Life Detection on the Early Earth

NASA Technical Reports Server (NTRS)

Runnegar, B.

2004-01-01

Finding evidence for first the existence, and then the nature of life on the early Earth or early Mars requires both the recognition of subtle biosignatures and the elimination of false positives. The history of the search for fossils in increasingly older Precambrian strata illustrates these difficulties very clearly, and new observational and theoretical approaches are both needed and being developed. At the microscopic level of investigation, three-dimensional morphological characterization coupled with in situ chemical (isotopic, elemental, structural) analysis is the desirable first step. Geological context is paramount, as has been demonstrated by the controversies over AH84001, the Greenland graphites, and the Apex chert microfossils . At larger scales, the nature of sedimentary bedforms and the structures they display becomes crucial, and here the methods of condensed matter physics prove most useful in discriminating between biological and non-biological constructions. Ultimately, a combination of geochemical, morphological, and contextural evidence may be required for certain life detection on the early Earth or elsewhere.

The positive and negative consequences of stressors during early life.

PubMed

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.

Sex differences in the consequences of early-life exposure to epidemiological stress--a life-history approach.

PubMed

Störmer, Charlotte

2011-01-01

Exposure to infectious disease in early life has been suggested to have a negative effect on later-life survival,possibly through the induction of inflammatory responses. Although a life-course perspective emphasizes the importance of both survival and reproduction for individual fitness, to date, no studies have investigated whether early-life exposure to infectious disease has an impact on reproduction as it has been suggested for later survival. To address this question, I have used family reconstitution data from a historical (18th and 19th century) human population in the Krummhörn (Germany) comparing survival and reproduction between an exposed and a non-exposed group. The exposed group comprised those exposed to a high-infectious disease load during prenatal and early postnatal development. The results show a marked sex difference in the impact of early-life exposure to infectious disease. Exposed females show no effect on their life expectancy but significantly reduced fertility (number of children). For exposed males, however, the effect on survival is opponent over time: mortality is increased during childhood but decreased in late adulthood. Above that, exposed males reproduce earlier and have a smaller proportion of surviving children. This study does not support former studies indicating a negative association between early-life disease load and later survival. I argue that due to differences in male and female life strategies, males in general are more vulnerable especially early in life. Hence, adverse environmental conditions may have a stronger effect on male survivability and reproductive performance.

Early-Life Social Origins of Later-Life Body Weight: The Role of Socioeconomic Status and Health Behaviors over the Life Course

PubMed Central

Logan, Ellis Scott; Richman, Aliza

2014-01-01

Using the 1957-2004 data from the Wisconsin Longitudinal Study, we apply structural equation modeling to examine gender-specific effects of family socioeconomic status (SES) at age 18 on body weight at age 65. We further explore SES and health behaviors over the life course as mechanisms linking family background and later-life body weight. We find that early-life socioeconomic disadvantage is related to higher body weight at age 65 and a steeper weight increase between midlife and late life. These adverse effects are stronger among women than men. Significant mediators of the effect of parents' SES include adolescent body mass (especially among women) as well as exercise and SES in midlife. Yet, consistent with the critical period mechanism, the effect of early-life SES on late-life body weight persists net of all mediating variables. This study expands current understanding of life-course mechanisms that contribute to obesity and increase biological vulnerability to social disadvantage. PMID:24767590

Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life

PubMed Central

Xiao, Lan; Kish, Vincent L.; Benders, Katherine M.

2016-01-01

Background: Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain. Methods: Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59. Results: Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain-derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group. Conclusions: These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life. PMID:26503133

Early life factors in the pathogenesis of osteoporosis.

PubMed

Winsloe, Chivon; Earl, Susie; Dennison, Elaine M; Cooper, Cyrus; Harvey, Nicholas C

2009-12-01

Osteoporosis is a major public health burden through associated fragility fractures. Bone mass, a composite of bone size and volumetric density, increases through early life and childhood to a peak in early adulthood. The peak bone mass attained is a strong predictor of future risk of osteoporosis. Evidence is accruing that environmental factors in utero and in early infancy may permanently modify the postnatal pattern of skeletal growth to peak and thus influence risk of osteoporosis in later life. This article describes the latest data in this exciting area of research, including novel epigenetic and translation work, which should help to elucidate the underlying mechanisms and give rise to potential public health interventions to reduce the burden of osteoporotic fracture in future generations.

Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

PubMed

Shalev, Idan; Belsky, Jay

2016-05-01

Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early-life origins of life-cycle well-being: research and policy implications.

PubMed

Currie, Janet; Rossin-Slater, Maya

2015-01-01

Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the life cycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population well-being, but also for economic growth and competitiveness in a global economy. In this paper, we first discuss the research on the strength of the link between early-life health and adult outcomes, and then provide an evidence-based review of the effectiveness of existing U.S. policies targeting the early-life environment. We conclude that there is a robust and economically meaningful relationship between early-life conditions and well-being throughout the life cycle, as measured by adult health, educational attainment, labor market attachment, and other indicators of socioeconomic status. However, there is some variation in the degree to which current policies in the United States are effective in improving early-life conditions. Among existing programs, some of the most effective are the Special Supplemental Program for Women, Infants, and Children (WIC), home visiting with nurse practitioners, and high-quality, center-based early-childhood care and education. In contrast, the evidence on other policies such as prenatal care and family leave is more mixed and limited.

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

PubMed

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.

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

PubMed Central

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

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

PubMed

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

Early Life Stages

EPA Pesticide Factsheets

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.

Early Life Stress Increases Metabolic Risk, HPA Axis Reactivity, and Depressive-Like Behavior When Combined with Postweaning Social Isolation in Rats.

PubMed

Vargas, Javier; Junco, Mariana; Gomez, Carlos; Lajud, Naima

2016-01-01

Early-life stress is associated with depression and metabolic abnormalities that increase the risk of cardiovascular disease and diabetes. Such associations could be due to increased glucocorticoid levels. Periodic maternal separation in the neonate and rearing in social isolation are potent stressors that increase hypothalamus-pituitary-adrenal axis activity. Moreover, social isolation promotes feed intake and body weight gain in rats subjected to periodic maternal separation; however, its effects on metabolic risks have not been described. In the present study, we evaluated whether periodic maternal separation, social isolation rearing, and a combination of these two stressors (periodic maternal separation + social isolation rearing) impair glucose homeostasis and its relation to the hypothalamus-pituitary-adrenal axis and depressive-like behavior. Periodic maternal separation increased basal corticosterone levels, induced a passive coping strategy in the forced swimming test, and was associated with a mild (24%) increase in fasting glucose, insulin resistance, and dyslipidemia. Rearing in social isolation increased stress reactivity in comparison to both controls and in combination with periodic maternal separation, without affecting the coping strategy associated with the forced swimming test. However, social isolation also increased body weight gain, fasting glucose (120%), and insulin levels in rats subjected to periodic maternal separation. Correlation analyses showed that stress-induced effects on coping strategy on the forced swimming test (but not on metabolic risk markers) are associated with basal corticosterone levels. These findings suggest that maternal separation and postweaning social isolation affect stress and metabolic vulnerability differentially and that early-life stress-related effects on metabolism are not directly dependent on glucocorticoid levels. In conclusion, our study supports the cumulative stress hypothesis, which suggests that

Impact of early life adversity on EMG stress reactivity of the trapezius muscle.

PubMed

Luijcks, Rosan; Vossen, Catherine J; Roggeveen, Suzanne; van Os, Jim; Hermens, Hermie J; Lousberg, Richel

2016-09-01

Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0-11 years) and adolescence (12-17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability.Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies.

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

PubMed

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.

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

PubMed

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.

African ancestry, early life exposures, and respiratory morbidity in early childhood.

PubMed

Kumar, R; Tsai, H-J; Hong, X; Gignoux, C; Pearson, C; Ortiz, K; Fu, M; Pongracic, J A; Burchard, E G; Bauchner, H; Wang, X

2012-02-01

Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02-1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19-1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14-1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05-1.34) and European ancestry (OR: 0.84, 95% CI: 0.74-0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (OR(whites) : 0.31, 95% CI: 0.09-1.14; OR(hispanic) : 0.47, 95% CI: 0.20-1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and

African ancestry, early life exposures, and respiratory morbidity in early childhood

PubMed Central

Kumar, R.; Tsai, H.-J.; Hong, X.; Gignoux, C.; Pearson, C.; Ortiz, K.; Fu, M.; Pongracic, J. A.; Burchard, E. G.; Bauchner, H.; Wang, X.

2012-01-01

Summary Background Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. Objective To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. Methods We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Results Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02–1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19–1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14–1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05–1.34) and European ancestry (OR: 0.84, 95% CI: 0.74–0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (ORwhites: 0.31, 95% CI: 0.09–1.14; ORhispanic: 0.47, 95% CI: 0.20–1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. Conclusions and Clinical Relevance In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to

Early-life nutritional effects on the female reproductive system.

PubMed

Chan, K A; Tsoulis, M W; Sloboda, D M

2015-02-01

There is now considerable epidemiological and experimental evidence indicating that early-life environmental conditions, including nutrition, affect subsequent development in later life. These conditions induce highly integrated responses in endocrine-related homeostasis, resulting in persistent changes in the developmental trajectory producing an altered adult phenotype. Early-life events trigger processes that prepare the individual for particular circumstances that are anticipated in the postnatal environment. However, where the intrauterine and postnatal environments differ markedly, such modifications to the developmental trajectory may prove maladaptive in later life. Reproductive maturation and function are similarly influenced by early-life events. This should not be surprising, because the primordial follicle pool is established early in life and is thus vulnerable to early-life events. Results of clinical and experimental studies have indicated that early-life adversity is associated with a decline in ovarian follicular reserve, changes in ovulation rates, and altered age at onset of puberty. However, the underlying mechanisms regulating the relationship between the early-life developmental environment and postnatal reproductive development and function are unclear. This review examines the evidence linking early-life nutrition and effects on the female reproductive system, bringing together clinical observations in humans and experimental data from targeted animal models. © 2015 Society for Endocrinology.

The Relationship Between Early Life Events, Parental Attachment, and Psychopathic Tendencies in Adolescent Detainees.

PubMed

Christian, Erica J; Meltzer, Christine L; Thede, Linda L; Kosson, David S

2017-04-01

Despite increasing interest in understanding psychopathic traits in youth, the role of early environmental factors in the development of psychopathic traits is not well understood. No prior studies have directly examined the relationship between early life events and psychopathic traits. We examined links between life events in the first 4 years of life and indices of the core affective and interpersonal components of psychopathy. Additionally, we examined relationships between early life events, psychopathic traits, and attachment to parents among 206 adjudicated adolescents. Results indicated that the total number of early life events was positively correlated with indices of the affective component of psychopathy. Moreover, psychopathic traits moderated the relationship between the number of early life events and later reports of attachment to parents. Findings suggest that early environmental factors could have important implications for the development of psychopathic traits and may impact attachment to parents for youth with psychopathic traits.

Early-Life Origins of Life-Cycle Well-Being: Research and Policy Implications

ERIC Educational Resources Information Center

Currie, Janet; Rossin-Slater, Maya

2015-01-01

Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the life cycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population…

Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2.

PubMed

Peña, Catherine J; Kronman, Hope G; Walker, Deena M; Cates, Hannah M; Bagot, Rosemary C; Purushothaman, Immanuel; Issler, Orna; Loh, Yong-Hwee Eddie; Leong, Tin; Kiraly, Drew D; Goodman, Emma; Neve, Rachael L; Shen, Li; Nestler, Eric J

2017-06-16

Early life stress increases risk for depression. Here we establish a "two-hit" stress model in mice wherein stress at a specific postnatal period increases susceptibility to adult social defeat stress and causes long-lasting transcriptional alterations that prime the ventral tegmental area (VTA)-a brain reward region-to be in a depression-like state. We identify a role for the developmental transcription factor orthodenticle homeobox 2 ( Otx2 ) as an upstream mediator of these enduring effects. Transient juvenile-but not adult-knockdown of Otx2 in VTA mimics early life stress by increasing stress susceptibility, whereas its overexpression reverses the effects of early life stress. This work establishes a mechanism by which early life stress encodes lifelong susceptibility to stress via long-lasting transcriptional programming in VTA mediated by Otx2 . Copyright © 2017, American Association for the Advancement of Science.

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

PubMed

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

Preventing Obesity Across Generations: Evidence for Early Life Intervention.

PubMed

Haire-Joshu, Debra; Tabak, Rachel

2016-01-01

To prevent the intergenerational transfer of obesity and end the current epidemic, interventions are needed across the early life stages, from preconception to prenatal to infancy through the age of 2 years. The foundation for obesity is laid in early life by actions and interactions passed from parent to child that have long-lasting biologic and behavioral consequences. The purpose of this paper is to examine the best evidence about (a) factors in parents and offspring that promote obesity during the early life stages, (b) the social determinants and dimensions of obesity in early life, (c) promising and effective interventions for preventing obesity in early life, and (d) opportunities for future research into strategies to disrupt the intergenerational cycle of obesity that begins early in life. The pathway for halting the intergenerational obesity epidemic requires the discovery and development of evidence-based interventions that can act across multiple dimensions of influence on early life.

Preventing Obesity Across Generations: Evidence for Early Life Intervention

PubMed Central

Haire-Joshu, Debra; Tabak, Rachel

2017-01-01

To prevent the intergenerational transfer of obesity and end the current epidemic, interventions are needed across the early life stages, from preconception to prenatal to infancy through the age of 2 years. The foundation for obesity is laid in early life by actions and interactions passed from parent to child that have long-lasting biologic and behavioral consequences. The purpose of this paper is to examine the best evidence about (a) factors in parents and offspring that promote obesity during the early life stages, (b) the social determinants and dimensions of obesity in early life, (c) promising and effective interventions for preventing obesity in early life, and (d) opportunities for future research into strategies to disrupt the intergenerational cycle of obesity that begins early in life. The pathway for halting the intergenerational obesity epidemic requires the discovery and development of evidence-based interventions that can act across multiple dimensions of influence on early life. PMID:26989828

Assessing Susceptibility from Early-Life Exposure to Carcinogens

PubMed Central

Barton, Hugh A.; Cogliano, V. James; Flowers, Lynn; Valcovic, Larry; Setzer, R. Woodrow; Woodruff, Tracey J.

2005-01-01

Cancer risk assessment methods currently assume that children and adults are equally susceptible to exposure to chemicals. We reviewed available scientific literature to determine whether this was scientifically supported. We identified more than 50 chemicals causing cancer after perinatal exposure. Human data are extremely limited, with radiation exposures showing increased early susceptibility at some tumor sites. Twenty-seven rodent studies for 18 chemicals had sufficient data after postnatal and adult exposures to quantitatively estimate potential increased susceptibility from early-life exposure, calculated as the ratio of juvenile to adult cancer potencies for three study types: acute dosing, repeated dosing, and lifetime dosing. Twelve of the chemicals act through a mutagenic mode of action. For these, the geometric mean ratio was 11 for lifetime exposures and 8.7 for repeat exposures, with a ratio of 10 for these studies combined. The geometric mean ratio for acute studies is 1.5, which was influenced by tissue-specific results [geometric mean ratios for kidney, leukemia, liver, lymph, mammary, nerve, reticular tissue, thymic lymphoma, and uterus/vagina > 1 (range, 1.6–8.1); forestomach, harderian gland, ovaries, and thyroid < 1 (range, 0.033–0.45)]. Chemicals causing cancer through other modes of action indicate some increased susceptibility from postnatal exposure (geometric mean ratio is 3.4 for lifetime exposure, 2.2 for repeat exposure). Early exposures to compounds with endocrine activity sometimes produce different tumors after exposures at different ages. These analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals acting through a mutagenic mode of action. PMID:16140616

A developmental perspective on early-life exposure to neurotoxicants.

PubMed

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.

Arsenic and Immune Response to Infection During Pregnancy and Early Life.

PubMed

Attreed, Sarah E; Navas-Acien, Ana; Heaney, Christopher D

2017-06-01

Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.

Impact of early life adversity on EMG stress reactivity of the trapezius muscle

PubMed Central

Luijcks, Rosan; Vossen, Catherine J.; Roggeveen, Suzanne; van Os, Jim; Hermens, Hermie J.; Lousberg, Richel

2016-01-01

Abstract Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0–11 years) and adolescence (12–17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability. Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies. PMID:27684800

Early-life gut microbiome and egg allergy.

PubMed

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.

Early life exposure to malaria and cognition in adulthood: evidence from Mexico.

PubMed

Venkataramani, Atheendar S

2012-09-01

This study examines the impact of early life malaria exposure on cognition in sample of Mexican adults, using the nationwide introduction of malaria eradication efforts to identify causal impacts. The core findings are that birth year exposure to malaria eradication was associated with increases in Raven Progressive Matrices test scores and consumption expenditures, but not schooling. Additionally, cohorts born after eradication both entered and exited school earlier than their pre-eradication counterparts. These effects were only seen for men and explanations for this are assessed. Collectively, these findings suggest that improvements in infant health help explain secular increases in cognitive test scores, that better cognition may link early life health to adulthood earnings, and that human capital investments through childhood and young adulthood respond sensitively to market returns to early life endowment shocks. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed

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.

Early-life family structure and microbially induced cancer risk.

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kippler, Maria; Bakhtiar Hossain, Mohammad; Department of Laboratory Medicine, Section of Occupational and Environmental Medicine, Lund University, Lund

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-oxodGmore » 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.« less

The Early Years: "Life" Science

ERIC Educational Resources Information Center

Ashbrook, Peggy

2013-01-01

Talking about death as part of a life cycle is often ignored or spoken about in hushed tones in early childhood. Books with "life cycle" in the title often do not include the death of the living organism in the information about the cycle. The concept of a complete life cycle does not appear in "A Framework for K-12 Science…

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

PubMed Central

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 consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221

Association of early- and adult-life socioeconomic circumstances with muscle strength in older age.

PubMed

Cheval, Boris; Boisgontier, Matthieu P; Orsholits, Dan; Sieber, Stefan; Guessous, Idris; Gabriel, Rainer; Stringhini, Silvia; Blane, David; van der Linden, Bernadette W A; Kliegel, Matthias; Burton-Jeangros, Claudine; Courvoisier, Delphine S; Cullati, Stéphane

2018-05-01

socioeconomic circumstances (SEC) during a person's lifespan influence a wide range of health outcomes. However, solid evidence of the association of early- and adult-life SEC with health trajectories in ageing is still lacking. This study assessed whether early-life SEC are associated with muscle strength in later life-a biomarker of health-and whether this relationship is caused by adult-life SEC and health behaviours. we used data from the Survey of Health Ageing and Retirement in Europe, a 12-year population-based cohort study with repeated measurement in six waves (2004-15) and retrospective collection of life-course data. Participants' grip strength was assessed by using a handheld dynamometer. Confounder-adjusted logistic mixed-effect models were used to examine the associations of early- and adult-life SEC with the risk of low muscle strength (LMS) in older age. a total of 24,179 participants (96,375 observations) aged 50-96 living in 14 European countries were included in the analyses. Risk of LMS was increased with disadvantaged relative to advantaged early-life SEC. The association between risk of LMS and disadvantaged early-life SEC gradually decreased when adjusting for adult-life SEC for both sexes and with unhealthy behaviours for women. After adjusting for these factors, all associations between risk of LMS and early-life SEC remained significant for women. early-life SEC are associated with muscle strength after adjusting for adult-life SEC and behavioural lifestyle factors, especially in women, which suggests that early life may represent a sensitive period for future health.

An experimental demonstration that early-life competitive disadvantage accelerates telomere loss.

PubMed

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.

Early Life on Earth: the Ancient Fossil Record

NASA Astrophysics Data System (ADS)

Westall, F.

2004-07-01

The evidence for early life and its initial evolution on Earth is lin= ked intimately with the geological evolution of the early Earth. The environment of the early Earth would be considered extreme by modern standards: hot (50-80=B0C), volcanically and hydrothermally active, a= noxic, high UV flux, and a high flux of extraterrestrial impacts. Habitats = for life were more limited until continent-building processes resulted in= the formation of stable cratons with wide, shallow, continental platforms= in the Mid-Late Archaean. Unfortunately there are no records of the first appearance of life and the earliest isotopic indications of the exist= ence of organisms fractionating carbon in ~3.8 Ga rocks from the Isua greenst= one belt in Greenland are tenuous. Well-preserved microfossils and micro= bial mats (in the form of tabular and domical stromatolites) occur in 3.5-= 3.3 Ga, Early Archaean, sedimentary formations from the Barberton (South Afri= ca) and Pilbara (Australia) greenstone belts. They document life forms that = show a relatively advanced level of evolution. Microfossil morphology inclu= des filamentous, coccoid, rod and vibroid shapes. Colonial microorganism= s formed biofilms and microbial mats at the surfaces of volcaniclastic = and chemical sediments, some of which created (small) macroscopic microbi= alites such as stromatolites. Anoxygenic photosynthesis may already have developed. Carbon, nitrogen and sulphur isotopes ratios are in the r= ange of those for organisms with anaerobic metabolisms, such as methanogenesi= s, sulphate reduction and photosynthesis. Life was apparently distribute= d widely in shallow-water to littoral environments, including exposed, evaporitic basins and regions of hydrothermal activity. Biomass in t= he early Archaean was restricted owing to the limited amount of energy t= hat could be produced by anaerobic metabolisms. Microfossils resembling o= xygenic photosynthesisers, such as cyanobacteria, probably first occurred in

Early Life Stress Differentially Modulates Distinct Forms of Brain Plasticity in Young and Adult Mice

PubMed Central

Reichardt, Wilfried; Clark, Kristin; Geiger, Julia; Gross, Claus M.; Heyer, Andrea; Neagu, Valentin; Bhatia, Harsharan; Atas, Hasan C.; Fiebich, Bernd L.; Bischofberger, Josef; Haas, Carola A.; Normann, Claus

2012-01-01

Background Early life trauma is an important risk factor for many psychiatric and somatic disorders in adulthood. As a growing body of evidence suggests that brain plasticity is disturbed in affective disorders, we examined the short-term and remote effects of early life stress on different forms of brain plasticity. Methodology/Principal Findings Mice were subjected to early deprivation by individually separating pups from their dam in the first two weeks after birth. Distinct forms of brain plasticity were assessed in the hippocampus by longitudinal MR volumetry, immunohistochemistry of neurogenesis, and whole-cell patch-clamp measurements of synaptic plasticity. Depression-related behavior was assessed by the forced swimming test in adult animals. Neuropeptides and their receptors were determined by real-time PCR and immunoassay. Early maternal deprivation caused a loss of hippocampal volume, which returned to normal in adulthood. Adult neurogenesis was unaffected by early life stress. Long-term synaptic potentiation, however, was normal immediately after the end of the stress protocol but was impaired in adult animals. In the forced swimming test, adult animals that had been subjected to early life stress showed increased immobility time. Levels of substance P were increased both in young and adult animals after early deprivation. Conclusion Hippocampal volume was affected by early life stress but recovered in adulthood which corresponded to normal adult neurogenesis. Synaptic plasticity, however, exhibited a delayed impairment. The modulation of synaptic plasticity by early life stress might contribute to affective dysfunction in adulthood. PMID:23071534

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

PubMed

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

Arsenic and Immune Response to Infection During Pregnancy and Early Life

PubMed Central

Attreed, Sarah E.; Navas-Acien, Ana

2017-01-01

Purpose of Review Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. Recent Findings The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Summary Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines. PMID:28488132

The influence of living conditions in early life on life satisfaction in old age.

PubMed

Deindl, Christian

2013-03-01

This article examines the influence of living conditions in early life on life satisfaction in old age in eleven Western European countries. It combines the influence of individual conditions, for example housing and family background, with country characteristics in the decade of birth. Using pooled data from the second and third wave of the Survey of Health, Ageing and Retirement in Europe, multilevel models show that early life living conditions have an influence on life satisfaction in old age. Furthermore, interaction effects between current and past living conditions show that adverse living conditions strengthen the effect of early life on life satisfaction in later life and therefore are an indication of cumulative inequality over the life course. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dietary protein intake and quality in early life: impact on growth and obesity.

PubMed

Lind, Mads V; Larnkjær, Anni; Mølgaard, Christian; Michaelsen, Kim F

2017-01-01

Obesity is an increasing problem and high-protein intake early in life seems to increase later risk of obesity. This review summarizes recent publications in the area including observational and intervention studies and publications on underlying mechanisms. Recent observational and randomized controlled trials confirmed that high-protein intake in early life seems to increase early weight gain and the risk of later overweight and obesity. Recent studies have looked at the effect of different sources of protein, and especially high-animal protein intake seems to have an effect on obesity. Specific amino acids, such as leucine, have also been implicated in increasing later obesity risk maybe via specific actions on insulin-like growth factor I. Furthermore, additional underlying mechanisms including epigenetics have been linked to long-term obesogenic programming. Finally, infants with catch-up growth or specific genotypes might be particularly vulnerable to high-protein intake. Recent studies confirm the associations between high-protein intake during the first 2 years and later obesity. Furthermore, knowledge of the mechanisms involved and the role of different dietary protein sources and amino acids has increased, but intervention studies are needed to confirm the mechanisms. Avoiding high-protein intake in early life holds promise as a preventive strategy for childhood obesity.

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

PubMed

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

Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

PubMed

Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

2016-10-01

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights

The effect of early-life stress on airway inflammation in adult mice.

PubMed

Vig, Rattanjeet; Gordon, John R; Thébaud, Bernard; Befus, A Dean; Vliagoftis, Harissios

2010-01-01

Neonatal stress induces permanent physiological changes that may influence the immune system. Early-life stress increases asthma disease severity in children. We investigated the effects of early-life stress on allergic airway inflammation using a murine model of asthma coupled to maternal separation as an early-life stress stimulus. Maternally separated (MS) and unseparated control (CON) mice were sensitized with ovalbumin (OVA) beginning at day 31 after birth. Challenging mice with OVA increased airway hyperresponsiveness (AHR) and the number of inflammatory cells recovered in the bronchoalveolar lavage (BAL), compared to saline-challenged mice. Challenging MS mice with OVA resulted in less total inflammatory cells, eosinophils, interferon-gamma, and interleukin-4 in BAL compared to CON mice. However, MS mice challenged with OVA exhibited AHR similar to CON mice challenged with OVA. In contrast, an enhanced stress protocol (MS+) involving removal of pups from their home cages following the removal of the dam resulted in inflammatory cell accumulation and cytokine levels in the BAL similar to CON mice and higher than MS mice. These findings indicate that the effect of early-life psychological factors on the development of airway inflammatory diseases such as asthma is very complex and depends on the quality of the psychological stress stimulus.

Early Life Nutrition and Energy Balance Disorders in Offspring in Later Life

PubMed Central

Reynolds, Clare M.; Gray, Clint; Li, Minglan; Segovia, Stephanie A.; Vickers, Mark H.

2015-01-01

The global pandemic of obesity and type 2 diabetes is often causally linked to changes in diet and lifestyle; namely increased intake of calorically dense foods and concomitant reductions in physical activity. Epidemiological studies in humans and controlled animal intervention studies have now shown that nutritional programming in early periods of life is a phenomenon that affects metabolic and physiological functions throughout 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. The mechanisms by which early environmental insults can have long-term effects on offspring remain poorly defined. However there is evidence from intervention studies which indicate altered wiring of the hypothalamic circuits that regulate energy balance and epigenetic effects including altered DNA methylation of key adipokines including leptin. Studies that elucidate the mechanisms behind these associations will have a positive impact on the health of future populations and adopting a life course perspective will allow identification of phenotype and markers of risk earlier, with the possibility of nutritional and other lifestyle interventions that have obvious implications for prevention of non-communicable diseases. PMID:26402696

Early Life Stress, Mood, and Anxiety Disorders.

PubMed

Syed, Shariful A; Nemeroff, Charles B

2017-02-01

Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective. Early life stress presents a complex dynamic featuring a wide spectrum of physiologic alterations: from epigenetic alterations, inflammatory changes, to dysregulation of the hypothalamic pituitary axis and has further added to the challenge of identifying biomarkers associated with psychiatric disorders. The National Institute of Mental Health's proposed Research Domain Criteria initiative incorporates a dimensional approach to assess discrete domains and constructs of behavioral function that are subserved by identifiable neural circuits. The current neurobiology of early life stress is reviewed in accordance with dimensional organization of Research Domain Criteria matrix and how the findings as a whole fit within the Research Domain Criteria frameworks.

Expression of glucocorticoid receptor and early growth response gene 1 during postnatal development of two inbred strains of mice exposed to early life stress.

PubMed

Navailles, Sylvia; Zimnisky, Ross; Schmauss, Claudia

2010-07-01

Early life stress can elicit profound changes in adult gene expression and behavior. One consequence of early life stress is a decreased expression of glucocorticoid receptors (GRs) in the frontal cortex and hippocampus. However, neither the time of onset nor the mechanism(s) leading to decreased GR expression during postnatal development are known. The present study used two inbred strains of mice that differ in their behavioral responsiveness to stress (Balb/c and C57Bl/6), exposed them to an established paradigm of early life stress (infant maternal separation), and measured their expression of frontal cortical and hippocampal GRs and the putative transcriptional activator of the GR gene, early growth response gene (egr)-1, at defined stages of postnatal development. In both strains, real-time RT-PCR experiments revealed that decreased expression of GR in adolescence and adulthood is, in fact, preceded by increased GR expression during early life stress exposure. Thus, the early life stress-induced disruption of the normal stress-hyporesponsive period during infancy is accompanied by increased GR expression. Moreover, chronic treatment with the antidepressant drug fluoxetine during adolescence or adulthood reversed the effect of early life stress on adult GR mRNA expression. In contrast to the strain-independent effect of early life stress on GR expression, however, changes in egr-1 expression occurred only in Balb/c mice, and unlike the biphasic developmental changes in GR mRNA expression, egr-1 mRNA was decreased throughout postnatal development. Moreover, there was no consistent overlap of anatomic regions affected by decreased GR and egr-1 protein expression. Thus, in Balb/c mice, changes in GR and egr-1 expression can independently contribute to the phenotypes resulting from early life stress exposure. These findings illustrate that the impact of early life stress on gene expression changes is modulated by the genetic background and that the persistent

An experimental demonstration that early-life competitive disadvantage accelerates telomere loss

PubMed Central

Nettle, Daniel; Monaghan, Pat; Gillespie, Robert; Brilot, Ben; Bedford, Thomas; Bateson, Melissa

2015-01-01

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. PMID:25411450

Social anxiety and negative early life events in university students.

PubMed

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.

Increased behavioral output but intact goal-directed and habitual responding for food reward following early-life social deprivation in rats.

PubMed

Lomanowska, Anna M; Kraemer, Gary W

2014-09-01

Early-life social adversity, such as child neglect and institutionalized rearing, is associated with later-life difficulties of inhibitory control that may reflect altered attribution of salience to external stimuli. Studies in rats demonstrate that early-life social deprivation results in enhanced responsiveness to reward stimuli and conditioned reward cues. This study examined whether these effects are related to fundamental changes in appetitive conditioning processes involving instrumental goal-directed and habitual responding for food reward. Rats were reared either by the mother (maternal rearing; MR) or in complete isolation from the mother and litter (artificial rearing; AR) and tested as adults in two appetitive conditioning tasks. AR and MR rats did not differ in the amount of goal-directed effort they exerted to obtain food reward on progressive ratio schedules of reinforcement. AR and MR rats also did not differ in the shift from goal-directed to habitual responding on a random interval schedule and they were equally sensitive to changes in reward value. The major difference between AR and MR rats was that AR rats exhibited more non-instrumental responses (empty food magazine entries, ineffective lever presses). Thus, early-life social deprivation of rats through AR affects the expression of unreinforced extraneous behaviors when motivational requirements are high, but does not affect conditioned goal-directed and habitual responding to reward. The findings have implications for understanding what aspects of responsiveness to external stimuli may be selectively affected in disorders of inhibition associated with early-life social adversity. Copyright © 2014 Elsevier B.V. All rights reserved.

Early life determinants of frailty in old age: the Helsinki Birth Cohort Study.

PubMed

Haapanen, M J; Perälä, M M; Salonen, M K; Kajantie, E; Simonen, M; Pohjolainen, P; Eriksson, J G; von Bonsdorff, M B

2018-04-12

there is evidence suggesting that several chronic diseases have their origins in utero and that development taking place during sensitive periods may affect the aging process. We investigated whether early life determinants would be associated with frailty in old age. at a mean age of 71 years, 1,078 participants belonging to the Helsinki Birth Cohort Study were assessed for frailty according to the Fried frailty criteria. Early life measurements (birth weight, length, mother body mass index [BMI] and parity) were obtained from birth, child welfare and school health records. Multinomial regression analysis was used to assess the association between early life determinants and frailty in old age. weight, length and BMI at birth were all inversely associated with frailty in old age. A 1 kg increase in birth weight was associated with a lower relative risk ratio (RRR) of frailty (age and sex-adjusted RRR = 0.40, 95% CI: 0.19, 0.82) compared to non-frailty. Associations persisted after adjusting for several confounding factors. Compared to cohort members in the upper middle class, those who as adults worked as manual workers or belonged to the lower middle class, were at an increased risk of frailty. those who were small at birth were at an increased risk of developing frailty in old age, suggesting that frailty is at least partly programmed in early life. A less privileged socioeconomic status in adulthood was associated with an increased risk of frailty in old age.

Early-Life Persistent Vitamin D Deficiency Alters Cardiopulmonary Responses to Particulate Matter-Enhanced Atmospheric Smog in Adult Mice

EPA Science Inventory

This study demonstrates that early-life persistent vitamin D deficiency alters the cardiopulmonary response to smog in mice and may increase risk of adverse effects. Early life nutritional deficiencies can lead to increased cardiovascular susceptibility to environme...

Early-Life Intelligence Predicts Midlife Biological Age

PubMed Central

Caspi, Avshalom; Belsky, Daniel W.; Harrington, Honalee; Houts, Renate; Israel, Salomon; Levine, Morgan E.; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Moffitt, Terrie E.

2016-01-01

Objectives: Early-life intelligence has been shown to predict multiple causes of death in populations around the world. This finding suggests that intelligence might influence mortality through its effects on a general process of physiological deterioration (i.e., individual variation in “biological age”). We examined whether intelligence could predict measures of aging at midlife before the onset of most age-related disease. Methods: We tested whether intelligence assessed in early childhood, middle childhood, and midlife predicted midlife biological age in members of the Dunedin Study, a population-representative birth cohort. Results: Lower intelligence predicted more advanced biological age at midlife as captured by perceived facial age, a 10-biomarker algorithm based on data from the National Health and Nutrition Examination Survey (NHANES), and Framingham heart age (r = 0.1–0.2). Correlations between intelligence and telomere length were less consistent. The associations between intelligence and biological age were not explained by differences in childhood health or parental socioeconomic status, and intelligence remained a significant predictor of biological age even when intelligence was assessed before Study members began their formal schooling. Discussion: These results suggest that accelerated aging may serve as one of the factors linking low early-life intelligence to increased rates of morbidity and mortality. PMID:26014827

EARLY LIFE RISKS, ANTISOCIAL TENDENCIES, AND PRETEEN DELINQUENCY.

PubMed

Staff, Jeremy; Whichard, Corey; Siennick, Sonja; Maggs, Jennifer

2015-11-01

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.

EARLY LIFE RISKS, ANTISOCIAL TENDENCIES, AND PRETEEN DELINQUENCY*

PubMed Central

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

Prevention of overweight and obesity in early life.

PubMed

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.

Cognitive functioning in healthy aging: the role of reserve and lifestyle factors early in life.

PubMed

Fritsch, Thomas; McClendon, McKee J; Smyth, Kathleen A; Lerner, Alan J; Friedland, Robert P; Larsen, Janet D

2007-06-01

According to the reserve perspective on cognitive aging, individuals are born with or can develop resources that help them resist normal and disease-related cognitive changes that occur in aging. The reserve perspective is becoming more sophisticated, but gaps in knowledge persist. In the present research, we considered three understudied questions about reserve: Is reserve primarily static (unchangeable) throughout the life course or dynamic (changeable, in terms of increases or decreases)? Can reserve be increased at any point in life, or are there optimal time periods--such as early life, midlife, or late life--to increase it? Does participation in different types of leisure and occupational activities in early life and midlife have different effects depending on specific domains of late-life cognitive functioning? Here we link early cognitive and activity data--gathered from archival sources--with cognitive data from older adults to examine these issues. 349 participants, all mid-1940s graduates of the same high school, underwent telephone cognitive screening. All participants provided access to adolescent IQ scores; we determined activity levels from yearbooks. We used path analysis to evaluate the complex relationships between early life, midlife, and late-life variables. Adolescent IQ had strong direct effects on global cognitive functioning, episodic memory, verbal fluency, and processing speed. Participants' high school mental activities had direct effects on verbal fluency, but physical and social activities did not predict any cognitive measure. Education had direct effects on global cognitive functioning, episodic memory, and, most strongly, processing speed, but other midlife factors (notably, occupational demands) were not significant predictors of late-life cognition. There were weak indirect effects of adolescent IQ on global cognitive functioning, episodic memory, and processing speed, working through high school mental activities and education

Early-Life Socioeconomic Status and Adult Physiological Functioning: A Life Course Examination of Biosocial Mechanisms.

