Variants in , encoding the presynaptic protein Bassoon, result in a novel neurodevelopmental disorder with a broad phenotypic range.

Disease-causing variants in synaptic function genes are a common cause of neurodevelopmental disorders and epilepsy. Here, we describe 14 individuals with disruptive variants in , which encodes the presynaptic protein Bassoon. To expand the phenotypic spectrum, we identified 15 additional individuals with protein-truncating variants (PTVs) from large biobanks.

Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage.

Background: The effect of a liberal red-cell transfusion strategy as compared with a restrictive strategy in patients during the critical care period after an aneurysmal subarachnoid hemorrhage is unclear.

Methods: We randomly assigned critically ill adults with acute aneurysmal subarachnoid hemorrhage and anemia to a liberal strategy (mandatory transfusion at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (optional transfusion at a hemoglobin level of ≤8 g per deciliter). The primary outcome was an unfavorable neurologic outcome, defined as a score of 4 or higher on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at 12 months.

Upregulation versus loss of function of NTRK2 in 44 affected individuals leads to 2 distinct neurodevelopmental disorders.

Purpose: Heterozygous pathogenic variants in NTRK2 (HGNC: 8032) have been associated with global developmental delay. However, only scattered cases have been described in small or general studies. The aim of our work was to consolidate our understanding of NTRK2-related disorders and to delineate the clinical presentation.

Fatal borealpox in an immunosuppressed patient treated with antivirals and vaccinia immunoglobulin - Alaska, 2023.

Background: Borealpox virus (BRPV, formerly known as Alaskapox virus) is a zoonotic member of the Orthopoxvirus genus first identified in a person in 2015. In the six patients with infection previously observed BRPV involved mild, self-limiting illness. We report the first fatal BRPV infection in an immunosuppressed patient.

Retrospective comparison of thyroid hormones in Steller sea lions Eumetopias jubatus under professional care with and without thyroid disease.

An evaluation of morbidity and mortality in Steller sea lions (SSLs) Eumetopias jubatus under professional care identified a high prevalence of thyroid disease in aged animals. While studies have investigated the effects of age, season, nutrition, stressors, and pollutants on thyroid hormones in pinnipeds, data from individuals with known thyroid disease are lacking. Histopathological reports of adult SSLs in North American aquariums from 1979 to 2022 with banked serum (n = 14) were reviewed.

CAUSES OF MORBIDITY AND MORTALITY IN STELLER SEA LIONS () UNDER PROFESSIONAL CARE IN NORTH AMERICAN AQUARIUMS FROM 1979 TO 2021.

To date, published comprehensive pathology investigations documented in Steller sea lions (SSL; ) are from free-ranging populations, whereas health data from those under professional care in aquariums are currently lacking. A retrospective review of gross and histopathologic reports of SSL under human care in North American aquariums from 1979 to 2021 ( = 20) was performed. Associations between age, sex, or birth origin (born in aquariums versus the wild) with cause of death (COD) and comorbidities were explored.

The drug drought in maternal health: an ongoing predicament.

We developed a comprehensive database of medicines that are used or are being investigated for pre-eclampsia or eclampsia, preterm birth or labour, postpartum haemorrhage, intrauterine growth restriction, and fetal distress and that were in active development between 2000 and 2021. A total of 444 candidates were identified: approximately half of candidates were in active development, two-thirds had been repurposed after initially being used for another condition, and just under half were in preclinical studies. Only 64 candidates were in active late-stage (phase 3) development as of Oct 25, 2021, and given the slow pace of biomedical development, it could take years before any of these products eventually make it to market.

Monkeypox Virus Infections After 2 Preexposure Doses of JYNNEOS Vaccine - United States, May 2022-May 2024.

Two doses of JYNNEOS vaccine are effective in preventing many mpox cases and can reduce the severity of symptoms in infected persons. However, infections among fully vaccinated persons can occur. During May 2022-May 2024, a total of 271 mpox cases among fully vaccinated persons were reported to CDC from 27 U.

Effect of photobiomodulation therapy as a multimodal approach to treatment of dermal abrasions in cownose rays (Rhinoptera bonasus).

