Androgen deprivation therapy (ADT) is the main treatment strategy for men with metastatic prostate cancer (PC). However, ADT is associated with various metabolic disturbances, including impaired glucose tolerance, insulin resistance and weight gain, increasing risk of diabetes and cardiovascular death. Much remains unknown about the metabolic pathways and disturbances altered by ADT and the mechanisms. We assessed the metabolomic effects of ADT in the serum of 20 men receiving ADT. Sera collected before (baseline), 3 and 6 months after initiation of ADT was used for the metabolomics and lipidomics analyses. The ADT-associated metabolic changes were identified by univariable and multivariable statistical analysis, ANOVA, and Pearson correlation. We found multiple key changes. First, ADT treatments reduced the steroid synthesis as reflected by the lower androgen sulfate and other steroid hormones. Greater androgen reduction was correlated with higher serum glucose levels, supporting the diabetogenic role of ADT. Second, ADT consistently decreased the 3-hydroxybutyric acid and ketogenesis. Third, many acyl-carnitines were reduced, indicating the effects on the fatty acid metabolism. Fourth, ADT was associated with a corresponding reduction in 3-formyl indole (a.k.a. indole-3-carboxaldehyde), a microbiota-derived metabolite from the dietary tryptophan. Indole-3-carboxaldehyde is an agonist for the aryl hydrocarbon receptor and regulates the mucosal reactivity and inflammation. Together, these ADT-associated metabolomic analyses identified reduction in steroid synthesis and ketogenesis as prominent features, suggesting therapeutic potential of restricted ketogenic diets, though this requires formal testing. ADT may also impact the microbial production of indoles related to the immune pathways. Future research is needed to determine the functional impact and underlying mechanisms to prevent ADT-linked comorbidities and diabetes risk.

Dental pulp with special structure has become a good reference sample in paleomicrobiology-related blood-borne diseases, many pathogens were detected by different methods based on the diagnosis of nucleic acids and proteins.

Soluble suppression of tumorigenicity-2 (sST2) is a strong prognostic biomarker in heart failure. The emerging understanding of circadian biology in cardiovascular disease may lead to novel applications in prognosis and diagnosis and may provide insight into mechanistic aspects of the disease-biomarker interaction. So far, it is unknown whether sST2 exhibits a diurnal rhythm. Repeated measurements of sST2 may aid in clinical decision making. The goal of this study was to investigate whether sST2 exhibits diurnal variation in patients with heart failure with reduced ejection fraction (HFrEF) and in control subjects, thereby enhancing its diagnostic and prognostic values.

There could be a gap between asthma management guidelines and current practice. We evaluated the awareness of and compliance with asthma management guidelines, and the internal and external barriers to compliance, for the first time in Korea.

Stress echocardiography has a 72%-85% sensitivity and an 80%-95% specificity. In this study, we characterized patients who received a false-positive stress echocardiogram result.

Pericytes (PCs) are multipotent vascular precursors that play a critical physiological role in the development and maintenance of blood vessel integrity. In this study, we aim to characterize PCs isolated from human abdominal adipose tissue and develop an integration-free induced pluripotent stem cells (iPSCs) using episomal vectors.

Cav3.2 T-type calcium channels play an essential role in the transmission of peripheral nociception in the dorsal root ganglia (DRG) and alteration of Cav3.2 expression is associated with the development of peripheral painful diabetic neuropathy (PDN). Several studies have previously documented the role of glycosylation in the expression and functioning of Cav3.2 and suggested that altered glycosylation of the channel may contribute to the aberrant expression of the channel in diabetic conditions. In this study, we aimed to analyze the expression of glycan-processing genes in DRG neurons from a leptin-deficient genetic mouse model of diabetes (db/db). Transcriptomic analysis revealed that several glycan-processing genes encoding for glycosyltransferases and sialic acid-modifying enzymes were upregulated in diabetic conditions. Functional analysis of these enzymes on recombinant Cav3.2 revealed an unexpected loss-of-function of the channel. Collectively, our data indicate that diabetes is associated with an alteration of the glycosylation machinery in DRG neurons. However, individual action of these enzymes when tested on recombinant Cav3.2 cannot explain the observed upregulation of T-type channels under diabetic conditions.Abbreviations: Galnt16: Polypeptide N-acetylgalactosaminyltransferase 16; B3gnt8: UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8; B4galt1: Beta-1,4-galactosyltransferase 1; St6gal1: Beta-galactoside alpha-2,6-sialyltransferase 1; Neu3: Sialidase-3.

