Hypoxia-Inducible Factor-2α Promotes Liver Fibrosis by Inducing Hepatocellular Death.

The activation of hypoxia-inducible factors (HIF)-1α and 2α in the liver is closely linked to the progression of fatty liver diseases. Prior studies indicated that disrupting hepatocyte HIF-2α attenuates diet-induced hepatic steatosis, subsequently decreasing fibrosis. However, the direct role of hepatocyte HIF-2α in liver fibrosis has not been addressed.

Lipidome profiling in advanced metabolic liver disease identifies phosphatidylserine synthase 1 as a regulator of hepatic lipoprotein metabolism.

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by defective lipid metabolism, which causes disease progression. MASH is also linked to various cardiometabolic risk factors, including obesity and type 2 diabetes. The contribution of defective lipid metabolism in MASH to cardiometabolic comorbidities is incompletely understood.

Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.

Cyclic nucleotide-dependent phosphodiesterases (PDEs) play essential roles in regulating the malaria parasite life cycle, suggesting that they may be promising antimalarial drug targets. PDE inhibitors are used safely to treat a range of noninfectious human disorders. Here, we report three subseries of fast-acting and potent PDEβ inhibitors that block asexual blood-stage parasite development and that are also active against human clinical isolates.

Vision screening for preschoolers with commercial insurance: impact of geography.

Background: The American Academy of Pediatrics recommends pediatric vision screening to detect and refer vision disorders during the critical early years when intervention yields the greatest benefits. We determined the rate of vision screening for US children 3-5 years of age with commercial insurance and compared rates among those living in rural versus urban areas. Children in rural compared with urban areas were expected to have lower rates of vision screening.

Access to vision care for children from immigrant and nonimmigrant households: evidence from the National Survey of Children's Health 2018-2019.

Purpose: To investigate whether immigrant generation is associated with caregiver-reported receipt of vision testing.

Methods: Nationally representative data from the 2018-2019 National Survey of Children's Health was used. The primary exposure was immigrant generation, with first generation defined as child and all reported parents born outside the United States; second generation, as child born in the United States but at least one parent born outside the United States; and third generation, as all parents in the household born in the United States.

Eliminating malaria transmission requires targeting immature and mature gametocytes through lipoidal uptake of antimalarials.

Novel antimalarial compounds targeting both the pathogenic and transmissible stages of the human malaria parasite, Plasmodium falciparum, would greatly benefit malaria elimination strategies. However, most compounds affecting asexual blood stage parasites show severely reduced activity against gametocytes. The impact of this activity loss on a compound's transmission-blocking activity is unclear.

Disrupting the interaction between AMBRA1 and DLC1 prevents apoptosis while enhancing autophagy and mitophagy.

AMBRA1 has critical roles in autophagy, mitophagy, cell cycle regulation, neurogenesis and apoptosis. Dysregulation of these processes are hallmarks of various neurodegenerative diseases and therefore AMBRA1 represents a potential therapeutic target. The flexibility of its intrinsically disordered regions allows AMBRA1 to undergo conformational changes and thus to perform its function as an adaptor protein for various different complexes.

Dogs receiving cyclooxygenase-2-sparing nonsteroidal anti-inflammatory drugs and/or nonphysiologic steroids are at risk of severe gastrointestinal ulceration.

Objective: To report the incidence and characteristics of gastrointestinal ulceration lesions in dogs receiving an NSAID and/or corticosteroid.

Animals: 33 dogs.

Clinical Presentation: Medical records of dogs with gastrointestinal ulceration receiving NSAIDs and/or corticosteroids within 30 days of diagnosis between January 2012 and July 2022 at multiple referral institutions were reviewed.

Potential for an Electronic Clinical Decision Support Tool to Support Appropriate Antibiotic Use for Pediatric Diarrhea Among Village Doctors in Bangladesh.

Village doctors in Bangladesh expressed broad interest in clinical decision support tools for pediatric diarrheal disease management and described their willingness to alter their antibiotic dispensing practices if guided by one. Future research should evaluate the tool’s impact on appropriate antibiotic use and patient outcomes.

Electronic Clinical Decision Support Tools: Strategies to Improve the Management of Lower Respiratory Tract Infections in Low-Resource Settings.

Lower respiratory tract infection (LRTI) is a common reason for hospitalization and antibacterial use globally. There is considerable overlap in the clinical presentation of bacterial and viral LRTIs. Low- or middle-income countries (LMICs) face the dual challenge of appropriately targeting antibacterials for bacterial LRTI while reducing inappropriate antibacterials for viral LRTI.

Factors associated with medications for opioid use disorder (MOUD) treatment success during the pregnancy and postpartum periods: A scoping review.

Background: Medications for opioid use disorder (MOUD) are a crucial intervention for pregnant and postpartum individuals with opioid use disorder (OUD). However, there is paucity of data on the factors associated with MOUD treatment success in this population. This scoping review aimed to evaluate factors associated with MOUD success during the pregnancy and postpartum period.

The Triple E project: a factorial randomised controlled trial to enhance engagement with eHealth approaches to improve health risk behaviours among adolescents.

