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The article presents information about a study which compares the quality of care for patients in the veterans health administration and patients in a national sample in the question and answer form. The U.S. Veterans Health Administration (VHA) provides comprehensive health care to veterans through VHA-run medical centers. Since the early 1990s, VHA has worked to improve the quality of the health care it delivers. An important part of that effort has been a program that measures health care quality and holds administrators of VHA medical centers responsible for maintaining high-quality care at their institutions.

Diabetic kidney disease (DKD) represents a major global health problem. Accelerated ageing is a key feature of DKD and, therefore, characteristics of accelerated ageing may provide useful biomarkers or therapeutic targets. Harnessing multi-omics, features affecting telomere biology and any associated methylome dysregulation in DKD were explored. Genotype data for nuclear genome polymorphisms in telomere-related genes were extracted from genome-wide case-control association data (n = 823 DKD/903 controls; n = 247 end-stage kidney disease (ESKD)/1479 controls). Telomere length was established using quantitative polymerase chain reaction. Quantitative methylation values for 1091 CpG sites in telomere-related genes were extracted from epigenome-wide case-control association data (n = 150 DKD/100 controls). Telomere length was significantly shorter in older age groups ( p = 7.6 × 10 -6 ). Telomere length was also significantly reduced ( p = 6.6 × 10 -5 ) in DKD versus control individuals, with significance remaining after covariate adjustment ( p = 0.028). DKD and ESKD were nominally associated with telomere-related genetic variation, with Mendelian randomisation highlighting no significant association between genetically predicted telomere length and kidney disease. A total of 496 CpG sites in 212 genes reached epigenome-wide significance ( p ≤ 10 -8 ) for DKD association, and 412 CpG sites in 193 genes for ESKD. Functional prediction revealed differentially methylated genes were enriched for Wnt signalling involvement. Harnessing previously published RNA-sequencing datasets, potential targets where epigenetic dysregulation may result in altered gene expression were revealed, useful as potential diagnostic and therapeutic targets for intervention.

Expression of executive dysfunctions is marked by substantial heterogeneity in people living with HIV infection (PLWH) and attributed to neuropathological degradation of frontostriatal circuitry with age and disease. We compared the neurophysiology of executive function in older PLWH and Parkinson's disease (PD), both affecting frontostriatal systems. Thirty-one older PLWH, 35 individuals with PD, and 28 older healthy controls underwent executive task-activated fMRI, neuropsychological testing, and a clinical motor exam. fMRI task conditions distinguished cognitive control operations, invoking a lateral frontoparietal network, and motor control operations, activating a cerebellar-precentral-medial prefrontal network. HIV-specific findings denoted a prominent sensorimotor hypoactivation during cognitive control and striatal hypoactivation during motor control related to CD4 + T cell count and HIV disease duration. Activation deficits overlapped for PLWH and PD, relative to controls, in dorsolateral frontal, medial frontal, and middle cingulate cortices for cognitive control, and in limbic, frontal, parietal, and cerebellar regions for motor control. Thus, despite well-controlled HIV infection, frontostriatal and sensorimotor activation deficits occurred during executive control in older PLWH. Overlapping activation deficits in posterior cingulate and hippocampal regions point toward similarities in mesocorticolimbic system aberrations among older PLWH and PD. The extent of pathophysiology in PLWH was associated with variations in immune system health, neural signature consistent with subclinical parkinsonism, and mild neurocognitive impairment. The failure to adequately engage these pathways could be an early sign for cognitive and motor functional decline in the aging population of PLWH., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Both active smoking and second-hand smoke (SHS) are important risk factors for many age-related diseases. Active smoking is associated with shortened telomere length. However, whether SHS accelerates telomere attrition with age is uncertain. The aim of this study was to examine the association between SHS exposure and shortening by age of leukocyte telomere length among adult non-smokers., Methods: We undertook a cross-sectional study of the association between self-reported levels of SHS exposure and telomere length shortening per annum on a subgroup of participants from the Scottish Family Health Study. Inclusion was restricted to non-smokers aged ≥ 18 years, who had provided self-reported overall usual SHS exposure (total hours per week) and blood samples for telomere analysis. Linear regression models were used to compare the ratio of telomere repeat copy number to single copy gene number (T/S)by age according to SHS exposure., Results: Of the 1303 eligible participants, 779 (59.8%) reported no SHS exposure, 495 (38.0%) low exposure (1-19 h per week) and 29 (2.2%) high exposure (≥20 h per week). In the univariate linear regression analyses, relative T/S ratio declined with increasing age in all exposure groups. Telomere length decreased more rapidly with increasing age among those with high exposure to SHS [adjusted coefficient -0.019, 95% confidence interval (CI) -0.031- -0.007) when compared with both those with no exposure to SHS (adjusted coefficient -0.006, 95% CI -0.008- -0.004) (high vs no SHS: P = 0.010) and those with low exposure to SHS (adjusted coefficient -0.005, 95% CI -0.007- -0.003) (high vs low SHS: P = 0.005)., Conclusions: Our findings suggest that high SHS exposure may accelerate normal biological ageing, and support efforts to protect the public from SHS exposure. Further studies on relevant mechanisms should be conducted., (© The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Our objective was to determine the clinical value of obtaining a chest radiograph after removal of a chest tube. We conducted a retrospective chart review of pediatric general surgical patients with a chest tube in place after a thoracic procedure over a 3-year time period. Postremoval films were considered to be of value if they led to a change in clinical management. Of 468 patients who had a thoracic procedure, 281 patients had a chest tube and a postremoval film. In 263 patients (93.6%) there was no change in the postremoval film result compared with baseline. Only two patients (0.7%) required an intervention based on symptoms, not based on the postremoval film. Eliminating routine postremoval radiographs after chest tube removal in pediatric patients will lessen radiation exposure and provide cost savings with no adverse impact on outcome., (Copyright © 2017 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Background: With increasing computerisation in general practice, national primary care networks are mooted as sources of data for health services and population health research and planning. Existing data collection programs - MedicinesInsight, Improvement Foundation, Bettering the Evaluation and Care of Health (BEACH) - vary in purpose, governance, methodologies and tools. General practitioners (GPs) have significant roles as collectors, managers and users of electronic health record (EHR) data. They need to understand the challenges to their clinical and managerial roles and responsibilities., Objective: The aim of this article is to examine the primary and secondary use of EHR data, identify challenges, discuss solutions and explore directions., Discussion: Representatives from existing programs, Medicare Locals, Local Health Districts and research networks held workshops on the scope, challenges and approaches to the quality and use of EHR data. Challenges included data quality, interoperability, fragmented governance, proprietary software, transparency, sustainability, competing ethical and privacy perspectives, and cognitive load on patients and clinicians. Proposed solutions included effective change management; transparent governance and management of intellectual property, data quality, security, ethical access, and privacy; common data models, metadata and tools; and patient/community engagement. Collaboration and common approaches to tools, platforms and governance are needed. Processes and structures must be transparent and acceptable to GPs.