PubMed

Yang, Yang Claire; Gerken, Karen; Schorpp, Kristen; Boen, Courtney; Harris, Kathleen Mullan

2017-01-01

A growing literature has demonstrated a link between early-life socioeconomic conditions and adult health at a singular point in life. No research exists, however, that specifies the life course patterns of socioeconomic status (SES) in relation to the underlying biological processes that determine health. Using an innovative life course research design consisting of four nationally representative longitudinal datasets that collectively cover the human life span from early adolescence to old age (Add Health, MIDUS, NSHAP, and HRS), we address this scientific gap and assess how SES pathways from childhood into adulthood are associated with biophysiological outcomes in different adult life stages. For each dataset, we constructed standardized composite measures of early-life SES and adult SES and harmonized biophysiological measurements of immune and metabolic functioning. We found that the relative importance of early-life SES and adult SES varied across young, mid, and late adulthood, such that early-life SES sets a life course trajectory of socioeconomic well-being and operates through adult SES to influence health as adults age. We also documented evidence of the detrimental health effects of downward mobility and persistent socioeconomic disadvantage. These findings are the first to specify the life course patterns of SES that matter for underlying biophysiological functioning in different stages of adulthood. The study thus contributes new knowledge critical for improving population health by identifying the particular points in the life course at which interventions might be most effective in preventing disease and premature mortality.

Early-Life Parent-Child Relationships and Adult Children's Support of Unpartnered Parents in Later Life.

PubMed

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.

Positive emotions in early life and longevity: findings from the nun study.

PubMed

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.

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

PubMed Central

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

Sex differences in early-life programming of the hypothalamic-pituitary-adrenal axis in humans.

PubMed

Gifford, Robert M; Reynolds, Rebecca M

2017-11-01

Increasing evidence supports fetal glucocorticoid exposure with associated altered offspring hypothalamic-pituitary-adrenal (HPA) axis activity as a key mechanism linking early life events with later life disease. Alterations in HPA axis activity are linked to a range of cardiometabolic and psychiatric diseases. As many of these diseases manifest sex differences in presentation we review the evidence for programmed sex-differences in the HPA axis. Available literature suggests vulnerability of the female HPA axis to prenatal stressors with female offspring demonstrating increased HPA axis reactivity. This may be due to changes in placental glucocorticoid metabolism leading to increased fetal glucocorticoid exposure. We discuss the potential consequences of increased vulnerability of the female HPA axis for later life health and consider the underlying mechanisms. Further studies are needed to determine whether sex-differences in early-life programming of the HPA axis represent a pathway underpinning the sex-differences in common cardiometabolic and psychiatric diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Diversity of the gut microbiota and eczema in early life.

PubMed

Forno, Erick; Onderdonk, Andrew B; McCracken, John; Litonjua, Augusto A; Laskey, Daniel; Delaney, Mary L; Dubois, Andrea M; Gold, Diane R; Ryan, Louise M; Weiss, Scott T; Celedón, Juan C

2008-09-22

A modest number of prospective studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results. To examine the relationship between the bacterial diversity of the gut and the development of eczema in early life by methods other than stool culture. Fecal samples were collected from 21 infants at 1 and 4 months of life. Nine infants were diagnosed with eczema by the age of 6 months (cases) and 12 infants were not (controls). After conducting denaturating gradient gel electrophoresis (DGGE) of stool samples, we compared the microbial diversity of cases and controls using the number of electrophoretic bands and the Shannon index of diversity (H') as indicators. Control subjects had significantly greater fecal microbial diversity than children with eczema at ages 1 (mean H' for controls = 0.75 vs. 0.53 for cases, P = 0.01) and 4 months (mean H' for controls = 0.92 vs. 0.59 for cases, P = 0.02). The increase in diversity from 1 to 4 months of age was significant in controls (P = 0.04) but not in children who developed eczema by 6 months of age (P = 0.32). Our findings suggest that reduced microbial diversity is associated with the development of eczema in early life.

Chemical defense of early life stages of benthic marine invertebrates.

PubMed

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.

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

PubMed

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 < 0.05). In addition, having a high school education or less includes people who have primary or secondary or high school diploma (OR = 1.65), having lived in a village (OR = 1.65), having a low family economic status (OR = 2.40), and having experienced one negative event (OR = 1.41) or two or more negative events (OR = 1.39) during their early lives were identified as important risk factors for low quality of life (P < 0.05). Early life factors are among the important determinants of the health and quality of life of older adults in Turkey. © 2017 Japanese Psychogeriatric Society.

Early-Life Origins of the Race Gap in Men's Mortality

ERIC Educational Resources Information Center

Warner, David F.; Hayward, Mark D.

2006-01-01

Using a life course framework, we examine the early life origins of the race gap in men's all-cause mortality. Using the National Longitudinal Survey of Older Men (1966-1990), we evaluate major social pathways by which early life conditions differentiate the mortality experiences of blacks and whites. Our findings indicate that early life…

Early-life origins of schizotypal traits in adulthood.

PubMed

Lahti, Jari; Raïkkönen, Katri; Sovio, Ulla; Miettunen, Jouko; Hartikainen, Anna-Liisa; Pouta, Anneli; Taanila, Anja; Joukamaa, Matti; Järvelin, Marjo-Riitta; Veijola, Juha

2009-08-01

Although schizotypal traits, such as anhedonia and aberrant perceptions, may increase the risk for schizophrenia-spectrum disorders, little is known about early-life characteristics that predict more pronounced schizotypal traits. To examine whether birth size or several other early-life factors that have been previously linked with schizophrenia predict schizotypal traits in adulthood. Participants of the Northern Finland 1966 Birth Cohort Study (n = 4976) completed a questionnaire on positive and negative schizotypal traits at the age of 31 years. Lower placental weight, lower birth weight and smaller head circumference at 12 months predicted elevated positive schizotypal traits in women after adjusting for several confounders (P<0.02). Moreover, higher gestational age, lower childhood family socioeconomic status, undesirability of pregnancy, winter/autumn birth, higher birth order and maternal smoking during pregnancy predicted some augmented schizotypal traits in women, some in men and some in both genders. The results point to similarities in the aetiology of schitzotypal traits and schizophrenia-spectrum disorders.

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

PubMed

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.

The Suckling Rat as a Model for Immunonutrition Studies in Early Life

PubMed Central

Pérez-Cano, Francisco J.; Franch, Àngels; Castellote, Cristina; Castell, Margarida

2012-01-01

Diet plays a crucial role in maintaining optimal immune function. Research demonstrates the immunomodulatory properties and mechanisms of particular nutrients; however, these aspects are studied less in early life, when diet may exert an important role in the immune development of the neonate. Besides the limited data from epidemiological and human interventional trials in early life, animal models hold the key to increase the current knowledge about this interaction in this particular period. This paper reports the potential of the suckling rat as a model for immunonutrition studies in early life. In particular, it describes the main changes in the systemic and mucosal immune system development during rat suckling and allows some of these elements to be established as target biomarkers for studying the influence of particular nutrients. Different approaches to evaluate these immune effects, including the manipulation of the maternal diet during gestation and/or lactation or feeding the nutrient directly to the pups, are also described in detail. In summary, this paper provides investigators with useful tools for better designing experimental approaches focused on nutrition in early life for programming and immune development by using the suckling rat as a model. PMID:22899949

Early-Life Intelligence Predicts Midlife Biological Age.

PubMed

Schaefer, Jonathan D; Caspi, Avshalom; Belsky, Daniel W; Harrington, Honalee; Houts, Renate; Israel, Salomon; Levine, Morgan E; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Moffitt, Terrie E

2016-11-01

Early-life intelligence has been shown to predict multiple causes of death in populations around the world. This finding suggests that intelligence might influence mortality through its effects on a general process of physiological deterioration (i.e., individual variation in "biological age"). We examined whether intelligence could predict measures of aging at midlife before the onset of most age-related disease. We tested whether intelligence assessed in early childhood, middle childhood, and midlife predicted midlife biological age in members of the Dunedin Study, a population-representative birth cohort. Lower intelligence predicted more advanced biological age at midlife as captured by perceived facial age, a 10-biomarker algorithm based on data from the National Health and Nutrition Examination Survey (NHANES), and Framingham heart age (r = 0.1-0.2). Correlations between intelligence and telomere length were less consistent. The associations between intelligence and biological age were not explained by differences in childhood health or parental socioeconomic status, and intelligence remained a significant predictor of biological age even when intelligence was assessed before Study members began their formal schooling. These results suggest that accelerated aging may serve as one of the factors linking low early-life intelligence to increased rates of morbidity and mortality. © The Author 2015. 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.

FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students.

PubMed

Lieberman, Richard; Armeli, Stephen; Scott, Denise M; Kranzler, Henry R; Tennen, Howard; Covault, Jonathan

2016-09-01

Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic-pituitary-adrenal (HPA) axis is susceptible to long-lasting changes in function following childhood trauma. Functional genetic variation within FKBP5, a gene encoding a modulator of HPA axis function, is associated with the development of psychiatric symptoms in adulthood, particularly among individuals exposed to trauma early in life. In the current study, we examined interactions between self-reported early life trauma, past-year life stress, past-year trauma, and a single nucleotide polymorphism (rs1360780) in FKBP5 on heavy alcohol consumption in a sample of 1,845 college students from two university settings. Although we found no effect of early life trauma on heavy drinking in rs1360780*T-allele carriers, rs1360780*C homozygotes exposed to early life trauma had a lower probability of heavy drinking compared to rs1360780*C homozygotes not exposed to early life trauma (P < 0.01). The absence of an interaction between either current life stress or past-year trauma, and FKBP5 genotype on heavy drinking suggests that there exists a developmental period of susceptibility to stress that is moderated by FKBP5 genotype. These findings implicate interactive effects of early life trauma and FKBP5 genetic variation on heavy drinking. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

PubMed

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.

The microbiome in early life: implications for health outcomes.

PubMed

Tamburini, Sabrina; Shen, Nan; Wu, Han Chih; Clemente, Jose C

2016-07-07

Recent studies have characterized how host genetics, prenatal environment and delivery mode can shape the newborn microbiome at birth. Following this, postnatal factors, such as antibiotic treatment, diet or environmental exposure, further modulate the development of the infant's microbiome and immune system, and exposure to a variety of microbial organisms during early life has long been hypothesized to exert a protective effect in the newborn. Furthermore, epidemiological studies have shown that factors that alter bacterial communities in infants during childhood increase the risk for several diseases, highlighting the importance of understanding early-life microbiome composition. In this review, we describe how prenatal and postnatal factors shape the development of both the microbiome and the immune system. We also discuss the prospects of microbiome-mediated therapeutics and the need for more effective approaches that can reconfigure bacterial communities from pathogenic to homeostatic configurations.

Early-life estrogen exposure and uterine pathogenesis: ?A model for gene-environment interactions

EPA Science Inventory

Aberrant cellular differentiation early in life can contribute to increased cancer risk later in life. In a classic model of this effect, female mice exposed on postnatal day (PND) 1-5 to the synthetic estrogen diethylstilbestrol (DES) have a high incidence of uterine carcinoma. ...

The Intestinal Microbiome in Early Life: Health and Disease

PubMed Central

Arrieta, Marie-Claire; Stiemsma, Leah T.; Amenyogbe, Nelly; Brown, Eric M.; Finlay, Brett

2014-01-01

Human microbial colonization begins at birth and continues to develop and modulate in species abundance for about 3 years, until the microbiota becomes adult-like. During the same time period, children experience significant developmental changes that influence their 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. PMID:25250028

Examination of associations between early life victimisation and alcohol's harm from others.

PubMed

Kaplan, Lauren M; Greenfield, Thomas K; Karriker-Jaffe, Katherine J

2018-03-01

Study aims were to examine: (i) how physical and sexual victimisation in early life are associated with alcohol's harm from others; and (ii) whether respondents' current drinking is a mediator of the association between early life victimisation and alcohol's harm from others among men and women. Data were from national computer-assisted telephone interviews, using the landline sample (3335 men and 3520 women ages ≥18) from the 2010 US National Alcohol Survey. Harms from someone else's drinking included family/marital problems, financial troubles, assault and vandalism in the past 12 months. Victimisation was measured with severe physical abuse or sexual assault before age 18. Severe physical or sexual victimisation before age 18 was reported by 3.4% of men and 8.1% of women. Significantly more men (5.2%) than women (2.4%) reported assault by other drinkers, and significantly more women reported family/marital (5.3%) and financial problems (2.8%) than did men (2.6 and 1% respectively). Severe early life victimisation was robustly associated with a greater likelihood of experiencing past-year harms from other drinkers for both men and women. Men's drinking partially mediated associations between early life victimisation and recent assaults and vandalism by other drinkers. Early life victimisation may increase risk of harms from someone else's drinking. Health services and interventions that screen for histories of victimisation may help decrease risk of later harms from others' drinking. Reductions in drinking among men with histories of victimisation also could help reduce their exposure to such harms. [Kaplan LM, Greenfield TK, Karriker-Jaffe KJ. Examination of associations between early life victimisation and alcohol's harm from others. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Early-life inflammation, immune response and ageing.

PubMed

Khan, Imroze; Agashe, Deepa; Rolff, Jens

2017-03-15

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

Early-life inflammation, immune response and ageing

PubMed Central

2017-01-01

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. PMID:28275145

Trans-Agency Early-Life Exposures and Cancer Working Group

Cancer.gov

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.

Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease.

PubMed

Rehkopf, David H; Eisen, Ellen A; Modrek, Sepideh; Mokyr Horner, Elizabeth; Goldstein, Benjamin; Costello, Sadie; Cantley, Linda F; Slade, Martin D; Cullen, Mark R

2015-08-01

We examined how state characteristics in early life are associated with individual chronic disease later in life. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes.

Alterations in Sociability and Functional Brain Connectivity Caused by Early-Life Seizures is Reversed by Bumetanide

PubMed Central

Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy

2015-01-01

There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure

Biodemography of Exceptional Longevity: Early-life and Mid-life predictors of Human Longevity

PubMed Central

Gavrilov, Leonid A.; Gavrilova, Natalia S.

2011-01-01

Effects of early-life and middle-life conditions on exceptional longevity are explored in this study using two matched case-control studies. The first study compares 198 validated centenarians born in the United States in 1890-1893 to their shorter-lived siblings. Family histories of centenarians were reconstructed and exceptional longevity validated using early U.S. censuses, Social Security Administration Death Master File, state death indexes, online genealogies and other supplementary data resources. Siblings born to young mothers (<25 years) had significantly higher chances to live to 100 compared to siblings born to older mothers (odds ratio = 2.03, 95% CI = 1.33 - 3.11, P = 0.001) while paternal age and birth order were not associated with exceptional longevity. The second study explores whether people living to 100 and beyond are any different in physical characteristics at young age from their shorter-lived peers. A random representative sample of 240 men born in 1887 and survived to age 100 was selected from the US Social Security Administration database and linked to the US WWI civil draft registration cards collected in 1917 when these men were 30 years old. These validated centenarians were then compared to randomly selected controls matched by calendar year of birth, race and place of draft registration in 1917. It was found that ‘stout’ body build (being in the heaviest 15% of population) was negatively associated with survival to age 100 years. Farmer occupation and large number of children (4+) at age 30 increased the chances of exceptional longevity. Detailed description of dataset development, data cleaning procedure and validation of exceptional longevity is provided for both studies. These results demonstrate that matched case-control design is a useful approach in exploring effects of early-life conditions and middle-life characteristics on exceptional longevity. PMID:22582891

Early Life Experience and Gut Microbiome: The Brain-Gut-Microbiota Signaling System.

PubMed

Cong, Xiaomei; Henderson, Wendy A; Graf, Joerg; McGrath, Jacqueline M

2015-10-01

Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuroimmune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short- and long-term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking, leading potentially to changes in practice and targeted interventions.

Early Life Factors and Adult Leisure Time Physical Inactivity Stability and Change.

PubMed

Pinto Pereira, Snehal M; Li, Leah; Power, Chris

2015-09-01

Physical inactivity has a high prevalence and associated disease burden. A better understanding of influences on sustaining and changing inactive lifestyles is needed. We aimed to establish whether leisure time inactivity was stable in midadulthood and whether early life factors were associated with inactivity patterns. In the 1958 British birth cohort (n = 12,271), leisure time inactivity (frequency, less than once a week) assessed at 33 and 50 yr was categorized as "never inactive," "persistently inactive," "deteriorating," or "improving." Early life factors (birth to 16 yr) were categorized into three (physical, social, and behavioral) domains. Using multinomial logistic regression, we assessed associations with inactivity persistence and change of factors within each early life domain and the three domains combined with and without adjustment for adult factors. Inactivity prevalence was similar at 33 and 50 yr (approximately 31%), but 17% deteriorated and 18% improved with age. In models adjusted for all domains simultaneously, factors associated with inactivity persistence versus never inactive were prepubertal stature (8% lower risk/height SD), poor hand control/coordination (17% higher risk/increase on four-point scale), cognition (16% lower/SD in ability) (physical); parental divorce (25% higher), class at birth (7% higher/reduction on four-point scale), minimal parental education (16% higher), household amenities (2% higher/increase in 19-point score (high = poor)) (social); and inactivity (22% higher/reduction in activity on four-point scale), low sports aptitude (47% higher), smoking (30% higher) (behavioral). All except stature, parental education, sports aptitude, and smoking were associated also with inactivity deterioration. Poor hand control/coordination was the only factor associated with improved status (13% lower/increase on four-point scale) versus persistently inactive. Adult leisure time inactivity is moderately stable. Early life factors are

Development of Life on Early Mars

NASA Technical Reports Server (NTRS)

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

Early life adversity potentiates the effects of later life stress on cumulative physiological dysregulation.

PubMed

Dich, Nadya; Hansen, Åse Marie; Avlund, Kirsten; Lund, Rikke; Mortensen, Erik Lykke; Bruunsgaard, Helle; Rod, Naja Hulvej

2015-01-01

Previous research indicates that early life adversity may heighten stress reactivity and impair mechanisms for adaptive coping, suggesting that experience of stress in early life may also potentiate adults' physiological vulnerability to stress in later life. The study tested this hypothesis by investigating whether the experience of stressful events and circumstances (SEC) in childhood or adolescence amplified the effect of adulthood SEC on physiological dysregulation (allostatic load, AL) in later midlife. Observational data were used in the present study. Physiological functioning was measured in later midlife (participants' age ranged from 49 to 63 years). Both childhood/adolescence and adulthood SEC were reported retrospectively on the same occasion. Participants were 5309 Danish men and women from Copenhagen Aging and Midlife Biobank (CAMB). SEC included socioeconomic and family factors. The AL index was based on nine cardiovascular, metabolic, and immune biomarkers. Experience of SEC in both early life and adulthood independently predicted higher AL. In men, experience of SEC in early life also potentiated the effect of SEC in adulthood on AL. The results provide further insight into the mechanisms behind the "biological embedding" of childhood stress.

Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

PubMed Central

Huang, Li-Tung

2014-01-01

Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

Commentary: On the Importance of Early Life Cognitive Abilities in Shaping Later Life Outcomes.

PubMed

Hofer, Scott M; Clouston, Sean

2014-01-01

Early life cognitive ability is likely to be dynamically related to life course factors including educational attainment, occupational outcomes, health behaviors, activities, health, and subsequent cognitive health. Disentangling the selective and causal processes contributing to cognitive functioning across the lifespan is challenging and requires long-term investments in longitudinal data. We discuss results from several analyses using data from the Individual Development and Adaptation longitudinal research program (Bergman, 2000; Magnusson, 1988) that provide fresh insights into the relation of early life cognition, particularly high levels of cognitive capabilities, to educational achievement, emotional adjustment, and career success. These papers and the longitudinal data provide a remarkable window into the development and impacts of cognition, and high cognitive functioning, on a variety of important life outcomes that we hope will continue to inform us about additional outcomes in middle life, transition to retirement, and cognition and health in later years and to robustly examine how the early years matter across the whole lifespan.

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

NASA Technical Reports Server (NTRS)

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.

Bioaccumulation of lipophilic substances in fish early life stages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petersen, G.I.; Kristensen, P.

1998-07-01

Accumulation of {sup 14}C-labeled polycyclic aromatic hydrocarbons, naphthalene, phenanthrene, pyrene, and benzo(a)pyrene and polychlorinated biphenyl (PCB) congeners PCB 31 and PCB 105 with a log octanol/water partition coefficient (K{sub ow}) range from 3.37 to 6.5 was investigated in eggs and larvae of zebra fish (Brachydanio rerio), and in larvae of cod (Gadus morhua), herring (Clupea harengus), and turbot (Scophthalmus maximus). Significant differences in the uptake and elimination rate constants between eggs and larvae of zebra fish were seen. The low rate of uptake and the lower elimination rate of eggs did, however, lead to bioconcentration factors (BCFs) comparable to thosemore » for larvae. As biotransformation of xenobiotics in embryonic and larval stages was indicated to be insignificant compared to juvenile/adult stages, body burdens of readily biotransformed chemicals may be higher in fish early life stages. Because weight and lipid content did not differ much between the investigated species, the main reason for the variability in BCFs between marine species and freshwater species was considered to be caused by differences in exposure temperatures that affect the degree of biotransformation. Due to the smaller size of larvae and thus an increased total surface of the membranes per unit fish weight, steady-state conditions were reached at a faster r/ate in early life stages than in juvenile/adult life stages. The lipid-normalized bioconcentration factors (BCF{sub L}) were linearly related to K{sub ow} but BCF{sub L} was, in general, higher than K{sub ow}, indicating that octanol is not a suitable surrogate for fish lipids. Differences in bioconcentration kinetics between larvae and juvenile/adult life stages are considered to be the main reason for the higher sensitivity, with respect to external effect concentrations, generally obtained for early life stages of fish.« less

Early Life Conditions, Adverse Life Events, and Chewing Ability at Middle and Later Adulthood

PubMed Central

Watt, Richard G.; Tsakos, Georgios

2014-01-01

Objectives. We sought to determine the extent to which early life conditions and adverse life events impact chewing ability in middle and later adulthood. Methods. Secondary analyses were conducted based on data from waves 2 and 3 of the Survey of Health, Ageing, and Retirement in Europe (SHARE), collected in the years 2006 to 2009 and encompassing information on current chewing ability and the life history of persons aged 50 years or older from 13 European countries. Logistic regression models were estimated with sequential inclusion of explanatory variables representing living conditions in childhood and adverse life events. Results. After controlling for current determinants of chewing ability at age 50 years or older, certain childhood and later life course socioeconomic, behavioral, and cognitive factors became evident as correlates of chewing ability at age 50 years or older. Specifically, childhood financial hardship was identified as an early life predictor of chewing ability at age 50 years or older (odds ratio = 1.58; 95% confidence interval = 1.22, 2.06). Conclusions. Findings suggest a potential enduring impact of early life conditions and adverse life events on oral health in middle and later adulthood and are relevant for public health decision-makers who design strategies for optimal oral health. PMID:24625140

Early life exposure to ambient air pollution and childhood asthma in China.

PubMed

Deng, Qihong; Lu, Chan; Norbäck, Dan; Bornehag, Carl-Gustaf; Zhang, Yinping; Liu, Weiwei; Yuan, Hong; Sundell, Jan

2015-11-01

Early life is suggested to be a critical time in determining subsequent asthma development, but the extent to which the effect of early-life exposure to ambient air pollution on childhood asthma is unclear. We investigated doctor-diagnosed asthma in preschool children due to exposure to ambient air pollution in utero and during the first year of life. In total 2490 children aged 3-6 years participated in a questionnaire study regarding doctor-diagnosed asthma between September 2011 and January 2012 in China. Children's exposure to critical air pollutants, sulfur dioxide (SO2) as proxy of industrial air pollution, nitrogen dioxide (NO2) as proxy of traffic pollution, and particulate matter≤10µm in diameter (PM10) as a mixture, was estimated from the concentrations measured at the ambient air quality monitoring stations by using an inverse distance weighted (IDW) method. Logistic regression analysis was employed to determine the relationship between early-life exposure and childhood asthma in terms of odds ratio (OR) and 95% confidence interval (CI). Association between early-life exposure to air pollutants and childhood asthma was observed. SO2 and NO2 had significant associations with adjusted OR (95% CI) of 1.45 (1.02-2.07) and 1.74 (1.15-2.62) in utero and 1.62 (1.01-2.60) and 1.90 (1.20-3.00) during the first year for per 50 µg/m(3) and 15 µg/m(3) increase respectively. Exposure to the combined high level of SO2 and NO2 in China significantly elevated the asthmatic risk with adjusted OR (95% CI) of 1.76 (1.18-2.64) in utero and 1.85 (1.22-2.79) during the first year compared to the low level exposure. The associations were higher for males and the younger children aged 3-4 than females and the older children aged 5-6. Early-life exposure to ambient air pollution is associated with childhood asthma during which the level and source of air pollution play important roles. The high level and nature of combined industrial and traffic air pollution in China may

The role of the early-life environment in the development of allergic disease.

PubMed

Wegienka, Ganesa; Zoratti, Edward; Johnson, Christine Cole

2015-02-01

A consensus has been reached that the development of allergic disorders is strongly influenced by early life exposures. An overview of several prenatal and early life factors that have been investigated for their associations with development of childhood allergy is presented. Delivery mode, the gut microbiome, vitamin D, folate, breastfeeding, pets, antibiotics, environmental tobacco smoke, and airborne traffic pollutants are discussed. Although many studies suggest an effect, overall, no risk factors clearly increase or reduce the risk of allergic outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

DNA methylation dynamics during early plant life.

PubMed

Bouyer, Daniel; Kramdi, Amira; Kassam, Mohamed; Heese, Maren; Schnittger, Arp; Roudier, François; Colot, Vincent

2017-09-25

Cytosine methylation is crucial for gene regulation and silencing of transposable elements in mammals and plants. While this epigenetic mark is extensively reprogrammed in the germline and early embryos of mammals, the extent to which DNA methylation is reset between generations in plants remains largely unknown. Using Arabidopsis as a model, we uncovered distinct DNA methylation dynamics over transposable element sequences during the early stages of plant development. Specifically, transposable elements and their relics show invariably high methylation at CG sites but increasing methylation at CHG and CHH sites. This non-CG methylation culminates in mature embryos, where it reaches saturation for a large fraction of methylated CHH sites, compared to the typical 10-20% methylation level observed in seedlings or adult plants. Moreover, the increase in CHH methylation during embryogenesis matches the hypomethylated state in the early endosperm. Finally, we show that interfering with the embryo-to-seedling transition results in the persistence of high CHH methylation levels after germination, specifically over sequences that are targeted by the RNA-directed DNA methylation (RdDM) machinery. Our findings indicate the absence of extensive resetting of DNA methylation patterns during early plant life and point instead to an important role of RdDM in reinforcing DNA methylation of transposable element sequences in every cell of the mature embryo. Furthermore, we provide evidence that this elevated RdDM activity is a specific property of embryogenesis.

Early-life experience affects honey bee aggression and resilience to immune challenge

PubMed Central

Rittschof, Clare C.; Coombs, Chelsey B.; Frazier, Maryann; Grozinger, Christina M.; Robinson, Gene E.

2015-01-01

Early-life social experiences cause lasting changes in behavior and health for a variety of animals including humans, but it is not well understood how social information ‘‘gets under the skin’’ resulting in these effects. Adult honey bees (Apis mellifera) exhibit socially coordinated collective nest defense, providing a model for social modulation of aggressive behavior. Here we report for the first time that a honey bee’s early-life social environment has lasting effects on individual aggression: bees that experienced high-aggression environments during pre-adult stages showed increased aggression when they reached adulthood relative to siblings that experienced low-aggression environments, even though all bees were kept in a common environment during adulthood. Unlike other animals including humans however, high-aggression honey bees were more, rather than less, resilient to immune challenge, assessed as neonicotinoid pesticide susceptibility. Moreover, aggression was negatively correlated with ectoparasitic mite presence. In honey bees, early-life social experience has broad effects, but increased aggression is decoupled from negative health outcomes. Because honey bees and humans share aspects of their physiological response to aggressive social encounters, our findings represent a step towards identifying ways to improve individual resiliency. Pre-adult social experience may be crucial to the health of the ecologically threatened honey bee. PMID:26493190

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

PubMed Central

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

High early life mortality in free-ranging dogs is largely influenced by humans

PubMed Central

Paul, Manabi; Sen Majumder, Sreejani; Sau, Shubhra; Nandi, Anjan K.; Bhadra, Anindita

2016-01-01

Free-ranging dogs are a ubiquitous part of human habitations in many developing countries, leading a life of scavengers dependent on human wastes for survival. The effective management of free-ranging dogs calls for understanding of their population dynamics. Life expectancy at birth and early life mortality are important factors that shape life-histories of mammals. We carried out a five year-long census based study in seven locations of West Bengal, India, to understand the pattern of population growth and factors affecting early life mortality in free-ranging dogs. We observed high rates of mortality, with only ~19% of the 364 pups from 95 observed litters surviving till the reproductive age; 63% of total mortality being human influenced. While living near people increases resource availability for dogs, it also has deep adverse impacts on their population growth, making the dog-human relationship on streets highly complex. PMID:26804633

Sex-Specific and Strain-Dependent Effects of Early Life Adversity on Behavioral and Epigenetic Outcomes

PubMed Central

Kundakovic, Marija; Lim, Sean; Gudsnuk, Kathryn; Champagne, Frances A.

2013-01-01

Early life adversity can have a significant long-term impact with implications for the emergence of psychopathology. Disruption to mother-infant interactions is a form of early life adversity that may, in particular, have profound programing effects on the developing brain. However, despite converging evidence from human and animal studies, the precise mechanistic pathways underlying adversity-associated neurobehavioral changes have yet to be elucidated. One approach to the study of mechanism is exploration of epigenetic changes associated with early life experience. In the current study, we examined the effects of postnatal maternal separation (MS) in mice and assessed the behavioral, brain gene expression, and epigenetic effects of this manipulation in offspring. Importantly, we included two different mouse strains (C57BL/6J and Balb/cJ) and both male and female offspring to determine strain- and/or sex-associated differential response to MS. We found both strain-specific and sex-dependent effects of MS in early adolescent offspring on measures of open-field exploration, sucrose preference, and social behavior. Analyses of cortical and hippocampal mRNA levels of the glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf) genes revealed decreased hippocampal Bdnf expression in maternally separated C57BL/6J females and increased cortical Bdnf expression in maternally separated male and female Balb/cJ offspring. Analyses of Nr3c1and Bdnf (IV and IX) CpG methylation indicated increased hippocampal Nr3c1 methylation in maternally separated C57BL/6J males and increased hippocampal Bdnf IX methylation in male and female maternally separated Balb/c mice. Overall, though effect sizes were modest, these findings suggest a complex interaction between early life adversity, genetic background, and sex in the determination of neurobehavioral and epigenetic outcomes that may account for differential vulnerability to later-life disorder. PMID:23914177

Accounting Early for Life Long Learning: The AcE Project.

ERIC Educational Resources Information Center

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…

Fragmentation and Unpredictability of Early-Life Experience in Mental Disorders

PubMed Central

Baram, Tallie Z.; Solodkin, Ana; Davis, Elysia P.; Stern, Hal; Obenaus, Andre; Sandman, Curt A.; Small, Steven L.

2012-01-01

Maternal sensory signals in early life play a crucial role in programming the structure and function of the developing brain, promoting vulnerability or resilience to emotional and cognitive disorders. In rodent models of early-life stress, fragmentation and unpredictability of maternally derived sensory signals provoke persistent cognitive and emotional dysfunction in offspring. Similar variability and inconsistency of maternal signals during both gestation and early postnatal human life may influence development of emotional and cognitive functions, including those that underlie later depression and anxiety. PMID:22885631

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

PubMed

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.

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

PubMed Central

McDonald, Fiona B.; Dempsey, Eugene M.; O'Halloran, Ken D.

2016-01-01

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. PMID:26973537

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

EPA Science Inventory

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...

Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient.

PubMed

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.

Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression

PubMed Central

Saravia, Jordy; You, Dahui; Thevenot, Paul; Lee, Greg I.; Shrestha, Bishwas; Lomnicki, Slawo; Cormier, Stephania A.

2013-01-01

Elevated levels of combustion-derived particulate matter (CDPM) are a risk factor for the development of lung diseases such as asthma. Studies have shown that CDPM exacerbates asthma, inducing acute lung dysfunction and inflammation; however, the impact of CDPM exposure on early immunological responses to allergens remains unclear. To determine the effects of early-life CDPM exposure on allergic asthma development in infants, we exposed infant mice to CDPM and then induced a mouse model of asthma using house dust mite (HDM) allergen. Mice exposed to CDPM+HDM failed to develop a typical asthma phenotype including airway hyperresponsiveness, Th2-inflammation, Muc5ac expression, eosinophilia, and HDM-specific Ig compared to HDM-exposed mice. Although HDM-specific IgE was attenuated, total IgE was two-fold higher in CDPM+HDM mice compared to HDM-mice. We further demonstrate that CDPM exposure during early life induced an immunosuppressive environment in the lung, concurrent with increases in tolerogenic dendritic cells and Tregs, resulting in suppression of Th2 responses. Despite having early immunosuppression, these mice develop severe allergic inflammation when challenged with allergen as adults. These findings demonstrate a mechanism whereby CDPM exposure modulates adaptive immunity, inducing specific-antigen tolerance while amplifying total IgE, and leading to a predisposition to develop asthma upon rechallenge later in life. PMID:24172848

Is epigenetics an important link between early life events and adult disease?

USDA-ARS?s Scientific Manuscript database

Epigenetic mechanisms provide one potential explanation for how environmental influences in early life cause long-term changes in chronic disease susceptibility. Whereas epigenetic dysregulation is increasingly implicated in various rare developmental syndromes and cancer, the role of epigenetics in...

Development of the Life Story in Early Adolescence

ERIC Educational Resources Information Center

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…

Early-life Origins of Lifecycle Well-being: Research and Policy Implications

PubMed Central

Currie, Janet; Rossin-Slater, Maya

2016-01-01

Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the lifecycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population well-being, but also for economic growth and competitiveness in a global economy. In this paper, we first discuss the research on the strength of the link between early-life health and adult outcomes, and then provide an evidence-based review of the effectiveness of existing U.S. policies targeting the early-life environment. We conclude that there is a robust and economically meaningful relationship between early-life conditions and well-being throughout the lifecycle, as measured by adult health, educational attainment, labor market attachment, and other indicators of socio-economic status. However, there is some variation in the degree to which current policies in the U.S. are effective in improving early-life conditions. Among existing programs, some of the most effective are the Special Supplemental Program for Women, Infants, and Children (WIC), home visiting with nurse practitioners, and high-quality, center-based early childhood care and education. In contrast, the evidence on other policies such as prenatal care and family leave is more mixed and limited. PMID:25558491

The habitat and nature of early life.

PubMed

Nisbet, E G; Sleep, N H

2001-02-22

Earth is over 4,500 million years old. Massive bombardment of the planet took place for the first 500-700 million years, and the largest impacts would have been capable of sterilizing the planet. Probably until 4,000 million years ago or later, occasional impacts might have heated the ocean over 100 degrees C. Life on Earth dates from before about 3,800 million years ago, and is likely to have gone through one or more hot-ocean 'bottlenecks'. Only hyperthermophiles (organisms optimally living in water at 80-110 degrees C) would have survived. It is possible that early life diversified near hydrothermal vents, but hypotheses that life first occupied other pre-bottleneck habitats are tenable (including transfer from Mars on ejecta from impacts there). Early hyperthermophile life, probably near hydrothermal systems, may have been non-photosynthetic, and many housekeeping proteins and biochemical processes may have an original hydrothermal heritage. The development of anoxygenic and then oxygenic photosynthesis would have allowed life to escape the hydrothermal setting. By about 3,500 million years ago, most of the principal biochemical pathways that sustain the modern biosphere had evolved, and were global in scope.

Early life experience alters behavior during social defeat: focus on serotonergic systems.

