Prevalence of latent tuberculosis infection in BCG-vaccinated healthcare workers by using an interferon-gamma release assay and the tuberculin skin test in an intermediate tuberculosis burden country

BackgroundThe risk of healthcare workers (HCWs) acquiring tuberculosis (TB) infection is high. We determined the prevalence of latent TB infection (LTBI) in HCWs with a high Bacille Calmette-Guérin (BCG) vaccine coverage in an intermediate TB burden country by using an interferon-gamma release assay [QuantiFERON-TB Gold (QFT-G)] and by using the tuberculin skin test (TST). Risk factors associated with a positive test were determined.MethodsThis prospective cross-sectional study enrolled HCWs from a medical center in Taiwan. Participants were grouped into workers without exposure (Group 1) and workers who self-reported a history of TB exposure (Group 2). All participants completed a questionnaire to collect demographic information and risk factors for acquiring TB. The QFT-G test and the TST were administered and risk factors for a positive test were analyzed.ResultsWe recruited 193 HCWs [149 (77.2%) female workers] with a mean age of 35.6 years. All were BCG-vaccinated. The prevalence of LTBI was 88.8% (based on the TST) and 14.5% (based on the QFT-G test). There was no difference between HCWs with and without known exposure to TB. Agreement between the tests was poor (i.e., the kappa value was less than 0.05). Multivariable logistic regression showed that only the QFT-G test was associated with age (35 years or greater) (adjusted OR, 2.53; p = 0.03).ConclusionBy using the QFT-G test or TST, this study found a similar prevalence of LTBI in HCWs with and without known exposure to TB. This suggests that in intermediate TB burden countries exposure to TB may occur within the hospital and within the community. Compared to the TST, the QFT-G test was correlated better with age, which is a known risk factor for latent TB infection

Prevalence of latent tuberculosis infection in persons with and without human immunodeficiency virus infection using two interferon-gamma release assays and tuberculin skin test in a low human immunodeficiency virus prevalence, intermediate tuberculosis-burden country

BackgroundThe risk of tuberculosis (TB) is higher in human immunodeficiency virus (HIV)-infected patients and intravenous drug users (IDUs). We determined the prevalence and risk factors of latent TB infection (LTBI) in individuals with or without HIV infection, including IDUs, in a country with a low HIV prevalence, an intermediate TB burden, and a high Bacillus Calmette-Guérin (BCG) vaccine coverage using two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST).MethodsFor this prospective, cross-sectional study, HIV-infected and -uninfected patients from a regional hospital and medical center in Taiwan were enrolled. Results of the two IGRAs [QuantiFERON-TB Gold (QFT-G) and QuantiFERON-TB Gold In-Tube (QFT-GIT)] and the TST were compared. Risk factors for positivity were analyzed.ResultsWe recruited 233 patients [198 (85%) men; mean age, 39.4 years]. Most patients (74%) were BCG vaccinated. The prevalence of LTBI was estimated to be 22.8% by TST, 15.9% by QFT-G, and 20.6% by QFT-GIT. HIV-infected individuals had fewer positive QFT-GIT [7.0% vs. 28.6%, p < 0.001, adjusted odds ratio (aOR) = 0.28, p = 0.05] and TST results, and more indeterminate QFT-G responses (9.3% vs. 0.7%, p = 0.002). Concordance between IGRAs and TST was very poor in HIV-infected patients (κ < 0.05). Independent risk factors for IGRA positivity were increasing age (QFT-G: aOR = 1.98, p = 0.03; QFT-GIT: aOR = 2.00, p = 0.01) and IDUs (aOR = 4.33, p = 0.05 by QFT-G).ConclusionHIV-infected persons had a significantly lower response to both IGRAs and TST. High discordance was found between the two generations of IGRAs and between IGRAs and TST. Increasing age, a known risk factor for LTBI, was significantly associated with IGRAs, but not with TST

The potential impact of primary headache disorders on stroke risk

Distribution of PHDs. (DOC 55 kb

Impact of DNA-binding position variants on yeast gene expression

Transcription factors (TFs) regulate gene expression by binding to specific binding sites (TFBSs) in gene promoters. TFBS motifs may contain one or more variable positions. Although the prevailing assumption is that nucleotide variants at such positions are functionally equivalent, there is increasing evidence that such variants play a role in regulation of gene expression. In this article, we propose a method for studying the relationship between the expression of target genes and nucleotide variants in TFBS motifs at a genome-wide scale in Saccharomyces cerevisiae, especially the combinatorial effects of variants at two positions. Our analysis shows that nucleotide variations in more than one-third of variable positions and in 20% of dependent position pairs are highly correlated to gene expression. We define such positions as ‘functional’. However, some positions are only functional as dependent pairs, but not individually. In addition, a significant proportion of the functional positions have been well conserved across all yeast-related species studied. We also find that some positions require the presence of co-occurring TFs, while others maintain their functionality in the absence of a co-occurring TF. Our analysis supports the importance of nucleotide variants at variable positions of TFBSs in gene regulation

Chronic Kidney Disease Stage Is a Modulator on the Association between High-Sensitivity C-Reactive Protein and Coronary Vasospastic Angina

The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1–3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD

Non-nosocomial healthcare-associated infective endocarditis in Taiwan: an underrecognized disease with poor outcome

<p>Abstract</p> <p>Background</p> <p>Non-nosocomial healthcare-associated infective endocarditis (NNHCA-IE) is a new category of IE of increasing importance. This study described the clinical and microbiological characteristics and outcome of NNHCA-IE in Taiwan.</p> <p>Methods</p> <p>A retrospective study was conducted of all patients with IE admitted to the Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan over a five-year period from July 2004 to July 2009. The clinical and microbiological features of NNHCA-IE were compared to those of community-acquired and nosocomial IE. Predictors for in-hospital death were determined.</p> <p>Results</p> <p>Two-hundred episodes of confirmed IE occurred during the study period. These included 148 (74%) community-acquired, 30 (15%) non-nosocomial healthcare-associated, and 22 (11%) nosocomial healthcare-associated IE. <it>Staphylococcus aureus </it>was the most frequent pathogen. Patients with NNHCA-IE compared to community-acquired IE, were older (median age, 67 vs. 44, years, <it>p </it>< 0.001), had more MRSA (43.3% vs. 9.5%, <it>p </it>< 0.001), more comorbidity conditions (median Charlson comorbidity index [interquartile range], 4[2-6] vs. 0[0-1], <it>p </it>< 0.001), a higher in-hospital mortality (50.0% vs. 17.6%, <it>p </it>< 0.001) and were less frequently recognized by clinicians on admission (16.7% vs. 47.7%, <it>p </it>= 0.002). The overall in-hospital mortality rate for all patients with IE was 25%. Shock was the strongest risk factor for in-hospital death (odds ratio 7.8, 95% confidence interval 2.4-25.2, <it>p </it>< 0.001).</p> <p>Conclusions</p> <p>NNHCA-IE is underrecognized and carries a high mortality rate. Early recognition is crucial to provide optimal management and improve outcome.</p

Sumoylation of Hypoxia-Inducible Factor-1α Ameliorates Failure of Brain Stem Cardiovascular Regulation in Experimental Brain Death

One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM). RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α) plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death.A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1), Ubc9 (the only known conjugating enzyme for the sumoylation pathway) or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase.We conclude that sumoylation of HIF-1α in RVLM ameliorates brain stem cardiovascular regulatory failure during experimental brain death via upregulation of nitric oxide synthase I/protein kinase G signaling. This information should offer new therapeutic initiatives against this fatal eventuality

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care