Hypertension as an Underlying Factor in Heart Failure With Preserved Ejection Fraction

The unique pathophysiology of heart failure with a preserved ejection fraction (HF-PEF) and the involvement of hypertension in its development are only poorly understood. The upregulation of the renin-angiotensin-aldosterone system (RAAS) has been identified as a key pathologic pathway contributing to fibrosis, cardiomyocyte abnormalities, inflammation, and endothelial dysfunction, all of which have been implicated in the progression of hypertension to HF-PEF. In addition, pharmacologic inhibition of the RAAS has been shown in animal models of diastolic dysfunction and in clinical trials to reduce these deleterious processes and to improve diastolic function. Despite these data, clinical trials performed with RAAS inhibitors in patients with HF-PEF have failed to demonstrate morbidity and mortality benefits. To date, there is no proven effective therapy specifically for HF-PEF. The deleterious effects of hypertension on mechanisms underlying the development of HF-PEF underscore the importance of effective and early control of hypertension for the prevention of HF-PEF

Global expression changes resulting from loss of telomeric DNA in fission yeast

BACKGROUND: Schizosaccharomyces pombe cells lacking the catalytic subunit of telomerase (encoded by trt1(+)) lose telomeric DNA and enter crisis, but rare survivors arise with either circular or linear chromosomes. Survivors with linear chromosomes have normal growth rates and morphology, but those with circular chromosomes have growth defects and are enlarged. We report the global gene-expression response of S. pombe to loss of trt1(+). RESULTS: Survivors with linear chromosomes had expression profiles similar to cells with native telomeres, whereas survivors with circular chromosomes showed continued upregulation of core environmental stress response (CESR) genes. In addition, survivors with circular chromosomes had altered expression of 51 genes compared to survivors with linear chromosomes, providing an expression signature. S. pombe progressing through crisis displayed two waves of altered gene expression. One coincided with crisis and consisted of around 110 genes, 44% of which overlapped with the CESR. The second was synchronized with the emergence of survivors and consisted of a single class of open reading frames (ORFs) with homology both to RecQ helicases and to dh repeats at centromeres targeted for heterochromatin formation via an RNA interference (RNAi) mechanism. Accumulation of transcript from the ORF was found not only in trt1(- )cells, but also in dcr1(- )and ago1(- )RNAi mutants, suggesting that RNAi may control its expression. CONCLUSIONS: These results demonstrate a correlation between a state of cellular stress, short telomeres and growth defects in cells with circular chromosomes. A putative new RecQ helicase was expressed as survivors emerged and appears to be transcriptionally regulated by RNAi, suggesting that this mechanism operates at telomeres

Mental Illness and the Law of Contracts

The traditional and most important problem relative to mental illness and the contract is the situation created when mental illness exists at the time of agreement (the problem of contractual capacity). One principal result of mental illness at this time may be the avoidance of the contract by the mentally ill person. Since case law in this area is extensive, the major portion of the study is concerned with this problem (parts II, III and IV) and the effects of such incapacity throughout the remaining course of the contract. Mental illness occurring after agreement and at the time of performance of a party to a contract can also have important effects on the remainder of the contract, and these effects are discussed in part V. Finally, there can be a number of other effects caused by mental illness which occur after agreement but do not directly affect performance. These are discussed in part VI

Astronaut Health Participant Summary Application

The Longitudinal Study of Astronaut Health (LSAH) Participant Summary software captures data based on a custom information model designed to gather all relevant, discrete medical events for its study participants. This software provides a summarized view of the study participant s entire medical record. The manual collapsing of all the data in a participant s medical record into a summarized form eliminates redundancy, and allows for the capture of entire medical events. The coding tool could be incorporated into commercial electronic medical record software for use in areas like public health surveillance, hospital systems, clinics, and medical research programs

Microbial cells can cooperate to resist high-level chronic ionizing radiation

Understanding chronic ionizing radiation (CIR) effects is of utmost importance to protecting human health and the environment. Diverse bacteria and fungi inhabiting extremely radioactive waste and disaster sites (e.g. Hanford, Chernobyl, Fukushima) represent new targets of CIR research. We show that many microorganisms can grow under intense gamma-CIR dose rates of 13–126 Gy/h, with fungi identified as a particularly CIR-resistant group of eukaryotes: among 145 phylogenetically diverse strains tested, 78 grew under 36 Gy/h. Importantly, we demonstrate that CIR resistance can depend on cell concentration and that certain resistant microbial cells protect their neighbors (not only conspecifics, but even radiosensitive species from a different phylum), from high-level CIR. We apply a mechanistically-motivated mathematical model of CIR effects, based on accumulation/removal kinetics of reactive oxygen species (ROS) and antioxidants, in bacteria (3 Escherichia coli strains and Deinococcus radiodurans) and in fungi (Candida parapsilosis, Kazachstania exigua, Pichia kudriavzevii, Rhodotorula lysinophila, Saccharomyces cerevisiae, and Trichosporon mucoides). We also show that correlations between responses to CIR and acute ionizing radiation (AIR) among studied microorganisms are weak. For example, in D. radiodurans, the best molecular correlate for CIR resistance is the antioxidant enzyme catalase, which is dispensable for AIR resistance; and numerous CIR-resistant fungi are not AIR-resistant. Our experimental findings and quantitative modeling thus demonstrate the importance of investigating CIR responses directly, rather than extrapolating from AIR. Protection of radiosensitive cell-types by radioresistant ones under high-level CIR is a potentially important new tool for bioremediation of radioactive sites and development of CIR-resistant microbiota as radioprotectors

Enhanced Planning Review of the Salt Lake and Ogden Metropolitan Area

ISTEA significantly changed the law governing metropolitan transportation planning. In response to the changes introduced by ISTEA, FHWA and FTA issued revised planning regulations on October 28, 1993, setting new requirements for the transportation planning processes. The requirements are presented in 23 CFR Part 450 and 49 CFR Part 613, Statewide and Metropolitan Planning Final Rule. The Clean Air Act Amendments of 1990 (CAAA) also imposed rigorous new transportation planning requirements in metropolitan areas, particularly those that are designated nonattainment or maintenance areas for air quality. In support of the implementation of the revised regulations, FHW A and FTA jointly established a schedule of EPRs. The EPRs are intended to determine the impact of planning on transportation investment processes. The EPRs also provide a technical assessment of the transportation planning and programming processes, including consideration of the six focal points identified by the FHW A and FTA Administrators for certification. The six focal points are: Financial Constraint and Financial Planning, Major Investment Studies, Congestion Management Systems, the Planning Process, and Links to the Conformity Requirements of the Clean Air Act Amendments of 1990; the Public Involvement Process; and the IS TEA Fifteen Planning Factors. 1 Of equal importance, EPRs will provide a forum for dialogue and the exchange of information on perspectives and concerns related to IS TEA between FT A and FHW A headquarters and field staff, and state and local officials responsible for metropolitan area transportation planning. Additionally, EPRs will provide information for future long-term federal policy-making, including possible legislative and regulatory changes; identify national issues and trends; and document national case studies of best professional practice. This information will also be used to help identify how future federal technical assistance programs can best assist MPOs and other planning agencies in carrying out the requirements of ISTEA. Finally, EPRs are intended to support progress toward meeting ISTEA requirements