Fertilization, the basis for sexual reproduction, culminates in the binding and fusion of sperm and egg. Although several proteins are known to be crucial for this process in vertebrates, the molecular mechanisms remain poorly understood. Using an AlphaFold-Multimer screen, we identified the protein Tmem81 as part of a conserved trimeric sperm complex with the essential fertilization factors Izumo1 and Spaca6.
View Article and Find Full Text PDFWith echocardiography standing as the most widely used cardiac imaging modality, echocardiography report interpretation is a core responsibility of junior doctors. The literature, however, reveals a deficit in echocardiography education. The implications of this for patient care should not be ignored.
View Article and Find Full Text PDFDiphtheria is a potentially fatal bacterial infection caused by toxin-producing strains of corynebacteria, most often and less commonly . Incidence of the disease has fallen significantly since the introduction of vaccination programs; it is now rare in countries with high vaccination coverage such as Australia. This article presents the most recent respiratory cases of diphtheria in two children in New South Wales-the first locally acquired childhood cases in Australia in 30 years-and discusses potential contributing factors.
View Article and Find Full Text PDFImportance: The indications, safety, and efficacy of chemical venous thromboembolism prophylaxis (cVTE) in pediatric trauma patients remain unclear. A set of high-risk criteria to guide cVTE use was recently recommended; however, these criteria have not been evaluated prospectively.
Objective: To examine high-risk criteria and cVTE use in a prospective multi-institutional study of pediatric trauma patients.
Background: There is a requirement for British Army personnel to operate in/around water. Assessing role-related swimming/water competence will support personnel to conduct their job-roles safely and effectively.
Objective: To undertake a Job-Task Analysis (JTA) of British Army personnel when working in/around water and use this information to develop a Swimming Representative Military Task (RMT) to assess swimming/water competence.
Background: The biological effects of SARS-CoV-2 infection in transplanted kidneys are uncertain with little pathological information.
Methods: This single-center, prospective observational study evaluated kidney transplant biopsies from recipients of deceased donors with COVID-19, current recipients contracting SARS-CoV-2 Omicron variant in 2022, against prior BK virus (BKV) infection and uninfected (without SARS-CoV-2 or BKV) samples, as respective positive and negative comparators (n = 503 samples).
Results: We demonstrated nonvirus tubular injury in implanted tissue from infected donors and prevalent recipients with mild acute COVID-19 and acute kidney injury, excluding direct viral infection as a cause of kidney damage.
Alternative splicing (AS) alters the -regulatory landscape of mRNA isoforms, leading to transcripts with distinct localization, stability, and translational efficiency. To rigorously investigate mRNA isoform-specific ribosome association, we generated subcellular fractionation and sequencing (Frac-seq) libraries using both conventional short reads and long reads from human embryonic stem cells (ESCs) and neural progenitor cells (NPCs) derived from the same ESCs. We performed de novo transcriptome assembly from high-confidence long reads from cytosolic, monosomal, light, and heavy polyribosomal fractions and quantified their abundance using short reads from their respective subcellular fractions.
View Article and Find Full Text PDFApplication of whole genome sequencing (WGS) has allowed monitoring of the emergence of variants of concern (VOC) of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) globally. Genomic investigation of emerging variants and surveillance of clinical progress has reduced the public health impact of infection during the COVID-19 pandemic. These steps required developing and implementing a proficiency testing program (PTP), as WGS has been incorporated into routine reference laboratory practice.
View Article and Find Full Text PDFBackground: The burden of screening for inherited cardiac conditions on health services grows ever larger, with each new diagnosis necessitating screening of additional family members. Screening these usually asymptomatic, low-risk individuals is currently performed by consultant cardiologists, consuming vital clinic resources that could otherwise be diverted to sicker patients requiring specialist consultant input. Clinical scientists now constitute a highly skilled and often underutilised group of individuals with training in areas such as clinical evaluation, 12-lead electrocardiography (ECG) interpretation, and echocardiography.
View Article and Find Full Text PDFEpidemiological studies have shown associations between whole-grain intake and lowered disease risk. A sufficient level of whole-grain intake to reach the health benefits has not been established, and there is limited knowledge about the impact of whole-grain intake on metabolite levels. In this clinical intervention study, we aimed to identify plasma and urine metabolites associated with two different intake levels of whole-grain wheat and rye and to correlate them with clinical plasma biomarkers.
View Article and Find Full Text PDFIntroduction: Previous studies on intraosseous (IO) anesthesia as a primary injection have shown high success rates. The TuttleNumbNow (TNN; Orem, UT) is a new primary IO injection technique that has not been scientifically evaluated. Therefore, the purpose of this prospective randomized, crossover study was to evaluate the anesthetic efficacy of the TNN IO technique using the Septoject Evolution needle (Septodont, Saint-Maur-des-Fosses, France) compared with buccal infiltration for pulpal anesthesia in mandibular first molars.
View Article and Find Full Text PDFThis study provides a laboratory framework to ensure ongoing relevance and performance of amplification-based whole genome sequencing to strengthen public health surveillance during extended outbreaks or pandemics. The framework integrates regular reviews of the performance of a genomic surveillance system and highlights the importance of ongoing monitoring and the identification and implementation of improvements to whole genome sequencing methods to enhance public health responses to pathogen outbreaks.
View Article and Find Full Text PDFBackground: Undergraduate nursing students spend a significant amount of time in clinical placements where they are involved in care at the end of a person's life and care after death. While their role is to provide compassionate care, some students feel wholly unprepared.
Aims: The aim of this qualitative study was to explore student nurses' experiences of care in death, dying and post death care, and to explore how students can be better prepared to provide such care.
Introduction: Mitochondrial dysfunction is observed in Alzheimer's disease (AD). Altered mitochondrial respiration, cytochrome oxidase (COX) Vmax, and mitophagy are observed in human subjects and animal models of AD. Models derived from induced pluripotent stem cells (iPSCs) may not recapitulate these phenotypes after reprogramming from differentiated adult cells.
View Article and Find Full Text PDFThe emergence of resistance to antiviral drugs increasingly used to treat SARS-CoV-2 infections has been recognised as a significant threat to COVID-19 control. In addition, some SARS-CoV-2 variants of concern appear to be intrinsically resistant to several classes of these antiviral agents. Therefore, there is a critical need for rapid recognition of clinically relevant polymorphisms in SARS-CoV-2 genomes associated with significant reduction of drug activity in virus neutralisation experiments.
View Article and Find Full Text PDFAlternative splicing (AS) alters messenger RNA (mRNA) coding capacity, localization, stability, and translation. Here we use comparative transcriptomics to identify cis-acting elements coupling AS to translational control (AS-TC). We sequenced total cytosolic and polyribosome-associated mRNA from human, chimpanzee, and orangutan induced pluripotent stem cells (iPSCs), revealing thousands of transcripts with splicing differences between subcellular fractions.
View Article and Find Full Text PDFShigella sonnei causes shigellosis, a severe gastrointestinal illness that is sexually transmissible among men who have sex with men (MSM). Multidrug resistance in S. sonnei is common including against World Health Organisation recommended treatment options, azithromycin, and ciprofloxacin.
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