Acute perioperative alterations in metabolism: A pilot study using mass spectrometry-based metabolomics.

Objective: To characterize early physiologic stresses imposed by surgery by applying metabolomic analyses to deeply phenotype pre- and postoperative plasma and urine of patients undergoing elective surgical procedures.

Background: Patients experience perioperative stress through depletion of metabolic fuels. Bowel stasis or injury might allow more microbiome-derived uremic toxins to enter the blood, while the liver and kidney are simultaneously clearing analgesic and anesthetic drugs.

Concordance and discordance of anticoagulation assays in children supported by ECMO: The truth is out there.

Introduction: Extracorporeal membrane oxygenation (ECMO) provides critical support to patients in severe cardiac and respiratory failure, but it requires anticoagulation to prevent complications like bleeding and thrombosis. Heparin, the primary anticoagulant utilized, is monitored by activated partial thromboplastin time (aPTT) and anti-Factor Xa (AntiXa) levels. Discordance between the two assays complicates its titration and the impact on patient outcomes is not well-established.

Clinical Actionability of Genetic Findings in Cerebral Palsy: A Systematic Review and Meta-Analysis.

Importance: Single gene variants can cause cerebral palsy (CP) phenotypes, yet the impact of genetic diagnosis on CP clinical management has not been systematically evaluated.

Objective: To evaluate how frequently genetic testing results would prompt changes in care for individuals with CP and the clinical utility of precision medicine therapies.

Data Sources: Published pathogenic or likely pathogenic variants in OMIM genes identified with exome sequencing in clinical (n = 1345) or research (n = 496) cohorts of CP were analyzed.

The MED13L Foundation strategic research plan: a roadmap to the future.

A strategic research plan (SRP) serves as a compass for the patient advocacy organizations driving the therapeutic options for their rare disorder. The MED13L Foundation commissioned the SRP in 2022 through COMBINEDBrain, a consortium of patient advocacy organizations of rare neurodevelopmental disorders, working toward clinical trial readiness. The MED13L Foundation SRP is an objective evaluation of MED13L literature including clinical and basic science knowledge interwoven with an assessment of preclinical trial readiness tools necessary for achieving therapeutic interventions.

Positive Autism Screening Rates in Toddlers Born During the COVID-19 Pandemic.

Importance: Stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Autism screening positivity for children born during the pandemic remains unknown.

Objective: To examine associations between prenatal exposure to the pandemic milieu and maternal SARS-CoV-2 infection with rates of positive Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) screenings.

Impaired macroautophagy confers substantial risk for intellectual disability in children with autism spectrum disorders.

Autism spectrum disorder (ASD) represents a complex of neurological and developmental disabilities characterized by clinical and genetic heterogeneity. While the causes of ASD are still unknown, many ASD risk factors are found to converge on intracellular quality control mechanisms that are essential for cellular homeostasis, including the autophagy-lysosomal degradation pathway. Studies have reported impaired autophagy in ASD human brain and ASD-like synapse pathology and behaviors in mouse models of brain autophagy deficiency, highlighting an essential role for defective autophagy in ASD pathogenesis.

Examining contaminant transport hotspots and their predictability across contrasted watersheds.

Hydrobiogeochemical processes governing water quantity and quality are highly variable in space and time. Focusing on thirty river locations in Québec, Canada, three water quality hotness indices were used to classify watersheds as contaminant transport hotspots. Concentration and load data for suspended solids (SS), total nitrogen (TN), and total phosphorous (TP) were used to identify transport hotspots, and results were compared across hotness indices with different data requirements.

A Prospective, Longitudinal Study of Caregiver-Reported Adaptive Skills and Function of Individuals with -related Neurodevelopmental Disorder.

Objectives: This study presents a cohort of individuals in a natural history study with de novo pathogenic missense variants in causative of -related neurodevelopmental disorder (NDD) to describe individuals' adaptive functional abilities.

Methods: We measured adaptive function using the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) and the Vineland Adaptive Behavior Scale (VABS-III). Results were compared using inferential statistics and regression analysis.

Clinical characteristics, longitudinal adaptive functioning, and association with electroencephalogram activity in PPP2R5D-related neurodevelopmental disorder.

Protein phosphatase 2 regulatory subunit B56δ related neurodevelopmental disorder (PPP2R5D-related NDD) is largely caused by de novo heterozygous missense PPP2R5D variants. We report medical characteristics, longitudinal adaptive functioning, and in-person neurological, motor, cognitive, and electroencephalogram (EEG) activity for PPP2R5D-related NDD. Forty-two individuals (median age 6 years, range = 0.

Antisense oligonucleotide therapy in an individual with KIF1A-associated neurological disorder.

KIF1A-associated neurological disorder (KAND) is a neurodegenerative and often lethal ultrarare disease with a wide phenotypic spectrum associated with largely heterozygous de novo missense variants in KIF1A. Antisense oligonucleotide treatments represent a promising approach for personalized treatments in ultrarare diseases. Here we report the case of one patient with a severe form of KAND characterized by refractory spells of behavioral arrest and carrying a p.

MicroRNA Biomarkers on Day of Injury Among Patients with Post Concussive Symptoms at 28-Days: A Prospective Cohort Study.

