Lifespan in rodents with MYT1L heterozygous mutation.

MYT1L syndrome is a newly recognized disorder characterized by intellectual disability, speech and motor delay, neuroendocrine disruptions, ADHD, and autism. In order to study this gene and its association with these phenotypes, our lab recently created a heterozygous mutant mouse inspired by a clinically relevant mutation. This model recapitulates several of the physical and neurologic abnormalities seen in humans with MYT1L syndrome, such as weight gain, microcephaly, and behavioral disruptions.

Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity.

Extracellular vesicles (EVs) are associated with intercellular communications, immune responses, viral pathogenicity, cardiovascular diseases, neurological disorders, and cancer progression. EVs deliver proteins, metabolites, and nucleic acids into recipient cells to effectively alter their physiological and biological response. During their transportation from the donor to the recipient cell EVs face differential ionic concentrations, which can be detrimental to their integrity and impact their cargo content.

Lost Work Due to Burn-Related Disability in a US Working Population.

Background: Burn injuries can require hospitalization, operations, and long-term reconstruction. Burn-injured patients can experience short- or long-term disability. We investigated lost workdays (LWDs), short-term disability (STD), and long-term disability (LTD) in the 12-month period following a burn injury.

A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice.

The transcription factor MYT1L supports proper neuronal differentiation and maturation during brain development. MYT1L haploinsufficiency results in a neurodevelopmental disorder characterized by intellectual disability, developmental delay, autism, behavioral disruptions, aggression, obesity and epilepsy. While MYT1L is expressed throughout the brain, how it supports proper neuronal function in distinct regions has not been assessed.

MYT1L deficiency impairs excitatory neuron trajectory during cortical development.

Mutations reducing the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder. MYT1L is used as a pro-neural factor in fibroblast-to-neuron transdifferentiation and is hypothesized to influence neuronal specification and maturation, but it is not clear which neuron types are most impacted by MYT1L loss. In this study, we profile 412,132 nuclei from the forebrains of wild-type and MYT1L-deficient mice at three developmental stages: E14 at the peak of neurogenesis, P1 when cortical neurons have been born, and P21 when neurons are maturing, to examine the role of MYT1L levels on neuronal development.

Efficacy of Neuromuscular Ultrasound in Diagnosing and Treating a Mammogram-Induced Brachial Plexus Injury-A Case Report.

A 40-year-old woman presented with chronic left anterior shoulder, upper arm, and axillary pain following a routine mammogram 3 years prior. Despite multiple interventions, her pain persisted significantly affecting her quality of life. Ultrasound examination revealed fascicular edema in the medial brachial cutaneous nerve (MBCN), intercostobrachial cutaneous nerve (ICBN), and a positive sono-Tinel.

Chromosomal and gonadal sex have differing effects on social motivation in mice.

Background: Sex differences in brain development are thought to lead to sex variation in social behavior. Sex differences are fundamentally driven by both gonadal (i.e.

"They already trusted us a lot": Allied health students' experiences of an innovative hospital, service-focussed placement model.

Background: A service-focussed placement model involves an innovative partnership between service and education providers to a) address service delivery needs and b) facilitate students' competency development. Services are collaboratively redesigned such that students are positioned as collaborators in service delivery with their learning supported through evidence-informed educational design. This model was implemented in the hospital setting and was found to promote positive patient outcomes.

A systematic review of cost-effectiveness analyses of gene therapy for hemophilia type A and B.

Background: In 2022-2023, the US Food and Drug Administration approved 2 novel gene therapies, valoctocogene roxaparvovec and etranacogene dezaparavovec, for hemophilia A and B, respectively. These one-time-administered gene therapies have been marketed at prices that create financial challenges for payers and patients. Understanding the magnitude and uncertainties around the long-term value of these therapies and how they can potentially relate to managed care practices is of high interest to the payer and patient community.

Mice lacking have ASD-like behaviors and altered cerebellar circuit properties.

Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. Individuals with mutations exhibit neurodevelopmental disorders, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, and language delay. To provide a genetic model for the role of the cerebellum in ASD-related behaviors and study the role of ASTN2 in cerebellar circuit function, we generated global and PC-specific conditional knockout (KO and cKO, respectively) mouse lines.

