WorldWideScience

Sample records for early life exposure

  1. Early Life Exposures and Cancer

    Science.gov (United States)

    Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

  2. A developmental perspective on early-life exposure to neurotoxicants.

    Science.gov (United States)

    Bellinger, David C; Matthews-Bellinger, Julia A; Kordas, Katarzyna

    2016-09-01

    Studies of early-life neurotoxicant exposure have not been designed, analyzed, or interpreted in the context of a fully developmental perspective. The goal of this paper is to describe the key principles of a developmental perspective and to use examples from the literature to illustrate the relevance of these principles to early-life neurotoxicant exposures. Four principles are discussed: 1) the effects of early-life neurotoxicant exposure depend on a child's developmental context; 2) deficits caused by early-life exposure initiate developmental cascades that can lead to pathologies that differ from those observed initially; 3) early-life neurotoxicant exposure has intra-familial and intergenerational impacts; 4) the impacts of early-life neurotoxicant exposure influence a child's ability to respond to future insults. The first principle is supported by considerable evidence, but the other three have received much less attention. Incorporating a developmental perspective in studies of early-life neurotoxicant exposures requires prospective collection of data on a larger array of covariates than usually considered, using analytical approaches that acknowledge the transactional processes between a child and the environment and the phenomenon of developmental cascades. Consideration of early-life neurotoxicant exposure within a developmental perspective reveals that many issues remain to be explicated if we are to achieve a deep understanding of the societal health burden associated with early-life neurotoxicant exposures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Trans-Agency Early-Life Exposures and Cancer Working Group

    Science.gov (United States)

    The Trans-Agency Early-Life Exposures and Cancer Working Group promotes integration of early-life events and exposures into public health cancer research, control, prevention, and policy strategies to reduce the cancer burden in the United States and globally.

  4. The OBELIX project: early life exposure to endocrine disruptors and obesity.

    Science.gov (United States)

    Legler, Juliette; Hamers, Timo; van Eck van der Sluijs-van de Bor, Margot; Schoeters, Greet; van der Ven, Leo; Eggesbo, Merete; Koppe, Janna; Feinberg, Max; Trnovec, Tomas

    2011-12-01

    The hypothesis of whether early life exposure (both pre- and early postnatal) to endocrine-disrupting chemicals (EDCs) may be a risk factor for obesity and related metabolic diseases later in life will be tested in the European research project OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life). OBELIX is a 4-y project that started in May 2009 and which has the following 5 main objectives: 1) to assess early life exposure in humans to major classes of EDCs identified as potential inducers of obesity (ie, dioxin-like compounds, non-dioxin-like polychlorinated biphenyls, organochlorine pesticides, brominated flame retardants, phthalates, and perfluorinated compounds) by using mother-child cohorts from 4 European regions with different food-contaminant exposure patterns; 2) to relate early life exposure to EDCs with clinical markers, novel biomarkers, and health-effect data related to obesity; 3) to perform hazard characterization of early life exposure to EDCs for the development of obesity later in life by using a mouse model; 4) to determine mechanisms of action of obesogenic EDCs on developmental programming with in vivo and in vitro genomics and epigenetic analyses; and 5) to perform risk assessments of prenatal exposure to obesogenic EDCs in food by integrating maternal exposure through food-contaminant exposure and health-effect data in children and hazard data in animal studies.

  5. The die is cast - Arsenic exposure in early life and disease susceptibility

    Science.gov (United States)

    Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

  6. The die is cast: arsenic exposure in early life and disease susceptibility.

    Science.gov (United States)

    Thomas, David J

    2013-12-16

    Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for the development and progression of disease in both species. Mode of action and dosimetric studies in the mouse may help assess the role of age at exposure as a factor in susceptibility to the toxic and carcinogenic effects of arsenic in humans.

  7. Early life exposures and the risk of adult glioma.

    Science.gov (United States)

    Anic, Gabriella M; Madden, Melissa H; Sincich, Kelly; Thompson, Reid C; Nabors, L Burton; Olson, Jeffrey J; LaRocca, Renato V; Browning, James E; Pan, Edward; Egan, Kathleen M

    2013-09-01

    Exposure to common infections in early life may stimulate immune development and reduce the risk for developing cancer. Birth order and family size are proxies for the timing of exposure to childhood infections with several studies showing a reduced risk of glioma associated with a higher order of birth (and presumed younger age at infection). The aim of this study was to examine whether birth order, family size, and other early life exposures are associated with the risk of glioma in adults using data collected in a large clinic-based US case-control study including 889 glioma cases and 903 community controls. A structured interviewer-administered questionnaire was used to collect information on family structure, childhood exposures and other potential risk factors. Logistic regression was used to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI) for the association between early life factors and glioma risk. Persons having any siblings were at significantly lower risk for glioma when compared to those reporting no siblings (OR=0.64; 95% CI 0.44-0.93; p=0.020). Compared to first-borns, individuals with older siblings had a significantly lower risk (OR=0.75; 95% CI 0.61-0.91; p=0.004). Birth weight, having been breast fed in infancy, and season of birth were not associated with glioma risk. The current findings lend further support to a growing body of evidence that early exposure to childhood infections reduces the risk of glioma onset in children and adults.

  8. Early life exposures and risk of atopy among Danish children

    DEFF Research Database (Denmark)

    Thomsen, SF; Ulrik, Charlotte Suppli; Porsbjerg, C

    2006-01-01

    A large proportion of atopy develops in childhood and early life exposures are suspected to play a considerable role in the inception. The aim of this study was to examine the association between early life exposures and development of atopic disease in children. We performed a case-cohort study...... to be independent of familial predisposition to atopic disease and significantly increases the likelihood for development of atopy in genetically susceptible individuals. Parental knowledge of atopic heredity significantly influences smoking and breast-feeding habits....... of a random population-based sample of children (n = 480) 7-17 years of age, living in urban Copenhagen, Denmark. Information on breast-feeding, supplementation, wheezy bronchitis, use of antibiotics, and parental smoking during pregnancy and in early life was obtained retrospectively by questionnaire. Skin...

  9. Latent carcinogenicity of early-life exposure to dichloroacetic acid in mice

    Science.gov (United States)

    AbstractEnvironmental exposures occurring early in life may have an important influence on cancer risk later in life. Here we investigated carryover effects of young-adult exposure to dichloroacetic acid (DCA), a small molecule analog of pyruvate and low-level environmental cont...

  10. Early-life chemical exposures and risk of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    De Long NE

    2017-03-01

    Full Text Available Nicole E De Long, Alison C Holloway Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada Abstract: The global prevalence of obesity has been increasing at a staggering pace, with few indications of any decline, and is now one of the major public health challenges worldwide. While obesity and metabolic syndrome (MetS have historically thought to be largely driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. There is now increasing evidence to suggest that exposure to synthetic chemicals in our environment may also play a key role in the etiology and pathophysiology of metabolic diseases. Importantly, exposures occurring in early life (in utero and early childhood may have a more profound effect on life-long risk of obesity and MetS. This narrative review explores the evidence linking early-life exposure to a suite of chemicals that are common contaminants associated with food production (pesticides; imidacloprid, chlorpyrifos, and glyphosate and processing (acrylamide, in addition to chemicals ubiquitously found in our household goods (brominated flame retardants and drinking water (heavy metals and changes in key pathways important for the development of MetS and obesity. Keywords: obesity, pesticides, polybrominated diphenyl ethers, heavy metals, acrylamide, endocrine-disrupting chemicals

  11. In utero and early life arsenic exposure in relation to long-term health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Farzan, Shohreh F.; Karagas, Margaret R. [Children' s Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, NH 03755 (United States); Section of Biostatistics and Epidemiology, Department of Community and Family Medicine and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 (United States); Chen, Yu, E-mail: yu.chen@nyumc.org [Department of Population Health, New York University School of Medicine, New York, NY 10016 (United States)

    2013-10-15

    Background: There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications. Objectives: Our goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models. Methods: We examined the current literature and identified relevant studies through PubMed by using combinations of the search terms “arsenic”, “in utero”, “transplacental”, “prenatal” and “fetal”. Discussion: Ecological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects. Conclusions: As millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels. - Highlights: • We review in utero and early-life As exposure impacts on lifelong disease risks. • Evidence indicates that early-life As increases risks of lung disease, cancer and CVD. • Animal work largely parallels human studies and may lead to new research directions. • Prospective studies and individual exposure assessments with biomarkers are needed. • Assessing intermediary

  12. In utero and early life arsenic exposure in relation to long-term health and disease

    International Nuclear Information System (INIS)

    Farzan, Shohreh F.; Karagas, Margaret R.; Chen, Yu

    2013-01-01

    Background: There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications. Objectives: Our goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models. Methods: We examined the current literature and identified relevant studies through PubMed by using combinations of the search terms “arsenic”, “in utero”, “transplacental”, “prenatal” and “fetal”. Discussion: Ecological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects. Conclusions: As millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels. - Highlights: • We review in utero and early-life As exposure impacts on lifelong disease risks. • Evidence indicates that early-life As increases risks of lung disease, cancer and CVD. • Animal work largely parallels human studies and may lead to new research directions. • Prospective studies and individual exposure assessments with biomarkers are needed. • Assessing intermediary endpoints may

  13. Epigenetics, obesity and early-life cadmium or lead exposure.

    Science.gov (United States)

    Park, Sarah S; Skaar, David A; Jirtle, Randy L; Hoyo, Cathrine

    2017-01-01

    Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures.

  14. Immune-mediated diseases and microbial exposure in early life

    DEFF Research Database (Denmark)

    Bisgaard, H; Bønnelykke, K; Stokholm, Jacob

    2014-01-01

    The non-communicable disease pandemic includes immune-mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system...

  15. Fluoride Exposure in Early Life as the Possible Root Cause of Disease In Later Life.

    Science.gov (United States)

    Nakamoto, Tetsuo; Rawls, H Ralph

    2018-05-15

    Fluoride, one of the most celebrated ingredients for the prevention of dental caries in the 20th century, has also been controversial for its use in dentifrices and other applications. In the current review, we have concentrated primarily on early-life exposure to fluoride and how it may affect the various organs. The most recent controversial aspects of fluoride are related to toxicity of the developing brain and how it may possibly result in the decrease of intelligence quotient (IQ), autism, and calcification of the pineal gland. In addition, it has been reported to have possible effects on bone and thyroid glands. If nutritional stress is applied during a critical period of growth and development, the organ(s) and/or body will never recover once they pass through the critical period. For example, if animals are force-fed during experiments, they will simply get fat but never reach the normal size. Although early-life fluoride exposure causing fluorosis is well reported in the literature, the dental profession considers it primarily as an esthetic rather than a serious systemic problem. In the current review, we wanted to raise the possibility of future disease as a result of early-life exposure to fluoride. It is not currently known how fluoride will become a cause of future disease. Studies of other nutritional factors have shown that the effects of early nutritional stress are a cause of disease in later life.

  16. Early life trauma exposure and stress sensitivity in young children.

    Science.gov (United States)

    Grasso, Damion J; Ford, Julian D; Briggs-Gowan, Margaret J

    2013-01-01

    The current study replicates and extends work with adults that highlights the relationship between trauma exposure and distress in response to subsequent, nontraumatic life stressors. The sample included 213 2-4-year-old children in which 64.3% had a history of potential trauma exposure. Children were categorized into 4 groups based on trauma history and current life stress. In a multivariate analysis of variance, trauma-exposed children with current life stressors had elevated internalizing and externalizing problems compared with trauma-exposed children without current stress and nontrauma-exposed children with and without current stressors. The trauma-exposed groups with or without current stressors did not differ on posttraumatic stress disorder symptom severity. Accounting for number of traumatic events did not change these results. These findings suggest that early life trauma exposure may sensitize young children and place them at risk for internalizing or externalizing problems when exposed to subsequent, nontraumatic life stressors.

  17. Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2013-01-01

    Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal lif...

  18. Disproportionate Exposure to Early-Life Adversity and Sexual Orientation Disparities in Psychiatric Morbidity

    Science.gov (United States)

    McLaughlin, Katie A.; Hatzenbuehler, Mark L.; Xuan, Ziming; Conron, Kerith J.

    2012-01-01

    Objectives: Lesbian, gay, and bisexual (LGB) populations exhibit elevated rates of psychiatric disorders compared to heterosexuals, and these disparities emerge early in the life course. We examined the role of exposure to early-life victimization and adversity--including physical and sexual abuse, homelessness, and intimate partner violence--in…

  19. Antibiotic Exposure in Early Life Increases Risk of Childhood Obesity: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xiaoqing Shao

    2017-07-01

    Full Text Available A number of studies have previously assessed the impact of antibiotic exposure in early life on the risk of childhood obesity, but no systematic assessment is currently available. A systematic review and meta-analysis was performed to comprehensively and quantitatively elucidate the risk of childhood obesity caused by antibiotic exposure in early life. Literature search was performed in PubMed, Embase, and Web of Science. Random-effect meta-analysis was used to pool the statistical estimates. Fifteen cohort studies involving 445,880 participants were finally included, and all those studies were performed in developed countries. Antibiotic exposure in early life significantly increased risk of childhood overweight [relative risk (RR = 1.23, 95% confidence interval (CI 1.13–1.35, P < 0.001] and childhood obesity (RR = 1.21, 95% CI 1.13–1.30, P < 0.001. Antibiotic exposure in early life also significantly increased the z-score of childhood body mass index (mean difference: 0.07, 95% CI 0.05–0.09, P < 0.00001. Importantly, there was an obvious dose–response relationship between antibiotic exposure in early life and childhood adiposity, with a 7% increment in the risk of overweight (RR = 1.07, 95% CI 1.01–1.15, P = 0.03 and a 6% increment in the risk of obesity (RR = 1.06, 95% CI 1.02–1.09, P < 0.001 for each additional course of antibiotic exposure. In conclusion, antibiotic exposure in early life significantly increases risk of childhood obesity. Moreover, current analyses are mainly taken from developed countries, and therefore the impact of antibiotic exposure on risk of childhood obesity in vulnerable populations or developing countries still needs to be evaluated in future studies.

  20. Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function.

    Science.gov (United States)

    Fleisch, Abby F; Rifas-Shiman, Sheryl L; Mora, Ana M; Calafat, Antonia M; Ye, Xiaoyun; Luttmann-Gibson, Heike; Gillman, Matthew W; Oken, Emily; Sagiv, Sharon K

    2017-03-01

    Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited. We studied 665 mother-child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999-2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex. Children with higher PFAS concentrations had lower HOMA-IR [e.g., -10.1% (95% CI: -17.3, -2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: -15.6% (95% CI: -25.4, -4.6) vs. -6.1% (95% CI: -16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481-487; http://dx.doi.org/10.1289/EHP303.

  1. Long-term Neurotoxic Effects of Early-life Exposure to Tetrachloroethylene-contaminated Drinking Water.

    Science.gov (United States)

    Aschengrau, Ann; Janulewicz, Patricia A; White, Roberta F; Vieira, Veronica M; Gallagher, Lisa G; Getz, Kelly D; Webster, Thomas F; Ozonoff, David M

    2016-01-01

    Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983, widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distribution pipes. A retrospective cohort study (the Cape Cod Health Study) was undertaken to examine possible health consequences of early-life exposure to PCE-contaminated drinking water. This review describes the study methods and findings regarding the effects of prenatal and childhood exposure on neurologic outcomes during early adulthood, including vision, neuropsychological functioning, brain structure, risky behaviors, and mental illness. The review also describes the strengths and challenges of conducting population-based epidemiologic research in this unique setting. Participants were identified by cross-matching birth certificates and water system data. Information on health outcomes and confounding variables was collected from self-administered surveys (n = 1689), neuropsychological tests (n = 63), vision examinations (n = 63), and magnetic resonance imaging (n = 42). Early-life exposure to PCE was estimated using a leaching and transport model. The data analysis compared the occurrence of each health outcome among individuals with prenatal and early childhood PCE exposure to unexposed individuals while considering the effect of confounding variables. The study found evidence that early-life exposure to PCE-contaminated drinking water has long-term neurotoxic effects. The strongest associations were seen with illicit drug use, bipolar disorder, and post-traumatic stress disorder. Key strengths of the study were availability of historical data on affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little confounding. Challenges arose mainly from the historical

  2. Risk of Hyperglycemia and Diabetes after Early-Life Famine Exposure: A Cross-Sectional Survey in Northeastern China

    Directory of Open Access Journals (Sweden)

    Yangyu Zhang

    2018-05-01

    Full Text Available Previous studies suggested that malnutrition during early life may play an essential role in later outcomes and disease risk in adulthood. We aimed to investigate the risks of hyperglycemia and diabetes 50 years after early-life famine exposure in a Northeastern Chinese population. We used the data from 5690 adults born between 1956 and 1965 in selected communities from a 2012 cross-sectional study. The early-childhood exposure cohort showed an increased risk of hyperglycemia compared with the unexposed cohort in the female population (odds ratio (OR 1.46; 95% confidence interval (CI 1.04, 2.06. The increased risk of diabetes in the early-childhood and fetal exposure cohorts was 37.0% (95% CI 1.05–1.79 and 50% (95% CI 1.15–1.96, respectively. For women, the risk of diabetes was more pronounced in the fetal-exposed cohort (OR 1.82; 95% CI 1.26–2.63 than in the early-childhood cohort (OR 1.57; 95% CI 1.08–2.26. Early-life exposure to famine increased the risk of diabetes. Furthermore, early-childhood exposure to famine might increase the risk of hyperglycemia in women. A policy for preventing early life malnutrition should be drafted by the government to prevent hyperglycemia and diabetes in adulthood.

  3. Early-Life Exposure to the Great Smog of 1952 and the Development of Asthma.

    Science.gov (United States)

    Bharadwaj, Prashant; Zivin, Joshua Graff; Mullins, Jamie T; Neidell, Matthew

    2016-12-15

    Little is known about the long-term effects of air pollution exposure and the root causes of asthma. We use exposure to intense air pollution from the 1952 Great Smog of London as a natural experiment to examine both issues. To determine whether exposure to extreme air pollution in utero or soon after birth affects asthma development later in life. This was a natural experiment using the unanticipated pollution event by comparing the prevalence of asthma between those exposed to the Great Smog in utero or the first year of life with those conceived well before or after the incident and those residing outside the affected area at the time of the smog. Prevalence of asthma during childhood (ages 0-15) and adulthood (ages >15) is analyzed for 2,916 respondents to the Life History portion of the English Longitudinal Study on Aging born from 1945 to 1955. Exposure to the Great Smog in the first year of life increases the likelihood of childhood asthma by 19.87 percentage points (95% confidence interval [CI], 3.37-36.38). We also find suggestive evidence that early-life exposure led to a 9.53 percentage point increase (95% CI, -4.85 to 23.91) in the likelihood of adult asthma and exposure in utero led to a 7.91 percentage point increase (95% CI, -2.39 to 18.20) in the likelihood of childhood asthma. These results are the first to link early-life pollution exposure to later development of asthma using a natural experiment, suggesting the legacy of the Great Smog is ongoing.

  4. Risk of childhood overweight after exposure to tobacco smoking in prenatal and early postnatal life

    DEFF Research Database (Denmark)

    Møller, Susanne Eifer; Ajslev, Teresa Adeltoft; Andersen, Camilla Schou

    2014-01-01

    OBJECTIVE: To investigate the association between exposure to mothers smoking during prenatal and early postnatal life and risk of overweight at age 7 years, while taking birth weight into account. METHODS: From the Danish National Birth Cohort a total of 32,747 families were identified with avai......OBJECTIVE: To investigate the association between exposure to mothers smoking during prenatal and early postnatal life and risk of overweight at age 7 years, while taking birth weight into account. METHODS: From the Danish National Birth Cohort a total of 32,747 families were identified...... with available information on maternal smoking status in child's pre- and postnatal life and child's birth weight, and weight and height at age 7 years. Outcome was overweight according to the International Obesity Task Force gender and age specific body mass index. Smoking exposure was categorized into four...... groups: no exposure (n = 25,076); exposure only during pregnancy (n = 3,343); exposure only postnatally (n = 140); and exposure during pregnancy and postnatally (n = 4,188). Risk of overweight according to smoking status as well as dose-response relationships were estimated by crude and adjusted odds...

  5. Early-life soy exposure and gender-role play behavior in children.

    Science.gov (United States)

    Adgent, Margaret A; Daniels, Julie L; Edwards, Lloyd J; Siega-Riz, Anna Maria; Rogan, Walter J

    2011-12-01

    Soy-based infant formula contains high levels of isoflavones. These estrogen-like compounds have been shown to induce changes in sexually dimorphic behaviors in animals exposed in early development. We examined gender-role play behavior in relation to soy-based and non-soy-based infant feeding methods among children in the Avon Longitudinal Study of Parents and Children. We studied 3,664 boys and 3,412 girls. Four exposure categories were created using data from questionnaires administered at 6 and 15 months postpartum: primarily breast, early formula (referent), early soy, and late soy. Gender-role play behavior was assessed using the Pre-School Activities Inventory (PSAI). Associations between infant feeding and PSAI scores at 42 months of age were assessed using linear regression. Post hoc analyses of PSAI scores at 30 and 57 months were also conducted. Early-infancy soy use was reported for approximately 2% of participants. Mean [95% confidence interval (CI)] PSAI scores at 42 months were 62.3 (62.0, 62.6) and 36.9 (36.6, 37.2) for boys and girls, respectively. After adjustment, early soy (vs. early formula) feeding was associated with higher (less feminine) PSAI scores in girls (β = 2.66; 95% CI: 0.19, 5.12) but was not significantly associated with PSAI scores in boys. The association between soy exposure and PSAI scores in girls was substantially attenuated at 30 and 57 months. Although not consistent throughout childhood, early-life soy exposure was associated with less female-typical play behavior in girls at 42 months of age. Soy exposure was not significantly associated with play behavior in boys.

  6. Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

    OpenAIRE

    Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

    2014-01-01

    Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequentl...

  7. Long-term effect of early-life stress from earthquake exposure on working memory in adulthood.

    Science.gov (United States)

    Li, Na; Wang, Yumei; Zhao, Xiaochuan; Gao, Yuanyuan; Song, Mei; Yu, Lulu; Wang, Lan; Li, Ning; Chen, Qianqian; Li, Yunpeng; Cai, Jiajia; Wang, Xueyi

    2015-01-01

    The present study aimed to investigate the long-term effect of 1976 Tangshan earthquake exposure in early life on performance of working memory in adulthood. A total of 907 study subjects born and raised in Tangshan were enrolled in this study. They were divided into three groups according to the dates of birth: infant exposure (3-12 months, n=274), prenatal exposure (n=269), and no exposure (born at least 1 year after the earthquake, n=364). The prenatal group was further divided into first, second, and third trimester subgroups based on the timing of exposure during pregnancy. Hopkins Verbal Learning Test-Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) were used to measure the performance of working memory. Unconditional logistic regression analysis was used to analyze the influential factors for impaired working memory. The Hopkins Verbal Learning Test-Revised scores did not show significant difference across the three groups. Compared with no exposure group, the BVMT-R scores were slightly lower in the prenatal exposure group and markedly decreased in the infant exposure group. When the BVMT-R scores were analyzed in three subgroups, the results showed that the subjects whose mothers were exposed to earthquake in the second and third trimesters of pregnancy had significantly lower BVMT-R scores compared with those in the first trimester. Education level and early-life earthquake exposure were identified as independent risk factors for reduced performance of visuospatial memory indicated by lower BVMT-R scores. Infant exposure to earthquake-related stress impairs visuospatial memory in adulthood. Fetuses in the middle and late stages of development are more vulnerable to stress-induced damage that consequently results in impaired visuospatial memory. Education and early-life trauma can also influence the performance of working memory in adulthood.

  8. Early life exposure to China's 1959-61 famine and midlife cognition.

    Science.gov (United States)

    Xu, Hongwei; Zhang, Zhenmei; Li, Lydia; Liu, Jinyu

    2018-02-01

    Existing studies of the 1944-45 Dutch famine found little evidence of the association between early life malnutrition and midlife cognition. Among 2446 rural participants born between 1958 and 1963 in the China Health and Retirement Longitudinal Study, we examined effects of exposure to China's 1959-61 Great Leap Forward famine during prenatal and early postnatal life, on four cognitive measures in 2011 (baseline) and changes in cognition between 2011 and 2013 (first follow-up). We obtained difference-in-differences (DID) estimates of the famine effects by exploiting temporal variation in the timing and duration of famine exposure across six birth cohorts born between 1958 and 1963, together with geographical variation in famine severity at the prefecture level. After adjusting for gender, marital status and provincial fixed effects, we found that the 1961 cohort who experienced full-term prenatal and partial-term postnatal exposures to famine had lower scores on the Telephone Interview of Cognitive Status (TICS), a test of drawing pentagons, and general cognition at age 50 years compared with the unexposed 1963 cohort. Adjusting for education, the famine effects on drawing pentagons and general cognition were fully attenuated, but the effect on TICS persisted. We also found a robust negative famine effect on the longitudinal change in general cognition during the 2-year follow-up in the 1959 cohort. Severe nutritional deprivation during prenatal and postnatal periods has a lasting impact on cognitive performance in Chinese adults in their early 50s. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  9. Family Instability and Exposure to Violence in the Early Life Course.

    Science.gov (United States)

    Cavanagh, Shannon E; Stritzel, Haley; Smith, Chelsea; Crosnoe, Robert

    2017-10-11

    Family instability has been linked with a host of outcomes across the early life course. This study extends this literature by connecting instability with violence in the community by examining the associations among family structure, family structure change, and secondary exposure to violence during adolescence across diverse segments of the population. Using longitudinal data from the Project on Human Development in Chicago Neighborhoods study, we found that living with a single parent and experiencing family structure changes were associated with secondary exposure to violence. Multiple group models suggest that partner change translated into more exposure for boys than girls. Findings also suggest that family instability may lead to more secondary exposure to violence for African American youth. © 2017 Society for Research on Adolescence.

  10. Early Life Stages

    Science.gov (United States)

    Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

  11. Early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in the first 2 years of life: the KOALA Birth Cohort Study

    NARCIS (Netherlands)

    Kummeling, Ischa; Stelma, Foekje F.; Dagnelie, Pieter C.; Snijders, Bianca E. P.; Penders, John; Huber, Machteld; van Ree, Ronald; van den Brandt, Piet A.

    2007-01-01

    OBJECTIVES: Antibiotic exposure in early life may be associated with atopic disease development either by interfering with bacterial commensal flora or by modifying the course of bacterial infections. We evaluated early life exposure to antibiotics and the subsequent development of eczema, wheeze,

  12. Early-life bisphenol a exposure and child body mass index: a prospective cohort study.

    Science.gov (United States)

    Braun, Joseph M; Lanphear, Bruce P; Calafat, Antonia M; Deria, Sirad; Khoury, Jane; Howe, Chanelle J; Venners, Scott A

    2014-11-01

    Early-life exposure to bisphenol A (BPA) may increase childhood obesity risk, but few prospective epidemiological studies have investigated this relationship. We sought to determine whether early-life exposure to BPA was associated with increased body mass index (BMI) at 2-5 years of age in 297 mother-child pairs from Cincinnati, Ohio (HOME Study). Urinary BPA concentrations were measured in samples collected from pregnant women during the second and third trimesters and their children at 1 and 2 years of age. BMI z-scores were calculated from weight/height measures conducted annually from 2 through 5 years of age. We used linear mixed models to estimate BMI differences or trajectories with increasing creatinine-normalized BPA concentrations. After confounder adjustment, each 10-fold increase in prenatal (β = -0.1; 95% CI: -0.5, 0.3) or early-childhood (β = -0.2; 95% CI: -0.6, 0.1) BPA concentrations was associated with a modest and nonsignificant reduction in child BMI. These inverse associations were suggestively stronger in girls than in boys [prenatal effect measure modification (EMM) p-value = 0.30, early-childhood EMM p-value = 0.05], but sex-specific associations were imprecise. Children in the highest early-childhood BPA tercile had lower BMI at 2 years (difference = -0.3; 95% CI: -0.6, 0.0) and larger increases in their BMI slope from 2 through 5 years (BMI increase per year = 0.12; 95% CI: 0.07, 0.18) than children in the lowest tercile (BMI increase per year = 0.07; 95% CI: 0.01, 0.13). All associations were attenuated without creatinine normalization. Prenatal and early-childhood BPA exposures were not associated with increased BMI at 2-5 years of age, but higher early-childhood BPA exposures were associated with accelerated growth during this period.

  13. Exposure to low dose benzo[a]pyrene during early life stages causes symptoms similar to cardiac hypertrophy in adult zebrafish.

    Science.gov (United States)

    Huang, Lixing; Gao, Dongxu; Zhang, Youyu; Wang, Chonggang; Zuo, Zhenghong

    2014-07-15

    Growing evidence indicates that polycyclic aromatic hydrocarbons (PAHs) can lead to cardiac hypertrophy and recent research indicates that exposure to low dose crude oil during early embryonic development may lead to impacts on heart health at later life stages. The aim of this study was to evaluate whether exposure during early life stages to low dose benzo[a]pyrene (BaP), as a high-ring PAH, would lead to cardiac hypertrophy at later life stages. Zebrafish were exposed to low dose BaP until 96 hpf, then transferred to clean water and maintained for a year before histological and molecular biological analysis. Our results showed that exposure to low level BaP during early life stages increased heart weight to body weight ratios and deposited collagen in the heart of adult zebrafish. ANP, BNP and c-Myc were also induced in the heart of adult zebrafish by BaP. These results proved that low level BaP exposure during early life stages caused symptoms similar to cardiac hypertrophy in adult zebrafish. Our results displayed an elevated expression of CdC42, RhoA, p-ERK1, 2 and Rac1. Therefore, the mechanism of the cardiac hypertrophy caused by BaP exposure during early life stages may be through inducing the expression of CdC42, RhoA and Rac1, together with activating ERK1, 2. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure.

    Science.gov (United States)

    Raineki, Charlis; Bodnar, Tamara S; Holman, Parker J; Baglot, Samantha L; Lan, Ni; Weinberg, Joanne

    2017-11-01

    The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Challenges to studying the health effects of early life environmental chemical exposures on children's health.

    Science.gov (United States)

    Braun, Joseph M; Gray, Kimberly

    2017-12-01

    Epidemiological studies play an important role in quantifying how early life environmental chemical exposures influence the risk of childhood diseases. These studies face at least four major challenges that can produce noise when trying to identify signals of associations between chemical exposure and childhood health. Challenges include accurately estimating chemical exposure, confounding from causes of both exposure and disease, identifying periods of heightened vulnerability to chemical exposures, and determining the effects of chemical mixtures. We provide recommendations that will aid in identifying these signals with more precision.

  16. The influence of early exposure to vitamin D for development of diseases later in life

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Abrahamsen, Bo; Bauerek, Marta Jadwiga

    2013-01-01

    Vitamin D deficiency is common among otherwise healthy pregnant women and may have consequences for them as well as the early development and long-term health of their children. However, the importance of maternal vitamin D status on offspring health later in life has not been widely studied....... The present study includes an in-depth examination of the influence of exposure to vitamin D early in life for development of fractures of the wrist, arm and clavicle; obesity, and type 1 diabetes (T1D) during child- and adulthood....

  17. Prenatal and Early Life Exposure to Traffic Pollution and Cardiometabolic Health in Childhood

    Science.gov (United States)

    Fleisch, Abby F.; Luttmann-Gibson, Heike; Perng, Wei; Rifas-Shiman, Sheryl L.; Coull, Brent A.; Kloog, Itai; Koutrakis, Petros; Schwartz, Joel D.; Zanobetti, Antonella; Mantzoros, Christos S.; Gillman, Matthew W.; Gold, Diane R.; Oken, Emily

    2016-01-01

    Background Prenatal exposure to traffic pollution has been associated with faster infant weight gain, but implications for cardiometabolic health in later childhood are unknown. Methods Among 1,418 children in Project Viva, a Boston-area pre-birth cohort, we assessed anthropometric and biochemical parameters of cardiometabolic health in early (median age 3.3 years) and mid- (median age 7.7 years) childhood. We used spatiotemporal models to estimate prenatal and early life residential PM2.5 and black carbon exposure as well as traffic density and roadway proximity. We performed linear regression analyses adjusted for sociodemographics Results Children whose mothers lived close to a major roadway at the time of delivery had higher markers of adverse cardiometabolic risk in early and mid-childhood. For example, total fat mass was 2.1kg (95%CI: 0.8, 3.5) higher in mid-childhood for children of mothers who lived < 50 m vs. ≥ 200m from a major roadway. Black carbon exposure and traffic density were generally not associated with cardiometabolic parameters, and PM2.5 exposure during the year prior was paradoxically associated with improved cardiometabolic profile Conclusions Infants whose mothers lived close to a major roadway at the time of delivery may be at later risk for adverse cardiometabolic health. PMID:26843357

  18. Early life low-level cadmium exposure is positively associated with increased oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Kippler, Maria [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Bakhtiar Hossain, Mohammad [International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka 1212 (Bangladesh); Department of Laboratory Medicine, Section of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Lindh, Christian [International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka 1212 (Bangladesh); Moore, Sophie E. [MRC Keneba, MRC Laboratories (Gambia); Kabir, Iqbal [Department of Laboratory Medicine, Section of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Vahter, Marie [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Broberg, Karin, E-mail: karin.broberg_palmgren@med.lu.se [International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka 1212 (Bangladesh)

    2012-01-15

    Environmental exposure to cadmium (Cd) is known to induce oxidative stress, a state of imbalance between the production of reactive oxygen species (ROS) and the ability to detoxify them, in adults. However, data are lacking on potential effects in early-life. We evaluated urinary concentrations of 8-oxo-7,8-dihydro-2 Prime -deoxyguanosine (8-oxodG), a recognized marker of oxidative DNA damage, in relation to Cd exposure in 96 predominantly breast-fed infants (11-17 weeks of age) in rural Bangladesh. Urinary 8-oxodG was measured using liquid chromatography tandem mass spectrometry and Cd in urine and breast milk by inductively coupled plasma mass spectrometry. Median concentration of 8-oxodG was 3.9 nmol/L, urinary Cd 0.30 {mu}g/L, and breast-milk Cd 0.13 {mu}g/L. In linear regression analyses, urinary 8-oxodG was positively associated with Cd in both urine (p=0.00067) and breast milk (p=0.0021), and negatively associated with body weight (kg; p=0.0041). Adjustment for age, body weight, socio-economic status, urinary arsenic, as well as magnesium, calcium, and copper in breast milk did not change the association between Cd exposure and urinary 8-oxodG. These findings suggest that early-life low-level exposure to Cd via breast milk induces oxidative stress. Further studies are warranted to elucidate whether this oxidative stress is associated with impaired child health and development.

  19. Early life low-level cadmium exposure is positively associated with increased oxidative stress

    International Nuclear Information System (INIS)

    Kippler, Maria; Bakhtiar Hossain, Mohammad; Lindh, Christian; Moore, Sophie E.; Kabir, Iqbal; Vahter, Marie; Broberg, Karin

    2012-01-01

    Environmental exposure to cadmium (Cd) is known to induce oxidative stress, a state of imbalance between the production of reactive oxygen species (ROS) and the ability to detoxify them, in adults. However, data are lacking on potential effects in early-life. We evaluated urinary concentrations of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), a recognized marker of oxidative DNA damage, in relation to Cd exposure in 96 predominantly breast-fed infants (11–17 weeks of age) in rural Bangladesh. Urinary 8-oxodG was measured using liquid chromatography tandem mass spectrometry and Cd in urine and breast milk by inductively coupled plasma mass spectrometry. Median concentration of 8-oxodG was 3.9 nmol/L, urinary Cd 0.30 μg/L, and breast-milk Cd 0.13 μg/L. In linear regression analyses, urinary 8-oxodG was positively associated with Cd in both urine (p=0.00067) and breast milk (p=0.0021), and negatively associated with body weight (kg; p=0.0041). Adjustment for age, body weight, socio-economic status, urinary arsenic, as well as magnesium, calcium, and copper in breast milk did not change the association between Cd exposure and urinary 8-oxodG. These findings suggest that early-life low-level exposure to Cd via breast milk induces oxidative stress. Further studies are warranted to elucidate whether this oxidative stress is associated with impaired child health and development.

  20. [European birth cohorts: Early life exposure to microorganisms and health impact].

    Science.gov (United States)

    Rocchi, S; Reboux, G

    2017-06-01

    In recent years, many birth cohorts have been initiated in Europe, to assess the early life microbiological exposure of children in the indoor environment and better understanding the different effects (adverse/protectors) on health. The results of 12 European cohorts, with different methodologies for exposure and allergic risk assessment are summarized in this review. Four meta-analyzes of cohort are presented too. Microbiological researches in indoor environment seem to turn to a metrology of microbiological exposure, but few studies provide real quantitative data. Thus, the establishment of dose-effect relationship is not possible and can only be done by having a global view of the situation, provided by an identical metrological approach in the different studies, in a large-scale, in the context of large birth cohorts with children followed with strict criteria to establish the clinical diagnosis. Copyright © 2017. Published by Elsevier Masson SAS.

  1. Early life exposure to a rodent carcinogen propiconazole fungicide induces oxidative stress and hepatocarcinogenesis in medaka fish

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Tzu-Yi; Hong, Chwan-Yang [Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan (China); Sasado, Takao [Laboratory of Bioresources, National Institute for Basic Biology, Okazaki (Japan); Kashiwada, Shosaku [Research Center for Life and Environmental Sciences, Department of Life Sciences, the Toyo University, Gunma (Japan); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan (China)

    2016-01-15

    Highlights: • Propiconazole initiates ROS-induced oxidative stress and damage in medaka fish. • Early life exposure to propiconazole increases incidence of hepatocarcionogensis in p53{sup −/−} medaka. • Oxidative stress and CYP induction involved in p53 regulation are key events in propiconazole-induced hepatotumorigenesis. • Propiconazole-induced toxic response in medaka is compatible with that in rodents. - Abstract: Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53{sup −/−} mutant of medaka fish (Oryzias latipes) to propiconazole (2.5–250 μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53{sup −/−} mutant medaka with early life exposure to propiconazole showed increased incidence of

  2. Early life exposure to a rodent carcinogen propiconazole fungicide induces oxidative stress and hepatocarcinogenesis in medaka fish

    International Nuclear Information System (INIS)

    Tu, Tzu-Yi; Hong, Chwan-Yang; Sasado, Takao; Kashiwada, Shosaku; Chen, Pei-Jen

    2016-01-01

    Highlights: • Propiconazole initiates ROS-induced oxidative stress and damage in medaka fish. • Early life exposure to propiconazole increases incidence of hepatocarcionogensis in p53"−"/"− medaka. • Oxidative stress and CYP induction involved in p53 regulation are key events in propiconazole-induced hepatotumorigenesis. • Propiconazole-induced toxic response in medaka is compatible with that in rodents. - Abstract: Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53"−"/"− mutant of medaka fish (Oryzias latipes) to propiconazole (2.5–250 μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53"−"/"− mutant medaka with early life exposure to propiconazole showed increased incidence of

  3. Early life adversity: Lasting consequences for emotional learning

    Directory of Open Access Journals (Sweden)

    Harm J. Krugers

    2017-02-01

    Full Text Available The early postnatal period is a highly sensitive time period for the developing brain, both in humans and rodents. During this time window, exposure to adverse experiences can lastingly impact cognitive and emotional development. In this review, we briefly discuss human and rodent studies investigating how exposure to adverse early life conditions – mainly related to quality of parental care - affects brain activity, brain structure, cognition and emotional responses later in life. We discuss the evidence that early life adversity hampers later hippocampal and prefrontal cortex functions, while increasing amygdala activity, and the sensitivity to stressors and emotional behavior later in life. Exposure to early life stress may thus on the one hand promote behavioral adaptation to potentially threatening conditions later in life –at the cost of contextual memory formation in less threatening situations- but may on the other hand also increase the sensitivity to develop stress-related and anxiety disorders in vulnerable individuals.

  4. Effects of early-life lead exposure on oxidative status and phagocytosis activity in great tits (Parus major)

    NARCIS (Netherlands)

    Rainio, Miia J.; Eeva, Tapio; Lilley, Thomas; Stauffer, Janina; Ruuskanen, Suvi

    2015-01-01

    Abstract Lead is a highly poisonous metal with a very long half-life, distributing throughout the body in blood and accumulating primarily in bones and kidney. We studied the short and long-term effects of early-life lead exposure on antioxidant defense and phagocytosis activity in a small passerine

  5. The human early-life exposome (HELIX): project rationale and design.

    Science.gov (United States)

    Vrijheid, Martine; Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R; Granum, Berit; Gražulevičienė, Regina; Gutzkow, Kristine B; Julvez, Jordi; Keun, Hector C; Kogevinas, Manolis; McEachan, Rosemary R C; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J; Zeman, Florence; Nieuwenhuijsen, Mark J

    2014-06-01

    Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome. The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project. In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

  6. Accounting for Life-Course Exposures in Epigenetic Biomarker Association Studies: Early Life Socioeconomic Position, Candidate Gene DNA Methylation, and Adult Cardiometabolic Risk.

    Science.gov (United States)

    Huang, Jonathan Y; Gavin, Amelia R; Richardson, Thomas S; Rowhani-Rahbar, Ali; Siscovick, David S; Hochner, Hagit; Friedlander, Yechiel; Enquobahrie, Daniel A

    2016-10-01

    Recent studies suggest that epigenetic programming may mediate the relationship between early life environment, including parental socioeconomic position, and adult cardiometabolic health. However, interpreting associations between early environment and adult DNA methylation may be difficult because of time-dependent confounding by life-course exposures. Among 613 adult women (mean age = 32 years) of the Jerusalem Perinatal Study Family Follow-up (2007-2009), we investigated associations between early life socioeconomic position (paternal occupation and parental education) and mean adult DNA methylation at 5 frequently studied cardiometabolic and stress-response genes (ABCA1, INS-IGF2, LEP, HSD11B2, and NR3C1). We used multivariable linear regression and marginal structural models to estimate associations under 2 causal structures for life-course exposures and timing of methylation measurement. We also examined whether methylation was associated with adult cardiometabolic phenotype. Higher maternal education was consistently associated with higher HSD11B2 methylation (e.g., 0.5%-point higher in 9-12 years vs. ≤8 years, 95% confidence interval: 0.1, 0.8). Higher HSD11B2 methylation was also associated with lower adult weight and total and low-density lipoprotein cholesterol. We found that associations with early life socioeconomic position measures were insensitive to different causal assumption; however, exploratory analysis did not find evidence for a mediating role of methylation in socioeconomic position-cardiometabolic risk associations. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Early life urban exposure as a risk factor for developing obesity and impaired fasting glucose in later adulthood: results from two cohorts in Thailand.

    Science.gov (United States)

    Angkurawaranon, Chaisiri; Wisetborisut, Anawat; Rerkasem, Kittipan; Seubsman, Sam-Ang; Sleigh, Adrian; Doyle, Pat; Nitsch, Dorothea

    2015-09-16

    Obesity and obesity related conditions, driven by processes such as urbanization and globalization, are contributing to pronounced cardiovascular morbidity and mortality in developing countries. There is limited evidence on the influence of living in an urban environment in early life on obesity and obesity related conditions later in life in developing countries such as Thailand. We used data from two cohort studies conducted in Thailand, the Thai Cohort Study (TCS) and the Chiang Mai University (CMU) Health Worker Study, to investigate the association between early life urban (vs rural) exposure and the later development of obesity. We additionally explored the association between early life urban exposure and impaired fasting glucose in adulthood using data from the CMU Health Worker Study. Among 48,490 adults from the TCS, 9.1 % developed obesity within 4 years of follow-up. Among 1,804 initially non-obese adults from CMU Health worker study, 13.6 % developed obesity within 5 years of follow-up. Early life urban exposure was associated with increased risk of developing obesity in adulthood in both cohorts. Adjusting for age and sex, those who spent their early lives in urban areas were 1.21 times more likely to develop obesity in the TCS (OR 1.21, 95 % CI 1.12 to 1.31) and 1.65 times more likely in the CMU Health Worker study (OR 1.65, 95 % CI 1.23 to 2.20). These associations remained significant despite adjustment for later life urban exposure and current household income. No evidence for an association was found for impaired fasting glucose. Early life urban exposure was associated with increased risk of developing obesity in adulthood. These findings support public health intervention programs to prevent obesity starting from early ages.

  8. Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

    International Nuclear Information System (INIS)

    Leu, Yu-Wei; Chu, Pei-Yi; Chen, Chien-Min; Yeh, Kun-Tu; Liu, Yu Ming; Lee, Yen-Hui; Kuo, Shan-Tsu; Hsiao, Shu-Huei

    2014-01-01

    Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms

  9. Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

    Energy Technology Data Exchange (ETDEWEB)

    Leu, Yu-Wei [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China); Chu, Pei-Yi [Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan (China); Chen, Chien-Min [Division of Neurosurgery, Changhua Christian Hospital, Changhua 500, Taiwan (China); Yeh, Kun-Tu [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Liu, Yu Ming; Lee, Yen-Hui; Kuo, Shan-Tsu [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China); Hsiao, Shu-Huei, E-mail: bioshh@ccu.edu.tw [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China)

    2014-10-24

    Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.

  10. Early Life Exposure to Endocrine Disrupting Chemicals and Childhood Obesity and Neurodevelopment

    Science.gov (United States)

    Braun, Joseph M.

    2017-01-01

    Endocrine disrupting chemicals (EDCs) may increase the risk of childhood diseases by disrupting hormonally mediated processes critical for growth and development during gestation, infancy, or childhood. The fetus, infant, and child may have enhanced sensitivity to environmental stressors like EDCs due to rapid development and greater exposure to some EDCs that results from their developmentally appropriate behavior, anatomy, and physiology. This review summarizes epidemiological studies examining the relations of early-life exposure to bisphenol A (BPA), phthalates, triclosan, and perfluoroalkyl substance (PFAS) with childhood neurobehavioral disorders and obesity. The available epidemiological evidence suggests that prenatal exposure to several of these ubiquitous EDCs is associated with adverse neurobehavior (BPA and phthalates) and excess adiposity or increased risk of obesity/overweight (PFAS). Quantifying the effects of EDC mixtures, improving EDC exposure assessment, reducing bias from confounding, identifying periods of heightened vulnerability, and elucidating the presence and nature of sexually dimorphic EDC effects would result in stronger inferences from epidemiological studies. Ultimately, better estimates of the causal effects of EDC exposures on child health could help identify susceptible sub-populations and lead to public health interventions to reduce these exposures. PMID:27857130

  11. Raw milk consumption and other early-life farm exposures and adult pulmonary function in the Agricultural Lung Health Study.

    Science.gov (United States)

    Wyss, Annah B; House, John S; Hoppin, Jane A; Richards, Marie; Hankinson, John L; Long, Stuart; Henneberger, Paul K; Beane Freeman, Laura E; Sandler, Dale P; O'Connell, Elizabeth Long; Cummings, Christie Barker; Umbach, David M; London, Stephanie J

    2018-03-01

    Literature suggests that early exposure to the farming environment protects against atopy and asthma; few studies have examined pulmonary function. We evaluated associations between early-life farming exposures and pulmonary function in 3061 adults (mean age=63) from a US farming population using linear regression. Childhood raw milk consumption was associated with higher FEV 1 (β=49.5 mL, 95% CI 2.8 to 96.1 mL, p=0.04) and FVC (β=66.2 mL, 95% CI 13.2 to 119.1 mL, p=0.01). We did not find appreciable associations with other early-life farming exposures. We report a novel association between raw milk consumption and higher pulmonary function that lasts into older adulthood. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Life course exposure to smoke and early menopause and menopausal transition.

    Science.gov (United States)

    Tawfik, Hebatullah; Kline, Jennie; Jacobson, Judith; Tehranifar, Parisa; Protacio, Angeline; Flom, Julie D; Cirillo, Piera; Cohn, Barbara A; Terry, Mary Beth

    2015-10-01

    Early age at menopause is associated with increased risk of cardiovascular disease, stroke, osteoporosis, and all-cause mortality. Cigarette smoke exposure in adulthood is an established risk factor for earlier age at natural menopause and may be related to age at the menopausal transition. Using data from two US birth cohorts, we examined the association between smoke exposure at various stages of the life course (prenatal exposure, childhood exposure to parental smoking, and adult smoke exposure) and menopause status in 1,001 women aged 39 to 49 years at follow-up. We used logistic regression analysis (adjusting for age at follow-up) to estimate odds ratios (ORs) and 95% confidence intervals (CI) relating smoke exposure to natural menopause and the menopausal transition. The magnitudes of the associations for natural menopause were similar but not statistically significant after adjustment for confounders among (i) women with prenatal smoke exposure who did not smoke on adult follow-up (OR, 2.7; 95% CI, 0.8-9.4) and (ii) current adult smokers who were not exposed prenatally (OR, 2.8; 95% CI, 0.9-9.0). Women who had been exposed to prenatal smoke and were current smokers had three times the risk of experiencing earlier natural menopause (adjusted OR, 3.4; 95% CI, 1.1-10.3) compared with women without smoke exposure in either period. Only current smoking of long duration (>26 y) was associated with the timing of the menopausal transition. Our data suggest that exposure to smoke both prenatally and around the time of menopause accelerates ovarian aging.

  13. Sucrose exposure in early life alters adult motivation and weight gain.

    Directory of Open Access Journals (Sweden)

    Cristianne R M Frazier

    2008-09-01

    Full Text Available The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.

  14. Sucrose exposure in early life alters adult motivation and weight gain.

    Science.gov (United States)

    Frazier, Cristianne R M; Mason, Peggy; Zhuang, Xiaoxi; Beeler, Jeff A

    2008-09-17

    The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.

  15. Life Course Exposure to Smoke and Early Menopause and Menopausal Transition

    Science.gov (United States)

    Tawfik, Heba; Kline, Jennie; Jacobson, Judith; Tehranifar, Parisa; Protacio, Angeline; Flom, Julie D.; Cirillo, Piera; Cohn, Barbara A.; Terry, Mary Beth

    2015-01-01

    Objective Early age at menopause is associated with increased risk of cardiovascular disease, stroke, osteoporosis and all-cause mortality. Cigarette smoke exposure in adulthood is an established risk factor for earlier age at natural menopause and may be related to age at menopausal transition. Using data from two U.S. birth cohorts, we examined the association between smoke exposure at various stages of the life course (prenatal, childhood exposure to parental smoking and adult smoke exposure) with menopause status in 1,001 women aged 39 – 49 years at follow-up. Methods We used logistic regression analysis, adjusting for age at follow-up, to estimate odds ratios (ORs) and 95% confidence intervals (CI) relating smoke exposure to natural menopause and menopausal transition. Results The magnitudes of the associations for natural menopause were similar, but not statistically significant after adjustment for confounders for i) women with prenatal smoke exposure who did not smoke at adult follow-up (OR= 2.7 [95% CI 0.8, 9.4]) and ii) current adult smokers who were not exposed prenatally (OR= 2.8 [95% CI 0.9, 9.0]). Women who had been exposed to prenatal smoke and were current smokers had three times the risk of experiencing natural menopause (adjusted OR=3.4 [95% CI 1.1, 10.3]) compared to women without smoke exposure in either time period. Only current smoking of long duration (>26 years) was associated with the timing of the menopausal transition. Conclusion Our data suggest that exposure to smoke both prenatally and around the time of menopause accelerates ovarian aging. PMID:25803667

  16. Early Life Trauma Exposure and Stress Sensitivity in Young Children

    OpenAIRE

    Grasso, Damion J.; Ford, Julian D.; Briggs-Gowan, Margaret J.

    2012-01-01

    Objective The current study replicates and extends work with adults that highlights the relationship between trauma exposure and distress in response to subsequent, nontraumatic life stressors. Methods The sample included 213 2–4-year-old children in which 64.3% had a history of potential trauma exposure. Children were categorized into 4 groups based on trauma history and current life stress. Results In a multivariate analysis of variance, trauma-exposed children with current life stressors h...

  17. Early-Life Antibiotic Exposure, Gut Microbiota Development, and Predisposition to Obesity.

    Science.gov (United States)

    Azad, Meghan B; Moossavi, Shirin; Owora, Arthur; Sepehri, Shadi

    2017-01-01

    Antibiotics are often prescribed inappropriately to infants and young children, with potentially adverse effects on the developing gut microbiota and related metabolic processes. We review evidence from 17 epidemiologic studies suggesting that antibiotic exposure during critical periods of early development may influence weight gain and the development of obesity. Complementary research in both humans and rodents indicates that gut microbiota play a key role in this process, although further research is needed to confirm and characterize the causal mechanisms involved. Obesity is a complex and multifactorial condition; thus, a multipronged prevention strategy will be required to curb the current obesity epidemic. Evidence to date suggests this strategy should include the judicious use of antibiotics, especially in early life when the developing gut microbiota is particularly susceptible to perturbations with long-lasting implications for metabolic programming and obesity risk. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

  18. Do early-life exposures explain why more advantaged children get eczema? Findings from the U.K. Millennium Cohort Study.

    Science.gov (United States)

    Taylor-Robinson, D C; Williams, H; Pearce, A; Law, C; Hope, S

    2016-03-01

    Atopic dermatitis (eczema) in childhood is socially patterned, with higher incidence in more advantaged populations. However, it is unclear what factors explain the social differences. To identify early-life risk factors for eczema, and to explore how early-life risk factors explain any differences in eczema. We estimated odds ratios (ORs) for ever having had eczema by age 5 years in 14 499 children from the U.K. Millennium Cohort Study (MCS), with a focus on maternal, antenatal and early-life risk factors and socioeconomic circumstances (SECs). Risk factors were explored to assess whether they attenuated associations between SECs and eczema. Overall 35·1% of children had ever had eczema by age 5 years. Children of mothers with degree-level qualifications vs. no educational qualifications were more likely to have eczema (OR 1·52, 95% confidence interval 1·31-1·76), and there was a gradient across the socioeconomic spectrum. Maternal atopy, breastfeeding (1-6 weeks and ≥ 6 months), introduction of solids under 4 months or cow's milk under 9 months, antibiotic exposure in the first year of life and grime exposure were associated with an increased odds of having eczema. Female sex, Pakistani and Bangladeshi ethnicity, smoking during pregnancy, exposure to environmental tobacco smoke and having more siblings were associated with reduced odds for eczema. Controlling for maternal, antenatal and early-life characteristics (particularly maternal smoking during pregnancy, breastfeeding and number of siblings) reduced the OR for eczema to 1·26 (95% confidence interval 1·03-1·50) in the group with the highest educational qualifications compared with the least. In a representative U.K. child cohort, eczema was more common in more advantaged children. This was explained partially by early-life factors including not smoking during pregnancy, breastfeeding and having fewer siblings. © 2015 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on

  19. Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.

    Science.gov (United States)

    Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L

    2017-09-01

    Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.

  20. Systematic review and meta-analysis of early life exposure to di(2-ethylhexyl) phthalate and obesity related outcomes in rodents

    NARCIS (Netherlands)

    Wassenaar, Pim Nicolaas Hubertus; Legler, Juliette

    Background It has been suggested that the plasticizer di(2-ethylhexyl) phthalate (DEHP) exerts obesogenic effects after pre- or perinatal exposure. Objective A systematic review with meta-analyses was conducted of early life exposure to DEHP, or its biologically active metabolite mono(2-ethylhexyl)

  1. Early life history pelagic exposure profiles of selected commercially important fish species in the Gulf of Alaska

    Science.gov (United States)

    Doyle, Miriam J.; Mier, Kathryn L.

