Healthy diet indicator and metabolic syndrome in the Czech Republic, Russia and Poland: cross-sectional findings from the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study

In Eastern Europe, cardiovascular disease (CVD) mortality is high, but the causes of this remain poorly understood. Metabolic syndrome (MetS) is a risk factor for CVD and is thought to be partly determined by diet. However, few studies have examined the prevalence of MetS and the associations between dietary quality and MetS in Eastern European populations. This cross-sectional study used data from the baseline wave of HAPIEE study—21519 randomly selected adults aged 45-69 years. MetS was defined using the ATP III definition. Healthy Diet Indicator (HDI) was derived using WHO 2003 recommendations: each component was scored from 0 (worst) to 10 (best adherence) and the total score ranged from 0 (worst) to 70 (best dietary quality). Anthropometric data and blood samples were collected during clinic visits. Prevalence of MetS was high in the Czech Republic (men: 37.1%, women: 35.7%), Russia (20.8%, 36.3%), and Poland (27.9%, 28.6%). In logistic regression, adherence to total HDI score was not associated with risk of MetS (P>0.05), but higher HDI was associated with lower risk of having raised blood pressure in the pooled sample (OR per 10 unit increase in HDI=0.82, 95% CI: 0.72-0.94). A better adherence to recommended protein intake was consistently associated with lower risk of having high blood glucose in three countries (Czech Republic: OR per 1 unit increase in protein score=0.87, 95% CI: 0.80-0.94; Russia: 0.93, 0.88-0.99; Poland: 0.82, 0.75-0.89), and also associated with lower risk of MetS (0.92, 0.86-0.98) and central obesity (0.90, 0.84-0.96) in Poland. Findings showed that MetS prevalence was high and diet quality was moderate to poor. Findings also provide some support for the beneficial role of diet quality (especially moderate protein intake) in lowering MetS prevalence. Future longitudinal studies should examine whether higher adherence to HDI reduces the risk of MetS and CVD

Long-term exposure to NO2 and O3 and all-cause and respiratory mortality: A systematic review and meta-analysis.

BACKGROUND: WHO has published several volumes of Global Air Quality Guidelines to provide guidance on the health risks associated with exposure to outdoor air pollution. As new scientific evidence is generated, air quality guidelines need to be periodically revised and, where necessary, updated. OBJECTIVES: The aims of the study were 1) to summarise the available evidence on the effect of long-term exposure to ozone (O3) and nitrogen dioxide (NO2) on mortality; 2) and to assess concentration response functions (CRF), their shape and the minimum level of exposures measured in studies to support WHO's update of the global air quality guidelines. DATA SOURCES: We conducted a systematic literature search of the Medline, Embase and Web of Science databases following a protocol proposed by WHO and applied Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines for reporting our results. STUDY ELIGIBILITY CRITERIA: Cohort studies in human populations (including sub-groups at risk) exposed to long-term concentrations of NO2 and O3. Outcomes assessed were all-cause, respiratory, Chronic Obstructive Pulmonary Disease (COPD) and Acute Lower Respiratory Infection (ALRI) mortality. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies included in the meta-analyses were assessed using a new Risk of Bias instrument developed by a group of experts convened by WHO. Study results are presented in forest plots and quantitative meta-analyses were conducted using random effects models. The certainty of evidence was assessed using a newly developed adaptation of GRADE. RESULTS: The review identified 2068 studies of which 95 were subject to full-text review with 45 meeting the inclusion criteria. An update in September 2018 identified 159 studies with 1 meeting the inclusion criteria. Of the 46 included studies, 41 reported results for NO2 and 20 for O3. The majority of studies were from the USA and Europe with the remainder from Canada, China and Japan. Forty-two studies reported results for all-cause mortality and 22 for respiratory mortality. Associations for NO2 and mortality were positive; random-effects summary relative risks (RR) were 1.02 (95% CI: 1.01, 1.04), 1.03 (1.00, 1.05), 1.03 (1.01, 1.04) and 1.06 (1.02, 1.10) per 10 μg/m3 for all-cause (24 cohorts), respiratory (15 cohorts), COPD (9 cohorts) and ALRI (5 cohorts) mortality respectively. The review identified high levels of heterogeneity for all causes of death except COPD. A small number of studies investigated the shape of the concentration-response relationship and generally found little evidence to reject the assumption of linearity across the concentration range. Studies of O3 using annual metrics showed the associations with all-cause and respiratory mortality were 0.97 (0.93, 1.02) and 0.99 (0.89, 1.11) per 10 μg/m3 respectively. For studies using peak O3 metrics, the association with all-cause mortality was 1.01 (1.00, 1.02) and for respiratory mortality 1.02 (0.99, 1.05), each per 10 μg/m3. The review identified high levels of heterogeneity. Few studies investigated the shape of the concentration-response relationship. Certainty in the associations (adapted GRADE) with mortality was rated low to moderate for each exposure-outcome pair, except for NO2 and COPD mortality which was rated high. LIMITATIONS: The substantial heterogeneity for most outcomes in the review requires explanation. The evidence base is limited in terms of the geographical spread of the study populations and, for some outcomes, the small number of independent cohorts for meta-analysis precludes meaningful meta-regression to explore causes of heterogeneity. Relatively few studies assessed specifically the shape of the CRF or multi-pollutant models. CONCLUSIONS: The short-comings in the existing literature base makes determining the precise nature (magnitude and linearity) of the associations challenging. Certainty of evidence assessments were moderate or low for both NO2 and O3 for all causes of mortality except for NO2 and COPD mortality where the certainty of the evidence was judged as high

