A Novel Rabbit Model of Meibomian Gland Dysfunction-Induced Dry Eye.

Purpose: The objective of this three-phase study was to develop a model of mild to moderate evaporative dry eye to be used to evaluate tear film stability endpoints during product development.

Methods: Rabbits were sedated prior to ophthalmic cautery of meibomian gland orifices. The orifices of eyelid meibomian glands were half-cauterized (to yield obstruction of every other meibomian gland orifices), fully cauterized (to yield obstruction of all meibomian gland orifices), or untreated.

Ocular Safety and Toxicology of Subretinal Gene Therapy With rAAV.hPDE6A in Nonhuman Primates.

Purpose: Reports of gene therapy-associated retinal atrophies and inflammation have highlighted the importance of preclinical safety assessments of adeno-associated virus (AAV) vector systems. We evaluated in nonhuman primates (NHPs) the ocular safety and toxicology of a novel AAV gene therapy targeting retinitis pigmentosa caused by mutations in PDE6A, which has since been used in a phase I/II clinical trial (NCT04611503).

Methods: A total of 34 healthy cynomolgus animals (Macaca fascicularis) were treated with subretinal injections of rAAV.

Racial Differences in Discrepancies Between Subjective Ratings and Objective Assessments of Hearing Impairment.

Background And Objectives: To better understand racial/ethnic disparities in hearing aid use, we examined racial differences in discrepancies between subjective hearing ratings and objective hearing tests as a potential source of this disparity.

Research Design And Methods: A cross-sectional assessment was conducted using the data from the Health and Retirement Study (HRS). Our analytic sample included 2,568 participants aged 50 and older: 1,814 non-Hispanic White Americans and 754 non-Hispanic Black Americans.

Oculomotor challenges in macular degeneration impact motion extrapolation.

Macular degeneration (MD), which affects the central visual field including the fovea, has a profound impact on acuity and oculomotor control. We used a motion extrapolation task to investigate the contribution of various factors that potentially impact motion estimation, including the transient disappearance of the target into the scotoma, increased position uncertainty associated with eccentric target positions, and increased oculomotor noise due to the use of a non-foveal locus for fixation and for eye movements. Observers performed a perceptual baseball task where they judged whether the target would intersect or miss a rectangular region (the plate).

Baseline Alpha-Fetoprotein Elevation and the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B: A Multicentre Cohort Study.

Alpha-fetoprotein (AFP) level and its changes in chronic hepatitis B (CHB) may influence the risk of future hepatocellular carcinoma (HCC). This study aims to evaluate the HCC risk in CHB patients with no overt HCC but with elevated AFP level and to explore the prognostic role of longitudinal changes in AFP and liver-related laboratory values. This multicentre cohort study included 10,639 CHB patients without a history of HCC from seven medical facilities in South Korea.

Family Size across the Life Course and Cognitive Decline in Older Mexican Adults.

Objectives: A growing body of research has identified associations between family size and cognition in older adults. These studies largely focus on older adults' own fertility history instead of sibship size, defined as one's number of siblings. Sibship size may impact cognitive development during early childhood, creating differences that may persist into late-life.

Developing an Intervention to Enhance Aging in Place for Older Veterans Living in Permanent Supportive Housing.

Background And Objectives: The Housing and Urban Development-Veterans Affairs Supported Housing (HUD-VASH) program provides rental subsidies, case management, and supportive services to Veterans who are currently or formerly homeless, 77% of whom are ages ≥50. Few interventions have been developed to address the needs of older Veterans in HUD-VASH.

Research Design And Methods: We conducted a 2-stage study to inform the development of an intervention to promote aging in place in HUD-VASH.

[Gene editing is changing the treatment of hereditary diseases].

Gene editing is a novel technology within gene therapy, which changes sequences in chromosomal DNA with precision. Even if there are alternative strategies, the Nobel Prize-winning CRISPR/Cas technology has become the dominating principle. During recent years base editing and prime editing, permitting editing without DNA double-strand breaks, have been developed.

Mechanism of chaperone recruitment and retention on mitochondrial precursors.

Nearly all mitochondrial proteins are imported into mitochondria from the cytosol. How nascent mitochondrial precursors acquire and sustain import-competence in the cytosol under normal and stress conditions is incompletely understood. Here, we show that under normal conditions, the Hsc70 and Hsp90 systems interact with and redundantly minimize precursor degradation.

Hepatocyte Rho-associated kinase signaling is required for mice to survive experimental porphyria-associated liver injury.

