Inequalities in urban greenness and epigenetic aging: Different associations by race and neighborhood socioeconomic status.

Slower epigenetic aging is associated with exposure to green space (greenness); however, the longitudinal relationship has not been well studied, particularly in minority groups. We investigated the association between 20-year exposure to greenness [Normalized Difference Vegetation Index (NDVI)] and epigenetic aging in a large, biracial (Black/white), U.S. urban cohort. Using generalized estimating equations adjusted for individual and neighborhood socioeconomic characteristics, greater greenness was associated with slower epigenetic aging. Black participants had less surrounding greenness and an attenuated association between greenness and epigenetic aging [ßNDVI5km: -0.80, 95% confidence interval (CI): -4.75, 3.13 versus ßNDVI5km: -3.03, 95% CI: -5.63, -0.43 in white participants]. Participants in disadvantaged neighborhoods showed a stronger association between greenness and epigenetic aging (ßNDVI5km: -3.36, 95% CI: -6.65, -0.08 versus ßNDVI5km: -1.57, 95% CI: -4.12, 0.96 in less disadvantaged). In conclusion, we found a relationship between greenness and slower epigenetic aging, and different associations by social determinants of health such as race and neighborhood socioeconomic status.

Assessment of Virological Contributions to COVID-19 Outcomes in a Longitudinal Cohort of Hospitalized Adults.

BACKGROUND: While several demographic and clinical correlates of coronavirus disease 2019 (COVID-19) outcome have been identified, their relationship to virological and immunological parameters remains poorly defined. METHODS: To address this, we performed longitudinal collection of nasopharyngeal swabs and blood samples from a cohort of 58 hospitalized adults with COVID-19. Samples were assessed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, viral genotype, viral diversity, and antibody titer. Demographic and clinical information, including patient blood tests and several composite measures of disease severity, was extracted from electronic health records. RESULTS: Several factors, including male sex, higher age, higher body mass index, higher 4C Mortality score, and elevated lactate dehydrogenase levels, were associated with intensive care unit admission. Of all measured parameters, only the retrospectively calculated median Deterioration Index score was significantly associated with death. While quantitative polymerase chain reaction cycle threshold (Ct) values and genotype of SARS-CoV-2 were not significantly associated with outcome, Ct value did correlate positively with C-reactive protein levels and negatively with D-dimer, lymphocyte count, and antibody titer. Intrahost viral genetic diversity remained constant through the disease course and resulted in changes in viral genotype in some participants. CONCLUSIONS: Ultimately, these results suggest that worse outcomes are driven by immune dysfunction rather than by viral load and that SARS-CoV-2 evolution in hospital settings is relatively constant over time.

Fundamental Cardiovascular Research: Returns on Societal Investment: A Scientific Statement From the American Heart Association.

Recent decades have witnessed robust successes in conquering the acutely lethal manifestations of heart and vascular diseases. Many patients who previously would have died now survive. Lifesaving successes like these provide a tremendous and easily recognized benefit to individuals and society. Although cardiovascular mortality has declined, the devastating impact of chronic heart disease and comorbidities on quality of life and healthcare resources continues unabated. Future strides, extending those made in recent decades, will require continued research into mechanisms underlying disease prevention, pathogenesis, progression, and therapeutic intervention. However, severe financial constraints currently jeopardize these efforts. To chart a path for the future, this report analyzes the challenges and opportunities we face in continuing the battle against cardiovascular disease and highlights the return on societal investment afforded by fundamental cardiovascular research.

Drug discovery in renal disease--towards a more efficient framework.

The time and cost involved in bringing new drugs to the market hamper their approval. This problem is especially apparent in the case of renal diseases. Efficient drug research requires an a priori understanding of disease pathophysiology, target validation, rational and efficient drug discovery strategies and early testing of the physiological and pharmacological effects of the new agent in humans. Drug development initiated by academia benefits from international research networks and relies on internationally acceptable high-quality nonclinical data packages and bulk investigational drugs. Academics should, therefore, better understand pharmaceutical practice regulations and novel, efficient drug-development strategies. Many researchers remain unfamiliar with these areas and should collaborate with regulatory authorities to discover and validate surrogate markers for use in drug development, and to efficiently and effectively maximize the benefits and minimize the adverse effects of new drugs. The Japanese government and regulatory authorities have implemented a framework to encourage such collaborations; extension of this framework beyond its current reach is envisaged.