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    16S Daten Galle

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    Rohdaten 16S Amplicon Sequencing (Illumina). Ausgangsmaterial sind 209 Galleproben von 117 Patienten aus der MHH. Gewinnung der Proben zwischen Januar 2008 und November 2014 mittels ERCP

    Die Qualität der Zusammenfassung klinischer Studien in Prüferinformationen

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    Comprehensive Questionnaire in postpartum women to Assess Women’s Knowledge of the Current Weight Gain Guidelines during Pregnancy in Lower Saxory

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    Introduction: Maternal body mass index and gestational weight gain (GWG) are important factors for maternal and neonatal health. The objective of this study was to assess women’s knowledge and examine adherence to the Institute of Medicine (IOM) criteria for weight gain during pregnancy by evaluating the information received from obstetricians and women’s knowledge about GWG. Methods: This is an analytical semi-longitudinal observational study. Weight data from a not consecutive convenience sample of 389 women who gave birth at the Hannover Medical School in the period from 08/2020 to 07/2021 were taken from their maternal records. Immediately after giving birth the whole collective (n=389) was asked to participate in a questionnaire study including questions that were taken from the EMat Health Survey inquiring about their knowledge and received information about GWG and about their eating behavior. Here a subset of 202 women participated. Results: 65% of the participants who answered the questionnaire reported that they had not been informed by their obstetrician about GWG recommendations. Additionally, a minority of women knew the correct IOM GWG category based on their pre-pregnancy weight. Meeting the IOM GWG guidelines did not depend on whether or not women received GWG recommendations or knew about the correct GWG category. The majority of women were not concerned about gaining too much weight during pregnancy. 20.7% of all women participating in the study were affected by obesity pre-pregnancy. According the IOM criteria for GWG 50.4% gained too much weight. The proportion of women exceeding IOM recommendations was highest in women with pre-pregnancy overweight and obesity (67%). Discussion: Weight gain outside of the IOM recommendations is widespread in our survey. Information received and knowledge about GWG recommendations were inadequate in our sample. Considering the fact that GWG outside recommended ranges can contribute to short- and long-term health complications, especially when a woman enters pregnancy already with overweight or obesity, identifying ways of achieving a healthier GWG is warranted

    Association of torque teno virus viremia with liver fibrosis in the first year after liver transplantation.

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    Introduction Torque teno virus (TTV) replication is controlled by immune status, mirroring a degree of immunosuppression after solid organ transplantation. TTV viraemia (TTVv) was associated with acute cellular rejection and infection within the first year after liver transplantation (LT). Long-term data on TTV after LT and correlation with graft injury from protocol biopsies are limited. Methods One hundred plasma samples paired with graft biopsies from a prospective single-center biorepository were analyzed. Results The median time post-LT was 23 months (range, 2-298). TTVv was detectable in 97%. TTVv decreased over time after LT and showed a significant decline from year 1 to later time points. Hence, TTVv correlated negatively with histologic liver fibrosis (liver allograft fibrosis and Ishak scores) and positively with the overall immunosuppression degree quantified by an immunosuppression score in the first year after LT. There was no association with dosages or trough levels of single immunosuppressants. The pharmacodynamic marker TTVv did not correlate with pharmacokinetic assessments of immunosuppression degree [calcineurin inhibitor (CNI) trough levels or immunosuppressant dosages]-our clinical gold standards to guide immunosuppressive therapy. TTVv was independently associated with histologically proven liver fibrosis after LT in the first year after LT in multivariate analysis. Discussion The independent association of histological graft fibrosis with lower TTVv in year 1 underscores that a pharmacodynamic marker would be preferable to individualize immunosuppression after LT. However, a high variability of TTVv at the low immunosuppression doses given after the first year precludes TTV as a clinically useful marker after LT in the long-term liver transplant recipients

    NEWS RESIST- Resolving Infection Susceptibility 02/2023

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    Single cell RNA sequencing reveals distinct clusters of Irf8-expressing pulmonary conventional dendritic cells

