Ideal respiratory health and chronic respiratory disease exist on a continuum. Between these two extremes lies an intermediate state of impaired respiratory health, characterized by clinical phenotypes that exist along the causal pathway. Identifying individuals with intermediate phenotypes of impaired respiratory health offers an opportunity to intercept progression to chronic respiratory disease.

In this review, we identify parameters associated with impaired respiratory health, including respiratory symptoms and illnesses, abnormal lung physiology, imaging abnormalities, and blood biomarkers. We then synthesize evidence linking these parameters to future respiratory impairment.

Drawing inspiration from advances in cardiovascular disease prevention, the respiratory field must adopt a holistic framework that considers the likely shared biologic mechanisms underpinning chronic lung diseases. Effective disease prevention depends on a multi-omic approach that integrates clinical, physiologic, imaging, and molecular data to identify individuals at increased risk for chronic respiratory disease. Prospective evaluation of these at-risk individuals can be utilized to evaluate the impact of targeted preventative strategies.

Aberrant cardiac fibrosis contributes to heart failure. It has been previously shown that the DNA dioxygenase ten-and-eleven translocator 3 (TET3) promotes cardiac fibrosis and heart failure. In the present study we examined the effects of a small-molecule TET3 degrader Bobcat339 on cardiac fibrosis and cellular transcriptome.

C57BL/6J mice were injected with isoprenaline (ISO) to induce cardiac fibrosis and heart failure. Cellular transcriptome was evaluated by RNA-seq and ATAC-seq.

Co-treatment with Bobcat339 significantly attenuated activation of cardiac fibroblasts subjected to ISO treatment. Compared to the mice injected with vehicle control, the mice injected with Bobcat339 displayed significantly amelioration of cardiac fibrosis as evidenced by histological staining, hydroxyproline levels, and expression of myofibroblast markers in the heart. Intervention with Bobcat339 rescued the mice from ISO-induced heart failure but did not influence cardiac hypertrophy. RNA-seq data indicated that Bobcat339 intervention led to massive transcriptomic alterations in cardiac fibroblasts. These changes could be attributed to, at least in part, by differential chromatin accessibility as uncovered by ATAC-seq. An integrated analysis of RNA-seq and ATAC-seq suggested that Bobcat339 primarily impacted genes regulating extracellular matrix and cytoskeletal remodeling.

Our data demonstrate that Bobcat339 antagonizes ISO-induced cardiac fibrosis in mice thus affirming that TET3 could be targeted for the intervention of heart failure. In addition our data shed additional light on the mechanism whereby TET3 contributes to activation of cardiac fibroblasts to promote cardiac fibrosis and heart failure.

High-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummingbirds, parrots, honeyeaters, and sunbirds by generating nine new genomes and 90 tissue-specific transcriptomes. Comparative screens revealed an excess of repeated selection in both protein-coding and regulatory sequences in sugar-feeding birds, suggesting reuse of genetic elements. Sequence or expression changes in sugar-feeders affect genes involved in blood pressure regulation and lipid, amino acid, and carbohydrate metabolism, with experiments showing functional changes in honeyeater hexokinase 3. MLXIPL, a key regulator of sugar and lipid homeostasis, showed convergent sequence and regulatory changes across all sugar-feeding clades; experiments revealed enhanced sugar-induced transcriptional activity of hummingbird MLXIPL, highlighting its adaptive role in high-sugar diets.

Cardiometabolic diseases (CMDs) refer to a broad spectrum of interconnected disorders, including heart attack, obesity, diabetes, atherosclerosis, and metabolic dysfunction-associated steatohepatitis, which represent the leading cause of mortality worldwide. In recent years, research on the role of gut microbiota in the pathogenesis of CMD has gradually shifted from correlation-based observations to mechanistic explorations. Within this context, microbial enzymes have gained increasing attention as key regulatory factors. These enzymes not only participate in the metabolic regulation of microorganisms themselves but also directly mediate host-microbe interactions, influencing the onset and progression of CMD. Specifically, microbial enzymes play a central role in CMD by modulating the homeostasis of key host metabolites such as cholesterol, generating bioactive molecules with metabolic and immunoregulatory functions, and participating in drug responses and the metabolic transformation of other xenobiotics. These enzymes provide novel and well-defined molecular targets for developing precision intervention strategies targeting the gut microbiota-such as enzyme replacement therapy, the design of enzyme agonists or inhibitors, and in vivo gene editing-thereby holding promise for advancing CMD prevention and treatment strategies toward greater specificity and controllability. This review systematically summarizes key microbial enzymes involved in the metabolism of endobiotics, including amino acids, peptides, and purines, and xenobiotics such as drugs, elucidating their specific mechanisms and functions in the development of CMD, strategies for mining these microbial enzymes, and the challenges and future of microbial enzyme-based interventions.

