Sample records for early life alters
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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...
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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
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Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.
Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R
2017-07-20
Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.
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Directory of Open Access Journals (Sweden)
Chunlong Mu
2017-05-01
Full Text Available Early-life antibiotic interventions can change the predisposition to disease by disturbing the gut microbiota. However, the impact of antibiotics on gut microbiota in the gastrointestinal tract is not completely understood, although antibiotic-induced alterations in the distal gut have been reported. Here, employing a piglet model, the microbial composition was analyzed by high-throughput 16S rRNA gene sequencing and PICRUSt predictions of metagenome function. The present study showed clear spatial variation of microbial communities in the stomach and intestine, and found that the administration of antibiotics (a mixture of olaquindox, oxytetracycline calcium, kitasamycin in early life caused markedly differential alterations in the compartmentalized microbiota, with major alterations in their spatial variation in the lumen of the stomach and small intestine. In piglets fed an antibiotic-free diet, most of the variation in microbial communities was concentrated in gut segments and niches (lumen/mucosa. The microbial diversity was higher in the lumen of stomach and duodenum than that in ileum. The early-life antibiotic intervention decreased the abundance of some Lactobacillus species and increased the abundance of potentially pathogenic Streptococcus suis in the lumen of the stomach and small intestine. Interestingly, the intervention increased the abundance of Treponema only in the colonic lumen and that of Faecalibacterium only in the ileal mucosa. Furthermore, the antibiotic intervention exerted location-specific effects on the functional potential involved in the phosphotransferase system (decreased sucrose phosphotransferase in the stomach and antibiotic-resistance genes (increased in the colon. These results point to an early-life antibiotic-induced dramatic and location-specific shift in the gut microbiota, with profound impact in the foregut and less impact in the hindgut. Collectively, these findings provide new insights into the
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Sucrose exposure in early life alters adult motivation and weight gain.
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Cristianne R M Frazier
2008-09-01
Full Text Available The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.
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Sucrose exposure in early life alters adult motivation and weight gain.
Frazier, Cristianne R M; Mason, Peggy; Zhuang, Xiaoxi; Beeler, Jeff A
2008-09-17
The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.
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Early life stress, HPA axis adaptation and mechanisms contributing to later health outcomes
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Jayanthi eManiam
2014-05-01
Full Text Available Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early life stress can impact on later health but less is known about how early life stress impairs HPA axis activity, contributing to maladaptation of the stress response system. Early life stress exposure (either prenatally or in the early postnatal period can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical and experimental studies have demonstrated that early life stress produces long-term hyper responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviours. Recently, evidence has emerged on early life stress induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1. We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early life stress induced maladaptation of the HPA axis, and its subsequent effects on energy utilisation and expenditure. The effects of positive later environments as a means of ameliorating early life stress induced health deficits, and proposed mechanisms underpinning the interaction between early life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early life stress and later health outcomes will also
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Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes
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
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Environmental insults in early life and submissiveness later in life in mouse models
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Seico eBenner
2015-03-01
Full Text Available Dominant and subordinate dispositions are not only determined genetically but also nurtured by environmental stimuli during neuroendocrine development. However, the relationship between early life environment and dominance behavior remains elusive. Using the IntelliCage-based competition task for group-housed mice, we have previously described two cases in which environmental insults during the developmental period altered the outcome of dominance behavior later in life. First, mice that were repeatedly isolated from their mother and their littermates (early deprivation; ED, and second, mice perinatally exposed to an environmental pollutant, dioxin, both exhibited subordinate phenotypes, defined by decreased occupancy of limited resource sites under highly competitive circumstances. Similar alterations found in the cortex and limbic area of these two models are suggestive of the presence of neural systems shared across generalized dominance behavior.
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Early life nutrition, epigenetics and programming of later life disease.
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
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Early Life Nutrition, Epigenetics and Programming of Later Life Disease
Directory of Open Access Journals (Sweden)
Mark H. Vickers
2014-06-01
Full Text Available The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how
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International Nuclear Information System (INIS)
Herring, M.J.; Putney, L.F.; St George, J.A.; Avdalovic, M.V.; Schelegle, E.S.; Miller, L.A.; Hyde, D.M.
2015-01-01
In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O 3 ) or HDMA/ozone (HDMA + O 3 ) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O 3 alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)
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Energy Technology Data Exchange (ETDEWEB)
Herring, M.J.; Putney, L.F.; St George, J.A. [California National Primate Research Center, Davis, CA (United States); Avdalovic, M.V. [Department of Internal Medicine, Division of Pulmonary and Critical Care, University of California, Davis, CA (United States); Schelegle, E.S.; Miller, L.A. [California National Primate Research Center, Davis, CA (United States); Hyde, D.M., E-mail: dmhyde@ucdavis.edu [California National Primate Research Center, Davis, CA (United States)
2015-02-15
In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O{sub 3}) or HDMA/ozone (HDMA + O{sub 3}) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O{sub 3} alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)
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Directory of Open Access Journals (Sweden)
Arpana Gupta, PhD
2017-12-01
Full Text Available Introduction: Early adverse life events (EALs increase the risk for chronic medical and psychiatric disorders by altering early neurodevelopment. The aim of this study was to examine associations between EALs and network properties of core brain regions in the emotion regulation and salience networks, and to test the influence of sex on these associations. Methods: Resting-state functional and diffusion tensor magnetic resonance imaging were obtained in healthy individuals (61 men, 63 women. Functional and anatomical network properties of centrality and segregation were calculated for the core regions of the two networks using graph theory. Moderator analyses were applied to test hypotheses. Results: The type of adversity experienced influences brain wiring differently, as higher general EALs were associated with decreased functional and anatomical centrality in salience and emotion regulation regions, while physical and emotional EALs were associated with increased anatomical centrality and segregation in emotion regulation regions. Sex moderated the associations between EALs and measures of centrality; with decreased centrality of salience and emotion regulation regions with increased general EALs in females, and increased centrality in salience regions with higher physical and emotional EALs in males. Increased segregation of salience regions was associated with increased general EALs in males. Centrality of the amygdala was associated with physical symptoms, and segregation of salience regions was correlated with higher somatization in men only. Conclusions: Emotion regulation and salience regions are susceptible to topological brain restructuring associated with EALs. The male and female brains appear to be differently affected by specific types of EALs. Keywords: Early adverse traumatic life events, Centrality, Segregation, Network metrics, Moderating effects of sex, Emotion regulation network, Salience network
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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.
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Immune-mediated diseases and microbial exposure in early life
DEFF Research Database (Denmark)
Bisgaard, H; Bønnelykke, K; Stokholm, Jacob
2014-01-01
The non-communicable disease pandemic includes immune-mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system...
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Mechanisms behind early life nutrition and adult disease outcome
Velkoska, Elena; Morris, Margaret J
2011-01-01
Obesity is increasing around the globe. While adult lifestyle factors undoubtedly contribute to the incidence of obesity and its attendant disorders, mounting evidence suggests that programming of obesity may occur following under- and over-nutrition during development. As hypothalamic control of appetite and energy expenditure is set early in life and can be perturbed by certain exposures such as undernutrition and altered metabolic and hormonal signals, in utero exposure to altered maternal...
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Directory of Open Access Journals (Sweden)
Ingrid eNylander
2012-07-01
Full Text Available The brain is constantly exposed to external and internal input and to function in an ever-changing environment we are dependent on processes that enable the brain to adapt to new stimuli. Exposure to postnatal environmental stimuli can interfere with vital adaption processes and cause long-term changes in physiological function and behaviour. Early-life alterations in brain function may result in impaired ability to adapt to new situations, in altered sensitivity to challenges later in life and thereby mediate risk or protection for psychopathology such as alcohol use disorders (AUD. In clinical research the studies of mechanisms, mediators and causal relation between early environmental factors and vulnerability to AUD are restricted and attempts are made to find valid animal models for studies of the early-life influence on the brain. This review focuses on rodent models and the effects of adverse and naturalistic conditions on peptide networks within the brain and pituitary gland. Importantly, the consequences of alcohol addiction are not discussed but rather neurobiological alterations that can cause risk consumption and vulnerability to addiction. The article reviews earlier results and includes new data with emphasis on endogenous opioid peptides but also oxytocin and vasopressin. These peptides are vital for developmental processes and it is hypothesized that early-life changes in peptide networks may interfere with neuronal processes and thereby contribute the individual vulnerability for AUD. The summarized results indicate a link between early-life rearing conditions, opioids and ethanol consumption and that the ethanol-induced effects and the treatment with opioid antagonists later in life are dependent on early-life experiences. Endogenous opioids are therefore of interest to further study in the early-life impact on individual differences in vulnerability to AUD and treatment outcome.
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Preterm birth and structural brain alterations in early adulthood
Nosarti, Chiara; Nam, Kie Woo; Walshe, Muriel; Murray, Robin M.; Cuddy, Marion; Rifkin, Larry; Allin, Matthew P.G.
2014-01-01
Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT) birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM) and white matter (WM) maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM) we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks) and 43 term-born controls aged 19–20 years, and their association w...
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Heun-Johnson, Hanke; Levitt, Pat
2018-02-01
Early adversity in childhood increases the risk of anxiety, mood, and post-traumatic stress disorders in adulthood, and specific gene-by-environment interactions may increase risk further. A common functional variant in the promoter region of the gene encoding the human MET receptor tyrosine kinase (rs1858830 ' C' allele) reduces expression of MET and is associated with altered cortical circuit function and structural connectivity. Mice with reduced Met expression exhibit changes in anxiety-like and conditioned fear behavior, precocious synaptic maturation in the hippocampus, and reduced neuronal arbor complexity and synaptogenesis. These phenotypes also can be produced independently by early adversity in wild-type mice. The present study addresses the outcome of combining early-life stress and genetic influences that alter timing of maturation on enduring functional and structural phenotypes. Using a model of reduced Met expression ( Met +/- ) and early-life stress from postnatal day 2-9, social, anxiety-like, and contextual fear behaviors in later life were measured. Mice that experienced early-life stress exhibited impairments in social interaction, whereas alterations in anxiety-like behavior and fear learning were driven by Met haploinsufficiency, independent of rearing condition. Early-life stress or reduced Met expression decreased arbor complexity of ventral hippocampal CA1 pyramidal neurons projecting to basolateral amygdala. Paradoxically, arbor complexity in Met +/- mice was increased following early-life stress, and thus not different from arbors in wild-type mice raised in control conditions. The changes in dendritic morphology are consistent with the hypothesis that the physiological state of maturation of CA1 neurons in Met +/- mice influences their responsiveness to early-life stress. The dissociation of behavioral and structural changes suggests that there may be phenotype-specific sensitivities to early-life stress.
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The composition of the gut microbiota throughout life, with an emphasis on early life
Directory of Open Access Journals (Sweden)
Juan Miguel Rodríguez
2015-02-01
Full Text Available The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3–5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health.
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The composition of the gut microbiota throughout life, with an emphasis on early life
Rodríguez, Juan Miguel; Murphy, Kiera; Stanton, Catherine; Ross, R. Paul; Kober, Olivia I.; Juge, Nathalie; Avershina, Ekaterina; Rudi, Knut; Narbad, Arjan; Jenmalm, Maria C.; Marchesi, Julian R.; Collado, Maria Carmen
2015-01-01
The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3–5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health. PMID:25651996
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An adverse early life environment can enhance stress resilience in adulthood.
Santarelli, Sara; Zimmermann, Christoph; Kalideris, Georgia; Lesuis, Sylvie L; Arloth, Janine; Uribe, Andrés; Dournes, Carine; Balsevich, Georgia; Hartmann, Jakob; Masana, Mercè; Binder, Elisabeth B; Spengler, Dietmar; Schmidt, Mathias V
2017-04-01
Chronic stress is a major risk factor for depression. Interestingly, not all individuals develop psychopathology after chronic stress exposure. In contrast to the prevailing view that stress effects are cumulative and increase stress vulnerability throughout life, the match/mismatch hypothesis of psychiatric disorders. The match/mismatch hypothesis proposes that individuals who experience moderate levels of early life psychosocial stress can acquire resilience to renewed stress exposure later in life. Here, we have tested this hypothesis by comparing the developmental effects of 2 opposite early life conditions, when followed by 2 opposite adult environments. Male Balb/c mice were exposed to either adverse early life conditions (limited nesting and bedding material) or a supportive rearing environment (early handling). At adulthood, the animals of each group were either housed with an ovariectomized female (supportive environment) or underwent chronic social defeat stress (socially adverse environment) for 3 weeks. At the end of the adult manipulations, all of the animals were returned to standard housing conditions. Then, we compared the neuroendocrine, behavioral and molecular effects of the interaction between early and adult environment. Our study shows that early life adversity does not necessarily result in increased vulnerability to stress. Specific endophenotypes, like hypothalamic-pituitary-adrenal axis activity, anxiety-related behavior and glucocorticoid receptor expression levels in the hippocampus were not significantly altered when adversity is experienced during early life and in adulthood, and are mainly affected by either early life or adult life adversity alone. Overall our data support the notion that being raised in a stressful environment prepares the offspring to better cope with a challenging adult environment and emphasize the role of early life experiences in shaping adult responsiveness to stress. Copyright © 2017 Elsevier Ltd. All rights
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Directory of Open Access Journals (Sweden)
Mayumi eNishi
2014-06-01
Full Text Available During postnatal development, adverse early life experiences can affect the formation of neuronal circuits and exert long-lasting influences on neural function. Many studies have shown that daily repeated MS, an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA axis and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been completely elucidated. In this review, we introduce various cases of MS in rodents and illustrate the alterations in HPA axis activity by focusing on corticosterone (CORT, an end product of the HPA axis in rodents. We then present a characterization of the brain regions affected by various patterns of MS, including repeated MS and single time MS at various stages before weaning, by investigating c-Fos expression, a biological marker of neuronal activity. These CORT and c-Fos studies suggest that repeated early life stress may affect neuronal function in region- and temporal-specific manners, indicating a critical period for habituation to early life stress. Next, we discuss how early life stress can impact behavior, namely by inducing depression, anxiety or eating disorders. Furthermore, alterations in gene expression in adult mice exposed to MS, especially epigenetic changes of DNA methylation, are discussed.
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Forebrain CRF1 Modulates Early-Life Stress-Programmed Cognitive Deficits
Wang, Xiao-Dong; Rammes, Gerhard; Kraev, Igor; Wolf, Miriam; Liebl, Claudia; Scharf, Sebastian H.; Rice, Courtney J.; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan M.; Baram, Tallie Z.; Stewart, Michael G.; Müller, Marianne B.; Schmidt, Mathias V.
2012-01-01
Childhood traumatic events hamper the development of the hippocampus and impair declarative memory in susceptible individuals. Persistent elevations of hippocampal corticotropin-releasing factor (CRF), acting through CRF receptor 1 (CRF1), in experimental models of early-life stress have suggested a role for this endogenous stress hormone in the resulting structural modifications and cognitive dysfunction. However, direct testing of this possibility has been difficult. In the current study, we subjected conditional forebrain CRF1 knock-out (CRF1-CKO) mice to an impoverished postnatal environment and examined the role of forebrain CRF1 in the long-lasting effects of early-life stress on learning and memory. Early-life stress impaired spatial learning and memory in wild-type mice, and postnatal forebrain CRF overexpression reproduced these deleterious effects. Cognitive deficits in stressed wild-type mice were associated with disrupted long-term potentiation (LTP) and a reduced number of dendritic spines in area CA3 but not in CA1. Forebrain CRF1 deficiency restored cognitive function, LTP and spine density in area CA3, and augmented CA1 LTP and spine density in stressed mice. In addition, early-life stress differentially regulated the amount of hippocampal excitatory and inhibitory synapses in wild-type and CRF1-CKO mice, accompanied by alterations in the neurexin-neuroligin complex. These data suggest that the functional, structural and molecular changes evoked by early-life stress are at least partly dependent on persistent forebrain CRF1 signaling, providing a molecular target for the prevention of cognitive deficits in adults with a history of early-life adversity. PMID:21940453
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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.
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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.
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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.
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van Hasselt, F.N.; Visser, L.; Tieskens, J.M.; Cornelisse, S.; Baars, A.M.; Lavrijsen, M.; Krugers, H.J.; van den Bos, R.; Joëls, M.
2012-01-01
Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology-e.g. depression, anxiety and schizophrenia- later in life. Here we investigated whether subtle natural variations among
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van Hasselt, F.N.; de Visser, L.; Tieskens, J.M.; Cornelisse, S.; Baars, A.M.; Lavrijsen, M.; Krugers, H.J.; van den Bos, R.; Joëls, M.
2012-01-01
Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology--e.g. depression, anxiety and schizophrenia--later in life. Here we investigated whether subtle natural variations among
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DEFF Research Database (Denmark)
Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria
2016-01-01
Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal...... the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...
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Early Life Exposures and Cancer
Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.
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Early and Later Life Stress Alter Brain Activity and Sleep in Rats
Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne
2013-01-01
Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way. PMID:23922857
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Preterm birth and structural brain alterations in early adulthood
Directory of Open Access Journals (Sweden)
Chiara Nosarti
2014-01-01
Full Text Available Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM and white matter (WM maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks and 43 term-born controls aged 19–20 years, and their association with cognitive outcomes (Hayling Sentence Completion Test, Controlled Oral Word Association Test, Visual Reproduction test of the Wechsler Memory Scale-Revised and gestational age. Structural MRI data were obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with a customized study-specific template. Similarly to results obtained at adolescent assessment, VPT young adults compared to controls demonstrated reduced GM volume in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and putamen. Increases in GM volume were noted in medial/anterior frontal gyrus. Smaller subcortical WM volume in the VPT group was observed in temporal, parietal and frontal regions, and in a cluster centred on posterior corpus callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in posterior brain regions, in areas beneath the parahippocampal and occipital gyri and in cerebellum. Gestational age was associated with GM and WM volumes in areas where VPT individuals demonstrated GM and WM volumetric alterations, especially in temporal, parietal and occipital regions. VPT participants scored lower than controls on measures of IQ, executive function and non-verbal memory. When investigating GM and WM alterations and cognitive outcome scores, subcortical WM volume in an area beneath the left inferior frontal gyrus accounted for 14% of the variance of full-scale IQ (F = 12.9, p < 0.0001. WM volume in posterior corpus
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Early-Life Effects on Adult Physical Activity: Concepts, Relevance, and Experimental Approaches.
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
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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.
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Effects of early life stress on amygdala and striatal development
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
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Effects of early life stress on amygdala and striatal development.
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.
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Effects of early life stress on amygdala and striatal development
Directory of Open Access Journals (Sweden)
Dominic S. Fareri
2016-06-01
Full Text Available Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS in the form of the absence of species expected caregiving (i.e., caregiver deprivation, can drastically impact one’s social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction.
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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
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ACTH Prevents Deficits in Fear Extinction Associated with Early Life Seizures
Directory of Open Access Journals (Sweden)
Andrew T Massey
2016-05-01
Full Text Available Early life seizures are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of early life seizures (ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action. We found that while rats with a history of ELS were able to acquire a conditioned fear learning paradigm as well as controls, these rats had significant deficits in their ability to extinguish fearful memories. ACTH treatment did not alter any seizure parameters but nevertheless was able to significantly improve this fear extinction, while dexamethasone treatment during the same period did not. This ACTH effect was specific for fear extinction deficits and not for spatial learning deficits in a water maze. Additionally, ACTH did not alter seizure latency or duration suggesting that cognitive and seizure outcomes may be dissociable. Expression levels of melanocortin receptors, which bind ACTH, were found to be significantly lower in animals that had experienced ELS than in control animals, potentially implicating central melanocortin receptor dysregulation in the effects of ELS and suggesting a mechanism of action for ACTH. Taken together, these data suggest that early treatment with ACTH can have significant long-term consequences for cognition in animals with a history of ELS independently of seizure cessation, and may act in part through a CNS melanocortin receptor pathway.
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Proinflammatory T Cell Status Associated with Early Life Adversity.
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 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.
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Epigenetics, obesity and early-life cadmium or lead exposure.
Park, Sarah S; Skaar, David A; Jirtle, Randy L; Hoyo, Cathrine
2017-01-01
Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures.
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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
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Alterations in the hypothalamic–pituitary–thyroid axis in animals submitted to early-life trauma
Directory of Open Access Journals (Sweden)
Tania Diniz Machado
2017-09-01
Full Text Available Introduction: Changes in maternal care can affect offspring’s thyroid hormone T3 levels. Pups from highly caring mothers have higher levels of thyroid hormone T3. In humans, physical abuse in childhood is related to lower levels of T3 in adolescence. This study aimed at verifying if early-life trauma in rodents is correlated with T3 levels in adulthood. Methods: From the second day of life, litters of Wistar rats were subjected to reduced nesting material (Early–Life Stress-ELS or standard care (Controls. In adult life, the animals were chronically exposed to standard diet or standard diet + palatable diet and plasma T3 levels were measured before and after the exposition to diet. Results: Thyroid hormone T3 levels in adult life correlated negatively with the licking and grooming (LG scores in the ELS group. This correlation disappeared when the animals had the opportunity to choose between two diets chronically. Conclusion: The adverse environment affected maternal behavior and caused marks on the metabolism of the intervention group (T3, which were reverted by chronic palatable food consumption. Keywords: Trauma; T3; stress
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Directory of Open Access Journals (Sweden)
Isabelle Laforest-Lapointe
2017-07-01
Full Text Available Alterations in gut microbial colonization during early life have been reported in infants that later developed asthma, allergies, type 1 diabetes, as well as in inflammatory bowel disease patients, previous to disease flares. Mechanistic studies in animal models have established that microbial alterations influence disease pathogenesis via changes in immune system maturation. Strong evidence points to the presence of a window of opportunity in early life, during which changes in gut microbial colonization can result in immune dysregulation that predisposes susceptible hosts to disease. Although the ecological patterns of microbial succession in the first year of life have been partly defined in specific human cohorts, the taxonomic and functional features, and diversity thresholds that characterize these microbial alterations are, for the most part, unknown. In this review, we summarize the most important links between the temporal mosaics of gut microbial colonization and the age-dependent immune functions that rely on them. We also highlight the importance of applying ecology theory to design studies that explore the interactions between this complex ecosystem and the host immune system. Focusing research efforts on understanding the importance of temporally structured patterns of diversity, keystone groups, and inter-kingdom microbial interactions for ecosystem functions has great potential to enable the development of biologically sound interventions aimed at maintaining and/or improving immune system development and preventing disease.
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Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.
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
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Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks
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
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Directory of Open Access Journals (Sweden)
Heidi Marjonen
Full Text Available The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v ethanol for the first 8 days of gestation (GD 0.5-8.5. Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60: we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in
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Zhang, Chi; Winnard, Paul T; Dasari, Sidarth; Kominsky, Scott L; Doucet, Michele; Jayaraman, Swaathi; Raman, Venu; Barman, Ishan
2018-01-21
Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbated by our limited ability to monitor early metastatic disease in bone and assess fracture risk. Spurred by its label-free, real-time nature and its exquisite molecular specificity, we employed spontaneous Raman spectroscopy to assess and quantify early metastasis driven biochemical alterations to bone composition. As early as two weeks after intracardiac inoculations of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurements in the femur and spine revealed consistent changes in carbonate substitution, overall mineralization as well as crystallinity increase in tumor-bearing bones when compared with their normal counterparts. Our observations reveal the possibility of early stage detection of biochemical changes in the tumor-bearing bones - significantly before morphological variations are captured through radiographic diagnosis. This study paves the way for a better molecular understanding of altered bone remodeling in such metastatic niches, and for further clinical studies with the goal of establishing a non-invasive tool for early metastasis detection and prediction of pathological fracture risk in breast cancer.
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Exogenous determinants of early-life conditions, and mortality later in life.
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.
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Using physiology and behaviour to understand the responses of fish early life stages to toxicants.
Sloman, K A; McNeil, P L
2012-12-01
The use of early life stages of fishes (embryos and larvae) in toxicity testing has been in existence for a long time, generally utilizing endpoints such as morphological defects and mortality. Behavioural endpoints, however, may represent a more insightful evaluation of the ecological effects of toxicants. Indeed, recent years have seen a considerable increase in the use of behavioural measurements in early life stages reflecting a substantial rise in zebrafish Danio rerio early life-stage toxicity testing and the development of automated behavioural monitoring systems. Current behavioural endpoints identified for early life stages in response to toxicant exposure include spontaneous activity, predator avoidance, capture of live food, shoaling ability and interaction with other individuals. Less frequently used endpoints include measurement of anxiogenic behaviours and cognitive ability, both of which are suggested here as future indicators of toxicant disruption. For many simple behavioural endpoints, there is still a need to link behavioural effects with ecological relevance; currently, only a limited number of studies have addressed this issue. Understanding the physiological mechanisms that underlie toxicant effects on behaviour so early in life has received far less attention, perhaps because physiological measurements can be difficult to carry out on individuals of this size. The most commonly established physiological links with behavioural disruption in early life stages are similar to those seen in juveniles and adults including sensory deprivation (olfaction, lateral line and vision), altered neurogenesis and neurotransmitter concentrations. This review highlights the importance of understanding the integrated behavioural and physiological response of early life stages to toxicants and identifies knowledge gaps which present exciting areas for future research. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.
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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.
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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.
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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
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Directory of Open Access Journals (Sweden)
Laura Bordoni
2015-11-01
Full Text Available Environmental exposure to pesticides during the early stages of development represents an important risk factor for the onset of neurodegenerative diseases in adult age. Neonatal exposure to Permethrin (PERM, a member of the family of synthetic pyrethroids, can induce a Parkinson-like disease and cause some alterations in striatum of rats, involving both genetic and epigenetic pathways. Through gene expression analysis and global DNA methylation assessment in both PERM-treated parents and their untreated offspring, we investigated on the prospective intergenerational effect of this pesticide. Thirty-three percent of progeny presents the same Nurr1 alteration as rats exposed to permethrin in early life. A decrease in global genome-wide DNA methylation was measured in mothers exposed in early life to permethrin as well as in their offspring, whereas untreated rats have a hypermethylated genomic DNA. Further studies are however needed to elucidate the molecular mechanisms, but, despite this, an intergenerational PERM-induced damage on progenies has been identified for the first time.
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Reinwald, Jonathan Rochus; Becker, Robert; Mallien, Anne Stephanie; Falfan-Melgoza, Claudia; Sack, Markus; Clemm von Hohenberg, Christian; Braun, Urs; Cosa Linan, Alejandro; Gass, Natalia; Vasilescu, Andrei-Nicolae; Tollens, Fabian; Lebhardt, Philipp; Pfeiffer, Natascha; Inta, Dragos; Meyer-Lindenberg, Andreas; Gass, Peter; Sartorius, Alexander; Weber-Fahr, Wolfgang
2017-12-28
To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for neurodevelopmental psychiatric disorders such as schizophrenia. Although changes in resting-state brain connectivity are a transdiagnostic key finding in neurodevelopmental diseases, a characterization of imaging correlates elicited by early-life social stress is lacking. We performed resting-state functional magnetic resonance imaging of postweaning social isolation rats (N = 23) 9 weeks after isolation. Addressing well-established transdiagnostic connectivity changes of psychiatric disorders, we focused on altered frontal and posterior connectivity using a seed-based approach. Then, we examined changes in regional network architecture and global topology using graph theoretical analysis. Seed-based analyses demonstrated reduced functional connectivity in frontal brain regions and increased functional connectivity in posterior brain regions of postweaning social isolation rats. Graph analyses revealed a shift of the regional architecture, characterized by loss of dominance of frontal regions and emergence of nonfrontal regions, correlating to our behavioral results, and a reduced modularity in isolation-reared rats. Our result of functional connectivity alterations in the frontal brain supports previous investigations postulating social neural circuits, including prefrontal brain regions, as key pathways for risk for mental disorders arising through social stressors. We extend this knowledge by demonstrating more widespread changes of brain network organization elicited by early-life social stress, namely a shift of hubness and dysmodularity. Our results highly resemble core alterations in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and attention-deficit/hyperactivity disorder in humans. Copyright © 2017
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Exogenous determinants of early-life conditions, and mortality later in life
DEFF Research Database (Denmark)
van den Berg, Gerard J; Doblhammer, Gabriele; Christensen, Kaare
2009-01-01
based on the estimation of duration models) indicate a significant negative causal effect of economic conditions early in life on individual mortality rates at higher ages. If the national economic performance in the year of birth exceeds its trend value (i.e., if the business cycle is favorable......) then the mortality rate later in life is lower. The implied effect on the median lifetime of those who survive until age 35 is about 10 months. A systematic empirical exploration of all macro-indicators reveals that economic conditions in the first years after birth also affect mortality rates later in life.......We analyze causal effects of conditions early in life on the individual mortality rate later in life. Conditions early in life are captured by transitory features of the macro-environment around birth, notably the state of the business cycle around birth, but also food price deviations, weather...
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A developmental perspective on early-life exposure to neurotoxicants.
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.
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Early-life risperidone enhances locomotor responses to amphetamine during adulthood.
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.
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Olive, Michael Foster
2014-01-01
Throughout the 20th century a body of literature concerning the long lasting effects of early environment was produced. Adverse experiences in early life, or early life stress (ELS), is associated with a higher risk for developing various psychiatric illnesses. The mechanisms driving the complex interplay between ELS and adult phenotype has baffled many investigators for decades. Over the last decade, the new field of neuroepigenetics has emerged as one possible mechanism by which ELS can have far reaching effects on adult phenotype, behavior, and risk for psychiatric illness. Here we review two commonly investigated epigenetic mechanisms, histone modifications and DNA methylation, and the emerging field of neuroepigenetics as they relate to ELS. We discuss the current animal literature demonstrating ELS induced epigenetic modulation of gene expression that results in altered adult phenotypes. We also briefly discuss other areas in which neuroepigenetics has emerged as a potential mechanism underlying environmental and genetic interactions. PMID:25003947
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Lewis, Candace R; Olive, M Foster
2014-09-01
Throughout the 20th century a body of literature concerning the long-lasting effects of the early environment was produced. Adverse experiences in early life, or early-life stress (ELS), is associated with a higher risk of developing various psychiatric illnesses. The mechanisms driving the complex interplay between ELS and adult phenotype has baffled many investigators for decades. Over the last decade, the new field of neuroepigenetics has emerged as one possible mechanism by which ELS can have far-reaching effects on adult phenotype, behavior, and risk for psychiatric illness. Here we review two commonly investigated epigenetic mechanisms, histone modifications and DNA methylation, and the emerging field of neuroepigenetics as they relate to ELS. We discuss the current animal literature demonstrating ELS-induced epigenetic modulation of gene expression that results in altered adult phenotypes. We also briefly discuss other areas in which neuroepigenetics has emerged as a potential mechanism underlying environmental and genetic interactions.
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Good daily habits during the early stages of life determine success throughout life
Directory of Open Access Journals (Sweden)
Jun Kohyama
2016-07-01
Full Text Available This paper assesses hypothesis that sufficient sleep duration and proper circadian rhythms during the early stages of life are indispensable to a successful life. Successful life was defined according to the famous cohort studies of Mischel's and Dunedin. To assess the hypothesis, neuronal elements presumably affecting early daily habits and successful life are reviewed. The effect of sufficient sleep duration and proper circadian rhythms during early stages of life on the development of the prefrontal cortex has been found to be the key issue to verify the hypothesis. Socioeconomic status is found to be another issue to be studied.
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Good daily habits during the early stages of life determine success throughout life.
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.
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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.
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Casas-Mulet, Roser; Saltveit, Svein Jakob; Alfredsen, Knut Tore
2016-12-15
Alterations in hydrological and thermal regimes can potentially affect salmonid early life stages development and survival. The dewatering of salmon spawning redds due to hydropeaking can lead to mortality in early life stages, with higher impact on the alevins as they have lower tolerance to dewatering than the eggs. Flow-related mitigation measures can reduce early life stage mortality. We present a set of modelling tools to assess impacts and mitigation options to minimise the risk of mortality in early life stages in hydropeaking rivers. We successfully modelled long-term hydrological and thermal alterations and consequences for development rates. We estimated the risk of early life stages mortality and assessed the cost-effectiveness of implementing three release-related mitigation options (A,B,C). The economic cost of mitigation was low and ranged between 0.7% and 2.6% of the annual hydropower production. Options reducing the flow during spawning (B and C) in addition to only release minimum flows during development (A) were considered more effective for egg and alevin survival. Options B and C were however constraint by water availability in the system for certain years, and therefore only option A was always feasible. The set of modelling tools used in this study were satisfactory and their applications can be useful especially in systems where little field data is available. Targeted measures built on well-informed modelling tools can be tested on their effectiveness to mitigate dewatering effects vs. the hydropower system capacity to release or conserve water for power production. Environmental flow releases targeting specific ecological objectives can provide better cost-effective options than conventional operational rules complying with general legislation. Copyright © 2016 Elsevier B.V. All rights reserved.
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Early life insults as determinants of chronic obstructive pulmonary disease in adult life
DEFF Research Database (Denmark)
Savran, Osman; Ulrik, Charlotte Suppli
2018-01-01
Background: Early life events may predispose to the development of chronic lung disease in adulthood. Aim: To provide an update on current knowledge of early nongenetic origins of COPD. Materials and methods: Systematic literature review was performed according to the Preferred Reporting Items...... in utero and early life is a risk factor for subsequent development of COPD. Furthermore, low birth weight, lower respiratory tract infections and asthma, including wheezy bronchitis, in childhood also seem to be important determinants for later development of COPD. Early life insults may, therefore...
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Early life adversity: Lasting consequences for emotional learning
Directory of Open Access Journals (Sweden)
Harm J. Krugers
2017-02-01
Full Text Available The early postnatal period is a highly sensitive time period for the developing brain, both in humans and rodents. During this time window, exposure to adverse experiences can lastingly impact cognitive and emotional development. In this review, we briefly discuss human and rodent studies investigating how exposure to adverse early life conditions – mainly related to quality of parental care - affects brain activity, brain structure, cognition and emotional responses later in life. We discuss the evidence that early life adversity hampers later hippocampal and prefrontal cortex functions, while increasing amygdala activity, and the sensitivity to stressors and emotional behavior later in life. Exposure to early life stress may thus on the one hand promote behavioral adaptation to potentially threatening conditions later in life –at the cost of contextual memory formation in less threatening situations- but may on the other hand also increase the sensitivity to develop stress-related and anxiety disorders in vulnerable individuals.
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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.
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International Nuclear Information System (INIS)
Leu, Yu-Wei; Chu, Pei-Yi; Chen, Chien-Min; Yeh, Kun-Tu; Liu, Yu Ming; Lee, Yen-Hui; Kuo, Shan-Tsu; Hsiao, Shu-Huei
2014-01-01
Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms
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Energy Technology Data Exchange (ETDEWEB)
Leu, Yu-Wei [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China); Chu, Pei-Yi [Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan (China); Chen, Chien-Min [Division of Neurosurgery, Changhua Christian Hospital, Changhua 500, Taiwan (China); Yeh, Kun-Tu [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Liu, Yu Ming; Lee, Yen-Hui; Kuo, Shan-Tsu [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China); Hsiao, Shu-Huei, E-mail: bioshh@ccu.edu.tw [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China)
2014-10-24
Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.
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Martin, Rocio; Makino, Hiroshi; Yavuz, Aysun Cetinyurek; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan
2016-01-01
Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with
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Evolutionary conserved neural signature of early life stress affects animal social competence.
Nyman, Cecilia; Fischer, Stefan; Aubin-Horth, Nadia; Taborsky, Barbara
2018-01-31
In vertebrates, the early social environment can persistently influence behaviour and social competence later in life. However, the molecular mechanisms underlying variation in animal social competence are largely unknown. In rats, high-quality maternal care causes an upregulation of hippocampal glucocorticoid receptors ( gr ) and reduces offspring stress responsiveness. This identifies gr regulation as a candidate mechanism for maintaining variation in animal social competence. We tested this hypothesis in a highly social cichlid fish, Neolamprologus pulcher , reared with or without caring parents. We find that the molecular pathway translating early social experience into later-life alterations of the stress axis is homologous across vertebrates: fish reared with parents expressed the glucocorticoid receptor gr1 more in the telencephalon. Furthermore, expression levels of the transcription factor egr-1 (early growth response 1) were associated with gr1 expression in the telencephalon and hypothalamus. When blocking glucocorticoid receptors (GR) with an antagonist, mifepristone (RU486), parent-reared individuals showed more socially appropriate, submissive behaviour when intruding on a larger conspecific's territory. Remarkably, mifepristone-treated fish were less attacked by territory owners and had a higher likelihood of territory takeover. Our results indicate that early social-environment effects on stress axis programming are mediated by an evolutionary conserved molecular pathway, which is causally involved in environmentally induced variation of animal social competence. © 2018 The Author(s).
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Gut microbiota modifications and weight gain in early life
Directory of Open Access Journals (Sweden)
Emmanouil Angelakis
2018-04-01
Full Text Available Childhood and adolescent obesity is a significant public health concern and has been associated with cardiovascular disease and related metabolic sequelae later in life. In recent years, several studies have postulated an imbalance in the composition of the early life gut microbiota results in pediatric obesity and its associated diseases. The early life gut microbiota is influenced by several factors including the mode of delivery, prematurity, breastfeeding, and the use of antibiotics and probiotics. It has been proposed that, when given early in life, antibiotics and probiotics disrupt the gut microbiota and consequently its metabolic activity, promoting weight gain. Probiotics have increasingly been administrated to children and studies on the perinatal use of probiotics on low birth weight and healthy infants revealed significantly increased body length and weight later in life in comparison with infants who did not receive probiotic supplements. Similarly, exposure to antibiotics is very high perinatally and in the early periods of life and there is evidence that antibiotic treatment decreases the biodiversity of the early life gut microbiota. In addition, studies have revealed that antibiotic treatment during the first months of life is associated with being overweight later in life. In this paper we review the effects of the administration of probiotics and antibiotics in early life on the gut microbiota and discuss their effects on weight gain. Keywords: Gut microbiota, Obesity, Newborn, Antibiotics, Probiotics
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Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions.
Dahmen, Brigitte; Puetz, Vanessa B; Scharke, Wolfgang; von Polier, Georg G; Herpertz-Dahlmann, Beate; Konrad, Kerstin
2018-01-01
Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life. © 2017 S. Karger
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Osteoporosis in survivors of early life starvation.
Weisz, George M; Albury, William R
2013-01-01
The objective of this study was to provide evidence for the association of early life nutritional deprivation and adult osteoporosis, in order to suggest that a history of such deprivation may be an indicator of increased risk of osteoporosis in later life. The 'fetal programming' of a range of metabolic and cardiovascular disorders in adults was first proposed in the 1990s and more recently extended to disorders of bone metabolism. Localised famines during World War II left populations in whom the long-term effects of maternal, fetal and infantile nutritional deprivation were studied. These studies supported the original concept of 'fetal programming' but did not consider bone metabolism. The present paper offers clinical data from another cohort of World War II famine survivors - those from the Holocaust. The data presented here, specifically addressing the issue of osteoporosis, report on 11 Holocaust survivors in Australia (five females, six males) who were exposed to starvation in early life. The cases show, in addition to other metabolic disorders associated with early life starvation, various levels of osteoporosis, often with premature onset. The cohort studied is too small to support firm conclusions, but the evidence suggests that the risk of adult osteoporosis in both males and females is increased by severe starvation early in life - not just in the period from gestation to infancy but also in childhood and young adulthood. It is recommended that epidemiological research on this issue be undertaken, to assist planning for the future health needs of immigrants to Australia coming from famine affected backgrounds. Pending such research, it would be prudent for primary care health workers to be alert to the prima facie association between early life starvation and adult osteoporosis, and to take this factor into account along with other indicators when assessing a patient's risk of osteoporosis in later life.
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Ros-Simó, Clara; Valverde, Olga
2012-09-01
Early-life stressful experiences are associated to alterations in behavioural responses and development of psychiatric and neurodegenerative diseases. In rodents, individual housing is considered as a stressful condition whilst enriched environment can protect against stress and its negative consequences. Neuroendocrine responses to stress can also be altered by early-life experiences and seem to contribute to behavioural alterations induced by changes in housing conditions. To develop an improved procedure of social isolation throughout development (from pre-adolescence to adulthood) in CD1 mice and to elucidate its effects on behavioural parameters related to stress and neuroendocrine responses compared to enriched or social conditions. CD1 male mice (PND 21) were housed in social/standard conditions, enriched conditions or isolated conditions during seven weeks. After that, different relevant behaviours were evaluated, including locomotor activity, anxiety-like and despair behaviour. Levels of plasma corticosterone were also analysed before and after a stressful event. CD1 mice exposed to an isolated environment exhibited higher locomotion and anxiety-like responses than animals exposed to social or enriched conditions. In addition, isolated animals showed lower basal plasma corticosterone than social or enriched ones but after a stressful event the elevation of plasma corticosterone was higher, suggesting an enhanced response of the HPA axis to a novel and stressful situation. Social interaction is an important feature to display an appropriate behavioural and neuronal development. Habituation to novel stimuli is impaired in subjects exposed to social isolation and induces increased excitability response to stressful events. Social deprivation increases the possibility of altered neuronal function and could facilitate the development of neuropsychiatric disorders in adulthood. Copyright © 2012 Elsevier Inc. All rights reserved.
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Raineki, Charlis; Sarro, Emma; Rincón-Cortés, Millie; Perry, Rosemarie; Boggs, Joy; Holman, Colin J; Wilson, Donald A; Sullivan, Regina M
2015-01-01
Caregiver-associated cues, including those learned in abusive attachment, provide a sense of safety and security to the child. Here, we explore how cues associated with abusive attachment, such as maternal odor, can modify the enduring neurobehavioral effects of early-life abuse. Two early-life abuse models were used: a naturalistic paradigm, where rat pups were reared by an abusive mother; and a more controlled paradigm, where pups underwent peppermint odor-shock conditioning that produces an artificial maternal odor through engagement of the attachment circuit. Animals were tested for maternal odor preference in infancy, forced swim test (FST), social behavior, and sexual motivation in adulthood—in the presence or absence of maternal odors (natural or peppermint). Amygdala odor-evoked local field potentials (LFPs) via wireless electrodes were also examined in response to the maternal odors in adulthood. Both early-life abuse models induced preference for the maternal odors in infancy. In adulthood, these early-life abuse models produced FST deficits and decreased social behavior, but did not change sexual motivation. Presentation of the maternal odors rescued FST and social behavior deficits induced by early-life abuse and enhanced sexual motivation in all animals. In addition, amygdala LFPs from both abuse animal models showed unique activation within the gamma frequency (70–90 Hz) bands in response to the specific maternal odor present during early-life abuse. These results suggest that attachment-related cues learned during infancy have a profound ability to rescue neurobehavioral dysregulation caused by early-life abuse. Paradoxically, abuse-associated cues seem to acquire powerful and enduring antidepressive properties and alter amygdala modulation. PMID:25284320
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Raineki, Charlis; Sarro, Emma; Rincón-Cortés, Millie; Perry, Rosemarie; Boggs, Joy; Holman, Colin J; Wilson, Donald A; Sullivan, Regina M
2015-03-01
Caregiver-associated cues, including those learned in abusive attachment, provide a sense of safety and security to the child. Here, we explore how cues associated with abusive attachment, such as maternal odor, can modify the enduring neurobehavioral effects of early-life abuse. Two early-life abuse models were used: a naturalistic paradigm, where rat pups were reared by an abusive mother; and a more controlled paradigm, where pups underwent peppermint odor-shock conditioning that produces an artificial maternal odor through engagement of the attachment circuit. Animals were tested for maternal odor preference in infancy, forced swim test (FST), social behavior, and sexual motivation in adulthood-in the presence or absence of maternal odors (natural or peppermint). Amygdala odor-evoked local field potentials (LFPs) via wireless electrodes were also examined in response to the maternal odors in adulthood. Both early-life abuse models induced preference for the maternal odors in infancy. In adulthood, these early-life abuse models produced FST deficits and decreased social behavior, but did not change sexual motivation. Presentation of the maternal odors rescued FST and social behavior deficits induced by early-life abuse and enhanced sexual motivation in all animals. In addition, amygdala LFPs from both abuse animal models showed unique activation within the gamma frequency (70-90 Hz) bands in response to the specific maternal odor present during early-life abuse. These results suggest that attachment-related cues learned during infancy have a profound ability to rescue neurobehavioral dysregulation caused by early-life abuse. Paradoxically, abuse-associated cues seem to acquire powerful and enduring antidepressive properties and alter amygdala modulation.
