Publications

Abstract Cytokines are the signalling molecules that underlie inflammatory processes. Here, we performed genome-wide association study (GWAS) analyses of 47 circulating cytokines in up to 13,365 individuals to identify protein quantitative trait loci (pQTL). Applying a novel approach, we incorporated pQTL and expression quantitative trait loci (eQTL) data of 10,361 tissue samples in 635 individuals to identify biologically plausible genetic instruments to proxy the effect of cytokines. Using Mendelian randomization analysis, we explored the causal determinants of inflammatory cytokines, investigated inflammatory cascades and evaluated their effects on 20 diseases. We show evidence of body mass index (BMI), smoking and systolic blood pressure (SBP) being associated with inflammation, and specifically BMI affecting levels of active PAI-1, HGF, MCP1, sE-Selectin, sICAM1, TRAIL, IL6 and CRP. Our analysis highlights a key role of VEGF in influencing the levels of eight other inflammatory cytokines. Finally, we report evidence of sICAM affecting waist circumference and risk of major depressive disorder, evidence for TRAIL affecting the risk of cardiovascular diseases, breast and prostate cancer, and evidence for MIG affecting the risk of stroke. Overall, our results offer insight into inflammatory mediators of BMI, smoking and SBP, pleiotropic effects of VEGF, and circulating cytokines that increase the risk of cancer, cardiovascular, metabolic and neuropsychiatric diseases. All the studied cytokines represent pharmacological targets and therefore offer opportunities for clinical translation in diseases with inflammatory components.

<p>Diabetes is a continuously growing global concern affecting >10% of adults, which may be mitigated by modifiable lifestyle factors. Consumption of nuts and their inclusion in dietary patterns has been associated with a range of beneficial health outcomes. Diabetes guidelines recommend dietary patterns that incorporate nuts; however, specific recommendations related to nuts have been limited. This review considers the epidemiological and clinical evidence to date for the role of nut consumption as a dietary strategy for the prevention and management of type 2 diabetes (T2D) and related complications. Findings suggest nut consumption may have a potential role in the prevention and management of T2D, with mechanistic studies assessing nuts and individual nut-related nutritional constituents supporting this possibility. However, limited definitive evidence is available to date, and future studies are needed to elucidate better the impact of nuts on the prevention and management of T2D.</p>

This paper describes the fabrication of arrays of nanostructures (rings, crescents, counterfacing split rings, cylinders, coaxial cylinders, and other structures) by a four-step process: (i) molding an array of epoxy posts by soft lithography, (ii) depositing thin films on the posts, (iii) embedding the posts in epoxy, and (iv) sectioning in a plane parallel to the plane defined by the array of posts, into slabs, with an ultramicrotome ("nanoskiving"). This work demonstrates the combination of four capabilities: (i) formation of structures that are submicrometer in all dimensions; (ii) fabrication of 3D structures, and arrays of structures, with gradients of height; (iii) patterning of arrays containing two or more materials, including metals, semiconductors, oxides, and polymers; and (iv) generation of as many as 60 consecutive slabs bearing contiguous arrays of nanostructures. These arrays can be transferred to different substrates, and arrays of gold rings exhibit plasmonic resonances in the range of wavelengths spanning 2-5 microm.

While dietary factors have been implicated in the risk of developing colon cancer, it is not clear whether diet influences the outcome in patients who have established disease. This question was addressed in a prospective observational study of 1009 patients with stage III colon cancer who enrolled in a randomized trial of adjuvant chemotherapy in 1999–2001. Participants were asked to complete a semiquantitative food frequency questionnaire midway in the course of chemotherapy and again about 6 months after adjuvant therapy ceased. Two major dietary patterns emerged: a prudent pattern with high intakes of fruits and vegetables, poultry, and fish; and a Western pattern with high intakes of meat, fat, refined grains, and deserts. The median follow-up interval was 5.3 years. Recurrent disease developed during follow-up in 324 patients, and 223 of them died with recurrent disease. Another 28 patients died without documented recurrent disease. Higher intake of a Western dietary pattern following diagnosis of colon cancer was associated with significantly worse disease-free survival. Compared with patients in the lowest quintile of the Western pattern, those in the highest quintile had an adjusted hazard ratio (AHR) for disease-free survival of 3.25 (95% confidence interval [CI], 2.04–5.19). The AHR for recurrence-free survival was 2.85 (95% CI, 1.75–4.63). For overall survival, the AHR associated with intake of a Western dietary pattern was 2.32, with a 95% CI of 1.36–3.96. The reduced disease-free survival associated with a Western diet was not significantly altered when adjusted for gender, age, lymph node stage, body mass index, level of physical activity, performance status at baseline, or treatment group. The prudent dietary pattern, in contrast, was not significantly associated with recurrent cancer or cancer mortality. The AHR for disease-free survival, comparing the highest and lowest quintiles of the prudent dietary pattern, was 1.20 (95% CI, 0.83–1.75). There also was no relationship between the prudent pattern and either recurrence-free survival or overall survival. The investigators believe this to be the first study in a potentially cured group of colon cancer survivors to analyze the effects of diet. Further studies hopefully will identify those elements of a Western dietary pattern that are most closely associated with an adverse outcome.

