Is Weight Loss the Main Driver for A1C Improvement by Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists? A 2.5-Year Analysis in Real-World Clinical Practice.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established treatment options for type 2 diabetes (T2D). In addition to their glycemic benefit, GLP-1 RAs also induce weight loss by suppressing appetite via hypothalamic pathways. However, it remains unclear whether weight reduction is the primary driver of glycemic improvement.

Alcohol-induced liver injury is mediated via α4-containing nicotinic acetylcholine receptors expressed in hepatocytes.

Background: Our previous study demonstrated that alcohol induced the expression of the α4 subunit of nicotinic acetylcholine receptors (nAChRs) in the livers of wild type mice (WT), and that whole-body α4 nAChR knockout mice (α4KO) showed protection against alcohol-induced steatosis, inflammation, and injury. Based on these findings, we hypothesized that hepatocyte-specific α4 nAChRs may directly contribute to the detrimental effects of alcohol on the liver.

Methods: Hepatocyte-specific α4 knockout mice (α4HepKO) were generated, and the absence of α4 nAChR was confirmed through PCR of genomic DNA.

Impacts of amino acid-linked platinum(II) complexes on DNA structure.

The discovery of cisplatin (cisPt) as an effective anticancer agent was a milestone in the health industry. Despite its success, undesired side effects and acquired resistance still limit the therapeutic usefulness of cisPt. Intrastrand adduct formation at consecutive purines and structural modifications of DNA caused by platinum(II) complexes are important factors for antitumor efficacy.

Biomonitoring PhIP, a Potential Prostatic Carcinogen, in the Hair of Healthy Men of African and European Ancestry.

Heterocyclic aromatic amines (HAAs), formed during the cooking of meat, are potential human carcinogens, underscoring the need for long-lived biomarkers to assess exposure and cancer risk. Frequent consumption of well-done meats containing 2-amino-1-methyl-6-phenylimidazo[4,5-]pyridine (PhIP), a prevalent HAA that is a prostatic carcinogen in rodents and DNA-damaging agent in human prostate cells, has been linked to aggressive prostate cancer (PC) pathology. African American (AA) men face nearly twice the risk for developing and dying from PC compared to White men.

The Role of Partnerships in Supporting COVID-19 Vaccine Uptake Among Migrants: A Qualitative Case Study from Tamil Nadu and Punjab, India.

Background: During the COVID-19 pandemic, migrant populations remained under-immunized due to limited access to health care, language barriers, and vaccine hesitancy. The USAID-funded MOMENTUM Routine Immunization Transformation and Equity project supported the government in collaborating with various local health and non-health partners to identify and vaccinate migrants. This case study examines the roles of project partners and the strategies each entity implemented to increase COVID-19 vaccine uptake among migrants, as well as the perceptions regarding the effectiveness of these strategies.

Fast Hadamard-Encoded 7T Spectroscopic Imaging of Human Brain.

: The increased SNR available at 7T combined with fast readout trajectories enables accelerated spectroscopic imaging acquisitions for clinical applications. In this report, we evaluate the performance of a Hadamard slice encoding strategy with a 2D rosette trajectory for multi-slice fast spectroscopic imaging at 7T. : Moderate-TE (~40 ms) spin echo and J-refocused polarization transfer sequences were acquired with simultaneous Hadamard multi-slice excitations and rosette in-plane encoding.

Modulation of Stemness and Differentiation Regulators by Valproic Acid in Medulloblastoma Neurospheres.

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest.

Differential Impact of Risk Factors for Cognitive Decline in Heterosexual and Sexual Minority Older Adults in England.

Background/objectives: Sexual minority older adults (SMOAs) report greater subjective cognitive decline (SCD) than heterosexual older adults (HOAs). This study aimed to compare the impact of multiple psycho-social risk factors on objective and subjective cognitive decline in HOAs and SMOAs.

Methods: Two samples of self-identified HOAs and SMOAs were selected from the English Longitudinal Study of Ageing.

