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  • Winters Kold posted an update 2 weeks, 1 day ago

    The results obtained by the cell deconvolution approach are supported by the analysis performed by WGCNA. Our report describes the largest differential gene expression profiling in peripheral blood of ASD subjects and controls conducted by RNASeq. The observed signatures are consistent with the hypothesis of immune alterations in autism and an increased risk of developing autism in subjects exposed to prenatal infections or stress. Our study also points to a potential role of NMUR1, HMGB3, and PTPRN2 in ASD.BACKGROUND Consumption coagulopathy post envenomation is one the most common complications after a snakebite. It occurs secondary to activation of a coagulation cascade by snake venom and could be followed by a syndrome consistent with thrombotic microangiopathy. The efficacy of plasma exchange for the treatment of thrombotic microangiopathy post envenomation is a matter of debate. CASE REPORT We reported the case of a 50-year-old male who had Arabian saw-scaled viper envenomation. He developed venom induced coagulopathy that improved within 24 hours of antivenom therapy. He subsequently developed micro-angiopathic hemolytic anemia, thrombocytopenia, and renal failure that was consistent with thrombotic microangiopathy. The patient was treated by plasma exchange and hemodialysis. He made a full recovery and was discharged after 4 weeks. CONCLUSIONS This case report supports plasmapheresis as an option for management of a patient who develops thrombotic microangiopathy secondary to snake bite, especially those who do not improve with antivenom and supportive therapy.BACKGROUND Throughout China, during the recent epidemic in Hubei province, frontline medical staff have been responsible for tracing contacts of patients infected with coronavirus disease 2019 (COVID‑19). This study aimed to investigate the psychological impact and coping strategies of frontline medical staff in Hunan province, adjacent to Hubei province, during the COVID‑19 outbreak between January and March 2020. MATERIAL AND METHODS A cross-sectional observational study included doctors, nurses, and other hospital staff throughout Hunan province between January and March 2020. The study questionnaire included five sections and 67 questions (scores, 0-3). The chi-squared χ² test was used to compare the responses between professional groups, age-groups, and gender. RESULTS Study questionnaires were completed by 534 frontline medical staff. The responses showed that they believed they had a social and professional obligation to continue working long hours. Medical staff were anxious regarding their safety and the safety of their families and reported psychological effects from reports of mortality from COVID‑19 infection. The availability of strict infection control guidelines, specialized equipment, recognition of their efforts by hospital management and the government, and reduction in reported cases of COVID‑19 provided psychological benefit. CONCLUSIONS The COVID‑19 outbreak in Hubei resulted in increased stress for medical staff in adjacent Hunan province. Continued acknowledgment of the medical staff by hospital management and the government, provision of infection control guidelines, specialized equipment and facilities for the management of COVID‑19 infection should be recognized as factors that may encourage medical staff to work during future epidemics.The world is currently facing an unprecedented global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Predicting the next source of the pandemic can be very challenging. As vaccination is the best way to prevent an infectious disease, the development of an effective vaccine against SARS-CoV-2 can not only reduce the morbidity and mortality associated with it, but can also lessen the economic impact. As the traditional method of vaccine development takes many years for a vaccine to be available to the society, the vaccine development for SARS-CoV-2 should be speeded up using a pandemic approach with fast-track approvals from the regulatory authorities. Various challenges associated with developing a vaccine during the pandemic such as technological hurdles, clinical development pathways, regulatory issues, and support from global funding agencies are expressed here.AKT signaling and M2 macrophage-guided tissue repair are key factors in cutaneous wound healing. A delay in this process threatens human health worldwide. However, the role of AKT3 in delayed cutaneous wound healing is largely unknown. In this study, histological staining and transcriptomics demonstrated that prolonged tissue remodeling delayed wound healing. This delay was accompanied by defects in AKT3, collagen alpha-1(I) chain (COL1A1), and collagen alpha-1(XI) chain (COL11A1) expression and AKT signaling. The defect in AKT3 expression was M2 macrophage-specific, and decreased AKT3 protein levels were observed in CD68/CD206-positive macrophages from delayed wound tissue. Downregulation of AKT3 in M2 macrophages did not influence cell polarization but impaired collagen organization by inhibiting COL1A1 and COL11A1 expression in human skin fibroblasts (HSFs). Moreover, a co-culture model revealed that the downregulation of AKT3 in the human monocytic cell line (THP-1)-derived M2 macrophages impaired HSF proliferation and migration. Finally, cutaneous wound healing in AKT3-/- mice was much slower than that of AKT3+/+ mice, and F4/80 macrophages from the AKT3-/- mice had an impaired ability to promote wound healing. Thus, the downregulation of AKT3 in M2 macrophages prolonged tissue remodeling and delayed cutaneous wound healing.Altered expression of