    2016-10-01

    A synthesis of nearly four decades of ichthyoplankton survey data from the Gulf of Alaska was undertaken to provide the most comprehensive information available on the early life history ecology of five focal species: Pacific Cod (Gadus macrocephalus), Walleye Pollock (Gadus chalcogrammus), Pacific Ocean Perch (Sebastes alutus), Sablefish (Anoplopoma fimbria), and Arrowtooth Flounder (Atheresthes stomias). This analysis of historical data, along with information from published studies, is presented here in the form of ecological reviews of the species during their planktonic phase. The reviews include descriptions of temporal and spatial patterns of exposure to the environment, and interpretation regarding associated sensitivities to environmental forcing. On a temporal scale, patterns in abundance of eggs and larvae are synthesized that characterize seasonal exposure to the pelagic environment, and interannual variation that is presumed to incorporate responses to long-term environmental forcing. Spatial patterns are synthesized to identify horizontal and vertical extent of egg and larval distributions, delineate areas of primary larval habitat, and illuminate egg and larval drift pathways. The observed patterns are discussed with respect to characterizing species early life history strategies, identifying long-term adaptations to the Gulf of Alaska environment, and associated resilience and vulnerability factors that may modulate early life responses to environmental forcing in this region. For each species, gaps in knowledge are identified and are concerned primarily with the period of transition between the larval and juvenile stage, and feeding habits and ecology across seasons, habitats and sub-intervals of early ontogeny. These early life history reviews advance our ecological understanding of the pelagic phase, and fine-tune our focus for the investigation of potential response mechanisms to environmental forcing at appropriate, species-specific temporal

  2. The positive and negative consequences of stressors during early life.

    Science.gov (United States)

    Monaghan, Pat; Haussmann, Mark F

    2015-11-01

    We discuss the long-term effects of stress exposure in pre- and early postnal life. We present an evolutionary framework within which such effects can be viewed, and describe how the outcomes might vary with species life histories. We focus on stressors that induce increases in glucocorticoid hormones and discuss the advantages of an experimental approach. We describe a number of studies demonstrating how exposure to these hormones in early life can influence stress responsiveness and have substantial long-term, negative consequences for adult longevity. We also describe how early life exposure to mild levels of stressors can have beneficial effects on resilience to stress in later life, and discuss how the balance of costs and benefits is likely dependent on the nature of the adult environment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Thyroid stimulating hormone levels in newborns and early life exposure to endocrine disrupting chemicals - analysis of three European mother-child cohorts

    NARCIS (Netherlands)

    de Cock, Marijke; de Boer, Michiel R; Govarts, Eva; Iszatt, Nina; Palkovicova, Lubica; Lamoree, Marja H; Schoeters, Greet; Eggesbø, Merete; Trnovec, Tomas; Legler, Juliette; van de Bor, Margot

    2017-01-01

    BACKGROUND: Various studies report interactions between thyroid hormones and early life chemical exposure. Our objective was to analyse associations between markers of endocrine disrupting chemical exposure and thyroid function in newborns, determined in heel prick blood spots. METHODS: Three

  4. Early Life Adversity as a Risk Factor for Fibromyalgia in Later Life

    Directory of Open Access Journals (Sweden)

    Lucie A. Low

    2012-01-01

    Full Text Available The impact of early life events is increasingly becoming apparent, as studies investigate how early childhood can shape long-term physiology and behaviour. Fibromyalgia (FM, which is characterised by increased pain sensitivity and a number of affective co-morbidities, has an unclear etiology. This paper discusses risk factors from early life that may increase the occurrence or severity of FM in later life: pain experience during neonatal life causes long-lasting changes in nociceptive circuitry and increases pain sensitivity in the older organism; premature birth and related stressor exposure cause lasting changes in stress responsivity; maternal deprivation affects anxiety-like behaviours that may be partially mediated by epigenetic modulation of the genome—all these adult phenotypes are strikingly similar to symptoms displayed by FM sufferers. In addition, childhood trauma and exposure to substances of abuse may cause lasting changes in developing neurotransmitter and endocrine circuits that are linked to anxiety and stress responses.

  5. Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson's disease.

    Science.gov (United States)

    Hare, Dominic J; Cardoso, Bárbara Rita; Raven, Erika P; Double, Kay L; Finkelstein, David I; Szymlek-Gay, Ewa A; Biggs, Beverley-Ann

    2017-01-01

    Iron accumulates gradually in the ageing brain. In Parkinson's disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors that limit iron regulatory capacity and/or dopamine metabolism, this may increase the risk of Parkinson's diseases. We propose to (a) validate a retrospective biomarker of iron exposure in children; (b) translate this biomarker to adults; (c) integrate it with in vivo brain iron in Parkinson's disease; and (d) longitudinally examine the relationships between early-life iron exposure and metabolism, brain iron deposition and Parkinson's disease risk. This approach will provide empirical evidence to support therapeutically addressing brain iron deposition in Parkinson's diseases and produce a potential biomarker of Parkinson's disease risk in preclinical individuals.

  6. Early-life exposures predicting onset and resolution of childhood overweight or obesity.

    Science.gov (United States)

    Kerr, Jessica A; Long, Catherine; Clifford, Susan A; Muller, Joshua; Gillespie, Alanna N; Donath, Susan; Wake, Melissa

    2017-10-01

    To determine which of multiple early-life exposures predict onset or resolution of overweight/obesity during a 9-year period. Design : longitudinal cohort from three harmonised community-based cohorts enriched for overweight and obesity. Early-life exposures : child-gestational age; delivery; birth weight; breast feeding; solids introduction; baseline body mass index (BMI); waist circumference; diet; activity; global, physical and psychosocial health. Mother-baseline BMI; education; age; neighbourhood disadvantage; concern for child's weight. Outcome : change in BMI category. Analyses : adjusted logistic regression. On average, the 363 children (57% retention) were 6 and 15 years old at baseline and follow-up. Children were classified as 'never' overweight/obese (38%), 'resolving' overweight/obese (15%), 'becoming' overweight/obese (8%) or 'always' overweight/obese (39%). Compared with 'never overweight/obese' children, odds of 'becoming overweight/obese' were greater with higher child (OR 2.33, 95% CI 1.02 to 5.29) and maternal BMI (OR 1.18, CI 1.07 to 1.31), and lower with higher maternal education (OR 0.09, CI 0.02 to 0.34). Compared with 'always overweight/obese' children, odds of 'resolving overweight/obese' were lower with higher maternal BMI (OR 0.87, CI 0.78 to 0.97), and higher with better child physical health (OR 1.06, CI 1.02 to 1.10) and higher maternal age (OR 1.11, CI 1.01 to 1.22) and education (OR 4.07, CI 1.02 to 16.19). Readily available baseline information (child/maternal BMI, maternal age, education and child health) were the strongest predictors of both onset and resolution of overweight/obesity between the primary school and adolescent years. Perinatal, breastfeeding and lifestyle exposures were not strongly predictive. Results could stimulate development of algorithms identifying children most in need of targeted prevention or treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under

  7. Early Life Fructose Exposure and Its Implications for Long-Term Cardiometabolic Health in Offspring.

    Science.gov (United States)

    Zheng, Jia; Feng, Qianyun; Zhang, Qian; Wang, Tong; Xiao, Xinhua

    2016-11-01

    It has become increasingly clear that maternal nutrition can strongly influence the susceptibility of adult offspring to cardiometabolic disease. For decades, it has been thought that excessive intake of fructose, such as sugar-sweetened beverages and foods, has been linked to increased risk of obesity, type 2 diabetes, and cardiovascular disease in various populations. These deleterious effects of excess fructose consumption in adults are well researched, but limited data are available on the long-term effects of high fructose exposure during gestation, lactation, and infancy. This review aims to examine the evidence linking early life fructose exposure during critical periods of development and its implications for long-term cardiometabolic health in offspring.

  8. Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global DNA Methylation and in Nurr1 Gene Expression

    Directory of Open Access Journals (Sweden)

    Laura Bordoni

    2015-11-01

    Full Text Available Environmental exposure to pesticides during the early stages of development represents an important risk factor for the onset of neurodegenerative diseases in adult age. Neonatal exposure to Permethrin (PERM, a member of the family of synthetic pyrethroids, can induce a Parkinson-like disease and cause some alterations in striatum of rats, involving both genetic and epigenetic pathways. Through gene expression analysis and global DNA methylation assessment in both PERM-treated parents and their untreated offspring, we investigated on the prospective intergenerational effect of this pesticide. Thirty-three percent of progeny presents the same Nurr1 alteration as rats exposed to permethrin in early life. A decrease in global genome-wide DNA methylation was measured in mothers exposed in early life to permethrin as well as in their offspring, whereas untreated rats have a hypermethylated genomic DNA. Further studies are however needed to elucidate the molecular mechanisms, but, despite this, an intergenerational PERM-induced damage on progenies has been identified for the first time.

  9. High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

    Energy Technology Data Exchange (ETDEWEB)

    Steinmaus, Craig, E-mail: craigs@berkeley.edu [Arsenic Health Effects Research Program, UC Berkeley School of Public Health, Berkeley, CA (United States); Ferreccio, Catterina; Acevedo, Johanna [School of Medicine, Pontificia Universidad Católica de Chile, Santiago (Chile); Advanced Center for Chronic Diseases (ACCDiS), FONDAP, Santiago (Chile); Balmes, John R [Arsenic Health Effects Research Program, UC Berkeley School of Public Health, Berkeley, CA (United States); Department of Medicine, University of California, San Francisco, San Francisco, CA (United States); Liaw, Jane [Arsenic Health Effects Research Program, UC Berkeley School of Public Health, Berkeley, CA (United States); Troncoso, Patricia [Laboratorio de Anatomía Patológica Dra. Patricia Troncoso, Iquique (Chile); Hospital Felix Bulnes, Departmento de Anatomía Patológica, Santiago (Chile); Dauphiné, David C [Arsenic Health Effects Research Program, UC Berkeley School of Public Health, Berkeley, CA (United States); Nardone, Anthony [Global Health Sciences Program, University of California, San Francisco, San Francisco, CA (United States); Smith, Allan H [Arsenic Health Effects Research Program, UC Berkeley School of Public Health, Berkeley, CA (United States)

    2016-12-15

    Background: Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods: We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤ 10 μg/L. Results: Compared to adults never exposed > 10 μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 mL decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 mL). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions: Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. - Highlights: • Based on its unique geology, lifetime arsenic exposure can be assessed in north Chile. • Signs and symptoms of lung disease were associated with early-life arsenic exposure. • Evidence of lung disease was also associated with moderate arsenic exposure.

  10. Association between Exposure to the Chinese Famine in Different Stages of Early Life and Decline in Cognitive Functioning in Adulthood.

    Science.gov (United States)

    Wang, Chao; An, Yu; Yu, Huanling; Feng, Lingli; Liu, Quanri; Lu, Yanhui; Wang, Hui; Xiao, Rong

    2016-01-01

    To investigate whether exposure to the Chinese Famine in different life stages of early life is associated with cognitive functioning decline in adulthood. We recruited 1366 adults born between 1950 and 1964 and divided them into fetal-exposed, early childhood-exposed (1-3 years old during the famine), mid childhood-exposed (4-6 years old during the famine), late childhood-exposed (7-9 years old during the famine), and non-exposed groups. A selection of cognitive tests was administered to assess their cognitive performance. Association between malnutrition in different famine exposure periods and adult cognitive performance was estimated by multivariate logistic and multiple linear regression analyses. There were significant differences in cognitive performance between subjects exposed to famine during different life stages. For the general cognitive tests, fetal-exposed period was associated with decreased scores of the Mini-Mental State Examination (MMSE), and late childhood-exposed with decreased scores of the Montreal Cognitive Assessment (MoCA). We also found exposure to famine during mid and late childhood was associated with worse performance on the Stroop color and word test. Famine exposure in utero and during childhood is associated with overall and specific cognitive decline, affecting selective attention and response inhibition particularly.

  11. Exposure to Mercury and Aluminum in Early Life: Developmental Vulnerability as a Modifying Factor in Neurologic and Immunologic Effects

    Directory of Open Access Journals (Sweden)

    José G. Dórea

    2015-01-01

    Full Text Available Currently, ethylmercury (EtHg and adjuvant-Al are the dominating interventional exposures encountered by fetuses, newborns, and infants due to immunization with Thimerosal-containing vaccines (TCVs. Despite their long use as active agents of medicines and fungicides, the safety levels of these substances have never been determined, either for animals or for adult humans—much less for fetuses, newborns, infants, and children. I reviewed the literature for papers reporting on outcomes associated with (a multiple exposures and metabolism of EtHg and Al during early life; (b physiological and metabolic characteristics of newborns, neonates, and infants relevant to xenobiotic exposure and effects; (c neurobehavioral, immunological, and inflammatory reactions to Thimerosal and Al-adjuvants resulting from TCV exposure in infancy. Immunological and neurobehavioral effects of Thimerosal-EtHg and Al-adjuvants are not extraordinary; rather, these effects are easily detected in high and low income countries, with co-exposure to methylmercury (MeHg or other neurotoxicants. Rigorous and replicable studies (in different animal species have shown evidence of EtHg and Al toxicities. More research attention has been given to EtHg and findings have showed a solid link with neurotoxic effects in humans; however, the potential synergic effect of both toxic agents has not been properly studied. Therefore, early life exposure to both EtHg and Al deserves due consideration.

  12. Impacts of triclosan exposure on zebrafish early-life stage: Toxicity and acclimation mechanisms.

    Science.gov (United States)

    Falisse, Elodie; Voisin, Anne-Sophie; Silvestre, Frédéric

    2017-08-01

    Triclosan (TCS) is a broad spectrum antibacterial agent widely used in personal care products and present in most aquatic ecosystems. This study investigated the occurrence of triclosan acclimation and the biological mechanisms underlying the stress response triggered in early-life stage of zebrafish. Zebrafish eggs were first exposed to four different sublethal concentrations of TCS (2, 20, 50 and 100μg/L) for 7days following fertilization and subsequently exposed to a lethal concentration of TCS (1000μg/L). During the time-to-death exposure (TTD), mortality was continuously recorded to evaluate if increased resistance occurred. Overall, larvae exposed to 50μg/L of TCS demonstrated higher sensitivity, with delayed hatching and increased mortality during the sub-lethal exposure and significant lower mean time-to-death (TTD) value compared to the other groups. Interestingly, fish exposed to the highest concentration of TCS (100μg/L) presented a similar mean TTD value as controls and a significantly better survival in comparison with embryos exposed to 50μg/L, suggesting that acclimation process has been triggered at this concentration. Proteomic and enzymatic analyses were conducted on 7days post fertilization (dpf) larvae exposed to 50μg/L and 100μg/L of TCS giving insights into the functional changes triggered at those specific concentrations. TCS seemed to affect proteins involved in cytoskeleton, stress response, eyes and neuronal development. This was endorsed by the enzymatic results, which suggest impairment in glutathione metabolism and acute neurotoxicity. A significant 2.5-fold and 3-fold increase of AChE activity was observed following TCS exposure. Moreover, GPx activity was significantly increased whereas a significant inhibition of GR activity was observed, suggesting that de novo synthesis of reduced GSH might occur in order to maintain the ratio between reduced and oxidized GSH. Proteomic results revealed possible candidate protein involved in

  13. Cat exposure in early life decreases asthma risk from the 17q21 high-risk variant.

    Science.gov (United States)

    Stokholm, Jakob; Chawes, Bo L; Vissing, Nadja; Bønnelykke, Klaus; Bisgaard, Hans

    2018-05-01

    Early-life exposure to cats and dogs has shown diverging associations with childhood asthma risk, and gene-environment interaction is one possible explanation. We investigated interactions between cat and dog exposure and single nucleotide polymorphism rs7216389 variants in the chromosome 17q21 locus, the strongest known genetic risk factor for childhood asthma. Genotyping was performed in 377 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 . The primary end point was the development of asthma until age 12 years. The secondary end point was the number of episodes with pneumonia and bronchiolitis from 0 to 3 years of age. Exposures included cat and dog ownership from birth and cat and dog allergen levels in bedding at age 1 year. Replication was performed in the unselected COPSAC 2010 cohort with follow-up until 5 years of age. Cat and/or dog exposure from birth was associated with a lower prevalence of asthma among children with the rs7216389 high-risk TT genotype (adjusted hazard ratio, 0.16; 95% CI, 0.04-0.71; P = .015), with no effect in those with the CC/CT genotype (adjusted P = .283), demonstrating interaction between cat and dog exposure and the rs7216389 genotype (adjusted P = .044). Cat allergen levels were inversely associated with asthma development in children with the TT genotype (adjusted hazard ratio, 0.83; 95% CI, 0.71-0.97; P = .022), supporting the cat-rs7216389 genotype interaction (adjusted P = .008). Dog allergen exposure did not show such interaction. Furthermore, the TT genotype was associated with higher risk of pneumonia and bronchiolitis, and this increased risk was likewise decreased in children exposed to cat. Replication showed similar effects on asthma risk. The observed gene-environment interaction suggests a role of early-life exposure, especially to cat, for attenuating the risk of childhood asthma, pneumonia, and bronchiolitis in genetically susceptible subjects. Copyright © 2017

  14. Early life exposure to bisphenol A investigated in mouse models of airway allergy, food allergy and oral tolerance.

    Science.gov (United States)

    Nygaard, Unni Cecilie; Vinje, Nina Eriksen; Samuelsen, Mari; Andreassen, Monica; Groeng, Else-Carin; Bølling, Anette Kocbach; Becher, Rune; Lovik, Martinus; Bodin, Johanna

    2015-09-01

    The impact of early life exposure to bisphenol A (BPA) through drinking water was investigated in mouse models of respiratory allergy, food allergy and oral tolerance. Balb/c mice were exposed to BPA (0, 10 or 100 μg/ml), and the offspring were intranasally exposed to the allergen ovalbumin (OVA). C3H/HeJ offspring were sensitized with the food allergen lupin by intragastric gavage, after exposure to BPA (0, 1, 10 or 100 μg/ml). In separate offspring, oral tolerance was induced by gavage of 5 mg lupin one week before entering the protocol for the food allergy induction. In the airway allergy model, BPA (100 μg/ml) caused increased eosinophil numbers in bronchoalveolar lavage fluid (BALF) and a trend of increased OVA-specific IgE levels. In the food allergy and tolerance models, BPA did not alter the clinical anaphylaxis or antibody responses, but induced alterations in splenocyte cytokines and decreased mouse mast cell protease (MMCP)-1 serum levels. In conclusion, early life exposure to BPA through drinking water modestly augmented allergic responses in a mouse model of airway allergy only at high doses, and not in mouse models for food allergy and tolerance. Thus, our data do not support that BPA promotes allergy development at exposure levels relevant for humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Early-Life Nutritional Programming of Health and Disease in The Gambia.

    Science.gov (United States)

    Moore, Sophie E

    2017-01-01

    Exposures during early life are increasingly being recognised as factors that play an important role in the aetiology of chronic non-communicable diseases (NCDs). The "Developmental Origins of Health and Disease" (DOHaD) hypothesis asserts that adverse early-life exposures - most notably unbalanced nutrition - leads to an increased risk for a range of NCDs and that disease risk is highest when there is a "mismatch" between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in settings undergoing a rapid nutrition transition. We investigated the link between early-life nutritional exposures and long-term health in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomised controlled trials of nutritional supplementation in pregnancy, and the "experiment of nature" that seasonality in this region provides, we investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs. Key Messages: Our work in rural Gambia suggests that in populations with high rates of under-nutrition in early life, the immune system may be sensitive to nutritional deficiencies early in life, resulting in a greater susceptibility to infection-related morbidity and mortality. © 2017 S. Karger AG, Basel.

  16. Early-life exposure to fibroblast growth factor-2 facilitates context-dependent long-term memory in developing rats.

    Science.gov (United States)

    Graham, Bronwyn M; Richardson, Rick

    2010-06-01

    Fibroblast growth factor-2 (FGF2) is a potent neurotrophic factor that is involved in brain development and the formation of long-term memory. It has recently been shown that acute FGF2, administered at the time of learning, enhances long-term memory for contextual fear conditioning as well as extinction of conditioned fear in developing rats. As other research has shown that administering FGF2 on the first day of life leads to long-term morphological changes in the hippocampus, in the present study we investigated whether early life exposure to FGF2 affects contextual fear conditioning, and renewal following extinction, later in life. Experiment 1 demonstrated that a single injection of FGF2 on Postnatal Day (PND) 1 did not lead to any detectable changes in contextual fear conditioning in PND 16 or PND 23 rats. Experiments 2 and 3 demonstrated that 5 days of injections of FGF2 (from PND 1-5) facilitated contextual fear conditioning in PND 16 and PND 23 rats. Experiment 4 demonstrated that the observed facilitation of memory was not due to FGF2 increasing rats' sensitivity to foot shock. Experiment 5 showed that early life exposure to FGF2 did not affect learning about a discrete conditioned stimulus, but did allow PND 16 rats to use contextual information in more complex ways, leading to context-dependent extinction of conditioned fear. These results further implicate FGF2 as a critical signal involved in the development of learning and memory.

  17. Exposure to Mobile Source Air Pollution in Early-life and Childhood Asthma Incidence: The Kaiser Air Pollution and Pediatric Asthma Study.

    Science.gov (United States)

    Pennington, Audrey Flak; Strickland, Matthew J; Klein, Mitchel; Zhai, Xinxin; Bates, Josephine T; Drews-Botsch, Carolyn; Hansen, Craig; Russell, Armistead G; Tolbert, Paige E; Darrow, Lyndsey A

    2018-01-01

    Early-life exposure to traffic-related air pollution exacerbates childhood asthma, but it is unclear what role it plays in asthma development. The association between exposure to primary mobile source pollutants during pregnancy and during infancy and asthma incidence by ages 2 through 6 was examined in the Kaiser Air Pollution and Pediatric Asthma Study, a racially diverse birth cohort of 24,608 children born between 2000 and 2010 and insured by Kaiser Permanente Georgia. We estimated concentrations of mobile source fine particulate matter (PM2.5, µg/m), nitrogen oxides (NOX, ppb), and carbon monoxide (CO, ppm) at the maternal and child residence using a Research LINE source dispersion model for near-surface releases. Asthma was defined using diagnoses and medication dispensings from medical records. We used binomial generalized linear regression to model the impact of exposure continuously and by quintiles on asthma risk. Controlling for covariates and modeling log-transformed exposure, a 2.7-fold increase in first year of life PM2.5 was associated with an absolute 4.1% (95% confidence interval, 1.6%, 6.6%) increase in risk of asthma by age 5. Quintile analysis showed an increase in risk from the first to second quintile, but similar risk across quintiles 2-5. Risk differences increased with follow-up age. Results were similar for NOX and CO and for exposure during pregnancy and the first year of life owing to high correlation. Results provide limited evidence for an association of early-life mobile source air pollution with childhood asthma incidence with a steeper concentration-response relationship observed at lower levels of exposure.

  18. Early-Life Phthalate Exposure and Adiposity at 8 Years of Age.

    Science.gov (United States)

    Shoaff, Jessica; Papandonatos, George D; Calafat, Antonia M; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P; Yolton, Kimberly; Braun, Joseph M

    2017-09-11

    Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022.

  19. Early Maternal Deprivation Enhances Voluntary Alcohol Intake Induced by Exposure to Stressful Events Later in Life

    Directory of Open Access Journals (Sweden)

    Sara Peñasco

    2015-01-01

    Full Text Available In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9, on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake.

  20. Early-life exposure to outdoor air pollution and respiratory health, ear infections, and eczema in infants from the INMA study

    DEFF Research Database (Denmark)

    Aguilera, Inmaculada; Pedersen, Marie; Garcia-Esteban, Raquel

    2013-01-01

    the first 12-18 months of age in a Spanish birth cohort of 2,199 infants. METHODS: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO...... and lower respiratory tract infections in infants.......BACKGROUND: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health. OBJECTIVES: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during...

  1. Cat exposure in early life decreases asthma risk from the 17q21 high-risk variant

    DEFF Research Database (Denmark)

    Stokholm, Jakob; Chawes, Bo L.; Vissing, Nadja

    2018-01-01

    Background: Early-life exposure to cats and dogs has shown diverging associations with childhood asthma risk, and gene-environment interaction is one possible explanation. Objectives: We investigated interactions between cat and dog exposure and single nucleotide polymorphism rs7216389 variants...... was the number of episodes with pneumonia and bronchiolitis from 0 to 3 years of age. Exposures included cat and dog ownership from birth and cat and dog allergen levels in bedding at age 1 year. Replication was performed in the unselected COPSAC2010 cohort with follow-up until 5 years of age. Results: Cat and....../or dog exposure from birth was associated with a lower prevalence of asthma among children with the rs7216389 high-risk TT genotype (adjusted hazard ratio, 0.16; 95% CI, 0.04-0.71; P =.015), with no effect in those with the CC/CT genotype (adjusted P =.283), demonstrating interaction between cat and dog...

  2. Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

    Science.gov (United States)

    Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

    2017-07-20

    Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

  3. Early life stress, HPA axis adaptation and mechanisms contributing to later health outcomes

    Directory of Open Access Journals (Sweden)

    Jayanthi eManiam

    2014-05-01

    Full Text Available Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early life stress can impact on later health but less is known about how early life stress impairs HPA axis activity, contributing to maladaptation of the stress response system. Early life stress exposure (either prenatally or in the early postnatal period can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical and experimental studies have demonstrated that early life stress produces long-term hyper responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviours. Recently, evidence has emerged on early life stress induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1. We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early life stress induced maladaptation of the HPA axis, and its subsequent effects on energy utilisation and expenditure. The effects of positive later environments as a means of ameliorating early life stress induced health deficits, and proposed mechanisms underpinning the interaction between early life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early life stress and later health outcomes will also

  4. Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

    Science.gov (United States)

    Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

    2014-01-01

    Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be

  5. Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

    Science.gov (United States)

    van Bodegom, Miranda; Homberg, Judith R.; Henckens, Marloes J. A. G.

    2017-01-01

    Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA

  6. Antibiotic exposure in early life and childhood overweight and obesity

    DEFF Research Database (Denmark)

    Rasmussen, Sara H; Shrestha, Sarita; Bjerregaard, Lise G

    2018-01-01

    We conducted a systematic review and meta-analysis of observational studies investigating the association between antibiotic exposure in infancy and risk of childhood overweight and obesity. Thirteen studies counting a total of 527,504 children were included in the systematic review and eight were...... included in meta-analyses. Exposure to antibiotics in infancy was associated with an increased odds ratio (OR) of childhood overweight and obesity (OR = 1.11 [95% CI 1.02-1.20]). Whereas exposure to one treatment only and exposure between 6 and 24 months were not associated with increased risk of childhood...... overweight and obesity, exposure to more than one treatment was associated with an OR of 1.24 (95% CI 1.09-1.43) and exposure within the first six months of life was associated with an OR of 1.20 (95% CI 1.04-1.37). In conclusion, antibiotic exposure in infancy is associated with a slightly increased risk...

  7. Exposure to dim light at night during early development increases adult anxiety-like responses.

    Science.gov (United States)

    Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

    2014-06-22

    Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

  8. Early-Life Effects on Adult Physical Activity: Concepts, Relevance, and Experimental Approaches.

    Science.gov (United States)

    Garland, Theodore; Cadney, Marcell D; Waterland, Robert A

    Locomotion is a defining characteristic of animal life and plays a crucial role in most behaviors. Locomotion involves physical activity, which can have far-reaching effects on physiology and neurobiology, both acutely and chronically. In human populations and in laboratory rodents, higher levels of physical activity are generally associated with positive health outcomes, although excessive exercise can have adverse consequences. Whether and how such relationships occur in wild animals is unknown. Behavioral variation among individuals arises from genetic and environmental factors and their interactions as well as from developmental programming (persistent effects of early-life environment). Although tremendous progress has been made in identifying genetic and environmental influences on individual differences in behavior, early-life effects are not well understood. Early-life effects can in some cases persist across multiple generations following a single exposure and, in principle, may constrain or facilitate the rate of evolution at multiple levels of biological organization. Understanding the mechanisms of such transgenerational effects (e.g., exposure to stress hormones in utero, inherited epigenetic alterations) may prove crucial to explaining unexpected and/or sex-specific responses to selection as well as limits to adaptation. One area receiving increased attention is early-life effects on adult physical activity. Correlational data from epidemiological studies suggest that early-life nutritional stress can (adversely) affect adult human activity levels and associated physiological traits (e.g., body composition, metabolic health). The few existing studies of laboratory rodents demonstrate that both maternal and early-life exercise can affect adult levels of physical activity and related phenotypes. Going forward, rodents offer many opportunities for experimental studies of (multigenerational) early-life effects, including studies that use maternal

  9. Uncovering the exposure mechanisms of sunken heavy oil that makes it chronically toxic to early life stages of fish

    International Nuclear Information System (INIS)

    Martin, J.; Young, G.; Lemire, B.; Hodson, P.

    2010-01-01

    A train derailment in 2005 caused the release of 150,000 litres of No. 6 heavy fuel oil into a lake in Alberta. The oil is a residue of the crude oil refinement process and contains 3-4 ringed alkylated forms of polycyclic aromatic hydrocarbons (PAH) that are known to cause sub-lethal toxic responses during the early life stages of rainbow trout. Because the oil does not disperse well, oil patches still persist in near-shore sediments of the lake where fish spawn. This study assessed how the behaviour of heavy oil in water interacts with exposure and toxicity to the early life stages of fish. Daily renewal tests with heavy fuel oil coated on glass plate demonstrated higher levels of toxicity to trout embryos than oil that was mechanically or chemically dispersed. A flow-through oil gravel column was used to assess whether the toxic constituents of the heavy oil are transferred quickly enough to cause toxicity. The aim of the study was to develop exposure and toxicity test methods that accurately reflect the behaviour of heavy oil after a spill.

  10. Early-life income inequality and adolescent health and well-being.

    Science.gov (United States)

    Elgar, Frank J; Gariépy, Geneviève; Torsheim, Torbjørn; Currie, Candace

    2017-02-01

    A prevailing hypothesis about the association between income inequality and poor health is that inequality intensifies social hierarchies, increases stress, erodes social and material resources that support health, and subsequently harms health. However, the evidence in support of this hypothesis is limited by cross-sectional, ecological studies and a scarcity of developmental studies. To address this limitation, we used pooled, multilevel data from the Health Behaviour in School-aged Children study to examine lagged, cumulative, and trajectory associations between early-life income inequality and adolescent health and well-being. Psychosomatic symptoms and life satisfaction were assessed in surveys of 11- to 15-year-olds in 40 countries between 1994 and 2014. We linked these data to national Gini indices of income inequality for every life year from 1979 to 2014. The results showed that exposure to income inequality from 0 to 4 years predicted psychosomatic symptoms and lower life satisfaction in females after controlling lifetime mean income inequality, national per capita income, family affluence, age, and cohort and period effects. The cumulative income inequality exposure in infancy and childhood (i.e., average Gini index from birth to age 10) related to lower life satisfaction in female adolescents but not to symptoms. Finally, individual trajectories in early-life inequality (i.e., linear slopes in Gini indices from birth to 10 years) related to fewer symptoms and higher life satisfaction in females, indicating that earlier exposures mattered more to predicting health and wellbeing. No such associations with early-life income inequality were found in males. These results help to establish the antecedent-consequence conditions in the association between income inequality and health and suggest that both the magnitude and timing of income inequality in early life have developmental consequences that manifest in reduced health and well-being in adolescent girls

  11. An adverse early life environment can enhance stress resilience in adulthood.

    Science.gov (United States)

    Santarelli, Sara; Zimmermann, Christoph; Kalideris, Georgia; Lesuis, Sylvie L; Arloth, Janine; Uribe, Andrés; Dournes, Carine; Balsevich, Georgia; Hartmann, Jakob; Masana, Mercè; Binder, Elisabeth B; Spengler, Dietmar; Schmidt, Mathias V

    2017-04-01

    Chronic stress is a major risk factor for depression. Interestingly, not all individuals develop psychopathology after chronic stress exposure. In contrast to the prevailing view that stress effects are cumulative and increase stress vulnerability throughout life, the match/mismatch hypothesis of psychiatric disorders. The match/mismatch hypothesis proposes that individuals who experience moderate levels of early life psychosocial stress can acquire resilience to renewed stress exposure later in life. Here, we have tested this hypothesis by comparing the developmental effects of 2 opposite early life conditions, when followed by 2 opposite adult environments. Male Balb/c mice were exposed to either adverse early life conditions (limited nesting and bedding material) or a supportive rearing environment (early handling). At adulthood, the animals of each group were either housed with an ovariectomized female (supportive environment) or underwent chronic social defeat stress (socially adverse environment) for 3 weeks. At the end of the adult manipulations, all of the animals were returned to standard housing conditions. Then, we compared the neuroendocrine, behavioral and molecular effects of the interaction between early and adult environment. Our study shows that early life adversity does not necessarily result in increased vulnerability to stress. Specific endophenotypes, like hypothalamic-pituitary-adrenal axis activity, anxiety-related behavior and glucocorticoid receptor expression levels in the hippocampus were not significantly altered when adversity is experienced during early life and in adulthood, and are mainly affected by either early life or adult life adversity alone. Overall our data support the notion that being raised in a stressful environment prepares the offspring to better cope with a challenging adult environment and emphasize the role of early life experiences in shaping adult responsiveness to stress. Copyright © 2017 Elsevier Ltd. All rights

  12. All that's mine I carry with me. Early life disease and adult health in Sweden during 250 years

    OpenAIRE

    Lindström, Martin

    2015-01-01

    The aim of this thesis is to study early life risk exposures in relation to adult health and mortality in Sweden during 250 years. A number of causal mechanisms by which exposure to diseases and stressful economic and social conditions early in life may lead to increased morbidity and mortality later in life are discussed (paper I). The early life exposures investigated are the foetal origins (nutrition) and the inflammation hypotheses. Longitudinal demographic and socioeconomic data for indi...

  13. Early life exposure to environmental levels of the aromatase inhibitor tributyltin causes masculinisation and irreversible sperm damage in zebrafish (Danio rerio).

    Science.gov (United States)

    McAllister, Brian G; Kime, David E

    2003-11-19

    To determine whether early life exposure to tributyltin (TBT), an aromatase inhibitor, impaired reproductive function in fish, Danio rerio were exposed to environmentally realistic levels (0.01-100 ng l(-1)) of TBT from 0 to 30, 30 to 60, and 0 to 70 days post-hatch, and the sex ratio and sperm motility of the adults examined 3-5 months after cessation of exposure. Fish exposed for 70 days to 0.1 ng l(-1) of TBT, a concentration presently below the detection limit in water, showed a male biased population which produced a high incidence of sperm lacking flagella. At 1 ng l(-1), the motility of sperm was significantly lower than that of control fish, while at 10 ng l(-1), all sperm lacked flagella and, at 100 ng l(-1), milt volume had increased. The effect of exposure on sex ratio was similar after exposure from 0 to 70 and 0 to 30 days, but even 100 ng l(-1) gave only 65% males after exposure from 30 to 60 days. Effects on sperm motility and morphology and on milt volume were less pronounced after 30 day than 70 day exposure. Our data suggest that screening for aromatase inhibiting activity and assessment of its risks in early life to human and wildlife fertility needs to be urgently addressed, and that the reproductive toxicity of TBT may presently be underestimated.

  14. Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence.

    Science.gov (United States)

    Vaiserman, Alexander M

    2017-03-05

    Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies ('natural experiments'). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world. Recent studies have highlighted the importance of epigenetic regulation of gene expression as a possible major contributor to the link between the early-life famine exposure and T2D in adulthood. Findings from these studies suggest that prenatal exposure to the famine may result in induction of persistent epigenetic changes that have adaptive significance in postnatal development but can predispose to metabolic disorders including T2D at the late stages of life. In this review, quasi-experimental data on the developmental programming of T2D are summarized and recent research findings on changes in DNA methylation that mediate these effects are discussed.

  15. The effects of pre-natal-, early-life- and indirectly-initiated exposures to maximum adversities on the course of schizophrenia.

    Science.gov (United States)

    Levine, Stephen Z; Levav, Itzhak; Yoffe, Rinat; Pugachova, Inna

    2014-09-01

    The effects of pre-natal-, early-life- and indirectly-initiated exposures to protracted maximum adversity on the course of schizophrenia are unknown. To compare the aforementioned Holocaust directly exposed subgroups with an indirectly exposed subgroup on the course of schizophrenia. The study population were: Israeli Jews in-uterus or born in Nazi-occupied or dominated European nations by the end of the persecution of the Jews, who were alive in 1950, and who had a last discharge diagnosis of schizophrenia in the Israel National Psychiatric Case Registry by 2013 (N=4933). The population was disaggregated into subgroups who (1) migrated after WWII and who had (1a) pre-natal (n=584, 11.8%) and (1b) early-life (n=3709, 75.2%) initiated exposures to the maximum adversities of the Holocaust, and (2) indirectly exposed individuals to the Holocaust who migrated before the Nazi-era persecution begun (n=640, 13%). Recurrent event survival analyses were computed to examine the psychiatric re-hospitalization risk of the study subgroups, unadjusted and adjusted for age of onset of the disorder and sex. The pre-natal initiated exposure subgroup had a significantly (pPoland-born individuals, the years 1922 and 1935; and followed at least 10 years and to the year 2000. Pre-natal initiated exposure to the maximal adversity of the holocaust constitutes a consistent risk factor for a worse course of schizophrenia, a possible byproduct of neurodevelopment disruptions induced by maternal stress and/or famine and/or infections. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Early life nutritional programming of health and disease in The Gambia

    OpenAIRE

    Moore, S. E.

    2015-01-01

    Exposures during the early life (periconceptional, prenatal and early postnatal) period are increasingly recognized as playing an important role in the aetiology of chronic non-communicable diseases (NCD), including coronary heart disease, stroke, hypertension, Type 2 diabetes and osteoporosis. The ?Developmental Origins of Health and Disease? (DOHaD) hypothesis states that these disorders originate through unbalanced nutrition early in life and risk is highest when there is a ?mismatch? betw...

  17. Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.

    Science.gov (United States)

    Fazeli, Walid; Zappettini, Stefania; Marguet, Stephan Lawrence; Grendel, Jasper; Esclapez, Monique; Bernard, Christophe; Isbrandt, Dirk

    2017-09-01

    The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy in humans, caffeine was added to the drinking water of female mice and their offspring were compared to control offspring. Caffeine altered the construction of GABAergic neuronal networks in V1, as reflected by a reduced number of somatostatin-containing GABA neurons at postnatal days 6-7, with the remaining ones showing poorly developed dendritic arbors. These findings were accompanied by increased synaptic activity in vitro and elevated network activity in vivo in V1. Similarly, in vivo hippocampal network activity was altered from the neonatal period until adulthood. Finally, caffeine-exposed offspring showed increased seizure susceptibility in a hyperthermia-induced seizure model. In summary, our results indicate detrimental effects of developmental caffeine exposure on mouse brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Blood pressure in young adulthood and residential greenness in the early-life environment of twins.

    Science.gov (United States)

    Bijnens, Esmée M; Nawrot, Tim S; Loos, Ruth Jf; Gielen, Marij; Vlietinck, Robert; Derom, Catherine; Zeegers, Maurice P

    2017-06-05

    Previous research shows that, besides risk factors in adult life, the early-life environment can influence blood pressure and hypertension in adults. However, the effects of residential traffic exposure and residential greenness in the early-life on blood pressure in young adulthood are currently unknown. Ambulatory (24-h) blood pressures of 278 twins (132 pairs) of the East Flanders Prospective Twins Study were obtained at the age of 18 to 25 years. Prenatal and adulthood residential addresses were geocoded and used to assign prenatal and postnatal traffic and greenness indicators. Mixed modelling was performed to investigate blood pressure in association with greenness while adjusting for potential confounding factors. Night-time systolic blood pressure was inversely associated with greenness at the residential address in twins living at the same address their entire life (non-movers, n = 97, 34.9%). An interquartile increase in residential greenness exposure (1000 m radius) was associated with a 3.59 mmHg (95% CI: -6.0 to -1.23; p = 0.005) lower adult night systolic blood pressure. Among twins who were living at a different address than their birth address at time of the measurement (n = 181, 65.1%), night-time blood pressure was inversely associated with residential surrounding greenness at adult age as well as with residential greenness in early-life. However after additional adjustment for residential greenness exposure in adulthood, only residential greenness exposure in early-life was significantly associated with night systolic blood pressure. While no significant effect of adult residential greenness with adult blood pressure was observed, while accounting for the early-life greenness exposure. Lower residential greenness in the early-life environment was independently associated with a higher adult blood pressure. This indicates that residential greenness has persistent effects on blood pressure.

  19. Sugar consumption produces effects similar to early life stress exposure on hippocampal markers of neurogenesis and stress response

    Directory of Open Access Journals (Sweden)

    Jayanthi eManiam

    2016-01-01

    Full Text Available Adverse early life experience is a known risk factor for psychiatric disorders. It is also known that stress influences food preference. We were interested in exploring whether the choice of diet following early life stress exerts long-lasting molecular changes in the brain, particularly the hippocampus, a region critically involved in stress regulation and behavioural outcomes. Here, we examined the impact of early life stress induced by limited nesting material (LN and chronic sucrose availability post-weaning on an array of hippocampal genes related to plasticity, neurogenesis, stress and inflammatory responses and mitochondrial biogenesis. To examine mechanisms underlying the impact of LN and sugar intake on hippocampal gene expression, we investigated the role of DNA methylation. As females are more likely to experience adverse life events, we studied female Sprague-Dawley rats. After mating LN was imposed from days 2-9 postpartum. From 3-15 weeks of age, female Control and LN siblings had unlimited to access to either chow and water, or chow, water and 25% sucrose solution. LN markedly reduced glucocorticoid receptor (GR and neurogenic differentiation 1 (Neurod1 mRNA, markers involved in stress and hippocampal plasticity respectively, by more than 40%, with a similar effect of sugar intake in control rats. However, no further impact was observed in LN rats consuming sugar. Hippocampal Akt3 mRNA expression was similarly affected by LN and sucrose consumption. Interestingly, DNA methylation across 4 CpG sites of the GR and Neurod1 promoters was similar in LN and control rats. In summary, early life stress and post-weaning sugar intake produced long-term effects on hippocampal GR and Neurod1 expression. Moreover we found no evidence of altered promoter DNA methylation. We demonstrate for the first time that chronic sucrose consumption alone produces similar detrimental effects on the expression of hippocampal genes as LN exposure.

  20. The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals.

    Science.gov (United States)

    Stel, Jente; Legler, Juliette

    2015-10-01

    Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.

  1. Gut microbiota modifications and weight gain in early life

    Directory of Open Access Journals (Sweden)

    Emmanouil Angelakis

    2018-04-01

    Full Text Available Childhood and adolescent obesity is a significant public health concern and has been associated with cardiovascular disease and related metabolic sequelae later in life. In recent years, several studies have postulated an imbalance in the composition of the early life gut microbiota results in pediatric obesity and its associated diseases. The early life gut microbiota is influenced by several factors including the mode of delivery, prematurity, breastfeeding, and the use of antibiotics and probiotics. It has been proposed that, when given early in life, antibiotics and probiotics disrupt the gut microbiota and consequently its metabolic activity, promoting weight gain. Probiotics have increasingly been administrated to children and studies on the perinatal use of probiotics on low birth weight and healthy infants revealed significantly increased body length and weight later in life in comparison with infants who did not receive probiotic supplements. Similarly, exposure to antibiotics is very high perinatally and in the early periods of life and there is evidence that antibiotic treatment decreases the biodiversity of the early life gut microbiota. In addition, studies have revealed that antibiotic treatment during the first months of life is associated with being overweight later in life. In this paper we review the effects of the administration of probiotics and antibiotics in early life on the gut microbiota and discuss their effects on weight gain. Keywords: Gut microbiota, Obesity, Newborn, Antibiotics, Probiotics

  2. Early Life Exposure to Chronic Intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle During Adulthood

    Directory of Open Access Journals (Sweden)

    Fiona B Mcdonald

    2016-03-01

    Full Text Available Intermittent hypoxia is a feature of apnea of prematurity, chronic lung disease and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH during postnatal development (pCIH causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 hours of delivery, pups and their respective dams were exposed to CIH: 90s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 hrs per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH, where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

  3. Early life exposure to chronic intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle during adulthood.

    LENUS (Irish Health Repository)

    McDonald, Fiona B

    2016-03-01

    Intermittent hypoxia is a feature of apnea of prematurity (AOP), chronic lung disease, and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH) during postnatal development (pCIH) causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and\\/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 h of delivery, pups and their respective dams were exposed to CIH: 90 s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 h per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH), where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm) weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

  4. Late effects of early exposures to endocrine disrupting chemicals in rats

    DEFF Research Database (Denmark)

    Boberg, Julie; Hass, Ulla

    2017-01-01

    Endocrine disrupting compounds may interfere with tissues at critical developmental stages and give rise to cancer later in life. This talk will focus on early-life exposure to endocrine disrupting chemicals which is associated with increased risk for carcinogenesis in mammary and prostate glands...

  5. Early-Life Exposure to Antibiotics, Alterations in the Intestinal Microbiome, and Risk of Metabolic Disease in Children and Adults.

    Science.gov (United States)

    Yallapragada, Sushmita G; Nash, Colleen B; Robinson, Daniel T

    2015-11-01

    The intestinal microbiome is a complex ecosystem of microorganisms that colonize the human gastrointestinal tract. The microbiome evolves rapidly in early life with contributions from diet, genetics and immunomodulatory factors. Changes in composition of the microbiota due to antibiotics may lead to negative long-term effects including obesity and diabetes mellitus, as evidenced by both animal and large human studies. Inappropriate exposures to antibiotics occur frequently in early childhood. Therefore, an evidence-based system of antimicrobial use should be employed by all providers, especially those who care for pediatric patients. This article explores the natural evolution of the intestinal microbiome from the perinatal period into early childhood, the effect of antibiotics on the microbial ecology, and the implications for future health and disease. Copyright 2015, SLACK Incorporated.

  6. No Smoke Without Fire: the hidden costs of early life exposure to landscape fire emissions in Indonesia

    Science.gov (United States)

    Jina, A.; Marlier, M. E.

    2012-12-01

    Air pollution from landscape fire emissions can have devastating effects upon public health. The consequent health costs place a burden upon the economies of many nations, particularly in developing countries. Recent research has assessed contemporaneous mortality due to respiratory infections or cardiovascular disease, but little has looked at the potential long-term consequences and hidden costs of exposure to fire pollution at a population scale. The difficulty of quantifying these costs is partly due to incomplete or inaccurate health data in many developing countries, and is further compounded by sparse air pollution monitoring data. While satellite data partially compensates for this, there can still be significant gaps in data availability and difficulty in retrieving surface concentrations. In this study, we demonstrate the dramatic long-term health and human development consequences of fine particulate matter (PM2.5) exposure by using modeled PM2.5 to quantify repeated exposure to landscape fire emissions in Indonesia, which is prone to large, catastrophic fires during El Niño conditions. Surface PM2.5 concentrations at 2x2.5° resolution are obtained from GISS-E2-Puccini (the new version of the NASA GISS ModelE general circulation model), run with monthly fire emissions from the Global Fire Emissions Database version 3 (GFED3). 24-hour ambient PM2.5 concentrations across Indonesia are matched to geographically and socioeconomically representative longitudinal surveys conducted by the Indonesian government. We find important medium- to long-term morbidity associated with early life exposure to ambient air pollution from fire emissions. Our analysis indicates that children exposed to high levels of PM2.5 in utero are more likely to suffer from impaired physical and cognitive development. A one standard deviation increase in ambient air pollution, derived from the GISS-E2-Puccini model, leads to effects that are directly comparable to those from indoor air

  7. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

    International Nuclear Information System (INIS)

    Herring, M.J.; Putney, L.F.; St George, J.A.; Avdalovic, M.V.; Schelegle, E.S.; Miller, L.A.; Hyde, D.M.

    2015-01-01

    In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O 3 ) or HDMA/ozone (HDMA + O 3 ) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O 3 alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)

  8. Association of early-life exposure to household gas appliances and indoor nitrogen dioxide with cognition and attention behavior in preschoolers.

    Science.gov (United States)

    Morales, Eva; Julvez, Jordi; Torrent, Maties; de Cid, Rafael; Guxens, Mònica; Bustamante, Mariona; Künzli, Nino; Sunyer, Jordi

    2009-06-01

    The authors investigated the association of early-life exposure to indoor air pollution with neuropsychological development in preschoolers and assessed whether this association differs by glutathione-S-transferase gene (GSTP1) polymorphisms. A prospective, population-based birth cohort was set up in Menorca, Spain, in 1997-1999 (n = 482). Children were assessed for cognitive functioning (McCarthy Scales of Children's Abilities) and attention-hyperactivity behaviors (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) at age 4 years. During the first 3 months of life, information about gas appliances at home and indoor nitrogen dioxide concentration was collected at each participant's home (n = 398, 83%). Genotyping was conducted for the GSTP1 coding variant Ile105Val. Use of gas appliances was inversely associated with cognitive outcomes (beta coefficient for general cognition = -5.10, 95% confidence interval (CI): -9.92, -0.28; odds ratio for inattention symptoms = 3.59, 95% CI: 1.14, 11.33), independent of social class and other confounders. Nitrogen dioxide concentrations were associated with cognitive function (a decrease of 0.27 point per 1 ppb, 95% CI: -0.48, -0.07) and inattention symptoms (odds ratio = 1.06, 95% CI: 1.01, 1.12). The deleterious effect of indoor pollution from gas appliances on neuropsychological outcomes was stronger in children with the GSTP1 Val-105 allele. Early-life exposure to air pollution from indoor gas appliances may be negatively associated with neuropsychological development through the first 4 years of life, particularly among genetically susceptible children.

  9. Early Life Exposure to Fructose and Offspring Phenotype: Implications for Long Term Metabolic Homeostasis

    Science.gov (United States)

    Sloboda, Deborah M.; Li, Minglan; Patel, Rachna; Clayton, Zoe E.; Yap, Cassandra; Vickers, Mark H.

    2014-01-01

    The consumption of artificially sweetened processed foods, particularly high in fructose or high fructose corn syrup, has increased significantly in the past few decades. As such, interest into the long term outcomes of consuming high levels of fructose has increased significantly, particularly when the exposure is early in life. Epidemiological and experimental evidence has linked fructose consumption to the metabolic syndrome and associated comorbidities—implicating fructose as a potential factor in the obesity epidemic. Yet, despite the widespread consumption of fructose-containing foods and beverages and the rising incidence of maternal obesity, little attention has been paid to the possible adverse effects of maternal fructose consumption on the developing fetus and long term effects on offspring. In this paper we review studies investigating the effects of fructose intake on metabolic outcomes in both mother and offspring using human and experimental studies. PMID:24864200

  10. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

    Energy Technology Data Exchange (ETDEWEB)

    Herring, M.J.; Putney, L.F.; St George, J.A. [California National Primate Research Center, Davis, CA (United States); Avdalovic, M.V. [Department of Internal Medicine, Division of Pulmonary and Critical Care, University of California, Davis, CA (United States); Schelegle, E.S.; Miller, L.A. [California National Primate Research Center, Davis, CA (United States); Hyde, D.M., E-mail: dmhyde@ucdavis.edu [California National Primate Research Center, Davis, CA (United States)

    2015-02-15

    In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O{sub 3}) or HDMA/ozone (HDMA + O{sub 3}) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O{sub 3} alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)

  11. Is lead exposure in early life an environmental risk factor for Schizophrenia? Neurobiological connections and testable hypotheses.

    Science.gov (United States)

    Guilarte, Tomás R; Opler, Mark; Pletnikov, Mikhail

    2012-06-01

    Schizophrenia is a devastating neuropsychiatric disorder of unknown etiology. There is general agreement in the scientific community that schizophrenia is a disorder of neurodevelopmental origin in which both genes and environmental factors come together to produce a schizophrenia phenotype later in life. The challenging questions have been which genes and what environmental factors? Although there is evidence that different chromosome loci and several genes impart susceptibility for schizophrenia; and epidemiological studies point to broad aspects of the environment, only recently there has been an interest in studying gene × environment interactions. Recent evidence of a potential association between prenatal lead (Pb(2+)) exposure and schizophrenia precipitated the search for plausible neurobiological connections. The most promising connection is that in schizophrenia and in developmental Pb(2+) exposure there is strong evidence for hypoactivity of the N-methyl-d-aspartate (NMDA) subtype of excitatory amino acid receptors as an underlying neurobiological mechanism in both conditions. A hypofunction of the NMDA receptor (NMDAR) complex during critical periods of development may alter neurobiological processes that are essential for brain growth and wiring, synaptic plasticity and cognitive and behavioral outcomes associated with schizophrenia. We also describe on-going proof of concept gene-environment interaction studies of early life Pb(2+) exposure in mice expressing the human mutant form of the disrupted in schizophrenia 1 (DISC-1) gene, a gene that is strongly associated with schizophrenia and allied mental disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Is Lead Exposure in Early Life An Environmental Risk Factor for Schizophrenia? Neurobiological Connections and Testable Hypotheses

    Science.gov (United States)

    Guilarte, Tomás R.; Opler, Mark; Pletnikov, Mikhail

    2013-01-01

    Schizophrenia is a devastating neuropsychiatric disorder of unknown etiology. There is general agreement in the scientific community that schizophrenia is a disorder of neurodevelopmental origin in which both genes and environmental factors come together to produce a schizophrenia phenotype later in life. The challenging questions have been which genes and what environmental factors? Although there is evidence that different chromosome loci and several genes impart susceptibility for schizophrenia; and epidemiological studies point to broad aspects of the environment, only recently there has been an interest in studying gene × environment interactions. Recent evidence of a potential association between prenatal lead (Pb2+) exposure and schizophrenia precipitated the search for plausible neurobiological connections. The most promising connection is that in schizophrenia and in developmental Pb2+ exposure there is strong evidence for hypoactivity of the N-methyl-d-aspartate (NMDA) subtype of excitatory amino acid receptors as an underlying neurobiological mechanism in both conditions. A hypofunction of the NMDA receptor (NMDAR) complex during critical periods of development may alter neurobiological processes that are essential for brain growth and wiring, synaptic plasticity and cognitive and behavioral outcomes associated with schizophrenia. We also describe on-going proof of concept gene-environment interaction studies of early life Pb2+ exposure in mice expressing the human mutant form of the disrupted in schizophrenia 1 (DISC-1) gene, a gene that is strongly associated with schizophrenia and allied mental disorders. PMID:22178136

  13. Dog and cat exposure and respective pet allergy in early childhood.

    Science.gov (United States)

    Pyrhönen, Kaisa; Näyhä, Simo; Läärä, Esa

    2015-05-01

    The association of dog and cat exposure in early childhood with the incidence of respective allergies has remained controversial. The aim of the study was to obtain population-based evidence on the association of early exposure to dog or cat, or both, with dog and cat allergies. The study population was identified from the nationwide population register comprising all children aged 1-4 yr (N = 4779) born between 2001 and 2005 and living in the province of South Karelia, Finland. Cross-sectional questionnaire data on pet exposure in infancy and physician-diagnosed pet allergies were obtained from 3024 participants and merged with longitudinally accumulated data on sIgE and skin prick tests indicating allergic sensitization abstracted from all patient records in the area. The adjusted relative incidence of positive test results (with 95% confidence intervals) was 2.69 (1.45-5.02) for dog and 5.03 (2.47-10.2) for cat allergens among children exposed to a respective pet alone compared with children without such exposure. The corresponding adjusted prevalence odds ratios for diagnosed dog and cat allergies were 1.75 (0.77-3.79) and 5.13 (2.30-11.4), respectively. The association between pet exposure and the incidence of positive test results was independent of parents' allergies. Early exposure to dog and cat at home is associated with a higher incidence of respective pet allergy during the first four years of life. Further evidence from population-based studies with longer follow-up is required to justify any recommendation concerning early pet contacts with a view to preventing pet allergies later in life. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Early Life Exposure to Fructose and Offspring Phenotype: Implications for Long Term Metabolic Homeostasis

    Directory of Open Access Journals (Sweden)

    Deborah M. Sloboda

    2014-01-01

    Full Text Available The consumption of artificially sweetened processed foods, particularly high in fructose or high fructose corn syrup, has increased significantly in the past few decades. As such, interest into the long term outcomes of consuming high levels of fructose has increased significantly, particularly when the exposure is early in life. Epidemiological and experimental evidence has linked fructose consumption to the metabolic syndrome and associated comorbidities—implicating fructose as a potential factor in the obesity epidemic. Yet, despite the widespread consumption of fructose-containing foods and beverages and the rising incidence of maternal obesity, little attention has been paid to the possible adverse effects of maternal fructose consumption on the developing fetus and long term effects on offspring. In this paper we review studies investigating the effects of fructose intake on metabolic outcomes in both mother and offspring using human and experimental studies.

