175 research outputs found

    Coupling of Smoothened to inhibitory G proteins reduces voltage-gated K

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    SMO (Smoothened), the central transducer of Hedgehog signaling, is coupled to heterotrimeric Gi proteins in many cell types, including cardiomyocytes. In this study, we report that activation of SMO with SHH (Sonic Hedgehog) or a small agonist, purmorphamine, rapidly causes a prolongation of the action potential duration that is sensitive to a SMO inhibitor. In contrast, neither of the SMO agonists prolonged the action potential in cardiomyocytes from transgenic GiCT/TTA mice, in which Gi signaling is impaired, suggesting that the effect of SMO is mediated by Gi proteins. Investigation of the mechanism underlying the change in action potential kinetics revealed that activation of SMO selectively reduces outward voltage-gated K+ repolarizing (Kv) currents in isolated cardiomyocytes and that it induces a down-regulation of membrane levels of Kv4.3 in cardiomyocytes and intact hearts from WT but not from GiCT/TTA mice. Moreover, perfusion of intact hearts with Shh or purmorphamine increased the ventricular repolarization time (QT interval) and induced ventricular arrhythmias. Our data constitute the first report that acute, noncanonical Hh signaling mediated by Gi proteins regulates K+ currents density in cardiomyocytes and sensitizes the heart to the development of ventricular arrhythmias. Ā© 2018 Cheng et al

    Stability of Hill Slopes and Foundation Condition at Radio Astronomy Centre Ootacamand

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    Stability aspects of hill slopes and foundation considerations of Radio Astronomy Centre at Ootacamand are described. The analysis of slopes indicated that if joints are not covered, the material in joints may lose strength and the slopes may enter a state of instability. Footings with inclined legs were found to resist the horizontal forces, pull and overturning movements. Lime piles adopted for strengthening soft material at one of the tower locations were found to be effective

    Nursing Perceptions of Patient Safety at Hamad Medical Corporation in the State of Qatar

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    Indiana University-Purdue University Indianapolis (IUPUI)The ability to improve the safety of patient care delivery is dependent on the safety culture, or the norms surrounding reactions following an error, the learning that takes place, and the proactive strategies in place to prevent future errors. While measurement of patient safety culture is now common in the United States (US) using instrument specifically developed for US healthcare organizations, no measurements of safety culture had been conducted at Hamad Medical Corporation in the State of Qatar, a Middle Eastern country; nor were valid or reliable instruments available. The purpose of this study was to assess registered nursesā€™ perceptions of the safety culture in the units where they provide nursing care at Hamad Medical Corporation using a modified version of the Agency for Healthcare Research and Quality (AHRQ) patient safety culture an instrument (Hospital Survey of Patient Safety Culture). Eight hundred surveys were distributed to all randomly-selected nurses from eight targeted clinical services with a response rate of 57%. Survey results were compared with those from US hospitals using the original AHRQ survey. Ranking of subscales for this study in terms of strengths and areas needing improvement were almost identical to the ordering of US hospital results, with teamwork within units ranked highest and indicating a strength; and the subscale non-punitive response to error the lowest and indicating an area for improvement. Positive response rates in terms of safety culture for this study were generally lower on most subscales compared to the US results and may reflect the intensity of patient safety improvement activity in the US over the last eight years in response to the Institute of Medicineā€™s report on medical errors in 1999. Results from this study provide a baseline measurement for safety culture at Hamad Medical Corporation and beginning adaptation of an instrument that can be used in other Middle Eastern healthcare organizations in the future

    A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells

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    Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptideā€“major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705ā€“restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1ā€“specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1ā€“specific CD8+ T cells, the HLA-B2705ā€“KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class Iā€“specific receptor expressed on myelomonocytic cells. Binding of the B2705ā€“KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversificatio

    Revisiting the Prevalence of Autism Spectrum Disorder among Omani Children: A multicentre study

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    Objectives: This study aimed to provide an updated estimate of the prevalence of autism spectrum disorder (ASD) among Omani children. Methods: This retrospective descriptive study was conducted from December 2011 to December 2018. Data were retrieved from the three main autism diagnostic centres in Oman: Sultan Qaboos University Hospital, Royal Hospital and Al-Massarah Hospital. The ASD diagnosis was made by experienced clinicians based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The overall population prevalence estimates per 10,000 children aged 0ā€“14 years old in Oman were calculated using the denominator of the mid-period population data. Results: A total of 1,705 ASD cases were identified with the majority of cases being male (78.1%). The overall prevalence rate of ASD was estimated at 20.35 per 10,000 children (95% confidence interval: 19.39ā€“21.32) between 2012ā€“2018. Boys were found to have a 3.4-fold higher prevalence of ASD than girls (31.23/10,000 versus 9.07/10,000). Regionally, the majority of cases were found in the capital, Muscat, where the highest prevalence was 36.51 cases per 10,000 children. Conclusion:Ā The prevalence of ASD among Omani children is 15-fold higher than estimates from 2011. This increase can be attributed to improvements in diagnostic services, increased awareness of ASD, better screening programmes and changes in diagnostic criteria. In addition, this increase in prevalence suggests a need for a registry of developmental disabilities and more extensive diagnostic and rehabilitation services in Oman.Keywords: Autism Spectrum Disorder; Epidemiology; Prevalence; Oman

    Successful Treatment of Novel H1N1 Influenza related Fulminant Myocarditis with Extracorporeal Life Support

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    The prevalence of myocardial involvement in influenza infection ranges from 0% to 12%. The 2009 pH1N1 influenza virus, formerly known as swine flu, first appeared in Mexico and the United States of America in March and April 2009 and has swept the globe with unprecedented speed. We report a case of fulminant myocarditis associated with this virus treated successfully using extra-corporal membrane oxygenator

    A successful chronic care program in Al Ain-United Arab Emirates

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    <p>Abstract</p> <p>Background</p> <p>The cost effective provision of quality care for chronic diseases is a major challenge for health care systems. We describe a project to improve the care of patients with the highly prevalent disorders of diabetes and hypertension, conducted in one of the major cities of the United Arab Emirates.</p> <p>Settings and Methods</p> <p>The project, using the principles of quality assurance cycles, was conducted in 4 stages.</p> <p>The assessment stage consisted of a community survey and an audit of the health care system, with particular emphasis on chronic disease care. The information gleaned from this stage provided feedback to the staff of participating health centers. In the second stage, deficiencies in health care were identified and interventions were developed for improvements, including topics for continuing professional development.</p> <p>In the third stage, these strategies were piloted in a single health centre for one year and the outcomes evaluated. In the still ongoing fourth stage, the project was rolled out to all the health centers in the area, with continuing evaluation. The intervention consisted of changes to establish a structured care model based on the predicted needs of this group of patients utilizing dedicated chronic disease clinics inside the existing primary health care system. These clinics incorporated decision-making tools, including evidence-based guidelines, patient education and ongoing professional education.</p> <p>Results</p> <p>The intervention was successfully implemented in all the health centers. The health care quality indicators that showed the greatest improvement were the documentation of patient history (e.g. smoking status and physical activity); improvement in recording physical signs (e.g. body mass index (BMI)); and an improvement in the requesting of appropriate investigations, such as HbA1c and microalbuminurea. There was also improvement in those parameters reflecting outcomes of care, which included HbA1c, blood pressure and lipid profiles. Indicators related to lifestyle changes, such as smoking cessation and BMI, failed to improve.</p> <p>Conclusion</p> <p>Chronic disease care is a joint commitment by health care providers and patients. This combined approach proved successful in most areas of the project, but the area of patient self management requires further improvement.</p
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