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Directory of Open Access Journals (Sweden)
Javier A. Bravo
2014-04-01
Full Text Available Early-life experience plays a major role in the stress response throughout life. Neonatal maternal separation (MS is an animal model of depression with an altered serotonergic response. We hypothesize that this alteration may be caused by differences in 5-HT1A receptor and serotonin transporter (SERT mRNA expression in brain areas involved in the control of emotions, memory and fear as well as in regions controlling the central serotonergic tone.To test this, Sprague-Dawley rats were subjected to MS for 3h daily during post-natal days 2-12. As control, age matched rats were not separated (NS from their dams. When animals reached adulthood (11-13 weeks brain was extracted and mRNA expression of 5-HT1A receptor in amygdala, hippocampus and dorsal raphé nucleus (DRN and SERT in the DRN was analyzed through in-situ hybridisation.Densitometric analysis revealed that MS increased 5-HT1A receptor mRNA expression in the amygdala, and reduced its expression in the DRN, but no changes were observed in the hippocampus in comparison to NS controls. Also, MS reduced SERT mRNA expression in the DRN when compared to NS rats.These results suggest that early-life stress induces persistent changes in 5-HT1A receptor and SERT mRNA expression in key brain regions involved in the development of stress-related psychiatric disorders. The reduction in SERT mRNA indicates an alteration that is in line with clinical findings such as polymorphic variants in individuals with higher risk of depression. These data may help to understand how early-life stress contributes to the development of mood disorders in adulthood.
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Lauterstein, Dana E.; Tijerina, Pamella B.; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S.; Gordon, Terry; Klein, Catherine B.; Zelikoff, Judith T.
2016-01-01
Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology. PMID:27077873
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Directory of Open Access Journals (Sweden)
Dana E. Lauterstein
2016-04-01
Full Text Available Electronic cigarettes (e-cigarettes, battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation throughout gestation (3 h/day; 5 days/week to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq. Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.
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Lauterstein, Dana E; Tijerina, Pamella B; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S; Gordon, Terry; Klein, Catherine B; Zelikoff, Judith T
2016-04-12
Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13-16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4-6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.
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Effects of early life factors on the health and quality of life of older adults.
Yilmaz, Fikriye; N Tekin, Rukiye
2018-01-01
Few studies on the effects of early life factors on the health and quality of life of adults have been conducted in Turkey. We aimed to investigate the effects of early life factors on the health and quality of life of older adults. We administered a questionnaire to 350 adults, aged 50-89 years, living in Cankaya, Ankara. The questionnaire covered sociodemographic characteristics, early life characteristics, health status, and the World Health Organization Quality of Life-Ageing scale. Data were analyzed using χ 2 tests, independent samples t-tests, one-way anova, and binary logistic regression analysis. The analyses showed that the most important risk factors for chronic disease were being ≥65 years (odds ratio (OR) = 2.34), having a chronic health problem before 18 years of age (OR = 2.48), experiencing prolonged hospitalization or bed rest before 18 years of age (OR = 2.65), and experiencing parental unconcern during early life (OR = 2.13) (P quality of life (P life factors are among the important determinants of the health and quality of life of older adults in Turkey. © 2017 Japanese Psychogeriatric Society.
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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.
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Early Life Adversity as a Risk Factor for Fibromyalgia in Later Life
Directory of Open Access Journals (Sweden)
Lucie A. Low
2012-01-01
Full Text Available The impact of early life events is increasingly becoming apparent, as studies investigate how early childhood can shape long-term physiology and behaviour. Fibromyalgia (FM, which is characterised by increased pain sensitivity and a number of affective co-morbidities, has an unclear etiology. This paper discusses risk factors from early life that may increase the occurrence or severity of FM in later life: pain experience during neonatal life causes long-lasting changes in nociceptive circuitry and increases pain sensitivity in the older organism; premature birth and related stressor exposure cause lasting changes in stress responsivity; maternal deprivation affects anxiety-like behaviours that may be partially mediated by epigenetic modulation of the genome—all these adult phenotypes are strikingly similar to symptoms displayed by FM sufferers. In addition, childhood trauma and exposure to substances of abuse may cause lasting changes in developing neurotransmitter and endocrine circuits that are linked to anxiety and stress responses.
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Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.
Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L
2017-09-01
Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.
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Luby, Joan L; Belden, Andy C; Jackson, Joshua J; Lessov-Schlaggar, Christina N; Harms, Michael P; Tillman, Rebecca; Botteron, Kelly; Whalen, Diana; Barch, Deanna M
2016-01-01
imaging scan. In contrast, no significant associations were found between development of gray matter and family history of depression or experiences of traumatic or stressful life events during this period. This study demonstrates an association between early childhood depression and the trajectory of cortical gray matter development in late school age and early adolescence. These findings underscore the significance of early childhood depression on alterations in neural development.
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Chemical defense of early life stages of benthic marine invertebrates.
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.
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Maternal separation with early weaning: a novel mouse model of early life neglect
Directory of Open Access Journals (Sweden)
Elwafi Hani M
2010-09-01
Full Text Available Abstract Background Childhood adversity is associated with increased risk for mood, anxiety, impulse control, and substance disorders. Although genetic and environmental factors contribute to the development of such disorders, the neurobiological mechanisms involved are poorly understood. A reliable mouse model of early life adversity leading to lasting behavioral changes would facilitate progress in elucidating the molecular mechanisms underlying these adverse effects. Maternal separation is a commonly used model of early life neglect, but has led to inconsistent results in the mouse. Results In an effort to develop a mouse model of early life neglect with long-lasting behavioral effects in C57BL/6 mice, we designed a new maternal separation paradigm that we call Maternal Separation with Early Weaning (MSEW. We tested the effects of MSEW on C57BL/6 mice as well as the genetically distinct DBA/2 strain and found significant MSEW effects on several behavioral tasks (i.e., the open field, elevated plus maze, and forced swim test when assessed more than two months following the MSEW procedure. Our findings are consistent with MSEW causing effects within multiple behavioral domains in both strains, and suggest increased anxiety, hyperactivity, and behavioral despair in the MSEW offspring. Analysis of pup weights and metabolic parameters showed no evidence for malnutrition in the MSEW pups. Additionally, strain differences in many of the behavioral tests suggest a role for genetic factors in the response to early life neglect. Conclusions These results suggest that MSEW may serve as a useful model to examine the complex behavioral abnormalities often apparent in individuals with histories of early life neglect, and may lead to greater understanding of these later life outcomes and offer insight into novel therapeutic strategies.
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Yallapragada, Sushmita G; Nash, Colleen B; Robinson, Daniel T
2015-11-01
The intestinal microbiome is a complex ecosystem of microorganisms that colonize the human gastrointestinal tract. The microbiome evolves rapidly in early life with contributions from diet, genetics and immunomodulatory factors. Changes in composition of the microbiota due to antibiotics may lead to negative long-term effects including obesity and diabetes mellitus, as evidenced by both animal and large human studies. Inappropriate exposures to antibiotics occur frequently in early childhood. Therefore, an evidence-based system of antimicrobial use should be employed by all providers, especially those who care for pediatric patients. This article explores the natural evolution of the intestinal microbiome from the perinatal period into early childhood, the effect of antibiotics on the microbial ecology, and the implications for future health and disease. Copyright 2015, SLACK Incorporated.
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Directory of Open Access Journals (Sweden)
Stephanie Moriceau
2009-09-01
Full Text Available Early life trauma alters later life emotions, including fear. To better understand mediating mechanisms, we subjected pups to either predictable or unpredictable trauma, in the form of paired or unpaired odor-0.5mA shock conditioning which, during a sensitive period, produces an odor preference and no learning respectively. Fear conditioning and its neural correlates were then assessed after the sensitive period at postnatal day (PN13 or in adulthood, ages when amygdala-dependent fear occurs. Our results revealed that paired odor-shock conditioning starting during the sensitive period (PN8-12 blocked fear conditioning in older infants (PN13 and pups continued to express olfactory bulb-dependent odor preference learning. This PN13 fear learning inhibition was also associated with suppression of shock-induced corticosterone, although the age appropriate amygdala-dependent fear learning was reinstated with systemic corticosterone (3mg/kg during conditioning. On the other hand, sensitive period odor-shock conditioning did not prevent adult fear conditioning, although freezing, amygdala and hippocampal 2-DG uptake and corticosterone levels were attenuated compared to adult conditioning without infant conditioning. Normal levels of freezing, amygdala and hippocampal 2-DG uptake were induced with systemic corticosterone (5mg/kg during adult conditioning. These results suggest that the contingency of early life trauma mediates at least some effects of early life stress through learning and suppression of corticosterone levels. However, developmental differences between infants and adults are expressed with PN13 infants’ learning consistent with the original learned preference, while adult conditioning overrides the original learned preference with attenuated amygdala-dependent fear learning.
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O'Mahony, S M; Felice, V D; Nally, K; Savignac, H M; Claesson, M J; Scully, P; Woznicki, J; Hyland, N P; Shanahan, F; Quigley, E M; Marchesi, J R; O'Toole, P W; Dinan, T G; Cryan, J F
2014-09-26
Disruption of bacterial colonization during the early postnatal period is increasingly being linked to adverse health outcomes. Indeed, there is a growing appreciation that the gut microbiota plays a role in neurodevelopment. However, there is a paucity of information on the consequences of early-life manipulations of the gut microbiota on behavior. To this end we administered an antibiotic (vancomycin) from postnatal days 4-13 to male rat pups and assessed behavioral and physiological measures across all aspects of the brain-gut axis. In addition, we sought to confirm and expand the effects of early-life antibiotic treatment using a different antibiotic strategy (a cocktail of pimaricin, bacitracin, neomycin; orally) during the same time period in both female and male rat pups. Vancomycin significantly altered the microbiota, which was restored to control levels by 8 weeks of age. Notably, vancomycin-treated animals displayed visceral hypersensitivity in adulthood without any significant effect on anxiety responses as assessed in the elevated plus maze or open field tests. Moreover, cognitive performance in the Morris water maze was not affected by early-life dysbiosis. Immune and stress-related physiological responses were equally unaffected. The early-life antibiotic-induced visceral hypersensitivity was also observed in male rats given the antibiotic cocktail. Both treatments did not alter visceral pain perception in female rats. Changes in visceral pain perception in males were paralleled by distinct decreases in the transient receptor potential cation channel subfamily V member 1, the α-2A adrenergic receptor and cholecystokinin B receptor. In conclusion, a temporary disruption of the gut microbiota in early-life results in very specific and long-lasting changes in visceral sensitivity in male rats, a hallmark of stress-related functional disorders of the brain-gut axis such as irritable bowel disorder. Copyright © 2014 IBRO. Published by Elsevier Ltd. All
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The Intestinal Microbiome in Early Life: Health and Disease
Directory of Open Access Journals (Sweden)
Marie-Claire eArrieta
2014-09-01
Full Text Available Human microbial colonization begins at birth and continues to develop and modulate in species abundance for about three years, until the microbiota becomes adult-like. During the same time period, children experience significant developmental changes that influence their current health status as well as their immune system. An ever-expanding number of articles associate several diseases with early life imbalances of the gut microbiota, also referred to as gut microbial dysbiosis. Whether early life dysbiosis precedes and plays a role in disease pathogenesis, or simply originates from the disease process itself is a question that is beginning to be answered in a few diseases, including IBD, obesity and asthma. This review describes the gut microbiome structure and function during the formative first years of life, as well as the environmental factors that determine its composition. It also aims to discuss the recent advances in understanding the role of the early life gut microbiota in the development of immune-mediated, metabolic, and neurological diseases. A greater understanding of how the early life gut microbiota impacts our immune development could potentially lead to novel microbial-derived therapies that target disease prevention at an early age.
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Directory of Open Access Journals (Sweden)
Millie eRincón-Cortés
2014-03-01
Full Text Available Over half a century of converging clinical and animal research indicates that early life experiences induce enduring neuroplasticity of the HPA-axis and the developing brain. This experience-induced neuroplasticity is due to alterations in the frequency and intensity of stimulation of pups’ sensory systems (i.e. olfactory, somatosensory, gustatory embedded in mother-infant interactions. This stimulation provides hidden regulators of pups’ behavioral, physiological and neural responses that have both immediate and enduring consequences, including those involving the stress response. While variation in stimulation can produce individual differences and adaptive behaviors, pathological early life experiences can induce maladaptive behaviors, initiate a pathway to pathology and increase risk for later life psychopathologies, such as mood and affective disorders, suggesting that infant attachment relationships program later life neurobehavioral function. Recent evidence suggests that the effects of maternal presence or absence during this sensory stimulation provide a major modulatory role in neural and endocrine system responses, which have minimal impact on pups’ immediate neurobehavior but a robust impact on neurobehavioral development. This concept is reviewed here using two complementary rodent models of infant trauma within attachment: infant paired odor-shock conditioning (mimicking maternal odor attachment learning and rearing with an abusive mother, that converge in producing a similar behavioral phenotype in later life including depressive-like behavior as well as disrupted HPA-axis and amygdala function. The importance of maternal social presence on pups’ immediate and enduring brain and behavior suggests unique processing of sensory stimuli in early life that could provide insight into the development of novel strategies for prevention and therapeutic interventions for trauma experienced with the abusive caregiver.
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Harms, Madeline B; Shannon Bowen, Katherine E; Hanson, Jamie L; Pollak, Seth D
2017-10-19
Children who experience severe early life stress show persistent deficits in many aspects of cognitive and social adaptation. Early stress might be associated with these broad changes in functioning because it impairs general learning mechanisms. To explore this possibility, we examined whether individuals who experienced abusive caregiving in childhood had difficulties with instrumental learning and/or cognitive flexibility as adolescents. Fifty-three 14-17-year-old adolescents (31 exposed to high levels of childhood stress, 22 control) completed an fMRI task that required them to first learn associations in the environment and then update those pairings. Adolescents with histories of early life stress eventually learned to pair stimuli with both positive and negative outcomes, but did so more slowly than their peers. Furthermore, these stress-exposed adolescents showed markedly impaired cognitive flexibility; they were less able than their peers to update those pairings when the contingencies changed. These learning problems were reflected in abnormal activity in learning- and attention-related brain circuitry. Both altered patterns of learning and neural activation were associated with the severity of lifetime stress that the adolescents had experienced. Taken together, the results of this experiment suggest that basic learning processes are impaired in adolescents exposed to early life stress. These general learning mechanisms may help explain the emergence of social problems observed in these individuals. © 2017 The Authors. Developmental Science Published by John Wiley & Sons Ltd.
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Trans-Agency Early-Life Exposures and Cancer Working Group
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.
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Stressful Life Events and Predictors of Post-traumatic Growth among High-Risk Early Emerging Adults.
Arpawong, Thalida E; Rohrbach, Louise A; Milam, Joel E; Unger, Jennifer B; Land, Helen; Sun, Ping; Spruijt-Metz, Donna; Sussman, Steve
2016-01-01
Stressful life events (SLEs) may elicit positive psychosocial change among youth, referred to as Post-traumatic Growth (PTG). We assessed types of SLEs experienced, degree to which participants reported PTG, and variables predicting PTG across 24 months among a sample of high risk, ethnically diverse early emerging adults. Participants were recruited from alternative high schools ( n = 564; mean age=16.8; 65% Hispanic). Multi-level regression models were constructed to examine the impact of environmental (SLE quantity, severity) and personal factors (hedonic ability, perceived stress, developmental stage, future time orientation) on a composite score of PTG. The majority of participants reported positive changes resulted from their most life-altering SLE of the past two years. Predictors of PTG included fewer SLEs, less general stress, having a future time perspective, and greater identification with the developmental stage of Emerging Adulthood. Findings suggest intervention targets to foster positive adaptation among early emerging adults who experience frequent SLEs.
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Early-life medical care and human capital accumulation
DEFF Research Database (Denmark)
Daysal, N. Meltem
2015-01-01
that both types of interventions may benefit not only child health but also long-term educational outcomes. In addition, early-life medical interventions may improve the educational outcomes of siblings. These findings can be used to design policies that improve long-term outcomes and reduce economic......Ample empirical evidence links adverse conditions during early childhood (the period from conception to age five) to worse health outcomes and lower academic achievement in adulthood. Can early-life medical care and public health interventions ameliorate these effects? Recent research suggests...
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Development of Life on Early Mars
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
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Effects of early life stress: Opportunities for pharmacological intervention
Loi, M
2016-01-01
Moderate acute activation of the body’s stress response system is considered an adaptive mechanism that increases the chance of survival, but severe stressors early in life may disturb brain development. In agreement, epidemiological data suggest that adverse experiences early in life, such as
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Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.
Fazeli, Walid; Zappettini, Stefania; Marguet, Stephan Lawrence; Grendel, Jasper; Esclapez, Monique; Bernard, Christophe; Isbrandt, Dirk
2017-09-01
The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy in humans, caffeine was added to the drinking water of female mice and their offspring were compared to control offspring. Caffeine altered the construction of GABAergic neuronal networks in V1, as reflected by a reduced number of somatostatin-containing GABA neurons at postnatal days 6-7, with the remaining ones showing poorly developed dendritic arbors. These findings were accompanied by increased synaptic activity in vitro and elevated network activity in vivo in V1. Similarly, in vivo hippocampal network activity was altered from the neonatal period until adulthood. Finally, caffeine-exposed offspring showed increased seizure susceptibility in a hyperthermia-induced seizure model. In summary, our results indicate detrimental effects of developmental caffeine exposure on mouse brain development. Copyright © 2017 Elsevier Inc. All rights reserved.
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Conditions on Early Mars Might Have Fostered Rapid and Early Development of Life
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.
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Early life physical activity and cognition at old age
Dik, Miranda; Deeg, Dorly J H; Visser, Marjolein; Jonker, Cees
Physical activity has shown to be inversely associated with cognitive decline in older people. Whether this association is already present in early life has not been investigated previously. The association between early life physical activity and cognition was studied in 1,241 subjects aged 62-85
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Mika, Agnieszka; Day, Heidi E W; Martinez, Alexander; Rumian, Nicole L; Greenwood, Benjamin N; Chichlowski, Maciej; Berg, Brian M; Fleshner, Monika
2017-02-01
Manipulating gut microbes may improve mental health. Prebiotics are indigestible compounds that increase the growth and activity of health-promoting microorganisms, yet few studies have examined how prebiotics affect CNS function. Using an acute inescapable stressor known to produce learned helplessness behaviours such as failure to escape and exaggerated fear, we tested whether early life supplementation of a blend of two prebiotics, galactooligosaccharide (GOS) and polydextrose (PDX), and the glycoprotein lactoferrin (LAC) would attenuate behavioural and biological responses to stress later in life. Juvenile, male F344 rats were fed diets containing either GOS and PDX alone, LAC alone, or GOS, PDX and LAC. All diets altered gut bacteria, while diets containing GOS and PDX increased Lactobacillus spp. After 4 weeks, rats were exposed to inescapable stress, and either immediately killed for blood and tissues, or assessed for learned helplessness 24 h later. Diets did not attenuate stress effects on spleen weight, corticosterone and blood glucose; however, all diets differentially attenuated stress-induced learned helplessness. Notably, in situ hybridization revealed that all diets reduced stress-evoked cfos mRNA in the dorsal raphe nucleus (DRN), a structure important for learned helplessness behaviours. In addition, GOS, PDX and LAC diet attenuated stress-evoked decreases in mRNA for the 5-HT 1A autoreceptor in the DRN and increased basal BDNF mRNA within the prefrontal cortex. These data suggest early life diets containing prebiotics and/or LAC promote behavioural stress resistance and uniquely modulate gene expression in corresponding circuits. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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Yam, Kit-Yi; Naninck, Eva F. G.; Abbink, M. R.; la Fleur, Susanne E.; Schipper, L.; de Beukelaar, J W K; Grefhorst, Aldo; Oosting, A.; van der Beek, E. M.; Lucassen, P. J.; Korosi, Aniko
Early-life stress (ES) increases the vulnerability to develop psychopathologies and cognitive decline in adulthood. Interestingly, this is often comorbid with metabolic disorders, such as obesity. However, it is unclear whether ES leads to lasting metabolic changes and to what extent this is
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Yam, K.Y.; Naninck, E.F.G.; Abbink, M.R.; la Fleur, S.E.; Schipper, L.; van den Beukel, J.C.; Grefhorst, A.; Oosting, A.; van der Beek, E.M.; Lucassen, P.J.; Korosi, A.
Early-life stress (ES) increases the vulnerability to develop psychopathologies and cognitive decline in adulthood. Interestingly, this is often comorbid with metabolic disorders, such as obesity. However, it is unclear whether ES leads to lasting metabolic changes and to what extent this is
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Ravinder, Shilpa; Donckels, Elizabeth A; Ramirez, Julian S B; Christakis, Dimitri A; Ramirez, Jan-Marino; Ferguson, Susan M
2016-01-01
Early life experiences affect the formation of neuronal networks, which can have a profound impact on brain function and behavior later in life. Previous work has shown that mice exposed to excessive sensory stimulation during development are hyperactive and novelty seeking, and display impaired cognition compared with controls. In this study, we addressed the issue of whether excessive sensory stimulation during development could alter behaviors related to addiction and underlying circuitry in CD-1 mice. We found that the reinforcing properties of cocaine were significantly enhanced in mice exposed to excessive sensory stimulation. Moreover, although these mice displayed hyperactivity that became more pronounced over time, they showed impaired persistence of cocaine-induced locomotor sensitization. These behavioral effects were associated with alterations in glutamatergic transmission in the nucleus accumbens and amygdala. Together, these findings suggest that excessive sensory stimulation in early life significantly alters drug reward and the neural circuits that regulate addiction and attention deficit hyperactivity. These observations highlight the consequences of early life experiences and may have important implications for children growing up in today's complex technological environment.
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Accounting Early for Life Long Learning: The AcE Project.
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…
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CDKL5 alterations lead to early epileptic encephalopathy in both genders.
Liang, Jao-Shwann; Shimojima, Keiko; Takayama, Rumiko; Natsume, Jun; Shichiji, Minobu; Hirasawa, Kyoko; Imai, Kaoru; Okanishi, Tohru; Mizuno, Seiji; Okumura, Akihisa; Sugawara, Midori; Ito, Tomoshiro; Ikeda, Hiroko; Takahashi, Yukitoshi; Oguni, Hirokazu; Imai, Katsumi; Osawa, Makiko; Yamamoto, Toshiyuki
2011-10-01
Genetic mutations of the cyclin-dependent kinase-like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe-to-profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders. A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG-binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations. One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features. We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
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Effect of Early- and Adult-Life Socioeconomic Circumstances on Physical Inactivity.
Cheval, Boris; Sieber, Stefan; Guessous, Idris; Orsholits, Dan; Courvoisier, Delphine S; Kliegel, Matthias; Stringhini, Silvia; Swinnen, Stephan P; Burton-Jeangros, Claudine; Cullati, Stéphane; Boisgontier, Matthieu P
2018-03-01
This study aimed to investigate the associations between early- and adult-life socioeconomic circumstances and physical inactivity (level and evolution) in aging using large-scale longitudinal data. This study used the Survey of Health Ageing and Retirement in Europe, a 10-yr population-based cohort study with repeated measurements in five waves, every 2 yr between 2004 and 2013. Self-reported physical inactivity (waves 1, 2, 4, and 5), household income (waves 1, 2, 4, and 5), educational attainment (wave of the first measurement occasion), and early-life socioeconomic circumstance (wave 3) were collected in 22,846 individuals 50 to 95 yr of age. Risk of physical inactivity was increased for women with the most disadvantaged early-life socioeconomic circumstances (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.20-1.86). With aging, the risk of physical inactivity increased for both sexes and was strongest for those with the most disadvantaged early-life socioeconomic circumstances (OR, 1.04 (95% CI, 1.02-1.06) for women; OR, 1.02 (95% CI, 1.00-1.05) for men), with the former effect being more robust than the latter one. The association between early-life socioeconomic circumstances and physical inactivity was mediated by adult-life socioeconomic circumstances, with education being the strongest mediator. Early-life socioeconomic circumstances predicted high levels of physical inactivity at older ages, but this effect was mediated by socioeconomic indicators in adult life. This finding has implications for public health policies, which should continue to promote education to reduce physical inactivity in people at older ages and to ensure optimal healthy aging trajectories, especially among women with disadvantaged early-life socioeconomic circumstances.
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Structural Alterations of the Glomerular Wall And Vessels in Early ...
African Journals Online (AJOL)
Structural Alterations of the Glomerular Wall And Vessels in Early Stages of Diabetes Mellitus: Light and Transmission Electron Microscopic Study. ... The second group of 20 (the experimental group) was injected intraperitoneally by a single dose of streptozotocin to induce hyperglycemia. Rats were sacrificed after ten days, ...
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Development of the Life Story in Early Adolescence
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…
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Serpentinization and its implications for life on the early Earth and Mars.
Schulte, Mitch; Blake, David; Hoehler, Tori; McCollom, Thomas
2006-04-01
Ophiolites, sections of ocean crust tectonically displaced onto land, offer significant potential to support chemolithoautotrophic life through the provision of energy and reducing power during aqueous alteration of their highly reduced mineralogies. There is substantial chemical disequilibrium between the primary olivine and pyroxene mineralogy of these ophiolites and the fluids circulating through them. This disequilibrium represents a potential source of chemical energy that could sustain life. Moreover, E (h)-pH conditions resulting from rock- water interactions in ultrabasic rocks are conducive to important abiotic processes antecedent to the origin of life. Serpentinization--the reaction of olivine- and pyroxene-rich rocks with water--produces magnetite, hydroxide, and serpentine minerals, and liberates molecular hydrogen, a source of energy and electrons that can be readily utilized by a broad array of chemosynthetic organisms. These systems are viewed as important analogs for potential early ecosystems on both Earth and Mars, where highly reducing mineralogy was likely widespread in an undifferentiated crust. Secondary phases precipitated during serpentinization have the capability to preserve organic or mineral biosignatures. We describe the petrology and mineral chemistry of an ophiolite-hosted cold spring in northern California and propose criteria to aid in the identification of serpentinizing terranes on Mars that have the potential to harbor chemosynthetic life.
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Holz, Nathalie E; Boecker, Regina; Hohm, Erika; Zohsel, Katrin; Buchmann, Arlette F; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Hohmann, Sarah; Wolf, Isabella; Plichta, Michael M; Esser, Günter; Schmidt, Martin; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred
2015-03-01
Converging evidence has highlighted the association between poverty and conduct disorder (CD) without specifying neurobiological pathways. Neuroimaging research has emphasized structural and functional alterations in the orbitofrontal cortex (OFC) as one key mechanism underlying this disorder. The present study aimed to clarify the long-term influence of early poverty on OFC volume and its association with CD symptoms in healthy participants of an epidemiological cohort study followed since birth. At age 25 years, voxel-based morphometry was applied to study brain volume differences. Poverty (0=non-exposed (N=134), 1=exposed (N=33)) and smoking during pregnancy were determined using a standardized parent interview, and information on maternal responsiveness was derived from videotaped mother-infant interactions at the age of 3 months. CD symptoms were assessed by diagnostic interview from 8 to 19 years of age. Information on life stress was acquired at each assessment and childhood maltreatment was measured using retrospective self-report at the age of 23 years. Analyses were adjusted for sex, parental psychopathology and delinquency, obstetric adversity, parental education, and current poverty. Individuals exposed to early life poverty exhibited a lower OFC volume. Moreover, we replicated previous findings of increased CD symptoms as a consequence of childhood poverty. This effect proved statistically mediated by OFC volume and exposure to life stress and smoking during pregnancy, but not by childhood maltreatment and maternal responsiveness. These findings underline the importance of studying the impact of early life adversity on brain alterations and highlight the need for programs to decrease income-related disparities.
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Arcego, Danusa Mar; Krolow, Rachel; Lampert, Carine; Toniazzo, Ana Paula; Berlitz, Carolina; Lazzaretti, Camilla; Schmitz, Felipe; Rodrigues, André Felipe; Wyse, Angela T S; Dalmaz, Carla
2016-05-01
Environmental factors, like early exposure to stressors or high caloric diets, can alter the early programming of central nervous system, leading to long-term effects on cognitive function, increased vulnerability to cognitive decline and development of psychopathologies later in life. The interaction between these factors and their combined effects on brain structure and function are still not completely understood. In this study, we evaluated long-term effects of social isolation in the prepubertal period, with or without chronic high fat diet access, on memory and on neurochemical markers in the prefrontal cortex of rats. We observed that early social isolation led to impairment in short-term and working memory in adulthood, and to reductions of Na(+),K(+)-ATPase activity and the immunocontent of phospho-AKT, in prefrontal cortex. Chronic exposure to a high fat diet impaired short-term memory (object recognition), and decreased BDNF levels in that same brain area. Remarkably, the association of social isolation with chronic high fat diet rescued the memory impairment on the object recognition test, as well as the changes in BDNF levels, Na(+),K(+)-ATPase activity, MAPK, AKT and phospho-AKT to levels similar to the control-chow group. In summary, these findings showed that a brief social isolation period and access to a high fat diet during a sensitive developmental period might cause memory deficits in adulthood. On the other hand, the interplay between isolation and high fat diet access caused a different brain programming, preventing some of the effects observed when these factors are separately applied. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.
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Reduced cortical thickness in veterans exposed to early life trauma.
Corbo, Vincent; Salat, David H; Amick, Melissa M; Leritz, Elizabeth C; Milberg, William P; McGlinchey, Regina E
2014-08-30
Studies have shown that early life trauma may influence neural development and increase the risk of developing psychological disorders in adulthood. We used magnetic resonance imaging to examine the impact of early life trauma on the relationship between current posttraumatic stress disorder (PTSD) symptoms and cortical thickness/subcortical volumes in a sample of deployed personnel from Operation Enduring Freedom/Operation Iraqi Freedom. A group of 108 service members enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) were divided into those with interpersonal early life trauma (EL-Trauma+) and Control (without interpersonal early life trauma) groups based on the Traumatic Life Events Questionnaire. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale. Cortical thickness and subcortical volumes were analyzed using the FreeSurfer image analysis package. Thickness of the paracentral and posterior cingulate regions was positively associated with PTSD severity in the EL-Trauma+ group and negatively in the Control group. In the EL-Trauma+ group, both the right amygdala and the left hippocampus were positively associated with PTSD severity. This study illustrates a possible influence of early life trauma on the vulnerability of specific brain regions to stress. Changes in neural morphometry may provide information about the emergence and maintenance of symptoms in individuals with PTSD. Published by Elsevier Ireland Ltd.
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Reynolds, Clare M; Perry, Jo K; Vickers, Mark H
2017-08-08
Evidence from human clinical, epidemiological, and experimental animal models has clearly highlighted a link between the early life environment and an increased risk for a range of cardiometabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and overnutrition, spanning exposure windows that cover the period from preconception through to early infancy, clearly highlight an increased risk for a range of disorders in offspring in later life. This process, preferentially termed "developmental programming" as part of the developmental origins of health and disease (DOHaD) framework, leads to phenotypic outcomes in offspring that closely resemble those of individuals with untreated growth hormone (GH) deficiency, including increased adiposity and cardiovascular disorders. As such, the use of GH as a potential intervention strategy to mitigate the effects of developmental malprogramming has received some attention in the DOHaD field. In particular, experimental animal models have shown that early GH treatment in the setting of poor maternal nutrition can partially rescue the programmed phenotype, albeit in a sex-specific manner. Although the mechanisms remain poorly defined, they include changes to endothelial function, an altered inflammasome, changes in adipogenesis and cardiovascular function, neuroendocrine effects, and changes in the epigenetic regulation of gene expression. Similarly, GH treatment to adult offspring, where an adverse metabolic phenotype is already manifest, has shown efficacy in reversing some of the metabolic disorders arising from a poor early life environment. Components of the GH-insulin-like growth factor (IGF)-IGF binding protein (GH-IGF-IGFBP) system, including insulin-like growth factor 1 (IGF-1), have also shown promise in ameliorating programmed metabolic disorders, potentially acting via epigenetic processes including changes in miRNA profiles and altered DNA methylation. However, as
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Can environmental conditions experienced in early life influence future generations?
Burton, Tim; Metcalfe, Neil B
2014-06-22
The consequences of early developmental conditions for performance in later life are now subjected to convergent interest from many different biological sub-disciplines. However, striking data, largely from the biomedical literature, show that environmental effects experienced even before conception can be transmissible to subsequent generations. Here, we review the growing evidence from natural systems for these cross-generational effects of early life conditions, showing that they can be generated by diverse environmental stressors, affect offspring in many ways and can be transmitted directly or indirectly by both parental lines for several generations. In doing so, we emphasize why early life might be so sensitive to the transmission of environmentally induced effects across generations. We also summarize recent theoretical advancements within the field of developmental plasticity, and discuss how parents might assemble different 'internal' and 'external' cues, even from the earliest stages of life, to instruct their investment decisions in offspring. In doing so, we provide a preliminary framework within the context of adaptive plasticity for understanding inter-generational phenomena that arise from early life conditions.
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Directory of Open Access Journals (Sweden)
Austin T. Mudd
2018-01-01
Full Text Available BackgroundIron deficiency is the most common micronutrient deficiency worldwide and children are at an increased risk due to the rapid growth occurring during early life. The developing brain is highly dynamic, requires iron for proper function, and is thus vulnerable to inadequate iron supplies. Iron deficiency early in life results in altered myelination, neurotransmitter synthesis, neuron morphology, and later-life cognitive function. However, it remains unclear if dietary iron repletion after a period of iron deficiency can recover structural deficits in the brain.MethodTwenty-eight male pigs were provided either a control diet (CONT; n = 14; 23.5 mg Fe/L milk replacer or an iron-deficient diet (ID; n = 14; 1.56 mg Fe/L milk replacer for phase 1 of the study, from postnatal day (PND 2 until 32. Twenty pigs (n = 10/diet from phase 1 were used in phase 2 of the study from PND 33 to 61, all pigs were provided a common iron sufficient diet, regardless of their early-life dietary iron status. All pigs remaining in the study were subjected to magnetic resonance imaging (MRI at PND 32 and again at PND 61 using structural imaging sequences and diffusion tensor imaging (DTI to assess volumetric and microstructural brain development, respectively. Data were analyzed using a two-way ANOVA to assess the main and interactive effects of early-life iron status and time.ResultsAn interactive effect was observed for absolute whole brain volumes, in which whole brain volumes of ID pigs were smaller at PND 32 but were not different than CONT pigs at PND 61. Analysis of brain region volumes relative to total brain volume indicated interactive effects (i.e., diet × day in the cerebellum, olfactory bulb, and putamen-globus pallidus. Main effects of early-life iron status, regardless of imaging time point, were noted for decreased relative volumes of the left hippocampus, right hippocampus, thalamus, and increased relative white matter volume
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Early life trauma, depression and the glucocorticoid receptor gene--an epigenetic perspective.
Smart, C; Strathdee, G; Watson, S; Murgatroyd, C; McAllister-Williams, R H
2015-12-01
Hopes to identify genetic susceptibility loci accounting for the heritability seen in unipolar depression have not been fully realized. Family history remains the 'gold standard' for both risk stratification and prognosis in complex phenotypes such as depression. Meanwhile, the physiological mechanisms underlying life-event triggers for depression remain opaque. Epigenetics, comprising heritable changes in gene expression other than alterations of the nucleotide sequence, may offer a way to deepen our understanding of the aetiology and pathophysiology of unipolar depression and optimize treatments. A heuristic target for exploring the relevance of epigenetic changes in unipolar depression is the hypothalamic-pituitary-adrenal (HPA) axis. The glucocorticoid receptor (GR) gene (NR3C1) has been found to be susceptible to epigenetic modification, specifically DNA methylation, in the context of environmental stress such as early life trauma, which is an established risk for depression later in life. In this paper we discuss the progress that has been made by studies that have investigated the relationship between depression, early trauma, the HPA axis and the NR3C1 gene. Difficulties with the design of these studies are also explored. Future efforts will need to comprehensively address epigenetic natural histories at the population, tissue, cell and gene levels. The complex interactions between the epigenome, genome and environment, as well as ongoing nosological difficulties, also pose significant challenges. The work that has been done so far is nevertheless encouraging and suggests potential mechanistic and biomarker roles for differential DNA methylation patterns in NR3C1 as well as novel therapeutic targets.
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The positive and negative consequences of stressors during early life.
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.
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The Serotonin Transporter and Early Life Stress: Translational Perspectives
Directory of Open Access Journals (Sweden)
Jocelien D. A. Olivier
2017-04-01
Full Text Available The interaction between the serotonin transporter (SERT linked polymorphic region (5-HTTLPR and adverse early life stressing (ELS events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human short allele carriers are at increased risk. This 5-HTTLPR polymorphism is absent in the rodent SERT gene, but heterozygous SERT knockout rodents (SERT+/− show several similarities to the human S-allele carrier, therefore creating an animal model of the human situation. Many rodent studies investigated ELS interactions in SERT knockout rodents combined with ELS. However, underlying neuromolecular mechanisms of the (maladaptive responses to adversity displayed by SERT rodents remain to be elucidated. Here, we provide a comprehensive review including studies describing mechanisms underlying SERT variation × ELS interactions in rodents. Alterations at the level of translation and transcription but also epigenetic alterations considerably contribute to underlying mechanisms of SERT variation × ELS interactions. In particular, SERT+/− rodents exposed to adverse early rearing environment may be of high translational and predictive value to the more stress sensitive human short-allele carrier, considering the similarity in neurochemical alterations. Therefore, SERT+/− rodents are highly relevant in research that aims to unravel the complex psychopathology of mental disorders. So far, most studies fail to show solid evidence for increased vulnerability to develop affective-like behavior after ELS in SERT+/− rodents. Several reasons may underlie these failures, e.g., (1 stressors used might not be optimal or severe enough to induce maladaptations, (2 effects in females are not sufficiently studied, and (3 few studies include both behavioral manifestations and molecular correlates of ELS-induced effects in SERT+/− rodents. Of course, one should not
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The Serotonin Transporter and Early Life Stress: Translational Perspectives
Houwing, Danielle J.; Buwalda, Bauke; van der Zee, Eddy A.; de Boer, Sietse F.; Olivier, Jocelien D. A.
2017-01-01
The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human short allele carriers are at increased risk. This 5-HTTLPR polymorphism is absent in the rodent SERT gene, but heterozygous SERT knockout rodents (SERT+/−) show several similarities to the human S-allele carrier, therefore creating an animal model of the human situation. Many rodent studies investigated ELS interactions in SERT knockout rodents combined with ELS. However, underlying neuromolecular mechanisms of the (mal)adaptive responses to adversity displayed by SERT rodents remain to be elucidated. Here, we provide a comprehensive review including studies describing mechanisms underlying SERT variation × ELS interactions in rodents. Alterations at the level of translation and transcription but also epigenetic alterations considerably contribute to underlying mechanisms of SERT variation × ELS interactions. In particular, SERT+/− rodents exposed to adverse early rearing environment may be of high translational and predictive value to the more stress sensitive human short-allele carrier, considering the similarity in neurochemical alterations. Therefore, SERT+/− rodents are highly relevant in research that aims to unravel the complex psychopathology of mental disorders. So far, most studies fail to show solid evidence for increased vulnerability to develop affective-like behavior after ELS in SERT+/− rodents. Several reasons may underlie these failures, e.g., (1) stressors used might not be optimal or severe enough to induce maladaptations, (2) effects in females are not sufficiently studied, and (3) few studies include both behavioral manifestations and molecular correlates of ELS-induced effects in SERT+/− rodents. Of course, one should not exclude the
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Albuquerque Filho, Manoel Osório; de Freitas, Betânia Souza; Garcia, Rebeca Carvalho Lacerda; Crivelaro, Pedro Castilhos de Freitas; Schröder, Nadja; de Lima, Maria Noêmia Martins
2017-03-06
Exposure to stress early in life may negatively impact nervous system functioning, including increasing the proneness to learning and memory impairments later in life. Maternal deprivation, a model of early-life stress, hinders memory in adult rats and lessens brain-derived neurotrophic factor (BDNF) levels in the hippocampus in a very heterogeneous way among individuals. The main goal of the present study was to investigate the possible epigenetic modulation underlying recognition memory impairment and reduced BDNF levels in the hippocampus of adult maternally deprived rats. We also evaluated the potential ameliorating properties of the histone deacetylase (HDAC) inhibitor, sodium butyrate, on memory deficits and BDNF changes related to maternal deprivation. Maternally deprived animals were categorized as 'inferior learners' and 'superior learners' according to their performance in object recognition memory task in comparison to controls. Results indicated that HDAC activity was higher in individuals submitted to maternal deprivation with the worst cognitive performance (inferior learners). Acute administration of sodium butyrate increased histone H3 acetylation and BDNF levels, and restored recognition memory in maternally deprived animals with the worst cognitive performance. Moreover, we also showed that there is a positive correlation between BDNF levels and memory performance. Taken together, the results indicated that HDAC inhibitors could be considered as a possible therapeutic agent to improve cognitive performance in inferior learners. Further studies need to be conducted for a better comprehension of the mechanisms related to persistent alterations observed in adult life induced by early stressful circumstances and those leading to resilience. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
Delia M Talos
Full Text Available Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1 signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46, phospho-p70S6K (Thr389 and phospho-S6 (Ser235/236, as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308 and phospho-ERK (Thr202/Tyr204. Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures.
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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.
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Directory of Open Access Journals (Sweden)
Eldin Jašarević
2015-01-01
Full Text Available Perturbations in the prenatal and early life environment can contribute to the development of offspring stress dysregulation, a pervasive symptom in neuropsychiatric disease. Interestingly, the vertical transmission of maternal microbes to offspring and the subsequent bacterial colonization of the neonatal gut overlap with a critical period of brain development. Therefore, environmental factors such as maternal stress that are able to alter microbial populations and their transmission can thereby shape offspring neurodevelopment. As the neonatal gastrointestinal tract is primarily inoculated at parturition through the ingestion of maternal vaginal microflora, disruption in the vaginal ecosystem may have important implications for offspring neurodevelopment and disease risk. Here, we discuss alterations that occur in the vaginal microbiome following maternal insult and the subsequent effects on bacterial assembly of the neonate gut, the production of neuromodulatory metabolites, and the developmental course of stress regulation.