PubMed

Gardner, K L; Thrivikraman, K V; Lightman, S L; Plotsky, P M; Lowry, C A

2005-01-01

Early life experience can have prolonged effects on neuroendocrine, autonomic, and behavioral responses to stress. The objective of this study was to investigate the effects of early life experience on behavior during social defeat, as well as on associated functional cellular responses in serotonergic and non-serotonergic neurons within the dorsal raphe nucleus, a structure which plays an important role in modulation of stress-related physiology and behavior. Male Long Evans rat pups were exposed to either normal animal facility rearing or 15 min or 180 min of maternal separation from postnatal days 2-14. As adults, these rats were exposed to a social defeat protocol. Differences in behavior were seen among the early life treatment groups during social defeat; rats exposed to 180 min of maternal separation from postnatal days 2-14 displayed more passive-submissive behaviors and less proactive coping behaviors. Analysis of the distribution of tryptophan hydroxylase and c-Fos-like immunoreactivity in control rats exposed to a novel cage and rats exposed to social defeat revealed that, independent of the early life experience, rats exposed to social defeat showed an increase in the number of c-Fos-like immunoreactive nuclei in serotonergic neurons in the middle and caudal parts of the dorsal dorsal raphe nucleus and caudal part of the ventral dorsal raphe nucleus, regions known to contain serotonergic neurons projecting to central autonomic and emotional motor control systems. This is the first study to show that the dorsomedial part of the mid-rostrocaudal dorsal raphe nucleus is engaged by a naturalistic stressor and supports the hypothesis that early life experience alters behavioral coping strategies during social conflict; furthermore, this study is consistent with the hypothesis that topographically organized subpopulations of serotonergic neurons principally within the mid-rostrocaudal and caudal part of the dorsal dorsal raphe nucleus modulate stress

Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity.

PubMed

Kaliannan, K; Wang, B; Li, X-Y; Bhan, A K; Kang, J X

2016-06-01

Early-life antibiotic exposure can disrupt the founding intestinal microbial community and lead to obesity later in life. Recent studies show that omega-3 fatty acids can reduce body weight gain and chronic inflammation through modulation of the gut microbiota. We hypothesize that increased tissue levels of omega-3 fatty acids may prevent antibiotic-induced alteration of gut microbiota and obesity later in life. Here, we utilize the fat-1 transgenic mouse model, which can endogenously produce omega-3 fatty acids and thereby eliminates confounding factors of diet, to show that elevated tissue levels of omega-3 fatty acids significantly reduce body weight gain and the severity of insulin resistance, fatty liver and dyslipidemia resulting from early-life exposure to azithromycin. These effects were associated with a reversal of antibiotic-induced dysbiosis of gut microbiota in fat-1 mice. These results demonstrate the beneficial effects of omega-3 fatty acids on antibiotic-induced gut dysbiosis and obesity, and suggest the potential utility of omega-3 supplementation as a safe and effective means for the prevention of obesity in children who are exposed to antibiotics.

Adverse early life environment increases hippocampal microglia abundance in conjunction with decreased neural stem cells in juvenile mice.

PubMed

Cohen, Susan; Ke, Xingrao; Liu, Qiuli; Fu, Qi; Majnik, Amber; Lane, Robert

2016-12-01

Adverse maternal lifestyle resulting in adverse early life environment (AELE) increases risks for neuropsychiatric disorders in offspring. Neuropsychiatric disorders are associated with impaired neurogenesis and neuro-inflammation in the hippocampus (HP). Microglia are neuro-inflammatory cells in the brain that regulate neurogenesis via toll-like receptors (TLR). TLR-9 is implicated in neurogenesis inhibition and is responsible for stress-related inflammatory responses. We hypothesized that AELE would increase microglia cell count and increase TLR-9 expression in juvenile mouse HP. These increases in microglia cell count and TLR-9 expression would be associated with decrease neural stem cell count and neuronal cell count. We developed a mouse model of AELE combining Western diet and a stress environment. Stress environment consisted of random change from embryonic day 13 (E13) to E17 as well as static change in maternal environment from E13 to postnatal day 21(P21). At P21, we measured hippocampal cell numbers of microglia, neural stem cell and neuron, as well as hippocampal TLR-9 expression. AELE significantly increased total microglia number and TLR-9 expression in the hippocampus. Concurrently, AELE significantly decreased neural stem cell and neuronal numbers. AELE increased the neuro-inflammatory cellular response in the juvenile HP. We speculate that increased neuro-inflammatory responses may contribute to impaired neurogenesis seen in this model. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Environmental determinants of allergy and asthma in early life.

PubMed

Burbank, Allison J; Sood, Amika K; Kesic, Matthew J; Peden, David B; Hernandez, Michelle L

2017-07-01

Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.

PubMed

Barbier, Estelle; Pierrefiche, Olivier; Vaudry, David; Vaudry, Hubert; Daoust, Martine; Naassila, Mickaël

2008-12-01

Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring.

Early life stress-induced alterations in rat brain structures measured with high resolution MRI.

PubMed

Sarabdjitsingh, R Angela; Loi, Manila; Joëls, Marian; Dijkhuizen, Rick M; van der Toorn, Annette

2017-01-01

Adverse experiences early in life impair cognitive function both in rodents and humans. In humans this increases the vulnerability to develop mental illnesses while in the rodent brain early life stress (ELS) abnormalities are associated with changes in synaptic plasticity, excitability and microstructure. Detailed information on the effects of ELS on rodent brain structural integrity at large and connectivity within the brain is currently lacking; this information is highly relevant for understanding the mechanism by which early life stress predisposes to mental illnesses. Here, we exposed rats to 24 hours of maternal deprivation (MD) at postnatal day 3, a paradigm known to increase corticosterone levels and thereby activate glucocorticoid receptors in the brain. Using structural magnetic resonance imaging we examined: i) volumetric changes and white/grey matter properties of the whole cerebrum and of specific brain areas; and ii) whether potential alterations could be normalized by blocking glucocorticoid receptors with mifepristone during the critical developmental window of early adolescence, i.e. between postnatal days 26 and 28. The results show that MD caused a volumetric reduction of the prefrontal cortex, particularly the ventromedial part, and the orbitofrontal cortex. Within the whole cerebrum, white (relative to grey) matter volume was decreased and region-specifically in prefrontal cortex and dorsomedial striatum following MD. A trend was found for the hippocampus. Grey matter fractions were not affected. Treatment with mifepristone did not normalize these changes. This study indicates that early life stress in rodents has long lasting consequences for the volume and structural integrity of the brain. However, changes were relatively modest and-unlike behavior- not mitigated by blockade of glucocorticoid receptors during a critical developmental period.

Precedents of perceived social support: personality and early life experiences.

PubMed

Kitamura, T; Kijima, N; Watanabe, K; Takezaki, Y; Tanaka, E

1999-12-01

In order to examine the effects of personality and early life experiences on perceived social support, a total of 97 young Japanese women were investigated. Current interpersonal relationships were measured by an interview modified from Henderson et al.'s Interview Schedule for Social Interaction (ISSI). Personality was measured by Cloninger et al.'s Temperament and Character Inventory. Early life experiences at home and outside of home were also identified in the interview. The number of sources of perceived support was correlated with self-directness, while satisfaction with perceived support was correlated with novelty seeking and with low harm avoidance. No early life experiences--early loss of a parent, perceived parenting, childhood abuse experiences, experiences of being bullied and/or other life events--showed significant correlations with the number or satisfaction of supportive people. The quantity and quality of perception of social support differ in their link to personality, and perceived social support may, to some extent, be explainable in terms of personality.

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

PubMed

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.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.

PubMed

Engert, Veronika; Efanov, Simona I; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C

2010-11-01

In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

Early Life Origins of Metabolic Syndrome: The Role of Environmental Toxicants

PubMed Central

Wang, Guoying; Chen, Zhu; Bartell, Tami; Wang, Xiaobin

2014-01-01

Metabolic syndrome (MetS) affects more than 47 million people in the U.S. Even more alarming, MetS, once regarded as an “adult problem”, has become increasingly common in children. To date, most related research and intervention efforts have occurred in the adult medicine arena, with limited understanding of the root causes and lengthy latency of MetS. This review highlights new science on the early life origins of MetS, with a particular focus on exposure to two groups of environmental toxicants: endocrine disrupting chemicals (EDCs) and metals during the prenatal and early postnatal periods, and their specific effects and important differences in the development of MetS. It also summarizes available data on epigenetic effects, including the role of EDCs in the androgen/estrogen pathways. Emerging evidence supports the link between exposures to environmental toxicants during early life and the development of MetS later in life. Additional research is needed to address important research gaps in this area, including prospective birth cohort studies to delineate temporal and dose-response relationships, important differences in the effects of various environmental toxicants and their joint effects on MetS, as well as epigenetic mechanisms underlying the effects of specific toxicants such as EDCs and metals. PMID:24883264

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

PubMed

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.

Posttraumatic stress disorder, alone or additively with early life adversity, is associated with obesity and cardiometabolic risk.

PubMed

Farr, O M; Ko, B-J; Joung, K E; Zaichenko, L; Usher, N; Tsoukas, M; Thakkar, B; Davis, C R; Crowell, J A; Mantzoros, C S

2015-05-01

There is some evidence that posttraumatic stress disorder (PTSD) and early life adversity may influence metabolic outcomes such as obesity, diabetes, and cardiovascular disease. However, whether and how these interact is not clear. We analyzed data from a cross-sectional and longitudinal study to determine how PTSD severity influences obesity, insulin sensitivity, and key measures and biomarkers of cardiovascular risk. We then looked at how PTSD and early life adversity may interact to impact these same outcomes. PTSD severity is associated with increasing risk of obesity, diabetes, and cardiovascular disease, with higher symptoms correlating with higher values of BMI, leptin, fibrinogen, and blood pressure, and lower values of insulin sensitivity. PTSD and early life adversity have an additive effect on these metabolic outcomes. The longitudinal study confirmed findings from the cross sectional study and showed that fat mass, leptin, CRP, sICAM-1, and sTNFRII were significantly increased with higher PTSD severity during a 2.5 year follow-up period. Individuals with early life adversity and PTSD are at high risk and should be monitored carefully for obesity, insulin resistance, and cardiometabolic risk. Copyright © 2015 Elsevier B.V. All rights reserved.

Early-life antibiotic treatment enhances the pathogenicity of CD4+ T cells during intestinal inflammation.

PubMed

Scheer, Sebastian; Medina, Tiago S; Murison, Alex; Taves, Matthew D; Antignano, Frann; Chenery, Alistair; Soma, Kiran K; Perona-Wright, Georgia; Lupien, Mathieu; Arrowsmith, Cheryl H; De Carvalho, Daniel D; Zaph, Colby

2017-04-01

The incidence of inflammatory bowel diseases (IBDs) has steadily increased in recent decades-a phenomenon that cannot be explained by genetic mutations alone. Other factors, including the composition of the intestinal microbiome, are potentially important contributors to the increased occurrence of this group of diseases. Previous reports have shown a correlation between early-life antibiotic (Abx) treatment and an increased incidence of IBD. In this report, we investigated the effects of early-life Abx treatments on the pathogenicity of CD4 + T cells using an experimental T cell transfer model of IBD. Our results show that CD4 + T cells isolated from adult mice that had been treated with Abx during gestation and in early life induced a faster onset of IBD in Rag1 -deficient mice compared with CD4 + T cells of untreated mice. Ex vivo functional analyses of IBD-inducing CD4 + T cells did not show significant differences in their immunologic potential ex vivo, despite their in vivo phenotype. However, genome-wide gene-expression analysis revealed that these cells displayed dysregulated expression of genes associated with cell-cycle regulation, metabolism, and cellular stress. Analysis of Abx-treated CD4 + T cell donors showed systemically elevated levels of the stress hormone corticosterone throughout life compared with untreated donors. The cohousing of Abx-treated mice with untreated mice decreased serum corticosterone, and a consequent transfer of the cells from cohoused mice into Rag1 -deficient mice restored the onset and severity of disease to that of untreated animals. Thus, our results suggest that early-life Abx treatment results in a stress response with high levels of corticosterone that influences CD4 + T cell function. © Society for Leukocyte Biology.

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

Early life influences on cognitive impairment among oldest old Chinese.

PubMed

Zhang, Zhenmei; Gu, Danan; Hayward, Mark D

2008-01-01

This article examines the effects of early life socioeconomic conditions on the risk of cognitive impairment among oldest old persons in China. We also examine whether adult socioeconomic status mediates the association between early life socioeconomic status and cognitive impairment in old age. Data derived from two waves (1998-2000) of the Chinese Longitudinal Healthy Longevity Survey. We estimated logistic and multinomial regression models of cognitive impairment for a nationwide sample of people aged 80 to 105 (N = 8,444). Among both men and women, urban residence in early life as well as education was associated with lower odds of cognitive impairment at baseline. We found modest support for a protective effect of advantaged childhood background on the odds of cognitive impairment onset during the 2-year follow-up, especially among women. Our findings suggest that socioeconomic environment throughout the life course, early life in particular, can influence the risk of cognitive impairment in old age. Not only can public policy that targets illiteracy, hunger, and poverty improve the lives of tens of thousands of children, but ultimately such investments will pay significant dividends many decades later in enhancing the cognitive well-being of older persons.

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

EPA Science Inventory

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...

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

PubMed

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.

Examination of age-related epigenetic changes following early-life exposure to dichloroacetic acid

EPA Science Inventory

Recent studies have shown that transient early-life exposure to dichloroacetic acid (DCA), a pyruvate analog and metabolic reprogramming agent, increases liver cancer incidence in older mice. This carcinogenic effect is not associated with direct mutagenicity, persistent cytotoxi...

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

PubMed

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.

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

PubMed

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.

New insights into a hot environment for early life.

PubMed

Dai, Jianghong

2017-06-01

Investigating the physical-chemical setting of early life is a challenging task. In this contribution, the author attempted to introduce a provocative concept from cosmology - cosmic microwave background (CMB), which is the residual thermal radiation from a hot early Universe - to the field. For this purpose, the author revisited a recently deduced biomarker, the 1,6-anhydro bond of sugars in bacteria. In vitro, the 1,6-anhydro bond of sugars reflects and captures residual thermal radiation in thermochemical processes and therefore is somewhat analogous to CMB. In vivo, the formation process of the 1,6-anhydro bond of sugars on the peptidoglycan of prokaryotic cell wall is parallel to in vitro processes, suggesting that the 1,6-anhydro bond is an ideal CMB-like analogue that suggests a hot setting for early life. The CMB-like 1,6-anhydro bond is involved in the life cycle of viruses and the metabolism of eukaryotes, underlying this notion. From a novel perspective, the application of the concept of the CMB to microbial ecology may give new insights into a hot environment, such as hydrothermal vents, supporting early life and providing hypotheses to test in molecular palaeontology. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Life satisfaction in early adolescence: personal, neighborhood, school, family, and peer influences.

PubMed

Oberle, Eva; Schonert-Reichl, Kimberly A; Zumbo, Bruno D

2011-07-01

Drawing from an ecological assets framework as well as research and theory on positive youth development, this study examined the relationship of early adolescents' satisfaction with life to trait optimism and assets representing the social contexts in which early adolescents spend most of their time. Self-reports of satisfaction with life, optimism, and ecological assets in the school (school connectedness), neighborhood (perceived neighborhood support), family (perceived parental support), and peer group (positive peer relationships) were assessed in a sample of 1,402 4th to 7th graders (47% female) from 25 public elementary schools. Multilevel modeling (MLM) was conducted to analyze the variability in life satisfaction both at the individual and the school level. As hypothesized, adding optimism and the dimensions representing the ecology of early adolescence to the model significantly reduced the variability in life satisfaction at both levels of analysis. Both personal (optimism) and all of the ecological assets significantly and positively predicted early adolescents' life satisfaction. The results suggest the theoretical and practical utility of an assets approach for understanding life satisfaction in early adolescence.

Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps

PubMed Central

Bailey, Kathryn A.; Smith, Allan H.; Tokar, Erik J.; Graziano, Joseph H.; Kim, Kyoung-Woong; Navasumrit, Panida; Ruchirawat, Mathuros; Thiantanawat, Apinya; Suk, William A.; Fry, Rebecca C.

2015-01-01

Background Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. Objectives This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. Discussion Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. Conclusions Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes. Citation Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360 PMID:26115410

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress

PubMed Central

Engert, Veronika; Efanov, Simona I.; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C.

2010-01-01

Background In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic–pituitary–adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. Methods In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Results Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Limitations Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. Conclusion We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group. PMID:20964960

Early developmental trajectories of number knowledge and math achievement from 4 to 10 years: Low-persistent profile and early-life predictors.

PubMed

Garon-Carrier, Gabrielle; Boivin, Michel; Lemelin, Jean-Pascal; Kovas, Yulia; Parent, Sophie; Séguin, Jean R; Vitaro, Frank; Tremblay, Richard E; Dionne, Ginette

2018-06-01

Little is known about the development of number knowledge (NK) and the antecedents of low-persistent NK profiles in early childhood. We documented the developmental trajectories of NK across the transition from preschool to elementary school, their predictive validity with respect to later math achievement, and the child and family early-life factors associated with low NK profiles. Children's NK was assessed four times at regular intervals between the ages 4 and 7 years in a large, representative population-based sample. Developmental trajectories of NK were established for 1597 children. These children were also assessed with respect to several features of their family environment at 5, 17, and 29 months, as well as their cognitive skills at age 41 months. Analyses revealed a best-fitting 4-trajectory model, characterized by Low-Increasing (10% of the children), Moderate-Increasing (39%), Moderate-Fast Increasing (32%) and High-Increasing (19%) groups. Children of these trajectory groups differed significantly with respect to math achievement at ages 8 and 10 years, with the Low-Increasing group persistently scoring lower than the other groups throughout these years. Children of Low-Increasing NK group were from household of lower income and father with low educational background, poorer early cognitive development, and more importantly, reduced visual-spatial skills and memory-span. Children displaying reduced cognitive abilities and impoverished living conditions early in life are at greater risk of low NK throughout late preschool and school entry, with ensuing difficulties in math achievement. They deserve early preventive attention to help alleviate later mathematic difficulties. Copyright © 2018 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Early life stress increases testosterone and corticosterone and alters stress physiology in zebra finches.

PubMed

Zito, J Bayley; Hanna, Angy; Kadoo, Nora; Tomaszycki, Michelle L

2017-09-01

Early life stress has enduring effects on behavior and physiology. However, the effects on hormones and stress physiology remain poorly understood. In the present study, parents of zebra finches of both sexes were exposed to an increased foraging paradigm from 3 to 33days post hatching. Plasma and brains were collected from chicks at 3 developmental time points: post hatching days 25, 60 and adulthood. Plasma was assayed for testosterone (T), estradiol (E2), and corticosterone (CORT). The paraventricular nucleus of the hypothalamus was assessed for corticotrophin releasing factor (CRH) and glucocorticoid receptor (GR) expression. As expected, body mass was lower in nutritionally stressed animals compared to controls at multiple ages. Nutritionally stressed animals overall had higher levels of CORT than did control and this was particularly apparent in females at post hatching day 25. Nutritionally stressed animals also had a higher number of cells expressing CRH and GR in the paraventricular nucleus of the hypothalamus than did controls. There was an interaction, such that both measures were higher in control animals at PHD 25, but higher in NS animals by adulthood. Females, regardless of treatment, had higher circulating CORT and a higher number of cells expressing CRH than did males. Nutritionally stressed animals also had higher levels of T than did control animals, and this difference was greatest for males at post hatching day 60. There were no effects of nutritional stress on E2. These findings suggest that nutritional stress during development has long-lasting effects on testosterone and stress physiology. Copyright © 2017 Elsevier Inc. All rights reserved.

Early Mars: A Warm Wet Niche for Life

NASA Technical Reports Server (NTRS)

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)

Early Adolescent Affect Predicts Later Life Outcomes.

PubMed

Kansky, Jessica; Allen, Joseph P; Diener, Ed

2016-07-01

Subjective well-being as a predictor for later behavior and health has highlighted its relationship to health, work performance, and social relationships. However, the majority of such studies neglect the developmental nature of well-being in contributing to important changes across the transition to adulthood. To examine the potential role of subjective well-being as a long-term predictor of critical life outcomes, we examined indicators of positive and negative affect at age 14 as predictors of relationship, adjustment, self-worth, and career outcomes a decade later at ages 23 to 25, controlling for family income and gender. We utilised multi-informant methods including reports from the target participant, close friends, and romantic partners in a demographically diverse community sample of 184 participants. Early adolescent positive affect predicted fewer relationship problems (less self-reported and partner-reported conflict, and greater friendship attachment as rated by close peers) and healthy adjustment to adulthood (lower levels of depression, anxiety, and loneliness). It also predicted positive work functioning (higher levels of career satisfaction and job competence) and increased self-worth. Negative affect did not significantly predict any of these important life outcomes. In addition to predicting desirable mean levels of later outcomes, early positive affect predicted beneficial changes across time in many outcomes. The findings extend early research on the beneficial outcomes of subjective well-being by having an earlier assessment of well-being, including informant reports in measuring a large variety of outcome variables, and by extending the findings to a lower socioeconomic group of a diverse and younger sample. The results highlight the importance of considering positive affect as an important component of subjective well-being distinct from negative affect. © 2016 The International Association of Applied Psychology.

Early Adolescent Affect Predicts Later Life Outcomes

PubMed Central

Kansky, Jessica; Allen, Joseph P.; Diener, Ed

2016-01-01

Background Subjective well-being as a predictor for later behavior and health has highlighted its relationship to health, work performance, and social relationships. However, the majority of such studies neglect the developmental nature of well-being in contributing to important changes across the transition to adulthood. Methods To examine the potential role of subjective well-being as a long-term predictor of critical life outcomes, we examined indicators of positive and negative affect at age 14 as a predictor of relationship, adjustment, self worth, and career outcomes a decade later at ages 23 to 25, controlling for family income and gender. We utilized multi-informant methods including reports from the target participant, close friends, and romantic partners in a demographically diverse community sample of 184 participants. Results Early adolescent positive affect predicted less relationship problems (less self-reported and partner-reported conflict, greater friendship attachment as rated by close peers), healthy adjustment to adulthood (lower levels of depression, anxiety, and loneliness). It also predicted positive work functioning (higher levels of career satisfaction and job competence) and increased self-worth. Negative affect did not significantly predict any of these important life outcomes. In addition to predicting desirable mean levels of later outcomes, early positive affect predicted beneficial changes across time in many outcomes. Conclusions The findings extend early research on the beneficial outcomes of subjective well-being by having an earlier assessment of well-being, including informant reports in measuring a large variety of outcome variables, and by extending the findings to a lower socioeconomic group of a diverse and younger sample. The results highlight the importance of considering positive affect as an important component of subjective well-being distinct from negative affect. PMID:27075545

Early-life conditions and older adult health in low- and middle-income countries: a review

PubMed Central

McEniry, M.

2012-01-01

Population aging and subsequent projected large increases in chronic conditions will be important health concerns in low- and middle-income countries. Although evidence is accumulating, little is known regarding the impact of poor early-life conditions on older adult (50 years and older) health in these settings. A systematic review of 1141 empirical studies was conducted to identify population-based and community studies in low- and middle-income countries, which examined associations between early-life conditions and older adult health. The resulting review of 20 studies revealed strong associations between (1) in utero/early infancy exposures (independent of other early life and adult conditions) and adult heart disease and diabetes; (2) poor nutrition during childhood and difficulties in adult cognition and diabetes; (3) specific childhood illnesses such as rheumatic fever and malaria and adult heart disease and mortality; (4) poor childhood health and adult functionality/disability and chronic diseases; (5) poor childhood socioeconomic status (SES) and adult mortality, functionality/disability and cognition; and (6) parental survival during childhood and adult functionality/disability and cognition. In several instances, associations remained strong even after controlling for adult SES and lifestyle. Although exact mechanisms cannot be identified, these studies reinforce to some extent the importance of early-life environment on health at older ages. Given the paucity of cohort data from the developing world to examine hypotheses of early-life conditions and older adult health, population-based studies are relevant in providing a broad perspective on the origins of adult health. PMID:23316272

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

PubMed Central

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

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

EPA Science Inventory

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...

Early Life Growth Predictors of Childhood Adiposity Trajectories and Future Risk for Obesity: Birth to Twenty Cohort.

PubMed

Munthali, Richard J; Kagura, Juliana; Lombard, Zané; Norris, Shane A

2017-10-01

There is growing evidence of variations in adiposity trajectories among individuals, but the influence of early life growth patterns on these trajectories is underresearched in low- and middle-income countries. Therefore, our aim was to examine the association between early life conditional weight gain and childhood adiposity trajectories. We previously identified distinct adiposity trajectories (four for girls and three for boys) in black South African children (boys = 877; girls = 947). The association between the trajectories and early life growth patterns, and future obesity risk was assessed by multivariate linear and multinomial logistic and logistic regressions. Conditional weight gain independent of height was computed for infancy (0-2 years) and early childhood (2-4 years). Conditional weight gain before 5 years of age was significantly associated with early onset of obesity or overweight (excess weight) BMI trajectories in both boys and girls. In girls, greater conditional weight gain in infancy was associated with increased relative risk of being in the early-onset obese to morbid obese trajectory, with relative risk ratios of 2.03 (95% confidence interval: 1.17-3.52) compared to belonging to a BMI trajectory in the normal range. Boys and girls in the early-onset obesity or overweight BMI trajectories were more likely to be overweight or obese in early adulthood. Excessive weight gain in infancy and early childhood, independent of linear growth, predicts childhood and adolescent BMI trajectories toward obesity. These results underscore the importance of early life factors in the development of obesity and other NCDs in later life.

The expression of human natural killer cell receptors in early life.

PubMed

Sundström, Y; Nilsson, C; Lilja, G; Kärre, K; Troye-Blomberg, M; Berg, L

2007-01-01

Natural killer (NK) cells play an important role in tumour immunosurveillance and the early defence against viral infections. Recognition of altered cells (i.e. infected- or tumour-cells) is achieved through a multiple receptor recognition strategy which gives the NK cells inhibitory or activating signals depending on the ligands present on the target cell. NK cells originate from the bone marrow where they develop and proliferate. However, further maturation processes and homeostasis of NK cells in peripheral blood are not well understood. To determine the proportions of cells and the expression of NK cell receptors, mononuclear cells from children at three time points during early childhood were compared, i.e. cord blood (CB), 2 and 5 years of age. The proportion of NK cells was high in CB, but the interferon-gamma (IFN-gamma) production low compared to later in life. In contrast, the proportion of T cells was low in CB. This may indicate a deviation of the regulatory function of NK cells in CB compared to later in life, implying an importance of innate immunity in early life before the adaptive immune system matures. Additionally, we found that the proportion of LIR-1(+) NK cells increased with increasing age while CD94(+)NKG2C(-) (NKG2A(+)) NK cells and the level of expression of NKG2D, NKp30 and NKp46 decreased with age. These age related changes in NK cell populations defined by the expression of activating and inhibitory receptors may be the result of pathogen exposure and/or a continuation of the maturation process that begins in the bone marrow.

The early Earth atmosphere and early life catalysts.

PubMed

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.

Falls, sarcopenia and growth in early life

PubMed Central

Sayer, Avan Aihie; Syddall, Holly E; Martin, Helen J; Dennison, Elaine M; Anderson, Frazer H; Cooper, Cyrus

2007-01-01

Recent studies have shown that people with poor early growth have an increased risk of sarcopenia. Sarcopenia is an important risk factor for falls but it is not known whether poor early growth is related to falls. We investigated this in the Hertfordshire Cohort Study where 2148 participants completed a falls history. Grip strength was used as a marker of sarcopenia. Birth weight, weight at one year and conditional infant growth were analysed in relation to falls history. The prevalence of any fall in the last year was 14.3% for men and 22.5% for women. Falls in the last year were inversely related to adult grip strength, height and walking speed in men and women as well as to lower conditional infant growth in men (OR 1.27 [95% CI 1.04, 1.56] per SD decrease in conditional infant growth, p=0.02). This association was attenuated after adjustment for grip strength. Our findings support an association between poor early growth and falls in older men which appears to be mediated partly through sarcopenia. The lack of relationship with birth weight suggests that postnatal rather than prenatal influences on muscle growth and development may be important for risk of falls in later life. PMID:16905644

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

PubMed

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.

Children of Misfortune: Early Adversity and Cumulative Inequality in Perceived Life Trajectories1

PubMed Central

Schafer, Markus H.; Ferraro, Kenneth F.; Mustillo, Sarah A.

2011-01-01

Adversity early in life may alter pathways of aging, but what interpretive processes can soften the blow of early insults? Drawing from cumulative inequality theory, the authors analyze trajectories of life evaluations and then consider whether early adversity offsets favorable expectations for the future. Results reveal that early adversity contributes to more negative views of the past but rising expectations for the future. Early adversity also has enduring effects on life evaluations, offsetting the influence of buoyant expectations. The findings draw attention to the limits of human agency under the constraints of early adversity—a process described as biographical structuration. PMID:21648247

Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

PubMed Central

Tain, You-Lin; Hsu, Chien-Ning

2017-01-01

Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called “developmental programming” or “developmental origins of health and disease” (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease. PMID:28208659

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

PubMed Central

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

Modeling old-age wealth with endogenous early-life outcomes: The case of Mexico

PubMed Central

DeGraff, Deborah S.; Wong, Rebeca

2014-01-01

This paper contributes to the literature on the life course and aging by examining the association between early-life outcomes and late-life well being, using data from the Mexican Health and Aging Study. Empirical research in this area has been challenged by the potential endogeneity of the early-life outcomes of interest, an issue which most studies ignore or downplay. Our contribution takes two forms: (1) we examine in detail the potential importance of two key life-cycle outcomes, age at marriage (a measure of family formation) and years of educational attainment (a measure of human capital investment) for old-age wealth, and (2) we illustrate the empirical value of past context variables that could help model the association between early-life outcomes and late-life well being. Our illustrative approach, matching macro-level historical policy and census variables to individual records to use as instruments in modeling the endogeneity of early-life behaviors, yields a statistically identified two-stage model of old-age wealth with minimum bias. We use simulations to show that the results for the model of wealth in old age are meaningfully different when comparing the approach that accounts for endogeneity with an approach that assumes exogeneity of early-life outcomes. Furthermore, our results suggest that in the Mexican case, models which ignore the potential endogeneity of early-life outcomes are likely to under-estimate the effects of such variables on old-age wealth. PMID:25170434

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

PubMed

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.

Reproductive Toxicity of T Cells in Early Life: Abnormal Immune Development and Postnatal Diseases.

PubMed

Liu, Han-Xiao; Jiang, Aifang; Chen, Ting; Qu, Wen; Yan, Hui-Yi; Ping, Jie

2017-01-01

Immunity is a balanced status with adequate biological defenses to recognize and fight "non-self", as well as adequate tolerance to recognize "self". To maintain this immune homeostasis, a well-organized T cell immune network is required, which in part depends on the well-controlled development of alternative effector T cells, with different cytokine repertoires. Recent researches have pointed that developing fetal T cells network is a remarkably sensitive toxicological target for adverse factors in early life. Epidemiological and experimental studies showed an inseparable relationship between T cell developmental toxicity and immune diseases in adults. Considering that the inflammatory and immune disorders have become a growing health problem worldwide, increasing attention is now being paid to the T cell developmental toxicity. We propose that adverse factors may have programming effects on the crucial functions of immune system during early life which is critical for fetal T cell development and the establishment of the distinct T cell repertoires balance. The permanently disturbed intrathymic or peripheral T cell development may in turn lead to the immune disorders in later life. In this manuscript, we reviewed how adverse factors affected T cell development in early-life with the consequence of the immune dysfunction and immune diseases, and further elucidate the mechanisms. These mechanisms will be helpful in prevention and treatment of the increased prevalence of immune diseases by interfering those pathways. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Early life programming and the risk of non-alcoholic fatty liver disease.

PubMed

Lynch, C; Chan, C S; Drake, A J

2017-06-01

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease and can be considered the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of disease, from the relatively benign simple steatosis to the more serious non-alcoholic steatohepatitis, which can progress to liver cirrhosis, hepatocellular carcinoma and end-stage liver failure, necessitating liver transplantation. Although the increasing prevalence of NAFLD in developed countries has substantial implications for public health, many of the precise mechanisms accounting for the development and progression of NAFLD are unclear. The environment in early life is an important determinant of cardiovascular disease risk in later life and studies suggest this also extends to NAFLD. Here we review data from animal models and human studies which suggest that fetal and early life exposure to maternal under- and overnutrition, excess glucocorticoids and environmental pollutants may confer an increased susceptibility to NAFLD development and progression in offspring and that such effects may be sex-specific. We also consider studies aimed at identifying potential dietary and pharmacological interventions aimed at reducing this risk. We suggest that further human epidemiological studies are needed to ensure that data from animal models are relevant to human health.

Dietary factors during early life program bone formation in female rats

USDA-ARS?s Scientific Manuscript database

Nutritional status during intrauterine and early postnatal life impacts the risk of chronic diseases; however, evidence for an association between early life dietary factors and bone health in adults is limited. Soy protein isolate (SPI) may be one such dietary factor that promotes bone accretion du...

Retinal vascular imaging in early life: insights into processes and risk of cardiovascular disease

PubMed Central

Li, Ling‐Jun; Ikram, Mohammad Kamran

2015-01-01

Abstract Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. In recent years, studies have shown that the origins of CVD may be traced to vascular and metabolic processes in early life. Retinal vascular imaging is a new technology that allows detailed non‐invasive in vivo assessment and monitoring of the microvasculature. In this systematic review, we described the application of retinal vascular imaging in children and adolescents, and we examined the use of retinal vascular imaging in understanding CVD risk in early life. We reviewed all publications with quantitative retinal vascular assessment in two databases: PubMed and Scopus. Early life CVD risk factors were classified into four groups: birth risk factors, environmental risk factors, systemic risk factors and conditions linked to future CVD development. Retinal vascular changes were associated with lower birth weight, shorter gestational age, low‐fibre and high‐sugar diet, lesser physical activity, parental hypertension history, childhood hypertension, childhood overweight/obesity, childhood depression/anxiety and childhood type 1 diabetes mellitus. In summary, there is increasing evidence supporting the view that structural changes in the retinal microvasculature are associated with CVD risk factors in early life. Thus, the retina is a useful site for pre‐clinical assessment of microvascular processes that may underlie the future development of CVD in adulthood. PMID:26435039

Sex-dependent effects of an early life treatment in rats that increases maternal care: vulnerability or resilience?

PubMed

Fuentes, Sílvia; Daviu, Núria; Gagliano, Humberto; Garrido, Pedro; Zelena, Dóra; Monasterio, Nela; Armario, Antonio; Nadal, Roser

2014-01-01

Early life stress (ELS) in rodents has profound long-term effects that are partially mediated by changes in maternal care. ELS not only induces "detrimental" effects in adulthood, increasing psychopathology, but also promotes resilience to further stressors. In Long-Evans rats, we evaluated a combination of two procedures as a model of ELS: restriction of bedding during the first post-natal days and exposure to a "substitute" mother. The maternal care of biological and "substitute" mothers was measured. The male and female offspring were evaluated during adulthood in several contexts. Anxiety was measured by the elevated plus-maze (EPM), acoustic startle response (ASR) and forced swim test (FST). In other group of animals, novelty-seeking was measured (activity in an inescapable novel environment, preference for novel environments and exploration of novel objects). Plasmatic ACTH and corticosterone in basal conditions and in response to stress were also measured. Cognitive impulsivity was assessed by a delay-discounting paradigm, and impulsive action, attention and compulsive-like behavior by a five choice serial reaction time task (5CSRTT). ELS decreased pup body weight and increased the care of the biological mother; however, the "substitute" mother did not exhibit overt maltreatment. A mixture of "detrimental" and "beneficial" effects was shown. In the 5CSRTT, attention was impaired in both genders, and in females, ELS increased compulsive-like behavior. Novel object exploration was only increased by ELS in males, but the preference for novel spaces decreased in both genders. Baseline anxiety (EPM and ASR) and recognition memory were not affected. Unexpectedly, ELS decreased the ACTH response to novelty and swim stress and increased active coping in the FST in both genders. Cognitive impulsivity was decreased only in females, but impulsive action was not affected. The enhancement in maternal care may "buffer" the effects of ELS in a context-dependent manner.

Microbial ecology and host-microbiota interactions during early life stages

PubMed Central

Collado, Maria Carmen; Cernada, Maria; Baüerl, Christine; Vento, Máximo; Pérez-Martínez, Gaspar

2012-01-01

The role of human microbiota has been redefined during recent years and its physiological role is now much more important than earlier understood. Intestinal microbial colonization is essential for the maturation of immune system and for the developmental regulation of the intestinal physiology. Alterations in this process of colonization have been shown to predispose and increase the risk to disease later in life. The first contact of neonates with microbes is provided by the maternal microbiota. Moreover, mode of delivery, type of infant feeding and other perinatal factors can influence the establishment of the infant microbiota. Taken into consideration all the available information it could be concluded that the exposure to the adequate microbes early in gestation and neonatal period seems to have a relevant role in health. Maternal microbial environment affects maternal and fetal immune physiology and, of relevance, this interaction with microbes at the fetal-maternal interface could be modulated by specific microbes administered to the pregnant mother. Indeed, probiotic interventions aiming to reduce the risk of immune-mediated diseases may appear effective during early life. PMID:22743759

Early-Life Stress: From Neuroendocrine Mechanisms to Stress-Related Disorders.

PubMed

Pervanidou, Panagiota; Chrousos, George P

2018-06-08

Stress exposure is highly prevalent in the general population; however, the experience of stress during vulnerable periods of development has substantial and permanent effects on brain structure and function and physical health in adulthood. Stress, the state of threatened homeostasis, is generally associated with a time-limited activation of the stress system, i.e., the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous system, tailored to the stressful stimulus also known as the stressor. On the other hand, chronic stress may be associated with lingering hyper- or hyposecretion of mediators of the stress system. This chronic condition is called dyshomeostasis, allostasis, or cacostasis and is associated with increased mental and physical morbidity in the long term. Stressful or traumatic experiences during fetal life, early childhood, and adolescence have been related to persistent neuroendocrine and epigenetic changes. Further, brain structures involved in the stress response, such as those of the stress system, the hippocampus, and the amygdala, may be programmed early on for a life of adversity. © 2018 S. Karger AG, Basel.

Early Environmental Origins of Neurodegenerative Disease in Later Life

PubMed Central

Landrigan, Philip J.; Sonawane, Babasaheb; Butler, Robert N.; Trasande, Leonardo; Callan, Richard; Droller, Daniel

2005-01-01

Parkinson disease (PD) and Alzheimer disease (AD), the two most common neurodegenerative disorders in American adults, are of purely genetic origin in a minority of cases and appear in most instances to arise through interactions among genetic and environmental factors. In this article we hypothesize that environmental exposures in early life may be of particular etiologic importance and review evidence for the early environmental origins of neurodegeneration. For PD the first recognized environmental cause, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), was identified in epidemiologic studies of drug abusers. Chemicals experimentally linked to PD include the insecticide rotenone and the herbicides paraquat and maneb; interaction has been observed between paraquat and maneb. In epidemiologic studies, manganese has been linked to parkinsonism. In dementia, lead is associated with increased risk in chronically exposed workers. Exposures of children in early life to lead, polychlorinated biphenyls, and methylmercury have been followed by persistent decrements in intelligence that may presage dementia. To discover new environmental causes of AD and PD, and to characterize relevant gene–environment interactions, we recommend that a large, prospective genetic and epidemiologic study be undertaken that will follow thousands of children from conception (or before) to old age. Additional approaches to etiologic discovery include establishing incidence registries for AD and PD, conducting targeted investigations in high-risk populations, and improving testing of the potential neurologic toxicity of chemicals. PMID:16140633

Antibiotic Use in Early Life, Rural Residence, and Allergic Diseases in Argentinean Children.

PubMed

Han, Yueh-Ying; Forno, Erick; Badellino, Héctor A; Celedón, Juan C

Little is known about differential effects of antibiotic use on allergic diseases in rural versus urban environments. To examine whether area of residence in the first year of life modifies the relation between antibiotic use in early life and allergic diseases during childhood. Cross-sectional study of allergic diseases in 1517 children (ages 6-7 years) attending 101 schools in urban and rural areas of San Francisco (Córdoba, Argentina). Current asthma, wheeze, and allergic rhinoconjunctivitis were defined on the basis of responses to a validated questionnaire from the International Study of Asthma and Allergies in Childhood. Multivariate logistic regression was used for the analysis of antibiotic use and allergic diseases. After adjustment for paracetamol use, bronchiolitis, and other covariates, antibiotic use in the first year of life was associated with increased odds of current wheeze (odds ratio [OR], 1.8; 95% CI, 1.3-2.6) and allergic rhinoconjunctivitis (OR, 1.9; 95% CI, 1.3-2.7). After stratification by area of residence, antibiotic use was associated with current wheeze (OR, 2.4; 95% CI, 1.5-4.0) and allergic rhinoconjunctivitis (OR, 2.1; 95% CI, 1.3-3.4) among children who lived in an urban area in their first year of life, but not among those who lived in a rural area in their first year of life. Early-life antibiotic use is associated with current wheeze and allergic rhinoconjunctivitis in Argentinean children who lived in urban areas during their first year of life. Exposure to a rural environment early in life may protect against the adverse effects of antibiotics on atopic diseases in children. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer's disease.

PubMed

Lesuis, Sylvie L; Maurin, Herve; Borghgraef, Peter; Lucassen, Paul J; Van Leuven, Fred; Krugers, Harm J

2016-06-28

Stress has been implicated as a risk factor for the severity and progression of sporadic Alzheimer's disease (AD). Early life experiences determine stress responsivity in later life, and modulate age-dependent cognitive decline. Therefore, we examined whether early life experiences influence AD outcome in a bigenic mouse model which progressively develops combined tau and amyloid pathology (biAT mice).Mice were subjected to either early life stress (ELS) or to 'positive' early handling (EH) postnatally (from day 2 to 9). In biAT mice, ELS significantly compromised long term survival, in contrast to EH which increased life expectancy. In 4 month old mice, ELS-reared biAT mice displayed increased hippocampal Aβ levels, while these levels were reduced in EH-reared biAT mice. No effects of ELS or EH were observed on the brain levels of APP, protein tau, or PSD-95. Dendritic morphology was moderately affected after ELS and EH in the amygdala and medial prefrontal cortex, while object recognition memory and open field performance were not affected. We conclude that despite the strong transgenic background, early life experiences significantly modulate the life expectancy of biAT mice. Parallel changes in hippocampal Aβ levels were evident, without affecting cognition of young adult biAT mice.

Early-Life Social Isolation Influences Mouse Ultrasonic Vocalizations during Male-Male Social Encounters.

PubMed

Keesom, Sarah M; Finton, Caitlyn J; Sell, Gabrielle L; Hurley, Laura M

2017-01-01

Early-life social isolation has profound effects on adult social competence. This is often expressed as increased aggression or inappropriate displays of courtship-related behaviors. The social incompetence exhibited by isolated animals could be in part due to an altered ability to participate in communicatory exchanges. House mice (Mus musculus) present an excellent model for exploring this idea, because social isolation has a well-established influence on their social behavior, and mice engage in communication via multiple sensory modalities. Here, we tested the prediction that social isolation during early life would influence ultrasonic vocalizations (USVs) emitted by adult male mice during same-sex social encounters. Starting at three weeks of age, male mice were housed individually or in social groups of four males for five weeks, after which they were placed in one of three types of paired social encounters. Pair types consisted of: two individually housed males, two socially housed males, or an individually housed and a socially housed male ("mixed" pairs). Vocal behavior (USVs) and non-vocal behaviors were recorded from these 15-minute social interactions. Pairs of mice consisting of at least one individually housed male emitted more and longer USVs, with a greater proportional use of USVs containing frequency jumps and 50-kHz components. Individually housed males in the mixed social pairs exhibited increased levels of mounting behavior towards the socially housed males. Mounting in these pairs was positively correlated with increased number and duration of USVs as well as increased proportional use of spectrally more complex USVs. These findings demonstrate that USVs are part of the suite of social behaviors influenced by early-life social isolation, and suggest that altered vocal communication following isolation reflects reduced social competence.

Early-Life Social Isolation Influences Mouse Ultrasonic Vocalizations during Male-Male Social Encounters

PubMed Central

Finton, Caitlyn J.; Sell, Gabrielle L.; Hurley, Laura M.

2017-01-01

Early-life social isolation has profound effects on adult social competence. This is often expressed as increased aggression or inappropriate displays of courtship-related behaviors. The social incompetence exhibited by isolated animals could be in part due to an altered ability to participate in communicatory exchanges. House mice (Mus musculus) present an excellent model for exploring this idea, because social isolation has a well-established influence on their social behavior, and mice engage in communication via multiple sensory modalities. Here, we tested the prediction that social isolation during early life would influence ultrasonic vocalizations (USVs) emitted by adult male mice during same-sex social encounters. Starting at three weeks of age, male mice were housed individually or in social groups of four males for five weeks, after which they were placed in one of three types of paired social encounters. Pair types consisted of: two individually housed males, two socially housed males, or an individually housed and a socially housed male (“mixed” pairs). Vocal behavior (USVs) and non-vocal behaviors were recorded from these 15-minute social interactions. Pairs of mice consisting of at least one individually housed male emitted more and longer USVs, with a greater proportional use of USVs containing frequency jumps and 50-kHz components. Individually housed males in the mixed social pairs exhibited increased levels of mounting behavior towards the socially housed males. Mounting in these pairs was positively correlated with increased number and duration of USVs as well as increased proportional use of spectrally more complex USVs. These findings demonstrate that USVs are part of the suite of social behaviors influenced by early-life social isolation, and suggest that altered vocal communication following isolation reflects reduced social competence. PMID:28056078

Proinflammatory T Cell Status Associated with Early Life Adversity.

PubMed

Elwenspoek, Martha M C; Hengesch, Xenia; Leenen, Fleur A D; Schritz, Anna; Sias, Krystel; Schaan, Violetta K; Mériaux, Sophie B; Schmitz, Stephanie; Bonnemberger, Fanny; Schächinger, Hartmut; Vögele, Claus; Turner, Jonathan D; Muller, Claude P

2017-12-15

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA ( n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69 + CD8 + T cells ( p = 0.022), increased numbers of HLA-DR + CD4 and HLA-DR + CD8 T cells ( p < 0.001), as well as increased numbers of CD25 + CD8 + T cells ( p = 0.036). ELA also showed a trend toward higher numbers of CCR4 + CXCR3 - CCR6 + CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells. Copyright © 2017 by The American Association of Immunologists, Inc.

Early evolution without a tree of life.

PubMed

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.

The Effect of Early Life Antibiotic Exposures on Diarrheal Rates Among Young Children in Vellore, India

PubMed Central

Westreich, Daniel; Becker-Dreps, Sylvia; Adair, Linda S.; Sandler, Robert S.; Sarkar, Rajiv; Kattula, Deepthi; Ward, Honorine D.; Meshnick, Steven R.; Kang, Gagandeep

2015-01-01

Background: Antibiotic treatment of childhood illnesses is common in India. In addition to contributing to antimicrobial resistance, antibiotics might result in increased susceptibility to diarrhea through interactions with the gastrointestinal microbiota. Breast milk, which enriches the microbiota early in life, may increase the resilience of the microbiota against perturbations by antibiotics. Methods: In a prospective observational cohort study, we assessed whether antibiotic exposures from birth to 6 months affected rates of diarrhea up to age 3 years among 465 children from Vellore, India. Adjusting for treatment indicators, we modeled diarrheal rates among children exposed and unexposed to antibiotics using negative binomial regression. We further assessed whether the effect of antibiotics on diarrheal rates was modified by exclusive breastfeeding at 6 months. Results: More than half of the children (n = 267, 57.4%) were given at least one course of antibiotics in the first 6 months of life. The adjusted relative incidence rate of diarrhea was 33% higher among children who received antibiotics under 6 months of age compared with those who did not (incidence rate ratio: 1.33, 95% confidence interval: 1.12, 1.57). Children who were exclusively breastfed until 6 months of age did not have increased diarrheal rates following antibiotic use. Conclusions: Antibiotic exposures early in life were associated with increased rates of diarrhea in early childhood. Exclusive breastfeeding might protect against this negative impact. PMID:25742244

The origin and early evolution of life on earth

NASA Technical Reports Server (NTRS)

Oro, J.; Miller, Stanley L.; Lazcano, Antonio

1990-01-01

Results of the studies that have provided insights into the cosmic and primitive earth environments are reviewed with emphasis on those environments in which life is thought to have originated. The evidence bearing on the antiquity of life on the earth and the prebiotic significance of organic compounds found in interstellar clouds and in primitive solar-system bodies such as comets, dark asteroids, and carbonaceous chondrites are assessed. The environmental models of the Hadean and early Archean earth are discussed, as well as the prebiotic formation of organic monomers and polymers essential to life. The processes that may have led to the appearance in the Archean of the first cells are considered, and possible effects of these processes on the early steps of biological evolution are analyzed. The significance of these results to the study of the distribution of life in the universe is evaluated.

The status of live viral vaccination in early life.

PubMed

Gans, Hayley A

2013-05-17

The need for neonatal vaccines is supported by the high disease burden during the first year of life particularly in the first month. Two-thirds of childhood deaths are attributable to infectious diseases of which viruses represent key pathogens. Many infectious diseases have the highest incidence, severity and mortality in the first months of life, and therefore early life vaccination would provide significant protection and life savings. For some childhood viral diseases successful vaccines exist, such as against measles, mumps, rubella, varicella, influenza poliovirus, and rotavirus, but their use in the first year particularly at birth is not yet practiced. Vaccines against other key pathogens continue to elude scientists such as against respiratory syncytial virus. The obstacles for early and neonatal vaccination are complex and include host factors, such as a developing immune system and the interference of passively acquired antibodies, as well vaccine-specific issues, such as optimal route of administration, titer and dosing requirements. Importantly, additional host and infrastructure barriers also present obstacles to neonatal vaccination in the developing world where morbidity and mortality rates are highest. This review will highlight the current live viral vaccines and their use in the first year of life, focusing on efficacy and entertaining the barriers that exist. It is important to understand the successes of current vaccines and use this knowledge to determine strategies that are successful in young infants and for the development of new vaccines for use in early life. Copyright © 2012 Elsevier Ltd. All rights reserved.

Zinc in Early Life: A Key Element in the Fetus and Preterm Neonate

PubMed Central

Terrin, Gianluca; Berni Canani, Roberto; Di Chiara, Maria; Pietravalle, Andrea; Aleandri, Vincenzo; Conte, Francesca; De Curtis, Mario

2015-01-01

Zinc is a key element for growth and development. In this narrative review, we focus on the role of dietary zinc in early life (including embryo, fetus and preterm neonate), analyzing consequences of zinc deficiency and adequacy of current recommendations on dietary zinc. We performed a systematic search of articles on the role of zinc in early life. We selected and analyzed 81 studies. Results of this analysis showed that preservation of zinc balance is of critical importance for the avoidance of possible consequences of low zinc levels on pre- and post-natal life. Insufficient quantities of zinc during embryogenesis may influence the final phenotype of all organs. Maternal zinc restriction during pregnancy influences fetal growth, while adequate zinc supplementation during pregnancy may result in a reduction of the risk of preterm birth. Preterm neonates are at particular risk to develop zinc deficiency due to a combination of different factors: (i) low body stores due to reduced time for placental transfer of zinc; (ii) increased endogenous losses; and (iii) marginal intake. Early diagnosis of zinc deficiency, through the measurement of serum zinc concentrations, may be essential to avoid severe prenatal and postnatal consequences in these patients. Typical clinical manifestations of zinc deficiency are growth impairment and dermatitis. Increasing data suggest that moderate zinc deficiency may have significant subclinical effects, increasing the risk of several complications typical of preterm neonates (i.e., necrotizing enterocolitis, chronic lung disease, and retinopathy), and that current recommended intakes should be revised to meet zinc requirements of extremely preterm neonates. Future studies evaluating the adequacy of current recommendations are advocated. PMID:26690476

EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

EPA Science Inventory

Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

Early-Life Food Nutrition, Microbiota Maturation and Immune Development Shape Life-Long Health.

PubMed

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.

Sucrose-induced analgesia during early life modulates adulthood learning and memory formation.

PubMed

Nuseir, Khawla Q; Alzoubi, Karem H; Alabwaini, Jehad; Khabour, Omar F; Kassab, Manal I

2015-06-01

This study is aimed at examining the long-term effects of chronic pain during early life (postnatal day 0 to 8weeks), and intervention using sucrose, on cognitive functions during adulthood in rats. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution or paracetamol was administered for analgesia before the paw prick. Control groups include tactile stimulation to account for handling and touching the paws, and sucrose alone was used. All treatments were started on day one of birth and continued for 8weeks. At the end of the treatments, behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM), as well as pain threshold via foot-withdrawal response to a hot plate apparatus. Additionally, the hippocampus was dissected, and blood was collected. Levels of neurotrophins (BDNF, IGF-1 and NT-3) and endorphins were assessed using ELISA. The results show that chronic noxious stimulation resulted in comparable foot-withdrawal latency between noxious and tactile groups. On the other hand, pretreatment with sucrose or paracetamol increased pain threshold significantly both in naive rats and noxiously stimulated rats (P<0.05). Chronic pain during early life impaired short-term memory, and sucrose treatment prevented such impairment (P<0.05). Sucrose significantly increased serum levels of endorphin and enkephalin. Chronic pain decreased levels of BDNF in the hippocampus and this decrease was prevented by sucrose and paracetamol treatments. Hippocampal levels of NT-3 and IGF-1 were not affected by any treatment. In conclusion, chronic pain induction during early life induced short memory impairment, and pretreatment with sucrose prevented this impairment via mechanisms that seem to involve BDNF. As evident in the results, sucrose, whether alone or in the presence of pre-noxious stimulation, increases pain threshold in such circumstances; most likely via a mechanism that involves an increase in endogenous

Effect of early life exposure to air pollution on development of childhood asthma.

PubMed

Clark, Nina Annika; Demers, Paul A; Karr, Catherine J; Koehoorn, Mieke; Lencar, Cornel; Tamburic, Lillian; Brauer, Michael

2010-02-01

There is increasing recognition of the importance of early environmental exposures in the development of childhood asthma. Outdoor air pollution is a recognized asthma trigger, but it is unclear whether exposure influences incident disease. We investigated the effect of exposure to ambient air pollution in utero and during the first year of life on risk of subsequent asthma diagnosis in a population-based nested case-control study. We assessed all children born in southwestern British Columbia in 1999 and 2000 (n = 37,401) for incidence of asthma diagnosis up to 34 years of age using outpatient and hospitalization records. Asthma cases were age- and sex-matched to five randomly chosen controls from the eligible cohort. We estimated each individual's exposure to ambient air pollution for the gestational period and first year of life using high-resolution pollution surfaces derived from regulatory monitoring data as well as land use regression models adjusted for temporal variation. We used logistic regression analyses to estimate effects of carbon monoxide, nitric oxide, nitrogen dioxide, particulate matter increased risk of asthma diagnosis with increased early life exposure to CO, NO, NO2, PM10, SO2, and black carbon and proximity to point sources. Traffic-related pollutants were associated with the highest risks: adjusted odds ratio = 1.08 (95% confidence interval, 1.041.12) for a 10-microg/m3 increase of NO, 1.12 (1.071.17) for a 10-microg/m3 increase in NO2, and 1.10 (1.061.13) for a 100-microg/m3 increase in CO. These data support the hypothesis that early childhood exposure to air pollutants plays a role in development of asthma.

Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.

PubMed

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.

The origin and early evolution of life on Earth.

PubMed

Oró, J; Miller, S L; Lazcano, A

1990-01-01

We do not have a detailed knowledge of the processes that led to the appearance of life on Earth. In this review we bring together some of the most important results that have provided insights into the cosmic and primitive Earth environments, particularly those environments in which life is thought to have originated. To do so, we first discuss the evidence bearing on the antiquity of life on our planet and the prebiotic significance of organic compounds found in interstellar clouds and in primitive solar system bodies such as comets, dark asteroids, and carbonaceous chondrites. This is followed by a discussion on the environmental models of the Hadean and early Archean Earth, as well as on the prebiotic formation of organic monomers and polymers essential to life. We then consider the processes that may have led to the appearance in the Archean of the first cells, and how these processes may have affected the early steps of biological evolution. Finally, the significance of these results to the study of the distribution of life in the Universe is discussed.

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

PubMed

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.

The effect of a low iron diet and early life methylmercury exposure in Daphnia pulex

PubMed Central

Hudson, Sherri L.; Doke, Dzigbodi A.; Gohlke, Julia M.

2016-01-01

Iron (Fe) deficiency increases risk for adverse health outcomes in humans; however little is known about the potential interaction with methylmercury (MeHg) exposure. Studies testing multiple stressor hypotheses are expensive and time consuming in mammalian model systems; therefore, determining relevance of alternative models is important. Daphnia pulex were fed standard or low-Fe diets of freshwater algae, Ankistrodesmus falcatus. MeHgCl (1600 ng/L) or vehicle was added to culture media for 24 h during early life, and the combinatorial effects of a low-Fe diet and MeHg exposure on lifespan, maturation time, and reproduction were evaluated. Lipid storage effects were measured using image analysis of Oil Red O staining and triacylglyceride quantification. Our results show a dose-dependent reduction in lifespan in D. pulex fed low Fe diets. Lipid analysis suggests an interactive effect of diet and MeHg exposure, with MeHg exposure increasing lipid storage in D. pulex fed a low-Fe diet. These findings suggest the effects of dietary iron intake and early life MeHg exposure in D. pulex may be mediated by changes in energetics that result in differential lipid storage. Therefore, lipid storage in D. pulex may be a useful screen for detecting long-term effects of multiple stressors early in life. PMID:26806633

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

PubMed

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.

Early life family conflict, Social interactions and Carotid Artery Intima-Media Thickness in Adulthood

PubMed Central

John-Henderson, Neha A.; Kamarck, Thomas W.; Muldoon, Matthew F.; Manuck, Stephen B.

2015-01-01

Objective 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. Methods Data were collected in a community sample of 503 adults (47.4 % male, mean age: 42.8 years [SD=7.3]). 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 (EMA) reports of social interactions, diversity of social roles, and perceived social support. Results 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=0.034, R2=0.46). Early life conflict was significantly related to diversity of social roles, perceived social support, and EMA 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% CI, 0.0001–0.0014 and β=0.001, 95% CI, 0.0002–0.0015, respectively). Conclusions 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. PMID:26809109

Early Life Family Conflict, Social Interactions, and Carotid Artery Intima-Media Thickness in Adulthood.

PubMed

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.

Impact of early life stress on the pathogenesis of mental disorders: relation to brain oxidative stress.

PubMed

Schiavone, Stefania; Colaianna, Marilena; Curtis, Logos

2015-01-01

Stress is an inevitable part of human life and it is experienced even before birth. Stress to some extent could be considered normal and even necessary for the survival and the regular psychological development during childhood or adolescence. However, exposure to prolonged stress could become harmful and strongly impact mental health increasing the risk of developing psychiatric disorders. Recent studies have attempted to clarify how the human central nervous system (CNS) reacts to early life stress, focusing mainly on neurobiological modifications. Oxidative stress, defined as a disequilibrium between the oxidant generation and the antioxidant response, has been recently described as a candidate for most of the observed modifications. In this review, we will discuss how prolonged stressful events during childhood or adolescence (such as early maternal separation, parental divorce, physical violence, sexual or psychological abuses, or exposure to war events) can lead to increased oxidative stress in the CNS and enhance the risk to develop psychiatric diseases such as anxiety, depression, drug abuse or psychosis. Defining the sources of oxidative stress following exposure to early life stress might open new beneficial insights in therapeutic approaches to these mental disorders.

Early life adversity influences stress response association with smoking relapse.

PubMed

al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

2017-11-01

We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

Analgesia for early-life pain prevents deficits in adult anxiety and stress in rats.

PubMed

Victoria, Nicole C; Karom, Mary C; Murphy, Anne Z

2015-01-01

Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this 'hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a 'hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants. © 2014 S. Karger AG, Basel.

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

PubMed

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

Reconceptualizing Early and Late Onset: A Life Course Analysis of Older Heroin Users

ERIC Educational Resources Information Center

Boeri, Miriam Williams; Sterk, Claire E.; Elifson, Kirk W.

2008-01-01

Purpose: Researchers' knowledge regarding older users of illicit drugs is limited despite the increasing numbers of users. In this article, we apply a life course perspective to gain a further understanding of older adult drug use, specifically contrasting early- and late-onset heroin users. Design and Methods: We collected qualitative data from…

Early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence.

PubMed

Rubner, Frederick J; Jackson, Daniel J; Evans, Michael D; Gangnon, Ronald E; Tisler, Christopher J; Pappas, Tressa E; Gern, James E; Lemanske, Robert F

2017-02-01

Early life rhinovirus (RV) wheezing illnesses and aeroallergen sensitization increase the risk of asthma at school age. Whether these remain risk factors for the persistence of asthma out to adolescence is not established. We sought to define the relationships among specific viral illnesses and the type and timing of aeroallergen sensitization with the persistence of asthma into adolescence. A total of 217 children were followed prospectively from birth to age 13 years. The etiology and timing of viral wheezing illnesses during the first 3 years of life were assessed along with patterns of allergen sensitization. The associations between viral wheezing illnesses, presence and pattern of aeroallergen sensitization, and asthma diagnosis at age 13 years were evaluated. When adjusted for all viral etiologies, wheezing with RV (odds ratio = 3.3; 95% CI, 1.5-7.1), but not respiratory syncytial virus (odds ratio = 1.0; 95% CI, 0.4-2.3), was associated with asthma at age 13 years. Age of aeroallergen sensitization also influenced asthma risk; 65% of children sensitized by age 1 year had asthma at age 13 years, compared with 40% of children not sensitized at age 1 year but sensitized by age 5 years, and 17% of children not sensitized at age 5 years. Early life aeroallergen sensitization and RV wheezing had additive effects on asthma risk at adolescence. In a high-risk birth cohort, the persistence of asthma at age 13 years was most strongly associated with outpatient wheezing illnesses with RV and aeroallergen sensitization in early life. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Childhood and later life stressors and increased inflammatory gene expression at older ages.

PubMed

Levine, M E; Cole, S W; Weir, D R; Crimmins, E M

2015-04-01

Adverse experiences in early life have the ability to "get under the skin" and affect future health. This study examined the relative influence of adversities during childhood and adulthood in accounting for individual differences in pro-inflammatory gene expression in late life. Using a pilot-sample from the Health and Retirement Study (N = 114) aged from 51 to 95, OLS regression models were run to determine the association between a composite score from three proinflammatory gene expression levels (PTGS2, ILIB, and IL8) and 1) childhood trauma, 2) childhood SES, 3) childhood health, 4) adult traumas, and 5) low SES in adulthood. Our results showed that only childhood trauma was found to be associated with increased inflammatory transcription in late life. Furthermore, examination of interaction effects showed that childhood trauma exacerbated the influence of low SES in adulthood on elevated levels of inflammatory gene expression-signifying that having low SES in adulthood was most damaging for persons who had experienced traumatic events during their childhood. Overall our study suggests that traumas experienced during childhood may alter the stress response, leading to more sensitive reactivity throughout the lifespan. As a result, individuals who experienced greater adversity in early life may be at higher risk of late life health outcomes, particularly if adulthood adversity related to SES persists. Copyright © 2015. Published by Elsevier Ltd.

Planetary Perspective on Life on Early Mars and the Early Earth

NASA Technical Reports Server (NTRS)

Sleep, Norman H.; Zahnle, Kevin

1996-01-01

Impacts of asteroids and comets posed a major hazard to the continuous existence of early life on Mars as on the Earth. The chief danger was presented by globally distributed ejecta, which for very large impacts takes the form of transient thick rock vapor atmospheres; both planets suffered such impacts repeatedly. The exposed surface on both planets was sterilized when it was quickly heated to the temperature of condensed rock vapor by radiation and rock rain. Shallow water bodies were quickly evaporated and sterilized. Any surviving life must have been either in deep water or well below the surface.

Effects of Increased Flight on the Energetics and Life History of the Butterfly Speyeria mormonia

PubMed Central

Niitepõld, Kristjan; Boggs, Carol L.

2015-01-01

Movement uses resources that may otherwise be allocated to somatic maintenance or reproduction. How does increased energy expenditure affect resource allocation? Using the butterfly Speyeria mormonia, we tested whether experimentally increased flight affects fecundity, lifespan or flight capacity. We measured body mass (storage), resting metabolic rate and lifespan (repair and maintenance), flight metabolic rate (flight capacity), egg number and composition (reproduction), and food intake across the adult lifespan. The flight treatment did not affect body mass or lifespan. Food intake increased sufficiently to offset the increased energy expenditure. Total egg number did not change, but flown females had higher early-life fecundity and higher egg dry mass than control females. Egg dry mass decreased with age in both treatments. Egg protein, triglyceride or glycogen content did not change with flight or age, but some components tracked egg dry mass. Flight elevated resting metabolic rate, indicating increased maintenance costs. Flight metabolism decreased with age, with a steeper slope for flown females. This may reflect accelerated metabolic senescence from detrimental effects of flight. These effects of a drawdown of nutrients via flight contrast with studies restricting adult nutrient input. There, fecundity was reduced, but flight capacity and lifespan were unchanged. The current study showed that when food resources were abundant, wing-monomorphic butterflies living in a continuous meadow landscape resisted flight-induced stress, exhibiting no evidence of a flight-fecundity or flight-longevity trade-off. Instead, flight changed the dynamics of energy use and reproduction as butterflies adopted a faster lifestyle in early life. High investment in early reproduction may have positive fitness effects in the wild, as long as food is available. Our results help to predict the effect of stressful conditions on the life history of insects living in a changing world

Mucosal IgA increase in rats by continuous CLA feeding during suckling and early infancy.

PubMed

Pérez-Cano, Francisco J; Ramírez-Santana, Carolina; Molero-Luís, Marta; Castell, Margarida; Rivero, Montserrat; Castellote, Cristina; Franch, Angels

2009-03-01

The aim of this work was to establish the effect of the cis9,trans11 conjugated linoleic acid (CLA) isomer on mucosal immunity during early life in rats, a period when mucosal immunoglobulin production is poorly developed, as is also the case in humans. CLA supplementation was performed during three life periods: gestation, suckling, and early infancy. The immune status of supplemented animals was evaluated at two time points: at the end of the suckling period (21-day-old rats) and 1 week after weaning (28-day-old rats). Secretory IgA was quantified in intestinal washes from 28-day-old rats by ELISA technique. IgA, TGFbeta, and PPARgamma mRNA expression was measured in small intestine and colon by real time PCR, using Taqman specific probes and primers. IgA mucosal production was enhanced in animals supplemented with CLA during suckling and early infancy: in 28-day-old rats, IgA mRNA expression was increased in small intestine and colon by approximately 6- and 4-fold, respectively, and intestinal IgA protein by approximately 2-fold. TGFbeta gene expression was independent of age and type of tissue considered, and was not modified by dietary CLA. Gene expression of PPARgamma, a possible mediator of CLA's effects was also upregulated in animals receiving CLA during early life. In conclusion, dietary supplementation with CLA during suckling and extended to early infancy enhances development of the intestinal immune response in rats.

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

USGS Publications Warehouse

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.

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

PubMed

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

Promoting Career Development and Life Design in the Early Years of a Person's Life

ERIC Educational Resources Information Center

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…

What doesn't kill you makes you poorer: Adult wages and early-life mortality in India.

PubMed

Lawson, Nicholas; Spears, Dean

2016-05-01

A growing literature indicates that effects of early-life health on adult economic outcomes could be substantial in developing countries, but the magnitude of this effect is debated. We document a robust gradient between the early-life mortality environment to which men in India were locally exposed in their district and year of birth and the wages that they earn as adults. A 1 percentage point reduction in infant mortality (or 10 point reduction in IMR) in an infant's district and year of birth is associated with an approximately 2 percent increase in his subsequent adult wages. Consistent with theories and evidence in the literature, we find that the level of schooling chosen for a child does not mediate this association. Because of its consequences for subsequent wages, early-life health could also have considerable fiscal externalities; if so, public health investments could come at very low net present cost. Copyright © 2015 Elsevier B.V. All rights reserved.

Probiotics in early life: a preventative and treatment approach.

PubMed

Hashemi, Ashkan; Villa, Christopher R; Comelli, Elena M

2016-04-01

Microbial colonization of the infant gut plays a key role in immunological and metabolic pathways impacting human health. Since the maturation of the gut microbiota coincides with early life development, failure to develop a health compatible microbiota composition may result in pathology and disease in later life. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Maternal transfer of microorganisms is possible during pregnancy and lactation, and the mother's diet and microbiota can influence that of her offspring. Furthermore, pre-term birth, Caesarean section birth, formula feeding, antibiotic use, and malnutrition have been linked to dysbiosis, which in turn is associated with several pathologies such as necrotizing enterocolitis, inflammatory bowel diseases, antibiotic associated diarrhea, colic, and allergies. Thus, early life should represent a preferred stage of life for probiotic interventions. In this context, they could be regarded as a means to 'program' the individual for health maintenance, in order to prevent pathologies associated with dysbiosis. In order to elucidate the mechanisms underlying the benefits of probiotic administration, pre-clinical studies have been conducted and found an array of positive results such as improved microbial composition, intestinal maturation, decreased pathogenic load and infections, and improved immune response. Moreover, specific probiotic strains administered during the perinatal period have shown promise in attenuating severity of necrotizing enterocolitis. The mechanisms elucidated suggest that probiotic interventions in early life can be envisaged for disease prevention in both healthy offspring and offspring at risk of chronic disease.

Early-late life trade-offs and the evolution of ageing in the wild.

PubMed

Lemaître, Jean-François; Berger, Vérane; Bonenfant, Christophe; Douhard, Mathieu; Gamelon, Marlène; Plard, Floriane; Gaillard, Jean-Michel

2015-05-07

Empirical evidence for declines in fitness components (survival and reproductive performance) with age has recently accumulated in wild populations, highlighting that the process of senescence is nearly ubiquitous in the living world. Senescence patterns are highly variable among species and current evolutionary theories of ageing propose that such variation can be accounted for by differences in allocation to growth and reproduction during early life. Here, we compiled 26 studies of free-ranging vertebrate populations that explicitly tested for a trade-off between performance in early and late life. Our review brings overall support for the presence of early-late life trade-offs, suggesting that the limitation of available resources leads individuals to trade somatic maintenance later in life for high allocation to reproduction early in life. We discuss our results in the light of two closely related theories of ageing-the disposable soma and the antagonistic pleiotropy theories-and propose that the principle of energy allocation roots the ageing process in the evolution of life-history strategies. Finally, we outline research topics that should be investigated in future studies, including the importance of natal environmental conditions in the study of trade-offs between early- and late-life performance and the evolution of sex-differences in ageing patterns. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Early evolution without a tree of life

PubMed Central

2011-01-01

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. PMID:21714942

Sex-dependent effects of an early life treatment in rats that increases maternal care: vulnerability or resilience?

PubMed Central

Fuentes, Sílvia; Daviu, Núria; Gagliano, Humberto; Garrido, Pedro; Zelena, Dóra; Monasterio, Nela; Armario, Antonio; Nadal, Roser

2014-01-01

Early life stress (ELS) in rodents has profound long-term effects that are partially mediated by changes in maternal care. ELS not only induces “detrimental” effects in adulthood, increasing psychopathology, but also promotes resilience to further stressors. In Long-Evans rats, we evaluated a combination of two procedures as a model of ELS: restriction of bedding during the first post-natal days and exposure to a “substitute” mother. The maternal care of biological and “substitute” mothers was measured. The male and female offspring were evaluated during adulthood in several contexts. Anxiety was measured by the elevated plus-maze (EPM), acoustic startle response (ASR) and forced swim test (FST). In other group of animals, novelty-seeking was measured (activity in an inescapable novel environment, preference for novel environments and exploration of novel objects). Plasmatic ACTH and corticosterone in basal conditions and in response to stress were also measured. Cognitive impulsivity was assessed by a delay-discounting paradigm, and impulsive action, attention and compulsive-like behavior by a five choice serial reaction time task (5CSRTT). ELS decreased pup body weight and increased the care of the biological mother; however, the “substitute” mother did not exhibit overt maltreatment. A mixture of “detrimental” and “beneficial” effects was shown. In the 5CSRTT, attention was impaired in both genders, and in females, ELS increased compulsive-like behavior. Novel object exploration was only increased by ELS in males, but the preference for novel spaces decreased in both genders. Baseline anxiety (EPM and ASR) and recognition memory were not affected. Unexpectedly, ELS decreased the ACTH response to novelty and swim stress and increased active coping in the FST in both genders. Cognitive impulsivity was decreased only in females, but impulsive action was not affected. The enhancement in maternal care may “buffer” the effects of ELS in a

Early-life glucocorticoids programme behaviour and metabolism in adulthood in zebrafish

PubMed Central

Wilson, K S; Tucker, C S; Al-Dujaili, E A S; Holmes, M C; Hadoke, P W F; Kenyon, C J

2016-01-01

Glucocorticoids (GCs) in utero influence embryonic development with consequent programmed effects on adult physiology and pathophysiology and altered susceptibility to cardiovascular disease. However, in viviparous species, studies of these processes are compromised by secondary maternal influences. The zebrafish, being fertilised externally, avoids this problem and has been used here to investigate the effects of transient alterations in GC activity during early development. Embryonic fish were treated either with dexamethasone (a synthetic GC), an antisense GC receptor (GR) morpholino (GR Mo), or hypoxia for the first 120h post fertilisation (hpf); responses were measured during embryonic treatment or later, post treatment, in adults. All treatments reduced cortisol levels in embryonic fish to similar levels. However, morpholino- and hypoxia-treated embryos showed delayed physical development (slower hatching and straightening of head–trunk angle, shorter body length), less locomotor activity, reduced tactile responses and anxiogenic activity. In contrast, dexamethasone-treated embryos showed advanced development and thigmotaxis but no change in locomotor activity or tactile responses. Gene expression changes were consistent with increased (dexamethasone) and decreased (hypoxia, GR Mo) GC activity. In adults, stressed cortisol values were increased with dexamethasone and decreased by GR Mo and hypoxia pre-treatments. Other responses were similarly differentially affected. In three separate tests of behaviour, dexamethasone-programmed fish appeared ‘bolder’ than matched controls, whereas Mo and hypoxia pre-treated fish were unaffected or more reserved. Similarly, the dexamethasone group but not the Mo or hypoxia groups were heavier, longer and had a greater girth than controls. Hyperglycaemia and expression of GC responsive gene (pepck) were also increased in the dexamethasone group. We conclude that GC activity controls many aspects of early-life growth and

Early-Life Nutrition and Neurodevelopment: Use of the Piglet as a Translational Model12

PubMed Central

Mudd, Austin T

2017-01-01

Optimal nutrition early in life is critical to ensure proper structural and functional development of infant organ systems. Although pediatric nutrition historically has emphasized research on the relation between nutrition, growth rates, and gastrointestinal maturation, efforts increasingly have focused on how nutrition influences neurodevelopment. The provision of human milk is considered the gold standard in pediatric nutrition; thus, there is interest in understanding how functional nutrients and bioactive components in milk may modulate developmental processes. The piglet has emerged as an important translational model for studying neurodevelopmental outcomes influenced by pediatric nutrition. Given the comparable nutritional requirements and strikingly similar brain developmental patterns between young pigs and humans, the piglet is being used increasingly in developmental nutritional neuroscience studies. The piglet primarily has been used to assess the effects of dietary fatty acids and their accretion in the brain throughout neurodevelopment. However, recent research indicates that other dietary components, including choline, iron, cholesterol, gangliosides, and sialic acid, among other compounds, also affect neurodevelopment in the pig model. Moreover, novel analytical techniques, including but not limited to MRI, behavioral assessments, and molecular quantification, allow for a more holistic understanding of how nutrition affects neurodevelopmental patterns. By combining early-life nutritional interventions with innovative analytical approaches, opportunities abound to quantify factors affecting neurodevelopmental trajectories in the neonate. This review discusses research using the translational pig model with primary emphasis on early-life nutrition interventions assessing neurodevelopment outcomes, while also discussing nutritionally-sensitive methods to characterize brain maturation. PMID:28096130

Early life permethrin exposure leads to hypervitaminosis D, nitric oxide and catecholamines impairment.

PubMed

Fedeli, Donatella; Carloni, Manuel; Nasuti, Cinzia; Gambini, Anna; Scocco, Vitangelo; Gabbianelli, Rosita

2013-09-01

The aim of this study is to gain more knowledge on the impact of early life pesticide exposure on premature aging. The effect of a low dose of the insecticide permethrin administered to rats during early life (1/50 LD50, from 6th to 21st day of life) was analyzed by measuring some metabolites in plasma and urine of 500-day-old animals. Significant differences in early life treated rats compared to the control group were found in the plasma levels of Ca(++), Na(+), 25-hydroxy-vitamin D, adrenaline, noradrenaline, nitric oxide, cholesterol and urea while in urine only Na(+) content was different. These results add information on the impact of permethrin during the neonatal period, supporting the evidence that early life environmental exposure to xenobiotics has long-term effects, inducing modifications in adulthood that can be revealed by the analysis of some macroelements, metabolites and catecholamines in plasma, when rats are 500 days old. Copyright © 2013 Elsevier Inc. All rights reserved.

Attentional avoidance of fearful facial expressions following early life stress is associated with impaired social functioning.

PubMed

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.

The march from early life food sensitization to allergic disease: a systematic review and meta-analyses of birth cohort studies.

PubMed

Alduraywish, S A; Lodge, C J; Campbell, B; Allen, K J; Erbas, B; Lowe, A J; Dharmage, S C

2016-01-01

There is growing evidence for an increase in food allergies. The question of whether early life food sensitization, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question. We aimed to systematically investigate and meta-analyse the evidence for associations between early food sensitization and allergic disease in birth cohorts. MEDLINE and SCOPUS databases were searched for birth cohorts that have investigated the association between food sensitization in the first 2 years and subsequent wheeze/asthma, eczema and/or allergic rhinitis. We performed meta-analyses using random-effects models to obtain pooled estimates, stratified by age group. The search yielded fifteen original articles representing thirteen cohorts. Early life food sensitization was associated with an increased risk of infantile eczema, childhood wheeze/asthma, eczema and allergic rhinitis and young adult asthma. Meta-analyses demonstrated that early life food sensitization is related to an increased risk of wheeze/asthma (pooled OR 2.9; 95% CI 2.0-4.0), eczema (pooled OR 2.7; 95% CI 1.7-4.4) and allergic rhinitis (pooled OR 3.1; 95% CI 1.9-4.9) from 4 to 8 years. Food sensitization in the first 2 years of life can identify children at high risk of subsequent allergic disease who may benefit from early life preventive strategies. However, due to potential residual confounding in the majority of studies combined with lack of follow-up into adolescence and adulthood, further research is needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

External-environmental and internal-health early life predictors of adolescent development.

PubMed

Hartman, Sarah; Li, Zhi; Nettle, Daniel; Belsky, Jay

2017-12-01

A wealth of evidence documents associations between various aspects of the rearing environment and later development. Two evolutionary-inspired models advance explanations for why and how such early experiences shape later functioning: (a) the external-prediction model, which highlights the role of the early environment (e.g., parenting) in regulating children's development, and (b) the internal-prediction model, which emphasizes internal state (i.e., health) as the critical regulator. Thus, by using data from the NICHD Study of Early Child Care and Youth Development, the current project draws from both models by investigating whether the effect of the early environment on later adolescent functioning is subject to an indirect effect by internal-health variables. Results showed a significant indirect effect of internal health on the relation between the early environment and adolescent behavior. Specifically, early environmental adversity during the first 5 years of life predicted lower quality health during childhood, which then led to problematic adolescent functioning and earlier age of menarche for girls. In addition, for girls, early adversity predicted lower quality health that forecasted earlier age of menarche leading to increased adolescent risk taking. The discussion highlights the importance of integrating both internal and external models to further understand the developmental processes that effect adolescent behavior.

Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

PubMed

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.

Life Satisfaction in Early Adolescence: Personal, Neighborhood, School, Family, and Peer Influences

ERIC Educational Resources Information Center

Oberle, Eva; Schonert-Reichl, Kimberly A.; Zumbo, Bruno D.

2011-01-01

Drawing from an ecological assets framework as well as research and theory on positive youth development, this study examined the relationship of early adolescents' satisfaction with life to trait optimism and assets representing the social contexts in which early adolescents spend most of their time. Self-reports of satisfaction with life,…

Low-grade disease activity in early life precedes childhood asthma and allergy.

PubMed

Chawes, Bo Lund Krogsgaard

2016-08-01

Asthma and allergies are today the most common chronic diseases in children and the leading causes of school absences, chronic medication usage, emergency department visits and hospitalizations, which affect all members of the family and represent a significant societal and scientific challenge. These highly prevalent disorders are thought to originate from immune distortion in early childhood, but the etiology and heterogeneity of the disease mechanisms are not understood, which hampers preventive initiatives and makes treatment inadequate. The objective of this thesis is to investigate the presence of an early life disease activity prior to clinical symptoms to understand the anteceding pathophysiological steps towards childhood asthma and allergy. The thesis is built on seven studies from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) birth cohort examining biomarkers of disease activity in 411 asymptomatic neonates in cord blood (I-II), urine (III), exhaled breath (IV-V) and infant lung function (VI-VII) in relation to the subsequent development of asthma and allergy during the first seven years of life. In papers I-II, we studied cord blood chemokines and 25(OH)-vitamin D, which represent a proxy of the inborn immature immune system, the intrauterine milieu, and the maternal immune health during pregnancy. High levels of the Th2-related chemokine CCL22 and high CCL22/CXCL11 ratio were positively correlated with total IgE level during preschool age (II). This suggests an inborn Th2 skewing of the immune system in healthy newborns subsequently developing elevated total IgE antibodies, which is considered to increase the risk of asthma and allergies later in life. Additionally, deficient cord blood 25(OH)-vitamin D levels were associated with a 2.7-fold increased risk of recurrent wheeze at age 0-7 years (I). Together, these findings support the concept that early life immune programming in the pre-symptomatic era plays an essential role

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

PubMed

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.

The Changing Life Space of Early Adolescence.

ERIC Educational Resources Information Center

Larson, Reed, Ed.; Richards, Maryse, H., Ed.

1989-01-01

Eight papers are presented that describe the daily experience of White American children in grades 5 through 9. Each paper examines a segment of daily activity (e.g., schoolwork, talking, sports) and the associated affective states for 401 participants to provide a picture of the life space of early adolescence. (SLD)

Early-Life Stress Is Associated with Gender-Based Vulnerability to Epileptogenesis in Rat Pups

PubMed Central

Desgent, Sébastien; Duss, Sandra; Sanon, Nathalie T.; Lema, Pablo; Lévesque, Maxime; Hébert, David; Rébillard, Rose-Marie; Bibeau, Karine; Brochu, Michèle; Carmant, Lionel

2012-01-01

During development, the risk of developing mesial temporal lobe epilepsy (MTLE) increases when the developing brain is exposed to more than one insult in early life. Early life insults include abnormalities of cortical development, hypoxic-ischemic injury and prolonged febrile seizures. To study epileptogenesis, we have developed a two-hit model of MTLE characterized by two early-life insults: a freeze lesion-induced cortical malformation at post-natal day 1 (P1), and a prolonged hyperthermic seizure (HS) at P10. As early life stressors lead to sexual dimorphism in both acute response and long-term outcome, we hypothesized that our model could lead to gender-based differences in acute stress response and long-term risk of developing MTLE. Male and female pups underwent a freeze-lesion induced cortical microgyrus at P1 and were exposed to HS at P10. Animals were monitored by video-EEG from P90 to P120. Pre and post-procedure plasma corticosterone levels were used to measure stress response at P1 and P10. To confirm the role of sex steroids, androgenized female pups received daily testosterone injections to the mother pre-natally and post-natally for nine days while undergoing both insults. We demonstrated that after both insults females did not develop MTLE while all males did. This correlated with a rise in corticosterone levels at P1 following the lesion in males only. Interestingly, all androgenized females showed a similar rise in corticosterone at P1, and also developed MTLE. Moreover, we found that the cortical lesion significantly decreased the latency to generalized convulsion during hyperthermia at P10 in both genders. The cortical dysplasia volumes at adulthood were also similar between male and female individuals. Our data demonstrate sexual dimorphism in long-term vulnerability to develop epilepsy in the lesion + hyperthermia animal model of MTLE and suggest that the response to early-life stress at P1 contributes significantly to epileptogenesis in a

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

PubMed

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.

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.

PubMed

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

Natural selection and sex differences in morbidity and mortality in early life.

PubMed

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.

Barium distributions in teeth reveal early life dietary transitions in primates

PubMed Central

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

Barium distributions in teeth reveal early-life dietary transitions in primates.

PubMed

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.

Bayesian analysis of the astrobiological implications of life's early emergence on Earth.

PubMed

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.

Early childhood growth failure and the developmental origins of adult disease: Do enteric infections and malnutrition increase risk for the metabolic syndrome?

PubMed Central

DeBoer, Mark D.; Lima, Aldo A. M.; Oría, Reinaldo B.; Scharf, Rebecca J.; Moore, Sean R.; Luna, Max A.; Guerrant, Richard L.

2012-01-01

Hypotheses regarding the developmental origins of health and disease postulate that developing fetuses–and potentially young children—undergo adaptive epigenetic changes with longstanding effects on metabolism and other processes. Ongoing research explores whether these adaptations occur during early life following malnutrition. In the developing world there remains a high degree of nutritional stunting—linear growth failure due to inadequate calories that may be exacerbated by inflammation from ongoing infections. In areas with poor sanitation children experience vicious cycles of enteric infections and malnutrition, resulting in poor nutrient absorption from intestinal mucosa changes now termed “environmental enteropathy.” Emerging evidence links early childhood diarrhea and/or growth failure with increased CVD risk factors in later life, including dyslipidemia, hypertension and glucose intolerance. The mechanisms for these associations remain poorly understood and may relate to epigenetic responses to poor nutrition, increased inflammation or both. Given increases in CVD in developing areas of the world, associations between childhood malnutrition, early life infections and increased CVD risk factors underscore further reasons to improve nutrition and infection-related outcomes for young children worldwide. PMID:23110643

Respiratory physiology during early life.

PubMed

Stocks, J

1999-08-01

Despite the rapid adaptation to extrauterine life, the respiratory system of an infant is not simply a miniaturized version of that of an adult, since the rapid somatic growth that occurs during the first year of life is accompanied by major developmental changes in respiratory physiology. The highly compliant chest wall of the infant results in relatively low transpulmonary pressures at end expiration with increased tendency of the small peripheral airways to close during tidal breathing. This not only impairs gas exchange and ventilation-perfusion balance, particularly in dependent parts of the lung, but, together with the small absolute size of the airways, renders the infant and young child particularly susceptible to airway obstruction. Premature airways are highly compliant structures compared with those of mature newborns or adults. This increased compliance can cause airway collapse, resulting in increased airways resistance, flow limitation, poor gas exchange and increased work of breathing. Although there is clear evidence that airway reactivity is present from birth, its role in wheezing lower respiratory tract illnesses in young infants may be overshadowed by pre-existing abnormalities of airway geometry and lung mechanics, or by pathological changes such as airway oedema and mucus hypersecretion. Attempts to assess age-related changes in airway reactivity or response to aerosol therapy in the very young is confounded by changes in breathing patterns and the fact that infants are preferential nose breathers. There is increasing evidence that pre-existing abnormalities of respiratory function, associated with adverse events during foetal life (including maternal smoking during pregnancy), and familial predisposition to wheezing are important determinants of wheezing illnesses during the first years of life. This emphasizes the need to identify and minimize any factors that threaten the normal development of the lung during this critical period if

Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh

PubMed Central

Smith, Allan H; Yunus, Mohammad; Khan, Al Fazal; Ercumen, Ayse; Yuan, Yan; Smith, Meera Hira; Liaw, Jane; Balmes, John; von Ehrenstein, Ondine; Raqib, Rubhana; Kalman, David; Alam, Dewan S; Streatfield, Peter K; Steinmaus, Craig

2013-01-01

Background Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited. Methods This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7–17 years. Children with in utero and early life arsenic exposure were compared with children exposed to less than 10 µg/l in utero and throughout childhood. Because most children drank the same water as their mother had drunk during pregnancy, we could not assess only in utero or only childhood exposure. Results Children exposed in utero to more than 500 µg/l of arsenic were more than eight times more likely to report wheezing when not having a cold [odds ratio (OR) = 8.41, 95% confidence interval (CI): 1.66–42.6, P < 0.01] and more than three times more likely to report shortness of breath when walking on level ground (OR = 3.86, 95% CI: 1.09–13.7, P = 0.02) and when walking fast or climbing (OR = 3.19, 95% CI: 1.22–8.32, P < 0.01]. However, there was little evidence of reduced lung function in either exposure category. Conclusions Children with high in utero and early life arsenic exposure had marked increases in several chronic respiratory symptoms, which could be due to in utero exposure or to early life exposure, or to both. Our findings suggest that arsenic in water has early pulmonary effects and that respiratory symptoms are a better marker of early life arsenic toxicity than changes in lung function measured by spirometry. PMID:24062297

Early life adversity and adult biological risk profiles.

PubMed

Friedman, Esther M; Karlamangla, Arun S; Gruenewald, Tara L; Koretz, Brandon; Seeman, Teresa E

2015-01-01

To determine whether there is a relationship between early life adversity (ELA) and biological parameters known to predict health risks and to examine the extent to which circumstances in midlife mediate this relationship. We analyzed data on 1180 respondents from the biomarker subsample of the second wave of the National Survey of Midlife Development in the United States. ELA assessments were based on childhood socioeconomic disadvantage (i.e., on welfare, perceived low income, and less educated parents) and other stressors (e.g., parental death, parental divorce, and parental physical abuse). The outcome variable was cumulative allostatic load (AL), a marker of biological risk. We also incorporate information on adult circumstances, including than following: education, social relationships, and health behaviors. Childhood socioeconomic adversity and physical abuse were associated with increased AL (B = 0.094, standard error = 0.041, and B = 0.263, standard error = 0.091 respectively), with nonsignificant associations for parental divorce and death with AL. Adult education mediated the relationship between socioeconomic ELA and cumulative AL to the point of nonsignificance, with this factor alone explaining nearly 40% of the relationship. The association between childhood physical abuse and AL remained even after adjusting for adult educational attainments, social relationships, and health behaviors. These associations were most pronounced for secondary stress systems, including inflammation, cardiovascular function, and lipid metabolism. The physiological consequences of early life socioeconomic adversity are attenuated by achieving high levels of schooling later on. The adverse consequences of childhood physical abuse, on the other hand, persist in multivariable-adjusted analysis.

Unhealthy lifestyle in early psychoses: the role of life stress and the hypothalamic-pituitary-adrenal axis.

PubMed

Manzanares, Núria; Monseny, Rosa; Ortega, Laura; Montalvo, Itziar; Franch, Joan; Gutiérrez-Zotes, Alfonso; Reynolds, Rebecca M; Walker, Brian R; Vilella, Elisabet; Labad, Javier

2014-01-01

An unhealthy lifestyle is thought to contribute to the metabolic syndrome in subjects with psychoses. In the present study we aimed to study whether life stress or cortisol measures may influence dietary patterns in subjects with early stages of psychoses. We studied 81 subjects with early psychoses (65 subjects with a psychotic disorder [PD] and <5 years of illness; 16 subjects at risk for psychosis [high-risk, HR]) and a control group of 25 healthy subjects (HS). Dietary habits were examined by a dietician, who registered food intake (24h recall). Physical activity was assessed by validated questionnaire. Life stress was assessed with Holmes-Rahe Social Readjustment Scale. Fasting morning salivary and plasma cortisol levels were determined. We found that PD and HR reported an unhealthier lifestyle with more smoking, reduced physical activity and poorer dietary habits. HR reported increased intake of calories and saturated fatty acids and reduced protein consumption, when compared to HS. Life stress was a predictor of these adverse behaviours, although we found opposite associations in HR and PD. Life stress was associated with increased intake of refined sugar in PD and decreased intake in HR and HS. Salivary cortisol was related to increased intake of saturated fat only in HR subjects, but cortisol levels in plasma or saliva were not associated with other dietary habits or obesity measures (BMI, waist circumference). Our study suggests that unhealthy diet in early psychoses is influenced by stress, but our data do not support this effect being mediated by hypercortisolism. Future preventive interventions in psychosis may target dietary habits, particularly for those who are at risk for psychosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Effects of early life stress on amygdala and striatal development

PubMed Central

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

Effects of early life stress on amygdala and striatal development.

PubMed

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.

Age Validation in the Long Life Family Study Through a Linkage to Early-Life Census Records

PubMed Central

2013-01-01

Objectives. Studies of health and longevity require accurate age reporting. Age misreporting among older adults in the United States is common. Methods. Participants in the Long Life Family Study (LLFS) were matched to early-life census records. Age recorded in the census was used to evaluate age reporting in the LLFS. The study population was 99% non-Hispanic white. Results. About 88% of the participants were matched to 1910, 1920, or 1930 U.S. censuses. Match success depended on the participant’s education, place of birth, and the number of censuses available to be searched. Age at the time of the interview based on the reported date of birth and early-life census age were consistent for about 89% of the participants, and age consistency within 1 year was found for about 99% of the participants. Discussion. It is possible to match a high fraction of older study participants to their early-life census records when detailed information is available on participants’ family of origin. Such record linkage can provide an important source of information for evaluating age reporting among the oldest old participants. Our results are consistent with recent studies suggesting that age reporting among older whites in the United States appears to be quite good. PMID:23704206

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

PubMed

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.

Growth in early life and the development of obesity by age 9 years: are there critical periods and a role for an early life stressor?

PubMed

Giles, L C; Whitrow, M J; Rumbold, A R; Davies, C E; de Stavola, B; Pitcher, J B; Davies, M J; Moore, V M

2013-04-01

Rapid growth, possibly occurring in critical periods in early life, may be important for the development of obesity. It is unknown whether this is influenced by postnatal exposures such as age-relevant sources of stress. Frequent house moves may be one such stressor. We aimed to examine if there is a period of growth in early life critical for the development of child obesity by age 9 years and assess the role of house moves in modifying any relationships between early life growth and obesity at age 9 years. Prospective Australian birth cohort study. In all, 392 children with serial body size measurements from birth to age 9 years. Standardized body mass index (z-BMI) was available for six time points (spanning birth to 3½ years), and the total number of house moves between birth and 3½ years. The outcomes considered were z-BMI and % body fat (%BF) at age 9 years. Linear regression models were used to estimate the effects of serial measurements of z-BMI and number of house moves on the outcomes. Life-course plots showed that z-BMI at 3½ years was a statistically significant predictor of z-BMI at 9 years (β=0.80; standard error (s.e.), 0.04), whereas z-BMI at 9 months (β=-1.13; s.e., 0.40) and 3½ years (β=4.82; s.e., 0.42) were significant predictors of %BF at age 9 years. There were statistically significant interactions between the number of house moves and change in z-BMI between 9 and 12 months, such that ≥ 3 house moves in early life amplified the detrimental effects of earlier rapid growth on both body size and composition at age 9 years. In the absence of evidence for a single critical period, efforts to prevent overweight and obesity are required throughout childhood. In addition, modifiable postnatal stressors may exacerbate effects of early growth on obesity in later childhood.

Predicting Negative Life Outcomes from Early Aggressive-Disruptive Behavior Trajectories: Gender Differences in Maladaptation across Life Domains

ERIC Educational Resources Information Center

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…

Tissue-Specific Expression of DNA Methyltransferases Involved in Early-Life Nutritional Stress of Chicken, Gallus gallus

PubMed Central

Kang, Seong W.; Madkour, Mahmoud; Kuenzel, Wayne J.

2017-01-01

DNA methylation was reported as a possible stress-adaptation mechanism involved in the transcriptional regulation of stress responsive genes. Limited data are available on effects of psychological stress and early-life nutritional stress on DNA methylation regulators [DNMTs: DNA (cytosine-5)-methyltransferase 1 (DNMT1), DNMT1 associated protein (DMAP1), DNMT 3 alpha (DNMT3A) and beta (DNMT3B)] in avian species. The objectives of this study were to: (1) investigate changes in expression of DNMT1, DMAP1, DNMT3A, and DNMT3B following acute (AS) or chronic immobilization stress (CS); (2) test immediate effect of early-life nutritional stress [food deprivation (FD) for 12 h (12hFD) or 36 h (36hFD) at the post-hatching period] on expression of DNA methylation regulators and glucocorticoid receptor (GR), and the long-term effect of early-life nutritional stress at 6 weeks of age. Expression of DNMTs and plasma corticosterone (CORT) concentration decreased by CS compared to AS (p < 0.05), indicating differential roles of DNA methylation regulators in the stress response. Plasma CORT at 12hFD and 36hFD birds increased compared to control birds (12hF and 36hF), but there were no significant differences in plasma CORT of 12hFD and 36hFD birds at 6 weeks of age compared to 6 week controls. DNMT1, DMAP1, and DNMT3B expression in the anterior pituitary increased by 12hFD, but decreased at 36hFD compared to their controls (P < 0.05). In liver, DNMT1, DNMT3A, and DNMT3B expression decreased by 12hFD, however, no significant changes occurred at 36hFD. Expression of DMAP1, DNMT3A, and DNMT3B in anterior pituitary and DMAP1 and DNMT3A expression in liver at 6 weeks of age were higher in 36hFD stressed birds compared to controls as well as 12hFD stressed birds. Hepatic GR expression decreased by 12hFD and increased by 36hFD (p < 0.05). Expression patterns of GR in the liver of FD stress-induced birds persisted until 6 weeks of age, suggesting the possible lifelong involvement of liver

Ammonia and urea handling by early life stages of fishes.

PubMed

Zimmer, Alex M; Wright, Patricia A; Wood, Chris M

2017-11-01

Nitrogen metabolism in fishes has been a focus of comparative physiologists for nearly a century. In this Review, we focus specifically on early life stages of fishes, which have received considerable attention in more recent work. Nitrogen metabolism and excretion in early life differs fundamentally from that of juvenile and adult fishes because of (1) the presence of a chorion capsule in embryos that imposes a limitation on effective ammonia excretion, (2) an amino acid-based metabolism that generates a substantial ammonia load, and (3) the lack of a functional gill, which is the primary site of nitrogen excretion in juvenile and adult fishes. Recent findings have shed considerable light on the mechanisms by which these constraints are overcome in early life. Perhaps most importantly, the discovery of Rhesus (Rh) glycoproteins as ammonia transporters and their expression in ion-transporting cells on the skin of larval fishes has transformed our understanding of ammonia excretion by fishes in general. The emergence of larval zebrafish as a model species, together with genetic knockdown techniques, has similarly advanced our understanding of ammonia and urea metabolism and excretion by larval fishes. It has also now been demonstrated that ammonia excretion is one of the primary functions of the developing gill in rainbow trout larvae, leading to new hypotheses regarding the physiological demands driving gill development in larval fishes. Here, we highlight and discuss the dramatic changes in nitrogen handling that occur over early life development in fishes. © 2017. Published by The Company of Biologists Ltd.

The Role of Early-Life Educational Quality and Literacy in Explaining Racial Disparities in Cognition in Late Life

PubMed Central

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.

2015-01-01

Objectives. 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. Method. 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. Results. The sample consisted of 1,679U.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. Discussion. Early-life educational quality and literacy in late life explain a substantial portion of race-related disparities in late-life cognitive function. PMID:24584038

Early-life Sodium-exposure Unmasks Susceptibility to Stroke in hyperlipidemic-hypertensive Tg[hCETP]25-Rats

PubMed Central

Decano, Julius L.; Viereck, Jason C.; McKee, Ann C.; Hamilton, James A.; Ruiz-Opazo, Nelson; Herrera, Victoria L.M.

2009-01-01

Background Early-life risk factor exposure increases aortic atherosclerosis and blood pressure in humans and animal models, however, limited insight has been made into end-organ complications. Methods and Results We investigated the effects of early-life Na-exposure (0.23% vs 0.4%NaCl regular-rat chow) on vascular disease outcomes using the inbred, transgenic[hCETP]25 Dahl salt-sensitive hypertensive rat model of male-predominant coronary atherosclerosis, Tg25. Rather than the expected increased coronary heart disease, fetal 0.4%Na-exposure (≤2g-Na/2000cal/diet/day) induced adult-onset stroke in both sexes (ANOVA P<0.0001), with earlier stroke-onset in Tg25-females. Analysis of later onsets of 0.4%Na-exposure resulted in decreased stroke-risk and later stroke-onsets, despite longer 0.4%Na-exposure durations, indicating increasing risk with earlier onsets of 0.4%Na-exposure. Histological analysis of stroke+rat brains revealed cerebral cortical hemorrhagic infarctions, microhemorrhages, neuronal ischemia, microvascular injury. Ex-vivo MRI of stroke+ rat brains detected cerebral hemorrhages, microhemorrhages and ischemia with middle cerebral artery-distribution, and cerebellar non-involvement. Ultrasound micro-imaging detected carotid artery disease. Pre-stroke analysis detected neuronal ischemia, and decreased mass of isolated cerebral, but not cerebellar, microvessels. Conclusions Early-life Na-exposure exacerbated hypertension and unmasked stroke susceptibility with greater female vulnerability in hypertensive-hyperlipidemic Tg25-rats. The reproducible modeling in Tg25sp rats of carotid artery disease, cerebral hemorrhagic-infarctions, neuronal ischemia, microhemorrhages, and microvascular alterations suggests a pathogenic spectrum with causal interrelationships. This “mixed-stroke” spectrum could represent paradigms of ischemic-hemorrhagic transformation, and/or a microangiopathic basis for the association of ischemic-lesions, microhemorrhages, and strokes

Depression is an independent determinant of life satisfaction early after stroke.

PubMed

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 < 0.001). Most stroke-surviving patients are satisfied with their 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.

Early life exposures and the risk of adult glioma.

PubMed

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.

Linguistic ability in early life and the neuropathology of Alzheimer's disease and cerebrovascular disease. Findings from the Nun Study.

PubMed

Snowdon, D A; Greiner, L H; Markesbery, W R

2000-04-01

Findings from the Nun Study indicate that low linguistic ability in early life has a strong association with dementia and premature death in late life. In the present study, we investigated the relationship of linguistic ability in early life to the neuropathology of Alzheimer's disease and cerebrovascular disease. The analyses were done on a subset of 74 participants in the Nun Study for whom we had handwritten autobiographies completed some time between the ages of 19 and 37 (mean = 23 years). An average of 62 years after writing the autobiographies, when the participants were 78 to 97 years old, they died and their brains were removed for our neuropathologic studies. Linguistic ability in early life was measured by the idea (proposition) density of the autobiographies, i.e., a standard measure of the content of ideas in text samples. Idea density scores from early life had strong inverse correlations with the severity of Alzheimer's disease pathology in the neocortex: Correlations between idea density scores and neurofibrillary tangle counts were -0.59 for the frontal lobe, -0.48 for the temporal lobe, and -0.49 for the parietal lobe (all p values < 0.0001). Idea density scores were unrelated to the severity of atherosclerosis of the major arteries at the base of the brain and to the presence of lacunar and large brain infarcts. Low linguistic ability in early life may reflect suboptimal neurological and cognitive development, which might increase susceptibility to the development of Alzheimer's disease pathology in late life.

The importance of early life family factors in the association between cardiovascular risk factors and early cardiovascular mortality.

PubMed

Kjøllesdal, Marte K R; Ariansen, Inger; Mortensen, Laust H; Næss, Øyvind

2017-01-01

To explore the importance of early life factors shared by siblings, such as parental socioeconomic position, parental practices, housing and neighbourhood, for the association between cardiovascular disease (CVD) risk factors and mortality from CVD, ischaemic heart disease (IHD) and cerebrovascular disease. Norwegian health surveys (1974-2003) were linked with data from the Norwegian Family Based Life Course Study and the Cause of Death Registry. Participants with at least one full sibling among survey participants (n=2 71 643) were included. Data on CVD risk factors, body mass index (BMI), height, systolic blood pressure (SBP) and total cholesterol (TC) were stratified into 'low', 'medium' and 'high' risk, and smoking to 'daily smoking' and 'not daily smoking'. Mean age of participants was 41 years, mean follow-up time was 19 years and during follow-up 2512 died from CVD. For each category of increased risk factor level, the per step HR of CVD mortality was increased by 1.91 (95% CI 1.78 to 2.05) for SBP, 1.67 (1.58 to 1.76) for TC, 1.44 (1.36 to 1.53) for BMI, 1.26 (1.18 to 1.35) for height and 2.89 (2.66 to 3.14) for smoking. In analyses where each sibship (groups of full siblings) had a group-specific baseline hazard, these associations were attenuated to 1.74, 1.51, 1.29, 1.18 and 2.63, respectively. The associations between risk factors and IHD mortality followed the same pattern. Early life family factors explained a small part of the association between risk factors and mortality from CVD and IHD in a relatively young sample.

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

ERIC Educational Resources Information Center

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…

Could the early environment of Mars have supported the development of life?

NASA Technical Reports Server (NTRS)

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.

The Porto Alegre Early Life Nutrition and Health Study.

PubMed

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.

Early life socioeconomic status, chronic physiological stress and hippocampal N-acetyl aspartate concentrations.

PubMed

McLean, John; Krishnadas, Rajeev; Batty, G David; Burns, Harry; Deans, Kevin A; Ford, Ian; McConnachie, Alex; McGinty, Agnes; McLean, Jennifer S; Millar, Keith; Sattar, Naveed; Shiels, Paul G; Tannahill, Carol; Velupillai, Yoga N; Packard, Chris J; Condon, Barrie R; Hadley, Donald M; Cavanagh, Jonathan

2012-12-01

Early life socioeconomic deprivation has been associated with cognitive and behavioural changes that persist through towards adulthood. In this study, we investigated whether early life socioeconomic status is associated with changes in the hippocampus N-acetyl aspartate (NAA), using the non-invasive technique of magnetic resonance spectroscopy (MRS). We performed proton magnetic resonance spectroscopy ((1)H-MRS) of the hippocampus at 3T in 30 adult males, selected from the PSOBID cohort. We conducted multiple regression analysis to examine the relationship between early socioeconomic status (SES) and concentration of N-acetyl-aspartate in the hippocampus. We also examined whether the relationship between these variables was mediated by markers of chronic physiological stress. Greater socioeconomic deprivation was associated with lower hippocampal NAA concentrations bilaterally. The relationship between early life SES and hippocampal NAA concentrations was mediated by allostatic load index - a marker of chronic physiological stress. Greater early life socioeconomic deprivation was associated with lower concentrations of NAA reflecting lesser neuronal integrity. This relationship was mediated by greater physiological stress. Further work, to better understand the biological processes underlying the effects of poverty, physiological stress on hippocampal metabolites is necessary. Copyright © 2012 Elsevier B.V. All rights reserved.

Work-Life Balance, Burnout, and Satisfaction of Early Career Pediatricians.

PubMed

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.

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

PubMed

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.

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

PubMed Central

Vaiserman, Alexander M.

2017-01-01

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. PMID:28273874

The effect of early-life education on later-life mortality.

PubMed

Black, Dan A; Hsu, Yu-Chieh; Taylor, Lowell J

2015-12-01

Many studies link cross-state variation in compulsory schooling laws to early-life educational attainment, thereby providing a plausible way to investigate the causal impact of education on various lifetime outcomes. We use this strategy to estimate the effect of education on older-age mortality of individuals born in the early twentieth century U.S. Our key innovation is to combine U.S. Census data and the complete Vital Statistics records to form precise mortality estimates by sex, birth cohort, and birth state. In turn we find that virtually all of the variation in these mortality rates is captured by cohort effects and state effects alone, making it impossible to reliably tease out any additional impact due to changing educational attainment induced by state-level changes in compulsory schooling. Copyright © 2015. Published by Elsevier B.V.

Early life disruption to the ghrelin system with over-eating is resolved in adulthood in male rats.

PubMed

Sominsky, Luba; Ziko, Ilvana; Nguyen, Thai-Xinh; Andrews, Zane B; Spencer, Sarah J

2017-02-01

Early life overweight is a significant risk factor for developmental programming of adult obesity due to changes in the availability of metabolic factors crucial for the maturation of brain appetite-regulatory circuitry. The appetite-stimulating hormone, ghrelin, has been recently identified as a major regulator of the establishment of hypothalamic feeding pathways. Ghrelin exists in circulation in two major forms, as acylated and des-acylated ghrelin. While most research has focused on acyl ghrelin, the role of neonatal des-acyl ghrelin in metabolic programming is currently unknown. Here we assessed the influences of early life overfeeding on the ghrelin system, including acyl and des-acyl ghrelin's ability to access the hypothalamus in male rats. Our data show that early life overfeeding influences the ghrelin system short-term, leading to an acute reduction in circulating des-acyl ghrelin and increased expression of the growth hormone secretagogue receptor (GHSR) in the arcuate nucleus of the hypothalamus (ARC). These changes are associated with increased neuronal activation in response to exogenous acyl, but not des-acyl, ghrelin in the ARC and the paraventricular nucleus of the hypothalamus (PVN). Interestingly, while we observed no differences in the accessibility of the ARC to acyl or des-acyl ghrelin, less exogenous acyl ghrelin reaches the PVN in the neonatally overfed. Importantly, the influences of neonatal overfeeding on the ghrelin system were not maintained into adulthood. Therefore, while early life overfeeding results in excess body weight and stimulates acute changes in the brain's sensitivity to metabolic signals, this developmental mal-programming is at least partially alleviated in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Discrete Element Model for Simulations of Early-Life Thermal Fracturing Behaviors in Ceramic Nuclear Fuel Pellets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hai Huang; Ben Spencer; Jason Hales

2014-10-01

A discrete element Model (DEM) representation of coupled solid mechanics/fracturing and heat conduction processes has been developed and applied to explicitly simulate the random initiations and subsequent propagations of interacting thermal cracks in a ceramic nuclear fuel pellet during initial rise to power and during power cycles. The DEM model clearly predicts realistic early-life crack patterns including both radial cracks and circumferential cracks. Simulation results clearly demonstrate the formation of radial cracks during the initial power rise, and formation of circumferential cracks as the power is ramped down. In these simulations, additional early-life power cycles do not lead to themore » formation of new thermal cracks. They do, however clearly indicate changes in the apertures of thermal cracks during later power cycles due to thermal expansion and shrinkage. The number of radial cracks increases with increasing power, which is consistent with the experimental observations.« less

Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities – A Population Based Cohort Study

PubMed Central

Murray, Alison D.; McNeil, Christopher J.; Salarirad, Sima; Whalley, Lawrence J.; Staff, Roger T.

