Cellular FXIII in Human Macrophage-Derived Foam Cells.

Macrophages express the A subunit of coagulation factor XIII (FXIII-A), a transglutaminase which cross-links proteins through Nε-(γ-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque; they may stabilize the plaque by cross-linking structural proteins and they may become transformed into foam cells by accumulating oxidized LDL (oxLDL). The combination of oxLDL staining by Oil Red O and immunofluorescent staining for FXIII-A demonstrated that FXIII-A is retained during the transformation of cultured human macrophages into foam cells. ELISA and Western blotting techniques revealed that the transformation of macrophages into foam cells elevated the intracellular FXIII-A content. This phenomenon seems specific for macrophage-derived foam cells; the transformation of vascular smooth muscle cells into foam cells fails to induce a similar effect. FXIII-A containing macrophages are abundant in the atherosclerotic plaque and FXIII-A is also present in the extracellular compartment. The protein cross-linking activity of FXIII-A in the plaque was demonstrated using an antibody labeling the iso-peptide bonds. Cells showing combined staining for FXIII-A and oxLDL in tissue sections demonstrated that FXIII-A-containing macrophages within the atherosclerotic plaque are also transformed into foam cells. Such cells may contribute to the formation of lipid core and the plaque structurization.

The Effect of Activated FXIII, a Transglutaminase, on Vascular Smooth Muscle Cells.

Plasma factor XIII (pFXIII) is a heterotetramer of FXIII-A and FXIII-B subunits. The cellular form (cFXIII), a dimer of FXIII-A, is present in a number of cell types. Activated FXIII (FXIIIa), a transglutaminase, plays an important role in clot stabilization, wound healing, angiogenesis and maintenance of pregnancy. It has a direct effect on vascular endothelial cells and fibroblasts, which have been implicated in the development of atherosclerotic plaques. Our aim was to explore the effect of FXIIIa on human aortic smooth muscle cells (HAoSMCs), another major cell type in the atherosclerotic plaque. Osteoblastic transformation induced by Pi and Ca2+ failed to elicit the expression of cFXIII in HAoSMCs. EZ4U, CCK-8 and CytoSelect Wound Healing assays were used to investigate cell proliferation and migration. The Sircol Collagen Assay Kit was used to monitor collagen secretion. Thrombospondin-1 (TSP-1) levels were measured by ELISA. Cell-associated TSP-1 was detected by the immunofluorescence technique. The TSP-1 mRNA level was estimated by RT-qPCR. Activated recombinant cFXIII (rFXIIIa) increased cell proliferation and collagen secretion. In parallel, a 67% decrease in TSP-1 concentration in the medium and a 2.5-fold increase in cells were observed. TSP-1 mRNA did not change significantly. These effects of FXIIIa might contribute to the pathogenesis of atherosclerotic plaques.

Cellular Factor XIII, a Transglutaminase in Human Corneal Keratocytes.

Cellular factor XIII (cFXIII, FXIII-A2), a transglutaminase, has been demonstrated in a few cell types. Its main function is to cross-link proteins by isopeptide bonds. Here, we investigated the presence of cFXIII in cells of human cornea. Tissue sections of the cornea were immunostained for FXIII-A in combination with staining for CD34 antigen or isopeptide cross-links. Isolated corneal keratocytes were also evaluated by immunofluorescent microscopy and flow cytometry. FXIII-A in the corneal stroma was quantified by Western blotting. FXIII-A mRNA was detected by RT-qPCR. The cornea of FXIII-A-deficient patients was evaluated by cornea topography. FXIII-A was detected in 68 ± 13% of CD34+ keratocytes. Their distribution in the corneal stroma was unequal; they were most abundant in the subepithelial tertile. cFXIII was of cytoplasmic localization. In the stroma, 3.64 ng cFXIII/mg protein was measured. The synthesis of cFXIII by keratocytes was confirmed by RT-qPCR. Isopeptide cross-links were detected above, but not within the corneal stroma. Slight abnormality of the cornea was detected in six out of nine FXIII-A-deficient patients. The presence of cFXIII in human keratocytes was established for the first time. cFXIII might be involved in maintaining the stability of the cornea and in the corneal wound healing process.

