Publications

<b><i>Objective</i></b><b> </b>Prospective associations between omega-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize prospective associations between biomarkers of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), and T2D risk through an individual participant-level pooled analysis. <p><b><i>Research Design and Methods </i></b>Our analysis incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline.</p> <p><i>De novo</i> harmonized analyses were performed in each cohort following a pre-specified protocol and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.</p> <p><b><i>Results</i></b><b> </b>A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per inter-quintile range (difference between the 90<sup>th</sup> and 10<sup>th</sup> percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89) and 0.81 (0.75, 0.88), respectively (all <i>P</i><0.001). ALA was not associated with T2D, 0.97 (0.92, 1.02) per inter-quintile range. Associations were robust across pre-specified subgroups as well as in sensitivity analyses. </p> <p><b><i>Conclusions </i></b><a></a><a>Higher circulating biomarkers of seafood-derived omega-3 fatty acids, including EPA, DPA, DHA, and their sum were associated with lower risk of T2D in a global consortium of prospective studies. </a>The biomarker of plant-derived ALA was not significantly associated with T2D risk. </p>

Hypertension and type 2 diabetes (T2D) commonly coexist, and both conditions are major risk factors for cardiovascular disease (CVD). We aimed to examine the association between genetic predisposition to high blood pressure and risk of CVD in individuals with T2D. The current study included 1,005 men and 1,299 women with T2D from the Health Professionals Follow-up Study and Nurses’ Health Study, of whom 732 developed CVD. A genetic predisposition score was calculated on the basis of 29 established blood pressure–associated variants. The genetic predisposition score showed consistent associations with risk of CVD in men and women. In the combined results, each additional blood pressure–increasing allele was associated with a 6% increased risk of CVD (odds ratio [OR] 1.06 [95% CI 1.03–1.10]). The OR was 1.62 (1.22–2.14) for risk of CVD comparing the extreme quartiles of the genetic predisposition score. The genetic association for CVD risk was significantly stronger in patients with T2D than that estimated in the general populations by a meta-analysis (OR per SD of genetic score 1.22 [95% CI 1.10–1.35] vs. 1.10 [1.08–1.12]; I2 = 71%). Our data indicate that genetic predisposition to high blood pressure is associated with an increased risk of CVD in individuals with T2D.

We report on the experimental observation of spontaneously nucleated ruptures occurring on frictionally held bimaterial interfaces with small amounts of wave speed mismatch. Rupture is always found to be asymmetric bilateral. In one direction, rupture always propagates at the generalized Rayleigh wave speed, whereas in the opposite direction it is subshear or it transitions to supershear. The lack of a preferred rupture direction and the conditions leading to supershear are discussed in relation to existing theory and to the earthquake sequence in Parkfield, California, and in North Anatolia.

Abstract Aim: To compare self‐reported emotional and behavioural problems among Greek and Finnish adolescents. Methods: Youth Self‐Report scores were analysed for 3373 Greek adolescents aged 18 years and 7039 Finnish adolescents aged 15–16 years from the general population in both countries. The impact of country, gender, place of residence, socioeconomic status (SES) and family stability on the scores was evaluated. Results: Only country and gender yielded small to medium effect on the scores. Greek boys scored significantly higher than Finns on 10 of the 11 YSR syndromes, particularly on the anxious/depressed scale. Greek girls scored significantly lower than Finnish girls on the somatic complaints and delinquent behaviour scales. In general, girls scored higher than boys on both internalising and externalising problems. The gender by country interaction revealed that Finnish girls reported more externalising problems. Conclusion: The main differences marked in this comparison were the higher level of anxiety and depression in Greeks than Finns and the higher level of externalising problems in Finnish girls than boys. Cultural standards could play an important role in explaining these differences. Overall, it seems that only a small number of differences exist between a northern and southern European region.

Objective. Cultural or ethnic factors may play an important role in subjects' pain reports. The aim of the study was to compare the prevalence of orofacial pain symptoms between Finnish and Thai populations. Materials and methods. The Finnish study population comprised the Northern Finland Birth Cohort 1966, of which 5696 subjects participated in the present study. The Thai sample consisted of 1501 randomly selected people living in 10 different districts in Bangkok. Data on orofacial pain was collected based on questionnaires. Results. After adjusting for age, gender and education, the logistic regression analysis showed that Thai subjects had an increased risk for reporting oral pain (OR = 4.5, 95% CI = 3.7–5.4), tooth pain (OR = 2.0, 95% CI = 1.8–2.4) and pain in the face (OR = 1.5, 95% CI = 1.2–1.7). Conclusions. It can be concluded that Thai people report more orofacial pain symptoms than Finnish subjects. Cross-cultural factors exist in the background of reporting pain symptoms in the oral and facial area.

Abstract Advanced glycation end products ( AGEs ) are formed upon nonenzymatic reactions of sugars or their metabolites with proteins and other cellular constituents. Many AGEs are long lived. Recent findings suggest that AGEs may predict diabetes and its complications and thus may warrant further study. The objective of this study was to assess the validity of our experimental procedures for measuring AGEs in stored blood sample and to conduct a pilot study for developing AGE biomarkers for diabetes and/or age‐related changes of glucose metabolism. We conducted a reliability study of the samples and methods using liquid chromatography–tandem mass spectrometry (LC‐MS)/MS assays for 10 AGEs (including methylglyoxal‐derived hydroimidazolone ( MG‐H1 ), glucosepane ( GSP ) and two oxidation measures, in stored repository blood samples from the Nurses' Health Study and the Health Professionals Follow‐up Study. We also analyzed data relating blood GSP levels to type 2 diabetes status in a case‐control study (25 cases and 15 controls). Among the AGEs, GSP, and MG‐H1 showed the highest reliability across the various measures: reliability in duplicate samples and stability with delayed processing and storage over 1–2 year period. Furthermore, plasma GSP was associated with older age ( P = 0.04) and type 2 diabetes status (age‐adjusted P = 0.0475). Our findings suggest that analysis of these AGEs may be developed as biomarkers for diabetes and/or age‐related changes of glucose metabolism. © 2018 BioFactors, 44(3):281–288, 2018

