Targeting inflammasome complexes as a novel therapeutic strategy for mood disorders.

Introduction: Inflammasome complexes, especially NLRP3, have gained great attention as a potential therapeutic target in mood disorders. NLRP3 triggers a caspase 1-dependent release of the inflammatory cytokines IL-1β and IL-18, and seems to interact with purinergic and kynurenine pathways, all of which are implicated in mood disorders development and progression.

Areas Covered: Emerging evidence supports NLRP3 inflammasome as a promising pharmacological target for mood disorders.

Quinolinic acid links kidney injury to brain toxicity.

Kidney dysfunction often leads to neurological impairment, yet the complex kidney-brain relationship remains elusive. We employed spatial and bulk metabolomics to investigate a mouse model of rapid kidney failure induced by mouse double minute 2 ( conditional deletion in the kidney tubules to interrogate kidney and brain metabolism. Pathway enrichment analysis of focused plasma metabolomics panel pinpointed tryptophan metabolism as the most altered pathway with kidney failure.

Long-term benefits of hematopoietic stem cell-based macrophage/microglia delivery of GDNF to the CNS in a mouse model of Parkinson's disease.

Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurons in various models of Parkinson's disease (PD). Cell-based GDNF gene delivery mitigates neurodegeneration and improves both motor and non-motor functions in PD mice. As PD is a chronic condition, this study aims to investigate the long-lasting benefits of hematopoietic stem cell (HSC)-based macrophage/microglia-mediated CNS GDNF (MMC-GDNF) delivery in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model.

The Influence of Branched-Chain Amino Acid Supplementation on Fatigue and Tryptophan Metabolism After Acute and Chronic Exercise in Older Adults: Protocol for a Pilot Randomized Controlled Trial.

Background: Fatigue is a strong predictor of negative health outcomes in older adults. Kynurenine, a metabolite of tryptophan, is strongly associated with fatigue. Reductions in fatigue are observed with exercise; however, exercise training does not completely alleviate symptoms.

Churn in Supplemental Nutrition Assistance Program: Changes in Medicaid Expenditure and Acute Care Utilization.

Background: The Supplemental Nutrition Assistance Program (SNAP) provides financial assistance to low-income individuals and families to help them purchase food. However, when participants experience short-term disenrollment from the program, known as churn, it can disrupt their health care usage patterns or result in acute health care needs due to the loss of financial benefits and time burden required to reapply for SNAP.

Objective: The objective of this study was to examine the changes in health care expenditures and acute care utilization during periods of SNAP churn compared with nonchurn periods among those who churn during the study period.

Association Between Hospital Adoption of an Emergency Department Treatment Pathway for Opioid Use Disorder and Patient Initiation of Buprenorphine After Discharge.

Importance: Emergency department (ED)-based initiation of buprenorphine has been shown to increase engagement in outpatient treatment and reduce the risk of subsequent opioid overdose; however, rates of buprenorphine treatment in the ED and follow-up care for opioid use disorder (OUD) remain low in the US. The Opioid Hospital Quality Improvement Program (O-HQIP), a statewide financial incentive program designed to increase engagement in OUD treatment for Medicaid-enrolled patients who have ED encounters, has the potential to increase ED-initiated buprenorphine treatment.

Objective: To evaluate the association between hospitals attesting to an ED buprenorphine treatment O-HQIP pathway and patients' subsequent initiation of buprenorphine treatment.

Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice.

Neuropathic pain is one of the most important clinical consequences of injury to the somatosensory system. Nevertheless, the critical pathophysiological mechanisms involved in neuropathic pain development are poorly understood. In this study, we found that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is ablated pharmacologically or genetically.

Randomization to Treadmill Training Improves Physical and Metabolic Health in Association With Declines in Oxidative Stress in Stroke.

Objective: To investigate the effect of aerobic exercise vs control (stretching/balance) on inflammatory and oxidative stress biomarkers in stroke survivors and whether these changes are associated with improvements in physical and metabolic health.

Design: Randomized controlled trial.

Setting: The general communities of Baltimore, Maryland, and Atlanta, Georgia.

Safety and Glycemic Outcomes With a Tubeless Automated Insulin Delivery System in Very Young Children With Type 1 Diabetes: A Single-Arm Multicenter Clinical Trial.

Objective: Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk for long-term complications and creating an immense management burden for caregivers. We conducted the first evaluation of the Omnipod 5 Automated Insulin Delivery System in this population.

Research Design And Methods: A total of 80 children aged 2.

Brain-derived neurotrophic factor and inflammation in depression: Pathogenic partners in crime?

Major depressive disorder is a debilitating disorder affecting millions of people each year. Brain-derived neurotrophic factor (BDNF) and inflammation are two prominent biologic risk factors in the pathogenesis of depression that have received considerable attention. Many clinical and animal studies have highlighted associations between low levels of BDNF or high levels of inflammatory markers and the development of behavioral symptoms of depression.

Brain derived neurotrophic factor deficiency exacerbates inflammation-induced anhedonia in mice.

Brain-derived neurotrophic factor (BDNF) is implicated in the pathology of major depression and influences the inflammatory response. Prolonged immune system activation can cause depression symptoms, and individuals with low BDNF expression may be vulnerable to inflammation-induced depression. We tested the hypothesis that BDNF deficient mice are vulnerable to the induction of depressive-like behavior following peripheral immune challenge.

Clinical Evaluation of a Novel CGM-Informed Bolus Calculator with Automatic Glucose Trend Adjustment.

