Cardiovascular Disease in Elders: Is It Inevitable?

Cardiovascular disease is the major cause of death and disability in America. The burden of cardiovascular disease is higher in elders than in younger populations, presumably because of life-long exposure to risk factors such as hypertension, smoking, abnormal blood lipids, lack of exercise, and/or obesity. Many assume that it is too late to attempt to modify risk factors in elders because behavior is so difficult to change. The purpose of this article is to argue that cardiovascular risk factor modification is effective in elders and should be vigorously pursued for the good of individuals, families, communities, and societies

Cognitive Impairment in Heart Failure: Issues of Measurement and Etiology

Background: Clinicians need easy methods of screening for cognitive impairment in patients with heart failure. If correlates of cognitive impairment could be identified, more patients with early cognitive impairment could be treated before the problem interfered with adherence to treatment. Objectives: To describe cognitive impairment in patients with heart failure, to explore the usefulness of 4 measures of cognitive impairment, and to assess correlates of cognitive impairment. Methods: A descriptive, correlational design was used. Four screening measures of cognition were assessed in 42 patients with heart failure: Commands subtest and Complex Ideational Material subtest of the Boston Diagnostic Aphasia Examination, Mini-Mental State Examination, and Draw-a-Clock Test. Cognitive impairment was defined as performance less than the standardized (T-score) cutoff point on at least 1 of the 4 measures. Possible correlates of cognitive impairment included age, education, hypotension, fluid overload (serum osmolality Results: Cognitive impairment was detected in 12 (28.6%) of 42 participants. The 4 screening tests varied in effectiveness, but the Draw-a-Clock Test indicated impairment in 50% of the 12 impaired patients. A summed standardized score for the 4 measures was not significantly associated with age, education, hypotension, fluid overload, or dehydration in this sample. Conclusions: Cognitive impairment is relatively common in patients with heart failure. The Draw-a-Clock Test was most useful in detecting cognitive impairment, although it cannot be used to detect problems with verbal learning or delayed recall and should not be used as the sole screening method for patients with heart failure. Correlates of cognitive impairment require further study

Conceptual Model of Comprehensive Research Metrics for Improved Human Health and Environment

Performance measurement predominantly consisted of near-term outputs measured through bibliometrics, but the recent focus is on accountability for investment based on long-term outcomes. Our objective is to build a logic model and associated metrics through which to measure the contribution of environmental health research programs to improvements in human health, the environment, and the economy. We developed a logic model that defines the components and linkages between extramural environmental health research grant programs and the outputs and outcomes related to health and social welfare, environmental quality and sustainability, economics, and quality of life, focusing on the environmental health research portfolio of the National Institute of Environmental Health Sciences (NIEHS) Division of Extramural Research and Training and delineates pathways for contributions by five types of institutional partners in the research process. The model is being applied to specific NIEHS research applications and the broader research community. We briefly discuss two examples and discuss the strengths and limits of outcome- based evaluation of research programs

Trimethylamine-N-Oxide, a Metabolite Associated with Atherosclerosis, Exhibits Complex Genetic and Dietary Regulation

SummaryCirculating trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis. We now examine genetic, dietary, and hormonal factors regulating TMAO levels. We demonstrate that two flavin mono-oxygenase family members, FMO1 and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to TMAO. Further, we show that FMO3 exhibits 10-fold higher specific activity than FMO1. FMO3 overexpression in mice significantly increases plasma TMAO levels while silencing FMO3 decreases TMAO levels. In both humans and mice, hepatic FMO3 expression is reduced in males compared to females. In mice, this reduction in FMO3 expression is due primarily to downregulation by androgens. FMO3 expression is induced by dietary bile acids by a mechanism that involves the farnesoid X receptor (FXR), a bile acid-activated nuclear receptor. Analysis of natural genetic variation among inbred strains of mice indicates that FMO3 and TMAO are significantly correlated, and TMAO levels explain 11% of the variation in atherosclerosis

Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized

The work of the audience: visual matrix methodology in museums

Visual matrix methodology has been designed for researching cultural imaginaries. It is an image-led, group-based method that creates a “third space” research setting to observe audience groups re-enacting lived experience of an event or process that takes place in the third space of a cultural setting. In this article the method is described through its use in relation to an art-science exhibition, Human + Future of the species, where three audience groups with investments in technology worked with exhibition material to achieve a complex, ambivalent state of mind regarding technological futures. The visual matrix has been designed to capture the affective and aesthetic quality of audience engagement in third space by showing what audiences do with what is presented to them. We argue that such methodologies are useful for museums as they grapple with their role as sites where citizens not only engage in dialogue with one another but actively re-work their imaginaries of the future

Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation

Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38; p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death-Summary Report

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada. METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory determination of death literature. Input from these sources drove drafting of actionable questions and Good Practice Statements, as defined by the Grading of Recommendations Assessment, Development, and Evaluation group. We performed additional literature reviews for all actionable questions. Evidence was assessed for quality using Grading of Recommendations Assessment, Development, and Evaluation and then formulated into evidence profiles that informed recommendations through the evidence-to-decision framework. Recommendations were revised through consensus among members of seven topic-specific working groups and finalized during meetings of working group leads and the planning committee. External review was provided by pediatric, critical care, and critical care nursing professional societies and patient partners. RESULTS: We generated 63 Good Practice Statements and seven Grading of Recommendations Assessment, Development, and Evaluation recommendations covering 1) ethics, consent, and withdrawal of life-sustaining therapy, 2) eligibility, 3) withdrawal of life-sustaining therapy practices, 4) ante and postmortem interventions, 5) death determination, 6) neonatal pediatric donation after circulatory determination of death, 7) cardiac and innovative pediatric donation after circulatory determination of death, and 8) implementation. For brevity, 48 Good Practice Statement and truncated justification are included in this summary report. The remaining recommendations, detailed methodology, full Grading of Recommendations Assessment, Development, and Evaluation tables, and expanded justifications are available in the full text report. CONCLUSIONS: This process showed that rigorous, transparent clinical practice guideline development is possible in the domain of pediatric deceased donation. Application of these recommendations will increase access to pediatric donation after circulatory determination of death across Canada and may serve as a model for future clinical practice guideline development in deceased donation

Plasma membrane-targeted PIN proteins drive shoot development in a moss.

BACKGROUND: Plant body plans arise by the activity of meristematic growing tips during development and radiated independently in the gametophyte (n) and sporophyte (2n) stages of the life cycle during evolution. Although auxin and its intercellular transport by PIN family efflux carriers are primary regulators of sporophytic shoot development in flowering plants, the extent of conservation in PIN function within the land plants and the mechanisms regulating bryophyte gametophytic shoot development are largely unknown. RESULTS: We have found that treating gametophytic shoots of the moss Physcomitrella patens with exogenous auxins and auxin transport inhibitors disrupts apical function and leaf development. Two plasma membrane-targeted PIN proteins are expressed in leafy shoots, and pin mutants resemble plants treated with auxins or auxin transport inhibitors. PIN-mediated auxin transport regulates apical cell function, leaf initiation, leaf shape, and shoot tropisms in moss gametophytes. pin mutant sporophytes are sometimes branched, reproducing a phenotype only previously seen in the fossil record and in rare natural moss variants. CONCLUSIONS: Our results show that PIN-mediated auxin transport is an ancient, conserved regulator of shoot development.C.J.H. is funded by a Royal Society University Research Fellowship, a Gatsby Charitable Foundation fellowship (GAT2962) and the BBSRC (BB/L00224811) and R.R. is funded by the Deutsche Forschungsgemeinschaft (SPP 1067, RE 837/6) and the Excellence Initiative of the German Federal and State Governments (EXC294).This is the final version. It was first published by Elsevier at http://www.cell.com/current-biology/abstract/S0960-9822%2814%2901217-2