Publications

Abstract Background Low-carbohydrate diets could lead to reduced fruit and vegetable intake, which may be protective against CVD. The role of carbohydrate intake in modifying the association between fruits and vegetables and CVD has not been evaluated. Objective To evaluate whether carbohydrate intake affects the association between fruits and vegetables and CVD. Design We included participants from two large prospective studies, the Nurses’ Health Study (NHS) and the Health Professionals’ Follow-Up Study (HPFS). We followed 70 870 eligible NHS females for 16 years and 38 918 eligible HPFS males for 14 years. Diet was assessed from an FFQ updated every 4 years. Our primary outcome was ischaemic CVD (fatal and non-fatal myocardial infarction and ischaemic stroke). We used Cox proportional hazards models to evaluate the relationship between fruits and vegetables and ischaemic CVD within groups with low, moderate or high carbohydrate intake. Results Fruit intake was strongly related with carbohydrate intake, but vegetables showed a very small correlation. Vegetable intake showed stronger associations with ischaemic CVD among the low carbohydrate group (multivariate risk ratio (RR) = 0·82 for an increment of 3 servings/d; 95 % CI 0·68, 0·99); green leafy vegetables and carotene-rich fruits and vegetables followed a similar pattern. Total fruit intake was associated with a lower risk of ischaemic CVD only among participants with moderate carbohydrate intake (RR = 0·81 comparing extreme quintiles; 95 % CI 0·70, 0·94). Conclusions Total vegetables, green leafy vegetables and carotene-rich fruits and vegetables showed stronger associations with ischaemic CVD among the low carbohydrate group. No consistent trends were observed for fruit intake.

Antenatal corticosteroid therapy (ACT) is used clinically to prepare the fetal lung for impending preterm birth, but animal and human studies link corticosteroids to smaller birth size. Whether ACT is associated with birth size is debated; therefore, we assessed differences in birth size in treated versus untreated pregnancies. Methods and findings This observational register-based study used data from the Finnish Medical Birth Register (FMBR) covering all births in Finland (January 1, 2006–December 31, 2010). We used unadjusted and adjusted regression analyses as well as propensity score matching (PSM) to analyze whether birth size differed by ACT exposure. PSM provides a stringent comparison, as subsamples were created matched on baseline and medical characteristics between treated and untreated women. All analyses were stratified by timing of birth. The primary study outcome was birth size: birth weight (BWT), birth length (BL), ponderal index (PI), and head circumference (HC) measured immediately after birth and recorded in the FMBR. Additional analyses explored indicators of neonatal health in relation to ACT exposure and birth size. A total of 278,508 live-born singleton births with ≥24 gestational completed weeks were registered in the FMBR during the 5-year study period. Over 4% of infants were born preterm, and 4,887 women were treated with ACT (1.75%). More than 44% of the exposed infants (n = 2,173) were born at term. First, results of unadjusted regression analyses using the entire sample showed the greatest reductions in BWT as compared to the other analytic methods: very preterm −61.26 g (±SE 24.12, P < 0.01), preterm −232.90 g (±SE 17.24, P < .001), near term −171.50 g (±SE 17.52, P < .001), and at term −101.95 g (±SE 10.89, P < .001). Second, using the entire sample, regression analyses adjusted for baseline and medical conditions showed significant differences in BWT between exposed and unexposed infants: very preterm −61.54 g (±SE 28.62, P < .03), preterm −222.78 g (±SE 19.64, P < .001), near term −159.25 g (±SE 19.14, P < .001), and at term −91.62 g (±SE 11.86, P < .03). Third, using the stringent PSM analyses based on matched subsamples, infants exposed to ACT weighed less at birth: −220.18 g (±SE 21.43, P < .001), −140.68 g (±SE 23.09, P < .001), and −89.38 g (±SE 14.16, P < .001), born preterm, near term, and at term, respectively. Similarly, significant reductions in BL and HC were also observed using the three analytic methods. There were no differences among postterm infants regardless of analytic method. Likewise, we observed no differences with respect to PI. Additional analyses showed that exposed and unexposed infants had generally similar Apgar scores at birth, yet the ACT-treated infants received greater medical care during the first 7 days of life and beyond. Our study is mainly limited by lack of data in FMBR specifying the interval between treatment and birth as well as other potential confounders that could not be tested. Conclusions In this study, ACT was consistently associated with reduction in birth size for infants born preterm, near term, or at term. Further investigation is warranted alongside reevaluation of guidelines. Efforts need to be made to correctly identify and target patients who will deliver preterm. Reduced growth should be considered when deliberating early care decisions.