Expert opinion guidelines and limited data from clinical trials recommend adjustment to bolus insulin doses based on continuous glucose monitor (CGM) trend data, yet minimal evidence exists to support this approach. We performed a clinical evaluation of a novel CGM-informed bolus calculator (CIBC) with automatic insulin bolus dose adjustment based on CGM trend used with sensor-augmented pump therapy. In this multicenter, outpatient study, participants 6-70 years of age with type 1 diabetes (T1D) used the Omnipod 5 System in Manual Mode, first for 7 days without a connected CGM (standard bolus calculator, SBC, phase 1) and then for 7 days with a connected CGM using the CIBC (CIBC phase 2).

Advancing Autism Research From Mice to Marmosets: Behavioral Development of Offspring Following Prenatal Maternal Immune Activation.

Understanding the mechanism(s) by which maternal immune activation (MIA) during gestation may disrupt neurodevelopment and increase the susceptibility for disorders such as autism spectrum disorder (ASD) or schizophrenia is a critical step in the development of better treatments and preventive measures. A large body of literature has investigated the pathophysiology of MIA in rodents. However, a translatability gap plagues pre-clinical research of complex behavioral/developmental diseases and those diseases requiring clinical diagnosis, such as ASD.

Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications.

Diseases of the central nervous system (CNS) remain a significant health, social and economic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options.

Chronic Unpredictable Stress Alters Brain Tryptophan Metabolism and Impairs Working Memory in Mice without Causing Depression-Like Behaviour.

Chronic stress is a well-known risk factor in major depressive disorder and disrupts the kynurenine and serotonin pathways of tryptophan metabolism. Here, we characterize the temporal central and peripheral changes in tryptophan metabolism and concomitant depressive-like behavioural phenotype induced during the progression of chronic unpredictable stress (CUS). Mice were exposed to 0, 10, 20, or 30 days of CUS followed by a panel of behavioural assays to determine depressive-like phenotypes.

First Outpatient Evaluation of a Tubeless Automated Insulin Delivery System with Customizable Glucose Targets in Children and Adults with Type 1 Diabetes.

The objective of this study was to assess the safety and effectiveness of the first commercial configuration of a tubeless automated insulin delivery system, Omnipod 5, in children (6-13.9 years) and adults (14-70 years) with type 1 diabetes (T1D) in an outpatient setting. This was a single-arm, multicenter, prospective clinical study.

Branched-Chain Amino Acids Depletion during Hemodialysis Is Associated with Fatigue.

Background: Fatigue is one of the most debilitating symptoms reported by maintenance hemodialysis (MHD) patients. Hemodialysis causes marked depletion in plasma essential amino acids. We studied the cross-sectional relationship of pre- and post-hemodialysis branched-chain amino acids (BCAAs) concentrations with fatigue in MHD patients.

Non-toxic HSC Transplantation-Based Macrophage/Microglia-Mediated GDNF Delivery for Parkinson's Disease.

Glial cell-line-derived neurotrophic factor (GDNF) is a potent neuroprotective agent in cellular and animal models of Parkinson's disease (PD). However, CNS delivery of GDNF in clinical trials has proven challenging due to blood-brain barrier (BBB) impermeability, poor diffusion within brain tissue, and large brain size. We report that using non-toxic mobilization-enabled preconditioning, hematopoietic stem cell (HSC) transplantation-based macrophage-mediated gene delivery may provide a solution to overcome these obstacles.

Safety and Performance of the Omnipod Hybrid Closed-Loop System in Adults, Adolescents, and Children with Type 1 Diabetes Over 5 Days Under Free-Living Conditions.

The objective of this study was to assess the safety and performance of the Omnipod personalized model predictive control (MPC) algorithm in adults, adolescents, and children aged ≥6 years with type 1 diabetes (T1D) under free-living conditions using an investigational device. A 96-h hybrid closed-loop (HCL) study was conducted in a supervised hotel/rental home setting following a 7-day outpatient standard therapy (ST) phase. Eligible participants were aged 6-65 years with A1C <10.

Performance of Omnipod Personalized Model Predictive Control Algorithm with Moderate Intensity Exercise in Adults with Type 1 Diabetes.

The objective of this study was to assess the safety and performance of the Omnipod personalized model predictive control (MPC) algorithm with variable glucose setpoints and moderate intensity exercise using an investigational device in adults with type 1 diabetes (T1D). A supervised 54-h hybrid closed-loop (HCL) study was conducted in a hotel setting after a 7-day outpatient standard treatment phase. Adults aged 18-65 years with T1D and HbA1c between 6.

Neuron-Derived Estrogen Regulates Synaptic Plasticity and Memory.

17β-estradiol (E2) is produced from androgens via the action of the enzyme aromatase. E2 is known to be made in neurons in the brain, but its precise functions in the brain are unclear. Here, we used a forebrain-neuron-specific aromatase knock-out (FBN-ARO-KO) mouse model to deplete neuron-derived E2 in the forebrain of mice and thereby elucidate its functions.

Novel Bluetooth-Enabled Tubeless Insulin Pump: Innovating Pump Therapy for Patients in the Digital Age.

The Omnipod DASH™ Insulin Management System (Insulet Corp, Billerica, MA) is a discreet, tubeless, wearable insulin pump that holds up to 200 units of U-100 insulin and delivers therapy through customizable basal rates and bolus amounts. This recently FDA-cleared system consists of the insulin pump ("Pod"), which is worn on body and delivers insulin, and the Personal Diabetes Manager (PDM), which is a handheld device used to wirelessly control and monitor the Pod functionality. The PDM can also be paired with the CONTOUR NEXT ONE blood glucose (BG) meter (Ascensia Diabetes Care, Basel, Switzerland) to wirelessly receive BG readings.