2014-01-01

Context There have been many reports confirming the association between lower childhood socioeconomic circumstance and cardiovascular disease but evidence for links with cerebrovascular disease is contradictory. Hyperintensities on brain magnetic resonance imaging are associated with vascular risk factors, cognitive decline, dementia and death. However, the relationship between childhood socioeconomic circumstance and these lesions is unclear. Objective To test the hypothesis that childhood socioeconomic circumstance is associated with late life hyperintensity burden and that neither adult socioeconomic circumstance nor change in socioeconomic circumstance during life influence this effect. Design Cohort study Setting Community Participants 227 community dwelling members of the 1936 Aberdeen Birth Cohort aged 68 years, who were free from dementia. Main Outcome Measures Relationship between early life socioeconomic circumstance (paternal occupation) and abundance of late life brain hyperintensities. Results We find significant negative correlations between childhood socioeconomic circumstance and white matter hyperintensities (ρ = −0.18, P<0.01), and periventricular hyperintensities (ρ = −0.15, P<0.05), between educational attainment and white matter hyperintensities (ρ = −0.15, P<0.05) and periventricular hyperintensities (ρ = −0.17, P<0.05), and between childhood intelligence and periventricular hyperintensities (ρ = −0.14, P<0.05). The relationship is strongest for childhood socioeconomic circumstance and regional white matter hyperintensities, where there is a step change in increased burden from paternal occupation grades equivalent to a shift from “white collar” to “blue collar” paternal occupation. Significant correlations were also found between hypertension and hyperintensity burden in all brain regions (ρ = 0.15–0.24, P<0.05). In models that include hypertension, the magnitude of the effect of childhood

Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats.

PubMed

Farrell, M R; Holland, F H; Shansky, R M; Brenhouse, H C

2016-09-01

Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to-nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Testing the cumulative stress and mismatch hypotheses of psychopathology in a rat model of early-life adversity.

PubMed

Daskalakis, Nikolaos P; Oitzl, Melly S; Schächinger, Hartmut; Champagne, Danielle L; de Kloet, E Ronald

2012-07-16

In the present study, we tested both the cumulative stress and the mismatch hypothesis of psychopathology. For this purpose the combined effects of early-life adversity and later-life stress exposure on behavioral markers of psychosis susceptibility were studied in male Wistar rats. Experiment I: rat pups divided on the basis of the levels of their maternal care experience in low, medium or high maternal care groups, were reared post-weaning in groups (Exp. IA) or in social isolation (Exp. IB) and tested at adulthood under basal conditions or after an acute corticosterone (CORT) administration. Maternal care levels were assessed by measuring the dam's licking and grooming (LG) the first postnatal week of life. Experiment II: rat pups exposed as neonates to daily sessions of 8h of maternal separation (MS) on postnatal days 3, 4 and 5 either altogether in their home cage (HOME SEP) or alone in a novel environment (NOVEL SEP), were reared post-weaning in groups and tested at adulthood under basal conditions. Adult testing included behaviors marking psychosis susceptibility: apomorphine-induced gnawing (APO-gnawing), acoustic startle response and its modulation by a prepulse stimulus (PPI). The behavior of the Medium LG offspring was used as baseline reference for all the three experiments. Experiment I: Low maternal LG history alone had limited effects on the behavior of Wistar offspring, although increased acoustic startle and increased PPI, at high prepulse intensity levels, were observed. When low maternal LG history was combined with post-weaning social isolation, basal APO-gnawing was decreased and PPI increased, compared to High LG and Med LG offspring. This reflects attenuated psychosis susceptibility. High LG offspring reared in isolation displayed, however, the highest APO-gnawing and the lowest PPI levels among rats reared in social isolation, which is indicative for increased psychosis susceptibility. These findings support the mismatch hypothesis. For

Early life stress and trauma and enhanced limbic activation to emotionally valenced faces in depressed and healthy children.

PubMed

Suzuki, Hideo; Luby, Joan L; Botteron, Kelly N; Dietrich, Rachel; McAvoy, Mark P; Barch, Deanna M

2014-07-01

Previous studies have examined the relationships between structural brain characteristics and early life stress in adults. However, there is limited evidence for functional brain variation associated with early life stress in children. We hypothesized that early life stress and trauma would be associated with increased functional brain activation response to negative emotional faces in children with and without a history of depression. Psychiatric diagnosis and life events in children (starting at age 3-5 years) were assessed in a longitudinal study. A follow-up magnetic resonance imaging (MRI) study acquired data (N = 115 at ages 7-12, 51% girls) on functional brain response to fearful, sad, and happy faces relative to neutral faces. We used a region-of-interest mask within cortico-limbic areas and conducted regression analyses and repeated-measures analysis of covariance. Greater activation responses to fearful, sad, and happy faces in the amygdala and its neighboring regions were found in children with greater life stress. Moreover, an association between life stress and left hippocampal and globus pallidus activity depended on children's diagnostic status. Finally, all children with greater life trauma showed greater bilateral amygdala and cingulate activity specific to sad faces but not the other emotional faces, although right amygdala activity was moderated by psychiatric status. These findings suggest that limbic hyperactivity may be a biomarker of early life stress and trauma in children and may have implications in the risk trajectory for depression and other stress-related disorders. However, this pattern varied based on emotion type and history of psychopathology. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Early life factors and dental caries in 5-year-old children in China.

PubMed

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.

The role of early-life educational quality and literacy in explaining racial disparities in cognition in late life.

PubMed

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.

Early life mortality and height in Indian states

PubMed Central

Coffey, Diane

2014-01-01

Height is a marker for health, cognitive ability and economic productivity. Recent research on the determinants of height suggests that postneonatal mortality predicts height because it is a measure of the early life disease environment to which a cohort is exposed. This article advances the literature on the determinants of height by examining the role of early life mortality, including neonatal mortality, in India, a large developing country with a very short population. It uses state level variation in neonatal mortality, postneonatal mortality, and pre-adult mortality to predict the heights of adults born between 1970 and 1983, and neonatal and postneonatal mortality to predict the heights of children born between 1995 and 2005. In contrast to what is found in the literature on developed countries, I find that state level variation in neonatal mortality is a strong predictor of adult and child heights. This may be due to state level variation in, and overall poor levels of, pre-natal nutrition in India. PMID:25499239

Effects of early life abuse differ across development: Infant social behavior deficits are followed by adolescent depressive-like behaviors mediated by the amygdala

PubMed Central

Raineki, Charlis; Cortés, Millie Rincón; Belnoue, Laure; Sullivan, Regina M.

2012-01-01

Abuse during early life, especially from the caregiver, increases vulnerability to develop later life psychopathologies such as depression. Although signs of depression are typically not expressed until later life, signs of dysfunctional social behavior have been found earlier. How infant abuse alters the trajectory of brain development to produce pathways to pathology is not completely understood. Here we address this question using two different but complementary rat models of early-life abuse from postnatal days (PN) 8–12: a naturalistic paradigm, where the mother is provided with insufficient bedding for nest building and a more controlled paradigm, where infants undergo olfactory classical conditioning. Amygdala neural assessment (c-Fos), as well as social behavior and forced swim tests were performed at preweaning (PN20) and adolescence (PN45). Our results show that both models of early life abuse induce deficits in social behavior, even during the preweaning period; however, depressive-like behaviors were observed only during adolescence. Adolescent depressive-like behavior corresponds with an increase in amygdala neural activity in response to forced swim test. A causal relationship between the amygdala and depressive-like behavior was suggested through amygdala temporary deactivation (muscimol infusions), which rescued the depressive-like behavior in the forced swim test. Our results indicate that social behavior deficits in infancy could serve as an early marker for later psychopathology. Moreover, the implication of the amygdala in the ontogeny of depressive-like behaviors in infant abused animals is an important step toward understanding the underlying mechanisms of later life mental disease associated with early-life abuse. PMID:22649253

The first thousand days - intestinal microbiology of early life: establishing a symbiosis.

PubMed

Wopereis, Harm; Oozeer, Raish; Knipping, Karen; Belzer, Clara; Knol, Jan

2014-08-01

The development of the intestinal microbiota in the first years of life is a dynamic process significantly influenced by early-life nutrition. Pioneer bacteria colonizing the infant intestinal tract and the gradual diversification to a stable climax ecosystem plays a crucial role in establishing host-microbe interactions essential for optimal symbiosis. This colonization process and establishment of symbiosis may profoundly influence health throughout life. Recent developments in microbiologic cultivation-independent methods allow a detailed view of the key players and factors involved in this process and may further elucidate their roles in a healthy gut and immune maturation. Aberrant patterns may lead to identifying key microbial signatures involved in developing immunologic diseases into adulthood, such as asthma and atopic diseases. The central role of early-life nutrition in the developmental human microbiota, immunity, and metabolism offers promising strategies for prevention and treatment of such diseases. This review provides an overview of the development of the intestinal microbiota, its bidirectional relationship with the immune system, and its role in impacting health and disease, with emphasis on allergy, in early life. © 2014 Danone Nutricia Research. Pediatric Allergy and Immunology published by John Wiley & Sons Ltd.

Application of Diversity Indices to Quantify Early Life-History Diversity for Chinook Salmon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Gary E.; Sather, Nichole K.; Skalski, John R.

2014-03-01

We developed an index of early life history diversity (ELHD) for Pacific salmon (Oncorhynchus spp.) Early life history diversity is the variation in morphological and behavioral traits expressed within and among populations by individual juvenile salmon during their downstream migration. A standard quantitative method does not exist for this prominent concept in salmon biology.

Racial and Gender Discrimination, Early Life Factors, and Chronic Physical Health Conditions in Midlife

PubMed Central

McDonald, Jasmine A.; Terry, Mary Beth; Tehranifar, Parisa

2013-01-01

Purpose Most studies of perceived discrimination have been cross-sectional and focused primarily on mental rather than physical health conditions. We examined the associations of perceived racial and gender discrimination reported in adulthood with early life factors and self-reported physician-diagnosis of chronic physical health conditions. Methods We used data from a racially diverse birth cohort of U.S. women (N=168, average age=41 years) with prospectively collected early life data (e.g., parental socioeconomic factors) and adult reported data on perceived discrimination, physical health conditions, and relevant risk factors. We performed modified robust Poisson regression due to the high prevalence of the outcomes. Results Fifty-percent of participants reported racial and 39% reported gender discrimination. Early life factors did not have strong associations with perceived discrimination. In adjusted regression models, participants reporting at least three experiences of gender or racial discrimination had a 38% increased risk of having at least one physical health conditions (RR=1.38, 95% CI: 1.01-1.87). Using standardized regression coefficients, the magnitude of the association of having physical health conditions was larger for perceived discrimination than for being overweight or obese. Conclusion Our results suggest a substantial chronic disease burden associated with perceived discrimination, which may exceed the impact of established risk factors for poor physical health. PMID:24345610

The effects of brain serotonin deficiency on behavioural disinhibition and anxiety-like behaviour following mild early life stress.

PubMed

Sachs, Benjamin D; Rodriguiz, Ramona M; Siesser, William B; Kenan, Alexander; Royer, Elizabeth L; Jacobsen, Jacob P R; Wetsel, William C; Caron, Marc G

2013-10-01

Aberrant serotonin (5-HT) signalling and exposure to early life stress have both been suggested to play a role in anxiety- and impulsivity-related behaviours. However, whether congenital 5-HT deficiency × early life stress interactions influence the development of anxiety- or impulsivity-like behaviour has not been established. Here, we examined the effects of early life maternal separation (MS) stress on anxiety-like behaviour and behavioural disinhibition, a type of impulsivity-like behaviour, in wild-type (WT) and tryptophan hydroxylase 2 (Tph2) knock-in (Tph2KI) mice, which exhibit ~60-80% reductions in the levels of brain 5-HT due to a R439H mutation in Tph2. We also investigated the effects of 5-HT deficiency and early life stress on adult hippocampal neurogenesis, plasma corticosterone levels and several signal transduction pathways in the amygdala. We demonstrate that MS slightly increases anxiety-like behaviour in WT mice and induces behavioural disinhibition in Tph2KI animals. We also demonstrate that MS leads to a slight decrease in cell proliferation within the hippocampus and potentiates corticosterone responses to acute stress, but these effects are not affected by brain 5-HT deficiency. However, we show that 5-HT deficiency leads to significant alterations in SGK-1 and GSK3β signalling and NMDA receptor expression in the amygdala in response to MS. Together, these findings support a potential role for 5-HT-dependent signalling in the amygdala in regulating the long-term effects of early life stress on anxiety-like behaviour and behavioural disinhibition.

Global Research Trends on Early-Life Feeding Practices and Early Childhood Caries: a Systematic Review

PubMed Central

Cheng, Ashley

2014-01-01

Objective Describe the epidemiologic literature related to early-life feeding practices and early childhood caries (ECC) with regard to publication attributes and trends in these attributes over time. Methods Systematic literature review including electronic and manual searches (in BIOSIS, CINAHL, Cochrane Library, LILACS, MEDLINE, Web of Science, and WHOLIS), covering the years 1990–2013. Attributes of publications meeting a priori inclusion criteria were abstracted and organized by global region and trends over time. Attributes included country of origin and study design of included publications and age and caries prevalence of the populations studied. Results 244 publications drawn from 196 independent study populations were included. The number of publications and the countries represented increased over time, although some world regions remained underrepresented. Most publications were cross sectional (75%); while this percentage remained fairly constant over time, the percentage of studies to account for confounding factors increased. Publications varied with respect to the caries experience and age range of children included in each study. Conclusions Publication productivity regarding feeding practices and ECC research has grown, but this growth has not been evenly distributed globally. Individual publication attributes (i.e. methods and context) can differ significantly and should be considered when interpreting and synthesizing the literature. PMID:25328911

Gut microbial functional maturation and succession during human early life.

PubMed

Cerdó, Tomás; Ruiz, Alicia; Acuña, Inmaculada; Jáuregui, Ruy; Jehmlich, Nico; Haange, Sven-Bastian; von Bergen, Martin; Suárez, Antonio; Campoy, Cristina

2018-04-24

The evolutional trajectory of gut microbial colonization from birth has been shown to prime for health later in life. Here, we combined cultivation-independent 16S rRNA gene sequencing and metaproteomics to investigate the functional maturation of gut microbiota in faecal samples from full-term healthy infants collected at 6 and 18 months of age. Phylogenetic analysis of the metaproteomes showed that Bifidobacterium provided the highest number of distinct protein groups. Considerable divergences between taxa abundance and protein phylogeny were observed at all taxonomic ranks. Age had a profound effect on early microbiota where compositional and functional diversity of less dissimilar communities increased with time. Comparisons of the relative abundances of proteins revealed the transition of taxon-associated saccharolytic and fermentation strategies from milk and mucin-derived monosaccharide catabolism feeding acetate/propanoate synthesis to complex food-derived hexoses fuelling butanoate production. Furthermore, co-occurrence network analysis uncovered two anti-correlated modules of functional taxa. A low-connected Bifidobacteriaceae-centred guild of facultative anaerobes was succeeded by a rich club of obligate anaerobes densely interconnected around Lachnospiraceae, underpinning their pivotal roles in microbial ecosystem assemblies. Our findings establish a framework to visualize whole microbial community metabolism and ecosystem succession dynamics, proposing opportunities for microbiota-targeted health-promoting strategies early in life. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

IL-2 Enhances Gut Homing Potential of Human Naive Regulatory T Cells Early in Life.

PubMed

Hsu, Peter S; Lai, Catherine L; Hu, Mingjing; Santner-Nanan, Brigitte; Dahlstrom, Jane E; Lee, Cheng Hiang; Ajmal, Ayesha; Bullman, Amanda; Arbuckle, Susan; Al Saedi, Ahmed; Gacis, Lou; Nambiar, Reta; Williams, Andrew; Wong, Melanie; Campbell, Dianne E; Nanan, Ralph

2018-06-15

Recent evidence suggests early environmental factors are important for gut immune tolerance. Although the role of regulatory T (Treg) cells for gut immune homeostasis is well established, the development and tissue homing characteristics of Treg cells in children have not been studied in detail. In this article, we studied the development and homing characteristics of human peripheral blood Treg cell subsets and potential mechanisms inducing homing molecule expression in healthy children. We found contrasting patterns of circulating Treg cell gut and skin tropism, with abundant β7 integrin + Treg cells at birth and increasing cutaneous lymphocyte Ag (CLA + ) Treg cells later in life. β7 integrin + Treg cells were predominantly naive, suggesting acquisition of Treg cell gut tropism early in development. In vitro, IL-7 enhanced gut homing but reduced skin homing molecule expression in conventional T cells, whereas IL-2 induced a similar effect only in Treg cells. This effect was more pronounced in cord compared with adult blood. Our results suggest that early in life, naive Treg cells may be driven for gut tropism by their increased sensitivity to IL-2-induced β7 integrin upregulation, implicating a potential role of IL-2 in gut immune tolerance during this critical period of development. Copyright © 2018 by The American Association of Immunologists, Inc.

Early life social stress induced changes in depression and anxiety associated neural pathways which are correlated with impaired maternal care.

PubMed

Murgatroyd, Christopher A; Peña, Catherine J; Podda, Giovanni; Nestler, Eric J; Nephew, Benjamin C

2015-08-01

Exposures to various types of early life stress can be robust predictors of the development of psychiatric disorders, including depression and anxiety. The objective of the current study was to investigate the roles of the translationally relevant targets of central vasopressin, oxytocin, ghrelin, orexin, glucocorticoid, and the brain-derived neurotrophic factor (BDNF) pathway in an early chronic social stress (ECSS) based rodent model of postpartum depression and anxiety. The present study reports novel changes in gene expression and extracellular signal related kinase (ERK) protein levels in the brains of ECSS exposed rat dams that display previously reported depressed maternal care and increased maternal anxiety. Decreases in oxytocin, orexin, and ERK proteins, increases in ghrelin receptor, glucocorticoid and mineralocorticoid receptor mRNA levels, and bidirectional changes in vasopressin underscore related work on the adverse long-term effects of early life stress on neural activity and plasticity, maternal behavior, responses to stress, and depression and anxiety-related behavior. The differences in gene and protein expression and robust correlations between expression and maternal care and anxiety support increased focus on these targets in animal and clinical studies of the adverse effects of early life stress, especially those focusing on depression and anxiety in mothers and the transgenerational effects of these disorders on offspring. Copyright © 2015 Elsevier B.V. All rights reserved.

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

EPA Science Inventory

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...

Flexible nonlinear estimates of the association between height and mental ability in early life.

PubMed

Murasko, Jason E

2014-01-01

To estimate associations between early-life mental ability and height/height-growth in contemporary US children. Structured additive regression models are used to flexibly estimate the associations between height and mental ability at approximately 24 months of age. The sample is taken from the Early Childhood Longitudinal Study-Birth Cohort, a national study whose target population was children born in the US during 2001. A nonlinear association is indicated between height and mental ability at approximately 24 months of age. There is an increasing association between height and mental ability below the mean value of height, but a flat association thereafter. Annualized growth shows the same nonlinear association to ability when controlling for baseline length at 9 months. Restricted growth at lower values of the height distribution is associated with lower measured mental ability in contemporary US children during the first years of life. Copyright © 2013 Wiley Periodicals, Inc.

Exposure to dust mite allergen and endotoxin in early life and asthma and atopy in childhood

PubMed Central

Celedón, Juan C.; Milton, Donald K.; Ramsey, Clare D.; Litonjua, Augusto A.; Ryan, Louise; Platts-Mills, Thomas A. E.; Gold, Diane R.

2013-01-01

Background There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age. Objectives To examine the relation between exposure to dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and atopy in high-risk children. Methods Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area. Results In multivariate analyses, early exposure to high levels of dust mite allergen (≥10 μg/g) was associated with increased risks of asthma at age 7 years (odds ratio [OR], 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% CI, 1.5-16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3 months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI, 0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure in early life was associated with an increased risk of any wheeze between ages 1 and 7 years that did not change significantly with time (hazard ratio for each quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43). Conclusion Among children at risk of atopy, early exposure to high levels of dust mite allergen is associated with increased risks of asthma and late-onset wheeze. In these children, endotoxin exposure is associated with a reduced risk of atopy but an increased risk of wheeze. Clinical implications Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children. PMID:17507083

Life, Labor, and, Song in New England during the Early Republic.

ERIC Educational Resources Information Center

Scott, John W., Ed.; Scott, John A., Ed.

1998-01-01

Singing the tunes in this collection will help students understand many of the realities of life during the early years of the United States. From hearth and home to the perils of the sea, and from factory life to Presidential elections, this journal offers a selection of 19 songs to introduce the life and labor of New England people during the…

The importance of early life family factors in the association between cardiovascular risk factors and early cardiovascular mortality

PubMed Central

Kjøllesdal, Marte K R; Ariansen, Inger; Mortensen, Laust H; Næss, Øyvind

2017-01-01

Objective To explore the importance of early life factors shared by siblings, such as parental socioeconomic position, parental practices, housing and neighbourhood, for the association between cardiovascular disease (CVD) risk factors and mortality from CVD, ischaemic heart disease (IHD) and cerebrovascular disease. Methods Norwegian health surveys (1974–2003) were linked with data from the Norwegian Family Based Life Course Study and the Cause of Death Registry. Participants with at least one full sibling among survey participants (n=2 71 643) were included. Data on CVD risk factors, body mass index (BMI), height, systolic blood pressure (SBP) and total cholesterol (TC) were stratified into ‘low’, ‘medium’ and ‘high’ risk, and smoking to ‘daily smoking’ and ‘not daily smoking’. Results Mean age of participants was 41 years, mean follow-up time was 19 years and during follow-up 2512 died from CVD. For each category of increased risk factor level, the per step HR of CVD mortality was increased by 1.91 (95% CI 1.78 to 2.05) for SBP, 1.67 (1.58 to 1.76) for TC, 1.44 (1.36 to 1.53) for BMI, 1.26 (1.18 to 1.35) for height and 2.89 (2.66 to 3.14) for smoking. In analyses where each sibship (groups of full siblings) had a group-specific baseline hazard, these associations were attenuated to 1.74, 1.51, 1.29, 1.18 and 2.63, respectively. The associations between risk factors and IHD mortality followed the same pattern. Conclusion Early life family factors explained a small part of the association between risk factors and mortality from CVD and IHD in a relatively young sample. PMID:28878947

The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

PubMed Central

Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

2014-01-01

Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

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

PubMed

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.

Early-life exposure to substance abuse and risk of type 2 diabetes in adulthood.

PubMed

Vaiserman, A M

2015-08-01

Type 2 diabetes (T2D) is a chronic non-communicable disease that is driven by insulin resistance as a result of increasing obesity and decreasing activity levels that occur with increasing age. This disease generally develops after the age of 40, but it is now increasingly diagnosed in children and young adults. Increasing evidence, however, suggests that T2D can originate during early development. It has been repeatedly found that malnutrition during the gestational period can result in intrauterine growth restriction and low birth weight, which in combination with postnatal catch-up growth may subsequently lead to the development of T2D. There is ample evidence that T2D may also be programmed by maternal substance abuse (the harmful use of psychoactive substances such as illicit drugs or alcohol) during pregnancy and/or lactation. The research activity in this field is currently mainly focused on the childhood health problems following prenatal exposures to substance abuse. The delayed programming effects on adult-onset disorders, including metabolic syndrome and T2D, however, have been reported only rarely. This review provides animal and human evidence that early-life exposure to substance abuse, including alcohol, nicotine, and cocaine, may program not only childhood health outcomes but also life-long metabolic health status, including risk of T2D and related conditions.

Early life risk factors and their cumulative effects as predictors of overweight in Spanish children.

PubMed

Iguacel, Isabel; Escartín, Laura; Fernández-Alvira, Juan M; Iglesia, Iris; Labayen, Idoia; Moreno, Luis A; Samper, María Pilar; Rodríguez, Gerardo

2018-05-01

To explore early life risk factors of overweight/obesity at age 6 years and their cumulative effects on overweight/obesity at ages 2, 4 and 6 years. Altogether 1031 Spanish children were evaluated at birth and during a 6-year follow-up. Early life risk factors included: parental overweight/obesity, parental origin/ethnicity, maternal smoking during pregnancy, gestational weight gain, gestational age, birth weight, caesarean section, breastfeeding practices and rapid infant weight gain collected via hospital records. Cumulative effects were assessed by adding up those early risk factors that significantly increased the risk of overweight/obesity. We conducted binary logistic regression models. Rapid infant weight gain (OR 2.29, 99% CI 1.54-3.42), maternal overweight/obesity (OR 1.93, 99% CI 1.27-2.92), paternal overweight/obesity (OR 2.17, 99% CI 1.44-3.28), Latin American/Roma origin (OR 3.20, 99% CI 1.60-6.39) and smoking during pregnancy (OR 1.61, 99% CI 1.01-2.59) remained significant after adjusting for confounders. A higher number of early life risk factors accumulated was associated with overweight/obesity at age 6 years but not at age 2 and 4 years. Rapid infant weight gain, parental overweight/obesity, maternal smoking and origin/ethnicity predict childhood overweight/obesity and present cumulative effects. Monitoring children with rapid weight gain and supporting a healthy parental weight are important for childhood obesity prevention.

Enhanced transcription and translation in clay hydrogel and implications for early life evolution

PubMed Central

Yang, Dayong; Peng, Songming; Hartman, Mark R.; Gupton-Campolongo, Tiffany; Rice, Edward J.; Chang, Anna Kathryn; Gu, Zi; Lu, G. Q. (Max); Luo, Dan

2013-01-01

In most contemporary life forms, the confinement of cell membranes provides localized concentration and protection for biomolecules, leading to efficient biochemical reactions. Similarly, confinement may have also played an important role for prebiotic compartmentalization in early life evolution when the cell membrane had not yet formed. It remains an open question how biochemical reactions developed without the confinement of cell membranes. Here we mimic the confinement function of cells by creating a hydrogel made from geological clay minerals, which provides an efficient confinement environment for biomolecules. We also show that nucleic acids were concentrated in the clay hydrogel and were protected against nuclease, and that transcription and translation reactions were consistently enhanced. Taken together, our results support the importance of localized concentration and protection of biomolecules in early life evolution, and also implicate a clay hydrogel environment for biochemical reactions during early life evolution. PMID:24196527

Relationship of early-life stress and resilience to military adjustment in a young adulthood population.

PubMed

Choi, Kang; Im, Hyoungjune; Kim, Joohan; Choi, Kwang H; Jon, Duk-In; Hong, Hyunju; Hong, Narei; Lee, Eunjung; Seok, Jeong-Ho

2013-11-01

Early-life stress (ELS) may mediate adjustment problems while resilience may protect individuals against adjustment problems during military service. We investigated the relationship of ELS and resilience with adjustment problem factor scores in the Korea Military Personality Test (KMPT) in candidates for the military service. Four hundred and sixty-one candidates participated in this study. Vulnerability traits for military adjustment, ELS, and resilience were assessed using the KMPT, the Korean Early-Life Abuse Experience Questionnaire, and the Resilience Quotient Test, respectively. Data were analyzed using multiple linear regression analyses. The final model of the multiple linear regression analyses explained 30.2 % of the total variances of the sum of the adjustment problem factor scores of the KMPT. Neglect and exposure to domestic violence had a positive association with the total adjustment problem factor scores of the KMPT, but emotion control, impulse control, and optimism factor scores as well as education and occupational status were inversely associated with the total military adjustment problem score. ELS and resilience are important modulating factors in adjusting to military service. We suggest that neglect and exposure to domestic violence during early life may increase problem with adjustment, but capacity to control emotion and impulse as well as optimistic attitude may play protective roles in adjustment to military life. The screening procedures for ELS and the development of psychological interventions may be helpful for young adults to adjust to military service.

The effects of parasites on the early life stages of a damselfish

NASA Astrophysics Data System (ADS)

Sun, D.; Blomberg, S. P.; Cribb, T. H.; McCormick, M. I.; Grutter, A. S.

2012-12-01

Early life history traits, such as larval growth, influence the success of coral reef fish in the transition from the larval to the juvenile life phase. Few studies, however, have examined the relationship between parasites and growth in the early life history stages of such fishes. This study examined how parasite prevalence (% infected) and load, and the relationship between parasite presence and fish growth, differed among life stages of the damselfish Pomacentrus amboinensis. Parasite prevalence decreased significantly between the larval stage, which was sampled immediately before settlement on the reef (97 %) and recently settled juveniles (60 %); prevalence was also high for 4-month-old juveniles (90 %), 7-month-old juveniles (100 %) and adult fish (100 %). Total numbers of parasites per fish decreased dramatically (fourfold) between larval and recently settled fish, and then increased in the older stages to levels similar to those observed in larvae, but they did so more gradually than did prevalence. One explanation for these patterns is that heavily infected larvae were preferentially removed from the population during or soon after settlement. Daily fish growth, determined from otolith increments, revealed that growth did not differ between parasitised and non-parasitised larval fish, whereas recently settled fish that were parasitised had faster growth; these parasitised recently settled fish also displayed faster growth prior to settlement. These data provide evidence that parasites may explain some of the variation in growth and survival observed among coral reef fishes after settlement and thereby have a greater impact on population dynamics than previously understood.

On the possibility of life on early Mars

NASA Technical Reports Server (NTRS)

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.

Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?

PubMed Central

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

Sudden Unexpected Death in Fetal Life Through Early Childhood

PubMed Central

Kinney, Hannah C.; Willinger, Marian

2016-01-01

In March 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop entitled “Sudden Unexpected Death in Fetal Life Through Early Childhood: New Opportunities.” Its objective was to advance efforts to understand and ultimately prevent sudden deaths in early life, by considering their pathogenesis as a potential continuum with some commonalities in biological origins or pathways. A second objective of this meeting was to highlight current issues surrounding the classification of sudden infant death syndrome (SIDS), and the implications of variations in the use of the term “SIDS” in forensic practice, and pediatric care and research. The proceedings reflected the most current knowledge and understanding of the origins and biology of vulnerability to sudden unexpected death, and its environmental triggers. Participants were encouraged to consider the application of new technologies and “omics” approaches to accelerate research. The major advances in delineating the intrinsic vulnerabilities to sudden death in early life have come from epidemiologic, neural, cardiac, metabolic, genetic, and physiologic research, with some commonalities among cases of unexplained stillbirth, SIDS, and sudden unexplained death in childhood observed. It was emphasized that investigations of sudden unexpected death are inconsistent, varying by jurisdiction, as are the education, certification practices, and experience of death certifiers. In addition, there is no practical consensus on the use of “SIDS” as a determination in cause of death. Major clinical, forensic, and scientific areas are identified for future research. PMID:27230764

The Nun study: clinically silent AD, neuronal hypertrophy, and linguistic skills in early life.

PubMed

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.

Earth's early biosphere

NASA Technical Reports Server (NTRS)

Des Marais, D. J.

1998-01-01

Understanding our own early biosphere is essential to our search for life elsewhere, because life arose on Earth very early and rocky planets shared similar early histories. The biosphere arose before 3.8 Ga ago, was exclusively unicellular and was dominated by hyperthermophiles that utilized chemical sources of energy and employed a range of metabolic pathways for CO2 assimilation. Photosynthesis also arose very early. Oxygenic photosynthesis arose later but still prior to 2.7 Ga. The transition toward the modern global environment was paced by a decline in volcanic and hydrothermal activity. These developments allowed atmospheric O2 levels to increase. The O2 increase created new niches for aerobic life, most notably the more advanced Eukarya that eventually spawned the megascopic fauna and flora of our modern biosphere.

An Increased Dietary Supply of Medium-Chain Fatty Acids during Early Weaning in Rodents Prevents Excessive Fat Accumulation in Adulthood

PubMed Central

van de Heijning, Bert J. M.; Oosting, Annemarie; Kegler, Diane; van der Beek, Eline M.

2017-01-01

Medium-chain fatty acids (MCFA) are a directly and readily absorbed source of energy. Exposure early-in-life to increased MCFA levels might affect development and impact (lipid) metabolism later in life. We tested whether an increased MCFA intake early-in-life positively affects adult body composition and metabolic status when challenged by a western-style diet (WSD). Male offspring of C57Bl/6j mice and Wistar rats were fed a control diet (CTRL; 10 w% fat, 14% MCFA) or a medium-chain triglycerides (MCT) diet with 20% MCFA until postnatal (PN) day 42, whereupon animals were fed a WSD (10 w% fat) until PN day 98. Body composition was monitored by Dual Energy X-ray Absorptiometry (DEXA). In rats, glucose homeostasis was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT); in mice, the HOmeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. At autopsy on PN day 98, plasma lipid profiles, glucose, insulin, and adipokines were measured; organs and fat pads were collected and the adipocyte size distribution was analysed. Milk analysis in mice showed that the maternal MCT diet was not translated into milk, and pups were thus only exposed to high MCT levels from early weaning onward: PN day 16 until 42. Mice exposed to MCT showed 28% less fat accumulation vs. CTRL during WSD. The average adipocyte cell size, fasting plasma triglycerides (TG), and leptin levels were reduced in MCT mice. In rats, no effects were found on the adult body composition, but the adipocyte cell size distribution shifted towards smaller adipocytes. Particularly mice showed positive effects on glucose homeostasis and insulin sensitivity. Increased MCFA intake early-in-life protected against the detrimental effects of an obesogenic diet in adulthood. PMID:28632178

Effects of early-life malnutrition on neurodevelopment and neuropsychiatric disorders and the potential mechanisms.

PubMed

Yan, Xintian; Zhao, Xinzhi; Li, Juxue; He, Lin; Xu, Mingqing

2018-04-20

Lines of evidence have demonstrated that early-life malnutrition is highly correlated with neurodevelopment and adulthood neuropsychiatric disorders, while some findings are conflicting with each other. In addition, the biological mechanisms are less investigated. We systematically reviewed the evidence linking early-life nutrition status with neurodevelopment and clinical observations in human and animal models. We summarized the effects of special nutritious on neuropsychiatric disorders and explored the underlying potential mechanisms. The further understanding of the biological regulation of early-life nutritional status on neurodevelopment might shed light on precision nutrition at an integrative systems biology framework. Copyright © 2018 Elsevier Inc. All rights reserved.

Prenatal Exposure to Respiratory Syncytial Virus Alters Postnatal Immunity and Airway Smooth Muscle Contractility during Early-Life Reinfections

PubMed Central

Harford, Terri J.; Agrawal, Vandana; Yen-Lieberman, Belinda; Rezaee, Fariba; Piedimonte, Giovanni

2017-01-01

Maternal viral infections can have pathological effects on the developing fetus which last long after birth. Recently, maternal-fetal transmission of respiratory syncytial virus (RSV) was shown to cause postnatal airway hyperreactivity (AHR) during primary early-life reinfection; however, the influence of prenatal exposure to RSV on offspring airway immunity and smooth muscle contractility during recurrent postnatal reinfections remains unknown. Therefore, we sought to determine whether maternal RSV infection impairs specific aspects of cell-mediated offspring immunity during early-life reinfections and the mechanisms leading to AHR. Red fluorescent protein-expressing recombinant RSV (rrRSV) was inoculated into pregnant rat dams at midterm, followed by primary and secondary postnatal rrRSV inoculations of their offspring at early-life time points. Pups and weanlings were tested for specific lower airway leukocyte populations by flow cytometry; serum cytokine/chemokine concentrations by multiplex ELISA and neurotrophins concentrations by standard ELISA; and ex vivo lower airway smooth muscle (ASM) contraction by physiological tissue bath. Pups born to RSV-infected mothers displayed elevated total CD3+ T cells largely lacking CD4+ and CD8+ surface expression after both primary and secondary postnatal rrRSV infection. Cytokine/chemokine analyses revealed reduced IFN-γ, IL-2, IL-12, IL-17A, IL-18, and TNF-α, as well as elevated nerve growth factor (NGF) expression. Prenatal exposure to RSV also increased ASM reactivity and contractility during early-life rrRSV infection compared to non-exposed controls. We conclude that maternal RSV infection can predispose offspring to postnatal lower airways dysfunction by altering immunity development, NGF signaling, and ASM contraction during early-life RSV reinfections. PMID:28178290

Innate Immunity to Respiratory Infection in Early Life

PubMed Central

Lambert, Laura; Culley, Fiona J.

