An alternatively translated isoform of PPARG proposes AF-1 domain inhibition as an insulin sensitization target.

PPARγ is the pharmacological target of thiazolidinediones (TZDs), potent insulin sensitizers that prevent metabolic disease morbidity but are accompanied by side effects such as weight gain, in part due to non-physiological transcriptional agonism. Using high throughput genome engineering, we targeted nonsense mutations to every exon of PPARG, finding an ATG in Exon 2 (chr3:12381414, CCDS2609 c.A403) that functions as an alternative translational start site.

Immune Dysregulation in Obesity.

The immune system plays fundamental roles in maintaining physiological homeostasis. With the increasing prevalence of obesity-a state characterized by chronic inflammation and systemic dyshomeostasis-there is growing scientific and clinical interest in understanding how obesity reshapes immune function. In this review, we propose that obesity is not merely an altered metabolic state but also a fundamentally altered immunological state.

Unraveling Mechanisms of Genetic Risks in Metabolic Dysfunction-Associated Steatotic Liver Diseases: A Pathway to Precision Medicine.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem, affecting ∼1 billion people. This condition is well established to have a heritable component with strong familial clustering. With the extraordinary breakthroughs in genetic research techniques coupled with their application to large-scale biobanks, the field of genetics in MASLD has expanded rapidly.

Treatment With Avacopan in Patients With Respiratory Tract Manifestations of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Objective: The ADVOCATE trial demonstrated that treatment of active granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) with avacopan was noninferior in achieving remission at week 26 and superior for sustained remission at week 52 compared with a prednisone taper. This analysis of ADVOCATE evaluated the efficacy and safety of avacopan in patients with ear, nose, throat (ENT), or lung manifestations.

Methods: This post hoc analysis included patients enrolled in ADVOCATE with ENT or lung manifestations at baseline.

Abnormal Esophageal Scintigraphy Associates With a Distinct Clinical Phenotype in Patients With Systemic Sclerosis.

Objective: In systemic sclerosis (SSc), absent contractility (AC) rather than ineffective esophageal motility on manometry is associated with a severe esophageal and extraintestinal phenotype. We sought to determine whether slow esophageal transit on scintigraphy associates with a comparable clinical phenotype to that of AC on manometry, as scintigraphy may serve as a noninvasive approach to risk-stratify patients with SSc.

Methods: Clinical, demographic, and serologic features were compared between patients with and without delayed esophageal transit on scintigraphy.

Biofield Therapies Clinical Research Landscape: A Scoping Review and Interactive Evidence Map.

Biofield Therapies, with a historical lineage spanning millennia and continuing relevance in contemporary practices, have been used to address various health conditions and promote wellbeing. The scientific study and adoption of these therapies have been hindered by cultural challenges and institutional barriers. In addition, the current research landscape for Biofield Therapies is insufficiently documented.

Regulatory B-Cells Are Associated Negatively With Regulatory T-Cells and Positively With Cytokines in Peripheral Blood of Pregnant Women.

Problem: Regulatory B-cells (Bregs, CD19CD24CD38) are a specialized B-cell subset that suppresses immune responses and potentially contribute to the maintenance of an immune-privileged environment for fetal development during pregnancy. However, little is known about the surrounding immunological environment of Bregs in gestational physiology. The relationship of regulatory T-cells (Tregs, CD4CD25CD127FoxP3) to Bregs in coordinating immunoregulation during pregnancy is unknown.

Vegetation Types Shift Physiological and Phenological Controls on Carbon Sink Strength in a Coastal Zone.

The carbon sink function performed by the different vegetation types along the environmental gradient in coastal zones plays a vital role in mitigating climate change. However, inadequate understanding of its spatiotemporal variations across different vegetation types and associated regulatory mechanisms hampers determining its potential shifts in a changing climate. Here, we present long-term (2011-2022) eddy covariance measurements of the net ecosystem exchange (NEE) of CO at three sites with different vegetation types (tidal wetland, nontidal wetland, and cropland) in a coastal zone to examine the role of vegetation type on annual carbon sink strength.

Testing One Primary and Two Secondary Endpoints in a Two-Stage Group Sequential Trial With Extensions.

We study the problem of testing multiple secondary endpoints conditional on a primary endpoint being significant in a two-stage group sequential procedure, focusing on two secondary endpoints. This extends our previous work with one secondary endpoint. The test for the secondary null hypotheses is a closed procedure.

mHealth-Based Diabetes Prevention Program for Chinese Mothers With Abdominal Obesity: Randomized Controlled Trial.

Background: Among people with abdominal obesity, women are more likely to develop diabetes than men. Mobile health (mHealth)-based technologies provide the flexibility and resource-saving opportunities to improve lifestyles in an individualized way. However, mHealth-based diabetes prevention programs tailored for busy mothers with abdominal obesity have not been reported yet.

