832 research outputs found

    Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

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    Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

    What happens if you single out? An experiment

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    We present an experiment investigating the effects of singling out an individual on trust and trustworthiness. We find that (a) trustworthiness falls if there is a singled out subject; (b) non-singled out subjects discriminate against the singled out subject when they are not responsible of the distinct status of this person; (c) under a negative frame, the singled out subject returns significantly less; (d) under a positive frame, the singled out subject behaves bimodally, either selecting very low or very high return rates. Overall, singling out induces a negligible effect on trust but is potentially disruptive for trustworthiness

    Boredom Makes Me Sick: Adolescents' Boredom Trajectories and Their Health-Related Quality of Life.

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    Existing research shows consistent links between boredom and depression, somatic complaints, substance abuse, or obesity and eating disorders. However, comparatively little is known about potential psychological and physical health-related correlates of academic boredom. Evidence for such a relationship can be derived from the literature, as boredom has adverse consequences in both work and achievement-related settings. The present study investigates latent correlations of 1.484 adolescents' (Mage = 13.23) mathematics boredom scores at three time points during a semester in 2018/19 and their Rasch scaled health-related quality of life (HRQoL). Moreover, we applied latent growth curve modeling to estimate boredom trajectories across the semester and determined the relationship between the latent growth parameters of student boredom and HRQoL in bivariate correlation analyses. Our results show that boredom is significantly negatively linked with all HRQoL dimensions (physical well-being, psychological well-being, autonomy and parent relation, social support and peers, school environment [SCH], and general HRQoL [GH]). Furthermore, stronger increases in boredom across the semester were negatively associated with SCH scores and GH. In conclusion, given that boredom is negatively linked with HRQoL and that stronger boredom growth is linked with more severe health-related problems, signs of academic boredom could be an early warning signal for adolescents' potentially severe problems

    Health workforce remuneration: Comparing wage levels, ranking, and dispersion of 16 occupational groups in 20 countries

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    Background: This article represents the first attempt to explore remuneration in Human Resources for Health (HRH), comparing wage levels, ranking and dispersion of 16 HRH occupational groups in 20 countries (Argentina, Belarus, Belgium, Brazil, Chile, Colombia, the Czech Republic, Finland, Germany, India, Mexico, the Netherlands, Poland, Russian Federation, Republic of South Africa (RSA), Spain, Sweden, Ukraine, United Kingdom (UK), and United States of America (USA)). The main aim is to examine to what extent the wage rankings, standardized wage levels, and wage dispersion are similar between the 16 occupational groups and across the selected countries and what factors can be shown to be related to the differences that emerge.Method: The pooled data from the continuous, worldwide, multilingual WageIndicator web survey between 2008 and 2011 (for selected HRH occupations, n=49,687) have been aggregated into a data file with median or mean remuneration values for 300 occupation/country cells. Hourly wages are expressed in standardized US Dollars (USD), all controlled for purchasing power parity (PPP) and indexed to 2011 levels.Results: The wage ranking of 16 HRH occupational groups is fairly similar across countries. Overall Medical Doctors have the highest and Personal Care Workers the lowest median wages. Wage levels of Nursing & Midwifery Professionals vary largely. Health Care Managers have lower earnings than Medical Doctors in all except six of the 20 countries. The largest wage differences are found for the Medical Doctors earning 20 times less in Ukraine than in the US, and the Personal Care Workers, who earn nine times less in the Ukraine than in the Netherlands. No support is found for the assumption that the ratio across the highest and lowest earning HRH occupations is similar between countries: it varies from 2.0 in Sweden to 9.7 in Brazil. Moreover, an increase in the percentage of women in an occupation has a large downward effect on its wage rank.Conclusions: This article breaks new ground by investigating for the first time the wage levels, ranking, and dispersion of occupational groups in the HRH workforce across countries. The explorative findings illustrate that the assumption of similarity in cross-country wage ranking holds, but that wage dispersion and wage levels are not similar. These findings might contribute to the policies for health workforce composition and the planning of healthcare provisions

    Polarized triple-collinear splitting functions at NLO for processes with photons

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    We compute the polarized splitting functions in the triple collinear limit at next-to-leading order accuracy (NLO) in the strong coupling alpha(S), for the splitting processes gamma -> qq gamma, gamma -> qqg and g -> qq gamma. The divergent structure of each splitting function was compared to the predicted behaviour according to Catani's formula. The results obtained in this paper are compatible with the unpolarized splitting functions computed in a previous article. Explicit results for NLO corrections are presented in the context of conventional dimensional regularization (CDR)