Background: Digital, or eHealth, interventions are highly promising approaches to help adolescents improve their health behaviours and reduce their risk of chronic disease. However, they often have low uptake and retention. There is also a paucity of high-quality research into the predictors of eHealth engagement, and a lack of studies that have systematically evaluated existing engagement strategies in adolescent populations.

Identification, mapping, and self-reported practice patterns of village doctors in Sitakunda subdistrict, Bangladesh.

Background: Informally trained health care providers, such as village doctors in Bangladesh, are crucial in providing health care services to the rural poor in low- and middle-income countries. Despite being one of the primary vendors of antibiotics in rural Bangladesh, village doctors often have limited knowledge about appropriate antibiotic use, leading to varied and potentially inappropriate dispensing and treatment practices. In this study, we aimed to identify, map, and survey village doctors in the Sitakunda subdistrict of Bangladesh to understand their distribution, practice characteristics, clinical behaviours, access to technologies, and use of these technologies for clinical decision-making.

Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model.

Primary liver cancer is an increasing problem worldwide and is associated with significant mortality. A popular method of modeling liver cancer in mice is plasmid hydrodynamic tail vein injection (HTVI). However, plasmid-HTVI models rarely recapitulate the chronic liver injury which precedes the development of most human liver cancer.

Antepartum vs postpartum amoxicillin oral challenge in pregnant patients with a reported penicillin allergy: A two-center prospective cohort study.

Introduction: While 10% of pregnant individuals report a penicillin allergy, there is no established best practice for penicillin allergy delabeling in pregnancy. To better understand options for penicillin delabeling, we aimed to evaluate two penicillin allergy delabeling protocols in pregnancy regarding efficacy, adverse events, and patient satisfaction.

Material And Methods: From July 2019 to December 2022, we completed a two-center prospective cohort study, where each site recruited pregnant patients over 24 weeks gestational age with a reported penicillin allergy.

Metabolic Plasticity of Glioblastoma Cells in Response to DHODH Inhibitor BAY2402234 Treatment.

Glioblastoma (IDH-wildtype) represents a formidable challenge in oncology, lacking effective chemotherapeutic or biological interventions. The metabolic reprogramming of cancer cells is a hallmark of tumor progression and drug resistance, yet the role of metabolic reprogramming in glioblastoma during drug treatment remains poorly understood. The dihydroorotate dehydrogenase (DHODH) inhibitor BAY2402234 is a blood-brain barrier penetrant drug showing efficiency in in vivo models of many brain cancers.

The Tuberculosis Drug Candidate SQ109 and Its Analogs Have Multistage Activity against .

Toward repositioning the antitubercular clinical candidate SQ109 as an antimalarial, analogs were investigated for structure-activity relationships for activity against asexual blood stages of the human malaria parasite pathogenic forms, as well as transmissible, sexual stage gametocytes. We show that equipotent activity (IC) in the 100-300 nM range could be attained for both asexual and sexual stages, with the activity of most compounds retained against a multidrug-resistant strain. The multistage activity profile relies on high lipophilicity ascribed to the adamantane headgroup, and antiplasmodial activity is critically dependent on the diamine linker.

Long-term prevention of hereditary angioedema attacks with lanadelumab in adolescents.

Background: Lanadelumab was well tolerated and effective in preventing hereditary angioedema (HAE) attacks in the phase 3, double-blind, placebo-controlled Hereditary angioEdema Long-term Prophylaxis (HELP) study and subsequent HELP open-label extension (OLE) study (NCT02741596).

Objective: To evaluate outcomes from HELP OLE for adolescent patients aged 12 to 17 years.

Methods: The HELP OLE study comprised patients who completed the HELP study (rollovers) and new eligible (lanadelumab-naive) patients.

Overcoming Barriers to Remission in Severe Eosinophilic Asthma: Two-Year Real-World Data With Benralizumab.

Background: Benralizumab has been reported to lead to clinical remission of severe eosinophilic asthma (SEA) at 1 year in some patients. However, whether this is maintained over a longer term remains unclear. Additionally, the impact of pulmonary and extrapulmonary comorbidities on the ability to meet remission is poorly understood.

Estimating the Health-Related Quality of Life Benefit of Prophylactic Treatment for COVID-19 in Immunocompromised People: A Multimethod Valuation Study.

Pre-exposure prophylaxis (PrEP) for COVID-19 provides additional protection, beyond vaccines alone, for individuals who are immunocompromised (IC). This may reduce the need for preventative behavioral modification, such as shielding-a behavioral restriction limiting an IC individual to minimize face-to-face interactions and/or crowded places. Therefore, PrEP may improve psychosocial well-being and health-related quality of life (HRQoL) for individuals with IC conditions.

Ecotourism and mangrove conservation in Southeast Asia: Current trends and perspectives.

Mangroves in Southeast Asia provide numerous supporting, provisioning, regulating, and cultural services that are crucial to the environment and local livelihoods since they support biodiversity conservation and climate change resilience. However, Southeast Asia mangroves face deforestation threats from the expansion of commercial aquaculture, agriculture, and urban development, along with climate change-related natural processes. Ecotourism has gained prominence as a financial incentive tool to support mangrove conservation and restoration.