Virally-Mediated Enhancement of Efferent Inhibition Reduces Acoustic Trauma in Wild Type Murine Cochleas.

Noise-induced hearing loss (NIHL) poses an emerging global health problem with only ear protection or sound avoidance as preventive strategies. In addition, however, the cochlea receives some protection from medial olivocochlear (MOC) efferent neurons, providing a potential target for therapeutic enhancement. Cholinergic efferents release ACh (Acetylycholine) to hyperpolarize and shunt the outer hair cells (OHCs), reducing sound-evoked activation.

The relationship between 'school readiness' and later persistent absenteeism.

Post-pandemic school absence is an increasing concern for governments worldwide. Absence is associated with poor academic outcomes and long-term illness (physical and mental). Absenteeism increases the risk of financial difficulties in adulthood and involvement in the criminal justice system.

Immunometabolic Blood Biomarkers of Developmental Trajectories of Depressive Symptoms: Findings From the ALSPAC Birth Cohort.

Studies of longitudinal trends of depressive symptoms in young people could provide insight into aetiologic mechanism, heterogeneity and origin of common cardiometabolic comorbidities for depression. Depression is associated with immunological and metabolic alterations, but immunometabolic characteristics of developmental trajectories of depressive symptoms remain unclear. Using depressive symptoms scores measured on 10 occasions between ages 10 and 25 years in the Avon Longitudinal Study of Parents and Children (n=7302), we identified four distinct trajectories: low-stable (70% of the sample), adolescent-limited (13%), adulthood-onset (10%) and adolescent-persistent (7%).

Risk of not being in employment, education or training (NEET) in late adolescence is signalled by school readiness measures at 4-5 years.

Background: Not being in employment, education, or training (NEET) is associated with poor health (physical and mental) and social exclusion. We investigated whether England's statutory school readiness measure conducted at 4-5 years provides a risk signal for NEET in late adolescence.

Methods: We identified 8,118 individuals with school readiness measures at 4-5 years and NEET records at 16-17 years using Connected Bradford, a bank of linked routinely collected datasets.

Click detection rate variability of central North Pacific sperm whales from passive acoustic towed arrays.

Passive acoustic monitoring (PAM) is an optimal method for detecting and monitoring cetaceans as they frequently produce sound while underwater. Cue counting, counting acoustic cues of deep-diving cetaceans instead of animals, is an alternative method for density estimation, but requires an average cue production rate to convert cue density to animal density. Limited information about click rates exists for sperm whales in the central North Pacific Ocean.

α-catenin middle- and actin-binding domain unfolding mutants differentially impact epithelial strength and sheet migration.

α-catenin (α-cat) displays force-dependent unfolding and binding to actin filaments through direct and indirect means, but features of adherens junction structure and function most vulnerable to loss of these allosteric mechanisms have not been directly compared. By reconstituting an α-cat F-actin-binding domain unfolding mutant known to exhibit enhanced binding to actin (α-cat-H0-FABD) into α-cat knockout Madin Darby Canine Kidney (MDCK) cells, we show that partial loss of the α-cat catch bond mechanism (via an altered H0 α-helix) leads to stronger epithelial sheet integrity with greater colocalization between the α-cat-H0-FABD mutant and actin. α-cat-H0-FABD -expressing cells are less efficient at closing scratch-wounds, suggesting reduced capacity for more dynamic cell-cell coordination.

Damage-evoked signals in cochlear neurons and supporting cells.

In addition to hearing loss, damage to the cochlea can lead to gain of function pathologies such as hyperacusis. It has been proposed that painful hyperacusis, noxacusis, may be carried to the central nervous system by type II cochlear afferents, sparse, unmyelinated neurons that share morphological and neurochemical traits with nociceptive C-fibers of the somatic nervous system. Also like in skin, damage elicits spreading calcium waves within cochlear epithelia.

Successful Crizotinib-targeted Therapy of Pediatric Unresectable ERC1::ALK Fusion Sarcoma.

Anaplastic lymphoma kinase ( ALK )-fusion sarcomas are rare part of the emerging theoretically targetable tyrosine kinase RAS::MAPK pathway fusion myopericytic-ovoid sarcomas. We report our clinicopathologic and treatment experience with an ALK fusion sarcoma. A novel ELKS/RAB6-interacting/CAST family member 1 - unaligned ALK fusion infiltrative nonmetastatic low-grade sarcoma of the right hand of a 15-month-old male was treated with crizotinib, an ALK tyrosine kinase inhibitor as oral monotherapy, inducing complete radiographic and clinical resolution by 10 months and sustained response now over 12 months after elective discontinuation.

Programmed Death Ligand 1-Expressing Macrophages and Their Protective Role in the Joint During Arthritis.

Objective: Arthritis associated with immune checkpoint inhibitor therapies highlights the importance of immune checkpoint expression for joint homeostasis. We investigated the role of programmed death ligand (PD-L) 1 in the synovium using a collagen-induced arthritis (CIA) mouse model.

Methods: We blocked PD-L1 using blocking antibodies during CIA and assessed the arthritis severity by clinical and histologic scoring.

Hypereosinophilia causes progressive cardiac pathologies in mice.

Hypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue damage would benefit therapeutic development.

Potential for England's statutory school entry assessment to identify special educational needs and reveal structural inequalities: a population-based study.

Objective: To investigate at a population level whether England's universal assessment of 'school readiness' is associated with later identification of special educational needs (SEN). Also, whether ethnic differences exist in SEN identification (white British versus ethnic minority) and whether this varies as a function of school readiness.

