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The prevalence of subclavian steal (defined as retrograde/bidirectional vertebral artery flow) in the general population and in patients undergoing cerebrovascular duplex ultrasound (CDUS) examinations is variable. This is the largest study to date to analyze the incidence of duplex-suggested subclavian steal in 5615 CDUS examinations over a 1-year period and to examine its clinical implications.<br /><br /> All consecutive CDUS examinations performed over a 1-year period were analyzed for the presence of subclavian steal. Indications of testing, presence of posterior cerebral circulation/subclavian steal symptoms, and any interventions for subclavian steal were analyzed.<br /><br /> A total of 171 of 5615 (3.1%) CDUS examinations were found to have subclavian steal (duplex-suggested). One hundred seventeen (2.1%) had retrograde flow and 54 (1%) had bidirectional flow. Of 171, 104 (60.8%) were left sided. Indications for CDUS were post-carotid endarterectomy/carotid artery stenting surveillance in 39 patients (22.8%), surveill71 patients (15.2%) had interventions for disabling symptoms. Eleven of 26 of all interventions were for disabling arm claudication, and only 10 of 171 patients (5.8%) were intervened for disabling posterior circulation symptoms with complete resolution of symptoms in all except one. At a late follow-up with a mean of 18months (range 1-37months), there was no late major stroke with only two lacunar infarcts (not subclavian steal related). There were also seven late deaths, none stroke related.<br /><br /> The incidence of subclavian steal in patients who undergo CDUS is relatively rare. Most of these patients are asymptomatic and can be treated conservatively, and only a few may need intervention for disabling symptoms with good symptom resolution.<br /><br />The incidence of subclavian steal in patients who undergo CDUS is relatively rare. Most of these patients are asymptomatic and can be treated conservatively, and only a few may need intervention for disabling symptoms with good symptom resolution.<br /><br /> Therapeutic phlebotomy allows for a controlled and gradual decrease in red cell mass leading to improved blood flow and symptomatic relief in polycythaemia. The present study was aimed to determine the impact of serial fixed volume and fixed interval therapeutic phlebotomy protocol on the laboratory and clinical parameters in patients of polycythaemia.<br /><br /> This prospective longitudinal study was conducted over 18months. The desired haematocrit for polycythemia vera and secondary polycythemia was 45% and 52% respectively. A fixed volume of 350ml phlebotomy was performed every-three days till the achievement of desired haematocrit. Complete blood count was performed before and after each procedure and iron studies were done at the time of enrolment and after the achievement of desired haematocrit. Post-procedure symptomatic relief was assessed by a 10-point visual analogue scale (VAS).<br /><br /> Of the 29 patients enrolled in the study, 3 patients were lost to follow up and data of 26 patients was analyzed. Mean Hb declined from 17.84±1.88 gdL<br /><br /> to 14.67±1.14 gdL<br /><br /> (p&lt;0.001) and mean haematocrit decreased from a baseline of 57.11±5.47% to 46.27±3.763% (p&lt;0.001) upon achievement of desired haematocrit. There was a significant decline in serum iron from the baseline of 132.85±94.136μg dL<br /><br /> to 69.41±58.643μg dL<br /><br /> at desired haematocrit. A significant change in VAS score of almost all clinical parameters was observed. Post phlebotomy hematocrit correlated negatively with the number of procedures (p=0.015).<br /><br /> Our protocol yielded rapid and marked improvement in patients of primary and secondary polycythemia with minimal adverse events and significant amelioration of clinical parameters.<br /><br />Our protocol yielded rapid and marked improvement in patients of primary and secondary polycythemia with minimal adverse events and significant amelioration of clinical parameters.<br /><br /> Blood donor deferral is a part and parcel of the commitment of the blood transfusion services to assure the safety and health of the blood donor as well as the recipient. Periodic review of blood donor deferral is to incorporate or revoke deferral reasons based on the evidence generated in the process of review. Therefore, emphasis must be laid on preparing strategies to only judiciously defer blood donors, recruit and retain first time blood donors, which needs critical appraisal of the existing deferral policies, so that the evidence based changes can be done.<br /><br /> A retrospective analysis of deferral in blood donors who presented at the blood donation centre of an institute of national importance over a span of nine years (2011-2019). Donors were screened as per the Drugs and Cosmetics Act 1940 and Rules 1945 given by the Ministry of Health and Family Welfare, Govt of India.<br /><br /> There were 1,37,935 donors attempts, out of which 20,167 (14.6%) donors were deferred from donating blood. Most of the deferred donoal is an essential quality indicator of the blood donor selection process. Initiatives like fortification of dietary ingredients with iron, optimizing protein in diet served in schools under mid-day meal program, screening for iron deficiency, hypertension and education about high-risk behavior in schools and colleges may have long term effects of promotion of better health.Paracoccidioides spp. are the etiological agent of paracoccidioidomycosis, a disease that causes skin lesions and affect the lungs and other organs. The current management of the disease is long and has several side effects that often lead the patient to give up the treatment, sequelae and even death. The search for new forms of treatment that minimize these drawbacks is very important. Thus, natural compounds are targets of great interest. Curcumin is one of the main components of the tubers of Curcuma longa, presenting medicinal effects well described in the literature, including the antifungal