Background: Rho-associated kinases 1 and 2 (ROCK1 and ROCK2) regulate critical cell functions, including actomyosin contractility, apoptosis, and proliferation. Some studies suggest that ROCK inhibition may serve as a treatment for liver fibrosis. More investigation is needed to understand the role of hepatocyte ROCK signaling in vivo, especially in the context of profibrotic liver injury.

Fatal overdoses among people with HIV experiencing nonfatal overdoses in British Columbia, Canada.

The breadth of the overdose crisis is underestimated because of a lack of quantifying nonfatal overdoses. We estimate the proportion of nonfatal overdoses among all people with HIV (PWH) in British Columbia, Canada, and the prevalence of fatal overdoses among people who had a nonfatal overdose, stratified by sex. A small proportion of PWH who experienced a nonfatal overdose subsequently died of a fatal overdose, signaling opportunities for crucial interventions and treatment to prevent overdose death.

Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration.

Rare inherited diseases caused by mutations in the copper transporters (CTR1) or induce copper deficiency in the brain, causing seizures and neurodegeneration in infancy through poorly understood mechanisms. Here, we used multiple model systems to characterize the molecular mechanisms by which neuronal cells respond to copper deficiency. Targeted deletion of CTR1 in neuroblastoma cells produced copper deficiency that produced a metabolic shift favoring glycolysis over oxidative phosphorylation.

Quantitative Profiling pH Heterogeneity of Acidic Endolysosomal Compartments using Fluorescence Lifetime Imaging Microscopy.

The endo-lysosomal system plays a crucial role in maintaining cellular homeostasis and promoting organism fitness. The pH of its acidic compartments is a crucial parameter for proper function, and it is dynamically influenced by both intracellular and environmental factors. Here, we present a method based on fluorescence lifetime imaging microscopy (FLIM) for quantitatively analyzing the pH profiles of acidic endolysosomal compartments in diverse types of primary mammalian cells and in live organism .

Short-term costs of alcohol-associated hepatitis care in different clinical settings.

Background: Alcohol-associated hepatitis (AH) leads to high rates of mortality and health care costs. Understanding the immediate costs after an AH diagnosis and identifying key cost factors is crucial for health care policies and clinical decisions.

Objectives: This study quantifies medical costs within 30 days of an AH diagnosis across outpatient (OP), emergency department (ED), and inpatient (IP) settings.

Negative Aging Stereotypes and Clinical Insomnia in Older U.S. Military Veterans.

Background And Objectives: Insomnia symptoms are more prevalent in older age and may be impacted by negative perceptions of aging; however, more research is needed. The present study characterizes the relationship between negative aging stereotypes and clinical insomnia symptoms in a nationally representative sample of older United States (U.S.

Tetraspanins 10 and 15 support Venezuelan equine encephalitis virus replication in astrocytoma cells.

Tetraspanins (Tspans) are transmembrane proteins that coordinate life cycle steps of viruses from distinct families. Here, we identify the human Tspan10 and Tspan15, both members of the TspanC8 subfamily, as replication factors for alphavirus Venezuelan equine encephalitis virus (VEEV) in astrocytoma cells. Pharmacological inhibition and siRNA-mediated silencing of TspanC8 interactor a disintegrin and metalloproteinase 10 (ADAM10) reduced VEEV infection.

2025 SWHR Women's Health Research Agenda: Prioritizing Uterine Fibroids, Lupus, and Metabolism.

Women face unique and multifaceted challenges throughout their lifespans, shaped by biological, societal, and health care-related factors. These challenges have led to gender disparities in disease burden, access to care, and representation in medical research, underscoring the need to increase targeted investments in women's health. Historically, research on diseases that disproportionately affect women has been underfunded, hindering progress in closing gender health gaps.

The eyes have it: Alcohol-induced eye movement impairment and perceived impairment in older adults with and without alcohol use disorder.

Background: While alcohol has been shown to impair eye movements in young adults, little is known about alcohol-induced oculomotor impairment in older adults with longer histories of alcohol use. Here, we examined whether older adults with chronic alcohol use disorder (AUD) exhibit more acute tolerance than age-matched light drinkers (LD), evidenced by less alcohol-induced oculomotor impairment and perceived impairment.

Method: Two random-order, double-blinded laboratory sessions with administration of alcohol (0.

Mitochondria-plasma membrane contact sites regulate the ER-mitochondria encounter structure.

Cells form multiple, molecularly distinct membrane contact sites (MCSs) between organelles. Despite knowing the molecular identity of several of these complexes, little is known about how MCSs are coordinately regulated in space and time to promote organelle function. Here, we examined two well-characterized mitochondria-ER MCSs - the ER-Mitochondria encounter structure (ERMES) and the mitochondria-ER-cortex anchor (MECA).