Random forest algorithm reveals novel sites in HA protein that shift receptor binding preference of the H9N2 avian influenza virus.

A switch from avian-type α-2,3 to human-type α-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus. Some H9N2 viruses exhibit a preference for binding to human-type α-2,6 receptors. This identifies their potential threat to public health.

Metformin for the Prevention of Antipsychotic-Induced Weight Gain: Guideline Development and Consensus Validation.

Background: Overweight and obesity are highly prevalent in people with severe mental illness (SMI). Antipsychotic-induced weight gain (AIWG) is one of the most commonly reported and distressing side effects of treatment and people living with SMI place a high value on the avoidance of this side effect. Metformin is the most effective pharmacological intervention studied for the prevention of AIWG yet clear guidelines are lacking and evidence has not translated into practice.

Measuring the rate of NADPH consumption by glutathione reductase in the cytosol and mitochondria.

Background: NADPH is an essential co-factor supporting the function of enzymes that participate in both inflammatory and anti-inflammatory pathways in myeloid cells, particularly macrophages. Although individual NADPH-dependent pathways are well characterized, how these opposing pathways are co-regulated to orchestrate an optimized inflammatory response is not well understood. To investigate this, techniques to track the consumption of NADPH need to be applied.

The role of autoantibodies in bridging obesity, aging, and immunosenescence.

Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, leading to inflammation and autoimmune diseases. While autoantibodies are well-studied in autoimmune and in some communicable diseases, their roles in chronic conditions, such as obesity and aging, are less understood.

The effect of surgical management in mitigating fragility fracture risk among individuals with primary hyperparathyroidism.

Background: Primary hyperparathyroidism predominately affects women who are postmenopausal and causes complications, including fragility fractures. Its treatment is parathyroidectomy, which is associated with low complication and >95% cure rates. Considering fractures are associated with premature death, we aimed to determine whether the surgical management of individuals with biochemical diagnosis of primary hyperparathyroidism was associated with a reduction in fracture risk.

Antipsychotic-Induced Dysregulation of Glucose Metabolism Through the Central Nervous System: A Scoping Review of Animal Models.

The use of antipsychotic drugs is associated with adverse metabolic effects. Disruptions in glucose metabolism such as hyperglycemia and insulin resistance have been shown to occur with antipsychotic use, independent of changes in body weight or adiposity. The regulation of whole-body glucose metabolism is partly mediated by the central nervous system.

The Dysregulation of the Glymphatic System in Patients with Psychosis Spectrum Disorders Minimally Exposed to Antipsychotics: La dérégulation du système glymphatique en présence de troubles psychotiques chez des patients peu exposés à des antipsychotiques.

Objective: The pathophysiological mechanisms influencing psychosis spectrum disorders are largely unknown. The glymphatic system, which is a brain waste clearance pathway, has recently been implicated in its pathophysiology and has also been shown to be disrupted in various neurodegenerative and vascular diseases. Initial studies examining the glymphatic system in psychosis spectrum disorders have reported disruptions, but the findings have been confounded by medication effects as they included antipsychotic-treated patients.

The impact of weight gain on antipsychotic nonadherence or discontinuation: A systematic review and meta-analysis.

Background: Nonadherence/discontinuation of antipsychotic (AP) medications represents an important clinical issue in patients across psychiatric disorders, including schizophrenia spectrum disorders (SSDs). While antipsychotic-induced weight gain (AIWG) is a reported contributor to nonadherence, a systematic review of the association between AIWG and medication nonadherence/discontinuation has not been explored previously.

Method: A systematic search was conducted in MEDLINE, EMBASE, PsychINFO, CINAHL, and CENTRAL databases, among others, to help identify all studies which explored adherence, study dropouts, AP switching and/or discontinuations attributable to AIWG among individuals with severe mental illness.

The neuromuscular basis of functional impairment in schizophrenia: A scoping review.