We appreciate the interest in our recent article on pre-pregnancy potato consumption and risk of gestational diabetes mellitus (GDM).1 Below we provide responses to a few major points raised by readers Pre-pregnancy consumption of potato in our study did not include sweet potato.2 Sweet potato consumption in our study population was too low (~95% consumed <1 serving a week) for us to reliably evaluate its association with the risk of GDM. The role of pre-pregnancy sweet potato consumption in the development of GDM warrants further investigation. We are aware that sweet potato—which is rich in complex carbohydrates, dietary fibre, β carotene, vitamin C, vitamin B6, anthocyanin, and minerals—is considered to be a nutritious vegetable.3 Studies in animal models indicated that sweet potatoes have hypoglycaemic effects through ameliorating oxidative stress and inflammation and improving pancreatic β cells mass.4 In humans, sweet potato has been used in traditional medicine for the treatment of type 2 diabetes. However, data from randomised controlled trials and large observational studied on the efficacy of sweet potato in glycaemic control in humans are insufficient and inconclusive.3 Our study was not designed to look at the underlying mechanisms of the observed positive association between pre-pregnancy potato intake and GDM risk; future studies will elucidate these.5 Evidence suggests that the potato’s high glycaemic index …

Background A healthful plant-based diet was associated with lower risks of coronary heart disease and type 2 diabetes, and a favourable profile of adiposity-associated biomarkers, while an unhealthful plant-based diet was associated with elevated risk of cardiometabolic disease in health professional populations. However, little is known about the associations between plant-based dietary patterns and risk of cardiovascular disease (CVD) in US veterans. Methods The study population consisted of 148 506 participants who were free of diabetes, CVD and cancer at baseline in the Veterans Affairs (VA) Million Veteran Program. Diet was assessed using a Food Frequency Questionnaire at baseline. We calculated an overall Plant-Based Diet Index (PDI), a healthful PDI (hPDI) and an unhealthful PDI (uPDI). The CVD endpoints included non-fatal myocardial infarction (MI) and acute ischaemic stroke (AIS) identified through high-throughput phenotyping algorithms approach and fatal CVD events identified by searching the National Death Index. Results With up to 8 years of follow-up, we documented 5025 CVD cases. After adjustment for confounding factors, a higher PDI was significantly associated with a lower risk of CVD (HR comparing extreme quintiles=0.75, 95% CI 0.68 to 0.82, P trend &lt;0.0001). We observed an inverse association between hPDI and the risk of CVD (HR comparing extreme quintiles=0.71, 95% CI 0.64 to 0.78, P trend &lt;0.001), whereas uPDI was positively associated with the risk of CVD (HR comparing extreme quintiles=1.12, 95% CI 1.02 to 1.24, P trend &lt;0.001). We found similar associations of hPDI with subtypes of CVD; a 10-unit increment in hPDI was associated with HRs (95% CI) of 0.81 (0.75 to 0.87) for fatal CVD, 0.86 (0.79 to 0.94) for non-fatal MI and 0.86 (0.78 to 0.95) for non-fatal AIS. Conclusions Plant-based dietary pattern enriched with healthier plant foods was associated with a substantially lower CVD risk in US veterans.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76–0.91]; P &lt;0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74–0.91]; P &lt;0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81–0.96]; P =0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78–0.95]; P =0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.