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."

Thirty-seven patients with pure red cell aplasia (PRCA) were seen between 1966 and 1982. Ten patients had accompanying diseases described in association with PRCA, while the remainder had primary PRCA. All but two patients were treated with some form of immune manipulation, including corticosteroids, cytotoxic drugs, antithymocyte globulin, splenectomy, thymectomy, and plasmapheresis. Twenty-three patients (66%) had a remission induced by immunosuppression. In addition, there were 5 spontaneous remissions (14%). Cytotoxic drugs administered in combination with corticosteroids were the most effective form of treatment, producing 18/32 remissions (56%). Twelve of these remissions were in patients resistant to corticosteroids or in patients who had relapsed while taking them. Thirteen of the 23 patients in whom remissions were induced and one-fifth of the patients with spontaneous remissions have relapsed to date. However, with additional treatment, a second remission was induced in 10/13. Fifty-four percent of the patients with induced remissions remained transfusion-free during most of the follow-up period. Median survival in patients with primary PRCA was greater than 10 yr, whereas in patients with secondary PRCA, it was 4 yr. Infection was a major cause of morbidity and mortality. This study demonstrates the value of a variety of immunosuppressive treatments of patients with PRCA.

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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.

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Patient: Male, 57 Final Diagnosis: Perforated diverticuli Symptoms: Asymptomatic Medication: — Clinical Procedure: — Specialty: Surgery Objective: Rare co-existance of disease or pathology Background: Perforation of the colon is associated with high mortality and requires early diagnosis. However, the diagnosis of perforation from atypical causes can be a diagnostic challenge. This report is of a rare case of recurrent sigmoid colonic perforation in a patient with diverticular disease who did not present with an acute abdomen but who had pemphigus vulgaris treated with immunosuppressive therapy. Case Report: A 57-year-old man with pemphigus vulgaris was treated with steroid s, non-steroidal anti-inflammatory drugs (NSAIDS), and azathioprine. He had episodes of abdominal bloating but denied any other symptoms. He was diagnosed with spontaneous sigmoid diverticular perforation without presenting with an acute abdomen. Conclusions: Diverticular perforation can be asymptomatic in patients on immunosuppressive therapy. Therefore, there should be a high index of suspicion for bowel perforation in patients with abdominal symptoms who are treated for skin diseases, such as pemphigus vulgaris, and are on steroids and other immunosuppressive treatments.

Cancer patients, due to their immunocompromised status, are at an increased risk for severe SARS-CoV-2 infection. Since severe SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation while stimulating hypoxia, and malignancy promotes hypoxia-induced cellular metabolic alterations leading to cell death, we propose a mechanistic interplay between both conditions that results in an upregulation of IL-6 secretion resulting in enhanced cytokine production and systemic injury. Hypoxia mediated by both conditions results in cell necrosis, dysregulation of oxidative phosphorylation, and mitochondrial dysfunction. This produces free radicals and cytokines that result in systemic inflammatory injury. Hypoxia also catalyzes the breakdown of COX-1 and 2 resulting in bronchoconstriction and pulmonary edema, which further exacerbates tissue hypoxia. Given this disease model, therapeutic options are currently being studied against severe SARS-COV-2. In this study, we review several promising therapies against severe disease supported by clinical trial evidence—including Allocetra, monoclonal antibodies (Tixagevimab–Cilgavimab), peginterferon lambda, Baricitinib, Remdesivir, Sarilumab, Tocilizumab, Anakinra, Bevacizumab, exosomes, and mesenchymal stem cells. Due to the virus’s rapid adaptive evolution and diverse symptomatic manifestation, the use of combination therapies offers a promising approach to decrease systemic injury. By investing in such targeted interventions, cases of severe SARS-CoV-2 should decrease along with its associated long-term sequelae and thereby allow cancer patients to resume their treatments.