The aim of the present study was to evaluate the clinical relevance of mutations in tumor suppressor genes using whole-exome sequencing data from centenarians and young healthy individuals.

Group B streptococcus (GBS), a gram-positive coccus that occasionally causes neonatal sepsis or invasive infection in the elderly, has been considered a rare cause of endogenous bacterial endophthalmitis (EBE). However, the number of invasive GBS infections is increasing, particularly in elderly patients with underlying conditions such as diabetes mellitus (DM), cardiovascular disease and cancer. We report 6 cases of EBE caused by GBS and review the literature.

Health educators aim to graduate students who are safe, effective and practice evidence-based medicine (EBM). Clinical Practice Guidelines (CPGs) are tools for translating evidence into clinical practice for health professionals and educators who lack time to appraise the evidence. There have been CPGs published for lateral ankle ligament sprains (LALS) for physiotherapists, nurses, and doctors. Clinical decision rules have also been developed for LALS to increase the safety of practice. The Ottawa Ankle Rules (OAR) were developed to screen for the need for an x-ray following an ankle or foot injury.

Digital assessment is becoming more and more popular within medical education. To analyse the dimensions of this digital trend, we investigated how exam questions (items) are created and designed for use in digital medical assessments in Germany. Thus, we want to explore whether different types of media are used for item creation and if a digital trend in medical assessment can be observed.

The purpose of this exploratory study was to investigate whether runners with certain biomechanical or clinical/anthropometrical characteristics sustain more running-related injuries than runners with other biomechanical or clinical/anthropometrical characteristics.

Bathyarchaeota, a newly proposed archaeal phylum, is considered as an important driver of the global carbon cycle. However, due to the great diversity of them, there is limited genomic information that accurately encompasses the metabolic potential of the entire archaeal phylum.

Saline-alkaline stress is a major abiotic stress that is harmful to plant growth worldwide. Two peach cultivars (GF677 and Maotao) display distinct phenotypes under saline-alkaline stress. The molecular mechanism explaining the differences between the two cultivars is still unclear.

Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study.

Bacterial exopolysaccharides (EPSs) are known to modulate immunity. To date, a plethora of studies have reported the effect of EPSs on intestinal cells; however few works have revealed a complete picture of the signalling events in intestinal epithelial cells induced by bacterial EPSs. Here, using transcriptomics, we comprehensively mapped the biological processes in porcine intestinal epithelial cells challenged with EPS derived from Lactobacillus reuteri alone, enterotoxigenic Escherichia coli (ETEC) or ETEC after pretreatment with EPS. The Gene Ontology analysis of differentially expressed genes (DEGs) showed that ETEC is able to evoke biological processes specifically involved in cell junction reorganization, extracellular matrix degradation, and activation of the innate immune response through the activation of pattern recognition receptors, such as TLRs and CTRs. A total of 495 DEGs were induced in ETEC-challenged cells. On the other hand, EPS pretreatment was able to attenuate overexpression of the genes induced by ETEC infection. The most relevant finding of this study is that EPS has a suppressive effect on the inflammatory response evoked by ETEC infection. On the basis of high-throughput RNA-seq, this report is the first to describe the effects of EPSs derived from L. reuteri used as a pretreatment of global gene expression in porcine epithelial cells.