effect on Paracocidioides brasiliensis. Nevertheless, the mechanisms related to the antifungal effect of such compound are still unknown, so the objective of the present research is to understand what changes occur in the metabolism of P. brasiliensis after exposure to curcumin and to identify the main targets of the compound. Proteomic analysis as based on nanoUPLC-MS analysis and the functional classification of thdioidomycosis often contributing to patients' withdrawal from treatment, leading to sequelae or even death. Thus, the search for new treatment options against this disease is growing. The discovery that curcumin is active against Paracoccidioides was previously reported by our study group. Here, we clarify how the compound acts on the fungus causing its growth inhibition and decreased viability. Understanding the mechanisms of action of curcumin on P. [https://www.selleckchem.com/products/tenalisib-rp6530.html learn more] brasiliensis elucidates how we can seek new alternatives and which metabolic pathways and molecular targets we should focus on in this incessant search to bring the patient a treatment with fewer adverse effects.Dengue virus (DENV) is a mosquito-borne virus with a rapid spread to humans, causing mild to potentially fatal illness in hundreds of millions of people each year. Due to the large number of serotypes of the virus, there remains an unmet need to develop protective vaccines for a broad spectrum of the virus. Here, we constructed a modified mRNA vaccine containing envelope domain III (E-DIII) and non-structural protein 1 (NS1) coated with lipid nanoparticles. This multi-target vaccine induced a robust antiviral immune response and increased neutralizing antibody titers that blocked all four types of DENV infection in vitro without significant antibody-dependent enhancement (ADE). In addition, there was more bias for Th1 than Th2 in the exact E-DIII and NS1-specific T cell responses after a single injection. Importantly, intramuscular immunization limited DENV transmission in vivo and eliminated vascular leakage. Our findings highlight that chimeric allogeneic structural and non-structural proteins can be effective targets for DENV vaccine and that they can prevent the further development of congenital DENV syndrome.<br /><br /> There is currently no evidence of an association between depressive symptoms and asthma among older adults in China. We explored the bi-directional associations between depressive symptoms and asthma, and their changes in middle-aged and elderly adults from a national cohort.<br /><br /> A longitudinal cohort study was conducted with a total of 17,708 individuals from 150 urban communities and 450 rural villages in 28 provinces in China.<br /><br /> After making exclusions, 11,492 and 8604 participants were included for incident asthma and incident depressive symptoms analysis, respectively. The incidence density was 4.46 and 10.24 for every 1000 person-years, respectively. Baseline depressive symptoms were associated with a higher risk of incident asthma (Hazard ratio [HR] = 1.60, 95 % confidence interval [CI] 1.27, 2.02). Decreased depressive symptoms during baseline or follow-ups or both baseline and follow-ups were associated with a lower risk of incident asthma (P<br /><br />  &lt; 0.0001). Every 1-score increment of CES-D score was associated with a 4 % increase in asthma, with a non-linear association (P = 0.04) between CES-D score (break point = 7) and asthma. Asthma status increased the risk of participants with severe depressive symptoms (HR = 1.51, 95 % CI 1.19, 1.92), especially in males (P<br /><br />  = 0.02).<br /><br /> Depressive symptoms and asthma were assessed by validated questionnaires instead of clinical diagnosis.<br /><br /> Bi-directional associations between asthma and depressive symptoms do exist. Effective measures should be taken to reduce depressive symptoms and the risk of incident asthma in middle aged and elderly adults in China.<br /><br />Bi-directional associations between asthma and depressive symptoms do exist. Effective measures should be taken to reduce depressive symptoms and the risk of incident asthma in middle aged and elderly adults in China.That reversible protein phosphorylation by kinases and phosphatases occurs in metabolic disorders is well known. Various studies have revealed that a multi-faceted and tightly regulated phosphatase, pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP)-1/2 displays robust effects in cardioprotection, ischaemia/reperfusion (I/R), and vascular remodelling. PHLPP1 promotes foamy macrophage development through ChREBP/AMPK-dependent pathways. Adipocyte-specific loss of PHLPP2 reduces adiposity, improves glucose tolerance,and attenuates fatty liver via the PHLPP2-HSL-PPARα axis. Discoveries of PHLPP1-mediated insulin resistance and pancreatic β cell death via the PHLPP1/2-Mst1-mTORC1 triangular loop have shed light on its significance in diabetology. PHLPP1 downregulation attenuates diabetic cardiomyopathy (DCM) by restoring PI3K-Akt-mTOR signalling. In this review, we summarise the functional role of, and cellular signalling mediated by, PHLPPs in metabolic tissues and discuss their potential as therapeutic targets.<br /><br /> Malignant Hyperthermia (MH) is a pharmacogenetic, hereditary and autosomal dominant syndrome triggered by halogenates/succinylcholine. The In Vitro Contracture Test (IVCT) is the gold standard diagnostic test for MH, and it evaluates abnormal skeletal muscle reactions of susceptible individuals (earlier/greater contracture) when exposed to caffeine/halothane. MH susceptibility episodes and IVCT seem to be related to individual features.<br /><br /> To assess variables that correlate with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH.<br /><br /> We examined IVCTs of 80 patients investigated for MH between 2004‒2019. We recorded clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation, IVCT result) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering contracture of 0.2g, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation).