Air pollution, a major global health concern, is well known for its impact on respiratory and cardiovascular systems. However, its effects on ocular health remain poorly understood. Exploring the potential pathways through which airborne particles interact with and enter the eye is essential to uncover the mechanisms underlying pollution-related ocular diseases. The importance of these questions is underscored by the seamless continuity between the eye's neural structures and the brain, forming a unified channel that drains through multiple tributaries into the cervical lymph nodes. In this review we explore several potential pathways through which particles may access the eye's neural structures. The first is the well-established pulmonary route, where inhaled pollutants induce inflammation via the circulatory system; the second a novel extrapulmonary pathway involving direct transmission through the olfactory-nervous system. This review is organized into three sections: an overview of ambient air pollution, a review of studies on air pollution's effects in ocular diseases; and, discussion derived from this body of research. Advancing our understanding of air pollution's interact with and impact on ocular health is essential for the development of targeted strategies to protect vision and reduce environmental health risks.

Sexual dysfunction (SD) is prevalent, yet underaddressed, among gay, bisexual and other men who have sex with men (GBM) living with HIV. We aimed at exploring the perceived causes and effects of SD from the perspective of Montreal-based GBM with HIV.

During 2024, semi-structured interviews were conducted with 31 Montreal-based GBM with HIV who experienced SD (reduced libido, erectile dysfunction, premature/delayed ejaculation or pain during sex) in the past 5 years, asking about perceived causes and impacts. Data were analyzed using reflexive thematic analysis.

Participants' median age was 46 years (range 27-74 years). The most common SDs were reduced libido (n = 26; 84%) and erectile dysfunction (n = 25; 81%). Participants reported a median of three concurrent SDs. Themes regarding the perceived causes of SD were: (1) biopsychosocial challenges across the lifespan, including aging, physical health (e.g. hormonal/cardiovascular problems), adverse life events and mental health problems; (2) living with HIV (in terms of HIV diagnosis and stigma) and concerns about antiretroviral therapy side-effects; and (3) gay sexual culture, which encompassed challenges in navigating expectations, relational/sexual ambivalence, and combining sex and drugs. Themes related to the impacts of SD included: (1) negative emotions (e.g. frustration, low self-esteem); (2) relational strain; and (3) adaptation (e.g. prioritizing intimacy over sex alone).

Findings highlight the multifaceted experience of SD among GBM with HIV. Participants perceived that biopsychosocial challenges across the lifespan, living with HIV and gay sexual culture contributed to SD. Although SD led to emotional and relational distress, participants indicated strategies to manage it.

Mass displacement is a grand public health challenge. Refugees and immigrants experience a disparate hypertension burden and disparities in self-management. Successful hypertension self-management is key for improving outcomes, but research on its feasibility in refugee and immigrant health care settings is limited.

This study aimed to identify clinic staff-perceived barriers to and facilitators of implementing a digital intervention for hypertension self-management among refugee and immigrant patients and to identify its feasibility and usability.

Primary care physicians and medical assistants who care for refugees and immigrants in San Diego were interviewed using human-centered semistructured methods (n=18). Interviews were analyzed using an inductive approach. Usability testing for the software (Med Pro Care) was conducted with participants (n=15) to test the feasibility of real-time tracking of blood pressure (BP) home readings for hypertension self-management. Clinical staff rated their satisfaction on the System Usability Scale and the NASA Task Load Index, which measured mental workload.

For refugee and immigrant patients self-managing hypertension, clinical staff identified barriers and facilitators in the following areas: (1) social determinants of health increase hypertension burden among refugee and immigrant patients, (2) clinical staff face challenges to effective hypertension care for refugee and immigrant patients, (3) perceived benefits of potential intervention for self-management, and (4) perceived barriers to potential intervention for self-management. Primary care physicians completed 90% of the tasks, and medical assistants completed 83% of the tasks successfully. Most clinic staff found the software system for monitoring BP to be easy to use with an average score for usability of 4.1 of 5.0 (SD 0.4).

Addressing identified barriers to and facilitators of self-management of hypertension is crucial to designing effective interventions in real-world refugee and immigrant health care settings. Telemonitoring interventions using software that transfers BP readings to clinical staff in real time may be feasible from the perspective of clinic staff and can address hypertension disparities in marginalized populations, such as immigrants and refugees. Addressing identified barriers to and facilitators of self-management is crucial to designing effective interventions in real-world refugee and immigrant health care settings. Our findings suggest that clinic staff view digital telemonitoring as both feasible and supportive of patient empowerment, health literacy, and improved communication-factors essential to addressing hypertension disparities in marginalized populations.

Programmed ribosomal frameshifting is a process where a proportion of ribosomes change their reading frame on an mRNA. While frameshifting is commonly used by viruses, very few phylogenetically conserved examples are known in nuclear encoded genes. Here, we report a +1 frameshifting event during decoding of the human gene PLEKHM2 that provides access to a second internally overlapping ORF. The new carboxyl-terminal domain of this frameshift protein forms an α helix, which relieves PLEKHM2 from autoinhibition and allows it to move to the tips of cells without activation by ARL8. Reintroducing both the canonically translated and frameshifted protein are necessary to restore normal contractile function of PLEKHM2 knockout cardiomyocytes, demonstrating the necessity of frameshifting for normal cardiac activity.

With the increasing proportion of elderly individuals, understanding biological mechanisms of aging is critical. Retinal vascular complexity, measured as fractal dimension (D_f) from fundus photographs, has emerged as a vascular aging indicator. We conducted a genome-wide association study of D_f on 74,434 participants from the Canadian Longitudinal Study on Aging, Genetics of Diabetes Audit and Research in Tayside Scotland, and UK Biobank cohorts. We identified a novel locus near DAAM1. We found negative genetic correlations between D_f and cardiovascular disease, stroke, and inflammation but a positive correlation with life span. By combining the genetic determinants of 1159 circulating proteins from the Prospective Urban and Rural Epidemiological cohort with those of D_f using Mendelian randomization, we identified eight causal mediators, including MMP12 and IgG-Fc receptor IIb, which link higher inflammation to lower D_f, increased cardiovascular disease risk, and shorter life span. These results extend our understanding of the biological pathways underlying aging processes and inform targets to prevention and treatment.

Antihypertensive treatment is widely known to reduce the risk of cardiovascular mortality; however, its protective effect, specifically against cardiac death, remains unclear. In this study, we examined whether a treatment strategy prioritizing the combined use of angiotensin-converting enzyme inhibitors and β-blockers reduces the risk of cardiac death in outpatient hypertensive patients. This retrospective observational cohort study was conducted at a single facility over a 30-year period, using data obtained between 1987 and 2016. Between 1992 and 2001, a combined treatment approach using angiotensin-converting enzyme inhibitors and β-blockers was preferentially used to suppress neurohumoral factors, with calcium channel blockers and diuretics used as supplementary medications. Standardized mortality ratios for all-cause mortality, cardiac death, and cerebrovascular death during each period were tracked and compared with nationwide data in Japan. Since 1992, the standardized mortality ratios for all-cause mortality and cardiac death in Tsunan Town have significantly decreased and fallen below the national averages. The present study focused on the role of neurohumoral factors, and we observationally evaluated the impact of combined therapy with angiotensin-converting enzyme inhibitors and β-blockers on the prognosis of patients with hypertension. While providing a perspective that has not been sufficiently examined to date, our findings should be regarded as the generation of an important hypothesis that warrants confirmation through future rigorous interventional studies.

Large-sample clinical research evidence in humans regarding the association between thyroid hormones and cardiovascular health is limited. The American Heart Association introduced the Life's Essential 8 (LE8) as a novel metric for assessing cardiovascular health. This study aimed to explore the plausible connection between thyroid hormone levels and LE8.

This study employed data extracted from the National Health and Nutrition Examination Survey spanning from 2007-2012, focusing on individuals aged 20 and above. To investigate the association between thyroid hormone and LE8, diverse analytical methods, including weighted multivariate linear regression, restricted cubic spline curves, and stratified analysis, were utilized.

A total of 3,019 participants were enrolled in this study. The highest LE8 score group (≥ 80) comprised 610 participants (20.21%). In the fully adjusted linear regression analysis, elevated levels of ln(FT3), ln(TT3), and ln(Tg) were significantly associated with a reduced level of LE8 (β (95% Confidence Interval): -6.31 (-12.13, -0.49), p = 0.035; -5.18 (-8.22, -2.15), p = 0.002; -0.98 (-1.74, -0.22), p = 0.014). The analysis revealed nonlinear relationships between ln(Tg), ln(TgAb), ln(TPOAb), and LE8. In the group with normal thyroid hormone levels, ln(TT3), ln(TT4), and ln(Tg) correlated with LE8 in the stratified analysis.

Alterations in FT3, TT3, TT4, Tg, TgAb, and TPOAb levels correlated with variations in LE8. Adherence to cardiovascular health recommendations may be pertinent to the preservation of thyroid health.

This study aimed to analyze the characteristics and trends of the disease burden of ischemic heart disease (IHD) in China and worldwide, across different age and sex groups, to provide a comprehensive understanding of the situation in China.

Using GBD 2023 data, we analyzed global and China-specific IHD incidence, prevalence, mortality, and DALYs. Joinpoint regression was used to assess trends, while factors such as aging and population growth were also examined. An ARIMA model projected the IHD burden from 2024 to 2050.

