Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNAs with radioactive and non-radioactive in situ hybridization techniques: diagnosis of trisomy 18 with probe L1.84

The localization of chromosome 18 in human interphase nuclei is demonstrated by use of radioactive and nonradioactive in situ hybridization techniques with a DNA clone designated L1.84. This clone represents a distinct subpopulation of the repetitive human alphoid DNA family, located in the centric region of chromosome 18. Under stringent hybridization conditions hybridization of L1.84 is restricted to chromosome 18 and reflects the number of these chromosomes present in the nuclei, namely, two in normal diploid human cells and three in nuclei from cells with trisomy 18. Under conditions of low stringency, cross-hybridization with other subpopulations of the alphoid DNA family occurs in the centromeric regions of the whole chromosome complement, and numerous hybridization sites are detected over interphase nuclei. Detection of chromosome-specific target DNAs by non-radioactive in situ hybridization with appropriate DNA probes cloned from individual chromosomal subregions presents a rapid means of identifying directly numerical or even structural chromosome aberrations in the interphase nucleus. Present limitations and future applications of interphase cytogenetics are discussed

Early dyspnoea relief in acute heart failure: prevalence, association with mortality, and effect of rolofylline in the PROTECT Study

AIMS: Dyspnoea and pulmonary and/or peripheral congestion are the most frequent manifestations of acute heart failure (AHF) and are important targets for therapy. We have assessed changes in dyspnoea, their relationship with mortality, and the effects of the adenosine A1 receptor antagonist rolofylline on these endpoints in patients enrolled in the PROTECT trial. METHODS AND RESULTS: PROTECT was a prospective, double-blind, placebo-controlled study assessing the effect of rolofylline in patients hospitalized for AHF with dyspnoea, fluid overload, increased plasma natriuretic peptides, and mild-to-moderate renal dysfunction. Early dyspnoea relief, prospectively defined as moderately or markedly better dyspnoea at both 24 and 48 h after the start of study drug administration, occurred in 49.8% of the patients. Early dyspnoea relief was associated with greater weight loss and with reduced mortality at Days 14 and 30 [hazard ratio (HR) 0.28, 95% confidence interval (CI): 0.15, 0.50; and 0.35, 95% CI: 0.22, 0.55, respectively]. Rolofylline administration was associated with an increase in the proportion of patients showing early dyspnoea relief (HR 1.30; 95% CI: 1.08, 1.57) and with a numerically lower mortality at 14 and 30 days, largely driven by the mortality due to HF [at 30 days, HR (95% CI, P-value): 0.65 (0.38-1.10, P= 0.107)]. Rolofylline did not reduce episodes of in-hospital worsening HF or post-discharge re-admissions, nor did it improve survival at 60 or 180 days. CONCLUSION: The present analysis from PROTECT demonstrated that more weight loss was associated with early dyspnoea relief and reduced short-term mortality

Consumption of alcohol, cigarettes and illegal substances among physicians and medical students in Brandenburg and Saxony (Germany)

<p>Abstract</p> <p>Background</p> <p>Patients regard health care professionals as role models for leading a healthy lifestyle. Health care professionals' own behaviour and attitudes concerning healthy lifestyle have an influence in counselling patients. The aim of this study was to assess consumption of alcohol, cigarettes and illegal substances among physicians and medical students in two German states: Brandenburg and Saxony.</p> <p>Methods</p> <p>Socio-demographic data and individual risk behaviour was collected by an anonymous self-administered questionnaire. Physicians were approached via mail and students were recruited during tutorials or lectures.</p> <p>Results</p> <p>41.6% of physicians and 60.9% of medical students responded to the questionnaire; more than 50% of the respondents in both groups were females. The majority of respondents consumed alcohol at least once per week; median daily alcohol consumption ranged from 3.88 g/d (female medical students) to 12.6 g/d (male physicians). A significantly higher percentage of men (p < 0.05) reported hazardous or harmful drinking compared to women. A quarter of all participating physicians and one third of all students indicated unhealthy alcohol-drinking behaviour. The majority of physicians (85.7%) and medical students (78.5%) were non-smokers. Both groups contained significantly more female non-smokers (p < 0.05). Use of illegal substances was considerably lower in physicians (5.1%) than medical students (33.0%). Male students indicated a significantly (p < 0.001) higher level of illegal drug-use compared to female students.</p> <p>Conclusion</p> <p>More than one third of the medical students and health care professionals showed problematic alcohol-drinking behaviour. Although the proportion of non-smokers in the investigated sample was higher than in the general population, when compared to the general population, medical students between 18-24 reported higher consumption of illegal substances.</p> <p>These results indicate that methods for educating and promoting healthy lifestyle, particularly with respect to excessive alcohol consumption, tobacco use and abuse of illegal drugs should be considered.</p

Conversion in Turkish : an overview

This paper presents an overview of possible cases of conversion in Turkish. I argue that apparent cases of conversion between nouns and adjectives are cases of syntactic transposition, and apparent cases of conversion between nouns/adjectives and verbs are end products of phonological changes in the history of the language, which resulted in pairs of lexemes that are formally identical synchronically, but not historically. This does not mean that no cases of morphological conversion can be traced in the language. I will present two cases of secondary word-class conversion from derived, inflected and uninflected words to toponyms which might be taken as instances of morphological conversion or derivation by zero-affixation

