Detailed characterisation of the Co-Smad protein in liver fluke .

Fasciolosis, caused by the liver flukes and , is a zoonotic parasitic disease associated with substantial economic losses in livestock. The transforming growth factor-beta signalling pathway is implicated in developmental processes and biological functions throughout the animal kingdom, including the spp. It may also mediate host-helminth interactions during infection.

The co-design of a digitally supported intervention for selecting implementation tools and actions for standards (SITAS).

Background: Health and social care standards are multi-faceted interventions that promote quality and safe care in health systems. There is a need to apply evidence-based, rigorous and transparent methods when selecting strategies to support the implementation of standards. We aimed to develop an evidence- and theory-informed intervention to guide researchers in identifying appropriate implementation strategies and then selecting tailored support tools and actions for use when implementing a set of standards.

The implementation of infant pain practice change resource to improve infant procedural pain practices: a hybrid type 1 effectiveness-implementation study.

Implementation of infant pain practice change (ImPaC) is a multifaceted web-based resource to support pain practice change in neonatal intensive care unit (NICU). We evaluated the (1) intervention effectiveness and (2) implementation effectiveness of ImPaC using a hybrid type 1 effectiveness-implementation study (ie, cluster randomized controlled trial and longitudinal descriptive study). Eligible level 2 and 3 Canadian NICUs were randomized to intervention (INT) or waitlisted to usual care (UC) for 6 months.

Gut microbiota carbon and sulfur metabolisms support Salmonella infections.

Salmonella enterica serovar Typhimurium is a pervasive enteric pathogen and ongoing global threat to public health. Ecological studies in the Salmonella impacted gut remain underrepresented in the literature, discounting microbiome mediated interactions that may inform Salmonella physiology during colonization and infection. To understand the microbial ecology of Salmonella remodeling of the gut microbiome, we performed multi-omics on fecal microbial communities from untreated and Salmonella-infected mice.

Multistakeholder Perspectives on the Determinants of Family Fundamental Movement Skills Practice: A Qualitative Systematic Review.

Background: Childhood obesity is a significant public health crisis that is exposing children to associated morbidities and premature mortality. However, parents can positively influence physical activity trajectories and improve health outcomes by nurturing fundamental movement skills (FMS) in children. This is the first study to explore the determinants of family FMS practice via a systematic synthesis of qualitative evidence.

O-glycosylation contributes to mammalian glycoRNA biogenesis.

There is an increasing appreciation for the role of cell surface glycans in modulating interactions with extracellular ligands and participating in intercellular communication. We recently reported the existence of sialoglycoRNAs, where mammalian small RNAs are covalently linked to N-glycans through the modified base acpU and trafficked to the cell surface. However, little is currently known about the role for O-glycosylation, another major class of carbohydrate polymer modifications.

The modified RNA base acpU is an attachment site for N-glycans in glycoRNA.

GlycoRNA consists of RNAs modified with secretory N-glycans that are presented on the cell surface. Although previous work supported a covalent linkage between RNA and glycans, the direct chemical nature of the RNA-glycan connection was not described. Here, we develop a sensitive and scalable protocol to detect and characterize native glycoRNAs.

Exploring the implementation of national health and social care standards in Ireland: A qualitative descriptive study.

Background: National health and social care standards are complex, quality improvement interventions. Standards typically describe a process and/or outcome of safe, quality, person-centred care according to best evidence. Currently, there are 11 national standards that apply to diverse services in Ireland including residential centres, acute hospitals and rehabilitation and community inpatient healthcare services.

Acute Primary Small Bowel Volvulus in a Male With Loeys-Dietz Syndrome.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder with features including, but not limited to, aortic dissections, skeletal abnormalities, and craniofacial defects. However, considering its relatively recent discovery, there are still many unknowns about LDS. The extent of a connective tissue disorder like LDS is yet to be defined throughout the various organ systems, including the gastrointestinal system.

Patient-specific quality assurance of dynamically-collimated proton therapy treatment plans.

Background: The dynamic collimation system (DCS) provides energy layer-specific collimation for pencil beam scanning (PBS) proton therapy using two pairs of orthogonal nickel trimmer blades. While excellent measurement-to-calculation agreement has been demonstrated for simple cube-shaped DCS-trimmed dose distributions, no comparison of measurement and dose calculation has been made for patient-specific treatment plans.

Purpose: To validate a patient-specific quality assurance (PSQA) process for DCS-trimmed PBS treatment plans and evaluate the agreement between measured and calculated dose distributions.

Community Group-Based Physical Activity Programs for Immigrant Older Adults: A Systematic Realist Review.

