Publications

Asthma prevalence is increasing in many countries. Some recent articles, however, claim that this tendency is drawing to an end. Hence, the incidence of persistent asthma was drawn from a birth cohort study in Finland.A cohort of 6107 men and 5839 women was followed from 1981 to 2004. The participants were members of the Northern Finland Birth Cohort 1966 Study (NFBC-66). The single-year birth cohort was followed from the age of 15 to 38 years by means of a complete register held by the national Social Insurance Institute (SII) in Finland. Within the register data, an incident case of asthma was defined by the received right for reimbursement for asthma medication from the SII.Over a 23-year follow-up period, persistent asthma occurred in 466 study participants of whom 54% were women. The incidence of persistent asthma increased from the rate of 10 cases per 10 000 person-years at the age of 15-20 years to 21 cases per 10 000 person-years at the age of 36-38 years. In females, a peak of incidence rate was found between the age of 31 and 35 years, up to 27 cases per 10 000 person-years.The follow-up of a population-based birth cohort among young working aged Finns shows the increasing incidence rate of persistent asthma. In recent years, however, a decline in new cases of asthma occurred in females aged between 36 and 38 years.

The authors aimed to determine whether 2 functional polymorphisms in the heme oxygenase-1 (HO-1) gene promoter are associated with type 2 diabetes mellitus (T2DM). A Chinese case-control study involving 1,103 newly diagnosed T2DM patients, 371 patients with impaired glucose regulation (IGR), and 1,615 controls was performed (December 2004-December 2007). A (GT)(n) microsatellite polymorphism and a single nucleotide polymorphism, T(-413)A, were genotyped, and their functional relevance was evaluated by examining the level of HO-1 protein expression. For the (GT)(n) microsatellite polymorphism, genotypes with the L (GT)(n) allele (>or=25 GT repeats) were associated with increased odds of IGR or T2DM compared with the S/S genotype (<25 GT repeats) (S/L genotype: odds ratio (OR) = 1.35, P = 0.048; L/L genotype: OR = 1.65, P = 0.006). Subsequent haplotype analysis showed that haplotype TL contributed to increased odds of IGR or T2DM compared with haplotype TS (OR = 1.56, P = 0.003). In functional analyses, HO-1 expression level was significantly reduced in persons with IGR and T2DM carrying the L/L (GT)(n) genotype compared with persons with the S/S genotype. Further haplotype combination assay confirmed the functional dominance of the (GT)(n) microsatellite polymorphism over the T(-413)A single nucleotide polymorphism. These results support an association between the HO-1 (GT)(n) microsatellite polymorphism, HO-1 expression levels, and the odds of T2DM.

This paper demonstrates a methodology for micromixing that is sufficiently simple that it can be used in portable microfluidic devices. It illustrates the use of the micromixer by incorporating it into an elementary, portable microfluidic system that includes sample introduction, sample filtration, and valving. This system has the following characteristics: (i) it is powered with a single hand-operated source of vacuum, (ii) it allows samples to be loaded easily by depositing them into prefabricated wells, (iii) the samples are filtered in situ to prevent clogging of the microchannels, (iv) the structure of the channels ensure mixing of the laminar streams by interaction with bubbles of gas introduced into the channels, (v) the device is prepared in a single-step soft-lithographic process, and (vi) the device can be prepared to be resistant to the adsorption of proteins, and can be used with or without surface-active agents.

Background Recent studies have revealed sexually dimorphic associations between the carbamoyl‐phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease ( CAD ) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl‐phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels. Methods and Results We sought to identify additional genetic determinants of circulating glycine levels by carrying out a meta‐analysis of genome‐wide association study data in up to 30 118 subjects of European ancestry. Mendelian randomization and other analytical approaches were used to determine whether glycine‐associated variants were associated with CAD and traditional risk factors. Twelve loci were significantly associated with circulating glycine levels, 7 of which were not previously known to be involved in glycine metabolism ( ACADM , PHGDH , COX 18‐ ADAMTS 3 , PSPH , TRIB 1 , PTPRD , and ABO ). Glycine‐raising alleles at several loci individually exhibited directionally consistent associations with decreased risk of CAD . However, these effects could not be attributed directly to glycine because of associations with other CAD ‐related traits. By comparison, genetic models that only included the 2 variants directly involved in glycine degradation and for which there were no other pleiotropic associations were not associated with risk of CAD or blood pressure, lipid levels, and obesity‐related traits. Conclusions These results provide additional insight into the genetic architecture of glycine metabolism, but do not yield conclusive evidence for a causal relationship between circulating levels of this amino acid and risk of CAD in humans.