family with sequence similarity 84, member B (FAM84B) has been found in various human cancers. However, the expression and function of FAM84B in pancreatic ductal adenocarcinoma (PDAC) has not been studied. Here, by analyzing The Cancer Genome Atlas cohort, we found that FAM84B amplification was observed in 11% of 141 PDAC patients, and FAM84B amplification was correlated with higher mRNA expression of FAM84B. FAM84B amplification and overexpression was significantly correlated with poor overall survival. Moreover, knockdown of FAM84B in PDAC cell lines suppressed cell proliferation and induced apoptosis. FAM84B knockdown also suppressed mitochondrial function and glycolysis of PDAC cells. Interestingly, knockdown of FAM84B decreased the nuclear accumulation of β-catenin, and the expression of c-Myc and lactate dehydrogenase A, but enhanced the expression of Survivin. On the contrary, FAM84B overexpression displayed reversed effects in cell proliferation, apoptosis, mitochondrial function, and glycolysis, which was blocked by the Wnt/β-catenin pathway inhibitor (XAV939). In addition, PDAC cells with lower expression of FAM84B were more sensitive to gemcitabine-induced cell proliferation inhibition both in vitro and in vivo. In conclusion, FAM84B plays an important role in aerobic glycolysis and tumorigenesis in PDAC and Wnt/β-catenin may be involved in this process.Targeting of PP2A suggests a close link to tau-related cognitive and functional declines. However, little is known about how the expression of PP2A subunits and PP2A activity are dysregulated in the course of AD, precluding any specific targeting strategy for restoring PP2A in AD patients. Although the PP2A heterotrimer containing the regulatory subunit PR55/Bα (encoded by the PPP2R2A gene) is the major tau phosphatase, the involvement of other brain-specific PP2A regulatory subunits in tau dephosphorylation remains unknown. PR55/Bγ (encoded by the PPP2R2C gene) is a pivotal phosphatase in the brain, and single-nucleotide polymorphisms (SNPs) of PPP2R2C are involved in several mental disorders. By measuring the differential spatiotemporal expression patterns of PPP2R2C in Wt and transgenic AD mice, we revealed that PPP2R2C expression is downregulated in the aged AD mouse brain as compared to the Wt mouse brain. In cultured cells, PPP2R2C expression regulates PP2A activity and tau dephosphorylation. These results suggest that dysregulation of PPP2R2C expression may be involved in the onset of AD and that specifically targeting PPP2R2C expression or activity is a promising strategy against brain dementia disorders, including AD and other tauopathies.Heatstroke is a life-threatening  and the most severe form of heat-related illnesses, characterized by body temperature >40ºC and central nervous system dysfunction. Heatstroke is classified into Non-Exertional Heatstroke (NEHS) and Exertional Heatstroke (EHS). The pathophysiology of heatstroke involves a combination of direct heat effects on the host, the systemic inflammatory and coagulopathic response. Bozitinib mouse The diagnosis of heatstroke based on Bouchama’s definition or Japan Association of Acute Medicine (JAAM) criteria. The basic principle of heatstroke management is early resuscitation and immediate cooling. Cold water immersion or convection evaporation method can be implemented based on the specific patient characteristic. Preventive strategies are early recognition by health workers, socialization to vulnerable groups and adequate acclimatization.Coronavirus disease 2019 (COVID-19) pandemic is an ongoing problem in more than 200 countries in the world. Indonesia has been greatly affected by COVID-19 with case fatality rate (CFR) being 8.9% in the end of March 2020. We have some room for improvement related to the unreadingess of healthcare facility and the major steps taken by the government. It is suggested that the country should have stricter Stay-at-Home notice, suppress the spread by imposing lockdown on a large scale, improve healthcare service, and increase the availability of personal protective equipments (PPE). It is important to avoid an epidemic peak that potentially overwhelms healthcare service by quarantining the case contacts. Lockdown may prolong the epidemic doubling time significantly. Demand of health system is likely to grow since the number of COVID-19 case is likely to rise. Effective procedures for protecting medical staff from infection are essential. Scientific research in Indonesia is also crucial to provide suggestion and recommendation pertinent to COVID-19.Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.Inhibition of the renin-angiotensin-aldosterone system (RAAS) is a key strategy in treating hypertension in cardiovascular and renal diseases. However, RAAS inhibitors (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone receptor antagonists, and direct renin inhibitors) increase the risk of hyperkalemia (serum potassium >5.5 mmol/L). This poses a therapeutic challenge because these patient groups comprise in whom the drugs are therapeutically indicated. Important considerations when initiating ACEI or ARB therapy include obtaining an estimate of glomerular filtration rate and a baseline serum potassium concentration, as well as assessing whether the patient has excessive potassium intake from diet, supplements, or drugs that can also increase serum potassium. Serum potassium monitoring shortly after initiation of therapy can assist in preventing hyperkalemia. If hyperkalemia does develop, prompt recognition of cardiac dysrhythmias and effective treatment to antagonize the cardiac effects of potassium, redistribute potassium into cells, and remove excess potassium from the body is important.