VA Palo Alto Healthcare System

About: VA Palo Alto Healthcare System is a healthcare organization based out in Palo Alto, California, United States. It is known for research contribution in the topics: Population & Health care. The organization has 2548 authors who have published 4605 publications receiving 209938 citations.

An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease

Abstract: Epigenetic biomarkers of aging (the “epigenetic clock”) have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors. We analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue. Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.

Assessment of Clinical Performance during Simulated Crises Using Both Technical and Behavioral Ratings

Abstract: BackgroundTechniques are needed to assess anesthesiologists' performance when responding to critical events. Patient simulators allow presentation of similar crisis situations to different clinicians. This study evaluated ratings of performance, and the interrater variability of the ratings, made by

SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation

Abstract: Sirtuin proteins regulate diverse cellular pathways that influence genomic stability, metabolism and ageing. SIRT7 is a mammalian sirtuin whose biochemical activity, molecular targets and physiological functions have been unclear. Here we show that SIRT7 is an NAD(+)-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase that stabilizes the transformed state of cancer cells. Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression. The spectrum of SIRT7 target genes is defined in part by its interaction with the cancer-associated E26 transformed specific (ETS) transcription factor ELK4, and comprises numerous genes with links to tumour suppression. Notably, selective hypoacetylation of H3K18Ac has been linked to oncogenic transformation, and in patients is associated with aggressive tumour phenotypes and poor prognosis. We find that deacetylation of H3K18Ac by SIRT7 is necessary for maintaining essential features of human cancer cells, including anchorage-independent growth and escape from contact inhibition. Moreover, SIRT7 is necessary for a global hypoacetylation of H3K18Ac associated with cellular transformation by the viral oncoprotein E1A. Finally, SIRT7 depletion markedly reduces the tumorigenicity of human cancer cell xenografts in mice. Together, our work establishes SIRT7 as a highly selective H3K18Ac deacetylase and demonstrates a pivotal role for SIRT7 in chromatin regulation, cellular transformation programs and tumour formation in vivo.

A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis.

Abstract: Factors that determine a post-menopausal woman's bone mineral density (BMD) include her mass at the time of skeletal maturity (peak BMD), menopause and the rate of loss she experiences as she ages. Understanding the relative influence of each of these factors may help identify important preventive treatments and provide new ways to identify women at risk for osteoporosis. In this analysis we utilize a computer model of the bone remodeling process to predict the relative influences of peak BMD, menopause and age-related bone loss on the development of osteoporosis. The delay in the onset of osteoporosis (defined as BMD <2.5 SD from the young adult mean) caused by modifying peak BMD, age-related bone loss or the age at menopause is quantified. A 10% increase in peak BMD is predicted to delay the development of osteoporosis by 13 years, while a 10% change in the age at menopause or the rate of non-menopausal bone loss is predicted to delay osteoporosis by approximately 2 years, suggesting that peak BMD may be the single most important factor in the development of osteoporosis.