Hornelott2773

Introduction Virus particles in respiratory droplets and aerosols generated during medical/dental procedures are a potential source of SARS-CoV-2 cross infection. In the dental setting, oral decontamination could be an important adjunct to personal protective equipment and is recommended by a number of national COVID-19 guidance documents for dental settings.Aim To assess the in vitrovirucidal activity of an oral povidone iodine (PVP-I) product against SARS-CoV-2.Material and methods BETADINE gargle and mouthwash (1% PVP-I) was tested against SARS-CoV-2 virus under both clean and dirty conditions using a suspension assay based on EN14476 methodology. Virucidal activity of the product, undiluted and at 12 dilution, was tested at contact times of 15, 30 and 60 seconds. Viral titres were calculated using the Spearman-Kärber method and reported as median tissue culture infectious dose (TCID50/ml).Results The undiluted product achieved >5 log10 reduction in viral titres compared to the control at 15, 30 and 60 seconds under both clean and dirty conditions. At a twofold dilution (0.5% PVP-I), the test product demonstrated >4 log10 kill at 15 seconds and >5 log10 kill at 30 and 60 seconds in both clean and dirty conditions.Conclusion PVP-I gargle and mouthwash product, undiluted and at 12 dilution, demonstrated potent and rapid virucidal activity (≥4 log10 reduction of viral titre) in 15 seconds against SARS-CoV-2 in vitro. The PVP-I gargle and mouthwash product is widely available and could be readily integrated into infection control measures during dental treatment including pre-procedural oral decontamination.Aims This study aims to elucidate the thoughts and experiences of community dental service (CDS) dentists on procurement. Interviews were conducted and accompanied by secondary analysis of census data.Methods Demographics and working conditions were examined and interview participants discussed the tendering process.Results CDS dentists were motivated by their patients and overall enjoyed their work. Interviews identified three key themes relating to commissioning 1) process - dentists' experience of the tendering process; 2) effects - what dentists believe their service looks like after tendering; and 3) results - how dentists believe tendering has affected patients. The point of commissioning was questioned. It was perceived to negatively affect the working environment and the care provided to patients, and was seen to cause a shift in service priorities. It was suggested that providers entered into a state of stasis during commissioning, leaving services to decay.Discussion This paper, the second in a series examining the community and public dental services, highlights the effects that commissioning has on staff and patient care, and builds on the understanding developed in the first paper of this series.Conclusions Further work is needed to examine the place of competitive commissioning in dentistry and, given its ubiquitous use, it is of importance to all dentistry stakeholders.MicroRNAs are small (~ 22nt long) noncoding RNAs (ncRNAs) that regulate gene expression at the post-transcriptional level. Over 2000 microRNAs have been described in humans and many are implicated in human pathologies including tissue fibrosis. Hepatic stellate cells (HSC) are the major cellular contributors to excess extracellular matrix deposition in the diseased liver and as such are important in the progression of liver fibrosis. We employed next generation sequencing to map alterations in the expression of microRNAs occurring across a detailed time course of culture-induced transdifferentiation of primary human HSC, this a key event in fibrogenesis. Furthermore, we compared profiling of human HSC microRNAs with that of rat HSC so as to identify those molecules that are conserved with respect to modulation of expression. Our analysis reveals that a total of 229 human microRNAs display altered expression as a consequence of HSC transdifferentiation and of these 104 were modulated early during the initiation phase. Typically modulated microRNAs were targeting kinases, transcription factors, chromatin factors, cell cycle regulators and growth factors. 162 microRNAs changed in expression during transdifferentiation of rat HSC, however only 17 underwent changes that were conserved in human HSC. Our study therefore identifies widespread changes in the expression of HSC microRNAs in fibrogenesis, but suggests a need for caution when translating data obtained from rodent HSC to events occurring in human cells.Volatile organic compounds (VOCs) represent a broad class of chemicals, many of which can be found in indoor air including residential indoor air. VOCs derive from a variety of sources including cleaning products, cooking practices, fragrances and fresheners, hobbies and at-home work behaviors. This study examined residential indoor air in homes (n = 99) in southeast Louisiana using passive organic vapor monitors and gas chromatography/mass spectrometry to determine if select VOCs were present, at what concentrations, and if those posed any potential long-term health risks. Twenty-nine VOCs were targeted in cross-sectional analyses using a 48-h sampling period. Twelve VOCs were detected in most of the homes sampled including xylenes, pinenes, benzene, toluene, ethylbenzene, hexane, pentane, chloroform, and carbon tetrachloride. Concentrations of alkanes and BTEX compounds were highly correlated (Spearman's r > 0.63, p  less then  0.0001). Using health risk measures (i.e. reference concentrations [RfCs] and inhalation unit risks [IURs]) available from the USEPA non-cancer