22,599 research outputs found

    Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis

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    Abstract: Background Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: \u3c0 = \u3c0rec\u3c1rec + \u3c0ex\u3c1ex + \u3c0non\u3c1non; \u3c0rec, \u3c0ex, and \u3c0non represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while \u3c1rec, \u3c1ex, and \u3c1non represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID

    A two-frame movie of X-ray induced structural dynamics in single free nanoparticles

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    International audienceBecause of their high pulse energies, X-ray free-electron lasers (FEL) allow to resolve the structure of individual nanoparticles via coherent diffractive imaging (CDI) within a single X-ray pulse. Since the inevitable rapid destruction of the sample limits the achievable resolution, a thorough understanding of the spatiotemporal evolution of matter on the nanoscale following the irradiation is crucial. We present a technique to track X-ray induced structural changes in time and space by recording two consecutive diffraction patterns of the same single, free-flying nanoparticle, acquired separately on two large-area detectors opposite to each other, thus examining both the initial and evolved particle structure. We demonstrate the method at the extreme ultraviolet (XUV) and soft X-ray Free-electron LASer in Hamburg (FLASH), investigating xenon clusters as model systems. By splitting a single XUV pulse, two diffraction patterns from the same particle can be obtained. For focus intensities of about 21012W/cm22\cdot10^{12}\,\text{W/cm}^2 we observe still largely intact clusters even at the longest delays of up to 650 picoseconds of the second pulse, indicating that in the highly absorbing systems the damage remains confined to one side of the cluster. Instead, in case of five times higher flux, the diffraction patterns show clear signatures of disintegration, namely increased diameters and density fluctuations in the fragmenting clusters. Future improvements to the accessible range of dynamics and time resolution of the approach are discussed

    Cardiac assessment and inflammatory markers in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 (PIMS-TS) treated with methylprednisolone versus intravenous immunoglobulins: 6-month follow-up outcomes of the randomised controlled Swissped RECOVERY trialResearch in context

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    Summary: Background: Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome–Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population. Methods: This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). Findings: Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2–12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) −0.05 to 1.0; p = 0.39). Interpretation: Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes. Funding: NOMIS, Vontobel, and Gaydoul Foundation

    Pneumonia outbreaks due to re-emergence of Mycoplasma pneumoniae

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    Supplementary Material for: Turpentine ointment for the treatment of folliculitis – an open, prospective, randomized, placebo- and comparator-controlled multicenter trial

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    Introduction: Folliculitis is a painful infection and inflammation of hair follicles, mostly caused by bacterial, fungal or, more rarely, viral infections. Turpentine derivatives have been used traditionally to treat various skin infections and could thus also be effective in treating folliculitis. We carried out an open, prospective, randomized, placebo- and comparator-controlled multicenter trial to evaluate the efficacy and safety of an ointment containing pine turpentine oil, larch turpentine, and eucalyptus oil in the treatment of acute folliculitis. Methods: 70 outpatients with acute folliculitis were treated with the turpentine ointment, a comparator (povidone iodine solution), or a placebo (Vaseline) for 7 days. Photographs of the affected skin areas were taken by the physicians at four visits, and by the patients on a daily basis. Photographs were evaluated by blinded observers. Primary efficacy endpoint was the change in total hair follicle lesion counts. Secondary endpoints included the evolution of the lesion counts in the course of the study, responder rate (improvement of follicle lesions by at least one count), and the patient’s global assessment. Safety endpoints were the tolerability of the treatments and adverse events recording. Results: A decrease of follicle lesions counts was detected for both active treatments, but not for placebo, but the differences among groups were not statistically significant. As for the secondary endpoints, the ointment showed statistically significant superiority over placebo for the evolution of the lesions during the course of the study (p=0.017), the responder rate (p=0.032), and the subjective efficacy assessment by patients (p=0.029). All treatments were equally well tolerated, with a similar number of treatment-emergent adverse events. Conclusion: The turpentine ointment is an effective and safe option for the treatment of folliculitis

    Modulation of IL‐23 signaling with guselkumab in biologic‐naïve patients versus TNF inhibitor‐inadequate responders with active psoriatic arthritis

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    Objective: Assess and compare immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)-23p19-subunit inhibitor, in participants with active PsA who were biologic-naïve or had inadequate response to tumor necrosis factor inhibitors (TNFi-IR). Methods: Serum biomarker levels at baseline and following treatment with guselkumab 100 mg Q8W were compared between biologic-naïve (N=251) and TNFi-IR (N=93) subgroups identified in the pooled DISCOVER-1/DISCOVER-2/COSMOS dataset. Baseline biomarker levels determined by achievement of Week-24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2-point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between subgroups. Results: Baseline IL-22, TNFα, and beta defensin (BD)-2 levels were significantly lower in biologic-naïve than in TNFi-IR participants. With guselkumab, Week-24 IL-17A, IL-17F, IL-22, serum amyloid A, C-reactive protein, IL-6, and BD-2 levels were significantly reduced from baseline in biologic-naïve and TNFi-IR participants (≥1.4-fold difference, nominal P<0.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL-17A, IL-17F, BD-2 in biologic-naïve PASI 90 responders; IL-17A, BD-2 in TNFi-IR IGA 0/1 responders; IL-22, BD-2 in TNFi-IR PASI 90 responders [nominal P<0.05]) and trended higher in TNFi-IR ACR20 responders. Conclusion: Guselkumab modulates IL-23 signaling and provides consistent pharmacodynamic effects in both biologic-naïve and TNFi-IR PsA patients. Significantly elevated baseline IL-22, TNFα, and BD-2 levels and associations between baseline IL-22, IL-17A, and BD-2 levels and skin responses with guselkumab suggest greater dysregulation of IL-23/Th17 signaling in TNFi-IR patients

    Aerosol emissions from a marine diesel engine running on different fuels and effects of exhaust gas cleaning measures.

