2,179 research outputs found

    N-acetylcysteine (NAC) and Hydrogen Sulfide (H<sub>2</sub>S) in Coronavirus Disease 2019 (COVID-19)

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    Significance: Hydrogen sulfide (H2S) is one of the three main gasotransmitters which is endogenously produced in humans and is protective against oxidative stress. Recent findings from studies focusing on coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shifted our attention to a potential modulatory role of H2S in this viral respiratory disease. Recent Advances: H2S levels at hospital admission may be of importance since this gasotransmitter has been shown to be protective against lung damage through its antiviral, antioxidant and anti-inflammatory actions. Furthermore, many COVID-19 cases have been described demonstrating remarkable clinical improvement upon administration of high doses of N-acetylcysteine (NAC). NAC is a renowned pharmacological antioxidant substance acting as a source of cysteine, thereby promoting endogenous glutathione (GSH) biosynthesis as well as generation of sulfane sulfur species when desulfurated to H2S. Critical Issues: Combining H2S physiology and currently available knowledge of COVID-19, H2S is hypothesized to target three main vulnerabilities of SARS-CoV-2: 1) cell entry through interfering with functional host receptors, 2) viral replication through acting on RNA-dependent RNA-polymerase (RdRp), and 3) the escalation of inflammation to a potentially lethal hyperinflammatory cytokine storm (TLR4 pathway and NLRP3 inflammasome). Future Directions: Dissecting the breakdown of NAC reveals the possibility of increasing endogenous H2S levels, which may provide a convenient rationale for the application of H2S-targeted therapeutics. Further randomized controlled trials (RCT) are warranted to investigate its definitive role

    Investigation of the Effect of a Diamine-Based Friction Modifier on Micropitting and the Properties of Tribofilms in Rolling-Sliding Contacts

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    The effect of N-Tallow-1,3-DiaminoPropane (TDP) on friction, rolling wear and micropitting has been investigated with the ultimate objective of developing lubricants with no or minimal environmental impact. A Mini Traction Machine (MTM-SLIM) has been utilised in order to generate tribofilms and observe the effect of TDP on anti-wear tribofilm formation and friction. Micropitting was induced on the surface of specimens using a MicroPitting Rig (MPR). The X-ray Photoelectron Spectroscopy (XPS) surface analytical technique has been employed to investigate the effect of TDP on the chemical composition of the tribofilm while Atomic Force Microscopy (AFM) was used to generate high resolution topographical images of the tribofilms formed on the MTM discs. Experimental and analytical results showed that TDP delays the Zinc DialkylDithioPhosphate (ZDDP) anti-wear tribofilm formation. TDP in combination with ZDDP induces a thinner and smoother anti-wear tribofilm with a modified chemical structure composed of mixed Fe/Zn (poly)phosphates. The sulphide contribution to the tribofilm and oxygen-to-phosphorous atomic concentration ratio are greater in the bulk of the tribofilm derived from a combination of TDP and ZDDP compared to a tribofilm derived from ZDDP alone. Surface analysis showed that utilising TDP effectively mitigates micropitting wear in the test conditions used in this study. Reduction of micropitting, relevant to rolling bearing applications, can be attributed to the improved running-in procedure, reduced friction, formation of a smoother tribofilm and modification of the tribofilm composition induced by TDP

    Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls

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    It is unknown how smoking behavior polygenic scores (PRS) relate to psychosis and psychotic symptoms. To elucidate this, genotype and phenotype data were collected from patients with schizophrenia, their unaffected siblings, and healthy controls in a six-year follow-up prospective cohort study. Associations between smoking behaviors, PRS and schizophrenia symptoms were explored using linear mixed-effect models. The mean number of cigarettes smoked per day were 18 for patients, 13 for siblings and 12 for controls. In the overall sample, PRSs-smoking initiation (i.e., ever smoking as a binary phenotype, PRS-SI) were positively associated with positive symptoms, negative symptoms, and depressive symptoms, whereas PRSs-AI (age at regular smoking initiation) were negatively associated with all symptom dimensions, with similar effect sizes. When considering groups separately, PRS were only associated with psychotic symptoms in siblings and controls. In conclusion, unaffected siblings show smoking behaviors at an intermediate level between patients and healthy controls. Additionally, PRS-SI and PRS-AI are associated with all symptom dimensions only in unaffected siblings and healthy controls, possibly owing to the dominant role of other (genetic) risk factors in patients. Future studies may examine mechanisms via which genetic risk for smoking affects mental health symptoms.</p

    Health Care-Seeking Behavior During Childhood Diarrheal Illness: Results of Health Care Utilization and Attitudes Surveys of Caretakers in Western Kenya, 2007-2010

