10/09/2024


Vitex megapotamica (Spreng.) Moldenke is a plant with medicinal properties popularly used in Brazil to treat diabetes and obesity. Despite the promising use of this plant, are still incipient toxicology studies on prolonged periods of treatment. The aim of this study was to evaluate the repeated dose 90-day oral toxicity study of V. megapotamica methanolic extract (VMME) in male and female Wistar rats. Different groups of rats (n = 8) were treated daily with three different doses of VMME (100, 300, and 900 mg/kg) or vehicle (filtered water). Body weight, water, and feed consumption, and clinical and behavioral changes were monitored daily. At the end of the experimental period, blood samples were obtained for hematological and biochemical analyzes. After euthanasia, the vital organs were removed for the determination of relative weight and for histopathological analysis. No clinical signs of toxicity or mortality were found during the experimental period. Treatment with VMME did not induce any change in body weight gain, eating patterns, and behavior. We found no statistically significant changes in the different hematological and biochemical parameters evaluated. The relative weight of the organs and histopathological analysis did not show any significant change when compared to animals treated with the vehicle. The data obtained in this study allow us to conclude that the VMME obtained from V. megapotamica is safe after a repeated-dose 90-day oral toxicity study in male and female Wistar rats.Our study established an effective next-generation sequencing (NGS) protocol for four-factor preimplantation genetic testing (PGT) using α- and β-thalassemia, human leukocyte antigen (HLA) typing, and aneuploidy screening. Three couples, in whom both partners were α- and β-double thalassemia carriers, underwent PGT between 2016 and 2018. These individuals sought an opportunity for hematopoietic stem cell transplantation to save their children from β-thalassemia major. A total of 35 biopsied trophectoderm samples underwent multiple displacement amplification (MDA). PGT for α- and β-thalassemia and HLA typing were performed on MDA products using NGS-based single-nucleotide polymorphism (SNP) haplotyping. Although two samples failed MDA, 94.3% (33/35) of samples were successfully amplified, achieving conclusive PGT results. Furthermore, 51.5% (17/33) of the embryos were diagnosed as unaffected non-carriers or carriers. Of the 17 unaffected embryos, nine (52.9%) were tested further and identified as euploid via NGS-based aneuploid screening, in which five had HLA types matching affected children. One family did not achieve any unaffected euploid embryos. The two other families transferred HLA-matched and unaffected euploid embryos, resulting in two healthy 'savior babies.' NGS-PGT results were confirmed in prenatal diagnosis. Therefore, NGS-SNP was effective in performing PGT for multipurpose detection within a single PGT cycle.Coronavirus disease 2019 (COVID-19) mainly affects the respiratory system, but the involvement of other organ systems has also been commonly reported. Acute acro-ischemia or chilblain like lesions were among the first recognized dermatological presentations of COVID-19. Though the occurrence of such lesions has been attributed to the similar interferon-1 mediated immune response in both COVID-19 and systemic lupus erythematosus, we propose another possible explanation based on a common genetic background. In a recent genome-wide association study, the 3p21.31 region was found to be associated with COVID-19 severity. This region also contains the TREX1 gene. Missense mutations of the TREX1 gene are responsible for familial chilblain lupus and its genetic polymorphisms have been implicated in the pathogenesis of systemic lupus erythematosus. Based on this observation, herein we have reviewed other COVID-19 risk loci for potential overlap with dermatological conditions.Myeloproliferative neoplasms (MPNs) are associated with pulmonary hypertension (PH). We studied MPN patients who underwent right-heart-catheterization (RHC) to identify hemodynamic differences between MPN-subtypes. Per RHC, hemodynamics were classified as pre, post or combined pre and post-capillary PH. One-way analysis-of-variance (ANOVA) was used to compare hemodynamic differences among MPN-subtypes. Correlation of RVSP between trans-thoracic echocardiography (TTE) and RHC was evaluated. We included 68 patients. Median age was 63. Fifty-nine percent were male and 87% Caucasian. Polycythemia vera and essential thrombocythemia were the most common subtypes. On TTE, 91.5% had PH. On RHC, only 29% met criteria for pre-capillary PH. No MPN-subtype was more likely than others to have pre-capillary PH. Bland-Altman analysis showed significant intra-person variability between TTE and RHC-derived right ventricular systolic pressures. Post-capillary involvement is more common than precapillary PH in MPN. Type of PH does not appear to differ by MPN-subtype.The aim of this study was to investigate risk factors of bleeding and mortality in patients with warfarin overdose (WOD). Totally, 783 patients were included, of which, 272 patients (34.7%) with an INR below 5,364 patients (46.5%) with an INR between 5-10, and 147 patients (18.8%) with an INR of 10 or above. Demographic, clinical, and laboratory findings of the patients were obtained from the Real Life Data Provision Center and Hospital Information Management System. https://www.selleckchem.com/products/gsk-2837808A.html Admittance in autumn (OR = 1.75; p = 0.012), INR = 5-10 (OR = 2.65; p 6.35 with 74.2% sensitivity and 72.7% specificity. The significant risk factors were determined in WOD development. INR level, autumn, and antiplatelet use were independently associated with bleeding due to WOD. In addition, bleeding, hypertension and INR levels were independently related to in-hospital-mortality due to WOD.Washingtonia filifera seeds have revealed to possess antioxidant properties, butyrylcholinesterase and xanthine oxidase inhibition activities. The literature has indicated a relationship between Alzheimer's disease (AD) and type-2 diabetes (T2D). Keeping this in mind, we have now evaluated the inhibitory properties of W. filifera seed extracts on α-amylase, α-glucosidase enzyme activity and the Islet Amyloid Polypeptide (IAPP) fibrils formation. Three extracts from seeds of W. filifera were evaluated for their enzyme inhibitory effect and IC50 values were calculated for all the extracts. The inhibition mode was investigated by Lineweaver-Burk plot analysis and the inhibition of IAPP aggregate formation was monitored. W. filifera methanol seed extract appears as the most potent inhibitor of α-amylase, α-glucosidase, and for the IAPP fibril formation. Current findings indicate new potential of this extract that could be used for the identification or development of novel potential agents for T2D and AD.