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    or French patient cohorts, we observed a good correlation of POSPOM with in-hospital mortality. Therefore, further adjustments of POSPOM considering also multicentre and transnational validation should be pursued based on this proof of concept.

    Very old patients (≥ 80 years-old, VOP) are increasingly admitted to intensive care units (ICUs). Community-acquired pneumonia (CAP) is a common reason for admission and the best strategy of support for respiratory failure in this scenario is not fully known. We evaluated whether noninvasive ventilation (NIV) would be beneficial compared to invasive mechanical ventilation (IMV) regarding hospital mortality.

    Multicenter cohort study of VOPs admitted with CAP in need of IMV or NIV to 11 Brazilian ICUs from 2009 through 2012. We used logistic regression models to evaluate the association between the initial ventilatory strategy (NIV vs. AICAR AMPK activator IMV) and hospital mortality adjusting for confounding factors. We evaluated effect modification with interaction terms in pre-specified sub-groups.

    Of 369 VOPs admitted for CAP with respiratory failure, 232 (63%) received NIV and 137 (37%) received IMV as initial ventilatory strategy. IMV patients were sicker at baseline (median SOFA 8 vs. 4). Hospital mortality was 114/232OP admitted with CAP, but there was no strong signal of harm from its use. The main confounders of this association were both the severity of respiratory dysfunction and of extra-respiratory organ failures.[This corrects the article DOI 10.1371/journal.pone.0216329.].Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, known genetic risk factors account for only 50% of the breast cancer genetic component and almost a quarter of hereditary cases are carriers of pathogenic mutations in BRCA1/2 genes. Hence, the genetic basis for a significant fraction of familial cases remains unsolved. This missing heritability may be explained in part by Copy Number Variations (CNVs). We herein aimed to evaluate the contribution of CNVs to hereditary breast cancer in Tunisia. Whole exome sequencing was performed for 9 BRCA negative cases with a strong family history of breast cancer and 10 matched controls. CNVs were called using the ExomeDepth R-package and investigated by pathway analysis and web-based bioinformatic tools. Overall, 483 CNVs have been identified in breast cancer patients. Rare CNVs affecting cancer genes were detected, of special interest were those disrupting APC2, POU5F1, DOCK8, KANSL1, TMTC3 and the mismatch repair gene PMS2. In addition, common CNVs known to be associated with breast cancer risk have also been identified including CNVs on APOBECA/B, UGT2B17 and GSTT1 genes. Whereas those disrupting SULT1A1 and UGT2B15 seem to correlate with good clinical response to tamoxifen. Our study revealed new insights regarding CNVs and breast cancer risk in the Tunisian population. These findings suggest that rare and common CNVs may contribute to disease susceptibility. Those affecting mismatch repair genes are of interest and require additional attention since it may help to select candidates for immunotherapy leading to better outcomes.[This corrects the article DOI 10.1371/journal.pone.0232391.].Emotion regulation is a central task of daily life. Difficulty regulating emotions is a core feature of borderline personality disorder (BPD), one of the most common and impairing personality disorder diagnoses. While anger and symptoms of depression are instantiated in the criteria for BPD, anxiety is not, despite being among the most common psychiatric symptoms. In a sample of online respondents (N = 471), we explored the interactions between anxiety symptoms and BPD traits in predicting well-being (WHO-5) as well as poorer work and social adjustment (WSAS), while controlling for anger and depression. We hypothesized that anxiety would lead to more impairment (i.e., lower well-being and poorer work and more difficulties with work and social adjustment) as BPD traits increased. BPD traits and symptoms of anxiety both contributed to overall lower levels well-being and higher levels of psychosocial dysfunction. However, contrary to our expectations, at higher (vs. lower) levels of BPD traits, symptoms of anxiety were less conducive to lower well-being on the WHO-5. For the WSAS, there was no consistent evidence for an interaction between BPD traits and anxiety in predicting functioning. By and large, our results do not support the idea that anxiety contributes to more impairment at higher levels of BPD traits.The objective of this study was to compare the effects of supplementation with two methionine isoforms, L-methionine (L-Met) or D-methionine (D-Met), on transcriptome expression in broiler chickens under acute heat stress. A total of 240 one-day-old chicks were randomly assigned to one of four treatments in a 2 × 2 factorial arrangement thermo-neutral vs. acute heat-stress and L-Met vs. D-Met supplementation. On day 14, the heat-stressed group was exposed to 32°C for 5 h, while the others remained at 25°C. Six chicks were randomly selected per treatment and total RNA was isolated from whole blood, ileum, and liver tissues. Two RNA samples from each tissue of each treatment group were randomly selected and pooled in equal amounts. A total of 1.87 billion raw reads obtained from 36 samples (four treatments × three tissues × three composited replicates) were mapped to the reference genome build (Gallus_gallus-5.0) and used to identify differentially expressed genes (DEGs) using DESeq2. Functional enrichment of DEGs was tested using DAVID. Comparing the two isoforms of supplemented methionine, two, three, and ten genes were differentially expressed (> 1 or less then -1 log2 fold change) in whole blood, ileum, and liver, respectively. A total of 38, 71, and 16 genes were differentially expressed in response to the interaction between heat stress and Met isoforms in the blood, ileum, and liver, respectively. Three-tissue-specific DEGs were functionally enriched for regulation of cholesterol homeostasis and metabolism, glucose metabolism, and vascular patterning. Chicks fed with L-Met had lower immune (e.g., IL4I1 and SERPINI1) and intestinal angiogenic responses (e.g., FLT1 and FGD5), and stable glucose and lipid metabolism (e.g., PCK1 and LDLR) under heat stress conditions. In conclusion, unlike D-Met, L-Met supplementation seems to help maintain physiological homeostasis and enhances cellular defense systems against external stresses like high environmental temperature.

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