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Van Leeuwen, C H A; Dokk, T; Haugen, T O; Kiffney, P M; Museth, J
2017-06-01
Behaviour of early life stages of the salmonid European grayling Thymallus thymallus was investigated by assessing the timing of larval downstream movement from spawning areas, the depth at which larvae moved and the distribution of juvenile fish during summer in two large connected river systems in Norway. Trapping of larvae moving downstream and electrofishing surveys revealed that T. thymallus larvae emerging from the spawning gravel moved downstream predominantly during the night, despite light levels sufficient for orientation in the high-latitude study area. Larvae moved in the water mostly at the bottom layer close to the substratum, while drifting debris was caught in all layers of the water column. Few young-of-the-year still resided close to the spawning areas in autumn, suggesting large-scale movement (several km). Together, these observations show that there may be a deliberate, active component to downstream movement of T. thymallus during early life stages. This research signifies the importance of longitudinal connectivity for T. thymallus in Nordic large river systems. Human alterations of flow regimes and the construction of reservoirs for hydropower may not only affect the movement of adult fish, but may already interfere with active movement behaviour of fish during early life stages. © 2017 The Fisheries Society of the British Isles.
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Early-Life Nutritional Programming of Health and Disease in The Gambia.
Moore, Sophie E
2017-01-01
Exposures during early life are increasingly being recognised as factors that play an important role in the aetiology of chronic non-communicable diseases (NCDs). The "Developmental Origins of Health and Disease" (DOHaD) hypothesis asserts that adverse early-life exposures - most notably unbalanced nutrition - leads to an increased risk for a range of NCDs and that disease risk is highest when there is a "mismatch" between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in settings undergoing a rapid nutrition transition. We investigated the link between early-life nutritional exposures and long-term health in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomised controlled trials of nutritional supplementation in pregnancy, and the "experiment of nature" that seasonality in this region provides, we investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs. Key Messages: Our work in rural Gambia suggests that in populations with high rates of under-nutrition in early life, the immune system may be sensitive to nutritional deficiencies early in life, resulting in a greater susceptibility to infection-related morbidity and mortality. © 2017 S. Karger AG, Basel.
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Early-life gut microbiome and egg allergy.
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.
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The OBELIX project: early life exposure to endocrine disruptors and obesity.
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.
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Teng, Miaomiao; Zhu, Wentao; Wang, Dezhen; Qi, Suzhen; Wang, Yao; Yan, Jin; Dong, Kai; Zheng, Mingqi; Wang, Chengju
2018-01-01
Difenoconazole is widely used to inhibit the growth of fungi, but its residue in the water environment may threaten ecosystem and human health. Here, 1 H nuclear magnetic resonance (NMR) and LC-MS/MS based metabolomics and transcriptomics approaches were used to assess the response of zebrafish to difenoconazole exposure. Early life stages of zebrafish were exposed to difenoconazole at environmentally relevant concentrations for 168h. Their comparison with the control group suggested an adverse development and disturbance of steroid hormones and VTG. KEGG pathway analysis identified five biological processes on the basis of differentially expressed genes (DEGs), as well as altered metabolites and amino acids in zebrafish following difenoconazole exposure. These affected processes included energy metabolism, amino acids metabolism, lipid metabolism, nucleotide metabolism, and an immune-related pathway. Collectively, these results bring us closer to an incremental understanding of the toxic effects of difenoconazole on zebrafish in its early development, and lend support to the continued use of the early life stages of zebrafish as a classical model to evaluate underlying environmental risks of xenobiotics in aquatic organisms. Copyright © 2017 Elsevier B.V. All rights reserved.
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Grosch, Eugene G; Hazen, Robert M
2015-10-01
Earth is the most mineralogically diverse planet in our solar system, the direct consequence of a coevolving geosphere and biosphere. We consider the possibility that a microbial biosphere originated and thrived in the early Hadean-Archean Earth subseafloor environment, with fundamental consequences for the complex evolution and habitability of our planet. In this hypothesis paper, we explore possible venues for the origin of life and the direct consequences of microbially mediated, low-temperature hydrothermal alteration of the early oceanic lithosphere. We hypothesize that subsurface fluid-rock-microbe interactions resulted in more efficient hydration of the early oceanic crust, which in turn promoted bulk melting to produce the first evolved fragments of felsic crust. These evolved magmas most likely included sialic or tonalitic sheets, felsic volcaniclastics, and minor rhyolitic intrusions emplaced in an Iceland-type extensional setting as the earliest microcontinents. With the further development of proto-tectonic processes, these buoyant felsic crustal fragments formed the nucleus of intra-oceanic tonalite-trondhjemite-granitoid (TTG) island arcs. Thus microbes, by facilitating extensive hydrothermal alteration of the earliest oceanic crust through bioalteration, promoted mineral diversification and may have been early architects of surface environments and microcontinents on young Earth. We explore how the possible onset of subseafloor fluid-rock-microbe interactions on early Earth accelerated metavolcanic clay mineral formation, crustal melting, and subsequent metamorphic mineral evolution. We also consider environmental factors supporting this earliest step in geosphere-biosphere coevolution and the implications for habitability and mineral evolution on other rocky planets, such as Mars.
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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.
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Early life stress paradigms in rodents: potential animal models of depression?
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.
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Early-Life Diet Affects Host Microbiota and Later-Life Defenses Against Parasites in Frogs.
Knutie, Sarah A; Shea, Lauren A; Kupselaitis, Marinna; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R
2017-10-01
Food resources can affect the health of organisms by altering their symbiotic microbiota and affecting energy reserves for host defenses against parasites. Different diets can vary in their macronutrient content and therefore they might favor certain bacterial communities of the host and affect the development and maintenance of the immune system, such as the inflammatory or antibody responses. Thus, testing the effect of diet, especially for animals with wide diet breadths, on host-associated microbiota and defenses against parasites might be important in determining infection and disease risk. Here, we test whether the early-life diet of Cuban tree frogs (Osteopilus septentrionalis) affects early- and later-life microbiota as well as later-life defenses against skin-penetrating, gut worms (Aplectana hamatospicula). We fed tadpoles two ecologically common diets: a diet of conspecifics or a diet of algae (Arthrospira sp.). We then: (1) characterized the gut microbiota of tadpoles and adults; and (2) challenged adult frogs with parasitic worms and measured host resistance (including the antibody-mediated immune response) and tolerance of infections. Tadpole diet affected bacterial communities in the guts of tadpoles but did not have enduring effects on the bacterial communities of adults. In contrast, tadpole diet had enduring effects on host resistance and tolerance of infections in adult frogs. Frogs that were fed a conspecific-based diet as tadpoles were more resistant to worm penetration compared with frogs that were fed an alga-based diet as tadpoles, but less resistant to worm establishment, which may be related to their suppressed antibody response during worm establishment. Furthermore, frogs that were fed a conspecific-based diet as tadpoles were more tolerant to the effect of parasite abundance on host mass during worm establishment. Overall, our study demonstrates that the diet of Cuban tree frog tadpoles affects the gut microbiota and defenses against
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Public health implications of altered puberty timing
DEFF Research Database (Denmark)
Golub, M.S.; Collman, G.W.; Foster, P.M.
2008-01-01
sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated...
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Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.
Directory of Open Access Journals (Sweden)
Amanda E Hernan
Full Text Available Children with epilepsy often present with pervasive cognitive and behavioral comorbidities including working memory impairments, attention deficit hyperactivity disorder (ADHD and autism spectrum disorder. These non-seizure characteristics are severely detrimental to overall quality of life. Some of these children, particularly those with epilepsies classified as Landau-Kleffner Syndrome or continuous spike and wave during sleep, have infrequent seizure activity but frequent focal epileptiform activity. This frequent epileptiform activity is thought to be detrimental to cognitive development; however, it is also possible that these IIS events initiate pathophysiological pathways in the developing brain that may be independently associated with cognitive deficits. These hypotheses are difficult to address due to the previous lack of an appropriate animal model. To this end, we have recently developed a rat model to test the role of frequent focal epileptiform activity in the prefrontal cortex. Using microinjections of a GABA(A antagonist (bicuculline methiodine delivered multiple times per day from postnatal day (p 21 to p25, we showed that rat pups experiencing frequent, focal, recurrent epileptiform activity in the form of interictal spikes during neurodevelopment have significant long-term deficits in attention and sociability that persist into adulthood. To determine if treatment with ACTH, a drug widely used to treat early-life seizures, altered outcome we administered ACTH once per day subcutaneously during the time of the induced interictal spike activity. We show a modest amelioration of the attention deficit seen in animals with a history of early life interictal spikes with ACTH, in the absence of alteration of interictal spike activity. These results suggest that pharmacological intervention that is not targeted to the interictal spike activity is worthy of future study as it may be beneficial for preventing or ameliorating adverse
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Directory of Open Access Journals (Sweden)
Jayanthi eManiam
2016-01-01
Full Text Available Adverse early life experience is a known risk factor for psychiatric disorders. It is also known that stress influences food preference. We were interested in exploring whether the choice of diet following early life stress exerts long-lasting molecular changes in the brain, particularly the hippocampus, a region critically involved in stress regulation and behavioural outcomes. Here, we examined the impact of early life stress induced by limited nesting material (LN and chronic sucrose availability post-weaning on an array of hippocampal genes related to plasticity, neurogenesis, stress and inflammatory responses and mitochondrial biogenesis. To examine mechanisms underlying the impact of LN and sugar intake on hippocampal gene expression, we investigated the role of DNA methylation. As females are more likely to experience adverse life events, we studied female Sprague-Dawley rats. After mating LN was imposed from days 2-9 postpartum. From 3-15 weeks of age, female Control and LN siblings had unlimited to access to either chow and water, or chow, water and 25% sucrose solution. LN markedly reduced glucocorticoid receptor (GR and neurogenic differentiation 1 (Neurod1 mRNA, markers involved in stress and hippocampal plasticity respectively, by more than 40%, with a similar effect of sugar intake in control rats. However, no further impact was observed in LN rats consuming sugar. Hippocampal Akt3 mRNA expression was similarly affected by LN and sucrose consumption. Interestingly, DNA methylation across 4 CpG sites of the GR and Neurod1 promoters was similar in LN and control rats. In summary, early life stress and post-weaning sugar intake produced long-term effects on hippocampal GR and Neurod1 expression. Moreover we found no evidence of altered promoter DNA methylation. We demonstrate for the first time that chronic sucrose consumption alone produces similar detrimental effects on the expression of hippocampal genes as LN exposure.
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Early Mars: A Warm Wet Niche for Life
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)
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Nygaard, Unni Cecilie; Vinje, Nina Eriksen; Samuelsen, Mari; Andreassen, Monica; Groeng, Else-Carin; Bølling, Anette Kocbach; Becher, Rune; Lovik, Martinus; Bodin, Johanna
2015-09-01
The impact of early life exposure to bisphenol A (BPA) through drinking water was investigated in mouse models of respiratory allergy, food allergy and oral tolerance. Balb/c mice were exposed to BPA (0, 10 or 100 μg/ml), and the offspring were intranasally exposed to the allergen ovalbumin (OVA). C3H/HeJ offspring were sensitized with the food allergen lupin by intragastric gavage, after exposure to BPA (0, 1, 10 or 100 μg/ml). In separate offspring, oral tolerance was induced by gavage of 5 mg lupin one week before entering the protocol for the food allergy induction. In the airway allergy model, BPA (100 μg/ml) caused increased eosinophil numbers in bronchoalveolar lavage fluid (BALF) and a trend of increased OVA-specific IgE levels. In the food allergy and tolerance models, BPA did not alter the clinical anaphylaxis or antibody responses, but induced alterations in splenocyte cytokines and decreased mouse mast cell protease (MMCP)-1 serum levels. In conclusion, early life exposure to BPA through drinking water modestly augmented allergic responses in a mouse model of airway allergy only at high doses, and not in mouse models for food allergy and tolerance. Thus, our data do not support that BPA promotes allergy development at exposure levels relevant for humans. Copyright © 2015 Elsevier Ltd. All rights reserved.
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The die is cast - Arsenic exposure in early life and disease susceptibility
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...
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Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders
Directory of Open Access Journals (Sweden)
Joan Y. Holgate
2015-06-01
Full Text Available Stress is a major driving force in alcohol use disorders (AUDs. It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual’s brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.
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International Nuclear Information System (INIS)
Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki
2013-01-01
Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life
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Energy Technology Data Exchange (ETDEWEB)
Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)
2013-12-06
Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.
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The early Earth atmosphere and early life catalysts.
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.
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Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P.; Klein, Jonathan D.; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.
2015-01-01
Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice. Methods: Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until d...
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The human early-life exposome (HELIX): project rationale and design.
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.
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Early-life income inequality and adolescent health and well-being.
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
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Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure
van Bodegom, Miranda; Homberg, Judith R.; Henckens, Marloes J. A. G.
2017-01-01
Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA
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Wet, Carbonaceous Asteroids: Altering Minerals, Changing Amino Acids
Taylor, G. J.
2011-04-01
Many carbonaceous chondrites contain alteration products from water-rock interactions at low temperature and organic compounds. A fascinating fact known for decades is the presence in some of them of an assortment of organic compounds, including amino acids, sometimes called the building blocks of life. Murchison and other CM carbonaceous chondrites contain hundreds of amino acids. Early measurements indicated that the amino acids in carbonaceous chondrites had equal proportions of L- and D-structures, a situation called racemic. This was in sharp contrast to life on Earth, which heavily favors L- forms. However, beginning in 1997, John Cronin and Sandra Pizzarello (Arizona State University) found L- excesses in isovaline and several other amino acids in the Murchison carbonaceous chondrite. In 2009, Daniel Glavin and Jason Dworkin (Astrobiology Analytical Lab, Goddard Space Flight Center) reported the first independent confirmation of L-isovaline excesses in Murchison using a different analytical technique than employed by Cronin and Pizzarello. Inspired by this work, Daniel Glavin, Michael Callahan, Jason Dworkin, and Jamie Elsila (Astrobiology Analytical Lab, Goddard Space Flight Center), have done an extensive study of the abundance and symmetry of amino acids in carbonaceous chondrites that experienced a range of alteration by water in their parent asteroids. The results show that amino acids are more abundant in the less altered meteorites, implying that aqueous processing changes the mix of amino acids. They also confirmed the enrichment in L-structures of some amino acids, especially isovaline, confirming earlier work. The authors suggest that aqueously-altered planetesimals might have seeded the early Earth with nonracemic amino acids, perhaps explaining why life from microorganisms to people use only L- forms to make proteins. The initial imbalance caused by non-biologic processes in wet asteroids might have been amplified by life on Earth. Alternatively
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Early Life Microbiota, Neonatal Immune Maturation and Hematopoiesis
DEFF Research Database (Denmark)
Kristensen, Matilde Bylov
Emerging epidemiologic data supports the hypothesis that early life colonization is a key player in development of a balanced immune system. Events in early life, as birth mode and infant diet, are shown to influence development of immune related diseases, like asthma, diabetes and inflammatory...... bowl disease, later in life. The intestinal epithelium makes up a physical and biochemical barrier between the bacteria in the gut lumen and the immune cells in the submocusal tissue. This monolayer of intestinal epithelial cells (IEC) makes up an extremely large surface and is highly important...... for the synergistic coexistence between trillions of bacteria in the gastrointestinal tract and their mammalian hosts. The IEC actively communicate with the microbiota of the gut lumen and tolerance establishment in the intestine is induced as a result of a balanced and controlled communication between IEC...
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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
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Early life nutritional programming of health and disease in The Gambia
Moore, S. E.
2015-01-01
Exposures during the early life (periconceptional, prenatal and early postnatal) period are increasingly recognized as playing an important role in the aetiology of chronic non-communicable diseases (NCD), including coronary heart disease, stroke, hypertension, Type 2 diabetes and osteoporosis. The ?Developmental Origins of Health and Disease? (DOHaD) hypothesis states that these disorders originate through unbalanced nutrition early in life and risk is highest when there is a ?mismatch? betw...
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The developing hypopharyngeal microbiota in early life
DEFF Research Database (Denmark)
Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael
2016-01-01
BACKGROUND: The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establi......BACKGROUND: The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand...... the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC2010 cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. RESULTS: Our analysis shows...... that majority of the hypopharyngeal microbiota of healthy infants belong to each individual's core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we...
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Ghosh, S; Banerjee, K K; Vaidya, V A; Kolthur-Seetharam, U
2016-09-01
Early-life adversity is associated with an enhanced risk for adult psychopathology. Psychiatric disorders such as depression exhibit comorbidity for metabolic dysfunction, including obesity and diabetes. However, it is poorly understood whether, besides altering anxiety and depression-like behaviour, early stress also evokes dysregulation of metabolic pathways and enhances vulnerability for metabolic disorders. We used the rodent model of the early stress of maternal separation (ES) to examine the effects of early stress on serum metabolites, insulin-like growth factor (IGF)-1 signalling, and muscle mitochondrial content. Adult ES animals exhibited dyslipidaemia, decreased serum IGF1 levels, increased expression of liver IGF binding proteins, and a decline in the expression of specific metabolic genes in the liver and muscle, including Pck1, Lpl, Pdk4 and Hmox1. These changes occurred in the absence of alterations in body weight, food intake, glucose tolerance, insulin tolerance or insulin levels. ES animals also exhibited a decline in markers of muscle mitochondrial content, such as mitochondrial DNA levels and expression of TFAM (transcription factor A, mitochondrial). Furthermore, the expression of several genes involved in mitochondrial function, such as Ppargc1a, Nrf1, Tfam, Cat, Sesn3 and Ucp3, was reduced in skeletal muscle. Adult-onset chronic unpredictable stress resulted in overlapping and distinct consequences from ES, including increased circulating triglyceride levels, and a decline in the expression of specific metabolic genes in the liver and muscle, with no change in the expression of genes involved in muscle mitochondrial function. Taken together, our results indicate that a history of early adversity can evoke persistent changes in circulating IGF-1 and muscle mitochondrial function and content, which could serve to enhance predisposition for metabolic dysfunction in adulthood. © 2016 British Society for Neuroendocrinology.
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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.
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Early life exposures and risk of atopy among Danish children
DEFF Research Database (Denmark)
Thomsen, SF; Ulrik, Charlotte Suppli; Porsbjerg, C
2006-01-01
A large proportion of atopy develops in childhood and early life exposures are suspected to play a considerable role in the inception. The aim of this study was to examine the association between early life exposures and development of atopic disease in children. We performed a case-cohort study...... to be independent of familial predisposition to atopic disease and significantly increases the likelihood for development of atopy in genetically susceptible individuals. Parental knowledge of atopic heredity significantly influences smoking and breast-feeding habits....... of a random population-based sample of children (n = 480) 7-17 years of age, living in urban Copenhagen, Denmark. Information on breast-feeding, supplementation, wheezy bronchitis, use of antibiotics, and parental smoking during pregnancy and in early life was obtained retrospectively by questionnaire. Skin...
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The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats.
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.
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Directory of Open Access Journals (Sweden)
Regina Boecker
Full Text Available Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD. 162 healthy young adults (mean age = 24.4 years; 58% female from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus, indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV, with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.
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Early evolution without a tree of life.
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.
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Specific synbiotics in early life protect against diet-induced obesity in adult mice
Mischke, Mona; Arora, Tulika; Tims, Sebastian; Engels, Eefje; Sommer, Nina; Limpt, van Kees; Baars, Annemarie; Oozeer, Raish; Oosting, Annemarie; Bäckhed, Fredrik; Knol, Jan
2018-01-01
Aims: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health throughout life. Here, we determined how beneficial microbiome interventions in early life
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Early-Life Food Nutrition, Microbiota Maturation and Immune Development Shape Life-Long Health.
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.
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An experimental demonstration that early-life competitive disadvantage accelerates telomere loss.
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.
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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.
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The Influence of Early Life Experience on Visceral Pain
Directory of Open Access Journals (Sweden)
Isabella M. Fuentes
2018-01-01
Full Text Available Pain is the most reported and troublesome symptom of nearly all functional disorders affecting the genitourinary and gastrointestinal organs. Patients with irritable bowel syndrome (IBS, interstitial cystitis/painful bladder syndrome (IC/PBS, vulvodynia, and/or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; collectively termed chronic pelvic pain syndromes report pain severe enough to impact quality of life and often suffer from symptoms of or are diagnosed with more than one of these syndromes. This increased comorbidity between chronic pelvic pain syndromes, and with pain disorders of disparate body regions, as well as with mood disorders, can be influenced by disruptions in the hypothalamic-pituitary-adrenal (HPA axis, which regulates the response to stress and influences the perception of pain. Experiencing trauma, neglect, or abuse in early life can permanently affect the functioning of the HPA axis. As such, a significant proportion of patients suffering from comorbid chronic pelvic pain syndromes report a history of early life stress or trauma. Here we will report on how these early life experiences influence chronic pelvic pain in patients. We will also discuss various rodent models that have been developed to study this phenomenon to understand the mechanisms underlying HPA axis dysfunction, as well as potential underlying mechanisms connecting these syndromes to one another.
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Exposure to dim light at night during early development increases adult anxiety-like responses.
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
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Early-life inflammation with LPS delays fear extinction in adult rodents.
Doenni, V M; Song, C M; Hill, M N; Pittman, Q J
2017-07-01
A large body of evidence has been brought forward connecting developmental immune activation to abnormal fear and anxiety levels. Anxiety disorders have extremely high lifetime prevalence, yet susceptibility factors that contribute to their emergence are poorly understood. In this research we investigated whether an inflammatory insult early in life can alter the response to fear conditioning in adulthood. Fear learning and extinction are important and adaptive behaviors, mediated largely by the amygdala and its interconnectivity with cortico-limbic circuits. Male and female rat pups were given LPS (100μg/kg i.p.) or saline at postnatal day 14; LPS activated cFos expression in the central amygdala 2.5h after exposure, but not the basal or lateral nuclei. When tested in adulthood, acquisition of an auditory cued or contextual learned fear memory was largely unaffected as was the extinction of fear to a conditioned context. However, we detected a deficit in auditory fear extinction in male and female rats that experienced early-life inflammation, such that there is a significant delay in fear extinction processes resulting in more sustained fear behaviors in response to a conditioned cue. This response was specific to extinction training and did not persist into extinction recall. The effect could not be explained by differences in pain threshold (unaltered) or in baseline anxiety, which was elevated in adolescent females only and unaltered in adolescent males and adult males and females. This research provides further evidence for the involvement of the immune system during development in the shaping of fear and anxiety related behaviors. Copyright © 2016 Elsevier Inc. All rights reserved.
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Fluoride Exposure in Early Life as the Possible Root Cause of Disease In Later Life.
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.
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association between early life malnutrition and the size of lumbar ...
African Journals Online (AJOL)
Objective: To determine the relationship between early life malnutrition and the development of lumbar ... incriminate such predictors as poverty, aridity and human development which can be reduced ..... relationship with early childhood caries.
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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.
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Prevention of overweight and obesity in early life.
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.
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Social anxiety and negative early life events in university students.
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.
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The associations between early life circum-stances and later life health and employment in Europe
Flores, M.; Kalwij, Adriaan
2014-01-01
We use data from the Survey of Health, Aging, and Retirement in Europe to estimate for thirteen European countries the associations of early life circumstances—measured by childhood health and socioeconomic status (SES)—with educational attainment, and later life health and employment (at ages
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Early life stress as an influence on limbic epilepsy: an hypothesis whose time has come?
Directory of Open Access Journals (Sweden)
Amelia S Koe
2009-10-01
Full Text Available The pathogenesis of mesial temporal lobe epilepsy (MTLE, the most prevalent form of refractory focal epilepsy in adults, is thought to begin in early life, even though seizures may not commence until adolescence or adulthood. Amongst the range of early life factors implicated in MTLE causation (febrile seizures, traumatic brain injury, etc., stress may be one important contributor. Early life stress is an a priori agent deserving study because of the large amount of neuroscientific data showing enduring effects on structure and function in hippocampus and amygdala, the key structures involved in MTLE. An emerging body of evidence directly tests hypotheses concerning early life stress and limbic epilepsy: early life stressors, such as maternal separation, have been shown to aggravate epileptogenesis in both status epilepticus and kindling models of limbic epilepsy. In addition to elucidating its influence on limbic epileptogenesis itself, the study of early life stress has the potential to shed light on the psychiatric disorder that accompanies MTLE. For many years, psychiatric comorbidity was viewed as an effect of epilepsy, mediated psychologically and/or neurobiologically. An alternative – or complementary – perspective is that of shared causation. Early life stress, implicated in the pathogenesis of several psychiatric disorders, may be one such causal factor. This paper aims to critically review the body of experimental evidence linking early life stress and epilepsy; to discuss the direct studies examining early life stress effects in current models of limbic seizures/epilepsy; and to suggest priorities for future research.
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Age- and sex-dependent effects of early life stress on hippocampal neurogenesis
Loi, M.; Koricka, S.; Lucassen, P.J.; Joëls, M.
2014-01-01
Early life stress is a well-documented risk factor for the development of psychopathology in genetically predisposed individuals. As it is hard to study how early life stress impacts human brain structure and function, various animal models have been developed to address this issue. The models
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International Nuclear Information System (INIS)
Pradhan, Prabhakar; Damania, Dhwanil; Turzhitsky, Vladimir; Subramanian, Hariharan; Backman, Vadim; Joshi, Hrushikesh M; Dravid, Vinayak P; Roy, Hemant K; Taflove, Allen
2011-01-01
Most cancers are curable if they are diagnosed and treated at an early stage. Recent studies suggest that nanoarchitectural changes occur within cells during early carcinogenesis and that such changes precede microscopically evident tissue alterations. It follows that the ability to comprehensively interrogate cell nanoarchitecture (e.g., macromolecular complexes, DNA, RNA, proteins and lipid membranes) could be critical to the diagnosis of early carcinogenesis. We present a study of the nanoscale mass-density fluctuations of biological tissues by quantifying their degree of disorder at the nanoscale. Transmission electron microscopy images of human tissues are used to construct corresponding effective disordered optical lattices. The properties of nanoscale disorder are then studied by statistical analysis of the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices at the nanoscale. Our results show an increase in the disorder of human colonic epithelial cells in subjects harboring early stages of colon neoplasia. Furthermore, our findings strongly suggest that increased nanoscale disorder correlates with the degree of tumorigenicity. Therefore, the IPR technique provides a practicable tool for the detection of nanoarchitectural alterations in the earliest stages of carcinogenesis. Potential applications of the technique for early cancer screening and detection are also discussed
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Promoting Career Development and Life Design in the Early Years of a Person's Life
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…
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Paternal effects on early life history traits in Northwest Atlantic cod, Gadus morhua
DEFF Research Database (Denmark)
Kroll, M.-M.; Peck, M.A.; Butts, Ian A.E.
2013-01-01
It is important to understand parental effects on early life history of fish as manifested, for example, in individual fitness of offspring. Immediately after fertilization, parental contributions (both genetic and non-genetic) to embryos will affect larval ontogeny, physiology, morphology...... and survival. In marine fish, rates of natural mortality are highest during early life and are negatively correlated with rates of growth and body size. In these early life stages (eggs, larvae, young juveniles) subtle differences in mortality can cause large differences in recruitment and year-class success...... and can serve as important sources of variation during early life stages in fishes. Overall, these findings have implications for furthering the understanding of recruitment variability and can be used to optimize reproductive output for the aquaculture industry. In addition, the data suggests...
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EARLY LIFE RISKS, ANTISOCIAL TENDENCIES, AND PRETEEN DELINQUENCY*
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
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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.
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Specific synbiotics in early life protect against diet-induced obesity in adult mice
DEFF Research Database (Denmark)
Mischke, Mona; Arora, Tulika; Tims, Sebastian
2018-01-01
AIMS: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health long-lastingly. Here, we determined how beneficial microbiome interventions in early life a...... as preventive measure to ameliorate obesity risk and improve metabolic health throughout life....
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Alteration of gene expression by alcohol exposure at early neurulation.
Zhou, Feng C; Zhao, Qianqian; Liu, Yunlong; Goodlett, Charles R; Liang, Tiebing; McClintick, Jeanette N; Edenberg, Howard J; Li, Lang
2011-02-21
We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube
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Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.
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.
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Collado, V; Pichot, H; Delfosse, C; Eschevins, C; Nicolas, E; Hennequin, M
2017-05-01
Early Childhood Caries (ECC) has become a major public health concern worldwide, mostly affecting children from disadvantaged families in increasingly severe forms. This condition has been frequently reported to alter children's nutrition, growth and general development. It negatively impacts their quality of life, through painful episodes and severe eating difficulties. While this period is crucial for oral praxes development, the impact of dental state on oro-facial functions is poorly documented. This study evaluated the impact of ECC and its treatment under general anesthesia on oro-facial functions and quality of life in pre-school children. The dysfunction and quality of life scores from 25 children with ECC were evaluated before treatment (T0), one month (T1) and three months after treatment (T2), using the Nordic Orofacial Test-Screening (NOT-S) and the Early Childhood Oral Health Impact Scale (ECOHIS), respectively, in comparison with 16 caries-free children. The number and extent of inter-arch dental contacts were also observed. The pre-operative higher NOT-S score observed in children with ECC decreased to reach the control level at T2. The mastication item was the most affected in the ECC group throughout the study. Their mean ECOHIS score also significantly decreased post-operatively and differences remaining between both groups were no longer clinically relevant. In addition, in children with ECC, values of functional inter-arch surfaces tended to increase over the follow-up period. Oro-facial functions and quality of life, altered by ECC, could be restored through a conservative treatment approach. Relations between dental state, orofacial functions and particularly chewing, and nutrition should be investigated further.
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VanTieghem, Michelle R; Tottenham, Nim
2017-04-25
Early adverse experiences are associated with heighted vulnerability for stress-related psychopathology across the lifespan. While extensive work has investigated the effects of early adversity on neurobiology in adulthood, developmental approaches can provide further insight on the neurobiological mechanisms that link early experiences and long-term mental health outcomes. In the current review, we discuss the role of emotion regulation circuitry implicated in stress-related psychopathology from a developmental and transdiagnostic perspective. We highlight converging evidence suggesting that multiple forms of early adverse experiences impact the functional development of amygdala-prefrontal circuitry. Next, we discuss how adversity-induced alterations in amygdala-prefrontal development are associated with symptoms of emotion dysregulation and psychopathology. Additionally, we discuss potential mechanisms through which protective factors may buffer the effects of early adversity on amygdala-prefrontal development to confer more adaptive long-term outcomes. Finally, we consider limitations of the existing literature and make suggestions for future longitudinal and translational research that can better elucidate the mechanisms linking early adversity, neurobiology, and emotional phenotypes. Together, these findings may provide further insight into the neuro-developmental mechanisms underlying the emergence of adversity-related emotional disorders and facilitate the development of targeted interventions that can ameliorate risk for psychopathology in youth exposed to early life stress.
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The die is cast: arsenic exposure in early life and disease susceptibility.
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.
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Directory of Open Access Journals (Sweden)
Sara Peñasco
2015-01-01
Full Text Available In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9, on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake.
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Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.
Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U; Gruber, Leonhard; Zebeli, Qendrim
2016-01-01
A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.
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Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum
Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U.; Gruber, Leonhard; Zebeli, Qendrim
2016-01-01
A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows. PMID:27383746
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Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.
Directory of Open Access Journals (Sweden)
Elke Humer
Full Text Available A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10, medium (n = 8, and high (n = 12 lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.
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Depression is an independent determinant of life satisfaction early after stroke.
Oosterveer, Daniëlla M; Mishre, Radha Rambaran; van Oort, Andrea; Bodde, Karin; Aerden, Leo A M
2017-03-06
Life satisfaction is reduced in stroke patients. However, as a rule, rehabilitation goals are not aimed at life satisfaction, but at activities and participation. In order to optimize life satisfaction in stroke patients, rehabilitation should take into account the determinants of life satisfaction. The aim of this study was therefore to determine what factors are independent determinants of life satisfaction in a large group of patients early after stroke. Stroke-surviving patients were examined by a specialized nurse 6 weeks after discharge from hospital or rehabilitation setting. A standardized history and several screening lists, including the Lisat-9, were completed. Step-wise regression was used to identify independent determinants of life satisfaction. A total of 284 stroke-surviving patients were included in the study. Of these, 117 answered all of the Lisat-9 questions. Most patients (66.5%) rated their life as a whole as "satisfying" or "very satisfying". More depressive symptoms were independently associated with lower life satisfaction (p life early after a stroke. The score on the Hospital Anxiety and Depression Scale depression items is independently associated with life satisfaction. Physicians should therefore pay close attention to the mood of these patients.
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Natural selection and sex differences in morbidity and mortality in early life.
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.
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Barium distributions in teeth reveal early-life dietary transitions in primates.
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.
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Barium distributions in teeth reveal early life dietary transitions in primates
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
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Bayesian analysis of the astrobiological implications of life's early emergence on Earth.
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.
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Early-life family structure and microbially induced cancer risk.
Directory of Open Access Journals (Sweden)
Martin J Blaser
2007-01-01
Full Text Available Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men.We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative, belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0 among those in a sibship of seven or more individuals than in a sibship of between one and three persons.These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions.
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Early-life family structure and microbially induced cancer risk.
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.
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Martin, Rocio; Makino, Hiroshi; Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan
2016-01-01
Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the
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Directory of Open Access Journals (Sweden)
Rocio Martin
Full Text Available Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to
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Early evolution without a tree of life
Directory of Open Access Journals (Sweden)
Martin William F
2011-06-01
Full Text Available Abstract Life is a chemical reaction. Three major transitions in early evolution are considered without recourse to a tree of life. The origin of prokaryotes required a steady supply of energy and electrons, probably in the form of molecular hydrogen stemming from serpentinization. Microbial genome evolution is not a treelike process because of lateral gene transfer and the endosymbiotic origins of organelles. The lack of true intermediates in the prokaryote-to-eukaryote transition has a bioenergetic cause. This article was reviewed by Dan Graur, W. Ford Doolittle, Eugene V. Koonin and Christophe Malaterre.
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Life history plasticity of a tropical seabird in response to El Niño anomalies during early life.
Directory of Open Access Journals (Sweden)
Sergio Ancona
Full Text Available Food shortage and other challenges associated with El Niño Southern Oscillation (ENSO experienced early in life may have long-term impacts on life history traits, but these potential impacts remain virtually unexplored. By monitoring 2556 blue-footed boobies from 11 cohorts, we showed that birds facing warm water ENSO conditions (and probably low food availability in the natal year were underweight at fledging, recruited earlier and bred less frequently, but showed no deficit in longevity or breeding success over the first 10 years. Life history impacts of ENSO were substantial when experienced in the prenatal year, the natal year, or the second year of life, and absent when experienced in the third year of life, implying that harsh conditions have greater effects when experienced earlier in life. Sexual differences in impacts depended on the age when warm water conditions were experienced: pre-natal and natal experience, respectively, induced early recruitment and influenced the relationship between age and laying date only in females, whereas second year experience reduced total breeding success only of males. Most surprising were positive transgenerational impacts in females: daughters of females that experienced ENSO conditions in their natal year showed improved breeding success. Developmental plasticity of boobies thus enables them to largely neutralize potential long-term impacts of harsh climatic conditions experienced early in life.
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Life history plasticity of a tropical seabird in response to El Niño anomalies during early life.
Ancona, Sergio; Drummond, Hugh
2013-01-01
Food shortage and other challenges associated with El Niño Southern Oscillation (ENSO) experienced early in life may have long-term impacts on life history traits, but these potential impacts remain virtually unexplored. By monitoring 2556 blue-footed boobies from 11 cohorts, we showed that birds facing warm water ENSO conditions (and probably low food availability) in the natal year were underweight at fledging, recruited earlier and bred less frequently, but showed no deficit in longevity or breeding success over the first 10 years. Life history impacts of ENSO were substantial when experienced in the prenatal year, the natal year, or the second year of life, and absent when experienced in the third year of life, implying that harsh conditions have greater effects when experienced earlier in life. Sexual differences in impacts depended on the age when warm water conditions were experienced: pre-natal and natal experience, respectively, induced early recruitment and influenced the relationship between age and laying date only in females, whereas second year experience reduced total breeding success only of males. Most surprising were positive transgenerational impacts in females: daughters of females that experienced ENSO conditions in their natal year showed improved breeding success. Developmental plasticity of boobies thus enables them to largely neutralize potential long-term impacts of harsh climatic conditions experienced early in life.
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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…
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DEFF Research Database (Denmark)
Laursen, Martin Frederik; Zachariassen, Gitte; Bahl, Martin Iain
Background: Early life infections and presence of older siblings or pets in the household are factors known to affect the risk of developing allergic diseases, and this effect is suggested to be mediated by interactions between microbes and the immune system. However, very limited research has been...... done on the effect of these factors on the developing gut microbiota in infants. Thus, we aimed to elucidate associations between older siblings, pets and early life infections, the microbial gut communities at 9 and 18 months of age and the prevalence of allergies in three year old children. Methods...... of respiratory allergy, eczema and presence of older siblings, pets and early life infections, previously collected through interviews with parents, were compared to the obtained data on bacterial taxonomy. Results: Early life infections were positively associated with the risk of developing respiratory allergy...
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McDonnell-Dowling, Kate; Miczek, Klaus A
2018-04-01
In order to assess the risk associated with early-life stress, there has been an increase in the amount of preclinical studies investigating early-life stress. There are many challenges associated with investigating early-life stress in animal models and ensuring that such models are appropriate and clinically relevant. The purpose of this review is to highlight the methodological considerations in the design of preclinical studies investigating the effects of early-life stress on alcohol and psychomotor-stimulant intake and behaviour. The protocols employed for exploring early-life stress were investigated and summarised. Experimental variables include animals, stress models, and endpoints employed. The findings in this paper suggest that there is little consistency among these studies and so the interpretation of these results may not be as clinically relevant as previously thought. The standardisation of these simple stress procedures means that results will be more comparable between studies and that results generated will give us a more robust understanding of what can and may be happening in the human and veterinary clinic.
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Directory of Open Access Journals (Sweden)
Roelf J. Cruz-Rizzolo
2017-12-01
Full Text Available Retrospective studies in human populations indicate that protein deprivation during pregnancy and early life (early protein malnutrition, EPM is associated with cognitive impairments, learning disabilities and may represent a risk factor for the late onset of some psychiatric disorders, fundamentally schizophrenia, a condition where the prefrontal cortex plays an important role. The purpose of this study was to analyze whether EPM affects structural aspects of the rat medial prefrontal cortex (mPFC, such as cortical volume, neuronal density and neuronal soma size, which seem altered in patients with schizophrenia. For this, a rat model of EPM (5% casein from conception to postnatal day 60 was adopted and the rat mPFC volume, total number of neurons and average neuronal volume were evaluated on postnatal day 60 (post-pubertal animals by histo- and immunohistochemical techniques using unbiased stereological analysis. EPM did not alter the number of NeuN+ neurons in the rat mPFC. However, a very significant decrease in mPFC volume and average neuronal size was observed in malnourished rats. Although the present study does not establish causal relationships between malnutrition and schizophrenia, our results may indicate a similar structural phenomenon in these two situations.
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Zhu, Hong; Luo, Xingwei; Cai, Taisheng; He, Jinbo; Lu, Yao; Wu, Siyao
2016-10-01
This study examined the relationships between life event stress, early maladaptive schemas, impulsivity and binge eating among adolescents and investigated the effects of early maladaptive schemas and impulsivity on the relationship between life event stress and binge eating. Specifically, we examined a moderated mediation model in which early maladaptive schemas mediated this relationship and impulsivity moderated the mediation effect. Life event stress, early maladaptive schemas, impulsivity and binge eating were investigated in a sample of 2172 seventh-, eighth- and tenth-grade middle and high school students (mean age = 14.55 years, standard deviation = 1.29). The results indicated that adolescents with greater life event stress, more early maladaptive schemas and higher levels of impulsivity displayed more severe binge eating. In addition, early maladaptive schemas mediated the relationship between life event stress and binge eating, while impulsivity moderated this relationship. Furthermore, impulsivity also moderated the mediation effect of early maladaptive schemas; as impulsivity levels increased, the strength of the association between life event stress and early maladaptive schemas increased. This study illustrates the importance of understanding individual differences and their effects on the relationship between life event stress and binge eating. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
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Early-life seizures alter synaptic calcium-permeable AMPA receptor function and plasticity
Lippman-Bell, Jocelyn J.; Zhou, Chengwen; Sun, Hongyu; Feske, Joel S.; Jensen, Frances E.
2016-01-01
Calcium (Ca2+)-mediated1 signaling pathways are critical to synaptic plasticity. In adults, the NMDA glutamate receptor (NMDAR) represents a major route for activity-dependent synaptic Ca2+ entry. However, during neonatal development, when synaptic plasticity is high, many AMPA glutamate receptors (AMPARs) are also permeable to Ca2+ (CP-AMPAR) due to low GluA2 subunit expression, providing an additional route for activity- and glutamate-dependent Ca2+ influx and subsequent signaling. Therefore, altered hippocampal Ca2+ signaling may represent an age-specific pathogenic mechanism. We thus aimed to assess Ca2+ responses 48 hours after hypoxia-induced neonatal seizures (HS) in postnatal day (P)10 rats, a post-seizure time point at which we previously reported LTP attenuation. We found that Ca2+ responses were higher in brain slices from post-HS rats than in controls and this increase was CP-AMPAR-dependent. To determine whether synaptic CP-AMPAR expression was also altered post-HS, we assessed the expression of GluA2 at hippocampal synapses and the expression of long-term depression (LTD), which has been linked to the presence of synaptic GluA2. Here we report a decrease 48 hours after HS in synaptic GluA2 expression at synapses and LTD in hippocampal CA1. Given the potentially critical role of AMPAR trafficking in disease progression, we aimed to establish whether post-seizure in vivo AMPAR antagonist treatment prevented the enhanced Ca2+ responses, changes in GluA2 synaptic expression, and diminished LTD. We found that NBQX treatment prevents all three of these post-seizure consequences, further supporting a critical role for AMPARs as an age-specific therapeutic target. PMID:27521497
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Stel, Jente; Legler, Juliette
2015-10-01
Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.
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Early life exposures and the risk of adult glioma.
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.
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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…
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Struggling to survive: early life challenges in relation to the backtest in pigs
Camerlink, I.; Ursinus, W.W.; Bolhuis, J.E.
2014-01-01
Intensively reared piglets may face many early life challenges and these may affect behavior. The objective of this study was to examine the relationship between piglets’ early life circumstances and their behavioral response in a backtest. Hereto, 992 piglets of 14 d of age were subjected to a
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Could the early environment of Mars have supported the development of life?
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.
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The Porto Alegre Early Life Nutrition and Health Study.
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.
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The Porto Alegre Early Life Nutrition and Health Study
Directory of Open Access Journals (Sweden)
Benjamin Wilk Chaffee
2014-12-01
Full Text Available Early childhood caries is a persistent worldwide problem. The etiologic contribution of feeding practices has been less frequently investigated in prospective studies of young children. The Porto Alegre Early Life Nutrition and Health Study has followed a birth cohort of 715 mother-child pairs, recruited from municipal health centers, originally involved in a cluster-randomized controlled trial of healthcare worker training. The birth cohort links prospectively collected socio-demographic, infant feeding, and general and oral health information. To date, oral health data, including caries status and oral health-related quality of life, have been collected for 458 children at the age of 2-3 years. Studies are underway to investigate possible determinants and consequences of oral health among these children.
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Victoria, Nicole C.; Murphy, Anne Z.
2016-01-01
Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10–18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. PMID:26210872
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Work-Life Balance, Burnout, and Satisfaction of Early Career Pediatricians.
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.
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Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence.
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.
