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Sample records for prenatal bystander stress

  1. Prenatal stress in pigs

    NARCIS (Netherlands)

    Kranendonk, Godelieve

    2006-01-01

    Studies in many species, including humans, have demonstrated that stress during gestation can have long-term developmental, neuroendocrine, and behavioural effects on the offspring. Because pregnant sows can be subjected to regular stressful situations, it is relevant to study whether prenatal

  2. Prenatal Maternal Stress Programs Infant Stress Regulation

    Science.gov (United States)

    Davis, Elysia Poggi; Glynn, Laura M.; Waffarn, Feizal; Sandman, Curt A.

    2011-01-01

    Objective: Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress.…

  3. Neurodevelopmental Outcomes of Prenatal Stress

    Directory of Open Access Journals (Sweden)

    M. Genco Usta

    2012-03-01

    Full Text Available The influence of prenatal stress on psychopathology has been observed in many animal and human studies. In many studies, stress during prenatal period has been shown to result in negative feedback dysregulation and hyperactivity of hypothalamo-pituitary-adrenocortical axis. Prenatal stres also may cause increased risk of birth complications, startle or distress in response to novel and surprising stimuli during infancy; lower Full Scale IQs, language abilities and attention deficiency in period of 3-5 years; increased risk of attention deficit hyperactivity syndrome, anxiety symptoms, depressive disorder and impulsivity during adolescence. Additionally, timing of prenatal stress is also important and 12-22 weeks of gestation seems to be the most vulnerable period. The results underline the need for early prevention and intervention programs for highly anxious women during pregnancy. Administration of prenatal stress monitoring to public health programs or removing pregnant women who have been exposed to life events such as natural disaster, terror attack to secure areas that provide basic needs may be crucial.

  4. Bystander effects, adaptive response and genomic instability induced by prenatal irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Streffer, Christian [Institute for Science and Ethics, University Duisburg-Essen, Auf dem Sutan 12, D-45239 Essen (Germany)]. E-mail: streffer.essen@t-online.de

    2004-12-02

    The developing human embryo and fetus undergo very radiosensitive stages during the prenatal development. It is likely that the induction of low dose related effects such as bystander effects, the adaptive response, and genomic instability would have profound effects on embryonic and fetal development. In this paper, I review what has been reported on the induction of these three phenomena in exposed embryos and fetuses. All three phenomena have been shown to occur in murine embryonic or fetal cells and structures, although the induction of an adaptive response (and also likely the induction of bystander effects) are limited in terms of when during development they can be induced and the dose or dose-rate used to treat animals in utero. In contrast, genomic instability can be induced throughout development, and the effects of radiation exposure on genome instability can be observed for long times after irradiation including through pre- and postnatal development and into the next generation of mice. There are clearly strain-specific differences in the induction of these phenomena and all three can lead to long-term detrimental effects. This is true for the adaptive response as well. While induction of an adaptive response can make fetuses more resistant to some gross developmental defects induced by a subsequent high dose challenge with ionizing radiation, the long-term effects of this low dose exposure are detrimental. The negative effects of all three phenomena reflect the complexity of fetal development, a process where even small changes in the timing of gene expression or suppression can have dramatic effects on the pattern of biological events and the subsequent development of the mammalian organism.

  5. Prenatal stress, prematurity and asthma

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    Medsker, Brock; Forno, Erick; Simhan, Hyagriv; Celedón, Juan C.

    2016-01-01

    Asthma is the most common chronic disease of childhood, affecting millions of children in the U.S. and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non-Hispanic Blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced “premature asthma”. Prenatal stress may not only cause abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring Th2 (allergic) immune responses characteristic of atopic asthma: IL-6, which has been associated with premature labor, can promote Th2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing “premature asthma”. If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common co-morbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (e.g. from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health. PMID:26676148

  6. New aspects of studies on stress response. Radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Matsumoto, Hideki; Hayashi, Sachiko; Jin, Zhao-Hui; Hatashita, Masanori; Kano, Eiichi

    2001-01-01

    This review describes the bystander effect which is the secondary stress response induced by the primary target affected by radiation and other environmental factors. The bystander effect can be exerted from the primary target cells through the gap junction, through interaction between ligands and receptors, through interaction between secreted bystander factors and receptors and through secreted bystander factors. Through the first, the typical one firstly shown in AG1521 cells is that, despite the pass of only 2% of irradiated α-particles through the target cell nucleus, much more cells respond to express p53 and p21/WAF1. Through the second, the Fas/Fas ligand in the target induce apoptosis of the non-target cells. As for the third, participation of cytokines and growth factors is suggested. Many investigations concern the fourth of bystander effects by the bystander factors: e.g., authors have studied the effects of X-ray, carbon beam or hyperthermia on nitric oxide synthase induction in A-172 cells. Studies of bystander effects possibly extend the concept of radiation biology. (K.H.)

  7. Bystander effects and compartmental stress response to X-ray irradiation in L929 cells.

    Science.gov (United States)

    Temelie, Mihaela; Stroe, Daniela; Petcu, Ileana; Mustaciosu, Cosmin; Moisoi, Nicoleta; Savu, Diana

    2016-08-01

    Bystander effects are indirect consequences of radiation and many other stress factors. They occur in cells that are not directly exposed to these factors, but receive signals from affected cells either by gap junctions or by molecules released in the medium. Characterizing these effects and deciphering the underlying mechanisms involved in radiation-induced bystander effects are relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation 0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei shortly after the treatment, through medium transfer and by co-cultures. Interestingly, bystander cells did not exhibit long-term adverse changes in viability. Evaluation of several compartmental stress markers (CHOP, BiP, mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at transcriptional level. We investigated the involvement of ROS and NO in this process by addition of specific scavengers of these molecules, DMSO or c-PTIO in the transferred medium. This approach proved that ROS but not NO is involved in the induction of lesions in the acceptor cells. These results indicate that L929 cells are susceptible to stress effects of radiation-induced bystander signaling.

  8. Prenatal stress changes learning strategies in adulthood.

    Science.gov (United States)

    Schwabe, Lars; Bohbot, Veronique D; Wolf, Oliver T

    2012-11-01

    It is well known that stressful experiences may shape hippocampus-dependent learning and memory processes. However, although most studies focused on the impact of stress at the time of learning or memory testing, very little is known about how stress during critical periods of brain development affects learning and memory later in life. In this study, we asked whether prenatal stress exposure may influence the engagement of hippocampus-dependent spatial learning strategies and caudate nucleus-dependent response learning strategies in later life. To this end, we tested healthy participants whose mothers had experienced major negative life events during their pregnancy in a virtual navigation task that can be solved by spatial and response strategies. We found that young adults with prenatal stress used rigid response learning strategies more often than flexible spatial learning strategies compared with participants whose mothers did not experience major negative life events during pregnancy. Individual differences in acute or chronic stress do not account for these findings. Our data suggest that the engagement of hippocampal and nonhippocampal learning strategies may be influenced by stress very early in life. Copyright © 2012 Wiley Periodicals, Inc.

  9. Masculinity and Bystander Attitudes: Moderating Effects of Masculine Gender Role Stress.

    Science.gov (United States)

    Leone, Ruschelle M; Parrott, Dominic J; Swartout, Kevin M; Tharp, Andra Teten

    2016-01-01

    The purpose of the current study was to examine the bystander decision-making process as a mechanism by which men's adherence to various dimensions of traditional masculinity is associated with their confidence to intervene in sexually aggressive events. Further, this study examined the stress men experience from their attempts to adhere to traditional male gender roles as a moderator of this mediational path. Participants ( n = 252) completed measures of traditional masculinity, decisional balance (i.e., weighing the pros and cons) for intervening, masculine gender roles stress, and bystander efficacy. The belief that men must attain social status was associated with more confidence in men's ability to intervene. This effect was mediated by greater perceived positive consequences for intervention among men high, but not low, in masculine gender role stress. The belief that men should be tough and aggressive was associated with greater perceived negative consequences for intervention and less confidence to intervene. The belief that men should not act in stereotypically feminine ways was directly associated with less confidence for intervention. Findings highlight the importance of examining masculinity from a multidimensional perspective to better understand how adherence to various norms differentially influences bystander behavior. These findings may help to inform bystander intervention programming.

  10. Protective effect of mild endoplasmic reticulum stress on radiation-induced bystander effects in hepatocyte cells

    Science.gov (United States)

    Xie, Yuexia; Ye, Shuang; Zhang, Jianghong; He, Mingyuan; Dong, Chen; Tu, Wenzhi; Liu, Peifeng; Shao, Chunlin

    2016-01-01

    Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the defense and self-protective mechanisms of bystander normal cells are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 cells under either normoxia or hypoxia, where the ratio of the yield of bystander MN induction to the yield of radiation-induced MN formation under hypoxia was much higher than that of normoxia. Nonetheless, thapsigargin induced endoplasmic reticulum (ER) stress and dramatically suppressed this bystander response manifested as the decrease of MN and apoptosis inductions. Meanwhile, the interference of BiP gene, a major ER chaperone, amplified the detrimental RIBE. More precisely, thapsigargin provoked ER sensor of PERK to initiate an instantaneous and moderate ER stress thus defensed the hazard form RIBE, while BiP depletion lead to persistently destroyed homeostasis of ER and exacerbated cell injury. These findings provide new insights that the mild ER stress through BiP-PERK-p-eIF2α signaling pathway has a profound role in protecting cellular damage from RIBE and hence may decrease the potential secondary cancer risk after cancer radiotherapy. PMID:27958308

  11. Masculinity and Bystander Attitudes: Moderating Effects of Masculine Gender Role Stress

    Science.gov (United States)

    Leone, Ruschelle M.; Parrott, Dominic J.; Swartout, Kevin M.; Tharp, Andra Teten

    2018-01-01

    Objective The purpose of the current study was to examine the bystander decision-making process as a mechanism by which men’s adherence to various dimensions of traditional masculinity is associated with their confidence to intervene in sexually aggressive events. Further, this study examined the stress men experience from their attempts to adhere to traditional male gender roles as a moderator of this mediational path. Method Participants (n = 252) completed measures of traditional masculinity, decisional balance (i.e., weighing the pros and cons) for intervening, masculine gender roles stress, and bystander efficacy. Results The belief that men must attain social status was associated with more confidence in men’s ability to intervene. This effect was mediated by greater perceived positive consequences for intervention among men high, but not low, in masculine gender role stress. The belief that men should be tough and aggressive was associated with greater perceived negative consequences for intervention and less confidence to intervene. The belief that men should not act in stereotypically feminine ways was directly associated with less confidence for intervention. Conclusions Findings highlight the importance of examining masculinity from a multidimensional perspective to better understand how adherence to various norms differentially influences bystander behavior. These findings may help to inform bystander intervention programming. PMID:29593932

  12. Prenatal stress may increase vulnerability to life events comparison with the effects of prenatal dexamethasone

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Kjaer, Sanna L

    2005-01-01

    naïve at the time of ASR testing, whereas the other had been through blood sampling for assessment of the hormonal stress response to restraint, 3 months previously. Both prenatal CMS and dexamethasone increased ASR in the offspring compared to controls, but only in prenatally stressed offspring......Prenatal stress has been associated with a variety of alterations in the offspring. The presented observations suggest that rather than causing changes in the offspring per se, prenatal stress may increase the organism's vulnerability to aversive life events. Offspring of rat dams stressed...... of the acoustic startle response. Further, a single aversive life event showed capable of changing the reactivity of prenatally stressed offspring, whereas offspring of dams going through a less stressful gestation was largely unaffected by this event. This suggests that circumstances dating back to the very...

  13. Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

    Science.gov (United States)

    Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2017-01-01

    Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

  14. Prenatal stress may increase vulnerability to life events

    DEFF Research Database (Denmark)

    Hougaard, Karin S; Andersen, Maibritt B; Kjaer, Sanna L

    2005-01-01

    Prenatal stress has been associated with a variety of alterations in the offspring. The presented observations suggest that rather than causing changes in the offspring per se, prenatal stress may increase the organism's vulnerability to aversive life events. Offspring of rat dams stressed...

  15. Prenatal stress alters amygdala functional connectivity in preterm neonates.

    Science.gov (United States)

    Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

    2016-01-01

    Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

  16. Impact of Prenatal Stress on Neuroendocrine Programming

    Directory of Open Access Journals (Sweden)

    Odile Viltart

    2007-01-01

    Full Text Available Since life emerged on the Earth, the development of efficient strategies to cope with sudden and/or permanent changes of the environment has been virtually the unique goal pursued by every organism in order to ensure its survival and thus perpetuate the species. In this view, evolution has selected tightly regulated processes aimed at maintaining stability among internal parameters despite external changes, a process termed homeostasis. Such an internal equilibrium relies quite heavily on three interrelated physiological systems: the nervous, immune, and endocrine systems, which function as a permanently activated watching network, communicating by the mean of specialized molecules: neurotransmitters, cytokines, and hormones or neurohormones. Potential threats to homeostasis might occur as early as during in utero life, potentially leaving a lasting mark on the developing organism. Indeed, environmental factors exert early-life influences on the structural and functional development of individuals, giving rise to changes that can persist throughout life. This organizational phenomenon, encompassing prenatal environmental events, altered fetal growth, and development of long-term pathophysiology, has been named early-life programming. Over the past decade, increased scientific activities have been devoted to deciphering the obvious link between states of maternal stress and the behavioral, cognitive, emotional, and physiological reactivity of the progeny. This growing interest has been driven by the discovery of a tight relationship between prenatal stress and development of short- and long-term health disorders. Among factors susceptible of contributing to such a deleterious programming, nutrients and hormones, especially steroid hormones, are considered as powerful mediators of the fetal organization since they readily cross the placental barrier. In particular, variations in circulating maternal glucocorticoids are known to impact this

  17. Impact of prenatal environmental stress on cortical development

    Directory of Open Access Journals (Sweden)

    Seiji eIshii

    2015-05-01

    Full Text Available Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS cells to demonstrate: 1. molecular mechanisms shared by various types of environmental stressors, 2. the mechanisms by which the affected extracortical tissues indirectly impact the cortical development and function, and 3. interaction between prenatal environmental stress and the genetic predisposition of neuropsychiatric disorders. Finally, we discuss current challenges for achieving a comprehensive understanding of the role of environmentally disturbed molecular expressions in cortical maldevelopment, knowledge of which may eventually facilitate discovery of interventions for prenatal environment-linked neuropsychiatric disorders.

  18. Association between prenatal psychological stress and oxidative stress during pregnancy.

    Science.gov (United States)

    Eick, Stephanie M; Barrett, Emily S; van 't Erve, Thomas J; Nguyen, Ruby H N; Bush, Nicole R; Milne, Ginger; Swan, Shanna H; Ferguson, Kelly K

    2018-03-30

    Prenatal psychological stress during pregnancy has been associated with adverse reproductive outcomes. A growing animal literature supports an association between psychological stress and oxidative stress. We assessed this relationship in pregnant women, hypothesising that psychological stress is associated with higher concentrations of oxidative stress biomarkers during pregnancy. Psychosocial status and stressful life events (SLE) were self-reported. 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) was measured as a biomarker of oxidative stress in urine samples at median 32 weeks' gestation. We examined SLEs individually (ever vs never) and in summary (any vs none) and psychosocial status as measured by individual subscales and in summary (poor vs good). Linear models estimated associations between these parameters and urinary 8-iso-PGF 2α concentrations after adjusting for covariates. The geometric mean of 8-iso-PGF 2α was significantly higher among pregnant women who were non-White, smokers, had less than a college education, higher pre-pregnancy BMI and were unmarried. Having ever had a death in the family (n = 39) during pregnancy was associated with a 22.9% increase in 8-iso-PGF 2α in unadjusted models (95% confidence interval [CI] 1.50, 48.8). Poor psychosocial status was associated with a 13.1% (95% CI 2.43, 25.0) greater mean 8-iso-PGF 2α in unadjusted analyses. Associations were attenuated, but remained suggestive, after covariate adjustment. These data suggest that 8-iso-PGF 2α is elevated in pregnant women with who are at a sociodemographic disadvantage and who have higher psychological stress in pregnancy. Previous studies have observed that 8-iso-PGF 2α levels are associated with adverse birth outcomes, oxidative stress could be a mediator in these relationships. © 2018 John Wiley & Sons Ltd.

  19. Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex.

    Science.gov (United States)

    Bose, Sonali; Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Di, Qian; Rosa, Maria José; Lee, Alison; Kloog, Itai; Wilson, Ander; Schwartz, Joel; Wright, Robert O; Cohen, Sheldon; Coull, Brent A; Wright, Rosalind J

    2017-12-01

    Impact of ambient pollution upon children's asthma may differ by sex, and exposure dose and timing. Psychosocial stress can also modify pollutant effects. These associations have not been examined for in utero ambient nitrate exposure. We implemented Bayesian-distributed lag interaction models to identify sensitive prenatal windows for the influence of nitrate (NO 3 - ) on child asthma, accounting for effect modification by sex and stress. Analyses included 752 mother-child dyads. Daily ambient NO 3 - exposure during pregnancy was derived using a hybrid chemical transport (Geos-Chem)/land-use regression model and natural log transformed. Prenatal maternal stress was indexed by a negative life events score (high [>2] vs. low [≤2]). The outcome was clinician-diagnosed asthma by age 6 years. Most mothers were Hispanic (54%) or black (29%), had a high school education or less (66%), never smoked (80%), and reported low prenatal stress (58%); 15% of children developed asthma. BDILMs adjusted for maternal age, race, education, prepregnancy obesity, atopy, and smoking status identified two sensitive windows (7-19 and 33-40 wk gestation), during which increased NO 3 - was associated with greater odds of asthma, specifically among boys born to mothers reporting high prenatal stress. Cumulative effects of NO 3 - across pregnancy were also significant in this subgroup (odds ratio = 2.64, 95% confidence interval = 1.27-5.39; per interquartile range increase in ln NO 3 - ). Prenatal NO 3 - exposure during distinct sensitive windows was associated with incident asthma in boys concurrently exposed to high prenatal stress.

  20. Fractalkine Attenuates Microglial Cell Activation Induced by Prenatal Stress

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    Joanna Ślusarczyk

    2016-01-01

    Full Text Available The potential contribution of inflammation to the development of neuropsychiatric diseases has recently received substantial attention. In the brain, the main immune cells are the microglia. As they are the main source of inflammatory factors, it is plausible that the regulation of their activation may be a potential therapeutic target. Fractalkine (CX3CL1 and its receptor CX3CR1 play a crucial role in the control of the biological activity of the microglia. In the present study, using microglial cultures we investigated whether fractalkine is able to reverse changes in microglia caused by a prenatal stress procedure. Our study found that the microglia do not express fractalkine. Prenatal stress decreases the expression of the fractalkine receptor, which in turn is enhanced by the administration of exogenous fractalkine. Moreover, treatment with fractalkine diminishes the prenatal stress-induced overproduction of proinflammatory factors such as IL-1β, IL-18, IL-6, TNF-α, CCL2, or NO in the microglial cells derived from prenatally stressed newborns. In conclusion, the present results revealed that the pathological activation of microglia in prenatally stressed newborns may be attenuated by fractalkine administration. Therefore, understanding of the role of the CX3CL1-CX3CR1 system may help to elucidate the mechanisms underlying the neuron-microglia interaction and its role in pathological conditions in the brain.

  1. Can prenatal social stress impact sex characteristics in piglets?

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    Prenatal stress (PNS) alters sex traits in rodents by androgenizing offspring resulting in reduced reproduction. In production, gestating sows are often exposed to social stress of mixing. This study examined if mixing gestating sows alters sexual development in piglets. At 34 ± 10 d of gestation, 6...

  2. Sex differences in prenatal epigenetic programming of stress pathways.

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    Bale, Tracy L

    2011-07-01

    Maternal stress experience is associated with neurodevelopmental disorders including schizophrenia and autism. Recent studies have examined mechanisms by which changes in the maternal milieu may be transmitted to the developing embryo and potentially translated into programming of the epigenome. Animal models of prenatal stress have identified important sex- and temporal-specific effects on offspring stress responsivity. As dysregulation of stress pathways is a common feature in most neuropsychiatric diseases, molecular and epigenetic analyses at the maternal-embryo interface, especially in the placenta, may provide unique insight into identifying much-needed predictive biomarkers. In addition, as most neurodevelopmental disorders present with a sex bias, examination of sex differences in the inheritance of phenotypic outcomes may pinpoint gene targets and specific windows of vulnerability in neurodevelopment, which have been disrupted. This review discusses the association and possible contributing mechanisms of prenatal stress in programming offspring stress pathway dysregulation and the importance of sex.

  3. Prenatal maternal stress in relation to the effects of prenatal lead exposure on toddler cognitive development.

    Science.gov (United States)

    Zhou, Leilei; Xu, Jian; Zhang, Jinsong; Yan, Chonghuai; Lin, Yanfen; Jia, Yinan; Hu, Wenjing

    2017-03-01

    To evaluate the effects of maternal lead exposure during pregnancy on toddler cognitive development and the potential effect modification by maternal stress. We conducted a prospective birth-cohort study in Shanghai from 2010 to 2012 and investigated 225 mother-infant pairs. The mothers were recruited in mid-to-late pregnancy and children were followed up until 24-36 months old. A self-administered Symptom Checklist-90-Revised Scale (SCL-90-R) was used to assess maternal emotional stress during pregnancy. Maternal whole blood lead levels were measured during gestational weeks 28-36. The toddlers' cognitive levels were assessed using the Gesell Development Scale. Multiple linear regression models were established to explore the main effects of prenatal lead exposure on toddlers' cognitive abilities and the modifying effects of maternal stress. Covariate information was collected through interviews, questionnaires and medical records. The mean maternal blood lead concentration was 3.30 (95%CI: 3.05, 3.57) μg/dL. After adjusting for relevant confounders, no significant associations of maternal blood lead concentrations with toddlers' cognitive levels were observed in all five domains of the Gesell scale (P>0.05). However, the interaction between prenatal maternal blood lead and stress was significant in the domains of adaptive behavior, language and social behavior. When stratified by maternal stress levels, compared with non-significant associations (P>0.05) among low (P1-P75) prenatal stress group, adverse associations between maternal blood lead concentrations (log10-transformed) and toddlers' cognitive levels were observed among high (P75-P100) prenatal stress group in the domains of language (β=-33.82, 95%CI: -60.04, -7.59), social behavior (β=-41.00, 95%CI: -63.11, -18.89) and adaptive behavior (β=-17.93, 95%CI: -35.83, -0.03). Prenatal maternal stress may exacerbate the deleterious effects of prenatal exposure to lead on toddler cognitive development

  4. Does Maternal Prenatal Stress Adversely Affect the Child's Learning and Memory at Age Six?

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    Gutteling, Barbara M.; de Weerth, Carolina; Zandbelt, Noortje; Mulder, Eduard J. H.; Visser, Gerard H. A.; Buitelaar, Jan K.

    2006-01-01

    Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50…

  5. Offspring psychopathology following preconception, prenatal, and postnatal maternal bereavement stress

    Science.gov (United States)

    Class, Quetzal A.; Abel, Kathryn M.; Khashan, Ali S.; Rickert, Martin E.; Dalman, Christina; Larsson, Henrik; Hultman, Christina M.; Långström, Niklas; Lichtenstein, Paul; D’Onofrio, Brian M.

    2013-01-01

    Background Preconception, prenatal, and postnatal maternal stress are associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt, and completed suicide. Methods Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992–2000 for childhood outcomes and 2,155,221 offspring born 1973–1997 for adult outcomes with follow-up through 2009. Maternal stress was defined as death of a first degree relative during 6 months before conception, across pregnancy, or the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HR) in unadjusted and adjusted analyses. Results Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third trimester prenatal stress increased risk of ASD (adjusted HR=1.58, 95% CI: 1.15–2.17) and ADHD (adjusted HR=1.31, 95% CI: 1.04–1.66). First postnatal year stress increased risk for offspring suicide attempt (adjusted HR=1.13, 95% CI: 1.02–1.25) and completed suicide (adjusted HR=1.51, 95% CI: 1.08–2.11). Bereavement stress during the second postnatal year increased risk of ASD (adjusted HR=1.30, 95% CI: 1.09–1.55). Conclusions Further research is needed on associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases risk of offspring suicide attempt, completed suicide, and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes. PMID:23591021

  6. Prenatal Transportation Stress Alters Temperament and Serum Cortisol Concentrations in Suckling Brahman Calves

    Science.gov (United States)

    This experiment examined the relationship between prenatal stress and subsequent calf temperament through weaning. The prenatal stressor utilized was repeated transportation of pregnant Brahman cows for 2 hours at 60, 80, 100, 120, and 140 days of gestation. Prenatally stressed calves (n = 41) were ...

  7. Glutamate neurotransmission is affected in prenatally stressed offspring

    DEFF Research Database (Denmark)

    Adrover, Ezequiela; Pallarés, Maria Eugenia; Baier, Carlos Javier

    2015-01-01

    Previous studies from our laboratory have shown that male adult offspring of stressed mothers exhibited higher levels of ionotropic and metabotropic glutamate receptors than control rats. These offspring also showed long-lasting astroglial hypertrophy and a reduced dendritic arborization with syn......Previous studies from our laboratory have shown that male adult offspring of stressed mothers exhibited higher levels of ionotropic and metabotropic glutamate receptors than control rats. These offspring also showed long-lasting astroglial hypertrophy and a reduced dendritic arborization...... with synaptic loss. Since metabolism of glutamate is dependent on interactions between neurons and surrounding astroglia, our results suggest that glutamate neurotransmitter pathways might be impaired in the brain of prenatally stressed rats. To study the effect of prenatal stress on the metabolism...... was not affected it was found that prenatal stress (PS) changed the expression of the transporters, thus, producing a higher level of vesicular vGluT-1 in the frontal cortex (FCx) and elevated levels of GLT1 protein and messenger RNA in the hippocampus (HPC) of adult male PS offspring. We also observed increased...

  8. Prenatal and early postnatal stress and later life inflammation

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  9. Effects of prenatal stress on vulnerability to stress in prepubertal and adult rats.

    Science.gov (United States)

    Fride, E; Dan, Y; Feldon, J; Halevy, G; Weinstock, M

    1986-01-01

    This study investigated the hypotheses that unpredictable prenatal stress has effects on the offspring, similar to those induced by perinatal administration of glucocorticoids and increases the vulnerability to stressful situations at adulthood. Rats were exposed to random noise and light stress throughout pregnancy. Offspring were tested for the development of spontaneous alternation behavior (SA) and at adulthood, their response to novel or aversive situations, open field, extinction and punishment following acquisition of an appetitive response and two-way active avoidance, were assessed. In prenatally stressed rats, the development of SA was significantly delayed. On repeated exposure to an open field they were less active; control rats had elevated plasma corticosterone (CCS) on days 2 and 4 of open field exposure, while prenatally stressed rats had significantly raised plasma CCS after each exposure (days 1-8). Furthermore, punishment-induced suppression of an appetitive response was enhanced. Acquisition of active avoidance was faciliated in female but reduced in male prenatally stressed offspring. It is suggested that random prenatal noise and light stress may cause impairment of development of hippocampal function which lasts into adulthood. This impairment is manifested as an increase in vulnerability and a decrease in habituation to stressful stimuli.

  10. The role of glucocorticoid, interleukin-1β, and antioxidants in prenatal stress effects on embryonic microglia.

    Science.gov (United States)

    Bittle, Jada; Stevens, Hanna E

    2018-02-16

    Maternal stress during pregnancy is associated with an increased risk of psychopathology in offspring. Resident immune cells of the brain, microglia, may be mediators of prenatal stress and altered neurodevelopment. Here, we demonstrate that neither the exogenous pro-inflammatory cytokine, interleukin-1β (IL-1β), nor the glucocorticoid hormone, corticosterone, recapitulated the full effects of prenatal stress on the morphology of microglial cells in the cortical plate of embryonic mice; IL-1β effects showed greater similarity to prenatal stress effects on microglia. Unexpectedly, oil vehicle alone, which has antioxidant properties, moderated the effects of prenatal stress on microglia. Microglia changes with prenatal stress were also sensitive to the antioxidant, N-acetylcysteine, suggesting redox dysregulation as a mechanism of prenatal stress.

  11. Prenatal stress, immunity and neonatal health in farm animal species.

    Science.gov (United States)

    Merlot, E; Quesnel, H; Prunier, A

    2013-12-01

    The high pre-weaning mortality in farm animal species and poor welfare conditions of reproductive females question modern industrial farming acceptability. A growing body of literature has been produced recently, investigating the impact of maternal stress during gestation on maternal and offspring physiology and behavior in farm animals. Until now, the possible impact of prenatal stress on neonatal health, growth and survival could not be consistently demonstrated, probably because experimental studies use small numbers of animals and thus do not allow accurate estimations. However, the data from literature synthesized in the present review show that in ungulates, maternal stress can sometimes alter important maternal parameters of neonatal survival such as colostrum production (ruminants) and maternal care to the newborn (pigs). Furthermore, maternal stress during gestation can affect maternal immune system and impair her health, which can have an impact on the transfer of pathogens from the mother to her fetus or neonate. Finally, prenatal stress can decrease the ability of the neonate to absorb colostral immunoglobulins, and alter its inflammatory response and lymphocyte functions during the first few weeks of life. Cortisol and reproductive hormones in the case of colostrogenesis are pointed out as possible hormonal mediators. Field data and epidemiological studies are needed to quantify the role of maternal welfare problems in neonatal health and survival.

  12. Thinking Across Generations: Unique Contributions of Maternal Early Life and Prenatal Stress to Infant Physiology.

    Science.gov (United States)

    Gray, Sarah A O; Jones, Christopher W; Theall, Katherine P; Glackin, Erin; Drury, Stacy S

    2017-11-01

    Respiratory sinus arrhythmia (RSA) is a parasympathetic-mediated biomarker of self-regulation linked to lifespan mental and physical health outcomes. Intergenerational impacts of mothers' exposure to prenatal stress have been demonstrated, but evidence for biological embedding of maternal preconception stress, including adverse childhood experiences (ACEs), on infant RSA is lacking. We examine the independent effects of maternal ACEs and prenatal stress on infant RSA, seeking to broaden the understanding of the earliest origins of mental and physical health risk. Mothers reported on ACEs and prenatal stress. RSA was recorded in a sample of 167 4-month-old infants (49% female and 51% male) during a dyadic stressor, the Still Face Paradigm. Independent contributions of maternal ACEs and prenatal stress to infant RSA were observed. High maternal ACEs were associated with lower RSA, whereas prenatal stress was associated with failure to recover following the stressor. Sex but not race differences were observed. Prenatal stress was associated with higher RSA among boys but lower RSA among girls. Infants' RSA is affected by mothers' life course experiences of stress, with ACEs predicting a lower set point and prenatal stress dampening recovery from stress. For prenatal stress but not ACEs, patterns vary across sex. Findings underscore that stress-reducing interventions for pregnant women or those considering pregnancy may lead to decreased physical and mental health risk across generations. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Impact of Combined Prenatal Ethanol and Prenatal Stress Exposures on Markers of Activity-Dependent Synaptic Plasticity in Rat Dentate Gyrus

    OpenAIRE

    Staples, Miranda C.; Porch, Morgan W.; Savage, Daniel D.

    2014-01-01

    Prenatal ethanol exposure and prenatal stress can each cause long-lasting deficits in hippocampal synaptic plasticity and disrupt learning and memory processes. However, the mechanisms underlying these perturbations following a learning event are still poorly understood. We examined the effects of prenatal ethanol exposure and prenatal stress exposure, either alone or in combination, on the cytosolic expression of activity-regulated cytoskeletal (ARC) protein and the synaptosomal expression o...

  14. Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment

    Science.gov (United States)

    Bourke, Chase H.; Capello, Catherine F.; Rogers, Swati M.; Yu, Megan L.; Boss-Williams, Katherine A.; Weiss, Jay M.; Stowe, Zachary N.; Owens, Michael J.

    2014-01-01

    Rationale A rigorously investigated model of stress and antidepressant administration during pregnancy is needed to evaluate possible effects on the mother. Objective The objective of this study was to develop a model of clinically relevant prenatal exposure to an antidepressant and stress during pregnancy to evaluate the effects on maternal care behavior. Results Female rats implanted with 28 day osmotic minipumps delivering the SSRI escitalopram throughout pregnancy had serum escitalopram concentrations in a clinically observed range (17-65 ng/mL). A separate cohort of pregnant females exposed to a chronic unpredictable mild stress paradigm on gestational days 10-20 showed elevated baseline (305 ng/mL), and acute stress-induced (463 ng/mL), plasma corticosterone concentrations compared to unstressed controls (109 ng/mL). A final cohort of pregnant dams were exposed to saline (control), escitalopram, stress, or stress and escitalopram to determine the effects on maternal care. Maternal behavior was continuously monitored over the first 10 days post parturition. A reduction of 35% in maternal contact and 11% in nursing behavior was observed due to stress during the light cycle. Licking and grooming behavior was unaffected by stress or drug exposure in either the light or dark cycle. Conclusions These data indicate that: 1) clinically relevant antidepressant treatment during human pregnancy can be modeled in rats using escitalopram; 2) chronic mild stress can be delivered in a manner that does not compromise fetal viability; and 3) neither of these prenatal treatments substantially altered maternal care post parturition. PMID:23436130

  15. Prenatal stress exposure related to maternal bereavement and risk of childhood overweight

    DEFF Research Database (Denmark)

    Li, Jiong; Olsen, Jørn; Vestergaard, Mogens

    2010-01-01

    It has been suggested that prenatal stress contributes to the risk of obesity later in life. In a population-based cohort study, we examined whether prenatal stress related to maternal bereavement during pregnancy was associated with the risk of overweight in offspring during school age....

  16. Prenatal Stress as a Risk-and an Opportunity-Factor.

    Science.gov (United States)

    Hartman, Sarah; Freeman, Sara M; Bales, Karen L; Belsky, Jay

    2018-04-01

    Two separate lines of research indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity and (b) that these postnatal phenotypes are associated with increased susceptibility to both positive and negative developmental experiences. Therefore, prenatal stress may increase sensitivity to the rearing environment. We tested this hypothesis by manipulating prenatal stress and rearing-environment quality, using a cross-fostering paradigm, in prairie voles. Results showed that prenatally stressed voles, as adults, displayed the highest behavioral and physiological reactivity when cross-fostered to low-contact (i.e., low-quality) rearing but the lowest behavioral and physiological reactivity when cross-fostered to high-contact (i.e., high-quality) rearing; non-prenatally stressed voles showed no effect of rearing condition. Additionally, while neither prenatal stress nor rearing condition affected oxytocin receptor binding, prenatally stressed voles cross-fostered to high-contact rearing showed the highest vasopressin-1a receptor binding in the amygdala. Results indicate that prenatal stress induces greater environmental sensitivity, making it both a risk and an opportunity factor.

  17. Bystander effects and radiotherapy.

    Science.gov (United States)

    Marín, Alicia; Martín, Margarita; Liñán, Olga; Alvarenga, Felipe; López, Mario; Fernández, Laura; Büchser, David; Cerezo, Laura

    2015-01-01

    Radiation-induced bystander effects are defined as biological effects expressed after irradiation by cells whose nuclei have not been directly irradiated. These effects include DNA damage, chromosomal instability, mutation, and apoptosis. There is considerable evidence that ionizing radiation affects cells located near the site of irradiation, which respond individually and collectively as part of a large interconnected web. These bystander signals can alter the dynamic equilibrium between proliferation, apoptosis, quiescence or differentiation. The aim of this review is to examine the most important biological effects of this phenomenon with regard to areas of major interest in radiotherapy. Such aspects include radiation-induced bystander effects during the cell cycle under hypoxic conditions when administering fractionated modalities or combined radio-chemotherapy. Other relevant aspects include individual variation and genetics in toxicity of bystander factors and normal tissue collateral damage. In advanced radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), the high degree of dose conformity to the target volume reduces the dose and, therefore, the risk of complications, to normal tissues. However, significant doses can accumulate out-of-field due to photon scattering and this may impact cellular response in these regions. Protons may offer a solution to reduce out-of-field doses. The bystander effect has numerous associated phenomena, including adaptive response, genomic instability, and abscopal effects. Also, the bystander effect can influence radiation protection and oxidative stress. It is essential that we understand the mechanisms underlying the bystander effect in order to more accurately assess radiation risk and to evaluate protocols for cancer radiotherapy.

  18. Associations between Prenatal Exposure to Black Carbon and Memory Domains in Urban Children: Modification by Sex and Prenatal Stress.

    Science.gov (United States)

    Cowell, Whitney J; Bellinger, David C; Coull, Brent A; Gennings, Chris; Wright, Robert O; Wright, Rosalind J

    2015-01-01

    Whether fetal neurodevelopment is disrupted by traffic-related air pollution is uncertain. Animal studies suggest that chemical and non-chemical stressors interact to impact neurodevelopment, and that this association is further modified by sex. To examine associations between prenatal traffic-related black carbon exposure, prenatal stress, and sex with children's memory and learning. Analyses included N = 258 mother-child dyads enrolled in a Boston, Massachusetts pregnancy cohort. Black carbon exposure was estimated using a validated spatiotemporal land-use regression model. Prenatal stress was measured using the Crisis in Family Systems-Revised survey of negative life events. The Wide Range Assessment of Memory and Learning (WRAML2) was administered at age 6 years; outcomes included the General Memory Index and its component indices [Verbal, Visual, and Attention Concentration]. Relationships between black carbon and WRAML2 index scores were examined using multivariable-adjusted linear regression including effect modification by stress and sex. Mothers were primarily minorities (60% Hispanic, 26% Black); 67% had ≤12 years of education. The main effect for black carbon was not significant for any WRAML2 index; however, in stratified analyses, among boys with high exposure to prenatal stress, Attention Concentration Index scores were on average 9.5 points lower for those with high compared to low prenatal black carbon exposure (P3-way interaction = 0.04). The associations between prenatal exposure to black carbon and stress with children's memory scores were stronger in boys than in girls. Studies assessing complex interactions may more fully characterize health risks and, in particular, identify vulnerable subgroups.

  19. Bystander deixis

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    1998-01-01

    The purpose of this contribution is to discuss non-standard speech forms of Romani and other languages in the larger context of bystander deixis, a subcategory of social deixis. First I will propose a three-way classification of instances of bystander deixis and illustrate them with examples from...... Romani and several other languages across the globe. The second part is concerned with the contextual factors that must have a place in a discourse model that wants to be able to handle linguistic manifestations of bystander deixis. Due the fact that Romani has typically been used for in......-group communication, this language presents a particularly rich source of information in the area of secret languages and other forms of bystander deixis. Moreover, as is also made abundantly clear in this volume, many jargons, trade varieties, secret languages and other more or less non-standard speech varieties...

  20. Associations among prenatal stress, maternal antioxidant intakes in pregnancy, and child temperament at age 30 months.

    Science.gov (United States)

    Lipton, L R; Brunst, K J; Kannan, S; Ni, Y-M; Ganguri, H B; Wright, R J; Bosquet Enlow, M

    2017-12-01

    Prenatal stress and prenatal nutrition each have demonstrable impact on fetal development, with implications for child neurodevelopment and behavior. However, few studies have examined their joint influences despite evidence of potential interactive effects. We examined associations among prenatal stress, prenatal antioxidant intakes, and child temperament in a sociodemographically diverse pregnancy cohort (N=137 mother-child dyads). In mid-pregnancy, mothers completed an assessment of recent negative life events as a measure of prenatal stress and an assessment of prenatal diet. When the children were 30 months of age, mothers completed the Early Childhood Behavior Questionnaire-Very Short form, which provides scores on child Negative Affectivity, Effortful Control, and Surgency/Extraversion. Linear regressions tested associations between maternal prenatal negative life events and child temperament, and effect modification by maternal prenatal antioxidant intakes (vitamins A, C, and E, magnesium, zinc, selenium, β-carotene). Analyses revealed that increased maternal prenatal negative life events were associated with higher child Negative Affectivity (β=0.08, P=0.009) but not with child Effortful Control (β=-0.03, P=0.39) or Surgency/Extraversion (β=0.04, P=0.14). Prenatal intakes of zinc and selenium modified this effect: Maternal exposure to prenatal negative life events was associated with higher child Negative Affectivity in the presence of lower intakes of zinc and selenium. Modification effects approached significance for vitamins A and C. The results suggest that the combination of elevated stress exposures and lower antioxidant intakes in pregnancy increases the likelihood of heightened child temperamental negative affectivity. Increased antioxidant intakes during pregnancy may protect against influences of prenatal stress on child temperament.

  1. Prenatal Maternal Stress and the Risk of Asthma in Children

    Directory of Open Access Journals (Sweden)

    Konstantinos Douros

    2017-09-01

    Full Text Available Emerging evidence indicate that maternal prenatal stress (MPS can result in a range of long-term adverse effects in the offspring. The underlying mechanism of MPS is not fully understood. However, its complexity is emphasized by the number of purportedly involved pathways namely, placental deregulated metabolism of maternal steroids, impaired maturation of fetal HPA axis, imbalanced efflux of commensal bacteria across the placenta, and skewed immune development toward Th2. Fetal programming probably exerts a pivotal role in the end result of the above pathways through the modulation of gene expression. In this review, we highlight the current knowledge from epidemiological and experimental studies regarding the effects of MPS on asthma development in the offspring.

  2. Brain plasticity of rats exposed to prenatal immobilization stress

    Directory of Open Access Journals (Sweden)

    Badalyan B. Yu.

    2011-10-01

    Full Text Available Aim. This histochemical and immunohistochemical study was aimed at examining the brain cellular structures of newborn rats exposed to prenatal immobilization (IMO stress. Methods. Histochemical method on detection of Ca2+-dependent acid phosphatase activity and ABC immunohistochemical technique. Results. Cell structures with radial astrocytes marker GFAP, neuroepithelial stem cell marker gene nestin, stem-cells marker and the hypothalamic neuroprotective proline-rich polypeptide PRP-1 (Galarmin, a natural cytokine of a common precursor to neurophysin vasopressin associated glycoprotein have been revealed in several brain regions. Conclusions. Our findings indicate the process of generation of new neurons in response to IMO and PRP-1 involvement in this recovery mechanism, as PRP-1-Ir was detected in the above mentioned cell structures, as well as in the neurons and nerve fibers.

