Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma

The discoidin domain receptors, (DDR)1 and DDR2, have been linked to numerous human cancers. We sought to determine expression levels of DDRs in human lung cancer, investigate prognostic determinates, and determine the prevalence of recently reported mutations in these receptor tyrosine kinases. Tumour samples from 146 non-small cell lung carcinoma (NSCLC) patients were analysed for relative expression of DDR1 and DDR2 using quantitative real-time PCR (qRT-PCR). An additional 23 matched tumour and normal tissues were tested for differential expression of DDR1 and DDR2, and previously reported somatic mutations. Discoidin domain receptor 1 was found to be significantly upregulated by 2.15-fold (P=0.0005) and DDR2 significantly downregulated to an equivalent extent (P=0.0001) in tumour vs normal lung tissue. Discoidin domain receptor 2 expression was not predictive for patient survival; however, DDR1 expression was significantly associated with overall (hazard ratio (HR) 0.43, 95% CI=0.22–0.83, P=0.014) and disease-free survival (HR=0.56, 95% CI=0.33–0.94, P=0.029). Multivariate analysis revealed DDR1 is an independent favourable predictor for prognosis independent of tumour differentiation, stage, histology, and patient age. However, contrary to previous work, we did not observe DDR mutations. We conclude that whereas altered expression of DDRs may contribute to malignant progression of NSCLC, it is unlikely that this results from mutations in the DDR1 and DDR2 genes that we investigated

Risk of high blood pressure in salt workers working near salt milling plants: A cross-sectional and interventional study

BACKGROUND: Workers working close to salt milling plants may inhale salt particles floating in the air, leading to a rise in plasma sodium, which, in turn, may increase the blood pressure and the risk of hypertension. METHODS: To test the above hypothesis, occupational health check-up camps were organized near salt manufacturing units and all workers were invited for a free health examination. The workers who worked with dry salt in the vicinity of salt milling plants were defined as "non-brine workers," while those working in brine pans located far away from milling plants were defined as "brine workers." Blood pressure (BP) was measured during each clinical examination. In all, 474 non-brine workers and 284 brine workers were studied. RESULTS: Mean systolic blood pressure of non-brine workers (122.1 ± 13.3 mm Hg) was significantly higher than that of brine workers (118.8 ± 12.8 mm Hg, p < 0.01). Mean diastolic blood pressure of non-brine workers (71.5 ± 10.4 mm Hg) was significantly higher than that of brine workers (69.7 ± 9.4 mm Hg, p = 0.02). The prevalence of hypertension was significantly higher in non-brine workers (12.2%) than in brine workers (7.0%, p = 0.02). Nineteen salt workers were monitored while they used face masks and spectacles, for six days. Systolic, as well as diastolic, blood pressure of these workers began declining on the third day and continued to decline on the fourth day, but remained stationary up to the sixth day. The concentration of salt particles in the breathing zone of these workers was 376 mg/m(3 )air. CONCLUSION: Inhalation of salt particles in non-brine workers may be an occupational cause of increased blood pressure

Indirect Effects of Wnt3a/β-Catenin Signalling Support Mouse Spermatogonial Stem Cells In Vitro

Proper regulation of spermatogonial stem cells (SSCs) is crucial for sustaining steady-state spermatogenesis. Previous work has identified several paracrine factors involved in this regulation, in particular, glial cell line-derived neurotrophic factor and fibroblast growth factor 2, which promote long-term SSC self-renewal. Using a SSC culture system, we have recently reported that Wnt5a promotes SSC self-renewal through a β-catenin-independent Wnt mechanism whereas the β-catenin-dependent Wnt pathway is not active in SSCs. In contrast, another study has reported that Wnt3a promotes SSC self-renewal through the β-catenin-dependent pathway, as it can stimulate the proliferation of a spermatogonia cell line. To reconcile these two contradictory reports, we assessed Wnt3a effects on SSCs and progenitor cells, rather than a cell line, in vitro. We observed that Wnt3a induced β-catenin-dependent signalling in a large subset of germ cells and increased SSC numbers. However, further investigation revealed that cell populations with greater β-catenin-signalling activity contained fewer SSCs. The increased maintenance of SSCs by Wnt3a coincided with more active cell cycling and the formation of germ cell aggregates, or communities, under feeder-free conditions. Therefore, the results of this study suggest that Wnt3a selectively stimulates proliferation of progenitors that are committed to differentiation or are in the process of exiting the SSC state, leading to enhanced formation of germ cell communities, which indirectly support SSCs and act as an in vitro niche