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Early life treatment with vancomycin reduces diabetes incidence in NOD mice
DEFF Research Database (Denmark)
Hansen, Camilla Hartmann Friis; Nielsen, Dennis Sandris; Vogensen, Finn Kvist
Type 1 diabetes (T1D) results from an uncontrolled T cell mediated destruction of the insulin-producing beta-cells in the pancreas. Causal factors include a combination of genetics, early life incidents and the food we eat. The involved adaptive immune response can be down regulated by a regulato...... of the mechanisms regulating intestinal immune homeostasis toward a proinflammatory mucosal environment.......Type 1 diabetes (T1D) results from an uncontrolled T cell mediated destruction of the insulin-producing beta-cells in the pancreas. Causal factors include a combination of genetics, early life incidents and the food we eat. The involved adaptive immune response can be down regulated by a regulatory...... immune response and a fine-tuned balance between these immunological components is crucial for characteristics of the disease, such as severity, onset time and recovery. The balance between the regulatory and the adaptive immune response is heavily influenced by early life bacterial stimulation...
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Early life nutritional programming of health and disease in The Gambia.
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.
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Réus, Gislaine Z; Fernandes, Gabrielly C; de Moura, Airam B; Silva, Ritele H; Darabas, Ana Caroline; de Souza, Thays G; Abelaira, Helena M; Carneiro, Celso; Wendhausen, Diogo; Michels, Monique; Pescador, Bruna; Dal-Pizzol, Felipe; Macêdo, Danielle S; Quevedo, João
2017-12-01
This study used an animal model of depression induced by maternal care deprivation (MCD) to investigate whether depressive behaviour, neuroinflammation and oxidative stress were underlying factors in developmental programming after early life stress. At postnatal days (PND) 20, 30, 40, and 60, individual subsets of animals were evaluated in behavioural tests and then euthanized to assess cytokine levels and oxidative stress parameters in the prefrontal cortex (PFC), hippocampus and serum. The results showed that MCD did not induce behavioural changes at PND 30 and 40. However, at PND 20 and 60, the rats displayed a depressive-like behaviour in the forced swimming test, without changes in locomotor spontaneous activity. In the brain and serum, the levels of pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)) were increased, and the anti-inflammatory cytokine (interleukin-10) level was reduced throughout developmental programming (PND 20, 30, 40 and 60). Protein carbonyl levels increased in the brain at PND 30, 40 and 60. Superoxide dismutase (SOD) activity was decreased during all developmental programming phases evaluated in the brain. Catalase (CAT) activity was decreased at PND 20, 40 and 60 in the brain. Our results revealed that "critical episodes" in early life stressful events are able to induce behavioural alterations that persist into adulthood and can stimulate inflammation and oxidative damage in both central and peripheral systems, which are required for distinct patterns of resilience against psychiatric disorders later in life. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Early-life chemical exposures and risk of metabolic syndrome
Directory of Open Access Journals (Sweden)
De Long NE
2017-03-01
Full Text Available Nicole E De Long, Alison C Holloway Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada Abstract: The global prevalence of obesity has been increasing at a staggering pace, with few indications of any decline, and is now one of the major public health challenges worldwide. While obesity and metabolic syndrome (MetS have historically thought to be largely driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. There is now increasing evidence to suggest that exposure to synthetic chemicals in our environment may also play a key role in the etiology and pathophysiology of metabolic diseases. Importantly, exposures occurring in early life (in utero and early childhood may have a more profound effect on life-long risk of obesity and MetS. This narrative review explores the evidence linking early-life exposure to a suite of chemicals that are common contaminants associated with food production (pesticides; imidacloprid, chlorpyrifos, and glyphosate and processing (acrylamide, in addition to chemicals ubiquitously found in our household goods (brominated flame retardants and drinking water (heavy metals and changes in key pathways important for the development of MetS and obesity. Keywords: obesity, pesticides, polybrominated diphenyl ethers, heavy metals, acrylamide, endocrine-disrupting chemicals
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Energy Technology Data Exchange (ETDEWEB)
Tu, Tzu-Yi; Hong, Chwan-Yang [Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan (China); Sasado, Takao [Laboratory of Bioresources, National Institute for Basic Biology, Okazaki (Japan); Kashiwada, Shosaku [Research Center for Life and Environmental Sciences, Department of Life Sciences, the Toyo University, Gunma (Japan); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan (China)
2016-01-15
Highlights: • Propiconazole initiates ROS-induced oxidative stress and damage in medaka fish. • Early life exposure to propiconazole increases incidence of hepatocarcionogensis in p53{sup −/−} medaka. • Oxidative stress and CYP induction involved in p53 regulation are key events in propiconazole-induced hepatotumorigenesis. • Propiconazole-induced toxic response in medaka is compatible with that in rodents. - Abstract: Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53{sup −/−} mutant of medaka fish (Oryzias latipes) to propiconazole (2.5–250 μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53{sup −/−} mutant medaka with early life exposure to propiconazole showed increased incidence of
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International Nuclear Information System (INIS)
Tu, Tzu-Yi; Hong, Chwan-Yang; Sasado, Takao; Kashiwada, Shosaku; Chen, Pei-Jen
2016-01-01
Highlights: • Propiconazole initiates ROS-induced oxidative stress and damage in medaka fish. • Early life exposure to propiconazole increases incidence of hepatocarcionogensis in p53"−"/"− medaka. • Oxidative stress and CYP induction involved in p53 regulation are key events in propiconazole-induced hepatotumorigenesis. • Propiconazole-induced toxic response in medaka is compatible with that in rodents. - Abstract: Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53"−"/"− mutant of medaka fish (Oryzias latipes) to propiconazole (2.5–250 μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53"−"/"− mutant medaka with early life exposure to propiconazole showed increased incidence of
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Early life experience : neuroendocrine adaptations to maternal absence
Enthoven, Leo
2007-01-01
An adverse early life event is considered a risk factor for stress-related psychiatric disorders in genetically predisposed individuals, probably because of its lasting effect on susceptibility to stress. The objective of this thesis research was to examine in the mouse CD1 strain the immediate and
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Early life factors and dental caries in 5-year-old children in China.
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.
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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.
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Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice
Ramsey, Kathryn A.; Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.
2013-01-01
Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal lif...
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Latent carcinogenicity of early-life exposure to dichloroacetic acid in mice
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...
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Effects of early life trauma are dependent on genetic predisposition: a rat study
Directory of Open Access Journals (Sweden)
Russell Vivienne A
2011-05-01
Full Text Available Abstract Background Trauma experienced early in life increases the risk of developing a number of psychological and/or behavioural disorders. It is unclear, however, how genetic predisposition to a behavioural disorder, such as attention-deficit/hyperactivity disorder (ADHD, modifies the long-term effects of early life trauma. There is substantial evidence from family and twin studies for susceptibility to ADHD being inherited, implying a strong genetic component to the disorder. In the present study we used an inbred animal model of ADHD, the spontaneously hypertensive rat (SHR, to investigate the long-term consequences of early life trauma on emotional behaviour in individuals predisposed to developing ADHD-like behaviour. Methods We applied a rodent model of early life trauma, maternal separation, to SHR and Wistar-Kyoto rats (WKY, the normotensive control strain from which SHR were originally derived. The effects of maternal separation (removal of pups from dam for 3 h/day during the first 2 weeks of life on anxiety-like behaviour (elevated-plus maze and depressive-like behaviour (forced swim test were assessed in prepubescent rats (postnatal day 28 and 31. Basal levels of plasma corticosterone were measured using radioimmunoassay. Results The effect of maternal separation on SHR and WKY differed in a number of behavioural measures. Similar to its reported effect in other rat strains, maternal separation increased the anxiety-like behaviour of WKY (decreased open arm entries but not SHR. Maternal separation increased the activity of SHR in the novel environment of the elevated plus-maze, while it decreased that of WKY. Overall, SHR showed a more active response in the elevated plus-maze and forced swim test than WKY, regardless of treatment, and were also found to have higher basal plasma corticosterone compared to WKY. Maternal separation increased basal levels of plasma corticosterone in SHR females only, possibly through adaptive
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On the possibility of life on early Mars
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.
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DEFF Research Database (Denmark)
Jensen, L.F.; Hansen, Michael Møller; Pertoldi, C.
2008-01-01
to adapt. Temperature-related adaptability in traits related to phenology and early life history are expected to be particularly important in salmonid fishes. We focused on the latter and investigated whether four populations of brown trout (Salmo trutta) are locally adapted in early life-history traits...
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Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?
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
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Positive emotions in early life and longevity: findings from the nun study.
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.
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Early life manipulations of vasopressin-family peptides alter vocal learning.
Baran, Nicole M; Peck, Samantha C; Kim, Tabitha H; Goldstein, Michael H; Adkins-Regan, Elizabeth
2017-07-26
Vocal learning from social partners is crucial for the successful development of communication in a wide range of species. Social interactions organize attention and enhance motivation to learn species-typical behaviour. However, the neurobiological mechanisms connecting social motivation and vocal learning are unknown. Using zebra finches ( Taeniopygia guttata ), a ubiquitous model for vocal learning, we show that manipulations of nonapeptide hormones in the vasopressin family (arginine vasotocin, AVT) early in development can promote or disrupt both song and social motivation. Young male zebra finches, like human infants, are socially gregarious and require interactive feedback from adult tutors to learn mature vocal forms. To investigate the role of social motivational mechanisms in song learning, in two studies, we injected hatchling males with AVT or Manning compound (MC, a nonapeptide receptor antagonist) on days 2-8 post-hatching and recorded song at maturity. In both studies, MC males produced a worse match to tutor song than controls. In study 2, which experimentally controlled for tutor and genetic factors, AVT males also learned song significantly better compared with controls. Furthermore, song similarity correlated with several measures of social motivation throughout development. These findings provide the first evidence that nonapeptides are critical to the development of vocal learning. © 2017 The Author(s).
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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.
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The wild life at Chernobyl. Analysis of a prosperous but genetically altered fauna
International Nuclear Information System (INIS)
Chesser, R.; Baker, R.
1996-01-01
The ecological study of zones contaminated by Chernobyl accident reveals that the wild life abounds, because of inhabitants absence, evacuated. On the other hand, significant genetical alterations are observed, whom functional consequences, low visible, stay, at term, unknown. This kind of studies illustrates the development of a new discipline, the evolving toxicology
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Database of Physiological Parameters for Early Life Rats and Mice
U.S. Environmental Protection Agency — The Database of Physiological Parameters for Early Life Rats and Mice provides information based on scientific literature about physiological parameters. Modelers...
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The Nun study: clinically silent AD, neuronal hypertrophy, and linguistic skills in early life.
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.
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Victoria, Nicole C; Murphy, Anne Z
2016-01-01
Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10-18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. Copyright © 2015 Elsevier Inc. All rights reserved.
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Thayer, Zaneta; Barbosa-Leiker, Celestina; McDonell, Michael; Nelson, Lonnie; Buchwald, Dedra; Manson, Spero
2017-05-06
Among American Indians, prior research has found associations between early life trauma and the development of post-traumatic stress disorder (PTSD) in adulthood. Given the physiological changes associated with PTSD, early life trauma could indirectly contribute to chronic disease risk. However, the impact of early life trauma on adult physical health in this population has not been previously investigated. We evaluated associations among early life trauma, PTSD, and 13 physiological biomarkers that index cardiovascular, metabolic, neuroendocrine, anthropometric, and immune function in adulthood by conducting correlation and structural equation modeling path analyses (N = 197). Physiological systems were analyzed individually as well as in a composite measure of allostatic load. We found early life trauma was related to PTSD, which in turn was related to elevated allostatic load in adulthood. Among the various components of allostatic load, the neuroendocrine system was the only one significantly related to early life stress and subsequent PTSD development. Changes in allostatic load might reflect adaptive adjustments that maximize short-term survival by enhancing stress reactivity, but at a cost to later health. Interventions should focus on improving access to resources for children who experience early life trauma in order to avoid PTSD and other harmful sequelae. © 2016 Wiley Periodicals, Inc.
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Coping with a changing environment: The effects of early life stress
DEFF Research Database (Denmark)
Vindas, Marco A.; Madaro, Angelico; Fraser, Thomas W.K.
2016-01-01
to environmental changes is particularly evident at early life stages. We investigated the performance of salmon, previously subjected to an unpredictable chronic stress (UCS) treatment at an early age (10 month old parr), over several months and life stages. The UCS fish showed overall higher specific growth...... rates compared with unstressed controls after smoltification, a particularly challenging life stage, and after seawater transfer. Furthermore, subjecting fish to acute stress at the end of the experiment, we found that UCS groups had an overall lower hypothalamic catecholaminergic and brain stem...... serotonergic response to stress compared with control groups. In addition, serotonergic activity was negatively correlated with final growth rates,which implies that serotonin responsive individuals have growth disadvantages. Altogether, our results may imply that a subduedmonoaminergic response in stressful...
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The serotonin transporter and early life stress : Translational perspectives
Houwing, Danielle J; Buwalda, Bauke; Zee, van der Eddy; de Boer, Sietse F; Olivier, Jocelien D A
2017-01-01
The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human
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Chang, Oliver; Choi, Eun-Kyung; Kim, Im-Ryung; Nam, Seok-Jin; Lee, Jeong Eon; Lee, Se Kyung; Im, Young-Hyuck; Park, Yeon Hee; Cho, Juhee
2014-01-01
Breast cancer patients experience a variety of altered appearance--such as loss or disfigurement of breasts, discolored skin, and hair loss--which result in psychological distress that affect their quality of life. This study aims to evaluate the impact of socioeconomic status on the altered appearance distress, body image, and quality of life among Korean breast cancer patients. A cross-sectional survey was conducted at advocacy events held at 16 different hospitals in Korea. Subjects were eligible to participate if they were 18 years of age or older, had a histologically confirmed diagnosis of breast cancer, had no evidence of recurrence or metastasis, and had no psychological problems at the time of the survey. Employment status, marital status, education, and income were assessed for patient socioeconomic status. Altered appearance distress was measured using the NCI's cancer treatment side effects scale; body image and quality of life were measured by the EORTC QLC-C30 and BR23. Means and standard deviations of each outcome were compared by socioeconomic status and multivariate linear regression models for evaluating the association between socioeconomic status and altered appearance distress, body image, and quality of life. A total of 126 breast cancer patients participated in the study; the mean age of participants was 47.7 (SD=8.4). Of the total, 83.2% were married, 85.6% received more than high school education, 35.2% were employed, and 41% had more than $3000 in monthly household income. About 46% had mastectomy, and over 30% were receiving either chemotherapy or radiation therapy at the time of the survey. With fully adjusted models, the employed patients had significantly higher altered appearance distress (1.80 vs 1.48; pappearance distress, body image, and quality of life in Korean women with breast cancer. Patients who suffer from altered appearance distress or lower body image are much more likely to experience psychosocial, physical, and
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Directory of Open Access Journals (Sweden)
Árpád Csathó
2018-03-01
Full Text Available 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.
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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.
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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.
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Yu, Peng; An, Shucheng; Tai, Fadao; Wang, Jianli; Wu, Ruiyong; Wang, Bo
2013-12-01
Early life stress has a long-term negative impact on emotion, learning, memory and adult sexual behavior, and these deficits most likely impair pair bonding. Here, we investigated whether early social deprivation (ED) affects the formation of pair bonds in socially monogamous mandarin voles (Microtus mandarinus). In a partner preference test (PPT), ED-reared adult females and males did not show a preference for their partner, spent more time exploring the cage of an unfamiliar animal and directed high levels of aggression toward unfamiliar animals. In social interaction test, ED increased exploring behavior only in females, but increased movement around the partner and reduced inactivity in both males and females. Three days of cohabitation did not alter serum corticosterone levels in ED-reared males, but increased corticosterone levels in males that received bi-parental care (PC). Interestingly, serum corticosterone levels in ED- and PC-reared females declined after cohabitation. ED significantly increased basal serum corticosterone levels in males, but had no effect on females. ED significantly up-regulated the levels of dopamine and the mRNA expression of dopamine 1-type receptor (D1R) in the nucleus accumbens (NAcc) in females and males. ED suppressed dopamine 2-type receptor mRNA (D2R) expression in females, but increased this in males. After three days of cohabitation, levels of D1R mRNA and D2R mRNA expression changed in opposite directions in PC-reared voles, but in the same direction in ED-reared males, and only the expression of D2R mRNA increased in ED-reared females. Our results indicate that early social deprivation inhibits pair bonding at adulthood. This inhibition is possibly associated with sex-specific alterations in serum corticosterone, levels of dopamine and mRNA expression of two types of dopamine receptors in the NAcc. Copyright © 2013 Elsevier Ltd. All rights reserved.
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In utero and early life arsenic exposure in relation to long-term health and disease
Energy Technology Data Exchange (ETDEWEB)
Farzan, Shohreh F.; Karagas, Margaret R. [Children' s Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, NH 03755 (United States); Section of Biostatistics and Epidemiology, Department of Community and Family Medicine and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 (United States); Chen, Yu, E-mail: yu.chen@nyumc.org [Department of Population Health, New York University School of Medicine, New York, NY 10016 (United States)
2013-10-15
Background: There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications. Objectives: Our goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models. Methods: We examined the current literature and identified relevant studies through PubMed by using combinations of the search terms “arsenic”, “in utero”, “transplacental”, “prenatal” and “fetal”. Discussion: Ecological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects. Conclusions: As millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels. - Highlights: • We review in utero and early-life As exposure impacts on lifelong disease risks. • Evidence indicates that early-life As increases risks of lung disease, cancer and CVD. • Animal work largely parallels human studies and may lead to new research directions. • Prospective studies and individual exposure assessments with biomarkers are needed. • Assessing intermediary
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In utero and early life arsenic exposure in relation to long-term health and disease
International Nuclear Information System (INIS)
Farzan, Shohreh F.; Karagas, Margaret R.; Chen, Yu
2013-01-01
Background: There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications. Objectives: Our goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models. Methods: We examined the current literature and identified relevant studies through PubMed by using combinations of the search terms “arsenic”, “in utero”, “transplacental”, “prenatal” and “fetal”. Discussion: Ecological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects. Conclusions: As millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels. - Highlights: • We review in utero and early-life As exposure impacts on lifelong disease risks. • Evidence indicates that early-life As increases risks of lung disease, cancer and CVD. • Animal work largely parallels human studies and may lead to new research directions. • Prospective studies and individual exposure assessments with biomarkers are needed. • Assessing intermediary endpoints may
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Blood pressure in young adulthood and residential greenness in the early-life environment of twins.
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.
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Directory of Open Access Journals (Sweden)
Ting Guo
2015-01-01
Conclusions: MAGeT-Brain is capable of segmenting hippocampi accurately in preterm neonates, even at early-in-life. Hippocampal asymmetry with a larger right side is demonstrated on early-in-life images, suggesting that this phenomenon has its onset in the 3rd trimester of gestation. Hippocampal volume assessed at the time of early-in-life and term-equivalent age is linearly associated with GA at birth, whereby smaller volumes are associated with earlier birth.
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[Quality of life in visual impaired children treated for Early Visual Stimulation].
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.
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Early Archaean collapse basins, a habitat for early bacterial life.
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
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Does early-life family income influence later dental pain experience? A prospective 14-year study.
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.
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Early-life Socio-economic Status and Adult Health: The Role of Positive Affect.
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.
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Nutrition in early life and the programming of adult disease: the first 1000 days
Moreno Villares, José Manuel
2016-07-12
Development during fetal life and infancy is characterized by rapid growth as well as the maturation of organs and systems. Changes, both in quality and quality, in nutrients during these periods may permanently infl uence the way these organs mature and function. These effects are termed as “programming” and play an important role in the presence of non-transmissible diseases through the lifespan. Specially cardiovascular disease, metabolic disorders and carbohydrate intolerance. Nutritional deficits during pregnancy, leading to intrauterine growth restriction, are associated to a higher risk of type 2 diabetes, and coronary disease among the offspring. This infl uence does not stop with the delivery but early nutrition in infancy, type of lactation, and the way and time solid foods are introduced, does play a role in this programming. Nutritional and non-nutritional factors alter the expression of some genes, resulting in effective remodeling of tissue structure and functionality. These epigenetic modifications can be transmitted to further generations, adding evidence that hereditable epigenetic modifications play a critical role in nutritional programming. But, at the same time, it opens a window of opportunity to decrease the burden of non-transmissible disease by a clever advise on nutrition during pregnancy and across the first 2 years of life (the so-called 1000 days strategy).
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Árpád Csathó; Béla Birkás
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 af...
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Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.
Arrigo, Alessandro; Rania, Laura; Calamuneri, Alessandro; Postorino, Elisa Imelde; Mormina, Enricomaria; Gaeta, Michele; Marino, Silvia; Di Lorenzo, Giuseppe; Quartarone, Angelo; Anastasi, Giuseppe; Puzzolo, Domenico; Aragona, Pasquale
2018-04-01
To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD). A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls. Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106). Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.
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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 (agelife (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.
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Imprinting: When Early Life Memories Make Food Smell Bad.
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.
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Nash, Michael J; Frank, Daniel N; Friedman, Jacob E
2017-01-01
The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the "Restaurant" hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate's gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.
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Gazea, Mary; Patchev, Alexandre V; Anderzhanova, Elmira; Leidmaa, Este; Pissioti, Anna; Flachskamm, Cornelia; Almeida, Osborne F X; Kimura, Mayumi
2018-01-10
Early-life obesity predisposes to obesity in adulthood, a condition with broad medical implications including sleep disorders, which can exacerbate metabolic disturbances and disrupt cognitive and affective behaviors. In this study, we examined the long-term impact of transient peripubertal diet-induced obesity (ppDIO, induced between 4 and 10 weeks of age) on sleep-wake behavior in male mice. EEG and EMG recordings revealed that ppDIO increases sleep during the active phase but reduces resting-phase sleep quality. This impaired sleep phenotype persisted for up to 1 year, although animals were returned to a non-obesiogenic diet from postnatal week 11 onwards. To better understand the mechanisms responsible for the ppDIO-induced alterations in sleep, we focused on the lateral hypothalamus (LH). Mice exposed to ppDIO did not show altered mRNA expression levels of orexin and melanin-concentrating hormone, two peptides that are important for sleep-wake behavior and food intake. Conversely, the LH of ppDIO-exposed mice had reduced contents of serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter involved in both sleep-wake and satiety regulation. Interestingly, an acute peripheral injection of the satiety-signaling peptide YY 3-36 increased 5-HT turnover in the LH and ameliorated the ppDIO-induced sleep disturbances, suggesting the therapeutic potential of this peptide. These findings provide new insights into how sleep-wake behavior is programmed during early life and how peripheral and central signals are integrated to coordinate sleep. SIGNIFICANCE STATEMENT Adult physiology and behavior are strongly influenced by dynamic reorganization of the brain during puberty. The present work shows that obesity during puberty leads to persistently dysregulated patterns of sleep and wakefulness by blunting serotonergic signaling in the lateral hypothalamus. It also shows that pharmacological mimicry of satiety with peptide YY 3-36 can reverse this neurochemical imbalance and
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Babies of the War: Effect of War Exposure Early in Life on Mortality Throughout Life
Lindeboom, M.; van Ewijk, R.J.G.
2015-01-01
There is increasing evidence that circumstances very early in our lives, and particularly during pregnancy, can affect our health for the remainder of life. Studies that have looked at this relationship have often used extreme situations, such as famines that occurred during wartime. Here we
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Early Adolescent Affect Predicts Later Life Outcomes.
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.
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Early-life home environment and risk of asthma among inner-city children.
O'Connor, George T; Lynch, Susan V; Bloomberg, Gordon R; Kattan, Meyer; Wood, Robert A; Gergen, Peter J; Jaffee, Katy F; Calatroni, Agustin; Bacharier, Leonard B; Beigelman, Avrahman; Sandel, Megan T; Johnson, Christine C; Faruqi, Ali; Santee, Clark; Fujimura, Kei E; Fadrosh, Douglas; Boushey, Homer; Visness, Cynthia M; Gern, James E
2018-04-01
Environmental exposures in early life appear to play an important role in the pathogenesis of childhood asthma, but the potentially modifiable exposures that lead to asthma remain uncertain. We sought to identify early-life environmental risk factors for childhood asthma in a birth cohort of high-risk inner-city children. We examined the relationship of prenatal and early-life environmental factors to the occurrence of asthma at 7 years of age among 442 children. Higher house dust concentrations of cockroach, mouse, and cat allergens in the first 3 years of life were associated with lower risk of asthma (for cockroach allergen: odds ratio per interquartile range increase in concentration, 0.55; 95% CI, 0.36-0.86; P < .01). House dust microbiome analysis using 16S ribosomal RNA sequencing identified 202 and 171 bacterial taxa that were significantly (false discovery rate < 0.05) more or less abundant, respectively, in the homes of children with asthma. A majority of these bacteria were significantly correlated with 1 of more allergen concentrations. Other factors associated significantly positively with asthma included umbilical cord plasma cotinine concentration (odds ratio per geometric SD increase in concentration, 1.76; 95% CI, 1.00-3.09; P = .048) and maternal stress and depression scores. Among high-risk inner-city children, higher indoor levels of pet or pest allergens in infancy were associated with lower risk of asthma. The abundance of a number of bacterial taxa in house dust was associated with increased or decreased asthma risk. Prenatal tobacco smoke exposure and higher maternal stress and depression scores in early life were associated with increased asthma risk. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.
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Fertility and early-life mortality: Evidence from smallpox vaccination in Sweden
DEFF Research Database (Denmark)
Ager, Philipp; Hansen, Casper Worm; Jensen, Peter Sandholt
2018-01-01
The smallpox vaccination method was the paramount medical innovation of the late 18th and early 19th centuries. We exploit the introduction of the smallpox vaccine in Sweden to identify the causal effect of early-life mortality on fertility. Our analysis shows that parishes in counties with highe...... a small insignificant effect on the number of surviving children and natural population growth....
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Long-Term Effects of Early-Life Otitis Media on Language Development
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;…
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The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice
DEFF Research Database (Denmark)
Rune, Ida; Ellekilde, Merete; Hansen, Camilla Hartmann Friis
Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily in the early life that altering of the gut microbiota will have an impact on glucose intoleance.....
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Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons.
McGill-Vargas, Lisa; Gastaldelli, Amalia; Liang, Hanyu; Anzueto Guerra, Diana; Johnson-Pais, Teresa; Seidner, Steven; McCurnin, Donald; Muscogiuri, Giovanna; DeFronzo, Ralph; Musi, Nicolas; Blanco, Cynthia
2017-05-01
Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor-β, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity. Copyright © 2017 Endocrine Society.
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All that's mine I carry with me. Early life disease and adult health in Sweden during 250 years
Lindström, Martin
2015-01-01
The aim of this thesis is to study early life risk exposures in relation to adult health and mortality in Sweden during 250 years. A number of causal mechanisms by which exposure to diseases and stressful economic and social conditions early in life may lead to increased morbidity and mortality later in life are discussed (paper I). The early life exposures investigated are the foetal origins (nutrition) and the inflammation hypotheses. Longitudinal demographic and socioeconomic data for indi...
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Nash, Michael J.; Frank, Daniel N.; Friedman, Jacob E.
2017-01-01
The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research. PMID:29326657
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Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function.
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.
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Intervention strategies for cesarean section–induced alterations in the microbiota-gut-brain axis
Moya-Pérez, Angela; Luczynski, Pauline; Renes, Ingrid B.; Wang, Shugui; Borre, Yuliya; Anthony Ryan, C.; Knol, Jan; Stanton, Catherine; Dinan, Timothy G.
2017-01-01
Microbial colonization of the gastrointestinal tract is an essential process that modulates host physiology and immunity. Recently, researchers have begun to understand how and when these microorganisms colonize the gut and the early-life factors that impact their natural ecological establishment. The vertical transmission of maternal microbes to the offspring is a critical factor for host immune and metabolic development. Increasing evidence also points to a role in the wiring of the gut-brain axis. This process may be altered by various factors such as mode of delivery, gestational age at birth, the use of antibiotics in early life, infant feeding, and hygiene practices. In fact, these early exposures that impact the intestinal microbiota have been associated with the development of diseases such as obesity, type 1 diabetes, asthma, allergies, and even neurodevelopmental disorders. The present review summarizes the impact of cesarean birth on the gut microbiome and the health status of the developing infant and discusses possible preventative and restorative strategies to compensate for early-life microbial perturbations. PMID:28379454
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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.
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Gavin, Amelia R; Hill, Karl G; Hawkins, J David; Maas, Carl
2011-08-01
This study examined three research questions: (1) Is there an association between maternal early-life economic disadvantage and the birth weight of later-born offspring? (2) Is there an association between maternal abuse in childhood and the birth weight of later-born offspring? (3) To what extent are these early-life risks mediated through adolescent and adult substance use, mental and physical health status, and adult socioeconomic status (SES)? Analyses used structural equation modeling to examine data from two longitudinal studies, which included three generations. The first generation (G1) and the second generation (G2) were enrolled in the Seattle Social Development Project (SSDP), and the third generation (G3) was enrolled in the SSDP Intergenerational Project. Data for the study (N = 136) focused on (G2) mothers enrolled in the SSDP and their children (G3). Analyses revealed that G2 low childhood SES predicted G3 offspring birth weight. Early childhood abuse among G2 respondents predicted G3 offspring birth weight through a mediated pathway including G2 adolescent substance use and G2 prenatal substance use. Birth weight was unrelated to maternal adult SES, depression, or obesity. To our knowledge, this is the first study to identify the effect of maternal early-life risks of low childhood SES and child maltreatment on later-born offspring birth weight. These findings have far-reaching effects on the cumulative risk associated with early-life economic disadvantage and childhood maltreatment. Such findings encourage policies and interventions that enhance child health at birth by taking the mother's own early-life and development into account. Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
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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.
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The role of marriage in the causal pathway from economic conditions early in life to mortality
van den Berg, G.J.; Gupta, S.
2015-01-01
This paper analyzes the interplay between early-life conditions and marital status, as determinants of adult mortality. We use individual data from Dutch registers (years 1815-2000), combined with business cycle conditions in childhood as indicators of early-life conditions. The empirical analysis
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Hyper-excitability and epilepsy generated by chronic early-life stress
Directory of Open Access Journals (Sweden)
Céline M. Dubé
2015-01-01
In conclusion, CES of limited duration has long-lasting effects on brain excitability and may promote age-specific seizures and epilepsy. Whereas the mechanisms involved require further study, these findings provide important insights into environmental contributions to early-life seizures.
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The effects of early life adversity on the immune system.
Elwenspoek, Martha M C; Kuehn, Annette; Muller, Claude P; Turner, Jonathan D
2017-08-01
Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences. We describe the current understanding of the 'ELA immune phenotype', characterized by inflammation, impairment of the cellular immune system, and immunosenescence. However, at present, data addressing specific immune functions are limited and there is a need for high-quality, well powered, longitudinal studies to unravel cause from effect. Besides the immune system, also the stress system and health behaviors are altered in ELA. We discuss probable underlying mechanisms based on epigenetic programming that could explain the ELA immune phenotype and whether this is a direct effect of immune programming or an indirect consequence of changes in behavior or stress reactivity. Understanding the underlying mechanisms will help define effective strategies to prevent or counteract negative ELA-associated outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.
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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
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Kubo, Kin-Ya; Murabayashi, Chika; Kotachi, Mika; Suzuki, Ayumi; Mori, Daisuke; Sato, Yuichi; Onozuka, Minoru; Azuma, Kagaku; Iinuma, Mitsuo
2017-02-01
Tooth loss induced neurological alterations through activation of a stress hormone, corticosterone. Age-related hippocampal morphological and functional changes were accelerated by early tooth loss in senescence-accelerated mouse prone 8 (SAMP8). In order to explore the mechanism underlying the impaired hippocampal function resulting from early masticatory dysfunction due to tooth loss, we investigated the effects of early tooth loss on plasma corticosterone levels, learning ability, neurogenesis, and synaptophysin expression in the hippocampus later in life of SAMP8 mice. We examined the effects of tooth loss soon after tooth eruption (1 month of age) on plasma corticosterone levels, learning ability in the Morris water maze, newborn cell proliferation, survival and differentiation in the hippocampal dentate gyrus, and synaptophysin expression in the hippocampus of aged (8 months of age) SAMP8 mice. Aged mice with early tooth loss exhibited increased plasma corticosterone levels, hippocampus-dependent learning deficits in the Morris water maze, decreased cell proliferation, and cell survival in the dentate gyrus, and suppressed synaptophysin expression in the hippocampus. Newborn cell differentiation in the hippocampal dentate gyrus, however, was not affected by early tooth loss. These findings suggest that learning deficits in aged SAMP8 mice with tooth loss soon after tooth eruption are associated with suppressed neurogenesis and decreased synaptophysin expression resulting from increased plasma corticosterone levels, and that long-term tooth loss leads to impaired cognitive function in older age. Copyright © 2016. Published by Elsevier Ltd.
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Early Life Experience and Gut Microbiome: The Brain-Gut-Microbiota Signaling System.
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.
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Selective alterations of neurons and circuits related to early memory loss in Alzheimer's disease
Directory of Open Access Journals (Sweden)
María eLlorens-Martín
2014-05-01
Full Text Available A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer’s disease (AD. The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC. Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII→dentate gyrus→CA3→CA1 and monosynaptic (ECIII→CA1 circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits.
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Resistance to early-life stress in mice: effects of genetic background and stress duration
Directory of Open Access Journals (Sweden)
Helene M. Savignac
2011-04-01
Full Text Available Early-life stress can induce marked behavioural and physiological impairments in adulthood including cognitive deficits, depression, anxiety and gastrointestinal dysfunction. Although robust rat models of early-life stress exist there are few established effective paradigms in the mouse. Genetic background and protocol parameters used are two critical variables in such model development.Thus we investigated the impact of two different early-life stress protocols in two commonly used inbred mouse strains. C57BL/6 and innately anxious BALB/c male mice were maternally deprived 3 hrs daily, either from postnatal day 1 to 14 (Protocol 1 or 6 to 10 (Protocol 2. Animals were assessed in adulthood for cognitive performance (spontaneous alternation behaviour test, anxiety (open field, light/dark box and elevated plus maze tests and depression-related behaviours (forced swim test in addition to stress-sensitive physiological changes. Overall, the results showed that early-life stressed mice from both strains displayed good cognitive ability and no elevations in anxiety. However, paradoxical changes occurred in C57BL/6 mice as the longer protocol (protocol 1 decreased anxiety in the light-dark box and increased exploration in the elevated plus maze. In BALB/c mice there were also limited effects of maternal separation with both separation protocols inducing reductions in stress-induced defecation and protocol 1 reducing the colon length. These data suggest that, independent of stress duration, mice from both strains were on the whole resilient to the maladaptive effects of early-life stress. Thus maternal-separation models of brain-gut axis dysfunction should rely on either different stressor protocols or other strains of mice.
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Early Stages of the Evolution of Life: a Cybernetic Approach
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.
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Temperature influences selective mortality during the early life stages of a coral reef fish.
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Tauna L Rankin
2011-05-01
Full Text Available For organisms with complex life cycles, processes occurring at the interface between life stages can disproportionately impact survival and population dynamics. Temperature is an important factor influencing growth in poikilotherms, and growth-related processes are frequently correlated with survival. We examined the influence of water temperature on growth-related early life history traits (ELHTs and differential mortality during the transition from larval to early juvenile stage in sixteen monthly cohorts of bicolor damselfish Stegastes partitus, sampled on reefs of the upper Florida Keys, USA over 6 years. Otolith analysis of settlers and juveniles coupled with environmental data revealed that mean near-reef water temperature explained a significant proportion of variation in pelagic larval duration (PLD, early larval growth, size-at-settlement, and growth during early juvenile life. Among all cohorts, surviving juveniles were consistently larger at settlement, but grew more slowly during the first 6 d post-settlement. For the other ELHTs, selective mortality varied seasonally: during winter and spring months, survivors exhibited faster larval growth and shorter PLDs, whereas during warmer summer months, selection on PLD reversed and selection on larval growth became non-linear. Our results demonstrate that temperature not only shapes growth-related traits, but can also influence the direction and intensity of selective mortality.
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Subcortical functional reorganization due to early blindness.
Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly
2015-04-01
Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. Copyright © 2015 the American Physiological Society.
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Early Life Adversity as a Predictor of Sense of Purpose during Adulthood
Hill, Patrick L.; Turiano, Nicholas A.; Burrow, Anthony L.
2018-01-01
Feeling a sense of purpose in life appears to hold consistent benefits for positive aging and well-being. As such, it is important to consider the potential factors that promote or hinder the development of purposefulness over the lifespan. For instance, it remains unclear whether early life experiences, particularly adverse ones, may hold lasting…
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Searching for Life on Early Mars: Lessons from the Pilbara
Clarke, J. D. A.; Stoker, C. R.
2016-01-01
Stromatolites in the Pilbara region of Western Australia constitute the earliest outcrop-scale evidence of life on Earth (Figure 1). The stromatolites in the 3.4 Ga Strelley Pool Formation (SPF) provide an important analog for searching for fossil evidence of early life on Mars, as Noachian aged sediments on Mars were formed under similar environmental conditions. Stromatolites represent possibly the best evidence that could be collected by a rover because they form recognizable macroscopic structures and are often associated with chemical and microscopic evidence.
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Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats.
Sofronova, Svetlana I; Gaynullina, Dina K; Shvetsova, Anastasia A; Borzykh, Anna A; Selivanova, Ekaterina K; Kostyunina, Daria S; Sharova, Anna P; Martyanov, Andrey A; Tarasova, Olga S
2017-11-01
The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α 1 -adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood. © 2017 Society for Endocrinology.
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Bullough, Robert V., Jr.
2016-01-01
In contrast to the wider education literature, rather little is known about the lives of early childhood education (ECE) teachers and the impact of those lives on their practice. Drawing on surveys completed by Head Start assistant and lead teachers, teacher lifelines, and interviews, and through the lens of life-course theory, the author portrays…
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McAdam, Margaret M.
This thesis investigates connections between low albedo asteroids and carbonaceous chondrite meteorites using spectroscopy. Meteorites and asteroids preserve information about the early solar system including accretion processes and parent body processes active on asteroids at these early times. One process of interest is aqueous alteration. This is the chemical reaction between coaccreted water and silicates producing hydrated minerals. Some carbonaceous chondrites have experienced extensive interactions with water through this process. Since these meteorites and their parent bodies formed close to the beginning of the Solar System, these asteroids and meteorites may provide clues to the distribution, abundance and timing of water in the Solar nebula at these times. Chapter 2 of this thesis investigates the relationships between extensively aqueously altered meteorites and their visible, near and mid-infrared spectral features in a coordinated spectral-mineralogical study. Aqueous alteration is a parent body process where initially accreted anhydrous minerals are converted into hydrated minerals in the presence of coaccreted water. Using samples of meteorites with known bulk properties, it is possible to directly connect changes in mineralogy caused by aqueous alteration with spectral features. Spectral features in the mid-infrared are found to change continuously with increasing amount of hydrated minerals or degree of alteration. Building on this result, the degrees of alteration of asteroids are estimated in a survey of new asteroid data obtained from SOFIA and IRTF as well as archived the Spitzer Space Telescope data. 75 observations of 73 asteroids are analyzed and presented in Chapter 4. Asteroids with hydrated minerals are found throughout the main belt indicating that significant ice must have been present in the disk at the time of carbonaceous asteroid accretion. Finally, some carbonaceous chondrite meteorites preserve amorphous iron-bearing materials
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Caron, Emilie; Ciofi, Philippe; Prevot, Vincent; Bouret, Sebastien G
2012-08-15
It is increasingly accepted that alterations of the early life environment may have lasting impacts on physiological functions. In particular, epidemiological and animal studies have indicated that changes in growth and nutrition during childhood and adolescence can impair reproductive function. However, the precise biological mechanisms that underlie these programming effects of neonatal nutrition on reproduction are still poorly understood. Here, we used a mouse model of divergent litter size to investigate the effects of early postnatal overnutrition and undernutrition on the maturation of hypothalamic circuits involved in reproductive function. Neonatally undernourished females display attenuated postnatal growth associated with delayed puberty and defective development of axonal projections from the arcuate nucleus to the preoptic region. These alterations persist into adulthood and specifically affect the organization of neural projections containing kisspeptin, a key neuropeptide involved in pubertal activation and fertility. Neonatal overfeeding also perturbs the development of neural projections from the arcuate nucleus to the preoptic region, but it does not result in alterations in kisspeptin projections. These studies indicate that alterations in the early nutritional environment cause lasting and deleterious effects on the organization of neural circuits involved in the control of reproduction, and that these changes are associated with lifelong functional perturbations.
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The first thousand days – intestinal microbiology of early life: establishing a symbiosis
Wopereis, H.; Oozeer, R.; Knipping, K.; Belzer, C.; Knol, J.
2014-01-01
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
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Helping families: childcare, early education and the work-life balance
Brewer, M.; Crawford, C.; Dearden, L.
2005-01-01
Since Labour came to power in May 1997, there have been substantial increases in spending aimed at helping families with formal childcare, early education and the work-life balance. We look at the effects of these reforms and at the proposals of the parties in this area.
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Early life trauma exposure and stress sensitivity in young children.
Grasso, Damion J; Ford, Julian D; Briggs-Gowan, Margaret J
2013-01-01
The current study replicates and extends work with adults that highlights the relationship between trauma exposure and distress in response to subsequent, nontraumatic life stressors. The sample included 213 2-4-year-old children in which 64.3% had a history of potential trauma exposure. Children were categorized into 4 groups based on trauma history and current life stress. In a multivariate analysis of variance, trauma-exposed children with current life stressors had elevated internalizing and externalizing problems compared with trauma-exposed children without current stress and nontrauma-exposed children with and without current stressors. The trauma-exposed groups with or without current stressors did not differ on posttraumatic stress disorder symptom severity. Accounting for number of traumatic events did not change these results. These findings suggest that early life trauma exposure may sensitize young children and place them at risk for internalizing or externalizing problems when exposed to subsequent, nontraumatic life stressors.
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Grégoire, Laurent; Caparos, Serge; Leblanc, Carole-Anne; Brisson, Benoit; Blanchette, Isabelle
2018-01-01
This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD) and no abuse participants. We focused particularly on an early wave (C1/P1), the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms) of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD) suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology. PMID:29379428
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Directory of Open Access Journals (Sweden)
Laurent Grégoire
2018-01-01
Full Text Available This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD and no abuse participants. We focused particularly on an early wave (C1/P1, the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology.
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Early Life Factors and Adult Leisure Time Physical Inactivity Stability and Change.
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
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Directory of Open Access Journals (Sweden)
Michael J. Nash
2017-12-01
Full Text Available The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD. This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.
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Harrison, E L; Baune, B T
2014-05-13
Childhood adversity alters the predisposition to psychiatric disorders later in life. Those with psychiatric conditions and a history of early adversity exhibit a higher incidence of treatment resistance compared with individuals with no such history. Modulation of the influence early stress exerts over neurobiology may help to prevent the development of psychiatric disorders in some cases, while attenuating the extent of treatment resistance in those with established psychiatric disorders. This review aims to critically evaluate the ability of behavioural, environmental and pharmacologic interventions to modulate neurobiological changes induced by early stress in animal models. Databases were systematically searched to locate literature relevant to this review. Early adversity was defined as stress that resulted from manipulation of the mother-infant relationship. Analysis was restricted to animal models to enable characterisation of how a given intervention altered specific neurobiological changes induced by early stress. A wide variety of changes in neurobiology due to early stress are amenable to intervention. Behavioural interventions in childhood, exercise in adolescence and administration of epigenetic-modifying drugs throughout life appear to best modulate cellar and behavioural alterations induced by childhood adversity. Other pharmacotherapies, such as endocannabinoid system modulators, anti-inflammatories and antidepressants can also influence these neurobiological and behavioural changes that result from early stress, although findings are less consistent at present and require further investigation. Further work is required to examine the influence that behavioural interventions, exercise and epigenetic-modifying drugs exert over alterations that occur following childhood stress in human studies, before possible translational into clinical practice is possible.