  3. Sleep patterning changes in a prenatal stress model of depression

    DEFF Research Database (Denmark)

    Sickmann, Helle Mark; Skoven, C; Bastlund, Jesper F

    2018-01-01

    /wakefulness behavior around the change from light-to-dark phase. Control and PNS Sprague-Dawley rats were implanted with electrodes for continuous monitoring of electroencephalic activity used to determine behavioral state. The distribution of slow-wave sleep (SWS), rapid eye movement sleep (REMS) and wakefulness......Clinical depression is accompanied by changes in sleep patterning, which is controlled in a circadian fashion. It is thus desirable that animal models of depression mirror such diurnally-specific state alterations, along with other behavioral and physiological changes. We previously found several...... changes in behavior indicative of a depression-like phenotype in offspring of rats subjected to repeated, variable prenatal stress (PNS), including increased locomotor activity during specific periods of the circadian cycle. We, therefore, investigated whether PNS rats also exhibit alterations in sleep...

  4. Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

    Science.gov (United States)

    Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

    2018-02-01

    Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A nationwide study on the risk of autism after prenatal stress exposure to maternal bereavement

    DEFF Research Database (Denmark)

    Li, Jiong; Vestergaard, Mogens; Obel, Carsten

    2009-01-01

    OBJECTIVE: Prenatal stress has been linked to several adverse neurobehavioral outcomes, which may share a common pathophysiology with autism. We aimed to examine whether prenatal stress exposure after maternal bereavement is associated with an increased risk of autism later in life. METHODS: We...... compared with those in the unexposed group. RESULTS: Maternal bereavement during the prenatal period was not associated with an increased risk of autism in the offspring. The hazard ratios did not differ by the nature of the exposure (maternal relationship to the deceased or cause of death). The hazard...... ratios were comparable between the 5 prenatal exposure periods under study (7-12 months before pregnancy, 0-6 months before pregnancy, first trimester, second trimester, and third trimester). CONCLUSIONS: This is the first population-based cohort study to examine the effect of prenatal stress on autism...

  6. Prenatal stress and cerebral palsy: a nationwide cohort study in Denmark

    DEFF Research Database (Denmark)

    Li, Jiong; Vestergaard, Mogens; Obel, Carsten

    2009-01-01

    OBJECTIVES: Exposure to prenatal stress may affect neurodevelopment of the fetus, but whether this exposure increases the risk of cerebral palsy (CP) later in life is unknown. We aimed to examine the association between maternal bereavement during the prenatal time period and CP in childhood...

  7. Impact of maternal prenatal psychosocial stress and maternal obesity on infant microbiota

    NARCIS (Netherlands)

    Browne, P.D.; Berg, E. van den; Weerth, C. de; Browne, P.D.; Claassen, E.; Cabena, M.D.

    2017-01-01

    The prenatal period is a critical window of development for all major physiological systems in the human body. During pregnancy, maternal prenatal psychosocial stress (PNS) and maternal obesity are identified as risk factors for infant and child health. Several possible mechanisms have been

  8. Prenatal fine particulate exposure and early childhood asthma: Effect of maternal stress and fetal sex.

    Science.gov (United States)

    Lee, Alison; Leon Hsu, Hsiao-Hsien; Mathilda Chiu, Yueh-Hsiu; Bose, Sonali; Rosa, Maria José; Kloog, Itai; Wilson, Ander; Schwartz, Joel; Cohen, Sheldon; Coull, Brent A; Wright, Robert O; Wright, Rosalind J

    2018-05-01

    The impact of prenatal ambient air pollution on child asthma may be modified by maternal stress, child sex, and exposure dose and timing. We prospectively examined associations between coexposure to prenatal particulate matter with an aerodynamic diameter of less than 2.5 microns (PM 2.5 ) and maternal stress and childhood asthma (n = 736). Daily PM 2.5 exposure during pregnancy was estimated using a validated satellite-based spatiotemporally resolved prediction model. Prenatal maternal negative life events (NLEs) were dichotomized around the median (high: NLE ≥ 3; low: NLE stress and child sex. Bayesian distributed lag interaction models identified a critical window of exposure (19-23 weeks' gestation, cumulative odds ratio, 1.15; 95% CI, 1.03-1.26; per interquartile range [1.7 μg/m 3 ] increase in prenatal PM 2.5 level) during which children concomitantly exposed to prenatal PM 2.5 and maternal stress had increased risk of asthma. No significant association was seen in children born to women reporting low prenatal stress. When examining modifying effects of prenatal stress and fetal sex, we found that boys born to mothers with higher prenatal stress were most vulnerable (19-21 weeks' gestation; cumulative odds ratio, 1.28; 95% CI, 1.15-1.41; per interquartile range increase in PM 2.5 ). Prenatal PM 2.5 exposure during sensitive windows is associated with increased risk of child asthma, especially in boys concurrently exposed to elevated maternal stress. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. Increased precipitation of spasms in an animal model of infantile spasms by prenatal stress exposure.

    Science.gov (United States)

    Shi, Xiu-Yu; Ju, Jun; Zou, Li-Ping; Wang, Juan; Shang, Ning-Xiu; Zhao, Jian-Bo; Wang, Jing; Zhang, Jun-Yan

    2016-05-01

    Infantile spasms (IS) represent a serious epileptic syndrome, called West syndrome (WS) that occurs in the early infantile age. Although several hypotheses and animal models have been proposed to explain the pathogenesis of IS, the pathophysiology of IS has not been elucidated. Recently, we proposed a hypothesis for IS under prenatal stress exposure (also called Zou's hypothesis) by correlating diverse etiologies and prenatal stresses with IS development. This research aims to determine the mechanism through which prenatal stress affects the offspring and establish the potential underlying mechanisms. Pregnant rats were subjected to forced swimming in cold water. Rat pups exposed to prenatal stress were administered with N-methyl-D-aspartate (NMDA). Exposure to prenatal stress sensitized the rats against development of NMDA-induced spasms. However, this phenomenon was altered by administering adrenocorticotropin. Prenatal stress exposure also altered the hormonal levels and neurotransmitter receptor expression of the developing rats as well as influenced the tissue structure of the brain. These findings suggest that maternal stress could alter the level of endogenous glucocorticoid, which is the basis of IS, and cerebral dysplasia, hypoxic-ischemic encephalopathy (HIE), inherited metabolic diseases, and other factors activated this disease in developmental brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Radiation Bystander Effects Mechanism

    Directory of Open Access Journals (Sweden)

    Shokohzaman Soleymanifard

    2009-06-01

    Full Text Available Introduction: Radiation Induced Bystander Effect (RIBE which cause radiation effects in non-irradiated cells, has challenged the principle according to which radiation traversal through the nucleus of a cell is necessary for producing biological responses. What is the mechanism of this phenomenon? To have a better understanding of this rather ambiguous concept substantial number of original and reviewed article were carefully examined. Results: Irradiated cells release molecules which can propagate in cell environment and/or transmit through gap junction intercellular communication. These molecules can reach to non-irradiated cells and transmit bystander signals. In many investigations, it has been confirmed that these molecules are growth factors, cytokines, nitric oxide and free radicals like reactive oxygen species (ROS. Transmission of by stander signal to neighboring cells persuades them to produce secondary growth factors which in their turn cause further cell injuries. Some investigators suggest, organelles other than nucleus (mitochondria and cell membrane are the origin of these signals.  There is another opinion which suggests double strand breaks (DSB are not directly generated in bystander cells, rather they are due to smaller damage like single strand breaks which accumulate and end up to DSB. Although bystander mechanisms have not been exactly known, it can be confirmed that multiple mechanisms and various pathways are responsible for this effect. Cell type, radiation type, experimental conditions and end points identify the dominant mechanism. Conclusion: Molecules and pathways which are responsible for RIBE, also cause systemic responses to other non-irradiation stresses. So RIBE is a kind of systemic stress or innate immune responses, which are performed by cell microenvironment. Irradiated cells and their signals are components of microenvironment for creating bystander effects.

  11. Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

    Science.gov (United States)

    Lorimore, S A; Wright, E G

    2003-01-01

    To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The

  12. Prenatal stress modifies behavior and hypothalamic-pituitary-adrenal function in female guinea pig offspring: effects of timing of prenatal stress and stage of reproductive cycle.

    Science.gov (United States)

    Kapoor, Amita; Matthews, Stephen G

    2008-12-01

    Prenatal stress is associated with altered behavior and hypothalamic-pituitary-adrenal (HPA) axis function postnatally. Recent studies suggest that these outcomes are dependent on the timing of the prenatal stress. The majority of these studies have been carried out in male offspring. We hypothesized that a short period of prenatal stress would result in female offspring that exhibit differences in open-field behavior and HPA axis activity, but the outcome would depend on the timing of the prenatal stress and the stage of the reproductive cycle. Pregnant guinea pigs were exposed to a strobe light during the fetal brain growth spurt [gestational d 50-52 (PS50)] or during the period of rapid brain myelination [gestational d 60-62 (PS60)]. Open-field activity was assessed in juvenile and adult female offspring. HPA axis function was tested in adult offspring. All tests in adulthood were carried out during the estrous and luteal phases of the reproductive cycle to determine the effect of stage on HPA axis programming. Tissues were collected upon completion of the study for analysis by in situ hybridization. PS60 offspring exhibited decreased activity in an open field during the estrous phase of the reproductive cycle compared with control offspring. Both PS50 and PS60 offspring exhibited a lower salivary cortisol response to a stressor, only during the estrous phase. Consistent with the behavioral and endocrine data, PS60 females exhibited lower plasma estradiol levels, reduced ovary weight, and increased glucocorticoid receptor mRNA in the paraventricular nucleus. In conclusion, we have demonstrated that there are effects of prenatal stress on behavior and HPA axis functioning in female offspring but that the outcomes are dependent on the timing of the prenatal stress together with the status of the reproductive cycle.

  13. Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

    Science.gov (United States)

    Takahashi, L K; Kalin, N H

    1991-08-30

    Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

  14. Behavioral and Biological Effects of Prenatal Stress and Social Enrichment: Relevance to Heart Disease

    Science.gov (United States)

    2009-08-17

    whom I am eternally grateful. The first person is my coach and mentor, Neil E. Grunberg, Ph.D. There is no one who knows the " sport " of training...reported that prenatally stressed male rats actually showed a demasculinization and feminization of their sexual behavior. If female rats show a...masculinization in response to prenatal stress and males show a feminization , then the current findings could be viewed in the context of femaleS

  15. Moderate Level Alcohol During Pregnancy, Prenatal Stress, or Both and Limbic-Hypothalamic-Pituitary-Adrenocortical Axis Response to Stress in Rhesus Monkeys

    Science.gov (United States)

    Schneider, Mary L.; Moore, Colleen F.; Kraemer, Gary W.

    2004-01-01

    This study examined the relationship between moderate-level prenatal alcohol exposure, prenatal stress, and postnatal response to a challenging event in 6-month-old rhesus monkeys. Forty-one rhesus monkey (Macaca mulatta) infants were exposed prenatally to moderate level alcohol, maternal stress, or both. Offspring plasma cortisol and…

  16. Corticosterone mediates some but not other behavioural changes induced by prenatal stress in rats.

    Science.gov (United States)

    Salomon, S; Bejar, C; Schorer-Apelbaum, D; Weinstock, M

    2011-02-01

    The effect of daily varied stress from days 13-21 of gestation in Wistar rats was investigated by tests of learning and memory and anxiogenic behaviour in the 60-day-old offspring of both sexes. Prenatal stress decreased the anogenital distance in males at 1 day of age. Anxiogenic behaviour in the elevated plus maze was seen in prenatally-stressed rats of both genders. There was no significant gender difference in the rate of spatial learning in the Morris water maze but prenatal stress only slowed that of males. In the object recognition test with an inter-trial interval of 40 min, females but not males, discriminated between a familiar and novel object. Prenatal stress did not affect object discrimination in females but feminised that in males. Maternal adrenalectomy with replacement of basal corticosterone levels in the drinking fluid prevented all of the above effects of prenatal stress in the offspring. To mimic the peak corticosterone levels and time course of elevation in response to stress, corticosterone (3 mg/kg) was injected twice (0 and 30 min) on days 13-16 and once on days 17-20 of gestation to adrenalectomised mothers. This treatment re-instated anxiogenic behaviour similar to that induced by prenatal stress, indicating that it is mediated by exposure of the foetal brain to raised levels of corticosterone. However, steroid administration to adrenalectomised dams did not decrease anogenital distance, feminise object recognition memory or slow spatial learning in their male offspring. The findings indicate that other adrenal hormones are necessary to induce these effects of prenatal stress. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  17. Effects of prenatal and postnatal maternal emotional stress on toddlers' cognitive and temperamental development.

    Science.gov (United States)

    Lin, Yanfen; Xu, Jian; Huang, Jun; Jia, Yinan; Zhang, Jinsong; Yan, Chonghuai; Zhang, Jun

    2017-01-01

    Maternal stress is associated with impairments in the neurodevelopment of offspring; however, the effects of the timing of exposure to maternal stress on a child's neurodevelopment are unclear. In 2010, we studied 225 mother-child pairs in Shanghai, recruiting mothers in mid-to-late pregnancy and monitoring offspring from birth until 30 months of age. Maternal stress was assessed prenatally (at 28-36 weeks of gestation) and postnatally (at 24-30 months postpartum) using the Symptom-Checklist-90-Revised Scale (SCL-90-R) and Life-Event-Stress Scale to evaluate mothers' emotional stress and life event stress levels, respectively. Children's cognition and temperament were assessed at 24-30 months of age using the Gesell Development Scale and Toddler Temperament Scale, respectively. Multi-variable linear regression models were used to associate prenatal and postnatal stress with child cognitive and temperamental development. Maternal prenatal and postnatal Global Severity Index (GSI) of SCL-90-R were moderately correlated (ICC r=0.30, Ptoddlers' gross motor, fine motor, adaptive and social behavior development independently of postnatal GSI, while the increase in postnatal GSI was associated with changes in multiple temperament dimensions independently of prenatal GSI. The effects of prenatal and postnatal depression scores of SCL-90-R were similar to those of GSI. Relatively small sample size. Compared with postnatal exposure, children's cognitive development may be more susceptible to prenatal exposure to maternal emotional stress, whereas temperamental development may be more affected by postnatal exposure to maternal emotional stress compared with prenatal exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Characterization of the cognitive impairments induced by prenatal exposure to stress in the rat

    Directory of Open Access Journals (Sweden)

    Julie A. Markham

    2010-11-01

    Full Text Available We have previously shown that male rats exposed to gestational stress exhibit phenotypes resembling what is observed in schizophrenia, including hypersensitivity to amphetamine, blunted sensory gating, disrupted social behavior, impaired stress axis regulation, and aberrant prefrontal expression of genes involved in synaptic plasticity. Maternal psychological stress during pregnancy has been associated with adverse cognitive outcomes among children, as well as an increased risk for developing schizophrenia, which is characterized by significant cognitive deficits. We sought to characterize the long-term cognitive outcome of prenatal stress using a preclinical paradigm, which is readily amenable to the development of novel therapeutic strategies. Rats exposed to repeated variable prenatal stress during the third week of gestation were evaluated using a battery of cognitive tests, including the novel object recognition task, cued and contextual fear conditioning, the Morris water maze, and iterative versions of a paradigm in which working and reference memory for both objects and spatial locations can be assessed (the ‘Can Test’. Prenatally stressed males were impaired relative to controls on each of these tasks, confirming the face validity of this preclinical paradigm and extending the cognitive implications of prenatal stress exposure beyond the hippocampus. Interestingly, in experiments where both sexes were included, the performance of females was found to be less affected by prenatal stress compared to that of males. This could be related to the finding that women are less vulnerable than men to schizophrenia, and merits further investigation.

  19. Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice

    OpenAIRE

    Balsevich, G.; Baumann, V.; Uribe, A.; Chen, A.; Schmidt, M.

    2016-01-01

    Background: There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. Methods: We used a mouse...

  20. Unpredictable Variable Prenatal Stress Programs Expression of Genes Involved in Appetite Control and Energy Expenditure

    Science.gov (United States)

    Moyer, E. L.; Al-Shayeb, B.; Baer, L. A.; Ronca, A. E.

    2016-01-01

    Exposure to stress in the womb shapes neurobiological and physiological outcomes of offspring in later life, including body weight regulation and metabolic profiles. Our previous work utilizing a centrifugation-induced hyper-gravity demonstrated significantly increased (8-15%) body mass in male, but not female, rats exposed throughout gestation to chronic 2-g from conception to birth. We reported a similar outcome in adult offspring exposed throughout gestation to Unpredictable Variable Prenatal Stress (UVPS). Here we examine gene expression changes and the plasma of animals treated with our UVPS model to identify a potential role for prenatal stress in this hypergravity programming effect. Specifically we focused on appetite control and energy expenditure pathways in prenatally stressed adult (90-day-old) male Sprague-Dawley rats.

  1. Effects of prenatal yoga on women's stress and immune function across pregnancy: A randomized controlled trial.

    Science.gov (United States)

    Chen, Pao-Ju; Yang, Luke; Chou, Cheng-Chen; Li, Chia-Chi; Chang, Yu-Cune; Liaw, Jen-Jiuan

    2017-04-01

    The effects of prenatal yoga on biological indicators have not been widely studied. Thus, we compared changes in stress and immunity salivary biomarkers from 16 to 36 weeks' gestation between women receiving prenatal yoga and those receiving routine prenatal care. For this longitudinal, prospective, randomized controlled trial, we recruited 94 healthy pregnant women at 16 weeks' gestation through convenience sampling from a prenatal clinic in Taipei. Participants were randomly assigned to intervention (n=48) or control (n=46) groups using Clinstat block randomization. The 20-week intervention comprised two weekly 70-min yoga sessions led by a midwife certified as a yoga instructor; the control group received only routine prenatal care. In both groups, participants' salivary cortisol and immunoglobulin A levels were collected before and after yoga every 4 weeks from 16 to 36 weeks' gestation. The intervention group had lower salivary cortisol (pcontrol group. Specifically, the intervention group had significantly higher long-term salivary immunoglobulin A levels than the control group (p=0.018), and infants born to women in the intervention group weighed more than those born to the control group (pPrenatal yoga significantly reduced pregnant women's stress and enhanced their immune function. Clinicians should learn the mechanisms of yoga and its effects on pregnant women. Our findings can guide clinicians to help pregnant women alleviate their stress and enhance their immune function. Copyright © 2017. Published by Elsevier Ltd.

  2. The Relations Between Maternal Prenatal Anxiety or Stress and Child's Early Negative Reactivity or Self-Regulation: A Systematic Review.

    Science.gov (United States)

    Korja, Riikka; Nolvi, Saara; Grant, Kerry Ann; McMahon, Cathy

    2017-12-01

    In the present review, we examine the association between maternal prenatal stress or anxiety and children's early negative reactivity or self-regulation. The review includes 32 studies that focus on pregnancy-related anxiety, state or trait anxiety, perceived stress, and stressful life events in relation to child's crying, temperament, or behavior during the first 2 years of life. We searched four electronic databases and 32 studies were selected based on the inclusion criteria. Twenty-three studies found an association between maternal prenatal anxiety or stress and a child's negative reactivity or self-regulation, and typically the effect sizes varied from low to moderate. The association was found regardless of the form of prenatal stress or anxiety and the trimester in which the prenatal stress or anxiety was measured. In conclusion, several forms of prenatal anxiety and stress may increase the risk of emotional and self-regulatory difficulties during the first 2 years of life.

  3. Prenatal and postnatal stress and asthma in children: Temporal- and sex-specific associations.

    Science.gov (United States)

    Lee, Alison; Mathilda Chiu, Yueh-Hsiu; Rosa, Maria José; Jara, Calvin; Wright, Robert O; Coull, Brent A; Wright, Rosalind J

    2016-09-01

    Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. We examined associations between prenatal and/or postnatal stress and children's asthma (n = 765) and effect modification by sex in a prospective cohort study. Maternal negative life events were ascertained prenatally and postpartum. Negative life event scores were categorized as 0, 1 to 2, 3 to 4, or 5 or greater to assess exposure-response relationships. We examined effects of prenatal and postnatal stress on children's asthma by age 6 years, modeling each as independent predictors, mutually adjusting for prenatal and postnatal stress, and finally considering interactions between prenatal and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. When considering stress in each period independently, among boys, a dose-response relationship was evident for each level increase on the ordinal scale prenatally (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P value for trend = .03) and postnatally (OR, 1.53; 95% CI, 1.16-2.01; P value for trend = .001); among girls, only the postnatal trend was significant (OR, 1.60; 95% CI, 1.14-2.22; P value for trend = .005). Higher stress in both the prenatal and postnatal periods was associated with increased odds of receiving a diagnosis of asthma in girls (OR, 1.37; 95% CI, 0.98-1.91; Pinteraction = .07) but not boys (OR, 1.08; 95% CI, 0.82-1.42; Pinteraction = .61). Although boys were more vulnerable to stress during the prenatal period, girls were more affected by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early-life stress might provide unique insight into the cause and natural history of asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

    Science.gov (United States)

    Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

    2016-11-15

    Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Bystander signaling via oxidative metabolism

    Directory of Open Access Journals (Sweden)

    Sawal HA

    2017-08-01

    Full Text Available Humaira Aziz Sawal,1 Kashif Asghar,2 Matthias Bureik,3 Nasir Jalal4 1Healthcare Biotechnology Department, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 2Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan; 3Health Science Platform, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China; 4Health Science Platform, Department of Molecular and Cellular Pharmacology, Tianjin University, Tianjin, China Abstract: The radiation-induced bystander effect (RIBE is the initiation of biological end points in cells (bystander cells that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to

  6. Prenatal stress perception and coping strategies: Insights from a longitudinal prospective pregnancy cohort.

    Science.gov (United States)

    Goletzke, J; Kocalevent, R-D; Hansen, G; Rose, M; Becher, H; Hecher, K; Arck, P C; Diemert, A

    2017-11-01

    Prenatal distress has been linked to pregnancy complications and poor offspring's health, despite the fact that longitudinal assessments of various stress dimensions are still lacking. Hence, we aimed to assess perceived stress over the course of pregnancy. Moreover, we examined whether social support and coping styles are linked to prenatal stress trajectories. Data from 543 women participating in the PRINCE (Prenatal Identification of Children Health) study, a prospective population-based cohort study, was used for the present analyses. Once per trimester the women completed questionnaires regarding different psychometric measures, including the Perceived Stress Scale (PSS). Linear mixed regression models were used to examine perceived stress development longitudinally and to relate social support and coping styles to stress trajectories during pregnancy. A significant decrease of perceived stress was observed over the course of pregnancy. Stratifying the study sample according to parity, women delivering their first child had continuously lower perceived stress scores compared to women having already one or more children, and a significant decrease during pregnancy was exclusively observed in primiparous women. Both, positive coping strategies and higher perceived and received social support were independently associated with lower perceived stress, while evasive coping strategies were associated with higher levels of perceived stress. Our study reveals stress perception trajectories during pregnancies in primi- and multiparous women. Our findings underscore the need for intervention strategies aiming to improve social support and positive coping strategies especially in multiparous women in order to reduce the risks for adverse pregnancy outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

    Science.gov (United States)

    Galvão, Marcella C; Chaves-Kirsten, Gabriela P; Queiroz-Hazarbassanov, Nicolle; Carvalho, Virgínia M; Bernardi, Maria M; Kirsten, Thiago B

    2015-01-01

    Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. We prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice.

    Science.gov (United States)

    Balsevich, Georgia; Baumann, Valentin; Uribe, Andres; Chen, Alon; Schmidt, Mathias V

    2016-01-01

    There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring. Long-lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus. These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity. © 2015 S. Karger AG, Basel.

  9. Effect of honey on the reproductive system of male rat offspring exposed to prenatal restraint stress.

    Science.gov (United States)

    Haron, M N; Mohamed, M

    2016-06-01

    Exposure to prenatal stress is associated with impaired reproductive function in male rat offspring. Honey is traditionally used by the Malays for enhancement of fertility. The aim of this study was to determine the effect of honey on reproductive system of male rat offspring exposed to prenatal restraint stress. Dams were divided into four groups (n = 10/group): control, honey, stress and honey + stress groups. Dams from honey and honey + stress groups received oral honey (1.2 g kg(-1) body weight) daily from day 1 of pregnancy, meanwhile dams from stress and honey + stress groups were subjected to restraint stress (three times per day) from day 11 of pregnancy until delivery. At 10 weeks old, each male rat offspring was mated with a regular oestrus cycle female. Male sexual behaviour and reproductive performance were evaluated. Then, male rats were euthanised for assessment on reproductive parameters. Honey supplementation during prenatal restraint stress significantly increased testis and epididymis weights as well as improved the percentages of abnormal spermatozoa and sperm motility in male rat offspring. In conclusion, this study might suggest that supplementation of honey during pregnancy seems to reduce the adverse effects of restraint stress on reproductive organs weight and sperm parameters in male rat offspring. © 2015 Blackwell Verlag GmbH.

  10. [Free radical modification of proteins in brain structure of Sprague-Dawley rats and some behaviour indicators after prenatal stress].

    Science.gov (United States)

    V'iushina, A V; Pritvorova, A V; Flerov, M A

    2012-08-01

    We studied the influence of late prenatal stress on free radical oxidation processes in Sprague-Dawley rats cortex, striatum, hippocampus, hypothalamus proteins. It was shown that after prenatal stress most changes were observed in hypothalamus and hippocampus. It was shown that in hypothalamus spontaneous oxidation level increased, but level of induced oxidation decreased, the opposite changes were found in hippocampus. Simultaneously minor changes of protein modification were observed in cortex and striatum. It was shown that prenatal stress changed both correlation of proteins free radical oxidation in studied structures and values of these data regarding to control. In test of "open field" motor activity in rats after prenatal stress decreased and time of freezing and grooming increased; opposite, in T-labyrinth motor activity and time of grooming in rats after prenatal stress increased, but time of freezing decreased.

  11. Prenatal stress puzzle, the oxytocin piece: Prenatal stress alters the behaviour and autonomic regulation in piglets, insights from oxytocin

    Science.gov (United States)

    Developmental changes in response to prenatal stressors (PNS) may represent an adaptive strategy to enhance survival traits in the offspring. Yet, PNS could be maladaptive for captive animals, causing anxiety and abnormal social development. Oxytocin (OT) reduces anxiety, whereas OT deficiencies are...

  12. Bystander signaling via oxidative metabolism.

    Science.gov (United States)

    Sawal, Humaira Aziz; Asghar, Kashif; Bureik, Matthias; Jalal, Nasir

    2017-01-01

    The radiation-induced bystander effect (RIBE) is the initiation of biological end points in cells (bystander cells) that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS) act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to pursue this field of science.

  13. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Hansen, Ase M

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated...... in female offspring of pregnant rats (Mol:WIST) exposed to chronic mild stress (CMS) during gestational days (GD) 9-20, or 1500 ppm toluene, 6 h/day during gestational days 7-20, or a combination of the two. Prenatal CMS was associated with decreased thymic weight and increased auditory startle response....... The corticosterone response to restraint seemed modified by prenatal exposure to toluene. Lactational body weight was decreased in offsprings subjected to CMS, primarily due to effects in the combined exposure group. Cognitive function was investigated in the Morris water maze, and some indications of improved...

  14. MATERNAL TRAUMA AFFECTS PRENATAL MENTAL HEALTH AND INFANT STRESS REGULATION AMONG PALESTINIAN DYADS.

    Science.gov (United States)

    Isosävi, Sanna; Diab, Safwat Y; Kangaslampi, Samuli; Qouta, Samir; Kankaanpää, Saija; Puura, Kaija; Punamäki, Raija-Leena

    2017-09-01

    We examined how diverse and cumulated traumatic experiences predicted maternal prenatal mental health and infant stress regulation in war conditions and whether maternal mental health mediated the association between trauma and infant stress regulation. Participants were 511 Palestinian mothers from the Gaza Strip who reported exposure to current war trauma (WT), past childhood emotional (CEA) and physical abuse, socioeconomic status (SES), prenatal mental health problems (posttraumatic stress disorder and depression symptoms), and perceived stress during their secondtrimester of pregnancy as well as infant stress regulation at 4 months. While all trauma types were associated with high levels of prenatal symptoms, CEA had the most wide-ranging effects and was uniquely associated with depression symptoms. Concerning infant stress regulation, mothers' CEA predicted negative affectivity, but only among mothers with low WT. Against hypothesis, the effects of maternal trauma on infant stress regulation were not mediated by mental health symptoms. Mothers' higher SES was associated with better infant stress regulation whereas infant prematurity and male sex predisposed for difficulties. Our findings suggest that maternal childhood abuse, especially CEA, should be a central treatment target among war-exposed families. Cumulated psychosocial stressors might increase the risk for transgenerational problems. © 2017 Michigan Association for Infant Mental Health.

  15. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Andersen, Maud Bering; Hansen, A. M.

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated in fe...

  16. Environmental Enrichment during Gestation Improves Behavior Consequences and Synaptic Plasticity in Hippocampus of Prenatal-Stressed Offspring Rats

    International Nuclear Information System (INIS)

    Li, Mingbo; Wang, Miao; Ding, Siqing; Li, Changqi; Luo, Xuegang

    2012-01-01

    Prenatal stress can result in various behavior deficits in offspring. Here we tested the effects of environmental enrichment during gestation used as a preventive strategy on the behavior deficits of prenatal-stressed offspring rats as well as the underlying structure basis. We compared the effect size of environmental enrichment during gestation on prenatal-stressed offspring to that of environmental enrichment after weaning. Our results showed that environmental enrichment during gestation partially prevented anxiety and the damage in learning and memory in prenatal-stressed offspring as evaluated by elevated plus-maze test and Morris water maze test. At the same time, environmental enrichment during gestation inhibited the decrease in spine density of CA1 and dentate gyrus neurons and preserved the expression of synaptophysin and glucocorticoid receptors (GRs) in the hippocampus of prenatal-stressed offspring. There was no significant difference in offspring behavior between 7-day environmental enrichment during gestation and 14-day offspring environmental enrichment after weaning. These data suggest that environmental enrichment during gestation effectively prevented the behavior deficits and the abnormal synapse structures in prenatal-stressed offspring, and that it can be used as an efficient preventive strategy against prenatal stresses

  17. Prenatal maternal stress and wheeze in children: novel insights into epigenetic regulation.

    Science.gov (United States)

    Trump, Saskia; Bieg, Matthias; Gu, Zuguang; Thürmann, Loreen; Bauer, Tobias; Bauer, Mario; Ishaque, Naveed; Röder, Stefan; Gu, Lei; Herberth, Gunda; Lawerenz, Christian; Borte, Michael; Schlesner, Matthias; Plass, Christoph; Diessl, Nicolle; Eszlinger, Markus; Mücke, Oliver; Elvers, Horst-Dietrich; Wissenbach, Dirk K; von Bergen, Martin; Herrmann, Carl; Weichenhan, Dieter; Wright, Rosalind J; Lehmann, Irina; Eils, Roland

    2016-06-28

    Psychological stress during pregnancy increases the risk of childhood wheeze and asthma. However, the transmitting mechanisms remain largely unknown. Since epigenetic alterations have emerged as a link between perturbations in the prenatal environment and an increased disease risk we used whole genome bisulfite sequencing (WGBS) to analyze changes in DNA methylation in mothers and their children related to prenatal psychosocial stress and assessed its role in the development of wheeze in the child. We evaluated genomic regions altered in their methylation level due to maternal stress based of WGBS data of 10 mother-child-pairs. These data were complemented by longitudinal targeted methylation and transcriptional analyses in children from our prospective mother-child cohort LINA for whom maternal stress and wheezing information was available (n = 443). High maternal stress was associated with an increased risk for persistent wheezing in the child until the age of 5. Both mothers and children showed genome-wide alterations in DNA-methylation specifically in enhancer elements. Deregulated neuroendocrine and neurotransmitter receptor interactions were observed in stressed mothers and their children. In children but not in mothers, calcium- and Wnt-signaling required for lung maturation in the prenatal period were epigenetically deregulated and could be linked with wheezing later in children's life.

  18. Prenatal psychosocial stress exposure is associated with subsequent working memory performance in young women.

    Science.gov (United States)

    Entringer, Sonja; Buss, Claudia; Kumsta, Robert; Hellhammer, Dirk H; Wadhwa, Pathik D; Wüst, Stefan

    2009-08-01

    The aim of the present study was to examine the association between prenatal psychosocial stress exposure and subsequent prefrontal cortex-dependent working memory performance in human adults. Working memory performance was assessed using an item-recognition task under 10 mg hydrocortisone (cortisol) and placebo conditions in a sample of 32 healthy young women (mean age = 25 +/- 4.34 years) whose mothers experienced a major negative life event during their pregnancy (Prenatal Stress, PS group), and in a comparison group of 27 healthy young women (mean age = 24 +/- 3.4 years). The two groups did not differ in the placebo condition, however, subjects in the PS group showed longer reaction times after hydrocortisone administration compared with subjects in the comparison group (p = .02). These findings provide support for an association between prenatal stress exposure and the potential modulatory effect of cortisol on working memory performance in young adults, which may reflect compromised development of the prefrontal cortex in prenatal life. 2009 APA, all rights reserved

  19. Prenatal exposure to noise stress: anxiety, impaired spatial memory, and deteriorated hippocampal plasticity in postnatal life.

    Science.gov (United States)

    Barzegar, Marzieh; Sajjadi, Fatemeh Sadat; Talaei, Sayyed Alireza; Hamidi, Gholamali; Salami, Mahmoud

    2015-02-01

    Sound pollution is known as an annoying phenomenon in modern life. Especially, development of organisms during fetal life is more sensitive to environmental tensions. To address a link between the behavioral and electrophysiological aspects of brain function with action of hypothalamus-pituitary-adrenal (HPA) axis in stressed animals, this study was carried out on the male Wistar rats prenatally exposed to sound stress. Groups of pregnant rats were exposed to noise stress for 1, 2, and 4 hour(s). The degree of anxiety and the spatial memory were evaluated by elevated plus maze and Morris water maze, respectively. Basic synaptic activity and long-term potentiation (LTP) induction were assessed in the CA3-CA1 pathway of hippocampus. The serum level of corticosterone was measured in the pregnant mothers and the offspring. The behavioral experiments appeared that the stressed animals performed considerably weaker than the control rats. The prenatal stress negatively affected the basic synaptic responses and led to a lower level of LTP. The pregnant animals showed an increased serum corticosterone in comparison with the nonpregnant females. Also the offspring exposed to the noise stress had a more elevated level of corticosterone than the control rats. Our findings indicate that the corticosterone concentration changes markedly coincides the results of behavioral and electrophysiological experiments. We conclude that, similar to other environmental stresses, the sound stress during fetal life efficiently disturbs both cognitive abilities and synaptic activities. The changes in action of HPA axis may contribute to problems of the brain function in the prenatally stress exposed animals. © 2014 Wiley Periodicals, Inc.

  20. Sex-specific impact of prenatal stress on growth and reproductive parameters of guinea pigs.

    Science.gov (United States)

    Schöpper, Hanna; Klaus, Teresa; Palme, Rupert; Ruf, Thomas; Huber, Susanne

    2012-12-01

    Body condition and reproductive maturation are parameters of reproductive success that are influenced by sexual hormones rising in the circulation during the time of puberty. Various endocrine systems can be programmed by conditions experienced during early life. Stress for instance is supposed to be capable of influencing fetal development, leading to adjustments of offspring's later physiology. We examined whether prenatal stress (induced by exposure to strobe light) during early- to mid-gestation was capable of affecting later reproductive parameters in guinea pigs (Cavia aperea f. porcellus). Therefore, we measured the levels of testosterone and progesterone from the age of day 12-124 in prenatally stressed (PS, n = 20) and unaffected control animals (n = 24). Furthermore, we determined the timing of puberty and growth. Body weight development revealed significantly faster growth in PS females compared to control animals. The onset of first estrus was slightly earlier in PS females, however not significantly so. Cycle lengths and levels of progesterone differed between groups over the course of time with higher progesterone levels and more constant cycles among PS females compared to control females who displayed marked differences between first and subsequent cycles. Levels of testosterone did not differ between groups. We conclude that prenatal stress accelerates growth and maturity in females, but not in males.

  1. Effects of prenatal stress and emotional reactivity of the mother on emotional and cognitive abilities in lambs.

    Science.gov (United States)

    Coulon, Marjorie; Nowak, Raymond; Andanson, Stephane; Petit, Bérengère; Lévy, Frédéric; Boissy, Alain

    2015-07-01

    Consequences of prenatal stress on emotional reactivity and cognitive abilities in offspring are under-documented in precocial mammals. Here, we investigated to what extent emotional reactivity, judgment bias and spatial learning abilities of lambs are affected by chronic stress during late pregnancy and by their dams' emotional reactivity. The 20 highest-responsive (HR) and 20 lowest-responsive (LR) ewes from a population of 120 Romane ewes were selected according to their pre-mating reactivity to social isolation in a new environment. Over the final third of pregnancy, 10 HR ewes and 10 LR ewes were exposed daily to various unpredictable aversive events such as restraint, mixing groups and transport while the other 20 selected ewes were not. In a human and an object test, prenatally-stressed lambs were more fearful than control lambs, but the prenatal stress effect was moderated by the reactivity of the mothers: prenatally-stressed lambs from ewes with high emotional reactivity were more affected. Prenatally-stressed lambs did not perform as well as control lambs in a maze test and showed pessimistic-like judgment in a cognitive bias test. Prenatally-stressed lambs were thus characterized by a negative affective state with increased fear reactions and impaired cognitive evaluation. The development of negative moods could have long-lasting consequences on the coping strategies of the lambs in response to their rearing conditions. © 2015 Wiley Periodicals, Inc.

  2. Sex-Specific Effects of Unpredictable Variable Prenatal Stress: Implications for Mammalian Developmental Programming During Spaceflight

    Science.gov (United States)

    Talyansky, Y.; Moyer, E. L.; Oijala, E.; Baer, L. A.; Ronca, A. E.

    2016-01-01

    During adaptation to the microgravity environment, adult mammals experience stress mediated by the Hypothalamic-Pituitary-Adrenal axis. In our previous studies of pregnant rats exposed to 2-g hypergravity via centrifugation, we reported decreased corticosterone and increased body mass and leptin in adult male, but not female, offspring. In this study, we utilized Unpredictable Variable Prenatal Stress to simulate the stressors of spaceflight by exposing dams to different stressors. Stress response modulation occurs via both positive and negative feedback in the hypothalamus, anterior pituitary gland, and adrenal cortex resulting in the differential release of corticosterone (CORT), a murine analog to human cortisol.

  3. Impact on family and parental stress of prenatal vs postnatal repair of myelomeningocele.

    Science.gov (United States)

    Antiel, Ryan M; Adzick, N Scott; Thom, Elizabeth A; Burrows, Pamela K; Farmer, Diana L; Brock, John W; Howell, Lori J; Farrell, Jody A; Houtrow, Amy J

    2016-10-01

    The Management of Myelomeningocele Study was a multicenter, randomized controlled trial that compared prenatal repair with standard postnatal repair for fetal myelomeningocele. We sought to describe the long-term impact on the families of the women who participated and to evaluate how the timing of repair influenced the impact on families and parental stress. Randomized women completed the 24-item Impact on Family Scale and the 36-item Parenting Stress Index Short Form at 12 and 30 months after delivery. A revised 15-item Impact on Family Scale describing overall impact was also computed. Higher scores reflected more negative impacts or greater stress. In addition, we examined Family Support Scale and Family Resource Scale scores along with various neonatal outcomes. Repeated measures analysis was conducted for each scale and subscale. Of 183 women randomized, 171 women completed the Impact on Family Scale and 172 completed the Parenting Stress Index at both 12 and 30 months. The prenatal surgery group had significantly lower revised 15-item Impact on Family Scale scores as well as familial-social impact subscale scores compared to the postnatal surgery group (P = .02 and .004, respectively). There was no difference in total parental stress between the 2 groups (P = .89) or in any of the Parenting Stress Index Short Form subscales. In addition, walking independently at 30 months and family resources at 12 months were associated with both family impact and parental stress. The overall negative family impact of caring for a child with spina bifida, up to 30 months of age, was significantly lower in the prenatal surgery group compared to the postnatal surgery group. Ambulation status and family resources were predictive of impact on family and parental stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Prenatal stress and risk of febrile seizures in children: a nationwide longitudinal study in Denmark

    DEFF Research Database (Denmark)

    Li, Jiong; Olsen, Jørn; Obel, Carsten

    2009-01-01

    We aimed to examine whether exposure to prenatal stress following maternal bereavement is associated with an increased risk of febrile seizures. In a longitudinal population-based cohort study, we followed 1,431,175 children born in Denmark. A total of 34,777 children were born to women who lost...... a close relative during pregnancy or within 1 year before the pregnancy and they were included in the exposed group. The exposed children had a risk of febrile seizures similar to that of the unexposed children (hazard ratio (HR) 1.00, 95% CI 0.94-1.06). The HRs did not differ according to the nature...... or timing of bereavement. Our data do not suggest any causal link between exposure to prenatal stress and febrile seizures in childhood....

  5. Communalism predicts prenatal affect, stress, and physiology better than ethnicity and socioeconomic status.

    Science.gov (United States)

    Abdou, Cleopatra M; Dunkel Schetter, Christine; Campos, Belinda; Hilmert, Clayton J; Dominguez, Tyan Parker; Hobel, Calvin J; Glynn, Laura M; Sandman, Curt

    2010-07-01

    The authors examined the relevance of communalism, operationalized as a cultural orientation emphasizing interdependence, to maternal prenatal emotional health and physiology and distinguished its effects from those of ethnicity and childhood and adult socioeconomic status (SES). African American and European American women (N = 297) were recruited early in pregnancy and followed through 32 weeks gestation using interviews and medical chart review. Overall, African American women and women of lower socioeconomic backgrounds had higher levels of negative affect, stress, and blood pressure, but these ethnic and socioeconomic disparities were not observed among women higher in communalism. Hierarchical multivariate regression analyses showed that communalism was a more robust predictor of prenatal emotional health than ethnicity, childhood SES, and adult SES. Communalism also interacted with ethnicity and SES, resulting in lower blood pressure during pregnancy for African American women and women who experienced socioeconomic disadvantage over the life course. The effects of communalism on prenatal affect, stress, and physiology were not explained by depressive symptoms at study entry, perceived availability of social support, self-esteem, optimism, mastery, nor pregnancy-specific factors, including whether the pregnancy was planned, whether the pregnancy was desired after conception, or how frequently the woman felt happy to be pregnant. This suggests that a communal cultural orientation benefits maternal prenatal emotional health and physiology over and above its links to better understood personal and social resources in addition to economic resources. Implications of culture as a determinant of maternal prenatal health and well-being and an important lens for examining ethnic and socioeconomic inequalities in health are discussed.

  6. Alterations of proliferation and differentiation of hippocampal cells in prenatally stressed rats.

    Science.gov (United States)

    Sun, Hongli; Su, Qian; Zhang, Huifang; Liu, Weimin; Zhang, Huiping; Ding, Ding; Zhu, Zhongliang; Li, Hui

    2015-06-01

    To clarify the alterations of proliferation and differentiation of hippocampal cells in prenatally stressed rats. We investigated the impact of prenatal restraint stress on the hipocampal cell proliferation in the progeny with 5-bromo-2'-deoxyuridine (BrdU), which is a marker of proliferating cells and their progeny. In addition, we observed the differentiation of neural stem cells (NSCs) with double labeling of BrdU/neurofilament (NF), BrdU/glial fibrillary acidic protein (GFAP) in the hipocampus. Prenatal stress (PS) increased cell proliferation in the dentate gyrus (DG) only in female and neuron differentiation of newly divided cells in the DG and CA4 in both male and female. Moreover, the NF and GFAP-positive cells, but not the BrdU-positive cells, BrdU/NF and BrdU/GFAP-positive cells, were found frequently in the CA3 and CA1 in the offspring of each group. These results possibly suggest a compensatory adaptive response to neuronal damage or loss in hippocampus induced by PS. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  7. Prenatal maternal stress shapes children's theory of mind: the QF2011 Queensland Flood Study.

    Science.gov (United States)

    Simcock, G; Kildea, S; Elgbeili, G; Laplante, D P; Cobham, V; King, S

    2017-08-01

    Research shows that stress in pregnancy has powerful and enduring effects on many facets of child development, including increases in behavior problems and neurodevelopmental disorders. Theory of mind is an important aspect of child development that is predictive of successful social functioning and is impaired in children with autism. A number of factors related to individual differences in theory of mind have been identified, but whether theory of mind development is shaped by prenatal events has not yet been examined. In this study we utilized a sudden onset flood that occurred in Queensland, Australia in 2011 to examine whether disaster-related prenatal maternal stress predicts child theory of mind and whether sex of the child or timing of the stressor in pregnancy moderates these effects. Higher levels of flood-related maternal subjective stress, but not objective hardship, predicted worse theory of mind at 30 months (n=130). Further, maternal cognitive appraisal of the flood moderated the effects of stress in pregnancy on girls' theory of mind performance but not boys'. These results illuminate how stress in pregnancy can shape child development and the findings are discussed in relation to biological mechanisms in pregnancy and stress theory.

  8. Impact on Family and Parental Stress of Prenatal versus Postnatal Repair of Myelomeningocele

    Science.gov (United States)

    Antiel, Ryan M.; Adzick, N. Scott; Thom, Elizabeth A.; Burrows, Pamela K.; Farmer, Diana L.; Brock, John W.; Howell, Lori J.; Farrell, Jody A.; Houtrow, Amy J.

    2016-01-01

    BACKGROUND The Management of Myelomeningocele Study (MOMS) was a multicenter, randomized controlled trial that compared prenatal repair with standard postnatal repair for fetal myelomeningocele. OBJECTIVE We sought to describe the long-term impact on the families of the women who participated and to evaluate how the timing of repair influenced the impact on families and parental stress. STUDY DESIGN Randomized women completed the 24-item Impact on Family Scale (IFS) and the 36-item Parenting Stress Index Short Form (PSI-SF) at 12 and 30 months after delivery. A revised 15-item score of the IFS (RIFS) describing overall impact was also computed. Higher scores reflect more negative impacts or greater stress. In addition, we examined Family Support Scale (FSS) and Family Resource Scale (FRS) scores along with various neonatal outcomes. Repeated measures analysis was conducted for each scale and subscale. RESULTS Of 183 women randomized, 171 women completed the IFS and 172 completed the PSI at both 12 and 30 months. The prenatal surgery group had significantly lower RIFS scores as well as familial-social impact subscale scores compared to the postnatal surgery group (p=0.02 and 0.004, respectively). There was no difference in total parental stress between the two groups (p=0.89) or in any of the PSI-SF subscales. In addition, walking independently at 30 months and family resources at 12 months are associated with both family impact and parental stress. CONCLUSION The overall negative family impact of caring for a child with spina bifida, up to 30 months of age, was significantly lower in the prenatal surgery group compared to the postnatal surgery group. Ambulation status and family resources were predictive of impact on family and parental stress. PMID:27263997

  9. From prenatal anxiety to parenting stress: a longitudinal study.

    Science.gov (United States)

    Huizink, A C; Menting, B; De Moor, M H M; Verhage, M L; Kunseler, F C; Schuengel, C; Oosterman, M

    2017-10-01

    The objective of this study was to explore how maternal mood during pregnancy, i.e., general anxiety, pregnancy-specific anxiety, and depression predicted parenting stress 3 months after giving birth, thereby shaping the child's early postnatal environmental circumstances. To this end, data were used from 1073 women participating in the Dutch longitudinal cohort Generations 2 , which studies first-time pregnant mothers during pregnancy and across the transition to parenthood. Women filled out the State Trait Anxiety Inventory (STAI), Pregnancy-Related Anxiety Questionnaire-revised (PRAQ-R), and Beck Depression Index (BDI) three times during pregnancy: at 12, 22, and 32 weeks gestational age. Three months postpartum, a parenting stress questionnaire was filled out yielding seven different parenting constructs. Latent scores were computed for each of the repeatedly measured maternal mood variables with Mplus and parenting stress constructs were simultaneously regressed on these latent scores. Results showed that trait anxiety and pregnancy-specific anxiety were uniquely related to almost all parenting stress constructs, taking depression into account. Early prevention and intervention to reduce maternal anxiety in pregnancy could hold the key for a more advantageous trajectory of early postnatal parenting.

  10. Relationship between prenatal maternal stress and sleep quality in Chinese pregnant women: the mediation effect of resilience.

    Science.gov (United States)

    Li, Guopeng; Kong, Linghua; Zhou, Haiyan; Kang, Xiaofei; Fang, Yueyan; Li, Ping

    2016-09-01

    To examine the relationship between prenatal maternal stress, resilience, and sleep quality, and to determine whether resilience plays a mediating role in the relationship between prenatal maternal stress and sleep quality among pregnant women. Two hundred and thirty-one pregnant women in their second trimester participated in the study. They completed questionnaires, including: the Pittsburgh Sleep Quality Index (PSQI), the Pregnancy Stress Rating Scale (PSRS), and the 10-item Connor-Davidson Resilience Scale (CD-RISC-10). A structural equation model was used to analyze the relationships among prenatal maternal stress, resilience, and sleep quality, with resilience as a mediator. Prenatal maternal stress was negatively associated with sleep quality in pregnant women (p relationship between prenatal maternal stress and sleep quality, and the mediation effect ratio was 22.0% (p stress; however, the protective factor for sleep quality was resilience. This finding could provide scientific evidence for the development of intervention strategies with which to improve sleep quality in pregnant women. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Maternal Prenatal Stress and Other Developmental Risk Factors for Adolescent Depression: Spotlight on Sex Differences.

    Science.gov (United States)

    Maxwell, Seth D; Fineberg, Anna M; Drabick, Deborah A; Murphy, Shannon K; Ellman, Lauren M

    2018-02-01

    Maternal stress during pregnancy has been linked to premorbid abnormalities associated with depression (e.g., difficult temperament, cognitive deficits) in offspring. However, few studies have looked across developmental periods to examine maternal stress during pregnancy and offspring depression during adolescence and whether these associations differ by sex. The current study used data from 1711 mother-offspring dyads (offspring sex: 49.8% male) in a longitudinal birth cohort study. Maternal narratives collected during pregnancy were qualitatively coded for stress-related themes by independent raters. Latent class analysis (LCA) identified distinct subgroups of offspring based on exposure to maternal prenatal stress and other developmental factors from the prenatal, childhood, and adolescent periods that have been associated with depression and/or maternal prenatal stress. LCA identified subgroups that were compared to determine whether and to what extent they differed on adolescent depressive symptoms. LCA revealed a subgroup of "high-risk" individuals, characterized by maternal factors during pregnancy (higher ambivalence/negativity and lower positivity towards the pregnancy, higher levels of hassles, lower maternal education and higher maternal age at birth, higher pre-pregnancy BMI) and offspring developmental factors (decreased cognitive functioning during childhood and adolescence, lower perceived parental support during adolescence, and higher levels of maternal depression during adolescence). High-risk females exhibited elevated conduct symptoms and higher birth order, while high-risk males exhibited decreased internalizing symptoms and lower birth order. Both high-risk males and females reported elevated depressive symptoms during adolescence relative to their "low-risk" counterparts.

  12. Radiation-induced bystander effects enhanced by elevated sodium chloride through sensitizing cells to bystander factors

    International Nuclear Information System (INIS)

    Zhu Lingyan; Han Wei; Chen Shaopeng; Zhao Ye; Jiang Erkang; Bao Lingzhi; Pei Bei; Yang Gen; Zhao Guoping; Wang Jun; Xu An; Wu Lijun

    2008-01-01

    Radiation-induced bystander effects (RIBE) have been demonstrated to occur widely in various cell lines. However, very little data is available on the genotoxic effects of RIBE combined with other factor(s). We reported previously that with a low dose of α-particle irradiation, the fraction of γ-H2AX foci-positive cells in non-irradiated bystander cells was significantly increased under elevated NaCl culture conditions. In this study, we further investigated the functional role of NaCl in the enhancement of RIBE using a specially designed co-culture system and micronucleus (MN) test. It was shown that the MN frequency was not increased significantly by elevated NaCl (9.0 g/L) alone or by medium exposure. However, with 1.0 cGy α-particle irradiation, the induced MN frequency increased significantly in both irradiated and non-irradiated bystander regions. Additional studies showed that elevated NaCl made the non-irradiated bystander cells more vulnerable to bystander factors. Furthermore, it was found that the induced MN frequency in cells both in irradiated and non-irradiated bystander regions was weakened when the hypertonic medium was changed to normotonic medium for 2 h before irradiation. Such observations were quite similar to the co-effect of NaCl and hydrogen peroxide (H 2 O 2 ), indicating that elevated NaCl might sensitize non-irradiated cells to bystander factors-induced oxidative stress

  13. Antecedents of maternal parenting stress: the role of attachment style, prenatal attachment, and dyadic adjustment in first-time mothers.

    Science.gov (United States)

    Mazzeschi, Claudia; Pazzagli, Chiara; Radi, Giulia; Raspa, Veronica; Buratta, Livia

    2015-01-01

    The transition to parenthood is widely considered a period of increased vulnerability often accompanied by stress. Abidin conceived parenting stress as referring to specific difficulties in adjusting to the parenting role. Most studies of psychological distress arising from the demands of parenting have investigated the impact of stress on the development of dysfunctional parent-child relationships and on adult and child psychopathology. Studies have largely focused on mothers' postnatal experience; less attention has been devoted to maternal prenatal characteristics associated with subsequent parental stress and studies of maternal prenatal predictors are few. Furthermore, no studies have examined that association exclusively with samples of first-time mothers. With an observational prospective study design with two time periods, the aim of this study was to investigate the role of mothers' attachment style, maternal prenatal attachment to the fetus and dyadic adjustment during pregnancy (7th months of gestation) and their potential unique contribution to parenting stress 3 months after childbirth in a sample of nulliparous women. Results showed significant correlations between antenatal measures. Maternal attachment style (especially relationship anxiety) was negatively correlated with prenatal attachment and with dyadic adjustment; positive correlations resulted between prenatal attachment and dyadic adjustment. Each of the investigated variables was also good predictor of parenting stress 3 months after childbirth. Findings suggested how these dimensions could be considered as risk factors in the transition to motherhood and in the very beginning of the emergence of the caregiving system, especially with first-time mothers.

  14. Antecedents of maternal parenting stress: the role of attachment style, prenatal attachment and dyadic adjustment in first-time mothers

    Directory of Open Access Journals (Sweden)

    Claudia eMazzeschi

    2015-09-01

    Full Text Available The transition to parenthood is widely considered a period of increased vulnerability often accompanied by stress. Abidin conceived parenting stress as referring to specific difficulties in adjusting to the parenting role. Most studies of psychological distress arising from the demands of parenting have investigated the impact of stress on the development of dysfunctional parent-child relationships and on adult and child psychopathology. Studies have largely focused on mothers’ postnatal experience; less attention has been devoted to maternal prenatal characteristics associated with the subsequent parental stress and studies of maternal prenatal predictors are few. Furthermore, no studies have examined that association exclusively with samples of first-time mothers. With an observational prospective study design with two time periods, the aim of this study was to investigate the role of mothers’ attachment style, maternal prenatal attachment to the fetus and dyadic adjustment during pregnancy (7th month of gestation and their potential unique contribution to parenting stress three months after childbirth in a sample of nulliparous women. Results showed significant correlations between antenatal measures. Maternal attachment style (especially relationship anxiety was negatively correlated with prenatal attachment and with dyadic adjustment; positive correlations resulted between prenatal attachment and dyadic adjustment. Each of the investigated variables was also good predictor of parenting stress three months after childbirth. Findings suggested how these dimensions could be considered as risk factors in the transition to motherhood and in the very beginning of the emergence of the caregiving system, especially with first-time mothers

  15. Mediating role of stress reactivity in the effects of prenatal tobacco exposure on childhood mental health outcomes.

    Science.gov (United States)

    Park, Aesoon; O'Malley, Stephanie S; King, Sarah L; Picciotto, Marina R

    2014-02-01

    Prenatal tobacco exposure, through maternal smoking during pregnancy, has been associated with adverse mental health outcomes in childhood. However, the mechanisms by which prenatal tobacco exposure compromises mental health later in life are unclear. We hypothesized that sensitized reactivity to stressful life events in early childhood mediates the effect of prenatal tobacco exposure on mental health outcomes in middle childhood, after accounting for earlier mental health outcomes. Data were from 12,308 mothers and their children drawn from the Avon Longitudinal Study of Parents and Children, a large prospective population-based study. Mothers' self-reports of smoking during pregnancy, mothers' ratings of their child's reactivity to stressful life events, and teachers' and mothers' ratings of the Strengths and Difficulties Questionnaire assessing 5 domains of mental health outcomes were measured. A positive association was found between prenatal tobacco exposure and stress reactivity between the ages of 2 and 6. In turn, stress reactivity was positively associated with peer (isolation), hyperactivity, conduct, and emotional problems (but not prosocial behaviors) between the ages of 7 and 11, after accounting for the mental health outcome at age 4 and other confounders. Heightened stress reactivity in preschool ages mediated the effect of prenatal tobacco exposure on adverse mental health outcomes between the ages of 7 and 11. Interventions to assist children exposed to tobacco smoke during gestation in coping with stressful life events may help mitigate psychiatric symptoms in this population.

  16. A self-medication hypothesis for increased vulnerability to drug abuse in prenatally restraint stressed rats.

    Science.gov (United States)

    Reynaert, Marie-Line; Marrocco, Jordan; Gatta, Eleonora; Mairesse, Jérôme; Van Camp, Gilles; Fagioli, Francesca; Maccari, Stefania; Nicoletti, Ferdinando; Morley-Fletcher, Sara

    Stress-related events that occur in the perinatal period can permanently change brain and behavior of the developing individual and there is increasing evidence that early-life adversity is a contributing factor in the etiology of drug abuse and mood disorders. Neural adaptations resulting from early-life stress may mediate individual differences in novelty responsiveness and in turn contribute to drug abuse vulnerability. Prenatal restraint stress (PRS) in rats is a well-documented model of early stress known to induce long-lasting neurobiological and behavioral alterations including impaired feedback mechanisms of the HPA axis, enhanced novelty seeking, and increased sensitiveness to psychostimulants as well as anxiety/depression-like behavior. Together with the HPA axis, functional alterations of the mesolimbic dopamine system and of the metabotropic glutamate receptors system appear to be involved in the addiction-like profile of PRS rats.

  17. Sleep Changes in a Rat Prenatal Stress Model of Depression

    DEFF Research Database (Denmark)

    Skoven, Christian; Sickman, Helle M.; Bastlund, Jesper Frank

    Major depression is one of the most frequently occurring mental health disorders, but is characterized by diverse symptomatology. Sleep disturbances, however, are commonplace in depressive patients. These alterations include increased duration of Rapid Eye Movement Sleep (REMS) and increased sleep...... determination of sleep-wakefulness state. As traumatic episodes can trigger episodes of clinical depression, we also investigated effects of an acute stressor during the recording period. PNS animals (n=21) had an 82% increase in amount of REMS (11.6±1.4% vs 6.3±0.9%; p...-related increase in REMS after lights-off (pREMS rebound thus seems blunted in PNS animals. PNS alters sleep-wakefulness behavior under baseline conditions and after acute stress. This underscores the value of the PNS...

  18. Prenatal flavor exposure affects flavor recognition and stress-related behavior of piglets.

    Science.gov (United States)

    Oostindjer, Marije; Bolhuis, J Elizabeth; van den Brand, Henry; Kemp, Bas

    2009-11-01

    Exposure to flavors in the amniotic fluid and mother's milk derived from the maternal diet has been shown to modulate food preferences and neophobia of young animals of several species. Aim of the experiment was to study the effects of pre- and postnatal flavor exposure on behavior of piglets during (re)exposure to this flavor. Furthermore, we investigated whether varying stress levels, caused by different test settings, affected behavior of animals during (re)exposure. Piglets were exposed to anisic flavor through the maternal diet during late gestation and/or during lactation or never. Piglets that were prenatally exposed to the flavor through the maternal diet behaved differently compared with unexposed pigs during reexposure to the flavor in several tests, suggesting recognition of the flavor. The differences between groups were more pronounced in tests with relatively high stress levels. This suggests that stress levels, caused by the design of the test, can affect the behavior shown in the presence of the flavor. We conclude that prenatal flavor exposure affects behaviors of piglets that are indicative of recognition and that these behaviors are influenced by stress levels during (re)exposure.

  19. Impact of prenatal stress on offspring glucocorticoid levels: A phylogenetic meta-analysis across 14 vertebrate species.

    Science.gov (United States)

    Thayer, Zaneta M; Wilson, Meredith A; Kim, Andrew W; Jaeggi, Adrian V

    2018-03-21

    Prenatal exposure to maternal stress is commonly associated with variation in Hypothalamic Pituitary Adrenal (HPA)-axis functioning in offspring. However, the strength or consistency of this response has never been empirically evaluated across vertebrate species. Here we meta-analyzed 114 results from 39 studies across 14 vertebrate species using Bayesian phylogenetic mixed-effects models. We found a positive overall effect of prenatal stress on offspring glucocorticoids (d' = 0.43) though the 95% Highest Posterior Density Interval overlapped with 0 (-0.16-0.95). Meta-regressions of potential moderators highlighted that phylogeny and life history variables predicted relatively little variation in effect size. Experimental studies (d' = 0.64) produced stronger effects than observational ones (d' = -0.01), while prenatal stress affected glucocorticoid recovery following offspring stress exposure more strongly (d' = 0.75) than baseline levels (d' = 0.48) or glucocorticoid peak response (d' = 0.36). These findings are consistent with the argument that HPA-axis sensitivity to prenatal stress is evolutionarily ancient and occurs regardless of a species' overall life history strategy. These effects may therefore be especially important for mediating intra-specific life-history variation. In addition, these findings suggest that animal models of prenatal HPA-axis programming may be appropriate for studying similar effects in humans.

  20. Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

    Science.gov (United States)

    Ehrlich, David E.; Neigh, Gretchen N.; Bourke, Chase H.; Nemeth, Christina L.; Hazra, Rimi; Ryan, Steven J.; Rowson, Sydney; Jairam, Nesha; Sholar, Courtney; Rainnie, Donald G.; Stowe, Zachary N.; Owens, Michael J.

    2015-01-01

    Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure. PMID:26032436

  1. Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

    Science.gov (United States)

    Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

    2015-01-01

    In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

  2. Prenatal nonylphenol exposure, oxidative and nitrative stress, and birth outcomes: A cohort study in Taiwan

    International Nuclear Information System (INIS)

    Wang, Pei-Wei; Chen, Mei-Lien; Huang, Li-Wei; Yang, Winnie; Wu, Kuen-Yuh; Huang, Yu-Fang

    2015-01-01

    Data concerning the effects of prenatal exposures to nonylphenol (NP) and oxidative stress on neonatal birth outcomes from human studies are limited. A total of 146 pregnant women were studied (1) to investigate the association between prenatal NP exposure and maternal oxidative/nitrative stress biomarkers of DNA damage (8-hydroxy-2’-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO 2 Gua)) and lipid peroxidation (8-iso-prostaglandin F 2α (8-isoPF 2α ), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) and (2) to explore the associations among oxidative stress biomarkers, NP exposure, and neonatal birth outcomes, including gestational age, birth weight, length, Ponderal index, and head and chest circumferences. NP significantly increased the 8-OHdG and 8-NO 2 Gua levels. All infants born to mothers with urinary 8-OHdG levels above the median exhibited a significantly shorter gestational duration (B adjusted  = −4.72 days; 95% CI: −8.08 to −1.36 days). No clear association was found between NP levels and birth outcomes. Prenatal 8-OHdG levels might be a novel biomarker for monitoring fetal health related to NP exposure. - Highlights: • A cohort of pregnant women was established and followed until delivery. • NP significantly increased 8-OHdG and 8-NO 2 Gua levels. • Maternal 8-OHdG levels were associated with significantly decreased gestational duration. • No clear association was observed between NP and birth outcomes. - NP increased 8-OHdG and 8-NO 2 Gua levels; high 8-OHdG levels significantly decreased gestation length.

  3. Bystander effects of radiation

    International Nuclear Information System (INIS)

    Umar, Neethu Fathima; Daniel, Nittu

    2013-01-01

    The Radiation-Induced Bystander Effect is the phenomenon in which unirradiated cells show irradiated effects due to the signals received from nearby irradiated cells. Evidence suggests that targeted cytoplasmic irradiation results in mutation in the nucleus of the hit cells. Cells that are not directly hit by an alpha particle, but are in the vicinity of one that is hit, also contribute to the genotoxic response of the cell population. When cells are irradiated, and the medium is transferred to unirradiated cells, these unirradiated cells show bystander responses when assayed for clonogenic survival and oncogenic transformation. The demonstration of a bystander effect in human tissues and, more recently, in whole organisms have clear implication of the potential relevance of the non-targeted response to human health. This effect may also contribute to the final biological consequences of exposure to low doses of radiation. The radiation-induced bystander effect represents a paradigm shift in our understanding of the radiobiological effects of ionizing radiation, in that extranuclear and extracellular events may also contribute to the final biological consequences of exposure to low doses of radiation. Multiple pathways are involved in the bystander phenomenon, and different cell types respond differently to bystander signalling. Using cDNA microarrays, a number of cellular signalling genes, including cyclooxygenase-2 (CQX-2), have been shown to be casually linked to the bystander phenomenon. The observation that inhibition of the phosphorylation of extracellular signal-related kinase (ERK) suppressed the bystander response further confirmed the important role of the mitogen-activated protein kinase (MAPK) signalling cascade in the bystander process. The cells deficient in mitochondrial DNA showed a significantly reduced response to bystander signalling, suggesting a functional role of mitochondria in the signalling process. (author)

  4. Prenatal Stress due to a Natural Disaster Predicts Adiposity in Childhood: The Iowa Flood Study

    Directory of Open Access Journals (Sweden)

    Kelsey N. Dancause

    2015-01-01

    Full Text Available Prenatal stress can affect lifelong physical growth, including increased obesity risk. However, human studies remain limited. Natural disasters provide models of independent stressors unrelated to confounding maternal characteristics. We assessed degree of objective hardship and subjective distress in women pregnant during severe flooding. At ages 2.5 and 4 years we assessed body mass index (BMI, subscapular plus triceps skinfolds (SS + TR, an index of total adiposity, and SS : TR ratio (an index of central adiposity in their children (n=106. Hierarchical regressions controlled first for several potential confounds. Controlling for these, flood exposure during early gestation predicted greater BMI increase from age 2.5 to 4, as well as total adiposity at 2.5. Greater maternal hardship and distress due to the floods, as well as other nonflood life events during pregnancy, independently predicted greater increase in total adiposity between 2.5 and 4 years. These results support the hypothesis that prenatal stress increases adiposity beginning in childhood and suggest that early gestation is a sensitive period. Results further highlight the additive effects of maternal objective and subjective stress, life events, and depression, emphasizing the importance of continued studies on multiple, detailed measures of maternal mental health and experience in pregnancy and child growth.

  5. Prenatal programing: at the intersection of maternal stress and immune activation.

    Science.gov (United States)

    Howerton, Christopher L; Bale, Tracy L

    2012-08-01

    Exposure to prenatal insults such as maternal stress and pathogenic infections has been associated with an increased risk for neurodevelopmental disorders. The mechanisms by which these programing events occur likely involve complex interactions between the maternal hormonal milieu, the placenta, and the developing fetus, in addition to compounding factors such as fetal sex and gestational stage of development. Despite the diverse biological processes involved, examination of common pathways in maternal stress and immune activation offers intriguing possibilities for elucidation of mechanistic insight. Further, the endocrine and sex-specific placenta is a tissue poised to be a key mediator in fetal programing, located at the intersection of the maternal and embryonic environments. In this review, we will discuss the potential shared mechanisms of maternal stress and immune pathway activation, with a particular focus on the important contribution and role of the placenta. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Lasting Differential Effects on Plasticity Induced by Prenatal Stress in Dorsal and Ventral Hippocampus

    Directory of Open Access Journals (Sweden)

    Gayane Grigoryan

    2016-01-01

    Full Text Available Early life adversaries have a profound impact on the developing brain structure and functions that persist long after the original traumatic experience has vanished. One of the extensively studied brain structures in relation to early life stress has been the hippocampus because of its unique association with cognitive processes of the brain. While the entire hippocampus shares the same intrinsic organization, it assumes different functions in its dorsal and ventral sectors (DH and VH, resp., based on different connectivity with other brain structures. In the present review, we summarize the differences between DH and VH and discuss functional and structural effects of prenatal stress in the two sectors, with the realization that much is yet to be explored in understanding the opposite reactivity of the DH and VH to stressful stimulation.

  7. Effects of prenatal stress on fetal and child development: a critical literature review.

    Science.gov (United States)

    Graignic-Philippe, R; Dayan, J; Chokron, S; Jacquet, A-Y; Tordjman, S

    2014-06-01

    Many studies have examined effects of prenatal stress on pregnancy and fetal development, especially on prematurity and birthweight, and more recently long-term effects on child behavioral and emotional development. These studies are reviewed and their limitations are discussed with regard to definitions (including the concepts of stress and anxiety), stress measurements, samples, and control for confounds such as depression. It appears necessary to assess individual stress reactivity prospectively and separately at each trimester of pregnancy, to discriminate chronic from acute stress, and to take into consideration moderator variables such as past life events, sociocultural factors, predictability, social support and coping strategies. Furthermore, it might be useful to examine simultaneously, during but also after pregnancy, stress, anxiety and depression in order to understand better their relationships and to evaluate their specific effects on pregnancy and child development. Finally, further research could benefit from an integrated psychological and biological approach studying together subjective perceived stress and objective physiological stress responses in pregnant women, and their effects on fetal and child development as well as on mother-infant interactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Bystander effects in unicellular organisms

    International Nuclear Information System (INIS)

    DeVeaux, Linda C.; Durtschi, Lynn S.; Case, Jonathan G.; Wells, Douglas P.

    2006-01-01

    Radiation-induced bystander effects have been seen in mammalian cells from diverse origins. These effects can be transmitted through the medium to cells not present at the time of irradiation. We have developed an assay for detecting bystander effects in the unicellular eukaryote, the fission yeast Schizosaccharomyces pombe. This assay allows maximal exposure of unirradiated cells to cells that have received electron beam irradiation. S. pombe cells were irradiated with 16-18 MeV electrons from a pulsed electron LINAC. When survival of the irradiated cells decreased to approximately 50%, forward-mutation to 2-deoxy-D-glucose resistance increased in the unirradiated bystander cells. Further increase in dose had no additional effect on this increase. In order to detect this response, it was necessary for the irradiated cell/unirradiated cell ratio to be high. Other cellular stresses, such as heat treatment, UV irradiation, and bleomycin exposure, also caused a detectable response in untreated cells grown with the treated cells. We discuss evolutionary implications of these results

  9. Bystander effects in unicellular organisms

    Energy Technology Data Exchange (ETDEWEB)

    DeVeaux, Linda C. [Idaho Accelerator Center, Campus Box 8263, Idaho State University, Pocatello, ID 83209 (United States) and Department of Biological Sciences, Campus Box 8007, Idaho State University, Pocatello, ID 83209 (United States)]. E-mail: develind@isu.edu; Durtschi, Lynn S. [Department of Biological Sciences, Campus Box 8007, Idaho State University, Pocatello, ID 83209 (United States); Case, Jonathan G. [Department of Physics, Campus Box 8106, Idaho State University, Pocatello, ID 83209 (United States); Wells, Douglas P. [Department of Physics, Campus Box 8106, Idaho State University, Pocatello, ID 83209 (United States)

    2006-05-11

    Radiation-induced bystander effects have been seen in mammalian cells from diverse origins. These effects can be transmitted through the medium to cells not present at the time of irradiation. We have developed an assay for detecting bystander effects in the unicellular eukaryote, the fission yeast Schizosaccharomyces pombe. This assay allows maximal exposure of unirradiated cells to cells that have received electron beam irradiation. S. pombe cells were irradiated with 16-18 MeV electrons from a pulsed electron LINAC. When survival of the irradiated cells decreased to approximately 50%, forward-mutation to 2-deoxy-D-glucose resistance increased in the unirradiated bystander cells. Further increase in dose had no additional effect on this increase. In order to detect this response, it was necessary for the irradiated cell/unirradiated cell ratio to be high. Other cellular stresses, such as heat treatment, UV irradiation, and bleomycin exposure, also caused a detectable response in untreated cells grown with the treated cells. We discuss evolutionary implications of these results.

  10. Bystander effects in unicellular organisms.

    Science.gov (United States)

    DeVeaux, Linda C; Durtschi, Lynn S; Case, Jonathan G; Wells, Douglas P

    2006-05-11

    Radiation-induced bystander effects have been seen in mammalian cells from diverse origins. These effects can be transmitted through the medium to cells not present at the time of irradiation. We have developed an assay for detecting bystander effects in the unicellular eukaryote, the fission yeast Schizosaccharomyces pombe. This assay allows maximal exposure of unirradiated cells to cells that have received electron beam irradiation. S. pombe cells were irradiated with 16-18 MeV electrons from a pulsed electron LINAC. When survival of the irradiated cells decreased to approximately 50%, forward-mutation to 2-deoxy-d-glucose resistance increased in the unirradiated bystander cells. Further increase in dose had no additional effect on this increase. In order to detect this response, it was necessary for the irradiated cell/unirradiated cell ratio to be high. Other cellular stresses, such as heat treatment, UV irradiation, and bleomycin exposure, also caused a detectable response in untreated cells grown with the treated cells. We discuss evolutionary implications of these results.

  11. Altered functional connectivity to stressful stimuli in prenatally cocaine-exposed adolescents.

    Science.gov (United States)

    Zakiniaeiz, Yasmin; Yip, Sarah W; Balodis, Iris M; Lacadie, Cheryl M; Scheinost, Dustin; Constable, R Todd; Mayes, Linda C; Sinha, Rajita; Potenza, Marc N

    2017-11-01

    Prenatal cocaine exposure (PCE) is linked to addiction and obesity vulnerability. Neural responses to stressful and appetitive cues in adolescents with PCE versus those without have been differentially linked to substance-use initiation. However, no prior studies have assessed cue-reactivity responses among PCE adolescents using a connectivity-based approach. Twenty-two PCE and 22 non-prenatally drug-exposed (NDE) age-, sex-, IQ- and BMI-matched adolescents participated in individualized guided imagery with appetitive (favorite-food), stressful and neutral-relaxing cue scripts during functional magnetic resonance imaging. Subjective favorite-food craving scores were collected before and after script exposure. A data-driven voxel-wise intrinsic connectivity distribution analysis was used to identify between-group differences and examine relationships with craving scores. A group-by-cue interaction effect identified a parietal lobe cluster where PCE versus NDE adolescents showed less connectivity during stressful and more connectivity during neutral-relaxing conditions. Follow-up seed-based connectivity analyses revealed that, among PCE adolescents, the parietal seed was positively connected to inferior parietal and sensory areas and negatively connected to corticolimbic during both stress and neutral-relaxing conditions. For NDE, greater parietal connectivity to parietal, cingulate and sensory areas and lesser parietal connectivity to medial prefrontal areas were found during stress compared to neutral-relaxing cueing. Craving scores inversely correlated with corticolimbic connectivity in PCE, but not NDE adolescents, during the favorite-food condition. Findings from this first data-driven intrinsic connectivity analysis of PCE influences on adolescent brain function indicate differences relating to PCE status and craving. These findings provide insight into the developmental impact of in utero drug exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Prenatal stress, fearfulness, and the epigenome: Exploratory analysis of sex differences in DNA methylation of the glucocorticoid receptor gene.

    Directory of Open Access Journals (Sweden)

    Brendan Dale Ostlund

    2016-07-01

    Full Text Available Exposure to stress in utero is a risk factor for the development of problem behavior in the offspring, though precise pathways are unknown. We examined whether DNA methylation of the glucocorticoid receptor gene, NR3C1, was associated with experiences of stress by an expectant mother and fearfulness in her infant. Mothers reported on prenatal stress and infant temperament when infants were 5 months old (n = 68. Buccal cells for methylation analysis were collected from each infant. Prenatal stress was not related to infant fearfulness or NR3C1 methylation in the sample as a whole. Exploratory sex-specific analysis revealed a trend-level association between prenatal stress and increased methylation of NR3C1 exon 1F for female, but not male, infants. In addition, increased methylation was significantly associated with greater fearfulness for females. Results suggest an experience-dependent pathway to fearfulness for female infants via epigenetic modification of the glucocorticoid receptor gene. Future studies should examine prenatal stress in a comprehensive fashion while considering sex differences in epigenetic processes underlying infant temperament.

  13. The influence of aripiprazole and olanzapine on neurotransmitters level in frontal cortex of prenatally stressed rats.

    Science.gov (United States)

    Ratajczak, P; Kus, K; Gołembiowska, K; Noworyta-Sokołowska, K; Woźniak, A; Zaprutko, T; Nowakowska, E

    2016-09-01

    The study aims to verify whether alterations in the level of neurotransmitters have occurred in prenatally stressed rats (animal model of schizophrenia), and whether aripiprazole (ARI) and olanzapine (OLA) modify this level. The effects of ARI (1.5mg/kg) and OLA (0.5mg/kg) were studied by means of microdialysis in freely moving rats (observation time 120min). The level of neurotransmitters (DA, 5-HT, NA) and their metabolites (DOPAC, HVA, 5-HIAA) was analyzed by HPLC with coulochemical detection. Obtained results indicate that after a single administration of ARI and OLA in the prenatally stressed rats the increase of DA, DOPAC, and 5-HT was observed. In turn ARI administration increase the level of HVA and 5-HIAA and also decrease the level of NA. After OLA administration the level of NA and HVA increased and no significant change in 5-HIAA was observed. Alterations observed as a result of ARI and OLA administration may be pivotal in identifying animal models of mental disorders and in the analysis of neuroleptics effectiveness. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Buspirone before prenatal stress protects against adverse effects of stress on emotional and inflammatory pain-related behaviors in infant rats: age and sex differences.

    Science.gov (United States)

    Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Otellin, Vladimir A; Aloisi, Anna Maria

    2011-10-24

    Prenatal stress strengthens tonic pain and provokes depression. The serotoninergic system is involved in these processes. We recently showed that maternal buspirone, a 5-HT1A receptor agonist, protects against the adverse effects of in utero stress on depression and pain in adult rat offspring. Using a similar maternal treatment with buspirone, we focus here on the infant stage, which is important for the correction of prenatal abnormalities. Maternal buspirone before restraint stress during the last week of pregnancy decreased the time of immobility in the forced swim test in the infant offspring. Prenatal stress increased formalin-induced pain in the second part of the time-course of the response to formalin in males of middle infancy but in the first part of the response in males of late infancy. The effect was reversed by maternal buspirone. Pain dominated in males of both middle and late infancy but the time-course of formalin pain in infant females revealed a slower development of the processes. The results show that the time-course of formalin-induced pain in infant rats reacts to prenatal stress in an age-dependent and sexually dimorphic manner. Our finding of opposite influences of prenatal stress and buspirone before prenatal stress on formalin-induced pain during the interphase indicates that functional maturity of the descending serotonergic inhibitory system occurs in late infancy males (11-day-olds), and 5-HT1A receptors participate in this process. The data provide evidence that maternal treatment with buspirone prior to stress during pregnancy alleviates depression-like and tonic pain-related behaviors in the infant offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Effects of prenatal stress on anxiety- and depressive-like behaviors are sex-specific in prepubertal rats.

    Science.gov (United States)

    Iturra-Mena, Ann Mary; Arriagada-Solimano, Marcia; Luttecke-Anders, Ariane; Dagnino-Subiabre, Alexies

    2018-05-17

    The fetal brain is highly susceptible to stress in late pregnancy, with lifelong effects of stress on physiology and behavior. The aim of this study was to determine the physiological and behavioral effects of prenatal stress during the prepubertal period of female and male rats. We subjected pregnant Sprague-Dawley rats to a restraint stress protocol from gestational day 14 until 21, a critical period for fetal brain susceptibility to stress effects. Male and female offspring were subsequently assessed at postnatal day 24 for anxiety- and depressive-like behaviors, and spontaneous social interaction. We also assessed maternal behaviors and two stress markers: basal vs. acute-evoked stress levels of serum corticosterone and body weight gain. Prenatal stress did not affect the maternal behavior, while both female and male offspring had higher body weight gain. On the other hand, lower levels of corticosterone after acute stress stimulation as well as anxiety- and depressive-like behaviors were only evident in stressed males compared to control males. These results suggest that prenatal stress induced sex-specific effects on the hypothalamus-pituitary-adrenal (HPA) axis activity and on behavior during prepuberty. The HPA axis of prenatally stressed male rats was less active compared to control males, as well as they were more anxious and experienced depressive-like behaviors. Our results can be useful to study the neurobiological basis of childhood depression at a pre-clinical level. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Prenatal maternal stress associated with ADHD and autistic traits in early childhood

    Directory of Open Access Journals (Sweden)

    Angelica eRonald

    2011-01-01

    Full Text Available Research suggests that offspring of mothers who experience high levels of stress during pregnancy are more likely to have problems in neurobehavioural development. There is preliminary evidence that prenatal maternal stress (PNMS is a risk factor for both autism and ADHD, however most studies do not control for confounding factors and no study has investigated PNMS as a risk factor for behaviors characteristic of these disorders in early childhood. A population cohort of 2900 pregnant women were recruited before their 18th week of pregnancy and investigated prospectively. Maternal experience of stressful life events was assessed during pregnancy. When offspring were age 2-years, mothers completed the Child Behavior Checklist. Multiple regression showed that maternal stressful events during pregnancy significantly predicted ADHD behaviours in offspring, after controlling for autistic traits and other confounding variables, in both males (p= .03 and females (p= .01. Similarly, stressful events during pregnancy significantly predicted autistic traits in the offspring after controlling for ADHD behaviours and confounding variables, in males only (p= .04. In conclusion, this study suggests that PNMS, in the form of typical stressful live events such as divorce or a residential move, show a small but significant association with both autistic traits and ADHD behaviours independently, in offspring at age 2 years, after controlling for multiple antenatal, obstetric, postnatal and sociodemographic covariates. This finding supports future research using epigenetic, cross-fostering, and gene-environment interaction designs to identify the causal processes underlying this association.

  17. Active coping of prenatally stressed rats in the forced swimming test: involvement of the Nurr1 gene.

    Science.gov (United States)

    Montes, Pedro; Ruiz-Sánchez, Elizabeth; Calvillo, Minerva; Rojas, Patricia

    2016-09-01

    Depending on genetic predisposition, prenatal stress may result in vulnerability or resilience to develop psychiatric disorders in adulthood. Nurr1 is an immediate early gene, important in the brain for the stress response. We tested the hypothesis that prenatal stress and the decrease of hippocampal Nurr1 alter offspring behavioral responses in the forced swimming test (FST). Pregnant Wistar rats were exposed to restraint stress (45 min, thrice daily) from gestation day 14. Prenatally stressed (PS) and non-prenatally stressed (NPS) male offspring were treated bilaterally with a Nurr1 antisense oligodeoxynucleotide (ODN; or control) into the hippocampus at 97 d of age. After 1 h, the rats were exposed to the FST (acute stressor) to analyze their behavioral responses. Thirty minutes after the FST, we analyzed the gene expression of Nurr1, Bdnf and Nr3c1 (genes for Nurr1, brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR), respectively) in the hippocampus, prefrontal cortex (PFC) and hypothalamus. Results showed that the decrease of hippocampal Nurr1 after the antisense ODN in adult NPS rats induces immobility (indicating depressive-like behavior). The PS adult rats, including the group with decreased hippocampal Nurr1, presented low immobility in the FST. This low immobility was concordant with maintenance of Nurr1 and Bdnf expression levels in the three analyzed brain regions; Nr3c1 gene expression was also maintained in the PFC and hypothalamus. These findings suggest that Nurr1 and associated genes could participate in the brain modifications induced by prenatal stress, allowing active coping (resilience) with acute stress in adulthood.

  18. Beyond the Situational Model: Bystander Action Consequences to Intervening in Situations Involving Sexual Violence.

    Science.gov (United States)

    Moschella, Elizabeth A; Bennett, Sidney; Banyard, Victoria L

    2016-03-02

    Sexual violence is a widely reported problem in college communities. To date, research has largely focused on bystander intervention as one way to help prevent this problem. Although perceived consequences of bystander intervention, such as the weighting of costs and benefits, have been examined, little research has explored what happens after a bystander intervenes. The current study investigated what bystanders report as perceived outcomes and actual consequences of their bystander actions in response to risk for sexual assault. Of the 545 surveyed, 150 reported having taking bystander action in the past month and qualitatively described their bystander behavior and the responses of those parties involved. A range of behavioral responses and intervention methods were identified. The most frequent responses reported by participants were victims conveying positive and perpetrators conveying negative responses. Different types of helping were associated with bystanders reporting different types of responses to their actions. Future research should incorporate additional measures of consequences of bystander intervention. Implications for policy and bystander intervention programs are discussed, stressing the need for bystander intervention programs to address a range of bystander behaviors and explain the potential consequences and risks of intervening. © The Author(s) 2016.

  19. DHA Mitigates Autistic Behaviors Accompanied by Dopaminergic Change in a Gene/Prenatal Stress Mouse Model.

    Science.gov (United States)

    Matsui, Fumihiro; Hecht, Patrick; Yoshimoto, Kanji; Watanabe, Yoshihisa; Morimoto, Masafumi; Fritsche, Kevin; Will, Matthew; Beversdorf, David

    2018-02-10

    Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction, social communication, and repetitive and stereotyped behaviors. Recent work has begun to explore gene × environmental interactions in the etiology of ASD. We previously reported that prenatal stress exposure in stress-susceptible heterozygous serotonin transporter (SERT) KO pregnant dams in a mouse model resulted in autism-like behavior in the offspring (SERT/S mice). The association between prenatal stress and ASD appears to be affected by maternal SERT genotype in clinical populations as well. Using the mouse model, we examined autistic-like behaviors in greater detail, and additionally explored whether diet supplementation with docosahexaenoic acid (DHA) may mitigate the behavioral changes. Only male SERT/S mice showed social impairment and stereotyped behavior, and DHA supplementation ameliorated some of these behaviors. We also measured monoamine levels in the SERT/S mice after three treatment paradigms: DHA-rich diet continuously from breeding (DHA diet), DHA-rich diet only after weaning (CTL/DHA diet) and control diet only (CTL diet). The dopamine (DA) content in the striatum was significantly increased in the SERT/S mice compared with wild-type (WT) mice, whereas no difference was observed with noradrenaline and serotonin content. Moreover, DA content in the striatum was significantly reduced in the SERT/S mice with the DHA-rich diet provided continuously from breeding. The results indicate that autism-associated behaviors and changes in the dopaminergic system in this setting can be mitigated with DHA supplementation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. No associations of prenatal maternal psychosocial stress with fasting glucose metabolism in offspring at 5-6 years of age

    NARCIS (Netherlands)

    van Dijk, A. E.; van Eijsden, M.; Stronks, K.; Gemke, R. J. B. J.; Vrijkotte, T. G. M.

    2014-01-01

    Highly prevalent maternal psychosocial complaints are accompanied by increases in glucocorticoid stress hormones, which may predispose the offspring for type 2 diabetes and cardiovascular disease later in adulthood. The aim of the current research is to study whether prenatal maternal psychosocial

  1. Changes in markers of oxidative stress and membrane properties in synaptosomes from rats exposed prenatally to toluene

    DEFF Research Database (Denmark)

    Edelfors, Sven; Hass, Ulla; Hougaard, Karin S.

    2002-01-01

    for the experiments, Synaptosomes from rats exposed prenatally to toluene exhibited an increased level of oxidative stress when incubated with toluene in vitro compared to synaptosomes from unexposed offspring. Also the cell membrane was affected, as the calcium leakage was more increased from exposed synaptosomes...

  2. Assessment of glucose homeostasis in crossbred steer progeny sired by Brahman bulls that experienced prenatal transportation stress

    Science.gov (United States)

    The objective of this experiment was to assess glucose homeostasis of crossbred male progeny whose Brahman sires experienced prenatal transportation stress (PS) in utero. Sixteen steers (PNS group) sired by 3 PS bulls gestating dams were transported for 2 h at 60, 80, 100, 120, and 140 ± 5 d of gest...

  3. Prenatal maternal stress and atopic diseases in the child: a systematic review of observational human studies.

    Science.gov (United States)

    Andersson, N W; Hansen, M V; Larsen, A D; Hougaard, K S; Kolstad, H A; Schlünssen, V

    2016-01-01

    A growing number of studies suggest that maternal stress during pregnancy promotes atopic disorders in the offspring. This is the first systematic review to address prenatal maternal stress (PNMS) and the subsequent risk of atopy-related outcomes in the child. The review was performed in accordance to the PRISMA criteria. We searched and selected studies in PubMed, Scopus, Embase and PsychINFO until November 2014. Sixteen (with 25 analyses) of 426 identified articles met the review criteria. Five main PNMS exposures (negative life events, anxiety/depression, bereavement, distress and job strain) and five main atopic outcomes (asthma, wheeze, atopic dermatitis, allergic rhinitis and IgE) were assessed across the studies. Overall, 21 of the 25 analyses suggested a positive association between PNMS and atopic outcomes. Of the 11 exposure-response analyses reported, six found statistically significant trends. This systematic review suggests a relationship between maternal stress during pregnancy and atopic disorders in the child. However, the existing studies are of diverse quality. The wide definitions of often self-reported stress exposures imply a substantial risk for information bias and false-positive results. Research comparing objective and subjective measures of PNMS exposure as well as objective measures for atopic outcome is needed. © 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.

  4. Sleep in prenatally restraint stressed rats, a model of mixed anxiety-depressive disorder.

    Science.gov (United States)

    Mairesse, Jérôme; Van Camp, Gilles; Gatta, Eleonora; Marrocco, Jordan; Reynaert, Marie-Line; Consolazione, Michol; Morley-Fletcher, Sara; Nicoletti, Ferdinando; Maccari, Stefania

    2015-01-01

    Prenatal restraint stress (PRS) can induce persisting changes in individual's development. PRS increases anxiety and depression-like behaviors and induces changes in the hypothalamo-pituitary-adrenal (HPA) axis in adult PRS rats after exposure to stress. Since adaptive capabilities also depend on temporal organization and synchronization with the external environment, we studied the effects of PRS on circadian rhythms, including the sleep-wake cycle, that are parameters altered in depression. Using a restraint stress during gestation, we showed that PRS induced phase advances in hormonal/behavioral circadian rhythms in adult rats, and an increase in the amount of paradoxical sleep, positively correlated to plasma corticosterone levels. Plasma corticosterone levels were also correlated with immobility in the forced swimming test, indicating a depressive-like profile in the PRS rats. We observed comorbidity with anxiety-like profile on PRS rats that was correlated with a reduced release of glutamate in the ventral hippocampus. Pharmacological approaches aimed at modulating glutamate release may represent a novel therapeutic strategy to treat stress-related disorders. Finally, since depressed patients exhibit changes in HPA axis activity and in circadian rhythmicity as well as in the paradoxical sleep regulation, we suggest that PRS could represent an original animal model of depression.

  5. Exposure to prenatal psychobiological stress exerts programming influences on the mother and her fetus.

    Science.gov (United States)

    Sandman, Curt A; Davis, Elysia P; Buss, Claudia; Glynn, Laura M

    2012-01-01

    Accumulating evidence from a relatively small number of prospective studies indicates that exposure to prenatal stress profoundly influences the developing human fetus with consequences that persist into childhood and very likely forever. Maternal/fetal dyads are assessed at ∼20, ∼25, ∼31 and ∼36 weeks of gestation. Infant assessments begin 24 h after delivery with the collection of cortisol and behavioral responses to the painful stress of the heel-stick procedure and measures of neonatal neuromuscular maturity. Infant cognitive, neuromotor development, stress and emotional regulation are evaluated at 3, 6 12 and 24 months of age. Maternal psychosocial stress and demographic information is collected in parallel with infant assessments. Child neurodevelopment is assessed with cognitive tests, measures of adjustment and brain imaging between 5 and 8 years of age. Psychobiological markers of stress during pregnancy, especially early in gestation, result in delayed fetal maturation, disrupted emotional regulation and impaired cognitive performance during infancy and decreased brain volume in areas associated with learning and memory in 6- to 8-year-old children. We review findings from our projects that maternal endocrine alterations that accompany pregnancy and influence fetal/infant/child development are associated with decreased affective responses to stress, altered memory function and increased risk for postpartum depression. Our findings indicate that the mother and her fetus both are influenced by exposure to psychosocial and biological stress. The findings that fetal and maternal programming occur in parallel may have important implications for long-term child development and mother/child interactions. Copyright © 2011 S. Karger AG, Basel.

  6. Oxidative stress as a significant factor for development of an adaptive response in irradiated and nonirradiated human lymphocytes after inducing the bystander effect by low-dose X-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ermakov, Aleksei V., E-mail: avePlato@mail.ru [Research Centre for Medical Genetics, Russian Academy of Medical Science, ul. Moskvorechye, 1, Moscow 115478 (Russian Federation); Konkova, Marina S.; Kostyuk, Svetlana V.; Egolina, Natalya A.; Efremova, Liudmila V.; Veiko, Natalya N. [Research Centre for Medical Genetics, Russian Academy of Medical Science, ul. Moskvorechye, 1, Moscow 115478 (Russian Federation)

    2009-10-02

    X-radiation (10 cGy) was shown to induce in human lymphocytes transposition of homologous chromosomes loci from the membrane towards the centre of the nucleus and activation of the chromosomal nucleolus-forming regions (NFRs). These effects are transmitted by means of extracellular DNA (ecDNA) fragments to nonirradiated cells (the so-called bystander effect, BE). We demonstrated that in the development of the BE an important role is played by oxidative stress (which is brought about by low radiation doses and ecDNA fragments of the culture medium of the irradiated cells), by an enzyme of apoptosis called caspase-3, and by DNA-binding receptors of the bystander cells, presumably TLR9. Proposed herein is a scheme of the development of an adaptive response and the BE on exposure to radiation. Ionizing radiation induces apoptosis of the radiosensitive fraction of cells due to the development of the 'primary' oxidative stress (OS). DNA fragments of apoptotic cells are released into the intercellular space and interact with the DNA-binding receptors of the bystander cells. This interaction activates in lymphocytes signalling pathways associated with synthesis of the reactive oxygen species and nitrogen species, i.e., induces secondary oxidative stress accompanied by apoptosis of part of the cells, etc. Hence, single exposure to radiation may be followed by relatively long-lasting in the cellular population oxidative stress contributing to the development of an adaptive response. We thus believe that ecDNA of irradiated apoptotic lymphocytes is a significant factor of stress-signalling.

  7. Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence.

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    Rayen, Ine; van den Hove, Daniël L; Prickaerts, Jos; Steinbusch, Harry W; Pawluski, Jodi L

    2011-01-01

    Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity.

  8. Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence.

    Directory of Open Access Journals (Sweden)

    Ine Rayen

    Full Text Available Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day or vehicle beginning on postnatal day 1 (P1. Adolescent male and female offspring were divided into 4 groups: 1 prenatal stress+fluoxetine exposure, 2 prenatal stress+vehicle, 3 fluoxetine exposure alone, and 4 vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity.

  9. The Influence of Maternal Prenatal and Early Childhood Nutrition and Maternal Prenatal Stress on Offspring Immune System Development and Neurodevelopmental Disorders

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    Andrea Horvath Marques

    2013-07-01

    Full Text Available The developing immune system and central nervous system in the fetus and child are extremely sensitive to both exogenous and endogenous signals. Early immune system programming, leading to changes that can persist over the life course, has been suggested, and other evidence suggests that immune dysregulation in the early developing brain may play a role in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. The timing of immune dysregulation with respect to gestational age and neurologic development of the fetus may shape the elicited response. This creates a possible sensitive window of programming or vulnerability. This review will explore the effects of prenatal maternal and infant nutritional status (from conception until early childhood as well as prenatal maternal stress and anxiety on early programming of immune function, and how this might influence neurodevelopment. We will describe fetal immune system development and maternal-fetal immune interactions to provide a better context for understanding the influence of nutrition and stress on the immune system. Finally, we will discuss the implications for prevention of neurodevelopmental disorders, with a focus on nutrition. Although certain micronutrient supplements have shown to both reduce the risk of neurodevelopmental disorders and enhance fetal immune development, we do not know whether their impact on immune development contributes to the preventive effect on neurodevelopmental disorders. Future studies are needed to elucidate this relationship, which may contribute to a better understanding of preventative mechanisms. Integrating studies of neurodevelopmental disorders and prenatal exposures with the simultaneous evaluation of neural and immune systems will shed light on mechanisms that underlie individual vulnerability or resilience to neurodevelopmental disorders and ultimately contribute to the development of primary preventions and early

  10. Prenatal stress alters progestogens to mediate susceptibility to sex-typical, stress-sensitive disorders, such as drug abuse: a review

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    Cheryl A Frye

    2011-10-01

    Full Text Available Maternal-offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between glucocorticoids and progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5α-reduced progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress may alter these responses and dysregulate allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric and/or neurodegenerative process, this review focuses on responsiveness to drugs of abuse, which is sensitive to prenatal stress and progestogen milieu. This review explores the notion that allopregnanolone may effect, or be influenced by, prenatal stress, with consequences for neurodevelopmental-, neuropsychiatric- and/or neurodegenerative- relevant processes, such as addiction.

  11. Early prenatal food supplementation ameliorates the negative association of maternal stress with birth size in a randomised trial.

    Science.gov (United States)

    Frith, Amy L; Naved, Ruchira T; Persson, Lars Ake; Frongillo, Edward A

    2015-10-01

    Low birthweight increases the risk of infant mortality, morbidity and poor development. Maternal nutrition and stress influence birth size, but their combined effect is not known. We hypothesised that an early-invitation time to start a prenatal food supplementation programme could reduce the negative influence of prenatal maternal stress on birth size, and that effect would differ by infant sex. A cohort of 1041 pregnant women, who had delivered an infant, June 2003-March 2004, was sampled from among 3267 in the randomised controlled trial, Maternal Infant Nutritional Interventions Matlab, conducted in Matlab, Bangladesh. At 8 weeks gestation, women were randomly assigned an invitation to start food supplements (2.5 MJ d(-1) ; 6 days a week) either early (∼9 weeks gestation; early-invitation group) or at usual start time for the governmental programme (∼20 weeks gestation; usual-invitation group). Morning concentration of cortisol was measured from one saliva sample/woman at 28-32 weeks gestation to assess stress. Birth-size measurements for 90% of infants were collected within 4 days of birth. In a general linear model, there was an interaction between invitation time to start the food supplementation programme and cortisol with birthweight, length and head circumference of male infants, but not female infants. Among the usual-invitation group only, male infants whose mothers had higher prenatal cortisol weighed less than those whose mothers had lower prenatal cortisol. Prenatal food supplementation programmes that begin first trimester may support greater birth size of male infants despite high maternal stress where low birthweight is a public health concern. © 2013 John Wiley & Sons Ltd.

  12. Developmental post-natal stress can alter the effects of pre-natal stress on the adult redox balance.

    Science.gov (United States)

    Marasco, Valeria; Spencer, Karen A; Robinson, Jane; Herzyk, Pawel; Costantini, David

    2013-09-15

    Across diverse vertebrate taxa, stressful environmental conditions during development can shape phenotypic trajectories of developing individuals, which, while adaptive in the short-term, may impair health and survival in adulthood. Regardless, the long-lasting benefits or costs of early life stress are likely to depend on the conditions experienced across differing stages of development. Here, we used the Japanese quail (Coturnix coturnix japonica) to experimentally manipulate exposure to stress hormones in developing individuals. We tested the hypothesis that interactions occurring between pre- and post-natal developmental periods can induce long-term shifts on the adult oxidant phenotype in non-breeding sexually mature individuals. We showed that early life stress can induce long-term alterations in the basal antioxidant defences. The magnitude of these effects depended upon the timing of glucocorticoid exposure and upon interactions between the pre- and post-natal stressful stimuli. We also found differences among tissues with stronger effects in the erythrocytes than in the brain in which the long-term effects of glucocorticoids on antioxidant biomarkers appeared to be region-specific. Recent experimental work has demonstrated that early life exposure to stress hormones can markedly reduce adult survival (Monaghan et al., 2012). Our results suggest that long-term shifts in basal antioxidant defences might be one of the potential mechanisms driving such accelerated ageing processes and that post-natal interventions during development may be a potential tool to shape the effects induced by pre-natally glucococorticoid-exposed phenotypes. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Radiation-induced bystander effects enhanced by elevated sodium chloride through sensitizing cells to bystander factors

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Lingyan; Han Wei; Chen Shaopeng; Zhao Ye; Jiang Erkang; Bao Lingzhi; Pei Bei; Yang Gen; Zhao Guoping; Wang Jun; Xu An [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, Anhui (China); Wu Lijun [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, Anhui (China)], E-mail: ljw@ipp.ac.cn

    2008-09-26

    Radiation-induced bystander effects (RIBE) have been demonstrated to occur widely in various cell lines. However, very little data is available on the genotoxic effects of RIBE combined with other factor(s). We reported previously that with a low dose of {alpha}-particle irradiation, the fraction of {gamma}-H2AX foci-positive cells in non-irradiated bystander cells was significantly increased under elevated NaCl culture conditions. In this study, we further investigated the functional role of NaCl in the enhancement of RIBE using a specially designed co-culture system and micronucleus (MN) test. It was shown that the MN frequency was not increased significantly by elevated NaCl (9.0 g/L) alone or by medium exposure. However, with 1.0 cGy {alpha}-particle irradiation, the induced MN frequency increased significantly in both irradiated and non-irradiated bystander regions. Additional studies showed that elevated NaCl made the non-irradiated bystander cells more vulnerable to bystander factors. Furthermore, it was found that the induced MN frequency in cells both in irradiated and non-irradiated bystander regions was weakened when the hypertonic medium was changed to normotonic medium for 2 h before irradiation. Such observations were quite similar to the co-effect of NaCl and hydrogen peroxide (H{sub 2}O{sub 2}), indicating that elevated NaCl might sensitize non-irradiated cells to bystander factors-induced oxidative stress.

  14. Mothers of IVF and spontaneously conceived twins: a comparison of prenatal maternal expectations, coping resources and maternal stress.

    Science.gov (United States)

    Baor, Liora; Soskolne, Varda

    2010-06-01

    This study explores the differences in prenatal maternal expectations, coping resources and maternal stress between first time mothers of IVF twins and first time mothers of spontaneously conceived twins. The role of prenatal maternal expectations in the prediction of maternal stress was examined, as well as the mediating and moderating effect of coping resources on the association between pregnancy-type group and maternal stress. Mothers of twins from various regions in Israel were included in this prospective and cross-sectional study in which 88 mothers of IVF-conceived twins and 98 mothers of spontaneously conceived twins were interviewed twice. First, at 33-36 weeks of their pregnancy they completed a socio-demographic questionnaire and the maternal expectations questionnaire; then at 6 months after birth they completed a questionnaire regarding the delivery and medical condition of the infants, and their coping resources and maternal stress. Compared with mothers who conceived spontaneously, IVF mothers had more positive prenatal maternal expectations, but poorer coping resources and higher levels of maternal stress 6 months after birth. Maternal expectations had no predictive power regarding maternal stress, although the mother's coping resources were significantly related to maternal stress and mediated the association between pregnancy type and maternal stress. IVF-pregnant women bearing twins should be considered a high-risk group. Early identification of these mothers is essential for timely psychosocial interventions in order to enhance their resources and decrease maternal stress. Further longitudinal studies are required to determine causality in more ethnically-diverse mothers of twins.

  15. Fetal sex modifies effects of prenatal stress exposure and adverse birth outcomes.

    Science.gov (United States)

    Wainstock, Tamar; Shoham-Vardi, Ilana; Glasser, Saralee; Anteby, Eyal; Lerner-Geva, Liat

    2015-01-01

    Prenatal maternal stress is associated with pregnancy complications, poor fetal development and poor birth outcomes. Fetal sex has also been shown to affect the course of pregnancy and its outcomes. The aim of this study was to evaluate whether fetal sex modifies the association between continuous exposure to life-threatening rocket attack alarms and adverse pregnancy outcomes. A retrospective cohort study was conducted in which the exposed group was comprised of 1846 women exposed to rocket-attack alarms before and during pregnancy. The unexposed group, with similar sociodemographic characteristics, delivered during the same period of time at the same medical center, but resided out of rocket-attack range. Multivariable models for each gender separately, controlling for possible confounders, evaluated the risk associated with exposure for preterm births (PTB), low birthweight (LBW), small for gestational age and small head circumference (HC). In both univariable and multivariable analyses exposure status was a significant risk factor in female fetuses only: PTB (adj. OR = 1.43; 1.04-1.96), LBW (adj. OR = 1.41; 1.02-1.95) and HC stress.

  16. Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status.

    Science.gov (United States)

    Scott, Karen A; de Kloet, Annette D; Smeltzer, Michael D; Krause, Eric G; Flak, Jonathan N; Melhorn, Susan J; Foster, Michelle T; Tamashiro, Kellie L K; Sakai, Randall R

    2017-09-01

    Mood disorders such as major depressive disorder (MDD) affect a significant proportion of the population. Although progress has been made in the development of therapeutics, a large number of individuals do not attain full remission of symptoms and adverse side effects affect treatment compliance for some. In order to develop new therapies, there is a push for new models that better reflect the multiple risk factors that likely contribute to the development of depressive illness. We hypothesized that early life stress would exacerbate the depressive-like phenotype that we have previously observed in socially subordinate (SUB) adult male rats in the visible burrow system (VBS), a semi-natural, ethologically relevant environment in which males in a colony form a dominance hierarchy. Dams were exposed to chronic variable stress (CVS) during the last week of gestation, resulting in a robust and non-habituating glucocorticoid response that did not alter maternal food intake, body weight or litter size and weight. As adults, one prenatal CVS (PCVS) and one non-stressed (NS) male were housed in the VBS with adult females. Although there were no overt differences between PCVS and NS male offspring prior to VBS housing, a greater percentage of PCVS males became SUB. However, the depressive-like phenotype of SUB males was not exacerbated in PCVS males; rather, they appeared to better cope with SUB status than NS SUB males. They had lower basal plasma corticosterone than NS SUB males at the end of VBS housing. In situ hybridization for CRH in the PVN and CeA did not reveal any prenatal treatment or status effects, while NPY expression was higher within the MeA of dominant and subordinate males exposed to the VBS in comparison with controls, but with no effect of prenatal treatment. These data suggest that prenatal chronic variable stress may confer resilience to offspring when exposed to social stress in adulthood. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Prenatal noise and restraint stress interact to alter exploratory behavior and balance in juvenile rats, and mixed stress reverses these effects.

    Science.gov (United States)

    Badache, Soumeya; Bouslama, Slim; Brahmia, Oualid; Baïri, Abdel Madjid; Tahraoui, Abdel Krim; Ladjama, Ali

    2017-05-01

    We aimed to investigate in adolescent rats the individual and combined effects of prenatal noise and restraint stress on balance control, exploration, locomotion and anxiety behavior. Three groups of pregnant rats were exposed to daily repeated stress from day 11 to day 19 of pregnancy: 3 min noise (Noise Stress, NS); 10 min restraint (restraint stress, RS); or 3 min noise followed by 10 min restraint (mixed stress, MS). On postnatal days (PND) 44, 45 and 46, four groups of male rats (Control, NS, RS:, MS; 16 rats each), were tested as follows: (1) beam walking (BW), (2) open field (OF) and (3) elevated plus maze (EPM). Our results show that the NS group had significantly impaired balance control, locomotion and both horizontal and vertical exploration (p time in EPM open arms: p time to complete BW: p < .05). Hence, combined prenatal stressors exert non-additive effects on locomotion, exploration and balance control, but induce greater anxiety through additive effects. Terminal plasma ACTH concentration was increased by prenatal stress, especially noise, which group had the largest adrenal glands. Overall, contrary to expectation, combined prenatal stressors can interact to increase anxiety level, but diminish alteration of exploration, locomotion and impaired balance control, which were strongly induced by noise stress. Lay summary: Experience of stress in pregnancy can have negative effects on the offspring that are long-lasting. Here, we used laboratory rats to see whether repeated episodes of exposure to loud noise or preventing free movement, alone or together, during pregnancy had different effects on behaviors of the adolescent offspring. Using standard tests, we found the prenatal stresses caused the offspring to be anxious, and not to balance when moving around as well as normal offspring; the degree of impairment depended on the type of stress - loud noise exposure had the greatest effects, but if the stresses were combined the effects

  18. Significance and nature of bystander responses induced by various agents.

    Science.gov (United States)

    Verma, Neha; Tiku, Ashu Bhan

    2017-07-01

    Bystander effects in a biological system are the responses shown by non-targeted neighbouring cells/tissues/organisms. These responses are triggered by factors released from targeted cells when exposed to a stress inducing agent. The biological response to stress inducing agents is complex, owing to the diversity of mechanisms and pathways activated in directly targeted and bystander cells. These responses are highly variable and can be either beneficial or hazardous depending on the cell lines tested, dose of agent used, experimental end points and time course selected. Recently non-targeted cells have even been reported to rescue the directly exposed cells by releasing protective signals that might be induced by non-targeted bystander responses. The nature of bystander signal/s is not yet clear. However, there are evidences suggesting involvement of ROS, RNS, protein factors and even DNA molecules leading to the activation of a number of signaling pathways. These can act independently or in a cascade, to induce events leading to changes in gene expression patterns that could elicit detrimental or beneficial effects. Many review articles on radiation induced bystander responses have been published. However, to the best of our knowledge, a comprehensive review on bystander responses induced by other genotoxic chemicals and stress inducing agents has not been published so far. Therefore, the aim of the present review is to give an overview of the literature on different aspects of bystander responses: agents that induce these responses, factors that can modulate bystander responses and the mechanisms involved. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Activity of the Hypothalamic-Pituitary-Adrenal System in Prenatally Stressed Male Rats on the Experimental Model of Post-Traumatic Stress Disorder.

    Science.gov (United States)

    Pivina, S G; Rakitskaya, V V; Akulova, V K; Ordyan, N E

    2016-03-01

    Using the experimental model of post-traumatic stress disorder (stress-restress paradigm), we studied the dynamics of activity of the hypothalamic-pituitary-adrenal system (HPAS) in adult male rats, whose mothers were daily subjected to restraint stress on days 15-19 of pregnancy. Prenatally stressed males that were subjected to combined stress and subsequent restress exhibited not only increased sensitivity of HPAS to negative feedback signals (manifested under restress conditions), but also enhanced stress system reactivity. These changes persisted to the 30th day after restress. Under basal conditions, the number of cells in the hypothalamic paraventricular nucleus of these animals expressing corticotropin-releasing hormone and vasopressin was shown to decrease progressively on days 1-30. By contrast, combined stress and restress in control animals were followed by an increase in the count of CRH-immunopositive cells in the magnocellular and parvocellular parts of the paraventricular nucleus and number of vasopressin-immunopositive cells in the magnocellular part of the nucleus (to the 10th day after restress). Our results indicate a peculiar level of functional activity of HPAS in prenatally stressed males in the stress-restress paradigm: decreased activity under basal conditions and enhanced reactivity during stress.

  20. Prenatal stress programs neuroendocrine stress responses and affective behaviors in second generation rats in a sex-dependent manner.

    Science.gov (United States)

    Grundwald, Natalia J; Brunton, Paula J

    2015-12-01

    An adverse environment in early life is often associated with dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis and higher rates of mood disorders in adulthood. In rats, exposure to social stress during pregnancy results in hyperactive HPA axis responses to stress in the adult offspring and heightened anxiety behavior in the males, but not the females. Here we tested whether, without further intervention, the effects of prenatal stress (PNS) in the first filial generation (F1) are transmitted to the F2 generation via the maternal line. F1 control and PNS female rats were mated with control males and housed under non-stress conditions throughout pregnancy. HPA axis responses to acute stress, anxiety- and depressive-like behavior were assessed in the adult F2 offspring. ACTH and corticosterone responses to an acute stressor were markedly enhanced in F2 PNS females compared with controls. This was associated with greater corticotropin releasing hormone (Crh) mRNA expression in the paraventricular nucleus and reduced hippocampal glucocorticoid (Gr) and mineralocorticoid receptor (Mr) mRNA expression. Conversely, in the F2 PNS males, HPA axis responses to acute stress were attenuated and hippocampal Gr mRNA expression was greater compared with controls. F2 PNS males exhibited heightened anxiety-like behavior (light-dark box and elevated plus maze) compared with F2 control males. Anxiety-like behavior did not differ between F2 control and PNS females during metestrus/diestrus, however at proestrus/estrus, F2 control females displayed a reduction in anxiety-like behavior, but this effect was not observed in the F2 PNS females. Heightened anxiety in the F2 PNS males was associated with greater Crh mRNA expression in the central nucleus of the amygdala compared with controls. Moreover, Crh receptor-1 (Crhr1) mRNA expression was significantly increased, whereas Crhr2 mRNA was significantly decreased in discrete regions of the amygdala in F2 PNS males compared

  1. Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats.

    Directory of Open Access Journals (Sweden)

    Anna Rita Zuena

    Full Text Available Prenatal Restraint Stress (PRS in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS ("PRS rats" showed increased anxiety-like behavior in the elevated plus maze (EPM, a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sex-dependent and that the behavioral outcome may diverge in males and females.

  2. Prenatal stress down-regulates Reelin expression by methylation of its promoter and induces adult behavioral impairments in rats.

    Directory of Open Access Journals (Sweden)

    Ismael Palacios-García

    Full Text Available Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that

  3. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

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    Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

    2013-12-01

    Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

  4. Alpha-particles microbeam irradiation: impact of reactive oxygen species in bystander effect

    International Nuclear Information System (INIS)

    Hanot, M.

    2008-11-01

    Ionizing radiation-induced bystander effects arise in bystander cells that receive signals from directly irradiated cells. To date, free radicals are believed to play an active role in the bystander response, but this is incompletely characterized. To mark temporal and spatial impacts of bystander effect, we employed a precise α-particle microbeam to target a small fraction of sub-confluent osteoblastic cell cultures (MC3T3-E1). We identified the cellular membrane and mitochondria like two distinct places generating reactive oxygen species. The global oxidative stress observed after irradiation was significantly attenuated after filipin treatment, evidencing the pivotal role of membrane in MC3T3-E1 cells bystander response. To determine impact of bystander effect at a cell level, cellular consequences of this membrane-dependant bystander effect were then investigated. A variable fraction of the cell population (10 to 100%) was individually targeted. In this case, mitotic death and micronuclei yield both increased in bystander cells as well as in targeted cells demonstrating a role of bystander signals between irradiated cells in an autocrine or paracrine manner. Our results indicate a complex interaction of direct irradiation and bystander signals that lead to a membrane-dependant amplification of cell responses. (author)

  5. Does prenatal maternal stress impair cognitive development and alter temperament characteristics in toddlers with healthy birth outcomes?

    Science.gov (United States)

    Zhu, Peng; Sun, Meng-Sha; Hao, Jia-Hu; Chen, Yu-Jiang; Jiang, Xiao-Min; Tao, Rui-Xue; Huang, Kun; Tao, Fang-Biao

    2014-03-01

    The aim of this study was to assess the cognitive and behavioural development of children with healthy birth outcomes whose mothers were exposed to prenatal stress but did not experience pregnancy complications. In this prospective study, self-reported data, including the Prenatal Life Events Checklist about stressful life events (SLEs) during different stages of pregnancy, were collected at 32 to 34 weeks' gestation. Thirty-eight healthy females (mean age 27 y 8 mo, SD 2 y 4 mo) who were exposed to severe SLEs in the first trimester were defined as the exposed infant group, and 114 matched comparison participants were defined as the unexposed infant group (1:3). Maternal postnatal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale. The Bayley Scales of Infant Development and the Toddler Temperament Scale were used to evaluate the cognitive development and temperament characteristics of the infants with healthy birth outcomes when they were 16 to 18 months old. A randomized block multivariate analysis of covariance showed that the mental development index scores of the infants of mothers with prenatal exposure to SLEs in the first trimester averaged seven points (95% confidence interval 3.23-10.73 points) lower than those of the unexposed infants. Moreover, the infants in the exposed group achieved higher scores for regularity (adjusted mean [SD] 2.77 [0.65] vs. 2.52 [0.78], F(5,146) =5.27, p=0.023) and for persistence and attention span (adjusted mean 3.61 [0.72] vs. 3.35 [0.52], F(5,146) =5.51, p=0.020). This study provides evidence that lower cognitive ability and less optimal worse behavioural response in infants might independently result from prenatal maternal stress. © 2014 Mac Keith Press.

  6. Hedonic sensitivity to natural rewards is affected by prenatal stress in a sex-dependent manner.

    Science.gov (United States)

    Reynaert, Marie-Line; Marrocco, Jordan; Mairesse, Jérôme; Lionetto, Luana; Simmaco, Maurizio; Deruyter, Lucie; Allorge, Delphine; Moles, Anna; Pittaluga, Anna; Maccari, Stefania; Morley-Fletcher, Sara; Van Camp, Gilles; Nicoletti, Ferdinando

    2016-11-01

    Palatable food is a strong activator of the reward circuitry and may cause addictive behavior leading to eating disorders. How early life events and sex interact in shaping hedonic sensitivity to palatable food is largely unknown. We used prenatally restraint stressed (PRS) rats, which show abnormalities in the reward system and anxious/depressive-like behavior. Some of the hallmarks of PRS rats are known to be sex-dependent. We report that PRS enhanced and reduced milk chocolate-induced conditioned place preference in males and females, respectively. Male PRS rats also show increases in plasma dihydrotestosterone (DHT) levels and dopamine (DA) levels in the nucleus accumbens (NAc), and reductions in 5-hydroxytryptamine (5-HT) levels in the NAc and prefrontal cortex (PFC). In male rats, systemic treatment with the DHT-lowering drug finasteride reduced both milk chocolate preference and NAc DA levels. Female PRS rats showed lower plasma estradiol (E 2 ) levels and lower DA levels in the NAc, and 5-HT levels in the NAc and PFC. E 2 supplementation reversed the reduction in milk chocolate preference and PFC 5-HT levels. In the hypothalamus, PRS increased ERα and ERβ estrogen receptor and CARTP (cocaine-and-amphetamine receptor transcript peptide) mRNA levels in males, and 5-HT 2 C receptor mRNA levels in females. Changes were corrected by treatments with finasteride and E 2 , respectively. These new findings show that early life stress has a profound impact on hedonic sensitivity to high-palatable food via long-lasting changes in gonadal hormones. This paves the way to the development of hormonal strategies aimed at correcting abnormalities in the response to natural rewards. © 2015 Society for the Study of Addiction.

  7. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

    LENUS (Irish Health Repository)

    Behan, Aine T

    2011-01-01

    Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.

  8. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

    LENUS (Irish Health Repository)

    Behan, Aine T

    2012-02-01

    Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.

  9. Impact of Monochorionicity and Twin to Twin Transfusion Syndrome on Prenatal Attachment, Post Traumatic Stress Disorder, Anxiety and Depressive Symptoms.

    Science.gov (United States)

    Beauquier-Maccotta, Berengere; Chalouhi, Gihad E; Picquet, Anne-Laure; Carrier, Aude; Bussières, Laurence; Golse, Bernard; Ville, Yves

    2016-01-01

    Monochronioric (MC) twin pregnancies are considered as high-risk pregnancies with potential complications requiring in-utero interventions. We aimed to assess prenatal attachment, anxiety, post-traumatic stress disorder (PTSD) and depressive symptoms in MC pregnancies complicated with Twin-To-Twin-transfusion syndrome (TTTS) in comparison to uncomplicated monochorionic (UMC) and dichorionic pregnancies (DC). Auto-questionnaires were filled out at diagnosis of TTTS and at successive milestones. Prenatal attachment, PTSD, anxiety and perinatal depression were evaluated respectively by the Prenatal Attachment Inventory (PAI) completed for each twin, the Post-traumatic Checklist Scale (PCLS), the State-Trait Anxiety Inventory (STAI) and the Edinburgh Perinatal Depression Scale (EPDS). There was no significant difference in the PAI scores between the two twins. In the DC and UMC groups, PAI scores increased throughout pregnancy, whilst it didn't for TTTS group. TTTS and DC had a similar prenatal attachment while MC mothers expressed a significantly higher attachment to their fetuses and expressed it earlier. At the announcement of TTTS, 72% of the patients present a score over the threshold at the EPDS Scale, with a higher score for TTTS than for DC (p = 0.005), and UMC (p = 0.007) at the same GA. 30% of mothers in TTTS group have PTSD during pregnancy. 50% of TTTS- patients present an anxiety score over the threshold (STAI-Scale), with a score significantly higher in TTTS than in UMC (panxiety and an alteration of the prenatal attachment. These results should guide the psychological support provided to these patients.

  10. The Association Between Prenatal Stress and Externalizing Symptoms in Childhood: Evidence From the Avon Longitudinal Study of Parents and Children.

    Science.gov (United States)

    MacKinnon, Nathalie; Kingsbury, Mila; Mahedy, Liam; Evans, Jonathan; Colman, Ian

    2018-01-15

    It has been suggested that prenatal maternal stress may increase the risk of childhood externalizing disorders, yet no large cohort study has investigated this association across a large range of acute stressors. Our objective was to estimate the association between prenatal stressful events and risk of offspring conduct disorder and hyperactivity. We used data from 10,184 mother-offspring pairs from the United Kingdom-based Avon Longitudinal Study of Parents and Children. Mothers self-reported 42 prenatal stressful life events at 18 weeks' gestation. Symptoms of conduct disorder and hyperactivity in their offspring were measured at 6, 9, 11, 13, and 16 years of age using the Strengths and Difficulties Questionnaire. The primary outcome was membership in high-symptom trajectories of 1) conduct disorder and 2) hyperactivity throughout childhood, identified using latent class growth modeling. Multinomial logistic regression models estimated the association between prenatal stress and both conduct disorder and hyperactivity, after adjusting for sex, parental education, low birth weight, preterm birth, parental social class, maternal smoking and drinking, maternal mental health, offspring stressful life events, and offspring depressive and anxious symptoms. Those exposed to the highest quartile of prenatal stress were more likely to belong to the high symptom trajectory for hyperactivity (B = 0.46, p < .05) and conduct disorder (B = 0.88, p < .01), respectively. Prenatal stress further demonstrated a positive, dose-response relationship with symptoms of externalizing disorders at independent time points. The findings suggest that prenatal stressful events may be an independent risk factor for offspring externalizing symptoms, regardless of maternal mental health and offspring internalizing. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Prenatal stress and balance of the child's cardiac autonomic nervous system at age 5-6 years.

    Directory of Open Access Journals (Sweden)

    Aimée E van Dijk

    Full Text Available OBJECTIVE: Autonomic nervous system (ANS misbalance is a potential causal factor in the development of cardiovascular disease. The ANS may be programmed during pregnancy due to various maternal factors. Our aim is to study maternal prenatal psychosocial stress as a potential disruptor of cardiac ANS balance in the child. METHODS: Mothers from a prospective birth cohort (ABCD study filled out a questionnaire at gestational week 16 [IQR 12-20], that included validated instruments for state anxiety, depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain. A cumulative stress score was also calculated (based on 80(th percentiles. Indicators of cardiac ANS in the offspring at age 5-6 years are: pre-ejection period (PEP, heart rate (HR, respiratory sinus arrhythmia (RSA and cardiac autonomic balance (CAB, measured with electrocardiography and impedance cardiography in resting supine and sitting positions. RESULTS: 2,624 mother-child pairs, only single births, were available for analysis. The stress scales were not significantly associated with HR, PEP, RSA and CAB (p≥0.17. Accumulation of maternal stress was also not associated with HR, PEP, RSA and CAB (p≥0.07. CONCLUSION: Results did not support the hypothesis that prenatal maternal psychosocial stress deregulates cardiac ANS balance in the offspring, at least in rest, and at the age of five-six years.

  12. Failure to upregulate Agrp and Orexin in response to activity based anorexia in weight loss vulnerable rats characterized by passive stress coping and prenatal stress experience.

    Science.gov (United States)

    Boersma, Gretha J; Liang, Nu-Chu; Lee, Richard S; Albertz, Jennifer D; Kastelein, Anneke; Moody, Laura A; Aryal, Shivani; Moran, Timothy H; Tamashiro, Kellie L

    2016-05-01

    We hypothesize that anorexia nervosa (AN) poses a physiological stress. Therefore, the way an individual copes with stress may affect AN vulnerability. Since prenatal stress (PNS) exposure alters stress responsivity in offspring this may increase their risk of developing AN. We tested this hypothesis using the activity based anorexia (ABA) rat model in control and PNS rats that were characterized by either proactive or passive stress-coping behavior. We found that PNS passively coping rats ate less and lost more weight during the ABA paradigm. Exposure to ABA resulted in higher baseline corticosterone and lower insulin levels in all groups. However, leptin levels were only decreased in rats with a proactive stress-coping style. Similarly, ghrelin levels were increased only in proactively coping ABA rats. Neuropeptide Y (Npy) expression was increased and proopiomelanocortin (Pomc) expression was decreased in all rats exposed to ABA. In contrast, agouti-related peptide (Agrp) and orexin (Hctr) expression were increased in all but the PNS passively coping ABA rats. Furthermore, DNA methylation of the orexin gene was increased after ABA in proactive coping rats and not in passive coping rats. Overall our study suggests that passive PNS rats have innate impairments in leptin and ghrelin in responses to starvation combined with prenatal stress associated impairments in Agrp and orexin expression in response to starvation. These impairments may underlie decreased food intake and associated heightened body weight loss during ABA in the passively coping PNS rats. Published by Elsevier Ltd.

  13. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

    Science.gov (United States)

    Woodman, Andrew G; Mah, Richard; Keddie, Danae; Noble, Ronan M N; Panahi, Sareh; Gragasin, Ferrante S; Lemieux, Hélène; Bourque, Stephane L

    2018-06-01

    Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

  14. Bystander effects: intercellular transmission of radiation damage signals

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B.; Azzam, E.I.; Toledo, S.M. de; Nagasawa, H

    2002-07-01

    Biological effects were examined in confluent cultures of fibroblasts and epithelial cells exposed to very low mean doses of alpha radiation, doses by which only 1-2% of the cells were actually traversed by an alpha particle. Enhanced frequencies of sister chromatid exchanges and HPRT mutations occurred in the non-irradiation, 'bystander' cells associated with a similar increase in the frequency of micronuclei, indicating the induction of DNA damage in these cells. In order to gain information concerning molecular pathways, changes in gene expression were examined in bystander cells by western analysis and in situ immunofluorescence staining. The expression levels of p53, p21 and MDM2 were significantly modulated in bystander cells: the damage signals leading to these changes were transmitted from irradiated to bystander cells by gap junction mediated intracellular communication. The bystander response was suppressed by incubation with superoxide dismutase as well as an inhibitor of NADPH oxidase, suggesting the effect may be mediated by oxidative stress. To examine other signalling pathways responsive to oxidative stress, the activation of stress-related kinases and their downstream transcription factors were analysed in bystander cells by western blotting and electrophoretic mobility shift assays: a 2-4 fold increase in the phosphorylation levels of JNK, EPK1/2, p90RSK, Elk-1 and ATF2 was observed. These changes were detected by 15 min after irradiation and persisted for at least 1 h. These findings indicate the activation of multiple signal transduction pathways in bystander cells, involving signals arising from the plasma membrane as well as from DNA damage. (author)

  15. Neurobiology and neurodevelopmental impact of childhood traumatic stress and prenatal alcohol exposure.

    Science.gov (United States)

    Henry, Jim; Sloane, Mark; Black-Pond, Connie

    2007-04-01

    Research reveals that prenatal alcohol exposure and child trauma (i.e., abuse, neglect, sexual abuse) can have deleterious effects on child development across multiple domains. This study analyzed the impact on childhood neurodevelopment of prenatal alcohol exposure and postnatal traumatic experience compared to postnatal traumatic experience alone. Although the harmful effects of both have been well documented individually, there is no research documenting the concurrent effects of prenatal alcohol exposure and postnatal trauma on a child's developmental process. Transdisciplinary assessment of the children included the core disciplines of medicine, speech-language pathology, occupational therapy, social work, and psychology. Medical examination, standardized developmental and intelligence testing, projective tools, parent questionnaires, and psychosocial interviews provided information in the primary developmental areas. Findings indicated that children who had been exposed prenatally to alcohol along with postnatal traumatic experience had lower intelligence scores and more severe neurodevelopmental deficits in language, memory, visual processing, motor skills, and attention than did traumatized children without prenatal alcohol exposure, as well as greater oppositional/defiant behavior, inattention, hyperactivity, impulsivity, and social problems. Successful teacher and speech-language pathologist interventions with traumatized children with prenatal alcohol exposure demand a paradigm shift that requires the development of new perspectives and ongoing training.

  16. The effects of prenatal sound stress on the spatial learning and memory of rat's male offspring

    Directory of Open Access Journals (Sweden)

    Barzegar M

    2011-01-01

    Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Numerous evidences indicate that various environmental stresses during pregnancy affect physiological behavior of the offspring. This experimental study was designed to investigate the effect of noise stress during prenatal period of rats on spatial learning and memory and plasma corticostrone level in postnatal life."n"nMethods: Three groups of pregnant rats were given daily noise stress with durations of two and/ or four hours in last week of pregnancy period. The fourth group was left unstressed. The male offspring from the unstressed and different stressed groups were assigned as controls and stressed groups. The animals were introduced to a spatial task in Morris water maze 4 trials/day for five consecutive days. The probe test was performed on the 5th day of the experiment. The delay in findings and the distance passed to locate the target platform were assessed as the spatial learning. "n"nResults: Our results showed that prenatal exposure to noise stress for two and/ or four hours a day, leads to impaired acquisition of spatial learning in the postnatal animals. The plasma level of corticostrone in the two stressed groups of rats markedly matched with their behavioral function. Prenatal exposure to 1- hour noise stress revealed no effects on the offsprings' behavior and plasma corticostrone level."n"nConclusion: Based on our study results, it seems that applied range of stress which is executed through the noise stress could increase the plasma corticostrone level and

  17. Prenatal stress produces anxiety prone female offspring and impaired maternal behaviour in the domestic pig.

    Science.gov (United States)

    Rutherford, Kenneth M D; Piastowska-Ciesielska, Agnieszka; Donald, Ramona D; Robson, Sheena K; Ison, Sarah H; Jarvis, Susan; Brunton, Paula J; Russell, John A; Lawrence, Alistair B

    2014-04-22

    Numerous studies have shown that prenatal stress (PNS) can have profound effects on postnatal well-being. Here, the domestic pig (Sus scrofa) was used to investigate PNS effects owing to the direct relevance for farm animal welfare and the developing status of the pig as a large animal model in translational research. Pregnant primiparous sows were exposed, in mid-gestation, to either a social stressor (mixing with unfamiliar conspecifics) or were kept in stable social groups. The ratio of levels of mRNAs for corticotropin releasing hormone (CRH) receptors 1 and 2 in the amygdala, measured for the first time in the pig, was substantially increased in 10-week-old female, but not male, PNS progeny indicating a neurobiological propensity for anxiety-related behaviour. Mature female offspring were observed at parturition in either a behaviourally restrictive crate or open pen. Such PNS sows showed abnormal maternal behaviour in either environment, following the birth of their first piglet. They spent more time lying ventrally, more time standing and showed a higher frequency of posture changes. They were also more reactive towards their piglets, and spent longer visually attending to their piglets compared to controls. Associated with this abnormal maternal care, piglet mortality was increased in the open pen environment, where protection for piglets is reduced. Overall, these data indicate that PNS females have their brain development shifted towards a pro-anxiety phenotype and that PNS can be causally related to subsequent impaired maternal behaviour in adult female offspring. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Methylphenidate and environmental enrichment ameliorate the deleterious effects of prenatal stress on attention functioning.

    Science.gov (United States)

    Zubedat, Salman; Aga-Mizrachi, Shlomit; Cymerblit-Sabba, Adi; Ritter, Ami; Nachmani, Maayan; Avital, Avi

    2015-01-01

    Either pre- or post-natal environmental factors seem to play a key role in brain and behavioral development and to exert long-term effects. Increasing evidence suggests that exposure to prenatal stress (PS) leads to motor and learning deficits and elevated anxiety, while enriched environment (EE) shows protective effects. The dopaminergic system is also sensitive to environmental life circumstances and affects attention functioning, which serves as the preliminary gate to cognitive processes. However, the effects of methylphenidate (MPH) on the dopaminergic system and attentional functioning, in the context of these life experiences, remain unclear. Therefore, we aimed to examine the effects of EE or PS on distinct types of attention, along with possible effects of MPH exposure. We found that PS impaired selective attention as well as partial sustained attention, while EE had beneficial effects. Both EE and MPH ameliorated the deleterious effects of PS on attention functioning. Considering the possible psychostimulant effect of MPH, we examined both anxiety-like behavior as well as motor learning. We found that PS had a clear anxiogenic effect, whereas EE had an anxiolytic effect. Nevertheless, the treatment with both MPH and/or EE recovered the deleterious effects of PS. In the motor-learning task, the PS group showed superior performance while MPH led to impaired motor learning. Performance decrements were prevented in both the PS + MPH and EE + MPH groups. This study provides evidence that peripubertal exposure to EE (by providing enhanced sensory, motor, and social opportunities) or MPH treatments might be an optional therapeutic intervention in preventing the PS long-term adverse consequences.

  19. Prenatal exposure to disaster-related traumatic stress and developmental trajectories of temperament in early childhood: Superstorm Sandy pregnancy study.

    Science.gov (United States)

    Zhang, Wei; Rajendran, Khushmand; Ham, Jacob; Finik, Jackie; Buthmann, Jessica; Davey, Kei; Pehme, Patricia M; Dana, Kathryn; Pritchett, Alexandra; Laws, Holly; Nomura, Yoko

    2018-07-01

    Little is known about the impact of prenatal maternal stress (PNMS) on the developmental trajectory of temperament and few studies have been able to incorporate a natural disaster as a quasi-experimental stressor. The current study investigated PNMS related to Superstorm Sandy ('Sandy'), a hurricane that struck the New York metropolitan area in October 2012, in terms of objective exposure during pregnancy, subjective stress reaction as assessed by maternal symptoms of post-traumatic stress, and their impact on the developmental changes in temperament during early childhood. A subsample of 318 mother-child dyads was drawn from the Stress in Pregnancy Study. Temperament was measured at 6, 12, 18, and 24 months of age. Objective exposure was associated with greater High-Intensity Pleasure, Approach, Perceptual Sensitivity and Fearfulness, but lower Cuddliness and Duration of Orientation at 6 months. Objective exposure and its interaction with subjective stress reaction predicted developmental changes in temperament. In particular, objective exposure was linked to greater increases in Activity Level but decreases in High-Intensity Pleasure, Approach, and Fearfulness. The combination of objective exposure and subjective stress reaction was also associated with greater increases in Activity Level. Temperament was measured solely via maternal report. Trimester-specific effects of Sandy on temperament were not examined. This is the first study to examine the effects of prenatal maternal exposure to a natural disaster on trajectories of early childhood temperament. Findings suggest that both objective stress exposure and subjective stress reaction in-utero predict developmental trajectories of temperament in early childhood. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Prenatal Stress, Methylation in Inflammation-Related Genes, and Adiposity Measures in Early Childhood: the Programming Research in Obesity, Growth Environment and Social Stress Cohort Study.

    Science.gov (United States)

    Wu, Shaowei; Gennings, Chris; Wright, Rosalind J; Wilson, Ander; Burris, Heather H; Just, Allan C; Braun, Joseph M; Svensson, Katherine; Zhong, Jia; Brennan, Kasey J M; Dereix, Alexandra; Cantoral, Alejandra; Schnaas, Lourdes; Téllez-Rojo, Martha Maria; Wright, Robert O; Baccarelli, Andrea A

    2018-01-01

    Maternal stress during pregnancy may influence childhood growth and adiposity, possibly through immune/inflammatory programming. We investigated whether exposure to prenatal stress and methylation in inflammation-related genes were associated with childhood adiposity in 424 mother-child pairs in Mexico City, Mexico. A stress index was created based on four prenatally administered stress-related scales (Exposure to Violence, Crisis in Family Systems, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale). We measured weight, height, body fat mass (BFM), percentage body fat (PBF), and waist circumference in early childhood (age range, 4-6 years). Body mass index (BMI) z scores were calculated according to World Health Organization standards. DNA methylation in gene promoters of tumor necrosis factor α, interleukin 8, and interleukin 6 (IL6) in umbilical cord blood were determined by pyrosequencing. An interquartile range increase in stress index (27.3) was associated with decreases of 0.14 unit in BMI z score (95% confidence interval [CI] = -0.28 to -0.005), 5.6% in BFM (95% CI = -9.7 to -1.4), 3.5% in PBF (95% CI = -6.3 to -0.5), and 1.2% in waist circumference (95% CI = -2.4 to -0.04) in multivariable-adjusted models. An interquartile range increase in IL6 methylation (3.9%) was associated with increases of 0.23 unit in BMI z score (95% CI = 0.06-0.40), 8.1% (95% CI = 2.3-14.3) in BFM, 5.5% (95% CI = 1.7-9.5) in PBF, and 1.7% (95% CI = 0.2-3.3) in waist circumference. Prenatal stress was associated with decreased childhood adiposity, whereas cord blood IL6 methylation was associated with increased childhood adiposity in Mexican children.

  1. Effective suppression of bystander effects by DMSO treatment of irradiated CHO cells

    International Nuclear Information System (INIS)

    Kashino, Genro; Prise, K.M.; Suzuki, Keiji

    2007-01-01

    Evidence is accumulating that irradiated cells produce some signals which interact with non-exposed cells in the same population via a bystander effect. Here, we examined whether dimethyl sulfoxide (DMSO) is effective in suppressing radiation induced bystander effects in Chinese hamster ovary (CHO) and repair deficient xrs5 cells. When 1 Gy-irradiated CHO cells were treated with 0.5% DMSO for 1 hr before irradiation, the induction of micronuclei in irradiated cells was suppressed to 80% of that in non-treated irradiated cells. The suppressive effect of DMSO on the formation of bystander signals was examined and the results demonstrated that 0.5% DMSO treatment of irradiated cells completely suppressed the induction of micronuclei by the bystander effect in non-irradiated cells. It is suggested that irradiated cells ceased signal formation for bystander effects by the action of DMSO. To determine the involvement of reactive oxygen species on the formation of bystander signals, we examined oxidative stress levels using the 2',7'-dichlorofluorescein (DCFH) staining method in irradiated populations. The results showed that the treatment of irradiated cells with 0.5% DMSO did not suppress oxidative stress levels. These results suggest that the prevention of oxidative stress is independent of the suppressive effect of DMSO on the formation of the bystander signal in irradiated cells. It is suggested that increased reactive oxygen species (ROS) in irradiated cells is not a substantial trigger of a bystander signal. (author)

  2. Bystanders Are the Key to Stopping Bullying

    Science.gov (United States)

    Padgett, Sharon; Notar, Charles E.

    2013-01-01

    Bullying is the dominance over another. Bullying occurs when there is an audience. Peer bystanders provide an audience 85% of instances of bullying. If you remove the audience bullying should stop. The article is a review of literature (2002-2013) on the role of bystanders; importance of bystanders; why bystanders behave as they do; resources to…

  3. A Potential Psychological Mechanism Linking Disaster-Related Prenatal Maternal Stress with Child Cognitive and Motor Development at 16 Months: The QF2011 Queensland Flood Study

    Science.gov (United States)

    Moss, Katrina M.; Simcock, Gabrielle; Cobham, Vanessa; Kildea, Sue; Elgbeili, Guillaume; Laplante, David P.; King, Suzanne

    2017-01-01

    Fetal exposure to prenatal maternal stress can have lifelong consequences, with different types of maternal stress associated with different areas of child development. Fewer studies have focused on motor skills, even though they are strongly predictive of later development across a range of domains. Research on mechanisms of transmission has…

  4. Expression profiles are different in carbon ion-irradiated normal human fibroblasts and their bystander cells

    International Nuclear Information System (INIS)

    Iwakawa, Mayumi; Hamada, Nobuyuki; Imadome, Kaori; Funayama, Tomoo; Sakashita, Testuya; Kobayashi, Yasuhiko; Imai, Takashi

    2008-01-01

    Evidence has accumulated that ionizing radiation induces biological effects in non-irradiated bystander cells having received signals from directly irradiated cells; however, energetic heavy ion-induced bystander response is incompletely characterized. Here we performed microarray analysis of irradiated and bystander fibroblasts in confluent cultures. To see the effects in bystander cells, each of 1, 5 and 25 sites was targeted with 10 particles of carbon ions (18.3 MeV/u, 103 keV/μm) using microbeams, where particles traversed 0.00026, 0.0013 and 0.0066% of cells, respectively. diated cells, cultures were exposed to 10% survival dose (D), 0.1D and 0.01D of corresponding broadbeams (108 keV/μm). Irrespective of the target numbers (1, 5 or 25 sites) and the time (2 or 6 h postirradiation), similar expression changes were observed in bystander cells. Among 874 probes that showed more than 1.5-fold changes in bystander cells, 25% were upregulated and the remainder downregulated. These included genes related to cell communication (PIK3C2A, GNA13, FN1, ANXA1 and IL1RAP), stress response (RAD23B, ATF4 and EIF2AK4) and cell cycle (MYCN, RBBP4 and NEUROG1). Pathway analysis revealed serial bystander activation of G protein/PI-3 kinase pathways. Instead, genes related to cell cycle or death (CDKN1A, GADD45A, NOTCH1 and BCL2L1), and cell communication (IL1B, TCF7 and ID1) were upregulated in irradiated cells, but not in bystander cells. Our results indicate different expression profiles in irradiated and bystander cells, and imply that intercellular signaling between irradiated and bystander cells activate intracellular signaling, leading to the transcriptional stress response in bystander cells

  5. Project ice storm : effects of prenatal stress on children's physical, cognitive and behavioral development

    Energy Technology Data Exchange (ETDEWEB)

    LaPlante, D.P.; King, S.; Brunet, A. [Douglas Hospital Research Centre, Montreal, PQ (Canada)

    2005-07-01

    The ice storm in the winter of 1998 left three million people in Quebec without power for as long as 40 days. This study recruited 224 women who were pregnant during the storm or who became pregnant within 3 months after the storm. The study examined the effects of prenatal maternal stress (PNMS) in an effort to fill gaps in literature regarding prenatal stress and increased risks and to assist in the development of preventive interventions for pregnant women who have experienced stress or trauma. Natural disaster studies provide good opportunities to study the effects of PNMS, as effects are random across large numbers of women and can be assessed independently of the pregnant women's own personality traits. The study examined whether there was an effect of the timing and severity of the ice storm on perinatal outcomes and later health; intellectual and linguistic functioning at two and a half and five years of age; behavioural and attention problems at four and five and a half years of age and physical features. The study concluded that pregnant women are a risk group and need proper interventions as children experienced delays or deficiencies in several key developmental areas. tabs., figs.

  6. Prenatal stress exposure, oxytocin receptor gene (OXTR) methylation, and child autistic traits: The moderating role of OXTR rs53576 genotype.

    Science.gov (United States)

    Rijlaarsdam, Jolien; van IJzendoorn, Marinus H; Verhulst, Frank C; Jaddoe, Vincent W V; Felix, Janine F; Tiemeier, Henning; Bakermans-Kranenburg, Marian J

    2017-03-01

    Findings of studies investigating OXTR SNP rs53576 (G-A) variation in social behavior have been inconsistent, possibly because DNA methylation after stress exposure was eliminated from consideration. Our goal was to examine OXTR rs53576 allele-specific sensitivity for neonatal OXTR DNA methylation in relation to (1) a prenatal maternal stress composite, and (2) child autistic traits. Prospective data from fetal life to age 6 years were collected in a total of 743 children participating in the Generation R Study. Prenatal maternal stress exposure was uniquely associated with child autistic traits but was unrelated to OXTR methylation across both OXTR rs53576 G-allele homozygous children and A-allele carriers. For child autistic traits in general and social communication problems in particular, we observed a significant OXTR rs53576 genotype by OXTR methylation interaction in the absence of main effects, suggesting that opposing effects cancelled each other out. Indeed, OXTR methylation levels were positively associated with social problems for OXTR rs53576 G-allele homozygous children but not for A-allele carriers. These results highlight the importance of incorporating epi-allelic information and support the role of OXTR methylation in child autistic traits. Autism Res 2017, 10: 430-438. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  7. Taurine promotes cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway.

    Science.gov (United States)

    Jia, Ning; Sun, Qinru; Su, Qian; Dang, Shaokang; Chen, Guomin

    2016-12-01

    Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS). Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM) was employed for testing the cognitive function in the one-month-old rat offspring. The mitochondrial reactive oxygen species (ROS) level,mitochondrial membrane potential (MMP), ATP and cytochrome c oxidase (CcO) activity and apoptosis-related proteins in the hippocampus were detected. The activity of the Akt-cyclic AMP response element-binding protein (CREB)-peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) pathway in the hippocampus was measured. The results showed that high dosage of taurine administration in the early postnatal period attenuated impairment of spatial learning and memory induced by PS. Meanwhile, taurine administration diminished the increase in mitochondrial ROS, and recovered the reduction of MMP, ATP level and the activities of CcO, superoxide dismutase 2 (SOD2) and catalase induced by PS in the hippocampus. In addition, taurine administration recovered PS-suppressed SOD2 expression level. Taurine administration blocked PS-induced decrease in the ratio of Bcl-2/Bax and increase in the ratio of cleaved caspase-3/full-length caspase-3. Notably, taurine inhibited PS-decreased phosphorylation of Akt (pAkt) and phosphorylation of CREB (pCREB), which consequently enhanced the mRNA and protein levels of PGC1α. Taken together, these results suggest that high dosage of taurine administration during the early postnatal period can significantly improve the cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway. Therefore

  8. Taurine promotes cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway

    Directory of Open Access Journals (Sweden)

    Ning Jia

    2016-12-01

    Full Text Available Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS. Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM was employed for testing the cognitive function in the one-month-old rat offspring. The mitochondrial reactive oxygen species (ROS level,mitochondrial membrane potential (MMP, ATP and cytochrome c oxidase (CcO activity and apoptosis-related proteins in the hippocampus were detected. The activity of the Akt-cyclic AMP response element-binding protein (CREB-peroxisome proliferator-activated receptor–γ coactivator-1α (PGC1α pathway in the hippocampus was measured. The results showed that high dosage of taurine administration in the early postnatal period attenuated impairment of spatial learning and memory induced by PS. Meanwhile, taurine administration diminished the increase in mitochondrial ROS, and recovered the reduction of MMP, ATP level and the activities of CcO, superoxide dismutase 2 (SOD2 and catalase induced by PS in the hippocampus. In addition, taurine administration recovered PS-suppressed SOD2 expression level. Taurine administration blocked PS-induced decrease in the ratio of Bcl-2/Bax and increase in the ratio of cleaved caspase-3/full-length caspase-3. Notably, taurine inhibited PS-decreased phosphorylation of Akt (pAkt and phosphorylation of CREB (pCREB, which consequently enhanced the mRNA and protein levels of PGC1α. Taken together, these results suggest that high dosage of taurine administration during the early postnatal period can significantly improve the cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1

  9. Prenatal Stress Produces Sex Specific Changes in Depression-like Behavior in Rats: Implications for Increased Vulnerability in Females

    DEFF Research Database (Denmark)

    Sickmann, Helle Mark; Arentzen, Tine S; Dyrby, Tim

    2015-01-01

    Stress during rat gestation can elicit depression-like physiological and behavioral responses in the offspring. However, human clinical depression is more prevalent among females than males. Accordingly, we examined how repeated variable prenatal stress (PS) alters rat anxiety- and depression...... and measured anxiety- (elevated plus maze, EPM) and depression-like (forced swim test, FST) behaviors in the offspring at a young adult age. As a stressful event later in life (in addition to PS) may be needed to actually trigger an episode of clinical depression, half of the animals were exposed to an acute...... affected in control animals after acute stressor exposure, however, this response was blunted in PS offspring. Moreover, FST immobility, as an indicator of depressive-like behavior, was increased in female but not male PS rats. Altogether, our results identify both sex- and circadian phase-specific effects...

  10. MRC5 and QU-DB bystander cells can produce bystander factors and induce radiation bystander effect

    Directory of Open Access Journals (Sweden)

    Mohammad Taghi Bahreyni Toossi

    2014-01-01

    Full Text Available Radiation damages initiated by radiation-induced bystander effect (RIBE are not limited to the first or immediate neighbors of the irradiated cells, but the effects have been observed in the cells far from the irradiation site. It has been postulated that bystander cells, by producing bystander factors, are actively involved in the propagation of bystander effect in the regions beyond the initial irradiated site. Current study was planned to test the hypothesis. MRC5 and QU-DB cell lines were irradiated, and successive medium transfer technique was performed to induce bystander effects in two bystander cell groups. Conditioned medium extracted from the target cells was transferred to the bystander cells (first bystander cells. After one hour, conditioned medium was substituted by fresh medium. Two hours later, the fresh medium was transferred to a second group of non-irradiated cells (second bystander cells. Micronucleated cells (MC were counted to quantify damages induced in the first and second bystander cell groups. Radiation effect was observed in the second bystander cells as well as in the first ones. Statistical analyses revealed that the number of MC in second bystander subgroups was significantly more than the corresponding value observed in control groups, but in most cases it was equal to the number of MC observed in the first bystander cells. MRC5 and QU-DB bystander cells can produce and release bystander signals in the culture medium and affect non-irradiated cells. Therefore, they may contribute to the RIBE propagation.

  11. Prenatal Stress Impairs Spatial Learning and Memory Associated with Lower mRNA Level of the CAMKII and CREB in the Adult Female Rat Hippocampus.

    Science.gov (United States)

    Sun, Hongli; Wu, Haibin; Liu, Jianping; Wen, Jun; Zhu, Zhongliang; Li, Hui

    2017-05-01

    Prenatal stress (PS) results in various behavioral and emotional alterations observed in later life. In particular, PS impairs spatial learning and memory processes but the underlying mechanism involved in this pathogenesis still remains unknown. Here, we reported that PS lowered the body weight in offspring rats, particularly in female rats, and impaired spatial learning and memory of female offspring rats in the Morris water maze. Correspondingly, the decreased CaMKII and CREB mRNA in the hippocampus were detected in prenatally stressed female offspring, which partially explained the effect of PS on the spatial learning and memory. Our findings suggested that CaMKII and CREB may be involved in spatial learning and memory processes in the prenatally stressed adult female offspring.

  12. Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats.

    Science.gov (United States)

    Mairesse, Jérôme; Gatta, Eleonora; Reynaert, Marie-Line; Marrocco, Jordan; Morley-Fletcher, Sara; Soichot, Marion; Deruyter, Lucie; Camp, Gilles Van; Bouwalerh, Hammou; Fagioli, Francesca; Pittaluga, Anna; Allorge, Delphine; Nicoletti, Ferdinando; Maccari, Stefania

    2015-12-01

    Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Heavy-ion radiation induced bystander effect in mice

    Science.gov (United States)

    Liang, Shujian; Sun, Yeqing; Zhang, Meng; Wang, Wei; Cui, Changna

    2012-07-01

    Radiation-induced bystander effect is defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, Low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic, metabolomics and proteomics play significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male mice head were exposed to 2000mGy dose of 12C heavy-ion radiation and the distant organ liver was detected on 1h, 6h, 12h and 24h after radiation, respectively. MSAP was used to monitor the level of polymorphic DNA methylation changes. The results show that heavy-ion irradiate mouse head can induce liver DNA methylation changes significantly. The percent of DNA methylation changes are time-dependent and highest at 6h after radiation. We also prove that the hypo-methylation changes on 1h and 6h after irradiation. But the expression level of DNA methyltransferase DNMT3a is not changed. UPLC/Synapt HDMS G2 was employed to detect the proteomics of bystander liver 1h after irradiation. 64 proteins are found significantly different between treatment and control group. GO process show that six of 64 which were unique in irradiation group are associated with apoptosis and DNA damage response. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo.

  14. Bystander or No Bystander for Gene Directed Enzyme Prodrug Therapy

    Directory of Open Access Journals (Sweden)

    Adam V. Patterson

    2009-11-01

    Full Text Available Gene directed enzyme prodrug therapy (GDEPT of cancer aims to improve the selectivity of chemotherapy by gene transfer, thus enabling target cells to convert nontoxic prodrugs to cytotoxic drugs. A zone of cell kill around gene-modified cells due to transfer of toxic metabolites, known as the bystander effect, leads to tumour regression. Here we discuss the implications of either striving for a strong bystander effect to overcome poor gene transfer, or avoiding the bystander effect to reduce potential systemic effects, with the aid of three successful GDEPT systems. This review concentrates on bystander effects and drug development with regard to these enzyme prodrug combinations, namely herpes simplex virus thymidine kinase (HSV-TK with ganciclovir (GCV, cytosine deaminase (CD from bacteria or yeast with 5-fluorocytodine (5-FC, and bacterial nitroreductase (NfsB with 5-(azaridin-1-yl-2,4-dinitrobenzamide (CB1954, and their respective derivatives.

  15. Involvement of MAPK proteins in bystander effects induced by chemicals and ionizing radiation

    International Nuclear Information System (INIS)

    Asur, Rajalakshmi; Balasubramaniam, Mamtha; Marples, Brian; Thomas, Robert A.; Tucker, James D.

    2010-01-01

    Many studies have examined bystander effects induced by ionizing radiation, however few have evaluated the ability of chemicals to induce similar effects. We previously reported the ability of two chemicals, mitomycin C (MMC) and phleomycin (PHL) to induce bystander effects in normal human lymphoblastoid cell lines. The focus of the current study was to determine the involvement of the MAPK proteins in bystander effects induced by physical and chemical DNA damaging agents and to evaluate the effects of MAPK inhibition on bystander-induced caspase 3/7 activation. The phosphorylation levels of the MAPK proteins ERK1/2, JNK, and p38, were measured from 1 to 24 h following direct or bystander exposure to MMC, PHL or radiation. We observed transient phosphorylation, at early time points, of all 3 proteins in bystander cells. We also evaluated the effect of MAPK inhibition on bystander-induced caspase 3/7 activity to determine the role of MAPK proteins in bystander-induced apoptosis. We observed bystander-induced activation of caspase 3/7 in bystander cells. Inhibition of MAPK proteins resulted in a decrease in caspase 3/7 activity at the early time points, and the caspase activity increased (in the case of ERK inhibition) or returned to basal levels (in the case of JNK or p38 inhibition) between 12 and 24 h. PHL is considered to be a radiomimetic agent, however in the present study PHL behaved more like a chemical and not like radiation in terms of MAPK phosphorylation. These results point to the involvement of MAPK proteins in the bystander effect induced by radiation and chemicals and provide additional evidence that this response is not limited to radiation but is a generalized stress response in cells.

  16. Prenatal stress-immune programming of sex differences in comorbidity of depression and obesity/metabolic syndrome.

    Science.gov (United States)

    Goldstein, Jill M; Holsen, Laura; Huang, Grace; Hammond, Bradley D; James-Todd, Tamarra; Cherkerzian, Sara; Hale, Taben M; Handa, Robert J

    2016-12-01

    Major depressive disorder (MDD) is the number one cause of disability worldwide and is comorbid with many chronic diseases, including obesity/metabolic syndrome (MetS). Women have twice as much risk for MDD and comorbidity with obesity/MetS as men, although pathways for understanding this association remain unclear. On the basis of clinical and preclinical studies, we argue that prenatal maternal stress (ie, excess glucocorticoid expression and associated immune responses) that occurs during the sexual differentiation of the fetal brain has sex-dependent effects on brain development within highly sexually dimorphic regions that regulate mood, stress, metabolic function, the autonomic nervous system, and the vasculature. Furthermore, these effects have lifelong consequences for shared sex-dependent risk of MDD and obesity/MetS. Thus, we propose that there are shared biologic substrates at the anatomical, molecular, and/or genetic levels that produce the comorbid risk for MDD-MetS through sex-dependent fetal origins.

  17. Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

    Science.gov (United States)

    Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

    2011-01-01

    Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

  18. Using Prenatal Advocates to Implement a Psychosocial Education Intervention for Posttraumatic Stress Disorder during Pregnancy: Feasibility, Care Engagement, and Predelivery Behavioral Outcomes.

    Science.gov (United States)

    Upshur, Carole C; Wenz-Gross, Melodie; Weinreb, Linda; Moffitt, Jennifer Jo Averill

    2016-01-01

    Pregnant women with posttraumatic stress disorder (PTSD) engage in more high-risk behavior and use less prenatal care. Although treating depression in pregnancy is becoming widespread, options for addressing PTSD are few. This study was designed to test the feasibility of implementing a manualized psychosocial PTSD intervention, Seeking Safety, delivered by prenatal advocates. All women entering prenatal care at two federally qualified health centers were screened for current symptoms of PTSD. One site was selected randomly to have prenatal care advocates deliver eight Seeking Safety topics for women that indicated clinical or subclinical PTSD symptoms. Baseline and pre-delivery interviews were conducted, which collected background characteristics and assessed PTSD severity and coping skills. Medical records were collected to document care visits. Documentation of participation rates, fidelity to the treatment, and qualitative feedback from advocates and participants was collected. More than one-half (57.3%) of the intervention women received all Seeking Safety sessions and fidelity ratings of the session showed acceptable quality. Using an intent-to-treat analysis, intervention women participated in significantly more prenatal care visits (M = 11.7 versus 8.9; p accounting for baseline differences, intervention women also reduced negative coping skills but not PTSD symptoms. Using prenatal care advocates to deliver Seeking Safety sessions to women screening positive for PTSD symptoms at entry to prenatal care is a promising intervention that seems to increase prenatal care participation and may reduce negative coping strategies. Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  19. Effect of Chronic Social Stress on Prenatal Transfer of Antitetanus Immunity in Captive Breeding Rhesus Macaques (Macaca mulatta).

    Science.gov (United States)

    Stammen, Rachelle L; Cohen, Joyce K; Meeker, Tracy L; Crane, Maria M; Amara, Rama R; Hicks, Sakeenah L; Meyer, Jerrold S; Ethun, Kelly F

    2018-05-15

    Because tetanus can cause significant morbidity and mortality in NHP, colonywide vaccination with tetanus toxoid is recommendedfor outdoor breeding colonies of rhesus macaques, with primary immunizations commonly given to infants at 6 mo of age followed by booster vaccines every 10 y. Maternal antibodies are thought to offer protective immunity to infants younger than 6 mo. However, historical colony data from the Yerkes National Primate Research Center show a higher incidence of tetanus among infants (≤ 6 mo old) born to subordinate dams. Whether this higher incidence of infantile tetanus is due to a higher incidence of trauma among subordinate animals or is a stress-induced impairment of maternal antibody protection is unknown. Studies in other NHP species suggest that chronic exposure to social stressors interferes with the receptor-mediated transplacental transfer of IgG. Therefore, the primary aim of this study was to determine whether chronic stress associated with social subordination impairs prenatal transfer of antitetanus immunity in breeding female rhesus macaques. Subjects included 26 high- and 26 low-ranking adult female rhesus macaques that were nearly 5 or 10 y after their initial immunization and their nonimmunized infants. We hypothesized that infants born to subordinate dams that were nearly 10 y after immunization would have the lowest infant-to-dam antibody ratios and thus would be at greatest risk for infection. Results revealed no significant intergroup differences in infant antitetanus IgG levels. However, infant-to-dam IgG ratios against tetanus were significantly lower among subordinate animals compared with dominant macaques, after accounting for the number of years since the dam's initial vaccination. In addition, higher maternal hair cortisol levels predicted lower infant-to-dam tetanus toxoid IgG ratios. Together, these findings suggest that chronic social stress in female rhesus macaques may hamper the prenatal transfer of

  20. Effect of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration and anxiety behaviors in adult rat offspring.

    Science.gov (United States)

    Nakhjiri, Elnaz; Saboory, Ehsan; Roshan-Milani, Shiva; Rasmi, Yousef; Khalafkhani, Davod

    2017-03-01

    Stressful events and exposure to opiates during gestation have important effects on the later mental health of the offspring. Anxiety is among the most common mental disorders. The present study aimed to identify effects of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration (PVC) and anxiety behaviors in rats. Pregnant rats were divided into four groups (n = 6, each): saline, morphine, stress + saline and stress + morphine treatment. The stress procedure consisted of restraint twice per day, two hours per session, for three consecutive days starting on day 15 of pregnancy. Rats in the saline and morphine groups received either 0.9% saline or morphine intraperitoneally on the same days. In the morphine/saline + stress groups, rats were exposed to restraint stress and received either morphine or saline intraperitoneally. All offspring were tested in an elevated plus maze (EPM) on postnatal day 90 (n = 6, each sex), and anxiety behaviors of each rat were recorded. Finally, blood samples were collected to determine PVC. Prenatal morphine exposure reduced anxiety-like behaviors. Co-administration of prenatal stress and morphine increased locomotor activity (LA) and PVC. PVC was significantly lower in female offspring of the morphine and morphine + stress groups compared with males in the same group, but the opposite was seen in the saline + stress group. These data emphasize the impact of prenatal stress and morphine on fetal neuroendocrine development, with long-term changes in anxiety-like behaviors and vasopressin secretion. These changes are sex specific, indicating differential impact of prenatal stress and morphine on fetal neuroendocrine system development. Lay Summary Pregnant women are sometimes exposed to stressful and painful conditions which may lead to poor outcomes for offspring. Opiates may provide pain and stress relief to these mothers. In this study, we used an experimental model of

  1. A Methyl-Balanced Diet Prevents CRF-Induced Prenatal Stress-Triggered Predisposition to Binge Eating-like Phenotype.

    Science.gov (United States)

    Schroeder, Mariana; Jakovcevski, Mira; Polacheck, Tamar; Lebow, Maya; Drori, Yonat; Engel, Mareen; Ben-Dor, Shifra; Chen, Alon

    2017-06-06

    Binge eating (BE) is a common aberrant form of eating behavior, characterized by overconsumption of food in a brief period of time. Recurrent episodes of BE constitute the BE disorder, which mostly affects females and is associated with early-life adversities. Here, we show that corticotropin releasing factor (CRF)-induced prenatal stress (PNS) in late gestation predisposes female offspring to BE-like behavior that coincides with hypomethylation of hypothalamic miR-1a and downstream dysregulation of the melanocortin system through Pax7/Pax3. Moreover, exposing the offspring to a methyl-balanced diet during adolescence prevents the dysregulation and predisposition from being triggered. We demonstrate that gestational programming, per se, will not lead to BE-like behavior, but pre-existing alterations due to prenatal programming are revealed only when challenged during adolescence. We provide experimental evidence for long-term epigenetic abnormalities stemming from PNS in predisposing female offspring to BE disorder as well as a potential non-invasive prevention strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Supplementation with fish oil and coconut fat prevents prenatal stress-induced changes in early postnatal development.

    Science.gov (United States)

    Borsonelo, Elizabethe C; Suchecki, Deborah; Calil, Helena Maria; Galduróz, José Carlos F

    2011-08-01

    Adequate development of the central nervous system depends on prenatal and postnatal factors. On one hand, prenatal stress (PNS) has been implicated in impaired development of the offspring. On other hand, nutritional factors during pregnancy and lactation can influence fetal and postnatal growth. This study assessed the postnatal development of rat offspring exposed to PNS, which consisted of restraint and bright lights, 3 times/day, from days 14 to 20 of pregnancy, whose mothers were fed different diets during pregnancy and lactation: regular diet, diet supplemented with coconut fat or fish oil. When pregnancy was confirmed, they were distributed into control (CTL) or PNS groups. At birth, PNS males and females weighed less than those in the group CTL. At 21 days of age, this alteration was no longer observed with fish oil and coconut fat groups. PNS and coconut fat diet induced increased locomotor activity in 13 day old male and female pups, and this effect was prevented by fish oil supplementation only in females. In conclusion, postnatal development from birth to weaning was influenced by PNS and diet and some of those alterations were prevented by coconut fat and fish oil. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. Group prenatal care.

    Science.gov (United States)

    Mazzoni, Sara E; Carter, Ebony B

    2017-06-01

    Patients participating in group prenatal care gather together with women of similar gestational ages and 2 providers who cofacilitate an educational session after a brief medical assessment. The model was first described in the 1990s by a midwife for low-risk patients and is now practiced by midwives and physicians for both low-risk patients and some high-risk patients, such as those with diabetes. The majority of literature on group prenatal care uses CenteringPregnancy, the most popular model. The first randomized controlled trial of CenteringPregnancy showed that it reduced the risk of preterm birth in low-risk women. However, recent meta-analyses have shown similar rates of preterm birth, low birthweight, and neonatal intensive care unit admission between women participating in group prenatal care and individual prenatal care. There may be subgroups, such as African Americans, who benefit from this type of prenatal care with significantly lower rates of preterm birth. Group prenatal care seems to result in increased patient satisfaction and knowledge and use of postpartum family planning as well as improved weight gain parameters. The literature is inconclusive regarding breast-feeding, stress, depression, and positive health behaviors, although it is theorized that group prenatal care positively affects these outcomes. It is unclear whether group prenatal care results in cost savings, although it may in large-volume practices if each group consists of approximately 8-10 women. Group prenatal care requires a significant paradigm shift. It can be difficult to implement and sustain. More randomized trials are needed to ascertain the true benefits of the model, best practices for implementation, and subgroups who may benefit most from this innovative way to provide prenatal care. In short, group prenatal care is an innovative and promising model with comparable pregnancy outcomes to individual prenatal care in the general population and improved outcomes in some

  4. Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo

    Science.gov (United States)

    Kertes, Darlene A.; Kamin, Hayley S.; Hughes, David A.; Rodney, Nicole C.; Bhatt, Samarth; Mulligan, Connie J.

    2016-01-01

    Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which…

  5. A milk-based wolfberry preparation prevents prenatal stress-induced cognitive impairment of offspring rats, and inhibits oxidative damage and mitochondrial dysfunction in vitro.

    Science.gov (United States)

    Feng, Zhihui; Jia, Haiqun; Li, Xuesen; Bai, Zhuanli; Liu, Zhongbo; Sun, Lijuan; Zhu, Zhongliang; Bucheli, Peter; Ballèvre, Olivier; Wang, Junkuan; Liu, Jiankang

    2010-05-01

    Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.

  6. Prenatal Stress and the Cortisol Awakening Response in African-American and Caucasian Women in the Third Trimester of Pregnancy.

    Science.gov (United States)

    Simon, Clarissa D; Adam, Emma K; Holl, Jane L; Wolfe, Kaitlin A; Grobman, William A; Borders, Ann E B

    2016-10-01

    Objectives Prior studies have shown significant racial disparities in psychosocial stressors for pregnant women. One physiological mechanism by which prenatal stress is expressed is via the stress-sensitive hormone cortisol, which itself differs by race. In this study, we examine differences in cortisol awakening response (CAR) for African-American and Caucasian pregnant women during late pregnancy, particularly whether racial disparities are evident after accounting for measures of psychosocial stress. Methods During their third trimester of pregnancy (32-40 weeks of gestation), we asked women to self-collect salivary samples at home over 2 days. We then measured salivary cortisol across the day for 30 pregnant women (18 Caucasian; 12 African-American) to examine the CAR by race and by multiple measures of self-reported psychosocial stress, including perceived discrimination. Results Although the women in our sample showed normative cortisol diurnal rhythms (high on waking, peak 30 min post-waking, lowest at bedtime), we found that African-American women had blunted (smaller) awakening responses compared to Caucasian women (p accounting for covariates in a multivariate equation. However, when we added measures of psychosocial stress to the multivariate equation, higher levels of stress were significantly associated with a smaller CAR (p < 0.05), and the association between maternal race and CAR was no longer significant. Conclusions Our results add to a growing body of evidence that racial differences in the activity of the hypothalamic-pituitary-adrenal axis are associated with psychosocial stress during pregnancy.

  7. On the Actual Risk of Bystander Intervention

    DEFF Research Database (Denmark)

    Liebst, Lasse Suonperä; Heinskou, Marie Bruvik; Ejbye-Ernst, Peter

    2018-01-01

    Objectives: Bystander studies have rarely considered the victimization risk associated with intervention into violent, dangerous emergencies. To address this gap, we aim to identify factors that influence bystanders’ risk of being physically victimized. Methods: We observed bystander behavior fro...

  8. Disruption of Fetal Hormonal Programming (Prenatal Stress) Implicates Shared Risk for Sex Differences in Depression and Cardiovascular Disease

    Science.gov (United States)

    Goldstein, JM; Handa, RJ; Tobet, SA

    2014-01-01

    Comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) represents the fourth leading cause of morbidity and mortality worldwide, and women have a two times greater risk than men. Thus understanding the pathophysiology has widespread implications for attenuation and prevention of disease burden. We suggest that sex-dependent MDD-CVD comorbidity may result from alterations in fetal programming consequent to the prenatal maternal environments that produce excess glucocorticoids, which then drive sex-dependent developmental alterations of the fetal hypothalamic-pituitary-adrenal (HPA) axis circuitry impacting mood, stress regulation, autonomic nervous system (ANS), and the vasculature in adulthood. Evidence is consistent with the hypothesis that disruptions of pathways associated with gamma aminobutyric acid (GABA) in neuronal and vascular development and growth factors have critical roles in key developmental periods and adult responses to injury in heart and brain. Understanding the potential fetal origins of these sex differences will contribute to development of novel sex-dependent therapeutics. PMID:24355523

  9. Genetic liability, prenatal health, stress and family environment: risk factors in the Harvard Adolescent Family High Risk for schizophrenia study.

