Publications

BACKGROUND: Animal studies demonstrate a clear link between prenatal exposure to glucocorticoids (GC) and altered offspring brain development. We aim to examine whether prenatal GC exposure programs long-term mental health in humans. METHODS: Using propensity-score-matching, children prenatally exposed to synthetic glucocorticoids (sGC), n=37, and controls, n=185, were balanced on important confounders related to sGC treatment - gestational age and pre-pregnancy BMI. We also used mixed-effects modeling to analyse the entire cohort - matching each sGC case, n=37, to all possible controls, n=6079, on gestational age and sex. We obtained data from the Northern Finland Birth Cohort 1986 at four waves - pregnancy, birth, 8 and 16 years. Data on pregnancy and birth outcomes came from medical records. Mental health was assessed at 8 years by teachers with the Rutter B2 scale, and at 16 years by parents with the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale and adolescents by the Youth Self-Report (YSR) scale. RESULTS: Prenatal sGC treatment was consistently associated with adverse mental health in childhood and adolescence, as shown by both the propensity-score method and mixed-effects model. Using the propensity-score-matched subsample, linear multiple regression showed prenatal sGC was significantly linked with general psychiatric disturbance (B=8.34 [95% CI: .23-16.45]) and inattention (B= .97 [95% CI: .16-1.80]) at 8 years after control for relevant confounders. Similar findings were obtained at 16 years, but did not reach statistical significance. Mediation by birthweight/placental weight was not detected. CONCLUSIONS: This study is the first to prospectively investigate the long-term associations between prenatal exposure to sGC treatment and mental health in children and adolescents. We report an association between prenatal exposure to sGC and child mental health, supportive of the idea that sGC has a programming effect on the fetal brain. Language: en

<title>Abstract</title> Hypertension is a leading cause of premature death affecting more than a billion individuals worldwide. Here we report on the genetic determinants of blood pressure (BP) traits (systolic, diastolic, and pulse pressure) in the largest single-stage genome-wide analysis to date (N = 1,028,980 European-descent individuals). We identified 2,103 independent genetic signals (P &lt; 5x10^{− 8}) for BP traits, including 113 novel loci. These associations explain ~ 40% of common SNP heritability of systolic and diastolic BP. Comparison of top versus bottom deciles of polygenic risk scores (PRS) based on these results reveal clinically meaningful differences in BP (12.9 mm Hg for systolic BP, 95% CI 11.5–14.2 mm Hg, p = 9.08×10^{− 73}) and hypertension risk (OR 5.41; 95% CI 4.12 to 7.10; P = 9.71×10^{− 33}) in an independent dataset. Compared with the area under the curve (AUC) for hypertension discrimination for a model with sex, age, BMI, and genetic ancestry, adding systolic and diastolic BP PRS increased discrimination from 0.791 (95% CI = 0.781–0.801) to 0.814 (95% CI = 0.805–0.824, ∆AUC = 0.023, P = 2.27x10^{− 22}). Our transcriptome-wide association study detected 2,793 BP colocalized associations with genetically-predicted expression of 1,070 genes in five cardiovascular tissues, of which 500 are previously unreported for BP traits. These findings represent an advance in our understanding of hypertension and highlight the role of increasingly large genomic studies for development of more accurate PRS, which may inform precision health research.

Background: Glucose management can be difficult in frail older adults with type 2 diabetes (T2D) on insulin therapy. As no study has examined the interrelationship between frailty, dysglycaemia and mortality, we used continuous glucose monitors (CGMs) to prospectively profile insulin-requiring frail and borderline frail older adults with T2D, explored circulating metabolic factors that influenced it, and determined the prognostic value of CGM metrics. Methods: This was a multi-centre, prospective, observational study using weeklong real-time CGMs (Medtronic iPro2) between August 2018 and October 2019. 28,608 hours of CGM recordings were compiled from 215 community-living T2D patients (mean age 74·7 years) on long-term insulin therapy, and analysed according to Advanced Technologies & Treatments for Diabetes 2019 standardised metrics. Frailty index was computed, and comprehensive frailty assessments and serum metabolic profiling were performed. Association and regression analyses were adjusted for age, sex, comorbidities, renal function, and insulin and anti-diabetic drug regimens. Survival analysis and proportional hazard modelling were performed. Findings: Incremental frailty was associated with older age, higher HbA1c, worse renal function, and past history of stroke. Decreased ‘time in range’ (TIR) and increased ‘time above range’ (TAR) metrics were strongly correlated with increased frailty and hyperglycaemia, whereas overall TBR was not different between frailty levels. Insulin and anti-diabetic drug regimen did not significantly affect regression estimates. Reduced serum albumin level was identified as a determinant of hyperglycaemia/dysglycaemia. Importantly, increased Level 2 TAR (glucose >13·9 mmol/L) was predictive of mortality (median follow-up 2·3 years) that was explainable by frailty. Each 1% increment of Level 2 TAR was associated with a 1·9% increase in mortality hazard. Interpretation: In insulin-requiring older adults with T2D, incremental frailty was associated with increased dysglycaemia and hyperglycaemia rather than hypoglycaemia. Mortality hazard was increased with prolonged severe hyperglycaemia. Funding: Health and Medical Research Fund (HMRF no.15162161), Food & Health Bureau, The Government of the Hong Kong SAR of China.Declaration of Interest: Ronald CW Ma received research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Novo Nordisk, Pfizer, Sanofi and Tricida Inc. for carrying out clinical trials, speaker honorarium or consultancy in advisory boards. All proceeds have been donated to the Chinese University of Hong Kong to support diabetes research. All others have nothing to declare. Ethical Approval: HARE is a multicentre, prospective, observational study approved by the institutional review board of The Chinese University of Hong Kong–New Territories East Cluster (CUHK-NTEC) Clinical Research Ethics Committee (CREC study no. 2017.702).