Spatial access to restaurants and grocery stores in relation to frequency of home cooking.

BACKGROUND: Little is known about the relation between the neighbourhood food environment and home cooking. We explored the independent and combined associations between residential neighbourhood spatial access to restaurants and grocery stores with home cooking in European adults. METHODS: Data of 5076 participants of the SPOTLIGHT study were collected across five European countries in 2014. Food retailers were classified into grocery stores (supermarkets and local food shops) and restaurants (full-service restaurants, fast food and take-away restaurants, café/bars). We used multinomial logistic regression models to test the associations between tertiles of spatial access to restaurants and spatial to access grocery stores and the outcome 'frequency of home cooking' categorized into 0-3; 4-5; and 6-7 days/week. Additive interaction analysis was used to test the combined association between access to grocery stores and to restaurants with home cooking. RESULTS: Mean age was 52.3 years; most participants were women (55.5%) and completed higher education (53.8%). Residents with highest access to restaurants had a reduced likelihood of home cooking 6-7 days/week (vs. 0-3 days/week) (relative risk ratio (RRR) 0.42; 95%CI = 0.23-0.76) when compared with lowest access to restaurants. No association was found for spatial access to grocery stores. Additive interaction analysis showed that individuals with medium access to grocery stores and highest access to restaurants had the lowest likelihood (RRR = 0.29, 95%CI = 0.10-0.84) of cooking 6-7 days/week when compared to individuals with lowest access to restaurants and highest access to grocery stores. CONCLUSION: Greater neighbourhood spatial access to restaurants was associated with lower frequency of home cooking, largely independent of access to grocery stores.

Exploring the cross-sectional association between outdoor recreational facilities and leisure-time physical activity: the role of usage and residential self-selection.

BACKGROUND: The availability of outdoor recreational facilities is associated with increased leisure-time physical activity (PA). We investigated how much of this association is attributable to selection effects, and explored whether usage of recreational facilities was an explanatory mechanism. METHODS: We analysed data from 5199 participants in the SPOTLIGHT survey residing in five European urban regions. Adults completed a survey and a Google Street View-based virtual audit was conducted to objectively measure the availability of outdoor recreational facilities in the residential neighbourhood. We used negative binomial GEE models to examine the association between objective and subjective availability of outdoor recreational facilities and leisure-time PA, and explored whether this association was attenuated after adjustment for socioeconomic status and preference for neighbourhoods with recreational facilities (as indicators of self-selection). We examined whether reported use of recreational facilities was associated with leisure-time PA (as explanatory mechanism), and summarized the most important motivations for (not) using recreational facilities. RESULTS: Subjective - but not objective - availability of outdoor recreational facilities was associated with higher levels of total leisure-time PA. After adjustment for self-selection (which attenuated the association by 25%), we found a 25% difference in weekly minutes of total leisure-time PA between individuals with and without self-reported availability of outdoor recreational facilities. For our study population, this translates to about 28 min per week. Participants who reported outdoor recreational facilities to be present but indicated not to use them (RR = 1.19, 95% CI = 1.03;1.22), and those reporting outdoor recreational facilities to be present and to use them (RR = 1.33, 95% CI = 1.22, 1.45) had higher levels of total leisure-time PA than those who reported outdoor recreational facilities not to be present. Proximity to outdoor recreational facilities was the most important motivation for use. CONCLUSION: The modest attenuation in the association between availability of outdoor recreational facilities and self-reported leisure-time PA suggests that individuals' higher activity levels may be due more to the perceived availability of outdoor recreational facilities than to self-selection. The use of these facilities seemed to be an important underlying mechanism, and proximity was the main motivator for using recreational facilities.

Lack of interest in physical activity - individual and environmental attributes in adults across Europe: The SPOTLIGHT project.