Prevalence of lipid abnormalities before and after introduction of lipid modifying therapy among Swedish patients with dyslipidemia (PRIMULA)

<p>Abstract</p> <p>Background</p> <p>Data on the prevalence of dyslipidemia and attainment of goal/normal lipid levels in a Swedish population are scarce. The objective of this study is to estimate the prevalence of dyslipidemia and attainment of goal/normal lipid levels in patients treated with lipid modifying therapy (LMT).</p> <p>Methods</p> <p>This longitudinal retrospective observational study covers time periods before and after treatment. Data were collected from 1994-2007 electronic patient records in public primary healthcare centers in Uppsala County, Sweden. Patients were included if they had been treated with LMT and had at least one lipid abnormality indicating dyslipidemia and if complete lipid profile data were available. Thresholds levels for lipids were defined as per Swedish guidelines.</p> <p>Results</p> <p>Among 5,424 patients included, at baseline, the prevalence of dyslipidemia (≥1 lipid abnormality) was by definition 100%, while this figure was 82% at follow-up. At baseline, 60% had elevated low-density lipoprotein (LDL-C) combined with low high-density lipoprotein (HDL-C) and/or elevated triglycerides (TG s), corresponding figure at follow-up was 36%. Low HDL-C and/or elevated TGs at follow-up remained at 69% for patients with type 2 diabetes mellitus (T2DM), 50% among patients with coronary heart disease (CHD) and 66% among patients with 10 year CHD risk >20%. Of the total sample, 40% attained goal levels of LDL-C and 18% attained goal/normal levels on all three lipid parameters.</p> <p>Conclusions</p> <p>Focusing therapy on LDL-C reduction allows 40% of patients to achieve LDL-C goal and helps reducing triglyceride levels. Almost 60% of patients experience persistent HDL-C and/or triglyceride abnormality independently of LDL-C levels and could be candidates for additional treatments.</p

The effectiveness of e-&amp; mHealth interventions to promote physical activity and healthy diets in developing countries: a systematic review

Background: Promoting physical activity and healthy eating is important to combat the unprecedented rise in NCDs in many developing countries. Using modern information-and communication technologies to deliver physical activity and diet interventions is particularly promising considering the increased proliferation of such technologies in many developing countries. The objective of this systematic review is to investigate the effectiveness of e-&amp; mHealth interventions to promote physical activity and healthy diets in developing countries.Methods: Major databases and grey literature sources were searched to retrieve studies that quantitatively examined the effectiveness of e-&amp; mHealth interventions on physical activity and diet outcomes in developing countries. Additional studies were retrieved through citation alerts and scientific social media allowing study inclusion until August 2016. The CONSORT checklist was used to assess the risk of bias of the included studies.Results: A total of 15 studies conducted in 13 developing countries in Europe, Africa, Latin-and South America and Asia were included in the review. The majority of studies enrolled adults who were healthy or at risk of diabetes or hypertension. The average intervention length was 6.4 months, and text messages and the Internet were the most frequently used intervention delivery channels. Risk of bias across the studies was moderate (55.7 % of the criteria fulfilled). Eleven studies reported significant positive effects of an e-&amp; mHealth intervention on physical activity and/or diet behaviour. Respectively, 50 % and 70 % of the interventions were effective in promoting physical activity and healthy diets.Conclusions: The majority of studies demonstrated that e-&amp; mHealth interventions were effective in promoting physical activity and healthy diets in developing countries. Future interventions should use more rigorous study designs, investigate the cost-effectiveness and reach of interventions, and focus on emerging technologies, such as smart phone apps and wearable activity trackers.Trial registration: The review protocol can be retrieved from the PROSPERO database (Registration ID: CRD42015029240)

Adiponectin Haploinsufficiency Promotes Mammary Tumor Development in MMTV-PyVT Mice by Modulation of Phosphatase and Tensin Homolog Activities

Background: Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive. Methodology/Principal Findings: In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT) transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K)/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN) activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1) and thioredoxin reductase (TrxR1) were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1. Conclusion: Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K/ Akt signalling pathway through a mechanism involving Trx1/TrxR1 redox regulations. © 2009 Lam et al.published_or_final_versio

Weight and mechanical performance optimization of blended composite wing panels using lamination parameters

In this paper, a lamination parameter-based approach to weight optimization of composite aircraft wing structures is addressed. It is a bi-level procedure where at the top level lamination parameters and numbers of plies of the pre-defined angles (0, 90, 45 and −45°) are used as design variables, the material volume is treated as an objective function to be minimized subject to the buckling, strength and ply percentage constraints. At the bottom level the optimum stacking sequence is obtained subject to the requirements on blending and preservation of mechanical properties. To ensure composite blending, a multi-stage optimization is performed by a permutation genetic algorithm aiming at matching the lamination parameters passed from the top level optimization as well as satisfying the layup rules. Two new additional criteria, the 90° ply angle jump index and the stack homogeneity index, are introduced to control the uniformity of the three ply angles (0, 90, 45 and −45) spread throughout the stack as well as improve the stack quality and mechanical performance by encouraging 45° angle change between neighbouring groups of plies. The results of the application of this approach are compared to published results to demonstrate the potential of the developed technique