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Abstract Background The opportunistic food-borne gram-positive pathogen Listeria monocytogenes can exist as a free-living microorganism in the environment and grow in the cytoplasm of vertebrate and invertebrate cells following infection. The general stress response, controlled by the alternative sigma factor, σB, has an important role for bacterial survival both in the environment and during infection. We used quantitative real-time PCR analysis and immuno-blot analysis to examine σB expression during growth of L. monocytogenes EGD-e. Whole genome-based transcriptional profiling was used to identify σB-dependent genes at different growth phases. Results We detected 105 σB-positively regulated genes and 111 genes which appeared to be under negative control of σB and validated 36 σB-positively regulated genes in vivo using a reporter gene fusion system. Conclusion Genes comprising the σB regulon encode solute transporters, novel cell-wall proteins, universal stress proteins, transcriptional regulators and include those involved in osmoregulation, carbon metabolism, ribosome- and envelope-function, as well as virulence and niche-specific survival genes such as those involved in bile resistance and exclusion. Ten of the σB-positively regulated genes of L. monocytogenes are absent in L. innocua. A total of 75 σB-positively regulated listerial genes had homologs in B. subtilis, but only 33 have been previously described as being σB-regulated in B. subtilis even though both species share a highly conserved σB-dependent consensus sequence. A low overlap of genes may reflects adaptation of these bacteria to their respective environmental conditions.

: Introduction: Extrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. Diagnosis can be especially challenging in under‐resourced settings. We studied diagnostic modalities and clinical outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV‐positive adults in antiretroviral therapy (ART) programmes in low‐ and middle‐income countries (LMIC). Methods: We collected data from HIV‐positive TB patients (≥16 years) in 22 ART programmes participating in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in sub‐Saharan Africa, Asia‐Pacific, and Caribbean, Central and South America regions between 2012 and 2014. We categorized TB as PTB or EPTB (EPTB included mixed PTB/EPTB). We used multivariable logistic regression to assess associations with clinical outcomes. Results and Discussion: We analysed 2695 HIV‐positive TB patients. Median age was 36 years (interquartile range (IQR) 30 to 43), 1102 were female (41%), and the median CD4 count at TB treatment start was 114 cells/μL (IQR 40 to 248). Overall, 1930 had PTB (72%), and 765 EPTB (28%). Among EPTB patients, the most frequently involved sites were the lymph nodes (24%), pleura (15%), abdomen (11%) and meninges (6%). The majority of PTB (1123 of 1930, 58%) and EPTB (582 of 765, 76%) patients were diagnosed based on clinical criteria. Bacteriological confirmation (using positive smear microscopy, culture, Xpert MTB/RIF, or other nucleic acid amplification tests result) was obtained in 897 of 1557 PTB (52%) and 183 of 438 EPTB (42%) patients. EPTB was not associated with higher mortality compared to PTB (adjusted odd ratio (aOR) 1.0, 95% CI 0.8 to 1.3), but TB meningitis was (aOR 1.9, 95% CI 1.0 to 3.1). Bacteriological confirmation was associated with reduced mortality among PTB patients (aOR 0.7, 95% CI 0.6 to 0.8) and EPTB patients (aOR 0.3 95% CI 0.1 to 0.8) compared to TB patients with a negative test result. Conclusions: Diagnosis of EPTB and PTB at ART programmes in LMIC was mainly based on clinical criteria. Greater availability and usage of TB diagnostic tests would improve the diagnosis and clinical outcomes of both EPTB and PTB., Introduction In low‐ and middle‐income countries (LMIC), tuberculosis (TB) accounts for approximately 40% of HIV/AIDS‐related deaths among adults, and half of those TB cases are undiagnosed at the time of [...]