    Science.gov (United States)

    Walder, Deborah J; Faraone, Stephen V; Glatt, Stephen J; Tsuang, Ming T; Seidman, Larry J

    2014-08-01

    The familial ("genetic") high-risk (FHR) paradigm enables assessment of individuals at risk for schizophrenia based on a positive family history of schizophrenia in first-degree, biological relatives. This strategy presumes genetic transmission of abnormal traits given high heritability of the illness. It is plausible, however, that adverse environmental factors are also transmitted in these families. Few studies have evaluated both biological and environmental factors within a FHR study of adolescents. We conceptualize four precursors to psychosis pathogenesis: two biological (genetic predisposition, prenatal health issues (PHIs)) and two environmental (family environment, stressful life events (SLEs)). Participants assessed between 1998 and 2007 (ages 13-25) included 40 (20F/20M) adolescents at FHR for schizophrenia (FHRs) and 55 (31F/24M) community controls. 'Genetic load' indexed number of affected family members relative to pedigree size. PHI was significantly greater among FHRs, and family cohesion and expressiveness were less (and family conflict was higher) among FHRs; however, groups did not significantly differ in SLE indices. Among FHRs, genetic liability was significantly associated with PHI and family expressiveness. Prenatal and family environmental disruptions are elevated in families with a first-degree relative with schizophrenia. Findings support our proposed 'polygenic neurodevelopmental diathesis-stress model' whereby psychosis susceptibility (and resilience) involves the independent and synergistic confluence of (temporally-sensitive) biological and environmental factors across development. Recognition of biological and social environmental influences across critical developmental periods points to key issues relevant for enhanced identification of psychosis susceptibility, facilitation of more precise models of illness risk, and development of novel prevention strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Early life disease programming during the preconception and prenatal period: making the link between stressful life events and type-1 diabetes.

    Directory of Open Access Journals (Sweden)

    Jasveer Virk

    Full Text Available BACKGROUND: To assess the risk of developing Type-1 diabetes among children who were exposed to maternal bereavement during the prenatal or 1-year preconception period. METHODS: We identified N = 1,548,746 singleton births born in Denmark between January 1(st 1979 through December 31(st 2004, and their next of kin. Altogether, 39,857 children were exposed to bereavement during their prenatal life. The main outcome of interest was hospitalization for type-1 diabetes (ICD 8: 249; ICD 10: E10. RESULTS: We found the strongest association for type-1 diabetes among children exposed to traumatic father or sibling deaths (aIRR: 2.03, 1.22-3.38; the association was mainly seen for girls (aIRR: 2.91, 1.61-5.26. CONCLUSIONS: We found evidence to suggest that female fetuses exposed to severe prenatal stress are at increased risk for developing type-1 diabetes.

  11. Characteristics and mechanisms of the bystander response in monolayer cell cultures exposed to very low fluences of alpha particles

    International Nuclear Information System (INIS)

    Little, John B.; Azzam, Edouard I.; Toledo, Sonia M. de; Nagasawa, Hatsumi

    2005-01-01

    When confluent cultures of mammalian cells are irradiated with very low fluences of alpha particles whereby only occasional cells receive any radiation exposure, genetic changes are observed in the non-irradiated ('bystander') cells. Upregulation of the p53 damage-response pathway as well as activation of proteins in the MAPK family occurred in bystander cells; p53 was phosphorylated on the serine 15 residue suggesting that the upregulation of p53 was a consequence of DNA damage. Damage signals were transmitted to bystander cells through gap junctions, as confirmed by the use of genetically manipulated cells including connexin43 knockouts. Expression of connexin43 was markedly enhanced by irradiation. A moderate bystander effect was observed for specific gene mutations and chromosomal aberrations. This effect was markedly enhanced in cells defective in the non-homologous end joining DNA repair pathway. Finally, an upregulation of oxidative metabolism occurred in bystander cells; the increased levels of reactive oxygen species appeared to be derived from flavine-containing oxidase enzymes. We hypothesize that genetic effects observed in non-irradiated bystander cells are a consequence of oxidative base damage; >90% of mutations in bystander cells were point mutations. When bystander cells cannot repair DNA double strand breaks, they become much more sensitive to the induction of chromosomal aberrations and mutations, the latter consisting primarily of deletion mutants. While we propose that the genetic effects occurring in bystander cells are a consequence of oxidative stress, the nature of the signal that initiates this process remains to be determined

  12. Developmental Exposure to Mild Variable Stress: Adult Offspring Performance in Trace Fear Conditioning after Prenatal and Postnatal Stress

    Science.gov (United States)

    In utero exposure to mild variable stress has been reported to influence learning and memory formation in offspring. Our research aims to examine whether nonchemical environmental stressors will exacerbate effects to chemical exposure. This study utilized a varying stress parad...

  13. Moral Disengagement Among Bystanders to School Bullying

    DEFF Research Database (Denmark)

    Obermann, Marie-Louise

    2011-01-01

    This study examined the use of moral disengagement among children indirectly involved in bullying (bystanders). A sample of Danish adolescents (N = 660, M age 12.6 years) were divided into four groups depending on their bystander status: (a) outsiders, who did not experience bullying among...... their peers; (b) defenders, who were likely to help the victims in bullying episodes; (c) guilty bystanders, who did nothing to help bullied peers but felt guilty about it; and (d) unconcerned bystanders, who witnessed peers being bullied, without feeling responsible. Results indicated that, besides from...... active personal involvement in bullying others, being an unconcerned bystander to bullying also associates with moral disengagement. Unconcerned bystanders had significantly higher moral disengagement than guilty bystanders and defenders. Outsiders also showed significant higher disengagement than...

  14. Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

    Science.gov (United States)

    Del Cerro, M C R; Ortega, E; Gómez, F; Segovia, S; Pérez-Laso, C

    2015-07-01

    Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. The role of prenatal, obstetric, and post-partum factors in the parenting stress of mothers and fathers of 9-month old infants.

    Science.gov (United States)

    Matvienko-Sikar, Karen; Murphy, Gillian; Murphy, Mike

    2018-03-01

    The aim of this paper was to examine the role of perinatal, obstetric and post partum factors on maternal and paternal stress. It will present the first examination of the role of prenatal, obstetric, post-partum, and demographic variables in parenting stress for mothers and fathers at 9 months. Data from 6821 parental dyads of 9-month-old infants were extracted from the Growing Up in Ireland National Longitudinal Study of Children. Participants completed the Parental Stress Scale, the Dyadic Adjustment Scale, the Quality of Attachment Sub-scale from the Maternal and Paternal Postnatal Attachment Scales, and a single item health status question from the Short Form 12 Health Survey. Information on prenatal care, pregnancy complications, obstetric outcomes, infant health, and participant demographics were also collected. Separate hierarchical linear regressions were conducted for mothers and fathers Results: Mothers reported higher levels of parenting stress than fathers (p stress was predicted by attachment, own health status, average sleep, occupation, household income, and having a very rapid labor. Paternal parenting stress was predicted by attachment and own health status. A range of perinatal factors was associated with an increased risk of higher parenting stress at 9 months post-partum and the roles of these factors differ between mothers and fathers. These findings are important for predicting and reducing risk of parenting stress in both genders.

  16. Molecular pathways in the bystander response of cells exposed to very low fluences of alpha particles

    International Nuclear Information System (INIS)

    Little, J.B.

    2000-01-01

    Full text: We have examined biological effects in cell populations exposed to very low mean doses of alpha radiation by which only a small fraction of the cells are actually traversed by an alpha particle. We showed earlier that an enhanced frequency of sister chromatid exchanges and HPRT mutations occur in the non-irradiated, 'bystander' cells. The frequency of mutations induced by a single alpha particle traversing the nucleus of a cell was increased nearly fivefold at the lowest fluence studied, a result of mutations occurring in bystander cells. This was associated with a similar increase in the induction of micronuclei, indicating the induction of DNA damage in bystander cells. In order to gain information concerning molecular pathways, we studied changes in gene expression in bystander cells in confluent cultures of human diploid fibroblasts or mouse embryo-derived fibroblasts (MEFs) by western analysis and in-situ immunofluorescence. The expression levels of p53, p21 Waf1 and p34 cdc2 were significantly modulated in bystander cells. The upregulation of p53 and p21 Waf1 did not occur in cultures irradiated at low density, and was markedly reduced in the presence of the gap junction inhibitor lindane. The importance of gap-junction mediated intercellular communication was confirmed in connexin-43 knockout MEFs. Western blot analyses and electrophoretic mobility shift assays indicate that the bystander response is suppressed by incubation with superoxide dismutase as well as an inhibitor of NADPH oxidase, and is associated with the induction of NFKB, suggesting the effect is mediated by oxidative stress. The stress-activated protein kinase p38 and its downstream effector ATF2 are also induced in bystander cells independent of oxidative stress. These results will be discussed in terms of whether activation of the p53 damage response pathway is the direct result of signaling from irradiated cells, or rather is a consequence of DNA induced damage in the bystander

  17. Prenatal Tests

    Science.gov (United States)

    ... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

  18. Bystander Effects of Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Little, John B. [Harvard T.H. Chan School of Public Health, Boston, MA (United States). Dept. of Genetics and Complex Diseases

    2017-01-17

    The objectives of this grant renewal are to provide administrative support and travel funds to allow the continued participation of the principal investigator (Dr. John B. Little) as an advisor to research initiated by several research fellows from his laboratory. The actual research will be carried out under the direction of Dr. Hatsumi Nagasawa with the collaboration of Dr. Joel Bedford at the Colorado State University, and by Drs. Edouard Azzam and Sonia de Toledo at the University of Medicine and Dentistry of New Jersey. Dr. Little will advise on the planning of experiments and development of experimental protocols, the analysis of data, and the preparation of manuscripts for publication. The Specific Aims for several of the planned experiments include: 1) to extend studies of the role of recombinational repair in the bystander effect by examining other genes in this pathway and cell lines deficient in excision repair; 2) to continue studies to determine the nature of the damage signal transmitted to bystander cells including the expression of several connexins in the bystander response, and the extent to which the enhanced oxidative metabolism observed in bystander cells may relate to the nature of the transmitted bystander signal; 3) to utilize a genome-wide approach to examine the genetic basis for the hypersensitivity to ionization we have observed in unaffected parents of patients with hereditary retinoblastoma, as well as from a group of apparently normal individuals that show similar radiosensitivity; 4) to complete studies concerning the induction of high frequencies of cells with massive chromosome damage in clonal derivatives of p53 and p21 knockout mouse cell lines; in particular to examine the role of telomere changes in this phenomenon. Overall, the results of these studies should enhance our understanding of the risk of low-dose exposures to ionizing radiation, including human populations to residential radon as well as occupational exposures.

  19. Mechanisms of the Bystander Effect

    International Nuclear Information System (INIS)

    Hall, Eric J.

    2008-01-01

    Generations of students in radiation biology have been taught that heritable biological damage requires direct damage to DNA. We now know that this is not true. The Bystander Effect is the name given to the phenomenon whereby biological effects are observed in cells that are not themselves traversed by a charged particle, but are in close proximity to cells that are. Several research groups have convincingly demonstrated a bystander effect for alpha particle, which are heavy and high LET, because charged particles can be focused into a tiny beam that can be directed onto individual cells. The biological effects seen in adjacent non-hit cells clearly represents a bystander effect. It is not so easy to demonstrate a similar effect for x-rays or for the electrons set in motion by the absorption of x-rays. In this project we used two types of cell that could be recognized one from the other. One cell type was fed radioactive tritiated thymidine, which is incorporated into the DNA, . The tritium emits electrons which have a very short range so that they do not even get out of the cell. These cells were then mixed with a different type of cell which are routinely used to assess mutations. The mixed cells formed a cluster, where the two types of cells were in close contact, and left for some hours. Subsequently, the two types of cells were separated and studied. A substantial fraction of the cells that had incorporated the tritiated thymidine were killed by the radiation. The interesting finding is that the cells that had not incorporated tritiated thymidine, but had been in close contact with cells that had, exhibited a significant incidence of mutations. These experiments clearly demonstrated a bystander effect for low LET electrons. In further experiments, it was possible to show that the bystander effect was greatest when the two cell types were in gap junction communication.

  20. Bystander Effects of Ionizing Radiation

    International Nuclear Information System (INIS)

    Little, John B.

    2017-01-01

    The objectives of this grant renewal are to provide administrative support and travel funds to allow the continued participation of the principal investigator (Dr. John B. Little) as an advisor to research initiated by several research fellows from his laboratory. The actual research will be carried out under the direction of Dr. Hatsumi Nagasawa with the collaboration of Dr. Joel Bedford at the Colorado State University, and by Drs. Edouard Azzam and Sonia de Toledo at the University of Medicine and Dentistry of New Jersey. Dr. Little will advise on the planning of experiments and development of experimental protocols, the analysis of data, and the preparation of manuscripts for publication. The Specific Aims for several of the planned experiments include: 1) to extend studies of the role of recombinational repair in the bystander effect by examining other genes in this pathway and cell lines deficient in excision repair; 2) to continue studies to determine the nature of the damage signal transmitted to bystander cells including the expression of several connexins in the bystander response, and the extent to which the enhanced oxidative metabolism observed in bystander cells may relate to the nature of the transmitted bystander signal; 3) to utilize a genome-wide approach to examine the genetic basis for the hypersensitivity to ionization we have observed in unaffected parents of patients with hereditary retinoblastoma, as well as from a group of apparently normal individuals that show similar radiosensitivity; 4) to complete studies concerning the induction of high frequencies of cells with massive chromosome damage in clonal derivatives of p53 and p21 knockout mouse cell lines; in particular to examine the role of telomere changes in this phenomenon. Overall, the results of these studies should enhance our understanding of the risk of low-dose exposures to ionizing radiation, including human populations to residential radon as well as occupational exposures.

  1. Discrimination and Acculturation Stress: A Longitudinal Study of Children's Well-Being from Prenatal Development to 5 Years of Age.

    Science.gov (United States)

    Zeiders, Katharine H; Umaña-Taylor, Adriana J; Jahromi, Laudan B; Updegraff, Kimberly A; White, Rebecca M B

    2016-09-01

    To examine whether cumulative family discrimination and acculturation stress (prenatally to 24 months postpartum) among Mexican-origin adolescent mothers and their mother-figures predicted children's socio-emotional functioning and academic achievement at 5 years of age, and the role of maternal depressive symptoms and mother-child interactions in the association. Mexican-origin families (N = 204) with an adolescent mother, a child, and a mother-figure participated in a 6-wave longitudinal study (2007-2013). Families were recruited and interviewed during the adolescent mother's pregnancy; adolescent mothers, mother-figures, and children were then assessed annually for the next 5 years using a combination of interview-based survey and observational methods. Maternal reports of children's socio-emotional behaviors (measured using the Child Behavior Checklist) and children's academic achievement (assessed with the Woodcock Johnson III Tests of Achievement/Bateria III Woodcock-Muñoz) were used. Structural equation modeling revealed that greater cumulative family discrimination and acculturation stress from pregnancy to 24 months postpartum predicted higher adolescent mothers' depressive symptoms, greater mother-child intrusive interactions, and less mother sensitivity at 36 months postpartum. Maternal depressive symptoms were positively related to children's CBCL symptoms at 60 months postpartum. Greater cumulative discrimination and acculturation stressors directly predicted children's lower Woodcock Johnson/Bateria test scores after accounting for socio-economic status. Mexican-origin adolescent mothers' and mother figures' cumulative discrimination and acculturation stress from pregnancy through children's second birthday predicted children's socio-emotional and academic achievement at age 5. Overall, the findings underscore the cumulative impact of these stressors on well-being in a population with substantial public health significance.

  2. Anxiety-like behaviour and associated neurochemical and endocrinological alterations in male pups exposed to prenatal stress.

    Science.gov (United States)

    Laloux, Charlotte; Mairesse, Jérôme; Van Camp, Gilles; Giovine, Angela; Branchi, Igor; Bouret, Sebastien; Morley-Fletcher, Sara; Bergonzelli, Gabriela; Malagodi, Marithé; Gradini, Roberto; Nicoletti, Ferdinando; Darnaudéry, Muriel; Maccari, Stefania

    2012-10-01

    Epidemiological studies suggest that emotional liability in infancy could be a predictor of anxiety-related disorders in the adulthood. Rats exposed to prenatal restraint stress ("PRS rats") represent a valuable model for the study of the interplay between environmental triggers and neurodevelopment in the pathogenesis of anxious/depressive like behaviours. Repeated episodes of restraint stress were delivered to female Sprague-Dawley rats during pregnancy and male offspring were studied. Ultrasonic vocalization (USV) was assessed in pups under different behavioural paradigms. After weaning, anxiety was measured by conventional tests. Expression of GABA(A) receptor subunits and metabotropic glutamate (mGlu) receptors was assessed by immunoblotting. Plasma leptin levels were measured using a LINCOplex bead assay kit. The offspring of stressed dams emitted more USVs in response to isolation from their mothers and showed a later suppression of USV production when exposed to an unfamiliar male odour, indicating a pronounced anxiety-like profile. Anxiety like behaviour in PRS pups persisted one day after weaning. PRS pups did not show the plasma peak in leptin levels that is otherwise seen at PND14. In addition, PRS pups showed a reduced expression of the γ2 subunit of GABA(A) receptors in the amygdala at PND14 and PND22, an increased expression of mGlu5 receptors in the amygdala at PND22, a reduced expression of mGlu5 receptors in the hippocampus at PND14 and PND22, and a reduced expression of mGlu2/3 receptors in the hippocampus at PND22. These data offer a clear-cut demonstration that the early programming triggered by PRS could be already translated into anxiety-like behaviour during early postnatal life. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis

    NARCIS (Netherlands)

    Beijers, R.; Buitelaar, J.K.; Weerth, C. de

    2014-01-01

    Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often

  4. The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by α-irradiated keratinocytes

    International Nuclear Information System (INIS)

    Tian, Wenqian; Yin, Xiaoming; Wang, Longxiao; Wang, Jingdong; Zhu, Wei; Cao, Jianping; Yang, Hongying

    2015-01-01

    Highlights: • After co-culture with α-irradiated HaCaT cells, WS1 cells displayed oxidative stress and DNA damage. • Increased miR-21 expression in bystander cells was critical to the occurrence of RIBEs. • SOD2 of bystander cells played an important role in bystander responses. • miR-21 mediated bystander effects through its regulation on SOD2. - Abstract: Radiation-induced bystander effect (RIBE) is well accepted in the radiation research field by now, but the underlying molecular mechanisms for better understanding this phenomenon caused by intercellular communication and intracellular signal transduction are still incomplete. Although our previous study has demonstrated an important role of miR-21 of unirradiated bystander cells in RIBEs, the direct evidence for the hypothesis that RIBE is epigenetically regulated is still limited and how miR-21 mediates RIBEs is unknown. Reactive oxygen species (ROS) have been demonstrated to be involved in RIBEs, however, the roles of anti-oxidative stress system of cells in RIBEs are unclear. Using transwell insert co-culture system, we investigated medium-mediated bystander responses in WS1 human fibroblasts after co-culture with HaCaT keratinocytes traversed by α-particles. Results showed that the ROS levels in unirradiated bystander WS1 cells were significantly elevated after 30 min of co-culture, and 53BP1 foci, a surrogate marker of DNA damage, were obviously induced after 3 h of co-culture. This indicates the occurrence of oxidative stress and DNA damage in bystander WS1 cells after co-culture with irradiated keratinocytes. Furthermore, the expression of miR-21 was increased in bystander WS1 cells, downregulation of miR-21 eliminated the bystander responses, overexpression of miR-21 alone could induce bystander-like oxidative stress and DNA damage in WS1 cells. These data indicate an important mediating role of miR-21 in RIBEs. In addition, MnSOD or SOD2 in WS1 cells was involved in the bystander effects

  5. The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by α-irradiated keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Wenqian; Yin, Xiaoming; Wang, Longxiao; Wang, Jingdong; Zhu, Wei; Cao, Jianping [School of Radiation Medicine and Protection, Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123 (China); Yang, Hongying, E-mail: yanghongying@suda.edu.cn [School of Radiation Medicine and Protection, Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123 (China); Institute of Radiotherapy & Oncology, Soochow University (China)

    2015-10-15

    Highlights: • After co-culture with α-irradiated HaCaT cells, WS1 cells displayed oxidative stress and DNA damage. • Increased miR-21 expression in bystander cells was critical to the occurrence of RIBEs. • SOD2 of bystander cells played an important role in bystander responses. • miR-21 mediated bystander effects through its regulation on SOD2. - Abstract: Radiation-induced bystander effect (RIBE) is well accepted in the radiation research field by now, but the underlying molecular mechanisms for better understanding this phenomenon caused by intercellular communication and intracellular signal transduction are still incomplete. Although our previous study has demonstrated an important role of miR-21 of unirradiated bystander cells in RIBEs, the direct evidence for the hypothesis that RIBE is epigenetically regulated is still limited and how miR-21 mediates RIBEs is unknown. Reactive oxygen species (ROS) have been demonstrated to be involved in RIBEs, however, the roles of anti-oxidative stress system of cells in RIBEs are unclear. Using transwell insert co-culture system, we investigated medium-mediated bystander responses in WS1 human fibroblasts after co-culture with HaCaT keratinocytes traversed by α-particles. Results showed that the ROS levels in unirradiated bystander WS1 cells were significantly elevated after 30 min of co-culture, and 53BP1 foci, a surrogate marker of DNA damage, were obviously induced after 3 h of co-culture. This indicates the occurrence of oxidative stress and DNA damage in bystander WS1 cells after co-culture with irradiated keratinocytes. Furthermore, the expression of miR-21 was increased in bystander WS1 cells, downregulation of miR-21 eliminated the bystander responses, overexpression of miR-21 alone could induce bystander-like oxidative stress and DNA damage in WS1 cells. These data indicate an important mediating role of miR-21 in RIBEs. In addition, MnSOD or SOD2 in WS1 cells was involved in the bystander effects

  6. Cocaine enhances resistance to extinction of responding for brain-stimulation reward in adult prenatally stressed rats.

    Science.gov (United States)

    Gao, Shuibo; Suenaga, Toshiko; Oki, Yutaka; Yukie, Masao; Nakahara, Daiichiro

    2011-10-01

    The present experiment assessed whether prenatal stress (PS) can alter the ability of acute and chronic cocaine administration to increase and decrease the rewarding effectiveness of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS), and also whether PS can affect the extinction of the MFB stimulation response. Adult male offspring of female rats that received PS or no PS (nPS) were implanted with MFB stimulating electrodes, and were then tested in ICSS paradigms. In both nPS and PS offspring, acute cocaine injection decreased ICSS thresholds dose-dependently. However, the threshold-lowering effects at any dose were not significantly different between groups. There was also no group-difference in the threshold-elevating effects of chronic cocaine administration. Nevertheless, chronically drug-administered PS rats exhibited a resistance to the extinguishing of the response for brain-stimulation reward when acutely treated with cocaine, as compared to extinction without cocaine treatment. The results suggest that PS may weaken the ability for response inhibition under cocaine loading in male adult offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Duloxetine prevents the effects of prenatal stress on depressive-like and anxiety-like behavior and hippocampal expression of pro-inflammatory cytokines in adult male offspring rats.

    Science.gov (United States)

    Zhang, Xiaosong; Wang, Qi; Wang, Yan; Hu, Jingmin; Jiang, Han; Cheng, Wenwen; Ma, Yuchao; Liu, Mengxi; Sun, Anji; Zhang, Xinxin; Li, Xiaobai

    2016-12-01

    Stress during pregnancy may cause neurodevelopmental and psychiatric disorders. However, the mechanisms are largely unknown. Currently, pro-inflammatory cytokines have been identified as a risk factor for depression and anxiety disorder. Unfortunately, there is very little research on the long-term effects of prenatal stress on the neuroinflammatory system of offspring. Moreover, the relationship between antidepressant treatment and cytokines in the central nervous system, especially in the hippocampus, an important emotion modulation center, is unclear. Therefore, the aim of this study was to determine the effects of prenatal chronic mild stress during development on affective-like behaviors and hippocampal cytokines in adult offspring, and to verify whether antidepressant (duloxetine) administration from early adulthood could prevent the harmful consequences. To do so, prenatally stressed and non-stressed Sprague-Dawley rats were treated with either duloxetine (10mg/kg/day) or vehicle from postnatal day 60 for 21days. Adult offspring were divided into four groups: 1) prenatal stress+duloxetine treatment, 2) prenatal stress+vehicle, 3) duloxetine treatment alone, and 4) vehicle alone. Adult offspring were assessed for anxiety-like behavior using the open field test and depression-like behavior using the forced swim test. Brains were analyzed for pro-inflammatory cytokine markers in the hippocampus via real-time PCR. Results demonstrate that prenatal stress-induced anxiety- and depression-like behaviors are associated with an increase in hippocampal inflammatory mediators, and duloxetine administration prevents the increased hippocampal pro-inflammatory cytokine interleukin-6 and anxiety- and depression-like behavior in prenatally stressed adult offspring. This research provides important evidence on the long-term effect of PNS exposure during development in a model of maternal adversity to study the pathogenesis of depression and its therapeutic interventions

  8. Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence.

    Science.gov (United States)

    Vesterinen, Hanna M; Morello-Frosch, Rachel; Sen, Saunak; Zeise, Lauren; Woodruff, Tracey J

    2017-01-01

    Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46-9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53-2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.

  9. Prenatal stress affects insulin-like growth factor-1 (IGF-1) level and IGF-1 receptor phosphorylation in the brain of adult rats.

    Science.gov (United States)

    Basta-Kaim, Agnieszka; Szczesny, Ewa; Glombik, Katarzyna; Stachowicz, Katarzyna; Slusarczyk, Joanna; Nalepa, Irena; Zelek-Molik, Agnieszka; Rafa-Zablocka, Katarzyna; Budziszewska, Boguslawa; Kubera, Marta; Leskiewicz, Monika; Lason, Wladyslaw

    2014-09-01

    It has been shown that stressful events occurring in early life have a powerful influence on the development of the central nervous system. Insulin-like growth factor-1 (IGF-1) promotes the growth, differentiation and survival of both neurons and glial cells and is thought to exert antidepressant-like activity. Thus, it is possible that disturbances in the function of the IGF-1 system may be responsible for disturbances observed over the course of depression. Prenatal stress was used as a valid model of depression. Adult male offspring of control and stressed rat dams were subjected to behavioural testing (forced swim test). The level of IGF-1 in the blood and the expression of IGF-1, IGF-1R, and IRS-1/2 in the hippocampus and frontal cortex using RT-PCR, ELISA and western blotting were measured. In addition the effect of intracerebroventricularly administered IGF-1 and/or the IGF-1R receptor antagonist JB1 in the forced swim test was studied. Prenatally stressed rats showed depressive like behaviour, including increased immobility time as well as decreased mobility and climbing. Intracerebroventricular administration of IGF-1 reversed these effects in stressed animals, whereas concomitant administration of the IGF-1R antagonist JB1 completely blocked the effects. Biochemical analysis of homogenates from the hippocampus and frontal cortex revealed decreases in IGF-1 level and IGF-1R phosphorylation along with disturbances in IRS-1 phosphorylation. These findings reveal that prenatal stress alters IGF-1 signalling, which may contribute to the behavioural changes observed in depression. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  10. Cardio-metabolic risk in children prenatally exposed to maternal psychosocial stress

    NARCIS (Netherlands)

    van Dijk, A.E.

    2012-01-01

    Dertig procent van zwangere vrouwen ervaart symptomen van angst en depressie. Zulke ‘reguliere’ psychosociale stress is geassocieerd met een kortere zwangerschapsduur en een lager geboortegewicht, maar de associaties zijn zwak. Er is geen bewijs gevonden voor de hypothese dat kinderen die worden

  11. How Prenatal Depression, Anxiety, and Stress May Affect Child Outcome: The Placenta and Child Development

    Science.gov (United States)

    Glover, Vivette; O'Connor, T. G.; O'Donnell, K.; Capron, Lauren

    2014-01-01

    There is good evidence that if a woman is depressed, anxious, or stressed while she is pregnant, then there is an increased risk that her child will have emotional, behavioral, or cognitive problems. Her own biology must cause these effects, but it is not known how. One important line of research suggests that the function of the placenta changes…

  12. Perceived Child Behavior Problems, Parenting Stress, and Maternal Depressive Symptoms among Prenatal Methamphetamine Users

    Science.gov (United States)

    Liles, Brandi D.; Newman, Elana; LaGasse, Linda L.; Derauf, Chris; Shah, Rizwan; Smith, Lynne M.; Arria, Amelia M.; Huestis, Marilyn A.; Haning, William; Strauss, Arthur; DellaGrotta, Sheri; Dansereau, Lynne M.; Neal, Charles; Lester, Barry M.

    2012-01-01

    The present study was designed to examine parenting stress, maternal depressive symptoms, and perceived child behavior problems among mothers who used methamphetamine (MA) during pregnancy. Participants were a subsample (n = 212; 75 exposed, 137 comparison) of biological mothers who had continuous custody of their child from birth to 36 months.…

  13. Prenatal maternal restraint stress exposure alters the reproductive hormone profile and testis development of the rat male offspring.

    Science.gov (United States)

    Pallarés, María Eugenia; Adrover, Ezequiela; Baier, Carlos Javier; Bourguignon, Nadia S; Monteleone, Melisa C; Brocco, Marcela A; González-Calvar, Silvia I; Antonelli, Marta C

    2013-07-01

    Several studies have demonstrated that the presence of stressors during pregnancy induces adverse effects on the neuroendocrine system of the offspring later in life. In the present work, we investigated the effects of early programming on the male reproductive system, employing a prenatal stress (PS) paradigm. This study found that when pregnant dams were placed in a plastic restrainer three times a day during the last week of pregnancy, the offspring showed reduced anogenital distance and delayed testicular descent. Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels were decreased at postnatal day (PND) 28 and testosterone was decreased at PND 75. Increased testosterone plus dihydrotestosterone (T + DHT) concentrations correlated with increased testicular 5α Reductase-1 (5αR-1) mRNA expression at PND 28. Moreover, PS accelerated spermatogenesis at PND 35 and 60, and increased mean seminiferous tubule diameter in pubertal offspring and reduced Leydig cell number was observed at PND 35 and 60. PS offspring had increased androgen receptor (AR) mRNA level at PND 28, and at PND 35 had increased the numbers of Sertoli cells immunopositive for AR. Overall, the results confirm that stress during gestation can induce long-term effects on the male offspring reproductive system. Of particular interest is the pre-pubertal imbalance of circulating hormones that probably trigger accelerated testicular development, followed by an increase in total androgens and a decrease in testosterone concentration during adulthood. Exposure to an unfavourable intrauterine environment might prepare for harsh external conditions by triggering early puberty, increasing reproductive potential.

  14. Bystander effect: Biological endpoints and microarray analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhry, M. Ahmad [Department of Medical Laboratory and Radiation Sciences, College of Nursing and Health Sciences, University of Vermont, 302 Rowell Building, Burlington, VT 05405 (United States) and DNA Microarray Facility, University of Vermont, Burlington, VT 05405 (United States)]. E-mail: mchaudhr@uvm.edu

    2006-05-11

    In cell populations exposed to ionizing radiation, the biological effects occur in a much larger proportion of cells than are estimated to be traversed by radiation. It has been suggested that irradiated cells are capable of providing signals to the neighboring unirradiated cells resulting in damage to these cells. This phenomenon is termed the bystander effect. The bystander effect induces persistent, long-term, transmissible changes that result in delayed death and neoplastic transformation. Because the bystander effect is relevant to carcinogenesis, it could have significant implications for risk estimation for radiation exposure. The nature of the bystander effect signal and how it impacts the unirradiated cells remains to be elucidated. Examination of the changes in gene expression could provide clues to understanding the bystander effect and could define the signaling pathways involved in sustaining damage to these cells. The microarray technology serves as a tool to gain insight into the molecular pathways leading to bystander effect. Using medium from irradiated normal human diploid lung fibroblasts as a model system we examined gene expression alterations in bystander cells. The microarray data revealed that the radiation-induced gene expression profile in irradiated cells is different from unirradiated bystander cells suggesting that the pathways leading to biological effects in the bystander cells are different from the directly irradiated cells. The genes known to be responsive to ionizing radiation were observed in irradiated cells. Several genes were upregulated in cells receiving media from irradiated cells. Surprisingly no genes were found to be downregulated in these cells. A number of genes belonging to extracellular signaling, growth factors and several receptors were identified in bystander cells. Interestingly 15 genes involved in the cell communication processes were found to be upregulated. The induction of receptors and the cell

  15. Bystander effect: Biological endpoints and microarray analysis

    International Nuclear Information System (INIS)

    Chaudhry, M. Ahmad

    2006-01-01

    In cell populations exposed to ionizing radiation, the biological effects occur in a much larger proportion of cells than are estimated to be traversed by radiation. It has been suggested that irradiated cells are capable of providing signals to the neighboring unirradiated cells resulting in damage to these cells. This phenomenon is termed the bystander effect. The bystander effect induces persistent, long-term, transmissible changes that result in delayed death and neoplastic transformation. Because the bystander effect is relevant to carcinogenesis, it could have significant implications for risk estimation for radiation exposure. The nature of the bystander effect signal and how it impacts the unirradiated cells remains to be elucidated. Examination of the changes in gene expression could provide clues to understanding the bystander effect and could define the signaling pathways involved in sustaining damage to these cells. The microarray technology serves as a tool to gain insight into the molecular pathways leading to bystander effect. Using medium from irradiated normal human diploid lung fibroblasts as a model system we examined gene expression alterations in bystander cells. The microarray data revealed that the radiation-induced gene expression profile in irradiated cells is different from unirradiated bystander cells suggesting that the pathways leading to biological effects in the bystander cells are different from the directly irradiated cells. The genes known to be responsive to ionizing radiation were observed in irradiated cells. Several genes were upregulated in cells receiving media from irradiated cells. Surprisingly no genes were found to be downregulated in these cells. A number of genes belonging to extracellular signaling, growth factors and several receptors were identified in bystander cells. Interestingly 15 genes involved in the cell communication processes were found to be upregulated. The induction of receptors and the cell

  16. Increased utilisation of primary healthcare in persons exposed to severe stress in prenatal life

    DEFF Research Database (Denmark)

    Li, Jiong; Yang, Hu; Guldin, Mai-Britt

    2015-01-01

    Meget tyder på, at stress i graviditeten kan skade det ufødte barn. Dette studie viser, at sorg hos moderen under graviditeten kan betyde, at barnet senere i livet søger læge mere hyppigt sammenlignet med børn, hvor moderen ikke har været i sorg under graviditeten. Det er især, hvis moderen under...... menneskes liv, og at det kan påvirke det ufødte barn, når moderen bliver stresset under graviditeten. Vi ved dog ikke helt, om den øgede lægesøgning hos børnene kun skyldes stress i graviditeten, eller om de også påvirkes af, om moderen fx har mistet sin ægtefælle, og den betydning det kan have for barnets...

  17. Prenatal irradiation: nitric oxide and oxidative stress roles in radiation-induced apoptosis of the developing central nervous system

    International Nuclear Information System (INIS)

    Sanjurjo, Julieta

    2001-01-01

    Full text: The effects of prenatal irradiation on developing brain should be considered at cellular, structural and functional levels, integrating the information obtained from different sources in an appropriated model to explain the mechanisms involved in neuronal damage. That would permit to make risk estimations and improve radiological protection. Human brain is especially sensitive to ionizing radiation during certain stages of prenatal development. At doses such as those received by Hiroshima and Nagasaki's atomic bomb explosions survivors that were prenatally exposed, the maximum risk was to those exposed between the 8th and 15th weeks of gestation, in coincidence with the highest rate of neuron production and its migration to the brain cortex. The major effect produced on both, brain growth and development, was the augmentation of the Severe Mental Retardation (SMR) incidence. Radiation-induced apoptosis of neuronal progenitors should be considered as one of the factors associated with this pathology, apart from those of migration and synaptogenesis. Apoptosis is an innate and evolutionally conserved process by which the cells provoke the inactivation, disorganisation and degradation of their structural and functional components in a systematic fashion, with the aim of producing its own death. It is also the main cell death mechanism induced by low linear energy transfer (LET) ionizing radiation in developing Central Nervous System (CNS). Radioinduced apoptosis characterization during the different developmental stages, its kinetics and the possible implicated mechanisms (like oxidative injury and nitric oxide) was done using an 'in vitro' system of cortical micro masses (primary cultures of brain cortex cells) from rat embryo brains. Cell cultures were exposed to a single dose of gamma radiation, between 0,2 and 2 Gy, supplied by a Co 60 source (Picker C4M60) at a 70 cm distance with a field area size of 25 cm x 25 cm and at a 0,34 Gy/minute dose rate

  18. Genomic instability induced in distant progeny of bystander cells depends on the connexins expressed in the irradiated cells.

    Science.gov (United States)

    de Toledo, Sonia M; Buonanno, Manuela; Harris, Andrew L; Azzam, Edouard I

    2017-10-01

    To examine the time window during which intercellular signaling though gap junctions mediates non-targeted (bystander) effects induced by moderate doses of ionizing radiation; and to investigate the impact of gap junction communication on genomic instability in distant progeny of bystander cells. A layered cell culture system was developed to investigate the propagation of harmful effects from irradiated normal or tumor cells that express specific connexins to contiguous bystander normal human fibroblasts. Irradiated cells were exposed to moderate mean absorbed doses from 3.7 MeV α particle, 1000 MeV/u iron ions, 600 MeV/u silicon ions, or 137 Cs γ rays. Following 5 h of co-culture, pure populations of bystander cells, unexposed to secondary radiation, were isolated and DNA damage and oxidative stress was assessed in them and in their distant progeny (20-25 population doublings). Increased frequency of micronucleus formation and enhanced oxidative changes were observed in bystander cells co-cultured with confluent cells exposed to either sparsely ionizing ( 137 Cs γ rays) or densely ionizing (α particles, energetic iron or silicon ions) radiations. The irradiated cells propagated signals leading to biological changes in bystander cells within 1 h of irradiation, and the effect required cellular coupling by gap junctions. Notably, the distant progeny of isolated bystander cells also exhibited increased levels of spontaneous micronuclei. This effect was dependent on the type of junctional channels that coupled the irradiated donor cells with the bystander cells. Previous work showed that gap junctions composed of connexin26 (Cx26) or connexin43 (Cx43) mediate toxic bystander effects within 5 h of co-culture, whereas gap junctions composed of connexin32 (Cx32) mediate protective effects. In contrast, the long-term progeny of bystander cells expressing Cx26 or Cx43 did not display elevated DNA damage, whereas those coupled by Cx32 had enhanced DNA

  19. Spatially Fractionated Radiation Induces Cytotoxicity and Changes in Gene Expression in Bystander and Radiation Adjacent Murine Carcinoma Cells

    Science.gov (United States)

    Asur, Rajalakshmi S.; Sharma, Sunil; Chang, Ching-Wei; Penagaricano, Jose; Kommuru, Indira M.; Moros, Eduardo G.; Corry, Peter M.; Griffin, Robert J.

    2012-01-01

    Radiation-induced bystander effects have been extensively studied at low doses, since evidence of bystander induced cell killing and other effects on unirradiated cells were found to be predominant at doses up to 0.5 Gy. Therefore, few studies have examined bystander effects induced by exposure to higher doses of radiation, such as spatially fractionated radiation (GRID) treatment. In the present study, we evaluate the ability of GRID treatment to induce changes in GRID adjacent (bystander) regions, in two different murine carcinoma cell lines following exposure to a single irradiation dose of 10 Gy. Murine SCK mammary carcinoma cells and SCCVII squamous carcinoma cells were irradiated using a brass collimator to create a GRID pattern of nine circular fields 12 mm in diameter with a center-to-center distance of 18 mm. Similar to the typical clinical implementation of GRID, this is approximately a 50:50 ratio of direct and bystander exposure. We also performed experiments by irradiating separate cultures and transferring the medium to unirradiated bystander cultures. Clonogenic survival was evaluated in both cell lines to determine the occurrence of radiation-induced bystander effects. For the purpose of our study, we have defined bystander cells as GRID adjacent cells that received approximately 1 Gy scatter dose or unirradiated cells receiving conditioned medium from irradiated cells. We observed significant bystander killing of cells adjacent to the GRID irradiated regions compared to sham treated controls. We also observed bystander killing of SCK and SCCVII cells cultured in conditioned medium obtained from cells irradiated with 10 Gy. Therefore, our results confirm the occurrence of bystander effects following exposure to a high-dose of radiation and suggest that cell-to-cell contact is not required for these effects. In addition, the gene expression profile for DNA damage and cellular stress response signaling in SCCVII cells after GRID exposure was studied

  20. A Bully's Bystanders Are Never Innocent

    Science.gov (United States)

    Coloroso, Barbara

    2005-01-01

    Though they play the least active role, bystanders are a critical element in bullying. With peers looking on and providing at least tacit support, the bully is no longer acting alone. The bystanders have become allies to the point of magnifying the supposed negative attributes of the target. If the bullying cycle is to be broken, the role of the…

  1. RAD9 deficiency enhances radiation induced bystander DNA damage and transcriptomal response

    International Nuclear Information System (INIS)

    Ghandhi, Shanaz A; Ponnaiya, Brian; Panigrahi, Sunil K; Hopkins, Kevin M; Cui, Qingping; Hei, Tom K; Amundson, Sally A; Lieberman, Howard B

    2014-01-01

    Radiation induced bystander effects are an important component of the overall response of cells to irradiation and are associated with human health risks. The mechanism responsible includes intra-cellular and inter-cellular signaling by which the bystander response is propagated. However, details of the signaling mechanism are not well defined. We measured the bystander response of Mrad9 +/+ and Mrad9 −/− mouse embryonic stem cells, as well as human H1299 cells with inherent or RNA interference-mediated reduced RAD9 levels after exposure to 1 Gy α particles, by scoring chromosomal aberrations and micronuclei formation, respectively. In addition, we used microarray gene expression analyses to profile the transcriptome of directly irradiated and bystander H1299 cells. We demonstrated that Mrad9 null enhances chromatid aberration frequency induced by radiation in bystander mouse embryonic stem cells. In addition, we found that H1299 cells with reduced RAD9 protein levels showed a higher frequency of radiation induced bystander micronuclei formation, compared with parental cells containing inherent levels of RAD9. The enhanced bystander response in human cells was associated with a unique transcriptomic profile. In unirradiated cells, RAD9 reduction broadly affected stress response pathways at the mRNA level; there was reduction in transcript levels corresponding to genes encoding multiple members of the UVA-MAPK and p38MAPK families, such as STAT1 and PARP1, suggesting that these signaling mechanisms may not function optimally when RAD9 is reduced. Using network analysis, we found that differential activation of the SP1 and NUPR1 transcriptional regulators was predicted in directly irradiated and bystander H1299 cells. Transcription factor prediction analysis also implied that HIF1α (Hypoxia induced factor 1 alpha) activation by protein stabilization in irradiated cells could be a negative predictor of the bystander response, suggesting that local hypoxic stress

  2. An extracellular DNA mediated bystander effect produced from low dose irradiated endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Ermakov, Aleksei V., E-mail: avePlato@mail.ru [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Konkova, Marina S.; Kostyuk, Svetlana V.; Smirnova, Tatiana D.; Malinovskaya, Elena M.; Efremova, Liudmila V.; Veiko, Natalya N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation)

    2011-07-01

    The human umbilical vein endothelial cells culture was exposed to X-ray radiation in a low dose of 10 cGy. The fragments of extracellular genomic DNA (ecDNA{sup R}) were isolated from the culture medium after the short-term incubation. A culture medium of unirradiated endothelial cells was then supplemented with ecDNA{sup R}, followed by analysing the cells along the series of parameters (bystander effect). The exposed cells and bystander endotheliocytes showed similar response to low doses: approximation of the 1q12 loci of chromosome 1 and their transposition into the cellular nucleus, change in shape of the endotheliocytic nucleus, activation of the nucleolus organizing regions (NORs), actin polymerization, and an elevated level of DNA double-stranded breaks. Following blockade of TLR9 receptors with oligonucleotide-inhibitor or chloroquine in the bystander cells these effects - except of activation of NORs - on exposure to ecDNA{sup R} disappeared, with no bystander response thus observed. The presence of the radiation-induced apoptosis in the bystander effect being studied suggests a possibility for radiation-modified ecDNA fragments (i.e., stress signaling factors) to be released into the culture medium, whereas inhibition of TLR9 suggests the binding these ligands to the recipient cells. A similar DNA-signaling pathway in the bystander effect we previously described for human lymphocytes. Integrity of data makes it possible to suppose that a similar signaling mechanism which we demonstrated for lymphocytes (humoral system) might also be mediated in a monolayer culture of cells (cellular tissue) after the development of the bystander effect in them and transfer of stress signaling factors (ecDNA{sup R}) through the culture medium.

