Non-ionotropic NMDAR signalling activates Panx1 to induce P2X4R-dependent long-term depression in the hippocampus.

In recent years, evidence supporting non-ionotropic signalling by the NMDA receptor (niNMDAR) has emerged, including roles in long-term depression (LTD). Here, we investigated whether niNMDAR-pannexin-1 (Panx1) contributes to LTD at the CA3-CA1 hippocampal synapse. Using whole-cell, patch clamp electrophysiology in rat hippocampal slices, we show that a low-frequency stimulation (3 Hz) of the Schaffer collaterals produces LTD that is blocked by continuous but not transient application of the NMDAR competitive antagonist, MK-801.

Outcomes of patients receiving urgent palliative radiotherapy for advanced lung cancer: an observational study.

Background: There is considerable variability in the management of patients with advanced lung cancer referred for palliative radiotherapy owing to uncertainties in prognosis and the benefit of treatment. This study presents the outcomes of patients seen in the Fast Track Lung Clinic, an urgent access palliative radiotherapy clinic, and aims to identify factors associated with treatment response and survival.

Methods: Consecutive patients with advanced lung cancer seen in the Fast Track Lung Clinic between January 2014 and July 2020 were included.

Non-Stenotic Carotid Plaques and Rate of DWI-positive MRI in Patients with Lower-Risk Transient or Persistent Minor Neurologic Events: DOUBT Sub Study.

Background & Purpose: Non-stenotic (< 50%) carotid plaques are increasingly recognized as a potential mechanism for ischemic stroke. We assessed the prevalence of such plaques in patients with low-risk neurologic events and evidence of DWI (Diffusion Weighted Imaging)-positive ischemia.

Methods: This is a post-hoc exploratory analysis from the DOUBT study, a prospective, observational, multicenter study of patients with low-risk transient or persistent minor focal neurological symptoms.

Liver assistive devices in acute liver failure: Current use and future directions.

Acute liver failure (ALF) is a rare syndrome where rapid deterioration of liver function occurs after an acute insult in a patient without prior chronic liver disease and leads to jaundice, hepatic encephalopathy (HE), and oftentimes multiorgan failure (MOF). At this time, the only definitive treatment for ALF is LT but some patients, particularly APAP-induced ALF patients, may have ongoing regenerative capacity of the liver and may not require LT with ongoing supportive management. As a result, extracorporeal liver support (ECLS) has been a topic of interest both as a bridge to LT and as a bridge to spontaneous recovery and aims to remove damaging toxins that further aggravate liver failure, stimulate regeneration of the liver, and improve pathophysiologic consequences of liver failure.

Breaking Down Bias: A Methodological Primer on Identifying, Evaluating, and Mitigating Bias in Cardiovascular Research.

Systematic error, often referred to as bias is an inherent challenge in observational cardiovascular research, and has the potential to profoundly influence the design, conduct, and interpretation of study results. If not carefully considered and managed, bias can lead to spurious results, which can misinform clinical practice or public health initiatives and compromise patient outcomes. This methodological primer offers a concise introduction to the identification, evaluation, and mitigation of bias in observational cardiovascular research studies assessing the causal association of an exposure (or treatment) on an outcome.

Guselkumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients: results of the phase 3, randomized, placebo-controlled PROTOSTAR study.

Background: No currently approved treatment for pediatric plaque psoriasis selectively targets interleukin (IL)-23. In adults, guselkumab (a selective IL-23 inhibitor targeting the p19 subunit) demonstrated substantial efficacy with a favorable safety profile in treating moderate-to-severe plaque psoriasis.

Objective: PROTOSTAR (NCT03451851) evaluated the efficacy and safety of guselkumab in pediatric patients with moderate-to-severe plaque psoriasis.

"FBT Is for the Rich": A Qualitative Study Examining Clinicians' Experiences and Perceptions of Treatment Access and Engagement for Diverse Families in Family-Based Treatment.

Objective: Family-based treatment (FBT) is the leading evidence-based treatment for adolescent eating disorders, but research exploring access and engagement in FBT is sparse. This paper focuses on findings from a broader study, specifically addressing the social determinants of health (SDH) impeding access and engagement in FBT for diverse families (i.e.

From 'publish or perish' to 'publish with purpose': perspectives from young adults with lived and living experience on transforming academic publishing in patient-oriented research.

Background: This commentary article critically assesses the inclusion and recognition of young adults with lived and living experiences (YALLE) in academic publishing. Stemming from our involvement in a health research study, this analysis interrogates the disparity between the stated importance of YALLE contributions in health research and their actual recognition, specifically in academic publications, which serve as the principal "currency" in research. This tokenism limits the potential for their unique insights to substantially enrich the discourse and dissemination of knowledge.

First record of Culex pipiens (Diptera: Culicidae) in Alberta: expanding distributions and ecotype patterns in a western Canadian province.

Culex pipiens is an invasive mosquito found in temperate regions globally. It is considered among the most important disease vectors worldwide and is responsible for the transmission of a range of pathogens, including West Nile virus, avian malaria, Saint Louis encephalitis, and filarial worms. Throughout its northern temperate range, this mosquito is found in 2 ecotypes: form pipiens and form molestus.

Approaches to ensure an equitable and fair admissions process for medical training.

