Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

Risk factors associated to tobacco and alcohol use in a large French cohort of pregnant women

Archives of Women's Mental Health - Tobacco and/or alcohol use during pregnancy is a major public health concern. The aim of our study was to identify risk factors associated to maternal...     

Intra-laboratory analytical variability of biochemical markers of fibrosis (Fibrotest) and activity (Actitest) and reference ranges in healthy blood donors.

Combinations of tests comprising alpha2-macroglobulin, haptoglobin, apolipoprotein Al, gamma-glutamyltransferase, total bilirubin (Fibrotest) and alanine aminotransferase (Actitest) are being developed as alternatives to liver biopsy in patients with chronic hepatitis C. The aim of this study was to assess in the same laboratory the impact of parameter assay variations on Fibrotest and Actitest results and intra-patient reproducibility of the two tests. The stability of the samples for each test was studied after storage at -80 degrees C and -20 degrees C. Within-run, between-run and total imprecision for each parameter assay, and for Fibrotest and Actitest results, were determined. Transferability of assay results between different analyzers was studied. Intra-patient reproducibility was assessed in 55 hospitalized patients. Fibrotest and Actitest reference ranges were determined in 300 blood donors (reference group). The stability of the parameters was affected by serum storage at -20 degrees C only. The impact of parameter analytical variability on Fibrotest and Actitest results was less than 10% and intra-patient reproducibility was acceptable (p > 0.05). The transferability between different analyzers of results of assays performed under the same standardized and calibration conditions was excellent. Fibrotest and Actitest reference ranges in blood donors were (mean+/-SE) 0.075+/-0.004 and 0.068+/-0.004, respectively. The low intra-laboratory and intra-patient variability in Fibrotest and Actitest results confirm Fibrotest and Actitest reliability.     

Tetracycline use in the community may promote decreased susceptibility to quinolones in <Emphasis Type="Italic">Escherichia coli</Emphasis> isolates

We previously found that the hospital use of tetracyclines is associated with quinolone resistance in hospital isolates of Enterobacteriaceae. Tetracyclines are heavily used in the community. Our aim was to assess whether their use in the community favors quinolone resistance in community isolates of Escherichia coli. Monthly data of community antibiotics use and E. coli quinolone resistance in a 1.3 million inhabitant French area were obtained from 2009 to 2014, and were analyzed with autoregressive integrated moving average (ARIMA) models. Quinolone use decreased from 10.1% of the total antibiotic use in 2009 to 9.3% in 2014 (trend, ? 0.016; p-value < 0.0001), while tetracycline use increased from 16.5% in 2009 to 17.1% in 2014 (trend, 0.016; p < 0.0001). The mean (95% confidence interval) monthly proportions of isolates that were non-susceptible to nalidixic acid and ciprofloxacin were 14.8% (14.2%–15.5%) and 9.5% (8.8%–10.1%), respectively, with no significant temporal trend. After adjusting on quinolone use, tetracycline use in the preceding month was significantly associated with nalidixic acid non-susceptibility (estimate [SD], 0.01 [0.007]; p-value, 0.04), but not with ciprofloxacin non-susceptibility (estimate [SD], 0.01 [0.009]; p-value, 0.23). Tetracycline use in the community may promote quinolone non-susceptibility in E. coli. Decreasing both tetracycline and quinolone use may be necessary to fight against the worldwide growth of quinolone resistance.     

Efficacy and tolerance of immune checkpoint inhibitors in transplant patients with cancer: A systematic review

Solid organ transplant (SOT) is frequently complicated by cancers, which render immunosuppression challenging. Immune checkpoint inhibitors have emerged as treatments for many cancers. Data are lacking regarding efficacy and rejection risk in the SOT population. We conducted a systematic literature review and analyzed 83 cases of immune checkpoint inhibitor use for cancer in SOT. Two thirds of these patients received anti–programmed death ligand 1 therapy, 15.7% received anti–cytotoxic T lymphocyte–associated protein 4 therapy, and 10.8% received a combination. Allograft rejection occurred in 39.8% of patients, leading to end‐stage organ failure in 71.0% of cases. Outcomes were similar across organs and immunotherapy regimens. The use of immunosuppressants other than steroids, time since transplant, and prior episodes of rejection were associated with the risk of rejection. The median overall survival of patients was 36 weeks. Most of the deaths were related to cancer progression. In nonkidney recipients, graft rejection was strongly associated with worse survival. At the end of the study, 19.3% of the patients were alive, free from rejection and tumor progression. This study highlights the difficult tradeoff facing oncologists and transplant specialists managing transplant recipients with cancer, and the need for prospective data and novel biomarkers for identifying the patients likely to benefit from immunotherapy in the SOT setting.     

Severe spontaneous epistaxis: retrospective study in a tertiary ENT centre

European Archives of Oto-Rhino-Laryngology - To investigate the clinical profile and outcomes of different treatment strategies in patients hospitalized for spontaneous severe epistaxis. This is a...