Photobiomodulation therapy (PBMT) has become increasingly utilized in the zoo and aquarium fields to treat ailments in various species; however, its use in teleosts and elasmobranchs is relatively underrepresented in the literature. This study examined the efficacy of PBMT as an adjunct treatment to reduce the healing time of dermal abrasions in cownose rays (Rhinoptera bonasus). Ten cownose rays were included in this study and separated into control (n = 5) and treatment groups (n = 5).

Landscape of toxin-neutralizing therapeutics for snakebite envenoming (2015-2022): Setting the stage for an R&D agenda.

Background: Progress in snakebite envenoming (SBE) therapeutics has suffered from a critical lack of data on the research and development (R&D) landscape. A database characterising this information would be a powerful tool for coordinating and accelerating SBE R&D. To address this need, we aimed to identify and categorise all active investigational candidates in development for SBE and all available or marketed products.

Thiophene-based lipids for mRNA delivery to pulmonary and retinal tissues.

Lipid nanoparticles (LNPs) largely rely on ionizable lipids to yield successful nucleic acid delivery via electrostatic disruption of the endosomal membrane. Here, we report the identification and evaluation of ionizable lipids containing a thiophene moiety (Thio-lipids). The Thio-lipids can be readily synthesized via the Gewald reaction, allowing for modular lipid design with functional constituents at various positions of the thiophene ring.

Single-Cell Analysis of Rohon-Beard Neurons Implicates Fgf Signaling in Axon Maintenance and Cell Survival.

Peripheral sensory neurons are a critical part of the nervous system that transmit a multitude of sensory stimuli to the central nervous system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory neurons (RBs). RBs are optically accessible and amenable to experimental manipulation, making them a powerful system for mechanistic investigation of sensory neurons.

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles.

Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney,caused by variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative (DN) mode-of-action, wherein an increased level of AFF3 resulted in pathological effects.

Methods: Evolutionary constraints suggest that other mode-of-inheritance could be at play.

Single-cell analysis of Rohon-Beard neurons implicates Fgf signaling in axon maintenance and cell survival.

Peripheral sensory neurons are a critical part of the nervous system that transmit a multitude of sensory stimuli to the central nervous system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory neurons (RBs). RBs are optically accessible and amenable to experimental manipulation, making them a powerful system for mechanistic investigation of sensory neurons.

Discovering novel barriers to eBook implementation.

Background: Medical errors when managing inpatient paediatric patients with diabetes mellitus can lead to significant morbidity and mortality, necessitating improvement in training of medical trainees. Previous educational interventions have focused on time and resource intensive methods, restricting their applicability to teaching in time-limited scenarios. We chose a blended learning approach to create and implement a novel eBook for use by trainees and then aimed to determine the efficacy and potential barriers to that implementation.

New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline.

Background: There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the most promising candidates.

Effect of Donor Sex on Recipient Mortality in Transfusion.

Background: Conflicting observational evidence exists regarding the association between the sex of red-cell donors and mortality among transfusion recipients. Evidence to inform transfusion practice and policy is limited.

Methods: In this multicenter, double-blind trial, we randomly assigned patients undergoing red-cell transfusion to receive units of red cells from either male donors or female donors.

Target product profiles for novel medicines to prevent and treat preeclampsia: An expert consensus.

Background: Preeclampsia and eclampsia are a leading cause of global maternal and newborn mortality. Currently, there are few effective medicines that can prevent or treat preeclampsia. Target Product Profiles (TPPs) are important tools for driving new product development by specifying upfront the characteristics that new products should take.

Analysis of a maternal health medicines pipeline database 2000-2021: New candidates for the prevention and treatment of fetal growth restriction.

Objective: The Accelerating Innovation for Mothers project established a new database of candidate medicines under development between 2000 and 2021 for five pregnancy-related conditions, including fetal growth restriction. The objective was to assess medicines for fetal growth restriction and their potential for clinical use globally.

Design: Landscape analysis.

RETROSPECTIVE REVIEW OF NEUROLOGIC DISEASE IN STRANDED ATLANTIC HARBOR SEALS () ALONG THE NEW ENGLAND COAST.

Harbor seals () are a common species admitted to marine mammal rehabilitation facilities. As important indicators of marine ecosystem health, monitoring trends of disease in harbor seal populations is critical. However, few studies have evaluated neurologic disease in this species.

CDC's COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs.