Mannduggan5883

Hiiti Sillo and colleagues reveal how the East African Community's Medicines Regulatory Harmonization initiative improves access to important medicines in Africa.Here we examine a class of neurons that have been recently explored, the somatosensory neuronal subclass of cold thermosensors. We create a mathematical model of a cold sensing neuron that has been formulated to understand the variety of ionic channels involved. In particular this model showcases the role of TRPM8 and voltage gated potassium channels in setting the temperature dependent activation and inactivation threshold level. Bifurcation analysis of the model demonstrates that a Hodgkin-Huxley type model with additional TRPM8 channels is sufficient to replicate observable experimental features of when different threshold level cold thermosensors turn on. Additionally, our analysis gives insight into what is happening at the temperature levels at which these neurons shut off and the role sodium and leak currents may have in this. This type of model construction and analysis provides a framework moving forward that will help tackle less well understood neuronal classes and their important ionic channels.Shiga toxin-producing Escherichia coli (STEC) that cause severe disease predominantly carry the toxin gene variant stx2a. However, the role of Shiga toxin in the ruminant reservoirs of this zoonotic pathogen is poorly understood and strains that cause severe disease in humans (HUSEC) likely constitute a small and atypical subset of the overall STEC flora. The aim of this study was to investigate the presence of stx2a in samples from cattle and to isolate and characterize stx2a-positive E. coli. In nationwide surveys in Sweden and Norway samples were collected from individual cattle or from cattle herds, respectively. Samples were tested for Shiga toxin genes by real-time PCR and amplicon sequencing and stx2a-positive isolates were whole genome sequenced. Among faecal samples from Sweden, stx1 was detected in 37%, stx2 in 53% and stx2a in 5% and in skin (ear) samples in 64%, 79% and 2% respectively. In Norway, 79% of the herds were positive for stx1, 93% for stx2 and 17% for stx2a. Based on amplicon sequencing the most common stx2 types in samples from Swedish cattle were stx2a and stx2d. Multilocus sequence typing (MLST) of 39 stx2a-positive isolates collected from both countries revealed substantial diversity with 19 different sequence types. Only a few classical LEE-positive strains similar to HUSEC were found among the stx2a-positive isolates, notably a single O121H19 and an O26H11. Lineages known to include LEE-negative HUSEC were also recovered including, such as O113H21 (sequence type ST-223), O130H11 (ST-297), and O101H33 (ST-330). We conclude that E. coli encoding stx2a in cattle are ranging from strains similar to HUSEC to unknown STEC variants. Comparison of isolates from human HUS cases to related STEC from the ruminant reservoirs can help identify combinations of virulence attributes necessary to cause HUS, as well as provide a better understanding of the routes of infection for rare and emerging pathogenic STEC.The scoping review aimed to examine the evidence on the role of synbiotics in caries prevention. PubMed, SCOPUS, and Web of Science databases search were performed. Any in vitro study, clinical trial, systematic review with/without meta-analysis, umbrella review/meta-evaluation, narrative review addressing the role of synbiotics in caries prevention were included in the scoping review. Data were extracted from the included studies using pre-approved registered protocol. Twenty-eight records were identified, of which 5 in vitro studies, 1 quasi-experimental clinical trial and 1 narrative review were included in the present review. No controlled clinical trials or systematic reviews on the role of synbiotics in caries prevention could be identified. Except 1, all in vitro studies examined the combined effect of saccharides and lactobacilli spp. as potential synbiotics on the growth of Streptococcus mutans. However, the proposed synbiotics in 4 in vitro studies either did not qualify or remained ambiguous of its eligibility as a potential synbiotic for caries prevention. One recent in vitro study explored the possibility of L-arginine and Lactobacillus rhamnosus GG synbiotic for caries prevention. The quasi-experimental clinical study without a control arm did not explicitly mention the intervention composition and thus, its synbiotic potential remains unclear. A narrative review highlighted the potential of combining arginine (prebiotic) with arginolytic bacteria (probiotic) as a synbiotic, which appears promising for caries prevention. The eligibility of the proposed synbiotics as a true synbiotic needs to be carefully addressed. Due to a lack of controlled clinical studies on synbiotics for caries prevention, evidence on their caries-preventive potential is weak. Future studies are needed to examine the combination of amino acids (esp. arginine) with probiotics as a potential synbiotic against cariogenic pathogens.Quantifying the association between lifetime exposures and the risk of developing a chronic disease is a recurrent challenge in epidemiology. Individual exposure trajectories are often heterogeneous and studying their associations with the risk of disease is not straightforward. We propose to use a latent class mixed model (LCMM) to identify profiles (latent classes) of exposure trajectories and estimate their association with the risk of disease. The methodology is applied to study the association between lifetime trajectories of smoking or occupational exposure to asbestos and the risk of lung cancer in males of the ICARE population-based case-control study. Asbestos exposure was assessed using a job exposure matrix. The classes of exposure trajectories were identified using two separate LCMM for smoking and asbestos, and the association between the identified classes and the risk of lung cancer was estimated in a second stage using weighted logistic regression and all subjects. A total of 2026/2610 cases/controls had complete information on both smoking and asbestos exposure, including 1938/1837 cases/controls ever smokers, and 1417/1520 cases/controls ever exposed to asbestos. The LCMM identified four latent classes of smoking trajectories which had different risks of lung cancer, all much stronger than never smokers. The most frequent class had moderate constant intensity over lifetime while the three others had either long-term, distant or recent high intensity. The latter had the strongest risk of lung cancer. We identified five classes of asbestos exposure trajectories which all had higher risk of lung cancer compared to men never occupationally exposed to asbestos, whatever the dose and the timing of exposure. check details The proposed approach opens new perspectives for the analyses of dose-time-response relationships between protracted exposures and the risk of developing a chronic disease, by providing a complete picture of exposure history in terms of intensity, duration, and timing of exposure.