  3. An extracellular DNA mediated bystander effect produced from low dose irradiated endothelial cells

    International Nuclear Information System (INIS)

    Ermakov, Aleksei V.; Konkova, Marina S.; Kostyuk, Svetlana V.; Smirnova, Tatiana D.; Malinovskaya, Elena M.; Efremova, Liudmila V.; Veiko, Natalya N.

    2011-01-01

    The human umbilical vein endothelial cells culture was exposed to X-ray radiation in a low dose of 10 cGy. The fragments of extracellular genomic DNA (ecDNA R ) were isolated from the culture medium after the short-term incubation. A culture medium of unirradiated endothelial cells was then supplemented with ecDNA R , followed by analysing the cells along the series of parameters (bystander effect). The exposed cells and bystander endotheliocytes showed similar response to low doses: approximation of the 1q12 loci of chromosome 1 and their transposition into the cellular nucleus, change in shape of the endotheliocytic nucleus, activation of the nucleolus organizing regions (NORs), actin polymerization, and an elevated level of DNA double-stranded breaks. Following blockade of TLR9 receptors with oligonucleotide-inhibitor or chloroquine in the bystander cells these effects - except of activation of NORs - on exposure to ecDNA R disappeared, with no bystander response thus observed. The presence of the radiation-induced apoptosis in the bystander effect being studied suggests a possibility for radiation-modified ecDNA fragments (i.e., stress signaling factors) to be released into the culture medium, whereas inhibition of TLR9 suggests the binding these ligands to the recipient cells. A similar DNA-signaling pathway in the bystander effect we previously described for human lymphocytes. Integrity of data makes it possible to suppose that a similar signaling mechanism which we demonstrated for lymphocytes (humoral system) might also be mediated in a monolayer culture of cells (cellular tissue) after the development of the bystander effect in them and transfer of stress signaling factors (ecDNA R ) through the culture medium.

  4. Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: A potential biological unifying mechanism for their corresponding disease profiles

    International Nuclear Information System (INIS)

    Rossi-George, A.; Virgolini, M.B.; Weston, D.; Cory-Slechta, D.A.

    2009-01-01

    Combined exposures to maternal lead (Pb) and prenatal stress (PS) can act synergistically to enhance behavioral and neurochemical toxicity in offspring. Maternal Pb itself causes permanent dysfunction of the body's major stress system, the hypothalamic pituitary adrenal (HPA) axis. The current study sought to determine the potential involvement of altered negative glucocorticoid feedback as a mechanistic basis of the effects in rats of maternal Pb (0, 50 or 150 ppm in drinking water beginning 2 mo prior to breeding), prenatal stress (PS; restraint on gestational days 16-17) and combined maternal Pb + PS in 8 mo old male and female offspring. Corticosterone changes were measured over 24 h following an i.p. injection stress containing vehicle or 100 or 300 μg/kg (females) or 100 or 150 μg/kg (males) dexamethasone (DEX). Both Pb and PS prolonged the time course of corticosterone reduction following vehicle injection stress. Pb effects were non-monotonic, with a greater impact at 50 vs. 150 ppm, particularly in males, where further enhancement occurred with PS. In accord with these findings, the efficacy of DEX in suppressing corticosterone was reduced by Pb and Pb + PS in both genders, with Pb efficacy enhanced by PS in females, over the first 6 h post-administration. A marked prolongation of DEX effects was found in males. Thus, Pb, PS and Pb + PS, sometimes additively, produced hypercortisolism in both genders, followed by hypocortisolism in males, consistent with HPA axis dysfunction. These findings may provide a plausible unifying biological mechanism for the reported links between Pb exposure and stress-associated diseases and disorders mediated via the HPA axis, including obesity, hypertension, diabetes, anxiety, schizophrenia and depression. They also suggest broadening of Pb screening programs to pregnant women in high stress environments

  5. Prenatal Diagnosis

    Directory of Open Access Journals (Sweden)

    Ozge Ozalp Yuregir

    2012-02-01

    Full Text Available Prenatal diagnosis is the process of determining the health or disease status of the fetus or embryo before birth. The purpose is early detection of diseases and early intervention when required. Prenatal genetic tests comprise of cytogenetic (chromosome assessment and molecular (DNA mutation analysis tests. Prenatal testing enables the early diagnosis of many diseases in risky pregnancies. Furthermore, in the event of a disease, diagnosing prenatally will facilitate the planning of necessary precautions and treatments, both before and after birth. Upon prenatal diagnosis of some diseases, termination of the pregnancy could be possible according to the family's wishes and within the legal frameworks. [Archives Medical Review Journal 2012; 21(1.000: 80-94

  6. Reduced levels of NR1 and NR2A with depression-like behavior in different brain regions in prenatally stressed juvenile offspring.

    Directory of Open Access Journals (Sweden)

    Hongli Sun

    Full Text Available Adolescence is a time of continued brain maturation, particularly in limbic and cortical regions, which undoubtedly plays a role in the physiological and emotional changes. Juvenile rats repeatedly exposed to prenatal stress (PS exhibit behavioral features often observed in neuropsychiatric disorders including depression. However, to date the underlying neurological mechanisms are still unclear. In the current study, juvenile offspring rats whose mothers were exposed to PS were evaluated for depression-related behaviors in open field and sucrose preference test. NMDA receptor subunits NR1 and NR2A in the hippocampus, frontal cortex and striatum were assayed by western blotting. The results indicated that PS resulted in several behavioral anomalies in the OFT and sucrose preference test. Moreover, reduced levels of NMDA receptor subunits NR1 and NR2A in the hippocampus, and NR1 in prefrontal cortex and striatum of prenatally stressed juvenile offspring were found. Treatment with MK-801 to pregnant dams could prevent all those changes in the juvenile offspring. Collectivity, these data support the argument that PS to pregnant dams could induce depression-like behavior, which may be involved with abnormal expression of NR1 and NR2A in specific brain regions, and MK-801 may have antidepressant-like effects on the juvenile offspring.

  7. Prenatal Tests

    Science.gov (United States)

    ... tests are considered routine — that is, almost all pregnant women receiving prenatal care get them. They include things like checking urine (pee) levels for protein, sugar, or signs of infection. Other non-routine ...

  8. Role of nitric oxide in the radiation-induced bystander effect.

    Science.gov (United States)

    Yakovlev, Vasily A

    2015-12-01

    Cells that are not irradiated but are affected by "stress signal factors" released from irradiated cells are called bystander cells. These cells, as well as directly irradiated ones, express DNA damage-related proteins and display excess DNA damage, chromosome aberrations, mutations, and malignant transformation. This phenomenon has been studied widely in the past 20 years, since its first description by Nagasawa and Little in 1992, and is known as the radiation-induced bystander effect (RIBE). Several factors have been identified as playing a role in the bystander response. This review will focus on one of them, nitric oxide (NO), and its role in the stimulation and propagation of RIBE. The hydrophobic properties of NO, which permit its diffusion through the cytoplasm and plasma membranes, allow this signaling molecule to easily spread from irradiated cells to bystander cells without the involvement of gap junction intercellular communication. NO produced in irradiated tissues mediates cellular regulation through posttranslational modification of a number of regulatory proteins. The best studied of these modifications are S-nitrosylation (reversible oxidation of cysteine) and tyrosine nitration. These modifications can up- or down-regulate the functions of many proteins modulating different NO-dependent effects. These NO-dependent effects include the stimulation of genomic instability (GI) and the accumulation of DNA errors in bystander cells without direct DNA damage. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Genotoxicity in the eyes of bystander cells

    International Nuclear Information System (INIS)

    Hei, Tom K.; Persaud, Rudranath; Zhou, Hongning; Suzuki, Masao

    2004-01-01

    The controversial use of a linear, no threshold extrapolation model for low dose risk assessment has become even more so in light of the recent reports on the bystander phenomenon. The answer to the question as to which of the two phenomena, bystander versus adaptive response, is more important has practical implication in terms of low dose radiation risk assessment. In this review, genotoxicity is used as an endpoint to introduce the two phenomena, provide some insight into the mechanisms of bystander effect and to bridge the two low dose phenomena which operate in opposite directions: the bystander effect tends to exaggerate the effect at low doses, by communicating damage from hit to non-hit cells whereas the adaptive response confers resistance to a subsequent challenging dose by an initial low priming dose

  10. The involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects.

    LENUS (Irish Health Repository)

    Lyng, F M

    2006-04-01

    Much evidence now exists regarding radiation-induced bystander effects, but the mechanisms involved in the transduction of the signal are still unclear. The mitogen-activated protein kinase (MAPK) pathways have been linked to growth factor-mediated regulation of cellular events such as proliferation, senescence, differentiation and apoptosis. Activation of multiple MAPK pathways such as the ERK, JNK and p38 pathways have been shown to occur after exposure of cells to radiation and a variety of other toxic stresses. Previous studies have shown oxidative stress and calcium signaling to be important in radiation-induced bystander effects. The aim of the present study was to investigate MAPK signaling pathways in bystander cells exposed to irradiated cell conditioned medium (ICCM) and the role of oxidative metabolism and calcium signaling in the induction of bystander responses. Human keratinocytes (HPV-G cell line) were irradiated (0.005-5 Gy) using a cobalt-60 teletherapy unit. The medium was harvested 1 h postirradiation and transferred to recipient HPV-G cells. Phosphorylated forms of p38, JNK and ERK were studied by immunofluorescence 30 min-24 h after exposure to ICCM. Inhibitors of the ERK pathway (PD98059 and U0126), the JNK pathway (SP600125), and the p38 pathway (SB203580) were used to investigate whether bystander-induced cell death could be blocked. Cells were also incubated with ICCM in the presence of superoxide dismutase, catalase, EGTA, verapamil, nifedipine and thapsigargin to investigate whether bystander effects could be inhibited because of the known effects on calcium homeostasis. Activated forms of JNK and ERK proteins were observed after exposure to ICCM. Inhibition of the ERK pathway appeared to increase bystander-induced apoptosis, while inhibition of the JNK pathway appeared to decrease apoptosis. In addition, reactive oxygen species, such as superoxide and hydrogen peroxide, and calcium signaling were found to be important modulators of

  11. Postnatal Treadmill Exercise Alleviates Prenatal Stress-Induced Anxiety in Offspring Rats by Enhancing Cell Proliferation Through 5-Hydroxytryptamine 1A Receptor Activation

    Directory of Open Access Journals (Sweden)

    Sam Jun Lee

    2016-05-01

    Full Text Available Purpose: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. Methods: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2ʹ- deoxyuridine and doublecortin (DCX in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT1A in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF and tyrosine kinase B (TrkB levels in the hippocampus were evaluated by western blot analysis. Results: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT1A expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. Conclusions: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT1A activation in offspring rats.

  12. Are Victims Truly Worse Off in the Presence of Bystanders? Revisiting the Bystander Effect

    NARCIS (Netherlands)

    Fromell, Hanna; Nosenzo, Daniele; Owens, Trudy; Tufano, Fabio

    2017-01-01

    Previous studies have shown that individuals are less likely to help a person in need when there are “bystanders” present who can also offer help. We designed an experiment to re-examine this “bystander effect” using modified dictator games. We find lower giving rates in the presence of bystanders,

  13. What Happens during Prenatal Visits?

    Science.gov (United States)

    ... smoke, drink, or take drugs, and whether you exercise regularly. Ask about your stress level. Perform prenatal blood tests to do the ... increased risk of health problems during pregnancy? Will stress during pregnancy affect my ... minerals linked to problem with ovulation Release: Elevated blood pressure before pregnancy may increase chance ...

  14. Radionuclides in radiation-induced bystander effect; may it share in radionuclide therapy?

    Science.gov (United States)

    Widel, M

    2017-01-01

    For many years in radiobiology and radiotherapy predominated the conviction that cellular DNA is the main target for ionizing radiation, however, the view has changed in the past 20 years. Nowadays, it is assumed that not only directed (targeted) radiation effect, but also an indirect (non-targeted) effect may contribute to the result of radiation treatment. Non-targeted effect is relatively well recognized after external beam irradiation in vitro and in vivo, and comprises such phenomena like radiation-induced bystander effect (RIBE), genomic instability, adaptive response and abscopal (out of field) effect. These stress-induced and molecular signaling mediated phenomena appear in non-targeted cells as variety responses resembling that observed in directly hit cells. Bystander effects can be both detrimental and beneficial in dependence on dose, dose-rate, cell type, genetic status and experimental condition. Less is known about radionuclide-induced non-targeted effects in radionuclide therapy, although, based on characteristics of the radionuclide radiation, on experiments in vitro utilizing classical and 3-D cell cultures, and preclinical study on animals it seems obvious that exposure to radionuclide is accompanied by various bystander effects, mostly damaging, less often protective. This review summarizes existing data on radionuclide induced bystander effects comprising radionuclides emitting beta- and alpha-particles and Auger electrons used in tumor radiotherapy and diagnostics. So far, separation of the direct effect of radionuclide decay from crossfire and bystander effects in clinical targeted radionuclide therapy is impossible because of the lack of methods to assess whether, and to what extent bystander effect is involved in human organism. Considerations on this topic are also included.

  15. Prenatal nicotine and maternal deprivation stress de-regulate the development of CA1, CA3, and dentate gyrus neurons in hippocampus of infant rats.

    Directory of Open Access Journals (Sweden)

    Hong Wang

    Full Text Available Adverse experiences by the developing fetus and in early childhood are associated with profound effects on learning, emotional behavior, and cognition as a whole. In this study we investigated the effects of prenatal nicotine exposure (NIC, postnatal maternal deprivation (MD or the combination of the two (NIC+MD to determine if hippocampal neuron development is modulated by exposure to drugs of abuse and/or stress. Growth of rat offspring exposed to MD alone or NIC+MD was repressed until after weaning. In CA1 but not CA3 of postnatal day 14 (P14 pups, MD increased pyramidal neurons, however, in dentate gyrus (DG, decreased granule neurons. NIC had no effect on neuron number in CA1, CA3 or DG. Unexpectedly, NIC plus MD combined caused a synergistic increase in the number of CA1 or CA3 neurons. Neuron density in CA regions was unaffected by treatment, but in the DG, granule neurons had a looser packing density after NIC, MD or NIC+MD exposure. When septotemporal axes were analyzed, the synergism of stress and drug exposure in CA1 and CA3 was associated with rostral, whereas MD effects were predominantly associated with caudal neurons. TUNEL labeling suggests no active apoptosis at P14, and doublecortin positive neurons and mossy fibers were diminished in NIC+MD relative to controls. The laterality of the effect of nicotine and/or maternal deprivation in right versus left hippocampus was also analyzed and found to be insiginificant. We report for the first time that early life stressors such as postnatal MD and prenatal NIC exposure, when combined, may exhibit synergistic consequences for CA1 and CA3 pyramidal neuron development, and a potential antagonistic influence on developing DG neurons. These results suggest that early stressors may modulate neurogenesis, apoptosis, or maturation of glutamatergic neurons in the hippocampus in a region-specific manner during critical periods of neurodevelopment.

  16. The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by α-irradiated keratinocytes.

    Science.gov (United States)

    Tian, Wenqian; Yin, Xiaoming; Wang, Longxiao; Wang, Jingdong; Zhu, Wei; Cao, Jianping; Yang, Hongying

    2015-10-01

    Radiation-induced bystander effect (RIBE) is well accepted in the radiation research field by now, but the underlying molecular mechanisms for better understanding this phenomenon caused by intercellular communication and intracellular signal transduction are still incomplete. Although our previous study has demonstrated an important role of miR-21 of unirradiated bystander cells in RIBEs, the direct evidence for the hypothesis that RIBE is epigenetically regulated is still limited and how miR-21 mediates RIBEs is unknown. Reactive oxygen species (ROS) have been demonstrated to be involved in RIBEs, however, the roles of anti-oxidative stress system of cells in RIBEs are unclear. Using transwell insert co-culture system, we investigated medium-mediated bystander responses in WS1 human fibroblasts after co-culture with HaCaT keratinocytes traversed by α-particles. Results showed that the ROS levels in unirradiated bystander WS1 cells were significantly elevated after 30min of co-culture, and 53BP1 foci, a surrogate marker of DNA damage, were obviously induced after 3h of co-culture. This indicates the occurrence of oxidative stress and DNA damage in bystander WS1 cells after co-culture with irradiated keratinocytes. Furthermore, the expression of miR-21 was increased in bystander WS1 cells, downregulation of miR-21 eliminated the bystander responses, overexpression of miR-21 alone could induce bystander-like oxidative stress and DNA damage in WS1 cells. These data indicate an important mediating role of miR-21 in RIBEs. In addition, MnSOD or SOD2 in WS1 cells was involved in the bystander effects, overexpression of SOD2 abolished the bystander oxidative stress and DNA damage, indicating that SOD2 was critical to the induction of RIBEs. Moreover, we found that miR-21 regulated SOD2, suggesting that miR-21 might mediate bystander responses through its regulation on SOD2. In conclusion, this study revealed a profound role of miR-21-regulated SOD2 of unirradiated WS1

  17. Prenatal Care.

    Science.gov (United States)

    Health Resources and Services Administration (DHHS/PHS), Rockville, MD. Office for Maternal and Child Health Services.

    This booklet is the first in a series of publications designed to provide parents with useful information about childrearing. Contents are organized into three parts. Part I focuses on the pregnancy, prenatal care, development of the baby, pregnant lifestyles, nutrition, common discomforts, and problems of pregnancy. Part II provides information…

  18. Bystander Programs: Accommodating or Derailing Sexism?

    Directory of Open Access Journals (Sweden)

    Adam Reid

    2017-09-01

    Full Text Available Bystander programs implemented to meet federal requirements to reduce sexual assaults on college campuses in the United States must include primary prevention. Survey data (n = 280 and interview data (n = 20 presented in this paper explore students’ hypothetical and actual willingness to intervene as bystanders. Although most students surveyed (57% claim they would be very likely to intervene, fewer than half would be very suspicious of someone leading away an intoxicated individual at a party (45% of women and 28% of men: p < 0.01. Interview data reveal how students perceive risk factors at college parties and what types of bystander measures they attempt, including “distractions”, a nonconfrontational tactic in which bystanders avoid more direct but socially risky interventions. Subsumed in many current bystander programs is an invisible element of valorizing harmony. Condoning bystanders’ unwillingness to directly confront seemingly predatory individuals could make change seem out of reach and could also embolden offenders whose behavior is observed and only temporarily thwarted.

  19. The bystander effect of cancer gene therapy

    International Nuclear Information System (INIS)

    Lumniczky, K.; Safrany, G.

    2008-01-01

    Cancer gene therapy is a new, promising therapeutic agent. In the clinic, it should be used in combination with existing modalities, such as tumour irradiation. First, we summarise the most important fields of cancer gene therapy: gene directed enzyme pro-drug therapy; the activation of an anti-tumour immune attack; restoration of the wild type p53 status; the application of new, replication competent and oncolytic viral vectors; tumour specific, as well as radiation- and hypoxia-induced gene expression. Special emphasizes are put on the combined effect of these modalities with local tumour irradiation. Using the available vector systems, only a small portion of the cancer cells will contain the therapeutic genes under therapeutic situations. Bystander cell killing might contribute to the success of various gene therapy protocols. We summarise the evidences that lethal bystander effects may occur during cancer gene therapy. Bystander effects are especially important in the gene directed enzyme pro-drug therapy. There, bystander cell killing might have different routes: cell communication through gap junction intercellular contacts; release of toxic metabolites into the neighbourhood or to larger distances; phagocytosis of apoptotic bodies; and the activation of the immune system. Bystander cell killing can be enhanced by the introduction of gap junction proteins into the cells, by further activating the immune system with immune-stimulatory molecules, or by introducing genes into the cells that help the transfer of cytotoxic genes and / or metabolites into the bystander cells. In conclusion, there should be additional improvements in cancer gene therapy for the more efficient clinical application. (orig.)

  20. Prenatal stress increases the obesogenic effects of a high-fat-sucrose diet in adult rats in a sex-specific manner.

    Science.gov (United States)

    Paternain, L; de la Garza, A L; Batlle, M A; Milagro, F I; Martínez, J A; Campión, J

    2013-03-01

    Stress during pregnancy can induce metabolic disorders in adult offspring. To analyze the possible differential response to a high-fat-sucrose (HFS) diet in offspring affected by prenatal stress (PNS) or not, pregnant Wistar rats (n = 11) were exposed to a chronic mild stress during the third week of gestation. The aim of this study was to model a chronic depressive-like state that develops over time in response to exposure of rats to a series of mild and unpredictable stressors. Control dams (n = 11) remained undisturbed. Adult offspring were fed chow or HFS diet (20% protein, 35% carbohydrate, 45% fat) for 10 weeks. Changes in adiposity, biochemical profile, and retroperitoneal adipose tissue gene expression by real-time polymerase chain reaction were analyzed. An interaction was observed between HFS and PNS concerning visceral adiposity, with higher fat mass in HFS-fed stressed rats, statistically significant only in females. HFS modified lipid profile and increased insulin resistance biomarkers, while PNS reduced insulin concentrations and the homeostasis model assessment index. HFS diet increased gene (mRNA) expression for leptin and apelin and decreased cyclin-dependent kinase inhibitor 1A and fatty acid synthase (Fasn), whereas PNS increased Fasn and stearoyl-CoA desaturase1. An interaction between diet and PNS was observed for adiponutrin (Adpn) and peroxisome proliferator-activated receptor-γ coactivator1-α (Ppargc1a) gene expression: Adpn was increased by the PNS only in HFS-fed rats, whereas Ppargc1a was increased by the PNS only in chow-fed rats. From these results, it can be concluded that experience of maternal stress during intrauterine development can enhance predisposition to obesity induced by a HFS diet intake.

  1. Childhood body mass index at 5.5 years mediates the effect of prenatal maternal stress on daughters' age at menarche: Project Ice Storm.

    Science.gov (United States)

    Duchesne, A; Liu, A; Jones, S L; Laplante, D P; King, S

    2017-04-01

    Early pubertal timing is known to put women at greater risk for adverse physiological and psychological health outcomes. Of the factors that influence girls' pubertal timing, stress experienced during childhood has been found to advance age at menarche (AAM). However, it is not known if stress experienced by mothers during or in the months before conception can be similarly associated with earlier pubertal timing. Prenatal maternal stress (PNMS) is associated with metabolic changes, such as increased childhood adiposity and risk of obesity, that have been associated with earlier menarchal age. Using a prospective longitudinal design, the present study tested whether PNMS induced by a natural disaster is either directly associated with earlier AAM, or whether there is an indirect association mediated through increased girls' body mass index (BMI) during childhood. A total of 31 girls, whose mothers were exposed to the Quebec's January 1998 ice storm during pregnancy were followed from 6 months to 5 1/2 to 5.5 years of age. Mother's stress was measured within 6 months of the storm. BMI was measured at 5.5 years, and AAM was assessed through teen's self-report at 13.5 and 15.5 years of age. Results revealed that greater BMI at 5.5 years mediated the effect of PNMS on decreasing AAM [B=-0.059, 95% confidence intervals (-0.18, -0.0035)]. The present study is the first to demonstrate that maternal experience of stressful conditions during pregnancy reduces AAM in the offspring through its effects on childhood BMI. Future research should consider the impact of AAM on other measures of reproductive ability.

  2. Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

    International Nuclear Information System (INIS)

    Stringari, James; Nunes, Adriana K.C.; Franco, Jeferson L.; Bohrer, Denise; Garcia, Solange C.; Dafre, Alcir L.; Milatovic, Dejan; Souza, Diogo O.; Rocha, Joao B.T.; Aschner, Michael; Farina, Marcelo

    2008-01-01

    During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/l, diluted in drinking water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PND) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F 2 -isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F 2 -isoprostanes levels at all time points. Significant negative correlations were found between F 2 -isoprostanes and GSH, as well as between F 2 -isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral levels of mercury at

  3. Membrane-Dependent Bystander Effect Contributes to Amplification of the Response to Alpha-Particle Irradiation in Targeted and Nontargeted Cells

    International Nuclear Information System (INIS)

    Hanot, Maite; Hoarau, Jim; Carriere, Marie; Angulo, Jaime F.; Khodja, Hicham

    2009-01-01

    Purpose: Free radicals are believed to play an active role in the bystander response. This study investigated their origin as well as their temporal and spatial impacts in the bystander effect. Methods and Materials: We employed a precise alpha-particle microbeam to target a small fraction of subconfluent osteoblastic cells (MC3T3-E1). γH2AX-53BP1 foci, oxidative metabolism changes, and micronuclei induction in targeted and bystander cells were assessed. Results: Cellular membranes and mitochondria were identified as two distinct reactive oxygen species producers. The global oxidative stress observed after irradiation was significantly attenuated after cells were treated with filipin, evidence for the primal role of membrane in the bystander effect. To determine the membrane's impact at a cellular level, micronuclei yield was measured when various fractions of the cell population were individually targeted while the dose per cell remained constant. Induction of micronuclei increased in bystander cells as well as in targeted cells and was attenuated by filipin treatment, demonstrating a role for bystander signals between irradiated cells in an autocrine/paracrine manner. Conclusions: A complex interaction of direct irradiation and bystander signals leads to a membrane-dependent amplification of cell responses that could influence therapeutic outcomes in tissues exposed to low doses or to environmental exposure.

  4. Rethinking the bystander role in school violence prevention.

    Science.gov (United States)

    Stueve, Ann; Dash, Kimberly; O'Donnell, Lydia; Tehranifar, Parisa; Wilson-Simmons, Renée; Slaby, Ronald G; Link, Bruce G

    2006-01-01

    Public concerns about school shootings and safety draw attention to the role bystanders can play in preventing school violence. Although school violence prevention plans are often required, there is little guidance about whether these should address the roles of bystanders and what actions bystanders should take in different circumstances, from more common instances of bullying and fighting to rare, but potentially lethal, threats and use of weapons. Literature pertaining to bystanders is reviewed and applied to the school setting. The definition of bystander is expanded, including parents, teachers, and other school staff as well as youths and those who have information about potential violence as well as those who witness its occurrence. Barriers preventing bystanders from taking positive actions are discussed. The authors call on health promotion researchers and practitioners to work with school communities to identify norms, attitudes, and outcome expectancies that shape bystander behaviors to inform prevention efforts.

  5. A correlation of long term effects and radiation quality in the progeny of bystander cells after microbeam radiations: The experimental study of radiotherapy for cancer risk mitigation

    Science.gov (United States)

    Autsavapromporn, N.; Konishi, T.; Liu, C.; Plante, I.; Funayama, T.; Usami, N.; Azzam, EI; Suzuki, M.

    2017-06-01

    The goal of this study is to investigate the role of radiation quality and gap junction intercellular communication (GJIC) in the propagation of delayed stressful effects in the progeny of bystander human skin fibroblasts cultures (NB1RGB). Briefly, confluent NB1RGB cells in the presence and absence of gap junction inhibitor (AGA) were exposed to ionizing radiation (IR) with a different linear energy transfer (LET) either 5.35 keV X rays (LET ∼6 keV/μm) or 18.3 MeV/u carbon (LET ∼103 keV/μm) microbeam radiations. Following 20 populations post-irradiation, the progeny of bystander NB1RGB cells were harvested and assayed for several of biological endpoints. Our results showed that expression of stressful effects in the progeny of bystander cells is dependent on LET. The progeny of bystander cells exposed to low-LET X rays showed the persistence of oxidative stress and it was correlated with the increased mutant fraction. Such effect were not observed after high-LET carbon ions. Interestingly, inhibition of GJIC mitigated the toxic effects in the progeny of bystander cells. Together, the results contribute to the understanding of the fundamental radiation biology relating to the high-LET carbon ions to mitigate cancer risk after radiotherapy. Furthermore, GJIC be considered as a critical mediator in the bystander mutagenic effect.

  6. Antecedents of maternal parenting stress: the role of attachment style, prenatal attachment, and dyadic adjustment in first-time mothers

    OpenAIRE

    Mazzeschi, Claudia; Pazzagli, Chiara; Radi, Giulia; Raspa, Veronica; Buratta, Livia

    2015-01-01

    The transition to parenthood is widely considered a period of increased vulnerability often accompanied by stress. Abidin conceived parenting stress as referring to specific difficulties in adjusting to the parenting role. Most studies of psychological distress arising from the demands of parenting have investigated the impact of stress on the development of dysfunctional parent-child relationships and on adult and child psychopathology. Studies have largely focused on mothers’ postnatal expe...

  7. Effect of fish oil and coconut fat supplementation on depressive-type behavior and corticosterone levels of prenatally stressed male rats.

    Science.gov (United States)

    Borsonelo, Elizabethe Cristina; Suchecki, Deborah; Galduróz, José Carlos Fernandes

    2011-04-18

    Prenatal stress (PNS) during critical periods of brain development has been associated with numerous behavioral and/or mood disorders in later life. These outcomes may result from changes in the hypothalamic-pituitary-adrenal (HPA) axis activity, which, in turn, can be modulated by environmental factors, such as nutritional status. In this study, the adult male offspring of dams exposed to restraint stress during the last semester of pregnancy and fed different diets were evaluated for depressive-like behavior in the forced swimming test and for the corticosterone response to the test. Female Wistar rats were allocated to one of three groups: regular diet, diet supplemented with coconut fat or with fish oil, offered during pregnancy and lactation. When pregnancy was confirmed, they were distributed into control or stress groups. Stress consisted of restraint and bright light for 45 min, three times per day, in the last week of pregnancy. The body weight of the adult offspring submitted to PNS was lower than that of controls. In the forced swimming test, time of immobility was reduced and swimming was increased in PNS rats fed fish oil and plasma corticosterone levels immediately after the forced swimming test were lower in PNS rats fed regular diet than their control counterparts; this response was reduced in control rats whose mothers were fed fish oil and coconut fat. The present results indicate that coconut fat and fish oil influenced behavioral and hormonal responses to the forced swimming test in both control and PNS adult male rats. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Bystander effects of ionizing radiation can be modulated by signaling amines

    International Nuclear Information System (INIS)

    Poon, R.C.C.; Agnihotri, N.; Seymour, C.; Mothersill, C.

    2007-01-01

    Actual risk and risk management of exposure to ionizing radiation are among the most controversial areas in environmental health protection. Recent developments in radiobiology especially characterization of bystander effects have called into question established dogmas and are thought to cast doubt on the scientific basis of the risk assessment framework, leading to uncertainty for regulators and concern among affected populations. In this paper we test the hypothesis that small signaling molecules widely used throughout the animal kingdom for signaling stress or environmental change, such as 5-Hydroxytryptamine (5-HT, serotonin), L-DOPA, glycine or nicotine are involved in bystander signaling processes following ionizing radiation exposure. We report data which suggest that nano to micromolar concentrations of these agents can modulate bystander-induced cell death. Depletion of 5-HT present in tissue culture medium, occurred following irradiation of cells. This suggested that 5-HT might be bound by membrane receptors after irradiation. Expression of 5-HT type 3 receptors which are Ca 2+ ion channels was confirmed in the cells using immunocytochemistry and receptor expression could be increased using radiation or 5-HT exposure. Zofran and Kitryl, inhibitors of 5-HT type 3 receptors, and reserpine a generic serotonin antagonist block the bystander effect induced by radiation or by serotonin. The results may be important for the mechanistic understanding of how low doses of radiation interact with cells to produce biological effects

  9. Signaling pathways underpinning the manifestations of ionizing radiation-induced bystander effects.

    Science.gov (United States)

    Hamada, Nobuyuki; Maeda, Munetoshi; Otsuka, Kensuke; Tomita, Masanori

    2011-06-01

    For nearly a century, ionizing radiation has been indispensable to medical diagnosis. Furthermore, various types of electromagnetic and particulate radiation have also been used in cancer therapy. However, the biological mechanism of radiation action remains incompletely understood. In this regard, a rapidly growing body of experimental evidence indicates that radiation exposure induces biological effects in cells whose nucleus has not been irradiated. This phenomenon termed the 'non-targeted effects' challenges the long-held tenet that radiation traversal through the cell nucleus is a prerequisite to elicit genetic damage and biological responses. The non-targeted effects include biological effects in cytoplasm-irradiated cells, bystander effects that arise in non-irradiated cells having received signals from irradiated cells, and genomic instability occurring in the progeny of irradiated cells. Such non-targeted responses are interrelated, and the bystander effect is further related with an adaptive response that manifests itself as the attenuated stressful biological effects of acute high-dose irradiation in cells that have been pre-exposed to low-dose or low-dose-rate radiation. This paper reviews the current body of knowledge about the bystander effect with emphasis on experimental approaches, in vitro and in vivo manifestations, radiation quality dependence, temporal and spatial dependence, proposed mechanisms, and clinical implications. Relations of bystander responses with the effects in cytoplasm-irradiated cells, genomic instability and adaptive response will also be briefly discussed.

  10. The Beneficial Impact of Antidepressant Drugs on Prenatal Stress-Evoked Malfunction of the Insulin-Like Growth Factor-1 (IGF-1) Protein Family in the Olfactory Bulbs of Adult Rats.

    Science.gov (United States)

    Trojan, Ewa; Głombik, Katarzyna; Ślusarczyk, Joanna; Budziszewska, Bogusława; Kubera, Marta; Roman, Adam; Lasoń, Władysław; Basta-Kaim, Agnieszka

    2016-02-01

    Insulin-like growth factor-1 (IGF-1) promotes the growth, differentiation, and survival of both neurons and glial cells, and it is believed to exert antidepressant-like activity. Thus, disturbances in the IGF-1 system could be responsible for the course of depression. To date, there have been no papers showing the impact of chronic antidepressant treatment on the IGF-1 network in the olfactory bulb (OB) in an animal model of depression. Prenatal stress was used as model of depression. Twenty-four 3-month-old male offspring of control and stressed mothers were subjected to behavioral testing (forced swim test). The mRNA expression of IGF-1 and IGF-1 receptor (IGF-1R) and the protein level of IGF-1 and its phosphorylation, as well as the concentrations of IGF-binding proteins (IGFBP-2, -4, -3, and -6), were measured in OBs before and after chronic imipramine, fluoxetine, or tianeptine administration. Adult rats exposed prenatally to stressful stimuli displayed not only depression-like behavior but also decreased IGF-1 expression, dysregulation in the IGFBP network, and diminished mRNA expression, as well as IGF-1R phosphorylation, in the OB. The administration of antidepressants normalized most of the changes in the IGF-1 system of the OB evoked by prenatal stress. These results suggested a beneficial effect of chronic antidepressant drug treatment in the alleviation of IGF-1 family malfunction in OBs in an animal model of depression.

  11. The Effect of Parenting Stress on Child Behavior Problems in High-Risk Children with Prenatal Drug Exposure

    Science.gov (United States)

    Bagner, Daniel M.; Sheinkopf, Stephen J.; Miller-Loncar, Cynthia; LaGasse, Linda L.; Lester, Barry M.; Liu, Jing; Bauer, Charles R.; Shankaran, Seetha; Bada, Henrietta; Das, Abhik

    2009-01-01

    Objective: To examine the relationship between early parenting stress and later child behavior in a high-risk sample and measure the effect of drug exposure on the relationship between parenting stress and child behavior. Methods: A subset of child-caregiver dyads (n = 607) were selected from the Maternal Lifestyle Study (MLS), which is a large…

  12. Bystanders not so innocent after all.

    Science.gov (United States)

    Batten, Marcel; Ghilardi, Nico

    2012-06-29

    Interleukin 27 (IL-27) regulates immune responses, including T helper 17 (Th17) cell activity. In this issue of Immunity, Hirahara et al. (2012) demonstrate that IL-27 suppresses Th17 cells in trans through induction of the inhibitory ligand PD-L1 on bystander T cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Discrimination and Acculturation Stress: A Longitudinal Study of Children’s Well-Being from Prenatal Development to 5 Years of Age

    Science.gov (United States)

    Zeiders, Katharine H.; Umaña-Taylor, Adriana J.; Jahromi, Laudan B.; Updegraff, Kimberly A.; White, Rebecca M. B.

    2016-01-01

    Objective To examine whether cumulative family discrimination and acculturation stress (prenatally to 24-months postpartum) among Mexican-origin adolescent mothers and their mother-figures predicted children’s socio-emotional functioning and academic achievement at 5 years of age, and the role of maternal depressive symptoms and mother-child interactions in the association. Methods Mexican-origin families (N = 204) with an adolescent mother, a child, and a mother-figure participated in a 6-wave longitudinal study (2007 to 2013). Families were recruited and interviewed during the adolescent mothers’ pregnancy; adolescent mothers, mother-figures, and children were then assessed annually for the next 5 years using a combination of interview-based survey and observational methods. Maternal reports of children’s socio-emotional behaviors (measured using the Child Behavior Checklist) and children’s academic achievement (assessed with the Woodcock Johnson III Tests of Achievement/Bateria III Woodcock-Muñoz) were used. Results Structural equation modeling revealed that greater cumulative family discrimination and acculturation stress from pregnancy to 24-months postpartum predicted higher adolescent mothers’ depressive symptoms, greater mother-child intrusive interactions, and less mother sensitivity at 36-months postpartum. Maternal depressive symptoms were positively related to children’s CBCL symptoms at 60-months postpartum. Greater cumulative discrimination and acculturation stressors directly predicted children’s lower Woodcock Johnson/Bateria test scores, after accounting for socio-economic status. Conclusions Mexican-origin adolescent mothers’ and mother figures’ cumulative discrimination and acculturation stress from pregnancy through children’s second birthday predicted children’s socio-emotional and academic achievement at age 5. Overall, the findings underscore the cumulative impact of these stressors on well-being in a population with

  14. Proteomic analysis of adrenocorticotropic hormone treatment of an infantile spasm model induced by N-methyl-D-aspartic acid and prenatal stress.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available Infantile spasms is an age-specific epileptic syndrome associated with poor developmental outcomes and poor response to nearly all traditional antiepileptic drugs except adrenocorticotropic hormone (ACTH. We investigated the protective mechanism of ACTH against brain damage. An infantile spasm rat model induced by N-methyl-D-aspartate (NMDA in neonate rats was used. Pregnant rats were randomly divided into the stress-exposed and the non-stress exposed groups, and their offspring were randomly divided into ACTH-treated spasm model, untreated spasm model, and control groups. A proteomics-based approach was used to detect the proteome differences between ACTH-treated and untreated groups. Gel image analysis was followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric protein identification and bioinformatics analysis. Prenatal stress exposure resulted in more severe seizures, and ACTH treatment reduced and delayed the onset of seizures. The most significantly up-regulated proteins included isoform 1 of tubulin β-5 chain, cofilin-1 (CFL1, synaptosomal-associated protein 25, malate dehydrogenase, N(G,N(G-dimethylarginine dimethylaminohydrolase 1, annexin A3 (ANXA3, and rho GDP-dissociation inhibitor 1 (ARHGDIA. In contrast, tubulin α-1A chain was down-regulated. Three of the identified proteins, ARHGDIA, ANXA3, and CFL1, were validated using western blot analysis. ARHGDIA expression was assayed in the brain samples of five infantile spasm patients. These proteins are involved in the cytoskeleton, synapses, energy metabolism, vascular regulation, signal transduction, and acetylation. The mechanism underlying the effects of ACTH involves the molecular events affected by these proteins, and protein acetylation is the mechanism of action of the drug treatment.

  15. Prenatal chronic mild stress induces depression-like behavior and sex-specific changes in regional glutamate receptor expression patterns in adult rats.

    Science.gov (United States)

    Wang, Y; Ma, Y; Hu, J; Cheng, W; Jiang, H; Zhang, X; Li, M; Ren, J; Li, X

    2015-08-20

    Chronic stress during critical periods of human fetal brain development is associated with cognitive, behavioral, and mood disorders in later life. Altered glutamate receptor (GluR) expression has been implicated in the pathogenesis of stress-dependent disorders. To test whether prenatal chronic mild stress (PCMS) enhances offspring's vulnerability to stress-induced behavioral and neurobiological abnormalities and if this enhanced vulnerability is sex-dependent, we measured depression-like behavior in the forced swimming test (FST) and regional changes in GluR subunit expression in PCMS-exposed adult male and female rats. Both male and female PCMS-exposed rats exhibited stronger depression-like behavior than controls. Males and females exhibited unique regional changes in GluR expression in response to PCMS alone, FST alone (CON-FST), and PCMS with FST (PCMS-FST). In females, PCMS alone did not alter N-methyl-d-aspartate receptor (NMDAR) or metabotropic glutamate receptor (mGluR) expression, while in PCMS males, higher mGluR2/3, mGluR5, and NR1 expression levels were observed in the prefrontal cortex. In addition, PCMS altered the change in GluR expression induced by acute stress (the FST test), and this too was sex-specific. Male PCMS-FST rats expressed significantly lower mGluR5 levels in the hippocampus, lower mGluR5, NR1, postsynaptic density protein (PSD)95, and higher mGluR2/3 in the prefrontal cortex, and higher mGluR5 and PSD95 in the amygdala than male CON-FST rats. Female PCMS-FST rats expressed lower NR1 in the hippocampus, lower NR2B and PSD95 in the prefrontal cortex, lower mGluR2/3 in the amygdala, and higher PSD95 in the amygdala than female CON-FST rats. PCMS may increase the offspring's vulnerability to depression by altering sex-specific stress-induced changes in glutamatergic signaling. Copyright © 2015. Published by Elsevier Ltd.

