Norwoodboyer1553

Ataxia telangiectasia mutated (ATM), a critical DNA damage sensor, also possesses non-nuclear functions owing to its presence in extra-nuclear compartments, including peroxisomes, lysosomes, and mitochondria. ATM is frequently altered in several human cancers. Recently, we and others have shown that loss of ATM is associated with defective mitochondrial autophagy (mitophagy) in ataxia-telangiectasia (A-T) fibroblasts and B-cell lymphomas. Further, we reported that ATM protein but not ATM kinase activity is required for mitophagy. However, the mechanism of ATM kinase activation during ionophore-induced mitophagy is unknown. In the work reported here, using several ionophores in A-T and multiple T-cell and B-cell lymphoma cell lines, we show that ionophore-induced mitophagy triggers oxidative stress-induced ATMSer1981 phosphorylation through ROS activation, which is different from neocarzinostatin-induced activation of ATMSer1981, Smc1Ser966, and Kap1Ser824. We used A-T cells overexpressed with WT or S1981A (auto-phosphorylation dead) ATM plasmids and show that ATM is activated by ROS-induced oxidative stress emanating from ionophore-induced mitochondrial damage and mitophagy. The antioxidants N-acetylcysteine and glutathione significantly inhibited ROS production and ATMSer1981 phosphorylation but failed to inhibit mitophagy as determined by retroviral infection with mt-mKeima construct followed by lysosomal dual-excitation ratiometric pH measurements. Our data suggest that while ATM kinase does not participate in mitophagy, it is activated via elevated ROS.Intraoperative MRI (ioMRI) has become a frequently used tool to improve maximum safe resection in brain tumor surgery. The usability of intraoperatively acquired diffusion-weighted imaging sequences to predict the extent and clinical relevance of new infarcts has not yet been studied. Furthermore, the question of whether more aggressive surgery after ioMRI leads to more or larger infarcts is of crucial interest for the surgeons' operative strategy. Retrospective single-center analysis of a prospective registry of procedures from 2013 to 2019 with ioMRI was used. Infarct volumes in ioMRI/poMRI, lesion localization, mRS, and NIHSS were analyzed for each case. A total of 177 individual operations (60% male, mean age 45.5 years old) met the inclusion criteria. In 61% of the procedures, additional resection was performed after ioMRI, which resulted in a significantly higher number of new ischemic lesions postoperatively (p less then  .001). Selleck HIF inhibitor The development of new or enlarged ischemic areas upon additional resection could also be shown volumetrically (mean volume in ioMRI 0.39 cm3 vs. poMRI 2.97 cm3; p less then  .001). Despite the surgically induced new infarcts, mRS and NIHSS did not worsen significantly in cases with additional resection. Additionally, new perilesional ischemia in eloquently located tumors was not associated with an impaired neurological outcome. Additional resection after ioMRI leads to new or enlarged ischemic areas. However, these new infarcts do not necessarily result in an impaired neurological outcome, even when in eloquent brain areas.To date, avian influenza viruses (AIVs) have persisted in domestic poultry in wet markets in East Asian countries. We have performed ongoing virus surveillance in poultry populations in Vietnam since 2011, with the goal of controlling avian influenza. Throughout this study, 110 H3 AIVs were isolated from 2760 swab samples of poultry in markets and duck farms. H3 hemagglutinin (HA) genes of the isolates were phylogenetically classified into eight groups (I-VIII). Genetic diversity was also observed in the other seven gene segments. Groups I-IV also included AIVs from wild waterbirds. The epidemic strains in poultry switched from groups I-III and VI to groups I, IV, V, and VIII around 2013. H3 AIVs in groups I and V were maintained in poultry until at least 2016, which likely accompanied their dissemination from the northern to the southern regions of Vietnam. Groups VI-VIII AIVs were antigenically distinct from the other groups. Some H3 AIV isolates had similar N6 neuraminidase and matrix genes as H5 highly pathogenic avian influenza viruses (HPAIVs). These results reveal that genetically and antigenically different H3 AIVs have been co-circulating in poultry in Vietnam. Poultry is usually reared outside in this country and is at risk of infection with wild waterbird-originating AIVs. In poultry flocks, the intruded H3 AIVs must have experienced antigenic drift/shift and genetic reassortment, which could contribute to the emergence of H5 HPAIVs with novel gene constellations.Background Community pharmacy services play an important role in controlling some factors related to medicine use and patients can benefit from these services to improve the adherence and knowledge of their medications, besides to reduce medicine-related problems. Objective The aim of the REVISA project is to carry out a study on preliminary implementation of the medicines use review service in Spanish community pharmacies. Setting Sixty-four community pharmacies from all regions of Spain. Method A preliminary implementation, cross-sectional multicentre study was conducted using a convenience sample of voluntary community pharmacies. A structured interview enabled to pharmacists to obtain a better understanding of patient's medicines use. Main outcome measure Medicines use review-related time and cost, satisfaction and willingness to pay. Results A total of 495 patients were enrolled. The mean age of the patients was 66.1 years, with the majority females (56.4%) and a mean consumption of 5.7 medicines. A total of 2811 medicines were evaluated and 550 referral recommendations were made (29.8% to Primary Care). The mean time employed by the pharmacists in the medicines use review service was 52.8 min (medicines use review-related cost of €17.27). Most patients expressed a high level of satisfaction with this service (98.5%) and a willingness to pay for it (84%). Conclusion Medicines use review service in community pharmacies in Spain can be delivered, that it appears to be acceptable to patients and that most patients said they would be willing to pay for it. This service may offer an opportunity to promote inter-professional collaboration between pharmacists and general practitioners.