Postsynaptic Cholinergic Control Of Cardiac Function In Aging

The present study using isolated constant flow-perfused heart from adult (8 month-old) and aged (26 month-old) Fischer 344 rats for the first time demonstrated a striking enhancement of the negative chronotropic, inotropic and coronary vasoconstriction responses of the aging heart to postsynaptic cholinergic stimulation.;The approaches used and the results demonstrated were the following. (i) Acetylcholinesterase activity measured by the method of Ellman et al (1961) declined significantly in the atria and ventricles of the aged compared to adult rats. (ii) No age-related difference was seen in muscarinic receptor number in the atria and ventricles as assessed by {dollar}\lbrack\sp3\rm H\rbrack QNB{dollar} binding, but the muscarinic receptor binding affinity for carbachol, a cholinergic agonist, was increased in the atria but not ventricles of aged compared to adult rats. (iii) The relative amount of {dollar}\rm Gi\alpha{dollar} protein measured by Western immunoblotting and ADP-ribosylation techniques was significantly greater in the atria and ventricles of the aged compared to adult rats. The fidelity of the signal transduction through muscarinic receptor-linked Gi protein, as judged from the guanine nucleotide-induced decrease in receptor affinity for carbachol, was unaltered with aging in atria and ventricles. (iv) It was found that aging was accompanied by (a) enhancement in carbachol-induced hyperpolarization of the resting membrane potential in atria but not ventricles and (b) more pronounced carbachol-induced shortening of the action potential duration measured at 50% of repolarization in the ventricles but not in the atria. (v) Aging did not alter the carbachol-induced prolongation of atrioventricular conduction time measured from electrocardiograms. All of the age-related differences mentioned above may contribute to the increased negative chronotropic and inotropic responses of the aged heart to cholinergic stimuli. The age-associated increase in the coronary vascular response to a cholinergic stimulus may be caused by a relatively greater influx of extracellular {dollar}\rm Ca\sp{lcub}2+{rcub},{dollar} since the age-related difference in the coronary vascular response was attenuated in the presence of verapamil, a calcium channel blocker. Neither impaired synthesis of endothelium-derived relaxing factor (EDRF) nor reduced sensitivity of coronary vascular smooth muscle to EDRF contributes to the enhanced coronary vasoconstrictive effect to cholinergic stimulation since there was no age-related difference in the L-NMMA-induced coronary vasoconstriction in the absence and presence of carbachol. The age-related increase in the coronary response was specific for the cholinergic receptor as the {dollar}\alpha{dollar}-adrenergic response of the coronary vasculature was not altered with aging.;In summary, the cholinergic response of the heart is increased in the aged compared to the adult rats. The mechanisms for the enhanced postsynaptic response is multi-factorial, and may be attributable to the age-related changes in acetylcholinesterase activity, characteristics of the muscarinic receptor, content of the Gi protein, and electrophysiological properties of the atria and ventricles. (Abstract shortened by UMI.

Improving Term Frequency Normalization for Multi-topical Documents, and Application to Language Modeling Approaches

Term frequency normalization is a serious issue since lengths of documents are various. Generally, documents become long due to two different reasons - verbosity and multi-topicality. First, verbosity means that the same topic is repeatedly mentioned by terms related to the topic, so that term frequency is more increased than the well-summarized one. Second, multi-topicality indicates that a document has a broad discussion of multi-topics, rather than single topic. Although these document characteristics should be differently handled, all previous methods of term frequency normalization have ignored these differences and have used a simplified length-driven approach which decreases the term frequency by only the length of a document, causing an unreasonable penalization. To attack this problem, we propose a novel TF normalization method which is a type of partially-axiomatic approach. We first formulate two formal constraints that the retrieval model should satisfy for documents having verbose and multi-topicality characteristic, respectively. Then, we modify language modeling approaches to better satisfy these two constraints, and derive novel smoothing methods. Experimental results show that the proposed method increases significantly the precision for keyword queries, and substantially improves MAP (Mean Average Precision) for verbose queries.Comment: 8 pages, conference paper, published in ECIR '0

Skill performance in Cardiopulmonary Resuscitation among Laypersons and health care professionals

Cardiopulmonary resuscitation (CPR) is the key determinant for survival from out-of-hospital cardiac arrest. The skill and ability of the rescuer to perform quality CPR are important to assure the success or failure of survival. This study aims to explore the differences and factors that affect performance of CPR skills, by taking into account demographic variations between the Health Care Professionals (HCP) and laypersons. A total of 144 responders were interviewed using a self-administered questionnaire and a skill evaluation checklist by two qualified instructors. HCP and laypersons groups report comparable skill retention in CPR but HCP shows better basic life support (BLS) knowledge. Results suggest female HCP has better BLS knowledge compared to male HCP and time length after first BLS course contributes to significant difference in BLS knowledge among laypersons. Laypersons who had attended refresher course have better CPR skill rentention compared to those who had not

Use staged reading to improve sentences reading skill in Chinese language teaching: qualitative research management

This study was to examine the effectiveness in improving the skills of reading sentences. Skills in reading sentences focus on teaching and learning Chinese. In the study, the samples were identified as non-Chinese students. They are among those who use or learn Chinese as a second language. The method used in this study is reading stages. The methodology of this study is qualitative. The study was conducted in one of Sekolah Jenis Kebangsaan Cina (SJKC) or Chinese National Type School in Lawas, Sarawak, Malaysia. The samples selected were 4 students who are studying in year one based on their results in the summative evaluation on the Chinese Language subject at this point. The research data will be collected and analyzed through observation, interviews, record reflections of researcher and also the supporting documents. Through the data obtained from the 3 cycles of studies, students can recognize available samples and pronounce of 5 simple words, 5 average difficult words and 5 difficult words with correct pronunciation. Samples students can also read at least two simple sentences, 1 average difficult sentence and 1 difficult sentence correctly, fluently and with the correct intonation

A Twin Study of Early-Childhood Asthma in Puerto Ricans

Background:The relative contributions of genetics and environment to asthma in Hispanics or to asthma in children younger than 3 years are not well understood.Objective:To examine the relative contributions of genetics and environment to early-childhood asthma by performing a longitudinal twin study of asthma in Puerto Rican children ≤3 years old.Methods:678 twin infants from the Puerto Rico Neo-Natal Twin Registry were assessed for asthma at age 1 year, with follow-up data obtained for 624 twins at age 3 years. Zygosity was determined by DNA microsatellite profiling. Structural equation modeling was performed for three phenotypes at ages 1 and 3 years: physician-diagnosed asthma, asthma medication use in the past year, and ≥1 hospitalization for asthma in the past year. Models were additionally adjusted for early-life environmental tobacco smoke exposure, sex, and age.Results:The prevalences of physician-diagnosed asthma, asthma medication use, and hospitalization for asthma were 11.6%, 10.8%, 4.9% at age 1 year, and 34.1%, 40.1%, and 8.5% at 3 years, respectively. Shared environmental effects contributed to the majority of variance in susceptibility to physician-diagnosed asthma and asthma medication use in the first year of life (84%-86%), while genetic effects drove variance in all phenotypes (45%-65%) at age 3 years. Early-life environmental tobacco smoke, sex, and age contributed to variance in susceptibility.Conclusion:Our longitudinal study in Puerto Rican twins demonstrates a changing contribution of shared environmental effects to liability for physician-diagnosed asthma and asthma medication use between ages 1 and 3 years. Early-life environmental tobacco smoke reduction could markedly reduce asthma morbidity in young Puerto Rican children. © 2013 Bunyavanich et al