ESPEN guideline on clinical nutrition in hospitalized patients with acute or chronic kidney disease. Possible benefits of a low protein diet in older patients with CKD at risk of malnutrition: a pilot randomized controlled trial. Therefore, older adults represent a growing proportion among patients with chronic kidney disease (CKD). Although no studies have specifically examined this issue extensively in CKD patients, observational studies indicate that a diet rich in plant-based proteins is associated with a reduced risk of developing new-onset CKD in middle-aged and older adults [[18]]. [Extracted from the article]

Anterior segment optical coherence tomography (AS-OCT), being non-invasive and well-tolerated, is the method of choice for an in vivo investigation of ciliary muscle morphology and function. The analysis requires the segmentation of the ciliary muscle, which is, when performed manually, both time-consuming and prone to examiner bias. Here, we present a convolutional neural network trained for the automatic segmentation of the ciliary muscle in AS-OCT images. Ciloctunet is based on the Freiburg U-net and was trained and validated using 1244 manually segmented OCT images from two previous studies. An accuracy of 97.5% for the validation dataset was achieved. Ciloctunet's performance was evaluated by replicating the findings of a third study with 180 images as the test data. The replication demonstrated that Ciloctunet performed on par with two experienced examiners. The intersection-over-union index (0.84) of the ciliary muscle thickness profiles between Ciloctunet and an experienced examiner was the same as between the two examiners. The mean absolute error between the ciliary muscle thickness profiles of Ciloctunet and the two examiners (35.16 µm and 45.86 µm) was comparable to the one between the examiners (34.99 µm). A statistically significant effect of the segmentation type on the derived biometric parameters was found for the ciliary muscle area but not for the selective thickness reading ("perpendicular axis"). Both the inter-rater and the intra-rater reliability of Ciloctunet were good to excellent. Ciloctunet avoids time-consuming manual segmentation, thus enabling the analysis of large numbers of images of ample study cohorts while avoiding possible examiner biases. Ciloctunet is available as open-source. [ABSTRACT FROM AUTHOR]

Background In people with human immunodeficiency virus [HIV] presenting with advanced disease, rates of virologic success may be lower than expected. The Reflate TB2 trial did not show non-inferiority of raltegravir versus efavirenz in people with HIV (PWH) treated for tuberculosis. We aimed to identify factors associated with virologic success and higher adherence in the trial. Methods In this analysis, we included participants enrolled in the Reflate TB2 trial with adherence data available. The primary outcome was virologic success (HIV-1 ribonucleic acid [RNA] <50 copies/mL) at week 48, and the secondary outcome was adherence as assessed by the pill count adherence ratio. We used logistic regression to study determinants of virologic success and optimal adherence in 2 separate analyses. Results Four hundred forty-four participants were included in the present analysis. Over the 48-week follow-up period, 290 of 444 (65%) participants had a pill count adherence ratio ≥95%. At week 48, 288 of 444 (65%) participants were in virologic success. In the multivariate analysis, female sex (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.16–2.72; P =.0084), lower baseline HIV-1 RNA levels (<100 000; aOR, 2.29; 95% CI, 1.33–3.96; P =.0087), and pill count adherence ratio ≥95% (aOR, 2.38; 95% CI, 1.56–3.62; P <.0001) were independently associated with virologic success. Antiretroviral pill burden was the only factor associated with pill count adherence ratio ≥95% (OR, 0.81; 95% CI,.71–.92; P =.0018). Conclusions In PWH with tuberculosis receiving raltegravir or efavirenz-based regimens, female sex, optimal adherence, and baseline HIV-1 RNA <100 000 copies/mL were associated with virologic success, and the number of antiretroviral tablets taken daily was a strong predictor of adherence. [ABSTRACT FROM AUTHOR]