A considerable proportion of European adults report little or no interest in physical activity. Identifying individual-level and environmental-level characteristics of these individuals can help designing effective interventions and policies to promote physical activity. This cross-sectional study additionally explored associations between level of interest and physical activity, after controlling for other individual and environmental variables. Measures of objective and perceived features of the physical environment of residence, self-reported physical activity and other lifestyle behaviors, barriers towards physical activity, general health, and demographics were obtained from 5205 European adults participating in the 2014 online SPOTLIGHT survey. t-Tests, chi-square tests, and generalized estimating equations with negative binomial log-link function were conducted. Adults not interested in physical activity reported a higher BMI and a lower self-rated health, were less educated, and to a smaller extent female and less frequently employed. They were more prone to have less healthy eating habits, and to perceive more barriers towards physical activity. Only minor differences were observed in environmental attributes: the non-interested were slightly more likely to live in neighborhoods objectively characterized as less aesthetic and containing more destinations, and perceived as less functional, safe, and aesthetic. Even after controlling for other individual and environmental factors, interest in physical activity remained a significant correlate of physical activity, supporting the importance of this association. This study is among the first to describe characteristics of individuals with reduced interest in physical activity, suggesting that (lack of) interest is a robust correlate of physical activity in several personal and environmental conditions.

Exploring the mediating role of energy balance-related behaviours in the association between sleep duration and obesity in European adults. The SPOTLIGHT project.

Sleep restriction is a risk factor for weight gain and obesity. Few studies have formally investigated the mediating role of energy balance-related behaviours in the sleep - obesity association. The aim of this study was to explore the mediating role of physical activity, sedentary behaviours and dietary habits in the association of sleep duration with obesity in adults in five European urban regions. Data on self-reported sleep duration, energy balance-related behaviours, height and weight and other covariates were collected between February and September 2014 from participants to the SPOTLIGHT survey (N=5900, mean age 52years). Participants were recruited from 60 urban neighbourhoods in Belgium, France, Hungary, the Netherlands and the United Kingdom. Multilevel logistic regression analyses were used to assess the associations of sleep duration, energy balance-related behaviours and obesity and mediating effects were calculated using MacKinnon's product-of-coefficients method. Results indicated that a 1h increase in sleeping time was associated with a 14% lower likelihood of being obese (OR=0.86, 95%CI=0.80; 0.93). Only work-related sedentary behaviour was identified as a statistically significant mediator in the association between sleep duration and obesity for the total sample, and youngest and oldest age group. We did not find evidence for a mediating role of dietary habits and physical activities.

The mediating role of social capital in the association between neighbourhood income inequality and body mass index.

Background: Neighbourhood income inequality may contribute to differences in body weight. We explored whether neighbourhood social capital mediated the association of neighbourhood income inequality with individual body mass index (BMI). Methods: A total of 4126 adult participants from 48 neighbourhoods in France, Hungary, the Netherlands and the UK provided information on their levels of income, perceptions of neighbourhood social capital and BMI. Factor analysis of the 13-item social capital scale revealed two social capital constructs: social networks and social cohesion. Neighbourhood income inequality was defined as the ratio of the amount of income earned by the top 20% and the bottom 20% in a given neighbourhood. Two single mediation analyses-using multilevel linear regression analyses-with neighbourhood social networks and neighbourhood social cohesion as possible mediators-were conducted using MacKinnon's product-of-coefficients method, adjusted for age, gender, education and absolute household income. Results: Higher neighbourhood income inequality was associated with elevated levels of BMI and lower levels of neighbourhood social networks and neighbourhood social cohesion. High levels of neighbourhood social networks were associated with lower BMI. Results stratified by country demonstrate that social networks fully explained the association between income inequality and BMI in France and the Netherlands. Social cohesion was only a significant mediating variable for Dutch participants. Conclusion: The results suggest that in some European urban regions, neighbourhood social capital plays a large role in the association between neighbourhood income inequality and individual BMI.

Lifestyle correlates of overweight in adults: a hierarchical approach (the SPOTLIGHT project).

