Publications

This work describes the binding of carbonic anhydrase (CA) to mixed self-assembled monolayers (SAMs) presenting benzenesulfonamide ligands at a surface consisting primarily of tri(ethylene glycol) [(EG)3OH] groups. Surface plasmon resonance (SPR) quantified the binding of CA to the benzenesulfonamide groups. Two factors influenced the binding of CA: (a) the density of benzenesulfonamide groups at the surface, and (b) the coverage of the surface with molecules of CA adsorbed to these benzenesulfonamide groups. At low mole-fractions of benzenesulfonamide groups in the mixed SAM where the binding of CA is highly (>90%) reversible, we observe: (a) an approximately 10-fold decrease in the observed bimolecular rate constant for association, kon,obs, during the binding of CA (as the fraction of the surface covered by adsorbed CA increases from ∼0.15 to ∼0.35, the value of kon,obs decreases from ∼40 × 103 M-1 s-1 to ∼4 × 103 M-1 s-1); (b) almost no corresponding changes in the observed unimolecular rate constant for dissociation (koff,obs ∼0.005 s-1) during the dissociation of CA from the surface. These observations establish that kon,obs is influenced by the extent of coverage of the surface with CA, but that koff,obs is not. At low surface densities of arylsulfonamide groups, one hypothesis that rationalizes these data is that the decrease in kon,obs reflects repulsive steric interactions between molecules of CA near the surface and those already adsorbed. Each molecule of biospecifically adsorbed CA shields proximal benzenesulfonamide ligands from binding to incoming molecules of CA, and decreases the surface density of these ligands that are accessible to CA, at a rate that increases nonlinearly with the quantity of CA already adsorbed.

Background Fetal and postnatal growth have been associated with adult blood pressure (BP), but findings about the relative importance of growth at different stages of life on BP are inconsistent. Methods The study population comprised 5198 participants from the Northern Finland Birth Cohort 1966 with data on birth weight, height and weight measurements until adolescence, systolic and diastolic BP at 31 years and several covariates. Structural equation modelling was used in the analysis. Results Negative direct effects of birth weight on adult systolic BP were observed (standardised regression coefficients: −0.08 (−0.14 to −0.03) in males and −0.04 (−0.09 to 0.01) in females, equalling −1.99 (−3.32 to −0.65) and −1.01 (−2.33 to 0.32) mm Hg/kg, respectively). Immediate postnatal growth was associated with adult BP only indirectly via growth later in life. In contrast, growth from adiposity rebound onwards had large direct, indirect and total effects on adult BP. Current body mass index was the strongest growth-related predictor of adult BP (0.36 (0.30 to 0.41) in males and 0.31 (0.24, 0.37) in females, equalling 1.29 (1.09 to 1.48) and 0.81 (0.63 to 0.99) mm Hg/(kg/m 2 ), respectively). Conclusions Our path analytical approach provides evidence for the importance of both fetal growth and postnatal growth, especially from adiposity rebound onwards, in determining adult BP, together with genetic predisposition and behavioural factors.

Introduction: Elevated body mass index (BMI) due to common genetic variants has been linked with the risk for future ischemic heart disease, yet it remains unclear how this association is mediated....

This paper reports a simple and versatile technique for generating structures on the surfaces of poly(dimethylsiloxane) (PDMS), approximately sinusoidal waves with periods between 0.1 and 10 μm, and the use of these structures to study cell contact guidance.1 The features are generated by stretching PDMS slabs mechanically, oxidizing them in an oxygen plasma, and allowing them to relax. These surface features are similar to photolithographically fabricated grooves that have traditionally been used to investigate cell contact guidance, although their edges are rounded rather than angular. Bovine capillary endothelial cells align and elongate on these features. The morphology and cytoskeletal structure of the aligned cells are similar to those of cells described in previous studies of contact guidance on surfaces with other types of topography. These observations and comparisons indicate that sharp edges in the features defining the grooves are not essential in eliciting contact guidance. This technique provides a method for fabricating microfeatures for the studies of the interactions between cells and their environment that does not require a cleanroom or access to photolithographic tools.