  15. Mechanisms behind early life nutrition and adult disease outcome

    OpenAIRE

    Velkoska, Elena; Morris, Margaret J

    2011-01-01

    Obesity is increasing around the globe. While adult lifestyle factors undoubtedly contribute to the incidence of obesity and its attendant disorders, mounting evidence suggests that programming of obesity may occur following under- and over-nutrition during development. As hypothalamic control of appetite and energy expenditure is set early in life and can be perturbed by certain exposures such as undernutrition and altered metabolic and hormonal signals, in utero exposure to altered maternal...

  16. Childhood developmental vulnerabilities associated with early life exposure to infectious and noninfectious diseases and maternal mental illness.

    Science.gov (United States)

    Green, Melissa J; Kariuki, Maina; Dean, Kimberlie; Laurens, Kristin R; Tzoumakis, Stacy; Harris, Felicity; Carr, Vaughan J

    2017-12-26

    Fetal exposure to infectious and noninfectious diseases may influence early childhood developmental functioning, on the path to later mental illness. Here, we investigated the effects of in utero exposure to maternal infection and noninfectious diseases during pregnancy on offspring developmental vulnerabilities at age 5 years, in the context of estimated effects for early childhood exposures to infectious and noninfectious diseases and maternal mental illness. We used population data for 66,045 children from an intergenerational record linkage study (the New South Wales Child Development Study), for whom a cross-sectional assessment of five developmental competencies (physical, social, emotional, cognitive, and communication) was obtained at school entry, using the Australian Early Development Census (AEDC). Child and maternal exposures to infectious or noninfectious diseases were determined from the NSW Ministry of Health Admitted Patients Data Collection (APDC) and maternal mental illness exposure was derived from both APDC and Mental Health Ambulatory Data collections. Multinomial logistic regression analyses were used to examine unadjusted and adjusted associations between these physical and mental health exposures and child developmental vulnerabilities at age 5 years. Among the physical disease exposures, maternal infectious diseases during pregnancy and early childhood infection conferred the largest associations with developmental vulnerabilities at age 5 years; maternal noninfectious illness during pregnancy also retained small but significant associations with developmental vulnerabilities even when adjusted for other physical and mental illness exposures and covariates known to be associated with early childhood development (e.g., child's sex, socioeconomic disadvantage, young maternal age, prenatal smoking). Among all exposures examined, maternal mental illness first diagnosed prior to childbirth conferred the greatest odds of developmental

  17. Imprinting: When Early Life Memories Make Food Smell Bad.

    Science.gov (United States)

    Rayes, Diego; Alkema, Mark J

    2016-05-09

    A recent study has found that pathogen exposure early in the life of the nematode Caenorhabditis elegans leads to a long-lasting aversion that requires distinct sets of neurons for the formation and retrieval of the imprinted memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Early-life exposure to Tris(1,3-dichloroisopropyl) phosphate induces dose-dependent suppression of sexual behavior in male rats.

    Science.gov (United States)

    Kamishima, Manami; Hattori, Tatsuya; Suzuki, Go; Matsukami, Hidenori; Komine, Chiaki; Horii, Yasuyuki; Watanabe, Gen; Oti, Takumi; Sakamoto, Hirotaka; Soga, Tomoko; Parhar, Ishwar S; Kondo, Yasuhiko; Takigami, Hidetaka; Kawaguchi, Maiko

    2018-05-01

    Exposure to endocrine-disrupting chemicals may adversely affect animals, particularly during development. Tris(1,3-dichloroisopropyl) phosphate (TDCIPP) is an organophosphate with anti-androgen function in vitro that is present in indoor dust at relatively high concentrations. In male rats, androgens are necessary for the development of reproductive organs, as well as the endocrine and central nervous systems. However, we currently do not know the exact effects of TDCIPP exposure through suckling on subsequent reproductive behavior in males. Here, we show that TDCIPP exposure (25-250 mg kg -1 via oral administration over 28 consecutive days post-birth) suppressed male sexual behavior and reduced testes size. These changes were dose-dependent and appeared first in adults rather than in juveniles. These results demonstrate that TDCIPP exposure led to normal body growth and appearance in juveniles, but disrupted the endocrine system and physiology in adults. Therefore, assays should be performed using adult animals to ensure accuracy, and to confirm the influence of chemical substances given during early mammalian life. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Babies of the War: Effect of War Exposure Early in Life on Mortality Throughout Life

    NARCIS (Netherlands)

    Lindeboom, M.; van Ewijk, R.J.G.

    2015-01-01

    There is increasing evidence that circumstances very early in our lives, and particularly during pregnancy, can affect our health for the remainder of life. Studies that have looked at this relationship have often used extreme situations, such as famines that occurred during wartime. Here we

  20. Balance between early life tolerance and sensitization in allergy: dependence on the timing and intensity of prenatal and postnatal allergen exposure of the mother.

    Science.gov (United States)

    Fusaro, Ana Elisa; de Brito, Cyro Alves; Taniguchi, Eliana Futata; Muniz, Bruno Pacola; Victor, Jefferson Russo; Orii, Noemia Mie; Duarte, Alberto José da Silva; Sato, Maria Notomi

    2009-09-01

    Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.

  1. Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice

    Directory of Open Access Journals (Sweden)

    Asquith Kelly L

    2010-02-01

    Full Text Available Abstract Background Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV, increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen exposure predisposed to the development of features of asthma. Methods We employed a unique combination of animal models in which BALB/c mice were neonatally infected with pneumonia virus of mice (PVM, which replicates severe RSV disease in human infants and following recovery, were intranasally sensitised with ovalbumin. Animals received low-level challenge with aerosolised antigen for 4 weeks to elicit changes of chronic asthma, followed by a single moderate-level challenge to induce an exacerbation of inflammation. We then assessed airway inflammation, epithelial changes characteristic of remodelling, airway hyperresponsiveness (AHR and host immunological responses. Results Allergic airway inflammation, including recruitment of eosinophils, was prominent only in animals that had recovered from neonatal infection with PVM and then been sensitised and chronically challenged with antigen. Furthermore, only these mice exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG1 as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. By comparison, development of AHR and mucous cell change were associated with recovery from PVM infection, regardless of subsequent allergen challenge. Increased expression of IL-25, which could contribute to induction of a Th2 response, was demonstrable in the lung following PVM infection. Signalling via the IL-4 receptor α chain was crucial to the development of allergic inflammation, mucous cell change and AHR, because all of these were absent in receptor-deficient mice. In contrast, changes of remodelling were evident in mice

  2. Early-life home environment and risk of asthma among inner-city children.

    Science.gov (United States)

    O'Connor, George T; Lynch, Susan V; Bloomberg, Gordon R; Kattan, Meyer; Wood, Robert A; Gergen, Peter J; Jaffee, Katy F; Calatroni, Agustin; Bacharier, Leonard B; Beigelman, Avrahman; Sandel, Megan T; Johnson, Christine C; Faruqi, Ali; Santee, Clark; Fujimura, Kei E; Fadrosh, Douglas; Boushey, Homer; Visness, Cynthia M; Gern, James E

    2018-04-01

    Environmental exposures in early life appear to play an important role in the pathogenesis of childhood asthma, but the potentially modifiable exposures that lead to asthma remain uncertain. We sought to identify early-life environmental risk factors for childhood asthma in a birth cohort of high-risk inner-city children. We examined the relationship of prenatal and early-life environmental factors to the occurrence of asthma at 7 years of age among 442 children. Higher house dust concentrations of cockroach, mouse, and cat allergens in the first 3 years of life were associated with lower risk of asthma (for cockroach allergen: odds ratio per interquartile range increase in concentration, 0.55; 95% CI, 0.36-0.86; P < .01). House dust microbiome analysis using 16S ribosomal RNA sequencing identified 202 and 171 bacterial taxa that were significantly (false discovery rate < 0.05) more or less abundant, respectively, in the homes of children with asthma. A majority of these bacteria were significantly correlated with 1 of more allergen concentrations. Other factors associated significantly positively with asthma included umbilical cord plasma cotinine concentration (odds ratio per geometric SD increase in concentration, 1.76; 95% CI, 1.00-3.09; P = .048) and maternal stress and depression scores. Among high-risk inner-city children, higher indoor levels of pet or pest allergens in infancy were associated with lower risk of asthma. The abundance of a number of bacterial taxa in house dust was associated with increased or decreased asthma risk. Prenatal tobacco smoke exposure and higher maternal stress and depression scores in early life were associated with increased asthma risk. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  3. Do perinatal and early life exposures influence the risk of malignant melanoma? A Northern Ireland birth cohort analysis.

    Science.gov (United States)

    O'Rorke, M A; Black, C; Murray, L J; Cardwell, C R; Gavin, A T; Cantwell, M M

    2013-03-01

    Intrauterine, early life and maternal exposures may have important consequences for cancer development in later life. The aim of this study was to examine perinatal and birth characteristics with respect to Cutaneous malignant melanoma (CMM) risk. The Northern Ireland Child Health System database was used to examine gestational age adjusted birth weight, infant feeding practices, parental age and socioeconomic factors at birth in relation to CMM risk amongst 447,663 infants delivered between January 1971 and December 1986. Follow-up of histologically verified CMM cases was undertaken from the beginning of 1993 to 31st December 2007. Multivariable adjusted unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of CMM risk. A total of 276 CMM cases and 440,336 controls contributed to the final analysis. In reference to normal (gestational age-adjusted) weight babies, those heaviest at birth were twice as likely to develop CMM OR 2.4 (95% CI 1.1-5.1). Inverse associations with CMM risk were observed with younger (birth and both a higher birth order and greater household density OR 0.61 (95% CI 0.37-0.99) and OR 0.56 (95% CI 0.30-1.0) respectively. This large study of early onset melanoma supports a positive association with higher birth weight (imperatively gestational age adjusted) and CMM risk which may be related to factors which drive intrauterine foetal growth. Strong inverse associations observed with higher birth order and household density suggest that early-life immune modulation may confer protection; findings which warrant further investigation in prospective analyses. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Impact of body size, nutrition and socioeconomic position in early life on the epigenome: a systematic review protocol.

    Science.gov (United States)

    Maddock, Jane; Wulaningsih, Wahyu; Hardy, Rebecca

    2017-07-05

    Body size, nutrition and socioeconomic position (SEP) in early life have been associated with a range of later life health outcomes. Epigenetic regulation is one mechanism through which these early life factors may impact later life health. The aim of this review protocol is to outline procedures to document the influence of body size, nutrition and SEP in early life on the epigenome. MEDLINE, Embase and BIOSIS will be systematically searched using pre-defined keywords. Additional studies will be identified through manual searching of reference lists. Two independent researchers will assess the eligibility and quality of each study, with disagreements being resolved through discussion or a third reviewer. Studies will be included if they have epigenetic markers measured either at the same time as, or after, the early life exposure and, have a measure of body size, nutrition or SEP in early life (up to 12 years), are in the English language and are from a sample of community-dwelling participants. This protocol will be used to collate the evidence for the effect of early life factors on the epigenome. Findings will form a component of a wider research study examining epigenetic responses to exposures in early life and over the life course and its impact on healthy ageing using data from population-based cohort studies. PROSPERO CRD42016050193.

  5. Toxicity of crude oil to early life stages of two fish species

    Energy Technology Data Exchange (ETDEWEB)

    Clarke, L.M.; Hodson, P.V. [Queen' s Univ., Kingston, ON (Canada). Dept. of Biology; Brown, R.S. [Queen' s Univ., Kingston, ON (Canada). Dept. of Chemistry; King, T.; Lee, K. [Department of Fisheries and Oceans, Dartmouth, NS (Canada). Bedford Inst. of Oceanography

    2004-07-01

    Fish exposed to crude oil in their early life stages exhibit signs of dioxin-like toxicity which is linked to the presence of alkyl-substituted polycyclic aromatic hydrocarbons (PAHs). Exposure is characterized by the presence of blue-sac disease which manifests itself in edema, hemorrhaging, deformities and induction of CYP1A enzymes. In this study, the extent of CYP1A induction and BSD was compared in the early life stages of rainbow trout and Japanese medaka following exposure to two crude oils (Scotian Shelf and Alaskan North Slope Crude). Embryos were exposed to a broad range of concentrations of chemically enhanced water fractions of both oils which have unique PAH composition and chemical characteristics. It was assumed that Alaskan North Slope Crude would be more toxic than Scotian Shelf because it has a higher PAH concentration. The occurrence and severity of BSD was characterized along with the extent of PAH exposure. Preliminary results confirm that PAH exposure is greater for Alaskan North Slope Crude and that the responses of the two fish species were highly correlated.

  6. Early life vaccination

    DEFF Research Database (Denmark)

    Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria

    2016-01-01

    Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal...... the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...

  7. Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders

    Directory of Open Access Journals (Sweden)

    Joan Y. Holgate

    2015-06-01

    Full Text Available Stress is a major driving force in alcohol use disorders (AUDs. It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual’s brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.

  8. Early-life adversity-induced long-term epigenetic programming associated with early onset of chronic physical aggression: Studies in humans and animals.

    Science.gov (United States)

    Chistiakov, Dimitry A; Chekhonin, Vladimir P

    2017-06-05

    To examine whether chronic physical aggression (CPA) in adulthood can be epigenetically programmed early in life due to exposure to early-life adversity. Literature search of public databases such as PubMed/MEDLINE and Scopus. Children/adolescents susceptible for CPA and exposed to early-life abuse fail to efficiently cope with stress that in turn results in the development of CPA later in life. This phenomenon was observed in humans and animal models of aggression. The susceptibility to aggression is a complex trait that is regulated by the interaction between environmental and genetic factors. Epigenetic mechanisms mediate this interaction. Subjects exposed to stress early in life exhibited long-term epigenetic programming that can influence their behaviour in adulthood. This programming affects expression of many genes not only in the brain but also in other systems such as neuroendocrine and immune. The propensity to adult CPA behaviour in subjects experienced to early-life adversity is mediated by epigenetic programming that involves long-term systemic epigenetic alterations in a whole genome.

  9. Diminished lifetime reproductive capacity in the female after early radiation exposure

    International Nuclear Information System (INIS)

    Dobson, R.L.; Kwan, T.C.; Brunckhorst, B.F.; Straume, T.

    1986-01-01

    To measure effects of early tritium-induced oocyte loss on lifetime reproduction, we determined total reproductive capacity (RC) of female mice in which known oocyte deficiencies had been produced in early life by chronic exposure to 3 HOH administered to their mothers in drinking water from the day of conception to 14 days postpartum. At that time 3 HOH administration was stopped, and oocytes were enumerated in the suckling young. Over the subsequent two years, RC was determined in these young by counting the litters and offspring they produced during continuous breeding over their entire reproductive life spans. Offspring were removed at birth to avoid interrupting the breeding process. Tritium-induced diminution of RC was found to be done dependent but less than - and, interestingly, different from - diminution of oocyte number. Oocyte loss was stochastic; RC reduction, nonstochastic. Also, despite oocyte deficiencies, productivity of exposed females tended to be normal during early reproductive life but failed prematurely as oocytes ran out. 15 refs., 4 figs., 3 tabs

  10. The consequences of early life adversity: neurobiological, behavioural and epigenetic adaptations

    NARCIS (Netherlands)

    Maccari, S.; Krugers, H.J.; Morley-Fletcher, S.; Szyf, M.; Brunton, P.J.

    2014-01-01

    During the perinatal period, the brain is particularly sensitive to remodelling by environmental factors. Adverse early life experiences, such as stress exposure or sub-optimal maternal care can have long-lasting detrimental consequences for an individual. This phenomenon is often referred to as

  11. Victims of Chinese famine in early life have increased risk of metabolic syndrome in adulthood.

    Science.gov (United States)

    Yu, Caizheng; Wang, Jing; Wang, Fei; Han, Xu; Hu, Hua; Yuan, Jing; Miao, Xiaoping; Yao, Ping; Wei, Sheng; Wang, Youjie; Liang, Yuan; Zhang, Xiaomin; Guo, Huan; Pan, An; Zheng, Dan; Tang, Yuhan; Yang, Handong; Wu, Tangchun; He, Meian

    2018-02-05

    To investigate the association of exposure to the Chinese famine during early life with metabolic syndrome risk in adults. There were 7,915 participants from Dongfeng-Tongji cohort were included in the present study. Participants were classified as non-exposed group, fetal exposed group, early childhood-, mid childhood-, and late childhood-exposed groups, respectively. Metabolic syndrome was defined according to International Diabetes Foundation criteria (2005). Logistic regression model was used to explore the association between famine exposure in early life and metabolic syndrome risk in adults. The metabolic syndrome prevalence in non-, fetal-, early childhood-, mid childhood-, and late childhood- exposed groups were 25.2%, 26.9%, 30.3%, 32.7%, and 32.7%, respectively. Compared with non-exposed group, participants exposed to famine in the fetal (0.96, 95% CI: 0.77-1.20), early childhood (1.24, 95% CI: 1.01-1.52), mid childhood (1.39, 95% CI: 1.13-1.72), and late childhood (1.33, 95% CI: 1.08-1.63) had higher metabolic syndrome prevalence risk in adults after adjustment for potential confounders (P for trend metabolic syndrome prevalence risk than non-exposed women (P for trend metabolic syndrome prevalence risk (P for interaction = 0.0001). Results in the present study indicated that exposure to famine in early life increases the risk of metabolic syndrome in adulthood, particularly in women. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Exposure to Famine at a Young Age and Unhealthy Lifestyle Behavior Later in Life.

    Science.gov (United States)

    Fransen, Heidi P; Peeters, Petra H M; Beulens, Joline W J; Boer, Jolanda M A; de Wit, G Ardine; Onland-Moret, N Charlotte; van der Schouw, Yvonne T; Bueno-de-Mesquita, H Bas; Hoekstra, Jeljer; Elias, Sjoerd G; May, Anne M

    2016-01-01

    A healthy diet is important for normal growth and development. Exposure to undernutrition during important developmental periods such as childhood and adolescence can have effects later in life. Inhabitants of the west of the Netherlands were exposed to severe undernutrition during the famine in the last winter of the second World War (1944-1945). We investigated if exposure of women to the Dutch famine during childhood and adolescence was associated with an unhealthy lifestyle later in life. We studied 7,525 women from the Prospect-EPIC cohort, recruited in 1993-97 and aged 0-18 years during the Dutch famine. An individual famine score was calculated based on self-reported information about experience of hunger and weight loss. We investigated the association between famine exposure in early life and four lifestyle factors in adulthood: smoking, alcohol consumption, physical activity level and a Mediterranean-style diet. Of the 7,525 included women, 46% were unexposed, 38% moderately exposed and 16% severely exposed to the Dutch famine. Moderately and severely exposed women were more often former or current smokers compared to women that did not suffer from the famine: adjusted prevalence ratio 1.10 (95% CI: 1.05; 1.14) and 1.18 (1.12; 1.25), respectively. They also smoked more pack years than unexposed women. Severely exposed women were more often physically inactive than unexposed women, adjusted prevalence ratio 1.32 (1.06; 1.64). Results did not differ between exposure age categories (0-9 and 10-17 years). We found no associations of famine exposure with alcohol consumption and no dose-dependent relations with diet. Exposure to famine early in female life may be associated with higher prevalence of smoking and physical inactivity later in life, but not with unhealthy diet and alcohol consumption.

  13. Development of atopic dermatitis and its association with prenatal and early life exposures

    OpenAIRE

    Roduit, Caroline

    2015-01-01

    Over 20% of children in industrialized countries are affected by atopic dermatitis. From epidemiological studies, it is quite obvious that the worldwide prevalence of atopic dermatitis has considerably increased over the past decades and constitutes a major public health problem. Atopic dermatitis is a chronic inflammatory skin disease that occurs in very early life and frequently precedes the development of asthma and allergic rhinitis during the first several years of life. Although a large...

  14. Associations among oxytocin receptor gene (OXTR) DNA methylation in adulthood, exposure to early life adversity, and childhood trajectories of anxiousness.

    Science.gov (United States)

    Gouin, J P; Zhou, Q Q; Booij, L; Boivin, M; Côté, S M; Hébert, M; Ouellet-Morin, I; Szyf, M; Tremblay, R E; Turecki, G; Vitaro, F

    2017-08-07

    Recent models propose deoxyribonucleic acid methylation of key neuro-regulatory genes as a molecular mechanism underlying the increased risk of mental disorder associated with early life adversity (ELA). The goal of this study was to examine the association of ELA with oxytocin receptor gene (OXTR) methylation among young adults. Drawing from a 21-year longitudinal cohort, we compared adulthood OXTR methylation frequency of 46 adults (23 males and 23 females) selected for high or low ELA exposure based on childhood socioeconomic status and exposure to physical and sexual abuse during childhood and adolescence. Associations between OXTR methylation and teacher-rated childhood trajectories of anxiousness were also assessed. ELA exposure was associated with one significant CpG site in the first intron among females, but not among males. Similarly, childhood trajectories of anxiousness were related to one significant CpG site within the promoter region among females, but not among males. This study suggests that females might be more sensitive to the impact of ELA on OXTR methylation than males.

  15. Photo-induced toxicity in early life stage fiddler crab (Uca longisignalis) following exposure to Deepwater Horizon oil.

    Science.gov (United States)

    Damare, Leigh M; Bridges, Kristin N; Alloy, Matthew M; Curran, Thomas E; Soulen, Brianne K; Forth, Heather P; Lay, Claire R; Morris, Jeffrey M; Stoeckel, James A; Roberts, Aaron P

    2018-05-01

    The 2010 explosion of the Deepwater Horizon (DWH) oil rig led to the release of millions of barrels of oil in the Gulf of Mexico. Oil in aquatic ecosystems exerts toxicity through multiple mechanisms, including photo-induced toxicity following co-exposure with UV radiation. The timing and location of the spill coincided with both fiddler crab reproduction and peak yearly UV intensities, putting early life stage fiddler crabs at risk of injury due to photo-induced toxicity. The present study assessed sensitivity of fiddler crab larvae to photo-induced toxicity during co-exposure to a range of environmentally relevant dilutions of high-energy water accommodated fractions of DWH oil, and either dark recovery period (duration: 17-h) in between. Survival was significantly decreased in treatments the presence of >10% UV and relatively low concentrations of oil. Results of the present study indicate fiddler crab larvae are sensitive to photo-induced toxicity in the presence of DWH oil. These results are of concern, as fiddler crabs play an important role as ecosystem engineers, modulating sediment biogeochemical processes via burrowing action. Furthermore, they occupy an important place in the food web in the Gulf of Mexico.

  16. Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study

    Directory of Open Access Journals (Sweden)

    Sandoval Carlos A

    2011-06-01

    Full Text Available Abstract Background Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease. Methods/Design A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3 during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also. Discussion The study will provide information on the potential effects of early exposures to

  17. Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats

    Science.gov (United States)

    Beaudin, Stephane A.; Strupp, Barbara J.; Strawderman, Myla; Smith, Donald R.

    2016-01-01

    Background: Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. Objectives: To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Methods: Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1–21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Results: Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. Conclusions: This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230–237; http://dx.doi.org/10.1289/EHP258 PMID:27384154

  18. Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats.

    Science.gov (United States)

    Beaudin, Stephane A; Strupp, Barbara J; Strawderman, Myla; Smith, Donald R

    2017-02-01

    Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1-21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230-237; http://dx.doi.org/10.1289/EHP258.

  19. Antibiotic Exposure During the First 6 Months of Life and Weight Gain During Childhood.

    Science.gov (United States)

    Gerber, Jeffrey S; Bryan, Matthew; Ross, Rachael K; Daymont, Carrie; Parks, Elizabeth P; Localio, A Russell; Grundmeier, Robert W; Stallings, Virginia A; Zaoutis, Theoklis E

    Early-life antibiotic exposure has been associated with increased adiposity in animal models, mediated through the gut microbiome. Infant antibiotic exposure is common and often inappropriate. Studies of the association between infant antibiotics and childhood weight gain have reported inconsistent results. To assess the association between early-life antibiotic exposure and childhood weight gain. Retrospective, longitudinal study of singleton births and matched longitudinal study of twin pairs conducted in a network of 30 pediatric primary care practices serving more than 200,000 children of diverse racial and socioeconomic backgrounds across Pennsylvania, New Jersey, and Delaware. Children born between November 1, 2001, and December 31, 2011, at 35 weeks' gestational age or older, with birth weight of 2000 g or more and in the fifth percentile or higher for gestational age, and who had a preventive health visit within 14 days of life and at least 2 additional visits in the first year of life. Children with complex chronic conditions and those who received long-term antibiotics or multiple systemic corticosteroid prescriptions were excluded. We included 38,522 singleton children and 92 twins (46 matched pairs) discordant in antibiotic exposure. Final date of follow-up was December 31, 2012. Systemic antibiotic use in the first 6 months of life. Weight, measured at preventive health visits from age 6 months through 7 years. Of 38,522 singleton children (50% female; mean birth weight, 3.4 kg), 5287 (14%) were exposed to antibiotics during the first 6 months of life (at a mean age of 4.3 months). Antibiotic exposure was not significantly associated with rate of weight change (0.7%; 95% CI, -0.1% to 1.5%; P = .07, equivalent to approximately 0.05 kg; 95% CI, -0.004 to 0.11 kg of added weight gain between age 2 years and 5 years). Among 92 twins (38% female; mean birth weight, 2.8 kg), the 46 twins who were exposed to antibiotics during the first 6 months of life

  20. Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Laura A E Hughes

    Full Text Available BACKGROUND: Exposure to energy restriction during childhood and adolescence is associated with a lower risk of developing colorectal cancer (CRC. Epigenetic dysregulation during this critical period of growth and development may be a mechanism to explain such observations. Within the Netherlands Cohort Study on diet and cancer, we investigated the association between early life energy restriction and risk of subsequent CRC characterized by the (promoter CpG island methylation phenotype (CIMP. METHODOLOGY/PRINCIPAL FINDINGS: Information on diet and risk factors was collected by baseline questionnaire (n = 120,856. Three indicators of exposure were assessed: place of residence during the Hunger Winter (1944-45 and World War II years (1940-44, and father's employment status during the Economic Depression (1932-40. Methylation specific PCR (MSP on DNA from paraffin embedded tumor tissue was performed to determine CIMP status according to the Weisenberger markers. After 7.3 years of follow-up, 603 cases and 4631 sub-cohort members were available for analysis. Cox regression was used to calculate hazard ratios (HR and 95% confidence intervals for CIMP+ (27.7% and CIMP- (72.3% tumors according to the three time periods of energy restriction, adjusted for age and gender. Individuals exposed to severe famine during the Hunger Winter had a decreased risk of developing a tumor characterized by CIMP compared to those not exposed (HR 0.65, 95%CI: 0.45-0.92. Further categorizing individuals by an index of '0-1' '2-3' or '4-7' genes methylated in the promoter region suggested that exposure to the Hunger Winter was associated with the degree of promoter hypermethylation ('0-1 genes methylated' HR = 1.01, 95%CI:0.74-1.37; '2-3 genes methylated' HR = 0.83, 95% CI:0.61-1.15; '4-7 genes methylated' HR = 0.72, 95% CI:0.49-1.04. No associations were observed with respect to the Economic Depression and WWII years. CONCLUSIONS: This is the first study indicating that

  1. Transplacental and early life exposure to inorganic arsenic affected development and behavior in offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Shuhua; Jin, Yaping; Sun, Guifan [China Medical University, Department of Environmental and Occupational Health, College of Public Health, Shenyang, Liaoning (China); Sun, Wenjuan; Wang, Fengzhi [Shenyang Medical College, Department of Preventive Medicine, Shenyang, Liaoning (China)

    2009-06-15

    To evaluate the developmental neurotoxicity of arsenic in offspring rats by transplacental and early life exposure to sodium arsenite in drinking water, the pregnant rats or lactating dams, and weaned pups were given free access to drinking water, which contained arsenic at concentrations of 0, 10, 50, 100 mg/L from GD 6 until PND 42. A battery of physical and behavioral tests was applied to evaluate the functional outcome of pups. Pups in arsenic exposed groups weighed less than controls throughout lactation and weaning. Body weight of 10, 50 and 100 mg/L arsenic exposed groups decreased significantly on PND 42, 16 and 12, respectively. Physical development (pinna unfolding, fur appearance, incisor eruption, or eye opening) in pups displayed no significant differences between control and arsenic treated groups. The number of incidences within the 100 mg/L arsenic treated group, in tail hung, auditory startle and visual placing showed significant decrease compared to the control group (p<0.05). In square water maze test, the trained numbers to finish the trials successfully in 50 and 100 mg/L arsenic exposed groups increased remarkably compared to control group, and there was a dose-related increase (p<0.01) observed. Taken together, these data show that exposure of inorganic arsenite to pregnant dams and offspring pups at levels up to 100 mg/L in drinking water may affect their learning and memory functions and neuromotor reflex. (orig.)

  2. Metabolic Disruption Early in Life is Associated With Latent Carcinogenic Activity of Dichloroacetic Acid in Mice

    Science.gov (United States)

    Early-life environmental factors can influence later-life susceptibility to cancer. Recent evidence suggests that metabolic pathways may mediate this type of latency effect. Previously, we reported that short-term exposure to dichloroacetic acid (DCA) increased liver cancer in mi...

  3. Sex and strain modify antioxidant response to early life ozone exposure in rats.

    Science.gov (United States)

    In the US, chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death. In women, its impact continues to increase. Oxidant insults like cigarette smoke and air pollution, especially during critical periods of early life, appear to further increase risk of COPD...

  4. Early life nutritional programming of health and disease in The Gambia.

    Science.gov (United States)

    Moore, S E

    2016-04-01

    Exposures during the early life (periconceptional, prenatal and early postnatal) period are increasingly recognized as playing an important role in the aetiology of chronic non-communicable diseases (NCD), including coronary heart disease, stroke, hypertension, Type 2 diabetes and osteoporosis. The 'Developmental Origins of Health and Disease' (DOHaD) hypothesis states that these disorders originate through unbalanced nutrition early in life and risk is highest when there is a 'mismatch' between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in countries where an excess of infants are born with low birth weight and where there is a rapid transition to nutritional adequacy or excess in adulthood. Here, I will review data from work conducted in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomized controlled trials of nutritional supplementation in pregnancy and the 'experiment of nature' that seasonality in this region provides, we have investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs.

  5. The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function

    Science.gov (United States)

    Hoeijmakers, Lianne; Lucassen, Paul J.; Korosi, Aniko

    2015-01-01

    Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity. PMID:25620909

  6. Early life exposure to antibiotics and the risk of childhood allergic diseases: an update from the perspective of the hygiene hypothesis.

    Science.gov (United States)

    Kuo, Chang-Hung; Kuo, Hsuan-Fu; Huang, Ching-Hua; Yang, San-Nan; Lee, Min-Sheng; Hung, Chih-Hsing

    2013-10-01

    The prevalence of allergic diseases has been growing rapidly in industrial countries during recent decades. It is postulated that growing up with less microbial exposure may render the immune system susceptible to a T helper type 2 (Th2)-predominant allergic response-also known as the hygiene hypothesis. This review delineates recent epidemiological and experimental evidence for the hygiene hypothesis, and integrates this hypothesis into the association between early life exposure to antibiotics and the development of allergic diseases and asthma. Several retrospective or prospective epidemiological studies reveal that early exposure to antibiotics may be positively associated with the development of allergic diseases and asthma. However, the conclusion is inconsistent. Experimental studies show that antibiotics may induce the Th2-skewed response by suppressing the T helper type 1 (Th1) response through inhibition of Th1 cytokines and disruption of the natural course of infection, or by disturbing the microflora of the gastrointestinal (GI) tract and therefore jeopardizing the establishment of oral tolerance and regulatory T cell immune responses. The hygiene hypothesis may not be the only explanation for the rapid increase in the prevalence of allergic diseases and asthma. Further epidemiological and experimental studies addressing the issue of the impact of environmental factors on the development of allergic diseases and the underlying mechanisms may unveil novel strategies for the prevention and treatment of allergic diseases in the future. Copyright © 2013. Published by Elsevier B.V.

  7. Evaluation of whole-mount in situ hybridization as a tool for pathway-based toxicological research with early-life stage fathead minnows

    Science.gov (United States)

    Early-life stage fish can be more sensitive to chemical exposure than adult fish. Therefore, determining possible adverse outcome pathways (AOPs) for early-life stages is crucial. To determine chemical effects and/or mechanisms of action in exposed fish embryos and larvae, whole-...

  8. Evaluation of whole mount in situ hybridization as a tool for pathway-based toxicological research in early-life stage fathead minnows

    Science.gov (United States)

    Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...

  9. Early-life family structure and microbially induced cancer risk.

    Directory of Open Access Journals (Sweden)

    Martin J Blaser

    2007-01-01

    Full Text Available Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men.We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative, belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0 among those in a sibship of seven or more individuals than in a sibship of between one and three persons.These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions.

  10. Early-life family structure and microbially induced cancer risk.

    Science.gov (United States)

    Blaser, Martin J; Nomura, Abraham; Lee, James; Stemmerman, Grant N; Perez-Perez, Guillermo I

    2007-01-01

    Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men. We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative), belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0) among those in a sibship of seven or more individuals than in a sibship of between one and three persons. These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions.

  11. Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

    Science.gov (United States)

    Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

    2015-01-01

    Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Effects of early exposure to phthalates and bisphenols on cardiometabolic outcomes in pregnancy and childhood

    NARCIS (Netherlands)

    Philips, E.M. (Elise M.); V.W.V. Jaddoe (Vincent); Trasande, L. (Leonardo)

    2017-01-01

    textabstractPregnant women are exposed to various chemicals, including endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenols. Increasing evidence suggests that early life exposures to phthalates and bisphenols may contribute to cardiometabolic risks. The aim of this narrative

  13. Early and Later Life Stress Alter Brain Activity and Sleep in Rats

    Science.gov (United States)

    Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

    2013-01-01

    Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way. PMID:23922857

  14. Early life influences on the development of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Stocks, Janet; Sonnappa, Samatha

    2013-06-01

    There is increasing evidence that chronic obstructive pulmonary disease (COPD) is not simply a disease of old age that is largely restricted to heavy smokers, but may be associated with insults to the developing lung during foetal life and the first few years of postnatal life, when lung growth and development are rapid. A better understanding of the long-term effects of early life factors, such as intrauterine growth restriction, prenatal and postnatal exposure to tobacco smoke and other pollutants, preterm delivery and childhood respiratory illnesses, on the subsequent development of chronic respiratory disease is imperative if appropriate preventive and management strategies to reduce the burden of COPD are to be developed. The extent to which insults to the developing lung are associated with increased risk of COPD in later life depends on the underlying cause, timing and severity of such derangements. Suboptimal conditions in utero result in aberrations of lung development such that affected individuals are born with reduced lung function, which tends to remain diminished throughout life, thereby increasing the risk both of wheezing disorders during childhood and subsequent COPD in genetically susceptible individuals. If the current trend towards the ever-increasing incidence of COPD is to be reversed, it is essential to minimize risks to the developing lung by improvements in antenatal and neonatal care, and to reduce prenatal and postnatal exposures to environmental pollutants, including passive tobacco smoke. Furthermore, adult physicians need to recognize that lung disease is potentially associated with early life insults and provide better education regarding diet, exercise and avoidance of smoking to preserve precious reserves of lung function in susceptible adults. This review focuses on factors that adversely influence lung development in utero and during the first 5 years of life, thereby predisposing to subsequent COPD.

  15. Does early-life family income influence later dental pain experience? A prospective 14-year study.

    Science.gov (United States)

    Ghorbani, Z; Peres, M A; Liu, P; Mejia, G C; Armfield, J M; Peres, K G

    2017-12-01

    The aim of this study was to investigate the association between early-life family income and dental pain experience from childhood to early adulthood. Data came from a 14-year prospective study (1991/1992-2005/2006) carried out in South Australia, which included children and adolescents aged 4-17 years (N = 9875) at baseline. The outcome was dental pain experience obtained at baseline, 14 years later in adulthood and at a middle point of time. The main explanatory variable was early-life family income collected at baseline. The prevalence of dental pain was 22.8% at baseline, 19.3% at 'middle time' and 39.3% at follow up. The proportion of people classified as 'poor' at baseline was 27.7%. Being poor early in life was significantly associated with dental pain at 14-year follow up (odds ratio = 1.45; 95% confidence interval = 1.27-1.66). Early-life relative poverty is associated with more frequent dental pain across the 14-year follow up and may be a key exposure variable for later dental conditions. © 2017 Australian Dental Association.

  16. A Systematic Literature Review and Meta-Regression Analysis on Early-Life Energy Restriction and Cancer Risk in Humans.

    Science.gov (United States)

    Elands, Rachel J J; Simons, Colinda C J M; Dongen, Martien van; Schouten, Leo J; Verhage, Bas A J; van den Brandt, Piet A; Weijenberg, Matty P

    2016-01-01

    In animal models, long-term moderate energy restriction (ER) is reported to decelerate carcinogenesis, whereas the effect of severe ER is inconsistent. The impact of early-life ER on cancer risk has never been reviewed systematically and quantitatively based on observational studies in humans. We conducted a systematic review of observational studies and a meta-(regression) analysis on cohort studies to clarify the association between early-life ER and organ site-specific cancer risk. PubMed and EMBASE (1982 -August 2015) were searched for observational studies. Summary relative risks (RRs) were estimated using a random effects model when available ≥3 studies. Twenty-four studies were included. Eleven publications, emanating from seven prospective cohort studies and some reporting on multiple cancer endpoints, met the inclusion criteria for quantitative analysis. Women exposed to early-life ER (ranging from 220-1660 kcal/day) had a higher breast cancer risk than those not exposed (RRRE all ages = 1.28, 95% CI: 1.05-1.56; RRRE for 10-20 years of age = 1.21, 95% CI: 1.09-1.34). Men exposed to early-life ER (ranging from 220-800kcal/day) had a higher prostate cancer risk than those not exposed (RRRE = 1.16, 95% CI: 1.03-1.30). Summary relative risks were not computed for colorectal cancer, because of heterogeneity, and for stomach-, pancreas-, ovarian-, and respiratory cancer because there were <3 available studies. Longer duration of exposure to ER, after adjustment for severity, was positively associated with overall cancer risk in women (p = 0.02). Ecological studies suggest that less severe ER is generally associated with a reduced risk of cancer. Early-life transient severe ER seems to be associated with increased cancer risk in the breast (particularly ER exposure at adolescent age) and prostate. The duration, rather than severity of exposure to ER, seems to positively influence relative risk estimates. This result should be interpreted with caution due to the

  17. Identifying important life stages for monitoring and assessing risks from exposures to environmental contaminants: results of a World Health Organization review.

    Science.gov (United States)

    Cohen Hubal, Elaine A; de Wet, Thea; Du Toit, Lilo; Firestone, Michael P; Ruchirawat, Mathuros; van Engelen, Jacqueline; Vickers, Carolyn

    2014-06-01

    In this paper, we summarize exposure-related issues to consider in determining the most appropriate age ranges and life stages for risk assessment. We then propose a harmonized set of age bins for monitoring and assessing risks from exposures to chemicals for global use. The focus is on preconception through adolescence, though the approach should be applicable to additional life stages. A two-tiered set of early life age groups is recommended. The first tier involves the adoption of guidance similar to the childhood age groups recommended by the U.S. Environmental Protection Agency, whereas the second tier consolidates some of those age groups to reduce the burden of developing age-specific exposure factors for different regions. While there is no single "correct" means of choosing a common set of age groups to use internationally in assessing early life exposure and risk, use of a set of defined age groups is recommended to facilitate comparisons of potential exposures and risks around the globe, the collection of data and analyses of aggregate exposure and cumulative risk. Application of these age groups for robust assessment of exposure and risk for specific populations will require region-specific exposure factors as well as local environmental monitoring data. Copyright © 2013 World Health Organization. Published by Elsevier Inc. All rights reserved.

  18. Evaluation of whole mount in situ hybridization as a tool for pathway-based toxicological research in early-life stage fathead minnows (poster)

    Science.gov (United States)

    Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...

  19. EVALUATING THE EFFECTS OF FLY ASH EXPOSURE ON FISH EARLY LIFE STAGES: FATHEAD MINNOW EMBRYO-LARVAL TESTS

    Energy Technology Data Exchange (ETDEWEB)

    Greeley Jr, Mark Stephen [ORNL; Elmore, Logan R [ORNL; McCracken, Kitty [ORNL

    2012-05-01

    On December 22, 2008, a dike containing fly ash and bottom ash in an 84-acre complex of the Tennessee Valley Authority's (TVA) Kingston Steam Plant in East Tennessee failed and released a large quantity of ash into the adjacent Emory River. Ash deposits extended as far as 4 miles upstream (Emory River mile 6) of the Plant, and some ash was carried as far downstream as Tennessee River mile 564 ({approx}4 miles downstream of the Tennessee River confluence with the Clinch River). A byproduct of coal burning power plants, fly ash contains a variety of metals and other elements which, at sufficient concentrations and in specific forms, can be toxic to biological systems. The effects of fly ash contamination on exposed fish populations depend on the magnitude and duration of exposure, with the most significant risk considered to be the effects of specific ash constituents, especially selenium, on fish early life stages. Uptake by adult female fish of fly ash constituents through the food chain and subsequent maternal transfer of contaminants to the developing eggs is thought to be the primary route of selenium exposure to larval fish (Woock and others 1987, Coyle and others 1993, Lemly 1999, Moscatello and others 2006), but direct contact of the fertilized eggs and developing embryos to ash constituents in river water and sediments is also a potential risk factor (Woock and others 1987, Coyle and others 1993, Jezierska and others 2009). To address the risk of fly ash from the Kingston spill to the reproductive health of downstream fish populations, ORNL has undertaken a series of studies in collaboration with TVA including: (1) a field study of the bioaccumulation of fly ash constituents in fish ovaries and the reproductive condition of sentinel fish species in reaches of the Emory and Clinch Rivers affected by the fly ash spill; (2) laboratory tests of the potential toxicity of fly ash from the spill area on fish embryonic and larval development (reported in the

  20. The impact of life stress on adult depression and anxiety is dependent on gender and timing of exposure.

    Science.gov (United States)

    Herbison, Carly E; Allen, Karina; Robinson, Monique; Newnham, John; Pennell, Craig

    2017-10-01

    There is debate about the relative importance of timing of stressful events prenatally and over the life course and risk for subsequent depressive/anxious illness. The aim of this study was to examine the relative roles of prenatal stress and postnatal stress trajectories in predicting depression and anxiety in early adulthood in males and females. Exposure to life stress events was examined in the Western Australian Pregnancy Cohort (Raine) Study during pregnancy and ages 1, 2, 3, 5, 8, 10, 14, and 17 years. At age 20, offspring completed the Depression Anxiety Stress Scale. Prenatal stress and trajectories of stress events from age 1 to 17 were analyzed in linear regression analyses. Five postnatal stress trajectories were identified. In females, medium to high chronic stress exposure or exposure during puberty/adolescence predicted depression and anxiety symptoms while low or reduced stress exposure over the life course did not, after adjustment for relevant confounders. High stress early in pregnancy contributed to male depression/anxiety symptoms independent of postnatal stress trajectory. In females, postnatal stress trajectory was more important than prenatal stress in predicting depression/anxiety symptoms. Interventions focused on reducing and managing stress events around conception/pregnancy and exposure to chronic stress are likely to have beneficial outcomes on rates of depression and anxiety in adults.

  1. Sense of coherence moderates late effects of early childhood Holocaust exposure.

    Science.gov (United States)

    van der Hal-van Raalte, Elisheva A M; van IJzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

    2008-12-01

    This study evaluated child Holocaust survivors with an emphasis on potential protective factors facilitating participants' adaptation to post-Holocaust life. We examined Antonovsky's (1979, 1987) salutogenic paradigm, testing the mediating and moderating effect of participants' sense of coherence (SOC) on the association between early childhood deprivation due to Holocaust persecution and posttraumatic stress later in life. The nonclinical sample, composed of 203 child Holocaust survivors born between 1935 and 1944 completed questionnaires on Holocaust survival exposure, inventories on current health, posttraumatic stress, and SOC. The results indicated that SOC moderates the association between traumatic experiences during the war and posttraumatic stress, and SOC acts as a protective factor, buffering the impact of traumatic Holocaust experiences on child survivors in old age. Survivors with a less coherent perspective on the meaning of their life showed greater vulnerability for posttraumatic complaints. The moderating role of the SOC may suggest promising avenues of therapeutic interventions for child Holocaust survivors and other adults with early childhood trauma. (c) 2008 Wiley Periodicals, Inc.

  2. Early life programming as a target for prevention of child and adolescent mental disorders

    OpenAIRE

    Lewis, Andrew James; Galbally, Megan; Gannon, Tara; Symeonides, Christos

    2014-01-01

    This paper concerns future policy development and programs of research for the prevention of mental disorders based on research emerging from fetal and early life programming. The current review offers an overview of findings on pregnancy exposures such as maternal mental health, lifestyle factors, and potential teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are common child and adolescent mental disorders including hyperactive, behavioral and emotional disorders...

  3. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages

    Science.gov (United States)

    Lauterstein, Dana E.; Tijerina, Pamella B.; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S.; Gordon, Terry; Klein, Catherine B.; Zelikoff, Judith T.

    2016-01-01

    Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology. PMID:27077873

  4. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages

    Directory of Open Access Journals (Sweden)

    Dana E. Lauterstein

    2016-04-01

    Full Text Available Electronic cigarettes (e-cigarettes, battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation throughout gestation (3 h/day; 5 days/week to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq. Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.

  5. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages.

    Science.gov (United States)

    Lauterstein, Dana E; Tijerina, Pamella B; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S; Gordon, Terry; Klein, Catherine B; Zelikoff, Judith T

    2016-04-12

    Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13-16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4-6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.

  6. Regional homogeneity and resting state functional connectivity: associations with exposure to early life stress.

    Science.gov (United States)

    Philip, Noah S; Kuras, Yuliya I; Valentine, Thomas R; Sweet, Lawrence H; Tyrka, Audrey R; Price, Lawrence H; Carpenter, Linda L

    2013-12-30

    Early life stress (ELS) confers risk for psychiatric illness. Previous literature suggests ELS is associated with decreased resting-state functional connectivity (rs-FC) in adulthood, but there are no studies of resting-state neuronal activity in this population. This study investigated whether ELS-exposed individuals demonstrate resting-state activity patterns similar to those found in PTSD. Twenty-seven adults (14 with at least moderate ELS), who were medication-free and without psychiatric or medical illness, underwent MRI scans during two 4-minute rest periods. Resting-state activity was examined using regional homogeneity (ReHo), which estimates regional activation patterns through indices of localized concordance. ReHo values were compared between groups, followed by rs-FC analyses utilizing ReHo-localized areas as seeds to identify other involved regions. Relative to controls, ELS subjects demonstrated diminished ReHo in the inferior parietal lobule (IPL) and superior temporal gyrus (STG). ReHo values were inversely correlated with ELS severity. Secondary analyses revealed decreased rs-FC between the IPL and right precuneus/posterior cingulate, left fusiform gyrus, cerebellum and caudate in ELS subjects. These findings indicate that ELS is associated with altered resting-state activity and connectivity in brain regions involved in trauma-related psychiatric disorders. Future studies are needed to evaluate whether these associations represent potential imaging biomarkers of stress exposure. Published by Elsevier Ireland Ltd.

  7. Impact of Early-Life Exposures to Infections, Antibiotics, and Vaccines on Perinatal and Long-term Health and Disease

    Directory of Open Access Journals (Sweden)

    Steven L. Raymond

    2017-06-01

    Full Text Available Essentially, all neonates are exposed to infections, antibiotics, or vaccines early in their lives. This is especially true for those neonates born underweight or premature. In contrast to septic adults and children who are at an increased risk for subsequent infections, exposure to infection during the neonatal period is not associated with an increased risk of subsequent infection and may be paradoxically associated with reductions in late-onset sepsis (LOS in the most premature infants. Perinatal inflammation is also associated with a decreased incidence of asthma and atopy later in life. Conversely, septic neonates are at increased risk of impaired long-term neurodevelopment. While the positive effects of antibiotics in the setting of infection are irrefutable, prolonged administration of broad-spectrum, empiric antibiotics in neonates without documented infection is associated with increased risk of LOS, necrotizing enterocolitis, or death. Vaccines provide a unique opportunity to prevent infection-associated disease; unfortunately, vaccinations have been largely unsuccessful when administered in the first month of life with the exception of vaccines against hepatitis B and tuberculosis. Future vaccines will require the use of novel adjuvants to overcome this challenge. This review describes the influence of infections, antibiotics, and vaccines during the first days of life, as well as the influence on future health and disease. We will also discuss potential immunomodulating therapies, which may serve to train the preterm immune system and reduce subsequent infectious burden without subjecting neonates to the risks accompanied by virulent pathogens.

  8. Effects of pyrene exposure and temperature on early development of two co-existing Arctic copepods

    DEFF Research Database (Denmark)

    Grenvald, Julie Cornelius; Nielsen, Torkel Gissel; Hjorth, Morten

    2013-01-01

    Oil exploration is expected to increase in the near future in Western Greenland. At present, effects of exposure to oil compounds on early life-stages of the ecologically important Calanus spp. are unknown. We investigated the effects of the oil compound pyrene, on egg hatching and naupliar...... with temperature at high pyrene concentration in C. finmarchicus. Both Calanus species were affected by pyrene exposure but C. finmarchicus was more sensitive compared to C. glacialis. Lowered growth rate and increased mortality of the naupliar stages entail reduced recruitment to copepod populations. Exposure...

  9. Differential effects of early-life NMDA receptor antagonism on aspartame-impaired insulin tolerance and behavior.

    Science.gov (United States)

    Collison, Kate S; Inglis, Angela; Shibin, Sherin; Andres, Bernard; Ubungen, Rosario; Thiam, Jennifer; Mata, Princess; Al-Mohanna, Futwan A

    2016-12-01

    We have previously showed that lifetime exposure to aspartame, commencing in utero via the mother's diet, may impair insulin tolerance and cause behavioral deficits in adulthood via mechanisms which are incompletely understood. The role of the CNS in regulating glucose homeostasis has been highlighted by recent delineation of the gut-brain axis, in which N-methyl-d-aspartic acid receptors (NMDARs) are important in maintaining glucose homeostasis, in addition to regulating certain aspects of behavior. Since the gut-brain axis can be modulated by fetal programming, we hypothesized that early-life NMDAR antagonism may affect aspartame-induced glucose deregulation in adulthood, and may alter the aspartame behavioral phenotype. Accordingly, C57Bl/6J mice were chronically exposed to aspartame commencing in utero, in the presence and absence of maternal administration of the competitive NMDAR antagonist CGP 39551, from conception until weaning. Drug/diet interactions in adulthood glucocentric and behavioral parameters were assessed. Aspartame exposure elevated blood glucose and impaired insulin-induced glucose disposal during an insulin tolerance test, which could be normalized by NMDAR antagonism. The same effects were not observed in control diet mice, suggesting an early-life drug/diet interaction. Behavioral analysis of adult offspring indicated that NMDAR antagonism of control diet mice caused hyperlocomotion and impaired spatial navigation. Conversely hypolocomotion, reduced exploratory activity and increased anxiety-related behavior were apparent in aspartame diet mice with early-life NMDAR antagonism. significant drug/diet interactions in glucocentric and behavioral parameters were identified in aspartame-exposed mice with early-life NMDAR antagonism. This suggests a possible involvement of early NMDAR interactions in aspartame-impaired glucose homeostasis and behavioral deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Years of life lost due to external radiation exposure

    Directory of Open Access Journals (Sweden)

    Raičević Jagoš J.

    2004-01-01

    Full Text Available In this paper a new approach for calculation of the years of life lost per excess death due to stochastic health effects is applied to external exposure pathways. The short-term external exposures are due to the passage of radioactive cloud and due to the skin and clothes contamination. The long-term external exposure is the one from the radioactive material deposited on the ground (groundshine. Three nuclides, 131I, 137Cs, and 239Pu, and with the extremely wide range of half-life are considered in order to examine their possible influence on the calculated values of years of life lost. For each of these nuclides, the number of years of life lost has been found as a decreasing function of the age at the expo sure and presented graphically in this paper. For protracted exposures, the fully averaged number of years of life lost is negative correlated with the nuclide’s half-life. On the other hand, the short-term external exposures do not depend on the nuclide’s half-life. In addition, a weak years of life lost dependence of the dose has been commented.

  11. Effect of early postnatal exposure to valproate on neurobehavioral development and regional BDNF expression in two strains of mice.

    Science.gov (United States)

    Bath, Kevin G; Pimentel, Tiare

    2017-05-01

    Valproate has been used for over 30years as a first-line treatment for epilepsy. In recent years, prenatal exposure to valproate has been associated with teratogenic effects, limiting its use in women that are pregnant or of childbearing age. However, despite its potential detrimental effects on development, valproate continues to be prescribed at high rates in pediatric populations in some countries. Animal models allow us to test hypotheses regarding the potential effects of postnatal valproate exposure on neurobehavioral development, as well as identify potential mechanisms mediating observed effects. Here, we tested the effect of early postnatal (P4-P11) valproate exposure (100mg/kg and 200mg/kg) on motor and affective development in two strains of mice, SVE129 and C57Bl/6N. We also assessed the effect of early valproate exposure on regional BDNF protein levels, a potential target of valproate, and mediator of neurodevelopmental outcomes. We found that early life valproate exposure led to significant motor impairments in both SVE129 and C57Bl/6N mice. Both lines of mice showed significant delays in weight gain, as well as impairments in the righting reflex (P7-8), wire hang (P17), open field (P12 and P21), and rotarod (P25 and P45) tasks. Interestingly, some of the early locomotor effects were strain- and dose-dependent. We observed no effects of valproate on early markers of anxiety-like behavior. Importantly, early life valproate exposure had significant effects on regional BDNF expression, leading to a near 50% decrease in BDNF levels in the cerebellum of both strains of mice, while not impacting hippocampal BDNF protein levels. These observations indicate that postnatal exposure to valproate may have significant, and region-specific effects, on neural and behavioral development, with specific consequences for cerebellar development and motor function. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Exogenous determinants of early-life conditions, and mortality later in life.

    Science.gov (United States)

    van den Berg, Gerard J; Doblhammer, Gabriele; Christensen, Kaare

    2009-05-01

    We analyze causal effects of conditions early in life on the individual mortality rate later in life. Conditions early in life are captured by transitory features of the macro-environment around birth, notably the state of the business cycle around birth, but also food price deviations, weather indicators, and demographic indicators. We argue that these features can only affect high-age mortality by way of the individual early-life conditions. Moreover, they are exogenous from the individual point of view, which is a methodological advantage compared to the use of unique characteristics of the newborn individual or his or her family or household as early-life indicators. We collected national annual time-series data on the above-mentioned indicators, and we combine these to the individual data records from the Danish Twin Registry covering births in 1873-1906. The empirical analyses (mostly based on the estimation of duration models) indicate a significant negative causal effect of economic conditions early in life on individual mortality rates at higher ages. If the national economic performance in the year of birth exceeds its trend value (i.e., if the business cycle is favorable) then the mortality rate later in life is lower. The implied effect on the median lifetime of those who survive until age 35 is about 10 months. A systematic empirical exploration of all macro-indicators reveals that economic conditions in the first years after birth also affect mortality rates later in life.

  13. Proteomic responses reveal the differential effects induced by cadmium in mussels Mytilus galloprovincialis at early life stages.