BACKGROUND: Obesity-related lifestyle behaviors usually co-exist but few studies have examined their simultaneous relation with body weight. This study aimed to identify the hierarchy of lifestyle-related behaviors associated with being overweight in adults, and to examine subgroups so identified. METHODS: Data were obtained from a cross-sectional survey conducted across 60 urban neighborhoods in 5 European urban regions between February and September 2014. Data on socio-demographics, physical activity, sedentary behaviors, eating habits, smoking, alcohol consumption, and sleep duration were collected by questionnaire. Participants also reported their weight and height. A recursive partitioning tree approach (CART) was applied to identify both main correlates of overweight and lifestyle subgroups. RESULTS: In 5295 adults, mean (SD) body mass index (BMI) was 25.2 (4.5) kg/m2, and 46.0 % were overweight (BMI ≥25 kg/m2). CART analysis showed that among all lifestyle-related behaviors examined, the first identified correlate was sitting time while watching television, followed by smoking status. Different combinations of lifestyle-related behaviors (prolonged daily television viewing, former smoking, short sleep, lower vegetable consumption, and lower physical activity) were associated with a higher likelihood of being overweight, revealing 10 subgroups. Members of four subgroups with overweight prevalence >50 % were mainly males, older adults, with lower education, and living in greener neighborhoods with low residential density. CONCLUSION: Sedentary behavior while watching television was identified as the most important correlate of being overweight. Delineating the hierarchy of correlates provides a better understanding of lifestyle-related behavior combinations which may assist in targeting preventative strategies aimed at tackling obesity.

Mediating role of energy-balance related behaviors in the association of neighborhood socio-economic status and residential area density with BMI: The SPOTLIGHT study.

OBJECTIVES: This study aimed to examine the mediating effects of energy-balance related behaviors on the association of neighborhood socio-economic status (SES) and neighborhood residential area density (RAD) with body mass index (BMI). METHODS: In total, 6037 adults from four neighborhood types (high SES/high RAD, high SES/low RAD, low SES/high RAD, and low SES/low RAD) in five Mid-European urban regions completed an online survey asking about their energy-balance related behaviors (physical activity [PA], sedentary behavior, and dietary behavior), determinants of these behaviors and their body weight and height. MacKinnon's product-of-coefficients test was used to assess mediating effects. RESULTS: Transport-related PA, leisure-time PA and vegetable intake seemed to mediate the association between neighborhood type and BMI. Residents from low SES/low RAD neighborhoods reported less transport-related PA, less leisure-time PA and less vegetable intake than high SES/high RAD residents, and these behaviors (i.e. transport-related PA, leisure-time PA and vegetable intake) were related to having a higher BMI. CONCLUSION: The association between neighborhood type and BMI can be explained, at least in part, by energy-balance related behaviors.

The associations between domain-specific sedentary behaviours and dietary habits in European adults: a cross-sectional analysis of the SPOTLIGHT survey.

BACKGROUND: Sedentary behaviour has been associated with obesity and related chronic diseases. Disentangling the nature of this association is complicated due to interactions with other lifestyle factors, such as dietary habits, yet limited research has investigated the relation between domain-specific sedentary behaviours and dietary habits in adults. The aim of this paper was to examine the association between domain-specific sedentary behaviours and dietary habits in adults and to test the moderating effect of age and gender on this association. METHODS: A total of 6,037 participants from five urban regions in Europe completed an online survey, of which 6,001 were included in the analyses. Multilevel mixed-effects logistic regression analyses were used to examine main associations and interaction effects. RESULTS: All domain-specific sedentary behaviours, except transport-related sitting time, were significantly related to dietary habits. In general, having a higher sitting time was related to having less healthy dietary habits, especially for television viewing. Gender did not moderate any of the relations, and age was only a significant moderator in the relation between other leisure sitting time and alcohol consumption. CONCLUSION: Domain-specific sitting behaviours were related to unhealthy dietary behaviours. However, the small effect sizes suggest that individual level behavioural interventions focusing on sedentary behaviour will not be sufficient to improve dietary habits. The fact that almost none of the associations were moderated by age or gender suggests that these associations, and possibly also the effects of interventions targeting both behaviours, may hold across age and gender groups.

The SPOTLIGHT virtual audit tool: a valid and reliable tool to assess obesogenic characteristics of the built environment.