2017-01-01

Early life is a period of particular susceptibility to respiratory infections and symptoms are frequently more severe in infants than in adults. The neonatal immune system is generally held to be deficient in most compartments; responses to innate stimuli are weak, antigen-presenting cells have poor immunostimulatory activity and adaptive lymphocyte responses are limited, leading to poor immune memory and ineffective vaccine responses. For mucosal surfaces such as the lung, which is continuously exposed to airborne antigen and to potential pathogenic invasion, the ability to discriminate between harmless and potentially dangerous antigens is essential, to prevent inflammation that could lead to loss of gaseous exchange and damage to the developing lung tissue. We have only recently begun to define the differences in respiratory immunity in early life and its environmental and developmental influences. The innate immune system may be of relatively greater importance than the adaptive immune system in the neonatal and infant period than later in life, as it does not require specific antigenic experience. A better understanding of what constitutes protective innate immunity in the respiratory tract in this age group and the factors that influence its development should allow us to predict why certain infants are vulnerable to severe respiratory infections, design treatments to accelerate the development of protective immunity, and design age specific adjuvants to better boost immunity to infection in the lung. PMID:29184555

Understanding Early Decisions to Withdraw Life-Sustaining Therapy in Cardiac Arrest Survivors. A Qualitative Investigation.

PubMed

Dale, Craig M; Sinuff, Tasnim; Morrison, Laurie J; Golan, Eyal; Scales, Damon C

2016-07-01

Early withdrawal of life-sustaining therapy contributes to the majority of deaths following out-of-hospital cardiac arrest (OHCA), despite current recommendations for delayed neurological prognostication (≥72 h) after treatment with targeted temperature management. Little is known about clinicians' experiences of early withdrawal of life support decisions in patients with OHCA. To explore clinicians' experiences and perceptions of early withdrawal of life support decisions and barriers to guideline-concordant neurological prognostication in comatose survivors of OHCA treated with targeted temperature management. We conducted qualitative interviews with intensive care unit (ICU) physicians and nurses following withdrawal of life support in comatose patients with OHCA treated with targeted temperature management. The study was carried out across 18 academic and community hospitals participating in a multicenter, stepped-wedge, cluster-randomized controlled trial designed to improve quality-of-care processes for patients after OHCA in Ontario, Canada. We used a focused thematic analysis to capture barriers to guideline-concordant neurological prognostication and used these barriers to identify potentially modifiable issues. The core thematic finding was a high emotional burden of ICU family-team communication in which strong feelings inhibited information transfer and delayed decision making following OHCA. Four subthemes describing sources of communication strain were identified: (1) requests from family members to provide early outcome predictions, (2) incomplete family comprehension of critical care, (3) family requests for early withdrawal of life support based on their understanding of patients' preferences and values, and (4) family-team communication gaps related to prognostic uncertainty. Participants worried that gaps in timely and clear prognostic information contributed to surrogates' perceptions of a poor outcome and to inappropriately early decisions to

Early-Life Stressors, Personality Development, and Fast Life Strategies: An Evolutionary Perspective on Malevolent Personality Features.

PubMed

Csathó, Árpád; Birkás, Béla

2018-01-01

Life history theory posits that behavioral adaptation to various environmental (ecological and/or social) conditions encountered during childhood is regulated by a wide variety of different traits resulting in various behavioral strategies. Unpredictable and harsh conditions tend to produce fast life history strategies, characterized by early maturation, a higher number of sexual partners to whom one is less attached, and less parenting of offspring. Unpredictability and harshness not only affects dispositional social and emotional functioning, but may also promote the development of personality traits linked to higher rates of instability in social relationships or more self-interested behavior. Similarly, detrimental childhood experiences, such as poor parental care or high parent-child conflict, affect personality development and may create a more distrustful, malicious interpersonal style. The aim of this brief review is to survey and summarize findings on the impact of negative early-life experiences on the development of personality and fast life history strategies. By demonstrating that there are parallels in adaptations to adversity in these two domains, we hope to lend weight to current and future attempts to provide a comprehensive insight of personality traits and functions at the ultimate and proximate levels.

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

PubMed

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.

The developing hypopharyngeal microbiota in early life.

PubMed

Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael; Abu Al-Soud, Waleed; Balle, Christina; Krogfelt, Karen Angeliki; Stokholm, Jakob; Thorsen, Jonathan; Waage, Johannes; Rasmussen, Morten Arendt; Bisgaard, Hans; Sørensen, Søren Johannes

2016-12-30

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 COPSAC 2010 cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. 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 show temporal pneumotype changes suggesting a rapid development towards maturation of the hypopharyngeal microbiota and a significant effect from older siblings. Despite an overall common trajectory towards maturation, individual infants' microbiota are more similar to their own, than to others, over time. Our findings demonstrate a consolidation of the population of indigenous bacteria in healthy airways and indicate distinct trajectories in the early development of the hypopharyngeal microbiota.

Early life exposure to traffic-related air pollution and allergic rhinitis in preschool children.

PubMed

Deng, Qihong; Lu, Chan; Yu, Yichen; Li, Yuguo; Sundell, Jan; Norbäck, Dan

2016-12-01

Evidence linking long-term exposure to outdoor air pollution with allergic rhinitis (AR) in children is scare, and the role of components of air pollution and timing of exposure remains unclear. To assess the association of pre- and post-natal exposure to air pollution with life-time prevalence of AR in preschool children. We conducted a cohort study of 2598 children aged 3-6 years in Changsha, China. The lifetime prevalence of AR was assessed by a questionnaire administered by parents. Children's exposures to dioxide nitrogen (NO 2 ), sulfur dioxide (SO 2 ) and particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ) during different pre- and post-natal timing windows were estimated using the measured concentrations at monitoring stations. The odds ratio (OR) and 95% confidence interval (CI) of childhood AR for exposure to different air pollutants during different timing windows were assessed by logistic regression model in terms of an interquartile range (IQR) increase in exposure level. Life-time prevalence of AR in preschool children (7.3%) was associated with both pre- and post-natal exposure to traffic-related air pollution (TRAP), but only significant during the third trimester of pregnancy with adjusted OR = 1.40 (95% CI: 1.08-1.82) for a 15 μg/m 3 increase in NO 2 and during the first-year of life with adjusted OR = 1.36 (95% CI: 1.03-1.78) and 1.54 (95% CI: 1.07-2.21) respectively for 11 and 12 μg/m 3 increase in NO 2 and PM 10 . The association of early life exposure to TRAP with childhood AR was robust by adjusting for other air pollutants and timing windows. Sensitivity analysis indicated that the association was higher in the children who are male, young, with genetic predisposition by parental atopy, and living in damp houses. Early life exposure to traffic-related air pollutant during pregnancy and first-year of life may contribute to childhood AR. Copyright © 2016 Elsevier Ltd. All rights reserved.

Racial and gender discrimination, early life factors, and chronic physical health conditions in midlife.

PubMed

McDonald, Jasmine A; Terry, Mary Beth; Tehranifar, Parisa

2014-01-01

Most studies of perceived discrimination have been cross-sectional and focused primarily on mental rather than physical health conditions. We examined the associations of perceived racial and gender discrimination reported in adulthood with early life factors and self-reported physician diagnosis of chronic physical health conditions. We used data from a racially diverse birth cohort of U.S. women (n = 168; average age, 41 years) with prospectively collected early life data (e.g., parental socioeconomic factors) and adult reported data on perceived discrimination, physical health conditions, and relevant risk factors. We performed modified robust Poisson regression owing to the high prevalence of the outcomes. Fifty percent of participants reported racial and 39% reported gender discrimination. Early life factors did not have strong associations with perceived discrimination. In adjusted regression models, participants reporting at least three experiences of gender or racial discrimination had a 38% increased risk of having at least one physical health condition (relative risk, 1.38; 95% confidence interval, 1.01-1.87). Using standardized regression coefficients, the magnitude of the association of having physical health condition(s) was larger for perceived discrimination than for being overweight or obese. Our results suggest a substantial chronic disease burden associated with perceived discrimination, which may exceed the impact of established risk factors for poor physical health. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Time course for memory dysfunction in early-life and late-life major depression: a longitudinal study from the Juntendo University Mood Disorder Project.

PubMed

Maeshima, Hitoshi; Baba, Hajime; Nakano, Yoshiyuki; Satomura, Emi; Namekawa, Yuki; Takebayashi, Naoko; Nomoto, Hiroshi; Suzuki, Toshihito; Mimura, Masaru; Arai, Heii

2013-10-01

Previous studies have demonstrated that patients with depression also have memory dysfunctions during depressive episodes. These dysfunctions partially remain immediately after remission from a depressive state; however, it is unclear whether these residual memory dysfunctions may disappear through long-term remission from depression. The present study compared patients during early-life (age<60) and late-life (age ≥ 60) depression while in their remitted stage with healthy controls to elucidate the impact of a long-term course on memory. Logical memory from the Wechsler Memory Scale-Revised was administered to 67 patients with major depressive disorder (MDD) (47 patients with early-life depression and residual 20 patients with late-life depression) and 50 healthy controls. MDD patients received memory assessments at the time of their initial remission and at a follow-up three years after remission. At the time of initial remission, scores for logical memory were significantly lower in both patient groups compared to matched controls. At follow-up, memory dysfunction for early-life MDD patients disappeared, whereas scores in the late-life MDD group remained significantly lower than those of matched controls. All patients in the present study were on antidepressant medications. Our findings suggested that the progress of memory performance in late-life MDD patients may be different from early-life MDD patients. © 2013 Elsevier B.V. All rights reserved.

TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

EPA Science Inventory

Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

EPA Science Inventory

Mammary Gland Development: Early Life Effects from the Environment

S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

As signs of precocious puberty in girls reach ...

[Quality of life in visual impaired children treated for Early Visual Stimulation].

PubMed

Messa, Alcione Aparecida; Nakanami, Célia Regina; Lopes, Marcia Caires Bestilleiro

2012-01-01

To evaluate the quality of life in visually impaired children followed in the Early Visual Stimulation Ambulatory of Unifesp in two moments, before and after rehabilitational intervention of multiprofessional team. A CVFQ quality of life questionnaire was used. This instrument has a version for less than three years old children and another one for children older than three years (three to seven years) divided in six subscales: General health, General vision health, Competence, Personality, Family impact and Treatment. The correlation between the subscales on two moments was significant. There was a statistically significant difference in general vision health (p=0,029) and other important differences obtained in general health, family impact and quality of life general score. The questionnaire showed to be effective in order to measure the quality of life related to vision on families followed on this ambulatory. The multidisciplinary interventions provided visual function and familiar quality of life improvement. The quality of life related to vision in children followed in Early Visual Stimulation Ambulatory of Unifesp showed a significant improvement on general vision health.

Does adversity early in life affect general population suicide rates? A cross-national study.

PubMed

Shah, Ajit; Bhandarkar, Ritesh

2011-01-01

Adversity early in life has been suggested as a protective factor for elderly suicides. However, studies examining this relationship in general population suicide rates are scarce. The relationship between general population suicide rates and four proxy measures of adversity earlier in life was examined using data from the World Health Organization and the United Nations data banks. General population suicide rates were negatively correlated with the percentage of children under the age of 5 years who were underweight, the percentage of children under the age of 5 years who were under height, the percentage of infants with low birth weight babies, and the percentage of the general population that was undernourished. The only independent predictor general population suicide rates in both sexes, on multiple regression analysis, was the Gini coefficient (a measure of income inequality). Income inequality may lead to low birth weight, undernourishment, underweight and under height because income inequality results in poor access to healthcare and nutrition. These adversities may increase child mortality rates and reduce life expectancy. Those surviving into adulthood in countries with greater adversity early in life may be at reduced risk of suicide because of selective survival of those at reduced risk of suicide due to constitutional or genetic factors and development of greater tolerance to hardship in adulthood. ‎

Early Archaean collapse basins, a habitat for early bacterial life.

NASA Astrophysics Data System (ADS)

Nijman, W.

For a better definition of the sedimentary environment in which early life may have flourished during the early Archaean, understanding of the basin geometry in terms of shape, depth, and fill is a prerequisite. The basin fill is the easiest to approach, namely from the well exposed, low-grade metamorphic 3.4 - 3.5 Ga rock successions in the greenstone belts of the east Pilbara (Coppin Gap Greenstone Belt and North Pole Dome) in West Australia and of the Barberton Greenstone Belt (Buck Ridge volcano-sedimentary complex) in South Africa. They consist of mafic to ultramafic volcanic rocks, largely pillow basalts, with distinct intercalations of intermediate to felsic intrusive and volcanic rocks and of silicious sediments. The, partly volcaniclastic, silicious sediments of the Buck Ridge and North Pole volcano-sedimentary complexes form a regressive-transgressive sequence. They were deposited close to base level, and experienced occasional emersion. Both North Pole Chert and the chert of the Kittys Gap volcano-sedimentary complex in the Coppin Gap Greenstone Belt preserve the flat-and-channel architecture of a shallow tidal environment. Thickness and facies distribution appear to be genetically linked to systems, i.e. arrays, of syn-depositionally active, extensional faults. Structures at the rear, front and bottoms of these fault arrays, and the fault vergence from the basin margin towards the centre characterize the basins as due to surficial crustal collapse. Observations in the Pilbara craton point to a non-linear plan view and persistence for the basin-defining fault patterns over up to 50 Ma, during which several of these fault arrays became superposed. The faults linked high-crustal level felsic intrusions within the overall mafic rock suite via porphyry pipes, black chert veins and inferred hydrothermal circulations with the overlying felsic lavas, and more importantly, with the cherty sediments. Where such veins surfaced, high-energy breccias, and in the

Early life exposure to a high fat diet promotes long-term changes in dietary preferences and central reward signaling.

PubMed

Teegarden, S L; Scott, A N; Bale, T L

2009-09-15

Overweight and obesity in the United States continues to grow at epidemic rates in large part due to the overconsumption of calorically-dense palatable foods. Identification of factors influencing long-term macronutrient preferences may elucidate points of prevention and behavioral modification. In our current study, we examined the adult macronutrient preferences of mice acutely exposed to a high fat diet during the third postnatal week. We hypothesized that the consumption of a high fat diet during early life would alter the programming of central pathways important in adult dietary preferences. As adults, the early-exposed mice displayed a significant preference for a diet high in fat compared to controls. This effect was not due to diet familiarity as mice exposed to a novel high carbohydrate diet during this same early period failed to show differences in macronutrient preferences as adults. The increased intake of high fat diet in early exposed mice was specific to dietary preferences as no changes were detected for total caloric intake or caloric efficiency. Mechanistically, mice exposed to a high fat diet during early life exhibited significant alterations in biochemical markers of dopamine signaling in the nucleus accumbens, including changes in levels of phospho-dopamine and cyclic AMP-regulated phosphoprotein, molecular weight 32 kDa (DARPP-32) threonine-75, DeltaFosB, and cyclin-dependent kinase 5. These results support our hypothesis that even brief early life exposure to calorically-dense palatable diets alters long-term programming of central mechanisms important in dietary preferences and reward. These changes may underlie the passive overconsumption of high fat foods contributing to the increasing body mass in the western world.

Life course effects of early parental loss among very old African Americans.

PubMed

Johnson, Colleen L; Barer, Barbara M

2002-03-01

To analyze the life course effects of the early loss of one or both parents on very old Black Americans. Open-ended, semistructured interviews were used with a sample of 109 respondents aged 85 years and older. Correlations identified significant associations, and qualitative data illustrate life course trajectories of selected respondents. Those who lost a parent through death or desertion were less integrated into family and friendship groups in late life, and they had fewer social resources in general. Qualitative data describe three outcomes in the sample: those who grew up with both parents present, those who lost a parent but still reported a contented childhood, and those with disrupted families and negative effects. The respondents' open-ended commentary about their past lives and their current situation enhances understanding of connections between early life events and adaptation in old age.

Exposure to the Chinese famine in early life and the risk of anaemia in adulthood.

PubMed

Shi, Zumin; Zhang, Cuilin; Zhou, Minghao; Zhen, Shiqi; Taylor, Anne W

2013-10-01

Famine exposure during the early stage of life is related to a number of adulthood diseases. The objective of this study was to examine the association of early life exposure to the famine in China (1959-1961) with the risk of anaemia in adulthood. We used the data of 2007 adults born between 1954 and 1964 in Jiangsu province from the 2002 Chinese National Nutrition and Health Survey. Anaemia was defined as haemoglobin concentration <12 g/dl in women and <13 g/dl in men. Prevalence of anaemia in adulthood in nonexposed, fetal-exposed, early-childhood, mid-childhood, and late-childhood exposed to famine groups were 26.0%, 33.8%, 28.1%, 28.2% and 29.7%, respectively. Overall, fetal-exposed to famine was associated with 37% increased risk of anaemia as compared with those non-exposed after adjusting for income, education, place of residence, smoking, alcohol drinking, job, hypertension and BMI; relative risk (95% confidence interval) (RR (95% CI)) was 1.37 (1.09, 1.71). In general, this association appeared to be stronger among men, those who were currently overweight or obese, or those of lower educational levels. Corresponding RR (95% CI) was 1.87 (1.21-2.87), 1.75 (1.20-2.56), and 2.07 (1.37-3.12), respectively. Fetal exposure to the Chinese famine was associated with an increased risk of anaemia in adulthood.

Persistent behavioral effects following early life exposure to retinoic acid or valproic acid in zebrafish

PubMed Central

Bailey, Jordan M.; Oliveri, Anthony N.; Karbhari, Nishika; Brooks, Roy A.J.; De La Rocha, Amberlene J.; Janardhan, Sheila; Levin, Edward D.

2015-01-01

BACKGROUND Moderate to severe dysregulation in retinoid signaling during early development is associated with a constellation of physical malformations and/or neural tube defects, including spina bifida. It is thought that more subtle dysregulation of this system, which might be achievable via dietary (i.e. hypervitaminosis A) or pharmacological (i.e. valproic acid) exposure in humans, will manifest on behavioral domains including sociability, without overt physical abnormalities. METHODS During early life, zebrafish were exposed to low doses of two chemicals that disrupt retinoid signaling. From 0-5 dpf, larvae were reared in aqueous solutions containing retinoic acid (0, 0.02, 0.2 or 2 nM) or valproic acid (0, 0.5, 5.0 or 50 uM). One cohort of zebrafish was assessed using a locomotor activity screen at 6-dpf; another was reared to adulthood and assessed using a neurobehavioral test battery (startle habituation, novel tank exploration, shoaling, and predator escape/avoidance). RESULTS There was no significant increase in the incidence of physical malformation among exposed fish compared to controls. Both retinoic acid and valproic acid exposures during development disrupted larval activity with persisting behavioral alterations later in life, primarily manifesting as decreased social affiliation. CONCLUSIONS Social behavior and some aspects of motor function were altered in exposed fish; the importance of examining emotional or psychological consequences of early life exposure to retinoid acting chemicals is discussed. PMID:26439099

HDAC1 links early life stress to schizophrenia-like phenotypes

PubMed Central

Bahari-Javan, Sanaz; Varbanov, Hristo; Halder, Rashi; Benito, Eva; Kaurani, Lalit; Burkhardt, Susanne; Anderson-Schmidt, Heike; Anghelescu, Ion; Budde, Monika; Stilling, Roman M.; Costa, Joan; Medina, Juan; Figge, Christian; Folkerts, Here; Gade, Katrin; Heilbronner, Urs; Koller, Manfred; Konrad, Carsten; Nussbeck, Sara Y.; Scherk, Harald; Spitzer, Carsten; Stierl, Sebastian; Stöckel, Judith; Thiel, Andreas; von Hagen, Martin; Zimmermann, Jörg; Zitzelsberger, Antje; Schulz, Sybille; Schmitt, Andrea; Delalle, Ivana; Falkai, Peter; Schulze, Thomas G.; Dityatev, Alexander; Sananbenesi, Farahnaz; Fischer, André

2017-01-01

Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS. Systemic administration of an HDAC inhibitor rescues the detrimental effects of ELS when applied after the manifestation of disease phenotypes. In addition to the hippocampus and prefrontal cortex, mice subjected to ELS exhibit increased Hdac1 expression in blood. Moreover, Hdac1 levels are increased in blood samples from patients with schizophrenia who had encountered ELS, compared with patients without ELS experience. Our data suggest that HDAC1 inhibition should be considered as a therapeutic approach to treat schizophrenia. PMID:28533418

Global Effects of Early Life Stress on Neurons and Glial Cells.

PubMed

Duenas, Zulma; Caicedo-Mera, Juan Carlos; Torner, Luz

2018-02-12

Early life stress is considered a risk factor for the development of many diseases in both adolescence and adulthood. It has been reported that chronic stress (for instance, due to maternal separation during breast feeding), causes damage to the central nervous system at the level of neurons and glial cells, which are reflected in behavioral disturbances and susceptibility to the development of primarily emotional psychopathology. The aim of this review is to identify the overall state of the scientific literature that relates the information about the consequences of early life stress, contextualizing the mechanisms that may be altered, the behavioral consequences that have been studied and the possible dimorphic effects and its causes. At the end a short overview of pharmacological treatments that have been proposed to reduce the behavioral and neuroendocrine consequences caused by early life stress is presented. This review pretends to integrate general but relevant information based primarily on studies in animal models, which allow the experimental approach and the study of the mechanisms involved. A series of questions remains for reflection and surely will be answered in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Impact of Early Life Adversity on Reward Processing in Young Adults: EEG-fMRI Results from a Prospective Study over 25 Years

PubMed Central

Boecker, Regina; Holz, Nathalie E.; Buchmann, Arlette F.; Blomeyer, Dorothea; Plichta, Michael M.; Wolf, Isabella; Baumeister, Sarah; Meyer-Lindenberg, Andreas; Banaschewski, Tobias

2014-01-01

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. PMID:25118701

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

PubMed

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.

Cumulative early life adversity predicts longevity in wild baboons

PubMed Central

Tung, Jenny; Archie, Elizabeth A.; Altmann, Jeanne; Alberts, Susan C.

2016-01-01

In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

Early-life Socio-economic Status and Adult Health: The Role of Positive Affect.

PubMed

Murdock, Kyle W; LeRoy, Angie S; Fagundes, Christopher P

2017-08-01

The aim of this paper is to develop a further understanding of the relationship between early-life socio-economic status (SES) and adult health disparities. This was accomplished through evaluation of state indicators of positive and negative affect as mechanisms through which early-life SES was associated with susceptibility to a rhinovirus (i.e. the common cold). Analyses were conducted among 286 adults in a viral challenge study in which participants were exposed to a rhinovirus via nasal drops and cold symptoms were evaluated over a period of 5 days. Participant age, body mass index, sex, education, ethnicity, pre-challenge virus-specific antibody titres and subjective adult SES, along with virus type and season of participation, were included as covariates. Early-life SES was associated with cold incidence through state positive affect, but not state negative affect. In addition, contrast analysis indicated that the indirect effect through state positive affect was stronger than the indirect effect through state negative affect. Findings provide further support for early-life SES being an important variable associated with adult health, and that state self-reported positive affect may be an underlying mechanism associated with susceptibility to rhinoviruses. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Assessment of health risks resulting from early-life exposures: Are current chemical toxicity testing protocols and risk assessment methods adequate?

PubMed

Felter, Susan P; Daston, George P; Euling, Susan Y; Piersma, Aldert H; Tassinari, Melissa S

2015-03-01

Abstract Over the last couple of decades, the awareness of the potential health impacts associated with early-life exposures has increased. Global regulatory approaches to chemical risk assessment are intended to be protective for the diverse human population including all life stages. However, questions persist as to whether the current testing approaches and risk assessment methodologies are adequately protective for infants and children. Here, we review physiological and developmental differences that may result in differential sensitivity associated with early-life exposures. It is clear that sensitivity to chemical exposures during early-life can be similar, higher, or lower than that of adults, and can change quickly within a short developmental timeframe. Moreover, age-related exposure differences provide an important consideration for overall susceptibility. Differential sensitivity associated with a life stage can reflect the toxicokinetic handling of a xenobiotic exposure, the toxicodynamic response, or both. Each of these is illustrated with chemical-specific examples. The adequacy of current testing protocols, proposed new tools, and risk assessment methods for systemic noncancer endpoints are reviewed in light of the potential for differential risk to infants and young children.

Early maternal separation induces preference for sucrose and aspartame associated with increased blood glucose and hyperactivity.

PubMed

Aya-Ramos, L; Contreras-Vargas, C; Rico, J L; Dueñas, Z

2017-07-19

Early life stress and exposure to sweeteners lead to physiological and behavioral alterations in adulthood. Nevertheless, many genetic and environmental factors as well as the neurobiological mechanisms that contribute to the development of these disorders are not fully understood. Similarly, evidence about the long-term metabolic effects of exposure to sweeteners in early life is limited and inconsistent. This study used an animal model of maternal separation during breastfeeding (MS) to analyze the effects of early life stress on consumption of sweeteners, weight gain, blood glucose and locomotion. Rats were housed under a reversed light/dark cycle (lights off at 7:00 h) with ad libitum access to water and food. In the MS protocol, MS pups were separated from the dam for 6 h per day in two periods of 180 minutes (7:00-10:00 and 13:00-16:00 h) during the dark phase of postnatal day (PND) 1 to PND 21. Non-separated (NS) pups served as controls. On PND 22 rats were grouped by sex and treatment. From PND 26 to PND 50 sucrose and aspartame were provided to rats, and sweetener intake, body weight and blood glucose-related measures were scored. On PND 50, both male and female rats were exposed to the open field test to obtain locomotion and anxiety-related measures. Results showed that both early maternal separation and sweetener intake during adolescence resulted in increased blood glucose and hyperactivity in male rats but not in female rats. Data suggest that the combination of early stress and exposure to sucrose and aspartame could be a risk factor for the development of chronic diseases such as diabetes, as well as for behavioral alterations.

Through the looking glass at early-life exposures and breast cancer risk.

PubMed

Forman, Michele R; Cantwell, Marie M; Ronckers, Cécile; Zhang, Yawei

2005-01-01

The global increase in the proportion of women diagnosed with breast cancer, inadequate access to screening and high cost of treatment for breast cancer argue strongly for a greater focus on preventive strategies. But at what age is it appropriate to begin targeting preventive approaches? The recognized role of perinatal nutrition in neurologic development and the relation of maternal nutritional status to birthweight and subsequent risk of hypertension, diabetes, and cardiovascular disease identify pregnancy and early childhood as potential phases for prevention. This review examines indicators of hormonal and nutritional exposures in early life and breast cancer risk through the lens of the life course paradigm integrated with maternal and child health research and methodology. Compared to women who were normal birthweight (2500-3999 g), women who weighed>or=4,000 g at birth have a 20 percent to 5-fold increased risk of premenopausal breast cancer. Women born preterm and likely to be small- or large-for-date also have an increased risk. Birth length is directly associated with risk and has a larger magnitude of effect than birthweight. Prior preeclamptics and their daughters have a lower risk of breast cancer than comparable normotensives. An association between infant feeding practices and breast cancer is unclear without improved exposure assessment and analysis. Rapid childhood and pubertal linear growth increases breast cancer risk, while greater body fat over the same periods reduces risk. Growth data thus far have not been calculated in Z-scores from reference growth curves for comparison across studies. Events and secular trends influencing birth cohorts may not be adequately addressed, thereby limiting the interpretation and implications of the findings. Research in nonhuman primates may help uncover underlying mechanisms.

Maternal Smoking and the Risk of Cancer in Early Life - A Meta-Analysis.

PubMed

Rumrich, Isabell Katharina; Viluksela, Matti; Vähäkangas, Kirsi; Gissler, Mika; Surcel, Heljä-Marja; Hänninen, Otto

2016-01-01

In spite of the well-known harmful effects on the fetus, many women continue smoking during pregnancy. Smoking as an important source of toxic chemicals may contribute to the developmental origin of diseases. The aim of this work was to pursue the possible association between maternal smoking and cancer in early life. Specifically, we wanted to identify the associated early life cancer types, and to quantify the associations. In a systematic literature search 825 articles were identified in PubMed and Web of Science, and 55 more through the reference lists. Of these 62 fulfilled the criteria for inclusion in meta-analyses. Using Mantel-Haenszel or DerSimonian and Laird method, depending on heterogeneity of the studies, pooled estimates and 95% confidence intervals for eight cancer types were calculated. Smoking during pregnancy was associated with an increased risk for for brain and central nervous system tumors (OR = 1.09; 95% CI = 1.02-1.17). Although the risk for lymphoma was also associated (OR = 1.21; 95% CI = 1.05-1.34), it did not hold up in subgroup analyses. Leukemia was not found to be associated with maternal smoking. Five other cancer types (bone, soft tissue, renal, hepatic, and germ cell cancer) were also examined, but the number of studies was too limited to exclude the possibility of maternal smoking as a risk factor for cancer in offspring. According to our meta-analyses, maternal smoking is associated with nervous system cancers, but not with leukemia in early life. Confirming or rejecting associations of maternal smoking with lymphoma and the five other cancer types requires further studies.

Imprinting: When Early Life Memories Make Food Smell Bad.

PubMed

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.

Preclinical Immunomodulation by the Probiotic Bifidobacterium breve M-16V in Early Life.

PubMed

Rigo-Adrover, Maria Del Mar; Franch, Àngels; Castell, Margarida; Pérez-Cano, Francisco José

2016-01-01

This study aimed to investigate the effect of supplementation with the probiotic Bifidobacterium breve M-16V on the maturation of the intestinal and circulating immune system during suckling. In order to achieve this purpose, neonatal Lewis rats were supplemented with the probiotic strain from the 6th to the 18th day of life. The animals were weighed during the study, and faecal samples were obtained and evaluated daily. On day 19, rats were euthanized and intestinal wash samples, mesenteric lymph node (MLN) cells, splenocytes and intraepithelial lymphocytes (IEL) were obtained. The probiotic supplementation in early life did not modify the growth curve and did not enhance the systemic immune maturation. However, it increased the proportion of cells bearing TLR4 in the MLN and IEL, and enhanced the percentage of the integrin αEβ7+ and CD62L+ cells in the MLN and that of the integrin αEβ7+ cells in the IEL, suggesting an enhancement of the homing process of naïve T lymphocytes to the MLN, and the retention of activated lymphocytes in the intraepithelial compartment. Interestingly, B. breve M-16V enhanced the intestinal IgA synthesis. In conclusion, supplementation with the probiotic strain B. breve M-16V during suckling improves the development of mucosal immunity in early life.

Preclinical Immunomodulation by the Probiotic Bifidobacterium breve M-16V in Early Life

PubMed Central

Rigo-Adrover, Maria del Mar; Franch, Àngels; Castell, Margarida; Pérez-Cano, Francisco José

2016-01-01

This study aimed to investigate the effect of supplementation with the probiotic Bifidobacterium breve M-16V on the maturation of the intestinal and circulating immune system during suckling. In order to achieve this purpose, neonatal Lewis rats were supplemented with the probiotic strain from the 6th to the 18th day of life. The animals were weighed during the study, and faecal samples were obtained and evaluated daily. On day 19, rats were euthanized and intestinal wash samples, mesenteric lymph node (MLN) cells, splenocytes and intraepithelial lymphocytes (IEL) were obtained. The probiotic supplementation in early life did not modify the growth curve and did not enhance the systemic immune maturation. However, it increased the proportion of cells bearing TLR4 in the MLN and IEL, and enhanced the percentage of the integrin αEβ7+ and CD62L+ cells in the MLN and that of the integrin αEβ7+ cells in the IEL, suggesting an enhancement of the homing process of naïve T lymphocytes to the MLN, and the retention of activated lymphocytes in the intraepithelial compartment. Interestingly, B. breve M-16V enhanced the intestinal IgA synthesis. In conclusion, supplementation with the probiotic strain B. breve M-16V during suckling improves the development of mucosal immunity in early life. PMID:27820846

Intestinal microbiota composition after antibiotic treatment in early life: the INCA study.

PubMed

Rutten, N B M M; Rijkers, G T; Meijssen, C B; Crijns, C E; Oudshoorn, J H; van der Ent, C K; Vlieger, A M

2015-12-09

The acquisition and development of infant gut microbiota can be influenced by numerous factors, of which early antibiotic treatment is an important one. However, studies on the effects of antibiotic treatment in early life on clinical outcomes and establishment and development of the gut microbiota of term infants are limited. Disturbed microbiota composition is hypothesized to be an underlying mechanism of an aberrant development of the immune system. This study aims to investigate the potential clinical and microbial consequences of empiric antibiotic use in early life. 450 term born infants, of whom 150 are exposed to antibiotic treatment in early life and 300 are not (control group), are included in this observational cohort study with a one-year follow-up. Clinical outcomes, including coughing, wheezing, fever >38 °C, runny nose, glue ear, rash, diarrhea and >3 crying hours a day, are recorded daily by parents and examined by previously defined doctor's diagnosis. A blood sample is taken at closure to investigate the infant's vaccination response and sensitization for food and inhalant allergens. Fecal samples are obtained at eight time points during the first year of life. Potential differences in microbial profiles of infants treated with antibiotics versus healthy controls will be determined by use of 16S-23S rRNA gene analysis (IS-pro). Microbiota composition will be described by means of abundance, diversity and (dis)similarity. Diversity is calculated using the Shannon index. Dissimilarities between samples are calculated as the cosine distance between each pair of samples and analyzed with principal coordinate analysis. Clinical variables and possible associations are assessed by appropriate statistics. Both clinical quantitative and qualitative microbial effects of antibiotic treatment in early life may be demonstrated. These findings can be important, since there is evidence that manipulation of the infant microbiota by using pre- or probiotics can

Reproductive and early life stages pathology - Histopathology workshop report

USGS Publications Warehouse

Bruno, D.W.; Nowak, B.; Elliott, Diane G.

2006-01-01

Pathology occurring during reproduction and larval development represents an important part of the life cycle of fish, and the diseases that affect eggs and larvae often result in significant losses. However, mortality during this period is frequently ignored or poorly researched as the temptation is to replace the losses rather than investigate the causes. A histopathology workshop organised at the newly refurnished laboratory within the Danish Veterinary School was an opportunity to discuss the pathology of selected diseases associated with Reproductive and Early Life Stages Pathology. Several people also kindly provided reference slides.

Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender

PubMed Central

Xu, Wanli; Janton, Susan; Henderson, Wendy A.; Matson, Adam; McGrath, Jacqueline M.; Maas, Kendra; Graf, Joerg

2016-01-01

Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05–0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother’s own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion

Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender.

PubMed

Cong, Xiaomei; Xu, Wanli; Janton, Susan; Henderson, Wendy A; Matson, Adam; McGrath, Jacqueline M; Maas, Kendra; Graf, Joerg

2016-01-01

Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05-0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother's own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion

Red-breasted nuthatches detect early increases in spruce budworm populations

Treesearch

Hewlette S. Crawford; Daniel T. Jennings; Timothy L. Stone

1990-01-01

Early suppression .of increasing spruce budworm populations is essential to prevent epidemics; however, early changes in budworm numbers are difficult to detect. An effective and inexpensive method to detect early increases is needed. Red-breasted nuthatches eat more spruce budworm larvae and pupae as the insect increases in number. We estimated the number of large...

Early life rhinovirus infection exacerbates house-dust-mite induced lung disease more severely in female mice.

PubMed

Phan, Jennifer A; Kicic, Anthony; Berry, Luke J; Sly, Peter D; Larcombe, Alexander N

2016-01-01

Recent studies have employed animal models to investigate links between rhinovirus infection and allergic airways disease, however, most do not involve early life infection, and none consider the effects of sex on responses. Here, we infected male and female mice with human rhinovirus 1B (or control) on day 7 of life. Mice were then subjected to 7 weeks of exposure to house-dust-mite prior to assessment of bronchoalveolar inflammation, serum antibodies, lung function, and responsiveness to methacholine. There were significant differences in responses between males and females in most outcomes. In males, chronic house-dust-mite exposure increased bronchoalveolar inflammation, house-dust-mite specific IgG1 and responsiveness of the lung parenchyma, however, there was no additional impact of rhinovirus infection. Conversely, in females, there were additive and synergistic effects of rhinovirus infection and house-dust-mite exposure on neutrophilia, airway resistance, and responsiveness of the lung parenchyma. We conclude that early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice.

