DEVELOPMENTAL ORIGINS OF METABOLIC DISEASES

Almost 2 billion adults in the world are overweight, and more than half of them are classified as obese, while nearly one-third of children globally experience poor growth and development. Given the vast amount of knowledge that has been gleaned from decades of research on growth and development, a number of questions remain as to why the world is now in the midst of a global epidemic of obesity accompanied by the “double burden of malnutrition,” where overweight coexists with underweight and micronutrient deficiencies. This challenge to the human condition can be attributed to nutritional and environmental exposures during pregnancy that may program a fetus to have a higher risk of chronic diseases in adulthood. To explore this concept, frequently called the developmental origins of health and disease (DOHaD), this review considers a host of factors and physiological mechanisms that drive a fetus or child toward a higher risk of obesity, fatty liver disease, hypertension, and/or type 2 diabetes (T2D). To that end, this review explores the epidemiology of DOHaD with discussions focused on adaptations to human energetics, placental development, dysmetabolism, and key environmental exposures that act to promote chronic diseases in adulthood. These areas are complementary and additive in understanding how providing the best conditions for optimal growth can create the best possible conditions for lifelong health. Moreover, understanding both physiological as well as epigenetic and molecular mechanisms for DOHaD is vital to most fully address the global issues of obesity and other chronic diseases

Association between sex steroid hormones and subsequent hyperglycemia during pregnancy

ObjectiveSex steroid hormones may play a role in insulin resistance and glucose dysregulation. However, evidence regarding associations between early-pregnancy sex steroid hormones and hyperglycemia during pregnancy is limited. The primary objective of this study was to assess the relationships between first trimester sex steroid hormones and the subsequent development of hyperglycemia during pregnancy; with secondary evaluation of sex steroid hormones levels in mid-late pregnancy, concurrent with and subsequent to diagnosis of gestational diabetes.MethodsRetrospective analysis of a prospective pregnancy cohort study was conducted. Medically low-risk participants with no known major endocrine disorders were recruited in the first trimester of pregnancy (n=319). Sex steroid hormones in each trimester, including total testosterone, free testosterone, estrone, estradiol, and estriol, were assessed using high-performance liquid chromatography and tandem mass spectrometry. Glucose levels of the 1-hour oral glucose tolerance test and gestational diabetes diagnosis were abstracted from medical records. Multivariable linear regression models were fitted to assess the associations of individual first trimester sex steroids and glucose levels.ResultsIn adjusted models, first trimester total testosterone (β=5.24, 95% CI: 0.01, 10.46, p=0.05) and free testosterone (β=5.98, 95% CI: 0.97, 10.98, p=0.02) were positively associated with subsequent glucose concentrations and gestational diabetes diagnosis (total testosterone: OR=3.63, 95% CI: 1.50, 8.78; free testosterone: OR=3.69; 95% CI: 1.56, 8.73). First trimester estrone was also positively associated with gestational diabetes (OR=3.66, 95% CI: 1.56, 8.55). In mid-late pregnancy, pregnant people with gestational diabetes had lower total testosterone levels (β=-0.19, 95% CI: -0.36, -0.02) after adjustment for first trimester total testosterone.ConclusionEarly-pregnancy sex steroid hormones, including total testosterone, free testosterone, and estrone, were positively associated with glucose levels and gestational diabetes in mid-late pregnancy. These hormones may serve as early predictors of gestational diabetes in combination with other risk factors

Children’s Developing Understanding of the Cognitive Abilities of Supernatural and Natural Minds: Evidence from Three Cultures

Despite a wealth of research exploring developmental patterns of children’s understanding of the thoughts and desires of another (or, their theory of mind), relatively little research has explored children’s developing understanding of supernatural minds. Of the work that exists, very few studies have explored whether patterns are similar in other cultural contexts, or religious traditions outside of Western, Educated, Industrialized, Rich, and Democratic (WEIRD) societies. To address this deficit, the present study recruited 2-to-5-year-old children from three countries (United Kingdom, Albania, and Israel) with different religious traditions (Christian, Muslim, and Jewish). Children completed two perception (audio and visual) tasks and one memory task assessing their understanding of natural and supernatural minds’ cognitive abilities. Analyses revealed different patterns for responses about human minds. However, there were similar results across samples for responses about God, suggesting a shared developmental pattern. We conclude that children from religious traditions with a High God (God, Allah, Ha-Shem) share a similar developing concept of God

Herbivorous dinosaur jaw disparity and its relationship to extrinsic evolutionary drivers

COPYRIGHT: © 2016 The Paleontological Society. All rights reserved This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.MacLaren JA, Anderson PSL, Barrett P, Rayfield EJ (2016) Data from: Herbivorous dinosaur jaw disparity and its relationship to extrinsic evolutionary drivers. Dryad Digital Repository. http://dx.doi.org/10.5061/dryad.c78k

Assessment of Personal Care Product Use and Perceptions of Use in a Sample of US Adults Affiliated with a University in the Northeast