    Science.gov (United States)

    Xu, Lanlan; Peng, Xiao; Yu, Deliang; Ji, Chenglong; Zhao, Jianmin; Wu, Huifeng

    2016-08-01

    Cadmium (Cd) has become an important metal contaminant and posed severe risk on the organisms in the coastal environments of the Bohai Sea. Marine mussel Mytilus galloprovincialis is widely distributed along the Bohai coast and consumed as seafood by local residents. Evidences indicate that the early stages of marine organisms are more sensitive to metal contaminants. In this study, we applied two-dimensional electrophoresis-based proteomics to characterize the biological effects of Cd (50 μg L(-1)) in the early life stages (D-shape larval and juvenile) of mussels. The different proteomic responses demonstrated the differential responsive mechanisms to Cd exposure in these two early life stages of mussels. In details, results indicated that Cd mainly induced immune and oxidative stresses in both D-shape larval and juvenile mussels via different pathways. In addition, the significant up-regulation of triosephosphate isomerase and metallothionein confirmed the enhanced energy demand and mobilized detoxification mechanism in D-shape larval mussels exposed to Cd. In juvenile mussels, Cd exposure also induced clear apoptosis. Overall, this work suggests that Cd is a potential immune toxicant to mussel M. galloprovincialis at early life stages. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge

    Directory of Open Access Journals (Sweden)

    Cristan Herbert

    2013-03-01

    Childhood exposure to environmental particulates increases the risk of development of asthma. The underlying mechanisms might include oxidant injury to airway epithelial cells (AEC. We investigated the ability of ambient environmental particulates to contribute to sensitization via the airways, and thus to the pathogenesis of childhood asthma. To do so, we devised a novel model in which weanling BALB/c mice were exposed to both ambient particulate pollutants and ovalbumin for sensitization via the respiratory tract, followed by chronic inhalational challenge with a low mass concentration of the antigen. We also examined whether these particulates caused oxidant injury and activation of AEC in vitro. Furthermore, we assessed the potential benefit of minimizing oxidative stress to AEC through the period of sensitization and challenge by dietary intervention. We found that characteristic features of asthmatic inflammation developed only in animals that received particulates at the same time as respiratory sensitization, and were then chronically challenged with allergen. However, these animals did not develop airway hyper-responsiveness. Ambient particulates induced epithelial injury in vitro, with evidence of oxidative stress and production of both pro-inflammatory cytokines and Th2-promoting cytokines such as IL-33. Treatment of AEC with an antioxidant in vitro inhibited the pro-inflammatory cytokine response to these particulates. Ambient particulates also induced pro-inflammatory cytokine expression following administration to weanling mice. However, early-life dietary supplementation with antioxidants did not prevent the development of an asthmatic inflammatory response in animals that were exposed to particulates, sensitized and challenged. We conclude that injury to airway epithelium by ambient environmental particulates in early life is capable of promoting the development of an asthmatic inflammatory response in sensitized and antigen-challenged mice. These

  15. Early-life lead exposure results in dose- and sex-specific effects on weight and epigenetic gene regulation in weanling mice

    Science.gov (United States)

    Faulk, Christopher; Barks, Amanda; Liu, Kevin; Goodrich, Jaclyn M; Dolinoy, Dana C

    2013-01-01

    Aims Epidemiological and animal data suggest that the development of adult chronic conditions is influenced by early-life exposure-induced changes to the epigenome. This study investigates the effects of perinatal lead (Pb) exposure on DNA methylation and bodyweight in weanling mice. Materials & methods Viable yellow agouti (Avy) mouse dams were exposed to 0, 2.1, 16 and 32 ppm Pb acetate before conception through weaning. Epigenetic effects were evaluated by scoring coat color of Avy/a offspring and quantitative bisulfite sequencing of two retrotransposon-driven (Avy and CDK5 activator-binding protein intracisternal A particle element) and two imprinted (Igf2 and Igf2r) loci in tail DNA. Results Maternal blood Pb levels were below the limit of detection in controls, and 4.1, 25.1 and 32.1 μg/dl for each dose, respectively. Pb exposure was associated with a trend of increased wean bodyweight in males (p = 0.03) and altered coat color in Avy/a offspring. DNA methylation at Avy and the CDK5 activator-binding protein intracisternal A-particle element was significantly different from controls following a cubic trend (p = 0.04; p = 0.01), with male-specific effects at the Avy locus. Imprinted genes did not shift in methylation across exposures. Conclusion Dose- and sex-specific responses in bodyweight and DNA methylation indicate that Pb acts on the epigenome in a locus-specific fashion, dependent on the genomic feature hosting the CpG site of interest, and that sex is a factor in epigenetic response. PMID:24059796

  16. Ibuprofen exposure in early neonatal life does not affect renal function in young adolescence.

    Science.gov (United States)

    Raaijmakers, Anke; Zhang, Zhen-Yu; Levtchenko, Elena; Simons, Sinno Hp; Cauwenberghs, Nicholas; Heuvel, Lambertus P van den; Jacobs, Lotte; Staessen, Jan A; Allegaert, Karel

    2018-03-01

    Ibuprofen exposure results in acute transient renal dysfunction in preterm neonates, but we are unaware of data on long-term renal safety. In a previously studied cohort of extreme low birth weight (ELBW, ibuprofen. In this post hoc analysis, we linked markers of renal function in young adolescence in ELBW cases with their perinatal (prenatal maternal, setting at birth, treatment modalities including drug prescription during neonatal stay, neonatal creatinine values, postdischarge growth) characteristics, including but not limited to ibuprofen exposure during neonatal stay. Ibuprofen exposure was not associated with significant differences in renal length or eGFR cysC . Moreover, we were unable to identify any other risk factor (perinatal characteristics, postnatal creatinine trends, postdischarge growth) on renal outcome in this cohort. Neonatal exposure to ibuprofen did not affect renal function. Larger studies are needed to explore the confounders of variability in renal function in former ELBW cases. This matters since ELBW relates to risk for hypertension, cardiovascular events and renal disease in later life and identification of risk factors holds the promise of secondary prevention. NCT02147457. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. No consistent effects of prenatal or neonatal exposure to Spanish flu on late-life mortality in 24 developed countries

    DEFF Research Database (Denmark)

    Cohen, Alan; Tillinghast, J; Canudas-Romo, V

    2010-01-01

    We test the effects of early life exposure to disease on later health by looking for differences in late-life mortality in cohorts born around the 1918-1919 flu pandemic using data from the Human Mortality Database for 24 countries. After controlling for age, period, and sex effects, residual...

  18. Early life exposure to polyunsaturated fatty acids and psychomotor development in children from the EDEN mother-child cohort

    Directory of Open Access Journals (Sweden)

    Bernard Jonathan Y.

    2016-01-01

    Full Text Available Epidemiological studies have reported that breastfed children have improved psychomotor development compared to never breastfed children. Human studies suggest that polyunsaturated fatty acids (PUFA, especially long chain PUFA (LC-PUFA which are highly contained in breast milk, could explain this link, since they are needed for pre- and postnatal brain development. Our aim was to study the relationships between several measures of pre- and postnatal exposures to PUFA and child’s psychomotor development at 2 and 3 years in the EDEN cohort. We evaluated breastfeeding duration, colostrum PUFA levels and maternal dietary PUFA intake during pregnancy, that we related with three scores of psychomotor development, after taking into account potential confounders. Breastfeeding duration was positively associated with psychomotor development. No relationship was found with both pre- and postnatal exposure to LC-PUFA. However, the maternal dietary omega-6/omega-3 ratio was negatively associated with psychomotor development, mainly driven by intake in linoleic acid (LA. Among breastfed children, linoleic acid levels were negatively associated with psychomotor development. Furthermore, children exposed to the highest colostrum LA levels tended to score closer to never breastfed children than to children exposed to the lowest colostrums LA levels. Taken together, these results do not provide evidence in favour of a positive role of pre- and postnatal exposure to LC-PUFA on later psychomotor development, but highlight a potential negative role of being exposed in early life to high LA levels. From a public health perspective, this work reiterates the need to promote breastfeeding duration, and to monitor the balance of PUFA intake during pregnancy and lactation periods.

  19. Early age exposure to moisture damage and systemic inflammation at the age of 6 years.

    Science.gov (United States)

    Karvonen, A M; Tischer, C; Kirjavainen, P V; Roponen, M; Hyvärinen, A; Illi, S; Mustonen, K; Pfefferle, P I; Renz, H; Remes, S; Schaub, B; von Mutius, E; Pekkanen, J

    2018-05-01

    Cross-sectional studies have shown that exposure to indoor moisture damage and mold may be associated with subclinical inflammation. Our aim was to determine whether early age exposure to moisture damage or mold is prospectively associated with subclinical systemic inflammation or with immune responsiveness in later childhood. Home inspections were performed in children's homes in the first year of life. At age 6 years, subclinical systemic inflammation was measured by serum C-reactive protein (CRP) and blood leukocytes and immune responsiveness by ex vivo production of interleukin 1-beta (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) in whole blood cultures without stimulation or after 24 hours stimulation with phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG) in 251-270 children. Moisture damage in child's main living areas in infancy was not significantly associated with elevated levels of CRP or leukocytes at 6 years. In contrast, there was some suggestion for an effect on immune responsiveness, as moisture damage with visible mold was positively associated with LPS-stimulated production of TNF-α and minor moisture damage was inversely associated with PI-stimulated IL-1β. While early life exposure to mold damage may have some influence on later immune responsiveness, it does not seem to increase subclinical systemic inflammation in later life. © 2018 National Institute for Health and Welfare, Finland Indoor Air published by John Wiley & Sons Ltd.

  20. Exogenous determinants of early-life conditions, and mortality later in life

    DEFF Research Database (Denmark)

    van den Berg, Gerard J; Doblhammer, Gabriele; Christensen, Kaare

    2009-01-01

    based on the estimation of duration models) indicate a significant negative causal effect of economic conditions early in life on individual mortality rates at higher ages. If the national economic performance in the year of birth exceeds its trend value (i.e., if the business cycle is favorable......) then the mortality rate later in life is lower. The implied effect on the median lifetime of those who survive until age 35 is about 10 months. A systematic empirical exploration of all macro-indicators reveals that economic conditions in the first years after birth also affect mortality rates later in life.......We analyze causal effects of conditions early in life on the individual mortality rate later in life. Conditions early in life are captured by transitory features of the macro-environment around birth, notably the state of the business cycle around birth, but also food price deviations, weather...

  1. Early life stress determines the effects of glucocorticoids and stress on hippocampal function: Electrophysiological and behavioral evidence respectively.

    Science.gov (United States)

    Pillai, Anup G; Arp, Marit; Velzing, Els; Lesuis, Sylvie L; Schmidt, Mathias V; Holsboer, Florian; Joëls, Marian; Krugers, Harm J

    2018-05-01

    Exposure to early-life adversity may program brain function to prepare individuals for adaptation to matching environmental contexts. In this study we tested this hypothesis in more detail by examining the effects of early-life stress - induced by raising offspring with limited nesting and bedding material from postnatal days 2-9 - in various behavioral tasks and on synaptic function in adult mice. Early-life stress impaired adult performance in the hippocampal dependent low-arousing object-in-context recognition memory task. This effect was absent when animals were exposed to a single stressor before training. Early-life stress did not alter high-arousing context and auditory fear conditioning. Early-life stress-induced behavioral modifications were not associated with alterations in the dendritic architecture of hippocampal CA1 pyramidal neurons or principal neurons of the basolateral amygdala. However, early-life stress reduced the ratio of NMDA to AMPA receptor-mediated excitatory postsynaptic currents and glutamate release probability specifically in hippocampal CA1 neurons, but not in the basolateral amygdala. These ex vivo effects in the hippocampus were abolished by acute glucocorticoid treatment. Our findings support that early-life stress can hamper object-in-context learning via pre- and postsynaptic mechanisms that affect hippocampal function but these effects are counteracted by acute stress or elevated glucocorticoid levels. Copyright © 2018. Published by Elsevier Ltd.

  2. Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives.

    Science.gov (United States)

    Grandjean, Philippe; Barouki, Robert; Bellinger, David C; Casteleyn, Ludwine; Chadwick, Lisa H; Cordier, Sylvaine; Etzel, Ruth A; Gray, Kimberly A; Ha, Eun-Hee; Junien, Claudine; Karagas, Margaret; Kawamoto, Toshihiro; Paige Lawrence, B; Perera, Frederica P; Prins, Gail S; Puga, Alvaro; Rosenfeld, Cheryl S; Sherr, David H; Sly, Peter D; Suk, William; Sun, Qi; Toppari, Jorma; van den Hazel, Peter; Walker, Cheryl L; Heindel, Jerrold J

    2015-10-01

    The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous "reprogramming" of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks.

  3. Early Exposure to Dogs and Farm Animals and the Risk of Childhood Asthma.

    Science.gov (United States)

    Fall, Tove; Lundholm, Cecilia; Örtqvist, Anne K; Fall, Katja; Fang, Fang; Hedhammar, Åke; Kämpe, Olle; Ingelsson, Erik; Almqvist, Catarina

    2015-11-01

    The association between early exposure to animals and childhood asthma is not clear, and previous studies have yielded contradictory results. To determine whether exposure to dogs and farm animals confers a risk of asthma. In a nationwide cohort study, the association between early exposure to dogs and farm animals and the risk of asthma was evaluated and included all children born in Sweden from January 1, 2001, to December 31, 2010 (N = 1,011,051), using registry data on dog and farm registration, asthma medication, diagnosis, and confounders for parents and their children. The association was assessed as the odds ratio (OR) for a current diagnosis of asthma at age 6 years for school-aged children and as the hazard ratio (HR) for incident asthma at ages 1 to 5 years for preschool-aged children. Data were analyzed from January 1, 2007, to September 30, 2012. Living with a dog or farm animal. Childhood asthma diagnosis and medication used. Of the 1,011,051 children born during the study period, 376,638 preschool-aged (53,460 [14.2%] exposed to dogs and 1729 [0.5%] exposed to farm animals) and 276,298 school-aged children (22,629 [8.2%] exposed to dogs and 958 [0.3%] exposed to farm animals) were included in the analyses. Of these, 18,799 children (5.0%) in the preschool-aged children's cohort experienced an asthmatic event before baseline, and 28,511 cases of asthma and 906,071 years at risk were recorded during follow-up (incidence rate, 3.1 cases per 1000 years at risk). In the school-aged children's cohort, 11,585 children (4.2%) experienced an asthmatic event during the seventh year of life. Dog exposure during the first year of life was associated with a decreased risk of asthma in school-aged children (OR, 0.87; 95% CI, 0.81-0.93) and in preschool-aged children 3 years or older (HR, 0.90; 95% CI, 0.83-0.99) but not in children younger than 3 years (HR, 1.03; 95% CI, 1.00-1.07). Results were comparable when analyzing only first-born children. Farm animal

  4. Secure Infant-Mother Attachment Buffers the Effect of Early-Life Stress on Age of Menarche.

    Science.gov (United States)

    Sung, Sooyeon; Simpson, Jeffry A; Griskevicius, Vladas; Kuo, Sally I-Chun; Schlomer, Gabriel L; Belsky, Jay

    2016-05-01

    Prior research indicates that being reared in stressful environments is associated with earlier onset of menarche in girls. In this research, we examined (a) whether these effects are driven by exposure to certain dimensions of stress (harshness or unpredictability) during the first 5 years of life and (b) whether the negative effects of stress on the timing of menarche are buffered by secure infant-mother attachment. Results revealed that (a) exposure to greater harshness (but not unpredictability) during the first 5 years of life predicted earlier menarche and (b) secure infant-mother attachment buffered girls from this effect of harsh environments. By connecting attachment research to its evolutionary foundations, these results illuminate how environmental stressors and relationships early in life jointly affect pubertal timing. © The Author(s) 2016.

  5. Recovery of gonadal development in tiger puffer Takifugu rubripes after exposure to 17β-estradiol during early life stages

    Science.gov (United States)

    Hu, Peng; Liu, Bin; Meng, Zhen; Liu, Xinfu; Jia, Yudong; Yang, Zhi; Lei, Jilin

    2017-05-01

    The aim of the present study was to investigate the long-term effects of 17β-estradiol (E2) exposure on gonadal development in the tiger puff er ( Takifugu rubripes), which has a genetic sex determination system of male homogametic XY-XX. Tiger puff er larvae were exposed to 1, 10 and 100 μg/L E2 from 15 to 100 days post-hatch (dph) and then maintained in clean seawater until 400 dph. Changes in sex ratio, gonadal structure and gonadosomatic index (GSI) were monitored at 100, 160, 270 and 400 dph. Sex-associated single nucleotide polymorphism (SNP) markers were used to analyze the genetic sex of samples, except those at 100 dph. Exposure had a positive effect on the conversion of genetically male gonads into phenotypically female gonads at 100 dph. However, gonads from 60% of genetic XY males in the 1-μg/L E2 group and 100% in the 10-μg/L E2 group developed intersexual gonads at 160 dph; gonads of all genetic XY males in the two treatment groups reverted to testis by 270 dph. While 38%, 57% and 44% of gonads of XY fish in the 100-μg/L E2 group reverted to intersexual gonads at 160, 270 and 400 dph, respectively, none reverted to testis after E2 treatment. In addition, E2 exposure inhibited gonadal growth of both genetic sexes, as indicated by the clear dose-dependent decrease in GSI at 270 and 400 dph. The results showed that exposure to E2 during the early life stages of tiger puff er disrupted gonadal development, but that fish recovered after migration to clean seawater. The study suggests the potential use of tiger puff er as a valuable indicator species to evaluate the effects of environmental estrogens on marine fish, thereby protecting valuable fishery resources.

  6. Using physiology and behaviour to understand the responses of fish early life stages to toxicants.

    Science.gov (United States)

    Sloman, K A; McNeil, P L

    2012-12-01

    The use of early life stages of fishes (embryos and larvae) in toxicity testing has been in existence for a long time, generally utilizing endpoints such as morphological defects and mortality. Behavioural endpoints, however, may represent a more insightful evaluation of the ecological effects of toxicants. Indeed, recent years have seen a considerable increase in the use of behavioural measurements in early life stages reflecting a substantial rise in zebrafish Danio rerio early life-stage toxicity testing and the development of automated behavioural monitoring systems. Current behavioural endpoints identified for early life stages in response to toxicant exposure include spontaneous activity, predator avoidance, capture of live food, shoaling ability and interaction with other individuals. Less frequently used endpoints include measurement of anxiogenic behaviours and cognitive ability, both of which are suggested here as future indicators of toxicant disruption. For many simple behavioural endpoints, there is still a need to link behavioural effects with ecological relevance; currently, only a limited number of studies have addressed this issue. Understanding the physiological mechanisms that underlie toxicant effects on behaviour so early in life has received far less attention, perhaps because physiological measurements can be difficult to carry out on individuals of this size. The most commonly established physiological links with behavioural disruption in early life stages are similar to those seen in juveniles and adults including sensory deprivation (olfaction, lateral line and vision), altered neurogenesis and neurotransmitter concentrations. This review highlights the importance of understanding the integrated behavioural and physiological response of early life stages to toxicants and identifies knowledge gaps which present exciting areas for future research. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

  7. Risk factors and life processes associated with the onset of suicidal behaviour during adolescence and early adulthood.

    Science.gov (United States)

    Fergusson, D M; Woodward, L J; Horwood, L J

    2000-01-01

    This study examined associations between childhood circumstances, adolescent mental health and life events, and the development of suicidal behaviour in young people aged between 15 and 21 years. Data were gathered over the course of a 21-year longitudinal study of a birth cohort of 1265 children born in New Zealand. The measures collected included: (1) patterns of suicidal behaviour (ideation, attempt) (15-21 years); (2) social background, family functioning, parental and individual adjustment during childhood (0-16 years); and (3) time dynamics of mental health and stressful life events during adolescence and early adulthood (15-21 years). By the age of 21 years, 28.8% of the sample reported having thought about killing themselves and 7.5% reported having made a suicide attempt. The childhood profile of those at greatest risk of suicidal behaviour was that of a young person reared in a family environment characterized by socio-economic adversity, marital disruption, poor parent-child attachment and exposure to sexual abuse, and who as a young adolescent showed high rates of neuroticism and novelty seeking. With the exception of the socio-economic and personality measures, the effects of childhood factors were largely mediated by mental health problems and exposure to stressful life events during adolescence and early adulthood. Mental health problems including depression, anxiety disorders, substance use disorder, and to some extent conduct disorder, in addition to exposure to adverse life events, were significantly associated with the onset of suicidal behaviours. Findings support a life course model of the aetiology of suicidal behaviour in which risk of developing suicidal behaviour depends on accumulative exposure to a series of social, family, personality and mental health factors.

  8. Early life exposure to permethrin: a progressive animal model of Parkinson's disease.

    Science.gov (United States)

    Nasuti, Cinzia; Brunori, Gloria; Eusepi, Piera; Marinelli, Lisa; Ciccocioppo, Roberto; Gabbianelli, Rosita

    Oxidative stress, alpha-synuclein changes, mitochondrial complex I defects and dopamine loss, observed in the striatum of rats exposed to the pesticide permethrin in early life, could represent neuropathological hallmarks of Parkinson's disease (PD). Nevertheless, an animal model of PD should also fulfill criteria of face and predictive validities. This study was designed to: 1) verify dopaminergic status in the striatum and substantia nigra pars compacta; 2) recognize non-motor symptoms; 3) investigate the time-course development of motor disabilities; 4) assess L-Dopa effectiveness on motor symptoms in rats previously exposed to permethrin in early life. The permethrin-treated group received 34mg/kg daily of permethrin from postnatal day 6 to 21, whereas the age-matched control group was administered with the vehicle only. At adolescent age, the permethrin-treated group showed decreased levels of dopamine in the striatum, loss of dopaminergic neurons in the substantia nigra pars compacta and cognitive impairments. Motor coordination defects appeared at adult age (150days old) in permethrin-treated rats on rotarod and beam walking tasks, whereas no differences between the treated and control groups were detected on the foot print task. Predictive validity was evaluated by testing the ability of L-Dopa (5, 10 or 15mg/kg, os) to restore the postural instability in permethrin-treated rats (150days old) tested in a beam walking task. The results revealed full reversal of motor deficits starting from 10mg/kg of L-Dopa. The overall results indicate that this animal model replicates the progressive, time-dependent nature of the neurodegenerative process in Parkinson's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Years of life lost due to external radiation exposure

    International Nuclear Information System (INIS)

    Raicevic, J.J.; Merkle, J.M.; Ehrhardt, J.; Ninkovic, M.M.

    2002-01-01

    A new approach for calculation of the years of life lost per excess death (YLL) due to stochastic health effects is applied to external exposure pathways. The short-term external exposures are due to the passage of radioactive cloud (CL) and due to the skin and clothes contamination (SK). The long-term external exposure is the one from the radioactive material deposited on ground (GR). Three nuclides, 131 I , 137 Cs and 239 Pu with extremely wide range of the half-life are considered to examine its possible influence on the calculated YLL values. For each of these nuclides, the YLL is found as a decreasing function of the age at exposure and presented graphically in this paper. Another negative correlation is established between the fully averaged YLL and the duration of the nuclide's half-life has been found for protracted exposure (GR). On the other hand, the YLL for the short-term external exposures (CL and SK) practically does not depend on the nuclide's half-life. In addition, a weak YLL dependence of the dose was commented. (author)

  10. Early Life Stress, Depression And Parkinson's Disease: A New Approach.

    Science.gov (United States)

    Dallé, Ernest; Mabandla, Musa V

    2018-03-19

    This review aims to shed light on the relationship that involves exposure to early life stress, depression and Parkinson's disease (PD). A systematic literature search was conducted in Pubmed, MEDLINE, EBSCOHost and Google Scholar and relevant data were submitted to a meta-analysis . Early life stress may contribute to the development of depression and patients with depression are at risk of developing PD later in life. Depression is a common non-motor symptom preceding motor symptoms in PD. Stimulation of regions contiguous to the substantia nigra as well as dopamine (DA) agonists have been shown to be able to attenuate depression. Therefore, since PD causes depletion of dopaminergic neurons in the substantia nigra, depression, rather than being just a simple mood disorder, may be part of the pathophysiological process that leads to PD. It is plausible that the mesocortical and mesolimbic dopaminergic pathways that mediate mood, emotion, and/or cognitive function may also play a key role in depression associated with PD. Here, we propose that a medication designed to address a deficiency in serotonin is more likely to influence motor symptoms of PD associated with depression. This review highlights the effects of an antidepressant, Fluvoxamine maleate, in an animal model that combines depressive-like symptoms and Parkinsonism.

  11. No consistent effects of prenatal or neonatal exposure to Spanish flu on late-life mortality in 24 developed countries

    Directory of Open Access Journals (Sweden)

    Alan Cohen

    2010-04-01

    Full Text Available We test the effects of early life exposure to disease on later health by looking for differences in late-life mortality in cohorts born around the 1918-1919 flu pandemic using data from the Human Mortality Database for 24 countries. After controlling for age, period, and sex effects, residual mortality rates did not differ systematically for flu cohorts relative to surrounding cohorts. We calculate at most a 20-day reduction in life expectancy for flu cohorts; likely values are much smaller. Estimates of influenza incidence during the pandemic suggest that exposure was high enough for this to be a robust negative result.

  12. The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats.

    Science.gov (United States)

    Maniam, Jayanthi; Antoniadis, Christopher P; Morris, Margaret J

    2015-01-01

    Early-life stress affects metabolic outcomes and choice of diet influences the development of metabolic disease. Here we tested the hypothesis that chronic sugar intake exacerbates metabolic deficits induced by early-life stress. Early-life stress was induced in Sprague-Dawley rats using limited nesting material in early lactation (LN, postnatal days 2-9), and siblings were given chow alone or with additional sucrose post weaning (n = 9-17 per group). Female control and LN siblings had unlimited access to either chow plus water, or chow and water plus 25% sucrose solution (Sucrose), from 3-15 weeks of age. Weekly body weight and food intake were measured. Glucose and insulin tolerance were tested at 13 and 14 weeks of age, respectively. Rats were killed at 15 weeks. Hepatic triglyceride and markers of lipid synthesis - fatty acid synthase, acetyl-CoA carboxylase alpha and oxidation - and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) were examined. Mediators of hepatic glucocorticoid metabolism, specifically 11-beta hydroxysteroid dehydrogenase-1 (11βHSD-1), 5-α reductase, and glucocorticoid and mineralocorticoid receptor mRNAs were also measured. Sucrose increased caloric intake in both groups, but overall energy intake was not altered by LN exposure. LN exposure had no further impact on sucrose-induced glucose intolerance and increased plasma and liver triglycerides. Hepatic markers of fat synthesis and oxidation were concomitantly activated and 11βHSD-1 mRNA expression was increased by 53% in LN-Sucrose versus Con-Sucrose rats. Adiposity was increased by 26% in LN-Sucrose versus Con-Sucrose rats. Thus, LN exposure had minimal adverse metabolic effects despite high-sugar diet postweaning.

  13. Good daily habits during the early stages of life determine success throughout life

    Directory of Open Access Journals (Sweden)

    Jun Kohyama

    2016-07-01

    Full Text Available This paper assesses hypothesis that sufficient sleep duration and proper circadian rhythms during the early stages of life are indispensable to a successful life. Successful life was defined according to the famous cohort studies of Mischel's and Dunedin. To assess the hypothesis, neuronal elements presumably affecting early daily habits and successful life are reviewed. The effect of sufficient sleep duration and proper circadian rhythms during early stages of life on the development of the prefrontal cortex has been found to be the key issue to verify the hypothesis. Socioeconomic status is found to be another issue to be studied.

  14. Good daily habits during the early stages of life determine success throughout life.

    Science.gov (United States)

    Kohyama, Jun

    2016-01-01

    This paper assesses hypothesis that sufficient sleep duration and proper circadian rhythms during the early stages of life are indispensable to a successful life. Successful life was defined according to the famous cohort studies of Mischel's and Dunedin. To assess the hypothesis, neuronal elements presumably affecting early daily habits and successful life are reviewed. The effect of sufficient sleep duration and proper circadian rhythms during early stages of life on the development of the prefrontal cortex has been found to be the key issue to verify the hypothesis. Socioeconomic status is found to be another issue to be studied.

  15. Neuropeptides as mediators of the early-life impact on the brain; implications for alcohol use disorders

    Directory of Open Access Journals (Sweden)

    Ingrid eNylander

    2012-07-01

    Full Text Available The brain is constantly exposed to external and internal input and to function in an ever-changing environment we are dependent on processes that enable the brain to adapt to new stimuli. Exposure to postnatal environmental stimuli can interfere with vital adaption processes and cause long-term changes in physiological function and behaviour. Early-life alterations in brain function may result in impaired ability to adapt to new situations, in altered sensitivity to challenges later in life and thereby mediate risk or protection for psychopathology such as alcohol use disorders (AUD. In clinical research the studies of mechanisms, mediators and causal relation between early environmental factors and vulnerability to AUD are restricted and attempts are made to find valid animal models for studies of the early-life influence on the brain. This review focuses on rodent models and the effects of adverse and naturalistic conditions on peptide networks within the brain and pituitary gland. Importantly, the consequences of alcohol addiction are not discussed but rather neurobiological alterations that can cause risk consumption and vulnerability to addiction. The article reviews earlier results and includes new data with emphasis on endogenous opioid peptides but also oxytocin and vasopressin. These peptides are vital for developmental processes and it is hypothesized that early-life changes in peptide networks may interfere with neuronal processes and thereby contribute the individual vulnerability for AUD. The summarized results indicate a link between early-life rearing conditions, opioids and ethanol consumption and that the ethanol-induced effects and the treatment with opioid antagonists later in life are dependent on early-life experiences. Endogenous opioids are therefore of interest to further study in the early-life impact on individual differences in vulnerability to AUD and treatment outcome.

  16. DNA methylome changes by estradiol benzoate and bisphenol A links early-life environmental exposures to prostate cancer risk.

    Science.gov (United States)

    Cheong, Ana; Zhang, Xiang; Cheung, Yuk-Yin; Tang, Wan-Yee; Chen, Jing; Ye, Shu-Hua; Medvedovic, Mario; Leung, Yuet-Kin; Prins, Gail S; Ho, Shuk-Mei

    2016-09-01

    Developmental exposure to endocrine-disrupting chemicals (EDCs), 17β-estradiol-3-benzoate (EB) and bisphenol A (BPA), increases susceptibility to prostate cancer (PCa) in rodent models. Here, we used the methylated-CpG island recovery assay (MIRA)-assisted genomic tiling and CpG island arrays to identify treatment-associated methylome changes in the postnatal day (PND)90 dorsal prostate tissues of Sprague-Dawley rats neonatally (PND1, 3, and 5) treated with 25 µg/pup or 2,500 µg EB/kg body weight (BW) or 0.1 µg BPA/pup or 10 µg BPA/kg BW. We identified 111 EB-associated and 86 BPA-associated genes, with 20 in common, that have significant differentially methylated regions. Pathway analysis revealed cancer as the top common disease pathway. Bisulfite sequencing validated the differential methylation patterns observed by array analysis in 15 identified candidate genes. The methylation status of 7 (Pitx3, Wnt10b, Paqr4, Sox2, Chst14, Tpd52, Creb3l4) of these 15 genes exhibited an inverse correlation with gene expression in tissue samples. Cell-based assays, using 5-aza-cytidine-treated normal (NbE-1) and cancerous (AIT) rat prostate cells, added evidence of DNA methylation-mediated gene expression of 6 genes (exception: Paqr4). Functional connectivity of these genes was linked to embryonic stem cell pluripotency. Furthermore, clustering analyses using the dataset from The Cancer Genome Atlas revealed that expression of this set of 7 genes was associated with recurrence-free survival of PCa patients. In conclusion, our study reveals that gene-specific promoter methylation changes, resulting from early-life EDC exposure in the rat, may serve as predictive epigenetic biomarkers of PCa recurrence, and raises the possibility that such exposure may impact human disease.

  17. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

    Science.gov (United States)

    Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

    2014-01-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

  18. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar.

    Science.gov (United States)

    Duffy, T A; Iwanowicz, L R; McCormick, S D

    2014-07-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights

  19. Early life insults as determinants of chronic obstructive pulmonary disease in adult life

    DEFF Research Database (Denmark)

    Savran, Osman; Ulrik, Charlotte Suppli

    2018-01-01

    Background: Early life events may predispose to the development of chronic lung disease in adulthood. Aim: To provide an update on current knowledge of early nongenetic origins of COPD. Materials and methods: Systematic literature review was performed according to the Preferred Reporting Items...... in utero and early life is a risk factor for subsequent development of COPD. Furthermore, low birth weight, lower respiratory tract infections and asthma, including wheezy bronchitis, in childhood also seem to be important determinants for later development of COPD. Early life insults may, therefore...

  20. Early androgen exposure and human gender development.

    Science.gov (United States)

    Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

    2015-01-01

    During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

  1. Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

    Energy Technology Data Exchange (ETDEWEB)

    Snijders, Antoine M.; Langley, Sasha A.; Kim, Young-Mo; Brislawn, Colin J.; Noecker, Cecilia; Zink, Erika M.; Fansler, Sarah J.; Casey, Cameron P.; Miller, Darla R.; Huang, Yurong; Karpen, Gary H.; Celniker, Susan E.; Brown, James B.; Borenstein, Elhanan; Jansson, Janet K.; Metz, Thomas O.; Mao, Jian-Hua

    2016-11-28

    Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut.We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts themicrobiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.

  2. Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

    Science.gov (United States)

    Buckley, Harriet; Owen, Robert; Marin, Ana Campos; Lu, Yongtau; Eyles, Darryl; Lacroix, Damien; Reilly, Gwendolen C.; Skerry, Tim M.; Bishop, Nick J.

    2018-01-01

    There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals. PMID:29370213

  3. Relationship between mediation analysis and the structured life course approach

    Science.gov (United States)

    Howe, Laura D; Smith, Andrew D; Macdonald-Wallis, Corrie; Anderson, Emma L; Galobardes, Bruna; Lawlor, Debbie A; Ben-Shlomo, Yoav; Hardy, Rebecca; Cooper, Rachel; Tilling, Kate; Fraser, Abigail

    2016-01-01

    Abstract Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome). PMID:27681097

  4. Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

    Science.gov (United States)

    Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

    2017-10-05

    Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Chromium Toxicity Test for Fall Chinook Salmon (Oncorhynchus tshawytscha) Using Hanford Site Groundwater: Onsite Early Life-Stage Toxicity Evaluation

    International Nuclear Information System (INIS)

    Patton, Gregory W; Dauble, Dennis D; Chamness, Mickie A; Abernethy, Cary S; McKinstry, Craig A

    2001-01-01

    The objective of this study was to evaluate site-specific effects for early life-stage (eyed eggs to free swimming juveniles) fall chinook salmon that might be exposed to hexavalent chromium from Hanford groundwater sources. Our exposure conditions included hexavalent chromium obtained from Hanford groundwater wells near the Columbia River, Columbia River water as the diluent, and locally adapted populations of fall chinook salmon. This report describes both a 96-hr pretest using rainbow trout eggs and an early life-stage test beginning with chinook salmon eggs

  6. Early parental loss and depression history: associations with recent life stress in major depressive disorder.

    Science.gov (United States)

    Slavich, George M; Monroe, Scott M; Gotlib, Ian H

    2011-09-01

    Although exposure to early adversity and prior experiences with depression have both been associated with lower levels of precipitating life stress in depression, it is unclear whether these stress sensitization effects are similar for all types of stress or whether they are specific to stressors that may be particularly depressogenic, such as those involving interpersonal loss. To investigate this issue, we administered structured, interview-based measures of early adversity, depression history, and recent life stress to one hundred adults who were diagnosed with major depressive disorder. As predicted, individuals who experienced early parental loss or prolonged separation (i.e., lasting one year or longer) and persons with more lifetime episodes of depression became depressed following lower levels of life stress occurring in the etiologically-central time period of three months prior to onset of depression. Importantly, however, additional analyses revealed that these effects were unique to stressors involving interpersonal loss. These data highlight potential stressor-specific effects in stress sensitization and demonstrate for the first time that individuals exposed to early parental loss or separation, and persons with greater histories of MDD, may be selectively sensitized to stressors involving interpersonal loss. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Neurosurgery Elective for Preclinical Medical Students: Early Exposure and Changing Attitudes.

    Science.gov (United States)

    Zuckerman, Scott L; Mistry, Akshitkumar M; Hanif, Rimal; Chambless, Lola B; Neimat, Joseph S; Wellons, John C; Mocco, J; Sills, Allen K; McGirt, Matthew J; Thompson, Reid C

    2016-02-01

    Exposure to surgical subspecialties is limited during the preclinical years of medical school. To offset this limitation, the authors created a neurosurgery elective for first- and second-year medical students. The objective was to provide each student with early exposure to neurosurgery by combining clinical experience with faculty discussions about the academic and personal realities of a career in neurosurgery. From 2012 to 2013, the authors offered a neurosurgery elective course to first- and second-year medical students. Each class consisted of the following: 1) peer-reviewed article analysis; 2) student presentation; 3) faculty academic lecture; 4) faculty personal lecture with question and answer period. Thirty-five students were enrolled over a 2-year period. After completing the elective, students were more likely to: consider neurosurgery as a future career (P life to be higher (P life, and family-work balance, while not altering the students' views about the difficulty of training. Adopting a neurosurgery elective geared towards preclinical medical students can significantly change attitudes about the field of neurosurgery and has potential to increase interest in pursuing a career in neurosurgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms.

    Science.gov (United States)

    Yam, Kit-Yi; Naninck, Eva F G; Schmidt, Mathias V; Lucassen, Paul J; Korosi, Aniko

    2015-01-01

    Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.

  9. Sensitivity of shovelnose sturgeon (Scaphirhynchus platorynchus) and pallid sturgeon (S. albus) early life stages to 3,30,4,40,5-pentachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure

    Science.gov (United States)

    Buckler, Justin; Candrl, James S.; McKee, Michael J.; Papoulias, Diana M.; Tillitt, Donald E.; Galat, David L.

    2015-01-01

    Concern exists that polychlorinated biphenyls (PCBs) may be contributing to the current decline of shovelnose sturgeon (Scaphirhynchus platorynchus) and the US federally endangered pallid sturgeon (Scaphirhynchus albus). Waterborne exposures with newly fertilized eggs were used to assess developmental and morphological effects of 2 of the most potent aryl hydrocarbon receptor (AhR) agonists, 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on early life stage shovelnose and pallid sturgeon. No dose-related effects of PCB-126 were observed on percent development or hatch in either species at concentrations as high as 1711 ng/g egg. Effects of TCDD on percent development were not assessed in shovelnose sturgeon. However, percent development was not affected by TCDD in pallid sturgeon, and percent hatch was unaffected by TCDD doses as high as 60 ng/g egg to 81 ng/g egg in either species. Morphological pathologies such as yolk sac edema and craniofacial deformities were typical of AhR agonist exposure and were similar in both species. Calculated PCB-126 50% lethal dose (LD50, 95% fiducial limits) values were 196 ng/g egg (188–203 ng/g) for shovelnose and 159 ng/g egg (122–199 ng/g) for pallid sturgeon. Likewise, calculated TCDD LD50 values were 13 ng/g egg (11–15 ng/g) for shovelnose and 12 ng/g egg (10–14 ng/g) for pallid sturgeon. These LD50 values are among the highest recorded in early life stage fish, suggesting that early life stage Scaphirhynchus sturgeon may be comparatively insensitive to AhR agonists.

  10. Study of the biological effects of uranium exposure on zebra fish (D. rerio). Impact on life stages

    International Nuclear Information System (INIS)

    Bourrachot, St.

    2009-05-01

    This work is part of an ongoing project (ENVIRHOM) started at IRSN in 2000, which consists in studying the environmental effects of radioactive substances at chronic low level of exposure. In this general frame, our aim was two fold: (i) to identify sensitivity of different critical life stages of zebra fish (fish of fresh water frequently used for tests standards in ecotoxicology) to uranium exposure and (ii) to evaluate underlying mechanisms. Experiments were conducted with eggs, larvae and genitors exposed to uranium at environmentally relevant concentrations (from 20 to 500 μg/L) in order to study survival, hatching of eggs, growth of larvae and reproduction of genitors. Bio-markers of exposure (i.e. U bioaccumulation) and bio-markers of effects at molecular level (i.e. genotoxic effects, reproductive-toxicity) were also measured. Sensitivity of fish to uranium was dependent of the life stage of development with the early life stage being the most sensitive to U either directly or maternally exposed. It underlines the relevance of including pro-larval stages for toxicity assessments in fish. Moreover drastic effects of uranium on reproductive success and DNA damages in the germ cells foretell a strong impact on the population for low concentration of exposure (20 μg/L). As it is increasingly recognized that population-level effects of toxic substances are more relevant in terms of ecological risk assessment, this study points out the need to include different life stages of organisms in eco-toxicological studies, especially the sensitive early stages. Moreover, it appears, through the comparative study of the radiological effects or by another isotope of the uranium of stronger radioactivity ( 233 U or by an irradiation with 137 Cs), that the effects of the uranium are due to its chemo-toxicity. (author)

  11. Relationship between mediation analysis and the structured life course approach.

    Science.gov (United States)

    Howe, Laura D; Smith, Andrew D; Macdonald-Wallis, Corrie; Anderson, Emma L; Galobardes, Bruna; Lawlor, Debbie A; Ben-Shlomo, Yoav; Hardy, Rebecca; Cooper, Rachel; Tilling, Kate; Fraser, Abigail

    2016-08-01

    Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome). © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

  12. A Population-based Prospective Birth Cohort Study of Childhood Neurocognitive and Psychological Functioning in Healthy Survivors of Early-life Meningitis

    Science.gov (United States)

    Khandaker, Golam M.; Stochl, Jan; Zammit, Stanley; Lewis, Glyn; Jones, Peter B.

    2015-01-01

    PURPOSE To determine neurocognitive, educational and psychological functioning during childhood and early-adolescence among survivors of early-life meningitis who are apparently healthy. METHODS In the general population-based Avon Longitudinal Study of Parents and Children birth cohort, meningitis exposure was determined at age 18 months. The outcomes of IQ, short-term memory, working memory, reading and spelling abilities, psychological and behavioural problems, depressive and anxiety symptoms, and psychotic experiences at ages 9 to 13 years were compared between those exposed and unexposed to meningitis. Individuals with special educational needs were excluded. RESULTS By age 18 months, 67 out of 11,035 children were reported to have suffered from meningitis (0.61%). These children, compared with the unexposed, performed worse on all neurocognitive and educational measures; mean difference in total IQ 7.36 (95% CI 1.60-13.11). Meningitis was associated with higher depressive and anxiety symptoms (p=0.02), psychological and behavioural problems (p=0.09), and increased risk of psychotic experiences; risk ratio 2.22 (95% CI 1.12-4.38). CONCLUSIONS Exposure to meningitis in the early-life is associated with neurocognitive, educational and psychological difficulties during childhood and early-adolescence among survivors who are apparently healthy. Therefore, focusing only on serious neurologic disabilities may underestimate the true impact of early-life meningitis. PMID:25794764

  13. A population-based prospective birth cohort study of childhood neurocognitive and psychological functioning in healthy survivors of early life meningitis.

    Science.gov (United States)

    Khandaker, Golam M; Stochl, Jan; Zammit, Stanley; Lewis, Glyn; Jones, Peter B

    2015-04-01

    To determine neurocognitive, educational, and psychological functioning during childhood and early adolescence among survivors of early life meningitis who are apparently healthy. In the general population-based Avon Longitudinal Study of Parents and Children birth cohort, meningitis exposure was determined at age of 18 months. The outcomes of intelligence quotient, short-term memory, working memory, reading and spelling abilities, psychological and behavioral problems, depressive and anxiety symptoms, and psychotic experiences at ages 9 to 13 years were compared between those exposed and unexposed to meningitis. Individuals with special educational needs were excluded. By age of 18 months, 67 of 11,035 children were reported to have suffered from meningitis (0.61%). These children, compared with the unexposed, performed worse on all neurocognitive and educational measures; mean difference in total intelligence quotient 7.36 (95% confidence interval, 1.60-13.11). Meningitis was associated with higher depressive and anxiety symptoms (P = .02), psychological and behavioral problems (P = .09), and increased risk of psychotic experiences; risk ratio 2.22 (95% confidence interval, 1.12-4.38). Exposure to meningitis in the early life is associated with neurocognitive, educational, and psychological difficulties during childhood and early adolescence among survivors who are apparently healthy. Therefore, focusing only on serious neurologic disabilities may underestimate the true impact of early life meningitis. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Persistent sexual dysfunction after early exposure to SSRIs

    DEFF Research Database (Denmark)

    Simonsen, Anders Lykkemark; Danborg, Pia Brandt; Gøtzsche, Peter Christian

    2016-01-01

    BACKGROUND: Sexual dysfunction is a common adverse effect of selective serotonin reuptake inhibitors (SSRIs) and there is a concern that the sexual harms might persist after discontinuation of therapy. OBJECTIVE: To assess whether the use of SSRIs in animals can lead to persistent sexual...... dysfunction. METHODS: Systematic review of animal studies measuring sexual behaviour after end of treatment with SSRIs or serotonin norepinephrine reuptake inhibitors. DATA SOURCES: We searched PubMed and EMBASE. RESULTS: We included 14 studies. The general quality of the studies was poor. Only four studies.......74; 95% CI = 0.60-0.92) and no ejaculation behaviour (RR = 0.49, 95% CI = 0.24-1.00). CONCLUSION: Our results showed substantial and lasting effects on sexual behaviour in rats after exposure to an SSRI early in life on important sexual outcomes....

  15. Risk estimation of radiation exposure in early pregnancy

    International Nuclear Information System (INIS)

    Neumeister, K.; Waesser, S.

    1977-01-01

    The biomedical effects of radiation exposure (occupational, by X-ray diagnosis or examinations in nuclear medicine) to low doses on early pregnancy have been subject of a research work dealing with the dose level which, in case of exceeding, may lead to somatic damage (1.5 to 10 rem), and with the type of radiation injuries (malformations, functional disorder, cancer induction, increase in morbidity rate, genetic damage). A pilot study was the basis for the programme which will record such cases from all over the GDR. Within the scope of the health centre at the National Board of Nuclear Safety and Radiation Protection of the GDR, medical opinion on the interruption or preservation of pregnancy at its early stage, after exposure, was delivered in more than 50 cases. Exposure of the foetus was exactly determined. These children were re-investigated at the age of 1 to 3 years by applying pediatric and genetic examinations. The latter were based on clinical and biochemical methods as well as chromosome analyses. From these results, the risk of exposure in early pregnancy is estimated and adequate dose limits are suggested. In case these limits are exceeded, an interruption should be advised

  16. Osteoporosis in survivors of early life starvation.

    Science.gov (United States)

    Weisz, George M; Albury, William R

    2013-01-01

    The objective of this study was to provide evidence for the association of early life nutritional deprivation and adult osteoporosis, in order to suggest that a history of such deprivation may be an indicator of increased risk of osteoporosis in later life. The 'fetal programming' of a range of metabolic and cardiovascular disorders in adults was first proposed in the 1990s and more recently extended to disorders of bone metabolism. Localised famines during World War II left populations in whom the long-term effects of maternal, fetal and infantile nutritional deprivation were studied. These studies supported the original concept of 'fetal programming' but did not consider bone metabolism. The present paper offers clinical data from another cohort of World War II famine survivors - those from the Holocaust. The data presented here, specifically addressing the issue of osteoporosis, report on 11 Holocaust survivors in Australia (five females, six males) who were exposed to starvation in early life. The cases show, in addition to other metabolic disorders associated with early life starvation, various levels of osteoporosis, often with premature onset. The cohort studied is too small to support firm conclusions, but the evidence suggests that the risk of adult osteoporosis in both males and females is increased by severe starvation early in life - not just in the period from gestation to infancy but also in childhood and young adulthood. It is recommended that epidemiological research on this issue be undertaken, to assist planning for the future health needs of immigrants to Australia coming from famine affected backgrounds. Pending such research, it would be prudent for primary care health workers to be alert to the prima facie association between early life starvation and adult osteoporosis, and to take this factor into account along with other indicators when assessing a patient's risk of osteoporosis in later life.

  17. Early life factors and being overweight at 4 years of age among children in Malmö, Sweden

    Directory of Open Access Journals (Sweden)

    Lindström Martin

    2010-12-01

    Full Text Available Abstract Background Rising rates of obesity and overweight is an increasing public health problem all over the world. Recent research has shown the importance of early life factors in the development of child overweight. However, to the best of our knowledge there are no studies investigating the potential synergistic effect of early life factors and presence of parental overweight on the development of child overweight. Methods The study was population-based and cross-sectional. The study population consisted of children who visited the Child Health Care (CHC centers in Malmö for their 4-year health check during 2003-2008 and whose parents answered a self-administered questionnaire (n = 9009 children. Results The results showed that having overweight/obese parents was strongly associated with the child being overweight or obese. Furthermore, there was an association between unfavorable early life factors (i.e., mother smoking during pregnancy, presence of secondhand tobacco smoke early in life, high birth weight and the development of child overweight/obesity at four years of age, while breastfeeding seemed to have a protective role. For example, maternal smoking during pregnancy was associated with an odds ratio (OR of 1.47 (95% CI: 1.22, 1.76 for overweight and 2.31 (95% CI: 1.68, 3.17 for obesity. The results further showed synergistic effects between parental overweight and exposure to unfavourable early life factors in the development of child overweight. Conclusions The present study shows the importance of early life factors in the development of child overweight and obesity, and thus puts focus on the importance of early targeted interventions.

  18. Environmental exposure of Atlantic horseshoe crab (Limulus polyphemus) early life stages to essential trace elements.

    Science.gov (United States)

    Bakker, Aaron K; Dutton, Jessica; Sclafani, Matthew; Santangelo, Nicholas

    2016-12-01

    This study investigated the accumulation Co, Cu, Fe, Mn, Ni, Se, and Zn in Atlantic horseshoe crab (Limulus polyphemus) early life stages (egg, embryo and larvae) and compared the concentrations to the concentration of each element in sediment, pore water and overlying water for 5 sites across Long Island, NY. For the majority of the sites, all essential trace elements accumulated in the embryos and larvae. However, many of the embryos and larvae at specific sites presented different concentration patterns which had no apparent relationship with the local habitat sediment and water values. Generally, Cu, Fe, and Se sequentially increased from egg stage through larval stages for the majority of sites, while Co, Mn, and Ni only did for a few sites. Zinc also showed an increase across sites from embryo to larval stage, however was the only one to show a decrease in concentration from egg to embryo stage at all sites. Interestingly, Mn at Manhasset Bay presented embryo and larval stages to be 50 fold greater than all other sites while the egg stage showed similar values to other sites; this high degree of uptake could be due to a high concentration in the overlying water. All essential trace elements can be accumulated from the environment but greater concentrations may be influenced by abiotic factors and the predominant uptake route (aqueous versus diet) at each life stage. Future laboratory experiments are required to investigate factors that influence essential trace element accumulation and loss in horseshoe crab early life stages. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Metabolomics and transcriptomics reveal the toxicity of difenoconazole to the early life stages of zebrafish (Danio rerio).

    Science.gov (United States)

    Teng, Miaomiao; Zhu, Wentao; Wang, Dezhen; Qi, Suzhen; Wang, Yao; Yan, Jin; Dong, Kai; Zheng, Mingqi; Wang, Chengju

    2018-01-01

    Difenoconazole is widely used to inhibit the growth of fungi, but its residue in the water environment may threaten ecosystem and human health. Here, 1 H nuclear magnetic resonance (NMR) and LC-MS/MS based metabolomics and transcriptomics approaches were used to assess the response of zebrafish to difenoconazole exposure. Early life stages of zebrafish were exposed to difenoconazole at environmentally relevant concentrations for 168h. Their comparison with the control group suggested an adverse development and disturbance of steroid hormones and VTG. KEGG pathway analysis identified five biological processes on the basis of differentially expressed genes (DEGs), as well as altered metabolites and amino acids in zebrafish following difenoconazole exposure. These affected processes included energy metabolism, amino acids metabolism, lipid metabolism, nucleotide metabolism, and an immune-related pathway. Collectively, these results bring us closer to an incremental understanding of the toxic effects of difenoconazole on zebrafish in its early development, and lend support to the continued use of the early life stages of zebrafish as a classical model to evaluate underlying environmental risks of xenobiotics in aquatic organisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Future Directions in the Study of Early-Life Stress and Physical and Emotional Health: Implications of the Neuroimmune Network Hypothesis.

    Science.gov (United States)

    Hostinar, Camelia E; Nusslock, Robin; Miller, Gregory E

    2018-01-01

    Early-life stress is associated with increased vulnerability to physical and emotional health problems across the lifespan. The recently developed neuroimmune network hypothesis proposes that one of the underlying mechanisms for these associations is that early-life stress amplifies bidirectional crosstalk between the brain and the immune system, contributing to several mental and physical health conditions that have inflammatory underpinnings, such as depression and coronary heart disease. Neuroimmune crosstalk is thought to perpetuate inflammation and neural alterations linked to early-life stress exposure, and also foster behaviors that can further compromise health, such as smoking, drug abuse and consumption of high-fat diets. The goal of the present review is to briefly summarize the neuroimmune network hypothesis and use it as a starting point for generating new questions about the role of early-life stress in establishing a dysregulated relationship between neural and immune signaling, with consequences for lifespan physical and emotional health. Specifically, we aim to discuss implications and future directions for theory and empirical research on early-life stress, as well as for interventions that may improve the health and well-being of children and adolescents living in adverse conditions.

  1. Lethal toxicity of industrial chemicals to early life stages of Tilapia guineensis.

    Science.gov (United States)

    Ezemonye, L I N; Ogeleka, D F; Okieimen, F E

    2008-08-30

    The toxic effects of industrial chemicals on three early life stages of an economically important fish, Tilapia guineensis were investigated using the Organisation for Economic Cooperation and Development (OECD) # 203 recommended semi-static renewal bioassay. The assessment was necessary for the uncontrollable disposal of Neatex (liquid detergent) and Norust CR 486 (corrosion inhibitor) into the Niger Delta environment of Nigeria. The estimated 96-h LC(50) for 7-, 14- and 28-day-old fish in Norust CR 486 exposure was considered "more toxic" than Neatex in all life stages and was dependent on species age, exposure duration and environment. In the fresh water test, for Neatex and Norust CR 486 exposures for day 7, 14 and 28, the 96-h LC50 were 8.79, 17.10 and 82.42 mg/l and 5.55, 13.58 and 20.21 mg/l, respectively. In the brackish test, 15.42 and 46.52 mg/l, not determined (ND) and 7.35, 13.95 and 24.50mg/l were obtained. Differential toxicity was observed in the fresh and brackish water fish for the two chemicals and controls at pchemicals provides a rationale for regulatory surveillance and monitoring of both chemicals in the fragile Niger Delta environment.

  2. Early-life residential exposure to soil components in rural areas and childhood respiratory health and allergy.

    Science.gov (United States)

    Devereux, Graham; Tagiyeva, Nara; Turner, Stephen W; Ayres, Jon G; Seaton, Anthony; Hudson, Gordon; Hough, Rupert L; Campbell, Colin D; Shand, Charles A

    2014-01-01

    The increase in asthma and allergies has been attributed to declining exposure to environmental microorganisms. The main source of these is soil, the composition of which varies geographically and which is a major component (40-45%) of household dust. Our hypothesis-generating study aimed to investigate associations between soil components, respiratory health and allergy in a Scottish birth cohort. The cohort was recruited in utero in 1997/8, and followed up at one, two and five years for the development of wheezing, asthma and eczema. Lung function, exhaled nitric oxide and allergic sensitization were measured at age five in a subset. The Scottish Soils Database held at The James Hutton Institute was linked to the birth cohort data by the residential postcode at birth and five years. The soil database contained information on size separates, organic matter concentration, pH and a range of inorganic elements. Soil and clinical outcome data were available for 869, 790 and 727 children at one, two and five years. Three hundred and fifty nine (35%) of children had the same address at birth and five years. No associations were found between childhood outcomes and soil content in the residential area at age five. The soil silt content (2-20 μm particle size) of the residential area at birth was associated with childhood wheeze (adjusted OR 1.20, 95% CI [1.05; 1.37]), wheeze without a cold (1.41 [1.18; 1.69]), doctor-diagnosed asthma (1.54 [1.04; 2.28]), lung function (FEV1: beta -0.025 [-0.047;-0.001]) and airway inflammation (FENO: beta 0.15 [0.03; 0.27]) at age five, but not with allergic status or eczema. Whilst residual confounding is the most likely explanation for the associations reported, the results of this study lead us to hypothesise that early life exposure to residential soil silt may adversely influence childhood respiratory health, possibly because of the organic components of silt. © 2013 Elsevier B.V. All rights reserved.