Patients with schizophrenia exhibit functional impairments in their locomotory tasks, which decreases their quality of life. Due to the limited current research, the neuromuscular mechanisms behind the functional impairments in patients is not fully understood. Thus, this review aims to summarize the neuromuscular mechanisms that underlie these deficits in daily functioning.

Hepatic function of glucagon-like peptide-1 and its based diabetes drugs.

Incretins are gut-produced peptide-hormones that potentiate insulin secretion, especially after food intake. The concept of incretin was formed more than 100 years ago, even before insulin was isolated and utilized in the treatment of subjects with type 1 diabetes. The first incretin, glucose-dependent insulinotropic polypeptide (GIP), was identified during later 1960's and early 1970's; while the second one, known as glucagon-like peptide-1 (GLP-1), was recognized during 1980's.

A metabolic balance of GLP-1 and NMDA receptors in the brain.

Glucagon-like peptide-1 (GLP-1) and N-methyl-D-aspartate (NMDA) receptors in the brain regulate metabolic homeostasis. In a paper published in Nature, Petersen et al. describe a bimodal molecule that conjugates a GLP-1 analog with MK-801 (NMDA receptor antagonist), which lowers feeding and body weight to a greater extent than the GLP-1R agonist alone.

Glycocalyx shedding patterns identifies antipsychotic-naïve patients with first-episode psychosis.

Psychotic disorders have been linked to immune-system abnormalities, increased inflammatory markers, and subtle neuroinflammation. Studies further suggest a dysfunctional blood brain barrier (BBB). The endothelial Glycocalyx (GLX) functions as a protective layer in the BBB, and GLX shedding leads to BBB dysfunction.

Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms.

The intricate anatomical structure and high cellular density of the myocardium complicate the bioengineering of perfusable vascular networks within cardiac tissues. In vivo neonatal studies highlight the key role of resident cardiac macrophages in post-injury regeneration and angiogenesis. Here, we integrate human pluripotent stem-cell-derived primitive yolk-sac-like macrophages within vascularized heart-on-chip platforms.

Metformin co-commencement at time of antipsychotic initiation for attenuation of weight gain: a systematic review and meta-analysis.

Background: Antipsychotic medications are associated with weight gain and metabolic derangement. However, comprehensive evidence for the efficacy of co-commenced pharmacological treatments to mitigate initial weight gain is limited. Metformin has been shown to be effective in reducing weight among people on antipsychotic medications who are already overweight, but the potential benefits of metformin co-commencement in mitigating antipsychotic-induced weight gain has not been systematically reviewed.

A novel fatty acid mimetic with pan-PPAR partial agonist activity inhibits diet-induced obesity and metabolic dysfunction-associated steatotic liver disease.

Objective: The prevalence of metabolic diseases is increasing globally at an alarming rate; thus, it is essential that effective, accessible, low-cost therapeutics are developed. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that tightly regulate glucose homeostasis and lipid metabolism and are important drug targets for the treatment of type 2 diabetes and dyslipidemia. We previously identified LDT409, a fatty acid-like compound derived from cashew nut shell liquid, as a novel pan-active PPARα/γ/δ compound.

Cholesterol accumulation impairs HIF-1α-dependent immunometabolic reprogramming of LPS-stimulated macrophages by upregulating the NRF2 pathway.

Lipid accumulation in macrophages (Mφs) is a hallmark of atherosclerosis. Yet, how lipid loading modulates Mφ inflammatory responses remains unclear. We endeavored to gain mechanistic insights into how pre-loading with free cholesterol modulates Mφ metabolism upon LPS-induced TLR4 signaling.

β-Cell Insulin Resistance Plays a Causal Role in Fat-Induced β-Cell Dysfunction In Vitro and In Vivo.

In the classical insulin target tissues of liver, muscle, and adipose tissue, chronically elevated levels of free fatty acids (FFA) impair insulin signaling. Insulin signaling molecules are also present in β-cells where they play a role in β-cell function. Therefore, inhibition of the insulin/insulin-like growth factor 1 pathway may be involved in fat-induced β-cell dysfunction.