There has been considerable discussion of how best to address racial and ethnic disparities in health outcomes, both globally and specifically in the United States. Increasing diversity among future clinicians and physician-scientists has been identified as a key strategy for addressing and correcting health disparities among underrepresented populations. Increasingly, medical schools, the institutions that train clinicians, have embraced the practice of holistic review for evaluating applicants and virtually all medical schools have reported contributing to a diverse physician workforce as an important aspect of their educational mission.

Motivators and barriers to neurodevelopmental research enrolment.

Participant recruitment for studies investigating neurodevelopmental conditions can be difficult, limited, and resource intensive. In this study, caregivers were surveyed to learn about the factors influencing their decision to enroll their neurodivergent child in research. Data were collected through an online survey from caregivers of neurodivergent children who were signing up for a research recruitment database (n = 46).

Developmental Mismatch Across Brain Modalities in Young Children.

Brain development during the preschool period is complex and extensive and underlies ongoing behavioral and cognitive maturation. Increasing understanding of typical brain maturation during this time is critical to early identification of atypical development and could inform treatments and interventions. Previous studies have suggested mismatches between brain structural and functional development in later childhood and adolescence.

Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): a global surveillance analysis.

Background: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally.

Methods: IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%.

Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages (the PSERENADE project): a global surveillance analysis.

Background: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages.

Methods: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%.

A review: Breeding behavior and management strategies for improving reproductive efficiency in bulls.

This review focuses on bull breeding behaviors and management strategies to improve reproductive efficiency. Breeding soundness evaluations are utilized to classify a bull's physical ability and sperm quality, yet roughly 20 % of bulls fail to meet the minimum criteria. Furthermore, despite achieving the minimum criteria, few bulls in multi-sire breeding groups sire the majority of calves, indicating a need for better understanding of bull behavior that impact siring capacity, and thus, a bull's reproductive efficiency.

Criminalizing public space through a decriminalization framework: The paradox of British Columbia, Canada.

This commentary explores a recent shift in British Columbia's drug policy under a novel drug "decriminalization" framework. We focus on the province's move toward "recriminalization" under this framework. In short, recriminalization was a shift in BC's drug decriminalization framework to only apply in private residences, and be removed from essentially all outdoor spaces.

Immunoregulatory and antiviral effect mediated by TLR7 and BMAP28 interaction in bovine alphaherpesvirus-infected respiratory primary cultures.

Varicellovirus bovinealpha 1 and 5 (formerly bovine alphaherpesvirus type 1 and 5, BoAHV-1 and BoAHV-5) are closely related and can be isolated from similar clinical conditions, including respiratory and nervous diseases, genital infections and abortion. Pathogens' activation of toll-like receptors (TLRs) induces the expression of proinflammatory cytokines and antimicrobial peptides such as cathelicidins. Cathelicidins are presumed to act as endogenous ligands of TLRs, stimulating, in turn, their activation.

Adaptive Platform Trials in Stroke.

Clinical trials of treatments for stroke have generally utilized 2-arm, randomized designs to evaluate a single intervention against a control. Running separate clinical trials, with each addressing a single therapeutic question, is resource intensive and slows evidence generation, especially in a field with rapidly expanding treatment options and evolving practices. Platform trials-randomized clinical trials designed to evaluate multiple interventions that may enter and exit the ongoing platform based on a master protocol-accelerate the investigation of multiple therapeutic options within a single infrastructure.

Tracking of spaceflight-induced bone remodeling reveals a limited time frame for recovery of resorption sites in humans.

Mechanical unloading causes bone loss, but it remains unclear whether disuse-induced changes to bone microstructure are permanent or can be recovered upon reloading. We examined bone loss and recovery in 17 astronauts using time-lapsed high-resolution peripheral quantitative computed tomography and biochemical markers to determine whether disuse-induced changes are permanent. During 6 months in microgravity, resorption was threefold higher than formation.

Repeated global adaptation across plant species.

Global adaptation occurs when all populations of a species undergo selection toward a common optimum. This can occur by a hard selective sweep with the emergence of a new globally advantageous allele that spreads throughout a species' natural range until reaching fixation. This evolutionary process leaves a temporary trace in the region affected, which is detectable using population genomic methods.

A national cross-sectional survey of health literacy of caregivers attending Canadian pediatric emergency departments.

Background: Health literacy assessment is key to better meeting family needs and developing informed strategies to promote positive health outcomes for children. The objective of this study was to describe the health literacy of caregivers who use Canadian pediatric emergency departments and relate it to demographic and visit-specific variables.

Methods: This study utilized a descriptive, cross-sectional survey design with medical record review.

Predictive factors for the diagnosis of coeliac disease in children and young people in primary care: A systematic review and meta-analysis.

Background: Coeliac Disease (CD) often has its onset in childhood and affects 1% of the population. This review aimed to identify important predictive factors for coeliac disease in children and young people which could help GPs decide when to offer testing.

Methods: We searched MEDLINE, Embase and Cochrane Library to April 2024.

Disparities in kidney care in vulnerable populations: A multinational study from the ISN-GKHA.

Vulnerable populations, such as the elderly, children, displaced people, and refugees, often encounter challenges in accessing healthcare. In this study, we used data from the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to describe kidney care access and delivery to vulnerable populations across countries and regions. Using data from an international survey of clinicians, policymakers, and patient advocates, we assessed the funding and coverage of vulnerable populations on all aspects of kidney replacement therapies (KRT).