Metabolic syndrome is associated with change in subclinical arterial stiffness - A community-based Taichung Community Health Study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the effect of MetS on arterial stiffness in a longitudinal study.</p> <p>Methods</p> <p>Brachial-ankle pulse wave velocity (baPWV), a measurement interpreted as arterial stiffness, was measured in 1518 community-dwelling persons at baseline and re-examined within a mean follow-up period of 3 years. Multivariate linear regression with generalized estimating equations (GEE) were used to examine the longitudinal relationship between MetS and its individual components and baPWV, while multivariate logistic regression with GEE was used to examine the longitudinal relationship between MetS and its individual components and the high risk group with arterial stiffness.</p> <p>Results</p> <p>Subjects with MetS showed significantly greater baPWV at the end point than those without MetS, after adjusting for age, gender, education, hypertension medication and mean arterial pressure (MAP). MetS was associated with the top quartile of baPWV (the high-risk group of arterial stiffness, adjusted odds ratio [95% confidence interval] 1.52 [1.21-1.90]), and a significant linear trend of risk for the number of components of MetS was found (p for trend < 0.05). In further considering the individual MetS component, elevated blood pressure and fasting glucose significantly predicted a high risk of arterial stiffness (adjusted OR [95% CI] 3.72 [2.81-4.93] and 1.35 [1.08-1.68], respectively).</p> <p>Conclusions</p> <p>MetS affects the subject's progression to arterial stiffness. Arterial stiffness increased as the number of MetS components increased. Management of MetS is important for preventing the progression to advanced arterial stiffness.</p

Breastfeeding and maternal cardiovascular risk factors and outcomes:A systematic review

There is growing evidence that breastfeeding has short- and long-term cardiovascular health benefits for mothers. The objectives of this systematic review were to examine the association between breastfeeding and maternal cardiovascular risk factors and outcomes that have not previously been synthesized systematically, including metabolic syndrome, hypertension and cardiovascular disease.This systematic review meets PRISMA guidelines. The MEDLINE, EMBASE and CINAHL databases were systematically searched for relevant publications of any study design from the earliest publication date to March 2016. The reference lists from selected articles were reviewed, and forward and backward referencing were conducted. The methodological quality of reviewed articles was appraised using validated checklists. Twenty-one studies meeting the inclusion criteria examined the association between self-reported breastfeeding and one or more of the following outcomes: metabolic syndrome/metabolic risk factors (n = 10), inflammatory markers/adipokines (n = 2), hypertension (n = 7), subclinical cardiovascular disease (n = 2), prevalence/incidence of cardiovascular disease (n = 3) and cardiovascular disease mortality (n = 2). Overall, 19 studies (10 cross-sectional/retrospective, 9 prospective) reported significant protective effects of breastfeeding, nine studies (3 cross-sectional/retrospective, 5 prospective, 1 cluster randomized controlled trial) reported non-significant findings and none reported detrimental effects of breastfeeding. In most studies reporting significant associations, breastfeeding remained associated with both short- and long-term maternal cardiovascular health risk factors/outcomes, even after covariate adjustment. Findings from several studies suggested that the effects of breastfeeding may diminish with age and a dose-response association between breastfeeding and several metabolic risk factors. However, further longitudinal studies, including studies that measure exclusive breastfeeding, are needed to confirm these findings.The evidence from this review suggests that breastfeeding is associated with cardiovascular health benefits. However, results should be interpreted with caution as the evidence gathered for each individual outcome was limited by the small number of observational studies. Additional prospective studies are needed.CRD42016047766