  3. Family poverty over the early life course and recurrent adolescent and young adult anxiety and depression: a longitudinal study.

    Science.gov (United States)

    Najman, Jake M; Hayatbakhsh, Mohammad R; Clavarino, Alexandra; Bor, William; O'Callaghan, Michael J; Williams, Gail M

    2010-09-01

    We determined whether exposure to family poverty over a child's early life course predicts adolescent and young adult anxiety and depression. We used a birth cohort study of a sample of women in Brisbane, Australia, who were recruited in early pregnancy and whose children were followed up on at ages 14 and 21 years. Some 2609 mothers and adolescents provided usable data at the 14- and 21-year follow-ups. After adjustment for poverty at other phases, poverty at the 14-year follow-up was the strongest predictor of adolescent and young adult anxiety and depression. The more frequently the child was exposed to poverty, the greater was the risk of that individual being anxious and depressed at both the 14- and 21-year follow-ups. Family poverty predicts higher rates of adolescent and young adult anxiety and depression. Increased frequency of child exposure to poverty is a consistent predictor of adolescent and young adult anxiety and depression. Repeated experiences of poverty over a child's early life course are associated with increased levels of poor mental health.

  4. Perinatal BPA Exposure Induces Hyperglycemia, Oxidative Stress and Decreased Adiponectin Production in Later Life of Male Rat Offspring

    Directory of Open Access Journals (Sweden)

    Shunzhe Song

    2014-04-01

    Full Text Available The main object of the present study was to explore the effect of perinatal bisphenol A (BPA exposure on glucose metabolism in early and later life of male rat offspring, and to establish the potential mechanism of BPA-induced dysglycemia. Pregnant rats were treated with either vehicle or BPA by drinking water at concentrations of 1 and 10 µg/mL BPA from gestation day 6 through the end of lactation. We measured the levels of fasting serum glucose, insulin, adiponectin and parameters of oxidative stress on postnatal day (PND 50 and PND100 in male offspring, and adiponectin mRNA and protein expression in adipose tissue were also examined. Our results showed that perinatal exposure to 1 or 10 µg/mL BPA induced hyperglycemia with insulin resistance on PND100, but only 10 µg/mL BPA exposure had similar effects as early as PND50. In addition, increased oxidative stress and decreased adiponectin production were also observed in BPA exposed male offspring. Our findings indicated that perinatal exposure to BPA resulted in abnormal glucose metabolism in later life of male offspring, with an earlier and more exacerbated effect at higher doses. Down-regulated expression of adiponectin gene and increased oxidative stress induced by BPA may be associated with insulin resistance.

  5. Modifications of glucocorticoid receptors mRNA expression in the hypothalamic-pituitary-adrenal axis in response to early-life stress in female Japanese quail.

    Science.gov (United States)

    Zimmer, C; Spencer, K A

    2014-12-01

    Stress exposure during early-life development can programme individual brain and physiology. The hypothalamic-pituitary-adrenal (HPA) axis is one of the primary targets of this programming, which is generally associated with a hyperactive HPA axis, indicative of a reduced negative-feedback. This reduced feedback efficiency usually results from a reduced level of the glucocorticoid receptor (GR) and/or the mineralocorticoid receptor (MR) within the HPA axis. However, a few studies have shown that early-life stress exposure results in an attenuated physiological stress response, suggesting an enhance feedback efficiency. In the present study, we aimed to determine whether early-life stress had long-term consequences on GR and MR levels in quail and whether the effects on the physiological response to acute stress observed in prenatally stressed individuals were underpinned by changes in GR and/or MR levels in one or more HPA axis components. We determined GR and MR mRNA expression in the hippocampus, hypothalamus and pituitary gland in quail exposed to elevated corticosterone during prenatal development, postnatal development, or both, and in control individuals exposed to none of the stressors. We showed that prenatal stress increased the GR:MR ratio in the hippocampus, GR and MR expression in the hypothalamus and GR expression in the pituitary gland. Postnatal stress resulted in a reduced MR expression in the hippocampus. Both early-life treatments permanently affected the expression of both receptor types in HPA axis regions. The effects of prenatal stress are in accordance with a more efficient negative-feedback within the HPA axis and thus can explain the attenuated stress response observed in these birds. Therefore, these changes in receptor density or number as a consequence of early-life stress exposure might be the mechanism that allows an adaptive response to later-life stressful conditions. © 2014 The Authors. Journal of Neuroendocrinology published by

  6. Effects of early life factors on the health and quality of life of older adults.

    Science.gov (United States)

    Yilmaz, Fikriye; N Tekin, Rukiye

    2018-01-01

    Few studies on the effects of early life factors on the health and quality of life of adults have been conducted in Turkey. We aimed to investigate the effects of early life factors on the health and quality of life of older adults. We administered a questionnaire to 350 adults, aged 50-89 years, living in Cankaya, Ankara. The questionnaire covered sociodemographic characteristics, early life characteristics, health status, and the World Health Organization Quality of Life-Ageing scale. Data were analyzed using χ 2 tests, independent samples t-tests, one-way anova, and binary logistic regression analysis. The analyses showed that the most important risk factors for chronic disease were being ≥65 years (odds ratio (OR) = 2.34), having a chronic health problem before 18 years of age (OR = 2.48), experiencing prolonged hospitalization or bed rest before 18 years of age (OR = 2.65), and experiencing parental unconcern during early life (OR = 2.13) (P quality of life (P life factors are among the important determinants of the health and quality of life of older adults in Turkey. © 2017 Japanese Psychogeriatric Society.

  7. Early-life sugar consumption has long-term negative effects on memory function in male rats.

    Science.gov (United States)

    Noble, Emily E; Hsu, Ted M; Liang, Joanna; Kanoski, Scott E

    2017-09-25

    Added dietary sugars contribute substantially to the diet of children and adolescents in the USA, and recent evidence suggests that consuming sugar-sweetened beverages (SSBs) during early life has deleterious effects on hippocampal-dependent memory function. Here, we test whether the effects of early-life sugar consumption on hippocampal function persist into adulthood when access to sugar is restricted to the juvenile/adolescent phase of development. Male rats were given ad libitum access to an 11% weight-by-volume sugar solution (made with high fructose corn syrup-55) throughout the adolescent phase of development (post-natal day (PN) 26-56). The control group received a second bottle of water instead, and both groups received ad libitum standard laboratory chow and water access throughout the study. At PN 56 sugar solutions were removed and at PN 175 rats were subjected to behavioral testing for hippocampal-dependent episodic contextual memory in the novel object in context (NOIC) task, for anxiety-like behavior in the Zero maze, and were given an intraperitoneal glucose tolerance test. Early-life exposure to SSBs conferred long-lasting impairments in hippocampal-dependent memory function later in life- yet had no effect on body weight, anxiety-like behavior, or glucose tolerance. A second experiment demonstrated that NOIC performance was impaired at PN 175 even when SSB access was limited to 2 hours daily from PN 26-56. Our data suggest that even modest SSB consumption throughout early life may have long-term negative consequences on memory function during adulthood.

  8. Sex differences in depression-like behavior after nerve injury are associated with differential changes in brain-derived neurotrophic factor levels in mice subjected to early life stress.

    Science.gov (United States)

    Nishinaka, Takashi; Kinoshita, Megumi; Nakamoto, Kazuo; Tokuyama, Shogo

    2015-04-10

    We recently demonstrated that exposure to early life stress exacerbates nerve injury-induced thermal and mechanical hypersensitivity in adult male and female mice. Accumulating evidence suggests that chronic pain causes emotional dysfunction, such as anxiety and depression. In the present study, we investigated the impact of early life stress on depression-like behavior after nerve injury in mice. In addition, we examined the expression of brain-derived neurotrophic factor (BDNF), which is known to be involved in the pathogenesis of depression. Early life stress was induced by maternal separation between 2 and 3 weeks of age combined with social isolation after weaning (MSSI). At 9 weeks of age, the sciatic nerve was partially ligated to elicit neuropathic pain. Depression-like behavior was evaluated using the forced swim test at 12 weeks of age. Tissue samples from different regions of the brain were collected at the end of maternal separation (3 weeks of age) or after the forced swim test (12 weeks of age). At 12 weeks of age, immobility time in the forced swim test was increased only in MSSI-stressed female mice with nerve injury. BDNF expression was increased in male, but not female, MSSI-stressed mice at 3 weeks of age. However, MSSI stress did not impact BDNF expression in male or female mice at 12 weeks of age. Our findings suggest that exposure to early life stress exacerbates emotional dysfunction induced by neuropathic pain in a sex-dependent manner. Changes in BDNF expression after early life stress may be associated with neuropathic pain-induced depression-like behavior in adulthood. Furthermore, sex differences in BDNF expression after exposure to early life stress may contribute to sex-specific susceptibility to neuropathic pain-induced emotional dysfunction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Early Sign Language Exposure and Cochlear Implantation Benefits.

    Science.gov (United States)

    Geers, Ann E; Mitchell, Christine M; Warner-Czyz, Andrea; Wang, Nae-Yuh; Eisenberg, Laurie S

    2017-07-01

    Most children with hearing loss who receive cochlear implants (CI) learn spoken language, and parents must choose early on whether to use sign language to accompany speech at home. We address whether parents' use of sign language before and after CI positively influences auditory-only speech recognition, speech intelligibility, spoken language, and reading outcomes. Three groups of children with CIs from a nationwide database who differed in the duration of early sign language exposure provided in their homes were compared in their progress through elementary grades. The groups did not differ in demographic, auditory, or linguistic characteristics before implantation. Children without early sign language exposure achieved better speech recognition skills over the first 3 years postimplant and exhibited a statistically significant advantage in spoken language and reading near the end of elementary grades over children exposed to sign language. Over 70% of children without sign language exposure achieved age-appropriate spoken language compared with only 39% of those exposed for 3 or more years. Early speech perception predicted speech intelligibility in middle elementary grades. Children without sign language exposure produced speech that was more intelligible (mean = 70%) than those exposed to sign language (mean = 51%). This study provides the most compelling support yet available in CI literature for the benefits of spoken language input for promoting verbal development in children implanted by 3 years of age. Contrary to earlier published assertions, there was no advantage to parents' use of sign language either before or after CI. Copyright © 2017 by the American Academy of Pediatrics.

  10. Chemical defense of early life stages of benthic marine invertebrates.

    Science.gov (United States)

    Lindquist, Niels

    2002-10-01

    Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.

  11. Early life stress affects mortality rate more than social behavior, gene expression or oxidative damage in honey bee workers.

    Science.gov (United States)

    Rueppell, Olav; Yousefi, Babak; Collazo, Juan; Smith, Daniel

    2017-04-01

    Early life stressors can affect aging and life expectancy in positive or negative ways. Individuals can adjust their behavior and molecular physiology based on early life experiences but relatively few studies have connected such mechanisms to demographic patterns in social organisms. Sociality buffers individuals from environmental influences and it is unclear how much early life stress affects later life history. Workers of the honey bee (Apis mellifera L.) were exposed to two stressors, Varroa parasitism and Paraquat exposure, early in life. Consequences were measured at the molecular, behavioral, and demographic level. While treatments did not significantly affect levels of oxidative damage, expression of select genes, and titers of the common deformed wing virus, most of these measures were affected by age. Some of the age effects, such as declining levels of deformed wing virus and oxidative damage, were opposite to our predictions but may be explained by demographic selection. Further analyses suggested some influences of worker behavior on mortality and indicated weak treatment effects on behavior. The latter effects were inconsistent among the two experiments. However, mortality rate was consistently reduced by Varroa mite stress during development. Thus, mortality was more responsive to early life stress than our other response variables. The lack of treatment effects on these measures may be due to the social organization of honey bees that buffers the individual from the impact of stressful developmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Pathways of Association from Stress to Obesity in Early Childhood.

    Science.gov (United States)

    Miller, Alison L; Lumeng, Julie C

    2018-04-14

    The objective of this study is to critically review the literature on early life stress in relation to obesity in humans, including the multiple biological and behavioral mechanisms through which early life stress exposure (birth to the age of 5 years) may associate with obesity risk during childhood. A review of the literature was conducted to identify studies on associations between early childhood stress and risk for obesity and the mechanisms of association. Multiple databases (PubMed, PsycInfo, Google Scholar) were used in the search as well as a "snowball" search strategy. All study designs were included. Early life stress and adverse childhood experiences are associated with obesity and overweight in adults. Evidence is less consistent in children. Studies vary in the nature of the stress examined (e.g., chronic vs. acute), sample characteristics, and study designs. Longitudinal studies are needed, as the effects of early life stress exposure may not emerge until later in the life-span. Early life stress exposure is associated with biological and behavioral pathways that may increase risk for childhood obesity. There is evidence that early life stress is associated with multiple biological and behavioral pathways in children that may increase risk for later obesity. Little work has detailed the interconnections among these mechanisms across development or identified potential moderators of the association. Mapping the mechanisms connecting early life stress exposure to obesity risk in young children longitudinally should be a priority for obesity researchers. Recommendations for developmentally sensitive approaches to research that can inform obesity prevention strategies are presented. © 2018 The Obesity Society.

  13. Effects of tributyltin on early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes).

    Science.gov (United States)

    Horie, Yoshifumi; Yamagishi, Takahiro; Shintaku, Yoko; Iguchi, Taisen; Tatarazako, Norihisa

    2018-07-01

    Tributyltin, an organotin compound, was used worldwide as an antifouling agent in aquatic environments and there has been much concern about the toxicological and ecotoxicological properties of organotin compounds. Even though it has been prohibited worldwide, tributyltin is still detected at low concentrations in aquatic environments. Here we investigated the effects of tributyltin on the early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes). In adults, exposure to tributyltin at 3.82 μg/L suppressed fecundity and fertility and increased mortality. At 10.48 μg/L all medaka died by the sixth day of exposure. Exposure to tributyltin during early life-stages induced no significant differences in mortality or embryonic development, but growth was suppressed in groups exposed to 0.13 and 0.68 μg/L. Furthermore, there was no abnormal gonadal development in Japanese medaka exposed to tributyltin. These results provide evidence of the negative effects of tributyltin on reproduction in a teleost fish. Tributyltin did not affect gonadal sex differentiation in Japanese medaka, but fecundity and fertility were suppressed, although it is not clear whether this suppression resulted from the endocrine-disrupting action of tributyltin or its toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

    Science.gov (United States)

    Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M.; Bindels, Laure B.; Cambier, Emmanuel; Ben-Amram, Hila; Koren, Omry; Forsythe, Paul; Bienenstock, John

    2017-01-01

    There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria. PMID:28375200

  15. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress

    NARCIS (Netherlands)

    Marit Arp, J; Ter Horst, Judith P; Loi, Manila; den Blaauwen, Jan; Bangert, Eline; Fernández, Guillén; Joëls, Marian; Oitzl, Melly S; Krugers, Harm

    2016-01-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal

  16. Maternal separation with early weaning: a novel mouse model of early life neglect

    Directory of Open Access Journals (Sweden)

    Elwafi Hani M

    2010-09-01

    Full Text Available Abstract Background Childhood adversity is associated with increased risk for mood, anxiety, impulse control, and substance disorders. Although genetic and environmental factors contribute to the development of such disorders, the neurobiological mechanisms involved are poorly understood. A reliable mouse model of early life adversity leading to lasting behavioral changes would facilitate progress in elucidating the molecular mechanisms underlying these adverse effects. Maternal separation is a commonly used model of early life neglect, but has led to inconsistent results in the mouse. Results In an effort to develop a mouse model of early life neglect with long-lasting behavioral effects in C57BL/6 mice, we designed a new maternal separation paradigm that we call Maternal Separation with Early Weaning (MSEW. We tested the effects of MSEW on C57BL/6 mice as well as the genetically distinct DBA/2 strain and found significant MSEW effects on several behavioral tasks (i.e., the open field, elevated plus maze, and forced swim test when assessed more than two months following the MSEW procedure. Our findings are consistent with MSEW causing effects within multiple behavioral domains in both strains, and suggest increased anxiety, hyperactivity, and behavioral despair in the MSEW offspring. Analysis of pup weights and metabolic parameters showed no evidence for malnutrition in the MSEW pups. Additionally, strain differences in many of the behavioral tests suggest a role for genetic factors in the response to early life neglect. Conclusions These results suggest that MSEW may serve as a useful model to examine the complex behavioral abnormalities often apparent in individuals with histories of early life neglect, and may lead to greater understanding of these later life outcomes and offer insight into novel therapeutic strategies.

  17. NR2B subunit-dependent long-term potentiation enhancement in the rat cortical auditory system in vivo following masking of patterned auditory input by white noise exposure during early postnatal life.

    Science.gov (United States)

    Hogsden, Jennifer L; Dringenberg, Hans C

    2009-08-01

    The composition of N-methyl-D-aspartate (NMDA) receptor subunits influences the degree of synaptic plasticity expressed during development and into adulthood. Here, we show that theta-burst stimulation of the medial geniculate nucleus reliably induced NMDA receptor-dependent long-term potentiation (LTP) of field postsynaptic potentials recorded in the primary auditory cortex (A1) of urethane-anesthetized rats. Furthermore, substantially greater levels of LTP were elicited in juvenile animals (30-37 days old; approximately 55% maximal potentiation) than in adult animals (approximately 30% potentiation). Masking patterned sound via continuous white noise exposure during early postnatal life (from postnatal day 5 to postnatal day 50-60) resulted in enhanced, juvenile-like levels of LTP (approximately 70% maximal potentiation) relative to age-matched controls reared in unaltered acoustic environments (approximately 30%). Rats reared in white noise and then placed in unaltered acoustic environments for 40-50 days showed levels of LTP comparable to those of adult controls, indicating that white noise rearing results in a form of developmental arrest that can be overcome by subsequent patterned sound exposure. We explored the mechanisms mediating white noise-induced plasticity enhancements by local NR2B subunit antagonist application in A1. NR2B subunit antagonists (Ro 25-6981 or ifenprodil) completely reversed white noise-induced LTP enhancement at concentrations that did not affect LTP in adult or age-matched controls. We conclude that white noise exposure during early postnatal life results in the maintenance of juvenile-like, higher levels of plasticity in A1, an effect that appears to be critically dependent on NR2B subunit activation.

  18. Relationship of early-life trauma, war-related trauma, personality traits, and PTSD symptom severity: a retrospective study on female civilian victims of war

    Directory of Open Access Journals (Sweden)

    Aleksandra Stevanović

    2016-04-01

    Full Text Available Background: Consequences of war-related traumatisation have mostly been investigated in military and predominant male populations, while research on female civilian victims of war has been neglected. Furthermore, research of post-war posttraumatic stress disorder (PTSD in women has rarely included early-life trauma in their prediction models, so the contribution of trauma in childhood and early youth is still unexplored. Objective: To examine the relationship of early-life trauma, war-related trauma, personality traits, and symptoms of posttraumatic stress among female civilian victims of the recent war in Croatia. Method: The cross-sectional study included 394 participants, 293 war-traumatised adult women civilians, and 101 women without war-related trauma. Participants were recruited using the snowball sampling method. The applied instruments included the Clinician-Administrated PTSD Scale (CAPS, the NEO Personality Inventory-Revised (NEO-PI-R, the War Stressors Assessment Questionnaire (WSAQ, and the Early Trauma Inventory Self Report-Short Form (ETISR-SF. A hierarchical multiple regression analysis was performed to assess the prediction model of PTSD symptom severity measured by CAPS score for current PTSD. Results: The prevalence of current PTSD (CAPS cut-off score=65 in this cohort was 20.7%. The regression model that included age, early-life trauma, war-related trauma, neuroticism, and extraversion as statistically significant predictors explained 45.8% of variance in PTSD symptoms. Conclusions: Older age, exposure to early-life trauma, exposure to war-related traumatic events, high neuroticism, and low extraversion are independent factors associated with higher level of PTSD symptoms among women civilian victims of war.

  19. Prenatal and Perinatal Determinants of Lung Health and Disease in Early Life: A National Heart, Lung, and Blood Institute Workshop Report.

    Science.gov (United States)

    Manuck, Tracy A; Levy, Philip T; Gyamfi-Bannerman, Cynthia; Jobe, Alan H; Blaisdell, Carol J

    2016-05-02

    Human lung growth and development begins with preconception exposures and continues through conception and childhood into early adulthood. Numerous environmental exposures (both positive and negative) can affect lung health and disease throughout life. Infant lung health correlates with adult lung function, but significant knowledge gaps exist regarding the influence of preconception, perinatal, and postnatal exposures on general lung health throughout life. On October 1 and 2, 2015, the National Heart, Lung, and Blood Institute convened a group of extramural investigators to develop their recommendations for the direction(s) for future research in prenatal and perinatal determinants of lung health and disease in early life and to identify opportunities for scientific advancement. They identified that future investigations will need not only to examine abnormal lung development, but also to use developing technology and resources to better define normal and/or enhanced lung health. Birth cohort studies offer key opportunities to capture the important influence of preconception and obstetric risk factors on lung health, development, and disease. These studies should include well-characterized obstetrical data and comprehensive plans for prospective follow-up. The importance of continued basic science, translational, and animal studies for providing mechanisms to explain causality using new methods cannot be overemphasized. Multidisciplinary approaches involving obstetricians, neonatologists, pediatric and adult pulmonologists, and basic scientists should be encouraged to design and conduct comprehensive and impactful research on the early stages of normal and abnormal human lung growth that influence adult outcome.

  20. The Intestinal Microbiome in Early Life: Health and Disease

    Directory of Open Access Journals (Sweden)

    Marie-Claire eArrieta

    2014-09-01

    Full Text Available Human microbial colonization begins at birth and continues to develop and modulate in species abundance for about three years, until the microbiota becomes adult-like. During the same time period, children experience significant developmental changes that influence their current health status as well as their immune system. An ever-expanding number of articles associate several diseases with early life imbalances of the gut microbiota, also referred to as gut microbial dysbiosis. Whether early life dysbiosis precedes and plays a role in disease pathogenesis, or simply originates from the disease process itself is a question that is beginning to be answered in a few diseases, including IBD, obesity and asthma. This review describes the gut microbiome structure and function during the formative first years of life, as well as the environmental factors that determine its composition. It also aims to discuss the recent advances in understanding the role of the early life gut microbiota in the development of immune-mediated, metabolic, and neurological diseases. A greater understanding of how the early life gut microbiota impacts our immune development could potentially lead to novel microbial-derived therapies that target disease prevention at an early age.

  1. Evidence of an IFN-γ by early life stress interaction in the regulation of amygdala reactivity to emotional stimuli.

    Science.gov (United States)

    Redlich, Ronny; Stacey, David; Opel, Nils; Grotegerd, Dominik; Dohm, Katharina; Kugel, Harald; Heindel, Walter; Arolt, Volker; Baune, Bernhard T; Dannlowski, Udo

    2015-12-01

    Since numerous studies have found that exposure to early life stress leads to increased peripheral inflammation and psychiatric disease, it is thought that peripheral immune activation precedes and possibly mediates the onset of stress-associated psychiatric disease. Despite early studies, IFNγ has received little attention relative to other inflammatory cytokines in the context of the pathophysiology of affective disorders. Neuroimaging endophenotypes have emerged recently as a promising means of elucidating these types of complex relationships including the modeling of the interaction between environmental factors and genetic predisposition. Here we investigate the GxE relationship between early-life stress and genetic variants of IFNγ on emotion processing. To investigate the impact of the relationship between genetic variants of IFNγ (rs1861494, rs2069718, rs2430561) and early life stress on emotion processing, a sample of healthy adults (n=409) undergoing an emotional faces paradigm in an fMRI study were genotyped and analysed. Information on early life stress was obtained via Childhood Trauma Questionnaire (CTQ). A positive association between early life stress and amygdala reactivity was found. Specifically, the main effect of genotype of rs1861494 on amygdala reactivity indicates a higher neural response in C allele carriers compared to T homozygotes, while we did not find main effects of rs2069718 and rs2430561. Importantly, interaction analyses revealed a specific interaction between IFNγ genotype (rs1861494) and early life stress affecting amygdala reactivity to emotional faces, resulting from a positive association between CTQ scores and amygdala reactivity in C allele carriers while this association was absent in T homozygotes. Our findings indicate that firstly the genetic variant of IFNγ (rs1861494) is involved with the regulation of amygdala reactivity to emotional stimuli and secondly, that this genetic variant moderates effects of early life

  2. CO2-level Dependent Effects of Ocean Acidification on Squid, Doryteuthis pealeii, Early Life History

    KAUST Repository

    Zakroff, Casey J.

    2013-12-01

    Ocean acidification is predicted to lead to global oceanic decreases in pH of up to 0.3 units within the next 100 years. However, those levels are already being reached currently in coastal regions due to natural CO2 variability. Squid are a vital component of the pelagic ecosystem, holding a unique niche as a highly active predatory invertebrate and major prey stock for upper trophic levels. This study examined the effects of a range of ocean acidification regimes on the early life history of a coastal squid species, the Atlantic longfin squid, Doryteuthis pealeii. Eggs were raised in a flow-through ocean acidification system at CO2 levels ranging from ambient (400ppm) to 2200ppm. Time to hatching, hatching efficiency, and hatchling mantle lengths, yolk sac sizes, and statoliths were all examined to elucidate stress effects. Delays in hatching time of at least a day were seen at exposures above 1300ppm in all trials under controlled conditions. Mantle lengths were significantly reduced at exposures above 1300 ppm. Yolk sac sizes varied between CO2 treatments, but no distinct pattern emerged. Statoliths were increasingly porous and malformed as CO2 exposures increased, and were significantly reduced in surface area at exposures above 1300ppm. Doryteuthis pealeii appears to be able to withstand acidosis stress without major effects up to 1300ppm, but is strongly impacted past that threshold. Since yolk consumption did not vary among treatments, it appears that during its early life stages, D. pealeii reallocates its available energy budget away from somatic growth and system development in order to mitigate the stress of acidosis.

  3. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life

    OpenAIRE

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P.; Klein, Jonathan D.; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

    2015-01-01

    Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice. Methods: Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until d...

  4. Early-life Nutrition and Cardiometabolic Health across the Life Course

    NARCIS (Netherlands)

    E.T.M. Leermakers (Lisan)

    2015-01-01

    markdownabstract__Abstract__ This thesis describes the relation between nutrition and cardiometabolic health, with the focus on nutritional exposures in pregnancy and early childhood. A systematic review of the literature was performed to describe the effects of the nutrients lutein and choline

  5. Early-life medical care and human capital accumulation

    DEFF Research Database (Denmark)

    Daysal, N. Meltem

    2015-01-01

    that both types of interventions may benefit not only child health but also long-term educational outcomes. In addition, early-life medical interventions may improve the educational outcomes of siblings. These findings can be used to design policies that improve long-term outcomes and reduce economic......Ample empirical evidence links adverse conditions during early childhood (the period from conception to age five) to worse health outcomes and lower academic achievement in adulthood. Can early-life medical care and public health interventions ameliorate these effects? Recent research suggests...

  6. Early exposure to media violence and later child adjustment.

    Science.gov (United States)

    Fitzpatrick, Caroline; Barnett, Tracie; Pagani, Linda S

    2012-05-01

    The extent to which early childhood exposure to violent media is associated with subsequent adverse child functioning remains disconcerting. In this study, we examine whether preschool child exposure to what parents generally characterize as violent television programming predicts a range of second-grade mental health outcomes. Participants are from the Quebec Longitudinal Study of Child Development (N = 1786). At 41 and 53 months, parents reported whether the child had viewed television shows and videos consisting of what they judged as violent content. According to parents, children watched on average 1.8 hours of mixed programming per day. Parent-reported child exposure to televised violence was associated with teacher-reported antisocial symptoms (β = 0.180, 95% confidence interval [CI]: 0.026-0.333), emotional distress (β = 0.224, 95% CI: 0.010-0.438), inattention (β = 0.349, 95% CI: 0.048-0.651), and lower global academic achievement (β = -0.127, 95% CI: -0.237-0.017) in second grade. Violent televiewing was also associated with less child-reported academic self-concept (β = -0.175, 95% CI: -0.296-0.053) and intrinsic motivation (β = -0.162, 95% CI: -0.016-0.307) in second grade. Effects remained significant after adjusting for preexisting child and family characteristics such as baseline child aggression. This prospective study suggests risks associated with early childhood violent media exposure for long-term mental health in children. These findings, suggesting diffusive relationships between early childhood violent media exposure and negative socioemotional and academic outcomes, empirically support the notion that access to early childhood violent television represents a threat to population health and should be discouraged by adult caregivers.

  7. A critical review: early life nutrition and prenatal programming for adult disease.

    Science.gov (United States)

    Carolan-Olah, Mary; Duarte-Gardea, Maria; Lechuga, Julia

    2015-12-01

    To present the evidence in relation to early life nutrition and foetal programming for adult disease. Epigenetics is a new and growing area of study investigating the impact of the intrauterine environment on the lifelong health of individuals. Discursive paper. Searches were conducted in a range of electronic health databases. Hand searches located additional articles for review. Maternal search terms included: pregnancy; nutrition; diet; obesity; over nutrition; under nutrition. Offspring related search terms included: macrosomia; intrauterine growth restriction; epigenetics; foetal programming; childhood obesity; adolescent obesity; adolescent type 2 diabetes. Results indicate that foetal programming for adult disease occurs in response to particular insults during vulnerable developmental periods. Four main areas of foetal exposure were identified in this review: (1) under nutrition; (2) over nutrition; (3) gestational diabetes mellitus; and (4) infant catch-up growth. Numerous studies also described the trans-generational nature of foetal programming. Overall, foetal exposure to excess or insufficient nutrition during vulnerable developmental periods appears to result in a lifelong predisposition to obesity and adult disease, such as type 2 diabetes and cardiac disease. For the infant who has been undernourished during early life, a predisposition to renal disease also occurs. Pregnancy is a time when women are engaged in health systems and are receptive to health messages. These factors suggest that pregnancy may be an optimal time for dietary education and intervention. There is a particular need for education on healthy diet and for interventions which aim to limit over consumption of calories. © 2015 John Wiley & Sons Ltd.

  8. Development of Life on Early Mars

    Science.gov (United States)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

    2009-01-01

    Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution encompassed conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water- as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at 3.9 Gy, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H20, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 My?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve). The commonly stated requirement that life would need hundreds of millions of year to get started is only an assumption; we know of no evidence that requires such a long interval for the development of life, if the proper habitable

  9. Biomarkers of carcinogen exposure and early effects.

    OpenAIRE

    2006-01-01

    The purpose of this review is to summarise the current situation regarding the types and uses of biomarkers of exposure and effect for the main classes of food-derived genotoxic carcinogens, and to consider some aspects of the intercomparison between these biomarkers. The biomarkers of exposure and early effects of carcinogens that have been most extensively developed are those for genotoxic agents and for compounds that generate hydroxyl radicals and other reactive radical species, and it is...

  10. Early Life Stress, Air Pollution, Inflammation, and Disease: An Integrative Review and Immunologic Model of Social-Environmental Adversity and Lifespan Health.

    Science.gov (United States)

    Olvera Alvarez, Hector A; Kubzansky, Laura D; Campen, Matthew J; Slavich, George M

    2018-06-03

    Socially disadvantaged individuals are at greater risk for simultaneously being exposed to adverse social and environmental conditions. Although the mechanisms underlying joint effects remain unclear, one hypothesis is that toxic social and environmental exposures have synergistic effects on inflammatory processes that underlie the development of chronic diseases, including cardiovascular disease, diabetes, depression, and certain types of cancer. In the present review, we examine how exposure to two risk factors that commonly occur with social disadvantage-early life stress and air pollution-affect health. Specifically, we identify neuroimmunologic pathways that could link early life stress, inflammation, air pollution, and poor health, and use this information to propose an integrated, multi-level model that describes how these factors may interact and cause health disparity across individuals based on social disadvantage. This model highlights the importance of interdisciplinary research considering multiple exposures across domains and the potential for synergistic, cross-domain effects on health, and may help identify factors that could potentially be targeted to reduce disease risk and improve lifespan health. Copyright © 2018. Published by Elsevier Ltd.

  11. Effects of early life stress: Opportunities for pharmacological intervention

    NARCIS (Netherlands)

    Loi, M

    2016-01-01

    Moderate acute activation of the body’s stress response system is considered an adaptive mechanism that increases the chance of survival, but severe stressors early in life may disturb brain development. In agreement, epidemiological data suggest that adverse experiences early in life, such as

  12. Conditions on Early Mars Might Have Fostered Rapid and Early Development of Life

    Science.gov (United States)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

    2007-01-01

    The exploration of Mars during the past decades has begun to unveil the history of the planet. The combinations of remote sensing, in situ geochemical compositional measurements and photographic observations from both above and on the surface have shown Mars to have a dynamic and active geologic evolution. Mars geologic evolution clearly had conditions that were suitable for supporting life. For a planet to be able to be habitable, it must have water, carbon sources, energy sources and a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water-carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001 well-dated at approx.3.9 Gy., (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, early active volcanism continuing throughout Martian history, and, and continuing impact processes, (iii) Carbon and water from possibly extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) some crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust. The question arises: "Why would life not evolve from these favorable conditions on early Mars in its first 600 My?" During this period, it seems likely that environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would all favor the formation of early life. Even if life developed elsewhere (on Earth, Venus, or on other solar systems) and was transported to Mars, the surface conditions were likely very hospitable for that introduced life to multiply and evolve.

  13. Early life physical activity and cognition at old age

    NARCIS (Netherlands)

    Dik, Miranda; Deeg, Dorly J H; Visser, Marjolein; Jonker, Cees

    Physical activity has shown to be inversely associated with cognitive decline in older people. Whether this association is already present in early life has not been investigated previously. The association between early life physical activity and cognition was studied in 1,241 subjects aged 62-85

  14. Early life stress in rats sex-dependently affects remote endocrine rather than behavioral consequences of adult exposure to contextual fear conditioning.

    Science.gov (United States)

    Fuentes, Sílvia; Daviu, Núria; Gagliano, Humberto; Belda, Xavier; Armario, Antonio; Nadal, Roser

    2018-05-30

    Exposure to electric foot-shocks can induce in rodents contextual fear conditioning, generalization of fear to other contexts and sensitization of the hypothalamic-pituitary-adrenal (HPA) axis to further stressors. All these aspects are relevant for the study of post-traumatic stress disorder. In the present work we evaluated in rats the sex differences and the role of early life stress (ELS) in fear memories, generalization and sensitization. During the first postnatal days subjects were exposed to restriction of nesting material along with exposure to a "substitute" mother. In the adulthood they were exposed to (i) a contextual fear conditioning to evaluate long-term memory and extinction and (ii) to a novel environment to study cognitive fear generalization and HPA axis heterotypic sensitization. ELS did not alter acquisition, expression or extinction of context fear conditioned behavior (freezing) in either sex, but reduced activity in novel environments only in males. Fear conditioning associated hypoactivity in novel environments (cognitive generalization) was greater in males than females but was not specifically affected by ELS. Although overall females showed greater basal and stress-induced levels of ACTH and corticosterone, an interaction between ELS, shock exposure and sex was found regarding HPA hormones. In males, ELS did not affect ACTH response in any situation, whereas in females, ELS reduced both shock-induced sensitization of ACTH and its conditioned response to the shock context. Also, shock-induced sensitization of corticosterone was only observed in males and ELS specifically reduced corticosterone response to stressors in males but not females. In conclusion, ELS seems to have only a minor impact on shock-induced behavioral conditioning, while affecting the unconditioned and conditioned responses of HPA hormones in a sex-dependent manner. Copyright © 2018. Published by Elsevier Inc.

  15. Opportunities During Early Life for Cancer Prevention: Highlights From a Series of Virtual Meetings With Experts

    Science.gov (United States)

    Holman, Dawn M.; Buchanan, Natasha D.

    2018-01-01

    Compelling evidence suggests that early life exposures can affect lifetime cancer risk. In 2014, the Centers for Disease Control and Prevention’s (CDC’s) Cancer Prevention Across the Lifespan Workgroup hosted a series of virtual meetings with select experts to discuss the state of the evidence linking factors during the prenatal period and early childhood to subsequent risk of both pediatric and adult cancers. In this article, we present the results from a qualitative analysis of the meeting transcripts and summarize themes that emerged from our discussions with meeting participants. Themes included the state of the evidence linking early life factors to cancer risk, research gaps and challenges, the level of evidence needed to support taking public health action, and the challenges of communicating complex, and sometimes conflicting, scientific findings to the public. Opportunities for collaboration among public health agencies and other stakeholders were identified during these discussions. Potential next steps for the CDC and its partners included advancing and building upon epidemiology and surveillance work, developing and using evidence from multiple sources to inform decision-making, disseminating and communicating research findings in a clear and effective way, and expanding collaborations with grantees and other partners. As the science on early life factors and cancer risk continues to evolve, there are opportunities for collaboration to translate science into actionable public health practice. PMID:27940972

  16. Effects of chronic copper exposure during early life in rhesus monkeys.

    Science.gov (United States)

    Araya, Magdalena; Kelleher, Shannon L; Arredondo, Miguel A; Sierralta, Walter; Vial, María Teresa; Uauy, Ricardo; Lönnerdal, Bo

    2005-05-01

    Whether infants regulate copper absorption and the potential effects of excess copper in early life remain poorly defined. The objective of the study was to assess copper retention, liver copper content, and liver function in infant rhesus monkeys fed infant formula containing 6.6 mg Cu/L. From birth to 5 mo of age, infant rhesus monkeys were fed formula that was supplemented with copper (0.6 mg Cu/L; n = 5) or not supplemented (n = 4). In all animals, weight and crown-rump length (by anthropometry), hemoglobin, hematocrit, plasma ceruloplasmin activity, and zinc and copper concentrations were measured monthly (birth to 6 mo) and at 8 and 12 mo. When the animals were 1, 5, and 8 mo old, liver copper and metallothionein concentrations, liver histology (by light and electron microscopy), and the number of Kupffer cells were assessed, and 67Cu retention was measured. Liver function was assessed by measurement of plasma alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase activities and protein, albumin, bilirubin, and blood urea nitrogen concentrations. 67Cu retention was 19.2% and 10.9% after 1 and 5 mo of copper treatment, respectively, compared with approximately 75% in controls at age 2 mo. At age 8 mo, 67Cu retention was 22.9% in copper-treated animals and 31.5% in controls. Liver histology remained normal by light microscopy, with mild ultrastructural signs of cell damage at 5 mo. Liver copper concentration was 4711, 1139, and 498 microg/g dry tissue at 1, 5, and 8 mo, respectively, in copper-treated animals and 250 microg/g at 2 mo in controls. Measurements could not be completed in all animals. No clinical evidence of copper toxicity was observed. Copper absorption was down-regulated; increases in liver copper content at ages 1 and 5 mo did not result in histologic damage. Ultrastructural changes at age 5 mo could signal early cellular damage.

  17. Early life programming as a target for prevention of child and adolescent mental disorders

    Science.gov (United States)

    2014-01-01

    This paper concerns future policy development and programs of research for the prevention of mental disorders based on research emerging from fetal and early life programming. The current review offers an overview of findings on pregnancy exposures such as maternal mental health, lifestyle factors, and potential teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are common child and adolescent mental disorders including hyperactive, behavioral and emotional disorders. This literature suggests that the preconception and perinatal periods offer important opportunities for the prevention of deleterious fetal exposures. As such, the perinatal period is a critical period where future mental health prevention efforts should be focused and prevention models developed. Interventions grounded in evidence-based recommendations for the perinatal period could take the form of public health, universal and more targeted interventions. If successful, such interventions are likely to have lifelong effects on (mental) health. PMID:24559477

  18. Affinity for risky behaviors following prenatal and early childhood exposure to tetrachloroethylene (PCE-contaminated drinking water: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Aschengrau Ann

    2011-12-01

    Full Text Available Abstract Background Many studies of adults with acute and chronic solvent exposure have shown adverse effects on cognition, behavior and mood. No prior study has investigated the long-term impact of prenatal and early childhood exposure to the solvent tetrachloroethylene (PCE on the affinity for risky behaviors, defined as smoking, drinking or drug use as a teen or adult. Objectives This retrospective cohort study examined whether early life exposure to PCE-contaminated drinking water influenced the occurrence of cigarette smoking, alcohol consumption, and drug use among adults from Cape Cod, Massachusetts. Methods Eight hundred and thirty-one subjects with prenatal and early childhood PCE exposure and 547 unexposed subjects were studied. Participants completed questionnaires to gather information on risky behaviors as a teenager and young adult, demographic characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure was estimated using the U.S. EPA's water distribution system modeling software (EPANET that was modified to incorporate a leaching and transport model to estimate PCE exposures from pipe linings. Results Individuals who were highly exposed to PCE-contaminated drinking water during gestation and early childhood experienced 50-60% increases in the risk of using two or more major illicit drugs as a teenager or as an adult (Relative Risk (RR for teen use = 1.6, 95% CI: 1.2-2.2; and RR for adult use = 1.5, 95% CI: 1.2-1.9. Specific drugs for which increased risks were observed included crack/cocaine, psychedelics/hallucinogens, club/designer drugs, Ritalin without a prescription, and heroin (RRs:1.4-2.1. Thirty to 60% increases in the risk of certain smoking and drinking behaviors were also seen among highly exposed subjects. Conclusions The results of this study suggest that risky behaviors, particularly drug use, are more frequent among adults with high PCE exposure levels during gestation

  19. Effect of mercury and cadmium on early life stages of Java medaka (Oryzias javanicus): A potential tropical test fish

    International Nuclear Information System (INIS)

    Ismail, Ahmad; Yusof, Shahrizad

    2011-01-01

    Research highlights: → Early life stages of Java medaka show high sensitivity to Cd and Hg. → Exposure of the early life stages caused several developmental impairments. → Java medaka is suitable to be established as test organism for ecotoxicology. → Results of testing using this fish reflect the environment of the tropical region. - Abstract: Several organisms have been used as indicators, bio-monitoring agents or test organisms in ecotoxicological studies. A close relative of the well established Japanese medaka, the Java medaka (Oryzias javanicus), has the potential to be a test organism. The fish is native to the estuaries of the Malaysian Peninsula, Thailand, Indonesia and Singapore. In this study, newly fertilised eggs were exposed to different concentrations of Cd and Hg. Observations were done on the development of the embryos. Exposure to low levels of Cd and Hg (0.01-0.05 ppm) resulted in several developmental disorders that led to death. Exposure to ≥1.0 ppm Cd resulted in immediate developmental arrest. The embryos of Java medaka showed tolerance to a certain extent when exposed to ≥1.0 ppm Hg compared to Cd. Based on the sensitivity of the embryos, Java medaka is a suitable test organism for ecotoxicology in the tropical region.

  20. Accounting Early for Life Long Learning: The AcE Project.

    Science.gov (United States)

    University Coll. Worcester (England). Centre for Research in Early Childhood Education.

    Building upon the work of the Effective Early Learning (EEL) Project in raising the quality of early learning for young children in the United Kingdom, the 3-year Accounting Early for Life Long Learning Project (AcE Project) focuses on enhancing in 3- to 6-year-olds those attitudes and dispositions that are important to life-long learning. This…

  1. Early life innate immune signatures of persistent food allergy.

    Science.gov (United States)

    Neeland, Melanie R; Koplin, Jennifer J; Dang, Thanh D; Dharmage, Shyamali C; Tang, Mimi L; Prescott, Susan L; Saffery, Richard; Martino, David J; Allen, Katrina J

    2017-11-14

    Food allergy naturally resolves in a proportion of food-allergic children without intervention; however the underlying mechanisms governing the persistence or resolution of food allergy in childhood are not understood. This study aimed to define the innate immune profiles associated with egg allergy at age 1 year, determine the phenotypic changes that occur with the development of natural tolerance in childhood, and explore the relationship between early life innate immune function and serum vitamin D. This study used longitudinally collected PBMC samples from a population-based cohort of challenge-confirmed egg-allergic infants with either persistent or transient egg allergy outcomes in childhood to phenotype and quantify the functional innate immune response associated with clinical phenotypes of egg allergy. We show that infants with persistent egg allergy exhibit a unique innate immune signature, characterized by increased numbers of circulating monocytes and dendritic cells that produce more inflammatory cytokines both at baseline and following endotoxin exposure when compared with infants with transient egg allergy. Follow-up analysis revealed that this unique innate immune signature continues into childhood in those with persistent egg allergy and that increased serum vitamin D levels correlate with changes in innate immune profiles observed in children who developed natural tolerance to egg. Early life innate immune dysfunction may represent a key immunological driver and predictor of persistent food allergy in childhood. Serum vitamin D may play an immune-modulatory role in the development of natural tolerance. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Transgenerational transmission of a stress-coping phenotype programmed by early-life stress in the Japanese quail

    Science.gov (United States)

    Zimmer, Cédric; Larriva, Maria; Boogert, Neeltje J.; Spencer, Karen A.

    2017-01-01

    An interesting aspect of developmental programming is the existence of transgenerational effects that influence offspring characteristics and performance later in life. These transgenerational effects have been hypothesized to allow individuals to cope better with predictable environmental fluctuations and thus facilitate adaptation to changing environments. Here, we test for the first time how early-life stress drives developmental programming and transgenerational effects of maternal exposure to early-life stress on several phenotypic traits in their offspring in a functionally relevant context using a fully factorial design. We manipulated pre- and/or post-natal stress in both Japanese quail mothers and offspring and examined the consequences for several stress-related traits in the offspring generation. We show that pre-natal stress experienced by the mother did not simply affect offspring phenotype but resulted in the inheritance of the same stress-coping traits in the offspring across all phenotypic levels that we investigated, shaping neuroendocrine, physiological and behavioural traits. This may serve mothers to better prepare their offspring to cope with later environments where the same stressors are experienced. PMID:28387355

  3. Effect of Early- and Adult-Life Socioeconomic Circumstances on Physical Inactivity.

    Science.gov (United States)

    Cheval, Boris; Sieber, Stefan; Guessous, Idris; Orsholits, Dan; Courvoisier, Delphine S; Kliegel, Matthias; Stringhini, Silvia; Swinnen, Stephan P; Burton-Jeangros, Claudine; Cullati, Stéphane; Boisgontier, Matthieu P

    2018-03-01

    This study aimed to investigate the associations between early- and adult-life socioeconomic circumstances and physical inactivity (level and evolution) in aging using large-scale longitudinal data. This study used the Survey of Health Ageing and Retirement in Europe, a 10-yr population-based cohort study with repeated measurements in five waves, every 2 yr between 2004 and 2013. Self-reported physical inactivity (waves 1, 2, 4, and 5), household income (waves 1, 2, 4, and 5), educational attainment (wave of the first measurement occasion), and early-life socioeconomic circumstance (wave 3) were collected in 22,846 individuals 50 to 95 yr of age. Risk of physical inactivity was increased for women with the most disadvantaged early-life socioeconomic circumstances (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.20-1.86). With aging, the risk of physical inactivity increased for both sexes and was strongest for those with the most disadvantaged early-life socioeconomic circumstances (OR, 1.04 (95% CI, 1.02-1.06) for women; OR, 1.02 (95% CI, 1.00-1.05) for men), with the former effect being more robust than the latter one. The association between early-life socioeconomic circumstances and physical inactivity was mediated by adult-life socioeconomic circumstances, with education being the strongest mediator. Early-life socioeconomic circumstances predicted high levels of physical inactivity at older ages, but this effect was mediated by socioeconomic indicators in adult life. This finding has implications for public health policies, which should continue to promote education to reduce physical inactivity in people at older ages and to ensure optimal healthy aging trajectories, especially among women with disadvantaged early-life socioeconomic circumstances.

  4. Development of the Life Story in Early Adolescence

    Science.gov (United States)

    Steiner, Kristina L.; Pillemer, David B.

    2018-01-01

    Life span developmental psychology proposes that the ability to create a coherent life narrative does not develop until early adolescence. Using a novel methodology, 10-, 12-, and 14-year-old participants were asked to tell their life stories aloud to a researcher. Later, participants separated their transcribed narratives into self-identified…

  5. Reduced cortical thickness in veterans exposed to early life trauma.

    Science.gov (United States)

    Corbo, Vincent; Salat, David H; Amick, Melissa M; Leritz, Elizabeth C; Milberg, William P; McGlinchey, Regina E

    2014-08-30

    Studies have shown that early life trauma may influence neural development and increase the risk of developing psychological disorders in adulthood. We used magnetic resonance imaging to examine the impact of early life trauma on the relationship between current posttraumatic stress disorder (PTSD) symptoms and cortical thickness/subcortical volumes in a sample of deployed personnel from Operation Enduring Freedom/Operation Iraqi Freedom. A group of 108 service members enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) were divided into those with interpersonal early life trauma (EL-Trauma+) and Control (without interpersonal early life trauma) groups based on the Traumatic Life Events Questionnaire. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale. Cortical thickness and subcortical volumes were analyzed using the FreeSurfer image analysis package. Thickness of the paracentral and posterior cingulate regions was positively associated with PTSD severity in the EL-Trauma+ group and negatively in the Control group. In the EL-Trauma+ group, both the right amygdala and the left hippocampus were positively associated with PTSD severity. This study illustrates a possible influence of early life trauma on the vulnerability of specific brain regions to stress. Changes in neural morphometry may provide information about the emergence and maintenance of symptoms in individuals with PTSD. Published by Elsevier Ireland Ltd.

  6. Prenatal and early life influences on epigenetic age in children

    DEFF Research Database (Denmark)

    Simpkin, Andrew J; Hemani, Gibran; Suderman, Matthew

    2016-01-01

    age for these samples. AA was defined as the residuals from regressing epigenetic age on actual age. AA was tested for associations with cross-sectional clinical variables in children. We identified associations between AA and sex, birth weight, birth by caesarean section and several maternal......). In children, epigenetic AA measures are associated with several clinically relevant variables, and early life exposures appear to be associated with changes in AA during adolescence. Further research into epigenetic aging, including the use of causal inference methods, is required to better our understanding......DNA methylation-based biomarkers of aging are highly correlated with actual age. Departures of methylation-estimated age from actual age can be used to define epigenetic measures of child development or age acceleration (AA) in adults. Very little is known about genetic or environmental...

  7. Long-term exposure to air pollution and asthma hospitalisations in older adults: a cohort study

    DEFF Research Database (Denmark)

    Andersen, Zorana Jovanovic; Bønnelykke, Klaus; Hvidberg, Martin

    2012-01-01

    Exposure to air pollution in early life contributes to the burden of childhood asthma, but it is not clear whether long-term exposure to air pollution can lead to asthma onset or progression in adulthood.......Exposure to air pollution in early life contributes to the burden of childhood asthma, but it is not clear whether long-term exposure to air pollution can lead to asthma onset or progression in adulthood....

  8. Inequality in oral health related to early and later life social conditions: a study of elderly in Norway and Sweden.

    Science.gov (United States)

    Gülcan, Ferda; Ekbäck, Gunnar; Ordell, Sven; Lie, Stein Atle; Åstrøm, Anne Nordrehaug

    2015-02-10

    A life course perspective recognizes influences of socially patterned exposures on oral health across the life span. This study assessed the influence of early and later life social conditions on tooth loss and oral impacts on daily performances (OIDP) of people aged 65 and 70 years. Whether social inequalities in oral health changed after the usual age of retirement was also examined. In accordance with "the latent effect life course model", it was hypothesized that adverse early-life social conditions increase the risk of subsequent tooth loss and impaired OIDP, independent of later-life social conditions. Data were obtained from two cohorts studies conducted in Sweden and Norway. The 2007 and 2012 waves of the surveys were used for the present study. Early-life social conditions were measured in terms of gender, education and country of birth, and later-life social conditions were assessed by working status, marital status and size of social network. Logistic regression and Generalized Estimating Equations (GEE) were used to analyse the data. Inverse probability weighting (IPW) was used to adjust estimates for missing responses and loss to follow-up. Early-life social conditions contributed to tooth loss and OIDP in each survey year and both countries independent of later-life social conditions. Lower education correlated positively with tooth loss, but did not influence OIDP. Foreign country of birth correlated positively with oral impacts in Sweden only. Later-life social conditions were the strongest predictors of tooth loss and OIDP across survey years and countries. GEE revealed significant interactions between social network and survey year, and between marital status and survey year on tooth loss. The results confirmed the latent effect life course model in that early and later life social conditions had independent effects on tooth loss and OIDP among the elderly in Norway and Sweden. Between age 65 and 70, inequalities in tooth loss related to marital

  9. Can environmental conditions experienced in early life influence future generations?

    Science.gov (United States)

    Burton, Tim; Metcalfe, Neil B

    2014-06-22

    The consequences of early developmental conditions for performance in later life are now subjected to convergent interest from many different biological sub-disciplines. However, striking data, largely from the biomedical literature, show that environmental effects experienced even before conception can be transmissible to subsequent generations. Here, we review the growing evidence from natural systems for these cross-generational effects of early life conditions, showing that they can be generated by diverse environmental stressors, affect offspring in many ways and can be transmitted directly or indirectly by both parental lines for several generations. In doing so, we emphasize why early life might be so sensitive to the transmission of environmentally induced effects across generations. We also summarize recent theoretical advancements within the field of developmental plasticity, and discuss how parents might assemble different 'internal' and 'external' cues, even from the earliest stages of life, to instruct their investment decisions in offspring. In doing so, we provide a preliminary framework within the context of adaptive plasticity for understanding inter-generational phenomena that arise from early life conditions.

  10. Forebrain CRF1 Modulates Early-Life Stress-Programmed Cognitive Deficits

    Science.gov (United States)

    Wang, Xiao-Dong; Rammes, Gerhard; Kraev, Igor; Wolf, Miriam; Liebl, Claudia; Scharf, Sebastian H.; Rice, Courtney J.; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan M.; Baram, Tallie Z.; Stewart, Michael G.; Müller, Marianne B.; Schmidt, Mathias V.