Aims: Elevated brain natriuretic peptide (BNP) and the N‐terminal fragment of its pro‐hormone (NT‐proBNP) have become established biomarkers for heart failure and are associated with cardiovascular morbidity and mortality. Investigating sources of inter‐individual heterogeneity, particularly genetic factors, could help better identify patients at risk of future cardiovascular disease. The aim of this study was to estimate the heritability of circulating NT‐proBNP levels, to perform a genome‐wide association study (GWAS) and gene‐candidate analysis focused on NPPB–NPPA genes on these levels, and to examine their association with cardiovascular or metabolic outcomes. Methods and results: A total of 1555 individuals from the STANISLAS study were included. The heritability of circulating NT‐proBNP levels was estimated at 15%, with seven single nucleotide polymorphisms (SNPs) reaching the significant threshold in the GWAS. All above SNPs were located on the same gene cluster constituted of MTHFR, CLCN6, NPPA, NPPB, and C1orf167. NPPA gene expression was also associated with NT‐proBNP levels. Moreover, six other SNPs from NPPA–NPPB genes were associated with diastolic function (lateral e′ on echocardiography) and metabolic features (glycated haemoglobin). Conclusions: The heritability of natriuretic peptides appears relatively low (15%) and mainly based on the same gene cluster constituted of MTHFR, CLCN6, NPPA, NPPB, and C1orf167. Natriuretic peptide polymorphisms are associated with natriuretic peptide levels and diastolic function. These results suggest that natriuretic peptide polymorphisms may have an impact in the early stages of cardiovascular and metabolic disease. [ABSTRACT FROM AUTHOR]

This article examines the recent literary form of mash-up novels by comparing the German mash-up Werther, der Werwolf (2010) to its original Die Leiden des jungen Werther (1774) by Johann Wolfgang von Goethe. In both novels, the protagonist Werther is conceptualised as an antihero. In Goethe's original, Werther's existential failure is a result of his mental condition and inability to integrate into the bourgeois society; in the mash-up he fails because he struggles with his metamorphosis into a werewolf. In both cases, Werther's obsessive love for a girl called Lotte aggravates the underlying conflict. This article aims to demonstrate the extent to which the antiheroic qualities of Goethe's Werther are reflected in the mash-up character Werewolf-Werther, and to highlight to what extent the figure of the werewolf is an apt and contemporary metaphor for Werther's story. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence available identifying best practices to promote and sustain optimal outpatient-to-inpatient handoff processes to ensure safe and reliable continuity of care. Local Problem: A sentinel event occurred during the transition of care from the outpatient-to-inpatient setting. A root cause analysis revealed that the facility's standard operating procedure for patient handoffs was not consistently followed. Methods: A Lean Six Sigma approach was used to improve patient transfer with the implementation of a Situation-Background-Assessment-Recommendation handoff policy. Inferential and statistical process control methods were used to assess performance outcomes pre- and postdissemination. Results: Over 36 months there was a slow, steady decrease in patient transfer time including reduced variability. The most significant improvement effect occurred in the third year with a 50% reduction in transfer time. Conclusions: Longitudinal monitoring provides the opportunity to accurately identify beneficial outcomes, which develop downstream from initial quality improvement efforts. [ABSTRACT FROM AUTHOR]

Objective: Determining the factors associated with new-onset pre-diabetes and type 2 diabetes mellitus (T2D) is important for improving the current prevention strategies and f or a better understanding of the disease. Design: To study the factors (clinical, circulating protein and geneti c) associated with new onset pre-diabetes and T2D in an initially healthy (without diabetes) populational familia l cohort with a long follow-up (STANISLAS cohort). Methods: A total of 1506 participants attended both the visit 1 and vis it 4, separated by ≈20 years. Over 400 proteins, GWAS and genetic associations were studied using models adjuste d for potential confounders. Both prospective (V1 to V4) and cross-sectional (V4) analyses were performed. Results: People who developed pre-diabetes (n = 555) and/or T2D (n = 73) were older, had higher BMI, blood pressure, glucose, LDL cholesterol, and lower eGFR. After multivariable s election, PAPP-A (pappalysin-1) was the only circulating protein associated with the onset of both pre-diabetes and T2D with associations persisting at visit 4 (i.e. ≈20 years later). FGF-21 (fibroblast growth factor 21) was a strong prognosticator for incident T2D in the longitudinal analysis, but not in the cross-sectional analysis. The heritability of the ci rculating PAPP-A was estimated at 44%. In GWAS analysis, the SNP rs634737 was associated with PAPP-A both at V1 and V4. External replication also showed lower levels of PAPP-A in patients with T2D. Conclusions: The risk of developing pre-diabetes and T2D increases with age and with features of the metabolic syndrome. Circulating PAPP-A, which has an important genetic co mponent, was associated with both the development and presence of pre-diabetes and T2D. [ABSTRACT FROM AUTHOR]