Background: The healthiest dietary pattern for myocardial infarction (MI) survivors is not known. Specific long-term benefits of a low carbohydrate diet (LCD) is unknown, whether it mainly be from animal or vegetable sources. Objective: To examine the associations between post-MI adherence to a low carbohydrate diet (LCD), measured by a total, plant- and animal-based low carbohydrate diet score (LCDS), in relation to all-cause and cardiovascular mortality. Design: We included 2,258 women from the Nurses’ Health Study and 1,840 men from the Health Professional Follow-Up Study, who had survived a first MI during follow-up, provided pre-MI and at least one post-MI food frequency questionnaire (FFQ). Results: Adherence to a LCD high in animal sources of protein and fat was associated with higher all-cause and cardiovascular mortality (HR=1.31, 95% CI: 1.05-1.63 for all-cause mortality; HR= 1.49, 95% CI: 1.08-2.06 for cardiovascular mortality comparing extreme quintiles). An increase in adherence to an animal-based LCD prospectively assessed from the pre- to post-MI period was associated with higher all-cause mortality and cardiovascular mortality (HR=1.29, 95% CI: 1.03-1.63 for all-cause mortality; HR=1.53, 95% CI: 1.10-2.12 for cardiovascular mortality comparing extreme quintiles). An increase in adherence to a plant-based LCD was not associated with lower all-cause or cardiovascular mortality. Conclusions: Greater adherence to a LCD high in animal sources of fat and protein was associated with higher all-cause and cardiovascular mortality post-MI. We did not find a health benefit from greater adherence to an overall LCD post MI.

This paper addresses the numerical simulation of plasticity and ductile fracture of large scale structures (e.g. ships, railcars, automobiles) fabricated with welds that exhibit appreciably lower strength than the plate material, often referred to as weld undermatching. It has been observed, both numerically and experimentally, that for such structures the weld undermatching often leads to plasticity and fracture being limited to the weld and heat affected zone (HAZ). While the large size of the structures of interest precludes the use of a refined three-dimensional element mesh capable of capturing the details of the weld/HAZ behavior, cohesive zones are ideal for capturing the overall effects of undermatched weld plasticity and fracture on a structural scale. This paper focuses on establishing a systematic calibration process for determining the cohesive zone constitutive behavior and examining the validity of this approach in the context of mode I tearing of a large welded two-layer AA6061-T6 sandwich panel. First, test data from a welded coupon is used to calibrate the cohesive law. Tearing fracture of this panel is examined using the established cohesive law to represent weld/HAZ along with elastic-plastic shell elements, with in-plane dimensions much greater than the layer thickness, to represent the parent metal. It was verified that, for this structure, plasticity was indeed confined to the welds and heat affected zones, and that the behavior of the panel was captured with reasonable fidelity.

This paper presents an incremental elastic-plastic finite element solution to the problem of small scale yielding near a crack in plane strain for a non-ha

Both reduced and prolonged habitual sleep durations are associated with increased risk of pneumonia. Further research is needed to understand how sleep habits can influence immunity.