    2012-01-01

    Childhood traumatic events hamper the development of the hippocampus and impair declarative memory in susceptible individuals. Persistent elevations of hippocampal corticotropin-releasing factor (CRF), acting through CRF receptor 1 (CRF1), in experimental models of early-life stress have suggested a role for this endogenous stress hormone in the resulting structural modifications and cognitive dysfunction. However, direct testing of this possibility has been difficult. In the current study, we subjected conditional forebrain CRF1 knock-out (CRF1-CKO) mice to an impoverished postnatal environment and examined the role of forebrain CRF1 in the long-lasting effects of early-life stress on learning and memory. Early-life stress impaired spatial learning and memory in wild-type mice, and postnatal forebrain CRF overexpression reproduced these deleterious effects. Cognitive deficits in stressed wild-type mice were associated with disrupted long-term potentiation (LTP) and a reduced number of dendritic spines in area CA3 but not in CA1. Forebrain CRF1 deficiency restored cognitive function, LTP and spine density in area CA3, and augmented CA1 LTP and spine density in stressed mice. In addition, early-life stress differentially regulated the amount of hippocampal excitatory and inhibitory synapses in wild-type and CRF1-CKO mice, accompanied by alterations in the neurexin-neuroligin complex. These data suggest that the functional, structural and molecular changes evoked by early-life stress are at least partly dependent on persistent forebrain CRF1 signaling, providing a molecular target for the prevention of cognitive deficits in adults with a history of early-life adversity. PMID:21940453

  11. Early-Life Stress Triggers Juvenile Zebra Finches to Switch Social Learning Strategies.

    Science.gov (United States)

    Farine, Damien R; Spencer, Karen A; Boogert, Neeltje J

    2015-08-17

    Stress during early life can cause disease and cognitive impairment in humans and non-humans alike. However, stress and other environmental factors can also program developmental pathways. We investigate whether differential exposure to developmental stress can drive divergent social learning strategies between siblings. In many species, juveniles acquire essential foraging skills by copying others: they can copy peers (horizontal social learning), learn from their parents (vertical social learning), or learn from other adults (oblique social learning). However, whether juveniles' learning strategies are condition dependent largely remains a mystery. We found that juvenile zebra finches living in flocks socially learned novel foraging skills exclusively from adults. By experimentally manipulating developmental stress, we further show that social learning targets are phenotypically plastic. While control juveniles learned foraging skills from their parents, their siblings, exposed as nestlings to experimentally elevated stress hormone levels, learned exclusively from unrelated adults. Thus, early-life conditions triggered individuals to switch strategies from vertical to oblique social learning. This switch could arise from stress-induced differences in developmental rate, cognitive and physical state, or the use of stress as an environmental cue. Acquisition of alternative social learning strategies may impact juveniles' fit to their environment and ultimately change their developmental trajectories. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants.

    Science.gov (United States)

    Goldstein-Piekarski, Andrea N; Korgaonkar, Mayuresh S; Green, Erin; Suppes, Trisha; Schatzberg, Alan F; Hastie, Trevor; Nemeroff, Charles B; Williams, Leanne M

    2016-10-18

    Amygdala circuitry and early life stress (ELS) are both strongly and independently implicated in the neurobiology of depression. Importantly, animal models have revealed that the contribution of ELS to the development and maintenance of depression is likely a consequence of structural and physiological changes in amygdala circuitry in response to stress hormones. Despite these mechanistic foundations, amygdala engagement and ELS have not been investigated as biobehavioral targets for predicting functional remission in translational human studies of depression. Addressing this question, we integrated human neuroimaging and measurement of ELS within a controlled trial of antidepressant outcomes. Here we demonstrate that the interaction between amygdala activation engaged by emotional stimuli and ELS predicts functional remission on antidepressants with a greater than 80% cross-validated accuracy. Our model suggests that in depressed people with high ELS, the likelihood of remission is highest with greater amygdala reactivity to socially rewarding stimuli, whereas for those with low-ELS exposure, remission is associated with lower amygdala reactivity to both rewarding and threat-related stimuli. This full model predicted functional remission over and above the contribution of demographics, symptom severity, ELS, and amygdala reactivity alone. These findings identify a human target for elucidating the mechanisms of antidepressant functional remission and offer a target for developing novel therapeutics. The results also offer a proof-of-concept for using neuroimaging as a target for guiding neuroscience-informed intervention decisions at the level of the individual person.

  13. Prenatal and early postnatal stress and later life inflammation

    DEFF Research Database (Denmark)

    Pedersen, Jolene Masters; Mortensen, Erik Lykke; Christensen, Dinne Skjærlund

    2018-01-01

    BACKGROUND: Evidence suggests that maternal psychological and social stress during the prenatal period and in childhood represent an important condition that may adversely impact the anatomy and physiology of the developing child with implications for a number of health-related conditions...... and postnatal stressor data was collected at year one follow-up. A series of ordinary least square regression models were performed with the stress measures as the exposures and C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor necrosis factor α (TNF-α) separately as the outcomes...... in the first year of life, was associated with higher levels of CRP and IL-6. The accumulation of social stressors in the early postnatal period was associated with higher levels of CRP and IL-6 but not IL-10 and TNF-α. The accumulation of stressors in the prenatal and postnatal periods combined was associated...

  14. Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study.

    Science.gov (United States)

    Itakura, Katsumasa; Takahashi, Ikuno; Nakashima, Eiji; Yanagi, Masahide; Kawasaki, Ryo; Neriishi, Kazuo; Wang, Jie Jin; Wong, Tien Yin; Hida, Ayumi; Ohishi, Waka; Kiuchi, Yoshiaki

    2015-08-01

    To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75-1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors.

  15. A STEREOLOGICAL ANALYSIS OF THE EFFECT OF EARLY POSTNATAL ETHANOL EXPOSURE ON NEURONAL NUMBERS IN RAT DENTATE GYRUS

    Directory of Open Access Journals (Sweden)

    Takanori Miki

    2011-05-01

    Full Text Available Maternal ethanol ingestion during pregnancy can cause fetal alcohol syndrome (FAS in their offspring. Among the symptoms of FAS, damage to the central nervous system has emerged as one of the most serious problems. We have previously shown that a relatively high dose of ethanol exposure during early postnatal life can cause alterations in spatial learning ability. This ability is controlled, at least in part, by the hippocampal formation. The purpose of the present study was to determine whether exposure of rat pups to ethanol during early postnatal life had effects on the total number of the dentate gyrus neurons. Wistar rats were exposed to a relatively high daily dose of ethanol between postnatal days 10 to 15. Ethanol exposure was achieved by placing rat pups in a chamber containing ethanol vapour for 3 hours a day. The blood ethanol concentration was found to be about 430 mg/dL at the end of the exposure period. Groups of ethanol treated (ET, separation controls (SC and mother reared controls (MRC were anaesthetised and killed at 16-days-of-age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle was used to determine the volume of subdivisions of the dentate gyrus, and the physical disector method was used to estimate the numerical densities of neurons within each subdivision. The total number of neurons was calculated by multiplying estimates of the numerical density with the volume. There was, on average, about 421,000 granule cells in all three treatment groups. In the hilus region, ET rats had about 27,000 neuronal cells. This value was significantly smaller than the average of 38,000 such neurons estimated to be present in both MRC and SC animals. It is concluded that neurons in the hilus region of the dentate gyrus may be particularly vulnerable to the effects of a high dose of ethanol exposure during PND 10-15. It is likely that this deficit was due to neuronal death induced by some mechanisms related to

  16. Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study.

    Science.gov (United States)

    Snowdon, D A; Kemper, S J; Mortimer, J A; Greiner, L H; Wekstein, D R; Markesbery, W R

    1996-02-21

    To determine if linguistic ability in early life is associated with cognitive function and Alzheimer's disease in late life. Two measures of linguistic ability in early life, idea density and grammatical complexity, were derived from autobiographies written at a mean age of 22 years. Approximately 58 years later, the women who wrote these autobiographies participated in an assessment of cognitive function, and those who subsequently died were evaluated neuropathologically. Convents in the United States participating in the Nun Study; primarily convents in the Milwaukee, Wis, area. Cognitive function was investigated in 93 participants who were aged 75 to 95 years at the time of their assessments, and Alzheimer's disease was investigated in the 14 participants who died at 79 to 96 years of age. Seven neuropsychological tests and neuropathologically confirmed Alzheimer's disease. Low idea density and low grammatical complexity in autobiographies written in early life were associated with low cognitive test scores in late life. Low idea density in early life had stronger and more consistent associations with poor cognitive function than did low grammatical complexity. Among the 14 sisters who died, neuropathologically confirmed Alzheimer's disease was present in all of those with low idea density in early life and in none of those with high idea density. Low linguistic ability in early life was a strong predictor of poor cognitive function and Alzheimer's disease in late life.

  17. The role of early life environmental risk factors in Parkinson disease: what is the evidence?

    Science.gov (United States)

    Logroscino, Giancarlo

    2005-09-01

    Parkinson disease (PD) is of unknown but presumably multifactorial etiology. Neuropathologic studies and animal models show that exposure to environmental neurotoxicants can determine progressive damage in the substantia nigra many years before the onset of clinical parkinsonism. Therefore, PD, like other neurologic diseases related to aging, may be determined by exposures present in the environment early during the life span or even during pregnancy. Recent epidemiologic studies have focused on the possible role of environmental risk factors present during adult life or aging. Smoking and coffee drinking have consistently been identified to have protective associations, whereas roles of other risk factors such as pesticide and infections have been reported in some studies but not replicated in others. Both genetic inheritance and sharing of common environment in the same family explain the increased risk of PD of relatives of PD cases compared with relatives of controls in familial aggregation studies. Much evidence indicates that risk factors that have a long latency or a slow effect could be important for late-onset PD. Further epidemiologic studies are warranted in this area.

  18. Early-life gut microbiome and egg allergy.

    Science.gov (United States)

    Fazlollahi, M; Chun, Y; Grishin, A; Wood, R A; Burks, A W; Dawson, P; Jones, S M; Leung, D Y M; Sampson, H A; Sicherer, S H; Bunyavanich, S

    2018-07-01

    Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10 -4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis P adj  = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10 -4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  19. Early Postnatal Lipopolysaccharide Exposure Leads to Enhanced Neurogenesis and Impaired Communicative Functions in Rats.

    Directory of Open Access Journals (Sweden)

    Yi Pang

    Full Text Available Perinatal infection is a well-identified risk factor for a number of neurodevelopmental disorders, including brain white matter injury (WMI and Autism Spectrum Disorders (ASD. The underlying mechanisms by which early life inflammatory events cause aberrant neural, cytoarchitectural, and network organization, remain elusive. This study is aimed to investigate how systemic lipopolysaccharide (LPS-induced neuroinflammation affects microglia phenotypes and early neural developmental events in rats. We show here that LPS exposure at early postnatal day 3 leads to a robust microglia activation which is characterized with mixed microglial proinflammatory (M1 and anti-inflammatory (M2 phenotypes. More specifically, we found that microglial M1 markers iNOS and MHC-II were induced at relatively low levels in a regionally restricted manner, whereas M2 markers CD206 and TGFβ were strongly upregulated in a sub-set of activated microglia in multiple white and gray matter structures. This unique microglial response was associated with a marked decrease in naturally occurring apoptosis, but an increase in cell proliferation in the subventricular zone (SVZ and the dentate gyrus (DG of hippocampus. LPS exposure also leads to a significant increase in oligodendrocyte lineage population without causing discernible hypermyelination. Moreover, LPS-exposed rats exhibited significant impairments in communicative and cognitive functions. These findings suggest a possible role of M2-like microglial activation in abnormal neural development that may underlie ASD-like behavioral impairments.

  20. Why are there lasting effects from exposure to stress during development? An analysis of current models of early stress.

    Science.gov (United States)

    Chaby, Lauren E

    2016-10-01

    The potential for stressful experiences in early life to cause lasting changes in phenotype is well documented, but the functional and evolutionary context of these changes is not well understood. Many hypotheses have been proposed to explain the role of lasting effects of stress exposure during gestation and early development; the purpose of this review is to discuss these hypotheses in the context of human and non-human animal research in the last three decades in order to (i) further dialogues between those approaching early stress from biomedical and evolutionary/ecological perspectives, (ii) outline strengths and limitations of current hypotheses, with respect to species and context-specific effects of exposure to stress in early development, and (iii) address recent evidence suggesting that stress in early development can have beneficial effects in adulthood. It is suggested that the hypotheses discussed are not mutually exclusive, but the applicability of each hypothesis will depend upon the environmental conditions and stability a species, or perhaps even an individual, experiences in their lifetime. Potential investigations to clarify applications of the current hypotheses are discussed, including longitudinal studies that span multiple developmental stages and investigations of species where measures of fitness are possible. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.

    Science.gov (United States)

    Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O

    2014-08-01

    Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.

  2. High novelty-seeking rats are resilient to negative physiological effects of the early life stress.

    Science.gov (United States)

    Clinton, Sarah M; Watson, Stanley J; Akil, Huda

    2014-01-01

    Exposure to early life stress dramatically impacts adult behavior, physiology, and neuroendocrine function. Using rats bred for novelty-seeking differences and known to display divergent anxiety, depression, and stress vulnerability, we examined the interaction between early life adversity and genetic predisposition for high- versus low-emotional reactivity. Thus, bred Low Novelty Responder (bLR) rats, which naturally exhibit high anxiety- and depression-like behavior, and bred High Novelty Responder (bHR) rats, which show low anxiety/depression together with elevated aggression, impulsivity, and addictive behavior, were subjected to daily 3 h maternal separation (MS) stress postnatal days 1-14. We hypothesized that MS stress would differentially impact adult bHR/bLR behavior, physiology (stress-induced defecation), and neuroendocrine reactivity. While MS stress did not impact bHR and bLR anxiety-like behavior in the open field test and elevated plus maze, it exacerbated bLRs' already high physiological response to stress - stress-induced defecation. In both tests, MS bLR adult offspring showed exaggerated stress-induced defecation compared to bLR controls while bHR offspring were unaffected. MS also selectively impacted bLRs' (but not bHRs') neuroendocrine stress reactivity, producing an exaggerated corticosterone acute stress response in MS bLR versus control bLR rats. These findings highlight how genetic predisposition shapes individuals' response to early life stress. Future work will explore neural mechanisms underlying the distinct behavioral and neuroendocrine consequences of MS in bHR/bLR animals.

  3. Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun Study.

    Science.gov (United States)

    Riley, Kathryn P; Snowdon, David A; Desrosiers, Mark F; Markesbery, William R

    2005-03-01

    The relationships between early life variables, cognitive function, and neuropathology were examined in participants in the Nun Study who were between the ages of 75 and 95. Our early life variable was idea density, which is a measure of linguistic ability, derived from autobiographies written at a mean age of 22 years. Six discrete categories of cognitive function, including mild cognitive impairments, were evaluated, using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Neuropathologic data included Braak staging, neurofibrillary tangle and senile plaque counts, brain weight, degree of cerebral atrophy, severity of atherosclerosis, and the presence of brain infarcts. Early-life idea density was significantly related to the categories of late-life cognitive function, including mild cognitive impairments: low idea density was associated with greater impairment. Low idea density also was significantly associated with lower brain weight, higher degree of cerebral atrophy, more severe neurofibrillary pathology, and the likelihood of meeting neuropathologic criteria for Alzheimer's disease.

  4. Early life stress paradigms in rodents: potential animal models of depression?

    Science.gov (United States)

    Schmidt, Mathias V; Wang, Xiao-Dong; Meijer, Onno C

    2011-03-01

    While human depressive illness is indeed uniquely human, many of its symptoms may be modeled in rodents. Based on human etiology, the assumption has been made that depression-like behavior in rats and mice can be modulated by some of the powerful early life programming effects that are known to occur after manipulations in the first weeks of life. Here we review the evidence that is available in literature for early life manipulation as risk factors for the development of depression-like symptoms such as anhedonia, passive coping strategies, and neuroendocrine changes. Early life paradigms that were evaluated include early handling, separation, and deprivation protocols, as well as enriched and impoverished environments. We have also included a small number of stress-related pharmacological models. We find that for most early life paradigms per se, the actual validity for depression is limited. A number of models have not been tested with respect to classical depression-like behaviors, while in many cases, the outcome of such experiments is variable and depends on strain and additional factors. Because programming effects confer vulnerability rather than disease, a number of paradigms hold promise for usefulness in depression research, in combination with the proper genetic background and adult life challenges.

  5. Early exposure to volatile anesthetics impairs long-term associative learning and recognition memory.

    Directory of Open Access Journals (Sweden)

    Bradley H Lee

    Full Text Available Anesthetic exposure early in life affects neural development and long-term cognitive function, but our understanding of the types of memory that are altered is incomplete. Specific cognitive tests in rodents that isolate different memory processes provide a useful approach for gaining insight into this issue.Postnatal day 7 (P7 rats were exposed to either desflurane or isoflurane at 1 Minimum Alveolar Concentration for 4 h. Acute neuronal death was assessed 12 h later in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. In separate behavioral experiments, beginning at P48, subjects were evaluated in a series of object recognition tests relying on associative learning, as well as social recognition.Exposure to either anesthetic led to a significant increase in neuroapoptosis in each brain region. The extent of neuronal death did not differ between groups. Subjects were unaffected in simple tasks of novel object and object-location recognition. However, anesthetized animals from both groups were impaired in allocentric object-location memory and a more complex task requiring subjects to associate an object with its location and contextual setting. Isoflurane exposure led to additional impairment in object-context association and social memory.Isoflurane and desflurane exposure during development result in deficits in tasks relying on associative learning and recognition memory. Isoflurane may potentially cause worse impairment than desflurane.

  6. Xenohormesis in early life: New avenues of research to explore anti-aging strategies through the maternal diet.

    Science.gov (United States)

    de Medina, Philippe

    2017-11-01

    Aging is a progressive internal physiological deterioration of the organism, leading to the occurrence of age-related lethal diseases. It has become a major societal challenge to understand the processes that drive aging and to develop rational pharmacological agents and dietary approaches to fight against age-related deterioration and diseases. Interestingly, several lines of evidence highlight an influence of the developmental period on the risk of age-related diseases later in life. This field is known as the developmental origins of health and disease. Following this logic, studying the modification of maternal diet during early life may provide innovative new anti-aging approaches. Nutritional and psychological stresses during gestation are associated with poorer offspring health conditions in late life, and must be avoided during pregnancy. Besides these recommendations, very little has been published about the possible use of maternal diet to program offspring for healthy aging and an extended lifespan. Such health benefits may be provided by different foreign molecules, and particularly the phytochemicals produced by stressed plants, or xenohormetins. The xenohormesis hypothesis proposes that xenohormetins are signals of environmental change and trigger a beneficial adaptive response in individuals who consume them. No studies to date have investigated whether the consumption of stressed plants during pregnancy and lactation could provide chemical cues that impact early life programming and thus influence the future health and lifespan of offspring. Investigating the effect of xenohormesis in early life will involve adding edible plants exposed to different stressors (i.e. UV light, heat, ozone, etc.) to maternal diet and the exposure of offspring to this xenohormetin-enriched maternal diet at different periods of their prenatal life. The hypothesis proposed in this article is a potential tool to decipher the possible impact of xenohormesis during early

  7. Early Mars: A Warm Wet Niche for Life

    Science.gov (United States)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.

    2010-01-01

    Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution had conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 Ma of Martian history were ripe for life to develop because of the abundance of: (i) Water-as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at approx.3.9 Ga, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic patterns in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 Ma?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve)

  8. The composition of the gut microbiota throughout life, with an emphasis on early life

    Directory of Open Access Journals (Sweden)

    Juan Miguel Rodríguez

    2015-02-01

    Full Text Available The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3–5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health.

  9. The composition of the gut microbiota throughout life, with an emphasis on early life

    Science.gov (United States)

    Rodríguez, Juan Miguel; Murphy, Kiera; Stanton, Catherine; Ross, R. Paul; Kober, Olivia I.; Juge, Nathalie; Avershina, Ekaterina; Rudi, Knut; Narbad, Arjan; Jenmalm, Maria C.; Marchesi, Julian R.; Collado, Maria Carmen

    2015-01-01

    The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3–5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health. PMID:25651996

  10. Dual influences of early-life maternal deprivation on histone deacetylase activity and recognition memory in rats.

    Science.gov (United States)

    Albuquerque Filho, Manoel Osório; de Freitas, Betânia Souza; Garcia, Rebeca Carvalho Lacerda; Crivelaro, Pedro Castilhos de Freitas; Schröder, Nadja; de Lima, Maria Noêmia Martins

    2017-03-06

    Exposure to stress early in life may negatively impact nervous system functioning, including increasing the proneness to learning and memory impairments later in life. Maternal deprivation, a model of early-life stress, hinders memory in adult rats and lessens brain-derived neurotrophic factor (BDNF) levels in the hippocampus in a very heterogeneous way among individuals. The main goal of the present study was to investigate the possible epigenetic modulation underlying recognition memory impairment and reduced BDNF levels in the hippocampus of adult maternally deprived rats. We also evaluated the potential ameliorating properties of the histone deacetylase (HDAC) inhibitor, sodium butyrate, on memory deficits and BDNF changes related to maternal deprivation. Maternally deprived animals were categorized as 'inferior learners' and 'superior learners' according to their performance in object recognition memory task in comparison to controls. Results indicated that HDAC activity was higher in individuals submitted to maternal deprivation with the worst cognitive performance (inferior learners). Acute administration of sodium butyrate increased histone H3 acetylation and BDNF levels, and restored recognition memory in maternally deprived animals with the worst cognitive performance. Moreover, we also showed that there is a positive correlation between BDNF levels and memory performance. Taken together, the results indicated that HDAC inhibitors could be considered as a possible therapeutic agent to improve cognitive performance in inferior learners. Further studies need to be conducted for a better comprehension of the mechanisms related to persistent alterations observed in adult life induced by early stressful circumstances and those leading to resilience. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. General anesthesia exposure in early life reduces the risk of allergic diseases: A nationwide population-based cohort study.

    Science.gov (United States)

    Kuo, Ho-Chang; Yang, Ya-Ling; Ho, Shu-Chen; Guo, Mindy Ming-Huey; Jiang, Jyun-Hong; Huang, Ying-Hsien

    2016-07-01

    General anesthesia (GA) has been used for second line treatment strategy for status asthmaticus in pediatric patients. The association between GA in children and risk of followed-up allergic diseases is unclear. This study aims to assess the risk of allergic diseases after GA in children.We did a nationwide retrospective cohort study by analyzing data from the National Health Insurance Research Database (NHIRD) in Taiwan. The subsequent risks for allergic diseases, including asthma (ICD-9: 493.X), allergic rhinitis (AR; ICD-9 CM code 477.X), and atopic dermatitis (AD; ICD-9-CM code 691.X), were compared between exposure to GA and none before 1 year of age throughout the follow-up period using the Cox proportional hazards model.Insurance claims data for 32,742 children younger than 1 year old from all insured children in the NHIRD. Of those, 2358 subjects were exposed to GA; 414 and 1944 children exposed to mask and intubation ventilation, respectively, served as the study cohort, whereas the remaining 30,384 children made up the comparison cohort. Children in the GA group were at a lower risk of developing asthma, AR and AD, with adjusted hazard ratios of 0.67 (0.62-0.72, 95%CI), 0.72 (0.68-0.77, 95%CI), 0.60 (0.56-0.64, 95%CI), respectively.Children who were exposed to GA in early life before 1 year of age had reduced risk of subsequently developing allergic diseases such as asthma, AD, and AR, when compared with general population.

  12. Exposure to chronic early-life stress lastingly alters the adipose tissue, the leptin system and changes the vulnerability to western-style diet later in life in mice

    NARCIS (Netherlands)

    Yam, Kit-Yi; Naninck, Eva F. G.; Abbink, M. R.; la Fleur, Susanne E.; Schipper, L.; de Beukelaar, J W K; Grefhorst, Aldo; Oosting, A.; van der Beek, E. M.; Lucassen, P. J.; Korosi, Aniko

    Early-life stress (ES) increases the vulnerability to develop psychopathologies and cognitive decline in adulthood. Interestingly, this is often comorbid with metabolic disorders, such as obesity. However, it is unclear whether ES leads to lasting metabolic changes and to what extent this is

  13. Exposure to chronic early-life stress lastingly alters the adipose tissue, the leptin system and changes the vulnerability to western-style diet later in life in mice.

    NARCIS (Netherlands)

    Yam, K.Y.; Naninck, E.F.G.; Abbink, M.R.; la Fleur, S.E.; Schipper, L.; van den Beukel, J.C.; Grefhorst, A.; Oosting, A.; van der Beek, E.M.; Lucassen, P.J.; Korosi, A.

    Early-life stress (ES) increases the vulnerability to develop psychopathologies and cognitive decline in adulthood. Interestingly, this is often comorbid with metabolic disorders, such as obesity. However, it is unclear whether ES leads to lasting metabolic changes and to what extent this is

  14. The early Earth atmosphere and early life catalysts.

    Science.gov (United States)

    Ramírez Jiménez, Sandra Ignacia

    2014-01-01

    Homochirality is a property of living systems on Earth. The time, the place, and the way in which it appeared are uncertain. In a prebiotic scenario two situations are of interest: either an initial small bias for handedness of some biomolecules arouse and progressed with life, or an initial slight excess led to the actual complete dominance of the known chiral molecules. A definitive answer can probably never be given, neither from the fields of physics and chemistry nor biology. Some arguments can be advanced to understand if homochirality is necessary for the initiation of a prebiotic homochiral polymer chemistry, if this homochirality is suggesting a unique origin of life, or if a chiral template such as a mineral surface is always required to result in an enantiomeric excess. A general description of the early Earth scenario will be presented in this chapter, followed by a general description of some clays, and their role as substrates to allow the concentration and amplification of some of the building blocks of life.

  15. Behavioral and cognitive impact of early life stress: Insights from an animal model.

    Science.gov (United States)

    Liu, Hesong; Atrooz, Fatin; Salvi, Ankita; Salim, Samina

    2017-08-01

    Children subjected to traumatic events during childhood are reported to exhibit behavioral and cognitive deficits later in life, often leading to post-traumatic stress disorder (PTSD) and major depression. Interestingly, some children continue to remain normal despite being exposed to the same risk factors. These trauma-related behavioral and cognitive profiles across different stages of life are not well understood. Animal studies can offer useful insights. The goal of this study was to determine the impact of early life exposure to traumatic events on behavioral and cognitive profile in rats by tracking the behavior of each rat at different ages. We utilized the single prolonged stress (SPS), a rodent model of PTSD, to study the effects of early life stress. Male Sprague-Dawley rats were exposed to SPS on post-natal day (PND) 25. Tests to assess anxiety- and depression-like behavior, as well as learning and memory function were performed at PND32, 60 and 90. Rats exposed to SPS exhibited both anxiety- and depression-like behavior at PND32. And, short-term (STM) but not long-term memory (LTM) was impaired. Rats exposed to SPS at PND60 exhibited anxiety- but not depression-like behavior. STM but not LTM was impaired. Rats exposed to SPS at PND90 exhibited fearful (as indicated by elevated plus maze test) but not an overall anxiety-like behavior (in light and dark test). These rats also displayed significant depression-like behavior with no changes in STM or LTM. Interestingly, when data was further analyzed, two subsets of PND90 rats exposed to SPS were identified, "susceptible": with depression-like behavior and "resilient": without depression-like behavior. Importantly, while resilient group expressed early signs of anxiety- (at PND32 and PND60) and depression-like behavior (at PND32), these behavioral deficits were absent at PND90. On the other hand, susceptible PND90 rats exposed to SPS expressed later onset of anxiety-like behavior (at PND60), while depression

  16. Transgenerational Effects of Early Environmental Insults on Aging and Disease Incidence

    NARCIS (Netherlands)

    Ambeskovic, Mirela; Roseboom, Tessa J.; Metz, Gerlinde A. S.

    2017-01-01

    Adverse early life experiences are major influences on developmental trajectories with potentially life-long consequences. Prenatal or early postnatal exposure to stress, undernutrition or environmental toxicants may reprogram brain development and increase risk of behavioural and neurological

  17. Effects of the herbicide diuron on the early life history stages of coral

    Energy Technology Data Exchange (ETDEWEB)

    Negri, Andrew [Australian Institute of Marine Science, PMB 3 Townsville, QLD 4810 (Australia)]. E-mail: a.negri@aims.gov.au; Vollhardt, Claudia [Australian Institute of Marine Science, PMB 3 Townsville, QLD 4810 (Australia); Humphrey, Craig [Australian Institute of Marine Science, PMB 3 Townsville, QLD 4810 (Australia); Heyward, Andrew [Australian Institute of Marine Science, PMB 3 Townsville, QLD 4810 (Australia); Jones, Ross [Centre for Marine Studies, University of Queensland, St Lucia, QLD 4072 (Australia); Queensland Health Scientific Services, 39 Kessels Road, Coopers Plains 4108 (Australia); Eaglesham, Geoff [Bermuda Biological Station for Research, Inc, Ferry Reach, St George' s GE 01 (Bermuda); Fabricius, Katharina [Australian Institute of Marine Science, PMB 3 Townsville, QLD 4810 (Australia)

    2005-07-01

    The effects of the herbicide diuron on the early life history stages of broadcast spawning and brooding corals were examined in laboratory experiments. Fertilisation of Acropora millepora and Montipora aequituberculata oocytes were not inhibited at diuron concentrations of up to 1000{mu}gl{sup -1}. Metamorphosis of symbiont-free A. millepora larvae was only significantly inhibited at 300{mu}gl{sup -1} diuron. Pocillopora damicornis larvae, which contain symbiotic dinoflagellates, were able to undergo metamorphosis after 24h exposure to diuron at 1000{mu}gl{sup -1}. Two-week old P. damicornis recruits on the other hand were as susceptible to diuron as adult colonies, with expulsion of symbiotic dinoflagellates (bleaching) evident at 10{mu}gl{sup -1} diuron after 96h exposure. Reversible metamorphosis was observed at high diuron concentrations, with fully bleached polyps escaping from their skeletons. Pulse amplitude modulation (PAM) chlorophyll fluorescence techniques demonstrated a reduction in photosynthetic efficiency ({delta}F/F{sub m}{sup '}) in illuminated P. damicornis recruits after a 2h exposure to 1{mu}gl{sup -1} diuron. The dark-adapted quantum yields (F{sub v}/F{sub m}) also declined, indicating chronic photoinhibition and damage to photosystem II.

  18. Effects of the herbicide diuron on the early life history stages of coral

    International Nuclear Information System (INIS)

    Negri, Andrew; Vollhardt, Claudia; Humphrey, Craig; Heyward, Andrew; Jones, Ross; Eaglesham, Geoff; Fabricius, Katharina

    2005-01-01

    The effects of the herbicide diuron on the early life history stages of broadcast spawning and brooding corals were examined in laboratory experiments. Fertilisation of Acropora millepora and Montipora aequituberculata oocytes were not inhibited at diuron concentrations of up to 1000μgl -1 . Metamorphosis of symbiont-free A. millepora larvae was only significantly inhibited at 300μgl -1 diuron. Pocillopora damicornis larvae, which contain symbiotic dinoflagellates, were able to undergo metamorphosis after 24h exposure to diuron at 1000μgl -1 . Two-week old P. damicornis recruits on the other hand were as susceptible to diuron as adult colonies, with expulsion of symbiotic dinoflagellates (bleaching) evident at 10μgl -1 diuron after 96h exposure. Reversible metamorphosis was observed at high diuron concentrations, with fully bleached polyps escaping from their skeletons. Pulse amplitude modulation (PAM) chlorophyll fluorescence techniques demonstrated a reduction in photosynthetic efficiency (ΔF/F m ' ) in illuminated P. damicornis recruits after a 2h exposure to 1μgl -1 diuron. The dark-adapted quantum yields (F v /F m ) also declined, indicating chronic photoinhibition and damage to photosystem II

  19. A Population-based Study Evaluating the Association between Surgery in Early Life and Child Development at Primary School Entry.

    Science.gov (United States)

    O'Leary, James D; Janus, Magdalena; Duku, Eric; Wijeysundera, Duminda N; To, Teresa; Li, Ping; Maynes, Jason T; Crawford, Mark W

    2016-08-01

    It is unclear whether exposure to surgery in early life has long-term adverse effects on child development. The authors aimed to investigate whether surgery in early childhood is associated with adverse effects on child development measured at primary school entry. The authors conducted a population-based cohort study in Ontario, Canada, by linking provincial health administrative databases to children's developmental outcomes measured by the Early Development Instrument (EDI). From a cohort of 188,557 children, 28,366 children who underwent surgery before EDI completion (age 5 to 6 yr) were matched to 55,910 unexposed children. The primary outcome was early developmental vulnerability, defined as any domain of the EDI in the lowest tenth percentile of the population. Subgroup analyses were performed based on age at first surgery (less than 2 and greater than or equal to 2 yr) and frequency of surgery. Early developmental vulnerability was increased in the exposed group (7,259/28,366; 25.6%) compared with the unexposed group (13,957/55,910; 25.0%), adjusted odds ratio, 1.05; 95% CI, 1.01 to 1.08. Children aged greater than or equal to 2 yr at the time of first surgery had increased odds of early developmental vulnerability compared with unexposed children (odds ratio, 1.05; 95% CI, 1.01 to 1.10), but children aged less than 2 yr at the time of first exposure were not at increased risk (odds ratio, 1.04; 95% CI, 0.98 to 1.10). There was no increase in odds of early developmental vulnerability with increasing frequency of exposure. Children who undergo surgery before primary school age are at increased risk of early developmental vulnerability, but the magnitude of the difference between exposed and unexposed children is small.

  20. Cumulative Effects of Nutrient Enrichment and Elevated Temperature Compromise the Early Life History Stages of the Coral Acropora tenuis

    Science.gov (United States)

    Noonan, Sam H. C.; Willis, Bette L.; Fabricius, Katharina E.; Negri, Andrew P.

    2016-01-01

    Inshore coral reefs are experiencing the combined pressures of excess nutrient availability associated with coastal activities and warming seawater temperatures. Both pressures are known to have detrimental effects on the early life history stages of hard corals, but studies of their combined effects on early demographic stages are lacking. We conducted a series of experiments to test the combined effects of nutrient enrichment (three levels) and elevated seawater temperature (up to five levels) on early life history stages of the inshore coral Acropora tenuis, a common species in the Indo-Pacific and Red Sea. Gamete fertilization, larval survivorship and larval settlement were all significantly reduced as temperature increased, but only fertilization was further affected by simultaneous nutrient enrichment. Combined high temperatures and nutrient enrichment affected fertilization in an additive manner, whereas embryo abnormalities increased synergistically. Higher than normal temperatures (32°C) increased coral juvenile growth rates 1.6-fold, but mortality also increased by 50%. The co-occurrence of nutrient enrichment with high temperatures reduced juvenile mortality to 36%, ameliorating temperature stress (antagonistic interaction). Overall, the types of effect (additive vs synergistic or antagonistic) and their magnitude varied among life stages. Gamete and embryo stages were more affected by temperature stress and, in some cases, also by nutrient enrichment than juveniles. The data suggest that coastal runoff events might exacerbate the impacts of warming temperatures on fertilization if these events co-occur during corals spawning. The cumulative impacts of simultaneous exposure to nutrient enrichment and elevated temperatures over all early life history stages increases the likelihood for failure of larval supply and recruitment for this coral species. Our results suggest that improving the water quality of river discharges into coastal areas might help to

  1. Cumulative Effects of Nutrient Enrichment and Elevated Temperature Compromise the Early Life History Stages of the Coral Acropora tenuis.

    Science.gov (United States)

    Humanes, Adriana; Noonan, Sam H C; Willis, Bette L; Fabricius, Katharina E; Negri, Andrew P

    2016-01-01

    Inshore coral reefs are experiencing the combined pressures of excess nutrient availability associated with coastal activities and warming seawater temperatures. Both pressures are known to have detrimental effects on the early life history stages of hard corals, but studies of their combined effects on early demographic stages are lacking. We conducted a series of experiments to test the combined effects of nutrient enrichment (three levels) and elevated seawater temperature (up to five levels) on early life history stages of the inshore coral Acropora tenuis, a common species in the Indo-Pacific and Red Sea. Gamete fertilization, larval survivorship and larval settlement were all significantly reduced as temperature increased, but only fertilization was further affected by simultaneous nutrient enrichment. Combined high temperatures and nutrient enrichment affected fertilization in an additive manner, whereas embryo abnormalities increased synergistically. Higher than normal temperatures (32°C) increased coral juvenile growth rates 1.6-fold, but mortality also increased by 50%. The co-occurrence of nutrient enrichment with high temperatures reduced juvenile mortality to 36%, ameliorating temperature stress (antagonistic interaction). Overall, the types of effect (additive vs synergistic or antagonistic) and their magnitude varied among life stages. Gamete and embryo stages were more affected by temperature stress and, in some cases, also by nutrient enrichment than juveniles. The data suggest that coastal runoff events might exacerbate the impacts of warming temperatures on fertilization if these events co-occur during corals spawning. The cumulative impacts of simultaneous exposure to nutrient enrichment and elevated temperatures over all early life history stages increases the likelihood for failure of larval supply and recruitment for this coral species. Our results suggest that improving the water quality of river discharges into coastal areas might help to

  2. Early Life Microbiota, Neonatal Immune Maturation and Hematopoiesis

    DEFF Research Database (Denmark)

    Kristensen, Matilde Bylov

    Emerging epidemiologic data supports the hypothesis that early life colonization is a key player in development of a balanced immune system. Events in early life, as birth mode and infant diet, are shown to influence development of immune related diseases, like asthma, diabetes and inflammatory...... bowl disease, later in life. The intestinal epithelium makes up a physical and biochemical barrier between the bacteria in the gut lumen and the immune cells in the submocusal tissue. This monolayer of intestinal epithelial cells (IEC) makes up an extremely large surface and is highly important...... for the synergistic coexistence between trillions of bacteria in the gastrointestinal tract and their mammalian hosts. The IEC actively communicate with the microbiota of the gut lumen and tolerance establishment in the intestine is induced as a result of a balanced and controlled communication between IEC...

  3. Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications

    Science.gov (United States)

    Pohl, Calvin S.; Medland, Julia E.

    2015-01-01

    Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. PMID:26451004

  4. The developing hypopharyngeal microbiota in early life

    DEFF Research Database (Denmark)

    Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael

    2016-01-01

    BACKGROUND: The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establi......BACKGROUND: The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand...... the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC2010 cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. RESULTS: Our analysis shows...... that majority of the hypopharyngeal microbiota of healthy infants belong to each individual's core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we...

  5. Inconstant sun: how solar evolution has affected cosmic and ultraviolet radiation exposure over the history of life on Earth.

    Science.gov (United States)

    Karam, P Andrew

    2003-03-01

    Four billion years ago, sea-level UV exposure was more than 400 times as intense as today, the dose from solar cosmic rays was five times present levels, and galactic cosmic rays accounted for only about 10% their current contribution to sea-level radiation doses. Exposure to cosmic radiation accounts for about 10% of natural background radiation exposure today and includes dose from galactic cosmic rays and solar charged particles. There is little exposure to ionizing wavelengths of UV due to absorption by ozone. The sun has evolved significantly over its life; in the past there were higher levels of particulate radiation and lower UV emissions from the sun, and a stronger solar wind reduced radiation dose in the inner solar system from galactic cosmic rays. Finally, since the early atmosphere contained little to no oxygen, surface levels of UV radiation were far higher in the past.

  6. Early Adolescent Exposure to Alcohol Advertising and Its Relationship to Underage Drinking

    Science.gov (United States)

    Collins, Rebecca L.; Ellickson, Phyllis L.; McCaffrey, Daniel; Hambarsoomians, Katrin

    2009-01-01

    Purpose To determine whether early adolescents who are exposed to alcohol marketing are subsequently more likely to drink. Recent studies suggest that exposure to alcohol ads has a limited influence on drinking in mid-adolescence. Early adolescents may be more vulnerable to alcohol advertising effects. Methods Two in-school surveys of 1,786 South Dakota youth measured exposure to television beer advertisements, alcohol ads in magazines, in-store beer displays and beer concessions, radio-listening time, and ownership of beer promotional items during sixth grade, and drinking intentions and behavior at seventh grade. Multivariate regression equations predicted the two drinking outcomes using the advertising exposure variables and controlling for psychosocial factors and prior drinking. Results After adjusting for covariates, the joint effect of exposure to advertising from all six sources at Grade 6 was strongly predictive of Grade 7 drinking and Grade 7 intentions to drink. Youth in the 75th percentile of alcohol marketing exposure had a predicted probability of drinking that was 50% greater than that of youth in the 25th percentile. Conclusions Although causal effects are uncertain, policy makers should consider limiting a variety of marketing practices that could contribute to drinking in early adolescence. PMID:17531759

  7. Early life nutrition, epigenetics and programming of later life disease.

    Science.gov (United States)

    Vickers, Mark H

    2014-06-02

    The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA) and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how these effects may be

  8. Early Life Nutrition, Epigenetics and Programming of Later Life Disease

    Directory of Open Access Journals (Sweden)

    Mark H. Vickers

    2014-06-01

    Full Text Available The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how

  9. Violence exposure in real-life, video games, television, movies, and the internet: is there desensitization?

    Science.gov (United States)

    Funk, Jeanne B; Baldacci, Heidi Bechtoldt; Pasold, Tracie; Baumgardner, Jennifer

    2004-02-01

    It is believed that repeated exposure to real-life and to entertainment violence may alter cognitive, affective, and behavioral processes, possibly leading to desensitization. The goal of the present study was to determine if there are relationships between real-life and media violence exposure and desensitization as reflected in related characteristics. One hundred fifty fourth and fifth graders completed measures of real-life violence exposure, media violence exposure, empathy, and attitudes towards violence. Regression analyses indicated that only exposure to video game violence was associated with (lower) empathy. Both video game and movie violence exposure were associated with stronger proviolence attitudes. The active nature of playing video games, intense engagement, and the tendency to be translated into fantasy play may explain negative impact, though causality was not investigated in the present design. The samples' relatively low exposure to real-life violence may have limited the identification of relationships. Although difficult to quantify, desensitization to violence should be further studied using related characteristics as in the present study. Individual differences and causal relationships should also be examined.

  10. Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications.

    Science.gov (United States)

    Pohl, Calvin S; Medland, Julia E; Moeser, Adam J

    2015-12-15

    Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. Copyright © 2015 the American Physiological Society.

  11. The Exposure Advantage: Early Exposure to a Multilingual Environment Promotes Effective Communication.

    Science.gov (United States)

    Fan, Samantha P; Liberman, Zoe; Keysar, Boaz; Kinzler, Katherine D

    2015-07-01

    Early language exposure is essential to developing a formal language system, but may not be sufficient for communicating effectively. To understand a speaker's intention, one must take the speaker's perspective. Multilingual exposure may promote effective communication by enhancing perspective taking. We tested children on a task that required perspective taking to interpret a speaker's intended meaning. Monolingual children failed to interpret the speaker's meaning dramatically more often than both bilingual children and children who were exposed to a multilingual environment but were not bilingual themselves. Children who were merely exposed to a second language performed as well as bilingual children, despite having lower executive-function scores. Thus, the communicative advantages demonstrated by the bilinguals may be social in origin, and not due to enhanced executive control. For millennia, multilingual exposure has been the norm. Our study shows that such an environment may facilitate the development of perspective-taking tools that are critical for effective communication. © The Author(s) 2015.

  12. Physical occupational exposures during working life and quality of life after labour market exit: results from the GAZEL study

    Science.gov (United States)

    Platts, Loretta; Netuveli, Gopalakrishnan; Webb, Elizabeth; Zins, Marie; Goldberg, Marcel; Blane, David; Wahrendorf, Morten

    2013-01-01

    Objective To investigate variations in quality of life at older ages we take a life course perspective to analyse long-term effects of physical working conditions upon quality of life after retirement. In doing so, we study to what extent these associations are explained by individuals’ health at older ages. Method We use administrative data and self-administered questionnaire responses from the French GAZEL cohort. Quality of life was assessed with CASP-19 in 2009 and related to three types of physical working conditions during previous working life: (1) ergonomic strain, (2) physical danger and (3) exposures to chemicals. Health was assessed in 2007 with the SF-36 Health Survey. Multiple regressions were calculated in retired men only, controlling for important confounders including social position. Results In contrast to men, few women were exposed to strenuous and dangerous working conditions in this cohort and were not included in subsequent analyses. Negative effects on retired men’s quality of life were found for the physical occupational exposures of ergonomic strain and physical danger, but not for chemical exposures. Effects were attenuated after the introduction of physical and mental health to the models, indicating an indirect effect of physical working conditions upon quality of life via health. Conclusion Adverse physical working conditions have long-term consequences for health and quality of life at older ages. Improvements to physical working conditions may improve individuals’ quality of life over the long term. PMID:23560563

  13. Physical occupational exposures during working life and quality of life after labour market exit: results from the GAZEL study.

    Science.gov (United States)

    Platts, Loretta G; Netuveli, Gopalakrishnan; Webb, Elizabeth; Zins, Marie; Goldberg, Marcel; Blane, David; Wahrendorf, Morten

    2013-01-01

    To investigate variations in quality of life at older ages, we take a life course perspective to analyse long-term effects of physical working conditions upon quality of life after retirement. In doing so, we study to what extent these associations are explained by individuals' health at older ages. We use administrative data and self-administered questionnaire responses from the French GAZEL cohort. Quality of life was assessed with CASP-19 in 2009 and related to three types of physical working conditions during previous working life: (1) ergonomic strain, (2) physical danger and (3) exposures to chemicals. Health was assessed in 2007 with the SF-36 Health Survey. Multiple regressions were calculated in retired men only, controlling for important confounders including social position. In contrast to men, few women were exposed to strenuous and dangerous working conditions in this cohort and were not included in subsequent analyses. Negative effects on retired men's quality of life were found for the physical occupational exposures of ergonomic strain and physical danger, but not for chemical exposures. Effects were attenuated after the introduction of physical and mental health to the models, indicating an indirect effect of physical working conditions upon quality of life via health. Adverse physical working conditions have long-term consequences for health and quality of life at older ages. Improvements to physical working conditions may improve individuals' quality of life over the long term.

  14. Roles of attachment and self-esteem: impact of early life stress on depressive symptoms among Japanese institutionalized children

    OpenAIRE

    Suzuki, Hanako; Tomoda, Akemi

    2015-01-01

    Background Although exposure to early life stress is known to affect mental health, the underlying mechanisms of its impacts on depressive symptoms among institutionalized children and adolescents have been little studied. Methods To investigate the role of attachment and self-esteem in association with adverse childhood experiences (ACEs) and depressive symptoms, 342 children (149 boys, 193 girls; age range 9-18 years old, mean age?=?13.5???2.4) living in residential foster care facilities i...

  15. Effects on metabolic parameters in young rats born with low birth weight after exposure to a mixture of pesticides

    DEFF Research Database (Denmark)

    Svingen, Terje; Ramhøj, Louise; Egebjerg, Karen Mandrup

    2018-01-01

    Pesticide exposure during fetal life can lead to low birth weight and is commonly observed in reproductive toxicology studies. Associations have also been found in low birth weight babies born from pesticide-exposed gardeners. Since low birth weight is also linked to metabolic disorders, it can...... be speculated that early life exposure to pesticides could increase the risk of becoming obese or developing diabetes later in life. We have analyzed potential long-term effects of gestational and lactational exposure to a low dose mixture of six pesticides that individually can cause low birth weight....... Our results suggest that early-life exposure to pesticides may contribute to the development of metabolic disorders later in life....

  16. Early evolution without a tree of life.

    Science.gov (United States)

    Martin, William F

    2011-06-30

    Life is a chemical reaction. Three major transitions in early evolution are considered without recourse to a tree of life. The origin of prokaryotes required a steady supply of energy and electrons, probably in the form of molecular hydrogen stemming from serpentinization. Microbial genome evolution is not a treelike process because of lateral gene transfer and the endosymbiotic origins of organelles. The lack of true intermediates in the prokaryote-to-eukaryote transition has a bioenergetic cause.

  17. Impact of a Comprehensive Early Clinical Exposure Program for Preclinical Year Medical Students

    Directory of Open Access Journals (Sweden)

    Sumitra Govindarajan

    2018-06-01

    Full Text Available Purpose: To study the impact of an early clinical exposure program designed to provide a wide variety (cognitive, affective and psychomotor of learning experiences for the preclinical year students. Method: One hundred and fifty preclinical students were posted in small groups to selected departments – Transfusion medicine, Catheterization lab, Simulation lab, Radiology, Neurology, Nephrology, Respiratory medicine and General surgery. Each student had atleast ten hours  of clinical exposure under this program. The program was evaluated through a series of pre and post-test questionnaires, which were designed based on the learning objectives of each session. Students who wished to participate in the program evaluation gave informed consent, took up the pre / post test and were also asked to give their written open comments about the program. Results: There was a significant increase in the post-test scores (ranging from 9.14±2.67 to 36.65±6.62 when compared to the pre-test scores (ranging from 7.94±2.31 to 28.69±6.11 for all the sessions (p value <0.001, n=144. Analysis of the open feedback showed that the program had significant impact on the cognitive, psychomotor and affective domains. “Application of basic sciences in clinical practice”, “motivation to learn”, “got familiar with various specialties”, “insight about what the patient undergoes” were the themes identified from the open comments. Conclusion: The innovative use of early clinical exposure program to teach/learn clinical skills like phlebotomy and Basic Life Support had been well appreciated by the students. The present design involving a variety of learning experiences has been successful in introducing the various dimensions of medical profession like scientific, ethical, interpersonal, professional and social to the new entrants in addition to enhancing their motivation to learn. Keywords: Attitude, Learning, Simulation lab, Medical education, Curriculum

  18. Gut microbiota in early life and its influence on health and disease: A position paper by the Malaysian Working Group on Gastrointestinal Health.

    Science.gov (United States)

    Lee, Yeong Yeh; Hassan, Siti Asma; Ismail, Intan Hakimah; Chong, Sze Yee; Raja Ali, Raja Affendi; Amin Nordin, Syafinaz; Lee, Way Seah; Majid, Noorizan Abdul

    2017-12-01

    The role of gut microbiota in early life and its impact on gut health and subsequent diseases remain unclear. There is a lack of research and awareness in this area, especially in the Asia-Pacific region, including Malaysia. This paper reports the position of a Malaysian Working Group on some key issues surrounding gut microbiota in early life and its role in gut health and diseases, as well as experts' stand on probiotics and prebiotics. The group reached a consensus that certain factors, including elective caesarean; premature deliveries; complementary feeding; use of antibiotics, prebiotics and/or probiotics; and exposure to the external environmental, have an impact on gut microbiota in early life. However, as evidence is lacking, especially from the Asia-Pacific region, further studies are needed to understand how gut microbiota in early life affects subsequent diseases, including allergy, inflammatory bowel disease, obesity and infantile colic. Lastly, although beneficial in acute diarrhoeal disease and probably allergic eczema, probiotics (and/or prebiotics) should be used cautiously in other gut dysbiotic conditions until more data are available. © 2017 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  19. Specific synbiotics in early life protect against diet-induced obesity in adult mice

    NARCIS (Netherlands)

    Mischke, Mona; Arora, Tulika; Tims, Sebastian; Engels, Eefje; Sommer, Nina; Limpt, van Kees; Baars, Annemarie; Oozeer, Raish; Oosting, Annemarie; Bäckhed, Fredrik; Knol, Jan

    2018-01-01

    Aims: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health throughout life. Here, we determined how beneficial microbiome interventions in early life

  20. Early life hormetic treatments decrease irradiation-induced oxidative damage, increase longevity, and enhance sexual performance during old age in the Caribbean fruit fly

    International Nuclear Information System (INIS)

    López-Martínez, Giancarlo; Hahn, Daniel A.

    2014-01-01

    Early life events can have dramatic consequences on performance later in life. Exposure to stressors at a young age affects development, the rate of aging, risk of disease, and overall lifespan. In spite of this, mild stress exposure early in life can have beneficial effects on performance later in life. These positive effects of mild stress are referred to as physiological conditioning hormesis. In our current study we used anoxia conditioning hormesis as a pretreatment to reduce oxidative stress and improve organismal performance, lifespan, and healthspan of Caribbean fruit flies. We used gamma irradiation to induce mild oxidative damage in a low-dose experiment, and massive oxidative damage in a separate high-dose experiment, in pharate adult fruit flies just prior to adult emergence. Irradiation-induced oxidative stress leads to reduced adult emergence, flight ability, mating performance, and lifespan. We used a hormetic approach, one hour of exposure to anoxia plus irradiation in anoxia, to lower post-irradiation oxidative damage. We have previously shown that this anoxic-conditioning treatment elevates total antioxidant capacity and lowers post-irradiation oxidative damage to lipids and proteins. In this study, conditioned flies had lower mortality rates and longer lifespan compared to those irradiated without hormetic conditioning. As a metric of healthspan, we tracked mating both at a young age (10 d) and old age (30 d). We found that anoxia-conditioned male flies were more competitive at young ages when compared to unconditioned irradiation stressed male flies, and that the positive effects of anoxic conditioning hormesis on mating success were even more pronounced in older males. Our data shows that physiological conditioning hormesis at a young age, not only improves immediate metrics of organismal performance (emergence, flight, mating), but the beneficial effects also carry into old age by reducing late life oxidative damage and improving lifespan and

  1. Early-Life Food Nutrition, Microbiota Maturation and Immune Development Shape Life-Long Health.

    Science.gov (United States)

    Zhou, Xiaoli; Du, Lina; Shi, Ronghua; Chen, Zhidong; Zhou, Yiming; Li, Zongjie

    2018-06-06

    The current knowledge about early-life nutrition and environmental factors that affect the interaction between the symbiotic microbiota and the host immune system has demonstrated novel regulatory target for treating allergic diseases, autoimmune disorders and metabolic syndrome. Various kinds of food nutrients (such as dietary fiber, starch, polyphenols and proteins) can provide energy resources for both intestinal microbiota and the host. The indigestible food components are fermented by the indigenous gut microbiota to produce diverse metabolites, including short-chain fatty acids, bile acids and trimethylamine-N-oxide, which can regulate the host metabolized physiology, immunity homeostasis and health state. Therefore it is commonly believed early-life perturbation of the microbial community structure and the dietary nutrition interference on the child mucosal immunity contribute to the whole life susceptibility to chronic diseases. In all, the combined interrelationship between food ingredients nutrition, intestinal microbiota configurations and host system immunity provides new therapeutic targets to treat various kinds of pathogenic inflammations and chronic diseases.

  2. An experimental demonstration that early-life competitive disadvantage accelerates telomere loss.

    Science.gov (United States)

    Nettle, Daniel; Monaghan, Pat; Gillespie, Robert; Brilot, Ben; Bedford, Thomas; Bateson, Melissa

    2015-01-07

    Adverse experiences in early life can exert powerful delayed effects on adult survival and health. Telomere attrition is a potentially important mechanism in such effects. One source of early-life adversity is the stress caused by competitive disadvantage. Although previous avian experiments suggest that competitive disadvantage may accelerate telomere attrition, they do not clearly isolate the effects of competitive disadvantage from other sources of variation. Here, we present data from an experiment in European starlings (Sturnus vulgaris) that used cross-fostering to expose siblings to divergent early experience. Birds were assigned either to competitive advantage (being larger than their brood competitors) or competitive disadvantage (being smaller than their brood competitors) between days 3 and 12 post-hatching. Disadvantage did not affect weight gain, but it increased telomere attrition, leading to shorter telomere length in disadvantaged birds by day 12. There were no effects of disadvantage on oxidative damage as measured by plasma lipid peroxidation. We thus found strong evidence that early-life competitive disadvantage can accelerate telomere loss. This could lead to faster age-related deterioration and poorer health in later life.

  3. Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.

    Science.gov (United States)

    Simon, K; de Vries Reilingh, G; Bolhuis, J E; Kemp, B; Lammers, A

    2015-09-01

    Early life conditions such as feed and water availability immediately post hatch (PH) and housing conditions may influence immune development and therefore immune reactivity later in life. The current study addressed the consequences of a combination of these 2 early life conditions for immune reactivity, i.e., the specific antibody response towards a non-infectious lung challenge. Broiler chicks received feed and water either immediately p.h. or with a 72 h delay and were either reared in a floor or a cage system. At 4 weeks of age, chicks received either an intra-tracheally administered Escherichia coli lipopolysaccharide (LPS)/Human Serum Albumin (HUSA) challenge or a placebo, and antibody titers were measured up to day 14 after administration of the challenge. Chicks housed on the floor and which had a delayed access to feed p.h. showed the highest antibody titers against HuSA. These chicks also showed the strongest sickness response and poorest performance in response to the challenge, indicating that chicks with delayed access to feed might be more sensitive to an environment with higher antigenic pressure. In conclusion, results from the present study show that early life feeding strategy and housing conditions influence a chick's response to an immune challenge later in life. These 2 early life factors should therefore be taken into account when striving for a balance between disease resistance and performance in poultry. © 2015 Poultry Science Association Inc.

