Progressive central cardiorespiratory rate downregulation and intensifying epilepsy lead to sudden unexpected death in epilepsy in mouse model of the most common human ATP1A3 mutation.

Objective: This study was undertaken to test the following hypotheses in the Atp1a3 mouse (which carries the most common human ATP1A3 (the major subunit of the neuronal Na/K-adenosine triphosphatase [ATPase]) mutation, D801N): sudden unexpected death in epilepsy (SUDEP) occurs during seizures and is due to terminal apneas in some and due to lethal cardiac arrhythmias in others; and Atp1a3 mice have central cardiorespiratory dysregulation and abnormal respiratory drive.

Methods: Comparison was made of littermate wild-type and Atp1a3 groups using (1) simultaneous in vivo video-telemetry recordings of electroencephalogram, electrocardiogram, and breathing; (2) whole-body plethysmography; and (3) hypoglossal nerve recordings.

Results: In Atp1a3 mice, (1) SUDEP consistently occurred during seizures that were more severe than preterminal seizures; (2) seizure clustering occurred in periods preceding SUDEP; (3) slowing of breathing rate (BR) and heart rate was observed preictally before preterminal and terminal seizures; and (4) the sequence during terminal seizures was as follows: bradypnea with bradycardia/cardiac arrhythmias, then terminal apnea, followed by terminal cardiac arrhythmias.

Acute and chronic cannabis vapor exposure influences basal and stress-induced release of glucocorticoids in male and female rats.

Management of stress and anxiety is often listed as the primary motivation behind cannabis use. Human research has found that chronic cannabis use is associated with increased basal cortisol levels but blunted neuroendocrine responses to stress. Preclinical research has demonstrated mixed effects of Δ-tetrahydrocannabinol (THC; the psychoactive constituent of cannabis), much of which is suggestive of dose-dependent effects; however, the predominance of this work has employed an injection method to deliver cannabis.

Endocannabinoid involvement in beneficial effects of caloric restriction in a rodent model of comorbid depression and epilepsy.

Clinically, patients with depression are at a heightened risk for developing epilepsy, and vice versa, suggesting shared mechanisms for this bidirectional comorbidity. Unfortunately, comorbid depression and epilepsy is associated with worsened quality of life and treatment refractoriness, highlighting the need for novel treatment targets and nonpharmacologic supplements to existing therapies. The present study used the Swim-Low Active rat, a well-validated model of depression and epilepsy comorbidity that was selectively bred based on forced swim test behavior, to assess the safety and efficacy of caloric restriction in treating this comorbidity.

Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

Introduction: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor.

Analysis of morphological properties of fibrous electrospun polyurethane grafts using image segmentation.

The concentration of the polymer in the electrospinning solution greatly influences the mechanical behaviour of electrospun vascular grafts due to the influence on scaffold morphology. The scaffold morphology (fiber diameter, fiber orientation and inter-fiber voids) of the grafts plays an important role in their behaviour during use. Even though manual methods and complex algorithms have been used so far for characterisation of the morphology of electrospun architecture, they still have several drawbacks that limit their reliability.

Vascular stenting of a malignant arterial blowout as a bridge to effective systemic and regional therapy.

Locally advanced cutaneous squamous cell carcinoma can erode into blood vessels, leading to vascular blowout, requiring emergent surgical intervention. We describe a first case of this disease complication which was effectively managed with endovascular stenting as a bridge to effective systemic and regional therapy. We discuss the efficacy of this staged approach which is novel and timely in a clinical environment of increasingly effective systemic therapies.

Brief Report: Comprehensive Clinicogenomic Profiling of Small Cell Transformation From -Mutant NSCLC Informs Potential Therapeutic Targets.

Introduction: NSCLC transformation to SCLC has been best characterized with -mutant NSCLC, with emerging case reports seen in , , and -altered NSCLC. Previous reports revealed transformed SCLC from -mutant NSCLC portends very poor prognosis and lack effective treatment. Genomic analyses revealed and loss of function increase the risk of SCLC transformation.

Prioritizing a research agenda on built environments and physical activity: a twin panel Delphi consensus process with researchers and knowledge users.

Background: The growth of urban dwelling populations globally has led to rapid increases of research and policy initiatives addressing associations between the built environment and physical activity (PA). Given this rapid proliferation, it is important to identify priority areas and research questions for moving the field forward. The objective of this study was to identify and compare research priorities on the built environment and PA among researchers and knowledge users (e.

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

Background: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result.

Integrative single-nucleus multi-omics analysis prioritizes candidate cis and trans regulatory networks and their target genes in Alzheimer's disease brains.