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Early life factors and being overweight at 4 years of age among children in Malmö, Sweden
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Lindström Martin
2010-12-01
Full Text Available Abstract Background Rising rates of obesity and overweight is an increasing public health problem all over the world. Recent research has shown the importance of early life factors in the development of child overweight. However, to the best of our knowledge there are no studies investigating the potential synergistic effect of early life factors and presence of parental overweight on the development of child overweight. Methods The study was population-based and cross-sectional. The study population consisted of children who visited the Child Health Care (CHC centers in Malmö for their 4-year health check during 2003-2008 and whose parents answered a self-administered questionnaire (n = 9009 children. Results The results showed that having overweight/obese parents was strongly associated with the child being overweight or obese. Furthermore, there was an association between unfavorable early life factors (i.e., mother smoking during pregnancy, presence of secondhand tobacco smoke early in life, high birth weight and the development of child overweight/obesity at four years of age, while breastfeeding seemed to have a protective role. For example, maternal smoking during pregnancy was associated with an odds ratio (OR of 1.47 (95% CI: 1.22, 1.76 for overweight and 2.31 (95% CI: 1.68, 3.17 for obesity. The results further showed synergistic effects between parental overweight and exposure to unfavourable early life factors in the development of child overweight. Conclusions The present study shows the importance of early life factors in the development of child overweight and obesity, and thus puts focus on the importance of early targeted interventions.
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Early Life Stress, Depression And Parkinson's Disease: A New Approach.
Dallé, Ernest; Mabandla, Musa V
2018-03-19
This review aims to shed light on the relationship that involves exposure to early life stress, depression and Parkinson's disease (PD). A systematic literature search was conducted in Pubmed, MEDLINE, EBSCOHost and Google Scholar and relevant data were submitted to a meta-analysis . Early life stress may contribute to the development of depression and patients with depression are at risk of developing PD later in life. Depression is a common non-motor symptom preceding motor symptoms in PD. Stimulation of regions contiguous to the substantia nigra as well as dopamine (DA) agonists have been shown to be able to attenuate depression. Therefore, since PD causes depletion of dopaminergic neurons in the substantia nigra, depression, rather than being just a simple mood disorder, may be part of the pathophysiological process that leads to PD. It is plausible that the mesocortical and mesolimbic dopaminergic pathways that mediate mood, emotion, and/or cognitive function may also play a key role in depression associated with PD. Here, we propose that a medication designed to address a deficiency in serotonin is more likely to influence motor symptoms of PD associated with depression. This review highlights the effects of an antidepressant, Fluvoxamine maleate, in an animal model that combines depressive-like symptoms and Parkinsonism.
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Directory of Open Access Journals (Sweden)
Yangyu Zhang
2018-05-01
Full Text Available Previous studies suggested that malnutrition during early life may play an essential role in later outcomes and disease risk in adulthood. We aimed to investigate the risks of hyperglycemia and diabetes 50 years after early-life famine exposure in a Northeastern Chinese population. We used the data from 5690 adults born between 1956 and 1965 in selected communities from a 2012 cross-sectional study. The early-childhood exposure cohort showed an increased risk of hyperglycemia compared with the unexposed cohort in the female population (odds ratio (OR 1.46; 95% confidence interval (CI 1.04, 2.06. The increased risk of diabetes in the early-childhood and fetal exposure cohorts was 37.0% (95% CI 1.05–1.79 and 50% (95% CI 1.15–1.96, respectively. For women, the risk of diabetes was more pronounced in the fetal-exposed cohort (OR 1.82; 95% CI 1.26–2.63 than in the early-childhood cohort (OR 1.57; 95% CI 1.08–2.26. Early-life exposure to famine increased the risk of diabetes. Furthermore, early-childhood exposure to famine might increase the risk of hyperglycemia in women. A policy for preventing early life malnutrition should be drafted by the government to prevent hyperglycemia and diabetes in adulthood.
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Early-life inflammation, immune response and ageing.
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).
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Early Life Factors and Type 2 Diabetes Mellitus
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Xinli Jiang
2013-01-01
Full Text Available Type 2 diabetes mellitus (T2DM is a multifactorial disease, and its aetiology involves a complex interplay between genetic, epigenetic, and environmental factors. In recent years, evidences from both human and animal experiments have correlated early life factors with programming diabetes risk in adult life. Fetal and neonatal period is crucial for organ development. Many maternal factors during pregnancy may increase the risk of diabetes of offsprings in later life, which include malnutrition, healthy (hyperglycemia and obesity, behavior (smoking, drinking, and junk food diet, hormone administration, and even stress. In neonates, catch-up growth, lactation, glucocorticoids administration, and stress have all been found to increase the risk of insulin resistance or T2DM. Unfavorable environments (socioeconomic situation and famine or obesity also has long-term negative effects on children by causing increased susceptibility to T2DM in adults. We also address the potential mechanisms that may underlie the developmental programming of T2DM. Therefore, it might be possible to prevent or delay the risk for T2DM by improving pre- and/or postnatal factors.
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Daskalakis, Nikolaos P; Bagot, Rosemary C; Parker, Karen J; Vinkers, Christiaan H; de Kloet, E R
2013-09-01
Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual's predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
Xiaoqing Shao
2017-07-01
Full Text Available A number of studies have previously assessed the impact of antibiotic exposure in early life on the risk of childhood obesity, but no systematic assessment is currently available. A systematic review and meta-analysis was performed to comprehensively and quantitatively elucidate the risk of childhood obesity caused by antibiotic exposure in early life. Literature search was performed in PubMed, Embase, and Web of Science. Random-effect meta-analysis was used to pool the statistical estimates. Fifteen cohort studies involving 445,880 participants were finally included, and all those studies were performed in developed countries. Antibiotic exposure in early life significantly increased risk of childhood overweight [relative risk (RR = 1.23, 95% confidence interval (CI 1.13–1.35, P < 0.001] and childhood obesity (RR = 1.21, 95% CI 1.13–1.30, P < 0.001. Antibiotic exposure in early life also significantly increased the z-score of childhood body mass index (mean difference: 0.07, 95% CI 0.05–0.09, P < 0.00001. Importantly, there was an obvious dose–response relationship between antibiotic exposure in early life and childhood adiposity, with a 7% increment in the risk of overweight (RR = 1.07, 95% CI 1.01–1.15, P = 0.03 and a 6% increment in the risk of obesity (RR = 1.06, 95% CI 1.02–1.09, P < 0.001 for each additional course of antibiotic exposure. In conclusion, antibiotic exposure in early life significantly increases risk of childhood obesity. Moreover, current analyses are mainly taken from developed countries, and therefore the impact of antibiotic exposure on risk of childhood obesity in vulnerable populations or developing countries still needs to be evaluated in future studies.
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Initial Treatment for Nonsyndromic Early-Life Epilepsy: An Unexpected Consensus.
Shellhaas, Renée A; Berg, Anne T; Grinspan, Zachary M; Wusthoff, Courtney J; Millichap, John J; Loddenkemper, Tobias; Coryell, Jason; Saneto, Russell P; Chu, Catherine J; Joshi, Sucheta M; Sullivan, Joseph E; Knupp, Kelly G; Kossoff, Eric H; Keator, Cynthia; Wirrell, Elaine C; Mytinger, John R; Valencia, Ignacio; Massey, Shavonne; Gaillard, William D
2017-10-01
There are no evidence-based guidelines on the preferred approach to treating early-life epilepsy. We examined initial therapy selection in a contemporary US cohort of children with newly diagnosed, nonsyndromic, early-life epilepsy (onset before age three years). Seventeen pediatric epilepsy centers participated in a prospective cohort study of children with newly diagnosed epilepsy with onset under 36 months of age. Details regarding demographics, seizure types, and initial medication selections were obtained from medical records. About half of the 495 enrolled children with new-onset, nonsyndromic epilepsy were less than 12 months old at the time of diagnosis (n = 263, 53%) and about half (n = 260, 52%) had epilepsy with focal features. Of 464 who were treated with monotherapy, 95% received one of five drugs: levetiracetam (n = 291, 63%), oxcarbazepine (n = 67, 14%), phenobarbital (n = 57, 12%), topiramate (n = 16, 3.4%), and zonisamide (n = 13, 2.8%). Phenobarbital was prescribed first for 50 of 163 (31%) infants less than six months old versus seven of 300 (2.3%) of children six months or older (P epilepsy presentation (focal, generalized, mixed/uncertain). Between the first and second treatment choices, 367 (74%) of children received levetiracetam within the first year after diagnosis. Without any specific effort, the pediatric epilepsy community has developed an unexpectedly consistent approach to initial treatment selection for early-life epilepsy. This suggests that a standard practice is emerging and could be utilized as a widely acceptable basis of comparison in future drug studies. Copyright © 2017 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Rubén Díaz-Rúa
2016-11-01
Full Text Available Background: Research on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC is a promising tool to identify subjects at risk of developing diet-related diseases. Objective: We analysed PBMC expression of key energy homeostasis-related genes in a time-course analysis in order to find out early markers of metabolic alterations due to sustained intake of high-fat (HF and high-protein (HP diets. Design: We administered HF and HP diets (4 months to adult Wistar rats in isocaloric conditions to a control diet, mainly to avoid overweight associated with the intake of hyperlipidic diets and, thus, to be able to characterise markers of metabolically obese normal-weight (MONW syndrome. PBMC samples were collected at different time points of dietary treatment and expression of relevant energy homeostatic genes analysed by real-time reverse transcription-polymerase chain reaction. Serum parameters related with metabolic syndrome, as well as fat deposition in liver, were also analysed. Results: The most outstanding results were those obtained for the expression of the lipolytic gene carnitine palmitoyltransferase 1a (Cpt1a. Cpt1a expression in PBMC increased after only 1 month of exposure to both unbalanced diets, and this increased expression was maintained thereafter. Interestingly, in the case of the HF diet, Cpt1a expression was altered even in the absence of increased body weight but correlated with alterations such as higher insulin resistance, alteration of serum lipid profile and, particularly, increased fat deposition in liver, a feature characteristic of metabolic syndrome, which was even observed in animals fed with HP diet. Conclusions: We propose Cpt1a gene expression analysis in PBMC as an early biomarker of metabolic alterations associated with MONW phenotype due to the intake of isocaloric HF diets, as
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Huang, Jonathan Y; Gavin, Amelia R; Richardson, Thomas S; Rowhani-Rahbar, Ali; Siscovick, David S; Hochner, Hagit; Friedlander, Yechiel; Enquobahrie, Daniel A
2016-10-01
Recent studies suggest that epigenetic programming may mediate the relationship between early life environment, including parental socioeconomic position, and adult cardiometabolic health. However, interpreting associations between early environment and adult DNA methylation may be difficult because of time-dependent confounding by life-course exposures. Among 613 adult women (mean age = 32 years) of the Jerusalem Perinatal Study Family Follow-up (2007-2009), we investigated associations between early life socioeconomic position (paternal occupation and parental education) and mean adult DNA methylation at 5 frequently studied cardiometabolic and stress-response genes (ABCA1, INS-IGF2, LEP, HSD11B2, and NR3C1). We used multivariable linear regression and marginal structural models to estimate associations under 2 causal structures for life-course exposures and timing of methylation measurement. We also examined whether methylation was associated with adult cardiometabolic phenotype. Higher maternal education was consistently associated with higher HSD11B2 methylation (e.g., 0.5%-point higher in 9-12 years vs. ≤8 years, 95% confidence interval: 0.1, 0.8). Higher HSD11B2 methylation was also associated with lower adult weight and total and low-density lipoprotein cholesterol. We found that associations with early life socioeconomic position measures were insensitive to different causal assumption; however, exploratory analysis did not find evidence for a mediating role of methylation in socioeconomic position-cardiometabolic risk associations. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Early evaluation of renal hemodynamic alterations in type I diabetes mellitus with duplex ultrasound
Directory of Open Access Journals (Sweden)
Saif Aasem
2010-01-01
Full Text Available To evaluate the role of renal duplex ultrasonography in the detection of early alte-ration of renal blood flow in type I diabetic patients, we studied with duplex ultrasound 32 patients with type I diabetes mellitus (19 males, 13 females, age range 8-19 years and 35 age and sex-matched controls. The resistivity indices (RIs and pulsatility indices (PIs of the main renal as well as intra-renal arteries were calculated. Compared with the healthy control subjects, diabetic patients had significantly higher resistivity indices (RIs in the intrarenal (segmental, arcuate and interlobar ar-teries (P= 0.001. The study, also revealed a significantly positive correlation between the RIs in the intrarenal arteries in diabetics and the albumin/creatinine ratio (r= 0.54, 0.52 and 0.51 respectively, glycated hemoglobin (r= 0.61, 0.59 and 0.63 respectively, as well as the estimated GFR (e-GFR (r= 0.53, 0.51 and 0.57 respectively. We conclude that the current study documented early intra-renal hemodynamic alterations in the form of pathologically elevated intrarenal RIs. This denotes the potential usefulness of duplex evaluation of the intrarenal arteries, as a noninvasive procedure, for monitoring type 1 diabetic patients to predict those at risk of diabetic nephropathy.
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Kropf, Christian; Segner, Helmut; Fent, Karl
2016-01-01
Embryos of oviparous fish, in contrast to (ovo) viviparous species, develop in the aquatic environment, and therefore need solute transport systems at their body surfaces for maintaining internal homeostasis and defending against potentially harmful substances. We hypothesized that solute transporters undergo changes in tissue distribution from the embryo to the larval stage. We therefore studied the mRNA profiles of eight ABC transporters (abcb1a, abcb1b, abcc1, abcc2, abcc3, abcc4, abcc5, abcg2) and three solute carriers (oatp1d, putative oatp2 putative, mate1) in different body regions (head, yolk sac epithelium, abdominal viscera, skin/muscles) of developing rainbow trout. Additionally, we investigated mRNA levels of phase I (cyp1a, cyp3a) and phase II (gstp, putative ugt1, putative ugt2) biotransformation enzymes. The study covered the developmental period from the eleuthero-embryo stage to the first-feeding larval stage (1-20days post-hatch, dph). At 1dph, transcripts of abcc2, abcc4, abcg2, cyp3a, gstp, putative mate1, and putative oatp2 occurred primarily in the yolk sac epithelium, whereas at later stages expression of these genes was predominantly observed in the abdominal viscera. The functional activity of ABC transporters in fish early life stages was assessed by rhodamine B accumulation assays. Finally, we investigated the potential impact of xenobiotics (clotrimazole, clofibric acid) on the ABC and biotransformation systems of trout early life stages. While clofibric acid had no effect, clotrimazole lead to an increased rhodamine B accumulation. The results provide evidence that the transition from the eleuthero-embryo to the larval stage is accompanied by a major alteration in tissue expression of ABC transporters. Copyright © 2016 Elsevier Inc. All rights reserved.
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Early life influences on the development of chronic obstructive pulmonary disease.
Stocks, Janet; Sonnappa, Samatha
2013-06-01
There is increasing evidence that chronic obstructive pulmonary disease (COPD) is not simply a disease of old age that is largely restricted to heavy smokers, but may be associated with insults to the developing lung during foetal life and the first few years of postnatal life, when lung growth and development are rapid. A better understanding of the long-term effects of early life factors, such as intrauterine growth restriction, prenatal and postnatal exposure to tobacco smoke and other pollutants, preterm delivery and childhood respiratory illnesses, on the subsequent development of chronic respiratory disease is imperative if appropriate preventive and management strategies to reduce the burden of COPD are to be developed. The extent to which insults to the developing lung are associated with increased risk of COPD in later life depends on the underlying cause, timing and severity of such derangements. Suboptimal conditions in utero result in aberrations of lung development such that affected individuals are born with reduced lung function, which tends to remain diminished throughout life, thereby increasing the risk both of wheezing disorders during childhood and subsequent COPD in genetically susceptible individuals. If the current trend towards the ever-increasing incidence of COPD is to be reversed, it is essential to minimize risks to the developing lung by improvements in antenatal and neonatal care, and to reduce prenatal and postnatal exposures to environmental pollutants, including passive tobacco smoke. Furthermore, adult physicians need to recognize that lung disease is potentially associated with early life insults and provide better education regarding diet, exercise and avoidance of smoking to preserve precious reserves of lung function in susceptible adults. This review focuses on factors that adversely influence lung development in utero and during the first 5 years of life, thereby predisposing to subsequent COPD.
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Flores, M.; Kalwij, A.S.
2011-01-01
Using data from the Survey of Health, Ageing and Retirement in Europe, this paper provides empirical evidence for the Netherlands and Spain on the associations between individuals’ early life circumstances—measured by health and socioeconomic status (SES) during childhood—educational attainment, and
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Directory of Open Access Journals (Sweden)
Katherinа Zhurba
2015-04-01
Full Text Available The article presents the conceptual approaches to the upbringing in the education of life-meaningful values of teenagers and early adolescence in Ukraine. The definition of life-meaningful values has been given up. The major problems and contradictions in the upbringing of the Ukrainian children were paid attention to. The dependence of the result of upbringing, from the desire and the participation of all actors: children, parents, teachers is pointed out. Conceptual approaches to education of life values meaning are analyzed on the methodological, theoretical and practical levels. The aspects of the previous researches have been underlined. In this context, a systematic approach determines the integrity of the educational process in primary and high school. Synergetic approach combines the organization and self-organization of the growing personality. Humanistic approach recognizes each child's highest value at school, family, and society. Personal-centered approach provides individual attention to him, to free choice of that or other life-meaningful values. Activity approach provides practice and deed activity of children and shows how the value of the meaning of life affects the behavior of the individual. The theoretical level of substantiation of the concept of education of children of teenagers and early youth gives ability to define key points and concepts. Practical level implies the corresponding experimental activity, the determination of propriate pedagogical conditions, the selection of content, forms and methods of education of teenagers and early adolescence. Conceptual approaches offer the opportunity to develop a modern system of education of the values of the meaning of life of teenagers and early adolescence in Ukraine. Implementation of conceptual approaches aimed at qualitative changes in the education of life-meaningful values among of teenagers and early adolescence.
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Habitability and the Possibility of Extraterrestrial Life in the Early Telescope Era
Reynolds, Sarah
2014-01-01
Early telescopic observations of the Moon and planets prompted great interest in the already-existing debate about the possibility of life on the Moon and other worlds. New observations of the lunar surface, revealing an apparently Earth-like terrain and possibly the presence of bodies of water, were often considered in relation to their implications for the existence of lunar inhabitants. This depended upon establishing what constituted the fundamental requirements for life and the boundaries of habitability. The growing support for the heliocentric Copernican astronomy was also changing perceptions of the relationships between the Earth, the Moon, and the planets. Works such as Johannes Kepler’s Somnium and John Wilkins’ The Discovery of a World in the Moone presented views of extraterrestrial life that were shifting from the supernatural to the natural, in correspondence with the celestial bodies’ new positions in the cosmos. This paper considers how these and other works from the early telescope era reveal changes in the nature of astronomical speculation about extraterrestrial life and the conditions construed as “habitability,” and what significance that history has for us today in the new era of extrasolar planet discovery.
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Rosa, Rui; Pimentel, Marta S.; Boavida-Portugal, Joana; Teixeira, Tatiana; Trübenbach, Katja; Diniz, Mário
2012-01-01
Background The knowledge about the capacity of organisms’ early life stages to adapt to elevated temperatures is very limited but crucial to understand how marine biota will respond to global warming. Here we provide a comprehensive and integrated view of biological responses to future warming during the early ontogeny of a keystone invertebrate, the squid Loligo vulgaris. Methodology/Principal Findings Recently-spawned egg masses were collected and reared until hatching at present day and projected near future (+2°C) temperatures, to investigate the ability of early stages to undergo thermal acclimation, namely phenotypic altering of morphological, behavioural, biochemical and physiological features. Our findings showed that under the projected near-future warming, the abiotic conditions inside the eggs promoted metabolic suppression, which was followed by premature hatching. Concomitantly, the less developed newborns showed greater incidence of malformations. After hatching, the metabolic burst associated with the transition from an encapsulated embryo to a planktonic stage increased linearly with temperature. However, the greater exposure to environmental stress by the hatchlings seemed to be compensated by physiological mechanisms that reduce the negative effects on fitness. Heat shock proteins (HSP70/HSC70) and antioxidant enzymes activities constituted an integrated stress response to ocean warming in hatchlings (but not in embryos). Conclusions/Significance The stressful abiotic conditions inside eggs are expected to be aggravated under the projected near-future ocean warming, with deleterious effects on embryo survival and growth. Greater feeding challenges and the lower thermal tolerance limits of the hatchlings are strictly connected to high metabolic demands associated with the planktonic life strategy. Yet, we found some evidence that, in the future, the early stages might support higher energy demands by adjusting some cellular functional properties
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Early life adversity influences stress response association with smoking relapse.
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.
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Gut microbiota in early life and its impact on allergic diseases
Rutten, N.B.M.M.
2016-01-01
This thesis addresses the development of the intestinal microbiota in infancy, investigated by different molecular approaches (all based on rRNA gene analysis), and includes studies describing consequences of early life modulation of microbiota, by supplementation of probiotics, on composition and
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McKee, Sarah E; Grissom, Nicola M; Herdt, Christopher T; Reyes, Teresa M
2017-06-01
During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)-fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior. Given that extensive brain development occurs during early postnatal life-particularly within the prefrontal cortex (PFC), a brain region critical for executive function-we examined whether early life methyl donor supplementation ( e.g., during adolescence) could ameliorate executive function deficits observed in offspring that were exposed to maternal HFD. By using operant testing, progressive ratio, and the PFC-dependent 5-choice serial reaction timed task (5-CSRTT), we determined that F1 female offspring (B6D2F1/J) from HFD-fed dams have decreased motivation (decreased progressive ratio breakpoint) and require a longer stimulus length to complete the 5-CSRTT task successfully, whereas early life methyl donor supplementation increased motivation and shortened the minimum stimulus length required for a correct response in the 5-CSRTT. Of interest, we found that expression of 2 chemokines, CCL2 and CXCL10, correlated with the median stimulus length in the 5-CSRTT. Furthermore, we found that acute adult supplementation of methyl donors increased motivation in HFD-fed offspring and those who previously received supplementation with methyl donors. These data point to early life as a sensitive time during which dietary methyl donor supplementation can alter PFC-dependent cognitive behaviors.-McKee, S. E., Grissom, N. M., Herdt, C. T., Reyes, T. M. Methyl donor supplementation alters
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Determinants of Growth, Adiposity and Bone Mass in Early Life : The Generation R Study
D.H.M. Heppe (Denise)
2016-01-01
markdownabstractAbstract Environmental influences during fetal life and early infancy have been suggested to influence body composition throughout the life-course. Especially poor fetal nutrition and fetal growth restriction have been designated important risk factors for gaining high fat mass
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The impact of environmental gradients on the early life inshore ...
African Journals Online (AJOL)
The impact of environmental gradients on the early life inshore migration of the short-finned squid Illex illecebrosus. JAA Perez, Rk O'dor. Abstract. Recruitment of the short-finned squid Illex illecebrosus to adult feeding grounds on the shelf off eastern Canada constitutes an important transition from warm food-limited Gulf ...
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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
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Marden, Jessica R; Tchetgen Tchetgen, Eric J; Kawachi, Ichiro; Glymour, M Maria
2017-10-01
Both early life and adult socioeconomic status (SES) predict late-life level of memory; however, evidence is mixed on the relationship between SES and rate of memory decline. Further, the relative importance of different life-course periods for rate of late-life memory decline has not been evaluated. We examined associations between life-course SES and late-life memory function and decline. Health and Retirement Study participants (n = 10,781) were interviewed biennially from 1998-2012 (United States). SES measurements for childhood (composite score including parents' educational attainment), early adulthood (high-school or college completion), and older adulthood (income, mean age 66 years) were all dichotomized. Word-list memory was modeled via inverse-probability weighted longitudinal models accounting for differential attrition, survival, and time-varying confounding, with nonrespondents retained via proxy assessments. Compared to low SES at all 3 points (referent), stable, high SES predicted the best memory function and slowest decline. High-school completion had the largest estimated effect on memory (β = 0.19; 95% confidence interval: 0.15, 0.22), but high late-life income had the largest estimated benefit for slowing declines (for 10-year memory change, β = 0.35; 95% confidence interval: 0.24, 0.46). Both early and late-life interventions are potentially relevant for reducing dementia risk by improving memory function or slowing decline. © The Author(s) 2017. 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.
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Mautner, Eva
2014-01-01
The aim of this paper is to provide results of two studies, which were conducted in Austria to examine the impact of internal and external factors on quality of life and depressive symptoms in early motherhood. In general early motherhood may be a critical life event for a woman and their partner and can lead to decreased well-being. Emotional aspects such as depression affects not only the quality of life of the mothers but also her new-born child, her other children, partner and relati...
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Kummeling, Ischa; Stelma, Foekje F.; Dagnelie, Pieter C.; Snijders, Bianca E. P.; Penders, John; Huber, Machteld; van Ree, Ronald; van den Brandt, Piet A.
2007-01-01
OBJECTIVES: Antibiotic exposure in early life may be associated with atopic disease development either by interfering with bacterial commensal flora or by modifying the course of bacterial infections. We evaluated early life exposure to antibiotics and the subsequent development of eczema, wheeze,
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Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.
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.
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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
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Universal biology and the statistical mechanics of early life
Goldenfeld, Nigel; Biancalani, Tommaso; Jafarpour, Farshid
2017-11-01
All known life on the Earth exhibits at least two non-trivial common features: the canonical genetic code and biological homochirality, both of which emerged prior to the Last Universal Common Ancestor state. This article describes recent efforts to provide a narrative of this epoch using tools from statistical mechanics. During the emergence of self-replicating life far from equilibrium in a period of chemical evolution, minimal models of autocatalysis show that homochirality would have necessarily co-evolved along with the efficiency of early-life self-replicators. Dynamical system models of the evolution of the genetic code must explain its universality and its highly refined error-minimization properties. These have both been accounted for in a scenario where life arose from a collective, networked phase where there was no notion of species and perhaps even individuality itself. We show how this phase ultimately terminated during an event sometimes known as the Darwinian transition, leading to the present epoch of tree-like vertical descent of organismal lineages. These examples illustrate concrete examples of universal biology: the quest for a fundamental understanding of the basic properties of living systems, independent of precise instantiation in chemistry or other media. This article is part of the themed issue 'Reconceptualizing the origins of life'.
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Directory of Open Access Journals (Sweden)
Emily K Hayes
Full Text Available Maternal obesity results in a number of obstetrical and fetal complications with both immediate and long-term consequences. The increased prevalence of obesity has resulted in increasing numbers of women of reproductive age in this high-risk group. Since many of these obese women have been subjected to hypercaloric diets from early childhood we have developed a rodent model of life-long maternal obesity to more clearly understand the mechanisms that contribute to adverse pregnancy outcomes in obese women. Female Sprague Dawley rats were fed a control diet (CON--16% of calories from fat or high fat diet (HF--45% of calories from fat from 3 to 19 weeks of age. Prior to pregnancy HF-fed dams exhibited significant increases in body fat, serum leptin and triglycerides. A subset of dams was sacrificed at gestational day 15 to evaluate fetal and placental development. The remaining animals were allowed to deliver normally. HF-fed dams exhibited a more than 3-fold increase in fetal death and decreased neonatal survival. These outcomes were associated with altered vascular development in the placenta, as well as increased hypoxia in the labyrinth. We propose that the altered placental vasculature may result in reduced oxygenation of the fetal tissues contributing to premature demise and poor neonatal survival.
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Chalan, Paulina; Bijzet, Johan; Kroesen, Bart-Jan; Boots, Annemieke M. H.; Brouwer, Elisabeth
Objective. The role of natural killer (NK) cells in the immunopathogenesis of rheumatoid arthritis (RA) is unclear. Therefore, numerical and functional alterations of CD56(dim) and CD56(bright) NK cells in the early stages of RA development were studied. Methods. Whole blood samples from newly
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DEFF Research Database (Denmark)
Hinrichsen, H-H.; Hüssy, K.; Huwer, B.
2012-01-01
Spatio-temporal variability in western Baltic cod early life stage survival mediated by egg buoyancy, hydrography and hydrodynamics. – ICES Journal of Marine Science, 69: 1744–1752.To disentangle the effects of different drivers on recruitment variability of marine fish, a spatially and temporally...... explicit understanding of both the spawning stock size and the early life stage dynamics is required. The objectives of this study are to assess the transport of western Baltic cod early life stages as well as the variability in environmentally-mediated survival along drift routes in relation to both...
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Smarr, Benjamin L; Grant, Azure D; Perez, Luz; Zucker, Irving; Kriegsfeld, Lance J
2017-06-12
Modern life involves chronic circadian disruption through artificial light and these disruptions are associated with numerous mental and physical health maladies. Because the developing nervous system is particularly vulnerable to perturbation, we hypothesized that early-life circadian disruption would negatively impact offspring development and adult function. Pregnant mice were subjected to chronic circadian disruption from the time of uterine implantation through weaning. To dissociate in utero from postnatal effects, a subset of litters was cross-fostered at birth from disrupted dams to control dams and vice versa. Postnatal circadian disruption was associated with reduced adult body mass, social avoidance, and hyperactivity. In utero disruption resulted in more pronounced social avoidance and hyperactivity, phenotypes not abrogated by cross-fostering to control mothers. To examine whether circadian disruption affects development by acting as an early life stressor, we examined birthweight, litter size, maternal cannibalism, and epigenetic modifications. None of these variables differed between control and disrupted dams, or resembled patterns seen following early-life stress. Our findings indicate that developmental chronic circadian disruption permanently affects somatic and behavioral development in a stage-of-life-dependent manner, independent of early life stress mechanisms, underscoring the importance of temporal structure during development, both in utero and early postnatal life.
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The consequences of early life adversity: neurobiological, behavioural and epigenetic adaptations
Maccari, S.; Krugers, H.J.; Morley-Fletcher, S.; Szyf, M.; Brunton, P.J.
2014-01-01
During the perinatal period, the brain is particularly sensitive to remodelling by environmental factors. Adverse early life experiences, such as stress exposure or sub-optimal maternal care can have long-lasting detrimental consequences for an individual. This phenomenon is often referred to as
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Rheumatoid cachexia and other nutritional alterations in rheumatologic diseases.
Hurtado-Torres, Gilberto Fabián; González-Baranda, Lourdes Larisa; Abud-Mendoza, Carlos
2015-01-01
The prevalence of nutritional alterations in rheumatologic diseases ranges from 4 to 95%, depending on the detection method used. Formerly described as the single term rheumatoid cachexia, nutritional alterations can currently be grouped and subdivided based on the physiopathological mechanisms involved: chronic disease-related inflammatory conditions (cachexia), malnutrition associated to acute malnutrition inflammatory conditions (protein-caloric malnutrition) and starvation-related malnutrition. Clinical manifestations of malnutrition associated to rheumatic diseases vary from the patient with low weight or overweight and obesity; with lean body mass depletion as well as functional repercussions, and impact of quality of life as a common denominator. Additionally, the associated increase in body fat mass increases the risk for cardiovascular morbidity. A multidisciplinary approach towards rheumatic diseases should include aspects oriented towards prevention, early identification, diagnosis and correction of nutritional alterations. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
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Early-life stress is associated with gender-based vulnerability to epileptogenesis in rat pups.
Directory of Open Access Journals (Sweden)
Sébastien Desgent
Full Text Available 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
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Banan, Ashkan; Kalbassi Masjed Shahi, Mohammad Reza; Bahmani, Mahmoud; Yazdani Sadati, Mohammad Ali
2016-05-01
Silver nanoparticles (AgNPs) are widely used in consumer products mainly due to their antimicrobial action. The rapidly increasing use of nanoparticles (NPs) has driven more attention to their possible ecotoxicological effects. In this study, the acute toxicity of colloidal AgNPs was evaluated during the embryonic stage of Persian sturgeon (Acipenser persicus) and starry sturgeon (Acipenser stellatus) at concentrations of 0, 0.25, 0.5, 1, 2, 4, and 8 mg/L. Fertilized eggs (75 eggs per replicate) were exposed to aforementioned concentrations for 96 h in triplicate. 96-h LC50 values in Persian sturgeon and starry sturgeon were calculated as 0.163 and 0.158 mg/L, respectively. Furthermore, in starry sturgeon, the short-term effects of AgNPs on the hatching rate, survival rate, and Ag accumulation during early life stages (before active feeding commences) were also analyzed at concentrations of 0, 0.025, 0.05, and 0.1 mg/L of colloidal AgNPs. The highest silver accumulation occurred in larvae exposed to 0.1 mg/L AgNPs; however, the body burden of silver did not alter survival rate, and there were no significant differences among treatments. Based on the obtained results from the acute toxicity exposures, AgNPs induced a concentration-dependent toxicity in both species during early life stages, while complementary studies are suggested for investigating their short-term effects in detail.
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Wang, Bo; Liu, Zhenyu; Liu, Jiaojiao; Tang, Zhenchao; Li, Hongjun; Tian, Jie
2016-06-01
To investigate both the gray matter (GM) and whiter matter (WM) alterations in a homogeneous cohort of early HIV-infected patients by combining voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS). Twenty-six HIV and 26 control subjects enrolled in this study with 3D T1 and diffusion-tensor imaging acquired on a 3.0T Siemens scanner. Group differences in regional GM were assessed using VBM analysis, while differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and relative anisotropy (RD) of WM were evaluated using TBSS analysis. After that, interactions between GM changes and white matter alterations were investigated by using a correlation analysis. The HIV-infected patients displayed decreased GM volume, mainly located in the bilateral frontal cortices, bilateral anterior cingulate cortex, and left supplementary motor area (P 0.05). Our results indicate that structural brain alterations occurred early in HIV-infected patients. The current study may shed further light on the potential brain effects of HIV. J. Magn. Reson. Imaging 2016;43:1474-1483. © 2015 Wiley Periodicals, Inc.
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Philosophical Approaches towards Sciences of Life in Early Cybernetics
Montagnini, Leone
2008-07-01
The article focuses on the different conceptual and philosophical approaches towards the sciences of life operating in the backstage of Early Cybernetics. After a short reconstruction of the main steps characterizing the origins of Cybernetics, from 1940 until 1948, the paper examines the complementary conceptual views between Norbert Wiener and John von Neumann, as a "fuzzy thinking" versus a "logical thinking", and the marked difference between the "methodological individualism" shared by both of them versus the "methodological collectivism" of most of the numerous scientists of life and society attending the Macy Conferences on Cybernetics. The main thesis sustained here is that these different approaches, quite invisible to the participants, were different, maybe even opposite, but they could provoke clashes, as well as cooperate in a synergic way.
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LIFE: The Case for Early Commercialization of Fusion Energy
International Nuclear Information System (INIS)
Anklam, T.; Simon, A.J.; Powers, S.; Meier, W.R.
2011-01-01
This paper presents the case for early commercialization of laser inertial fusion energy (LIFE). Results taken from systems modeling of the US electrical generating enterprise quantify the benefits of fusion energy in terms of carbon emission, nuclear waste and plutonium production avoidance. Sensitivity of benefits-gained to timing of market-entry is presented. These results show the importance of achieving market entry in the 2030 time frame. Economic modeling results show that fusion energy can be competitive with other low-carbon energy sources. The paper concludes with a description of the LIFE commercialization path. It proposes constructing a demonstration facility capable of continuous fusion operations within 10 to 15 years. This facility will qualify the processes and materials needed for a commercial fusion power plant.
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Directory of Open Access Journals (Sweden)
Ho-Sun Lee
2015-11-01
Full Text Available Exposure to environmental factors in early life can influence developmental processes and long-term health in humans. Early life nutrition and maternal diet are well-known examples of conditions shown to influence the risk of developing metabolic diseases, including type 2 diabetes mellitus and cardiovascular diseases, in adulthood. It is increasingly accepted that environmental compounds, including nutrients, can produce changes in the genome activity that, in spite of not altering the DNA sequence, can produce important, stable and, in some instances, transgenerational alterations in the phenotype. Epigenetics refers to changes in gene function that cannot be explained by changes in the DNA sequence, with DNA methylation patterns/histone modifications that can make important contributions to epigenetic memory. The epigenome can be considered as an interface between the genome and the environment that is central to the generation of phenotypes and their stability throughout the life course. To better understand the role of maternal health and nutrition in the initiation and progression of diseases in childhood and adulthood, it is necessary to identify the physiological and/or pathological roles of specific nutrients on the epigenome and how dietary interventions in utero and early life could modulate disease risk through epigenomic alteration.
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Directory of Open Access Journals (Sweden)
Sam H C Noonan
Full Text Available Ocean acidification is expected to alter community composition on coral reefs, but its effects on reef community metabolism are poorly understood. Here we document how early successional benthic coral reef communities change in situ along gradients of carbon dioxide (CO2, and the consequences of these changes on rates of community photosynthesis, respiration, and light and dark calcification. Ninety standardised benthic communities were grown on PVC tiles deployed at two shallow-water volcanic CO2 seeps and two adjacent control sites in Papua New Guinea. Along the CO2 gradient, both the upward facing phototrophic and the downward facing cryptic communities changed in their composition. Under ambient CO2, both communities were dominated by calcifying algae, but with increasing CO2 they were gradually replaced by non-calcifying algae (predominantly green filamentous algae, cyanobacteria and macroalgae, which increased from ~30% to ~80% cover. Responses were weaker in the invertebrate communities, however ascidians and tube-forming polychaetes declined with increasing CO2. Differences in the carbonate chemistry explained a far greater amount of change in communities than differences between the two reefs and successional changes from five to 13 months, suggesting community successions are established early and are under strong chemical control. As pH declined from 8.0 to 7.8, rates of gross photosynthesis and dark respiration of the 13-month old reef communities (upper and cryptic surfaces combined significantly increased by 10% and 20%, respectively, in response to altered community composition. As a consequence, net production remained constant. Light and dark calcification rates both gradually declined by 20%, and low or negative daily net calcification rates were observed at an aragonite saturation state of <2.3. The study demonstrates that ocean acidification as predicted for the end of this century will strongly alter reef communities, and
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Association of early-life antibiotic use and protective effects of breastfeeding
Korpela, Katri; Salonen, Anne; Virta, Lauri J.; Kekkonen, Riina A.; Vos, de Willem M.
2016-01-01
Importance: Long duration of breastfeeding is known to reduce the frequency of infections and the risk of overweight, both of which are prevalent health problems among children, but the mechanisms are unclear. Objectives: To test whether early-life antibiotic use in children prevents the
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Early Life Experiences and Exercise Associate with Canine Anxieties.
Tiira, Katriina; Lohi, Hannes
2015-01-01
Personality and anxiety disorders across species are affected by genetic and environmental factors. Shyness-boldness personality continuum exists across species, including the domestic dog, with a large within- and across-breed variation. Domestic dogs are also diagnosed for several anxiety-related behavioral conditions, such as generalized anxiety disorders, phobias, and separation anxiety. Genetic and environmental factors contributing to personality and anxiety are largely unknown. We collected questionnaire data from a Finnish family dog population (N = 3264) in order to study the associating environmental factors for canine fearfulness, noise sensitivity, and separation anxiety. Early life experiences and exercise were found to associate with anxiety prevalence. We found that fearful dogs had less socialization experiences (p = 0.002) and lower quality of maternal care (p daily exercise; dogs with noise sensitivity and separation anxiety had less daily exercise. Our findings suggest that dogs share many of the same environmental factors that contribute to anxiety in other species as well, such as humans and rodents. Our study highlights the importance of early life experiences, especially the quality of maternal care and daily exercise for the welfare and management of the dogs, and reveals important confounding factors to be considered in the genetic characterization of canine anxiety.
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Early-life sugar consumption has long-term negative effects on memory function in male rats.
Noble, Emily E; Hsu, Ted M; Liang, Joanna; Kanoski, Scott E
2017-09-25
Added dietary sugars contribute substantially to the diet of children and adolescents in the USA, and recent evidence suggests that consuming sugar-sweetened beverages (SSBs) during early life has deleterious effects on hippocampal-dependent memory function. Here, we test whether the effects of early-life sugar consumption on hippocampal function persist into adulthood when access to sugar is restricted to the juvenile/adolescent phase of development. Male rats were given ad libitum access to an 11% weight-by-volume sugar solution (made with high fructose corn syrup-55) throughout the adolescent phase of development (post-natal day (PN) 26-56). The control group received a second bottle of water instead, and both groups received ad libitum standard laboratory chow and water access throughout the study. At PN 56 sugar solutions were removed and at PN 175 rats were subjected to behavioral testing for hippocampal-dependent episodic contextual memory in the novel object in context (NOIC) task, for anxiety-like behavior in the Zero maze, and were given an intraperitoneal glucose tolerance test. Early-life exposure to SSBs conferred long-lasting impairments in hippocampal-dependent memory function later in life- yet had no effect on body weight, anxiety-like behavior, or glucose tolerance. A second experiment demonstrated that NOIC performance was impaired at PN 175 even when SSB access was limited to 2 hours daily from PN 26-56. Our data suggest that even modest SSB consumption throughout early life may have long-term negative consequences on memory function during adulthood.
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Conceptual model for quality of life among adults with congenital or early deafness.
Kushalnagar, Poorna; McKee, Michael; Smith, Scott R; Hopper, Melinda; Kavin, Denise; Atcherson, Samuel R
2014-07-01
A conceptual model of health-related quality of life (QoL) is needed to describe key themes that impact perceived QoL in adults with congenital or early deafness. To revise University of Washington Center for Disability Policy and Research's conceptual model of health promotion and QoL, with suggestions for applying the model to improving programs or services that target deaf adults with early deafness. Purposive and theoretical sampling of 35 adults who were born or became deaf early was planned in a 1-year study. In-depth semi-structured interviews probed deaf adult participants' perceptions about quality of life as a deaf individual. Data saturation was reached at the 17th interview with 2 additional interviews for validation, resulting in a total sample of 19 deaf adults. Coding and thematic analysis were conducted to develop the conceptual model. Our conceptual model delineates the relationships between health status (self-acceptance, coping with limitations), intrinsic (functional communication skills, navigating barriers/self-advocacy, resilience) and extrinsic (acceptance by others, access to information, educating others) factors in their influence on deaf adult quality of life outcomes at home, college, work, and in the community. Findings demonstrate the need for the programs and services to consider not only factors intrinsic to the deaf individual but also extrinsic factors in enhancing perceived quality of life outcomes among people with a range of functional hearing and language preferences, including American Sign Language. Copyright © 2014 Elsevier Inc. All rights reserved.
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Increased amygdala reactivity following early life stress: a potential resilience enhancer role.