Physical activity program interventions often lack sensitivity to the needs of older immigrant adults. The objective of this systematic realist review is to explain how, why, for whom, and under which circumstances community group-based physical activity programs work for immigrant older adults. The initial program theory was developed using prior research, team expertise, social cognitive theory, and knowledge user consultations.

Synthetic genomes unveil the effects of synonymous recoding.

Engineering the genetic code of an organism provides the basis for (i) making any organism safely resistant to natural viruses and (ii) preventing genetic information flow into and out of genetically modified organisms while (iii) allowing the biosynthesis of genetically encoded unnatural polymers. Achieving these three goals requires the reassignment of multiple of the 64 codons nature uses to encode proteins. However, synonymous codon replacement-recoding-is frequently lethal, and how recoding impacts fitness remains poorly explored.

Pharmacokinetics and pharmacodynamics of intravenously and subcutaneously administered pantoprazole in sheep (Ovis aries).

Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.

hnRNPM protects against the dsRNA-mediated interferon response by repressing LINE-associated cryptic splicing.

RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites.

Microbial polyphenol metabolism is part of the thawing permafrost carbon cycle.

With rising global temperatures, permafrost carbon stores are vulnerable to microbial degradation. The enzyme latch theory states that polyphenols should accumulate in saturated peatlands due to diminished phenol oxidase activity, inhibiting resident microbes and promoting carbon stabilization. Pairing microbiome and geochemical measurements along a permafrost thaw-induced saturation gradient in Stordalen Mire, a model Arctic peatland, we confirmed a negative relationship between phenol oxidase expression and saturation but failed to support other trends predicted by the enzyme latch.

Effect of timed dosing of usual antihypertensives according to patient chronotype on cardiovascular outcomes: the Chronotype sub-study cohort of the Treatment in Morning versus Evening (TIME) study.

Background: Timing drug administration to endogenous circadian rhythms may enhance treatment efficacy. In the Chronotype sub-study of the Treatment in Morning versus Evening (TIME) clinical trial we examined whether timing of usual antihypertensive medications according to patient chronotype (a behavioural marker of personal circadian rhythm) may influence clinical cardiovascular outcomes.

Methods: This was a cohort sub-study of TIME, a prospective, randomised, open-label, blinded-endpoint, UK clinical trial of morning versus evening dosing of usual antihypertensive medications and cardiovascular outcomes.

Tools to investigate the cell surface: Proximity as a central concept in glycoRNA biology.

Proximity is a fundamental concept in chemistry and biology, referring to the convergence of molecules to facilitate new molecular interactions or reactions. Hybrid biopolymers like glycosylphosphatidylinositol (GPI)-anchored proteins, ubiquitinated proteins, glycosylated RNAs (glycoRNAs), and RNAylated proteins exemplify this by covalent bonding of moieties that are often orthogonally active. Hybrid molecules like glycoRNAs are localized to new physical spaces, generating new interfaces for biological functions.

Contextually appropriate nurse staffing models: a realist review protocol.

Introduction: Decisions about nurse staffing models are a concern for health systems globally due to workforce retention and well-being challenges. Nurse staffing models range from all Registered Nurse workforce to a mix of differentially educated nurses and aides (regulated and unregulated), such as Licensed Practical or Vocational Nurses and Health Care Aides. Systematic reviews have examined relationships between specific nurse staffing models and client, staff and health system outcomes (eg, mortality, adverse events, retention, healthcare costs), with inconclusive or contradictory results.

Impact and Implementation of an Early Years Fundamental Motor Skills Intervention for Children 4-5 Years.

Unlabelled: Fundamental motor skills (FMS) are the cornerstone of a child's motor development, but concerns remain on the current level of FMS competencies, and intervention is required. This evaluation investigated if a targeted Early Years FMS intervention, delivered by a specialist physical education (PE) provider, improved the FMS of 4-5-year-old children across multiple sites.

Methods: The Early Years FMS intervention ran for 18 weeks, 1 h/week, using a standardised programme of activities to develop FMS competencies across 219 children from 15 schools in the Midlands, UK.

Lessons Learned on Observed-to-Expected Analysis Using Spontaneous Reports During Mass Vaccination.

During the COVID-19 vaccination campaign, observed-to-expected analysis was used by the European Medicines Agency to contextualise data from spontaneous reports to generate real-time evidence on emerging safety concerns that may impact the benefit-risk profile of COVID-19 vaccines. Observed-to-expected analysis compares the number of cases spontaneously reported for an event of interest after vaccination ('observed') to the 'expected' number of cases anticipated to occur in the same number of individuals had they not been vaccinated. Observed-to-expected analysis is a robust methodology that relies on several assumptions that have been described in regulatory guidelines and scientific literature.