Effect of subsidies on healthful consumption: a protocol for a systematic review update.

INTRODUCTION: The prevalence of diet-related non-communicable diseases (NCDs) are rapidly increasing in most parts of the world. In order to ameliorate the related public health burden, evidence-informed policies to improve diet need to be implemented. Financial subsidies that promote healthful consumption patterns have the potential to reduce NCD risk and may also reduce inequality if targeted at those of low socio-economic position. This protocol is for an updated systematic review of such evidence. METHODS AND ANALYSIS: A systematic search strategy will be used to identify publications on fiscal intervention studies indexed in Embase, CINAHL, Web of Science, EconLit and PubMed in between January 2013 to February 2019. Two reviewers will independently sift identified citations using prespecified inclusion and exclusion criteria to inform full-text review. The outcomes of interest are: consumption patterns (% change in targeted items and in overall dietary patterns), purchasing patterns (% change) or body mass index. Pretested data capture forms will be used for double data extraction. Any inconsistencies in citation sifting or data extraction will be resolved by a third investigator and study authors will be contacted if needed. Systematic searches will be supplemented by reference checking of key articles. Study quality will be assessed and a narrative summary of findings will be produced. Meta-analyses and exploration of heterogeneity will be completed if appropriate. ETHICS AND DISSEMINATION: The review aims to strengthen findings of the primary studies it incorporates. It will synthesise existing published aggregated patient data and only present further aggregate data. Given this, no concerns are held relating to confidentiality and informed consent due to re-use of patient data.If publications or data with ethical concerns are identified, they will be excluded from the review.Results of the systematic review will be published in full and authors will engage directly with research audiences and key stakeholders to share findings. PROSPERO REGISTRATION NUMBER: CRD42019125013

Generation of Stable Pluripotent Stem Cells From NOD Mouse Tail-Tip Fibroblasts

OBJECTIVE: The NOD mouse strain has been widely used to investigate the pathology and genetic susceptibility for type 1 diabetes. Induced pluripotent stem cells (iPSCs) derived from this unique mouse strain would enable new strategies for investigating type 1 diabetes pathogenesis and potential therapeutic targets. The objective of this study was to determine whether somatic fibroblasts from NOD mice could be reprogrammed to become iPSCs, providing an alternative source of stem cells for the production of genetically modified NOD cells and mice. RESEARCH DESIGN AND METHODS: Adult tail-tip fibroblasts from male NOD mice were reprogrammed by retroviral transduction of the coding sequences of three transcription factors, OCT4, SOX2, and KLF4, in combination with a histone deacetylase inhibitor, valproic acid. RESULTS: Eighteen NOD iPSC lines were generated, and three of these cell lines were further characterized. All three cell lines exhibited silencing of the three reprogramming transgenes and reactivation of endogenous pluripotent markers (OCT4, SOX2, NANOG, REX1, and SSEA1). These NOD iPSCs readily differentiated in vitro to form embryoid bodies and in vivo by teratoma formation in immunodeficient mice. Moreover, NOD iPSCs were successfully transfected with a reporter transgene and were capable of contributing to the inner cell mass of C57BL/6 blastocysts, leading to the generation of a chimeric mouse. CONCLUSIONS: Adult tail-tip fibroblasts from NOD mice can be reprogrammed, without constitutive ectopic expression of transcription factors, to produce iPSCs that exhibit classic mouse embryonic stem cell (ESC) features. These NOD iPSCs can be maintained and propagated under normal ESC culture conditions to produce genetically altered cell lines, differentiated cells, and chimeric mice