Yamamoto, Tetsuya; Toki, Shigeru; Siegle, Greg J; Takamura, Masahiro; Takaishi, Yoshiyuki; Yoshimura, Shinpei; Okada, Go; Matsumoto, Tomoya; Nakao, Takashi; Muranaka, Hiroyuki; Kaseda, Yumiko; Murakami, Tsuneji; Okamoto, Yasumasa; Yamawaki, Shigeto
2017-01-18
Amygdala hyper-reactivity is sometimes assumed to be a vulnerability factor that predates depression; however, in healthy people, who experience early life stress but do not become depressed, it may represent a resilience mechanism. We aimed to test these hypothesis examining whether increased amygdala activity in association with a history of early life stress (ELS) was negatively or positively associated with depressive symptoms and impact of negative life event stress in never-depressed adults. Twenty-four healthy participants completed an individually tailored negative mood induction task during functional magnetic resonance imaging (fMRI) assessment along with evaluation of ELS. Mood change and amygdala reactivity were increased in never-depressed participants who reported ELS compared to participants who reported no ELS. Yet, increased amygdala reactivity lowered effects of ELS on depressive symptoms and negative life events stress. Amygdala reactivity also had positive functional connectivity with the bilateral DLPFC, motor cortex and striatum in people with ELS during sad memory recall. Increased amygdala activity in those with ELS was associated with decreased symptoms and increased neural features, consistent with emotion regulation, suggesting that preservation of robust amygdala reactions may reflect a stress buffering or resilience enhancing factor against depression and negative stressful events.
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Directory of Open Access Journals (Sweden)
Felisa N van Hasselt
Full Text Available Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology--e.g. depression, anxiety and schizophrenia--later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG, correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT. In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures.
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Early childhood development coming of age: science through the life course.
Black, Maureen M; Walker, Susan P; Fernald, Lia C H; Andersen, Christopher T; DiGirolamo, Ann M; Lu, Chunling; McCoy, Dana C; Fink, Günther; Shawar, Yusra R; Shiffman, Jeremy; Devercelli, Amanda E; Wodon, Quentin T; Vargas-Barón, Emily; Grantham-McGregor, Sally
2017-01-07
Early childhood development programmes vary in coordination and quality, with inadequate and inequitable access, especially for children younger than 3 years. New estimates, based on proxy measures of stunting and poverty, indicate that 250 million children (43%) younger than 5 years in low-income and middle-income countries are at risk of not reaching their developmental potential. There is therefore an urgent need to increase multisectoral coverage of quality programming that incorporates health, nutrition, security and safety, responsive caregiving, and early learning. Equitable early childhood policies and programmes are crucial for meeting Sustainable Development Goals, and for children to develop the intellectual skills, creativity, and wellbeing required to become healthy and productive adults. In this paper, the first in a three part Series on early childhood development, we examine recent scientific progress and global commitments to early childhood development. Research, programmes, and policies have advanced substantially since 2000, with new neuroscientific evidence linking early adversity and nurturing care with brain development and function throughout the life course. Copyright © 2017 Elsevier Ltd. All rights reserved.
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The Everyday Life of Children Across Early Childhood Institution and The Family
DEFF Research Database (Denmark)
Kousholt, Dorte
2008-01-01
This article focuses on the everyday life of Danish children across different social practices and explores what this outset can tell us about the life of children and families. Building on the critique of classical approaches in developmental psychology (e.g. Burman 1994; James, Jenks, & Prout...... 1998) and family research (e.g. Leira 1993; Thorne & Yalom 1982) the article puts forward a decentred approach to family life. The aim is to show how the institutional context and family context sets conditions for each other - and that interplay sets conditions for the development of the children...... and professionals influences the parents' possibilities for supporting their children's life outside the family. That means that the institutional practice influences their possibilities as parents. Keywords: children's perspectives; family life; early childhood institution; communities of children; parent (and...
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Victims of Chinese famine in early life have increased risk of metabolic syndrome in adulthood.
Yu, Caizheng; Wang, Jing; Wang, Fei; Han, Xu; Hu, Hua; Yuan, Jing; Miao, Xiaoping; Yao, Ping; Wei, Sheng; Wang, Youjie; Liang, Yuan; Zhang, Xiaomin; Guo, Huan; Pan, An; Zheng, Dan; Tang, Yuhan; Yang, Handong; Wu, Tangchun; He, Meian
2018-02-05
To investigate the association of exposure to the Chinese famine during early life with metabolic syndrome risk in adults. There were 7,915 participants from Dongfeng-Tongji cohort were included in the present study. Participants were classified as non-exposed group, fetal exposed group, early childhood-, mid childhood-, and late childhood-exposed groups, respectively. Metabolic syndrome was defined according to International Diabetes Foundation criteria (2005). Logistic regression model was used to explore the association between famine exposure in early life and metabolic syndrome risk in adults. The metabolic syndrome prevalence in non-, fetal-, early childhood-, mid childhood-, and late childhood- exposed groups were 25.2%, 26.9%, 30.3%, 32.7%, and 32.7%, respectively. Compared with non-exposed group, participants exposed to famine in the fetal (0.96, 95% CI: 0.77-1.20), early childhood (1.24, 95% CI: 1.01-1.52), mid childhood (1.39, 95% CI: 1.13-1.72), and late childhood (1.33, 95% CI: 1.08-1.63) had higher metabolic syndrome prevalence risk in adults after adjustment for potential confounders (P for trend metabolic syndrome prevalence risk than non-exposed women (P for trend metabolic syndrome prevalence risk (P for interaction = 0.0001). Results in the present study indicated that exposure to famine in early life increases the risk of metabolic syndrome in adulthood, particularly in women. Copyright © 2018 Elsevier Inc. All rights reserved.
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Slavich, George M; Monroe, Scott M; Gotlib, Ian H
2011-09-01
Although exposure to early adversity and prior experiences with depression have both been associated with lower levels of precipitating life stress in depression, it is unclear whether these stress sensitization effects are similar for all types of stress or whether they are specific to stressors that may be particularly depressogenic, such as those involving interpersonal loss. To investigate this issue, we administered structured, interview-based measures of early adversity, depression history, and recent life stress to one hundred adults who were diagnosed with major depressive disorder. As predicted, individuals who experienced early parental loss or prolonged separation (i.e., lasting one year or longer) and persons with more lifetime episodes of depression became depressed following lower levels of life stress occurring in the etiologically-central time period of three months prior to onset of depression. Importantly, however, additional analyses revealed that these effects were unique to stressors involving interpersonal loss. These data highlight potential stressor-specific effects in stress sensitization and demonstrate for the first time that individuals exposed to early parental loss or separation, and persons with greater histories of MDD, may be selectively sensitized to stressors involving interpersonal loss. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Park, Jee Hoon; Lee, KyongWeon; Hand, Michelle D; Anderson, Keith A; Schleitwiler, Tess E
2016-01-01
Prior to and during World War II, thousands of girls and young women were abducted from Korea and forced into sexual slavery by the Japanese government. Termed comfort women, these girls and young women suffered extreme sexual, physical, and emotional abuse and trauma. Research on this group is not well-developed and people know little of the impact of this early life trauma on the lives of these women who are now in later life. Using snowball sampling, 16 older adult survivors of the comfort women system participated in semistructured qualitative interviews. Thematic analysis was conducted to gain an understanding of the trauma that these women suffered and how it impacted their lives. Results revealed the depths of the abuse these women suffered, including repeated rapes, physical beatings, humiliation, forced surgery and sterilization, and social exclusion. These early traumatic experiences appeared to reverberate throughout their lives in their family relations, their inability to marry and to conceive children, and their emotional and physical well-being throughout the life course and into later life. The experiences of these survivors illustrate the lasting impact of early-life trauma and can guide interventions with current survivors of sexual abuse or trafficking.
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Sex-specific impact of early-life adversity on chronic pain: a large population-based study in Japan
Directory of Open Access Journals (Sweden)
Yamada K
2017-02-01
Full Text Available Keiko Yamada,1,2 Ko Matsudaira,3,4 Eizaburo Tanaka,1,5 Hiroyuki Oka,3 Junji Katsuhira,3,6 Hiroyasu Iso1 1Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 2Center for Pain Management, Osaka University Hospital, Suita, Osaka, 3Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Tokyo, 4Japan Labour Health & Welfare Organization, Tokyo, 5Hyogo Institute for Traumatic Stress, Kobe, 6Department of Prosthetics & Orthotics and Assistive Technology, Faculty of Medical Technology, Niigata University of Health and Welfare, Niigata, Japan Background: Responses to early-life adversity may differ by sex. We investigated the sex-specific impact of early-life adversity on chronic pain, chronic multisite pain, and somatizing tendency with chronic pain. Methods: We examined 4229 respondents aged 20–79 years who participated in the Pain Associated Cross-Sectional Epidemiological Survey in Japan. Outcomes were: 1 chronic pain prevalence, 2 multisite pain (≥3 sites prevalence, and 3 multiple somatic symptoms (≥3 symptoms among respondents with chronic pain related to the presence or absence of early-life adversity. Multivariable-adjusted odds ratios (ORs were calculated with 95% confidence intervals using a logistic regression model including age, smoking status, exercise routine, sleep time, body mass index, household expenditure, and the full distribution of scores on the Mental Health Inventory-5. We further adjusted for pain intensity when we analyzed the data for respondents with chronic pain. Results: The prevalence of chronic pain was higher among respondents reporting the presence of early-life adversity compared with those reporting its absence, with multivariable ORs of 1.62 (1.22–2.15, p<0.01 in men and 1.47 (1.13–1.90, p<0.01 in women. Among women with chronic pain, early-life
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Biomarkers as tracers for life on early earth and Mars
Simoneit, B. R.; Summons, R. E.; Jahnke, L. L.
1998-01-01
Biomarkers in geological samples are products derived from biochemical (natural product) precursors by reductive and oxidative processes (e.g., cholestanes from cholesterol). Generally, lipids, pigments and biomembranes are preserved best over longer geological times and labile compounds such as amino acids, sugars, etc. are useful biomarkers for recent times. Thus, the detailed characterization of biomarker compositions permits the assessment of the major contributing species of extinct and/or extant life. In the case of the early Earth, work has progressed to elucidate molecular structure and carbon isotropic signals preserved in ancient sedimentary rocks. In addition, the combination of bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems permits the modeling of the nature, behavior and preservation potential of primitive microbial communities. This approach uses combined molecular and isotopic analyses to characterize lipids produced by cultured bacteria (representative of ancient strains) and to test a variety of culture conditions which affect their biosynthesis. On considering Mars, the biomarkers from lipids and biopolymers would be expected to be preserved best if life flourished there during its early history (3.5-4 x 10(9) yr ago). Both oxidized and reduced products would be expected. This is based on the inferred occurrence of hydrothermal activity during that time with the concomitant preservation of biochemically-derived organic matter. Both known biomarkers (i.e., as elucidated for early terrestrial samples and for primitive terrestrial microbiota) and novel, potentially unknown compounds should be characterized.
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Stable carbon isotope fractionation in the search for life on early Mars
Rothschild, L. J.; Desmarais, D.
1989-01-01
The utility of measurements of C-13/C-12 ratios in organic vs inorganic deposits for searching for signs of life on early Mars is considered. It is suggested that three assumptions are necessary. First, if there was life on Mars, it caused the fractionation of carbon isotopes in analogy with past biological activity on earth. Second, the fractionation would be detectable. Third, if a fractionation would be observed, there exist no abiotic explanations for the observed fractionation pattern.
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Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat
2014-01-01
Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequentl...
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Is epigenetics an important link between early life events and adult disease?
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...
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Effects of hydroelectric turbine passage on fish early life stages
International Nuclear Information System (INIS)
Cada, G.F.
1991-01-01
Turbine-passage mortality has been studied extensively for juveniles and adults of migratory fish species, but few studies have directly quantified orality of fish eggs and larvae. This paper provides an analysis of literature relating to component stresses of turbine passage (i.e., pressure changes, blade contact, and shear) which indicates that mortality of early life stages of fish would be relatively low at low-head, bulb turbine installations. The shear forces and pressure regimes normally experienced are insufficient to cause high mortality rates. The probability of contact with turbine blades is related to the size of the fish; less than 5% of entrained ichthyoplankton would be killed by the blades in a bulb turbine. Other sources of mortality (e.g., cavitation and entrainment of fish acclimated to deep water) are controlled by operation of the facility and thus are mitigable. Because turbine-passage mortality among fish early life stages can be very difficult to estimate directly, it may be more fruitful to base the need for mitigation at any given site on detailed knowledge of turbine characteristics and the susceptibility of the fish community to entrainment
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Rueppell, Olav; Yousefi, Babak; Collazo, Juan; Smith, Daniel
2017-04-01
Early life stressors can affect aging and life expectancy in positive or negative ways. Individuals can adjust their behavior and molecular physiology based on early life experiences but relatively few studies have connected such mechanisms to demographic patterns in social organisms. Sociality buffers individuals from environmental influences and it is unclear how much early life stress affects later life history. Workers of the honey bee (Apis mellifera L.) were exposed to two stressors, Varroa parasitism and Paraquat exposure, early in life. Consequences were measured at the molecular, behavioral, and demographic level. While treatments did not significantly affect levels of oxidative damage, expression of select genes, and titers of the common deformed wing virus, most of these measures were affected by age. Some of the age effects, such as declining levels of deformed wing virus and oxidative damage, were opposite to our predictions but may be explained by demographic selection. Further analyses suggested some influences of worker behavior on mortality and indicated weak treatment effects on behavior. The latter effects were inconsistent among the two experiments. However, mortality rate was consistently reduced by Varroa mite stress during development. Thus, mortality was more responsive to early life stress than our other response variables. The lack of treatment effects on these measures may be due to the social organization of honey bees that buffers the individual from the impact of stressful developmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.
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How emotional abilities modulate the influence of early life stress on hippocampal functioning.
Aust, Sabine; Alkan Härtwig, Elif; Koelsch, Stefan; Heekeren, Hauke R; Heuser, Isabella; Bajbouj, Malek
2014-07-01
Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual's degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
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Early environmental predictors of the affective and interpersonal constructs of psychopathy.
Daversa, Maria T
2010-02-01
Early childhood maltreatment (i.e., physical, sexual, emotional abuse) and caregiver disruptions are hypothesized to be instrumental in altering the neurobiology of the brain, particularly the amygdala, and contributing to the development of the affective deficits examined in individuals with psychopathy. Exposure to early untoward life events in models of rodent and nonhuman primates changes the neurobiology of the stress response. It is hypothesized that these changes may permanently shape brain regions that mediate stress and emotion and therefore play a role in the etiology of affective disorders in humans. The significance of experience (e.g., the intensity/severity, chronicity/duration, and developmental timing of experiences) and how the accompanying changes in the activity of the hypothalamic-pituitary-adrenocortical system affect alterations in the amygdala are discussed as critical contributors to the etiology of psychopathy. A model is proposed in which early maltreatment experiences contribute to alterations to the amygdala and produce a blunted or dissociative response to stress, a key factor in the affective deficits observed in psychopaths.
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Fish early life stage: Developing AOPs to support targeted reduction and replacement
There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse chronic toxicity outcomes (e.g., impacts on growth and survival). Development and characterization of adverse outcome pathways (AOPs) related...
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The influence of early exposure to vitamin D for development of diseases later in life
DEFF Research Database (Denmark)
Jacobsen, Ramune; Abrahamsen, Bo; Bauerek, Marta Jadwiga
2013-01-01
Vitamin D deficiency is common among otherwise healthy pregnant women and may have consequences for them as well as the early development and long-term health of their children. However, the importance of maternal vitamin D status on offspring health later in life has not been widely studied....... The present study includes an in-depth examination of the influence of exposure to vitamin D early in life for development of fractures of the wrist, arm and clavicle; obesity, and type 1 diabetes (T1D) during child- and adulthood....
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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.
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Nisbet, E. G.; Fowler, C. M. R.
2003-12-01
The youth of the Earth is strange to us. Many of the most fundamental constraints on life may have been different, especially the oxidation state of the surface. Should we suddenly land on its Hadean or early Archean surface by some sci-fi accident, we would not recognize our home. Above, the sky may have been green or some other unworldly color, and above that the weak young Sun might have been unrecognizable to someone trying to identify it from its spectrum. Below, seismology would show a hot, comparatively low-viscosity interior, possibly with a magma ocean in the deeper part of the upper mantle (Drake and Righter, 2002; Nisbet and Walker, 1982), and a core that, though present, was perhaps rather smaller than today. The continents may have been small islands in an icy sea, mostly frozen with some leads of open water, ( Sleep et al., 2001). Into these icy oceans, huge protruding Hawaii-like volcanoes would have poured out vast far-spreading floods of komatiite lavas in immense eruptions that may have created sudden local hypercane storms to disrupt the nearby icebergs. And meteorites would rain down.Or perhaps it was not so strange, nor so violent. The child is father to the man; young Earth was mother to Old Earth. Earth had hydrogen, silicate rock below and on the surface abundant carbon, which her ancient self retains today. Moreover, Earth was oxygen-rich, as today. Today, a tiny part of the oxygen is free, as air; then the oxygen would have been in the mantle while the surface oxygen was used to handcuff the hydrogen as dihydrogen monoxide. Oxygen dihydride is dense, unlikely to fly off to space, and at the poles, rock-forming. Of all the geochemical features that make Earth unique, the initial degassing (Genesis 2 : b) and then the sustained presence of liquid water is the defining oddity of this planet. Early Earth probably also kept much of its carbon, nitrogen, and sulfur as oxide or hydride. And, after the most cataclysmic events had passed, ˜4.5 Ga
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Quality of life of early stage colorectal cancer patients in Morocco.
Mrabti, Hind; Amziren, Mounia; ElGhissassi, Ibrahim; Bensouda, Youssef; Berrada, Narjiss; Abahssain, Halima; Boutayeb, Saber; El Fakir, Samira; Nejjari, Chakib; Benider, Abdellatif; Mellas, Nawfel; El Mesbahi, Omar; Bennani, Maria; Bekkali, Rachid; Zidouh, Ahmed; Errihani, Hassan
2016-10-12
A multicentre cohort study was held in Morocco, designed to evaluate the quality of life of cancer patients. The aim of this paper is to report the assessment of the quality of life of early colorectal cancer patients, before and after cancer treatment, to identify other factors which are related to this quality of life. We used the third version of the QLQ-C30 questionnaire of the European organization for Research and treatment of Cancer (EORTC) after a transcultural validation. The Data collection was done at inclusion and then every twelve weeks to achieve one year of follow up. Overall 294 patients presented with early colorectal cancer, the median age was 56 years (range: 21-88). The male-female sex ratio was 1.17. At inclusion, the global health status was the most affected functional dimension. For symptoms: financial difficulties and fatigue scores were the highest ones. Emotional and social functions were significantly worse in rectal cancer. Most symptoms were more present in rectal cancer. At inclusion, global health status score was significantly worse in stage III. Anorexia was significantly more important among colorectal female patients. For Patients over 70 years-old, the difference was statistically significant for the physical function item which was lower. Overall, Functional dimensions scores were improved after chemotherapy. The symptoms scores did not differ significantly for patients treated by radiotherapy, between inclusion and at one year. Our EORTC QLQ C30 scores are overall comparable to the reference values. Neither chemotherapy, nor radiotherapy worsened the quality of life at one year.
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Hsu, Bin-Yan; Dijkstra, Cor; Groothuis, Ton G. G.
Early-life food conditions can have profound impact on adult behavioural performance. In song birds, early-life food conditions affect adult physiology and cognitive performance such as song learning and spatial learning. However, effects on reproductive behaviour other than song, such as visual
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Alteration of consciousness in focal epilepsy: the global workspace alteration theory.
Bartolomei, Fabrice; McGonigal, Aileen; Naccache, Lionel
2014-01-01
Alteration of consciousness (AOC) is an important clinical manifestation of partial seizures that greatly impacts the quality of life of patients with epilepsy. Several theories have been proposed in the last fifty years. An emerging concept in neurology is the global workspace (GW) theory that postulates that access to consciousness (from several sensorial modalities) requires transient coordinated activity from associative cortices, in particular the prefrontal cortex and the posterior parietal associative cortex. Several lines of evidence support the view that partial seizures alter consciousness through disturbance of the GW. In particular, a nonlinear relation has been shown between excess of synchronization in the GW regions and the degree of AOC. Changes in thalamocortical synchrony occurring during the spreading of the ictal activity seem particularly involved in the mechanism of altered consciousness. This link between abnormal synchrony and AOC offers new perspectives in the treatment of the AOC since means of decreasing consciousness alteration in seizures could improve patients' quality of life. © 2013.
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External-environmental and internal-health early life predictors of adolescent development.
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.
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Tarantini, Stefano; Giles, Cory B; Wren, Jonathan D; Ashpole, Nicole M; Valcarcel-Ares, M Noa; Wei, Jeanne Y; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna
2016-08-01
Epidemiological findings support the concept of Developmental Origins of Health and Disease, suggesting that early-life hormonal influences during a sensitive period of development have a fundamental impact on vascular health later in life. The endocrine changes that occur during development are highly conserved across mammalian species and include dramatic increases in circulating IGF-1 levels during adolescence. The present study was designed to characterize the effect of developmental IGF-1 deficiency on the vascular aging phenotype. To achieve that goal, early-onset endocrine IGF-1 deficiency was induced in mice by knockdown of IGF-1 in the liver using Cre-lox technology (Igf1 f/f mice crossed with mice expressing albumin-driven Cre recombinase). This model exhibits low-circulating IGF-1 levels during the peripubertal phase of development, which is critical for the biology of aging. Due to the emergence of miRNAs as important regulators of the vascular aging phenotype, the effect of early-life IGF-1 deficiency on miRNA expression profile in the aorta was examined in animals at 27 months of age. We found that developmental IGF-1 deficiency elicits persisting late-life changes in miRNA expression in the vasculature, which significantly differed from those in mice with adult-onset IGF-1 deficiency (TBG-Cre-AAV8-mediated knockdown of IGF-1 at 5 month of age in Igf1 f/f mice). Using a novel computational approach, we identified miRNA target genes that are co-expressed with IGF-1 and associate with aging and vascular pathophysiology. We found that among the predicted targets, the expression of multiple extracellular matrix-related genes, including collagen-encoding genes, were downregulated in mice with developmental IGF-1 deficiency. Collectively, IGF-1 deficiency during a critical period during early in life results in persistent changes in post-transcriptional miRNA-mediated control of genes critical targets for vascular health, which likely contribute to the
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Wei, Q.W.; Kynard, B.; Yang, D.G.; Chen, X.H.; Du, H.; Shen, L.; Zhang, H.
2009-01-01
A sampling system for capturing sturgeon eggs using a D-shaped bottom anchored drift net was used to capture early life stages (ELS) of Chinese sturgeon, Acipenser sinensis, and monitor annual spawning success at Yichang on the Yangtze River, 1996-2004, before and just after the Three Gorges Dam began operation. Captured were 96 875 ELS (early life stages: eggs, yolk-sac larvae = eleuthero embryos, and larvae); most were eggs and only 2477 were yolk-sac larvae. Most ELS were captured in the main river channel and inside the bend at the Yichang spawning reach. Yolk-sac larvae were captured for a maximum of 3 days after hatching began, indicating quick dispersal downstream. The back-calculated day of egg fertilization over the eight years indicated a maximum spawning window of 23 days (20 October-10 November). Spawning in all years was restricted temporally, occurred mostly at night and during one or two spawning periods, each lasting several days. The brief temporal spawning window may reduce egg predation by opportunistic predators by flooding the river bottom with millions of eggs. During 1996-2002, the percentage of fertilized eggs in an annual 20-egg sample was between 63.5 to 94.1%; however, in 2003 the percentage fertilized was only 23.8%. This sudden decline may be related to the altered environmental conditions at Yichang caused by operation of the Three Gorges Dam. Further studies are needed to monitor spawning and changes in egg fertilization in this threatened population. ?? 2009 Blackwell Verlag GmbH.
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Akman, Ozlem; Moshé, Solomon L; Galanopoulou, Aristea S
2015-02-01
Neonatal status epilepticus (SE) is often associated with adverse cognitive and epilepsy outcomes. We investigate the effects of three episodes of kainic acid-induced SE (3KA-SE) and maternal separation in immature rats on subsequent learning, seizure susceptibility, and consequences, and the anticonvulsant effects of phenobarbital, according to sex, type, and age at early life (EL) event. 3KA-SE or maternal separation was induced on postnatal days (PN) 4-6 or 14-16. Rats were tested on Barnes maze (PN16-19), or lithium-pilocarpine SE (PN19) or flurothyl seizures (PN32). The anticonvulsant effects of phenobarbital (20 or 40 mg/kg/rat, intraperitoneally) pretreatment were tested on flurothyl seizures. FluoroJadeB staining assessed hippocampal injury. 3KA-SE or separation on PN4-6 caused more transient learning delays in males and did not alter lithium-pilocarpine SE latencies, but aggravated its outcomes in females. Anticonvulsant effects of phenobarbital were preserved and potentiated in specific groups depending on sex, type, and age at EL event. Early life 3KA-SE and maternal separation cause more but transient cognitive deficits in males but aggravate the consequences of subsequent lithium-pilocarpine SE in females. In contrast, on flurothyl seizures, EL events showed either beneficial or no effect, depending on gender, type, and age at EL events. © 2014 John Wiley & Sons Ltd.
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Aschengrau, Ann; Janulewicz, Patricia A; White, Roberta F; Vieira, Veronica M; Gallagher, Lisa G; Getz, Kelly D; Webster, Thomas F; Ozonoff, David M
2016-01-01
Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983, widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distribution pipes. A retrospective cohort study (the Cape Cod Health Study) was undertaken to examine possible health consequences of early-life exposure to PCE-contaminated drinking water. This review describes the study methods and findings regarding the effects of prenatal and childhood exposure on neurologic outcomes during early adulthood, including vision, neuropsychological functioning, brain structure, risky behaviors, and mental illness. The review also describes the strengths and challenges of conducting population-based epidemiologic research in this unique setting. Participants were identified by cross-matching birth certificates and water system data. Information on health outcomes and confounding variables was collected from self-administered surveys (n = 1689), neuropsychological tests (n = 63), vision examinations (n = 63), and magnetic resonance imaging (n = 42). Early-life exposure to PCE was estimated using a leaching and transport model. The data analysis compared the occurrence of each health outcome among individuals with prenatal and early childhood PCE exposure to unexposed individuals while considering the effect of confounding variables. The study found evidence that early-life exposure to PCE-contaminated drinking water has long-term neurotoxic effects. The strongest associations were seen with illicit drug use, bipolar disorder, and post-traumatic stress disorder. Key strengths of the study were availability of historical data on affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little confounding. Challenges arose mainly from the historical
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LENUS (Irish Health Repository)
Packard, Chris J
2011-01-17
Abstract Background Socioeconomic gradients in health persist despite public health campaigns and improvements in healthcare. The Psychosocial and Biological Determinants of Ill-health (pSoBid) study was designed to uncover novel biomarkers of chronic disease that may help explain pathways between socioeconomic adversity and poorer physical and mental health. Methods We examined links between indicators of early life adversity, possible intermediary phenotypes, and markers of ill health in adult subjects (n = 666) recruited from affluent and deprived areas. Classical and novel risk factors for chronic disease (lung function and atherosclerosis) and for cognitive performance were assessed, and associations sought with early life variables including conditions in the parental home, family size and leg length. Results Associations were observed between father\\'s occupation, childhood home status (owner-occupier; overcrowding) and biomarkers of chronic inflammation and endothelial activation in adults (C reactive protein, interleukin 6, intercellular adhesion molecule; P < 0.0001) but not number of siblings and leg length. Lung function (forced expiratory volume in 1 second) and cognition (Choice Reaction Time, the Stroop test, Auditory Verbal Learning Test) were likewise related to early life conditions (P < 0.001). In multivariate models inclusion of inflammatory variables reduced the impact and independence of early life conditions on lung function and measures of cognitive ability. Including variables of adult socioeconomic status attenuated the early life associations with disease biomarkers. Conclusions Adverse levels of biomarkers of ill health in adults appear to be influenced by father\\'s occupation and childhood home conditions. Chronic inflammation and endothelial activation may in part act as intermediary phenotypes in this complex relationship. Reducing the \\'health divide\\' requires that these life course determinants are taken into account.
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Directory of Open Access Journals (Sweden)
Goodwin Renee D
2011-11-01
Full Text Available Abstract Background The objective of this study was to examine the association between infection early in life and mental disorders among youth in the community. Methods Data were drawn from the MECA (Methods in Epidemiology of Child and Adolescent psychopathology, a community-based study of 1,285 youth in the United States conducted in 1992. Multiple logistic regression analyses were used to investigate the association between parent/caregiver-reported infection early in life and DSM/DISC diagnoses of mental disorders at ages 9-17. Results Infection early in life was associated with a significantly increased odds of major depression (OR = 3.9, social phobia (OR = 5.8, overanxious disorder (OR = 6.1, panic disorder (OR = 12.1, and oppositional defiant disorder (OR = 3.7. Conclusions These findings are consistent with and extend previous results by providing new evidence suggesting a link between infection early in life and increased risk of depression and anxiety disorders among youth. These results should be considered preliminary. Replication of these findings with longitudinal epidemiologic data is needed. Possible mechanisms are discussed.
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Balangoda, Anusha; Deepananda, K H M Ashoka; Wegiriya, H C E
2018-02-01
This study investigated the potential toxic effects of environmentally relevant nitrate concentrations on development, growth, and mortality of early life stages of common hour-glass tree frog, Polypedates cruciger. Tadpoles from hatchlings through pre-adult were exposed to environmentally relevant nitrate concentrations detected in Mirissa, Sri Lanka. Newly hatched, external gill stage, and internal gill stage tadpoles were exposed to potassium nitrate for bioassay tests. No behavioral changes or abnormalities were observed in control and nitrate-induced group. However, detected environmental nitrate concentration significantly increased (p nitrate pollution than internal gill stage. The results suggest that environmentally relevant nitrate can cause mortality on the amphibian population in ecosystems associated with agro-pastoral activities through altering the growth and direct toxicological effects on the survivorship.
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Diaz-Rua, Ruben
2016-11-23
Background: Research on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC) is a promising tool to identify subjects at risk of developing diet-related diseases.
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DEFF Research Database (Denmark)
Marina, Djordje; Klose, Marianne; Nordenbo, Annette
2015-01-01
OBJECTIVE: Severe brain injury poses a risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective was to assess the pattern and prevalence...
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Family Quality of Life for Families in Early Intervention in Spain
Mas, Joana M.; Baqués, Natasha; Balcells-Balcells, Anna; Dalmau, Mariona; Giné, Climent; Gràcia, Marta; Vilaseca, Rosa
2016-01-01
Early intervention (EI) has been shown to be an essential resource for meeting the needs and priorities of children with intellectual and developmental disability and their families. The objective of this study was to examine (a) the perceived quality of life of families attending EI centers in Spain and (b) its relationship with characteristics…
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Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M
2016-01-01
Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life.
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Östlund, Gunnel; Björk, Mathilda; Valtersson, Eva; Sverker, Annette
2015-12-01
Men and women with rheumatoid arthritis (RA) experience restrictions in everyday life, in spite of the development of new medications. Recent research has described in detail how participation limitations are experienced in everyday life from a patient perspective. However, knowledge of how sex and intimate relationships are affected is still scarce. The aim of the present study was to explore sex life experiences in relation to sexual function and sexual relationships in men and women with early RA. The study formed part of TIRA-2 (the Swedish acronym for the prospective multicentre early arthritis project). The data collection included 45 interviews with 21 men and 24 women, aged 20-63, which were recorded and transcribed verbatim. The critical incident technique was used to collect data, and content analysis to categorize the results. Half the participants stated that RA affected their sex life. The general descriptions formed five categories: sex life and tiredness; sex life and ageing; emotional consequences of impaired sexual function; facilitators of sexual function and sexual relationships; and strain on the sexual relationship. Sex life is affected in early RA, in spite of new effective treatment strategies. New strategies of communication, assessment and self-managing interventions concerning the sex lives of patients with RA need to be implemented by a multidisciplinary healthcare team. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
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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.
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Directory of Open Access Journals (Sweden)
Jessica L. Bolton
2018-02-01
Full Text Available Early-life adversity increases the risk for emotional disorders such as depression and schizophrenia. Anhedonia, thought to be a core feature of these disorders, is provoked by our naturalistic rodent model of childhood adversity (i.e., rearing pups for one week in cages with limited bedding and nesting, LBN. Drug use and addiction are highly comorbid with psychiatric disorders featuring anhedonia, yet effects of LBN on drug-seeking behavior and the reward and stress-related circuits that underlie it remain unknown. Here we examined the effects of LBN on cocaine intake and seeking, using a battery of behavioral tests measuring distinct aspects of cocaine reward, and for comparison, chocolate intake. We also examined activation of neurons within the pleasure/reward and stress circuits following cocaine in LBN and control rats. Early-life adversity reduced spontaneous intake of palatable chocolate, extending prior reports of sucrose and social-play anhedonia. In a within-session cocaine behavioral economic test, LBN rats self-administered lower dosages of cocaine under low-effort conditions, consistent with a reduced hedonic set-point for cocaine, and potentially anhedonia. In contrast, cocaine demand elasticity was not consistently affected, indicating no major changes in motivation to maintain preferred cocaine blood levels. These changes were selective, as LBN did not cause an overt anxiety-like phenotype, nor did it affect sensitivity to self-administered cocaine dose, responding for cocaine under extinction conditions, cocaine- or cue-induced reinstatement of cocaine seeking, or locomotor response to acute cocaine. However, high Fos expression was seen after cocaine in both reward- and stress-related brain regions of LBN rats, including nucleus accumbens core, central amygdala, and lateral habenula. In contrast, hypothalamic orexin neuron activation after cocaine was significantly attenuated in LBN rats. Together, these findings demonstrate
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Directory of Open Access Journals (Sweden)
Chomiak Taylor
2010-08-01
Full Text Available Abstract Background Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking. Results We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA in vivo. Brain sections obtained from postnatal rat pups treated with VPA in vivo revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour. Conclusions The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism.
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Brain grey matter volume alterations in late-life depression.
Du, Mingying; Liu, Jia; Chen, Ziqi; Huang, Xiaoqi; Li, Jing; Kuang, Weihong; Yang, Yanchun; Zhang, Wei; Zhou, Dong; Bi, Feng; Kendrick, Keith M; Gong, Qiyong
2014-11-01
Voxel-based morphometry (VBM) studies have demonstrated that grey matter abnormalities are involved in the pathophysiology of late-life depression (LLD), but the findings are inconsistent and have not been quantitatively reviewed. The aim of the present study was to conduct a meta-analysis that integrated the reported VBM studies, to determine consistent grey matter alterations in individuals with LLD. A systematic search was conducted to identify VBM studies that compared patients with LLD and healthy controls. We performed a meta-analysis using the effect size signed differential mapping method to quantitatively estimate regional grey matter abnormalities in patients with LLD. We included 9 studies with 11 data sets comprising 292 patients with LLD and 278 healthy controls in our meta-analysis. The pooled and subgroup meta-analyses showed robust grey matter reductions in the right lentiform nucleus extending into the parahippocampus, the hippocampus and the amygdala, the bilateral medial frontal gyrus and the right subcallosal gyrus as well as a grey matter increase in the right lingual gyrus. Meta-regression analyses showed that mean age and the percentage of female patients with LLD were not significantly related to grey matter changes. The analysis techniques, patient characteristics and clinical variables of the studies included were heterogeneous, and most participants were medicated. The present meta-analysis is, to our knowledge, the first to overcome previous inconsistencies in the VBM studies of LLD and provide robust evidence for grey matter alterations within fronto-striatal-limbic networks, thereby implicating them in the pathophysiology of LLD. The mean age and the percentage of female patients with LLD did not appear to have a measurable impact on grey matter changes, although we cannot rule out the contributory effects of medication.
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Parent Attachment and Early Adolescents' Life Satisfaction: The Mediating Effect of Hope
Jiang, Xu; Huebner, E. Scott; Hills, Kimberly J.
2013-01-01
Research using an attachment theory framework has provided evidence that parent attachment is one of the crucial determinants of psychological adjustment in adolescents, including global life satisfaction (LS). This study investigated the interrelationships among parent attachment, hope, and LS during early adolescence, including the mediation…
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Behavioral and cognitive impact of early life stress: Insights from an animal model.
Liu, Hesong; Atrooz, Fatin; Salvi, Ankita; Salim, Samina
2017-08-01
Children subjected to traumatic events during childhood are reported to exhibit behavioral and cognitive deficits later in life, often leading to post-traumatic stress disorder (PTSD) and major depression. Interestingly, some children continue to remain normal despite being exposed to the same risk factors. These trauma-related behavioral and cognitive profiles across different stages of life are not well understood. Animal studies can offer useful insights. The goal of this study was to determine the impact of early life exposure to traumatic events on behavioral and cognitive profile in rats by tracking the behavior of each rat at different ages. We utilized the single prolonged stress (SPS), a rodent model of PTSD, to study the effects of early life stress. Male Sprague-Dawley rats were exposed to SPS on post-natal day (PND) 25. Tests to assess anxiety- and depression-like behavior, as well as learning and memory function were performed at PND32, 60 and 90. Rats exposed to SPS exhibited both anxiety- and depression-like behavior at PND32. And, short-term (STM) but not long-term memory (LTM) was impaired. Rats exposed to SPS at PND60 exhibited anxiety- but not depression-like behavior. STM but not LTM was impaired. Rats exposed to SPS at PND90 exhibited fearful (as indicated by elevated plus maze test) but not an overall anxiety-like behavior (in light and dark test). These rats also displayed significant depression-like behavior with no changes in STM or LTM. Interestingly, when data was further analyzed, two subsets of PND90 rats exposed to SPS were identified, "susceptible": with depression-like behavior and "resilient": without depression-like behavior. Importantly, while resilient group expressed early signs of anxiety- (at PND32 and PND60) and depression-like behavior (at PND32), these behavioral deficits were absent at PND90. On the other hand, susceptible PND90 rats exposed to SPS expressed later onset of anxiety-like behavior (at PND60), while depression
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McKee, Sarah E.; Grissom, Nicola M.; Herdt, Christopher T.; Reyes, Teresa M.
2017-01-01
During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)–fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior. Given that extensive brain development occurs during early postnatal life—particularly within the prefrontal cortex (PFC), a brain region critical for executive function—we examined whether early life methyl donor supplementation (e.g., during adolescence) could ameliorate executive function deficits observed in offspring that were exposed to maternal HFD. By using operant testing, progressive ratio, and the PFC-dependent 5-choice serial reaction timed task (5-CSRTT), we determined that F1 female offspring (B6D2F1/J) from HFD-fed dams have decreased motivation (decreased progressive ratio breakpoint) and require a longer stimulus length to complete the 5-CSRTT task successfully, whereas early life methyl donor supplementation increased motivation and shortened the minimum stimulus length required for a correct response in the 5-CSRTT. Of interest, we found that expression of 2 chemokines, CCL2 and CXCL10, correlated with the median stimulus length in the 5-CSRTT. Furthermore, we found that acute adult supplementation of methyl donors increased motivation in HFD-fed offspring and those who previously received supplementation with methyl donors. These data point to early life as a sensitive time during which dietary methyl donor supplementation can alter PFC-dependent cognitive behaviors.—McKee, S. E., Grissom, N. M., Herdt, C. T., Reyes, T. M. Methyl donor supplementation
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Faith, Hope, and Spirituality: SUPPORTING PARENTS WHEN THEIR CHILD HAS A LIFE-LIMITING ILLNESS.
Crisp, Cheryl L
2016-01-01
When a child has a life-limiting illness, parents' goals and strategies for their child's life may need to be drastically altered, especially if early death looms. This article reviews literature and research about how families employ faith, hope, spirituality, and biblical perspectives as their child becomes critically ill and faces death. Suggestions are made for best caring practices for families and children encountering this difficult journey.
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What doesn't kill you makes you poorer: Adult wages and early-life mortality in India.
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.
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da Silva, Flávia R M; Grassi, Tony F; Zapaterini, Joyce R; Bidinotto, Lucas T; Barbisan, Luis F
2017-06-01
Zinc deficiency during pregnancy and postnatal life can adversely increase risk of developing human diseases at adulthood. The present study was designed to evaluate whether dietary zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interferes in the development of mammary tumors induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA - 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters' weaning. Female offspring received the same diets as their dams until postnatal day (PND) 51. At PND 51, the animals received a single dose of DMBA (50 mg/kg, ig) and zinc-adequate diets. At PND 180, female were euthanized, and tumor samples were processed for histological evaluation and gene expression microarray analysis. The ZnD induced a significant reduction in female offspring body weight evolution and in mammary gland development. At late in life, the ZnD or ZnS did not alter the latency, incidence, multiplicity, volume or histological types of mammary tumors in relation to the ZnA group. However, the total tumor number in ZnS group was higher than in ZnA group, accompanied by distinct expression of 4 genes up- and 15 genes down-regulated. The present findings indicate that early-in-life dietary zinc supplementation, differently to zinc deficiency, has a potential to modify the susceptibility to the development of mammary tumors induced by DMBA. Copyright © 2017 Elsevier Inc. All rights reserved.
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Development of early communication skills in the first two years of life.
Beuker, Karin T; Rommelse, Nanda N J; Donders, Rogier; Buitelaar, Jan K
2013-02-01
The first two years of life is a crucially important period for the development of communication skills. In this study joint attention and language development were monthly assessed between 8 and 24 months of age in a sample of 23 typically developing children to establish the developmental trajectory of specific joint attention skills, to investigate the developmental interrelations of these different joint attention skills with vocabulary size, and to examine whether the order of development of following and directing attention influences the development of other early communication skills such as language. All joint attention skills emerged between 8 and 15 months of age and responsive joint attention skills tend to emerge before initiative joint attention. Early joint attention skills influenced later language development, but not the other way around. Children in whom directing attention with gaze alternation developed early (in age or order) showed a relatively larger early vocabulary growth. A fine grained mapping of the normal development of early communication skills can be helpful in the early detection of abnormalities in these skills. Copyright © 2012 Elsevier Inc. All rights reserved.
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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.
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Development of atopic dermatitis and its association with prenatal and early life exposures
Roduit, Caroline
2015-01-01
Over 20% of children in industrialized countries are affected by atopic dermatitis. From epidemiological studies, it is quite obvious that the worldwide prevalence of atopic dermatitis has considerably increased over the past decades and constitutes a major public health problem. Atopic dermatitis is a chronic inflammatory skin disease that occurs in very early life and frequently precedes the development of asthma and allergic rhinitis during the first several years of life. Although a large...
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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
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Czech Academy of Sciences Publication Activity Database
Duval, C.; Zimmer, C.; Mikšík, Ivan; Cassey, P.; Spencer, K.A.
2014-01-01
Roč. 208, Nov 1 (2014), s. 146-153 ISSN 0016-6480 Institutional support: RVO:67985823 Keywords : breeding conditions * early-life stress * eggshell pigmentation * Japanese quail Subject RIV: ED - Physiology Impact factor: 2.470, year: 2014
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Roosa, Mark W.; Burrell, Ginger L.; Nair, Rajni L.; Coxe, Stefany; Tein, Jenn-Yun; Knight, George P.
2010-01-01
This study examined a stress process model in which stressful life events and association with delinquent peers mediated the relationship of neighborhood disadvantage to Mexican American early adolescents' mental health. The authors also proposed that child gender, child generation, and neighborhood informal social control would moderate the…
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Organizational design configurations in the early stages of firm’s life cycle
Mosca, Luigi; Gianecchini, Martina; Campagnolo, Diego
2017-01-01
http://ocs.editorial.upv.es/index.php/CARMA/CARMA2016 Mosca, L.; Gianecchini, M.; Campagnolo, D. (2017). Organizational design configurations in the early stages of firm’s life cycle. Editorial Universitat Politècnica de València. doi:10.4995/CARMA2016.2015.3104. OCS
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Early Life Experiences and Exercise Associate with Canine Anxieties.
