Impairment of Glucose Uptake Induced by Elevated Intracellular Ca in Hippocampal Neurons of Malignant Hyperthermia-Susceptible Mice.

Malignant hyperthermia (MH) is a genetic disorder triggered by depolarizing muscle relaxants or halogenated inhalational anesthetics in genetically predisposed individuals who have a chronic elevated intracellular Ca concentration ([Ca]) in their muscle cells. We have reported that the muscle dysregulation of [Ca] impairs glucose uptake, leading to the development of insulin resistance in two rodent experimental models. In this study, we simultaneously measured the [Ca] and glucose uptake in single enzymatically isolated hippocampal pyramidal neurons from wild-type (WT) and MH-R163C mice.

Socioeconomic Determinants of Health and Reflux Management: Insights from a Tertiary Medical Center.

Objectives: To assess the correlation of social determinants of health (SDOH) with the general care patterns related to gastroesophageal reflux disease and laryngopharyngeal reflux. Determine correlation of SDOH on utilization rates for medication, reflux testing and surgical intervention for patients diagnosed with reflux. Describe overall care patterns for gastroesophageal reflux disease care at a tertiary academic facility.

Hepatocyte Period 1 dictates oxidative substrate selection independent of the core circadian clock.

Organisms integrate circadian and metabolic signals to optimize substrate selection to survive starvation, yet precisely how this occurs is unclear. Here, we show that hepatocyte Period 1 (Per1) is selectively induced during fasting, and mice lacking hepatocyte Per1 fail to initiate autophagic flux, ketogenesis, and lipid accumulation. Transcriptomic analyses show failed induction of the fasting hepatokine Fgf21 in Per1-deficient mice, and single-nucleus multiome sequencing defines a putative responding hepatocyte subpopulation that fails to induce the chromatin accessibility near the Fgf21 locus.

Age- and Sex-Specific Differences in Lyme Disease Health-Related Behaviors, Ontario, Canada, 2015-2022.

We investigated differences in risk factors and preventive behaviors by age and sex among persons with reported Lyme disease in Ontario, Canada, during 2015-2022. Incidence rates peaked among children 5-9 and adults 50-79 years of age. Median age was higher for female than male case-patients (54 vs.

Hepatocyte MMP14 mediates liver and inter-organ inflammatory responses to diet-induced liver injury.

The matrix metalloproteinase MMP14 is a ubiquitously expressed, membrane-bound, secreted endopeptidase that proteolyzes substrates to regulate development, signaling, and metabolism. However, the spatial and contextual events inciting MMP14 activation and its metabolic sequelae are not fully understood. Here, we introduce an inducible, hepatocyte-specific MMP14-deficient model (MMP14 mice) to elucidate cell-intrinsic and systemic MMP14 function.

Epidemiology of sporadic and outbreak-associated hepatitis A infections in Ontario, Canada: A descriptive summary, 2015-2022.

Background: Hepatitis A is a disease of public health significance that typically causes acute, self-limiting infection. Understanding the risk factors and demographics associated with individual infections and outbreaks can guide public health communication and interventions.

Objective: To assess the number of hepatitis A cases and outbreaks in Ontario from January 1, 2015, to November 22, 2022, and to identify common risk factors associated with sporadic and outbreak-associated infections in Ontario.

Hierarchical tricarboxylic acid cycle regulation by hepatocyte arginase 2 links the urea cycle to oxidative metabolism.

Urea cycle impairment and its relationship to obesity and inflammation remained elusive, partly due to the dramatic clinical presentation of classical urea cycle defects. We generated mice with hepatocyte-specific arginase 2 deletion (Arg2) and revealed a mild compensated urea cycle defect. Stable isotope tracing and respirometry revealed hepatocyte urea and TCA cycle flux defects, impaired mitochondrial oxidative metabolism, and glutamine anaplerosis despite normal energy and glucose homeostasis during early adulthood.

Wound Healing Complications Associated with Staged Reconstruction after Facial Lentigo Maligna Resection.

