Systematic Analysis of Gene Expression Differences between Left and Right Atria in Different Mouse Strains and in Human Atrial Tissue

Background: Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria. Methods: We compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery. Results: We identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGFb family, showed highest enrichment in right atrium. These differences were validated by RT-qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c+/2 atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c. Conclusions: Our study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining ‘‘leftness’’ in the atrium in adult murine and human hearts

Упрощенная система учета и налогообложения

Объём работы – 76 с., иллюстраций – 2, таблиц – 12, формул – 2, источников – 52. Актуальность выбранной темы исследования заключается в уникальности КПКГ, как некоммерческих организаций, подлежащих упрощенной системе налогообложения, несмотря на наличие в них кредиторской деятельности. Объектом исследования является кредитно-потребительский кооператив граждан «Традиция». Предмет исследования – упрощенная система налогообложения КПКГ. Цель ВКР – исследование сущности и практики применения упрощенной системы налогообложения потребительских кредитных кооперативов граждан на примере КПКГ «Традиция».Volume of work - 76, illustration -. 2, tables - 12, formulas - 2, sources - 52. The relevance of the chosen research topic is unique CCCC as non-profit organizations are subject to a simplified system of taxation, despite the presence of accounts activity. The object of this study is to credit and consumer cooperative citizens "Tradition". Subject of research - the simplified taxation system CCCC. The purpose of the WRC - study the nature and practice of application of the simplified tax system consumer credit cooperatives of citizens the example of CCCC "Tradition"

A new protein evaluation system for horse feed from literature data

Few data on apparent pre-caecal digestibility (APCD) of crude protein (CP) and particularly amino acids (AA) are available from studies with horses. Protein bound in cell walls (i.e. neutral detergent insoluble CP (NDICP)) is unlikely to be decomposed by digestive enzymes in the small intestine. In contrast the corresponding analytical fraction of neutral detergent soluble CP (NDSCP) (NDSCP = CP-NDICP) is likely to be available for auto-enzymatic digestion. A literature analysis on the relationship between NDICP/NDSCP and pre-caecal indigestible/digestible CP was carried out. There was a strong positive relationship between NDICP and pre-caecal indigestible CP, which suggests that NDICP can be used to estimate the part of protein that is not available for digestion in the small intestine. There was also a correlation between NDSCP and pre-caecal digestible protein. The slope of the linear regression line between NDICP and pre-caecal digestible CP was 0.9, suggesting an APCD of NDSCP of 90 %. Thus pre-caecal digestible CP may be predicted by multiplying NDSCP by 0.9. Because the literature identifies a similar AA profile in NDICP and NDSCP within a given feed the presented concept may preliminarily be transferred to AA. The proposed system can at any time be adapted to the scientific progress without altering its structure. Such adaptations would be necessary particularly when new knowledge exist on the distribution of AA onto NDICP/NDSCP, the APCD of individual AA from NDSCP, and the impact of feed processing and chewing on particle sizes and protein digestibility

A new protein evaluation system for horse feed from literature data

Few data on apparent pre-caecal digestibility (APCD) of crude protein (CP) and particularly amino acids (AA) are available from studies with horses. Protein bound in cell walls (i.e. neutral detergent insoluble CP (NDICP)) is unlikely to be decomposed by digestive enzymes in the small intestine. In contrast the corresponding analytical fraction of neutral detergent soluble CP (NDSCP) (NDSCP = CP-NDICP) is likely to be available for auto-enzymatic digestion. A literature analysis on the relationship between NDICP/NDSCP and pre-caecal indigestible/digestible CP was carried out. There was a strong positive relationship between NDICP and pre-caecal indigestible CP, which suggests that NDICP can be used to estimate the part of protein that is not available for digestion in the small intestine. There was also a correlation between NDSCP and pre-caecal digestible protein. The slope of the linear regression line between NDICP and pre-caecal digestible CP was 0.9, suggesting an APCD of NDSCP of 90 %. Thus pre-caecal digestible CP may be predicted by multiplying NDSCP by 0.9. Because the literature identifies a similar AA profile in NDICP and NDSCP within a given feed the presented concept may preliminarily be transferred to AA. The proposed system can at any time be adapted to the scientific progress without altering its structure. Such adaptations would be necessary particularly when new knowledge exist on the distribution of AA onto NDICP/NDSCP, the APCD of individual AA from NDSCP, and the impact of feed processing and chewing on particle sizes and protein digestibility

Can we improve outcomes in AF patients by early therapy?