The association between maternal gestational diabetes (GDM) and manifestations of metabolic syndrome among Caucasian adolescents was studied with data from the population-based Northern Finland 1986 Birth Cohort. This is a longitudinal cohort study from early pregnancy until offspring age 16 years and includes data from a risk group-based GDM screen of pregnant mothers by an oral glucose tolerance test. Metabolic outcomes were compared between the offspring of women with GDM (OGDM; n = 95) and reference group offspring (n = 3,909). The prevalence of overweight was significantly higher in the OGDM group (18.8 vs. 8.4%; P < 0.001) than in the reference group. The median body mass index (20.8 vs. 20.2 kg/m2, 95% confidence interval (CI) for the percentage difference adjusted for sex: 3.5%, 9.5%), waist circumference (73.3 vs. 71.5 cm, 95% CI: 3.2%, 7.5%), and fasting insulin (10.20 vs. 9.30 milliunits/L, 95% CI: 5.9%, 26.0%) were higher, and homeostatic model assessment-insulin sensitivity (74.7 vs. 82.3, 95% CI: −20.6%, −5.4%) was lower in the OGDM group. These differences were similar after an additional adjustment for birth weight and gestational age. The differences in waist circumference, insulin, and homeostatic model assessment-insulin sensitivity were attenuated but remained statistically significant after additional adjustment for body mass index at 16 years. These findings highlight the importance of prevention strategies among children born to women with GDM.

OBJECTIVES: Plant-based diets may lower type 2 diabetes (T2D) risk. Whether changes in adherence to plant-based diets are associated with subsequent T2D risk remains unknown. We aimed to evaluate the associations between 4 year changes in plant based diets and subsequent 4 year risk of T2D. METHODS: We prospectively followed 76,530 women in the Nurses’ Health Study (NHS, 1986–2012), 81,586 women in NHS II (1991–2017), and 34,468 men in the Health Professionals’ Follow-up Study (1986–2016). Diet was assessed every 4 years using validated food-frequency questionnaires. Adherence to plant-based diets was assessed using previously developed indices – the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). Self reported T2D cases were validated by supplementary questionnaires. We used multivariable time dependent Cox proportional hazards models to estimate hazard ratios (HR) and 95% CIs for T2D associated with 4 year changes in adherence to plant based diets. Results of the three cohorts were pooled using an inverse variance-weighted meta-analysis. RESULTS: We documented 12,016 cases of T2D during 2818,485 person-years of follow-up. After adjustment for initial BMI, initial and 4-year changes in lifestyle and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest 4-year decrease (>10%) in PDI and hPDI had a 12%-23% higher T2D risk in the subsequent 4 years (HR for PDI, 1.12 (95% CI 1.05, 1.20), HR for hPDI, 1.23 (1.16, 1.31)). Conversely, each 10% incremental increase in PDI and hPDI over 4 years was associated with a 7%–9% lower T2D risk in subsequent 4 years (HR for PDI, 0.93 (0.90, 0.95), HR for hPDI, 0.91 (0.87, 0.95)). Changes in uPDI were not associated with T2D risk. Further adjustment for concurrent changes in body weight, a potential mediator, modestly attenuated the associations but results remained significant. We estimated that body weight changes explained 6.0%–36% of the associations between 4 year changes in PDI and hPDI and subsequent T2D risk. CONCLUSIONS: Improving adherence to overall and healthful plant based diets over a 4 year period was associated with a lower T2D risk, whereas decreased adherence to overall and healthful plant based diets was associated with a higher T2D risk. FUNDING SOURCES: Nutricia Research Foundation/NIH.