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    The emissions of marine diesel engines have gained both global and regional attentions because of their impact on human health and climate change. To reduce ship emissions, the International Maritime Organization capped the fuel sulfur content of marine fuels. Consequently, either low-sulfur fuels or additional exhaust gas cleaning devices for the reduction in sulfur dioxide (SO2) emissions became mandatory. Although a wet scrubber reduces the amount of SO2 significantly, there is still a need to consider the reduction in particle emissions directly. We present data on the particle removal efficiency of a scrubber regarding particle number and mass concentration with different marine fuel types, marine gas oil, and two heavy fuel oils (HFOs). An open-loop sulfur scrubber was installed in the exhaust line of a marine diesel test engine. Fine particulate matter was comprehensively characterized in terms of its physical and chemical properties. The wet scrubber led up to a 40% reduction in particle number, whereas a reduction in particle mass emissions was not generally determined. We observed a shift in the size distribution by the scrubber to larger particle diameters when the engine was operated on conventional HFOs. The reduction in particle number concentrations and shift in particle size were caused by the coagulation of soot particles and formation/growing of sulfur-containing particles. Combining the scrubber with a wet electrostatic precipitator as an additional abatement system showed a reduction in particle number and mass emission factors by >98%. Therefore, the application of a wet scrubber for the after-treatment of marine fuel oil combustion will reduce SO2 emissions, but it does not substantially affect the number and mass concentration of respirable particulate matters. To reduce particle emission, the scrubber should be combined with additional abatement systems

    Absence of gut microbiota impairs depletion of Paneth cells but not goblet cells in germ-free Atoh1lox/lox VilCreERT2 mice.

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    Mouse atonal homolog 1 (Math1/Atoh1) is a basic helix-loop-helix transcription factor important for the differentiation of secretory cells within the intestinal epithelium. The analysis of Paneth depletion efficiency upon Math1lox/loxVilCreERT2 (Math1∆IEC) mice treatment with Tamoxifen in the presence or absence of intestinal microbiota, showed a failure on Paneth cell depletion in germ-free mice as compared to SPF mice. However, goblet cells were efficiently depleted in Math1∆IEC germ-free mice. The gene expression of Math1 was significantly reduced in the ileum of germ-free Math1∆IEC mice 5 days post tamoxifen injection as compared to germ-free control, but its protein expression was still detectable in the nuclei of epithelial cells in the crypts. Germ-free mice showed low proliferative ileal crypts as well as apoptotic cells that were mainly detected in the tip of the villus, consistent with a slow turnover rate of epithelial cells. Although Paneth cells were not depleted in germ-free Math1∆IEC mice for the first 7 weeks after the last tamoxifen injection - far already from the 5 days timelaps observed in SPF conditions- but an incomplete depletion of Paneth cells was observed 14 weeks after last tamoxifen injection. Colonization of germ-free mice restored the phenotype observed in SPF mice, highlighting the regulatory role of gut microbes in our model. We conclude that absence of intestinal microbiota in Math1∆IEC mice is associated with reduced epithelial cell renewal and delays the depletion of preexisting Paneth cells

    Mobilise-D insights to estimate real-world walking speed in multiple conditions with a wearable device

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    This study aimed to validate a wearable device’s walking speed estimation pipeline, considering complexity, speed, and walking bout duration. The goal was to provide recommendations on the use of wearable devices for real-world mobility analysis. Participants with Parkinson’s Disease, Multiple Sclerosis, Proximal Femoral Fracture, Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and healthy older adults (n = 97) were monitored in the laboratory and the real-world (2.5 h), using a lower back wearable device. Two walking speed estimation pipelines were validated across 4408/1298 (2.5 h/laboratory) detected walking bouts, compared to 4620/1365 bouts detected by a multi-sensor reference system. In the laboratory, the mean absolute error (MAE) and mean relative error (MRE) for walking speed estimation ranged from 0.06 to 0.12 m/s and − 2.1 to 14.4%, with ICCs (Intraclass correlation coefficients) between good (0.79) and excellent (0.91). Real-world MAE ranged from 0.09 to 0.13, MARE from 1.3 to 22.7%, with ICCs indicating moderate (0.57) to good (0.88) agreement. Lower errors were observed for cohorts without major gait impairments, less complex tasks, and longer walking bouts. The analytical pipelines demonstrated moderate to good accuracy in estimating walking speed. Accuracy depended on confounding factors, emphasizing the need for robust technical validation before clinical application. Trial registration: ISRCTN – 12246987