Inflammatory signaling compromises cell responses to interferon alpha.

Interferon alpha (IFNα) is widely used for treatment of melanoma and certain other malignancies. This cytokine as well as the related IFNβ exerts potent anti-tumorigenic effects; however, their efficacy in patients is often suboptimal. Here, we report that inflammatory signaling impedes the effects of IFNα/β. Melanoma cells can secrete pro-inflammatory cytokines that inhibit cellular responses to IFNα/β via activating the ligand-independent pathway for the phosphorylation and subsequent ubiquitination and accelerated degradation of the IFNAR1 chain of type I IFN receptor. Catalytic activity of the p38 protein kinase was required for IFNAR1 downregulation and inhibition of IFNα/β signaling induced by proinflammatory cytokines such as interleukin 1 (IL-1). Activation of p38 kinase inversely correlated with protein levels of IFNAR1 in clinical melanoma specimens. Inhibition of p38 kinase augmented the inhibitory effects of IFNα/β on cell viability and growth in vitro and in vivo. The roles of inflammation and p38 protein kinase in regulating cellular responses to IFNα/β in normal and tumor cells are discussed

Impact of trends and gender disparity in obesity on future type 2 diabetes in Turkey: a mathematical modelling analysis.

BACKGROUND: Using a previously developed and validated mathematical model, we predicted future prevalence of type 2 diabetes mellitus (T2DM) and major modifiable risk factors (obesity, physical inactivity and smoking) stratified by age and sex in Turkey up to the year 2050. METHODS: Our deterministic compartmental model fitted nationally representative demographic and risk factor data simultaneously for Turkish adults (aged 20-79) between 1997 and 2017, then estimated future trends. Our novel approach explored the impact of future obesity trends on these projections, specifically modelling (1) a gradual fall in obesity in women after the year 2020 until it equalled the age-specific levels seen in men and (2) cessation of the rise in obesity after 2020. RESULTS: T2DM prevalence is projected to rise from an estimated 14.0% (95% uncertainty interval (UI) 12.8% to 16.0%) in 2020 to 18.4% (95% UI 16.9% to 20.9%) by 2050; 19.7% in women and 17.2% in men by 2050; reflecting high levels of obesity (39.7% for women and 22.0% for men in 2050). Overall, T2DM prevalence could be reduced by about 4% if obesity stopped rising after 2020 or by 12% (22% in women) if obesity prevalence among women could be lowered to equal that of men. The higher age-specific obesity prevalence among women resulted in 2 076 040 additional women developing T2DM by the year 2050. CONCLUSION: T2DM is common in Turkey and will remain so. Interventions and policies targeting the high burden of obesity (and low physical activity levels), particularly in women, could significantly impact future disease burdens

A systematic review of interventions to promote physical activity in six Gulf countries.