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Katriina Tiira
Full Text Available Personality and anxiety disorders across species are affected by genetic and environmental factors. Shyness-boldness personality continuum exists across species, including the domestic dog, with a large within- and across-breed variation. Domestic dogs are also diagnosed for several anxiety-related behavioral conditions, such as generalized anxiety disorders, phobias, and separation anxiety. Genetic and environmental factors contributing to personality and anxiety are largely unknown. We collected questionnaire data from a Finnish family dog population (N = 3264 in order to study the associating environmental factors for canine fearfulness, noise sensitivity, and separation anxiety. Early life experiences and exercise were found to associate with anxiety prevalence. We found that fearful dogs had less socialization experiences (p = 0.002 and lower quality of maternal care (p < 0.0001 during puppyhood. Surprisingly, the largest environmental factor associating with noise sensitivity (p < 0.0001 and separation anxiety (p = 0.007 was the amount of daily exercise; dogs with noise sensitivity and separation anxiety had less daily exercise. Our findings suggest that dogs share many of the same environmental factors that contribute to anxiety in other species as well, such as humans and rodents. Our study highlights the importance of early life experiences, especially the quality of maternal care and daily exercise for the welfare and management of the dogs, and reveals important confounding factors to be considered in the genetic characterization of canine anxiety.
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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...
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Moody, Laura; Chen, Hong; Pan, Yuan-Xiang
2017-03-01
The perinatal period is a window of heightened plasticity that lays the groundwork for future anatomic, physiologic, and behavioral outcomes. During this time, maternal diet plays a pivotal role in the maturation of vital organs and the establishment of neuronal connections. However, when perinatal nutrition is either lacking in specific micro- and macronutrients or overloaded with excess calories, the consequences can be devastating and long lasting. The brain is particularly sensitive to perinatal insults, with several neurologic and psychiatric disorders having been linked to a poor in utero environment. Diseases characterized by learning and memory impairments, such as autism, schizophrenia, and Alzheimer disease, are hypothesized to be attributed in part to environmental factors, and evidence suggests that the etiology of these conditions may date back to very early life. In this review, we discuss the role of the early-life diet in shaping cognitive outcomes in offspring. We explore the endocrine and immune mechanisms responsible for these phenotypes and discuss how these systemic factors converge to change the brain's epigenetic landscape and regulate learning and memory across the lifespan. Through understanding the maternal programming of cognition, critical steps may be taken toward preventing and treating diseases that compromise learning and memory. © 2017 American Society for Nutrition.
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Gould, Elizabeth A; Busquet, Nicolas; Shepherd, Douglas; Dietz, Robert M; Herson, Paco S; Simoes de Souza, Fabio M; Li, Anan; George, Nicholas M; Restrepo, Diego; Macklin, Wendy B
2018-02-13
Myelin, the insulating sheath around axons, supports axon function. An important question is the impact of mild myelin disruption. In the absence of the myelin protein proteolipid protein (PLP1), myelin is generated but with age, axonal function/maintenance is disrupted. Axon disruption occurs in Plp1 -null mice as early as 2 months in cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase in oligodendrocyte density in the olfactory bulb and rostral corpus callosum that increased during adulthood. A distinct proliferative response of progenitor cells was observed in the subventricular zone (SVZ), while the number and proliferation of parenchymal oligodendrocyte progenitor cells was unchanged. This SVZ proliferative response occurred prior to evidence of axonal disruption. Thus, a novel SVZ response contributes to the region-specific increase in oligodendrocytes in Plp1 -null mice. Young adult Plp1- null mice exhibited subtle but substantial behavioral alterations, indicative of an early impact of mild myelin disruption. © 2018, Gould et al.
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Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.
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Eniko Nagy
Full Text Available Studies in transgenic murine models have provided insight into the complexity underlying inflammatory bowel disease (IBD, a disease hypothesized to result from an injurious immune response against intestinal microbiota. We recently developed a mouse model of IBD that phenotypically and histologically resembles human childhood-onset ulcerative colitis (UC, using mice that are genetically modified to be deficient in the cytokines TNF and IL-10 ("T/I" mice. Here we report the effects of early life onset of colon inflammation on growth and reproductive performance of T/I mice. T/I dams with colitis often failed to get pregnant or had small litters with pups that failed to thrive. Production was optimized by breeding double homozygous mutant T/I males to females homozygous mutant for TNF deficiency and heterozygous for deficiency of IL-10 ("T/I-het" dams that were not susceptible to spontaneous colon inflammation. When born to healthy (T/I-het dams, T/I pups initially gained weight similarly to wild type (WT pups and to their non-colitis-susceptible T/I-het littermates. However, their growth curves diverged between 8 and 13 weeks, when most T/I mice had developed moderate to severe colitis. The observed growth failure in T/I mice occurred despite a significant increase in their food consumption and in the absence of protein loss in the stool. This was not due to TNF-induced anorexia or altered food consumption due to elevated leptin levels. Metabolic studies demonstrated increased consumption of oxygen and water and increased production of heat and CO2 in T/I mice compared to their T/I-het littermates, without differences in motor activity. Based on the clinical similarities of this early life onset model of IBD in T/I mice to human IBD, these results suggest that mechanisms previously hypothesized to explain growth failure in children with IBD require re-evaluation. The T/I mouse model may be useful for further investigation of such mechanisms and
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Diaz Rua, Ruben; Palou, Andreu; Oliver, Paula
2016-01-01
subjects at risk of developing diet-related diseases.Objective: We analysed PBMC expression of key energy homeostasis-related genes in a time-course analysis in order to find out early markers of metabolic alterations due to sustained intake of high-fat (HF) and highprotein (HP) diets.Design: We administered HF and HP diets (4 months) to adult Wistar rats in isocaloric conditions to a control diet, mainly to avoid overweight associated with the intake of hyperlipidic diets and, thus, to be able to characterise markers of metabolically obese normal-weight (MONW) syndrome. PBMC samples were collected at different time points of dietary treatment and expression of relevant energy homeostatic genes analysed by real-time reverse transcription-polymerase chain reaction. Serum parameters related with metabolic syndrome, as well as fat deposition in liver, were also analysed.Results: The most outstanding results were those obtained for the expression of the lipolytic gene carnitine palmitoyltransferase 1a (Cpt1a). Cpt1a expression in PBMC increased after only 1 month of exposure to both unbalanced diets, and this increased expression was maintained thereafter. Interestingly, in the case of the HF diet, Cpt1a expression was altered even in the absence of increased body weight but correlated with alterations such as higher insulin resistance, alteration of serum lipid profile and, particularly, increased fat deposition in liver, a feature characteristic of metabolic syndrome, which was even observed in animals fed with HP diet.Conclusions: We propose Cpt1a gene expression analysis in PBMC as an early biomarker of metabolic alterations associated with MONW phenotype due to the intake of isocaloric HF diets, as well as a marker of increased risk of metabolic diseases
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Getting serious about the early-life epilepsies: Lessons from the world of pediatric oncology.
Berg, Anne T; Goldman, Stewart
2018-05-01
Early-life epilepsies represent a group of many individually rare and often complex developmental brain disorders associated with lifelong devastating consequences and high risk for early mortality. The quantity and quality of evidence needed to guide the evaluation and treatment to optimize outcomes of affected children is minimal; most children are treated within an evidence-free practice zone based solely on anecdote and lore. The remarkable advances in diagnostics and therapeutics are implemented haphazardly with no systematic effort to understand their effects and value. This stands in stark contrast to the evidence-rich practice of the Children's Oncology Group, where standard of care treatments are identified through rigorous, multicenter research studies, and the vast majority of patients are treated on protocols developed from that research. As a consequence, overall mortality for childhood cancers has declined from ∼90% in the 1950s to ∼20% today. The situations of these 2 rare disease specialties are contrasted, and some suggestions for moving early-life epilepsy onto a fast track for success are offered. Chief amongst these is that early-life epilepsy should be treated with the same urgency as pediatric cancer. The best diagnostics and evidence-based treatments should be used in a systematic fashion right from the start, not after the child and family have been subjected to the ravages of the disorder for months or years. This will require unity and cooperation among physicians, researchers, and institutions across state and national borders. © 2018 American Academy of Neurology.
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Directory of Open Access Journals (Sweden)
Emmanuel Somm
Full Text Available Poor fetal growth, also known as intrauterine growth restriction (IUGR, is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN. Physiological (glucose and insulin tolerance, morphometric (automated tissue image analysis and transcriptomic (quantitative PCR approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.
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Altered Dynamic Postural Control during Step Turning in Persons with Early-Stage Parkinson’s Disease
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Jooeun Song
2012-01-01
Full Text Available Persons with early-stage Parkinson’s disease (EPD do not typically experience marked functional deficits but may have difficulty with turning tasks. Studies evaluating turning have focused on individuals in advanced stages of the disease. The purpose of this study was to compare postural control strategies adopted during turning in persons with EPD to those used by healthy control (HC subjects. Fifteen persons with EPD, diagnosed within 3 years, and 10 HC participated. Participants walked 4 meters and then turned 90°. Dynamic postural control was quantified as the distance between the center of pressure (COP and the extrapolated center of mass (eCOM. Individuals with EPD demonstrated significantly shorter COP-eCOM distances compared to HC. These findings suggest that dynamic postural control during turning is altered even in the early stages of PD.
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Ramsey, Kathryn A.; Bosco, Anthony; McKenna, Katherine L.; Carter, Kim W.; Elliot, John G.; Berry, Luke J.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.
2012-01-01
Background: Exposure to arsenic via drinking water is a global environmental health problem. In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in early adulthood. Objectives: We aimed to investigate how arsenic exposure in early life alters lung development and pathways involved in innate immunity. Methods: Pregnant BALB/c, C57BL/6, and C3H/HeARC mice were exposed to 0 (control) or 100 ?g/L...
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Directory of Open Access Journals (Sweden)
Daniel Nettle
Full Text Available Early-life adversity is associated with poorer health and survival in adulthood in humans and other animals. One pathway by which early-life environmental stressors could affect the adult phenotype is via effects on telomere dynamics. Several studies have shown that early-life adversity is associated with relatively short telomeres, but these are often cross-sectional and usually correlational in design. Here, we present a novel experimental system for studying the relationship between early-life adversity and telomere dynamics using a wild bird, the European starling (Sturnus vulgaris. We used cross-fostering to experimentally assign sibling chicks to either small or large broods for twelve days of the growth period. We measured telomere length in red blood cells using quantitative PCR near the beginning of the experimental manipulation (4 days old, at the end of the experimental manipulation (15 days old, and once the birds were independent (55 days old. Being in a larger brood slowed growth and retarded wing development and the timing of fledging. We found no evidence that overall brood size affected telomere dynamics. However, the greater the number of competitors above the focal bird in the within-brood size hierarchy, the greater was the telomere loss during the period of the experimental manipulation. The number of competitors below the focal in the hierarchy had no effect. The effect of heavier competitors was still evident when we controlled for the weight of the focal bird at the end of the manipulation, suggesting it was not due to retarded growth per se. Moreover, the impact of early competition on telomeres was still evident at independence, suggesting persistence beyond early life. Our study provides experimental support for the hypothesis that social stress, in this case induced by the presence of a greater number of dominant competitors, accelerates the rate of telomere loss.
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DNA Methylation: A Mechanism for Embedding Early Life Experiences in the Genome
Szyf, Moshe; Bick, Johanna
2013-01-01
Although epidemiological data provide evidence that early life experience plays a critical role in human development, the mechanism of how this works remains in question. Recent data from human and animal literature suggest that epigenetic changes, such as DNA methylation, are involved not only in cellular differentiation but also in the…
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Alonso-Andrés, Patricia; Albasanz, José Luis; Ferrer, Isidro; Martín, Mairena
2018-01-24
Adenosine, hypoxanthine, xanthine, guanosine and inosine levels were assessed by HPLC, and the activity of related enzymes 5'-nucleotidase (5'-NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) measured in frontal (FC), parietal (PC) and temporal (TC) cortices at different stages of disease progression in Alzheimer's disease (AD) and in age-matched controls. Significantly decreased levels of adenosine, guanosine, hypoxanthine and xanthine, and apparently less inosine, are found in FC from the early stages of AD; PC and TC show an opposing pattern, as adenosine, guanosine and inosine are significantly increased at least at determinate stages of AD whereas hypoxanthine and xanthine levels remain unaltered. 5'-NT is reduced in membranes and cytosol in FC mainly at early stages but not in PC, and only at advanced stages in cytosol in TC. ADA activity is decreased in AD when considered as a whole but increased at early stages in TC. Finally, PNP activity is increased only in TC at early stages. Purine metabolism alterations occur at early stages of AD independently of neurofibrillary tangles and β-amyloid plaques. Alterations are stage dependent and region dependent, the latter showing opposite patterns in FC compared with PC and TC. Adenosine is the most affected of the assessed purines. © 2018 International Society of Neuropathology.
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Brand, Serge; Kalak, Nadeem; Gerber, Markus; Clough, Peter J; Lemola, Sakari; Pühse, Uwe; Holsboer-Trachsler, Edith
2016-06-01
The aim of this study was to explore the association between mental toughness, subjective sleep, physical activity, and quality of life during early and mid-adolescence. A total of 1475 participants (mean age = 13.4 years; range: 11-16 years) took part in the study. They completed questionnaires related to mental toughness, physical activity, subjective sleep, and quality of life. Greater mental toughness was related to more favorable quality of life and increased subjective sleep. Mental toughness was not related to physical activity. Increased mental toughness, favorable quality of life, and sleep are related during early and mid-adolescence. Against our expectations, mental toughness was not related to physical activity. © The Author(s) 2014.
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Family Quality of Life: A Key Outcome in Early Childhood Intervention Services--A Scoping Review
Bhopti, Anoo; Brown, Ted; Lentin, Primrose
2016-01-01
A scoping review was conducted to identify factors influencing the quality of life of families of children with disability. The review also explored the scales used to measure family quality of life (FQOL) as an outcome in early childhood intervention services (ECIS). Multiple databases were searched from 2000 to 2013 to include studies pertinent…
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Directory of Open Access Journals (Sweden)
Carley A Karsten
2013-08-01
Full Text Available Exciting information is emerging about epigenetic mechanisms and their role in long-lasting changes of neuronal gene expression. Whereas these mechanisms are active throughout life, recent findings point to a critical window of early postnatal development during which neuronal gene expression may be persistently re-programmed via epigenetic modifications. However, it remains unclear how the epigenetic machinery is modulated. Here we focus on an important example of early-life programming: the effect of sensory input from the mother on expression patterns of key stress-related genes in the developing brain. We focus on the lasting effects of this early life experience on corticotropin releasing hormone (CRH gene expression in the hypothalamus, and describe recent work that integrates organism-wide signals with cellular signals that in turn impact epigenetic regulation. We describe the operational brain networks that convey sensory input to CRH-expressing cells, and highlight the resulting re-wiring of synaptic connectivity to these neurons. We then move from intercellular to intracellular mechanisms, speculating about the induction and maintenance of lifelong CRH repression provoked by early-life experience. Elucidating such pathways is critical for understanding the enduring links between experience and gene expression. In the context of responses to stress, such mechanisms should contribute to vulnerability or resilience to post-traumatic stress disorder (PTSD and other stress-related disorders.
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Rödel, Heiko G; Starkloff, Anett
2014-10-01
Conditions experienced during early life have been frequently shown to exert long-term consequences on an animal's fitness. In mammals and birds, the time around and shortly after weaning is one of the crucial periods early in life. However, little is known about how social and abiotic environmental conditions experienced around this time affect fitness-related traits such as endoparasite loads. We studied consequences of social interactions and rainy weather conditions around and after weaning on gastro-intestinal nematode loads in juvenile European rabbits Oryctolagus cuniculus. Infestations with the gastric nematode Graphidium strigosum and with the intestinal nematode Passalurus ambiguus were higher in animals experiencing more rain during early life. This might have been due to the higher persistence of nematodes' infective stages outside the host body together with the animals' lower energy allocation for immune defence under more humid and thus energetically challenging conditions. In contrast, infestations with P. ambiguus were lower in animals with more positive social interactions with mother and litter siblings. We propose that social support provided by familiar group members buffered negative stress effects on immune function, lowering endoparasite infestations. This is supported by the negative correlation between positive social behaviour and serum corticosterone concentrations, indicating lower stress in juveniles which integrated more successfully into the social network of their group. In conclusion, the findings offer a pathway showing how differences in the abiotic environment and social life conditions experienced early in life could translate into long-term fitness consequences via the effects on endoparasite loads.
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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.
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Valderrama, Jorge; Miranda, Regina
2017-12-01
The present study examined the interaction between early life stress and 5-HTT genotypes in predicting two risk factors for suicidal behavior - the brooding subtype of rumination and impulsivity, in the form of negative urgency - over time. Furthermore, we examined early life stress, brooding, and impulsivity as predictors of suicidal ideation over time. Participants with and without a history of early life stress were genotyped for the 5-HTTLPR polymorphism and completed assessments assessing brooding and negative urgency at baseline and 6-month follow up. Early life emotional abuse was associated with negative urgency at follow-up. We found an indirect effect of early life emotional abuse on negative urgency through brooding among individuals with 5-HTT low expressing genotypes but not among individuals with 5-HTT high expressing genotypes. Further, a logistic regression analysis revealed that negative urgency was associated with higher odds (O.R. = 16.2) of reporting suicide ideation (versus no ideation) at follow-up. Our findings suggest that brooding and negative urgency may result from the interaction between early life emotional abuse and 5-HTT low expressing genotypes. Further research is necessary to understand how early life stress interacts with 5-HTT genotypes to confer risk for suicidal behavior through psychological mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.
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Energy Technology Data Exchange (ETDEWEB)
Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J., E-mail: Gregory.Czarnota@sunnybrook.ca [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Vorauer, Eric [Department of Medical Physics, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Chin, Lee [Department of Radiation Oncology, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Physics, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Tran, William T. [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Wright, Frances C. [Division of General Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Surgery, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Gandhi, Sonal [Division of Medical Oncology, Sunnybrook Health Sciences Centre, and Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Yaffe, Martin J. [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario M4N 3M5 (Canada)
2015-11-15
Purpose: Changes in textural characteristics of diffuse optical spectroscopic (DOS) functional images, accompanied by alterations in their mean values, are demonstrated here for the first time as early surrogates of ultimate treatment response in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC). NAC, as a standard component of treatment for LABC patient, induces measurable heterogeneous changes in tumor metabolism which were evaluated using DOS-based metabolic maps. This study characterizes such inhomogeneous nature of response development, by determining alterations in textural properties of DOS images apparent at early stages of therapy, followed later by gross changes in mean values of these functional metabolic maps. Methods: Twelve LABC patients undergoing NAC were scanned before and at four times after treatment initiation, and tomographic DOS images were reconstructed at each time. Ultimate responses of patients were determined clinically and pathologically, based on a reduction in tumor size and assessment of residual tumor cellularity. The mean-value parameters and textural features were extracted from volumetric DOS images for several functional and metabolic parameters prior to the treatment initiation. Changes in these DOS-based biomarkers were also monitored over the course of treatment. The measured biomarkers were applied to differentiate patient responses noninvasively and compared to clinical and pathologic responses. Results: Responding and nonresponding patients demonstrated different changes in DOS-based textural and mean-value parameters during chemotherapy. Whereas none of the biomarkers measured prior the start of therapy demonstrated a significant difference between the two patient populations, statistically significant differences were observed at week one after treatment initiation using the relative change in contrast/homogeneity of seven functional maps (0.001 < p < 0.049), and mean value of water
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Huang, Lixing; Gao, Dongxu; Zhang, Youyu; Wang, Chonggang; Zuo, Zhenghong
2014-07-15
Growing evidence indicates that polycyclic aromatic hydrocarbons (PAHs) can lead to cardiac hypertrophy and recent research indicates that exposure to low dose crude oil during early embryonic development may lead to impacts on heart health at later life stages. The aim of this study was to evaluate whether exposure during early life stages to low dose benzo[a]pyrene (BaP), as a high-ring PAH, would lead to cardiac hypertrophy at later life stages. Zebrafish were exposed to low dose BaP until 96 hpf, then transferred to clean water and maintained for a year before histological and molecular biological analysis. Our results showed that exposure to low level BaP during early life stages increased heart weight to body weight ratios and deposited collagen in the heart of adult zebrafish. ANP, BNP and c-Myc were also induced in the heart of adult zebrafish by BaP. These results proved that low level BaP exposure during early life stages caused symptoms similar to cardiac hypertrophy in adult zebrafish. Our results displayed an elevated expression of CdC42, RhoA, p-ERK1, 2 and Rac1. Therefore, the mechanism of the cardiac hypertrophy caused by BaP exposure during early life stages may be through inducing the expression of CdC42, RhoA and Rac1, together with activating ERK1, 2. Copyright © 2014 Elsevier B.V. All rights reserved.
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Life satisfaction of women in early stages of fertility treatment.
Ben Shlomo, Shirley; Pascal, Mor; Taubman Ben-Ari, Orit; Azuri, Yoseph; Horowtz, Eran
2017-01-01
As many women perceive motherhood to be a central component of identity that enhances life satisfaction, difficulties conceiving may lead to stress. This study examined women in the early stages of fertility treatment to ascertain the relations of perceived stress, cognitive appraisal, and self-mastery to the life satisfaction of women embarking on fertility treatment and whether the associations were the same for women who were already mothers versus those who were not. Women were recruited for the study over a period of 18 months, from January 2013 to June 2014. The final sample was composed of 145 women; of these, 67 had 1 or 2 children and 78 had no children. No significant differences were found in perceived stress and life satisfaction between women with and without children. However, in the sample as a whole, higher levels of self-mastery and lower levels of stress were associated with greater life satisfaction. Moreover, the associations between self-mastery and cognitive appraisals of threat and self-efficacy were mediated by perceived stress. The findings highlight the importance of developing interventions at fertility clinics that begin at the very first point of contact to promote the psychological well-being of women being treated for infertility.
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COMPENSATORY GROWTH AND FAT PARAMETERS ON BROILER FASTED IN EARLY LIFE
Directory of Open Access Journals (Sweden)
S. Sugiharto
2014-10-01
Full Text Available The experiment was carried out to investigate the effect of feed withholding in the very early life ofbird on its compensatory growth capacity and fat parameters. A total of 60 mixed-sexes of one day oldRoss chicks were used in the experiment conducted with completely randomized design of 2 differentfeeding times after hatching, i.e.: T1: given access to feed and water ad libitum immediately afterhatching until 35d of age; and T2: withheld from feed (fasted but not from water for 48h after hatchingand then fed ad libitum until d35. The birds were weighed at the start of experiment and weeklythereafter, and DWG was then calculated. Feed intakes and FCR were also recorded weekly. At d36,abdominal fat was taken out from 2 birds per pen and was weighed. Breast meat (skinless from thesame birds was also sampled for total FA analysis. Final BW (d35 and total feed consumption of earlyfastedbirds were 1935.17±43.90 kg and 2745.55±47.48 kg and those of unfasted birds were2019.00±50.85 kg and 2910.84±128.10 kg, respectively. FCR of early-fasted and unfasted birds at d35were 1.42±0.03 and 1.45±0.07. The magnitude difference of DWG between early-fasted and unfastedbirds was 27% at d7, whereas at d35 the difference was only 4.5%. Abdominal fat percentage to live BWof early-fasted birds was 1.65±0.09% (male and 1.60±0.10% (female and that of unfasted birds was2.00±0.19% (male and 1.89±0.38% (female. Total FA contained in meat of early-fasted and unfastedbirds were 0.82±0.10 and 0.85±0.10 g/100gDM. Overall, BW and feed consumption of early-fastedbirds were significantly lower (P<0.05 than unfasted birds. DWG, FCR, abdominal fat and total FAcontained in meat were not significantly different (P>0.05 between early-fasted and unfasted birds. Inconclusion, holding birds without feed following hatch (under practical conditions may limit thecompensatory growth capacity of birds in the later age. Fasting applied in the very early life of broilerleads to
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Early-life sensitization to hen's egg predicts asthma and rhinoconjunctivitis at 14 years of age
DEFF Research Database (Denmark)
Christiansen, Elisabeth Soegaard; Kjaer, Henrik Fomsgaard; Eller, Esben
2017-01-01
to groups of and to individual allergens and asthma and RC at 6 and 14 years compared to a reference group with no sensitization. RESULTS: Both transient and persistent early-life sensitization to cow's milk or hen's egg proteins were associated with asthma (aOR 3.99(1.41-11.32) and 5.95(1.78-19.92)) and RC...... (aOR 2.94(1.19-7.28) and 6.18(1.86-20.53)) at 14 years, this association being driven mainly by sensitization to hen's egg. Transient early-life sensitization to HDM had increased risk of asthma (aOR 3.80(1.17-12.41)) at 14 years. CONCLUSIONS: Early transient and persistent IgE sensitization to hen......'s egg was associated with asthma and RC at 14 years. Furthermore, sensitization to HDM was associated with asthma at 14 years. This article is protected by copyright. All rights reserved....
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Molina, Danielle K.
2016-01-01
Emergency response is an essential function of all residential life staff, but particularly for resident assistants serving on the front line. This organizational ethnography examined the role that professional identity played for early-career residential life practitioners engaged in emergency management. The data elucidated heroism as a…
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Does adversity early in life affect general population suicide rates? a cross-national study
Ritesh Bhandarkar; Ajit Shah
2011-01-01
Abstract: Background: 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. Methods: 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. Results: General population suicide rates were negatively correlated with the pe...
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Early life risk factors for testicular cancer
DEFF Research Database (Denmark)
Piltoft, Johanne Spanggaard; Larsen, Signe Benzon; Dalton, Susanne Oksbjerg
2017-01-01
of this study is to utilize data from the Copenhagen School Health Records Register (CSHRR) to evaluate cryptorchidism, birth weight and birth order as risk factors for testicular cancer. METHODS: The study population consisted of 408 cases of testicular cancer identified by a government issued identification...... in crude analyses [hazard ratio (HR) = 3.60, 95% CI 2.79-4.65]. Birth weight was inversely associated with testicular cancer and no clear association with birth order was observed. The positive association between cryptorchidism and testicular cancer was only slightly attenuated controlling for birth......PURPOSE: One established risk factors for testicular cancer is cryptorchidism. However, it remains unclear whether cryptorchidism is a risk factor in itself or whether the two conditions share common causes in early life (estrogen hypothesis), such as birth weight and birth order. The objective...
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Early life innate immune signatures of persistent food allergy.
Neeland, Melanie R; Koplin, Jennifer J; Dang, Thanh D; Dharmage, Shyamali C; Tang, Mimi L; Prescott, Susan L; Saffery, Richard; Martino, David J; Allen, Katrina J
2017-11-14
Food allergy naturally resolves in a proportion of food-allergic children without intervention; however the underlying mechanisms governing the persistence or resolution of food allergy in childhood are not understood. This study aimed to define the innate immune profiles associated with egg allergy at age 1 year, determine the phenotypic changes that occur with the development of natural tolerance in childhood, and explore the relationship between early life innate immune function and serum vitamin D. This study used longitudinally collected PBMC samples from a population-based cohort of challenge-confirmed egg-allergic infants with either persistent or transient egg allergy outcomes in childhood to phenotype and quantify the functional innate immune response associated with clinical phenotypes of egg allergy. We show that infants with persistent egg allergy exhibit a unique innate immune signature, characterized by increased numbers of circulating monocytes and dendritic cells that produce more inflammatory cytokines both at baseline and following endotoxin exposure when compared with infants with transient egg allergy. Follow-up analysis revealed that this unique innate immune signature continues into childhood in those with persistent egg allergy and that increased serum vitamin D levels correlate with changes in innate immune profiles observed in children who developed natural tolerance to egg. Early life innate immune dysfunction may represent a key immunological driver and predictor of persistent food allergy in childhood. Serum vitamin D may play an immune-modulatory role in the development of natural tolerance. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Lidyane V Camelo
Full Text Available BACKGROUND: Chronic inflammation has been postulated to be one mediating mechanism explaining the association between low socioeconomic position (SEP and cardiovascular disease (CVD. We sought to examine the association between life course SEP and C-reactive protein (CRP levels in adulthood, and to evaluate the extent to which health-risk behaviors and metabolic alterations mediate this association. Additionally, we explored the possible modifying influence of gender. METHODS AND FINDINGS: Our analytical sample comprised 13,371 participants from ELSA-Brasil baseline, a multicenter prospective cohort study of civil servants. SEP during childhood, young adulthood, and adulthood were considered. The potential mediators between life course SEP and CRP included clusters of health-risk behaviors (smoking, low leisure time physical activity, excessive alcohol consumption, and metabolic alterations (obesity, hypertension, low HDL, hypertriglyceridemia, and diabetes. Linear regression models were performed and structural equation modeling was used to evaluate mediation. Although lower childhood SEP was associated with higher levels of CRP in adult life, this association was not independent of adulthood SEP. However, CRP increased linearly with increasing number of unfavorable social circumstances during the life course (p trend <0.001. The metabolic alterations were the most important mediator between cumulative SEP and CRP. This mediation path accounted for 49.5% of the total effect of cumulative SEP on CRP among women, but only 20.2% among men. In consequence, the portion of the total effect of cumulative SEP on CRP that was mediated by risk behaviors and metabolic alterations was higher among women (55.4% than among men (36.8%. CONCLUSIONS: Cumulative SEP across life span was associated with elevated systemic inflammation in adulthood. Although health-risk behaviors and metabolic alterations were important mediators of this association, a sizable
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Lesuis, S.L.; Maurin, H.; Borghgraef, P.; Lucassen, P.J.; Van Leuven, F.; Krugers, H.J.
2016-01-01
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
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Development of the cortisol circadian rhythm in the light of stress early in life.
Simons, Sterre S H; Beijers, Roseriet; Cillessen, Antonius H N; de Weerth, Carolina
2015-12-01
The secretion of the stress hormone cortisol follows a diurnal circadian rhythm. There are indications that this rhythm is affected by stress early in life. This paper addresses the development of the cortisol circadian rhythm between 1 and 6 years of age, and the role of maternal stress and anxiety early in the child's life on this (developing) rhythm. Participants were 193 healthy mother-child dyads from a community sample. Self-reported maternal stress and anxiety and physiological stress (saliva cortisol), were assessed prenatally (gestational week 37). Postnatally, self-reported maternal stress and anxiety were measured at 3, 6, 12, 30, and 72 months. Saliva cortisol samples from the children were collected on two days (four times each day) at 12, 30, and 72 months of age. The total amount of cortisol during the day and the cortisol decline over the day were determined to indicate children's cortisol circadian rhythm. Multilevel analyses showed that the total amount of cortisol decreased between 1 and 6 years. Furthermore, more maternal pregnancy-specific stress was related to higher total amounts of cortisol in the child. Higher levels of early postnatal maternal anxiety were associated with flatter cortisol declines in children. Higher levels of early postnatal maternal daily hassles were associated with steeper child cortisol declines over the day. These results indicated developmental change in children's cortisol secretion from 1 to 6 years and associations between maternal stress and anxiety early in children's lives and children's cortisol circadian rhythm in early childhood. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Neural Basis of Brain Dysfunction Produced by Early Sleep Problems
Directory of Open Access Journals (Sweden)
Jun Kohyama
2016-01-01
Full Text Available There is a wealth of evidence that disrupted sleep and circadian rhythms, which are common in modern society even during the early stages of life, have unfavorable effects on brain function. Altered brain function can cause problem behaviors later in life, such as truancy from or dropping out of school, quitting employment, and committing suicide. In this review, we discuss findings from several large cohort studies together with recent results of a cohort study using the marshmallow test, which was first introduced in the 1960s. This test assessed the ability of four-year-olds to delay gratification and showed how this ability correlated with success later in life. The role of the serotonergic system in sleep and how this role changes with age are also discussed. The serotonergic system is involved in reward processing and interactions with the dorsal striatum, ventral striatum, and the prefrontal cortex are thought to comprise the neural basis for behavioral patterns that are affected by the quantity, quality, and timing of sleep early in life.
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Neural Basis of Brain Dysfunction Produced by Early Sleep Problems.
Kohyama, Jun
2016-01-29
There is a wealth of evidence that disrupted sleep and circadian rhythms, which are common in modern society even during the early stages of life, have unfavorable effects on brain function. Altered brain function can cause problem behaviors later in life, such as truancy from or dropping out of school, quitting employment, and committing suicide. In this review, we discuss findings from several large cohort studies together with recent results of a cohort study using the marshmallow test, which was first introduced in the 1960s. This test assessed the ability of four-year-olds to delay gratification and showed how this ability correlated with success later in life. The role of the serotonergic system in sleep and how this role changes with age are also discussed. The serotonergic system is involved in reward processing and interactions with the dorsal striatum, ventral striatum, and the prefrontal cortex are thought to comprise the neural basis for behavioral patterns that are affected by the quantity, quality, and timing of sleep early in life.
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DEFF Research Database (Denmark)
Seitzberg, A.; Lind, M.; Biering-Sørensen, Fin
2008-01-01
OBJECTIVE: The objective of this study was to evaluate the prediction of ambulation in adults with myelomeningocele from muscle strength testing and ambulation in early life. MATERIALS AND METHODS: Fifty-two myelomeningocele (MMC) individuals at the age 18-37 years at follow-up were studied....... Information on muscle strength and ambulatory function in early life was retrieved from medical records. The motor levels determined by the muscle strength were used to predict ambulatory function later in life. At follow-up, a clinical examination was performed. RESULTS: Of 20 MMC individuals assessed...... life than predicted. Good strength in quadriceps muscles gave significant better prospect for adult walking. Of the 52 participants, 41 retained their ambulation status from 5-8 years of age. CONCLUSION: For MMC individuals with motor levels L3-L5, adult ambulatory function cannot be determined from...
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Toxicity of crude oil to early life stages of two fish species
Energy Technology Data Exchange (ETDEWEB)
Clarke, L.M.; Hodson, P.V. [Queen' s Univ., Kingston, ON (Canada). Dept. of Biology; Brown, R.S. [Queen' s Univ., Kingston, ON (Canada). Dept. of Chemistry; King, T.; Lee, K. [Department of Fisheries and Oceans, Dartmouth, NS (Canada). Bedford Inst. of Oceanography
2004-07-01
Fish exposed to crude oil in their early life stages exhibit signs of dioxin-like toxicity which is linked to the presence of alkyl-substituted polycyclic aromatic hydrocarbons (PAHs). Exposure is characterized by the presence of blue-sac disease which manifests itself in edema, hemorrhaging, deformities and induction of CYP1A enzymes. In this study, the extent of CYP1A induction and BSD was compared in the early life stages of rainbow trout and Japanese medaka following exposure to two crude oils (Scotian Shelf and Alaskan North Slope Crude). Embryos were exposed to a broad range of concentrations of chemically enhanced water fractions of both oils which have unique PAH composition and chemical characteristics. It was assumed that Alaskan North Slope Crude would be more toxic than Scotian Shelf because it has a higher PAH concentration. The occurrence and severity of BSD was characterized along with the extent of PAH exposure. Preliminary results confirm that PAH exposure is greater for Alaskan North Slope Crude and that the responses of the two fish species were highly correlated.
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Early-life stage fish can be more sensitive to chemical exposure than adult fish. Therefore, determining possible adverse outcome pathways (AOPs) for early-life stages is crucial. To determine chemical effects and/or mechanisms of action in exposed fish embryos and larvae, whole-...
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Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...
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de Medina, Philippe
2017-11-01
Aging is a progressive internal physiological deterioration of the organism, leading to the occurrence of age-related lethal diseases. It has become a major societal challenge to understand the processes that drive aging and to develop rational pharmacological agents and dietary approaches to fight against age-related deterioration and diseases. Interestingly, several lines of evidence highlight an influence of the developmental period on the risk of age-related diseases later in life. This field is known as the developmental origins of health and disease. Following this logic, studying the modification of maternal diet during early life may provide innovative new anti-aging approaches. Nutritional and psychological stresses during gestation are associated with poorer offspring health conditions in late life, and must be avoided during pregnancy. Besides these recommendations, very little has been published about the possible use of maternal diet to program offspring for healthy aging and an extended lifespan. Such health benefits may be provided by different foreign molecules, and particularly the phytochemicals produced by stressed plants, or xenohormetins. The xenohormesis hypothesis proposes that xenohormetins are signals of environmental change and trigger a beneficial adaptive response in individuals who consume them. No studies to date have investigated whether the consumption of stressed plants during pregnancy and lactation could provide chemical cues that impact early life programming and thus influence the future health and lifespan of offspring. Investigating the effect of xenohormesis in early life will involve adding edible plants exposed to different stressors (i.e. UV light, heat, ozone, etc.) to maternal diet and the exposure of offspring to this xenohormetin-enriched maternal diet at different periods of their prenatal life. The hypothesis proposed in this article is a potential tool to decipher the possible impact of xenohormesis during early
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Early life exposure to China's 1959-61 famine and midlife cognition.
Xu, Hongwei; Zhang, Zhenmei; Li, Lydia; Liu, Jinyu
2018-02-01
Existing studies of the 1944-45 Dutch famine found little evidence of the association between early life malnutrition and midlife cognition. Among 2446 rural participants born between 1958 and 1963 in the China Health and Retirement Longitudinal Study, we examined effects of exposure to China's 1959-61 Great Leap Forward famine during prenatal and early postnatal life, on four cognitive measures in 2011 (baseline) and changes in cognition between 2011 and 2013 (first follow-up). We obtained difference-in-differences (DID) estimates of the famine effects by exploiting temporal variation in the timing and duration of famine exposure across six birth cohorts born between 1958 and 1963, together with geographical variation in famine severity at the prefecture level. After adjusting for gender, marital status and provincial fixed effects, we found that the 1961 cohort who experienced full-term prenatal and partial-term postnatal exposures to famine had lower scores on the Telephone Interview of Cognitive Status (TICS), a test of drawing pentagons, and general cognition at age 50 years compared with the unexposed 1963 cohort. Adjusting for education, the famine effects on drawing pentagons and general cognition were fully attenuated, but the effect on TICS persisted. We also found a robust negative famine effect on the longitudinal change in general cognition during the 2-year follow-up in the 1959 cohort. Severe nutritional deprivation during prenatal and postnatal periods has a lasting impact on cognitive performance in Chinese adults in their early 50s. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association
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Sex and strain modify antioxidant response to early life ozone exposure in rats.
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...
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Effect of early-life gut mucosal compromise on disease progression in NOD mice
DEFF Research Database (Denmark)
Bendtsen, Katja M.; Hansen, Camilla HF; Krych, Lukasz
2017-01-01
Disease expression in spontaneous nonobese diabetic (NOD) mice depends on environmental stimuli such as stress, diet, and gut microbiota composition. We evaluated a brief, early-life gut intervention in which pups were weaned to low-dose dextran sulfate sodium (DSS). We hypothesized that the mucus...
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Early-Life Exposure to the Great Smog of 1952 and the Development of Asthma.
Bharadwaj, Prashant; Zivin, Joshua Graff; Mullins, Jamie T; Neidell, Matthew
2016-12-15
Little is known about the long-term effects of air pollution exposure and the root causes of asthma. We use exposure to intense air pollution from the 1952 Great Smog of London as a natural experiment to examine both issues. To determine whether exposure to extreme air pollution in utero or soon after birth affects asthma development later in life. This was a natural experiment using the unanticipated pollution event by comparing the prevalence of asthma between those exposed to the Great Smog in utero or the first year of life with those conceived well before or after the incident and those residing outside the affected area at the time of the smog. Prevalence of asthma during childhood (ages 0-15) and adulthood (ages >15) is analyzed for 2,916 respondents to the Life History portion of the English Longitudinal Study on Aging born from 1945 to 1955. Exposure to the Great Smog in the first year of life increases the likelihood of childhood asthma by 19.87 percentage points (95% confidence interval [CI], 3.37-36.38). We also find suggestive evidence that early-life exposure led to a 9.53 percentage point increase (95% CI, -4.85 to 23.91) in the likelihood of adult asthma and exposure in utero led to a 7.91 percentage point increase (95% CI, -2.39 to 18.20) in the likelihood of childhood asthma. These results are the first to link early-life pollution exposure to later development of asthma using a natural experiment, suggesting the legacy of the Great Smog is ongoing.
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Zigdon, Hila; Meshcheriakova, Anna; Farfel-Becker, Tamar; Volpert, Giora; Sabanay, Helena; Futerman, Anthony H
2017-03-01
In the lysosomal storage disorder Gaucher disease (GD), glucosylceramide (GlcCer) accumulates due to the defective activity of glucocerebrosidase. A subset of GD patients develops neuropathology. We now show mislocalization of Limp2-positive puncta and a large reduction in the number of Lamp1-positive puncta, which are associated with impaired tubulin. These changes occur at an early stage in animal models of GD, prior to development of overt symptoms and considerably earlier than neuronal loss. Altered lysosomal localization and cytoskeleton disruption precede the neuroinflammatory pathways, axonal dystrophy and neuronal loss previously characterized in neuronal forms of GD. © 2017 Federation of European Biochemical Societies.
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Fischer, Jessica; Schoppmann, Kathrin; Laforsch, Christian
2017-06-01
Manned space missions, as for example to the planet Mars, are a current objective in space exploration. During such long-lasting missions, aquatic bioregenerative life support systems (BLSS) could facilitate independence of resupply from Earth by regenerating the atmosphere, purifying water, producing food and processing waste. In such BLSS, microcrustaceans could, according to their natural role in aquatic ecosystems, link oxygen liberating, autotrophic algae and higher trophic levels, such as fish. However, organisms employed in BLSS will be exposed to high acceleration (hyper- g) during launch of spacecrafts as well as to microgravity (μ g) during space travel. It is thus essential that these organisms survive, perform and reproduce under altered gravity conditions. In this study we present the first data in this regard for the microcrustaceas Daphnia magna and Heterocypris incongruens. We found that after hyper- g exposure (centrifugation) approximately one third of the D. magna population died within one week (generally indicating that possible belated effects have to be considered when conducting and interpreting experiments during which hyper- g occurs). However, suchlike and even higher losses could be countervailed by the surviving daphnids' unaltered high reproductive capacity. Furthermore, we can show that foraging and feeding behavior of D. magna (drop tower) and H. incongruens (parabolic flights) are rarely altered in μ g. Our results thus indicate that both species are suitable candidates for BLSS utilized in space.
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Eitle, David; Taylor, John; Pih, Kay Kei-ho
2010-01-01
Few studies exploring the association between adolescent self-esteem and crime have considered whether the early adolescent self-esteem has any enduring consequences for young adult crime. Inspired by the life course and developmental criminology approaches, Arnett's notion of emerging adulthood, and Kaplan's self-derogation theory, this article…
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Wielinga, P.Y.; Harthoorn, L.F.; Verschuren, L.; Schoemaker, M.H.; Jouni, Z.E.; Tol, E.A.F. van; Kleemann, R.; Kooistra, T.
2012-01-01
Scope: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic
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Low-grade disease activity in early life precedes childhood asthma and allergy.
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
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Holman, Dawn M.; Buchanan, Natasha D.