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    A single population of interferon-regulatory factor 8 (Irf8)-dependent conventional dendritic cell (cDC type1) is considered to be responsible for both immunogenic and tolerogenic responses depending on the surrounding cytokine milieu. Here, we challenge this concept of an omnipotent single Irf8-dependent cDC1 cluster through analysis of pulmonary cDCs at single cell resolution. We report existence of a pulmonary cDC1 cluster lacking Xcr1 with an immunogenic signature that clearly differs from the Xcr1 positive cDC1 cluster. The Irf8+Batf3+Xcr1- cluster expresses high levels of pro-inflammatory genes associated with antigen presentation, migration and co-stimulation such as Ccr7, Cd74, MHC-II, Ccl5, Il12b and Relb while, the Xcr1+ cDC1 cluster expresses genes corresponding to immune tolerance mechanisms like Clec9a, Pbx1, Cadm1, Btla and Clec12a. In concordance with their pro-inflammatory gene expression profile, the ratio of Xcr1- cDC1s but not Xcr1+cDC1 is increased in the lungs of allergen-treated mice compared to the control group, in which both cDC1 clusters are present in comparable ratios. The existence of two distinct Xcr1+ and Xcr1- cDC1 clusters is furthermore supported by velocity analysis showing markedly different temporal patterns of Xcr1- and Xcr1+cDC1s. In summary, we present evidence for the existence of two different cDC1 clusters with distinct immunogenic profiles in vivo. Our findings have important implications for DC-targeting immunomodulatory therapies

    Determinants of severe QTc prolongation in a real-world gerontopsychiatric setting

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    Introduction QTc prolongation carries the risk of ventricular tachyarrhythmia (Torsades de Pointes) and sudden cardiac death. Psychotropic drugs can affect ventricular repolarization and thus prolong the QTc interval. The present study sought to investigate the risk factors (pharmacological and non-pharmacological) of severe QTc prolongation in gerontopsychiatric patients. Methods Electrocardiograms of patients on a gerontopsychiatric ward were screened for QTc prolongation. Medication lists were examined utilizing the AzCERT classification. Potential drug interactions were identified with the electronic drug interaction program mediQ. Results The overall prevalence of QTc prolongation was 13.6%, with 1.9% displaying severe QTc prolongation (≥ 500 ms). No statistically significant differences between patients with moderate and severe QTc prolongation were identified; however, patients with severe QTc prolongation tended to take more drugs (p = 0.063). 92.7% of patients with QTc prolongation took at least one AzCERT-listed drug, most frequently risperidone and pantoprazole. Risperidone and pantoprazole, along with pipamperone, were also most frequently involved in potential drug interactions. All patients displayed additional risk factors for QTc prolongation, particularly cardiac diseases. Conclusion In addition to the use of potentially QTc-prolonging drugs, other risk factors, especially cardiac diseases, appear to be relevant for the development of QTc prolongation in gerontopsychiatric patients. Pantoprazole was frequently involved in potential drug interactions and should generally not be used for more than 8 weeks in geriatric populations. As clinical consequences of QTc prolongation were rare, potentially QTc-prolonging drugs should not be used overcautiously; their therapeutic benefit should be considered as well. It is paramount to perform diligent benefit-risk analyses prior to the initiation of potentially QTc-prolonging drugs and to closely monitor their clinical (side) effects

    Systematic genetic analysis of pediatric patients with autoinflammatory diseases.

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    Monogenic autoinflammatory diseases (AID) encompass a growing group of inborn errors of the innate immune system causing unprovoked or exaggerated systemic inflammation. Diagnosis of monogenic AID requires an accurate description of the patients' phenotype, and the identification of highly penetrant genetic variants in single genes is pivotal. We performed whole exome sequencing (WES) of 125 pediatric patients with suspected monogenic AID in a routine genetic diagnostic setting. Datasets were analyzed in a step-wise approach to identify the most feasible diagnostic strategy. First, we analyzed a virtual gene panel including 13 genes associated with known AID and, if no genetic diagnosis was established, we then analyzed a virtual panel including 542 genes published by the International Union of Immunological Societies associated including all known inborn error of immunity (IEI). Subsequently, WES data was analyzed without pre-filtering for known AID/IEI genes. Analyzing 13 genes yielded a definite diagnosis in 16.0% (n = 20). The diagnostic yield was increased by analyzing 542 genes to 20.8% (n = 26). Importantly, expanding the analysis to WES data did not increase the diagnostic yield in our cohort, neither in single WES analysis, nor in trio-WES analysis. The study highlights that the cost- and time-saving analysis of virtual gene panels is sufficient to rapidly confirm the differential diagnosis in pediatric patients with AID. WES data or trio-WES data analysis as a first-tier diagnostic analysis in patients with suspected monogenic AID is of limited benefit

    Self-efficacy and its impact on the health behaviours during pregnancy

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