Participating in a comprehensive lifestyle intervention can reduce the risk of cardiovascular disease-the leading cause of death among Veterans.

We assessed whether a national, virtual lifestyle change program (Telephone Lifestyle Coaching, TLC) promoted equal access to care across vulnerable Veteran subgroups (women, racial/ethnic minorities, rural Veterans).

We conducted a retrospective evaluation of reach (referrals) and engagement (enrollment) during TLC's implementation at 44 Veterans Health Administration (VA) sites (March 2019-September 2023). We used bivariate analyses to compare referred vs. non-referred and enrolled vs. not enrolled Veterans, and multivariate logistic regression-among all Veterans and stratified by sex-to assess factors associated with referral and enrollment.

All TLC-eligible Veterans at the 44 implementation sites (N = 2,333,586).

We evaluated factors associated with referrals and enrollment in terms of sex, race, ethnicity, and urban/rural residence, controlling for age, prior VA lifestyle program participation, mental health diagnoses, trauma, and cardiovascular health in regression analyses adjusting for clustering by site.

TLC referral was associated with being female, prior lifestyle program participation, and diagnoses of depression, PTSD, military sexual trauma, overweight/obesity, and cardiovascular risk. Among men, the odds of referral were higher among Black/other race Veterans compared to White Veterans. Enrollment was associated with being female, prior lifestyle program participation, and overweight/obesity diagnosis. Among females, Hispanic/Latino ethnicity increased odds of enrollment while among males, rural residence increased odds of enrollment.

TLC demonstrated success in reach and engagement across a diverse Veteran population. Rurality and mental health conditions were not a barrier to TLC program referral, while prior participation in a VA lifestyle change intervention may facilitate subsequent engagement in lifestyle change programs. Providing a virtual option for lifestyle-focused counseling programs is essential for addressing persistent disparities in Veterans' cardiovascular health outcomes.

Housing precarity (HP) is a fundamental determinant of well-being and health among older adults.

We explored the association between housing precarity and cognitive function among older adults in South Korea.

Population-based, cross-sectional survey.

A nationwide community-dwelling sample of 9796 adults aged ≥ 65 years was analyzed.

Based on the theoretical framework established in the existing literature, HP was assessed across five dimensions: housing affordability, housing tenure, housing satisfaction, neighborhood quality, and community cohesion. The overall HP level was scored on a scale ranging from 0 to 10 and categorized into four levels: lowest, low, high, and highest. Cognitive function was assessed using the Korean version of the Mini-Mental State Examination, 2nd edition (K-MMSE~2), and z-scores were calculated. A higher K-MMSE~2 score indicated better cognitive functioning. Linear regression analysis was performed to determine the association between HP and cognitive function. Beta coefficients (β) and 95% confidence intervals (CI) were estimated.

The mean age of the sample was 73.9 years, with a mean MMSE score of 24.6. Compared to participants with the lowest HP levels, those with the high or highest HP levels had lower MMSE z-scores (β [95% CI] -0.21 [-0.27, -0.15] for high HP; and β [95% CI] -0.29 [-0.35, -0.22] for the highest HP levels). Regarding individual indicators, insecure tenure (not owning a home), housing dissatisfaction, poor neighborhood quality, and low community cohesion were negatively associated with cognitive function.

Among older adults, high HP levels were associated with poor cognitive function.

Informed and self-determined decisions are a central element of human-rights-compliant abortion care. This article examines the framework conditions for informed, self-determined decisions and interdisciplinary cooperation from the perspectives of counsellors from pregnancy counselling centres in Germany. The data are based on a qualitative study conducted as part of a sub-project on psychosocial care within the joint project "Experiences and life situations of women with unwanted pregnancies-counselling and care services".

In the fourth quarter of 2022, six guided focus group interviews were conducted with 25 professionals at four locations and analysed using content-structuring analysis.

Informed decisions are understood as a relational process that offers guidance beyond the transfer of knowledge. Information barriers, a lack of language mediation and social inequalities complicate the process, especially for migrants and people facing multiple challenges. Interdisciplinary collaboration reveals asymmetries between psychosocial and medical care. Collaborations are often dependent on individuals, structurally insecure and in need of improvement.

Informed and self-determined decisions can be supported by improved interdisciplinary networking, accessible and reliable information services, and institutionalised language mediation. The reduction of structural inequalities and the normalisation of abortion are described as central issues, and the criminal law framework and compulsory counselling are reflected upon critically in some cases. Pregnancy counselling centres play a key role in this process.