Visceral adiposity index and 10-year cardiovascular disease incidence:the ATTICA study

Background and aims: Visceral adiposity index (VAI) has been proposed as a marker of visceral adipose tissue accumulation/dysfunction. Our aim was to evaluate potential associations between the VAI and the 10-year cardiovascular disease (CVD) incidence. Methods and results: During 2001-2002, 3042 Greek adults (1514 men; age: ≥18 years) without previous CVD were recruited into the ATTICA study, whilst the 10-year study follow-up was performed in 2011-2012, recording the fatal/non-fatal CVD incidence in 2020 (1010 men) participants. The baseline VAI scores for these participants were calculated based on anthropometric and lipid variables, while VAI tertiles were extracted for further analyses. During the study follow-up a total of 317 CVD events (15.7%) were observed. At baseline, the participants' age and the prevalence of hypertension, diabetes, hypercholesterolemia and metabolic syndrome increased significantly across the VAI tertiles. After adjusting for multiple confounders, VAI exhibited a significantly independent positive association with the 10-year CVD incidence (OR = 1.05, 95%CI: 1.01, 1.10), whereas the association of the body mass index (HR = 1.03, 95%CI: 0.99, 1.08), or the waist circumference (HR = 1.01, 95%CI: 0.99, 1.02) was less prominent. Sex-specific analysis further showed that VAI remained significantly predictive of CVD in men alone (HR = 1.06, 95%CI: 1.00, 1.11) but not in women (HR = 1.06, 95%CI: 0.96, 1.10). Conclusions: Our findings show for the first time in a large-sample, long-term, prospective study in Europe that the VAI is independently associated with elevated 10-year CVD risk, particularly in men. This suggests that the VAI may be utilized as an additional indicator of long-term CVD risk for Caucasian/Mediterranean men without previous CVD

Work-Family Life Courses and Metabolic Markers in the MRC National Survey of Health and Development

The aim was to investigate whether the combined work-family life courses of British men and women were associated with differences in metabolic markers?waist circumference, blood pressure, high density lipoprotein cholesterol, triglycerides, and glycated haemoglobin?in mid-life. We used data from the Medical Research Council?s National Survey of Health and Development?the 1946 British birth cohort. Multi-channel sequence analysis was used to create a typology of eight work-family life course types combining information on work, partnerships and parenthood between ages 16?51. Linear regression tested associations between work-family types and metabolic outcomes at age 53 on multiply imputed data (20 imputations) of >2,400 participants. Compared with men with strong ties to employment and early transitions to family life, men who made later transitions to parenthood and maintained strong ties to paid work had smaller waist circumferences (-2.16cm, 95% CI: -3.73, -0.59), lower triglycerides (9.78% lower, 95% CI: 0.81, 17.94) and lower blood pressure (systolic: -4.03mmHg, 95% CI: -6.93, -1.13; diastolic: -2.34mmHg, 95% CI: -4.15, -0.53). Married men and women who didn?t have children had increased high density lipoprotein cholesterol (7.23% higher, 95% CI: 0.68, 14.21) and lower waist circumferences (-4.67cm, 95% CI: -8.37, -0.97), respectively. For men later transitions to parenthood combined with strong ties to paid work were linked to reduced metabolic risk in mid-life. Fewer differences between work-family types and metabolic markers were seen for women

Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

Aims/hypothesis Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulatory macrophage-derived factor that increases with obesity and leads to a higher risk of cardiovascular disease (CVD). Despite this, its role in adipose tissue and the adipocyte is unknown. Therefore, the aims of this study were to clarify the expression of Lp-PLA2 in relation to different adipose tissue depots and type 2 diabetes, and ascertain whether markers of obesity and type 2 diabetes correlate with circulating Lp-PLA2. A final aim was to evaluate the effect of cholesterol on cellular Lp-PLA2 in an in vitro adipocyte model. Methods Analysis of anthropometric and biochemical variables from a cohort of lean (age 44.4 ± 6.2 years; BMI 22.15 ± 1.8 kg/m2, n = 23), overweight (age 45.4 ± 12.3 years; BMI 26.99 ± 1.5 kg/m2, n = 24), obese (age 49.0 ± 9.1 years; BMI 33.74 ± 3.3 kg/m2, n = 32) and type 2 diabetic women (age 53.0 ± 6.13 years; BMI 35.08 ± 8.6 kg/m2, n = 35), as part of an ethically approved study. Gene and protein expression of PLA2 and its isoforms were assessed in adipose tissue samples, with serum analysis undertaken to assess circulating Lp-PLA2 and its association with cardiometabolic risk markers. A human adipocyte cell model, Chub-S7, was used to address the intracellular change in Lp-PLA2 in adipocytes. Results Lp-PLA2 and calcium-independent PLA2 (iPLA2) isoforms were altered by adiposity, as shown by microarray analysis (p < 0.05). Type 2 diabetes status was also observed to significantly alter gene and protein levels of Lp-PLA2 in abdominal subcutaneous (AbdSc) (p < 0.01), but not omental, adipose tissue. Furthermore, multivariate stepwise regression analysis of circulating Lp-PLA2 and metabolic markers revealed that the greatest predictor of Lp-PLA2 in non-diabetic individuals was LDL-cholesterol (p = 0.004). Additionally, in people with type 2 diabetes, oxidised LDL (oxLDL), triacylglycerols and HDL-cholesterol appeared important predictors, accounting for 59.7% of the variance (p < 0.001). Subsequent in vitro studies determined human adipocytes to be a source of Lp-PLA2, as confirmed by mRNA expression, protein levels and immunochemistry. Further in vitro experiments revealed that treatment with LDL-cholesterol or oxLDL resulted in significant upregulation of Lp-PLA2, while inhibition of Lp-PLA2 reduced oxLDL production by 19.8% (p < 0.05). Conclusions/interpretation Our study suggests adipose tissue and adipocytes are active sources of Lp-PLA2, with differential regulation by fat depot and metabolic state. Moreover, levels of circulating Lp-PLA2 appear to be influenced by unfavourable lipid profiles in type 2 diabetes, which may occur in part through regulation of LDL-cholesterol and oxLDL metabolism in adipocytes

Variation in gas and volatile compound emissions from human urine as it ages, measured by an electronic nose

The medical profession is becoming ever more interested in the use of gas-phase biomarkers for disease identification and monitoring. This is due in part to its rapid analysis time and low test cost, which makes it attractive for many different clinical arenas. One technology that is showing promise for analyzing these gas-phase biomarkers is the electronic nose-an instrument designed to replicate the biological olfactory system. Of the possible biological media available to "sniff", urine is becoming ever more important as it is easy to collect and to store for batch testing. However, this raises the question of sample storage shelf-life, even at -80 °C. Here we investigated the effect of storage time (years) on stability and reproducibility of total gas/vapour emissions from urine samples. Urine samples from 87 patients with Type 2 Diabetes Mellitus were collected over a four-year period and stored at -80 °C. These samples were then analyzed using FAIMS (field-asymmetric ion mobility spectrometry-a type of electronic nose). It was discovered that gas emissions (concentration and diversity) reduced over time. However, there was less variation in the initial nine months of storage with greater uniformity and stability of concentrations together with tighter clustering of the total number of chemicals released. This suggests that nine months could be considered a general guide to a sample shelf-life

Author Correction: A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

The prevalence of obstructive sleep apnoea in women with polycystic ovary syndrome:a systematic review and meta-analysis

Background: Obesity is a common risk factor for polycystic ovary syndrome (PCOS) and obstructive sleep apnoea (OSA). Both PCOS and OSA are associated with increased risk of type 2 diabetes and cardiovascular disease. Hence, it is important to determine the burden of OSA in women with PCOS. Methods: We searched electronic databases (MEDLINE, Embase, CINAHL, PsycINFO, Scopus, Web of Science, OpenGrey, CENTRAL), conference abstracts, and reference lists of relevant articles, up to January 2019. No restriction for language or publication status. Studies that examined the presence of OSA in women with PCOS using polysomnography and/or level III devices were eligible for inclusion. Results: Seventeen studies involving 648 participants were included. Our meta-analysis showed that 35.0% (95% CI 22.2–48.9%) of women with PCOS had OSA. This prevalence was not affected by variation in PCOS definition between studies. Approximately one-tenth of the variation in OSA prevalence was related to differences in study population (higher in adults than adolescents and mixed populations), and around one-tenth was related to sample size (higher in smaller studies). OSA prevalence was markedly higher in obese versus lean women with PCOS, and in women with PCOS compared to controls (odds ratio = 3.83, 95% CI 1.43–10.24, eight studies, 957 participants (349 PCOS and 608 controls)). However, most of the studies were at high risk of selection bias, did not account for important confounders, included predominantly women with class II obesity, and were conducted in one country (USA). Conclusions: Future studies need to examine the true prevalence of OSA in a more representative sample of women with PCOS. Nevertheless, our results suggest that the prevalence of OSA in women with PCOS and obesity is high and clinicians should have a high index of suspicion of OSA in these women

Modeling anthropometric indices in relation to 10-year (2002-2012) incidence of cardiovascular disease, among apparently healthy individuals:the ATTICA study