Background: After mild traumatic brain injury (mTBI), some patients experience symptoms that persist for weeks to months. Recovery from mTBI is primarily assessed using selfreported symptom questionnaires. Blood biomarkers, including microRNA species, have shown promise to assist diagnosis of mTBI, however, little is known about how blood microRNA measures might predict symptom recovery.

Modeling cellular responses to serum and vitamin D in microgravity using a human kidney microphysiological system.

The microgravity environment aboard the International Space Station (ISS) provides a unique stressor that can help understand underlying cellular and molecular drivers of pathological changes observed in astronauts with the ultimate goals of developing strategies to enable long- term spaceflight and better treatment of diseases on Earth. We used this unique environment to evaluate the effects of microgravity on kidney proximal tubule epithelial cell (PTEC) response to serum exposure and vitamin D biotransformation capacity. To test if microgravity alters the pathologic response of the proximal tubule to serum exposure, we treated PTECs cultured in a microphysiological system (PT-MPS) with human serum and measured biomarkers of toxicity and inflammation (KIM-1 and IL-6) and conducted global transcriptomics via RNAseq on cells undergoing flight (microgravity) and respective controls (ground).

Biomarkers of Neurobiologic Recovery in Adults With Sport-Related Concussion.

Importance: Sport-related concussion (SRC), a form of mild traumatic brain injury, is a prevalent occurrence in collision sports. There are no well-established approaches for tracking neurobiologic recovery after SRC.

Objective: To examine the levels of serum glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in Australian football athletes who experience SRC.

Legacy copper/nickel mine tailings potentially harbor novel iron/sulfur cycling microorganisms within highly variable communities.

The oxidation of sulfide-bearing mine tailings catalyzed by acidophilic iron and sulfur-oxidizing bacteria releases toxic metals and other contaminants into soil and groundwater as acid mine drainage. Understanding the environmental variables that control the community structure and metabolic activity of microbes indigenous to tailings (especially the abiotic stressors of low pH and high dissolved metal content) is crucial to developing sustainable bioremediation strategies. We determined the microbial community composition along two continuous vertical gradients of Cu/Ni mine tailings at each of two tailings impoundments near Sudbury, Ontario.

Heterogeneity of comprehensive clinical phenotype and longitudinal adaptive function and correlation with computational predictions of severity of missense genotypes in KIF1A-associated neurological disorder.

Purpose: Pathogenic variants in kinesin family member 1A (KIF1A) are associated with KIF1A-associated neurological disorder. We report the clinical phenotypes and correlate genotypes of individuals with KIF1A-associated neurological disorder.

Methods: Medical history and adaptive function were assessed longitudinally.

Development of a kidney microphysiological system hardware platform for microgravity studies.

Determining the physiological effects of microgravity on the human kidney is limited to relatively insensitive tests of biofluids (blood and urine) that do not return abnormal results until more than 50% of kidney function is lost. We have developed an "organ on chip" microphysiological model of the human kidney proximal tubule (PT-MPS) that can recapitulate many kidney functions and disease states and could play a critical role in determining mechanisms of early kidney dysfunction in microgravity. However, the ground-based PT-MPS system is incompatible with spaceflight as it requires a large pneumatic system coupled to a cell incubator for perfusion and intensive hand-on manipulation.

Racial Differences in Vaginal Fluid Metabolites and Association with Systemic Inflammation Markers among Ovarian Cancer Patients: A Pilot Study.

The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022.

Peripheral nerve decompression for pain relief in the setting of previous obstetrical brachial plexus injury: a retrospective case series.

Purpose: In children with previous obstetrical brachial plexus injury (OBPI), upper extremity pain is present in 45 to 66% of patients. Recent literature reports this as musculoskeletal or neuropathic in nature. The purpose of the study is to demonstrate that peripheral nerve decompression, and neurolysis may be an effective treatment for patients with upper extremity pain in the context of previous OBPI.

Measured optical losses of Sc doped AlN waveguides.

Although Sc doped AlN (ScAlN) has been used extensively in micro-electro-mechanical systems (MEMS) devices and more recently in optical devices, there have not been thorough studies of its intrinsic optical losses. Here we explore the optical losses of the ScAlN waveguide system by observing racetrack resonator waveguide quality factors. Using a partial physical etch, we fabricate waveguides and extract propagation losses as low as 1.

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined.

Metabolomic and genetic architecture of gestational diabetes subtypes.

Aims/hypothesis: Physiological gestational diabetes mellitus (GDM) subtypes that may confer different risks for adverse pregnancy outcomes have been defined. The aim of this study was to characterise the metabolome and genetic architecture of GDM subtypes to address the hypothesis that they differ between GDM subtypes.

Methods: This was a cross-sectional study of participants in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study who underwent an OGTT at approximately 28 weeks' gestation.

Utilization of the Rat Tibial Nerve Transection Model to Evaluate Cellular and Molecular Mechanisms Underpinning Denervation-Mediated Muscle Injury.

Peripheral nerve injury denervates muscle, resulting in muscle paralysis and atrophy. This is reversible if timely muscle reinnervation occurs. With delayed reinnervation, the muscle's reparative ability declines, and muscle-resident fibro-adipogenic progenitor cells (FAPs) proliferate and differentiate, inducing fibro-fatty muscle degradation and thereby physical disability.