Background: Previous studies have linked full-calorie sugarsweetened beverages (SSBs) with greater weight gain and an increased risk of type 2 diabetes. Objective: We prospectively examined the association between consumption of SSBs and the risk of coronary heart disease (CHD) in women. Design: Women (n ¼ 88,520) from the Nurses’ Health Study aged 34–59 y, without previously diagnosed coronary heart disease (CHD), stroke, or diabetes in 1980, were followed from 1980 to 2004. Consumption of SSBs was derived from 7 repeated foodfrequency questionnaires administered between 1980 and 2002. Relative risks (RRs) for CHD were calculated by using Cox proportional hazards models and adjusted for known cardiovascular disease risk factors. Results: During 24 y of follow-up, we ascertained 3105 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). After standard and dietary risk factors were adjusted for, the RRs (and 95% CIs) of CHD according to categories of cumulative average of SSB consumption (,1/mo, 1–4/mo, 2–6/wk, 1/d, and � 2 servings/ d) were 1.0, 0.96 (0.87, 1.06), 1.04 (0.95, 1.14), 1.23 (1.06, 1.43), and 1.35 (1.07, 1.69) (P for trend , 0.001). Additional adjustment for body mass index, energy intake, and incident diabetes attenuated the associations, but they remained significant. Artificially sweetened beverages were not associated with CHD. Conclusion: Regular consumption of SSBs is associated with a higher risk of CHD in women, even after other unhealthful lifestyle or dietary factors are accounted for. Am J Clin Nutr

This report presents a simple and convenient method to generate nanoscale fractures (cracks) in smooth, single-crystalline Si substrates. The cracks propagated as approximately straight lines along the {100} crystal planes with controllable length defined by a stabilizing backlayer. Close to its tip, the crack presented a vertical offset of the two planes as step of smoothly decreasing height, ranging from the microscale to the atomic scale. The edges of a crack were in close contact at the tip of the crack but were separated at the edge where the crack was initiated. These steps served as ideal test features for probing the limits of the replication of soft lithography. Analysis of topography of original and replicated features (in "hard" poly(dimethylsiloxane and polyurethane) by atomic force microscopy demonstrated that steps down to 0.4 nm could be reproduced; these features approach the dimensions of atoms.

Abstract Background Branched chain amino acids (BCAAs) are essential amino acids common throughout the US diet. Although circulating BCAAs have been implicated in insulin resistance and some obesity-related cancers, the relationship between dietary intake of BCAAs and incident breast cancer is unknown. We sought to evaluate the association between long-term dietary intakes of BCAAs and invasive breast cancer risk. Methods Our analyses included 196 161 women from the Nurses’ Health Study and Nurses’ Health Study II longitudinal cohorts. Average intakes of total and individual BCAAs (isoleucine, leucine, valine) were estimated from repeated diet questionnaires and incident self-reported breast cancer cases were confirmed via medical record review. Cox proportional hazards models, adjusted for reproductive history, lifestyle, body mass index, and other breast cancer risk factors, were used to estimate hazard ratios and 95% confidence intervals. Results We observed 10 046 incident cases of breast cancer over a median of 20.8 years of follow-up. No associations between dietary intakes of total or individual BCAAs with breast cancer risk were observed. Compared with women in the bottom quintile of BCAA intake, the hazard ratio of breast cancer for those in the top quintile was 1.05 (95% confidence interval = 0.98 to 1.12; 2-sided Ptrend = .20). Findings were consistent across molecular subtypes and according to type 2 diabetes diagnosis and body mass index categories. Conclusions Dietary intakes of BCAAs are not likely a risk factor for breast cancer.

We consider the prediction of weak effects in a multiple-output regression setup, when covariates are expected to explain a small amount, less than $\approx 1%$, of the variance of the target variables. To facilitate the prediction of the weak effects, we constrain our model structure by introducing a novel Bayesian approach of sharing information between the regression model and the noise model. Further reduction of the effective number of parameters is achieved by introducing an infinite shrinkage prior and group sparsity in the context of the Bayesian reduced rank regression, and using the Bayesian infinite factor model as a flexible low-rank noise model. In our experiments the model incorporating the novelties outperformed alternatives in genomic prediction of rich phenotype data. In particular, the information sharing between the noise and regression models led to significant improvement in prediction accuracy.