Patient "No-Show" Prior to Elective Primary Total Hip Arthroplasty Increases Risk of Postoperative Anemia.

Background: Patients who "no-show" (NS) clinical appointments are at a higher risk of poor healthcare outcomes. The objective of this study was to evaluate and characterize the relationship between patient NS prior to primary total hip arthroplasty (THA) and 90-day complication risk after THA.

Methods: We retrospectively reviewed 4147 patients undergoing primary THA.

Attenuating hyperammonemia preserves protein synthesis and muscle mass via restoration of perturbed metabolic pathways in bile duct-ligated rats.

Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia's toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to investigate the effect of attenuating hyperammonemia with ornithine phenylacetate (OP) on muscle mass loss and associated molecular mechanisms in rats with CLD.

Cushing's syndrome related to higher rates and earlier onset of cataract: A nationwide retrospective cohort study.

Purpose: To investigate the risk of cataract in patients with Cushing's syndrome (CS) and evaluate whether disease onset occurs at an earlier age compared to general population.

Methods: A nationwide retrospective matched-cohort study including individuals diagnosed with endogenous CS from 2000 to 2023. Patients with CS were matched in a 1:5 ratio with a control group individually matched for age, sex, socioeconomic status, and body mass index.

Two Clinically Implementable Digital PCR Assessments of DNA Methylation for Diagnosing Heavy Alcohol Consumption.

Background: Heavy alcohol consumption (HAC) has a profound adverse effect on human health. Unfortunately, there is a relative lack of tools that are easily implementable in clinical settings and that can be used to supplement self-reporting in the diagnosis and management of HAC. In part, this paucity is due to limitations of currently available biological measures and a mismatch between available biological measures and the needs of clinicians managing HAC.

Chemical structure-biological activity of 1,4-naphthoquinone analogs as potential Aedes aegypti larvicides.

Background: 1,4-Naphthoquinone compounds have shown pesticidal activity against Aedes aegypti larvae, a key vector of diseases such as dengue and Zika. However, limited knowledge of their structure-activity relationships has hindered their optimization for pesticide development. This study investigates the structure-activity relationships of 1,4-naphthoquinone, particularly 2-hydroxy-1,4-naphthoquinone and its derivatives.

Practical and economic challenges of implementing group auricular acupuncture treatment for chronic pain in primary care.

Background: Although growing numbers of patients seek acupuncture for pain management, few acupuncturists with insurance credentialing work in the conventional medical settings. This has resulted in increasing frustration among patients wishing to receive acupuncture in primary care settings as part of their insurance benefits.

Methods: A course of eight weekly sessions of group auricular acupuncture (AA) for chronic musculoskeletal pain was implemented in a US primary care clinic and billed to insurance.

Long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata and at least 25% scalp hair loss: Results from the ALLEGRO-LT phase 3, open-label study.

Background: ALLEGRO-LT is an ongoing, long-term, open-label, multicentre, phase 3 study of ritlecitinib in adults and adolescents with alopecia areata (AA).

Objectives: To evaluate ritlecitinib safety and efficacy through Month 24 in patients with AA and ≥25% scalp hair loss.

Methods: ALLEGRO-LT enrolled rollover patients who previously received study intervention in either ALLEGRO phase 2a or 2b/3 studies and de novo patients who had not received treatment in either study.

Measuring the effects of motion corruption in fetal fMRI.

Irregular and unpredictable fetal movement is the most common cause of artifacts in in utero functional magnetic resonance imaging (fMRI), affecting analysis and limiting our understanding of early functional brain development. The accurate detection of corrupted functional connectivity (FC) resulting from motion artifacts or preprocessing, instead of neural activity, is a prerequisite for reliable and valid analysis of FC and early brain development. Approaches to address this problem in adult data are of limited utility in fetal fMRI.

Examining the Proximal Relationship between Religious Coping and Depression among Trauma-Exposed Adults.