Method: Analysis included 53 229 individuals aged 5-12 years from the Connected Bradford Database (2012/2013-2019/2020).

Engineering olivocochlear inhibition to reduce acoustic trauma.

Efferent brain-stem neurons release acetylcholine to desensitize cochlear hair cells and can protect the inner ear from acoustic trauma. That protection is absent from knockout mice lacking efferent inhibition and is stronger in mice with a gain-of-function point mutation of the hair cell-specific nicotinic acetylcholine receptor. The present work uses viral transduction of gain-of-function receptors to restore acoustic prophylaxis to the knockout mice.

Heavy silicone oil tamponade: a multicentre experience.

Objective: To report multicentred use of the heavy silicone oil Densiron 68 for anatomical reattachment following rhegmatogenous retinal detachment (RRD) repair and its associated complications.

Methods And Analysis: Patients from seven vitreoretinal units within the UK that underwent RRD repair with Densiron 68 between January 2015 and December 2019 were identified. Primary outcome measures were primary and final reattachment rate, retained Densiron and failure rate.

Connected Bradford: a Whole System Data Linkage Accelerator.

The richness of linked population data provides exciting opportunities to understand local health needs, identify and predict those in most need of support and evaluate health interventions. There has been extensive investment to unlock the potential of clinical data for health research in the UK. However, most of the determinants of our health are social, economic, education, environmental, housing, food systems and are influenced by local authorities.

Cardiac myosin-specific autoimmune T cells contribute to immune-checkpoint-inhibitor-associated myocarditis.

Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear.

Exclusion of Reproductive-aged Women in COVID-19 Vaccination and Clinical Trials.

Introduction: We analyzed the exclusion of pregnant and breastfeeding individuals and those capable of pregnancy in COVID-19 vaccine and clinical treatment trials.

Methods: Inclusion and exclusion criteria were extracted from all listed COVID-19 vaccine and treatment clinical trials from May 1, 2020, to October 31, 2020, using the U.S.

Patterns and Predictors of Air Cleaner Adherence Among Adults with COPD.

Rational: Poor indoor air quality has been associated with worse chronic obstructive pulmonary disease (COPD) morbidity. In-home portable air cleaners reduce indoor pollutants and could improve respiratory health. Factors associated with air cleaner adherence among adults with COPD remains unknown.

High-Speed Human Temporal Bone Sectioning for the Assessment of COVID-19-Associated Middle Ear Pathology.

Histopathologic analysis of human temporal bone sections is a fundamental technique for studying inner and middle ear pathology. Temporal bone sections are prepared by postmortem temporal bone harvest, fixation, decalcification, embedding, and staining. Due to the density of the temporal bone, decalcification is a time-consuming and resource-intensive process; complete tissue preparation may take 9-10 months on average.

Non-native red alga Gracilaria vermiculophylla compensates for seagrass loss as blue crab nursery habitat in the emerging Chesapeake Bay ecosystem.

Non-native species can become deleterious or potentially beneficial as components of novel ecosystems. The non-native red macroalga Gracilaria vermiculophylla may provide nursery habitat where eelgrass Zostera marina has been extirpated in Chesapeake Bay. A mensurative experiment was conducted monthly May-October 2013 and 2014 in the York River, Chesapeake Bay, to evaluate hypotheses that Gracilaria (1) can compensate for the loss of seagrass nurseries by colonizing habitats where seagrass has been eliminated by environmental stress, and (2) is utilized by juvenile blue crabs (Callinectes sapidus) as nursery habitat.

Update on frequency decline of Northeast Pacific blue whale (Balaenoptera musculus) calls.

Worldwide, the frequency (pitch) of blue whale (Balaenoptera musculus) calls has been decreasing since first recorded in the 1960s. This frequency decline occurs over annual and inter-annual timescales and has recently been documented in other baleen whale species, yet it remains unexplained. In the Northeast Pacific, blue whales produce two calls, or units, that, when regularly repeated, are referred to as song: A and B calls.

Characterization of fin whale song off the Western Antarctic Peninsula.

Song is produced by a variety of terrestrial and marine animals and is particularly common among baleen whales. Fin whale (Balaenoptera physalus) song is comprised of relatively simple 20 Hz pulses produced at regular intervals. The timing of these intervals, in addition to the presence and frequency of overtones, appears to be unique to each population.

Increased Interleukin 18-Dependent Immune Responses Are Associated With Myopericarditis After COVID-19 mRNA Vaccination.

Myocarditis and myopericarditis may occur after COVID-19 vaccination with an incidence of two to twenty cases per 100,000 individuals, but underlying mechanisms related to disease onset and progression remain unclear. Here, we report a case of myopericarditis following the first dose of the mRNA-1273 COVID-19 vaccine in a young man who had a history of mild COVID-19 three months before vaccination. The patient presented with chest pain, elevated troponin I level, and electrocardiogram abnormality.

Large-scale assessment of 7-11-year-olds' cognitive and sensorimotor function within the Born in Bradford longitudinal birth cohort study.

Cognitive ability and sensorimotor function are crucial aspects of children's development, and are associated with physical and mental health outcomes and educational attainment. This paper describes cross-sectional sensorimotor and cognitive function data collected on over 15,000 children aged 7-10 years, collected as part of the Born in Bradford (BiB) longitudinal birth-cohort study. Methodological details of the large-scale data collection process are described, along with initial analyses of the data involving the relationship between cognition/sensorimotor ability and age and task difficulty, and associations between tasks.