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    We interviewed caretakers of 1,043 children 20,000 children on five separate subsequent occasions (May of 2009 to December 31, 2010) to assess healthcare seeking patterns for diarrhea. Diarrhea prevalence during the preceding 2 weeks ranged from 26% at baseline to 4–11% during 2009–2010. Caretakers were less likely to seek healthcare outside the home for infants (versus older children) with diarrhea (adjusted odds ratio [aOR] = 0.33, confidence interval [CI] = 0.12–0.87). Caretakers of children with reduced food intake (aOR = 3.42, CI = 1.37–8.53) and sunken eyes during their diarrheal episode were more likely to seek care outside home (aOR = 4.76, CI = 1.13–8.89). Caretakers with formal education were more likely to provide oral rehydration solution (aOR = 3.01, CI = 1.41–6.42) and visit a healthcare facility (aOR = 3.32, CI = 1.56–7.07). Studies calculating diarrheal incidence and healthcare seeking should account for seasonal trends. Improving caretakers' knowledge of home management could prevent severe diarrhea

    Sensitivity to light sterile neutrino mixing parameters with KM3NeT/ORCA

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    KM3NeT/ORCA is a next-generation neutrino telescope optimised for atmospheric neutrino oscillations studies. In this paper, the sensitivity of ORCA to the presence of a light sterile neutrino in a 3+1 model is presented. After three years of data taking, ORCA will be able to probe the active-sterile mixing angles θ14, θ24, θ34 and the effective angle θμe, over a broad range of mass squared difference Δm241 ∼ [10−5, 10] eV2, allowing to test the eV-mass sterile neutrino hypothesis as the origin of short baseline anomalies, as well as probing the hypothesis of a very light sterile neutrino, not yet constrained by cosmology. ORCA will be able to explore a relevant fraction of the parameter space not yet reached by present measurements

    Testing J/psi Production and Decay Properties in Hadronic Collisions

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    The polar and azimuthal angular distributions for the lepton pair arising from the decay of a J/psi meson produced at transverse momentum p_T balanced by a photon [or gluon] in hadronic collisions are calculated in the color singlet model (CSM). It is shown that the general structure of the decay lepton distribution is controlled by four invariant structure functions, which are functions of the transverse momentum and the rapidity of the J/psi. We found that two of these structure functions [the longitudinal and transverse interference structure functions] are identical in the CSM. Analytical and numerical results are given in the Collins-Soper and in the Gottfried-Jackson frame. We present a Monte Carlo study of the effect of acceptance cuts applied to the leptons and the photon for J/psi+ gamma production at the Tevatron.Comment: 22 pages (LaTeX) plus 11 postscript figures, MAD/PH/822, YUMS94-11. Figures are available from the authors or as a compressed tar file via anonymous ftp at phenom.physics.wisc.edu in directory {}~pub/preprints/madph-94-822-figs.tar.

    External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium

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    BackgroundIdentification of tumor-derived variants in circulating tumor DNA (ctDNA) has potential as a sensitive and reliable surrogate for tumor tissue-based routine diagnostic testing. However, variations in pre(analytical) procedures affect the efficiency of ctDNA recovery. Here, an external quality assessment (EQA) was performed to determine the performance of ctDNA mutation detection work flows that are used in current diagnostic settings across laboratories within the Dutch COIN consortium (ctDNA on the road to implementation in The Netherlands).MethodsAliquots of 3 high-volume diagnostic leukapheresis (DLA) plasma samples and 3 artificial reference plasma samples with predetermined mutations were distributed among 16 Dutch laboratories. Participating laboratories were requested to perform ctDNA analysis for BRAF exon 15, EGFR exon 18–21, and KRAS exon 2–3 using their regular circulating cell-free DNA (ccfDNA) analysis work flow. Laboratories were assessed based on adherence to the study protocol, overall detection rate, and overall genotyping performance.ResultsA broad range of preanalytical conditions (e.g., plasma volume, elution volume, and extraction methods) and analytical methodologies (e.g., droplet digital PCR [ddPCR], small-panel PCR assays, and next-generation sequencing [NGS]) were used. Six laboratories (38%) had a performance score of &gt;0.90; all other laboratories scored between 0.26 and 0.80. Although 13 laboratories (81%) reached a 100% overall detection rate, the therapeutically relevant EGFR p.(S752_I759del) (69%), EGFR p.(N771_H773dup) (50%), and KRAS p.(G12C) (48%) mutations were frequently not genotyped accurately.ConclusionsDivergent (pre)analytical protocols could lead to discrepant clinical outcomes when using the same plasma samples. Standardization of (pre)analytical work flows can facilitate the implementation of reproducible liquid biopsy testing in the clinical routine

    J/psi Production via Fragmentation at the Tevatron

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    The production of \jpsi at large transverse momenta (\pt > M_\jpsi) in ppˉp\bar p collisions is considered by including the mechanism of fragmentation. Both contributions of fragmentation to \jpsi and of fragmentation to χ\chi states followed by radiative decay to \jpsi are taken into account. The latter is found to be dominant and larger than direct production. The overall theoretical estimate is shown to be nearly consistent with the experimental observation.Comment: LaTeX, 7 pages. Preprint FNT/T-94/13, LNF-94/024(P). Data taken from a reference were incorrect and have been changed. Complete postscript file available via anonymous ftp at cobra1.pv.infn.it, as pub/jpsi.ps(.Z)(.gz
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