Depression is a common consequence of sexual victimization. Although religious coping has been previously studied within the context of sexual victimization, there is a dearth of research examining the potential reciprocal relationships between religious coping and depression among adults with a history of sexual victimization at the daily level. The current study addresses this important gap by leveraging an intensive longitudinal design and data analysis to explore bidirectional daily relations between religious coping and depression symptoms in a community sample of adults with a history of sexual victimization.

Empowering African Expertise: Enhancing Safety Data Integration and Signal Detection for COVID-19 Vaccines Through the African Union Smart Safety Surveillance Joint Signal Management Group.

Introduction: The COVID-19 pandemic accelerated new vaccine development. Limited safety data necessitated robust global safety surveillance to accurately identify and promptly communicate potential safety issues. The African Union Smart Safety Surveillance (AU-3S) program established the Joint Signal Management (JSM) group to support identification of potential vaccine safety concerns in five pilot countries (Ethiopia, Ghana, Kenya, Nigeria, South Africa), accounting for approximately 35% of the African population.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

RELMβ sets the threshold for microbiome-dependent oral tolerance.

Tolerance to dietary antigens is critical for avoiding deleterious type 2 immune responses resulting in food allergy (FA) and anaphylaxis. However, the mechanisms resulting in both the maintenance and failure of tolerance to food antigens are poorly understood. Here we demonstrate that the goblet-cell-derived resistin-like molecule β (RELMβ) is a critical regulator of oral tolerance.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Cardiovascular and locomotor effects of binary mixtures of common 'bath salts' constituents: Studies with methylone, methylenedioxypyrovalerone and caffeine in rats.

Background And Purpose: The use of 'bath salts' drug preparations has been associated with high rates of toxicity and death. Preparations often contain mixtures of drugs, including multiple synthetic cathinones or synthetic cathinones and caffeine. Little is known about the interactions of 'bath salts' constituents and adverse effects often reported by users.

Integrating the modified amphiphilic Eleocharis tuberosa starch to stabilize curcuminoid-enriched Pickering emulsions for enhanced bioavailability, thermal stability, and retention of the hydrophobic bioactive compound.

The study involves the modification of a non-conventional starch isolated from the under-utilized variety of Chinese water chestnut (CWC (Eleocharis tuberosa) and integrating it to fabricate stabilized and curcumin-enriched Pickering emulsions with enhanced bioavailability, thermal stability, and retention of encapsulated curcumin. A time-efficient, semi-dried esterification method was used to prepare modified amphiphilic starches using 3, 6, or 9 % (w/v) octenyl succinic anhydride (OSA) and characterized through degree of substitution (DS), contact angle, particle size, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and in-vitro digestibility. Moreover, Pickering emulsions were formulated using CWCS-OSA at 3 %, 6 %, or 9 % concentrations to serve as a carrier for curcumin to improve its water solubility and storage stability.

Gemcitabine-induced myositis in a patient with pancreatic cancer.

Gemcitabine, a cytosine analogue, is a cytotoxic agent commonly used in the treatment of patients with a variety of solid tumours, including non-small cell lung cancer, cholangiocarcinoma and breast, pancreatic, testicular and ovarian cancers. Although generally well-tolerated, several reports suggest that it can rarely cause myositis. We present a case of gemcitabine-induced myositis in a patient with pancreatic adenocarcinoma and review the literature on this topic.

Exceeding the limits of paediatric heat stress tolerance: the risk of losing a generation to climate inaction.

Greenhouse gas (GHG) emissions are creating unprecedented climate-driven extreme weather, with levels of heat and humidity surpassing human physiological tolerance for heat stress. These conditions create a risk of mass casualties, with some populations particularly vulnerable due to physiological, behavioural and socioeconomic conditions (eg, lack of adequate shelter, limited healthcare infrastructure, sparse air conditioning access and electrical grid vulnerabilities). Children, especially young children, are uniquely vulnerable to extreme heat-related morbidity and mortality due to factors including low body mass, high metabolism, suboptimal thermoregulatory mechanisms and behavioural vulnerabilities.