Ozone exposure induces a myriad of adverse cardiopulmonary outcomes in humans. Although advanced age and chronic disease are factors that may exacerbate a person\'s negative response to ozone exposure, there are no molecular biomarkers of susceptibility. Here, we examine whether epigenetic age acceleration (EAA) is associated with responsiveness to short-term ozone exposure. Using data from a crossover-controlled exposure study (n = 17), we examined whether EAA, as measured in lung epithelial cells collected 24 h after clean air exposure, modifies the observed effect of ozone on autonomic function, cardiac electrophysiology, hemostasis, pulmonary function, and inflammation. EAA was assessed in lung epithelial cells extracted from bronchoalveolar lavage fluids, using the pan-tissue aging clock. We used two analytic approaches: (i) median regression to estimate the association between EAA and the estimated risk difference for subclinical responses to ozone and (ii) a block randomization approach to estimate EAA\'s effect modification of subclinical responses. For both approaches, we calculated Fisher-exact P-values, allowing us to bypass large sample size assumptions. In median regression analyses, accelerated epigenetic age modified associations between ozone and heart rate-corrected QT interval (QTc) ([Formula: see text]= 0.12, P-value = 0.007) and between ozone and C-reactive protein ([Formula: see text] = -0.18, P = 0.069). During block randomization, the directions of association remained consistent for QTc and C-reactive protein; however, the P-values weakened. Block randomization also revealed that responsiveness of plasminogen activator inhibitor-1 (PAI-1) to ozone exposure was modified by accelerated epigenetic aging (PAI-1 difference between accelerated aging-defined block groups = -0.54, P-value = 0.039). In conclusion, EAA is a potential biomarker for individuals with increased susceptibility to ozone exposure even among young, healthy adults.

UNASSIGNED: To explore the functional consequences of two common variants, p.V37I and c.299-300delAT in hearing loss associated gene GJB2.
UNASSIGNED: Connexin 26 expression and gap junctional permeability were studied in HEK 293T cells transfected with plasmids expressing GJB2 wild-type, p.V37I, or c.299-300delAT CX26 proteins with fluorescent tags. Functional analyses of different GJB2 haplotypes were performed to fully assess the alteration of ionic and small-molecule coupling.
UNASSIGNED: The p.V37I protein was localized at the plasma membrane, but failed to effectively transport intercellular propidium iodide or Ca2+ efficiently, indicating impairment of both biochemical and ionic coupling. The presence of GJB2 p.V37I appeared to increase the sensitivity of cells to H2O2 treatment. In contrast, the known variant c.299-300delAT protein was not transported to the cell membrane and could not form gap junctions, instead being confined to the cytoplasm. Ionic and biochemical coupling was defective in c.299-300delAT-transfected cells.
UNASSIGNED: The p.V37I and c.299-300delAT GJB2 mutations resulted in deficient gap junction-mediated coupling. Environmental factors may impact the functional consequences of GJB2 p.V37I. These results may inspire the development of molecular therapies targeting GJB2 mutations for hearing loss.

The article investigates how socioeconomic background affects noise annoyance caused by residential road traffic in urban areas. It is argued that the effects of socioeconomic variables (migration background, education, and income) on noise annoyance tend to be underestimated because these effects are mainly indirect. We specify three indirect pathways. (1) A \"noise exposure path\" assumes that less privileged households are exposed to a higher level of noise and therefore experience stronger annoyance. (2) A \"housing attributes path\" argues that less privileged households can shield themselves less effectively from noise due to unfavorable housing conditions and that this contributes to annoyance. (3) Conversely, an \"environmental susceptibility path\" proposes that less privileged people are less concerned about the environment and have a lower noise sensitivity, and that this reduces their noise annoyance. Our analyses rest on a study carried out in four European cities (Mainz and Hanover in Germany, Bern and Zurich in Switzerland), and the results support the empirical validity of the three indirect pathways.

Cognitive reserve reflects the brain\'s intrinsic adaptive capacity against the neurodegenerative effects of aging. The maintenance or enhancement of the brain\'s cognitive reserve plays a crucial role in mitigating the severity of pathologies associated with aging. A new movement, social prescribing, which focuses on prescribing lifestyle activities as a treatment for patients, is growing in popularity as a solution against aging pathologies. However, few studies have demonstrated a clear impact of lifestyle activities on individual cognitive health, outside of floor and ceiling effects. Understanding who benefits from which lifestyle factors remains unclear. Here, we investigated the potential effects of lifestyle activities on individuals\' cognitive health from more than 3,530 older adults using a stratification method and advanced analysis technique. Our stratification methods allowed us to observe a new result: older adults who had relatively average cognitive scores were not impacted by lifestyle factors. By comparison, older adults with very high or very low cognitive scores were highly impacted by lifestyle factors. These findings expand the orchid and dandelion theory to the aging field, regarding the biological sensitivity of individuals to harmful and protective environmental effects. Our discoveries demonstrate the role of individual differences in the aging process and its importance for social prescribing programs.

While urban greenspace is increasingly recognized as important to mental health, its role in substance use is understudied. This exploratory study investigates the interaction of greenspace with peer network health, sex, and executive function (EF) in models of substance use among a sample of disadvantaged, urban youth. Adolescents and their parents were recruited from a hospital in the mid-Atlantic region of the U.S. Residential greenspace at the streetscape level was derived from analysis of Google Street View imagery. Logistic regression models were used to test the moderating effect of greenspace on the association between peer network health and substance use, as well as additional moderating effects of sex and EF. The significant negative association of peer network health with substance use occurred only among youth residing in high greenspace environments, a moderating effect which was stronger among youth with high EF deficit. The moderating effect of greenspace did not differ between girls and boys. Greenspace may play an important role in moderating peer influences on substance use among disadvantaged, urban adolescents, and such moderation may differ according to an individual\'s level of EF. This research provides evidence of differences in environmental susceptibility regarding contextual mechanisms of substance use among youth, and it informs the development of targeted substance use interventions that leverage social and environmental influences on adolescent substance use.

Large fires are the most important disturbances at landscape-level due to their ecological and socioeconomic impacts. This study aimed to develop an approach for the assessment of the socio-economic landscape susceptibility to fire. Our methodology focuses on the integration of economic components of landscape management based on contingent valuation method (CVM) and net-value change (NVC). This former component has been estimated using depreciation rates or changes on the number of arrivals to different natural protected areas after a large fire occurrence. Landscape susceptibility concept has been motivated by the need to assist fire prevention programs and environmental management. There was a remarkable variation in annual economic value attributed to each protected area based on the CVM scenario, ranging from 40,189-46,887$/year (\"Tolhuaca National Park\") to 241,000-341,953$/year (\"Conguillio National Park\"). We added landscape susceptibility using depreciation rates or tourist arrival decrease which varied from 2.04% (low fire intensity in \"Tolhuaca National Park\") to 76.67% (high fire intensity in \"Conguillio National Park\"). The integration of this approach and future studies about vegetation resilience should seek management strategies to increase economic efficiency in the fire prevention activities.