An electrical junction formed by mechanical contact between two self-assembled monolayers (SAMs)a SAM formed from an dialkyl disulfide with a covalently linked tetracyanoquinodimethane group that is supported by silver (or gold) and a SAM formed from an alkanethiolate SAM that is supported by mercuryrectifies current. The precursor to the SAM on silver (or gold) was bis(20-(2-((2,5-cyclohexadiene-1,4-diylidene)dimalonitrile))decyl)) disulfide and that for the SAM on mercury was HS(CH2)n-1CH3 (n = 14, 16, 18). The electrical properties of the junctions were characterized by current−voltage measurements. The ratio of the conductivity of the junction in the forward bias (Hg cathodic) to that in the reverse bias (Hg anodic), at a potential of 1 V, was 9 ± 2 when the SAM on mercury was derived from HS(CH2)15CH3. The ratio of the conductivity in the forward bias to that in the reverse bias increased with decreasing chain length of the alkanethiol used to form the SAM on mercury. These results demonstrate that a single redox center asymmetrically placed in a metal−insulator−metal junction can cause the rectification of current and indicate that a fixed dipole in the insulating region of a metal−insulator−metal junction is not required for rectification.

Lower levels of physical activity and cardiorespiratory fitness are key risk factors of chronic adult diseases. Physical activity and cardiorespiratory fitness are predicted by birth weight, but the underlying parental and pregnancy-related factors remain largely unknown. We examined how prenatal determinants are associated with physical activity and cardiorespiratory fitness in adolescence. Of the 16-year-old members of the population-based Northern Finland Birth Cohort 1986 (NFBC 1986), 6682 singletons with no major physical disability reported their amount of physical activity outside school hours, and 4706 completed a submaximal cycle ergometer test assessing cardiorespiratory fitness. Physical activity was expressed as metabolic equivalent hours per week (METh/week) and cardiorespiratory fitness as peak oxygen uptake (ml·kg−1·min−1). Prenatal determinants included birth weight, length of gestation, mother's and father's body mass index (BMI), maternal gestational diabetes mellitus (GDM), and maternal hypertension and smoking during pregnancy. Data were analyzed by multiple linear regression. A higher birth weight and longer length of gestation predicted lower levels of physical activity and cardiorespiratory fitness at 16 years, although the association between length of gestation and physical activity was inverse U-shaped. Mother's or father's overweight or obesity before pregnancy were associated with lower levels of their offspring's physical activity and fitness in adolescence. Adjusting for maternal pregnancy disorders and the adolescent's own BMI attenuated the associations with the mother's but not the father's overweight/obesity. Furthermore, maternal GDM predicted lower cardiorespiratory fitness. A high birth weight and parental overweight/obesity are associated with lower levels of both physical activity and cardiorespiratory fitness in adolescence, while maternal GDM and longer length of gestation are associated with lower cardiorespiratory fitness. Both long and short lengths of gestation predict low physical activity.

No abstract is provided for this article.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign of Organic Structures in the Solid State: Molecular Tapes Based on the Network of Hydrogen Bonds Present in the Cyanuric Acid.cntdot.Melamine ComplexJonathan A. Zerkowski, John C. MacDonald, Christopher T. Seto, Derk A. Wierda, and George M. WhitesidesCite this: J. Am. Chem. Soc. 1994, 116, 6, 2382–2391Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/ja00085a018https://doi.org/10.1021/ja00085a018research-articleACS PublicationsRequest reuse permissionsArticle Views1106Altmetric-Citations160LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (8)»Supporting Information Supporting Information Get e-Alerts

Specific dietary and lifestyle factors are independently associated with long-term weight gain, with a substantial aggregate effect and implications for strategies to prevent obesity. (Funded by the National Institutes of Health and others.).

Objective: To investigate the effect of adulthood obesity on work ability in early midlife during a 15-year follow-up. Methods: The study population included men and women (n = 5470), born in northern Finland in 1966. Participants evaluated their current perceived work ability compared with their lifetime best at the age of 46. Participants’ weight and height were measured at 31 years and self-reported at 46 years, and body mass indexes were calculated. Results: Obesity at both ages, and developing obesity between the ages of 31 and 46 increased the relative risk of poor work ability at 46 years among sexes, and among those in both low and high physically strenuous work. Conclusions: Long-term obesity and developing obesity in mid-adulthood increase the risk of poor work ability. Thus, the promotion of healthy behaviors by policies, healthcare services, and at workplaces is important.