The rates and risk factors for wound complications following staged reconstruction after facial lentigo maligna (LM) resection have not been well described. (1) To identify the rate and types of wound complications, including infection, graft necrosis, distal flap necrosis, hematoma, superficial epidermolysis, and seroma among patients undergoing staged reconstruction after resection of LM as documented in the surgeon's clinical notes within 30 days of the procedure. (2) To determine a threshold defect size that may predict the development of wound complications.

The Impact of Sociodemographic Factors on Rates of Tympanostomy Tube Placement for Pediatric Otitis Media.

Objective: To identify the impact of race, ethnicity, and socioeconomic status (SES) on the rate of tympanostomy tube placement.

Study Design: Retrospective medical review and population-level analyses.

Setting: Tertiary referral center.

Learning in context: Undergraduate students' knowledge and the content retention of anatomy between discipline-specific and integrated course approaches.

Undergraduate introductory human anatomy and human physiology courses are either taught as discipline-specific or integrated anatomy and physiology (A&P) sequences. An institution underwent a curricular revision to change the course approach from discipline-specific Human Anatomy and Human Physiology to an integrated A&P I and II sequence, allowing the unique opportunity to explore the potential role of contextual learning in academic achievement and content retention. Mediation and moderation analysis was used to evaluate lecture examinations, laboratory practical examinations, and anatomical content retention between the different course approaches.

Disparities in polysomnography referral in a high-risk cardiac population.

Purpose: Obstructive sleep apnea (OSA) is associated with metabolic, cardiovascular, and cerebrovascular comorbidities. Appropriate diagnosis and treatment of OSA might mitigate these comorbidities. This retrospective review sought to assess the impact of sex, age, race, ethnicity, and insurance status on polysomnography (PSG) referral rates.

Near infrared fluorescent nanosensors for high spatiotemporal oxytocin imaging.

Oxytocin is a neuropeptide thought to play a central role in regulating social and emotional behavior. Current techniques for neuropeptide imaging are generally limited in spatial and temporal resolution, real-time imaging capacity, selectivity for oxytocin over vasopressin, and application in young and non-model organisms. To avoid the use of endogenous oxytocin receptors for oxytocin probe development, we employed a protocol to evolve purely synthetic molecular recognition on the surface of near-infrared fluorescent single-walled carbon nanotubes (SWCNT) using single-stranded DNA (ssDNA).

The PML1-WDR5 axis regulates H3K4me3 marks and promotes stemness of estrogen receptor-positive breast cancer.

The alternative splicing of PML precursor mRNA gives rise to various PML isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers. PML depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER+ breast cancer, in a mouse model.

Harnessing Passive Pulsatile Shear Stress for Alzheimer's Disease Prevention and Intervention.

 Alzheimer's disease (AD) affects more than 40 million people worldwide and is the leading cause of dementia. This disease is a challenge for both patients and caregivers and puts a significant strain on the global healthcare system. To address this issue, the Lancet Commission recommends focusing on reducing modifiable lifestyle risk factors such as hypertension, diabetes, and physical inactivity.

How to implement a "standard of care" regulatory model for pharmacists.

National pharmacy associations have increasingly explored regulation according to a "standard of care." In such a model, pharmacists can provide a wide range of clinical services aligned with their education and training. Based on Idaho's experience implementing this model, there are five critical steps states must take to enact a standard of care: 1) Adopt a broad definition of "practice of pharmacy;" 2) Allow elasticity for practice innovation over time; 3) Decide which limited instances still necessitate prescriptive regulation; 4) Eliminate all unnecessary regulations; and 5) Strengthen accountability for deviations from the standard of care.

Post-Anesthesia Cognitive Dysfunction in Mice Is Associated with an Age-Related Increase in Neuronal Intracellular [Ca]-Neuroprotective Effect of Reducing Intracellular [Ca]: In Vivo and In Vitro Studies.