BACKGROUND: A lack of physical activity and overconsumption of energy dense food is associated with overweight and obesity. The neighbourhood environment may stimulate or hinder the development and/or maintenance of a healthy lifestyle. To improve research on the obesogenicity of neighbourhood environments, reliable, valid and convenient assessment methods of potential obesogenic characteristics of neighbourhood environments are needed. This study examines the reliability and validity of the SPOTLIGHT-Virtual Audit Tool (S-VAT), which uses remote sensing techniques (Street View feature in Google Earth) for desk-based assessment of environmental obesogenicity. METHODS: A total of 128 street segments in four Dutch urban neighbourhoods - heterogeneous in socio-economic status and residential density - were assessed using the S-VAT. Environmental characteristics were categorised as walking related items, cycling related items, public transport, aesthetics, land use-mix, grocery stores, food outlets and physical activity facilities. To assess concordance of inter- and intra-observer reliability of the Street View feature in Google Earth, and validity scores with real life audits, percentage agreement and Cohen's Kappa (k) were calculated. RESULTS: Intra-observer reliability was high and ranged from 91.7% agreement (k = 0.654) to 100% agreement (k = 1.000) with an overall agreement of 96.4% (k = 0.848). Inter-observer reliability results ranged from substantial agreement 78.6% (k = 0.440) to high agreement, 99.2% (k = 0.579), with an overall agreement of 91.5% (k = 0.595). Criterion validity was substantial to high for most of the categories ranging from 87.3% agreement (k = 0.539) to 99.9% agreement (k = 0.887) with an overall score of 95.6% agreement (k = 0.747). CONCLUSION: These study results suggest that the S-VAT is a highly reliable and valid remote sensing tool to assess potential obesogenic environmental characteristics.

Diet quality as assessed by Healthy Eating Index-2015 among Hungarian Roma living in settlements of Northeast Hungary.

Inequalities in diet quality are increasingly reported, but such studies among Roma are scarce and challenging. Here we attempt to examine diet quality and adherence to food based dietary guidelines among Hungarian Roma (HR) ethnic minority living in segregated settlements while comparing a sample of Hungarian adults from the general population (HG). Data were obtained from a complex comparative health survey conducted in Northeast Hungary in 2018, including sociodemographic and physical examination data. Dietary data were collected using two non-consecutive 24-h dietary recalls. We assessed diet quality based on using a 13-component Healthy Eating Index-2015 (HEI-2015, range 0-100). Differences in median intakes of food and nutrients and HEI-2015 scores were evaluated by Mann-Whitney test or Kruskal-Wallis test. Quantile regression was used to adjust HEI-2015 scores for socioeconomic factors including age, sex, educational status, and perceived financial status. This analysis included 393 and 415 subjects, aged between 18 to 70 years, of HR and HG populations, respectively. Results showed overall low median HEI-2015 scores for both HR and HG, with significantly lower total score among HR participants (41.6, interquartile range (IQR): 39.5-42.8) compared to HG (47.2, IQR: 45.7-51.1). Scores for individual components, such as intake of fruits, greens and beans, whole grains, seafood, and plant proteins were particularly suboptimal among both groups, but significantly lower among the HR population. Scores for refined grains, sodium, saturated fats and added sugar reflected high intakes of these components but did not differ between study groups. Our findings revealed an unfavorable diet quality among the HR compared to HG and a potentially increased risk for diet-related NCDs. Future health intervention programs are warranted to address dietary disparities of segregated minorities in Hungary while considering ethnic and cultural differences.

Activation mechanism dependent surface exposure of cellular factor XIII on activated platelets and platelet microparticles.