Evidence supports unequal burdens of chemical exposures from personal care products (PCPs) among some groups, namely femme-identifying and racial and ethnic minorities. In this study, we implemented an online questionnaire to assess PCP purchasing and usage behaviors and perceptions of use among a sample of US adults recruited at a Northeastern university. We collected PCP use across seven product categories (hair, beauty, skincare, perfumes/colognes, feminine hygiene, oral care, other), and behaviors, attitudes, and perceptions of use and safety across sociodemographic factors to evaluate relationships between sociodemographic factors and the total number of products used within the prior 24–48 h using multivariable models. We also summarized participants’ perceptions and attitudes. Among 591 adults (20.0% Asian American/Pacific Islander [AAPI], 5.9% Hispanic, 9.6% non-Hispanic Black [NHB], 54.6% non-Hispanic White [NHW], and 9.9% multiracial or other), the average number of PCPs used within the prior 24–48 h was 15.6 ± 7.7. PCP use was greater among females than males (19.0 vs. 7.9, P \u3c 0.01) and varied by race and ethnicity among females. Relative to NHWs, AAPI females used fewer hair products (2.5 vs. 3.1) and more feminine hygiene products (1.5 vs. 1.1), NHB females used more hair products (3.8 vs. 3.1), perfumes (1.0 vs. 0.6), oral care (2.3 vs. 1.9), and feminine hygiene products (1.8 vs. 1.1), and multiracial or other females used more oral care (2.2 vs. 1.9) and feminine hygiene products (1.5 vs. 1.1) (P-values \u3c0.05). Generally, study participants reported moderate concern about exposures and health effects from using PCPs, with few differences by gender, race, and ethnicity. These findings add to the extant literature on PCP use across sociodemographic characteristics. Improving the understanding of patterns of use for specific products and their chemical ingredients is critical for developing interventions to reduce these exposures, especially in vulnerable groups with an unequal burden of exposure

Association between maternal occupational exposure to cleaning chemicals during pregnancy and childhood wheeze and asthma

BackgroundAsthma is a leading cause of childhood morbidity in the U.S. and a significant public health concern. The prenatal period is a critical window during which environmental influences, including maternal occupational exposures, can shape child respiratory health. Cleaning chemicals are commonly encountered in occupational settings, yet few studies have examined the potential link between prenatal occupational exposures to cleaning chemicals and risk of childhood wheeze and asthma.MethodsWe evaluated the potential influence of maternal occupational exposure to cleaning chemicals during pregnancy on pediatric asthma and wheeze at child age 4–6 years in 453 mother-child pairs from two longitudinal pregnancy cohorts, TIDES and GAPPS, part of the ECHO prenatal and early childhood pathways to health (ECHO-PATHWAYS) consortium. Maternal occupational exposure to cleaning chemicals was defined based on reported occupation and frequency of occupational use of chemicals during pregnancy. Child current wheeze and asthma outcomes were defined by parental responses to a widely-used, standardized respiratory outcomes questionnaire administered at child age 4–6 years. Multivariable Poisson regression with robust standard errors was used to estimate relative risk (RR) of asthma in models adjusted for confounding. Effect modification by child sex was assessed using product interaction terms.ResultsOverall, 116 mothers (25.6%) reported occupational exposure to cleaning chemicals during pregnancy, 11.7% of children had current wheeze, and 10.2% had current asthma. We did not identify associations between prenatal exposure to cleaning chemicals and current wheeze [RRadjusted 1.03, 95% confidence interval (CI): 0.56, 1.90] or current asthma (RRadjusted 0.89, CI: 0.46, 1.74) in the overall sample. Analyses of effect modification suggested an adverse association among females for current wheeze (RR 1.82, CI: 0.76, 4.37), compared to males (RR 0.68, CI: 0.29, 1.58), though the interaction p-value was >0.05.ConclusionWe did not observe evidence of associations between maternal prenatal occupational exposure to cleaning chemicals and childhood wheeze or asthma in the multi-site ECHO-PATHWAYS consortium. We leveraged longitudinal U.S. pregnancy cohorts with rich data characterization to expand on limited and mixed literature. Ongoing research is needed to more precisely characterize maternal occupational chemical exposures and impacts on child health in larger studies

Brexit and the everyday politics of emotion: methodological lessons from history

The 2016 European Union referendum campaign has been depicted as a battle between ‘heads’ and ‘hearts’, reason and emotion. Voters’ propensity to trust their feelings over expert knowledge has sparked debate about the future of democratic politics in what is increasingly believed to be an ‘age of emotion’. In this article, we argue that we can learn from the ways that historians have approached the study of emotions and everyday politics to help us make sense of this present moment. Drawing on William Reddy’s concept of ‘emotional regimes’, we analyse the position of emotion in qualitative, ‘everyday narratives’ about the 2016 European Union referendum. Using new evidence from the Mass Observation Archive, we argue that while reason and emotion are inextricable facets of political decision-making, citizens themselves understand the two processes as distinct and competing

Phenotypic drug screen uncovers the metabolic GCH1/BH4 pathway as key regulator of EGFR/KRAS-mediated neuropathic pain and lung cancer

Increased tetrahydrobiopterin (BH4) generated in injured sensory neurons contributes to increased pain sensitivity and its persistence. GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the de novo BH4 synthetic pathway, and human single-nucleotide polymorphism studies, together with mouse genetic modeling, have demonstrated that decreased GCH1 leads to both reduced BH4 and pain. However, little is known about the regulation of Gch1 expression upon nerve injury and whether this could be modulated as an analgesic therapeutic intervention. We performed a phenotypic screen using about 1000 bioactive compounds, many of which are target-annotated FDA-approved drugs, for their effect on regulating Gch1 expression in rodent injured dorsal root ganglion neurons. From this approach, we uncovered relevant pathways that regulate Gch1 expression in sensory neurons. We report that EGFR/KRAS signaling triggers increased Gch1 expression and contributes to neuropathic pain; conversely, inhibiting EGFR suppressed GCH1 and BH4 and exerted analgesic effects, suggesting a molecular link between EGFR/KRAS and pain perception. We also show that GCH1/BH4 acts downstream of KRAS to drive lung cancer, identifying a potentially druggable pathway. Our screen shows that pharmacologic modulation of GCH1 expression and BH4 could be used to develop pharmacological treatments to alleviate pain and identified a critical role for EGFR-regulated GCH1/BH4 expression in neuropathic pain and cancer in rodents