Postoperative cognitive dysfunction (POCD) is a common disorder after general anesthesia in elderly patients, the precise mechanisms of which remain unclear. We investigated the effect of isoflurane with or without dantrolene pretreatment on intracellular calcium concentration ([Ca]), reactive oxygen species (ROS) production, cellular lactate dehydrogenase (LDH) leak, calpain activity, and cognitive function using the Morris water maze test of young (3 months), middle-aged (12-13 months), and aged (24-25 months) C57BL6/J mice. Aged cortical and hippocampal neurons showed chronically elevated [Ca] compared to young neurons.

A Structure-function Analysis of Hepatocyte Arginase 2 Reveals Mitochondrial Ureahydrolysis as a Determinant of Glucose Oxidation.

Background & Aims: Restoring hepatic and peripheral insulin sensitivity is critical to prevent or reverse metabolic syndrome and type 2 diabetes. Glucose homeostasis comprises in part the complex regulation of hepatic glucose production and insulin-mediated glucose uptake and oxidation in peripheral tissues. We previously identified hepatocyte arginase 2 (Arg2) as an inducible ureahydrolase that improves glucose homeostasis and enhances glucose oxidation in multiple obese, insulin-resistant models.

Single Ion Pair Is Essential for Stabilizing SHP2's Open Conformation.

Src-homology-2-domain-containing PTP-2 (SHP2) is a widely expressed signaling enzyme whose misregulation is associated with multiple human pathologies. SHP2's enzymatic activity is controlled by a conformational equilibrium between its autoinhibited ("closed") state and its activated ("open") state. Although SHP2's closed state has been extensively characterized, the putative structure of its open form has only been revealed in the context of a highly activated mutant (E76K), and no systematic studies of the biochemical determinants of SHP2's open-state stabilization have been reported.

Enhancing Muscle Intracellular Ca Homeostasis and Glucose Uptake: Passive Pulsatile Shear Stress Treatment in Type 2 Diabetes.

Type 2 diabetes mellitus (T2D) is a significant global public health problem that has seen a substantial increase in the number of affected individuals in recent decades. In a murine model of T2D (db/db), we found several abnormalities, including aberrant intracellular calcium concentration ([Ca]), decreased glucose transport, increased production of reactive oxygen species (ROS), elevated levels of pro-inflammatory interleukins and creatine phosphokinase (CK), and muscle weakness. Previously, we demonstrated that passive pulsatile shear stress, generated by sinusoidal (headward-forward) motion, using a motion platform that provides periodic acceleration of the whole body in the Z plane (pGz), induces the synthesis of nitric oxide (NO) mediated by constitutive nitric oxide synthase (eNOS and nNOS).

Factors associated with delayed referral and hearing rehabilitation for congenital sensorineural hearing loss.

Objectives: To identify the impact of social determinants of health and clinical status on referral and intervention for congenital sensorineural hearing loss.

Study Design: Retrospective chart review of children with confirmed sensorineural or mixed hearing loss between 2013 and 2021 at a single academic medical institution.

Methods: Referral rates and timing for hearing rehabilitation, rates and timing of completed evaluation, and rate and timing of amplification were recorded.

Interpretation of medical findings in suspected child sexual abuse: An update for 2023.

Health care professionals who examine children who may have been sexually abused need to be able to recognize, and photo-document any physical signs, and to have access to expert reviewers, particularly when signs concerning for sexual abuse are found. Although the general consensus among practitioners is that children will show few signs of sexual abuse on examination, there is considerable variability and rates of positive exam findings among practitioners of different professions, practice settings, and countries. This review will summarize new data and recommendations regarding the interpretation of medical findings and sexually transmitted infections (STIs); assessment and management of pediatric patients presenting with suspected sexual abuse or assault; and testing and treating patients for STIs.

Evaluation of Social Determinants of Health on Dysphagia Care Pathways at a Tertiary Care Facility.

Objectives: Limited research exists evaluating the impact of social determinants of health in influencing care pathways for patients with dysphagia. A better understanding of whether these determinants correlate to altered care and resource utilization is essential as it relates to patient outcomes.

Study Design: Retrospective chart review.