Identification of a mitotic recombination hotspot on chromosome III of the asexual fungus Aspergillus niger and its possible correlation elevated basal transcription

Genetic recombination is an important tool in strain breeding in many organisms. We studied the possibilities of mitotic recombination in strain breeding of the asexual fungus Aspergillus niger. By identifying genes that complemented mapped auxotrophic mutations, the physical map was compared to the genetic map of chromosome III using the genome sequence. In a program to construct a chromosome III-specific marker strain by selecting mitotic crossing-over in diploids, a mitotic recombination hotspot was identified. Analysis of the mitotic recombination hotspot revealed some physical features, elevated basal transcription and a possible correlation with purine stretches

Using a community-based definition of poverty for targeting poor households for premium subsidies in the context of a community health insurance in Burkina Faso

Background: One of the biggest challenges in subsidizing premiums of poor households for community health insurance is the identification and selection of these households. Generally, poverty assessments in developing countries are based on monetary terms. The household is regarded as poor if its income or consumption is lower than a predefined poverty cut-off. These measures fail to recognize the multi-dimensional character of poverty, ignoring community members? perception and understanding of poverty, leaving them voiceless and powerless in the identification process. Realizing this, the steering committee of Nouna's health insurance devised a method to involve community members to better define `perceived? poverty, using this as a key element for the poor selection. The community-identified poor were then used to effectively target premium subsidies for the insurance scheme. Methods: The study was conducted in the Nouna's Health District located in northwest Burkina Faso. Participants in each village were selected to take part in focus-group discussions (FGD) organized in 41 villages and 7 sectors of Nouna's town to discuss criteria and perceptions of poverty. The discussions were audio recorded, transcribed and analyzed in French using the software NVivo 9. Results: From the FGD on poverty and the subjective definitions and perceptions of the community members, we found that poverty was mainly seen as scarcity of basic needs, vulnerability, deprivation of capacities, powerlessness, voicelessness, indecent living conditions, and absence of social capital and community networks for support in times of need. Criteria and poverty groups as described by community members can be used to identify poor who can then be targeted for subsidies. Conclusion: Policies targeting the poorest require the establishment of effective selection strategies. These policies are well-conditioned by proper identification of the poor people. Community perceptions and criteria of poverty are grounded in reality, to better appreciate the issue. It is crucial to take these perceptions into account in undertaking community development actions which target the poor. For most community-based health insurance schemes with limited financial resources, using a community-based definition of poverty in the targeting of the poorest might be a less costly alternative

A reappraisal of the impact of dairy foods and milk fat on cardiovascular disease risk

Background This review provides a reappraisal of the potential effects of dairy foods, including dairy fats, on cardiovascular disease (CVD)/coronary heart disease (CHD) risk. Commodities and foods containing saturated fats are of particular focus as current public dietary recommendations are directed toward reducing the intake of saturated fats as a means to improve the overall health of the population. A conference of scientists from different perspectives of dietary fat and health was convened in order to consider the scientific basis for these recommendations. Aims This review and summary of the conference focus on four key areas related to the biology of dairy foods and fats and their potential impact on human health: (a) the effect of dairy foods on CVD in prospective cohort studies; (b) the impact of dairy fat on plasma lipid risk factors for CVD; (c) the effects of dairy fat on non-lipid risk factors for CVD; and (d) the role of dairy products as essential contributors of micronutrients in reference food patterns for the elderly. Conclusions Despite the contribution of dairy products to the saturated fatty acid composition of the diet, and given the diversity of dairy foods of widely differing composition, there is no clear evidence that dairy food consumption is consistently associated with a higher risk of CVD. Thus, recommendations to reduce dairy food consumption irrespective of the nature of the dairy product should be made with cautionJ. Bruce German, Robert A. Gibson, Ronald M. Krauss, Paul Nestel, Benoît Lamarche, Wija A. van Staveren, Jan M. Steijns, Lisette C. P. G. M. de Groot, Adam L. Lock and Frédéric Destaillat