Early Life Factors and Inter-Country Heterogeneity in BMI Growth Trajectories of European Children: The IDEFICS Study

PubMed Central

Börnhorst, Claudia; Siani, Alfonso; Russo, Paola; Kourides, Yannis; Sion, Isabelle; Molnár, Denés; Moreno, Luis A.; Rodríguez, Gerardo; Ben-Shlomo, Yoav; Howe, Laura; Lissner, Lauren; Mehlig, Kirsten; Regber, Susann; Bammann, Karin; Foraita, Ronja

2016-01-01

Background Starting from birth, this explorative study aimed to investigate between-country differences in body mass index (BMI) trajectories and whether early life factors explain these differences. Methods The sample included 7,644 children from seven European countries (Belgium, Cyprus, Germany, Hungary, Italy, Spain, Sweden) participating in the multi-centre IDEFICS study. Information on early life factors and in total 53,409 repeated measurements of height and weight from 0 to <12 years of age were collected during the baseline (2007/2008) and follow-up examination (2009/2010) supplemented by records of routine child health visits. Country-specific BMI growth curves were estimated using fractional polynomial mixed effects models. Several covariates focussing on early life factors were added to the models to investigate their role in the between-countries differences. Results Large between-country differences were observed with Italian children showing significantly higher mean BMI values at all ages ≥ 3 years compared to the other countries. For instance, at age 11 years mean BMI values in Italian boys and girls were 22.3 [21.9;22.8; 99% confidence interval] and 22.0 [21.5;22.4], respectively, compared to a range of 18.4 [18.1;18.8] to 20.3 [19.8;20.7] in boys and 18.2 [17.8;18.6] to 20.3 [19.8;20.7] in girls in the other countries. After adjustment for early life factors, differences between country-specific BMI curves became smaller. Maternal BMI was the factor being most strongly associated with BMI growth (p<0.01 in all countries) with associations increasing during childhood. Gestational weight gain (GWG) was weakly associated with BMI at birth in all countries. In some countries, positive associations between BMI growth and children not being breastfed, mothers’ smoking during pregnancy and low educational level of parents were found. Conclusion Early life factors seem to explain only some of the inter-country variation in growth. Maternal BMI showed

Automatic segmentation of the hippocampus for preterm neonates from early-in-life to term-equivalent age.

PubMed

Guo, Ting; Winterburn, Julie L; Pipitone, Jon; Duerden, Emma G; Park, Min Tae M; Chau, Vann; Poskitt, Kenneth J; Grunau, Ruth E; Synnes, Anne; Miller, Steven P; Mallar Chakravarty, M

2015-01-01

The hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life. First, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm neonates and apply this protocol on 22 early-in-life and 22 term images. These manual segmentations are considered the gold standard in assessing the automatic segmentations. MAGeT-Brain, automatic hippocampal segmentation pipeline, requires only a small number of input atlases and reduces the registration and resampling errors by employing an intermediate template library. We assess the segmentation accuracy of MAGeT-Brain in three validation studies, evaluate the hippocampal growth from early-in-life to term-equivalent age, and study the effect of preterm birth on the hippocampal volume. The first experiment thoroughly validates MAGeT-Brain segmentation in three sets of 10-fold Monte Carlo cross-validation (MCCV) analyses with 187 different groups of input atlases and templates. The second experiment segments the neonatal hippocampi on 168 early-in-life and 154 term images and evaluates the hippocampal growth rate of 125 infants from early-in-life to term-equivalent age. The third experiment analyzes the effect of gestational age (GA) at birth on the average hippocampal volume at early-in-life and term-equivalent age using linear regression. The final segmentations demonstrate that MAGeT-Brain consistently provides accurate segmentations in comparison to manually

Automatic segmentation of the hippocampus for preterm neonates from early-in-life to term-equivalent age

PubMed Central

Guo, Ting; Winterburn, Julie L.; Pipitone, Jon; Duerden, Emma G.; Park, Min Tae M.; Chau, Vann; Poskitt, Kenneth J.; Grunau, Ruth E.; Synnes, Anne; Miller, Steven P.; Mallar Chakravarty, M.

2015-01-01

Introduction The hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life. Methods First, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm neonates and apply this protocol on 22 early-in-life and 22 term images. These manual segmentations are considered the gold standard in assessing the automatic segmentations. MAGeT-Brain, automatic hippocampal segmentation pipeline, requires only a small number of input atlases and reduces the registration and resampling errors by employing an intermediate template library. We assess the segmentation accuracy of MAGeT-Brain in three validation studies, evaluate the hippocampal growth from early-in-life to term-equivalent age, and study the effect of preterm birth on the hippocampal volume. The first experiment thoroughly validates MAGeT-Brain segmentation in three sets of 10-fold Monte Carlo cross-validation (MCCV) analyses with 187 different groups of input atlases and templates. The second experiment segments the neonatal hippocampi on 168 early-in-life and 154 term images and evaluates the hippocampal growth rate of 125 infants from early-in-life to term-equivalent age. The third experiment analyzes the effect of gestational age (GA) at birth on the average hippocampal volume at early-in-life and term-equivalent age using linear regression. Results The final segmentations demonstrate that MAGeT-Brain consistently provides accurate segmentations

Manipulating rumen microbiome and fermentation through interventions during early life: a review

PubMed Central

Yáñez-Ruiz, David R.; Abecia, Leticia; Newbold, Charles J.

2015-01-01

The nutritional manipulations of the rumen microbiome to enhance productivity and health are rather limited by the resilience of the ecosystem once established in the mature rumen. Based on recent studies, it has been suggested that the microbial colonization that occurs soon after birth opens a possibility of manipulation with potential to produce lasting effects into adult life. This paper presents the state-of-the-art in relation to early life nutritional interventions by addressing three areas: the development of the rumen as an organ in regards to the nutrition of the new-born, the main factors that determine the microbial population that first colonizes and establishes in the rumen, and the key immunity players that contribute to shaping the commensal microbiota in the early stage of life to understand host-microbiome specificity. The development of the rumen epithelium and muscularization are differently affected by the nature of the diet and special care should be taken with regards to transition from liquid (milk) to solid feed. The rumen is quickly colonized by all type of microorganisms straight after birth and the colonization pattern may be influenced by several factors such as presence/absence of adult animals, the first solid diet provided, and the inclusion of compounds that prevent/facilitate the establishment of some microorganisms or the direct inoculation of specific strains. The results presented show how early life events may be related to the microbial community structure and/or the rumen activity in the animals post-weaning. This would create differences in adaptive capacity due to different early life experiences and leads to the idea of microbial programming. However, many elements need to be further studied such as: the most sensitive window of time for interventions, the best means to test long term effectiveness, the role of key microbial groups and host-immune regulations. PMID:26528276

The microbial environment and its influence on asthma prevention in early life.

PubMed

von Mutius, Erika

2016-03-01

There is accumulating evidence to suggest that the environmental microbiome plays a significant role in asthma development. The very low prevalence of asthma in populations highly exposed to microbial environments (farm children and Amish populations) highlights its preventive potential. This microbial diversity might be necessary to instruct a well-adapted immune response and regulated inflammatory responses to other inhaled and ingested environmental elements, such as allergens, particles, and viruses. Like the internal gut microbiome, which is increasingly recognized as an important instructor of immune maturation, the external environmental microbiome might shape immune responses on the skin, airway mucosal surfaces, and potentially also the gut early in life. The diversity of the external microbial world will ensure that of the many maladapted pathways leading to asthma development, most, if not all, will be counterbalanced. Likewise, important contributors to asthma, such as allergen sensitization and allergic manifestations early in life, are being suppressed. Thus the facets of innate immunity targeted by microbes and their compounds and metabolites might be the master switch to asthma and allergy protection, which has been found in environments rich in microbial exposures. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

HIV Clade-C Infection and Cognitive Impairment, Fatigue, Depression, and Quality of Life in Early-Stage Infection in Northern Indians

PubMed Central

Cook, R.; Jones, D. L.; Nehra, R.; Kumar, A. M.; Prabhakar, S.; Waldrop-Valverde, D.; Sharma, S.; Kumar, M.

2017-01-01

HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm3) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population. PMID:23722088

HIV Clade-C Infection and Cognitive Impairment, Fatigue, Depression, and Quality of Life in Early-Stage Infection in Northern Indians.

PubMed

Cook, R; Jones, D L; Nehra, R; Kumar, A M; Prabhakar, S; Waldrop-Valverde, D; Sharma, S; Kumar, M

2016-07-01

HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm(3)) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population. © The Author(s) 2013.

The early life nutritional environment and early life stress as potential pathways towards the metabolic syndrome in mid-life? A lifecourse analysis using the 1958 British Birth cohort.

PubMed

Delpierre, C; Fantin, R; Barboza-Solis, C; Lepage, B; Darnaudéry, M; Kelly-Irving, M

2016-08-18

Lifecourse studies suggest that the metabolic syndrome (MetS) may be rooted in the early life environment. This study aims to examine the pathways linking early nutritional and psychosocial exposures and the presence of MetS in midlife. Data are from the National Child Development Study including individuals born during 1 week in 1958 in Great Britain and followed-up until now. MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III classification. Mother's pre-pregnancy body mass index (BMI) was used as a proxy of the early nutritional environment and Adverse Childhood Experiences (ACE) as a proxy for early psychosocial stress. Socioeconomic characteristics, pregnancy and birth conditions were extracted as potential confounders. Adult health behaviors, BMI, socioeconomic environment and psychological state were considered as mediating variables. Multivariate models were performed by including variables sequentially taking a lifecourse approach. 37.5 % of men and 19.8 % of women had MetS. Participants with an obese/overweight mother presented a higher risk of MetS than those whose mother had a normal pre-pregnancy BMI. Men exposed to two ACE or more, and women exposed to one ACE, were more at risk of MetS compared to unexposed individuals. After including confounders and mediators, mother's pre-pregnancy BMI was still associated with MetS in midlife but the association was weakened after including participant's adult BMI. ACE was no longer associated with MetS after including confounders in models. The early nutritional environment, represented by mother's pre-pregnancy BMI, was associated with the risk of MetS in midlife. An important mechanism involves a mother-to-child BMI transmission, independent of birth or perinatal conditions, socioeconomic characteristics and health behaviors over the lifecourse. However this mechanism is not sufficient for explaining the influence of mother's pre-pregnancy BMI which implies the

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

PubMed

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.

Purpose in life and tobacco use among community-dwelling mothers of early adolescents

PubMed Central

Ando, Shuntaro; Koike, Shinsuke; Fujikawa, Shinya; Kanata, Sho; Endo, Kaori; Nakanishi, Miharu; Hatch, Stephani L; Richards, Marcus; Kasai, Kiyoto; Hiraiwa-Hasegawa, Mariko; Nishida, Atsushi

2018-01-01

Objectives The rising prevalence of tobacco use and tobacco-attributable deaths among women is of worldwide concern. In particular, smoking prevention for mothers in early midlife is a significant international public health goal. A higher sense of purpose in life (PIL) is thought to reduce detrimental health behaviours. However, little is known about the association between a sense of PIL and tobacco use. This study investigates this association among community-dwelling mothers of early adolescents. Design This population-based cross-sectional study uses a self-reported questionnaire from the Tokyo Early Adolescence Survey, a large community-based survey conducted in Japan between 2012 and 2015. Setting Participants were randomly recruited from the resident registries of three municipalities in Tokyo, Japan. Participants A total of 4478 children and their primary parents participated. Responses from 4063 mothers with no missing data were analysed (mean age=42.0 years (SD=4.2)). Measures Participants’ tobacco use, including the number of cigarettes smoked per day, was documented using a questionnaire. PIL was assessed using a Purpose in Life scale derived from Ryff’s Psychological Well-Being Scale. Results Greater PIL was associated with a decreased likelihood of tobacco use, even when adjusted for confounders (OR=0.80, 95% CI 0.70 to 0.91). Multinomial logistic regression analyses revealed that PIL was inversely associated with tobacco consumption among mothers. These associations remained after controlling for psychological distress, socioeconomic factors and frequency of alcohol consumption among moderate to heavy smokers (OR=0.70, 95% CI 0.57 to 0.86), while attenuated among light smokers. Conclusions Increasing PIL may be a valuable intervention for reducing tobacco use among women in early midlife. This study can contribute to our understanding of the psychology of smoking behaviour and shed light on the targeted intervention to reduce tobacco use

Long-Term Effects of Early-Life Otitis Media on Language Development

ERIC Educational Resources Information Center

Zumach, Anne; Gerrits, Ellen; Chenault, Michelene; Anteunis, Lucien

2010-01-01

Purpose: The aim of the present study was to examine the long-term consequences of early-life otitis media (OM) and the associated hearing loss (HL) on language skills of school-aged children. Method: In a prospective study, the middle-ear status of 65 Dutch healthy-born children was documented every 3 months during their first 2 years of life;…

Mice Producing Reduced Levels of Insulin-Like Growth Factor Type 1 Display an Increase in Maximum, but not Mean, Life Span

PubMed Central

2014-01-01

Reduced signaling through the IGF type 1 (IGF-1) receptor increases life span in multiple invertebrate organisms. Studies on mammalian longevity suggest that reducing levels of IGF-1 may also increase life span. However, the data are conflicting and complicated by the physiology of the mammalian neuroendocrine system. We have performed life-span analysis on mice homozygous for an insertion in the Igf1 gene. These mice produce reduced levels of IGF-1 and display a phenotype consistent with a significant decrease in IGF-1. Life-span analysis was carried out at three independent locations. Although the life-span data varied between sites, the maximum life span of the IGF-1-deficient mice was significantly increased and age-specific mortality rates were reduced in the IGF-1-deficient mice; however, mean life span did not differ except at one site, where mean life span was increased in female IGF-1-deficient animals. Early life mortality was noted in one cohort of IGF-1-deficient mice. The results are consistent with a significant role for IGF-1 in the modulation of life span but contrast with the published life-span data for the hypopituitary Ames and Snell dwarf mice and growth hormone receptor null mice, indicating that a reduction in IGF-1 alone is insufficient to increase both mean and maximal life span in mice. PMID:23873963

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

PubMed

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.

Exposure to the Chinese famine in early life and the risk of anaemia in adulthood

PubMed Central

2013-01-01

Background Famine exposure during the early stage of life is related to a number of adulthood diseases. The objective of this study was to examine the association of early life exposure to the famine in China (1959–1961) with the risk of anaemia in adulthood. Methods We used the data of 2007 adults born between 1954 and 1964 in Jiangsu province from the 2002 Chinese National Nutrition and Health Survey. Anaemia was defined as haemoglobin concentration <12 g/dl in women and <13 g/dl in men. Results Prevalence of anaemia in adulthood in nonexposed, fetal-exposed, early-childhood, mid-childhood, and late-childhood exposed to famine groups were 26.0%, 33.8%, 28.1%, 28.2% and 29.7%, respectively. Overall, fetal-exposed to famine was associated with 37% increased risk of anaemia as compared with those non-exposed after adjusting for income, education, place of residence, smoking, alcohol drinking, job, hypertension and BMI; relative risk (95% confidence interval) (RR (95% CI)) was 1.37 (1.09, 1.71). In general, this association appeared to be stronger among men, those who were currently overweight or obese, or those of lower educational levels. Corresponding RR (95% CI) was 1.87 (1.21-2.87), 1.75 (1.20-2.56), and 2.07 (1.37-3.12), respectively. Conclusions Fetal exposure to the Chinese famine was associated with an increased risk of anaemia in adulthood. PMID:24079608

Early-life factors affect risk of pain and fever in infants during teething periods.

PubMed

Un Lam, Carolina; Hsu, Chin-Ying Stephen; Yee, Robert; Koh, David; Lee, Yung Seng; Chong, Mary Foong-Fong; Cai, Meijin; Kwek, Kenneth; Saw, Seang Mei; Gluckman, Peter; Chong, Yap Seng

2016-11-01

This longitudinal study aimed to investigate the prevalence of teething-related pain and fever and the early-life factors that may affect the risk of experiencing these disturbances within the first 1.5 years of life. Participants were recruited (n = 1033) through the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort (n = 1237). Interviews were performed tri-monthly regarding the prevalence of teething pain and fever in children from 6 to 18 months of age. Crude and multivariable analyses were conducted using Poisson-log regression models. Prevalence rates for teething pain and fever were 35.5 and 49.9 % respectively. Multivariable Poisson regression analysis showed maternal second-hand tobacco smoke (SHS) exposure to increase the risk of both pain (mean ratio = 1.35; p = 0.006) and fever (mean ratio = 1.22; p = 0.025), whereas SHS exposure plus active smoking further increased risk of teething pain in the children (mean ratio = 1.89; p = 0.029). Delivery via Caesarean section increased risk of teething pain (mean ratio = 1.27; p = 0.033), while prenatal plasma vitamin D insufficiency lowered such a risk (mean ratio = 0.62; p = 0.012). Compared to Chinese infants, Indian babies exhibited lower risk of teething pain and fever (both p ≤ 0.001). Early-life factors such as tobacco smoke exposure and vitamin insufficiency during pregnancy, ethnicity and childbirth via Caesarean section may significantly affect the child's susceptibility to teething-related pain and fever. Knowledge of prevalence and risk factors of teething disturbances may better equip primary caregivers and healthcare professionals to accurately detect teething-related local and/or systemic signs/symptoms and effectively facilitate tobacco cessation among pregnant women.

Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children

PubMed Central

Murray-Kolb, Laura E.; Scharf, Rebecca J.; Pendergast, Laura L.; Lang, Dennis R.; Kolling, Glynis L.; Guerrant, Richard L.

2016-01-01

The intestinal microbiota undergoes active remodeling in the first 6 to 18 months of life, during which time the characteristics of the adult microbiota are developed. This process is strongly influenced by the early diet and enteric pathogens. Enteric infections and malnutrition early in life may favor microbiota dysbiosis and small intestinal bacterial overgrowth, resulting in intestinal barrier dysfunction and translocation of intestinal bacterial products, ultimately leading to low-grade, chronic, subclinical systemic inflammation. The leaky gut–derived low-grade systemic inflammation may have profound consequences on the gut–liver–brain axis, compromising normal growth, metabolism, and cognitive development. This review examines recent data suggesting that early-life enteric infections that lead to intestinal barrier disruption may shift the intestinal microbiota toward chronic systemic inflammation and subsequent impaired cognitive development. PMID:27142301

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

PubMed

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.

Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function

PubMed Central

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.

2016-01-01

Background: 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. Methods: 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. Results: 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. Conclusions: 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 PMID:27586368

Early Head Start, Pediatric Dental Use, and Oral Health–Related Quality of Life

PubMed Central

Burgette, J.M.; Preisser, J.S.; Weinberger, M.; King, R.S.; Rozier, R.G.

2017-01-01

The objective of the study was to examine the mediating effect of child dental use on the effectiveness of North Carolina Early Head Start (EHS) in improving oral health–related quality of life (OHRQoL). In total, 479 parents of children enrolled in EHS and 699 parents of Medicaid-matched children were interviewed at baseline when children were approximately 10 mo old and 24 mo later. In this quasi-experimental study, mediation analysis was performed using the counterfactual framework analysis, which employed 2 logit models with random effects: 1) for the mediator as a function of the treatment and covariates and 2) for the outcome as a function of the treatment, mediator, and covariates. The covariates were baseline dental OHRQoL, dental need, survey language, and a propensity score. We used in-person computer-assisted, structured interviews to collect information on demographic characteristics and dental use and to administer the Early Childhood Oral Health Impact Scale, a measure of OHRQoL. Dental use had a mediation effect in the undesired direction with a 2–percentage point increase in the probability of any negative impact to OHRQoL (95% confidence interval [CI], 0.3%–3.9%). Even with higher dental use by EHS participants, the probability of any negative impact to OHRQoL was approximately 8 percentage points lower if an individual were moved from the non-EHS group to the EHS group (95% CI, −13.9% to −1.2%). EHS increases child dental use, which worsens family OHRQoL. However, EHS is associated with improved OHRQoL overall. Knowledge Transfer Statement: Study results can inform policy makers that comprehensive early childhood education programs improve oral health–related quality of life (OHRQoL) for disadvantaged families with young children in pathways outside of clinical dental care. This awareness and its promotion can lead to greater resource investments in early childhood education programs. Information about the negative impacts of dental

Does educating patients about the Early Palliative Care Study increase preferences for outpatient palliative cancer care? Findings from Project EMPOWER.

PubMed

Hoerger, Michael; Perry, Laura M; Gramling, Robert; Epstein, Ronald M; Duberstein, Paul R

2017-06-01

Randomized controlled trials, especially the Early Palliative Care Study (Temel et al., 2010), have shown that early outpatient palliative cancer care can improve quality of life for patients with advanced cancer or serious symptoms. However, fear and misconceptions drive avoidance of palliative care. Drawing from an empowerment perspective, we examined whether educating patients about evidence from the Early Palliative Care Study would increase preferences for palliative care. A sample of 598 patients with prostate, breast, lung, colon/rectal, skin, and other cancer diagnoses completed an Internet-mediated experiment using a between-group prepost design. Intervention participants received a summary of the Early Palliative Care Study; controls received no intervention. Participants completed baseline and posttest assessments of preferences of palliative care. Analyses controlled for age, gender, education, cancer type, presence of metastases, time since diagnosis, and baseline preferences. As hypothesized, the intervention had a favorable impact on participants' preferences for outpatient palliative cancer care relative to controls (d = 1.01, p < .001), while controlling for covariates. Intervention participants came to view palliative care as more efficacious (d = 0.79, p < .001) and less scary (d = 0.60, p < .001) and exhibited stronger behavioral intentions to utilize outpatient palliative care if referred (d = 0.60, p < .001). Findings were comparable in patients with metastatic disease, those with less education, and those experiencing financial strain. Educating patients about the Early Palliative Care Study increases preferences for early outpatient palliative care. This research has implications for future studies aimed at improving quality of life in cancer by increasing palliative care utilization. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The curvilinear relationship of early-life adversity and successful aging: the mediating role of mental health.

PubMed

Höltge, Jan; Mc Gee, Shauna L; Thoma, Myriam V

2018-02-15

The steeling effect suggests that early-life adversity can have a beneficial impact later in life. However, little is known about its underlying mechanisms and long-term outcomes . The study aimed to examine the role of early-life adversity (ELA) on successful aging, and whether this relationship can be explained by mental and physical health. Socio-demographics, early-life adversity (ELA), individual quality of life (iQoL), and mental and physical health of 270 individuals (M age = 66.82 years, 71.5% female) were assessed. Polynomial regressions and mediation analyses were conducted. Significant inverse U-shaped associations were found between ELA and iQoL (β = -.59, p = .005) and between ELA and mental health (β = -.64, p = .002), but not between ELA and physical health. Furthermore, mental health significantly mediated the relationship between ELA and iQoL (b = -.84, BCa CI [-1.66, -.27]). Highest level of individual quality of life (i.e. successful aging) was related to a moderate amount of ELA. Additionally, mental health significantly mediated this relationship. These findings suggest that some amount of ELA could be beneficial for successful aging. Resource-focused interventions are needed to improve health and promote successful aging for an underdetected, at-risk subgroup with low early-life adversity.

Early-life predictors of leisure-time physical inactivity in midadulthood: findings from a prospective British birth cohort.

PubMed

Pinto Pereira, Snehal M; Li, Leah; Power, Chris

2014-12-01

Much adult physical inactivity research ignores early-life factors from which later influences may originate. In the 1958 British birth cohort (followed from 1958 to 2008), leisure-time inactivity, defined as activity frequency of less than once a week, was assessed at ages 33, 42, and 50 years (n = 12,776). Early-life factors (at ages 0-16 years) were categorized into 3 domains (i.e., physical, social, and behavioral). We assessed associations of adult inactivity 1) with factors within domains, 2) with the 3 domains combined, and 3) allowing for adult factors. At each age, approximately 32% of subjects were inactive. When domains were combined, factors associated with inactivity (e.g., at age 50 years) were prepubertal stature (5% lower odds per 1-standard deviation higher height), hand control/coordination problems (14% higher odds per 1-point increase on a 4-point scale), cognition (10% lower odds per 1-standard deviation greater ability), parental divorce (21% higher odds), institutional care (29% higher odds), parental social class at child's birth (9% higher odds per 1-point reduction on a 4-point scale), minimal parental education (13% higher odds), household amenities (2% higher odds per increase (representing poorer amenities) on a 19-point scale), inactivity (8% higher odds per 1-point reduction in activity on a 4-point scale), low sports aptitude (13% higher odds), and externalizing behaviors (i.e., conduct problems) (5% higher odds per 1-standard deviation higher score). Adjustment for adult covariates weakened associations slightly. Factors from early life were associated with adult leisure-time inactivity, allowing for early identification of groups vulnerable to inactivity. © The Author 2014. 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.

Family Quality of Life Following Early Identification of Deafness

ERIC Educational Resources Information Center

Jackson, Carla W.; Wegner, Jane R.; Turnbull, Ann P.

2010-01-01

Purpose: Family members' perceptions of their quality of life were examined following early identification of deafness in children. Method: A questionnaire was used to solicit ratings of satisfaction from the family members of 207 children who were deaf and younger than 6 years of age. Results: Results indicated that families were generally…

Conditions for the emergence of life on the early Earth: summary and reflections

PubMed Central

Jortner, Joshua

2006-01-01

This review attempts to situate the emergence of life on the early Earth within the scientific issues of the operational and mechanistic description of life, the conditions and constraints of prebiotic chemistry, together with bottom-up molecular fabrication and biomolecular nanofabrication and top-down miniaturization approaches to the origin of terrestrial life. PMID:17008225

T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection.

PubMed

Elwenspoek, Martha M C; Sias, Krystel; Hengesch, Xenia; Schaan, Violetta K; Leenen, Fleur A D; Adams, Philipp; Mériaux, Sophie B; Schmitz, Stephanie; Bonnemberger, Fanny; Ewen, Anouk; Schächinger, Hartmut; Vögele, Claus; Muller, Claude P; Turner, Jonathan D

2017-01-01

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n  = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n  = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57 + ) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts.

T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection

PubMed Central

Elwenspoek, Martha M. C.; Sias, Krystel; Hengesch, Xenia; Schaan, Violetta K.; Leenen, Fleur A. D.; Adams, Philipp; Mériaux, Sophie B.; Schmitz, Stephanie; Bonnemberger, Fanny; Ewen, Anouk; Schächinger, Hartmut; Vögele, Claus; Muller, Claude P.; Turner, Jonathan D.

2017-01-01

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57+) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts. PMID:29089944

Attic still life southsoutheast looking northnorthwest. Shows an early toilet, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Attic still life south-southeast looking north-northwest. Shows an early toilet, what is possibly the original front door, and a lead lined reservoir. Also shows the attic framing. - Samuel P. Grindle House, 13 School Street, Castine, Hancock County, ME

Early-life conditions and health at older ages: The mediating role of educational attainment, family and employment trajectories.

PubMed

Arpino, Bruno; Gumà, Jordi; Julià, Albert

2018-01-01

We examine to what extent the effect of early-life conditions (health and socioeconomic status) on health in later life is mediated by educational attainment and life-course trajectories (fertility, partnership, employment). Using data from the Survey of Health, Ageing and Retirement in Europe (N = 12,034), we apply, separately by gender, multichannel sequence analysis and cluster analysis to obtain groups of similar family and employment histories. The KHB method is used to disentangle direct and indirect effects of early-life conditions on health. Early-life-conditions indirectly impact on health in later life as result of their influence on education and family and employment trajectories. For example, between 22% and 42% of the effect of low parental socio-economic status at childhood on the three considered health outcomes at older age is explained by educational attainment for women. Even higher percentages are found for men (35% - 57%). On the contrary, the positive effect of poor health at childhood on poor health at older ages is not significantly mediated by education and life-course trajectories. Education captures most of the mediating effect of parental socio-economic status. More specifically, between 66% and 75% of the indirect effect of low parental socio-economic status at childhood on the three considered health outcomes at older age is explained by educational attainment for women. Again, higher percentages are found for men (86% - 93%). Early-life conditions, especially socioeconomic status, influence family and employment trajectories indirectly through their impact on education. We also find a persistent direct impact of early-life conditions on health at older ages. Our findings demonstrate that early-life experiences influence education and life-course trajectories and health in later life, suggesting that public investments in children are expected to produce long lasting effects on people's lives throughout the different phases of their

Brain glutathione reductase induction increases early survival and decreases lipofuscin accumulation in aging frogs.

PubMed

López-Torres, M; Pérez-Campo, R; Fernandez, A; Barba, C; Barja de Quiroga, G

1993-02-01

Brain catalase was continuously depleted throughout the life span starting with a large population of initially young and old frogs. Free radical-related parameters were measured in the brain tissue once per year after 2.5, 14.5, and 26.5 months of experimentation. Brain lipofuscin accumulation was observed after 14.5 and 26.5 months, and survival was continuously followed during 33 months. The age of the animal did not decrease endogenous antioxidants nor increase tissue peroxidation either in cross-sectional or longitudinal comparisons. Continuous catalase depletion similarly affected young and old animals, inducing glutathione reductase, tending to decrease oxidized glutathione/reduced glutathione (GSSG/GSH) ratio, decreasing lipofuscin accumulation in the brain, and increasing survival from 46% to 91% after 14.5 months. At 26.5 months of experimentation the loss of the glutathione reductase induction in catalase-depleted animals was accompanied by the presence of higher lipofuscin deposits than in controls and was followed by a great increase in mortality rate. Even though the maximal life span (7 years) was the same in the control and treated animals which were already old (4.2 years) at the beginning of the experiment, the treated animals showed a strong reduction in the rates of early death. It is proposed that the maintenance of a high antioxidant/prooxidant balance in the vertebrate brain greatly increases the probability of the individual to reach the final segments of its species-specific life span.

Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

EPA Science Inventory

Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

Population density and climate shape early-life survival and recruitment in a long-lived pelagic seabird.

PubMed

Fay, Rémi; Weimerskirch, Henri; Delord, Karine; Barbraud, Christophe

2015-09-01

1. Our understanding of demographic processes is mainly based on analyses of traits from the adult component of populations. Early-life demographic traits are poorly known mainly for methodological reasons. Yet, survival of juvenile and immature individuals is critical for the recruitment into the population and thus for the whole population dynamic, especially for long-lived species. This bias currently restrains our ability to fully understand population dynamics of long-lived species and life-history theory. 2. The goal of this study was to estimate the early-life demographic parameters of a long-lived species with a long immature period (9-10 years), to test for sex and age effects on these parameters and to identify the environmental factors encountered during the period of immaturity that may influence survival and recruitment. 3. Using capture-mark-recapture multievent models allowing us to deal with uncertain and unobservable individual states, we analysed a long-term data set of wandering albatrosses to estimate both age- and sex-specific early-life survival and recruitment. We investigated environmental factors potentially driving these demographic traits using climatic and fisheries covariates and tested for density dependence. 4. Our study provides for the first time an estimate of annual survival during the first 2 years at sea for an albatross species (0·801 ± 0·014). Both age and sex affected early-life survival and recruitment processes of this long-lived seabird species. Early-life survival and recruitment were highly variable across years although the sensitivity of young birds to environmental variability decreased with age. Early-life survival was negatively associated with sea surface temperature, and recruitment rate was positively related to both Southern Annular Mode and sea surface temperature. We found strong evidence for density-dependent mortality of juveniles. Population size explained 41% of the variation of this parameter over the

A Review of the Relationship Between Socioeconomic Position and the Early-Life Predictors of Obesity.

PubMed

Cameron, Adrian J; Spence, Alison C; Laws, Rachel; Hesketh, Kylie D; Lioret, Sandrine; Campbell, Karen J

2015-09-01

A range of important early-life predictors of later obesity have been identified. Children of lower socioeconomic position (SEP) have a steeper weight gain trajectory from birth with a strong socioeconomic gradient in child and adult obesity prevalence. An assessment of the association between SEP and the early-life predictors of obesity has been lacking. The review involved a two-stage process: Part 1, using previously published systematic reviews, we developed a list of the potentially modifiable determinants of obesity observable in the pre-natal, peri-natal or post-natal (pre-school) periods; and part 2, conducting a literature review of evidence for socioeconomic patterning in the determinants identified in part 1. Strong evidence was found for an inverse relationship between SEP and (1) pre-natal risk factors (pre-pregnancy maternal body mass index (BMI), diabetes and pre-pregnancy diet), (2) antenatal/peri natal risk factors (smoking during pregnancy and low birth weight) and (3) early-life nutrition (including breastfeeding initiation and duration, early introduction of solids, maternal and infant diet quality, and some aspects of the home food environment), and television viewing in young children. Less strong evidence (because of a lack of studies for some factors) was found for paternal BMI, maternal weight gain during pregnancy, child sleep duration, high birth weight and lack of physical activity in young children. A strong socioeconomic gradient exists for the majority of the early-life predictors of obesity suggesting that the die is cast very early in life (even pre-conception). Lifestyle interventions targeting disadvantaged women at or before child-bearing age may therefore be particularly important in reducing inequality. Given the likely challenges of reaching this target population, it may be that during pregnancy and their child's early years are more feasible windows for engagement.

Gene–environment interplay in Drosophila melanogaster: Chronic food deprivation in early life affects adult exploratory and fitness traits

PubMed Central

Burns, James Geoffrey; Svetec, Nicolas; Rowe, Locke; Mery, Frederic; Dolan, Michael J.; Boyce, W. Thomas; Sokolowski, Marla B.

2012-01-01

Early life adversity has known impacts on adult health and behavior, yet little is known about the gene–environment interactions (GEIs) that underlie these consequences. We used the fruit fly Drosophila melanogaster to show that chronic early nutritional adversity interacts with rover and sitter allelic variants of foraging (for) to affect adult exploratory behavior, a phenotype that is critical for foraging, and reproductive fitness. Chronic nutritional adversity during adulthood did not affect rover or sitter adult exploratory behavior; however, early nutritional adversity in the larval period increased sitter but not rover adult exploratory behavior. Increasing for gene expression in the mushroom bodies, an important center of integration in the fly brain, changed the amount of exploratory behavior exhibited by sitter adults when they did not experience early nutritional adversity but had no effect in sitters that experienced early nutritional adversity. Manipulation of the larval nutritional environment also affected adult reproductive output of sitters but not rovers, indicating GEIs on fitness itself. The natural for variants are an excellent model to examine how GEIs underlie the biological embedding of early experience. PMID:23045644

Non-lethal effects of an invasive species in the marine environment: the importance of early life-history stages.

PubMed

Rius, Marc; Turon, Xavier; Marshall, Dustin J

2009-04-01

Studies examining the effects of invasive species have focussed traditionally on the direct/lethal effects of the invasive on the native community but there is a growing recognition that invasive species may also have non-lethal effects. In terrestrial systems, non-lethal effects of invasive species can disrupt early life-history phases (such as fertilisation, dispersal and subsequent establishment) of native species, but in the marine environment most studies focus on adult rather than early life-history stages. Here, we examine the potential for an introduced sessile marine invertebrate (Styela plicata) to exert both lethal and non-lethal effects on a native species (Microcosmus squamiger) across multiple early life-history stages. We determined whether sperm from the invasive species interfered with the fertilisation of eggs from the native species and found no effect. However, we did find strong effects of the invasive species on the post-fertilisation performance of the native species. The invasive species inhibited the settlement of native larvae and, in the field, the presence of the invasive species was associated with a ten-fold increase in the post-settlement mortality of the native species, as well as an initial reduction of growth in the native. Our results suggest that larvae of the native species avoid settling near the invasive species due to reduced post-settlement survival in its presence. Overall, we found that invasive species can have complex and pervasive effects (both lethal and non-lethal) across the early life-history stages of the native species, which are likely to result in its displacement and to facilitate further invasion.

Early Life Manipulations Alter Learning and Memory in Rats

PubMed Central

Kosten, Therese A; Kim, Jeansok J; Lee, Hongjoo J.

2012-01-01

Much research shows early life manipulations have enduring behavioral, neural, and hormonal effects. However, findings of learning and memory performance vary widely across studies. We reviewed studies in which pre-weaning rat pups were exposed to stressors and tested on learning and memory tasks in adulthood. Tasks were classified as aversive conditioning, inhibitory learning, or spatial/relational memory. Variables of duration, type, and timing of neonatal manipulation and sex and strain of animals were examined to determine if any predict enhanced or impaired performance. Brief separations enhanced and prolonged separations impaired performance on spatial/relational tasks. Performance was impaired in aversive conditioning and enhanced in inhibitory learning tasks regardless of manipulation duration. Opposing effects on performance for spatial/relational memory also depended upon timing of manipulation. Enhanced performance was likely if the manipulation occurred during postnatal week 3 but performance was impaired if it was confined to the first two postnatal weeks. Thus, the relationship between early life experiences and adulthood learning and memory performance is multifaceted and decidedly task-dependent. PMID:22819985

Early Stages of the Evolution of Life: a Cybernetic Approach

NASA Astrophysics Data System (ADS)

Melkikh, Alexey V.; Seleznev, Vladimir D.

2008-08-01

Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

Early stages of the evolution of life: a cybernetic approach.

PubMed

Melkikh, Alexey V; Seleznev, Vladimir D

2008-08-01

Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

The importance of early life in childhood obesity and related diseases: a report from the 2014 Gravida Strategic Summit.

PubMed

Macaulay, E C; Donovan, E L; Leask, M P; Bloomfield, F H; Vickers, M H; Dearden, P K; Baker, P N

2014-12-01