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OBJECTIVES: The objective was to assess the effectiveness of a Water Fluoridation program on a contemporary population of children. METHODS: The study used a longitudinal prospective cohort design. In Cumbria, England, two groups of children were recruited and observed over a period of 5-6 years. The Birth Cohort consisted of families recruited from two hospitals in Cumbria where children were conceived after water fluoridation was reintroduced. The systemic and topical effects of community water fluoridation were evaluated in the Birth Cohort...

PURPOSE: To evaluate pre- and post-operative resonance, surgical technique, revision rate, and revision indication among syndromic and non-syndromic children with velopharyngeal insufficiency (VPI). MATERIALS AND METHODS: A systematic review was conducted through July 2022. Children surgically treated for VPI were included. A meta-analysis of single means, proportions, comparison of proportions, and mean differences with 95 % confidence interval [CI] was conducted...

Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells...

To improve current and future use of existing (oral, injectable) and potential future (implants, douches) PrEP products, we must understand product preferences relative to one another, among gay and bisexual men (GBM), and physicians who prescribe PrEP. We completed an online discrete choice experiment (DCE) with separate groups of GBM and/or physicians from the U.S., South Africa, Spain, and Thailand. Participants were presented information on PrEP products, including daily pills, event-driven pills (2-1-1 regimen), injections, subdermal implants (dissolvable, removable), and rectal douches...

Despite its wide distribution, relatively little is known of the foraging ecology and habitat use of the black-faced cormorant (Phalacrocorax fuscescens), an Australian endemic seabird. Such information is urgently required in view of the rapid oceanic warming of south-eastern Australia, the stronghold of the species. The present study used a combination of opportunistically collected regurgitates and GPS/dive behaviour data loggers to investigate diet, foraging behaviour and habitat-use of black-faced cormorants during four chick-rearing periods (2020-2023) on Notch Island, northern Bass Strait...

Outbreaks of highly pathogenic H5N1 clade 2.3.4.4b viruses in farmed mink and seals combined with isolated human infections suggest these viruses pose a pandemic threat. To assess this threat, using the ferret model, we show an H5N1 isolate derived from mink transmits by direct contact to 75% of exposed ferrets and, in airborne transmission studies, the virus transmits to 37.5% of contacts. Sequence analyses show no mutations were associated with transmission. The H5N1 virus also has a low infectious dose and remains virulent at low doses...

Clerkship directors must balance the mental wellbeing of their medical students with the demanding schedule that rotations in procedural specialties such as surgery and obstetrics and gynecology require. In this paper, the Undergraduate Medical Education Committee of the Association of Professors of Obstetrics and Gynecology argues the importance of maintaining adequate clinical exposure for learners. Involving students in overnight call provides additional clinical involvement, improved relationships with the clinical team, and a better perspective on specialist lifestyle...

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement...

Humans are living longer, but this is accompanied by an increased incidence of age-related chronic diseases. Many of these diseases are influenced by age-associated metabolic dysregulation, but how metabolism changes in multiple organs during aging in males and females is not known. Answering this could reveal new mechanisms of aging and age-targeted therapeutics. In this study, we describe how metabolism changes in 12 organs in male and female mice at 5 different ages. Organs show distinct patterns of metabolic aging that are affected by sex differently...

Computational simulations with data-driven physiological detail can foster a deeper understanding of the neural mechanisms involved in cognition. Here, we utilize the wealth of cellular properties from Hippocampome.org to study neural mechanisms of spatial coding with a spiking continuous attractor network model of medial entorhinal cortex circuit activity. The primary goal was to investigate if adding such realistic constraints could produce firing patterns similar to those measured in real neurons. Biological characteristics included in the work are excitability, connectivity, and synaptic signaling of neuron types defined primarily by their axonal and dendritic morphologies...

This study investigated if paraxanthine (PX) impacts energy expenditure, lipolysis and perceptual responses. In a randomized, double-blind, placebo-controlled, crossover fashion, 21 adults (13 M, 8 F; 26.0 ± 6.4 years, 174.9 ± 11.5 cm, 81.0 ± 15.7 kg body mass, 26.3 ± 3.4 kg/m2 ) consumed a placebo (PLA), 100 mg (PX100), 200 mg (PX200), and 300 mg of PX (PX300, enfinity®, Ingenious Ingredients, L...