Adult physical performance is recognized as a marker of both current physical capacity and future health. The aim of the study was to examine the independent influences of birth weight, infant weight gain, and infant motor development on a variety of adult physical performance outcomes, in terms of muscular strength, muscular endurance, and aerobic fitness.The study population consisted of 4304 individuals from the Northern Finland Birth Cohort 1966 (NFBC 1966) with anthropometry measured at birth and at 1 yr. Infant motor development at age 1 yr was assessed by parentally reported age at first walking supported and standing unaided. At follow-up, aged 31 yr, muscle strength was measured using a handgrip dynamometer, muscle endurance was measured using a timed trunk extension test, and aerobic fitness was estimated from heart rate immediately after a standardized step test.Birth weight was positively associated with muscle strength and aerobic fitness at age 31 yr, and these associations were independent of adult body size (P < 0.001). Greater infant weight gain between 0 and 1 yr was associated with lower muscle endurance (P = 0.004) and poorer aerobic fitness (P = 0.002); these associations seemed to be mediated by adult body size. Independent of infant birth weight and adult body size (height and weight), earlier infant motor development was associated with greater adult muscle strength (P < or = 0.001), muscle endurance (P < 0.001), and aerobic fitness (P < 0.001).Higher birth weight, lower infant weight gain, and earlier infant motor development independently predict higher levels of adult physical performance for muscle strength, muscle endurance, and aerobic fitness at age 31 yr.

Background: There are various maternal prenatal biopsychosocial (BPS) predictors of birth weight, making it difficult to quantify their cumulative relationship. Methods: We studied two birth cohorts: Northern Finland Birth Cohort 1986 (NFBC1986) born in 1985-1986 and the Generation R Study (from the Netherlands) born in 2002-2006. In NFBC1986, we selected variables depicting BPS exposure in association with birth weight and performed factor analysis to derive latent constructs representing the relationship between these variables. In Generation R, the same factors were generated weighted by loadings of NFBC1986. Factor scores from each factor were then allocated into tertiles and added together to calculate a cumulative BPS score. In all cases, we used regression analyses to explore the relationship with birth weight corrected for sex and gestational age and additionally adjusted for other factors. Results: Factor analysis supported a four-factor structure, labelled closely to represent their characteristics as â € Factor1-BMI' (body mass index), â € Factor2-DBP' (diastolic blood pressure), â € Factor3-Socioeconomic-Obstetric-Profile' and â € Factor4-Parental-Lifestyle'. In both cohorts, â € Factor1-BMI' was positively associated with birth weight, whereas other factors showed negative association. â € Factor3-Socioeconomic-Obstetric-Profile' and â € Factor4-Parental-Lifestyle' had the greatest effect size, explaining 30% of the variation in birth weight. Associations of the factors with birth weight were largely driven by â € Factor1-BMI'. Graded decrease in birth weight was observed with increasing cumulative BPS score, jointly evaluating four factors in both cohorts. Conclusion: Our study is a proof of concept for maternal prenatal BPS hypothesis, highlighting the components snowball effect on birth weight in two different European birth cohorts.

Vitamin D deficiency has been linked to the increased risk of several chronic diseases, especially in people living in the Northern Latitudes. The aim of this study was to assess the vitamin D status in older subjects born in 1945 in Northern Finland (latitude 65°North), and to examine its associations to components of metabolic syndrome (MetS). In this cross-sectional study, we invited 904 subjects born in 1945 from the Oulu region (Oulu45 cohort), out of an original cohort of 1332 subjects. In the cohort, plasma 25 hydroxyvitamin D (25OHD) levels were determined by an enzyme immunoassay of 263 men and 373 women, with a mean age baseline of 69±0.5 years old. We assessed the participants' usage of vitamin D supplements, as well as their lifestyle factors, using a questionnaire. Nearly 80% of the subjects had low vitamin D levels [either vitamin D deficient (<50 nmol/L) or insufficient (50 - 75 nmol/L)], and only 20% of the participants had sufficient vitamin D levels (>75 nmol/L) (based on the American Endocrine Society guidelines). The low vitamin D status was associated with a high prevalence of MetS; a significantly higher number of subjects with MetS (41%) had low vitamin D levels in comparison to the non-MetS subjects (38%) (p ≤ 0.05). The subjects under vitamin D supplementation had a significantly lower incidence of MetS (42.6% vs 57.4%) and its components in comparison to the non-supplemented subjects (p ≤ 0.05). Low vitamin D levels are a risk factor for MetS amongst other lifestyle factors, such as dietary habits and physical inactivity, among older subjects in the Northern Latitudes (65°North). Optimal supplementation of vitamin D, along with rich dietary sources of vitamin D, are highly recommended for older subjects as a means to positively affect, e.g., hypertension, insulin resistance, and obesity, as components of the MetS.