Sex-specific activation of platelet purinergic signaling is key in local cytokine release and phagocytosis in the peritoneal cavity in intra-abdominal sepsis.

Intra-abdominal sepsis is a life-threatening complex syndrome caused by microbes in the gut microbiota invading the peritoneal cavity. It is one of the major complications of intra-abdominal surgery. To date, only supportive therapies are available.

Rejunctive Moves Toward Systemic Healing: A Contextual Family Therapy Approach to Father's Absence.

The phenomena of father's absence and the disruption of a family unit due to social justice issues like incarceration and mental health/substance misuse challenges are widely documented, and their effects on the whole family are well established in the literature. This paper specifically examines how systemic inequities like racism contribute to destructive entitlements that can occur transgenerationally within families affected by father's absence. The consideration of racial trauma is crucial, as father's absence and family disruption are not limited to any one racial or ethnic group, but the effects are often exacerbated for families of color due to the intersecting impacts of systemic racism.

Health Care Spending Increases and Value in South Korea.

Importance: Health care spending in South Korea (hereafter Korea) nearly doubled from 2010 to 2019. However, little is known about the drivers and effectiveness of these spending increases in terms of changes in disability-adjusted life-years (DALYs).

Objectives: To evaluate the factors contributing to changes in health care spending and DALYs and estimate the value of health care spending from 2010 to 2019 in Korea.

Duration in Immigration Detention and Health Harms.

Importance: Length of custody is a mechanism by which carceral systems can worsen health. However, there are fewer studies examining US immigration detention, in large part because US immigration detention is largely privately operated and opaque by design.

Objectives: To examine the association between duration spent in US immigration detention with subsequent health outcomes.

City-Level Sugar-Sweetened Beverage Taxes and Changes in Adult Body Mass Index.

Importance: Sugar-sweetened beverage (SSB) excise taxes are popular policy interventions aimed at decreasing SSB purchasing and consumption to improve cardiometabolic health and generate revenue for public health initiatives. There is limited evidence that these taxes in the US are associated with weight-related outcomes in adults, a primary contributor to cardiometabolic health.

Objective: To determine the association between SSB excise taxes and adult body mass index (BMI) and proportion of adults with overweight or obesity among California cities and assess whether associations vary by demographic characteristics.

Outpatient Low-Dose Initiation of Buprenorphine for People Using Fentanyl.

Importance: The rise of high-potency opioids such as fentanyl makes buprenorphine initiation challenging due to the risks of precipitated withdrawal, prompting the exploration of strategies, such as low-dose initiation (LDI) of buprenorphine. However, no comparative studies on LDI outcomes exist.

Objective: To evaluate outpatient outcomes associated with 2 LDI protocols of buprenorphine among individuals with opioid use disorder (OUD) using fentanyl.

Optimizing orthobiologic therapies with exercise, diet, and supplements.

Orthobiologic injections including platelet-rich plasma (PRP) and cell-based injections are becoming increasingly popular. Evidence suggests that these therapies can be effective in certain situations. The efficacy of these injections may be more dependent on the quality of the injectate, which given their autologous nature, may be dependent on lifestyle choices like exercise, diet, and supplements.

The Songdo consensus: Development of minimum reporting standards for studies of intervention in idiopathic anal fistula using a modified nominal group technique.

Aim: Cryptoglandular anal fistulas carry a substantial burden to quality of life. Surgery is the only effective curative treatment but requires balancing fistula healing against pain, wounds and continence impairment. Sphincter-preserving procedures do exist but demonstrate variable rates of success.

Mcl-1 is a Gatekeeper Molecule to Regulate the Crosstalk Between Ferroptotic Agent-Induced ER Stress and TRAIL-Induced Apoptosis.

We previously reported that ferroptosis interplays with apoptosis through the integration of two independent pathways: the endoplasmic reticulum (ER) stress signaling pathway and the mitochondria-dependent apoptotic signaling pathway. In this study, we investigated a potential gatekeeper molecule, Mcl-1, between the two signal transduction pathways. Morphology studies and cell death analyses confirmed that a combination treatment of ferroptotic agent erastin (ERA) and apoptotic agent TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) synergistically enhances TRAIL-induced apoptosis in human pancreatic adenocarcinoma BxPC3 and human colorectal carcinoma HCT116 cells.

Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease-A Review.

The coexistence of Alzheimer's disease (AD) and chronic pain (CP) in the elderly population has been extensively documented, and a growing body of evidence supports the potential interconnections between these two conditions. This comprehensive review explores the mechanisms by which CP may contribute to the development and progression of AD, with a particular focus on neuroinflammatory pathways and the role of microglia, as well as the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The review proposes that prolonged pain processing in critical brain regions can dysregulate the activity of the NLRP3 inflammasome within microglia, leading to the overproduction of pro-inflammatory cytokines and excessive oxidative stress in these regions.

Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.

Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.

Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.