Aims: Body fat accumulation is implicated in the development of cardiovascular disease (CVD). Our objective was to explore potential associations between anthropometric indices and the 10-year CVD incidence in Greek adults without previous CVD. Methods: During 2001–2, we enrolled 3042 adults without CVD from the general population of Attica, Greece. In 2011–2, the 10-year study follow-up was performed, recording the CVD incidence in 1958 participants with baseline body mass index (BMI) ≥18.5 kg/m2. Results: The study 10-year CVD incidence was 15.8%, exhibiting a gradual increase according to the baseline body mass index (BMI) category. Baseline BMI ≥30 kg/m2 was related with significantly higher 10-year CVD risk compared to BMI <25 kg/m2, even after adjustment for age and other known CVD risk factors. Baseline BMI, waist circumference, waist-to-hip ratio, waist-to-height ratio and waist-to-hip-to-height ratio were independently associated with the 10-year CVD risk in multi-adjusted models. Gender-specific analyses showed that these associations were more evident in men compared to women, with baseline BMI exhibiting an independent association with the 10-year CVD incidence in men. Conclusions: Our results indicate that even simple anthropometric indices exhibit independent associations with CVD risk in a representative sample of the Greek general population without previous CVD

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Exercise interventions significantly reduce fasting insulin, but not fasting glucose, in women with polycystic ovary syndrome when compared with no intervention: A systematic review and meta-analysis

Aims: Polycystic ovary syndrome (PCOS) is a common condition that affects approximately 20% of reproductive‐aged women. PCOS is also associated with insulin resistance; women with PCOS are more insulin resistant than body mass index–matched controls. Methods: A systematic review was completed; randomised controlled trials that compared physical activity with control groups were evaluated in a meta‐analysis. Outcomes related to glucose homeostasis were analysed. Change from baseline to end of intervention values were reported as mean difference (MD) and 95% confidence intervals (CI). Results: There was evidence of a favourable effect of exercise on fasting insulin levels (MD −2.62 μIU/ml, CI −4.46 to −0.77; I2 = 92%; 236 participants, eight trials), but not for fasting blood glucose. Reductions in fasting insulin were found for all exercise modalities (aerobic, resistance or combined exercise), but were strongest in resistance training groups (MD −3.99 μIU/ml, CI −5.97 to −2.00; I2 = 54%; 50 participants, three trials). Change from baseline HOMA index also favoured exercise (MD −0.59, CI −1.02 to −0.17; I2 = 89%; 146 participants, seven trials) but evidence of effect was only present in aerobic exercise groups (MD −0.77, CI −1.28 to −0.26; I2 = 65%; 75 participants, four trials). Summary: Exercise, regardless of modality, reduces fasting insulin, but not fasting blood glucose, in women with PCOS compared with those receiving no intervention. However, a cautious approach should be adopted in interpreting these findings due to the wide CIs and evidence of considerable heterogeneity. Despite the statistically significant results, it is unclear if these improvements are clinically relevant

Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation

Background: Endocrine-disrupting chemicals (EDCs) are environmental chemicals/toxicants that humans are exposed to, interfering with the action of multiple hormones. Bisphenol A (BPA) is classified as an EDC with xenoestrogenic activity with potentially adverse effects in reproduction. Currently, a significant knowledge gap remains regarding the complete spectrum of BPA-induced effects on the human placenta. As such, the present study examined the effects of physiologically relevant doses of BPA in vitro. Methods: qRT-PCR, Western blotting, immunofluorescence, ELISA, microarray analyses, and bioinformatics have been employed to study the effects of BPA using nonsyncytialised (non-ST) and syncytialised (ST) BeWo cells. Results: Treatment with 3 nM BPA led to an increase in cell number and altered the phosphorylation status of p38, an effect mediated primarily via the membrane-bound estrogen receptor (GPR30). Nonbiased microarray analysis identified 1195 and 477 genes that were differentially regulated in non-ST BeWo cells, whereas in ST BeWo cells, 309 and 158 genes had altered expression when treated with 3 and 10 nM, respectively. Enriched pathway analyses in non-ST BeWo identified a leptin and insulin overlap (3 nM), methylation pathways (10 nM), and differentiation of white and brown adipocytes (common). In the ST model, most significantly enriched were the nuclear factor erythroid 2-related factor 2 (NRF2) pathway (3 nM) and mir-124 predicted interactions with cell cycle and differentiation (10 nM). Conclusion: Collectively, our data offer a new insight regarding BPA effects at the placental level, and provide a potential link with metabolic changes that can have an impact on the developing fetus.Isambard PhD Scholarship, Brunel University Londo