreted molecule FNDC5, known to mediate Bdnf expression. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF, and identify lactate as a potential endogenous molecule that may have therapeutic value for CNS diseases in which BDNF signaling is disrupted.It is established that exercise promotes learning and memory formation and alleviates the symptoms of depression. These effects are mediated through inducing Bdnf expression and signaling in the hippocampus. Understanding how exercise induces Bdnf and identifying the molecules that mediate this induction will allow us to design therapeutic strategies that can mimic the effects of exercise on the brain, especially for patients with CNS disorders characterized by a decrease in Bdnf expression and who cannot exercise because of their conditions. We identify lactate as an endogenous metabolite that is produced during exercise, crosses the blood-brain barrier and promotes hippocampal dependent learning and memory in a BDNF-dependent manner. Our work identifies lactate as a component of the "exercise pill."

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BackgroundCOVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population.MethodsA retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation.Results242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation.ConclusionThe use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.

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Objective: Since the emergence of the COVID-19 pandemic at the end of 2019, the number of affected cases has not stopped rising. Similarly, the number of scientific publications and pre-prints has been increasing exponentially, with an effort to understand this disease more and find a proper solution. The purpose of this article is to review the current understanding of the novel coronavirus. Background: The latest COVID-19 pandemic caused by the SARS-CoV-2 has spread globally ever since it emerged in Wuhan's city in China. This rapidly spreading disease has changed our lives in unimaginable ways, spreading fear and uncertainty due to the lack of knowledge and the flooding with new information, which lacks the scientific method and cannot be critically appraised. The purpose of this article is to gather some of the best knowledge that has been published so far in a unified narrative review, making it easy for the scientific community to review the most accurate and recent understandings about COVID-19. Methods: We screened relevant articles using a specified number of keywords and specific databases, including PubMed and Embase. We selected peer-reviewed English published material related to the topic, except for a few pre-prints that we deemed necessary to include. We also screened the reference lists of these articles to find relevant publications with the same criteria. Discussion: This narrative overview comprises several subsections that discuss the epidemiology, virology, pathogenesis, clinical manifestations, diagnostic methods, and management of the disease. We also presented a section on the implications of the disease in pregnancy. We wrapped up the review with a special division regarding the response to COVID-19,  which has been diverse in different countries. Conclusion: COVID-19 has been a serious global health threat with a high transmission and case fatality rate, particularly in vulnerable populations. Epidemiologic models have so far guided the response, but they need to be interpreted carefully, with an understanding of their limitations. The disease's response has varied among different countries; with no current vaccine or standard treatment, the world stands in fear, maximizing preventive strategies to reduce the damages caused by this virus. This manuscript presents a summary of everything that is so far known about COVID-19 to make it easier for the medical community to overview the disease that has changed the world.

Severe tricuspid regurgitation (TR) is an undertreated common pathology associated with significant morbidity and mortality. Classically, surgical repair or valve replacement were the only therapeutic options and are associated with up to 10% postprocedural mortality. Transcatheter tricuspid valve interventions are a novel and effective therapeutic option for the treatment of significant TR. Several devices have been developed with different mechanisms of action. They are classified as annuloplasty devices, replacement devices, caval valve implantation and coaptation devices. In this review, we provide a step-by-step description of the procedural steps and techniques of every device along with video support.

Background COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. Purpose Currently, prophylactic dose anticoagulation is considered the standard of care antithrombotic regimen in hospitalised patients with COVID-19. However, high-quality data about the subject is unavailable. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population. Methods A retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation. Results 242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation. Conclusion The use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection. Funding Acknowledgement Type of funding sources: None.

Objective: The purpose of this article is to review the cases of myocarditis in COVID-19 patients and synthesize the current understanding regarding the presentation, diagnosis, and management of myocarditis in the setting of COVID-19 disease. Background: The novel coronavirus disease has shown serious implications for the cardiovascular system, including acute myocardial injury, arrhythmias, venous thromboembolism, and myocarditis. Several cases of myocarditis in COVID-19 patients have been reported since the disease's emergence at the end of 2019. The diagnostic approach and management have been variable. The purpose of this narrative review is to gather the most reliable published material regarding myocarditis in COVID-19 and present it as an overview to simplify the current understanding we have of this disease. Methods: We screened PubMed, Scopus, and Embase. We then selected peer-reviewed and pre-print articles published in English that were related to the involvement of the cardiovascular system in COVID-19, with a focus on myocarditis. We included case reports describing myocarditis in COVID-19 patients and summarized their clinical presentation, diagnosis, and management. References of the selected articles were also screened, and some were included when relevant. Discussion: This article is subdivided into sections that discuss the clinical presentation of COVID-19 myocarditis and move on to various diagnostic approaches and management options. Each subsection presents a brief literature review followed by a summary and interpretation of what was found in the reported cases. Conclusion: After noticing the involvement of the cardiovascular system in COVID-19 patients, specifically through myocarditis, we present this narrative review to provide the medical community with a unified article regarding the current understanding of myocarditis in COVID-19 patients. This article further stresses the necessity of establishing proper treatment guidelines for COVID-19 myocarditis.