Atrial fibrillation affects at least 1% of the population and causes marked society-wide morbidity and mortality. Current management of atrial fibrillation including antithrombotic therapy and management of concomitant conditions in all patients, rate control therapy in most patients, and rhythm control therapy in patients with severe atrial fibrillation-related symptoms can alleviate atrial fibrillation-related symptoms but can neither effectively prevent recurrent atrial fibrillation nor suppress atrial fibrillation-related complications. Hence, there is a need for better therapy of atrial fibrillation

Influence of the carbon and the titanium sublayers on the eletrophysical preporties of the thin film system ALN/SI

The carbon (C) and titanium (Ti) ions were implanted onto the surface of the silicon (Si), and the thin films of aluminum nitride (AlN) were prepared on Si(100) substrate by magnetron sputtering after the implantations. The compositions of these thin film systems were studied by optical microscopy and Raman spectroscopy, and the surface conductivity of those samples were measured. It was indicated that the implanted C and Ti ions did have made a difference to the electro physical properties of the systems AlN/Si

How often should we monitor for reliable detection of atrial fibrillation recurrence? Efficiency considerations and implications for study design

OBJECTIVE: Although atrial fibrillation (AF) recurrence is unpredictable in terms of onset and duration, current intermittent rhythm monitoring (IRM) diagnostic modalities are short-termed and discontinuous. The aim of the present study was to investigate the necessary IRM frequency required to reliably detect recurrence of various AF recurrence patterns. METHODS: The rhythm histories of 647 patients (mean AF burden: 12±22% of monitored time; 687 patient-years) with implantable continuous monitoring devices were reconstructed and analyzed. With the use of computationally intensive simulation, we evaluated the necessary IRM frequency to reliably detect AF recurrence of various AF phenotypes using IRM of various durations. RESULTS: The IRM frequency required for reliable AF detection depends on the amount and temporal aggregation of the AF recurrence (p<0.0001) as well as the duration of the IRM (p<0.001). Reliable detection (>95% sensitivity) of AF recurrence required higher IRM frequencies (>12 24-hour; >6 7-day; >4 14-day; >3 30-day IRM per year; p<0.0001) than currently recommended. Lower IRM frequencies will under-detect AF recurrence and introduce significant bias in the evaluation of therapeutic interventions. More frequent but of shorter duration, IRMs (24-hour) are significantly more time effective (sensitivity per monitored time) than a fewer number of longer IRM durations (p<0.0001). CONCLUSIONS: Reliable AF recurrence detection requires higher IRM frequencies than currently recommended. Current IRM frequency recommendations will fail to diagnose a significant proportion of patients. Shorter duration but more frequent IRM strategies are significantly more efficient than longer IRM durations. CLINICAL TRIAL REGISTRATION URL: Unique identifier: NCT00806689

Assessment of proximal outcomes of self-management programs : translation and psychometric evaluation of a German version of the Health Education Impact Questionnaire (heiQtm)

Purpose This paper describes the translation, cultural adaption, and psychometric evaluation of a German version of the Health Education Impact Questionnaire (heiQ&trade;), a widely used generic instrument assessing a wide range of proximal outcomes of self-management programs.Methods The translation was carried out according to international standards and included forward and backward translations. Comprehensibility and content validity were tested using cognitive interviews with 10 rehabilitation inpatients. Psychometric properties were examined in rehabilitation inpatients (n = 1,202) with a range of chronic conditions. Factorial validity was assessed using confirmatory factor analysis; concurrent validity was explored by correlations with comparator scales.Results The items of the German heiQ&trade; were well understood by rehabilitation inpatients. The structure of the eight heiQ&trade; scales was replicated after minor adjustment. heiQ&trade; scales had higher correlations with comparator scales with similar constructs, particularly mental health concepts than with physical health. Moreover, all heiQ&trade; scales differentiated between individuals across different levels of depression.Conclusion The German heiQ&trade; is comprehensible for German-speaking patients suffering from different types of chronic conditions; it assesses relevant outcomes of self-management programs in a reliable and valid manner. Further studies involving its practical application are warranted.<br /