BACKGROUND: Platelets contain a high amount of potentially active A subunit dimer of coagulation factor XIII (cellular FXIII; cFXIII). It is of cytoplasmic localization, not secreted, but becomes translocated to the surface of platelets activated by convulxin and thrombin (CVX+Thr). OBJECTIVE: To explore the difference in cFXIII translocation between receptor mediated and non-receptor mediated platelet activation and if translocation can also be detected on platelet-derived microparticles. Our aim was also to shed some light on the mechanism of cFXIII translocation. METHODS: Gel-filtered platelets were activated by CVX+Thr or Ca2+ -ionophore (calcimycin). The translocation of cFXIII and phosphatidylserine (PS) to the surface of activated platelets and platelet-derived microparticles was investigated by flow cytometry, immunofluorescence, and immune electron microscopy. Fluo-4-AM fluorescence was used for the measurement of intracellular Ca2+ concentration. RESULTS: Receptor mediated activation by CVX+Thr exposed cFXIII to the surface of more than 60% of platelets. Electron microscopy revealed microparticles with preserved membrane structure and microparticles devoid of labeling for membrane glycoprotein CD41a. cFXIII was observed on both types of microparticles but was more abundant in the absence of CD41a. Rhosin, a RhoA inhibitor, significantly decreased cFXIII translocation. Non-receptor mediated activation of platelets by calcimycin elevated intracellular Ca2+ concentration, induced the translocation of PS to the surface of platelets and microparticles, but failed to expose cFXIII. CONCLUSIONS: The elevation of intracellular Ca2+ concentration is sufficient for the translocation of PS from the internal layer of the membrane, while the translocation of cFXIII from the platelet cytoplasm requires additional receptor mediated mechanism(s).

Deteriorated Dietary Patterns with Regards to Health and Environmental Sustainability among Hungarian Roma Are Not Differentiated from Those of the General Population.

Nutritional epidemiology studies on Roma people are scarce and, to date, their nutrient-based dietary patterns with regards to both healthy and sustainable dietary considerations have never been reported. We report, for the first time, adherence to healthy and sustainable dietary patterns using scoring and regression models, based on recommendations defined by the World Health Organization, in the Dietary Approaches to Stop Hypertension (DASH) study and the EAT-Lancet report, as well as dietary quality based on Dietary Inflammatory Index (DII) among the Hungarian Roma (HR) population living in North East Hungary, with Hungarian general (HG) adults as reference. Data were obtained from a complex, comparative health survey involving dietary assessment, structured questionnaire-based interview, physical and laboratory examinations on 359 HG and 344 HR subjects in Northeast Hungary. Poisson regressions were fit to models that included DASH, EAT, DII and Healthy Diet Indicator as dependent variables to assess the influence of ethnicity on healthy and sustainable nutrient-based patterns. Adjusted models controlled for all relevant covariates using the residual method indicated poor dietary quality with regards to the selected dietary patterns. These associations were not ethnicity-sensitive, except for DII, where Roma ethnicity was linked to a decrease of DII score (ß = -0.455, 95%CI: -0.720; -0.191, p < 0.05). Currently, HR dietary patterns appear to be relatively unhealthy and unsustainable, rendering them vulnerable to elevated risk of ill-health. Nevertheless, their dietary patterns did not strongly differ from HG, which may contribute to Hungarians being one of the most obese and malnourished nations in Europe. Further prospective research on the potential public and environmental health effects of these findings is warranted.

Silencing Osteopontin Expression Inhibits Proliferation, Invasion and Induce Altered Protein Expression in Melanoma Cells.

Osteopontin (OPN) is a multifunctional phosphoprotein that is expressed in different types of cancers, including melanoma. OPN overexpression is associated with tumor progression and metastasis formation; however, the role of OPN in cell invasion and metastasis formation is not completely understood. In this study we aimed to define OPN expression in melanoma tissues and cell lines and investigate the effect of OPN expression on cell proliferation and invasion after inhibiting OPN expression with small interfering RNA (siRNA). OPN gene expression was determined by qRT-PCR, while protein expression was examined using a Proteome Profiler Oncology Array. siRNA-mediated OPN knockdown led to decreased OPN expression in melanoma cell lines, which was associated with decreased cell proliferation and invasion. Proteome profile analysis revealed significantly different protein expression between the original and transfected cell lines. The altered expression of the differently expressed proteins was validated at the mRNA level. Furthermore, OPN-specific siRNA was able to reduce OPN expression and inhibit the invasiveness of melanoma cells. Our results revealed for the first time that silencing the OPN gene influences proliferation and invasion of melanoma cells by effecting EGFR, tenascin C, survivin, galectin-3 and enolase 2 expression. To predict protein-protein interactions along with putative pathways we used STRING analysis for the differentially expressed proteins. These proteins formed multiple clusters, including extracellular matrix organization, regulation of angiogenesis, cell death and cell migration, PI3K-Akt, MAPK and focal adhesion signaling pathways. Taken together these data suggest that OPN might be an ideal target for drug development and therapies.

