Microgravity's effects on miRNA-mRNA regulatory networks in a mouse model of segmental bone defects.

Rehabilitation from musculoskeletal injuries (MSKI) complicate healing dynamics typically by sustained disuse of bone and muscles. Microgravity naturally allows limb disuse and thus an effective model to understand MSKI. The current study examined epigenetic changes in a segmental bone defect (SBD) mouse model in a prolonged unloading condition after spaceflight (FLT).

G protein-coupled receptor 17 inhibits glucagon-like peptide-1 secretion via a Gi/o-dependent mechanism in enteroendocrine cells.

Gut peptides, including glucagon-like peptide-1 (GLP-1), regulate metabolic homeostasis and have emerged as the basis for multiple state-of-the-art diabetes and obesity therapies. We previously showed that G protein-coupled receptor 17 (GPR17) is expressed in intestinal enteroendocrine cells (EECs) and modulates nutrient-induced GLP-1 secretion. However, the GPR17-mediated molecular signaling pathways in EECs have yet to be fully deciphered.

Heterogeneous endocrine cell composition defines human islet functional phenotypes.

Phenotyping and genotyping initiatives within the Integrated Islet Distribution Program (IIDP), the largest source of human islets for research in the U.S., provide standardized assessment of islet preparations distributed to researchers, enabling the integration of multiple data types.

Thrombopoietic agents enhance bone healing in mice, rats, and pigs.

Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, has renewed interest in investigating alternatives that provide safer, yet effective bone regeneration.

Bone loss with aging is independent of gut microbiome in mice.

Emerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice.

Do mindfulness interventions cause harm? Findings from the Learning to Apply Mindfulness to Pain (LAMP) Pragmatic Clinical Trial.

Background: Although mindfulness-based interventions (MBIs) are widely used in clinical and nonclinical settings, there has been little systematic study of their potential risks. To address this gap, we examined differences in psychological and physical worsening among participants in the usual care and intervention conditions of a 3-group, randomized pragmatic trial (Learning to Apply Mindfulness to Pain [LAMP]) that tested the effectiveness of 2 approaches to delivering MBIs to patients with chronic pain.

Methods: The sample consisted of 374 male and 334 female patients with chronic pain enrolled in the LAMP trial who completed a 10-week follow-up survey, 61% of whom had a mental health diagnosis.

The translation-to-policy learning cycle to improve public health.

Objective: Learning Health Systems (LHSs) have not directly informed evidence-based policymaking. The Translation-to-Policy (T2P) Learning Cycle aligns scientists, end-users, and policymakers to support a repeatable roadmap of innovation and quality improvement to optimize effective policies toward a common public health goal. We describe T2P learning cycle components and provide examples of their application.

miR-146a-5p mediates inflammation-induced β cell mitochondrial dysfunction and apoptosis.

We previously showed that miR-146a-5p is upregulated in pancreatic islets treated with proinflammatory cytokines. Others have reported that miR-146a-5p overexpression is associated with β cell apoptosis and impaired insulin secretion. However, the molecular mechanisms mediating these effects remain elusive.

Comparison of clinical pharmacist practitioners' headache care roles across clinical contexts within the Veterans Health Administration: Optimizing pharmacist integration.

Background: Studies show interdisciplinary treatment is highly effective for addressing chronic pain syndromes, including headache disorders. Increasingly, advanced practice pharmacists work collaboratively with physicians to apply their unique skills to enhance patient outcomes.

Objective: This qualitative study aimed to elucidate the potential in the Veterans Health Administration (VHA) for increased roles of clinical pharmacist practitioners (CPPs)-advanced practice pharmacists with a scope of practice-in collaborative, interdisciplinary headache care teams.

Characterization of age-associated inflammasome activation reveals tissue specific differences in transcriptional and post-translational inflammatory responses.

Aging is associated with systemic chronic, low-grade inflammation, termed 'inflammaging'. This pattern of inflammation is multifactorial and is driven by numerous inflammatory pathways, including the inflammasome. However, most studies to date have examined changes in the transcriptomes that are associated with aging and inflammaging, despite the fact that inflammasome activation is driven by a series of post-translational activation steps, culminating in the cleavage and activation of caspase-1.

The islet tissue plasminogen activator/plasmin system is upregulated with human islet amyloid polypeptide aggregation and protects beta cells from aggregation-induced toxicity.

Aims/hypothesis: Apart from its fibrinolytic activity, the tissue plasminogen activator (tPA)/plasmin system has been reported to cleave the peptide amyloid beta, attenuating brain amyloid deposition in Alzheimer's disease. As aggregation of human islet amyloid polypeptide (hIAPP) is toxic to beta cells, we sought to determine whether activation of the fibrinolytic system can also reduce islet amyloid deposition and its cytotoxic effects, which are both observed in type 2 diabetes.

Methods: The expression of Plat (encoding tPA) and plasmin activity were measured in isolated islets from amyloid-prone hIAPP transgenic mice or non-transgenic control islets expressing non-amyloidogenic mouse islet amyloid polypeptide cultured in the absence or presence of the amyloid inhibitor Congo Red.

Accommodating patients with obesity in ambulatory care: A clinical environment checklist.

Objective: Individuals with obesity face unique challenges when visiting healthcare providers, including inadequate equipment. These negative care experiences, often exacerbated by weight stigma, frequently lead to mistrust and reluctance to seek future care. Currently, few instruments exist to ensure that an ambulatory clinic is welcoming to patients with obesity.

Health Care Discrimination Affects Patient Activation, Communication Self-Efficacy, and Pain for Black Americans.

This study examines whether a key psychosocial factor-perceiving racial discrimination in health care-is associated with worse patient activation, communication self-efficacy, and physical health outcomes for Black veterans with chronic pain. Moreover, we explore the role of physician-patient working alliance as a moderator that may alleviate the potential consequences of perceiving racial discrimination. This work is a secondary analysis of baseline data from a clinical trial with 250 U.