Background: Telomere length is a putative biomarker of ageing, morbidity and mortality. Its application is hampered by lack of widely applicable reference ranges and uncertainty regarding the present limits of measurement reproducibility within and between laboratories., Methods: We instigated an international collaborative study of telomere length assessment: 10 different laboratories, employing 3 different techniques [Southern blotting, single telomere length analysis (STELA) and real-time quantitative PCR (qPCR)] performed two rounds of fully blinded measurements on 10 human DNA samples per round to enable unbiased assessment of intra- and inter-batch variation between laboratories and techniques., Results: Absolute results from different laboratories differed widely and could thus not be compared directly, but rankings of relative telomere lengths were highly correlated (correlation coefficients of 0.63-0.99). Intra-technique correlations were similar for Southern blotting and qPCR and were stronger than inter-technique ones. However, inter-laboratory coefficients of variation (CVs) averaged about 10% for Southern blotting and STELA and more than 20% for qPCR. This difference was compensated for by a higher dynamic range for the qPCR method as shown by equal variance after z-scoring. Technical variation per laboratory, measured as median of intra- and inter-batch CVs, ranged from 1.4% to 9.5%, with differences between laboratories only marginally significant (P = 0.06). Gel-based and PCR-based techniques were not different in accuracy., Conclusions: Intra- and inter-laboratory technical variation severely limits the usefulness of data pooling and excludes sharing of reference ranges between laboratories. We propose to establish a common set of physical telomere length standards to improve comparability of telomere length estimates between laboratories., (© The Author 2014. Published by Oxford University Press on behalf of the International Epidemiological Association.)

The nongovernmental organization, Uyisenga N'Manzi (UNM), provides Rwandan orphans of genocide and HIV/AIDS with education, social, and mental health services. Many orphans in UNM report symptoms of psychological trauma. The primary study objective was to evaluate a multidisciplinary program integrating HIV prevention with an existing package of mental health services. We randomly selected 120 orphans between ages 15-25 years served by UNM and evaluated sexually-transmitted infections, HIV risk-taking behaviors and knowledge, and mental health at baseline, 5, 9, and 12 months. Increased trauma symptoms at baseline were associated with poorer coping skills and social functioning, and increased psychological distress and HIV risk-taking behavior. Following the 12-month intervention, trauma symptoms declined significantly, with those accessing counseling services showing greatest improvement. Orphans with the highest trauma scores benefited most from the intervention. In this at-risk population, addressing mental health issues in the context of HIV prevention is critical.

