Frostploug0901

The National Institute for Health and Care Excellence (NICE) has been presented as politically independent, asserting it is free from industry influence and conflicts of interest so that its decisions may be led by evidence and science. We consider the ways in which soft political factors operate in guideline development processes at NICE such that guidelines are not truly led by science. We suggest that while NICE procedures explicitly incorporate scientific principles and mechanisms, including independent committees and quality assurance, these fail to operate as scientific practices because, for example, decisions may only be challenged through the courts, which regard NICE as a scientific authority. We then examine what the NICE rapid guideline procedure for COVID-19 reveals about the practical reality of claims about the scientific integrity of NICE guidelines. Changes to guideline development processes during the COVID-19 emergency demonstrated how easy it is to undermine the scientific integrity of NICE's decision-making. The cancellation of the guideline programme and the publication of a rapid guideline process specifically to address the COVID-19 pandemic removed scientific checks and balances, including independent committees, stakeholder consultation and quality assurance, demonstrating that the relationship between NICE and the UK government is more complex than a scientific principle truism. We suggest that NICE is not (and indeed cannot be) truly independent of government in practice, nor can it be truly led by science, in part because of its relationship to the state, which it is simultaneously constituted by and constitutive of.

Under the Canadian

, medical assistance in dying (MAiD) requires that patients give informed consent and that their ability to consent is assessed by 2 clinicians. In this study, we intended to understand how Canadian clinicians assessed capacity in people requesting MAiD.

This qualitative study used interviews conducted between August 2019 and February 2020, by phone, video and email, to explore how clinicians assessed capacity in people requesting MAiD, what challenges they had encountered and what tools they used. 1-Thioglycerol cell line The participants were recruited from provider mailing listserves of the Canadian Association of MAiD Assessors and Providers and Aide médicale à mourir. Interviews were audio-recorded and transcribed verbatim. The research team met to review transcripts and explore themes as they emerged in an iterative manner. We used abductive reasoning for thematic analysis and coding, and continued to discuss until we reached consensus.

The 20 participants worked in 5 of 10 provinces across Canada, reg MAiD.

The participants were comfortable doing MAiD assessments and used their clinical judgment and experience to assess capacity in ways similar to other clinical practices. The findings of this study suggest that experienced MAiD assessors do not routinely require formal capacity assessments or tools to assess capacity in patients requesting MAiD.

In February 2018, Canada's National Advisory Committee on Immunization recommended maternal vaccination with tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy to prevent severe pertussis infection in young infants. This study assessed the relation between maternal Tdap vaccination and obstetric and perinatal outcomes in Ontario.

We performed a population-based cohort study of all births from April 2012 to March 2017 using multiple linked health administrative databases. We used Cox regression with a time-dependent exposure variable to estimate adjusted hazard ratios (HRs) for preterm birth (< 37 wk), very preterm birth (< 32 wk) and stillbirth. We assessed remaining outcomes (gestational hypertension, chorioamnionitis, postpartum hemorrhage, severe postpartum hemorrhage, being small for gestational age, neonatal intensive care unit stay > 24 h, composite neonatal morbidity) using log-binomial regression to generate adjusted risk ratios (RRs). We adjusted estimates for potentiutcomes in mothers or infants. Ongoing evaluation in Canada is needed as maternal Tdap vaccination coverage increases in coming years.

Our results complement evidence that maternal Tdap vaccination is not associated with adverse outcomes in mothers or infants. Ongoing evaluation in Canada is needed as maternal Tdap vaccination coverage increases in coming years.

Medical cannabis has been legally available in Canada since 2001, but its benefits and harms remain uncertain. We explored attitudes toward medical cannabis among family physicians practising in Ontario.

Between January and October 2019, we conducted a qualitative study of Ontario family physicians using semistructured telephone interviews. We applied thematic analysis to interview transcripts and identified representative quotes.

Eleven physicians agreed to be interviewed, and 3 themes regarding medical cannabis emerged reluctance to authorize use, concern over harms and lack of practical knowledge. Participants raised concerns about the limited evidence for, and their lack of education regarding, the therapeutic use of cannabis, particularly the harms associated with neurocognitive development, exacerbation of mental illness and drug interactions in older adults. Some participants thought medical cannabis was overly accessible and questioned their role following legalization of recreational cannabis.

Despite the increasing availability of medical cannabis, family physicians expressed reluctance to authorize its use because of lack of knowledge and concerns regarding harms. Family physicians may benefit from guidance and education that address concerns they have surrounding medical cannabis.