    Who Is at Risk for Diagnostic Discrepancies? Comparison of Pre- and Postmortal Diagnoses in 1800 Patients of 3 Medical Decades in East and West Berlin

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    <div><h3>Background</h3><p>Autopsy rates in Western countries consistently decline to an average of <5%, although clinical autopsies represent a reasonable tool for quality control in hospitals, medically and economically. Comparing pre- and postmortal diagnoses, diagnostic discrepancies as uncovered by clinical autopsies supply crucial information on how to improve clinical treatment. The study aimed at analyzing current diagnostic discrepancy rates, investigating their influencing factors and identifying risk profiles of patients that could be affected by a diagnostic discrepancy.</p> <h3>Methods and Findings</h3><p>Of all adult autopsy cases of the Charité Institute of Pathology from the years 1988, 1993, 1998, 2003 and 2008, the pre- and postmortal diagnoses and all demographic data were analyzed retrospectively. Based on power analysis, 1,800 cases were randomly selected to perform discrepancy classification (class I-VI) according to modified Goldman criteria. The rate of discrepancies in major diagnoses (class I) was 10.7% (95% CI: 7.7%–14.7%) in 2008 representing a reduction by 15.1%. Subgroup analysis revealed several influencing factors to significantly correlate with the discrepancy rate. Cardiovascular diseases had the highest frequency among class-I-discrepancies. Comparing the 1988-data of East- and West-Berlin, no significant differences were found in diagnostic discrepancies despite an autopsy rate differing by nearly 50%. A risk profile analysis visualized by intuitive heatmaps revealed a significantly high discrepancy rate in patients treated in low or intermediate care units at community hospitals. In this collective, patients with genitourinary/renal or infectious diseases were at particularly high risk.</p> <h3>Conclusions</h3><p>This is the current largest and most comprehensive study on diagnostic discrepancies worldwide. Our well-powered analysis revealed a significant rate of class-I-discrepancies indicating that autopsies are still of value. The identified risk profiles may aid both pathologists and clinicians to identify patients at increased risk for a discrepant diagnosis and possibly suboptimal treatment intra vitam.</p> </div

    The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

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    1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

    Theorems for asymptotic safety of gauge theories

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    We classify the weakly interacting fixed points of general gauge theories coupled to matter and explain how the competition between gauge and matter fluctuations gives rise to a rich spectrum of high- and low-energy fixed points. The pivotal role played by Yukawa couplings is emphasised. Necessary and sufficient conditions for asymptotic safety of gauge theories are also derived, in conjunction with strict no go theorems. Implications for phase diagrams of gauge theories and physics beyond the Standard Model are indicated

    Alcohol, metabolic risk and elevated serum gamma-glutamyl transferase (GGT) in Indigenous Australians

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    <p>Abstract</p> <p>Background</p> <p>The interaction between overweight/obesity and alcohol intake on liver enzyme concentrations have been demonstrated. No studies have yet examined the interaction between metabolic syndrome or multiple metabolic risk factors and alcohol intake on liver enzymes. The aim of this study was to examine if alcohol consumption modifies the effect of metabolic risk on elevated serum GGT in Indigenous Australians.</p> <p>Methods</p> <p>Data were from N = 2609 Indigenous Australians who participated in a health screening program in rural far north Queensland in 1999-2000 (44.5% response rate). The individual and interactive effects of metabolic risk and alcohol drinking on elevated serum GGT concentrations (≥50 U/L) were analyzed using logistic regression.</p> <p>Results</p> <p>Overall, 26% of the population had GGT≥50 U/L. Elevated GGT was associated with alcohol drinking (moderate drinking: OR 2.3 [95%CI 1.6 - 3.2]; risky drinking: OR 6.0 [4.4 - 8.2]), and with abdominal obesity (OR 3.7 [2.5 - 5.6]), adverse metabolic risk cluster profile (OR 3.4 [2.6 - 4.3]) and metabolic syndrome (OR 2.7 [2.1 - 3.5]) after adjustment for age, sex, ethnicity, smoking, physical activity and BMI. The associations of obesity and metabolic syndrome with elevated GGT were similar across alcohol drinking strata, but the association of an adverse metabolic risk cluster profile with elevated GGT was larger in risky drinkers (OR 4.9 [3.7 - 6.7]) than in moderate drinkers (OR 2.8 [1.6 - 4.9]) and abstainers (OR 1.6 [0.9 - 2.8]).</p> <p>Conclusions</p> <p>In this Indigenous population, an adverse metabolic profile conferred three times the risk of elevated GGT in risky drinkers compared with abstainers, independent of sex and ethnicity. Community interventions need to target both determinants of the population's metabolic status and alcohol consumption to reduce the risk of elevated GGT.</p
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