Objectives: Little is known about the impact of HIV infection on biological ageing in sub-Saharan Africa. The study aimed to assess biological ageing in South African HIV-infected adults and HIV-seronegative individuals using two validated biomarkers, telomere length and CDKN2A expression (a mediator of cellular senescence)., Design: A case-control study., Methods: Two hundred and thirty-six HIV-infected adults aged at least 30 years and 250 age and sex frequency matched HIV-seronegative individuals were recruited from clinics in township communities in Cape Town. Biological ageing was evaluated by measurement of telomere length and CDKN2A expression in peripheral blood leukocytes., Results: The median ages of the HIV-infected and HIV-seronegative participants were 39 and 40 years, respectively. Among HIV-infected participants, 87.1% were receiving antiretroviral therapy (ART), their median CD4⁺ cell count was 468 cells/μl and 84.3% had undetectable viral load. Both biomarkers were validated against chronological age in HIV-seronegative individuals. Telomere length was significantly shorter in HIV-infected individuals than in HIV-seronegative individuals (mean relative T/S ratio ±SE:0.91 ± 0.007 vs. 1.07 ± 0.008, P < 0.0001). CD2NKA expression was higher in HIV-infected participants than in HIV-seronegative individuals (mean expression: 0.45 ± 0.02 vs. 0.36 ± 0.03, P = 0.003). Socioeconomic factors were not associated with biological ageing in HIV-infected participants. However, in participants on ART with undetectable viral load, biomarker levels indicated greater biological ageing in those with lower current CD4⁺ cell counts., Conclusion: Telomere length and CDKN2A expression were both consistent with increased biological ageing in HIV-infected individuals. Prospective studies of the impact of HIV on biological ageing in sub-Saharan Africa are warranted., (© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins)

Objective: Psychological factors such as the stress of caregiving are emerging as predictors of telomere length, an index of biological aging. However, although lifetime major depressive disorder is associated with shorter telomeres, less is known about depressive symptoms. Depression and depressive symptoms are associated with a range of morbidities and mortality, but the extent to which they predict biological aging is unclear. The present study examined participants in the West of Scotland Twenty-07 Study across three age cohorts and four waves of data collection from 1992/1993 to 2007/2008., Methods: Participants were 37, 57, and 76 years old at final data collection. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale at each time point. Telomere length was assessed from 1063 blood samples collected at the final wave in 2007/2008 for respondents who also had depression data., Results: Average depression symptoms (β= -.12, p = .047) and their change over time (β = -.12, p = .031) were negatively associated with telomere length, but only in the youngest cohort. Depressive symptoms were not cross sectionally associated with telomere length in 2007 to 2008 (β= -.03, p = .45). In the youngest cohort only, depressive symptoms assessed in 1995 to 1997 and 2000 to 2004 were associated with shorter telomere length (β = .14 [p = .046] and β = .18 [p = .012], respectively), but not 1992 to 1993 or 2007 to 2008; associations in the middle- and older-aged cohorts were nonsignificant., Conclusions: Depressive symptoms are longitudinally associated with shorter telomere length, but only in younger adults.

Reprogramming of cellular metabolism is a key event during tumorigenesis. Despite being known for decades (Warburg effect), the molecular mechanisms regulating this switch remained unexplored. Here, we identify SIRT6 as a tumor suppressor that regulates aerobic glycolysis in cancer cells. Importantly, loss of SIRT6 leads to tumor formation without activation of known oncogenes, whereas transformed SIRT6-deficient cells display increased glycolysis and tumor growth, suggesting that SIRT6 plays a role in both establishment and maintenance of cancer. By using a conditional SIRT6 allele, we show that SIRT6 deletion in vivo increases the number, size, and aggressiveness of tumors. SIRT6 also functions as a regulator of ribosome metabolism by corepressing MYC transcriptional activity. Lastly, Sirt6 is selectively downregulated in several human cancers, and expression levels of SIRT6 predict prognosis and tumor-free survival rates, highlighting SIRT6 as a critical modulator of cancer metabolism. Our studies reveal SIRT6 to be a potent tumor suppressor acting to suppress cancer metabolism., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The search for biomarkers of aging (BoAs) has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA. We investigate whether it meets the criteria to be considered as a single biomarker of aging, and whether it makes a useful contribution to a composite measure., Methodology/principal Findings: Using data from a large population based study, we show that telomere length is associated with age, with several measures of physical and cognitive functioning that are related to normal aging, and with three measures of overall health. In the majority of cases, telomere length adds predictive power to that of age, although it was not nearly as good a predictor overall. We used principal components analysis to form two composites from the measures of functioning, one including telomere length and the other not including it. These composite BoAs were better predictors of the health outcomes than chronological age. There was little difference between the two composites., Conclusions: Telomere length does not satisfy the strict criteria for a BoA, but does add predictive power to that of chronological age. Equivocal results from previous studies might be due to lack of power or the choice of measures examined together with a focus on single biomarkers. Composite biomarkers of aging have the potential to outperform age and should be considered for future research in this area.