From 1971 to 2012, in New York State, years with human Eastern equine encephalitis (EEE) were more strongly associated with the presence of Aedes canadensis, Coquillettidia perturbans and Culiseta melanura mosquitoes infected with the EEE virus (Fisher's exact test, one-sided P = 0.005, 0.03, 0.03) than with Culiseta morsitans, Aedes vexans, Culex pipiens-restuans, Anopheles quadrimaculatus or Anopheles punctipennis (P = 0.05, 0.40, 0.33, 1.00, 1.00). The estimated relative risk of a case in a year in which the virus was detected vs. not detected was 14.67 for Ae. canadensis, 6.38 for Cq. perturbans and 5.50 for Cs. morsitans. In all 5 years with a case, Cs. melanura with the virus was detected. In no year was there a case in the absence of Cs. melanura with the virus. There were 18 years with no case in the presence of Cs. melanura with the virus. Such observations may identify the time of increased risk, and when the methods may be used to prevent or reduce exposure to vector mosquito species in this geographic region.

Understanding host and pathogen factors that influence tuberculosis (TB) transmission can inform strategies to eliminate the spread of Mycobacterium tuberculosis (Mtb). Determining transmission links between cases of TB is complicated by a long and variable latency period and undiagnosed cases, although methods are improving through the application of probabilistic modelling and whole-genome sequence analysis. Using a large dataset of 1857 whole-genome sequences and comprehensive metadata from Karonga District, Malawi, over 19 years, we reconstructed Mtb transmission networks using a two-step Bayesian approach that identified likely infector and recipient cases, whilst robustly allowing for incomplete case sampling. We investigated demographic and pathogen genomic variation associated with transmission and clustering in our networks. We found that whilst there was a significant decrease in the proportion of infectors over time, we found higher transmissibility and large transmission clusters for lineage 2 (Beijing) strains. By performing evolutionary convergence testing (phyC) and genome-wide association analysis (GWAS) on transmitting versus non-transmitting cases, we identified six loci, PPE54, accD2, PE_PGRS62, rplI, Rv3751 and Rv2077c, that were associated with transmission. This study provides a framework for reconstructing large-scale Mtb transmission networks. We have highlighted potential host and pathogen characteristics that were linked to increased transmission in a high-burden setting and identified genomic variants that, with validation, could inform further studies into transmissibility and TB eradication.

Klebsiella pneumoniae has emerged as an important nosocomial pathogen, with whole-genome sequencing (WGS) significantly improving our ability to characterize associated outbreaks. Our study sought to perform a genome-wide analysis of multiclonal K. pneumoniae isolates (n=39; 23 patients) producing extended spectrum beta-lactamases and/or carbapenemases sourced between 2011 and 2016 in a Portuguese tertiary-care hospital. All isolates showed resistance to third-generation cephalosporins and six isolates (five patients) were also carbapenem resistant. Genome-wide-based phylogenetic analysis revealed a topology representing ongoing dissemination of three main sequence-type (ST) clades (ST15, ST147 and ST307) and transmission across different wards, compatible with missing links that can take the form of undetected colonized patients. Two carbapenemase-coding genes were detected: blaKPC-3, located on a Tn4401d transposon, and blaGES-5 on a novel class 3 integron. Additionally, four genes coding for ESBLs (blaBEL-1, blaCTX-M-8, blaCTX-M-15 and blaCTX-M-32) were also detected. ESBL horizontal dissemination across five clades is highlighted by the similar genetic environments of blaCTX-M-15 gene upstream of ISEcp1 on a Tn3-like transposon. Overall, this study provides a high-resolution genome-wide perspective on the epidemiology of ESBL and carbapenemase-producing K. pneumoniae in a healthcare setting while contributing for the adoption of appropriate intervention and prevention strategies.

Understanding of the molecular basis of host cell-miRNA interactions is prerequisite to the successful application of miRNAs as potential therapeutic agents. We studied the morphological and molecular consequences of over expression of three sequence divergent miRNAs previously implicated in the mesenchymal-to-epithelial transition process (MET) in three distinct mesenchymal-like cancer cell lines. The ability of miRNAs to induce morphological changes characteristic of MET positively correlated with induced changes in the expression of genes previously implicated in the process. Variability in the responses of different mesenchymal-like cells to over expression of the same miRNAs was attributable to inherent differences in trans-regulatory profiles pre-disposing these cells to miRNA-induced MET. Collectively our results indicate that miRNA-mediated regulation of MET is a highly integrated process that is significantly modulated by the molecular background of individual cells.