  4. The Influence of Early Life Experience on Visceral Pain

    Directory of Open Access Journals (Sweden)

    Isabella M. Fuentes

    2018-01-01

    Full Text Available Pain is the most reported and troublesome symptom of nearly all functional disorders affecting the genitourinary and gastrointestinal organs. Patients with irritable bowel syndrome (IBS, interstitial cystitis/painful bladder syndrome (IC/PBS, vulvodynia, and/or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; collectively termed chronic pelvic pain syndromes report pain severe enough to impact quality of life and often suffer from symptoms of or are diagnosed with more than one of these syndromes. This increased comorbidity between chronic pelvic pain syndromes, and with pain disorders of disparate body regions, as well as with mood disorders, can be influenced by disruptions in the hypothalamic-pituitary-adrenal (HPA axis, which regulates the response to stress and influences the perception of pain. Experiencing trauma, neglect, or abuse in early life can permanently affect the functioning of the HPA axis. As such, a significant proportion of patients suffering from comorbid chronic pelvic pain syndromes report a history of early life stress or trauma. Here we will report on how these early life experiences influence chronic pelvic pain in patients. We will also discuss various rodent models that have been developed to study this phenomenon to understand the mechanisms underlying HPA axis dysfunction, as well as potential underlying mechanisms connecting these syndromes to one another.

  5. Endocrine disruptors and the breast: early life effects and later life disease.

    Science.gov (United States)

    Macon, Madisa B; Fenton, Suzanne E

    2013-03-01

    Breast cancer risk has both heritable and environment/lifestyle components. The heritable component is a small contribution (5-27 %), leaving the majority of risk to environment (e.g., applied chemicals, food residues, occupational hazards, pharmaceuticals, stress) and lifestyle (e.g., physical activity, cosmetics, water source, alcohol, smoking). However, these factors are not well-defined, primarily due to the enormous number of factors to be considered. In both humans and rodent models, environmental factors that act as endocrine disrupting compounds (EDCs) have been shown to disrupt normal mammary development and lead to adverse lifelong consequences, especially when exposures occur during early life. EDCs can act directly or indirectly on mammary tissue to increase sensitivity to chemical carcinogens or enhance development of hyperplasia, beaded ducts, or tumors. Protective effects have also been reported. The mechanisms for these changes are not well understood. Environmental agents may also act as carcinogens in adult rodent models, directly causing or promoting tumor development, typically in more than one organ. Many of the environmental agents that act as EDCs and are known to affect the breast are discussed. Understanding the mechanism(s) of action for these compounds will be critical to prevent their effects on the breast in the future.

  6. association between early life malnutrition and the size of lumbar ...

    African Journals Online (AJOL)

    Objective: To determine the relationship between early life malnutrition and the development of lumbar ... incriminate such predictors as poverty, aridity and human development which can be reduced ..... relationship with early childhood caries.

  7. Early Life Family Conflict, Social Interactions, and Carotid Artery Intima-Media Thickness in Adulthood.

    Science.gov (United States)

    John-Henderson, Neha A; Kamarck, Thomas W; Muldoon, Matthew F; Manuck, Stephen B

    2016-04-01

    Conflict in early life family environments is known to affect psychosocial functioning and coping styles into adulthood and is reported to negatively affect access to psychosocial resources that are critical to the management of stress. However, it remains unknown whether early life family conflict similarly affects subclinical cardiovascular disease (CVD) in adulthood. We predicted that family conflict in early life would be associated with greater mean intima-media thickness (IMT), a subclinical marker of CVD risk, in adulthood. Data were collected in a community sample of 503 adults (47.4 % male, mean [standard deviation] age = 42.8 [7.3] years). Associations between family conflict in early life with IMT (assessed using B-mode ultrasound) in adulthood were examined using regression analysis. We also tested for indirect effects of early life family conflict on mean IMT through ecological momentary assessment reports of social interactions, diversity of social roles, and perceived social support. Linear regression analyses adjusted for demographics and physiological risk factors showed conflict in early life associated with greater mean IMT (β = 0.08, t(447) = 2.13, p = .034, R = 0.46). Early life conflict was significantly related to diversity of social roles, perceived social support, and ecological momentary assessment reports of pleasant and social conflict interactions. Significant indirect effects of early life conflict on mean IMT were observed through fewer pleasant social interactions and more frequent social conflict interactions in adulthood (β = 0.001 [95% confidence interval = 0.0001-0.0014] and β = 0.001 [95% confidence interval = 0.0002-0.0015], respectively). These findings provide initial evidence that family conflict in early life heightens CVD risk in adulthood, in part by shaping the quality of adulthood social interactions.

  8. Perinatal and Early Childhood Environmental Factors Influencing Allergic Asthma Immunopathogenesis

    Science.gov (United States)

    Gaffin, Jonathan M.; Kanchongkittiphon, Watcharoot; Phipatanakul, Wanda

    2014-01-01

    Background The prevalence of asthma has increased dramatically over the past several decades. While hereditary factors are highly important, the rapid rise outstrips the pace of genomic variation. Great emphasis has been placed on potential modifiable early life exposures leading to childhood asthma. Methods We reviewed the recent medical literature for important studies discussing the role of the perinatal and early childhood exposures and the inception of childhood asthma. Results and Discussion Early life exposure to allergens (House dust mite (HDM), furred pets, cockroach, rodent and mold)air pollution (nitrogen dioxide (NO2), ozone (O3), volatile organic compounds (VOCs), and particulate matter (PM)) and viral respiratory tract infections (Respiratory syncytial virus (RSV) and human rhinovirus (hRV)) have been implicated in the development of asthma in high risk children. Conversely, exposure to microbial diversity in the perinatal period may diminish the development of atopy and asthma symptoms. PMID:24952205

  9. Exposure to stressful life events during pregnancy predicts psychotic experiences via behaviour problems in childhood.

    Science.gov (United States)

    Betts, Kim S; Williams, Gail M; Najman, Jakob M; Scott, James; Alati, Rosa

    2014-12-01

    Exposure to stressful life events during pregnancy has been associated with later schizophrenia in offspring. We explore how prenatal stress and neurodevelopmental abnormalities in childhood associate to increase the risk of later psychotic experiences. Participants from the Mater University Study of Pregnancy (MUSP), an Australian based, pre-birth cohort study were examined for lifetime DSM-IV positive psychotic experiences at 21 years by a semi-structured interview (n = 2227). Structural equation modelling suggested psychotic experiences were best represented with a bifactor model including a general psychosis factor and two group factors. We tested for an association between prenatal stressful life events with the psychotic experiences, and examined for potential moderation and mediation by behaviour problems and cognitive ability in childhood. Prenatal stressful life events predicted psychotic experiences indirectly via behaviour problems at child age five years, and this relationship was not confounded by maternal stressful life events at child age five. We found no statistical evidence for an interaction between prenatal stressful life events and behaviour problems or cognitive ability. The measurable effect of prenatal stressful life events on later psychotic experiences in offspring manifested as behaviour problems by age 5. By identifying early abnormal behavioural development as an intermediary, this finding further confirms the role of prenatal stress to later psychotic disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Lung function in adults following in utero and childhood exposure to arsenic in drinking water: preliminary findings.

    Science.gov (United States)

    Dauphiné, David C; Ferreccio, Catterina; Guntur, Sandeep; Yuan, Yan; Hammond, S Katharine; Balmes, John; Smith, Allan H; Steinmaus, Craig

    2011-08-01

    Evidence suggests that arsenic in drinking water causes non-malignant lung disease, but nearly all data concern exposed adults. The desert city of Antofagasta (population 257,976) in northern Chile had high concentrations of arsenic in drinking water (>800 μg/l) from 1958 until 1970, when a new treatment plant was installed. This scenario, with its large population, distinct period of high exposure, and accurate data on past exposure, is virtually unprecedented in environmental epidemiology. We conducted a pilot study on early-life arsenic exposure and long-term lung function. We present these preliminary findings because of the magnitude of the effects observed. We recruited a convenience sample consisting primarily of nursing school employees in Antofagasta and Arica, a city with low drinking water arsenic. Lung function and respiratory symptoms in 32 adults exposed to >800 μg/l arsenic before age 10 were compared to 65 adults without high early-life exposure. Early-life arsenic exposure was associated with 11.5% lower forced expiratory volume in 1 s (FEV(1)) (P = 0.04), 12.2% lower forced vital capacity (FVC) (P = 0.04), and increased breathlessness (prevalence odds ratio = 5.94, 95% confidence interval 1.36-26.0). Exposure-response relationships between early-life arsenic concentration and adult FEV(1) and FVC were also identified (P trend = 0.03). Early-life exposure to arsenic in drinking water may have irreversible respiratory effects of a magnitude similar to smoking throughout adulthood. Given the small study size and non-random recruitment methods, further research is needed to confirm these findings.

  11. Prevention of overweight and obesity in early life.

    Science.gov (United States)

    Lanigan, Julie

    2018-05-29

    Childhood obesity is a serious challenge for public health. The problem begins early with most excess childhood weight gained before starting school. In 2016, the WHO estimated that 41 million children under 5 were overweight or obese. Once established, obesity is difficult to reverse, likely to persist into adult life and is associated with increased risk of CVD, type 2 diabetes and certain cancers. Preventing obesity is therefore of high importance. However, its development is multi-factorial and prevention is a complex challenge. Modifiable lifestyle behaviours such as diet and physical activity are the most well-known determinants of obesity. More recently, early-life factors have emerged as key influencers of obesity in childhood. Understanding risk factors and how they interact is important to inform interventions that aim to prevent obesity in early childhood. Available evidence supports multi-component interventions as effective in obesity prevention. However, relatively few interventions are available in the UK and only one, TrimTots, has been evaluated in randomised controlled trials and shown to be effective at reducing obesity risk in preschool children (age 1-5 years). BMI was lower in children immediately after completing TrimTots compared with waiting list controls and this effect was sustained at long-term follow-up, 2 years after completion. Developing and evaluating complex interventions for obesity prevention is a challenge for clinicians and researchers. In addition, parents encounter barriers engaging with interventions. This review considers early-life risk factors for obesity, highlights evidence for preventative interventions and discusses barriers and facilitators to their success.

  12. Neonatal exposure to phenobarbital potentiates schizophrenia-like behavioral outcomes in the rat.

    Science.gov (United States)

    Bhardwaj, S K; Forcelli, P A; Palchik, G; Gale, K; Srivastava, L K; Kondratyev, A

    2012-06-01

    Previous work has indicated an association between seizures early in life and increased risk of psychiatric disorders, including schizophrenia. However, because early-life seizures are commonly treated with antiepileptic drugs (AEDs) such as phenobarbital, the possibility that drug treatment may affect later-life psychiatric outcomes needs to be evaluated. We therefore tested the hypothesis that phenobarbital exposure in the neonatal rat increases the risk of schizophrenia-like behavioral abnormalities in adulthood. Thus, in this study, we examined the effects of a single acute neonatal exposure to phenobarbital on adult behavioral outcomes in the rat neonatal ventral hippocampal (nVH) lesion model of schizophrenia. We compared these outcomes to those in rats a) without nVH lesions and b) with nVH lesions, without phenobarbital. The tasks used for behavioral evaluation were: amphetamine-induced locomotion, prepulse inhibition, elevated plus-maze, and novel object recognition task. We found that neonatal phenobarbital treatment (in the absence of nVH lesions) was sufficient to disrupt sensorimotor gating (as tested by prepulse inhibition) in adulthood to an extent equivalent to nVH lesions. Additionally, neonatal phenobarbital exposure enhanced the locomotor response to amphetamine in adult animals with and without nVH lesions. Our findings suggest that neonatal exposure to phenobarbital can predispose to schizophrenia-like behavioral abnormalities. Our findings underscore the importance of examining AED exposure early in life as a potential risk factor for later-life neuropsychiatric abnormalities in clinical populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Social anxiety and negative early life events in university students.

    Science.gov (United States)

    Binelli, Cynthia; Ortiz, Ana; Muñiz, Armando; Gelabert, Estel; Ferraz, Liliana; S Filho, Alaor; Crippa, José Alexandre S; Nardi, Antonio E; Subirà, Susana; Martín-Santos, Rocío

    2012-06-01

    There is substantial evidence regarding the impact of negative life events during childhood on the aetiology of psychiatric disorders. We examined the association between negative early life events and social anxiety in a sample of 571 Spanish University students. In a cross-sectional survey conducted in 2007, we collected data through a semistructured questionnaire of sociodemographic variables, personal and family psychiatric history, and substance abuse. We assessed the five early negative life events: (i) the loss of someone close, (ii) emotional abuse, (iii) physical abuse, (iv) family violence, and (v) sexual abuse. All participants completed the Liebowitz Social Anxiety Scale. Mean (SD) age was 21 (4.5), 75% female, LSAS score was 40 (DP = 22), 14.2% had a psychiatric family history and 50.6% had negative life events during childhood. Linear regression analyses, after controlling for age, gender, and family psychiatric history, showed a positive association between family violence and social score (p = 0.03). None of the remaining stressors produced a significant increase in LSAS score (p > 0.05). University students with high levels of social anxiety presented higher prevalence of negative early life events. Thus, childhood family violence could be a risk factor for social anxiety in such a population.

  14. The associations between early life circum-stances and later life health and employment in Europe

    NARCIS (Netherlands)

    Flores, M.; Kalwij, Adriaan

    2014-01-01

    We use data from the Survey of Health, Aging, and Retirement in Europe to estimate for thirteen European countries the associations of early life circumstances—measured by childhood health and socioeconomic status (SES)—with educational attainment, and later life health and employment (at ages

  15. Early enriched environment exposure protects spatial memory and accelerates amyloid plaque formation in APP(Swe/PS1(L166P mice.

    Directory of Open Access Journals (Sweden)

    Francesca Montarolo

    Full Text Available Enriched environment exposure improves several aspects of cognitive performance in Alzheimer's disease patients and in animal models and, although the role of amyloid plaques is questionable, several studies also assessed their response to enriched environment, with contrasting results. Here we report that rearing APP(Swe/PS1(L166P mice in an enriched environment since birth rescued the spatial memory impairment otherwise present at 6 months of age. At the same time, the exposure to the enriched environment caused a transient acceleration of plaque formation, while there was no effect on intracellular staining with the 6E10 antibody, which recognizes β-amyloid, full length amyloid precursor protein and its C-terminal fragments. The anticipation of plaque formation required exposure during early development, suggesting an action within critical periods for circuits formation. On the other hand, chronic neuronal activity suppression by tetrodotoxin decreased the number of plaques without affecting intracellular amyloid. These results indicate that enriched environment exposure since early life has a protective effect on cognitive deterioration although transiently accelerates amyloid deposition. In addition, the effects of the enriched environment might be due to increased neuronal activity, because plaques were reduced by suppression of electrical signaling by tetrodotoxin.

  16. Exposure of BALB/c mice to diesel engine exhaust origin secondary organic aer-osol (DE-SOA during the developmental stages impairs the social behavior in adult life of the males

    Directory of Open Access Journals (Sweden)

    Tin-Tin eWin-Shwe

    2016-01-01

    Full Text Available Secondary organic aerosol (SOA is a component of particulate matter (PM 2.5 and formed in the atmosphere by oxidation of volatile organic compounds. Recently, we have reported that inhalation exposure to diesel engine exhaust (DE originated SOA (DE-SOA affect novel object recognition ability and impair maternal behavior in adult mice. However, it is not clear whether early life exposure to SOA during the de-velopmental stages affect social behavior in adult life or not. In the present study, to investigate the effects of early life exposure to DE-SOA during the gestational and lactation stages on the social behavior in the adult life, BALB/c mice were exposed to clean air (control, DE, DE-SOA and gas without any particulate matter in the inhala-tion chambers from gestational day 14 to postnatal day 21 for 5 h a day and 5 days per week. Then adult mice were examined for changes in their social behavior at the age of 13 week by a sociability and social novelty preference, social interaction with a juvenile mouse and light-dark transition test, hypothalamic mRNA expression levels of social behavior-related genes, estrogen receptor-alpha and oxytocin receptor as well as of the oxidative stress marker gene, heme oxygenase (HO-1 by real-time RT-PCR method. In addition, hypothalamic level of neuronal excitatory marker, glutamate was determined by ELISA method. We observed that sociability and social novelty pref-erence as well as social interaction were remarkably impaired, expression levels of es-trogen receptor-alpha, oxytocin receptor mRNAs were significantly decreased, ex-pression levels of HO-1 mRNAs and glutamate levels were significantly increased in adult male mice exposed to DE-SOA compared to the control ones. Findings of this study indicate early life exposure of BALB/c mice to DE-SOA may affect their late-onset hypothalamic expression of social behavior related genes, trigger neurotoxi-city and impair social behavior in the males.

  17. Prenatal Exposure to Perfluoroalkyl Substances and Adiposity in Early and Mid-Childhood

    Science.gov (United States)

    Mora, Ana María; Oken, Emily; Rifas-Shiman, Sheryl L.; Webster, Thomas F.; Gillman, Matthew W.; Calafat, Antonia M.; Ye, Xiaoyun; Sagiv, Sharon K.

    2016-01-01

    Background: Few studies have examined whether prenatal exposure to perfluoroalkyl substances (PFASs) is associated with childhood adiposity. Objective: We examined associations of prenatal exposure to PFASs with adiposity in early and mid-childhood. Methods: We measured plasma PFAS concentrations in 1,645 pregnant women (median, 9.6 weeks gestation) enrolled in Project Viva, a prospective pre-birth cohort study in Massachusetts (USA), between 1999 and 2002. We assessed overall and central adiposity in 1,006 children in early childhood (median, 3.2 years) and 876 in mid-childhood (median, 7.7 years) using anthropometric and dual X-ray absorptiometry (DXA) measurements. We fitted multivariable linear regression models to estimate exposure-outcome associations and evaluated effect modification by child sex. Results: Median (25–75th percentiles) prenatal plasma perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) concentrations in children assessed in early childhood were 5.6 (4.1–7.7), 24.8 (18.4–33.9), 2.4 (1.6–3.8), and 0.6 (0.5–0.9) ng/mL, respectively. Among girls, each interquartile range increment of prenatal PFOA concentrations was associated with 0.21 kg/m2 (95% CI: –0.05, 0.48) higher body mass index, 0.76 mm (95% CI: –0.17, 1.70) higher sum of subscapular and triceps skinfold thickness, and 0.17 kg/m2 (95% CI: –0.02, 0.36) higher DXA total fat mass index in mid-childhood. Similar associations were observed for PFOS, PFHxS, and PFNA. We observed null associations for boys and early-childhood adiposity measures. Conclusions: In this cohort, prenatal exposure to PFASs was associated with small increases in adiposity measurements in mid-childhood, but only among girls. Citation: Mora AM, Oken E, Rifas-Shiman SL, Webster TF, Gillman MW, Calafat AM, Ye X, Sagiv SK. 2017. Prenatal exposure to perfluoroalkyl substances and adiposity in early and mid-childhood. Environ Health

  18. Early life stress as an influence on limbic epilepsy: an hypothesis whose time has come?

    Directory of Open Access Journals (Sweden)

    Amelia S Koe

    2009-10-01

    Full Text Available The pathogenesis of mesial temporal lobe epilepsy (MTLE, the most prevalent form of refractory focal epilepsy in adults, is thought to begin in early life, even though seizures may not commence until adolescence or adulthood. Amongst the range of early life factors implicated in MTLE causation (febrile seizures, traumatic brain injury, etc., stress may be one important contributor. Early life stress is an a priori agent deserving study because of the large amount of neuroscientific data showing enduring effects on structure and function in hippocampus and amygdala, the key structures involved in MTLE. An emerging body of evidence directly tests hypotheses concerning early life stress and limbic epilepsy: early life stressors, such as maternal separation, have been shown to aggravate epileptogenesis in both status epilepticus and kindling models of limbic epilepsy. In addition to elucidating its influence on limbic epileptogenesis itself, the study of early life stress has the potential to shed light on the psychiatric disorder that accompanies MTLE. For many years, psychiatric comorbidity was viewed as an effect of epilepsy, mediated psychologically and/or neurobiologically. An alternative – or complementary – perspective is that of shared causation. Early life stress, implicated in the pathogenesis of several psychiatric disorders, may be one such causal factor. This paper aims to critically review the body of experimental evidence linking early life stress and epilepsy; to discuss the direct studies examining early life stress effects in current models of limbic seizures/epilepsy; and to suggest priorities for future research.

  19. Age- and sex-dependent effects of early life stress on hippocampal neurogenesis

    NARCIS (Netherlands)

    Loi, M.; Koricka, S.; Lucassen, P.J.; Joëls, M.

    2014-01-01

    Early life stress is a well-documented risk factor for the development of psychopathology in genetically predisposed individuals. As it is hard to study how early life stress impacts human brain structure and function, various animal models have been developed to address this issue. The models

  20. Epigenetics as a mechanism linking developmental exposures to long-term toxicity

    DEFF Research Database (Denmark)

    Barouki, R; Melén, E; Herceg, Z

    2018-01-01

    A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA methylat......A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA...

  1. Promoting Career Development and Life Design in the Early Years of a Person's Life

    Science.gov (United States)

    Maree, Jacobus G.

    2018-01-01

    The article discusses the changing world of work and the attendant uncertainty and loss of work-life identity. Little research has been done on career development and life design in the early years of a person's life, especially in developing countries characterized by disadvantage. The underlying theoretical models of career development are…

  2. Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years.

    Directory of Open Access Journals (Sweden)

    Regina Boecker

    Full Text Available Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD. 162 healthy young adults (mean age = 24.4 years; 58% female from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus, indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV, with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.

  3. The interaction of corticotropin-releasing hormone receptor gene and early life stress on emotional empathy.

    Science.gov (United States)

    Grimm, Simone; Wirth, Katharina; Fan, Yan; Weigand, Anne; Gärtner, Matti; Feeser, Melanie; Dziobek, Isabel; Bajbouj, Malek; Aust, Sabine

    2017-06-30

    Early life stress (ELS) is associated with increased vulnerability for depression, changes to the corticotropin-releasing hormone (CRH) system and structural and functional changes in hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS to predict depression, cognitive functions and hippocampal activity. Social cognition has been related to hippocampal function and might be crucial for maintaining mental health. However, the interaction of CRHR1 gene variation and ELS on social cognition has not been investigated yet. We assessed social cognition in 502 healthy subjects to test effects of ELS and the CRHR1 gene. Participants were genotyped for rs110402 and rs242924. ELS was assessed by Childhood Trauma Questionnaire, social cognition was measured via Multifaceted Empathy Test and Empathy Quotient. Severity of ELS was associated with decreased emotional, but not cognitive empathy. Subjects with the common homozygous GG GG genotype showed decreased implicit emotional empathy after ELS exposure regardless of its severity. The results reveal that specific CRHR1 polymorphisms moderate the effect of ELS on emotional empathy. Exposure to ELS in combination with a vulnerable genotype results in impaired emotional empathy in adulthood, which might represent an early marker of increased vulnerability after ELS. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life

    Science.gov (United States)

    Lee, Debbie C P; Walker, Simone A; Byrne, Adam J; Gregory, Lisa G; Buckley, James; Bush, Andrew; Shaheen, Seif O; Saglani, Sejal; Lloyd, Clare M

    2015-01-01

    Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma. PMID:25841236

  5. Tracking exposure to child poverty during the first 10 years of life in a Quebec birth cohort.

    Science.gov (United States)

    Séguin, Louise; Nikiema, Beatrice; Gauvin, Lise; Lambert, Marie; Thanh Tu, Mai; Kakinami, Lisa; Paradis, Gilles

    2012-04-27

    Early childhood poverty is associated with adult chronic diseases. The objectives of this study were to examine patterns of exposure to poverty during the first 10 years of life in the Quebec Longitudinal Study of Child Development (QLSCD) cohort according to three measures of poverty and to explore family characteristics associated with different poverty exposures. Data from 1,334 participants from the QLSCD were collected annually at home from ages 5 months through 10 years. Household income (previous 12 months) and sources of income were recorded at each data round. Poverty status was operationalized as 1) living below the low income cut-off of Statistics Canada, 2) receiving social welfare and 3) being in the lowest quintile of socio-economic status. We plotted trends in the prevalence of child poverty over time. We used latent class growth modelling to identify subgroups with similar poverty trajectories. Duration of poverty according to each measure was computed separately for early childhood, middle childhood, and the entire 10 years of life. Four trajectories of poverty were identified: stable poor, decreasing likelihood, increasing likelihood, and never poor. The three measures of poverty do not cover the same population, yet the characteristics of those identified as poor are similar. Children of non-European, immigrant mothers were most likely to be poor, and there was a higher likelihood of children from single-parent families to live in chronic poverty during the first 10 years. A large proportion of children are exposed to poverty before 10 years of age. More effective public policies could reduce child poverty.

  6. Paternal effects on early life history traits in Northwest Atlantic cod, Gadus morhua

    DEFF Research Database (Denmark)

    Kroll, M.-M.; Peck, M.A.; Butts, Ian A.E.

    2013-01-01

    It is important to understand parental effects on early life history of fish as manifested, for example, in individual fitness of offspring. Immediately after fertilization, parental contributions (both genetic and non-genetic) to embryos will affect larval ontogeny, physiology, morphology...... and survival. In marine fish, rates of natural mortality are highest during early life and are negatively correlated with rates of growth and body size. In these early life stages (eggs, larvae, young juveniles) subtle differences in mortality can cause large differences in recruitment and year-class success...... and can serve as important sources of variation during early life stages in fishes. Overall, these findings have implications for furthering the understanding of recruitment variability and can be used to optimize reproductive output for the aquaculture industry. In addition, the data suggests...

  7. Environmental insults in early life and submissiveness later in life in mouse models

    Directory of Open Access Journals (Sweden)

    Seico eBenner

    2015-03-01

    Full Text Available Dominant and subordinate dispositions are not only determined genetically but also nurtured by environmental stimuli during neuroendocrine development. However, the relationship between early life environment and dominance behavior remains elusive. Using the IntelliCage-based competition task for group-housed mice, we have previously described two cases in which environmental insults during the developmental period altered the outcome of dominance behavior later in life. First, mice that were repeatedly isolated from their mother and their littermates (early deprivation; ED, and second, mice perinatally exposed to an environmental pollutant, dioxin, both exhibited subordinate phenotypes, defined by decreased occupancy of limited resource sites under highly competitive circumstances. Similar alterations found in the cortex and limbic area of these two models are suggestive of the presence of neural systems shared across generalized dominance behavior.

  8. Dog Exposure During the First Year of Life and Type 1 Diabetes in Childhood.

    Science.gov (United States)

    Wernroth, Mona-Lisa; Svennblad, Bodil; Fall, Katja; Fang, Fang; Almqvist, Catarina; Fall, Tove

    2017-07-01

    The association between early exposure to animals and type 1 diabetes in childhood is not clear. To determine whether exposure to dogs during the first year of life is associated with the development of type 1 diabetes in childhood. A nationwide cohort study utilizing high-quality Swedish national demographic and health registers was conducted. A total of 840 593 children born in Sweden from January 1, 2001, to December 31, 2010, were evaluated. Type 1 diabetes was identified using diagnosis codes from hospitals and dispensed prescriptions of insulin. Cox proportional hazards regression models were used to assess the association between exposure to dogs and risk of type 1 diabetes in childhood. The possible association was further investigated by performing dose-response and breed group-specific analyses. The cohort was followed up until September 30, 2012. Data analysis was conducted from October 15, 2015, to February 8, 2017. Having a parent who was registered as a dog owner during the child's first year of life. Childhood-onset type 1 diabetes. Of the 840 593 children reviewed, 408 272 (48.6%) were girls; mean (SD) age at diagnosis of type 1 diabetes was 5.1 (2.6) years. Dog exposure was identified in 102 035 children (12.1%). Follow-up started at age 1 year, and the children were followed up for as long as 10.7 years (median, 5.5 years). During follow-up, 1999 children developed type 1 diabetes. No association was found between exposure to dogs (adjusted hazard ratio [HR], 1.00; 95% CI, 0.86-1.16) and type 1 diabetes in childhood. The size of the dog (adjusted HR per 10-cm increase in height, 0.96; 95% CI, 0.86-1.06) or number of dogs in the household (1 dog: adjusted HR, 1.07; 95% CI, 0.91-1.26; 2 dogs: 0.79; 95% CI, 0.54-1.15; ≥3 dogs: 0.50; 95% CI, 0.23-1.12; compared with nonexposed children) also was not associated with type 1 diabetes risk. An analysis of children whose parent had type 1 diabetes (210 events) yielded an adjusted HR of 0.71 (95% CI, 0

  9. EARLY LIFE RISKS, ANTISOCIAL TENDENCIES, AND PRETEEN DELINQUENCY*

    Science.gov (United States)

    Staff, Jeremy; Whichard, Corey; Siennick, Sonja; Maggs, Jennifer

    2015-01-01

    Early age-of-onset delinquency and substance use confer a major risk for continued criminality, alcohol and drug abuse, and other serious difficulties throughout the life course. Our objective is to examine the developmental roots of preteen delinquency and substance use. Using nationally representative longitudinal data from the UK Millennium Cohort Study (n = 13,221), we examine the influence of early childhood developmental and family risks on latent pathways of antisocial tendencies from ages 3 to 7, and the influence of those pathways on property crime and substance use by age 11. We identified a normative, non-antisocial pathway; a pathway marked by oppositional behavior and fighting; a pathway marked by impulsivity and inattention; and a rare pathway characterized by a wide range of antisocial tendencies. Children with developmental and family risks that emerged by age 3—specifically difficult infant temperament, low cognitive ability, weak parental closeness, and disadvantaged family background—face increased odds of antisocial tendencies. There is minimal overlap between the risk factors for early antisocial tendencies and those for preteen delinquency. Children on an antisocial pathway are more likely to engage in preteen delinquency and substance use by age 11, even after accounting for early life risk factors. PMID:26900167

  10. Attentional avoidance of fearful facial expressions following early life stress is associated with impaired social functioning.

    Science.gov (United States)

    Humphreys, Kathryn L; Kircanski, Katharina; Colich, Natalie L; Gotlib, Ian H

    2016-10-01

    Early life stress is associated with poorer social functioning. Attentional biases in response to threat-related cues, linked to both early experience and psychopathology, may explain this association. To date, however, no study has examined attentional biases to fearful facial expressions as a function of early life stress or examined these biases as a potential mediator of the relation between early life stress and social problems. In a sample of 154 children (ages 9-13 years) we examined the associations among interpersonal early life stressors (i.e., birth through age 6 years), attentional biases to emotional facial expressions using a dot-probe task, and social functioning on the Child Behavior Checklist. High levels of early life stress were associated with both greater levels of social problems and an attentional bias away from fearful facial expressions, even after accounting for stressors occurring in later childhood. No biases were found for happy or sad facial expressions as a function of early life stress. Finally, attentional biases to fearful faces mediated the association between early life stress and social problems. Attentional avoidance of fearful facial expressions, evidenced by a bias away from these stimuli, may be a developmental response to early adversity and link the experience of early life stress to poorer social functioning. © 2016 Association for Child and Adolescent Mental Health.

  11. What are the elements required to improve exposure estimates in life cycle assessments?

    DEFF Research Database (Denmark)

    Ernstoff, Alexi; Rosenbaum, Ralph K.; Margni, Manuele

    2016-01-01

    human toxicity and ecosystem toxicity of chemicals posed by different product life cycle stages are characterized in the life cycle impact assessment (LCIA) phase. Exposure and effect quantification as part of LCIA toxicity characterization faces numerous challenges related to inventory analysis (e.......g. number and quantity of chemicals emitted), substance-specific modelling (e.g. organics, inorganics, nano-materials) in various environments and time horizons, human and ecosystem exposure quantification (e.g. exposed organisms and exposure pathways), and toxicity end-points (e.g. carcinogenicity...... chemical exposure and harmful effects. Thereby, we structure this study of key elements identified as areas of elevated public, industrial, regulatory, and scientific concerns. We found the majority of missing elements are directly related to the definition of exposed populations (both ecosystems...

  12. Specific synbiotics in early life protect against diet-induced obesity in adult mice

    DEFF Research Database (Denmark)

    Mischke, Mona; Arora, Tulika; Tims, Sebastian

    2018-01-01

    AIMS: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health long-lastingly. Here, we determined how beneficial microbiome interventions in early life a...... as preventive measure to ameliorate obesity risk and improve metabolic health throughout life....

  13. Early-life inflammation with LPS delays fear extinction in adult rodents.

    Science.gov (United States)

    Doenni, V M; Song, C M; Hill, M N; Pittman, Q J

    2017-07-01

    A large body of evidence has been brought forward connecting developmental immune activation to abnormal fear and anxiety levels. Anxiety disorders have extremely high lifetime prevalence, yet susceptibility factors that contribute to their emergence are poorly understood. In this research we investigated whether an inflammatory insult early in life can alter the response to fear conditioning in adulthood. Fear learning and extinction are important and adaptive behaviors, mediated largely by the amygdala and its interconnectivity with cortico-limbic circuits. Male and female rat pups were given LPS (100μg/kg i.p.) or saline at postnatal day 14; LPS activated cFos expression in the central amygdala 2.5h after exposure, but not the basal or lateral nuclei. When tested in adulthood, acquisition of an auditory cued or contextual learned fear memory was largely unaffected as was the extinction of fear to a conditioned context. However, we detected a deficit in auditory fear extinction in male and female rats that experienced early-life inflammation, such that there is a significant delay in fear extinction processes resulting in more sustained fear behaviors in response to a conditioned cue. This response was specific to extinction training and did not persist into extinction recall. The effect could not be explained by differences in pain threshold (unaltered) or in baseline anxiety, which was elevated in adolescent females only and unaltered in adolescent males and adult males and females. This research provides further evidence for the involvement of the immune system during development in the shaping of fear and anxiety related behaviors. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Ghrelin and hypothalamic NPY/AgRP expression in mice are affected by chronic early-life stress exposure in a sex-specific manner

    NARCIS (Netherlands)

    Yam, K.Y.; Ruigrok, S.R.; Ziko, I.; De Luca, S.N.; Lucassen, P.J.; Spencer, S.J.; Korosi, A.

    2017-01-01

    Early-life stress (ES) is a risk factor for metabolic disorders (e.g. obesity) with a notoriously higher prevalence in women compared to men. However, mechanisms underlying these effects remain elusive. The development of the hypothalamic feeding and metabolic regulatory circuits occurs mostly in

  15. Early renal effects of occupational exposure to low-level hexavalent chromium

    Energy Technology Data Exchange (ETDEWEB)

    Nagaya, Teruo (Dept. of Public Health, Gifu Univ. School of Medicine, Tsukasa-machi (Japan)); Ishikawa, Noriko (Occupational Hygiene Center, Gifu Labour Standards Association, Hikie (Japan)); Hata, Hideo (Occupational Hygiene Center, Gifu Labour Standards Association, Hikie (Japan)); Takahashi, Akemi (Gifu-shi Central Public Health Center, Miyako-dori (Japan)); Yoshida, Izumi (Gifu-shi Central Public Health Center, Miyako-dori (Japan)); Okamoto, Yoshinari (Gifu-shi Central Public Health Center, Miyako-dori (Japan))

    1994-05-01

    To detect early renal effects of occupational exposure to hexavalent chromium (Cr), urinary total proteins (U-TP), urinary albumin (U-Alb) and urinary retinol-binding protein (U-RBP) were determined in 166 male Cr platers and 106 male controls. The mean employment time in Cr plating for the platers was 12.6 years. Urinary Cr (U-Cr), which was determined as an index of Cr exposure, ranged from ''not detected'' to 19.91 [mu]g/g creatinine in the platers. The U-Cr level was lower than those in other previous studies. Age-adjusted U-TP, U-Alb or U-RBP levels were not different between the platers and the controls. In the platers, a significant positive correlation was found between age-adjusted U-TP and U-Cr, but U-Cr had no significant relation to age-adjusted U-Alb or U-RBP level. Employment time had no effect on any age-adjusted urinary proteins. The Cr exposure may have been too low to induce definite renal dysfunction. Early renal effects of low-level Cr exposure may be mild, and may not be specific to renal function. (orig.)

  16. A Life Course Model of Self-Reported Violence Exposure and Ill-health with A Public Health Problem Perspective.

    Science.gov (United States)

    Olofsson, Niclas

    2014-01-01

    Violence has probably always been part of the human experience. Its impact can be seen, in various forms, in all parts of the world. In 1996, WHO:s Forty-Ninth World Health Assembly adopted a resolution, declaring violence a major and growing public health problem around the world. Public health work centers around health promotion and disease prevention activities in the population and public health is an expression of the health status of the population taking into account both the level and the distribution of health. Exposure to violence can have many aspects, differing throughout the life course - deprivation of autonomy, financial exploitation, psychological and physical neglect or abuse - but all types share common characteristics: the use of destructive force to control others by depriving them of safety, freedom, health and, in too many instances, life; the epidemic proportions of the problem, particularly among vulnerable groups; a devastating impact on individuals, families, neighborhoods, communities, and society. There is considerable evidence that stressful early life events influence a variety of physical and/or psychological health problems later in life. Childhood adversity has been linked to elevated rates of morbidity and mortality from number of chronic diseases. A model outlining potential biobehavioural pathways is put forward that may be a potential explanation of how exposure to violence among both men and women work as an important risk factor for ill health and should receive greater attention in public health work.

  17. Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

    Science.gov (United States)

    Shapero, Benjamin G; Weiss, Rachel B; Burke, Taylor A; Boland, Elaine M; Abramson, Lyn Y; Alloy, Lauren B

    2017-05-01

    Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors. Copyright © 2017. Published by Elsevier Ltd.

  18. Lithium prevents long-term neural and behavioral pathology induced by early alcohol exposure.

    Science.gov (United States)

    Sadrian, B; Subbanna, S; Wilson, D A; Basavarajappa, B S; Saito, M

    2012-03-29

    Fetal alcohol exposure can cause developmental defects in offspring known as fetal alcohol spectrum disorder (FASD). FASD symptoms range from obvious facial deformities to changes in neuroanatomy and neurophysiology that disrupt normal brain function and behavior. Ethanol exposure at postnatal day 7 in C57BL/6 mice induces neuronal cell death and long-lasting neurobehavioral dysfunction. Previous work has demonstrated that early ethanol exposure impairs spatial memory task performance into adulthood and perturbs local and interregional brain circuit integrity in the olfacto-hippocampal pathway. Here we pursue these findings to examine whether lithium prevents anatomical, neurophysiological, and behavioral pathologies that result from early ethanol exposure. Lithium has neuroprotective properties that have been shown to prevent ethanol-induced apoptosis. Here we show that mice co-treated with lithium on the same day as ethanol exposure exhibit dramatically reduced acute neurodegeneration in the hippocampus and retain hippocampal-dependent spatial memory as adults. Lithium co-treatment also blocked ethanol-induced disruption in synaptic plasticity in slice recordings of hippocampal CA1 in the adult mouse brain. Moreover, long-lasting dysfunctions caused by ethanol in olfacto-hippocampal networks, including sensory-evoked oscillations and resting state coherence, were prevented in mice co-treated with lithium. Together, these results provide behavioral and physiological evidence that lithium is capable of preventing or reducing immediate and long-term deleterious consequences of early ethanol exposure on brain function. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats

    Directory of Open Access Journals (Sweden)

    Jessica Saalfield

    2015-12-01

    Full Text Available Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively would affect ethanol conditioned taste aversions 2 days (CTA1 and >3 weeks (CTA2 post-exposure using supersaccharin and saline as conditioning stimuli (CS, respectively. Pair-housed male Sprague-Dawley rats received 4 g/kg i.g. ethanol (25% or water every 48 h from postnatal day (P 25–45 (early AIE or P45-65 (late AIE, or were left non-manipulated (NM. During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5 g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence.

  20. Risk modification and combined exposures in occupational respiratory allergy

    NARCIS (Netherlands)

    Portengen, Lützen

    2004-01-01

    The main objective of the studies described in this thesis was to investigate the impact of combined exposure to allergens and non-allergenic agents on the development of respiratory allergy in occupational populations. The effect of early life exposure to the farming environment and endotoxin

  1. Does physical exposure throughout working life influence chair-rise performance in midlife?

    DEFF Research Database (Denmark)

    Møller, Anne; Reventlow, Susanne; Hansen, Åse Marie

    2015-01-01

    OBJECTIVES: Our aim was to study associations between physical exposures throughout working life and physical function measured as chair-rise performance in midlife. METHODS: The Copenhagen Aging and Midlife Biobank (CAMB) provided data about employment and measures of physical function. Individual...... and confirmed the findings. CONCLUSIONS: Higher physical exposure throughout working life is associated with slightly poorer chair-rise performance. The associations between exposure and outcome were non-linear.......-years and chair-rise performance (number of chair-rises in 30 s) were analysed in multivariate linear and non-linear regression models adjusted for covariates. RESULTS: Mean age among the 5095 participants was 59 years in both genders, and, on average, men achieved 21.58 (SD=5.60) and women 20.38 (SD=5.33) chair...

  2. Impact of Early Versus Late Diuretic Exposure on Metabolic Bone Disease and Growth in Premature Neonates.

    Science.gov (United States)

    Orth, Lucas E; O'Mara, Keliana L

    2018-01-01

    This study aimed to determine whether there are differences in the incidence of metabolic bone disease (MBD) between preterm neonates first exposed to diuretics prior to 2 weeks of life versus those exposed after 2 weeks. This study was a retrospective analysis of premature neonates born at a tertiary care center between 2011 and 2015 who received either furosemide or chlorothiazide. The primary outcome was incidence of MBD. Secondary outcomes included growth, electrolyte disturbances, oxygen requirement, and length of stay. A total of 147 patients were included. Early initiation (n = 90) and late initiation (n = 57) arms were balanced with respect to birth weight and gestational age. There was no difference in incidence of MBD in the early group (76%) versus the late group (65%; p = 0.164). Stratification by cumulative dose showed incidence of 85% in patients receiving ≥8 mg/kg of furosemide, compared with 68% and 64% of those in the <4 mg/kg and 4 to 7.9 mg/kg strata, respectively (p = 0.06). The early group experienced greater reductions in length-for-age growth during diuretic therapy (-70% versus -40%; p = 0.009). Electrolyte abnormalities were more prevalent in the early group. Although there was no difference in duration of mechanical ventilation, duration of supplemental oxygen requirement was reduced in the late group (75 versus 89 days; p = 0.003). Timing of diuretic initiation did not affect incidence of MBD. Increased cumulative furosemide exposure may be associated with higher incidence. Patients first exposed to diuretics within 2 weeks of life are at higher risk for electrolyte abnormalities and reduced growth velocity.

  3. Reduced infant birthweight consequent upon maternal exposure to severe life events

    DEFF Research Database (Denmark)

    Khashan, Ali; McNamee, R.; Pedersen, Marianne Giørtz

    2008-01-01

    OBJECTIVE: To investigate the association between maternal exposure to severe life events and fetal growth (birthweight and small for gestational age). Stress has been associated with adverse pregnancy outcome. METHODS: Mothers of 1.38 million singleton live births in Denmark between January 1......). There was a significant association between maternal exposure to death of a relative and risk of a baby weighing below the 10th percentile (adjusted relative risk (RR) = 1.17, 95% CI = 1.13, 1.22) and 5th percentile (adjusted RR = 1.22, 95% CI = 1.15, 1.29). CONCLUSIONS: Mothers exposed to severe life events before...... conception or during pregnancy have babies with significantly lower birthweight. If this association is causal, the potential mechanisms of stress-related effects on birthweight include changes in lifestyle due to the exposure and stress-related dysregulation of the hypothalamic-pituitary-adrenal axis during...

  4. Early-life gut bacteria associate with IL-4-, IL-10- and IFN-γ production at two years of age.

    Directory of Open Access Journals (Sweden)

    Maria A Johansson

    Full Text Available Microbial exposure early in life influences immune maturation and potentially also the development of immune-mediated disease. Here we studied early-life gut colonization in relation to cytokine responses at two years of age. Fecal samples were collected from infants during the first two months of life. DNA was extracted from the fecal samples and Bifidobacterium (B. adolescentis, B. breve, B. bifidum, a group of lactobacilli (L. casei, L. paracasei and L. rhamnosus as well as Staphylococcus (S. aureus were detected with real time PCR. Peripheral mononuclear cells were stimulated with phytohaemagglutinin (PHA and numbers of IL-4-, IL-10- and IFN-γ secreting cells were evaluated using ELISpot. We further stimulated peripheral blood mononuclear cells with bacterial supernatants in vitro and assessed the IL-4-, IL-10- and IFN-γ inducing capacity by flow cytometry and ELISA. Early S. aureus colonization associated with higher numbers of IL-4- (p = 0.022 and IL-10 (p = 0.016 producing cells at two years of age. In contrast to colonization with S. aureus alone, co-colonization with lactobacilli associated with suppression of IL-4- (p = 0.004, IL-10- (p = 0.004 and IFN-γ (p = 0.034 secreting cells. In vitro stimulations of mononuclear cells with bacterial supernatants supported a suppressive role of L. rhamnosus GG on S. aureus-induced cytokine responses. We demonstrate that the early gut colonization pattern associates with the PHA-induced cytokine profile at two years of age and our in vitro findings support that specific bacterial species influence the T helper cell subsets. This suggests that dysbiosis in the early microbiota may modulate the risk of developing inflammatory conditions like allergy.

  5. Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.

    Science.gov (United States)

    Chen, Yuncai; Baram, Tallie Z

    2016-01-01

    Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational

  6. Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

    Science.gov (United States)

    Chen, Yuncai; Baram, Tallie Z

    2016-01-01

    Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes ‘normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational

  7. Gender/Sex Differences in the Relationship between Psychosocial Work Exposures and Work and Life Stress.

    Science.gov (United States)

    Padkapayeva, Kathy; Gilbert-Ouimet, Mahée; Bielecky, Amber; Ibrahim, Selahadin; Mustard, Cameron; Brisson, Chantal; Smith, Peter

    2018-04-18

    Stress is an important factor affecting the health of working population. While work exposures are determinants of levels of work and life stress, we do not know whether similar or different exposures are related to stress levels for men and women. This study aimed to formally examine male/female differences in the relationships between psychosocial work exposures and work and life stress in a representative sample of Canadian labour market participants. We used data from 2012 cycle of the Canadian Community Health Survey (CCHS), a representative population-based survey conducted by Statistics Canada. The sample was restricted to employed labour force participants working 15+ hours per week (N = 8328, 48% female). To examine the relationship between work exposures and work and life stress, we conducted path analyses. Psychosocial work exposures included social support, job insecurity, job control, and job strain. Differences between estimates for men and women were explored using multigroup analyses, constraining paths between male and female models to be equivalent and examining the impact on change in model fit. Male/female differences were observed in the relationships between supervisor support and work stress levels as well as between job control, job insecurity, job strain, and life stress levels. Higher levels of supervisor support at work were associated with lower work stress among women, but not among men. Low job control had a direct protective effect on life stress for men but not for women, while high job strain had a direct adverse effect on life stress among women but not among men. Higher job insecurity was more strongly associated with higher life stress among men compared with women. The relationship between work stress and life stress was similar among men and women. The findings of this study suggest that the relationships between psychosocial exposures and work and life stress differ for men and women. Our study also raised important questions

  8. Depression is an independent determinant of life satisfaction early after stroke.

    Science.gov (United States)

    Oosterveer, Daniëlla M; Mishre, Radha Rambaran; van Oort, Andrea; Bodde, Karin; Aerden, Leo A M

    2017-03-06

    Life satisfaction is reduced in stroke patients. However, as a rule, rehabilitation goals are not aimed at life satisfaction, but at activities and participation. In order to optimize life satisfaction in stroke patients, rehabilitation should take into account the determinants of life satisfaction. The aim of this study was therefore to determine what factors are independent determinants of life satisfaction in a large group of patients early after stroke. Stroke-surviving patients were examined by a specialized nurse 6 weeks after discharge from hospital or rehabilitation setting. A standardized history and several screening lists, including the Lisat-9, were completed. Step-wise regression was used to identify independent determinants of life satisfaction. A total of 284 stroke-surviving patients were included in the study. Of these, 117 answered all of the Lisat-9 questions. Most patients (66.5%) rated their life as a whole as "satisfying" or "very satisfying". More depressive symptoms were independently associated with lower life satisfaction (p life early after a stroke. The score on the Hospital Anxiety and Depression Scale depression items is independently associated with life satisfaction. Physicians should therefore pay close attention to the mood of these patients.

  9. Natural selection and sex differences in morbidity and mortality in early life.

    Science.gov (United States)

    Wells, J C

    2000-01-07

    Both morbidity and mortality are consistently reported to be higher in males than in females in early life, but no explanation for these findings has been offered. This paper argues that the sex difference in early vulnerability can be attributed to the natural selection of optimal maternal strategies for maximizing lifetime reproductive success, as modelled previously by Trivers and Willard. These authors theorized that males and females offer different returns on parental investment depending on the state of the environment. Natural selection has therefore favoured maternal ability to manipulate offspring sex in response to environmental conditions in early life, as shown in variation in the sex ratio at birth. This argument can be extended to the whole period of parental investment until weaning. Male vulnerability in response to environmental stress in early life is predicted to have been favoured by natural selection. This vulnerability is most evident in the harsh conditions resulting from pre-term birth, but can also be seen in term infants, and manifests as greater morbidity and mortality persisting into early childhood. Malnutrition, interacting with infection after birth, is suggested as the fundamental trigger mechanism. The model suggests that whatever improvements are made in medical care, any environmental stress will always affect males more severely than females in early life. Copyright 2000 Academic Press.

  10. Fetal and infant exposure to severe Chinese famine increases the risk of adult dyslipidemia: Results from the China health and retirement longitudinal study.

    Science.gov (United States)

    Wang, Zhenghe; Li, Changwei; Yang, Zhongping; Ma, Jun; Zou, Zhiyong

    2017-06-14

    To explore the associations between the Chinese famine exposure in early life and the dyslipidemia in adulthood. We selected 2752 participants from the baseline survey of China Health and Retirement Longitudinal Study (CHARLS) 2011-2012 to evaluate the associations of early life the Chinese famine exposure with risk of dyslipidemia in adulthood. Dyslipidemia was defined as TC (Total Cholesterol): HDL-C (High-Density Lipoprotein Cholesterol) ratio ≥ 5.0 or use cholesterol lowering drugs. Famine exposure cohorts were categorized by birthdates of participants. Binary logistics regression model was used to examine the associations of early-life famine exposure with the risk of dyslipidemia. The dyslipidemia prevalence of the non-exposed cohort, fetal stage-, infant stage-, and preschool stage-exposed cohorts in adulthood was 15.7%, 23.1%, 22.0%, and 18.6%, respectively. Early-life exposure to the Chinese famine significantly increased LDL cholesterol concentrations in adulthood after adjusted for age. The risks of dyslipidemia in fetal (OR = 1.58; 95% CI: 1.23-2.03; P dyslipidemia in female adults. However, the similar association was not observed for male adults. Early-life exposure to severe Chinese famine could link with the higher dyslipidemia risk in female adulthood, but not in male adulthood. This gender-specific effect might be associated with the hypothesis that parents in China prefer boys to girls traditionally or survivors' bias.

  11. Barium distributions in teeth reveal early-life dietary transitions in primates.

    Science.gov (United States)

    Austin, Christine; Smith, Tanya M; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J; Doble, Philip; Eskenazi, Brenda; Arora, Manish

    2013-06-13

    Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth. Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization. Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother's milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, indicating an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.

  12. Barium distributions in teeth reveal early life dietary transitions in primates

    Science.gov (United States)

    Austin, Christine; Smith, Tanya M.; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J.; Doble, Philip; Eskenazi, Brenda; Arora, Manish

    2013-01-01

    Early life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations1,2. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth3. Uncovering early life dietary history in fossils is hampered by the absence of prospectively-validated biomarkers that are not modified during fossilisation4. Here we show that major dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively-recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother’s milk and through the weaning process. We also document transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, suggesting an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history. PMID:23698370

  13. Bayesian analysis of the astrobiological implications of life's early emergence on Earth.

    Science.gov (United States)

    Spiegel, David S; Turner, Edwin L

    2012-01-10

    Life arose on Earth sometime in the first few hundred million years after the young planet had cooled to the point that it could support water-based organisms on its surface. The early emergence of life on Earth has been taken as evidence that the probability of abiogenesis is high, if starting from young Earth-like conditions. We revisit this argument quantitatively in a bayesian statistical framework. By constructing a simple model of the probability of abiogenesis, we calculate a bayesian estimate of its posterior probability, given the data that life emerged fairly early in Earth's history and that, billions of years later, curious creatures noted this fact and considered its implications. We find that, given only this very limited empirical information, the choice of bayesian prior for the abiogenesis probability parameter has a dominant influence on the computed posterior probability. Although terrestrial life's early emergence provides evidence that life might be abundant in the universe if early-Earth-like conditions are common, the evidence is inconclusive and indeed is consistent with an arbitrarily low intrinsic probability of abiogenesis for plausible uninformative priors. Finding a single case of life arising independently of our lineage (on Earth, elsewhere in the solar system, or on an extrasolar planet) would provide much stronger evidence that abiogenesis is not extremely rare in the universe.

  14. Investigating Epigenetic Effects of Prenatal Exposure to Toxic Metals in Newborns: Challenges and Benefits.

    Science.gov (United States)

    Nye, Monica D; Fry, Rebecca C; Hoyo, Cathrine; Murphy, Susan K

    2014-01-01

    Increasing evidence suggest that epigenetic alterations can greatly impact human health, and that epigenetic mechanisms (DNA methylation, histone modifications, and microRNAs) may be particularly relevant in responding to environmental toxicant exposure early in life. The epigenome plays a vital role in embryonic development, tissue differentiation and disease development by controlling gene expression. In this review we discuss what is currently known about epigenetic alterations in response to prenatal exposure to inorganic arsenic (iAs) and lead (Pb), focusing specifically on their effects on DNA methylation. We then describe how epigenetic alterations are being studied in newborns as potential biomarkers of in utero environmental toxicant exposure, and the benefits and challenges of this approach. In summary, the studies highlighted herein indicate how epigenetic mechanisms are impacted by early life exposure to iAs and Pb, and the research that is being done to move towards understanding the relationships between toxicant-induced epigenetic alterations and disease development. Although much remains unknown, several groups are working to understand the correlative and causal effects of early life toxic metal exposure on epigenetic changes and how these changes may result in later development of disease.

  15. Early evolution without a tree of life

    Directory of Open Access Journals (Sweden)

    Martin William F

    2011-06-01

    Full Text Available Abstract Life is a chemical reaction. Three major transitions in early evolution are considered without recourse to a tree of life. The origin of prokaryotes required a steady supply of energy and electrons, probably in the form of molecular hydrogen stemming from serpentinization. Microbial genome evolution is not a treelike process because of lateral gene transfer and the endosymbiotic origins of organelles. The lack of true intermediates in the prokaryote-to-eukaryote transition has a bioenergetic cause. This article was reviewed by Dan Graur, W. Ford Doolittle, Eugene V. Koonin and Christophe Malaterre.

  16. Quartz exposure, retention, and early silicosis in sheep.

    Science.gov (United States)

    Bégin, R; Dufresne, A; Cantin, A; Possmayer, F; Sébastien, P; Fabi, D; Bilodeau, G; Martel, M; Bisson, D; Pietrowski, B

    1989-05-01

    The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To

  17. Effects of early life stress on amygdala and striatal development

    Science.gov (United States)

    Fareri, Dominic S.; Tottenham, Nim

    2016-01-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one’s social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. PMID:27174149

  18. Effects of early life stress on amygdala and striatal development.

    Science.gov (United States)

    Fareri, Dominic S; Tottenham, Nim

    2016-06-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one's social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Effects of early life stress on amygdala and striatal development

    Directory of Open Access Journals (Sweden)

    Dominic S. Fareri

    2016-06-01

    Full Text Available Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS in the form of the absence of species expected caregiving (i.e., caregiver deprivation, can drastically impact one’s social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction.