From 1990 to 2023, the age-standardized incidence rate (ASIR) and prevalence rate (ASPR) of IHD in China exhibited an upward trend. The ASIR per 100,000 increased from 109.7 (95% uncertainty interval [UI]: 93-128) to 110.3 (95% UI: 89-131), while the age-standardized mortality rate (ASMR) decreased from 126.8 (95% UI: 92-163) to 109.5 (95% UI: 94-127), mirroring global trends. The highest incidence of IHD was observed in individuals aged 60-89 years, with mortality peaking between 80-89 years. AAPC analysis revealed that China's ASIR (AAPC = -0.091%; 95% CI: -0.152 to -0.029) and ASPR (AAPC = 0.227%; 95% CI: 0.115 to 0.34) increased more rapidly than the global average. Decomposition analysis indicated that the rise in IHD burden in China was primarily driven by population aging and growth, a pattern observed globally. Forecasting models suggest that the ASIR will continue to rise in China through 2050, while the ASMR and age-standardized DALYs rates (ASDR) are expected to decline further.

The incidence and prevalence of IHD in China are projected to rise through approximately 2030. Older males bear a disproportionate burden of the disease. More targeted preventive, diagnostic, and therapeutic strategies are urgently needed and should be informed by the findings of this study.

Epidemiologic evidence regarding the association between per- and polyfluoroalkyl substances (PFAS) exposure and stroke risk remains limited and inconclusive. Consequently, the current study sought to further examine this association and clarify the underlying molecular mechanisms.

This cohort study analyzed data from 8081 participants of the 2003-2012 National Health and Nutrition Examination Survey (NHANES), employing multistage weighted logistic regression, weighted quantile sum (WQS) modeling, and partial least squares discriminant analysis (PLS-DA) to systematically evaluate the association between per- and polyfluoroalkyl substances (PFAS) exposure and stroke. Restricted cubic spline analysis was subsequently used to examine the nonlinear dose-response relationships. To investigate the underlying mechanisms, we integrated data from six databases (e.g., ChEMBL and GeneCards) to identify common molecular targets of PFAS and stroke. A protein-protein interaction (PPI) network was then constructed to identify core genes, while the binding interactions between PFAS and key targets were evaluated through molecular docking and dynamics simulations. Finally, functional enrichment analysis was performed on these core genes using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases.

After adjusting for potential confounders, six individual PFAS compounds, including perfluorooctane sulfonic acid (PFOS) (Odds Ratio [OR] = 1.59, 95% CI: 1.09-2.31), exhibited a significant positive association with the risk of stroke. The WQS model revealed a significant positive association for the PFAS mixture (OR = 1.027, 95% CI: 1.017-1.036), with PFOS contributing the highest weight (0.379). These findings were corroborated by the PLS-DA model, and the association remained significant in all subgroup analyses. The network toxicology analysis identified 183 common targets between PFOS and stroke, while the subsequent PPI network analysis identified six core genes, including AKT1 and HSP90AA1. GO and KEGG enrichment analyses demonstrated that these targets were markedly enriched in pathways associated with lipid and atherosclerosis metabolism, in addition to the PI3K-Akt and MAPK signaling pathways. Furthermore, molecular docking and molecular dynamics simulations supported potential interactions between PFOS and core targets such as AKT1. This suggests that PFOS may contribute to stroke pathogenesis by disrupting pathways involved in inflammatory regulation and apoptosis.

This study identified a positive association between PFOS exposure and stroke risk, suggesting that the PI3K/AKT signaling pathway, along with its key effector molecule AKT1, may play a crucial role in mediating PFOS-induced stroke, thereby offering a theoretical foundation for the prevention and management of PFOS-associated stroke.

Neurogenic claudication (NC) due to lumbar spinal stenosis is the most common reason for spinal surgery in older adults. Prehabilitation may improve outcomes and reduce costs, but current evidence is conflicting. It remains unclear who benefits most, which mechanisms optimise outcomes and what outcomes matter to patients. This review aimed to develop a programme theory explaining what works, for whom, how and in what contexts for prehabilitation of NC surgical candidates.

An initial programme theory, comprising context-mechanism-outcome configurations (CMOCs), was developed through iterative mapping and consultation with experts (n = 6) and patients (n = 7). This theory was refined via two systematic literature searches and further stakeholder feedback. Studies were assessed for relevance, richness and rigour. Data were holistically coded using abductive and retroductive reasoning to create causal maps, which informed CMOC refinement.

From 1422 records, 67 papers were included. The final programme theory included 14 CMOCs focused on patient engagement, a priority identified through patient consultation. Engagement was contingent on clear, consistent communication and addressing misconceptions among both patients and professionals. A shared understanding increased perceived value and avoided missed opportunities for preparation. Personalisation and collaborative goal-setting enhanced ownership and motivation. Ongoing support-via healthcare professional contact and peer input-helped counteract anxiety and feelings of abandonment during the surgical wait.

Engagement with prehabilitation for NC can be improved through clear communication, tailored interventions and sustained support. Further research is needed to test whether theory-informed programmes improve outcomes in this population.