Affordability and adherence gains for Medicare Part D low-income subsidy recipients when low-income subsidy benefits expanded in 2024.

Background: The lowest-income beneficiaries enrolled in the Medicare Part D prescription drug program receive "full subsidies" that waive the premium and deductible and impose minimal copayments. Those with slightly higher incomes and assets may be eligible for "partial subsidies." Prior to 2024, individuals receiving partial subsidies faced reduced Part D premiums and deductibles and paid 15% coinsurance.

Bioorthogonal non-canonical amino acid tagging to track transplanted human induced pluripotent stem cell-specific proteome.

Background: Human induced pluripotent stem cells (hiPSCs) and their differentiated cell types have a great potential for tissue repair and regeneration. While the primary focus of using hiPSCs has historically been to regenerate damaged tissue, emerging studies have shown a more potent effect of hiPSC-derived paracrine factors on tissue regeneration. However, the precise contents of the transplanted hiPSC-derived cell secretome are ambiguous.

At the onset of active whisking, the input layer of barrel cortex exhibits a 24 h window of increased excitability that depends on prior experience.

The development of motor control over sensory organs is a critical milestone in sensory processing, enabling active exploration and shaping of the sensory environment. However, whether the onset of sensory organ motor control directly influences the development of corresponding sensory cortices remains unknown. Here, we exploit the late onset of whisking behavior in mice to address this question in the somatosensory system.

Variation in Risk-Adjusted Ventilator-Associated Pneumonia Days Within a Quality Collaborative.

Introduction: Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged mechanical ventilation, and longer intensive care unit stays. The rate of VAP (VAPs per 1000 ventilator days) within a hospital is an important quality metric. Despite adoption of preventative strategies, rates of VAP in injured patients remain high in trauma centers.

A glial circadian gene expression atlas reveals cell type and disease-specific reprogramming in response to amyloid pathology or aging.

While circadian rhythm disruption may promote neurodegenerative disease, how aging and neurodegenerative pathology impact circadian gene expression patterns in different brain cell types is unknown. Here, we used translating ribosome affinity purification methods to define the circadian translatomes of astrocytes, microglia, and bulk cerebral cortex, in healthy mouse brain and in the settings of amyloid-beta plaque pathology or aging. Our data reveal that glial circadian translatomes are highly cell type-specific and exhibit profound, context-dependent reprogramming of rhythmic transcripts in response to amyloid pathology or aging.

Relationship between sex biases in gene expression and sex biases in autism and Alzheimer's disease.

Background: Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions.

Methods: In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks.

Results: We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals.

Norepinephrine Signals Through Astrocytes To Modulate Synapses.

Locus coeruleus (LC)-derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit connectivity, but the underlying synapse-level mechanisms are elusive. Here, we show that NE remodeling of synaptic function is independent from its binding on neuronal receptors. Instead, astrocytic adrenergic receptors and Ca dynamics fully gate the effect of NE on synapses as the astrocyte-specific deletion of adrenergic receptors and three independent astrocyte-silencing approaches all render synapses insensitive to NE.

Calculation and Feedback of Risk-Adjusted Antibiotic Days as a Process Measure in a Statewide Trauma Collaborative.

Background: Optimization of antibiotic stewardship requires determining appropriate antibiotic treatment and duration of use. Our current method of identifying infectious complications alone does not attempt to measure the resources actually utilized to treat infections in patients. We sought to develop a method accounting for treatment of infections and length of antibiotic administration to allow benchmarking of trauma hospitals with regard to days of antibiotic use.

Characterization of early markers of disease in the mouse model of mucopolysaccharidosis IIIB.

Background: Mucopolysaccharidosis (MPS) IIIB, also known as Sanfilippo Syndrome B, is a devastating childhood disease. Unfortunately, there are currently no available treatments for MPS IIIB patients. Yet, animal models of lysosomal storage diseases have been valuable tools in identifying promising avenues of treatment.

Examining Sex Differences in Autism Heritability.

Importance: Autism spectrum disorder (ASD) is a neurodevelopmental disorder more prevalent in males than in females. The cause of ASD is largely genetic, but the association of genetics with the skewed sex ratio is not yet understood. To our knowledge, no large population-based study has provided estimates of heritability by sex.