  20. Industrial Exposures at Birth are Associated with Reduced Forced Vital Capacity in Childhood

    Science.gov (United States)

    Rationale: Previous studies have reported associations of ambient air pollutant exposures with childhood decrements in lung volumes. While the current study was designed primarily to examine traffic exposures, we also examined the impact of other early life exposures on pulmonary...

  1. Life history plasticity of a tropical seabird in response to El Niño anomalies during early life.

    Directory of Open Access Journals (Sweden)

    Sergio Ancona

    Full Text Available Food shortage and other challenges associated with El Niño Southern Oscillation (ENSO experienced early in life may have long-term impacts on life history traits, but these potential impacts remain virtually unexplored. By monitoring 2556 blue-footed boobies from 11 cohorts, we showed that birds facing warm water ENSO conditions (and probably low food availability in the natal year were underweight at fledging, recruited earlier and bred less frequently, but showed no deficit in longevity or breeding success over the first 10 years. Life history impacts of ENSO were substantial when experienced in the prenatal year, the natal year, or the second year of life, and absent when experienced in the third year of life, implying that harsh conditions have greater effects when experienced earlier in life. Sexual differences in impacts depended on the age when warm water conditions were experienced: pre-natal and natal experience, respectively, induced early recruitment and influenced the relationship between age and laying date only in females, whereas second year experience reduced total breeding success only of males. Most surprising were positive transgenerational impacts in females: daughters of females that experienced ENSO conditions in their natal year showed improved breeding success. Developmental plasticity of boobies thus enables them to largely neutralize potential long-term impacts of harsh climatic conditions experienced early in life.

  2. Life history plasticity of a tropical seabird in response to El Niño anomalies during early life.

    Science.gov (United States)

    Ancona, Sergio; Drummond, Hugh

    2013-01-01

    Food shortage and other challenges associated with El Niño Southern Oscillation (ENSO) experienced early in life may have long-term impacts on life history traits, but these potential impacts remain virtually unexplored. By monitoring 2556 blue-footed boobies from 11 cohorts, we showed that birds facing warm water ENSO conditions (and probably low food availability) in the natal year were underweight at fledging, recruited earlier and bred less frequently, but showed no deficit in longevity or breeding success over the first 10 years. Life history impacts of ENSO were substantial when experienced in the prenatal year, the natal year, or the second year of life, and absent when experienced in the third year of life, implying that harsh conditions have greater effects when experienced earlier in life. Sexual differences in impacts depended on the age when warm water conditions were experienced: pre-natal and natal experience, respectively, induced early recruitment and influenced the relationship between age and laying date only in females, whereas second year experience reduced total breeding success only of males. Most surprising were positive transgenerational impacts in females: daughters of females that experienced ENSO conditions in their natal year showed improved breeding success. Developmental plasticity of boobies thus enables them to largely neutralize potential long-term impacts of harsh climatic conditions experienced early in life.

  3. Exposure to Childhood Sexual and Physical Abuse and Adjustment in Early Adulthood

    Science.gov (United States)

    Fergusson, David M.; Boden, Joseph M.; Horwood, L. John

    2008-01-01

    Objective: This research examined linkages between exposure to childhood sexual abuse (CSA) and childhood physical punishment/abuse (CPA) and mental health issues in early adulthood. Method: The investigation analyzed data from a birth cohort of over 1,000 New Zealand young adults studied to the age of 25. Results: Exposure to CSA and CPA was…

  4. Oral treatment with enrofloxacin early in life promotes Th2-mediated immune response in mice.

    Science.gov (United States)

    Strzępa, Anna; Majewska-Szczepanik, Monika; Kowalczyk, Paulina; Woźniak, Dorota; Motyl, Sylwia; Szczepanik, Marian

    2016-02-01

    Th2 lymphocytes play a crucial role in the development of allergy. These pathologies are caused by coordinated production of the cytokines IL-4, IL-5 and IL-13 that regulate the activity of eosinophils, basophils and B cells. According to the 'hygiene hypothesis', the reduced exposure to microorganisms favors allergy occurrence. The advances in medicine in the field of infection therapy promoted an increasing application of antibiotics which, apart from eliminating pathogens, also partially eliminate the microbiota. Epicutaneous (EC) immunization with ovalbumin (OVA) followed by OVA challenge was used to study the influence of partial gut flora depletion by oral treatment with enrofloxacin on type-2 immune response. Current work describes the influence of enrofloxacin application on anti-OVA antibody production and cytokine synthesis in young and adult mice. Immune response in adult mice is less sensitive to modification of natural gut flora. We observed that enrofloxacin treatment of adult mice leads to significant decrease of anti-OVA IgG2a production while synthesis of anti-OVA IgE was not changed. The production of type-1 (IFN-γ), type-2 (IL-4, IL-5, IL-10, IL-13) and Th17-associated (IL-17A) cytokines was inhibited. On the other hand, treatment of young mice with enrofloxacin significantly upregulates the production of anti-OVA IgE and inhibits the secretion of anti-OVA IgG2a antibodies. Additionally, treatment with enrofloxacin early in life prior to OVA immunization results in increased production of type-2 (IL-4, IL-10 and IL-13) cytokines. Our results clearly indicate that the immune system is more vulnerable to decreased bacterial exposure early in life that may promote development of allergy. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. Predicting Negative Life Outcomes from Early Aggressive-Disruptive Behavior Trajectories: Gender Differences in Maladaptation across Life Domains

    Science.gov (United States)

    Bradshaw, Catherine P.; Schaeffer, Cindy M.; Petras, Hanno; Ialongo, Nicholas

    2010-01-01

    Transactional theories of development suggest that displaying high levels of antisocial behavior early in life and persistently over time causes disruption in multiple life domains, which in turn places individuals at risk for negative life outcomes. We used longitudinal data from 1,137 primarily African American urban youth (49.1% female) to…

  6. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats.

    Science.gov (United States)

    Saalfield, Jessica; Spear, Linda

    2015-12-01

    Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4g/kg i.g. ethanol (25%) or water every 48 h from postnatal day (P) 25-45 (early AIE) or P45-65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Addressing bystander exposure to agricultural pesticides in life cycle impact assessment

    DEFF Research Database (Denmark)

    Ryberg, Morten Walbech; Rosenbaum, Ralph K.; Mosqueron, Luc

    2018-01-01

    Residents living near agricultural fields may be exposed to pesticides drifting from the fields after application to different field crops. To address this currently missing exposure pathway in life cycle assessment (LCA), we developed a modeling framework for quantifying exposure of bystanders...... magnitude of individual bystanders can be substantially larger than the exposure of populations not living in the proximity to agricultural fields. Our framework for assessing bystander exposure to pesticide applications closes a relevant gap in the exposure assessment included in LCA for agricultural...... to pesticide spray drift from agricultural fields. Our framework consists of three parts addressing: (1) loss of pesticides from an agricultural field via spray drift; (2) environmental fate of pesticide in air outside of the treated field; and (3) exposure of bystanders to pesticides via inhalation...

  8. Older siblings, pets and early life infections: impact on gut microbiota and allergy prevalence during the first three years of life

    DEFF Research Database (Denmark)

    Laursen, Martin Frederik; Zachariassen, Gitte; Bahl, Martin Iain

    Background: Early life infections and presence of older siblings or pets in the household are factors known to affect the risk of developing allergic diseases, and this effect is suggested to be mediated by interactions between microbes and the immune system. However, very limited research has been...... done on the effect of these factors on the developing gut microbiota in infants. Thus, we aimed to elucidate associations between older siblings, pets and early life infections, the microbial gut communities at 9 and 18 months of age and the prevalence of allergies in three year old children. Methods...... of respiratory allergy, eczema and presence of older siblings, pets and early life infections, previously collected through interviews with parents, were compared to the obtained data on bacterial taxonomy. Results: Early life infections were positively associated with the risk of developing respiratory allergy...

  9. Alcohol, psychomotor-stimulants and behaviour: methodological considerations in preclinical models of early-life stress.

    Science.gov (United States)

    McDonnell-Dowling, Kate; Miczek, Klaus A

    2018-04-01

    In order to assess the risk associated with early-life stress, there has been an increase in the amount of preclinical studies investigating early-life stress. There are many challenges associated with investigating early-life stress in animal models and ensuring that such models are appropriate and clinically relevant. The purpose of this review is to highlight the methodological considerations in the design of preclinical studies investigating the effects of early-life stress on alcohol and psychomotor-stimulant intake and behaviour. The protocols employed for exploring early-life stress were investigated and summarised. Experimental variables include animals, stress models, and endpoints employed. The findings in this paper suggest that there is little consistency among these studies and so the interpretation of these results may not be as clinically relevant as previously thought. The standardisation of these simple stress procedures means that results will be more comparable between studies and that results generated will give us a more robust understanding of what can and may be happening in the human and veterinary clinic.

  10. Life Event Stress and Binge Eating Among Adolescents: The Roles of Early Maladaptive Schemas and Impulsivity.

    Science.gov (United States)

    Zhu, Hong; Luo, Xingwei; Cai, Taisheng; He, Jinbo; Lu, Yao; Wu, Siyao

    2016-10-01

    This study examined the relationships between life event stress, early maladaptive schemas, impulsivity and binge eating among adolescents and investigated the effects of early maladaptive schemas and impulsivity on the relationship between life event stress and binge eating. Specifically, we examined a moderated mediation model in which early maladaptive schemas mediated this relationship and impulsivity moderated the mediation effect. Life event stress, early maladaptive schemas, impulsivity and binge eating were investigated in a sample of 2172 seventh-, eighth- and tenth-grade middle and high school students (mean age = 14.55 years, standard deviation = 1.29). The results indicated that adolescents with greater life event stress, more early maladaptive schemas and higher levels of impulsivity displayed more severe binge eating. In addition, early maladaptive schemas mediated the relationship between life event stress and binge eating, while impulsivity moderated this relationship. Furthermore, impulsivity also moderated the mediation effect of early maladaptive schemas; as impulsivity levels increased, the strength of the association between life event stress and early maladaptive schemas increased. This study illustrates the importance of understanding individual differences and their effects on the relationship between life event stress and binge eating. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Exposure to stress across the life course and its association with anxiety and depressive symptoms: Results from the Australian Women's Wellness After Cancer Program (WWACP).

    Science.gov (United States)

    Seib, Charrlotte; McCarthy, Alexandra; McGuire, Amanda; Porter-Steele, Janine; Balaam, Sarah; Ware, Robert S; Anderson, Debra

    2017-11-01

    Earlier life stressors can increase the risk of persistent anxiety and depressive symptoms in women after cancer, though our understanding of the underlying mechanisms is limited. In this study, we tested alternative life course models to determine which best described associations between exposure to stressors in childhood, adolescence, and adulthood, and self-reported health in women previously treated for breast, gynaecological, and blood cancer. Data were drawn from 351 Australian women within 2 years of completing active cancer treatment who were participating in the Women's Wellness After Cancer Program (WWACP) randomised controlled trial. A model-building framework compared "accumulative risk" and "sensitive period" stress exposure hypotheses with the saturated model to determine best fit. Symptoms of anxiety and depression were measured using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Zung Self-rating Anxiety Scale (SAS). Participants with the greatest number of stressful life events (SLEs) reported higher anxiety scores and more depressive symptoms. Alternative life course models for psychological distress (measured through the CES-D and SAS) and stress were compared with the saturated model (i.e., the accumulative risk). The more restrictive "sensitive period" models were the best fit for depressive symptoms though none was significantly better than another. In contrast, an "early sensitive" model provided the best fit for anxiety data. Anxiety scores were higher in women with early life stressors. This study highlights the need for whole-of-life supportive care approaches for women previously treated for cancer, which should include targeted strategies for effective management of stress, anxiety and depression. Copyright © 2017. Published by Elsevier B.V.

  12. [Suicide exposure and its modulatory effects on relations between life events and suicide risk in Chinese college students].

    Science.gov (United States)

    Zhao, Jiubo; Zhao, Jingbo; Xiao, Rong; Yang, Xueling; Zhang, Xiaoyuan

    2013-08-01

    To explore the incidence of suicide exposure and its association with suicide risk in Chinese college students, and study the modulatory effects of suicide exposure on the relations between life events and suicide risks. A total of 8202 college students from 12 Chinese colleges and universities in mainland China completed a cross-sectional survey that included suicidal behaviors questionnaire-revised (SBQ-R), Adolescent Self-Rating Life Events Check List (ASLEC), suicide exposure questionnaire, social and demographic characteristics questionnaire. The incidence of exposure to suicide events involving close relatives and acquaintances were 3.9% and 11.8% among sampled Chinese college students, respectively. Students exposed to suicide events involving close relatives had significantly higher total SBQ-R scores than those who did not (5.51∓2.44 vs 4.68∓2.11, P0.05), but exposure to acquaintance suicide events moderated the effects of life events on suicide risk (P<0.01), and the college students with a high level of life events and history of acquaintance suicide had the highest risk for suicide. In Chinese college students, the risk of suicide is closely associated with exposure to suicide events and life events, and exposure to suicide events involving acquaintances can modulate the effects of life events on suicide risk.

  13. The Effect of Early Mosquito Insecticides Exposure on Spraque Dawley Rat Testis: A Histopathological Feature Towards Malignancy?

    Science.gov (United States)

    Indah Winarni, Tri; Auzan Aziman, Milzam; Abshar Andar, Anindyo; Pawitra, Ika

    2017-02-01

    The incidence of health problems associated with endocrine-disruption have increased. Many studies suggesting that endocrine disruptor chemicals (EDC) do contribute to cancer through estrogen-related receptors. Many chemicals have EDCs properties including insecticides. Early life exposure to EDCs can increased the risk of testicular cancer have been reported in the last decade. This study was aimed to determine the effect of insecticides exposure on histopathological tumor cell development of germ and Leydig cell. True experiment research design with posttest only control group design was applied. Sprague Dawley (SD) rat (n = 25) were randomly divided into 5 groups (control group, 25 mg β estradiol 3-benzoate, spiral mosquito coil repellent, 3 ml of liquid mosquito repellent, and 4 ml of liquid mosquito repellent). The exposure were administered for 20 days started at aged 3 days. At the age of 100 days (older adult), testis was stained using Hematoxyllin Eosin (HE) and histological features predicting malignancy were observed. The number of tumor cell development in both testicular germ cells and Leydig cells significantly increased in all treated group compared to those of control and the changes towards malignancy were also observed in all treated group. Exposure to mosquito insecticides causes significant changes in testicular germ and Leydig cell histological features that leads to malignancy.

  14. Early-life school, neighborhood, and family influences on adult health: a multilevel cross-classified analysis of the Aberdeen children of the 1950s study.

    Science.gov (United States)

    Dundas, Ruth; Leyland, Alastair H; Macintyre, Sally

    2014-07-15

    Lifetime exposures to adverse social environments influence adult health, as do exposures in early life. It is usual to examine the influences of school on teenage health and of adult area of residence on adult health. We examined the combined long-term association of the school attended, as well as the area of residence in childhood, with adult health. A total of 6,285 children from Aberdeen, Scotland, who were aged 5-12 years in 1962, were followed up at a mean age of 47 years in 2001. Cross-classified multilevel logistic regression was used to estimate the associations of family, school, and area of residence with self-reported adult health and mental health, adjusting for childhood family-, school-, and neighborhood-level factors, as well as current adult occupational position. Low early-life social position (as determined by the father's occupational level) was associated with poor adult self-rated health but not poor mental health. There were small contextual associations between childhood school environment (median odds ratio = 1.08) and neighborhood environment (median odds ratio = 1.05) and adult self-rated health. The share of the total variance in health at the family level was 10.1% compared with 89.6% at the individual level. Both socioeconomic context and composition in early life appear to have an influence on adult health, even after adjustment for current occupational position. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

  15. Effects of High-Temperature Exposures on the Fatigue Life of Superalloy Udimet(Registered Trademark) 720

    Science.gov (United States)

    Gabb, Timothy P.; Telesman, Jack; Kantzos, Peter T.; Sweeney, Joseph W.; Browning, Paul F.

    2002-01-01

    The purpose of this study was to examine the effects of extended exposures on the near-surface fatigue resistance of a disk superalloy. Powder metallurgy processed, supersolvus heat-treated Udimet 720 (U720) fatigue specimens were exposed in air at temperatures from 650 to 705 C for 100 hr to over 1000 hr. They were then tested using conventional fatigue tests at 650 C to determine the effects of exposure on fatigue resistance. The exposures reduced life by up to 70% and increased the scatter in life, compared to unexposed levels. Fractographic evaluations indicated the failure mode was shifted by the exposures from internal to surface crack initiations. The increased scatter in life was related to the competition between internal crack initiations at inclusions or large grains producing longer lives, and surface crack initiations at an environmentally affected surface layer producing shorter lives.

  16. Struggling to survive: early life challenges in relation to the backtest in pigs

    NARCIS (Netherlands)

    Camerlink, I.; Ursinus, W.W.; Bolhuis, J.E.

    2014-01-01

    Intensively reared piglets may face many early life challenges and these may affect behavior. The objective of this study was to examine the relationship between piglets’ early life circumstances and their behavioral response in a backtest. Hereto, 992 piglets of 14 d of age were subjected to a

  17. Could the early environment of Mars have supported the development of life?

    Science.gov (United States)

    Mckay, Christopher P.; Stoker, Carol R.

    1990-01-01

    The environment of Mars and its correlation to the origin of life on earth are examined. Evidence of liquid water and nitrogen on early Mars is discussed. The similarities between the early Mars and early earth environments are described.

  18. The Porto Alegre Early Life Nutrition and Health Study.

    Science.gov (United States)

    Chaffee, Benjamin Wilk; Vítolo, Márcia Regina; Feldens, Carlos Alberto

    2014-12-01

    Early childhood caries is a persistent worldwide problem. The etiologic contribution of feeding practices has been less frequently investigated in prospective studies of young children. The Porto Alegre Early Life Nutrition and Health Study has followed a birth cohort of 715 mother-child pairs, recruited from municipal health centers, originally involved in a cluster-randomized controlled trial of healthcare worker training. The birth cohort links prospectively collected socio-demographic, infant feeding, and general and oral health information. To date, oral health data, including caries status and oral health-related quality of life, have been collected for 458 children at the age of 2-3 years. Studies are underway to investigate possible determinants and consequences of oral health among these children.

  19. The Porto Alegre Early Life Nutrition and Health Study

    Directory of Open Access Journals (Sweden)

    Benjamin Wilk Chaffee

    2014-12-01

    Full Text Available Early childhood caries is a persistent worldwide problem. The etiologic contribution of feeding practices has been less frequently investigated in prospective studies of young children. The Porto Alegre Early Life Nutrition and Health Study has followed a birth cohort of 715 mother-child pairs, recruited from municipal health centers, originally involved in a cluster-randomized controlled trial of healthcare worker training. The birth cohort links prospectively collected socio-demographic, infant feeding, and general and oral health information. To date, oral health data, including caries status and oral health-related quality of life, have been collected for 458 children at the age of 2-3 years. Studies are underway to investigate possible determinants and consequences of oral health among these children.

  20. Work-Life Balance, Burnout, and Satisfaction of Early Career Pediatricians.

    Science.gov (United States)

    Starmer, Amy J; Frintner, Mary Pat; Freed, Gary L

    2016-04-01

    Data describing factors associated with work-life balance, burnout, and career and life satisfaction for early career pediatricians are limited. We sought to identify personal and work factors related to these outcomes. We analyzed 2013 survey data of pediatricians who graduated residency between 2002 and 2004. Dependent variables included: (1) balance between personal and professional commitments, (2) current burnout in work, (3) career satisfaction, and (4) life satisfaction. Multivariable logistic regression examined associations of personal and work characteristics with each of the 4 dependent variables. A total of 93% of participants completed the survey (n = 840). A majority reported career (83%) and life (71%) satisfaction. Fewer reported current appropriate work-life balance (43%) or burnout (30%). In multivariable modeling, excellent/very good health, having support from physician colleagues, and adequate resources for patient care were all found to be associated with a lower prevalence of burnout and a higher likelihood of work-life balance and career and life satisfaction. Having children, race, and clinical specialty were not found to be significantly associated with any of the 4 outcome measures. Female gender was associated with a lower likelihood of balance and career satisfaction but did not have an association with burnout or life satisfaction. Burnout and struggles with work-life balance are common; dissatisfaction with life and career are a concern for some early career pediatricians. Efforts to minimize these outcomes should focus on encouragement of modifiable factors, including health supervision, peer support, and ensuring sufficient patient care resources. Copyright © 2016 by the American Academy of Pediatrics.

  1. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice.

    Science.gov (United States)

    Yanai, Shogo; Hirano, Tetsushi; Omotehara, Takuya; Takada, Tadashi; Yoneda, Naoki; Kubota, Naoto; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2017-07-07

    Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life.

  2. Postnatal treatment with metyrapone attenuates the effects of diet-induced obesity in female rats exposed to early-life stress.

    Science.gov (United States)

    Murphy, Margaret O; Herald, Joseph B; Wills, Caleb T; Unfried, Stanley G; Cohn, Dianne M; Loria, Analia S

    2017-02-01

    Experimental studies in rodents have shown that females are more susceptible to exhibiting fat expansion and metabolic disease compared with males in several models of fetal programming. This study tested the hypothesis that female rat pups exposed to maternal separation (MatSep), a model of early-life stress, display an exacerbated response to diet-induced obesity compared with male rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 h/day, postnatal days 2-14). Upon weaning, male and female rats were placed on a normal (ND; 18% kcal fat) or high-fat diet (HFD; 60% kcal fat). Nondisturbed littermates served as controls. In male rats, no diet-induced differences in body weight (BW), glucose tolerance, and fat tissue weight and morphology were found between MatSep and control male rats. However, female MatSep rats displayed increased BW gain, fat pad weights, and glucose intolerance compared with control rats (P obesity risk factors, including elevated adiposity, hyperleptinemia, and glucose intolerance. These findings show that exposure to stress hormones during early life could be a key event to enhance diet-induced obesity and metabolic disease in female rats. Thus, pharmacological and/or behavioral inflection of the stress levels is a potential therapeutic approach for prevention of early life stress-enhanced obesity and metabolic disease. Copyright © 2017 the American Physiological Society.

  3. Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.)

    Energy Technology Data Exchange (ETDEWEB)

    Steinbach, Christoph, E-mail: steinbach@frov.jcu.cz [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic); Fedorova, Ganna [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic); Prokes, Miroslav [Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, v.v.i., Kvetna 8, 603 65 Brno (Czech Republic); Grabicova, Katerina; Machova, Jana; Grabic, Roman; Valentova, Olga; Kroupova, Hana Kocour [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic)

    2013-09-01

    Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L{sup −1} to μg L{sup −1}. In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC{sub 50} values of verapamil were estimated at 16.4 ± 9.2, 7.3 ± 1.5 and 4.8 ± 0.2 mg L{sup −1} for embryos (E5–E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 μg L{sup −1}. Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 μg L{sup −1} of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF > 500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2 ± 1.6 days and 44.2 ± 8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations. - Highlights: • Study of the acute and sub-chronic toxicity of verapamil on early-life stages of common carp. • Acute exposure to verapamil reduced the heart rate in early-life stages of

  4. Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.)

    International Nuclear Information System (INIS)

    Steinbach, Christoph; Fedorova, Ganna; Prokes, Miroslav; Grabicova, Katerina; Machova, Jana; Grabic, Roman; Valentova, Olga; Kroupova, Hana Kocour

    2013-01-01

    Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L −1 to μg L −1 . In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC 50 values of verapamil were estimated at 16.4 ± 9.2, 7.3 ± 1.5 and 4.8 ± 0.2 mg L −1 for embryos (E5–E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 μg L −1 . Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 μg L −1 of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF > 500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2 ± 1.6 days and 44.2 ± 8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations. - Highlights: • Study of the acute and sub-chronic toxicity of verapamil on early-life stages of common carp. • Acute exposure to verapamil reduced the heart rate in early-life stages of common carp. • The

  5. Exposure to Violence Predicting Cortisol Response During Adolescence and Early Adulthood: Understanding Moderating Factors

    Science.gov (United States)

    Heinze, Justin E.; Miller, Alison L.; Stoddard, Sarah A.; Zimmerman, Marc A.

    2014-01-01

    Previous research on the association between violence and biological stress regulation has been largely cross-sectional, and has also focused on childhood. Using longitudinal data from a low-income, high-risk, predominantly African-American sample (n = 266; 57 % female), we tested hypotheses about the influence of cumulative exposure to violence during adolescence and early adulthood on cortisol responses in early adulthood. We found that cumulative exposure to violence predicted an attenuated cortisol response. Further, we tested whether sex, mothers’ support, or fathers’ support moderated the effect of exposure to violence on cortisol responses. We found that the effect of cumulative exposure to violence on cortisol was modified by sex; specifically, males exposed to violence exhibited a more attenuated response pattern. In addition, the effect of cumulative exposure to violence on cortisol was moderated by the presence of fathers’ support during adolescence. The findings contribute to a better understanding of how cumulative exposure to violence influences biological outcomes, emphasizing the need to understand sex and parental support as moderators of risk. PMID:24458765

  6. Early life treatment with vancomycin reduces diabetes incidence in NOD mice

    DEFF Research Database (Denmark)

    Hansen, Camilla Hartmann Friis; Nielsen, Dennis Sandris; Vogensen, Finn Kvist

    Type 1 diabetes (T1D) results from an uncontrolled T cell mediated destruction of the insulin-producing beta-cells in the pancreas. Causal factors include a combination of genetics, early life incidents and the food we eat. The involved adaptive immune response can be down regulated by a regulato...... of the mechanisms regulating intestinal immune homeostasis toward a proinflammatory mucosal environment.......Type 1 diabetes (T1D) results from an uncontrolled T cell mediated destruction of the insulin-producing beta-cells in the pancreas. Causal factors include a combination of genetics, early life incidents and the food we eat. The involved adaptive immune response can be down regulated by a regulatory...... immune response and a fine-tuned balance between these immunological components is crucial for characteristics of the disease, such as severity, onset time and recovery. The balance between the regulatory and the adaptive immune response is heavily influenced by early life bacterial stimulation...

  7. Effects of coal contamination on early life history processes of a reef-building coral, Acropora tenuis.

    Science.gov (United States)

    Berry, Kathryn L E; Hoogenboom, Mia O; Brinkman, Diane L; Burns, Kathryn A; Negri, Andrew P

    2017-01-15

    Successful reproduction and larval dispersal are important for the persistence of marine invertebrate populations, and these early life history processes can be sensitive to marine pollution. Coal is emerging as a contaminant of interest due to the proximity of ports and shipping lanes to coral reefs. To assess the potential hazard of this contaminant, gametes, newly developed embryos, larvae and juveniles of the coral Acropora tenuis were exposed to a range of coal leachate, suspended coal, and coal smothering treatments. Fertilisation was the most sensitive reproductive process tested. Embryo survivorship decreased with increasing suspended coal concentrations and exposure duration, effects on larval settlement varied between treatments, while effects on juvenile survivorship were minimal. Leachate exposures had negligible effects on fertilisation and larval settlement. These results indicate that coral recruitment could be affected by spills that produce plumes of suspended coal particles which interact with gametes and embryos soon after spawning. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.

    Science.gov (United States)

    Martin, Rocio; Makino, Hiroshi; Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

    2016-01-01

    Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the

  9. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Rocio Martin

    Full Text Available Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to

  10. Environmental proxies of antigen exposure explain variation in immune investment better than indices of pace of life.

    Science.gov (United States)

    Horrocks, Nicholas P C; Hegemann, Arne; Ostrowski, Stéphane; Ndithia, Henry; Shobrak, Mohammed; Williams, Joseph B; Matson, Kevin D; Tieleman, B I

    2015-01-01

    Investment in immune defences is predicted to covary with a variety of ecologically and evolutionarily relevant axes, with pace of life and environmental antigen exposure being two examples. These axes may themselves covary directly or inversely, and such relationships can lead to conflicting predictions regarding immune investment. If pace of life shapes immune investment then, following life history theory, slow-living, arid zone and tropical species should invest more in immunity than fast-living temperate species. Alternatively, if antigen exposure drives immune investment, then species in antigen-rich tropical and temperate environments are predicted to exhibit higher immune indices than species from antigen-poor arid locations. To test these contrasting predictions we investigated how variation in pace of life and antigen exposure influence immune investment in related lark species (Alaudidae) with differing life histories and predicted risks of exposure to environmental microbes and parasites. We used clutch size and total number of eggs laid per year as indicators of pace of life, and aridity, and the climatic variables that influence aridity, as correlates of antigen abundance. We quantified immune investment by measuring four indices of innate immunity. Pace of life explained little of the variation in immune investment, and only one immune measure correlated significantly with pace of life, but not in the predicted direction. Conversely, aridity, our proxy for environmental antigen exposure, was predictive of immune investment, and larks in more mesic environments had higher immune indices than those living in arid, low-risk locations. Our study suggests that abiotic environmental variables with strong ties to environmental antigen exposure can be important correlates of immunological variation.

  11. Gene expression in the mouse brain following early pregnancy exposure to ethanol

    Directory of Open Access Journals (Sweden)

    Christine R. Zhang

    2016-12-01

    Full Text Available Exposure to alcohol during early embryonic or fetal development has been linked with a variety of adverse outcomes, the most common of which are structural and functional abnormalities of the central nervous system [1]. Behavioural and cognitive deficits reported in individuals exposed to alcohol in utero include intellectual impairment, learning and memory difficulties, diminished executive functioning, attention problems, poor motor function and hyperactivity [2]. The economic and social costs of these outcomes are substantial and profound [3,4]. Improvement of neurobehavioural outcomes following prenatal alcohol exposure requires greater understanding of the mechanisms of alcohol-induced damage to the brain. Here we use a mouse model of relatively moderate ethanol exposure early in pregnancy and profile gene expression in the hippocampus and caudate putamen of adult male offspring. The effects of offspring sex and age on ethanol-sensitive hippocampal gene expression were also examined. All array data are available at the Gene Expression Omnibus (GEO repository under accession number GSE87736.

  12. Early life experience : neuroendocrine adaptations to maternal absence

    NARCIS (Netherlands)

    Enthoven, Leo

    2007-01-01

    An adverse early life event is considered a risk factor for stress-related psychiatric disorders in genetically predisposed individuals, probably because of its lasting effect on susceptibility to stress. The objective of this thesis research was to examine in the mouse CD1 strain the immediate and

  13. Early life factors and dental caries in 5-year-old children in China.

    Science.gov (United States)

    Sun, Xiangyu; Bernabé, Eduardo; Liu, Xuenan; Gallagher, Jennifer E; Zheng, Shuguo

    2017-09-01

    This study aimed to explore the association between early life factors and dental caries among 5-year-old Chinese children. Data from 9722 preschool children who participated in the third National Oral Health Survey of China were analysed. Information on early life (birth weight, breastfeeding and age when toothbrushing started), child (sex, ethnicity, birth order and dental behaviours) and family factors (parental education, household income, place of residence, number of children in the family, respondent's age and relation to the child) were obtained from parental questionnaires. Children were also clinically examined to assess dental caries experience using the decayed, missing and filled teeth (dmft) index. The association of early life factors with dmft was evaluated in negative binomial regression models. We found that birth weight was not associated with dental caries experience; children who were exclusively and predominantly formula-fed had lower dmft values than those exclusively breastfed; and children who started brushing later in life had higher dmft values than those who were brushing within the first year. Only one in seven of all children received regular toothbrushing twice per day, and only 34.7% had commenced toothbrushing by the age of 3 years. This study shows certain early life factors play a role in dental caries among Chinese preschool children and provides important insights to shape public health initiatives on the importance of introducing early toothbrushing. The early environment, especially the age when parents introduce toothbrushing to their children, can be an important factor to prevent childhood dental caries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. The role of early-life educational quality and literacy in explaining racial disparities in cognition in late life.

    Science.gov (United States)

    Sisco, Shannon; Gross, Alden L; Shih, Regina A; Sachs, Bonnie C; Glymour, M Maria; Bangen, Katherine J; Benitez, Andreana; Skinner, Jeannine; Schneider, Brooke C; Manly, Jennifer J

    2015-07-01

    Racial disparities in late-life cognition persist even after accounting for educational attainment. We examined whether early-life educational quality and literacy in later life help explain these disparities. We used longitudinal data from the Washington Heights-Inwood Columbia Aging Project (WHICAP). Educational quality (percent white students; urban/rural school; combined grades in classroom) was operationalized using canonical correlation analysis. Late-life literacy (reading comprehension and ability, writing) was operationalized using confirmatory factor analysis. We examined whether these factors attenuated race-related differences in late-life cognition. The sample consisted of 1,679 U.S.-born, non-Hispanic, community-living adults aged 65-102 (71% black, 29% white; 70% women). Accounting for educational quality and literacy reduced disparities by 29% for general cognitive functioning, 26% for memory, and 32% for executive functioning but did not predict differences in rate of cognitive change. Early-life educational quality and literacy in late life explain a substantial portion of race-related disparities in late-life cognitive function. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Early childhood exposure to media violence: What parents and policymakers ought to know

    OpenAIRE

    Caroline Fitzpatrick; Michael J Oghia; Jad Melki; Linda S Pagani

    2016-01-01

    We review the state of evidence supporting a link between violent media exposure in preschool- aged children and subsequent well-being outcomes. We searched through four decades (1971–2011) of literature for enlightening details on the relationship between early exposure to media violence and health outcomes in later childhood and adolescence. Evidence suggests that preschool exposure may be linked to increased aggression and self-regulation problems. Results are discussed in the context of d...

  16. Prenatal and Postnatal Cell Phone Exposures and Headaches in Children

    NARCIS (Netherlands)

    Sudan, Madhuri; Kheifets, Leeka; Arah, Onyebuchi; Olsen, Jorn; Zeltzer, Lonnie

    2012-01-01

    Children today are exposed to cell phones early in life, and may be at the greatest risk if exposure is harmful to health. We investigated associations between cell phone exposures and headaches in children. The Danish National Birth Cohort enrolled pregnant women between 1996 and 2002. When their

  17. Excess iron: considerations related to development and early growth.

    Science.gov (United States)

    Wessling-Resnick, Marianne

    2017-12-01

    What effects might arise from early life exposures to high iron? This review considers the specific effects of high iron on the brain, stem cells, and the process of erythropoiesis and identifies gaps in our knowledge of what molecular damage may be incurred by oxidative stress that is imparted by high iron status in early life. Specific areas to enhance research on this topic include the following: longitudinal behavioral studies of children to test associations between iron exposures and mood, emotion, cognition, and memory; animal studies to determine epigenetic changes that reprogram brain development and metabolic changes in early life that could be followed through the life course; and the establishment of human epigenetic markers of iron exposures and oxidative stress that could be monitored for early origins of adult chronic diseases. In addition, efforts to understand how iron exposure influences stem cell biology could be enhanced by establishing platforms to collect biological specimens, including umbilical cord blood and amniotic fluid, to be made available to the research community. At the molecular level, there is a need to better understand stress erythropoiesis and changes in iron metabolism during pregnancy and development, especially with respect to regulatory control under high iron conditions that might promote ineffective erythropoiesis and iron-loading anemia. These investigations should focus not only on factors such as hepcidin and erythroferrone but should also include newly identified interactions between transferrin receptor-2 and the erythropoietin receptor. Finally, despite our understanding that several key micronutrients (e.g., vitamin A, copper, manganese, and zinc) support iron's function in erythropoiesis, how these nutrients interact remains, to our knowledge, unknown. It is necessary to consider many factors when formulating recommendations on iron supplementation. © 2017 American Society for Nutrition.

  18. Early Childhood Lead Exposure and Academic Achievement: Evidence From Detroit Public Schools, 2008–2010

    Science.gov (United States)

    Baker, Harolyn W.; Tufts, Margaret; Raymond, Randall E.; Salihu, Hamisu; Elliott, Michael R.

    2013-01-01

    Objectives. We assessed the long-term effect of early childhood lead exposure on academic achievement in mathematics, science, and reading among elementary and junior high school children. Methods. We linked early childhood blood lead testing surveillance data from the Detroit Department of Health and Wellness Promotion to educational testing data from the Detroit, Michigan, public schools. We used the linked data to investigate the effect of early childhood lead exposure on academic achievement among school-aged children, both marginally and adjusted for grade level, gender, race, language, maternal education, and socioeconomic status. Results. High blood lead levels before age 6 years were strongly associated with poor academic achievement in grades 3, 5, and 8. The odds of scoring less than proficient for those whose blood lead levels were greater than 10 micrograms per deciliter were more than twice the odds for those whose blood lead levels were less than 1 micrograms per deciliter after adjustment for potential confounders. Conclusions. Early childhood lead exposure was negatively associated with academic achievement in elementary and junior high school, after adjusting for key potential confounders. The control of lead poisoning should focus on primary prevention of lead exposure in children and development of special education programs for students with lead poisoning. PMID:23327265

  19. Life cycle responses of the midge Chironomus riparius to polycyclic aromatic compound exposure

    NARCIS (Netherlands)

    León Paumen, M.; Borgman, E.; Kraak, M.H.S.; van Gestel, C.A.M.; Admiraal, W.

    2008-01-01

    During acute exposure, polycyclic aromatic compounds (PACs) act mainly by narcosis, but during chronic exposure the same compounds may exert sublethal life cycle effects. The aim of this study was therefore to evaluate the chronic effects of sediment spiked PACs on the emergence of the midge

  20. 17α-Ethinylestradiol (EE2) treatment of wild roach (Rutilus rutilus) during early life development disrupts expression of genes directly involved in the feedback cycle of estrogen.

    Science.gov (United States)

    Nikoleris, Lina; Hultin, Cecilia L; Hallgren, Per; Hansson, Maria C

    2016-02-01

    Fish are more sensitive to introduced disturbances from synthetic endocrine disrupting compounds during early life phases compared with mature stages. 17α-Ethinylestradiol (EE2), which is the active compound in human oral contraceptives and hormone replacement therapies, is today ever present in the effluents from sewage treatment plants. EE2 targets and interacts with the endogenous biological systems of exposed vertebrates resulting in to large extents unknown short- and long-term effects. We investigated how EE2 exposure affects expression profiles of a large number of target genes during early life of roach (Rutilus rutilus). We exposed fertilized roach eggs collected from a lake in Southern Sweden to EE2 for 12weeks together with 1+-year-old roach in aquaria. We measured the gene expression of the estrogen receptor (esr)1/2a/2b, androgen receptor (ar), vitellogenin, cytochrome P450 (cyp)19a1a/1b in fertilized eggs; newly hatched larvae; 12-week-old fry; and juvenile wild roach (1+-year-old). Results shows that an EE2 concentration as low as 0.5ng/L significantly affects gene expression during early development. Gene expression responses vary both among life stages and molecular receptors. We also show that the gene profile of the estrogen feedback cycle to a large extent depends on the relationship between the three esr genes and the two cyp19a1 genes, which are all up-regulated with age. Results indicate that a disruption of the natural activity of the dominant esr gene could lead to detrimental biological effects if EE2 exposure occurs during development, even if this exposure occurred for only a short period. Copyright © 2015. Published by Elsevier Inc.

  1. Feeding blueberry diets in early life prevent senescence of osteoblasts and bone loss in ovariectomized adult female rats.

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    Full Text Available Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied.In this report, we show that feeding a high quality diet supplemented with blueberries (BB to pre-pubertal rats throughout development or only between postnatal day 20 (PND20 and PND34 prevented ovariectomy (OVX-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation.These results indicate: 1 a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2 the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence.

  2. Life cycle responses of the midge Chironomus riparius to polycyclic aromatic compound exposure

    Energy Technology Data Exchange (ETDEWEB)

    Paumen, Miriam Leon [Department of Aquatic Ecology and Ecotoxicology, Institute of Biodiversity and Ecosystem Dynamics (IBED), University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam (Netherlands)], E-mail: mleon@science.uva.nl; Borgman, Eefje [Department of Aquatic Ecology and Ecotoxicology, Institute of Biodiversity and Ecosystem Dynamics (IBED), University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam (Netherlands); Kraak, Michiel H.S. [Department of Aquatic Ecology and Ecotoxicology, Institute of Biodiversity and Ecosystem Dynamics (IBED), University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam (Netherlands)], E-mail: castella@science.uva.nl; Gestel, Cornelis A.M. van [Department of Animal Ecology, Institute of Ecological Sciences (IEW), Vrije Universiteit Amsterdam, de Boelelaan 1085, 1081 HV Amsterdam (Netherlands)], E-mail: kees.van.gestel@falw.vu.nl; Admiraal, Wim [Department of Aquatic Ecology and Ecotoxicology, Institute of Biodiversity and Ecosystem Dynamics (IBED), University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam (Netherlands)

    2008-03-15

    During acute exposure, polycyclic aromatic compounds (PACs) act mainly by narcosis, but during chronic exposure the same compounds may exert sublethal life cycle effects. The aim of this study was therefore to evaluate the chronic effects of sediment spiked PACs on the emergence of the midge Chironomus riparius. Three isomer pairs were selected, and 28-day LC{sub 50} values and 50% emergence times (EMt{sub 50}) were determined. Concentration-response relationships were observed for phenanthrene, acridine, phenanthridine and acridone. Anthracene and phenanthridone had no effect on total emergence, but did cause a delay in emergence. Calculated porewater LC{sub 50} values correlated well with logK{sub ow} values, suggesting narcosis as mode of action. In contrast, effect concentrations for delay in emergence (EMt{sub 50}) deviated from narcosis, suggesting a specific mode of action during chronic exposure. It is concluded that emergence is a powerful endpoint to detect life cycle effects of PACs on a key sediment inhabiting invertebrate. - Emergence of Chironomus riparius is a sensitive endpoint to detect life cycle effects of PACs.

  3. Effects of early life trauma are dependent on genetic predisposition: a rat study

    Directory of Open Access Journals (Sweden)

    Russell Vivienne A

    2011-05-01

    Full Text Available Abstract Background Trauma experienced early in life increases the risk of developing a number of psychological and/or behavioural disorders. It is unclear, however, how genetic predisposition to a behavioural disorder, such as attention-deficit/hyperactivity disorder (ADHD, modifies the long-term effects of early life trauma. There is substantial evidence from family and twin studies for susceptibility to ADHD being inherited, implying a strong genetic component to the disorder. In the present study we used an inbred animal model of ADHD, the spontaneously hypertensive rat (SHR, to investigate the long-term consequences of early life trauma on emotional behaviour in individuals predisposed to developing ADHD-like behaviour. Methods We applied a rodent model of early life trauma, maternal separation, to SHR and Wistar-Kyoto rats (WKY, the normotensive control strain from which SHR were originally derived. The effects of maternal separation (removal of pups from dam for 3 h/day during the first 2 weeks of life on anxiety-like behaviour (elevated-plus maze and depressive-like behaviour (forced swim test were assessed in prepubescent rats (postnatal day 28 and 31. Basal levels of plasma corticosterone were measured using radioimmunoassay. Results The effect of maternal separation on SHR and WKY differed in a number of behavioural measures. Similar to its reported effect in other rat strains, maternal separation increased the anxiety-like behaviour of WKY (decreased open arm entries but not SHR. Maternal separation increased the activity of SHR in the novel environment of the elevated plus-maze, while it decreased that of WKY. Overall, SHR showed a more active response in the elevated plus-maze and forced swim test than WKY, regardless of treatment, and were also found to have higher basal plasma corticosterone compared to WKY. Maternal separation increased basal levels of plasma corticosterone in SHR females only, possibly through adaptive

  4. Television During Meals in the First 4 Years of Life.

    Science.gov (United States)

    Thimmig, Lindsay M; Cabana, Michael D; Bentz, Michael G; Potocka, Katherine; Beck, Amy; Fong, Lawrence; Chao, Cewin; Caughey, Aaron B; Wong, Angela; McKean, Michelle

    2017-06-01

    The development of children's mealtime television (TV) habits has not been well studied. We assessed whether mealtime TV habits established in infancy will persist into early childhood. We analyzed data collected through parent surveys at birth and at 6-month intervals from a randomized controlled trial. We used t-tests, χ 2 tests, and a multivariable logistic regression to determine if family characteristics were associated with mealtime TV. A McNemar test was used to assess whether mealtime TV exposure changed over time. College-educated fathers and families with an annual income >$50 000 were associated with less-frequent TV exposure during children's mealtimes. It was found that 84% of children retained their level of exposure to TV during mealtimes from the first 24 months through 48 months of life. Clinicians should counsel families about mealtime TV use within the first 2 years of life because these habits seem to develop early and persist into at least early childhood.

  5. On the possibility of life on early Mars

    Science.gov (United States)

    Oberbeck, V. R.; Fogleman, G.

    1990-01-01

    Prebiotic reactants, liquid water, and temperatures low enough for organic compounds to be stable are requirements for the origination of life as we know it. Prebiotic reactants and sufficiently low temperatures were present on Mars before liquid water vanished. Early in this time period, however, large planetesimal impacts may have periodically sterilized Mars, pyrolyzed organic compounds, and interrupted chemical origination of life. However, the calculated time interval between such impacts on Mars was larger just before liquid water vanished 3.8 Gyr (billion years) ago than it was on earth just before life originated. Therefore, there should have been sufficient time for life to originate on Mars. Ideal sites to search for microfossils are in the heavily cratered terrain of Upper Noachian age. Craters and channels in this terrain may have been the sites of ancient lakes and streams that could have provided habitats for the first microorganisms.

  6. Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient.

    Science.gov (United States)

    Darcy, Justin; Fang, Yimin; Hill, Cristal M; McFadden, Sam; Sun, Liou Y; Bartke, Andrzej

    2016-10-01

    Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not. Possible mechanisms by which early life growth hormone replacement therapy shortens longevity include deleterious effects on glucose homeostasis and energy metabolism, which are long lasting. A mechanism explaining why early life T4 replacement therapy does not shorten longevity remains elusive. Here, we look for a possible explanation as to why early life T4 replacement therapy does not impact longevity of Ames dwarf mice. We found that early life T4 replacement therapy increased body weight and advanced the age of sexual maturation. We also find that early life T4 replacement therapy does not impact glucose tolerance or insulin sensitivity, and any deleterious effects on oxygen consumption, respiratory quotient and heat production are transient. Lastly, we find that early life T4 replacement therapy has long-lasting effects on bone mineral density and bone mineral content. We suggest that the transient effects on energy metabolism and lack of effects on glucose homeostasis are the reasons why there is no shortening of longevity after early life T4 replacement therapy in Ames dwarf mice. © 2016 by the Society for Experimental Biology and Medicine.

  7. Local adaptation in brown trout early life-history traits: implications for climate change adaptability

    DEFF Research Database (Denmark)

    Jensen, L.F.; Hansen, Michael Møller; Pertoldi, C.

    2008-01-01

    to adapt. Temperature-related adaptability in traits related to phenology and early life history are expected to be particularly important in salmonid fishes. We focused on the latter and investigated whether four populations of brown trout (Salmo trutta) are locally adapted in early life-history traits...

  8. Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?

    Science.gov (United States)

    Danese, Andrea; J Lewis, Stephanie

    2017-01-01

    The brain and the immune system are not fully formed at birth, but rather continue to mature in response to the postnatal environment. The two-way interaction between the brain and the immune system makes it possible for childhood psychosocial stressors to affect immune system development, which in turn can affect brain development and its long-term functioning. Drawing from experimental animal models and observational human studies, we propose that the psychoneuroimmunology of early-life stress can offer an innovative framework to understand and treat psychopathology linked to childhood trauma. Early-life stress predicts later inflammation, and there are striking analogies between the neurobiological correlates of early-life stress and of inflammation. Furthermore, there are overlapping trans-diagnostic patterns of association of childhood trauma and inflammation with clinical outcomes. These findings suggest new strategies to remediate the effect of childhood trauma before the onset of clinical symptoms, such as anti-inflammatory interventions and potentiation of adaptive immunity. Similar strategies might be used to ameliorate the unfavorable treatment response described in psychiatric patients with a history of childhood trauma. PMID:27629365

  9. Update on Early Nutrition and Food Allergy in Children.

    Science.gov (United States)

    Lee, Sun Eun; Kim, Hyeyoung

    2016-05-01

    With growing evidence of an increase in the prevalence, food allergy has been emerged as a new public health problem. As treatment and management of food allergy remain challenging, more attention has been paid to the importance of prevention of food allergy. Although the exact mechanism of recent epidemic is not fully understood, it is suggested that nutritional exposure in early life may play an important role in food allergy development. The underlying hypothesis is that nutritional status or food exposure in the critical period of fetal development can affect the programming of immune system and modify the risk of immunologic reactions to foods in postnatal life. We review accumulating epidemiological studies to examine an association between nutritional exposure during pregnancy or early infancy and food allergy development in children. We also discuss recent advances in the studies of the genetic and epigenetic regulation of food allergy and evaluate the role of early nutrition in food allergy development to provide a new perspective on the prevention of food allergy.

  10. Positive emotions in early life and longevity: findings from the nun study.

    Science.gov (United States)

    Danner, D D; Snowdon, D A; Friesen, W V

    2001-05-01

    Handwritten autobiographies from 180 Catholic nuns, composed when participants were a mean age of 22 years, were scored for emotional content and related to survival during ages 75 to 95. A strong inverse association was found between positive emotional content in these writings and risk of mortality in late life (p < .001). As the quartile ranking of positive emotion in early life increased, there was a stepwise decrease in risk of mortality resulting in a 2.5-fold difference between the lowest and highest quartiles. Positive emotional content in early-life autobiographies was strongly associated with longevity 6 decades later. Underlying mechanisms of balanced emotional states are discussed.

  11. Early-Life Parent-Child Relationships and Adult Children's Support of Unpartnered Parents in Later Life.

    Science.gov (United States)

    Lin, I-Fen; Wu, Hsueh-Sheng

    2018-02-08

    The proportion of older adults who are unpartnered has increased significantly over the past 25 years. Unpartnered older adults often rely on their adult children for support. Most previous studies have focused on proximal factors associated with adult children's support of their parents, while few have examined distal factors, such as parent-child relationships formed during childhood. This study fills the gap by investigating the direct and indirect associations between early-life parent-child relationships and adult children's upward transfers to unpartnered parents. Data came from two supplements to the Panel Study of Income Dynamics, in which respondents were asked about their relationships with mothers and fathers before age 17 and their transfers of time and money to parents in 2013. Path models were estimated for unpartnered mother-adult child dyads and father-adult child dyads separately. For adult children of unpartnered mothers, psychological closeness has a direct, positive association with time transfer, while physical violence has an indirect association with time transfer through adult children's marital status. For adult children of unpartnered fathers, psychological closeness has neither a direct nor an indirect association with time or money transfer, but physical violence has a direct, negative association with time transfer. Early-life parent-child relationships play a pivotal role in influencing adult children's caregiving behavior, both directly and indirectly. Our findings suggest that by improving their relationships with children early in life, parents may be able to increase the amount of time transfer that they receive in late life. © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Database of Physiological Parameters for Early Life Rats and Mice

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Database of Physiological Parameters for Early Life Rats and Mice provides information based on scientific literature about physiological parameters. Modelers...

  13. The Nun study: clinically silent AD, neuronal hypertrophy, and linguistic skills in early life.

    Science.gov (United States)

    Iacono, D; Markesbery, W R; Gross, M; Pletnikova, O; Rudow, G; Zandi, P; Troncoso, J C

    2009-09-01

    It is common to find substantial Alzheimer disease (AD) lesions, i.e., neuritic beta-amyloid plaques and neurofibrillary tangles, in the autopsied brains of elderly subjects with normal cognition assessed shortly before death. We have termed this status asymptomatic AD (ASYMAD). We assessed the morphologic substrate of ASYMAD compared to mild cognitive impairment (MCI) in subjects from the Nun Study. In addition, possible correlations between linguistic abilities in early life and the presence of AD pathology with and without clinical manifestations in late life were considered. Design-based stereology was used to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in the CA1 region of hippocampus (CA1). Four groups of subjects were compared: ASYMAD (n = 10), MCI (n = 5), AD (n = 10), and age-matched controls (n = 13). Linguistic ability assessed in early life was compared among all groups. A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in ASYMAD compared with MCI. Similar differences were observed with controls. Furthermore, significant higher idea density scores in early life were observed in controls and ASYMAD group compared to MCI and AD groups. 1) Neuronal hypertrophy may constitute an early cellular response to Alzheimer disease (AD) pathology or reflect compensatory mechanisms that prevent cognitive impairment despite substantial AD lesions; 2) higher idea density scores in early life are associated with intact cognition in late life despite the presence of AD lesions.

  14. Later life swimming performance and persistent heart damage following subteratogenic PAH mixture exposure in the Atlantic killifish (Fundulus heteroclitus).

    Science.gov (United States)

    Brown, Daniel R; Thompson, Jasmine; Chernick, Melissa; Hinton, David E; Di Giulio, Richard T

    2017-12-01

    High-level, acute exposures to individual polycyclic aromatic hydrocarbons (PAHs) and complex PAH mixtures result in cardiac abnormalities in developing fish embryos. Whereas acute PAH exposures can be developmentally lethal, little is known about the later life consequences of early life, lower level PAH exposures in survivors. A population of PAH-adapted Fundulus heteroclitus from the PAH-contaminated Superfund site, Atlantic Wood Industries, Elizabeth River, Portsmouth, Virginia, United States, is highly resistant to acute PAH cardiac teratogenicity. We sought to determine and characterize long-term swimming performance and cardiac histological alterations of a subteratogenic PAH mixture exposure in both reference killifish and PAH-adapted Atlantic Wood killifish embryos. Killifish from a relatively uncontaminated reference site, King's Creek, Virginia, United States, and Atlantic Wood killifish were treated with dilutions of Elizabeth River sediment extract at 24 h post fertilization (hpf). Two proven subteratogenic dilutions, 0.1 and 1.0% Elizabeth River sediment extract (total PAH 5.04 and 50.4 µg/L, respectively), were used for embryo exposures. Then, at 5-mo post hatching, killifish were subjected to a swim performance test. A separate subset of these individuals was processed for cardiac histological analysis. Unexposed King's Creek killifish significantly outperformed the unexposed Atlantic Wood killifish in swimming performance as measured by Ucrit (i.e., critical swimming speed). However, King's Creek killifish exposed to Elizabeth River sediment extract (both 0.1 and 1.0%) showed significant declines in Ucrit. Histological analysis revealed the presence of blood in the pericardium of King's Creek killifish. Although Atlantic Wood killifish showed baseline performance deficits relative to King's Creek killifish, their pericardial cavities were nearly free of blood and atrial and ventricular alterations. These findings may explain, in part, the

  15. Early life trauma, post-traumatic stress disorder, and allostatic load in a sample of American Indian adults.

    Science.gov (United States)

    Thayer, Zaneta; Barbosa-Leiker, Celestina; McDonell, Michael; Nelson, Lonnie; Buchwald, Dedra; Manson, Spero

    2017-05-06

    Among American Indians, prior research has found associations between early life trauma and the development of post-traumatic stress disorder (PTSD) in adulthood. Given the physiological changes associated with PTSD, early life trauma could indirectly contribute to chronic disease risk. However, the impact of early life trauma on adult physical health in this population has not been previously investigated. We evaluated associations among early life trauma, PTSD, and 13 physiological biomarkers that index cardiovascular, metabolic, neuroendocrine, anthropometric, and immune function in adulthood by conducting correlation and structural equation modeling path analyses (N = 197). Physiological systems were analyzed individually as well as in a composite measure of allostatic load. We found early life trauma was related to PTSD, which in turn was related to elevated allostatic load in adulthood. Among the various components of allostatic load, the neuroendocrine system was the only one significantly related to early life stress and subsequent PTSD development. Changes in allostatic load might reflect adaptive adjustments that maximize short-term survival by enhancing stress reactivity, but at a cost to later health. Interventions should focus on improving access to resources for children who experience early life trauma in order to avoid PTSD and other harmful sequelae. © 2016 Wiley Periodicals, Inc.

  16. Coping with a changing environment: The effects of