Despite the increasing availability of medical cannabis, family physicians expressed reluctance to authorize its use because of lack of knowledge and concerns regarding harms. Family physicians may benefit from guidance and education that address concerns they have surrounding medical cannabis.The fungi are an enormously successful eukaryotic lineage that has colonized every aerobic habitat on Earth. This spectacular expansion is reflected in the dynamism and diversity of the fungal cell wall, a matrix of polysaccharides and glycoproteins pivotal to fungal life history strategies and a major target in the development of antifungal compounds. Cell wall polysaccharides are typically synthesized by Leloir glycosyltransferases, enzymes that are notoriously difficult to characterize, but their nucleotide-sugar substrates are well known and provide the opportunity to inspect the monosaccharides available for incorporation into cell wall polysaccharides and glycoproteins. In this work, we have used phylogenomic analyses of the enzymatic pathways that synthesize and interconvert nucleotide-sugars to predict potential cell wall monosaccharide composition across 491 fungal taxa. The results show a complex evolutionary history of these cell wall enzyme pathways and, by association, of the fungal cell wall. In particular, we see a significant reduction in monosaccharide diversity during fungal evolution, most notably in the colonization of terrestrial habitats. However, monosaccharide distribution is also shown to be varied across later-diverging fungal lineages.IMPORTANCE This study provides new insights into the complex evolutionary history of the fungal cell wall. We analyzed fungal enzymes that convert sugars acquired from the environment into the diverse sugars that make up the fundamental building blocks of the cell wall. Species-specific profiles of these nucleotide-sugar interconverting (NSI) enzymes for 491 fungi demonstrated multiple losses and gains of NSI proteins, revealing the rich diversity of cell wall architecture across the kingdom. Pragmatically, because cell walls are essential to fungi, our observations of variation in sugar diversity have important implications for the development of antifungal compounds that target the sugar profiles of specific pathogens.Bacterial mRNAs often harbor upstream open reading frames (uORFs) in the 5' untranslated regions (UTRs). Translation of the uORF usually affects downstream gene expression at the levels of transcription and/or translation initiation. Unlike other uORFs mostly located in the 5' UTR, we discovered an 8-amino-acid ORF, designated mgtQ, in the intergenic region between the mgtC virulence gene and the mgtB Mg2+ transporter gene in the Salmonella mgtCBRU operon. Translation of mgtQ promotes downstream mgtB Mg2+ transporter expression at the level of translation by releasing the ribosome-binding sequence of the mgtB gene that is sequestered in a translation-inhibitory stem-loop structure. Interestingly, mgtQ Asp2 and Glu5 codons that induce ribosome destabilization are required for mgtQ-mediated mgtB translation. Moreover, the mgtQ Asp and Glu codons-mediated mgtB translation is counteracted by the ribosomal subunit L31 that stabilizes ribosome. Substitution of the Asp2 and Glu5 codons in mgtQ decreases MgtB Mg2+ trred for Salmonella virulence, this pathogen seems to control the virulence determinant production exquisitely via this uORF during infection.JC polyomavirus (JCV), a DNA virus that leads to persistent infection in humans, is the causative agent of progressive multifocal leukoencephalopathy, a lethal brain disease that affects immunocompromised individuals. Almost nothing is currently known about how JCV infection is controlled by the innate immune response and, further, whether JCV has evolved mechanisms to antagonize antiviral immunity. Here, we show that the innate immune sensors retinoic acid-inducible gene I (RIG-I) and cGMP-AMP synthase (cGAS) control JCV replication in human astrocytes. We further identify that the small t antigen (tAg) of JCV functions as an interferon (IFN) antagonist by suppressing RIG-I-mediated signal transduction. JCV tAg interacts with the E3 ubiquitin ligase TRIM25, thereby preventing its ability to bind RNA and to induce the K63-linked ubiquitination of RIG-I, which is known to facilitate RIG-I-mediated cytokine responses. Antagonism of RIG-I K63-linked ubiquitination and antiviral signaling is also conserved in ther innate immune sensors responsible for controlling JCV infection and also demonstrate a novel mechanism by which a JCV-encoded protein acts as an antagonist of the type I interferon-mediated innate immune response.Animals that are competent reservoirs of zoonotic pathogens commonly suffer little morbidity from the infections. To investigate mechanisms of this tolerance of infection, we used single-dose lipopolysaccharide (LPS) as an experimental model of inflammation and compared the responses of two rodents Peromyscus leucopus, the white-footed deermouse and reservoir for the agents of Lyme disease and other zoonoses, and the house mouse Mus musculus Four hours after injection with LPS or saline, blood, spleen, and liver samples were collected and subjected to transcriptome sequencing (RNA-seq), metabolomics, and specific reverse transcriptase quantitative PCR (RT-qPCR). Differential expression analysis was at the gene, pathway, and network levels. LPS-treated deermice showed signs of sickness similar to those of exposed mice and had similar increases in corticosterone levels and expression of interleukin 6 (IL-6), tumor necrosis factor, IL-1β, and C-reactive protein. By network analysis, the M. musculus response to LPS was characterized as cytokine associated, while the P.