A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding. We estimated the effects of age at menarche on forced vital capacity (FVC), a proxy for restrictive lung impairment, and ratio of forced expiratory volume in one second to FVC (FEV1/FVC), a measure of airway obstruction, in both adulthood and adolescence. We derived SNP-age at menarche association estimates for 122 variants from a published genome-wide meta-analysis (N = 182,416), with SNP-lung function estimates obtained by meta-analysing three studies of adult women (N = 46,944) and two of adolescent girls (N = 3025). We investigated the impact of departures from the assumption of no pleiotropy through sensitivity analyses. In adult women, in line with previous evidence, we found an effect on restrictive lung impairment with a 24.8 mL increase in FVC per year increase in age at menarche (95% CI 1.8-47.9; p = 0.035); evidence was stronger after excluding potential pleiotropic variants (43.6 mL; 17.2-69.9; p = 0.001). In adolescent girls we found an opposite effect (-56.5 mL; -108.3 to -4.7; p = 0.033), suggesting that the detrimental effect in adulthood may be preceded by a short-term post-pubertal benefit. Our secondary analyses showing results in the same direction in men and boys, in whom age at menarche SNPs have also shown association with sexual development, suggest a role for pubertal timing in general rather than menarche specifically. We found no effect on airway obstruction (FEV1/FVC).

Abstract Background It remains unclear whether maternal hypertensive disorders could impact cognitive development of the child. The aim of this study was to explore the association between hypertensive disorders and other maternal biological and social factors on the risk of mild cognitive limitations (intelligence quotient 50–85) in the offspring. Methods An 11.5‐year follow‐up study of the N orthern F inland B irth C ohort 1986 ( n = 9432) was utilised. The analysis included 8847 singleton children, of whom 198 had mild cognitive limitations. Gestational hypertension was defined as de novo hypertension (blood pressure ≥ 140/90), diagnosed mid‐pregnancy in a previously normotensive woman. Data on intelligence level of the children were based on standardised intelligence test results. Results Eleven per cent ( n = 20) of mothers having a child with mild cognitive limitations had gestational hypertension. Maternal gestational hypertension was independently associated with increased odds of mild cognitive limitation in the offspring (odds ratio 2.4 [95% confidence interval 1.4, 3.9]). Other independent maternal risk factors for mild cognitive limitation were high pre‐pregnancy body mass index (≥30 kg/m 2 ), multiparity (≥4) and low education. In addition family's socio‐economic status lower than professional, male gender and small birthweight‐for‐gestational age appeared as independent risk factors for mild cognitive limitation. Conclusions Gestational hypertension should be considered as one of the adverse early risk factors that may predispose to impaired cognitive development in childhood.

OBJECTIVE We examined the associations of inflammatory and insulinemic diets with type 2 diabetes (T2D) risk among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We followed 4,318 women with a history of GDM in the Nurses’ Health Study II for incident T2D between 1991 and 2019. Empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores were calculated using prevalidated methods. Cox models were used to calculate hazard ratios (HRs) and 95% CIs for the risk of T2D. Additionally, we estimated the least squares means of cardiometabolic biomarkers according to EDIP and EDIH quintiles in a subset of participants who were free of T2D at the time of blood collection. RESULTS During 84,174 person-years of follow-up, 1,037 women developed T2D. After adjusting for major covariates, including BMI, higher EDIP and EDIH scores, which indicated greater dietary inflammatory and insulinemic potential, were associated with an increased risk of T2D. Compared with those for the lowest quintile, adjusted HRs (95% CIs) for the highest quintile were 1.32 (1.06, 1.64) for EDIP and 1.44 (1.14, 1.82) for EDIH (both Ptrend &amp;lt; 0.05). Higher EDIP scores were significantly associated with higher concentrations of insulin and lower levels of HDL cholesterol, and EDIH scores were significantly positively associated with insulin and C-peptide concentrations. CONCLUSIONS Among women with a history of GDM, those with greater dietary inflammatory and insulinemic potential were found to be at a higher risk of T2D and to have unfavorable cardiometabolic profiles.