Understanding complex neuronal networks requires monitoring long-term neuronal activity in various regions of the brain. Significant progress has been made in multi-site implantations of well-designed probes, such as multi-site implantation of Si-based and polymer-based probes. However, these multi-probe strategies have been limited by the sizes and weights of interfaces to the multiple probes and the inability to track the activity of the same neurons and changes in neuronal activity over longer time periods. Here, we report a long single flexible probe that can be implanted by stitching into multiple regions of the mouse brain and subsequently transmit chronically-stable neuronal signals from the multiple sites via a single low-mass interface. We implanted the probe at four different sites using a glass capillary needle or two sites using an ultrathin metal needle. In-vitro tests in brain-mimicking hydrogel showed that multi-site probe implantations achieved a high connection yield of >86%. In-vivo histological images at each site of probes, implanted by stitching using either glass capillary or ultrathin metal insertion needles exhibit seamless tissue-probe interfaces with negligible chronic immune response. In addition, electrophysiology studies demonstrated the ability to track single neuron activities at every injection site with chronic stability over at least one month. Notably, the measured spike amplitudes and signal-to-noise ratios at different implantation sites showed no statistically significant differences. Multi-site stitching implantation of flexible electronics in the brain opens up new opportunities for both fundamental neuroscience research and electrotherapeutic applications.

BACKGROUND Pre- and perinatal factors and preschool body size may help identify children developing overweight, but these factors might have changed during the development of the obesity epidemic. OBJECTIVE We aimed to assess the associations between early life risk indicators and overweight at the age of 9 and 15 years at different stages of the obesity epidemic. METHODS We used two population-based Northern Finland Birth Cohorts including 4111 children born in 1966 (NFBC1966) and 5414 children born in 1985-1986 (NFBC1986). In both cohorts, we used the same a priori defined prenatal factors, maternal body mass index (BMI), birth weight, infant weight (age 5 months and 1 year), and preschool BMI (age 2-5 years). We used internal references in early childhood to define percentiles of body size ( 90) and generalized linear models to study the association with overweight, according to the International Obesity Taskforce (IOTF) definitions, at the ages of 9 and 15 years. RESULTS The prevalence of overweight at the age of 15 was 9% for children born in 1966 and 16% for children born in 1986. However, medians of infant weight and preschool BMI changed little between the cohorts, and we found similar associations between maternal BMI, infant weight, preschool BMI, and later overweight in the two cohorts. At 5 years, children above the 90th percentile had approximately a 12 times higher risk of being overweight at the age of 15 years compared to children below the 50th percentile in both cohorts. CONCLUSIONS The associations between early body size and adolescent overweight showed remarkable stability, despite the increase in prevalence of overweight over the 20 years between the cohorts. Using consequently defined internal percentiles may be a valuable tool in clinical practice.

OBJECTIVE Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics. RESULTS During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94–1.25); cis/trans-18:2, 0.89 (0.73–1.07); and trans/cis-18:2, 0.87 (0.73–1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67–0.99], 0.86 [0.75–0.99], and 0.84 [0.74–0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P ≥ 0.1). CONCLUSIONS Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.

Objective We tested whether genetic variants near fatty acid desaturases gene ( FADS ) cluster, which were recently identified to be signatures of adaptation to fish-rich and n-3 polyunsaturated fatty acids (PUFAs)-rich diet, interacted with these dietary factors on change in body mass index (BMI). Design Three FADS variants were examined for gene-diet interactions on long-term (~10 years) changes in BMI and body weight in four prospective cohort studies. Setting Population based study. Participants 11 323 women from the Nurses’ Health Study (NHS), 6833 men from the Health Professionals Follow-up Study (HPFS) and replicated in 6254 women from the Women’s Health Initiative (WHI) and 5 264 Chinese from the Singapore Chinese Health Study (SCHS). Main outcomes Long-term (~10 years) changes in BMI and body weight. Results In the NHS and HPFS cohorts, food-sourced n-3 PUFAs intake showed interactions with the FADS rs174570 on changes of BMI (P for interaction=0.02 in NHS, 0.05 in HPFS and 0.007 in combined). Such interactions were replicated in two independent cohorts WHI and SCHS (P for interaction=0.04 in WHI, 0.02 in SCHS and 0.001 in combined). The genetic associations of the FADS rs174570 with changes in BMI increased across the tertiles of n-3 PUFAs in all the cohorts. Fish intake also accentuated the genetic associations of the FADS rs174570 with long-term changes in BMI (pooled P for interaction=0.006). Viewed differently, long chain n-3 PUFAs intake showed stronger association with long-term changes in BMI among the rs174570 T carriers (beta=0.79 kg/m 2 per g, p=3×10 −5 ) than the rs174570 non-T carriers (beta=0.16 kg/m 2 per g, p=0.08). Similar results were observed for fish intake. Conclusions Our hypothesis-driven analyses provide replicable evidence that long chain n-3 PUFAs and fish intakes may interact with the FADS variant on long-term weight gain. Further investigation is needed to confirm our findings in other cohorts.

'Pulsed High-Intensity Focused Ultrasound' published in 'Encyclopedia of Nanotechnology'