risk assessments and cancer risk assessments were developed for some of these VOCs. Alkanes and BTEX compounds likely come from the same indoor source(s). Using existing health standards published by the USEPA, no unacceptable non-cancer risks were evident except under extremely high concentrations. Lifetime cancer risks, on the other hand, may well be considered unacceptable for chloroform and benzene (upper IUR) and for the combination of chloroform, benzene, and carbon tetrachloride. These exceeded a 1 in 10,000 cancer risk threshold in 35-50% of our simulations. Further study of residential indoor air in low-income women's homes in this area is needed. Including a larger number of VOCs may reveal yet more potential health risks.Proteins with a metallo-beta-lactamase (MBL) fold have been largely studied in bacteria in the framework of resistance to beta-lactams, but their spectrum of activities is broader. We show here that the giant Tupanvirus also encodes a MBL fold-protein that has orthologs in other giant viruses, a deep phylogenetic root and is clustered with tRNases. This protein is significantly associated with translation components in giant viruses. PF-573228 After expression in Escherichia coli, it was found to hydrolyse nitrocefin, a beta-lactam, and penicillin G. This was inhibited by sulbactam, a beta-lactamase inhibitor. In addition, the tupanvirus MBL fold-protein was not active on single- or double-stranded DNA, but degraded RNAs from bacteria and Acanthamoeba castellanii, the tupanvirus amoebal host. This activity was not neutralized by sulbactam. Overall, our results still broaden the host range of MBL fold-proteins, showing dual beta-lactamase/nuclease activities in giant viruses.A heterotrimeric transcription factor NF-Y is crucial for cell-cycle progression in various types of cells. In contrast, studies using NF-YA knockout mice have unveiled its essential role in endoplasmic reticulum (ER) homeostasis in neuronal cells. However, whether NF-Y modulates a different transcriptome to mediate distinct cellular functions remains obscure. Here, we knocked down NF-Y in two types of neuronal cells, neuro2a neuroblastoma cells and mouse brain striatal cells, and performed gene expression profiling. link2 We found that down-regulated genes preferentially contained NF-Y-binding motifs in their proximal promoters, and notably enriched genes related to ER functions rather than those for cell cycle. This contrasts with the profiling data of HeLa and embryonic stem cells in which distinct down-regulation of cell cycle-related genes was observed. Clustering analysis further identified several functional clusters where populations of the down-regulated genes were highly distinct. Further analyses using chromatin immunoprecipitation and RNA-seq data revealed that the transcriptomic difference was not correlated with DNA binding of NF-Y but with splicing of NF-YA. These data suggest that neuronal cells have a different type of transcriptome in which ER-related genes are dominantly modulated by NF-Y, and imply that NF-YA splicing alteration could be involved in this cell type-specific gene modulation.Extracytoplasmic function (ECF) sigma factors are key transcriptional regulators that prokaryotes have evolved to respond to environmental challenges. Streptomyces tsukubaensis harbours 42 ECFs to reprogram stress-responsive gene expression. Among them, SigG1 features a minimal conserved ECF σ2-σ4 architecture and an additional C-terminal extension that encodes a SnoaL_2 domain, which is characteristic for ECF σ factors of group ECF56. Although proteins with such domain organisation are widely found among Actinobacteria, the functional role of ECFs with a fused SnoaL_2 domain remains unknown. Our results show that in addition to predicted self-regulatory intramolecular amino acid interactions between the SnoaL_2 domain and the ECF core, SigG1 activity is controlled by the cognate anti-sigma protein RsfG, encoded by a co-transcribed sigG1-neighbouring gene. Characterisation of ∆sigG1 and ∆rsfG strains combined with RNA-seq and ChIP-seq experiments, suggests the involvement of SigG1 in the morphological differentiation programme of S. tsukubaensis. SigG1 regulates the expression of alanine dehydrogenase, ald and the WhiB-like regulator, wblC required for differentiation, in addition to iron and copper trafficking systems. link3 Overall, our work establishes a model in which the activity of a σ factor of group ECF56, regulates morphogenesis and metal-ions homeostasis during development to ensure the timely progression of multicellular differentiation.Cystic fibrosis (CF) is characterized by chronic bacterial infections and heightened inflammation. Widespread ineffective antibiotic use has led to increased isolation of drug resistant bacterial strains from respiratory samples. (R)-roscovitine (Seliciclib) is a unique drug that has many benefits in CF studies. We sought to determine roscovitine's impact on macrophage function and killing of multi-drug resistant bacteria. Human blood monocytes were isolated from CF (F508del/F508del) and non-CF persons and derived into macrophages (MDMs). MDMs were infected with CF clinical isolates of B. cenocepacia and P. aeruginosa. MDMs were treated with (R)-roscovitine or its main hepatic metabolite (M3). Macrophage responses to infection and subsequent treatment were determined. (R)-roscovitine and M3 significantly increased killing of B. cenocepacia and P. aeruginosa in CF MDMs in a dose-dependent manner. (R)-roscovitine-mediated effects were partially dependent on CFTR and the TRPC6 channel. (R)-roscovitine-mediated killing of B.