Health impact assessment of quality wine production in Hungary.

Alcohol-related health outcomes show strikingly high incidence in Hungary. The effects of alcohol consumption are influenced not only by the quantity, but also the quality of drinks; therefore, wine production can have an important effect on public health outcomes. Nevertheless, the Hungarian wine sector faces several vital problems and challenges influenced by the country's accession to the European Union and by the need for restructuring. A comprehensive health impact assessment (HIA) based on the evaluation of the Hungarian legislation related to the wine sector has been carried out, aiming to assess the impact of the production of quality wine versus that of table wine, using a range of public health and epidemiological research methods and data as well as HIA guidelines. The study finds that the toxic effects of alcohol can be reduced with an increased supply of quality wine and with decreased overall consumption due to higher cost, although this might drive some people to seek illegal sources. Quality wine production allows for improved use of land, creates employment opportunities and increases the incomes of producers and local communities; however, capital-scarce producers unable to manage restructuring may lose their source of subsistence. The supply of quality wine can promote social relations, contribute to a healthy lifestyle and reduce criminality related to alcohol's influence and adulteration. In general, the production and supply of quality wine can have an overall positive impact on health. Nevertheless, because of the several possible negative effects expected without purposeful restructuring, recommendations for the maximization of favourable outcomes and suggestions for monitoring the success of the analysis have been provided.

The Moderating Role of Social Neighbourhood Factors in the Association between Features of the Physical Neighbourhood Environment and Weight Status.

BACKGROUND: This paper investigated the independent and joint associations between aspects of the physical neighbourhood environment and social neighbourhood factors with BMI and overweight status in European adults. METHODS: Data from 5,199 participants in the SPOTLIGHT survey were analysed. Participants reported on their height, weight and perceptions of the neighbourhood. Objectively measured aspects of the physical neighbourhood environment included: presence of recreational facilities, features of the active transportation environment, neighbourhood aesthetics and presence of different types of food outlets. Social factors included the self-reported variables social network, social cohesion, social trust and perceived crime and the census variable neighbourhood socioeconomic status. Outcome measures were BMI and overweight status. Main associations between physical and social factors and BMI/overweight status were analysed using multilevel regression analyses adjusted for confounders. Moderation analysis was conducted by adding the interaction terms between physical and social neighbourhood factors one by one to the multivariable models. Significant interaction terms were then stratified. RESULTS: Significant associations with BMI/overweight status were found for features of the active transportation environment and all social factors, except perceived crime. Several significant interaction terms were detected, but no significant associations between the physical neighbourhood environment and BMI/overweight status were found after stratification. CONCLUSION: We did not find consistent interactions between physical and social neighbourhood factors to explain BMI and overweight status.

Factor XDebrecen: Gly204Arg mutation in factor X causes the synthesis of a non-secretable protein and severe factor X deficiency.

Due to a homozygous Gly204Arg mutation in the factor X (FX) gene no detectable FX antigen was found in the plasma of a one-year old patient with severe bleeding diathesis. The amino acid replacement destabilized the disulfide bond that holds the two FX chains together, decreasing the interaction between the Cys201-Cys206 loop region and the region connecting the EGF2 and serine protease domains. Both Gly204 FX and Arg204 FX were synthesized in transfected cells, but only the wild type protein became secreted. The mutant protein was diverted from the normal secretory pathway and retained at the trans Golgi-late endosome level.

Poverty and household food insecurity in Mongolia.

This study was designed to review the food security of the country and to study the household food insecurity of poor households in relation to the poverty level. Cross-sectional survey design was used to assess the perceptions of socio-economic changes, food insecurity in national and household levels, and their health impact. A total of 731 poor households were involved in our study. One third of the total households were in a status of severe food insecurity with hunger. Analysis on the risk factors of household food insecurity showed that the household income was significantly inversely associated with household food insecurity (RR = -0.489; 95% CI -0.540, -0.398; P < .001). Food insecurity with hunger in the households is significantly related to poverty of the households.