&lt;i&gt;Background:&lt;/i&gt; Type 2 diabetes has been associated with an increased risk of dementia. To assess possible independent effects of insulin, we investigated the relation of insulin levels to cognitive decline in nondiabetic women. &lt;i&gt;Methods:&lt;/i&gt; Fasting plasma insulin levels were measured in mid-life in 1,416 nondiabetic Nurses’ Health Study participants, who also completed cognitive testing that began 10 years later (current age: 70–75 years). Over 4 years, 3 assessments of general cognition, verbal memory, category fluency and attention were administered. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) performance, the global score (average of all tests) and verbal memory (average of verbal recall tests). Linear mixed-effects models were used to calculate the association between insulin and cognitive decline. &lt;i&gt;Results:&lt;/i&gt; Higher insulin levels were associated with a faster decline on the TICS and verbal memory. For analysis, batch-specific quartiles of insulin levels were constructed. Compared to the lowest quartile, adjusted differences in the annual rates of decline (with 95% CI values in parentheses) for the second, third and fourth quartiles were: TICS, –0.06 (–0.16, 0.03), –0.14 (–0.24, –0.04), and –0.09 (–0.19, 0.01) points (p trend = 0.04); verbal memory, –0.01 (–0.04, 0.02), –0.05 (–0.08, –0.02), and –0.02 (–0.05, 0.01) units (p trend = 0.02). These associations remained after multivariable adjustment. &lt;i&gt;Conclusions:&lt;/i&gt; Our study provides evidence for a potential role of higher fasting insulin levels in cognitive decline, possibly independent of diabetes.

This paper uses capillary electrophoresis to follow a globular metalloproteinbovine carbonic anhydrase II (BCA, EC 4.2.1.1)on unfolding upon treatment with sodium dodecyl sulfate (SDS) and refolding upon removal of SDS, both in the presence and the absence of its Zn(II) cofactor. This research demonstrates that the Zn(II) cofactor is not required for refolding into a nativelike conformation, does not remain associated with the unfolded protein, and does not significantly change the rate of refolding. The presence of the Zn(II) cofactor, however, does increase the total amount of recovered protein by a factor of 2. Capillary electrophoresis could distinguish between native and denatured protein, based on the difference in electrophoretic mobility between the native protein and the aggregate of denatured protein and SDS. In addition, the active site was probed by observing binding of BCA to a charged arylsulfonamide using affinity capillary electrophoresis. These studies provide a foundation for future physical-organic studies using BCA as a model to examine interactions between proteins and SDS.

Abstract Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. We conducted a genome-wide association study (GWAS) of alcohol use in ~480,000 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 novel, common loci, and investigated their potential functional significance using magnetic resonance imaging data, gene expression and behavioral studies in Drosophila . Our results identify new genetic pathways associated with alcohol consumption and suggest common genetic mechanisms with several neuropsychiatric disorders including schizophrenia.

BACKGROUND AND AIM: The relationship between pesticide exposures and metabolomics biomarkers is not well understood. We examined the changes in the serum metabolome (early biomarkers) and the metabolic pathways associated with various pesticide exposure scenarios (OPE: overall exposure, PEM: exposure in months, PEY: exposure in years, and PEU: reported specific pesticides use). METHOD: We utilized questionnaire data on pesticide exposures and blood samples for nuclear magnetic resonance (NMR)-based metabolomics analyses from the Northern Finland Birth Cohort 1966 31-year cross-sectional examination. For exposures and metabolites associations, participants size varied between 2361 and 5035. To investigate associations between metabolomics biomarkers and exposure to pesticide scenarios compared to those who reported no exposures multivariable regression analyses stratified for sex and adjustment with covariates (season of pesticide use, socioeconomic position (SEP), alcohol consumption, BMI, and latitude of residence) were performed. Multiple testing by Benjamini–Hochberg false discovery rate (FDR) correction. RESULTS: Pesticide exposures differed by sex, season of pesticide use, alcohol, SEP, latitude of residence. Our results showed that all pesticide exposure scenarios were negatively associated with decreased HDL concentrations across all lipoprotein subclasses in women. OPE, PEY, and PEU were associated with decreased branched-chain amino acid concentrations in men and decreased albumin concentrations in women. OPE, PEY and PEU were also associated with changes in glycolysis metabolites and ketone bodies in both sexes. Specific pesticides exposure was negatively associated with sphingolipids and inflammatory biomarkers in men. In women, OPE, PEM, and PEU were associated with decreased apolipoprotein A1 and increased apolipoprotein B/apolipoprotein A1 ratio. CONCLUSIONS: Our findings suggest that identification of early biomarkers of disease risk related to pesticide exposures can inform strategies to reduce exposure and investigate causal pathways. Women may be more susceptible to non-occupational pesticide exposures when compared to men, and future sex-specific studies are warranted.