Emphysematous pyelonephritis (EPN) is a severe necrotizing infection of the renal parenchyma. The clinical course of EPN can be severe and life-threatening if not recognized and treated promptly. Most of the information has been from case reports, a few large series have also been reported. Using an evidence-based approach, this review describes the pathogenesis, classification, complications, and management of EPN. Emphysematous pyelonephritis (EPN) is an acute severe necrotizing infection of the renal parenchyma and its surrounding tissues that results in the presence of gas in the renal parenchyma, collecting system, or perinephric tissue. The cause for mortality in EPN is primarily due to septic complications. Up to 95% of the cases with EPN have underlying uncontrolled diabetes mellitus. The risk of developing EPN secondary to a urinary tract obstruction is about 25-40%. There are three classifications of EPN based on radiological findings. Acute renal failure, microscopic or macroscopic haematuria, severe proteinuria are other positive findings in EPN. Escherichia coli is the most common causative pathogen with the organism isolated on urine or pus cultures in nearly 70% of the reported cases. A plain radiograph shows an abnormal gas shadow in the renal bed raising the suspicion whereas an ultrasound scan or computed tomography (CT) will confirm the presence of intra-renal gas thus supporting the diagnosis of EPN. Gas may extend beyond the site of inflammation to the sub capsular, perinephric and pararenal spaces. In some cases, gas was found to be extending into the scrotal sac and spermatic cord. Subsequent case studies have shown patients being successfully treated with PCD when used in addition to medical management, with significant reduction in the morality rates. PCD should be performed on patients who have localized areas of gas and functioning renal tissue is present. The treatment strategies include MM alone, PCD plus MM, MM plus emergency nephrectomy, and PCD plus MM plus emergency nephrectomy. In small proportion of patients managed with MM and PCD, subsequent nephrectomy will be required and in these patients the reported mortality is 6.6% Nephrectomy in patients with EPN can be simple, radical or laparoscopic., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

We have isolated a novel progenitor cell population from adult rat pancreatic ducts, termed pancreatic-derived progenitor cells (PDPCs). Here, we report the in vitro culture, selection, and characterization of Thy1.1-positive and Thy1.1-negative PDPC subpopulations. These cells exhibit bipotentiality for differentiation into both pancreatic and hepatic cell types. Significantly, they express Pdx-1. Using a serum-free FGF-4-containing differentiation protocol, we have observed a time course of both morphological and gene expression changes indicative of hepatic lineage differentiation for the Thy1.1-positive subpopulation. These cells express albumin and store glycogen, typical features of mature hepatocytes. The Thy1.1-positive subpopulation could also readily be induced to differentiate into a pancreatic lineage with characteristic morphological changes resulting in three-dimensional islet-like structures and the transcriptional expression of insulin and glucagon in addition to Pdx-1. No morphological evidence of islet-like clusters was observed using the Thy1.1-negative population. However, Thy1.1-negative cells grown in pancreatic differentiation medium did show insulin gene transcription. Glucagon was not expressed in the undifferentiated Thy1.1-negative cells, nor was it induced in vitro after differentiation. The detection of Pdx-1 transcriptional expression in both populations indicates their potential as a novel source of non-beta-cell-derived insulin.

Factor VIII is a trace plasma glycoprotein involved as a cofactor in the activation of factor X by factor IXa. Inherited deficiency of factor VIII results in the X-linked bleeding disorder hemophilia A which has been documented in humans, horses, sheep and dogs. In this report, the putative proximal promoter, 5' untranslated region, complete coding sequence and 3' untranslated region of the canine factor VIII gene have been characterized. When compared to the human gene, the 5' flanking region shows conservation of transcription factor binding sites in the 5' untranslated region. Alignment of the amino acid sequence with that of the previously reported human, mouse and pig proteins demonstrates sequence identity of between 77 and 92% for the A1, A2, A3, C1 and C2 domains but an identity of only between 44 and 62% for the central B domain. The three thrombin cleavage sites are conserved in the canine sequence as are the protein C cleavage sites and the von Willebrand factor binding region. In addition, all six tyrosine residues that are known to undergo sulfation in the human protein are conserved in the dog. The 3' untranslated region of the canine gene extends 1.5 kilobases. The initial 700 basepairs of this sequence are highly GC rich and the sequence terminates with 2 alternative potential polyadenylation sites. The knowledge of this sequence, in combination with a well described canine model of hemophilia A, provides the necessary starting point for studies addressing the long-term evaluation of factor VIII gene therapy using a homologous transgene.