2018-01-01
Compelling evidence suggests that early life exposures can affect lifetime cancer risk. In 2014, the Centers for Disease Control and Prevention’s (CDC’s) Cancer Prevention Across the Lifespan Workgroup hosted a series of virtual meetings with select experts to discuss the state of the evidence linking factors during the prenatal period and early childhood to subsequent risk of both pediatric and adult cancers. In this article, we present the results from a qualitative analysis of the meeting transcripts and summarize themes that emerged from our discussions with meeting participants. Themes included the state of the evidence linking early life factors to cancer risk, research gaps and challenges, the level of evidence needed to support taking public health action, and the challenges of communicating complex, and sometimes conflicting, scientific findings to the public. Opportunities for collaboration among public health agencies and other stakeholders were identified during these discussions. Potential next steps for the CDC and its partners included advancing and building upon epidemiology and surveillance work, developing and using evidence from multiple sources to inform decision-making, disseminating and communicating research findings in a clear and effective way, and expanding collaborations with grantees and other partners. As the science on early life factors and cancer risk continues to evolve, there are opportunities for collaboration to translate science into actionable public health practice. PMID:27940972
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Guilarte, Tomás R; Opler, Mark; Pletnikov, Mikhail
2012-06-01
Schizophrenia is a devastating neuropsychiatric disorder of unknown etiology. There is general agreement in the scientific community that schizophrenia is a disorder of neurodevelopmental origin in which both genes and environmental factors come together to produce a schizophrenia phenotype later in life. The challenging questions have been which genes and what environmental factors? Although there is evidence that different chromosome loci and several genes impart susceptibility for schizophrenia; and epidemiological studies point to broad aspects of the environment, only recently there has been an interest in studying gene × environment interactions. Recent evidence of a potential association between prenatal lead (Pb(2+)) exposure and schizophrenia precipitated the search for plausible neurobiological connections. The most promising connection is that in schizophrenia and in developmental Pb(2+) exposure there is strong evidence for hypoactivity of the N-methyl-d-aspartate (NMDA) subtype of excitatory amino acid receptors as an underlying neurobiological mechanism in both conditions. A hypofunction of the NMDA receptor (NMDAR) complex during critical periods of development may alter neurobiological processes that are essential for brain growth and wiring, synaptic plasticity and cognitive and behavioral outcomes associated with schizophrenia. We also describe on-going proof of concept gene-environment interaction studies of early life Pb(2+) exposure in mice expressing the human mutant form of the disrupted in schizophrenia 1 (DISC-1) gene, a gene that is strongly associated with schizophrenia and allied mental disorders. Copyright © 2011 Elsevier Inc. All rights reserved.
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Guilarte, Tomás R.; Opler, Mark; Pletnikov, Mikhail
2013-01-01
Schizophrenia is a devastating neuropsychiatric disorder of unknown etiology. There is general agreement in the scientific community that schizophrenia is a disorder of neurodevelopmental origin in which both genes and environmental factors come together to produce a schizophrenia phenotype later in life. The challenging questions have been which genes and what environmental factors? Although there is evidence that different chromosome loci and several genes impart susceptibility for schizophrenia; and epidemiological studies point to broad aspects of the environment, only recently there has been an interest in studying gene × environment interactions. Recent evidence of a potential association between prenatal lead (Pb2+) exposure and schizophrenia precipitated the search for plausible neurobiological connections. The most promising connection is that in schizophrenia and in developmental Pb2+ exposure there is strong evidence for hypoactivity of the N-methyl-d-aspartate (NMDA) subtype of excitatory amino acid receptors as an underlying neurobiological mechanism in both conditions. A hypofunction of the NMDA receptor (NMDAR) complex during critical periods of development may alter neurobiological processes that are essential for brain growth and wiring, synaptic plasticity and cognitive and behavioral outcomes associated with schizophrenia. We also describe on-going proof of concept gene-environment interaction studies of early life Pb2+ exposure in mice expressing the human mutant form of the disrupted in schizophrenia 1 (DISC-1) gene, a gene that is strongly associated with schizophrenia and allied mental disorders. PMID:22178136
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Early-life bisphenol a exposure and child body mass index: a prospective cohort study.
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.
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Directory of Open Access Journals (Sweden)
Claudia Börnhorst
Full Text Available 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.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.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.Early life factors seem to explain only some of the inter-country variation in growth. Maternal BMI showed the strongest association
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The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats
Directory of Open Access Journals (Sweden)
Lu-jing Chen
2014-01-01
Full Text Available 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.
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The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats
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
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Early Life Factors, Obesity Risk, and the Metabolome of Young Adults.
Rauschert, Sebastian; Mori, Trevor A; Beilin, Lawrence J; Jacoby, Peter; Uhl, Olaf; Koletzko, Berthold; Oddy, Wendy H; Hellmuth, Christian
2017-09-01
Noncommunicable diseases such as obesity have become a serious global public health epidemic. This study aimed to examine whether there was an association between early life factors (with a special focus on breastfeeding) BMI, waist circumference, and the metabolome in offspring at 20 years. Data from the Western Australian Pregnancy Cohort (Raine) Study were analyzed using 1,024 plasma samples from the 20-year follow-up. A liquid chromatography, tandem mass spectrometry metabolomics approach was used to measure metabolites. Multiple linear regression models were performed and adjusted for relevant confounders. Inverse probability weighting was used to adjust the 20-year data for differences in socioeconomic variables between participants and nonparticipants since the commencement of the study. An inverse association between breastfeeding and BMI or waist circumference at 20 years was lost after adjusting for parental prepregnancy BMI and maternal smoking during pregnancy. There was no significant effect of breastfeeding on metabolite concentrations at 20 years. Although other studies have shown associations between breastfeeding, obesity, and metabolite concentrations at younger ages, this was not evident in our study in young adults. We found no association of metabolites previously associated with waist circumference at 20 years and breastfeeding in early life. © 2017 The Obesity Society.
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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.
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Pomilio, Carlos; Pavia, Patricio; Gorojod, Roxana Mayra; Vinuesa, Angeles; Alaimo, Agustina; Galvan, Veronica; Kotler, Monica Lidia; Beauquis, Juan; Saravia, Flavia
2016-02-01
Alzheimer's disease (AD) is a progressive neurodegenerative disease without effective therapy. Brain amyloid deposits are classical histopathological hallmarks that generate an inflammatory reaction affecting neuronal and glial function. The identification of early cell responses and of brain areas involved could help to design new successful treatments. Hence, we studied early alterations of hippocampal glia and their progression during the neuropathology in PDAPP-J20 transgenic mice, AD model, at 3, 9, and 15 months (m) of age. At 3 m, before deposits formation, microglial Iba1+ cells from transgenic mice already exhibited signs of activation and larger soma size in the hilus, alterations appearing later on stratum radiatum. Iba1 immunohistochemistry revealed increased cell density and immunoreactive area in PDAPP mice from 9 m onward selectively in the hilus, in coincidence with prominent amyloid Congo red + deposition. At pre-plaque stages, GFAP+ astroglia showed density alterations while, at an advanced age, the presence of deposits was associated with important glial volume changes and apparently being intimately involved in amyloid degradation. Astrocytes around plaques were strongly labeled for LC3 until 15 m in Tg mice, suggestive of increased autophagic flux. Moreover, β-Amyloid fibrils internalization by astrocytes in in vitro conditions was dependent on autophagy. Co-localization of Iba1 with ubiquitin or p62 was exclusively found in microglia contacting deposits from 9 m onward, suggesting torpid autophagy. Our work characterizes glial changes at early stages of the disease in PDAPP-J20 mice, focusing on the hilus as an especially susceptible hippocampal subfield, and provides evidence that glial autophagy could play a role in amyloid processing at advanced stages. © 2015 Wiley Periodicals, Inc.
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Gori, Andrea; Tincati, Camilla; Rizzardini, Giuliano; Torti, Carlo; Quirino, Tiziana; Haarman, Monique; Ben Amor, Kaouther; van Schaik, Jacqueline; Vriesema, Aldwin; Knol, Jan; Marchetti, Giulia; Welling, Gjalt; Clerici, Mario
Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the
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Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar
2018-06-01
TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain
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Xu, Lanlan; Peng, Xiao; Yu, Deliang; Ji, Chenglong; Zhao, Jianmin; Wu, Huifeng
2016-08-01
Cadmium (Cd) has become an important metal contaminant and posed severe risk on the organisms in the coastal environments of the Bohai Sea. Marine mussel Mytilus galloprovincialis is widely distributed along the Bohai coast and consumed as seafood by local residents. Evidences indicate that the early stages of marine organisms are more sensitive to metal contaminants. In this study, we applied two-dimensional electrophoresis-based proteomics to characterize the biological effects of Cd (50 μg L(-1)) in the early life stages (D-shape larval and juvenile) of mussels. The different proteomic responses demonstrated the differential responsive mechanisms to Cd exposure in these two early life stages of mussels. In details, results indicated that Cd mainly induced immune and oxidative stresses in both D-shape larval and juvenile mussels via different pathways. In addition, the significant up-regulation of triosephosphate isomerase and metallothionein confirmed the enhanced energy demand and mobilized detoxification mechanism in D-shape larval mussels exposed to Cd. In juvenile mussels, Cd exposure also induced clear apoptosis. Overall, this work suggests that Cd is a potential immune toxicant to mussel M. galloprovincialis at early life stages. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Body size in early life and risk of breast cancer.
Shawon, Md Shajedur Rahman; Eriksson, Mikael; Li, Jingmei
2017-07-21
Body size in early life is inversely associated with adult breast cancer (BC) risk, but it is unclear whether the associations differ by tumor characteristics. In a pooled analysis of two Swedish population-based studies consisting of 6731 invasive BC cases and 28,705 age-matched cancer-free controls, we examined the associations between body size in early life and BC risk. Self-reported body sizes at ages 7 and 18 years were collected by a validated nine-level pictogram (aggregated into three categories: small, medium and large). Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated from multivariable logistic regression models in case-control analyses, adjusting for study, age at diagnosis, age at menarche, number of children, hormone replacement therapy, and family history of BC. Body size change between ages 7 and 18 were also examined in relation to BC risk. Case-only analyses were performed to test whether the associations differed by tumor characteristics. Medium or large body size at age 7 and 18 was associated with a statistically significant decreased BC risk compared to small body size (pooled OR (95% CI): comparing large to small, 0.78 (0.70-0.86), P trend <0.001 and 0.72 (0.64-0.80), P trend <0.001, respectively). The majority of the women (~85%) did not change body size categories between age 7 and 18 . Women who remained medium or large between ages 7 and 18 had significantly decreased BC risk compared to those who remained small. A reduction in body size between ages 7 and 18 was also found to be inversely associated with BC risk (0.90 (0.81-1.00)). No significant association was found between body size at age 7 and tumor characteristics. Body size at age 18 was found to be inversely associated with tumor size (P trend = 0.006), but not estrogen receptor status and lymph node involvement. For all analyses, the overall inferences did not change appreciably after further adjustment for adult body mass index. Our data
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Zinc in Early Life: A Key Element in the Fetus and Preterm Neonate
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
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White-Schwoch, Travis; Woodruff Carr, Kali; Anderson, Samira; Strait, Dana L; Kraus, Nina
2013-11-06
Aging results in pervasive declines in nervous system function. In the auditory system, these declines include neural timing delays in response to fast-changing speech elements; this causes older adults to experience difficulty understanding speech, especially in challenging listening environments. These age-related declines are not inevitable, however: older adults with a lifetime of music training do not exhibit neural timing delays. Yet many people play an instrument for a few years without making a lifelong commitment. Here, we examined neural timing in a group of human older adults who had nominal amounts of music training early in life, but who had not played an instrument for decades. We found that a moderate amount (4-14 years) of music training early in life is associated with faster neural timing in response to speech later in life, long after training stopped (>40 years). We suggest that early music training sets the stage for subsequent interactions with sound. These experiences may interact over time to sustain sharpened neural processing in central auditory nuclei well into older age.
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Penile alterations at early stage of type 1 diabetes in rats
Directory of Open Access Journals (Sweden)
Mingfang Tao
Full Text Available ABSTRACT Objective Diabetes affects the erectile function significantly. However, the penile alterations in the early stage of diabetes in experimental animal models have not been well studied. We examined the changes of the penis and its main erectile components in diabetic rats. Materials and methods Male Sprague-Dawley rats were divided into 2 groups: streptozotocin (STZ-induced diabetics and age-matched controls. Three or nine weeks after diabetes induction, the penis was removed for immunohistochemical staining of smooth muscle and neuronal nitric oxide synthase (nNOS in midshaft penile tissues. The cross-sectional areas of the whole midshaft penis and the corpora cavernosa were quantified. The smooth muscle in the corpora cavernosa and nNOS in the dorsal nerves were quantified. Results The weight, but not the length, of the penis was lower in diabetics. The cross-sectional areas of the total midshaft penis and the corpora cavernosa were lower in diabetic rats compared with controls 9 weeks, but not 3 weeks after diabetes induction. The cross-sectional area of smooth muscle in the corpora cavernosa as percentage of the overall area of the corpora cavernosa was lower in diabetic rats than in controls 9 weeks, but not 3 weeks after diabetes induction. Percentage change of nNOS in dorsal nerves was similar at 3 weeks, and has a decreased trend at 9 weeks in diabetic rats compared with controls. Conclusions Diabetes causes temporal alterations in the penis, and the significant changes in STZ rat model begin 3-9 weeks after induction. Further studies on the reversibility of the observed changes are warranted.
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Doyle, Miriam J.; Mier, Kathryn L.
2016-10-01
A synthesis of nearly four decades of ichthyoplankton survey data from the Gulf of Alaska was undertaken to provide the most comprehensive information available on the early life history ecology of five focal species: Pacific Cod (Gadus macrocephalus), Walleye Pollock (Gadus chalcogrammus), Pacific Ocean Perch (Sebastes alutus), Sablefish (Anoplopoma fimbria), and Arrowtooth Flounder (Atheresthes stomias). This analysis of historical data, along with information from published studies, is presented here in the form of ecological reviews of the species during their planktonic phase. The reviews include descriptions of temporal and spatial patterns of exposure to the environment, and interpretation regarding associated sensitivities to environmental forcing. On a temporal scale, patterns in abundance of eggs and larvae are synthesized that characterize seasonal exposure to the pelagic environment, and interannual variation that is presumed to incorporate responses to long-term environmental forcing. Spatial patterns are synthesized to identify horizontal and vertical extent of egg and larval distributions, delineate areas of primary larval habitat, and illuminate egg and larval drift pathways. The observed patterns are discussed with respect to characterizing species early life history strategies, identifying long-term adaptations to the Gulf of Alaska environment, and associated resilience and vulnerability factors that may modulate early life responses to environmental forcing in this region. For each species, gaps in knowledge are identified and are concerned primarily with the period of transition between the larval and juvenile stage, and feeding habits and ecology across seasons, habitats and sub-intervals of early ontogeny. These early life history reviews advance our ecological understanding of the pelagic phase, and fine-tune our focus for the investigation of potential response mechanisms to environmental forcing at appropriate, species-specific temporal
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LaVigne, M.; Hill, T. M.; Sanford, E.; Gaylord, B.; Russell, A. D.; Lenz, E. A.; Hosfelt, J. D.; Young, M. K.
2013-06-01
incorporation under elevated pCO2 (Sr / Ca = 2.10 ± 0.06 mmol mol-1; Mg / Ca = 67.4 ± 3.9 mmol mol-1), juveniles of Southern California origin partitioned ~8% more Sr into their skeletons when exposed to higher pCO2 (Sr / Ca = 2.26 ± 0.08 vs. 2.09 ± 0.005 mmol mol-1 1 SD). Together these results suggest that the diversity of carbonate minerologies present across different skeletal structures and life stages in purple sea urchins does not translate into an equivalent geochemical plasticity of response associated with geographic variation or temporal shifts in seawater properties. Rather, composition of S. purpuratus skeleton precipitated during both early and adult life history stages appears relatively robust to spatial gradients and predicted future changes in carbonate chemistry. An exception to this trend may arise during early life stages, where certain populations of purple sea urchins may alter skeletal mineral precipitation rates and composition beyond a given pCO2 threshold. This potential for geochemical plasticity during early development in contrast to adult stage geochemical resilience adds to the growing body of evidence that ocean acidification can have differing effects across organismal life stages.
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Directory of Open Access Journals (Sweden)
M. LaVigne
2013-06-01
incorporation under elevated pCO2 (Sr / Ca = 2.10 ± 0.06 mmol mol−1; Mg / Ca = 67.4 ± 3.9 mmol mol−1, juveniles of Southern California origin partitioned ~8% more Sr into their skeletons when exposed to higher pCO2 (Sr / Ca = 2.26 ± 0.08 vs. 2.09 ± 0.005 mmol mol−1 1 SD. Together these results suggest that the diversity of carbonate minerologies present across different skeletal structures and life stages in purple sea urchins does not translate into an equivalent geochemical plasticity of response associated with geographic variation or temporal shifts in seawater properties. Rather, composition of S. purpuratus skeleton precipitated during both early and adult life history stages appears relatively robust to spatial gradients and predicted future changes in carbonate chemistry. An exception to this trend may arise during early life stages, where certain populations of purple sea urchins may alter skeletal mineral precipitation rates and composition beyond a given pCO2 threshold. This potential for geochemical plasticity during early development in contrast to adult stage geochemical resilience adds to the growing body of evidence that ocean acidification can have differing effects across organismal life stages.
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Philip, Noah S; Kuras, Yuliya I; Valentine, Thomas R; Sweet, Lawrence H; Tyrka, Audrey R; Price, Lawrence H; Carpenter, Linda L
2013-12-30
Early life stress (ELS) confers risk for psychiatric illness. Previous literature suggests ELS is associated with decreased resting-state functional connectivity (rs-FC) in adulthood, but there are no studies of resting-state neuronal activity in this population. This study investigated whether ELS-exposed individuals demonstrate resting-state activity patterns similar to those found in PTSD. Twenty-seven adults (14 with at least moderate ELS), who were medication-free and without psychiatric or medical illness, underwent MRI scans during two 4-minute rest periods. Resting-state activity was examined using regional homogeneity (ReHo), which estimates regional activation patterns through indices of localized concordance. ReHo values were compared between groups, followed by rs-FC analyses utilizing ReHo-localized areas as seeds to identify other involved regions. Relative to controls, ELS subjects demonstrated diminished ReHo in the inferior parietal lobule (IPL) and superior temporal gyrus (STG). ReHo values were inversely correlated with ELS severity. Secondary analyses revealed decreased rs-FC between the IPL and right precuneus/posterior cingulate, left fusiform gyrus, cerebellum and caudate in ELS subjects. These findings indicate that ELS is associated with altered resting-state activity and connectivity in brain regions involved in trauma-related psychiatric disorders. Future studies are needed to evaluate whether these associations represent potential imaging biomarkers of stress exposure. Published by Elsevier Ireland Ltd.
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Dittrich, Katja; Fuchs, Anna; Bermpohl, Felix; Meyer, Justus; Führer, Daniel; Reichl, Corinna; Reck, Corinna; Kluczniok, Dorothea; Kaess, Michael; Hindi Attar, Catherine; Möhler, Eva; Bierbaum, Anna-Lena; Zietlow, Anna-Lena; Jaite, Charlotte; Winter, Sibylle Maria; Herpertz, Sabine C; Brunner, Romuald; Bödeker, Katja; Resch, Franz
2018-01-01
There is a well-established link between maternal depression and child mental health. Similar effects have been found for maternal history of early life maltreatment (ELM). However, studies investigating the relationship of children's quality of life and maternal depression are scarce and none have been conducted for the association with maternal ELM. The aim of the present study was to investigate the effects of maternal history of ELM and depression on children's health-related quality of life and to identify mediating factors accounting for these effects. Our study involved 194 mothers with and without history of depression and/or ELM and their children between five and 12 years. Children's health-related quality of life was assessed by maternal proxy- and child self-ratings using the KIDSCREEN. We considered maternal sensitivity and maternal parenting stress as potential mediators. We found an effect of maternal history of depression but not of maternal history of ELM on health-related quality of life. Maternal stress and sensitivity mediated the effects of maternal depression on child global health-related quality of life, as well as on the dimensions Autonomy & Parent Relation, School Environment (maternal and child rating), and Physical Wellbeing (child rating). Due to the cross-sectional design of the study, causal interpretations must be made with caution. Some scales yielded low internal consistency. Maternal impairments in areas of parenting which possibly developed during acute depression persist even after remission of acute affective symptoms. Interventions should target parenting stress and sensitivity in parents with prior depression. Copyright © 2017 Elsevier B.V. All rights reserved.
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Lovallo, William R; Enoch, Mary-Anne; Acheson, Ashley; Cohoon, Andrew J; Sorocco, Kristen H; Hodgkinson, Colin A; Vincent, Andrea S; Goldman, David
2016-06-01
Exposure to stress during critical periods of development can have adverse effects on adult health behaviors, and genetic vulnerabilities may enhance these stress effects. We carried out an exploratory examination of psychological, physiological, and behavioral characteristics of 252 healthy young adults for the impact of early-life adversity (ELA) in relation to the G-to-A single nucleotide polymorphism (SNP), rs9296158, of the FKBP5 gene. FKBP5 is a molecular cochaperone that contributes to the functional status of the glucocorticoid receptor (GR) and to the quality of corticosteroid signaling. FKBP5 expression is upregulated by cortisol exposure during stressful episodes, with greater upregulation seen in A-allele carriers. As such, FKBP5 expression and GR function may be environmentally sensitive in A-allele carriers and therefore suitable for the study of gene-by-environment (G × E) interactions. Compared with FKBP5, GG homozygotes (N=118), A-allele carriers (N = 132) without psychiatric morbidity had progressively worse performance on the Stroop color-word task with increasing levels of ELA exposure (Genotype × ELA, F=5.14, P=0.007), indicating a G × E interaction on working memory in early adulthood. In addition, heart rate response to mental stress was diminished overall in AA/AG-allele carriers (F=5.15, P=0.024). Diminished working memory and attenuated autonomic responses to stress are both associated with risk for alcoholism and other substance use disorders. The present data suggest that FKBP5 in the GR pathway may be a point of vulnerability to ELA, as seen in this group of non-traumatized young adults. FKBP5 is accordingly a potential target for more extensive studies of the impact of ELA on health and health behaviors in adulthood.
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Orofacial pain and quality of life in early adolescents in India.
Kumar, Sandeep; Badiyani, Bhumika K; Kumar, Amit; Dixit, Garima; Sharma, Prachi; Agrawal, Sugandha
2016-08-18
Orofacial pain may have an impact on quality of life. It may affect the overall well-being of an individual. To assess the prevalence of orofacial pain and its impact on quality of life in early adolescents in Indore city, India. This was a cross-sectional study which included a total of 800 children selected from various public and private schools located in Indore city, India. A questionnaire was developed which collected information on sociodemographic characteristics and previous dental visits. The severity of pain was assessed using Von Korff pain scale and quality of life using the General Health Questionnaire 12 (GHQ-12). The chi-square test and logistic regression analysis were performed. The overall prevalence of orofacial pain was found to be 17.9%. Toothache (10.1%) was found to be the most prevalent orofacial pain followed by temporomandibular joint pain (4.3%). The highest severity of pain (Grades 3 and 4) was reported for toothache followed by temporomandibular joint pain. The results of the logistic regression model showed that the prevalence of orofacial pain (odds ratio=7.18, p-valueorofacial pain has a negative influence on the quality of life of adolescents. Effective policies should be created to improve the quality of life of adolescents focusing on oral health education and prevention of oral diseases.
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Sverker, Annette; Östlund, Gunnel; Thyberg, Mikael; Thyberg, Ingrid; Valtersson, Eva; Björk, Mathilda
2015-01-01
To explore the experiences of today's patients with early rheumatoid arthritis (RA) with respect to dilemmas of everyday life, especially regarding patterns of participation restrictions in valued life activities. A total of 48 patients, aged 20-63, three years post-RA diagnosis were interviewed using the Critical Incident Technique. Transcribed interviews were condensed into meaningful units describing actions/situations. These descriptions were linked to ICF participation codes according to the International Classification of Functioning, Disability and Health (ICF) linking rules. Dilemmas in everyday life were experienced in domestic life, interpersonal interactions and relationships, community, social and civic life. Most dilemmas were experienced in domestic life, including participation restrictions in, e.g. gardening, repairing houses, shovelling snow, watering pot plants, sewing or walking the dog. Also many dilemmas were experienced related to recreation and leisure within the domain community, social and civic life. The different dilemmas were often related to each other. For instance, dilemmas related to community life were combined with dilemmas within mobility, such as lifting and carrying objects. Participation restrictions in today's RA patients are complex. Our results underline that the health care needs to be aware of the patients' own preferences and goals to support the early multi-professional interventions in clinical practice. Implications of Rehabilitation Today's rheumatoid arthritis (RA) patients experience participation restrictions in activities not included in International Classification of Functioning, Disability and Health (ICF) core set for RA or in traditionally questionnaires with predefined activities. The health care need to be aware of the patients' own preferences and goals to meet the individual needs and optimize the rehabilitation in early RA in clinical practice.
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Landgraf, Kathrin; Rockstroh, Denise; Wagner, Isabel V; Weise, Sebastian; Tauscher, Roy; Schwartze, Julian T; Löffler, Dennis; Bühligen, Ulf; Wojan, Magdalena; Till, Holger; Kratzsch, Jürgen; Kiess, Wieland; Blüher, Matthias; Körner, Antje
2015-04-01
Accumulation of fat mass in obesity may result from hypertrophy and/or hyperplasia and is frequently associated with adipose tissue (AT) dysfunction in adults. Here we assessed early alterations in AT biology and function by comprehensive experimental and clinical characterization of 171 AT samples from lean and obese children aged 0 to 18 years. We show an increase in adipocyte size and number in obese compared with lean children beginning in early childhood. These alterations in AT composition in obese children were accompanied by decreased basal lipolytic activity and significantly enhanced stromal vascular cell proliferation in vitro, potentially underlying the hypertrophy and hyperplasia seen in obese children, respectively. Furthermore, macrophage infiltration, including the formation of crown-like structures, was increased in AT of obese children from 6 years on and was associated with higher hs-CRP serum levels. Clinically, adipocyte hypertrophy was not only associated with leptin serum levels but was highly and independently correlated with HOMA-IR as a marker of insulin resistance in children. In summary, we show that adipocyte hypertrophy is linked to increased inflammation in AT in obese children, thereby providing evidence that obesity-associated AT dysfunction develops in early childhood and is related to insulin resistance. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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Life cycle assessment of nanoadsorbents at early stage technological development
DEFF Research Database (Denmark)
Kazemi, Ali; Bahramifar, Nader; Heydari, Akbar
2018-01-01
the process of the functionalization of nanoadsorbents leads to the increase of the adsorption capacity of nanoadsorbents, it is also paired with a significant enhancement of negative environmental impacts. The results of t-test comparing the cradle-to-use life cycle impacts of studied impact categories for 1...... in the control and removal of environmental pollutants. This application is still an emerging technology at the early stages of development. Hence, the heart of this study enables an environmental assessment of nanoadsorbents as an emerging product. In addition, the environmental impacts of synthesized...
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Does adversity early in life affect general population suicide rates? A cross-national study.
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.
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Does adversity early in life affect general population suicide rates? a cross-national study
Directory of Open Access Journals (Sweden)
Ritesh Bhandarkar
2011-01-01
Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Schwaiger, Marion; Grinberg, Marianna; Moser, Dirk; Zang, Johannes C S; Heinrichs, Markus; Hengstler, Jan G; Rahnenführer, Jörg; Cole, Steve; Kumsta, Robert
2016-09-01
Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.
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Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...
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Early-life soy exposure and gender-role play behavior in children.
Adgent, Margaret A; Daniels, Julie L; Edwards, Lloyd J; Siega-Riz, Anna Maria; Rogan, Walter J
2011-12-01
Soy-based infant formula contains high levels of isoflavones. These estrogen-like compounds have been shown to induce changes in sexually dimorphic behaviors in animals exposed in early development. We examined gender-role play behavior in relation to soy-based and non-soy-based infant feeding methods among children in the Avon Longitudinal Study of Parents and Children. We studied 3,664 boys and 3,412 girls. Four exposure categories were created using data from questionnaires administered at 6 and 15 months postpartum: primarily breast, early formula (referent), early soy, and late soy. Gender-role play behavior was assessed using the Pre-School Activities Inventory (PSAI). Associations between infant feeding and PSAI scores at 42 months of age were assessed using linear regression. Post hoc analyses of PSAI scores at 30 and 57 months were also conducted. Early-infancy soy use was reported for approximately 2% of participants. Mean [95% confidence interval (CI)] PSAI scores at 42 months were 62.3 (62.0, 62.6) and 36.9 (36.6, 37.2) for boys and girls, respectively. After adjustment, early soy (vs. early formula) feeding was associated with higher (less feminine) PSAI scores in girls (β = 2.66; 95% CI: 0.19, 5.12) but was not significantly associated with PSAI scores in boys. The association between soy exposure and PSAI scores in girls was substantially attenuated at 30 and 57 months. Although not consistent throughout childhood, early-life soy exposure was associated with less female-typical play behavior in girls at 42 months of age. Soy exposure was not significantly associated with play behavior in boys.
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Early deprivation, atypical brain development, and internalizing symptoms in late childhood.
Bick, J; Fox, N; Zeanah, C; Nelson, C A
2017-02-07
Children exposed to extreme early-life neglect such as in institutional rearing are at heightened risk for developing depression and anxiety disorders, and internalizing problems more broadly. These outcomes are believed to be due to alterations in the development of neural circuitry that supports emotion regulation. The specific neurodevelopmental changes that contribute to these difficulties are largely unknown. This study examined whether microstructural alterations in white matter pathways predicted long-term risk for internalizing problems in institutionally reared children. Data from 69 children were drawn from the Bucharest Early Intervention Project, a randomized clinical trial of foster care for institutionally reared children. White matter was assessed using diffusion tensor imaging (DTI) when children were between 8 and 10years of age. Internalizing symptoms were assessed at the time of the MRI scan, and once children reached 12-14years of age. Results indicated that neglect-associated alterations in the external capsule and corpus callosum partially explained links between institutional rearing status and internalizing symptoms in middle childhood and early adolescence. Findings shed light on neural mechanisms contributing to increased risk for emotional difficulties among children reared in adverse conditions and have implications for prevention and intervention. Copyright © 2015. Published by Elsevier Ltd.
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International Nuclear Information System (INIS)
Plaire, Delphine
2013-01-01
Understanding how toxicants affect species at various levels of biological organization is a major research goal in both ecotoxicology and radioecology. As part of IRSN program ENVIRHOM, which aims to assess environmental risks related to the presence of radionuclides in the environment, this PhD work explored how depleted uranium alters DNA and affects life history traits (survival, growth and reproduction) of an aquatic invertebrate, Daphnia magna. To answer to this problematic, an experimental approach and a modeling approach are conducted. An experimental study is performed to evaluate DNA accumulation and transmission during an uranium exposure (0; 2; 9.9; 22.2 and 50 μg.L -1 ) over two successive generations (F0 and F1). Different exposures scenarios (continuous, post-hatching and embryo exposure) are achieved to test the specific sensitivity of several life stages to uranium. Genotoxic effects are estimated using random amplified DNA technique combined with PCR (PCR-RAPD). In continuous and post-hatching exposure scenarios, results highlighted an accumulation and a transmission of DNA damage across generations with an increase in effect severity. DNA alterations are reported at hatching of the F1 generation at a concentration as low as 2 μg.L -1 . Effects on growth and reproduction are stronger when the embryo stage is exposed and remain visible at 9.9 μg.L -1 despite a return in a clean medium at hatching. Results suggest that DNA damage could be used as early indicators of future effects on life history traits. A mechanistic analysis of experimental results is conducted using a DEBtox model (dynamic energy budget applied to toxicology) to better understand the causes of the increase in effect severity across generations. A model with two stress factors (one correlated to external concentration and another correlated to a damage level) is developed. Results of fits suggest the involvement of one second mode of action to explain immediate effects of
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An exploration of addiction in adults experiencing early-life stress: a metasynthesis
Directory of Open Access Journals (Sweden)
Carla Araujo Bastos Teixeira
2017-10-01
Full Text Available ABSTRACT Objective: to review and synthesize qualitative research on the links between early-life stress and addiction behaviours in adulthood. Method: metasynthesis to review qualitative research findings based on procedures that outline how to identify themes or constructs across studies in a specific area. Comprehensive searches of multiple electronic databases were performed. The initial search yielded 1050 articles and the titles and abstracts were screened for inclusion based on predetermined criteria. Thirty-eight full text, peer-reviewed articles were retrieved and assessed by three independent reviewers. Twelve articles were eligible for full review and appraised using the Critical Appraisal Skills Programme (CASP tools. Results: the findings revealed that clear associations exist between early-life stress and addictive behaviours in adulthood, such as between trauma in childhood, violence, and addictive behaviours. A common theme in the findings indicates that participants turn to addictive substances as a way of strategically coping with stressful childhood experiences, regardless of the harmful side effects or detrimental social outcomes. Conclusion: it can be inferred that addiction may be viewed as a way to deal with adversity in childhood and that there is an interrelationship between addiction, domestic violence and crime.
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Are behavioral effects of early experience mediated by oxytocin?
Directory of Open Access Journals (Sweden)
Karen Lisa Bales
2011-05-01
Full Text Available Early experiences can alter adaptive emotional responses necessary for social behavior as well as physiological reactivity in the face of challenge. In the highly social prairie vole (Microtus ochrogaster, manipulations in early life or hormonal treatments specifically targeted at the neuropeptides oxytocin (OT and arginine vasopressin (AVP, have long-lasting, often sexually-dimorphic, consequences for social behavior. Here we examine the hypothesis that behavioral changes associated with differential early experience, in this case handling the family during the first week of life, may be mediated by changes in OT or AVP or their brain receptors. Four early treatment groups were used, differing only in the amount of manipulation received during the first week of life. MAN1 animals were handled once on post-natal day 1; MAN1 treatment produces a pattern of behavior usually considered typical of this species, against which other groups were compared. MAN 1-7 animals were handled once a day for post-natal days 1-7, MAN 7 animals were handled once on post-natal day 7, and MAN0 animals received no handling during the first week of life. When tested following weaning, males in groups that had received manipulation during the first few days of life (MAN1 and MAN1-7 displayed higher alloparenting than other groups. Neuroendocrine measures, including OT receptor binding and OT and AVP immunoreactivity, varied by early treatment. In brain areas including the nucleus accumbens, bed nucleus of stria terminalis and lateral septum, MAN0 females showed increased OT receptor binding. MAN1 animals also displayed higher numbers of immunoreactive OT cell bodies in the supraoptic nucleus. Taken together these findings support the broader hypothesis that experiences in the first few days of life, mediated in part by sexually-dimorphic changes in neuropeptides, especially in the receptor for OT, may have adaptive consequences for sociality and emotion regulation.
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Walzer, Andreas; Schausberger, Peter
2013-01-01
Background Food limitation early in life may be compensated for by developmental plasticity resulting in accelerated development enhancing survival at the expense of small adult body size. However and especially for females in non-matching maternal and offspring environments, being smaller than the standard may incur considerable intra- and trans-generational costs. Methodology/Principal Findings Here, we evaluated the costs of small female body size induced by food limitation early in life i...
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Farell, Ann
2005-01-01
Globalisation in early childhood teacher education is examined in light of a study of the life histories and course experience of students in early childhood teacher education in Queensland, Australia. Contemporary teacher education is embedded in global economies, new technologies and marketisation, which, in turn, may contribute to students…
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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 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.
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Maternal Early Life Experiences and Parenting: The Mediating Role of Cortisol and Executive Function
Gonzalez, Andrea; Jenkins, Jennifer M.; Steiner, Meir; Fleming, Alison S.
2012-01-01
Objective: Research suggests that early life adversity may affect subsequent parenting. Animal studies investigating mechanisms of transmission have focused on biological factors; whereas research in humans has emphasized cognitive and psychosocial factors. We hypothesized that neuropsychological and physiological factors would act as mediators…
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Dietary protein intake and quality in early life
DEFF Research Database (Denmark)
Lind, Mads V; Larnkjær, Anni; Mølgaard, Christian
2017-01-01
programming. Finally, infants with catch-up growth or specific genotypes might be particularly vulnerable to high-protein intake. SUMMARY: Recent studies confirm the associations between high-protein intake during the first 2 years and later obesity. Furthermore, knowledge of the mechanisms involved......PURPOSE OF REVIEW: 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 FINDINGS...... 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...
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Directory of Open Access Journals (Sweden)
K.A. Sagar
2015-12-01
Full Text Available Marijuana (MJ use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n = 24 and late onset (age 16 or later; n = 26, and 34 healthy control participants (HCs. All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth.
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Rainio, Miia J.; Eeva, Tapio; Lilley, Thomas; Stauffer, Janina; Ruuskanen, Suvi
2015-01-01
Abstract Lead is a highly poisonous metal with a very long half-life, distributing throughout the body in blood and accumulating primarily in bones and kidney. We studied the short and long-term effects of early-life lead exposure on antioxidant defense and phagocytosis activity in a small passerine
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Developmental rate and behavior of early life stages of bighead carp and silver carp
Chapman, Duane C.; George, Amy E.
2011-01-01
The early life stages of Asian carp are well described by Yi and others (1988), but since these descriptions are represented by line drawings based only on live individuals and lacked temperature controls, further information on developmental time and stages is of use to expand understanding of early life stages of these species. Bighead carp and silver carp were cultured under two different temperature treatments to the one-chamber gas bladder stage, and a photographic guide is provided for bighead carp and silver carp embryonic and larval development, including notes about egg morphology and larval swimming behavior. Preliminary information on developmental time and hourly thermal units for each stage is also provided. Both carp species developed faster under warmer conditions. Developmental stages and behaviors are generally consistent with earlier works with the exception that strong vertical swimming immediately after hatching was documented in this report.
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van Rijn, Sophie; Barneveld, Petra; Descheemaeker, Mie-Jef; Giltay, Jacques; Swaab, Hanna
2018-02-01
Studies on gene-environment interactions suggest that some individuals may be more susceptible to life adversities than others due to their genetic profile. This study assesses whether or not children with an extra X chromosome are more vulnerable to the negative impact of early life stress on cognitive functioning than typically-developing children. A total of 50 children with an extra X chromosome and 103 non-clinical controls aged 9 to 18 years participated in the study. Cognitive functioning in domains of language, social cognition and executive functioning were assessed. Early life stress was measured with the Questionnaire of Life Events. High levels of early life stress were found to be associated with compromised executive functioning in the areas of mental flexibility and inhibitory control, irrespective of group membership. In contrast, the children with an extra X chromosome were found to be disproportionally vulnerable to deficits in social cognition on top of executive dysfunction, as compared to typically-developing children. Within the extra X group the number of negative life events is significantly correlated with more problems in inhibition, mental flexibility and social cognition. It is concluded that children with an extra X chromosome are vulnerable to adverse life events, with social cognition being particularly impacted in addition to the negative effects on executive functioning. The findings that developmental outcome is codependent on early environmental factors in genetically vulnerable children also underscores opportunities for training and support to positively influence the course of development.
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Analgesia for early-life pain prevents deficits in adult anxiety and stress in rats.
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.
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DEFF Research Database (Denmark)
Nielsen, Per Rotbøll; Andreasen, Jakob Huus; Asmussen, Mikael
2008-01-01
During the recent years improved operation techniques and administrative procedures have been developed for early rehabilitation. At the same time preoperative lifestyle intervention (prehabilitation) has revealed a large potential for additional risk reduction. The aim was to assess the quality...... of life and to estimate the cost-effectiveness of standard care versus an integrated programme including prehabilitation and early rehabilitation....
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Directory of Open Access Journals (Sweden)
Ashok Daniel Prabakaran
2018-03-01
Full Text Available Although the existence of a close relationship between the early maternal developmental environment, fetal size at birth and the risk of developing disease in adulthood has been suggested, most studies, however, employed experimentally induced intrauterine growth restriction as a model to link this with later adult disease. Because embryonic size variation also occurs under normal growth and differentiation, elucidating the molecular mechanisms underlying these changes and their relevance to later adult disease risk becomes important. The birth weight of rat pups vary according to the uterine horn positions. Using birth weight as a marker, we compared two groups of rat pups – lower birth weight (LBW, 5th to 25th percentile and average birth weight (ABW, 50th to 75th percentile – using morphological, biochemical and molecular biology, and genetic techniques. Our results show that insulin metabolism, Pi3k/Akt and Pparγ signaling and the genes regulating growth and metabolism are significantly different in these groups. Methylation at the promoter of the InsII (Ins2 gene and DNA methyltransferase 1 in LBW pups are both increased. Additionally, the Dnmt1 repressor complex, which includes Hdac1, Rb (Rb1 and E2f1, was also upregulated in LBW pups. We conclude that the Dnmt1 repressor complex, which regulates the restriction point of the cell cycle, retards the rate at which cells traverse the G1 or G0 phase of the cell cycle in LBW pups, thereby slowing down growth. This regulatory mechanism mediated by Dnmt1 might contribute to the production of small-size pups and altered physiology and pathology in adult life.
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Directory of Open Access Journals (Sweden)
Robyn Jane McQuaid
2013-07-01
Full Text Available Several prosocial behaviors may be influenced by the hormone oxytocin. In line with this perspective, the oxytocin receptor (OXTR gene single nucleotide polymorphism (SNP, rs53576, has been associated with a broad range of social behaviors. In this regard, the G allele of the OXTR SNP has been accompanied by beneficial attributes such as increased empathy, optimism and trust. In the current study among university students (N = 288, it was shown that early-life maltreatment was associated with depressive symptoms, and that the OXTR genotype moderated this relationship, such that under high levels of childhood maltreatment, only individuals with GG/GA genotype demonstrated increased depressive symptomatology compared to those with the AA genotype. In addition, the role of distrust in mediating the relation between childhood maltreatment and depression seemed to be more important among G allele carriers compared to individuals with the AA genotype. Thus, a breach in trust (i.e. in the case of early-life abuse or neglect may have a more deleterious effect among G carriers, who have been characterized as more prosocial and attuned to social cues. The data suggested that G carriers of the OXTR might favor social sensitivity and thus might have been more vulnerable to the effects of early-life adversity.
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Podocyte number and density changes during early human life.
Kikuchi, Masao; Wickman, Larysa; Rabah, Raja; Wiggins, Roger C
2017-05-01
Podocyte depletion, which drives progressive glomerulosclerosis in glomerular diseases, is caused by a reduction in podocyte number, size or function in the context of increasing glomerular volume. Kidneys obtained at autopsy from premature and mature infants who died in the first year of life (n = 24) were used to measure podometric parameters for comparison with previously reported data from older kidneys. Glomerular volume increased 4.6-fold from 0.13 ± 0.07 μm 3 x10 6 in the pre-capillary loop stage, through 0.35 μm 3 x10 6 at the capillary loop, to 0.60 μm 3 x10 6 at the mature glomerular stage. Podocyte number per glomerulus increased from 326 ± 154 per glomerulus at the pre-capillary loop stage to 584 ± 131 per glomerulus at the capillary loop stage of glomerular development to reach a value of 589 ± 166 per glomerulus in mature glomeruli. Thus, the major podocyte number increase occurs in the early stages of glomerular development, in contradistinction to glomerular volume increase, which continues after birth in association with body growth. As glomeruli continue to enlarge, podocyte density (number per volume) rapidly decreases, requiring a parallel rapid increase in podocyte size that allows podocyte foot processes to maintain complete coverage of the filtration surface area. Hypertrophic stresses on the glomerulus and podocyte during development and early rapid growth periods of life are therefore likely to play significant roles in determining how and when defects in podocyte structure and function due to genetic variants become clinically manifest. Therapeutic strategies aimed at minimizing mismatch between these factors may prove clinically useful.