Association of plasma neurofilament light chain with microstructural white matter changes in Down syndrome.

Introduction: Both micro- and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross-sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.

Sustained Positive Practice Change After Targeted Education in the Management of Ovarian Torsion.

Background: Failure to perform ovarian conservation surgery (OCS) for patients who present with adnexal torsion was recognized as a practice gap by the American Pediatric Surgical Association (APSA) in 2017. A targeted educational campaign was conducted to promote detorsion and ovarian conservation surgery as the standard of care for ovarian torsion. We evaluated the practice change that has occurred for pediatric and adolescent patients with ovarian torsion from 2012 to 2022.

Calcineurin/NFAT inhibitors maintain cognition in a preclinical prevention study in an aging canine model of Alzheimer disease.

Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT) transcription factor increases in Alzheimer disease (AD) and is associated with synaptic loss, neurodegeneration, neuroinflammation, amyloid-β (Aβ) production, and cognitive decline. CN/NFAT inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic use of tacrolimus in transplant patients reduces risk of AD.

Shape optimized acoustic metagratings for anomalous refraction under strong thermoviscous effects.

The recent development of microacoustic metagratings opens up promising possibilities for manipulating acoustic wavefronts passively, particularly in applications such as flat acoustic lenses and ultra-high frequency ultrasound imaging. The emergence of two-photon polymerization has made it feasible to precisely manufacture microscopic structures, as required when metagratings are scaled to MHz frequencies in airborne ultrasound. Nevertheless, the downsizing process presents another hurdle as the increased thermoviscous effects result in substantial losses that must be considered during the design phase.

Nicorandil treatment improves survival and spatial learning in aged granulin knockout mice.

Mutations in the human granulin (GRN) gene are associated with multiple diseases, including dementia disorders such as frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). We studied a Grn knockout (Grn-KO) mouse model in order to evaluate a potential therapeutic strategy for these diseases using nicorandil, a commercially available agonist for the ABCC9/Abcc9-encoded regulatory subunit of the "KATP" channel that is well-tolerated in humans. Aged (13 months) Grn-KO and wild-type (WT) mice were treated as controls or with nicorandil (15 mg/kg/day) in drinking water for 7 months, then tested for neurobehavioral performance, neuropathology, and gene expression.

A small molecule p38α MAPK inhibitor, MW150, attenuates behavioral deficits and neuronal dysfunction in a mouse model of mixed amyloid and vascular pathologies.

Background: Inhibition of p38 alpha mitogen activated protein kinase (p38α) has shown great promise as a treatment for Alzheimer's disease (AD) in preclinical tests. However, previous preclinical studies were performed in "pure" models of AD pathology. A vast majority of AD patients have comorbid dementia-contributing pathologies, particularly some form of vascular damage.

Investigating the complexity of naloxone distribution: Which policies matter for pharmacies and potential recipients.

Despite efforts to expand naloxone access, opioid-related overdoses remain a significant contributor to mortality. We study state efforts to expand naloxone distribution through pharmacies by reducing the non-monetary costs to prescribers, dispensers, and/or potential recipients of naloxone. We find that laws that only address liability costs have small and insignificant effects on the volume of naloxone dispensed through pharmacies.

Reproductive potential and implant loss in female hamadryas baboons (Papio hamadryas) previously contracepted with melengestrol acetate contraceptive implants at AZA institutions.

Melengestrol acetate (MGA) implants are a progestin-based reversible contraceptive used to manage fertility in animals. MGA implants are recommended for replacement every 2 years; however, reproduction may be suppressed longer if implants are not removed. In this study, we investigated whether the probability of reproducing (pR) differed among nonimplanted females, females with MGA implants removed, and females whose implants were not removed.

Mice Lacking Mrs2 Magnesium Transporter are Hypophagic and Thin When Maintained on a High-Fat Diet.

Genes regulating body fat are shared with high fidelity by mice and humans, indicating that mouse knockout (KO) phenotyping might identify valuable antiobesity drug targets. Male Mrs2 magnesium transporter (Mrs2) KO mice were recently reported as thin when fed a high-fat diet (HFD). They also exhibited increased energy expenditure (EE)/body weight and had beiged adipocytes that, along with isolated hepatocytes, demonstrated increased oxygen consumption, suggesting that increased EE drove the thin phenotype.

Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs.

A major question in developmental and regenerative biology is how organ size and architecture are controlled by progenitor cells. While limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse fetal cartilage is repaired postnatally, via a two-step process.

Age-Related Brain Atrophy and the Positive Effects of Behavioral Enrichment in Middle-Aged Beagles.

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments.

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.

Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group.

Methods: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions.

Opioid Prescribing Patterns After Imposition of Setting-Specific Limits on Prescription Duration.

Importance: Despite their widespread adoption across the US, policies imposing one-size-fits-all limits on the duration of prescriptions for opioids have shown modest and mixed implications for prescribing.

Objective: To assess whether a prescription duration limit policy tailored to different clinical settings was associated with shorter opioid prescription lengths.

Design, Setting, And Participants: This cross-sectional study examined changes in opioid prescribing patterns for opioid-naive Medicaid enrollees aged 12 to 64 years before and after implementation of a statewide prescription duration limit policy in West Virginia in June 2018.

Nuclear factor Y is a pervasive regulator of neuronal gene expression.

Nervous system function relies on the establishment of complex gene expression programs that provide neuron-type-specific and core pan-neuronal features. These complementary regulatory paradigms are controlled by terminal selector and parallel-acting transcription factors (TFs), respectively. Here, we identify the nuclear factor Y (NF-Y) TF as a pervasive direct and indirect regulator of both neuron-type-specific and pan-neuronal gene expression.

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.

Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group.

Methods: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions.

Realistic prediction and engineering of high-Q modes to implement stable Fano resonances in acoustic devices.

Quasi-bound states in the continuum (QBICs) coupling into the propagating spectrum manifest themselves as high-quality factor (Q) modes susceptible to perturbations. This poses a challenge in predicting stable Fano resonances for realistic applications. Besides, where and when the maximum field enhancement occurs in real acoustic devices remains elusive.

Active maintenance of CD8 T cell naivety through regulation of global genome architecture.

The differentiation of naive CD8 T lymphocytes into cytotoxic effector and memory CTL results in large-scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organization underpin these transcriptional programs. We use Hi-C to map changes in the spatial organization of long-range genome contacts within naive, effector, and memory virus-specific CD8 T cells.

A genomic survey of isolates from hospitalized patients in Melbourne, Australia.

There has been a decrease in healthcare-associated infection in Australia, but an increase in the genetic diversity of infecting strains, and an increase in community-associated cases. Here, we studied the genetic relatedness of isolated from patients at a major hospital in Melbourne, Australia. Diverse ribotypes were detected, including those associated with community and environmental sources.

Educational Attainment and US Drug Overdose Deaths.

Importance: Educational attainment in the US is associated with life expectancy. As the opioid crisis worsens, it is critical to understand how overdose death rate trends evolve across education groups.

Objective: To investigate the association between educational attainment and overdose death rates, with emphasis on trends during the COVID-19 pandemic.

Relationship of POLST to Hospitalization and ICU Care Among Nursing Home Residents in California.

Background: Physician Orders for Life Sustaining Treatment (POLST) document instructions for intensity of care based upon patient care preferences. POLST forms generally reflect patients' wishes and dictate subsequent medical care, but it is not known how POLST use and content among nursing home residents is associated with inpatient utilization across a large population.

Objective: Evaluate the relationship between POLST use and content with hospital utilization among nursing home residents in California.