Physical activity (PA) levels are low in Gulf Cooperation Council countries (GCC; Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates). We carried out a systematic review (PROSPERO registration number 131817) to assess the effect of interventions to increase PA levels in this region. We also assessed their effects on anthropometry and cardiovascular risk. A systematic search of six databases (Medline, EMBASE, SPORTDiscus, CINAHL, Cochrane, Web of Science) was performed to identify randomized and non-randomized intervention studies performed in adults and children published between January 1985 and November 2020. We included studies published in English or Arabic, and included PA interventions regardless of setting, delivery, and duration. The primary outcomes were changes in PA duration and intensity. Secondary outcomes included anthropometric measures (e.g., weight, body mass index) and cardiovascular risk profiles (e.g., lipid measures, blood glucose). Two independent reviewers screened studies in accordance with pre-determined criteria, extracted data, assessed risk of bias (Cochrane Risk of Bias 2 and Newcastle Ottawa Scale) and undertook a narrative synthesis. From 13,026 records identified, 14 studies were included. Nine studies focussed exclusively on changing PA behaviour, resulting in statistically significant increases in step count ranging from an additional 757 steps/day (95% confidence interval [CI] 0-1,513) to 3,853 steps/day (95% CI 3,703-4,002). Five identified studies were multi-component lifestyle interventions, targeting people at higher risk (due to obesity or type 2 diabetes). Evidence for increases in PA from multi-component studies was limited, although improvements were seen in outcomes e.g. body weight and blood lipid levels. In conclusion, relatively few studies have focussed on changing PA behaviour, despite the urgent need in the GCC. Limited evidence suggested that pedometer-based programmes encouraging step counting and walking were effective in promoting PA, at least in the short term. Policies to roll out such interventions should be implemented and evaluated

Efficient Non-Viral Reprogramming of Myoblasts to Stemness with a Single Small Molecule to Generate Cardiac Progenitor Cells

The current protocols for generation of induced pluripotent stem (iPS) cells involve genome integrating viral vectors which may induce tumorgenesis. The aim of this study was to develop and optimize a non-viral method without genetic manipulation for reprogramming of skeletal myoblasts (SMs) using small molecules

Characterizing the type 2 diabetes mellitus epidemic in Jordan up to 2050.

We aimed to characterize the type 2 diabetes mellitus (T2DM) epidemic and the role of key risk factors in Jordan between 1990-2050, and to forecast the T2DM-related costs. A recently-developed population-level T2DM mathematical model was adapted and applied to Jordan. The model was fitted to six population-based survey data collected between 1990 and 2017. T2DM prevalence was 14.0% in 1990, and projected to be 16.0% in 2020, and 20.6% in 2050. The total predicted number of T2DM cases were 218,326 (12,313 were new cases) in 1990, 702,326 (36,941 were new cases) in 2020, and 1.9 million (79,419 were new cases) in 2050. Out of Jordan's total health expenditure, 19.0% in 1990, 21.1% in 2020, and 25.2% in 2050 was forecasted to be spent on T2DM. The proportion of T2DM incident cases attributed to obesity was 55.6% in 1990, 59.5% in 2020, and 62.6% in 2050. Meanwhile, the combined contribution of smoking and physical inactivity hovered around 5% between 1990 and 2050. Jordan's T2DM epidemic is predicted to grow sizably in the next three decades, driven by population ageing and high and increasing obesity levels. The national strategy to prevent T2DM needs to be strengthened by focusing it on preventive interventions targeting T2DM and key risk factors

Impact of price reductions, subsidies, or financial incentives on healthy food purchases and consumption: a systematic review and meta-analysis.

Poor diets are a global concern and are linked with various adverse health outcomes. Healthier foods such as fruit and vegetables are often more expensive than unhealthy options. This study aimed to assess the effect of price reductions for healthy food (including fruit and vegetables) on diet. We performed a systematic review and meta-analysis on studies that looked at the effects of financial incentives on healthy food. Main outcomes were change in purchase and consumption of foods following a targeted price reduction. We searched electronic databases (MEDLINE, EconLit, Embase, Cinahl, Cochrane Library, and Web of Science), citations, and used reference screening to identify relevant studies from Jan 1, 2013, to Dec 20, 2021, without language restrictions. We stratified results by population targeted (low-income populations vs general population), the food group that the reduction was applied to (fruit and vegetables, or other healthier foods), and study design. Percentage price reduction was standardised to assess the effect in meta-analyses. Study quality was assessed using the Cochrane Risk of Bias tool and Newcastle-Ottawa Scale. 34 studies were eligible; 15 took place in supermarkets and eight took place in workplace canteens in high-income countries, and 21 were targeted at socioeconomically disadvantaged communities. Pooled analyses of 14 studies showed a price reduction of 20% resulted in increases in fruit and vegetable purchases by 16·62% (95% CI 12·32 to 20·91). Few studies had maintained the price reduction for over 6 months. In conclusion, price reductions can lead to increases in purchases of fruit and vegetables, potentially sufficient to generate health benefits, if sustained