Background: The genetic underpinnings of late-onset Alzheimer's disease (LOAD) are yet to be fully elucidated. Although numerous LOAD-associated loci have been discovered, the causal variants and their target genes remain largely unknown. Since the brain is composed of heterogenous cell subtypes, it is imperative to study the brain on a cell subtype specific level to explore the biological processes underlying LOAD.

Brief Report: Clinical Response, Toxicity, and Resistance Mechanisms to Osimertinib Plus MET Inhibitors in Patients With EGFR-Mutant MET-Amplified NSCLC.

Introduction: amplification is a known resistance mechanism to tyrosine kinase inhibitor (TKI) treatment in -mutant NSCLC. Dual EGFR-MET inhibition has been reported with success in overcoming such resistance and inducing clinical benefit. Resistance mechanisms to dual EGFR-MET inhibition require further investigation and characterization.

Quality of life and psychological health after mild traumatic brain injury in older people: Three- and six-month follow up.

Objectives: Examine quality of life (QoL) and psychological health after mild traumatic brain injury (mTBI) in older people (65+ years) at 3- and 6-month follow-up and explore which injury factors predicted QoL.

Methods: mTBI patients were compared to trauma comparison (TC) and community comparison (CC) groups. QoL and psychological health were measured at both timepoints.

School lunchboxes as an opportunity for health and environmental considerations: a scoping review.

Very little research has focussed on children's school lunchboxes from both a health and environment standpoint. This scoping review explores studies that considered children's lunchbox food consumption trends at school and the environmental impacts of lunchbox contents. We conducted a scoping review of peer-reviewed literature with a focus on lunchboxes of children in preschool or primary school settings that contained food packed from home, through the lens of food and nutrition in combination with environmental outcomes-particularly food and/or packaging waste.

Mild Traumatic Brain Injury and Functional Outcome in Older Adults: Pain Interference But Not Cognition Mediates the Relationship Between Traumatic Injury and Functional Difficulties.

Objective: To examine functional status of older people 3 months after mild traumatic brain injury (mTBI) and identify whether pain interference or cognition mediates any relationship found between injury status and functional outcomes.

Setting: Patients admitted to a Melbourne-based emergency department.

Participants: Older adults 65 years and older: 40 with mTBI, 66 with orthopedic injury without mTBI (TC), and 47 healthy controls (CC) without injury.

Is level of implementation linked with intervention outcomes? Process evaluation of the TransformUs intervention to increase children's physical activity and reduce sedentary behaviour.

Background: TransformUs was a four-arm school-based intervention to increase physical activity and reduce sedentary behaviour among primary school children. Pedagogical and environmental strategies targeted the classroom, school grounds and family setting. The aims of this study were to evaluate program fidelity, dose, appropriateness, satisfaction and sustainability, and associations between implementation level and outcomes among the three intervention arms.

Cognitive performance in older people after mild traumatic brain injury: Trauma effects and other risk factors.

Objective: Cognitive symptoms are common in the initial weeks after mTBI, but recovery is generally expected within three months. However, there is limited information about recovery specifically in older age cohorts. Therefore, this study investigated cognitive outcome three months after mTBI in older adults (≥ 65 years) compared to trauma and community age-matched controls and explored risk factors for outcome after traumatic injury.

Selective activation of Gαob by an adenosine A receptor agonist elicits analgesia without cardiorespiratory depression.

The development of therapeutic agonists for G protein-coupled receptors (GPCRs) is hampered by the propensity of GPCRs to couple to multiple intracellular signalling pathways. This promiscuous coupling leads to numerous downstream cellular effects, some of which are therapeutically undesirable. This is especially the case for adenosine A receptors (ARs) whose clinical potential is undermined by the sedation and cardiorespiratory depression caused by conventional agonists.

Intervention effects on children's movement behaviour accumulation as a result of the Transform-Us! school- and home-based cluster randomised controlled trial.

Background: It is unknown if and how children's movement behaviour accumulation patterns change as a result of physical activity and/or sedentary behaviour interventions. It is important to establish the effectiveness of interventions targeting changes in such accumulation patterns. This study aimed to investigate the effect of the Transform-Us! school- and home-based intervention program on children's movement behaviour accumulation patterns, focusing on sporadic accumulation versus time in bouts.

The Perspectives of Diabetes Educators and Dietitians on Diet and Lifestyle Management for Gestational Diabetes Mellitus: A Qualitative Study.

This study explores the knowledge and practice of diabetes educators and dietitians on diet and lifestyle management in women with gestational diabetes mellitus (GDM). Diabetes educators and dietitians were recruited from three maternity hospitals in Adelaide (Australia), through snowball and purposive sampling. Thirteen semistructured interviews were conducted, audio recorded, transcribed verbatim, and analysed for codes and themes.