AIMS: To evaluate the effectiveness of a mental health screening form for early identification and care escalation of mental health issues in general settings. A secondary aim was to explore general nurses' use of the form and their confidence to discuss mental health issues with patients. METHODS: A cross-sectional design comprising a review of clinical records to determine use of the form, instances of missed care and escalation to the mental health team. The survey focused on nurses' confidence in general settings to engage in discussions with patients about mental health...

High-risk human papillomavirus (HR-HPV; HPV-16) and cigarette smoking are associated with cervical cancer (CC); however, the underlying mechanism(s) remain unclear. Additionally, the carcinogenic components of tobacco have been found in the cervical mucus of women smokers. Here, we determined the effects of cigarette smoke condensate (CSC; 3R4F) on human ectocervical cells (HPV-16 Ect/E6E7) exposed to CSC at various concentrations (10-6 -100 μg/mL). We found CSC (10-3 or 10 μg/mL)-induced proliferation, enhanced migration, and histologic and electron microscopic changes consistent with EMT in ectocervical cells with a significant reduction in E-cadherin and an increase in the vimentin expression compared to controls at 72 h...

Elucidating the underlying principles of amyloid protein self-assembly at nanobio interfaces is extremely challenging due to the diversity in physicochemical properties of nanomaterials and their physical interactions with biological systems. It is, therefore, important to develop nanoscale materials with dynamic features and heterogeneities. In this work, through engineering of hierarchical polyethylene glycol (PEG) structures on gold nanoparticle (GNP) surfaces, tailored nanomaterials with different surface properties and conformations (GNPs-PEG) are created for modulating the self-assembly of a widely studied protein, insulin, under amyloidogenic conditions...

Proteomics analysis of mass-limited samples has become increasingly important for understanding biological systems in physiologically relevant contexts such as patient samples, multicellular organoids, spheroids, and single cells. However, relatively low sensitivity in top-down proteomics methods makes their application to mass-limited samples challenging. Capillary electrophoresis (CE) has emerged as an ideal separation method for mass-limited samples due to its high separation resolution, ultralow detection limit, and minimal sample volume requirements...

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INTRODUCTION: Reducing waiting times is a major policy objective in publicly-funded healthcare systems. However, reductions in waiting times can produce a demand response, which may offset increases in capacity. Early detection and diagnosis of cancer is a policy focus in many OECD countries, but prolonged waiting periods for specialist confirmation of diagnosis could impede this goal. We examine whether urgent GP referrals for suspected cancer patients are responsive to local hospital waiting times...

Atopic dermatitis (AD) is an inflammatory skin condition with a childhood prevalence of up to 25%. Microbial dysbiosis is characteristic of AD, with Staphylococcus aureus the most frequent pathogen associated with disease flares and increasingly implicated in disease pathogenesis. Therapeutics to mitigate the effects of S. aureus have had limited efficacy and S. aureus-associated temporal disease flares are synonymous with AD. An alternative approach is an anti-S. aureus vaccine, tailored to AD. Experimental vaccines have highlighted the importance of T cells in conferring protective anti-S...

Child abuse and masculinity have been linked to intimate partner violence (IPV) perpetration. However, there is a lack of work examining multiple aspects of masculinity as links between early abuse experiences and men's IPV perpetration. Grounded in notions of gendered power and patriarchy, this study aimed to examine hostile masculinity, male peer support for violence against women, and problematic anger as aspects of masculinity connecting childhood victimization and men's violence against women. Structural equation modeling results demonstrated that childhood adversity was indirectly related to IPV perpetration via the proposed factors...

Muscle health is a critical component of overall health and quality of life. However, current measures of skeletal muscle health take limited account of microstructural variations within muscle, which play a crucial role in mediating muscle function. To address this, we present a physics-inspired, machine learning-based framework for the non-invasive estimation of microstructural organization in skeletal muscle from diffusion-weighted MRI (dMRI) in an uncertainty-aware manner. To reduce the computational expense associated with direct numerical simulations of dMRI physics, a polynomial meta-model is developed that accurately represents the input/output relationships of a high-fidelity numerical model...