  16. Sex-Dependent Effects of Prenatal Stress on Social Memory in Rats: A Role for Differential Expression of Central Vasopressin-1a Receptors.

    Science.gov (United States)

    Grundwald, N J; Benítez, D P; Brunton, P J

    2016-04-01

    Prenatal stress (PNS) affects a number of traits in the offspring, including stress axis regulation, emotionality and cognition; however, much less is known about the effects of PNS on social memory and the underlying central mechanisms. In the present study, we investigated social preference, social memory under basal and stress conditions and olfactory memory for social and nonsocial odours in the adult offspring of dams exposed to social stress during late pregnancy. Given the key roles that the central oxytocin and vasopressin systems play in facilitating social memory, we further investigated the effects of PNS on the central expression of mRNA for oxytocin (Oxtr) and vasopressin-1a (Avpr1a) receptors. PNS did not affect social preference in either sex; however, social memory was impaired under basal conditions in PNS females but not PNS males. Accordingly, Avpr1a mRNA expression in the lateral septum and bed nucleus of stria terminalis (BNST) was unaltered in males but was significantly lower in PNS females compared to controls. No differences in Oxtr mRNA expression were detected between control and PNS offspring in either sex in any of the brain regions examined. Social memory deficits in PNS females persisted when social odours were used; however, this does not appear to be a result of impaired olfaction because memory for nonsocial odours was similar in control and PNS females. Under acute stress conditions, deficits in social memory were observed in both male and female control offspring; however, PNS males were unaffected. Moreover, acute stress facilitated social memory in PNS females and this was associated with an up-regulation of Avpr1a mRNA in the lateral septum and BNST. Our data support a role for altered signalling via central Avpr1a in PNS-induced sex-dependent changes in social memory and may have implications for understanding the aetiology of neurodevelopmental disorders characterised by social behaviour deficits in humans. © 2015 The

  17. Long-term effects of prenatal atrazine exposure on physiology, body composition, and stress reactivity in rats

    Science.gov (United States)

    Low birth weight in humans is associated with increased risk of coronary heart disease, hypertension, and diabetes in adulthood. Experimental studies have also reported that undernutrition, stress or exposure to glucocorticoids during pregnancy is associated with hypertension, gl...

  18. Prenatal Maternal Stress and Physical Abuse among Homeless Women and Infant Health Outcomes in the United States

    OpenAIRE

    Merrill, Ray M.; Richards, Rickelle; Sloan, Arielle

    2011-01-01

    Background. This study examines whether the relationship between maternal stress or abuse situations and infant birth weight differs between homeless and non-homeless women. Methods. Analyses are based on data from the Pregnancy Risk Assessment Monitoring System (PRAMS), 2002–2007. Results. Homeless women were significantly more likely to experience stressful life events, abusive situations, and poor maternal health than non-homeless women during pregnancy. Birth weight among infant...

  19. Maternal prenatal stress and child atopic dermatitis up to age 2 years: The Ulm SPATZ health study.

    Science.gov (United States)

    Braig, Stefanie; Weiss, Johannes M; Stalder, Tobias; Kirschbaum, Clemens; Rothenbacher, Dietrich; Genuneit, Jon

    2017-03-01

    Evidence linking maternal psychosocial stress during pregnancy to subsequent child atopic dermatitis (AD) is growing, but the definition of AD is diverse and results are inconsistent. We aimed to analyze the relationship between stress and AD using alternative measurements of stress and AD. In the Ulm SPATZ Health Study, chronic stress and symptoms of anxiety and depression were assessed by standardized self-reported questionnaires in 934 mothers of singletons following delivery in Ulm, Germany, from 04/2012-05/2013. Maternal hair cortisol concentrations (HCCs, n = 626) at childbirth and the cumulative incidences of parent-reported child AD symptoms, parent-, and pediatrician-reported AD diagnoses were assessed until age 2 years (n = 787). Overall, 205 dermatologic examinations were performed in 167 children showing AD symptoms. Crude and adjusted risk ratios (RR, aRR) with 95% confidence intervals were estimated. Maternal stress and anxiety were associated with child AD symptoms by trend (RR and aRR: 1.5 (1.0,2.3) for the highest vs. the lowest quarter of chronic stress; aRR: 1.4 (1.0,2.0) for possible anxiety symptoms vs. no symptoms). No relationship was found between stress or related constructs and AD diagnoses nor could we show consistent associations between maternal HCC and child AD. However, a higher RR of child AD was evident in families not yet affected by AD in siblings given maternal depressive symptoms, examined in the crude model. Stress measurements or related constructs are linked to AD symptoms, but association with AD diagnoses is limited. The reason for this divergence still needs further research. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Reciprocal bystander effect between α-irradiated macrophage and hepatocyte is mediated by cAMP through a membrane signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    He, Mingyuan [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Department of Radiation Oncology, China–Japan Union Hospital of Jilin University, Changchun 130033 (China); Dong, Chen; Xie, Yuexia; Li, Jitao; Yuan, Dexiao; Bai, Yang [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)

    2014-05-15

    Highlights: • α-Irradiation induced reciprocal effects between macrophage and hepatocyte cells. • cAMP played a protective role in regulating the reverse bystander effect. • cAMP communication contributed to the reciprocal effects via membrane signaling. • p53 was required for cAMP-regulated bystander effect in the recipient cells. - Abstract: Irradiated cells can induce biological effects on vicinal non-irradiated bystander cells, meanwhile the bystander cells may rescue the irradiated cells through a feedback signal stress. To elucidate the nature of this reciprocal effect, we examined the interaction between α-irradiated human macrophage cells U937 and its bystander HL-7702 hepatocyte cells using a cell co-culture system. Results showed that after 6 h of cell co-culture, mitochondria depolarization corresponding to apoptosis was significantly induced in the HL-7702 cells, but the formation of micronuclei in the irradiated U937 cells was markedly decreased compared to that without cell co-culture treatment. This reciprocal effect was not observed when the cell membrane signaling pathway was blocked by filipin that inhibited cAMP transmission from bystander cells to irradiated cells. After treatment of cells with exogenous cAMP, forskolin (an activator of cAMP) or KH-7 (an inhibitor of cAMP), respectively, it was confirmed that cAMP communication from bystander cells to targeted cells could mitigate radiation damage in U739 cells, and this cAMP insufficiency in the bystander cells contributed to the enhancement of bystander apoptosis. Moreover, the bystander apoptosis in HL-7702 cells was aggravated by cAMP inhibition but it could not be evoked when p53 of HL-7702 cells was knocked down no matter of forskolin and KH-7 treatment. In conclusion, this study disclosed that cAMP could be released from bystander HL-7702 cells and compensated to α-irradiated U937 cells through a membrane signaling pathway and this cAMP communication played a profound role in

  1. Reciprocal bystander effect between α-irradiated macrophage and hepatocyte is mediated by cAMP through a membrane signaling pathway

    International Nuclear Information System (INIS)

    He, Mingyuan; Dong, Chen; Xie, Yuexia; Li, Jitao; Yuan, Dexiao; Bai, Yang; Shao, Chunlin

    2014-01-01

    Highlights: • α-Irradiation induced reciprocal effects between macrophage and hepatocyte cells. • cAMP played a protective role in regulating the reverse bystander effect. • cAMP communication contributed to the reciprocal effects via membrane signaling. • p53 was required for cAMP-regulated bystander effect in the recipient cells. - Abstract: Irradiated cells can induce biological effects on vicinal non-irradiated bystander cells, meanwhile the bystander cells may rescue the irradiated cells through a feedback signal stress. To elucidate the nature of this reciprocal effect, we examined the interaction between α-irradiated human macrophage cells U937 and its bystander HL-7702 hepatocyte cells using a cell co-culture system. Results showed that after 6 h of cell co-culture, mitochondria depolarization corresponding to apoptosis was significantly induced in the HL-7702 cells, but the formation of micronuclei in the irradiated U937 cells was markedly decreased compared to that without cell co-culture treatment. This reciprocal effect was not observed when the cell membrane signaling pathway was blocked by filipin that inhibited cAMP transmission from bystander cells to irradiated cells. After treatment of cells with exogenous cAMP, forskolin (an activator of cAMP) or KH-7 (an inhibitor of cAMP), respectively, it was confirmed that cAMP communication from bystander cells to targeted cells could mitigate radiation damage in U739 cells, and this cAMP insufficiency in the bystander cells contributed to the enhancement of bystander apoptosis. Moreover, the bystander apoptosis in HL-7702 cells was aggravated by cAMP inhibition but it could not be evoked when p53 of HL-7702 cells was knocked down no matter of forskolin and KH-7 treatment. In conclusion, this study disclosed that cAMP could be released from bystander HL-7702 cells and compensated to α-irradiated U937 cells through a membrane signaling pathway and this cAMP communication played a profound role in

  2. Epigenetic Analysis of Heavy-ion Radiation Induced Bystander Effects in Mice

    Science.gov (United States)

    Zhang, Meng; Sun, Yeqing; Cui, Changna; Xue, Bei

    Abstract: Radiation-induced bystander effect was defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic and proteomics plays significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were exposed head-only to 40, 200, 2000mGy dose of (12) C heavy-ion radiation, while the rest of the animal body was shielded. Directly radiation organ ear and the distant organ liver were detected on 1h, 6h, 12h and 24h after radiation, respectively. Methylation-sensitive amplification polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that heavy-ion irradiated mouse head could induce genomic DNA methylation changes significantly in both the directly radiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate was highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation. The global DNA methylation changes tended to occur in the CG sites. The results illustrated that genomic methylation changes of heavy ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of

  3. Negotiating the transition from adolescence to motherhood: Coping with prenatal and parenting stress in teenage mothers in Mulago hospital, Uganda

    Directory of Open Access Journals (Sweden)

    Kaye Dan K

    2008-03-01

    Full Text Available Abstract Background Adolescence is a transitional stage from childhood to adulthood that is characterized by physical, physiological, psychosocial and behavioral changes that are influenced to a large extent by the age, culture and socialization of the individual. To explore what adolescent mothers perceive as their struggles during the period of transition from childhood to parenthood (through motherhood and to describe strategies employed in coping with stress of pregnancy, motherhood and parenthood. Methods Longitudinal qualitative study involving twenty two in-depth interviews and six focus group discussions among pregnant adolescents who were followed from pregnant to delivery, from January 2004 to August 2005. Participant were selected by theoretical sampling and data was analyzed using grounded theory. Results Overall, young adolescents reported more anxiety, loss of self esteem (when they conceived, difficulty in accessing financial, moral and material support from parents or partners and stigmatization by health workers when they sought care from health facilities. Three strategies by which adolescent mothers cope with parenting and pregnancy stress that were described as utilizing opportunities (thriving, accommodating the challenges (bargaining and surviving, or failure (despairing, and varied in the extent to which they enabled adolescents to cope with the stress. Conclusion Adolescents on the transition to motherhood have variable needs and aspirations and utilize different strategies to cope with the stress of pregnancy and parenthood.

  4. Cardio-metabolic risk in 5-year-old children prenatally exposed to maternal psychosocial stress: the ABCD study

    NARCIS (Netherlands)

    van Dijk, Aimée E.; van Eijsden, Manon; Stronks, Karien; Gemke, Reinoud J. B. J.; Vrijkotte, Tanja G. M.

    2010-01-01

    Recent evidence, both animal and human, suggests that modifiable factors during fetal and infant development predispose for cardiovascular disease in adult life and that they may become possible future targets for prevention. One of these factors is maternal psychosocial stress, but so far, few

  5. A Socioecological Predication Model of Posttraumatic Stress Disorder in Low-Income, High-Risk Prenatal Native Hawaiian/Pacific Islander Women.

    Science.gov (United States)

    Dodgson, Joan E; Oneha, Mary Frances; Choi, Myunghan

    2014-01-01

    Only recently has perinatal posttraumatic stress disorder (PTSD) been researched in any depth; however, the causes and consequences of this serious illness remain unclear. Most commonly, childbirth trauma and interpersonal violence have been reported as contributing factors. However, not all Native Hawaiian/Pacific Islander (NHPI) women who experience these events experience PTSD. The factors affecting PTSD are many and complex, intertwining individual, family, and community contexts. Using a socioecological framework, 3 levels of contextual variables were incorporated in this study (individual, family, and social/community). The purpose of this study was to determine the socioecological predictors associated with prenatal PTSD among NHPI. A case-control design was used to collect retrospective data about socioecological variables from medical record data. The sample was low-income, high-risk NHPI women receiving perinatal health care at a rural community health center in Hawaii who screened positive (n = 55) or negative (n = 91) for PTSD. Hierarchical logistic regression was conducted to determine socioecological predictors of positive PTSD screening. Although the majority of women (66.4%) experienced some form of interpersonal violence, a constellation of significant predictor variables from all 3 levels of the model were identified: depression (individual level), lack of family support and family stress (family level), and violence (social/community level). Each of the predictor variables has been identified by other researchers as significantly affecting perinatal PTSD. However, it is because these variables occur together that a more complex picture emerges, suggesting the importance of considering multiple variables in context when identifying and caring for these women. Although additional research is needed, it is possible that the significant predictor variables could be useful in identifying women who are at higher risk for PTSD in other similar

  6. Prenatal Exposure to Maternal Depression and Cortisol Influences Infant Temperament

    Science.gov (United States)

    Davis, Elysia Poggi; Glynn, Laura M.; Schetter, Christine Dunkel; Hobel, Calvin; Chicz-Demet, Aleksandra; Sandman, Curt A.

    2007-01-01

    Background: Accumulating evidence indicates that prenatal maternal and fetal processes can have a lasting influence on infant and child development. Results from animal models indicate that prenatal exposure to maternal stress and stress hormones has lasting consequences for development of the offspring. Few prospective studies of human pregnancy…

  7. Control Prenatal

    Directory of Open Access Journals (Sweden)

    P. Susana Aguilera, DRA.

    2014-11-01

    Full Text Available Los principales objetivos del control prenatal son identificar aquellos pacientes de mayor riesgo, con el fin de realizar intervenciones en forma oportuna que permitan prevenir dichos riesgos y así lograr un buen resultado perinatal. Esto se realiza a través de la historia médica y reproductiva de la mujer, el examen físico, la realización de algunos exámenes de laboratorio y exámenes de ultrasonido. Además es importante promover estilos de vida saludables, la suplementación de ácido fólico, una consejería nutricional y educación al respecto.

  8. Bystander Tactics: Life on Turf in Karachi

    Directory of Open Access Journals (Sweden)

    Tania Ahmad

    2012-03-01

    Full Text Available This article posits an analytic of the bystander, as a supplement to studies of perpetrators and victims, in relation to political affiliation, mobilization and violence in Karachi. In particular, I use ethnographic findings to elucidate the tactics of anticipation used by Karachi residents of neighborhoods widely considered the turf of the Muttahida Qaumi Movement (MQM. The examples of students’ and teachers’ reactions to a college rumble between rival groups, parents’ attempts to keep their sons from being recruited into party politics, and young people confident in their ability to navigate an economy of affiliation demonstrate a range of bystander tactics, in which subjection and subversion are aligned. Although metanarratives of democratization frequently elide the everyday activity of standing by, it constitutes a pervasive mode of participation in Karachi’s political landscape.

  9. Neutron induced bystander effect among zebrafish embryos

    Science.gov (United States)

    Ng, C. Y. P.; Kong, E. Y.; Kobayashi, A.; Suya, N.; Uchihori, Y.; Cheng, S. H.; Konishi, T.; Yu, K. N.

    2015-12-01

    The present paper reported the first-ever observation of neutron induced bystander effect (NIBE) using zebrafish (Danio rerio) embryos as the in vivo model. The neutron exposure in the present work was provided by the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. Two different strategies were employed to induce NIBE, namely, through directly partnering and through medium transfer. Both results agreed with a neutron-dose window (20-50 mGy) which could induce NIBE. The lower dose limit corresponded to the threshold amount of neutron-induced damages to trigger significant bystander signals, while the upper limit corresponded to the onset of gamma-ray hormesis which could mitigate the neutron-induced damages and thereby suppress the bystander signals. Failures to observe NIBE in previous studies were due to using neutron doses outside the dose-window. Strategies to enhance the chance of observing NIBE included (1) use of a mono-energetic high-energy (e.g., between 100 keV and 2 MeV) neutron source, and (2) use of a neutron source with a small gamma-ray contamination. It appeared that the NASBEE facility used in the present study fulfilled both conditions, and was thus ideal for triggering NIBE.

  10. Impact of Prenatal Cognitive-Behavioral Stress Management Intervention on Maternal Anxiety and Depression and Newborns’ Apgar Scores

    Directory of Open Access Journals (Sweden)

    Mahsa Karamoozian

    2015-06-01

    Full Text Available Background: Motherhood is a transformative and pleasing experience in a woman’s life. However, given the physical and psychological changes, it can induce a degree of stress and anxiety in mothers. The aim of the present study was to evaluate the effects of cognitive-behavioral stress management (CBSM on maternal anxiety and depression during pregnancy and newborns’ Apgar scores. Methods: This semi-experimental study was performed by applying a pretest-posttest control-group design. Overall, 30 primiparous mothers were selected among women referring to health clinics of Kerman, Iran, using convenience sampling. Subjects were randomly allocated to experimental and control groups. Data were collected, using Pregnancy-Related Anxiety Questionnaire and Edinburgh Postnatal Depression Questionnaire. After completing the pretest, the experimental group was subjected to 12 sessions of CBSM training; posttest data were collected after the intervention. Multivariate analysis of covariance was performed, using SPSS version 16. P-value < 0.05 was considered statistically significant. Results: The obtained results revealed a significant decrement in the average posttest scores of anxiety and depression in the experimental group, compared to pretest scores and the control group. Moreover, differences in 1- and 5-minute Apgar scores between the two groups were statistically significant. These findings indicated the effectiveness of CBSM during pregnancy in reducing maternal anxiety and depression. Conclusion: Pregnant women can benefit from psychological interventions such as CBSM in medical and health care centers.

  11. Bystander-witnessed cardiac arrest is associated with reported agonal breathing and leads to less frequent bystander CPR.

    Science.gov (United States)

    Brinkrolf, P; Metelmann, B; Scharte, C; Zarbock, A; Hahnenkamp, K; Bohn, A

    2018-04-18

    Although the importance of bystander cardiopulmonary resuscitation has been shown in multiple studies, the rate of bystander cardiopulmonary resuscitation is still relatively low in many countries. Little is known on bystanders' perceptions influencing the decision to start cardiopulmonary resuscitation. Our study aims to determine such factors. Semi-structured telephone interviews with bystanders of out-of-hospital cardiac arrests between December 2014 and April 2016 were performed in a prospective manner. This single-center survey was conducted in the city of Münster, Germany. The bystander's sex and age, the perception of the victim's breathing and initial condition were correlated with the share of bystander cardiopulmonary resuscitation in the corresponding group. 101 telephone interviews were performed with 57 male and 44 female participants showing a mean age of 52.7 (SD ± 16.3). In case of apnoea 38 out of 46 bystanders (82.6%) started cardiopulmonary resuscitation; while in case of descriptions indicating agonal breathing 19 out of 35 bystanders (54.3%) started cardiopulmonary resuscitation (p = .007). If the patient was found unconscious 47 out of 63 bystanders (74.7%) performed cardiopulmonary resuscitation, while in cases of witnessed cardiac arrest 19 out of 38 bystanders (50%) attempted cardiopulmonary resuscitation (p = .012). Witnessed change of consciousness is an independent factor significantly lowering the probability of starting cardiopulmonary resuscitation (regression coefficient -1.489, p bystander-CPR was started. These data reinforce the importance of teaching the recognition of early cardiac arrest. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Measuring Bystander Attitudes and Behavior to Prevent Sexual Violence

    Science.gov (United States)

    McMahon, Sarah; Allen, Christopher T.; Postmus, Judy L.; McMahon, Sheila M.; Peterson, N. Andrew; Lowe Hoffman, Melanie

    2014-01-01

    Objective: The purpose of this study is to further investigate the factor structure and strength of the Bystander Attitude Scale-Revised and Bystander Behavior Scale-Revised (BAS-R and BBS-R). Participants: First-year students (N = 4,054) at a large public university in the Northeast completed a survey in 2010 as part of a larger longitudinal…

  13. Lipids, atherosclerosis and CVD risk: is CRP an innocent bystander?

    DEFF Research Database (Denmark)

    Nordestgaard, B G; Zacho, J

    2009-01-01

    AIM: To evaluate recent human studies with respect to the interpretation of whether elevated plasma levels of C-reactive protein (CRP) cause cardiovascular disease (CVD), or whether elevated CRP levels more likely is an innocent bystander. DATA SYNTHESIS: Elevated CRP concentrations...... and vulnerability of atherosclerotic plaques, and thus simply an innocent bystander in CVD....

  14. The Bystander in Commercial Life : Obliged by Beneficence or Rescue

    NARCIS (Netherlands)

    Dubbink, Wim

    2016-01-01

    Liberalist thinking argues that moral agents have a right (or duty) to pursue an ordinary life. It also insists that moral agent can be bystanders. A bystander is involved with morally bad states of affairs in the sense that they are bound by moral duty, but for a non-blameworthy reason. A common

  15. Rape Myth Beliefs and Bystander Attitudes among Incoming College Students

    Science.gov (United States)

    McMahon, Sarah

    2010-01-01

    Objective: The bystander approach to rape prevention is gaining popularity on college campuses, although research is limited. This study explored bystander attitudes and their relationship with rape myths in a sample of college students. Participants: Surveys from 2,338 incoming undergraduate students at a large, northeastern university were…

  16. Bystander cells enhance NK cytotoxic efficiency by reducing search time.

    Science.gov (United States)

    Zhou, Xiao; Zhao, Renping; Schwarz, Karsten; Mangeat, Matthieu; Schwarz, Eva C; Hamed, Mohamed; Bogeski, Ivan; Helms, Volkhard; Rieger, Heiko; Qu, Bin

    2017-03-13

    Natural killer (NK) cells play a central role during innate immune responses by eliminating pathogen-infected or tumorigenic cells. In the microenvironment, NK cells encounter not only target cells but also other cell types including non-target bystander cells. The impact of bystander cells on NK killing efficiency is, however, still elusive. In this study we show that the presence of bystander cells, such as P815, monocytes or HUVEC, enhances NK killing efficiency. With bystander cells present, the velocity and persistence of NK cells were increased, whereas the degranulation of lytic granules remained unchanged. Bystander cell-derived H 2 O 2 was found to mediate the acceleration of NK cell migration. Using mathematical diffusion models, we confirm that local acceleration of NK cells in the vicinity of bystander cells reduces their search time to locate target cells. In addition, we found that integrin β chains (β1, β2 and β7) on NK cells are required for bystander-enhanced NK migration persistence. In conclusion, we show that acceleration of NK cell migration in the vicinity of H 2 O 2 -producing bystander cells reduces target cell search time and enhances NK killing efficiency.

  17. The bystander effect in an N-person dictator game

    NARCIS (Netherlands)

    Panchanathan, K.; Frankenhuis, W.E.; Silk, J.B.

    2013-01-01

    Dozens of studies show that bystanders are less likely to help victims as bystander number increases. However, these studies model one particular situation, in which victims need only one helper. Using a multi-player dictator game, we study a different but common situation, in which a recipient’s

  18. Bystander Approaches: Empowering Students to Model Ethical Sexual Behavior

    Science.gov (United States)

    Lynch, Annette; Fleming, Wm. Michael

    2005-01-01

    Sexual violence on college campuses is well documented. Prevention education has emerged as an alternative to victim-- and perpetrator--oriented approaches used in the past. One sexual violence prevention education approach focuses on educating and empowering the bystander to become a point of ethical intervention. In this model, bystanders to…

  19. Photon hormesis deactivates alpha-particle induced bystander effects between zebrafish embryos

    International Nuclear Information System (INIS)

    Ng, C.Y.P.; Cheng, S.H.; Yu, K.N.

    2017-01-01

    In the present work, we studied the effects of low-dose X-ray photons on the alpha-particle induced bystander effects between embryos of the zebrafish, Danio rerio. The effects on the naive whole embryos were studied through quantification of apoptotic signals (amounts of cells undergoing apoptosis) at 24 h post fertilization (hpf) using vital dye acridine orange staining, followed by counting the stained cells under a fluorescent microscope. We report data showing that embryos at 5 hpf subjected to a 4.4 mGy alpha-particle irradiation could release a stress signal into the medium, which could induce bystander effect in partnered naive embryos sharing the same medium. We also report that the bystander effect was deactivated when the irradiated embryos were subjected to a concomitant irradiation of 10 or 14 mGy of X-rays, but no such deactivation was achieved if the concomitant X-ray dose dropped to 2.5 or 5 mGy. In the present study, the significant drop in the amount of apoptotic signals on the embryos having received 4.4 mGy alpha particles together X-rays irradiation from 2.5 or 5 mGy to 10 or 14 mGy, together with the deactivation of RIBE with concomitant irradiation of 10 or 14 mGy of X-rays supported the participation of photon hormesis with an onset dose between 5 and 10 mGy, which might lead to removal of aberrant cells through early apoptosis or induction of high-fidelity DNA repair. As we found that photons and alpha particles could have opposite biological effects when these were simultaneously irradiated onto living organisms, these ionizing radiations could be viewed as two different environmental stressors, and the resultant effects could be regarded as multiple stressor effects. The present work presented the first study on a multiple stressor effect which occurred on bystander organisms. In other words, this was a non-targeted multiple stressor effect. The photon hormesis could also explain some failed attempts to observe neutron-induced bystander

  20. When bystanders become bothersome : The negative consequences of bystander conflict and the moderating role of resilience

    NARCIS (Netherlands)

    van Erp, Kim J.P.M.; Rispens, Sonja; Gevers, Josette M.P.; Demerouti, Evangelia

    2015-01-01

    Bystander conflict is a situation in which employees are hindered in their work by parties not involved in the primary process. Public service employees and emergency care workers, such as ambulance employees and firefighters, often encounter this kind of conflict with potentially far-reaching

  1. When bystanders become bothersome : the negative consequences of bystander conflict and the moderating role of resilience

    NARCIS (Netherlands)

    van Erp, Kim; Rispens, Sonja; Gevers, Josette M.P.; Demerouti, Evangelia

    2014-01-01

    Bystander conflict is a situation in which employees are hindered in their work by parties not involved in the primary process. Public service employees and emergency care workers, such as ambulance employees and firefighters, often encounter this kind of conflict with potentially far-reaching

  2. The lonely bystander: ostracism leads to less helping in virtual bystander situations

    NARCIS (Netherlands)

    van Bommel, Marco; van Prooijen, Jan-Willem; Elffers, Henk; van Lange, Paul A.M.

    2016-01-01

    People are less likely to help when they have been ostracized, or when they are in the presence of bystanders. In the current manuscript we test both these influences simultaneously. We postulated two opposing hypotheses: first, helping decreases after ostracism, even when intervention is already

  3. The bystander effect: is reactive oxygen species the driver?

    International Nuclear Information System (INIS)

    Szumiel, I.

    2003-01-01

    The paper reviews selected examples of the bystander effect, such as clonogenic survival decrease, chromosomal aberrations and mutations. The similarities and differences between the biological effects in directly targeted and bystander cells are briefly discussed. Also reviewed are the experimental data which support the role of reactive oxygen species (ROS), especially *O 2 - , as mediators of the bystander effect. Endogenously generated ROS, due to activation of NAD(P)H oxidases, play a kay role in the introduction of DNA damage in bystander cells. All the observed effects in bystander cells, such as alteration in gene expression patterns, chromosomal aberrations, sister chromatid exchanges, mutations, genome instability and neoplastic transformation are the consequence of DNA damage. (author)

  4. Non-targeted bystander effects induced by ionizing radiation

    International Nuclear Information System (INIS)

    Morgan, William F.; Sowa, Marianne B.

    2007-01-01

    Radiation-induced bystander effects refer to those responses occurring in cells that were not subject to energy deposition events following ionizing radiation. These bystander cells may have been neighbors of irradiated cells, or physically separated but subject to soluble secreted signals from irradiated cells. Bystander effects have been observed in vitro and in vivo and for various radiation qualities. In tribute to an old friend and colleague, Anthony V. Carrano, who would have said 'well what are the critical questions that should be addressed, and so what?', we review the evidence for non-targeted radiation-induced bystander effects with emphasis on prevailing questions in this rapidly developing research field, and the potential significance of bystander effects in evaluating the detrimental health effects of radiation exposure

  5. Prenatal Care Checkup

    Science.gov (United States)

    ... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

  6. Prenatal stress from trawl capture affects mothers and neonates: a case study using the southern fiddler ray (Trygonorrhina dumerilii)

    Science.gov (United States)

    Guida, L.; Awruch, C.; Walker, T. I.; Reina, R. D.

    2017-04-01

    Assessing fishing effects on chondrichthyan populations has predominantly focused on quantifying mortality rates. Consequently, sub-lethal effects of capture stress on the reproductive capacity of chondrichthyans are largely unknown. We investigated the reproductive consequences of capture on pregnant southern fiddler rays (Trygonorrhina dumerilii) collected from Swan Bay, Australia, in response to laboratory-simulated trawl capture (8 h) followed immediately by air exposure (30 min). Immediately prior to, and for up to 28 days post trawling, all females were measured for body mass (BM), sex steroid concentrations (17-β estradiol, progesterone, testosterone) and granulocyte to lymphocyte (G:L) ratio. At parturition, neonates were measured for total length (TL), BM and G:L ratio. Trawling reduced maternal BM and elevated the G:L ratio for up to 28 days. Trawling did not significantly affect any sex steroid concentrations relative to controls. Neonates from trawled mothers were significantly lower in BM and TL than control animals, and had an elevated G:L ratio. Our results show that capture of pregnant T. dumerilii can influence their reproductive potential and affect the fitness of neonates. We suggest other viviparous species are likely to be similarly affected. Sub-lethal effects of capture, particularly on reproduction, require further study to improve fisheries management and conservation of chondrichthyans.

  7. A pivotal role of the jasmonic acid signal pathway in mediating radiation-induced bystander effects in Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ting; Xu, Wei; Deng, Chenguang; Xu, Shaoxin; Li, Fanghua; Wu, Yuejin; Wu, Lijun [Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Key Laboratory of Environmental Toxicology and Pollution Control Technology of Anhui Province, Hefei 230031 (China); Bian, Po, E-mail: bianpo@ipp.ac.cn [Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Key Laboratory of Environmental Toxicology and Pollution Control Technology of Anhui Province, Hefei 230031 (China)

    2016-09-15

    Highlights: • The JA signal pathway plays a pivotal role in mediating radiation-induced bystander effects in Arabidopsis thaliana. • The JA signal pathway is involved in both the generation of bystander signals in irradiated roots and radiation responses in bystander aerial plants. • Over-accumulation of endogenous JA enhances the radiosensitivity of plants in terms of RIBE. - Abstract: Although radiation-induced bystander effects (RIBE) in Arabidopsis thaliana have been well demonstrated in vivo, little is known about their underlying mechanisms, particularly with regard to the participating signaling molecules and signaling pathways. In higher plants, jasmonic acid (JA) and its bioactive derivatives are well accepted as systemic signal transducers that are produced in response to various environmental stresses. It is therefore speculated that the JA signal pathway might play a potential role in mediating radiation-induced bystander signaling of root-to-shoot. In the present study, pretreatment of seedlings with Salicylhydroxamic acid, an inhibitor of lipoxigenase (LOX) in JA biosynthesis, significantly suppressed RIBE-mediated expression of the AtRAD54 gene. After root irradiation, the aerial parts of A. thaliana mutants deficient in JA biosynthesis (aos) and signaling cascades (jar1-1) showed suppressed induction of the AtRAD54 and AtRAD51 genes and TSI and 180-bp repeats, which have been extensively used as endpoints of bystander genetic and epigenetic effects in plants. These results suggest an involvement of the JA signal pathway in the RIBE of plants. Using the root micro-grafting technique, the JA signal pathway was shown to participate in both the generation of bystander signals in irradiated root cells and radiation responses in the bystander aerial parts of plants. The over-accumulation of endogenous JA in mutant fatty acid oxygenation up-regulated 2 (fou2), in which mutation of the Two Pore Channel 1 (TPC1) gene up-regulates expression of the LOX

  8. The Bystander-Effect: A Meta-Analytic Review on Bystander Intervention in Dangerous and Non-Dangerous Emergencies

    Science.gov (United States)

    Fischer, Peter; Krueger, Joachim I.; Greitemeyer, Tobias; Vogrincic, Claudia; Kastenmuller, Andreas; Frey, Dieter; Heene, Moritz; Wicher, Magdalena; Kainbacher, Martina

    2011-01-01

    Research on bystander intervention has produced a great number of studies showing that the presence of other people in a critical situation reduces the likelihood that an individual will help. As the last systematic review of bystander research was published in 1981 and was not a quantitative meta-analysis in the modern sense, the present…

  9. Enteropathogenic Escherichia coli: foe or innocent bystander?

    Science.gov (United States)

    Hu, Jia; Torres, Alfredo G.

    2015-01-01

    Enteropathogenic Escherichia coli (EPEC) remain one the most important pathogens infecting children and they are one of the main causes of persistent diarrhea worldwide. Historically, typical EPEC (tEPEC), defined as those isolates with the attaching and effacement (A/E) genotype (eae+), which possess bfpA+ and lack the stx- genes are found strongly associated with diarrheal cases. However, occurrence of atypical EPEC (aEPEC; eae+ bfpA- stx-) in diarrheal and asymptomatic hosts has made investigators question the role of these pathogens in human disease. Current epidemiological data is helping answering the question whether EPEC is mainly a foe or an innocent bystander during infection. PMID:25726041

  10. Selective replication of oncolytic virus M1 results in a bystander killing effect that is potentiated by Smac mimetics.

    Science.gov (United States)

    Cai, Jing; Lin, Yuan; Zhang, Haipeng; Liang, Jiankai; Tan, Yaqian; Cavenee, Webster K; Yan, Guangmei

    2017-06-27

    Oncolytic virotherapy is a treatment modality that uses native or genetically modified viruses that selectively replicate in and kill tumor cells. Viruses represent a type of pathogen-associated molecular pattern and thereby induce the up-regulation of dozens of cytokines via activating the host innate immune system. Second mitochondria-derived activator of caspases (Smac) mimetic compounds (SMCs), which antagonize the function of inhibitor of apoptosis proteins (IAPs) and induce apoptosis, sensitize tumor cells to multiple cytokines. Therefore, we sought to determine whether SMCs sensitize tumor cells to cytokines induced by the oncolytic M1 virus, thus enhancing a bystander killing effect. Here, we report that SMCs potentiate the oncolytic effect of M1 in vitro, in vivo, and ex vivo. This strengthened oncolytic efficacy resulted from the enhanced bystander killing effect caused by the M1 virus via cytokine induction. Through a microarray analysis and subsequent validation using recombinant cytokines, we identified IL-8, IL-1A, and TRAIL as the key cytokines in the bystander killing effect. Furthermore, SMCs increased the replication of M1, and the accumulation of virus protein induced irreversible endoplasmic reticulum stress- and c-Jun N-terminal kinase-mediated apoptosis. Nevertheless, the combined treatment with M1 and SMCs had little effect on normal and human primary cells. Because SMCs selectively and significantly enhance the bystander killing effect and the replication of oncolytic virus M1 specifically in cancer cells, this combined treatment may represent a promising therapeutic strategy.

  11. Radiation-induced bystander effects in vivo are sex specific

    International Nuclear Information System (INIS)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

    2008-01-01

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes

  12. Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone.

  13. Bystander effects and their implications for clinical radiotherapy

    International Nuclear Information System (INIS)

    Munro, Alastair J

    2009-01-01

    Radiation-induced bystander effects are defined as those biological effects expressed, after irradiation, by cells whose nuclei have not been directly irradiated. Radiation oncologists are only gradually beginning to appreciate the clinical relevance of radiation-induced bystander effects and associated phenomena: adaptive responses, genomic instability and abscopal effects. Incorporating bystander effects into the science underpinning clinical radiotherapy will involve moving beyond simple mechanistic models and towards a more systems-based approach. It is, given the protean nature of bystander effects, difficult to devise a coherent research strategy to investigate the clinical impact and relevance of bystander phenomena. Epidemiological approaches will be required, the traditional research models based on randomised controlled trials are unlikely to be adequate for the task. Any consideration of bystander effects challenges not only clinicians' preconceptions concerning the effects of radiation on tumours and normal tissues but also their ingenuity. This review covers, from a clinical perspective, the issues and problems associated with radiation-induced bystander effects.

  14. Radiation-induced bystander effects in vivo are sex specific

    Energy Technology Data Exchange (ETDEWEB)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada); Kovalchuk, Olga [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada)], E-mail: olga.kovalchuk@uleth.ca

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  15. Radiation-induced bystander effects in vivo are sex specific.

    Science.gov (United States)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naïve cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  16. Obstacles to bystander cardiopulmonary resuscitation in Japan.

    Science.gov (United States)

    Shibata, K; Taniguchi, T; Yoshida, M; Yamamoto, K

    2000-05-01

    bystander cardiopulmonary resuscitation (CPR) is performed infrequently in Japan. We conducted this study to identify Japanese attitudes toward the performance of bystander CPR. participants were asked about their willingness to perform CPR with varying scenarios and CPR techniques (mouth-to-mouth ventilation plus chest compression (MMV plus CC) versus chest compression alone (CC)). a total of 1302/1355 individuals completed the questionnaire, including high school students, teachers, emergency medical technicians, medical nurses, and medical students. About 2% of high school students, 3% of teachers, 26% of emergency medical technicians, 3% of medical nurses and 16% of medical students claimed they would 'definitely' perform MMV plus CC on a stranger. However, 21-72% claimed they would prefer the alternative of performing CC alone. Respondents claimed their unwillingness to perform MMV is not due to the fear of contracting a communicable disease, but the lack of confidence in their ability to perform CPR properly. in all categories of respondents, willingness to perform MMV plus CC for a stranger was disappointingly low. Better training in MMV together with teaching awareness that CC alone can be given should be instituted to maximize the number of potential providers of CPR in the community, even in communities where the incidence of HIV is very low.

  17. Genetic Signatures of HIV-1 Envelope-mediated Bystander Apoptosis

    Science.gov (United States)

    Joshi, Anjali; Lee, Raphael T. C.; Mohl, Jonathan; Sedano, Melina; Khong, Wei Xin; Ng, Oon Tek; Maurer-Stroh, Sebastian; Garg, Himanshu

    2014-01-01

    The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4+ T cell loss. However, most of the studies testing this phenomenon have been conducted with laboratory-adapted HIV-1 isolates. This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. A specific role of these residues was also confirmed experimentally. These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4+ T cells. Furthermore, we identify specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype. PMID:24265318

  18. Nonuse of Prenatal Care: Implications for Social Work Involvement.

    Science.gov (United States)

    Bedics, Bonnie C.

    1994-01-01

    Interviewed 44 women who did not obtain prenatal care. Identified four categories of reasons for nonuse: women's lifestyles differed from mainstream; stressful events took priority over prenatal care; women attempted to receive care but were discouraged, turned away, or given poor information by service delivery system personnel; and women did not…

  19. Bystander effect induced by ionizing radiation and its application

    International Nuclear Information System (INIS)

    Chen Feng; Tu Yu

    2009-01-01

    An indirect effect induced by ionizing radiation called bystander effect is being highly concentrated. Many domestic and foreign researchers have verified the existence of bystander effect and have got more understanding of the mechanism with advanced detection techniques and methods. So far, the research about it has expanded from a single cell to multiple cells, from the in vitro to the whole, and has extended to in vivo from in vitro, which provides powerful evidence to explain how bystander effects happen and the regulation mechanism and especially gives scientific evidence to clinical radiation oncology application in the future. (authors)

  20. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

    Science.gov (United States)

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  1. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    Directory of Open Access Journals (Sweden)

    Sejal Desai

    Full Text Available Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2 and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper

  2. Are nonparticipants in prosocial behavior merely innocent bystanders?

    Science.gov (United States)

    Anker, Ashley E; Feeley, Thomas Hugh

    2011-01-01

    Latané and Darley's (1970) bystander intervention theory was used to model individuals' participation in two prosocial behaviors (organ donation, green living). It is argued that nonparticipants in prosocial helping are innocent bystanders who likely fail to notice the need, do not interpret the cause as an emergency, do not accept responsibility for the need to help, and have little knowledge on how to help. Data in study 1 (n = 494) indicate support for the proposed innocent bystander path model (notice event → interpret event as emergency → accept responsibility → knowledge of how to help) in organ donation. Study 2 (n = 519) replicated the model in the context of green living and additionally found a direct path from noticing the event to knowledge of how to help. Implications of framing nonparticipation in prosocial behaviors as innocent bystander effects are discussed in context of campaign communication.

  3. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    International Nuclear Information System (INIS)

    Jiang Erkang; Wu Lijun

    2009-01-01

    In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy α-particle irradiated and non-irradiated bystander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensitive to damage signals. Treated by c-PTIO(2-(4-carboxy-phenyl)- 4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide), a nitric oxide (NO) scavenger, the MN frequencies were effectively inhibited, showing that nitric oxide might be very important in mediating the enhanced damage. These results indicated that caffeine enhanced the low dose α-particle radiation-induced damage in irradiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE). (ion beam bioengineering)

  4. Computer modelling of radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Khvostunov, Igor K.; Nikjoo, Hooshang

    2002-01-01

    Radiation-induced genomic instability and bystander effects are now well established consequences of exposure of living cells to ionising radiation. It has been observed that cells not directly hit by radiation tracks may still exhibit radiation effects. We present a quantitative modelling of the radiation-induced bystander effect based on a diffusion model of spreading the bystander signal. The model assumes the bystander factor to be a protein of low molecular weight, given out by the hit cell, diffusing in the medium and reacting with non-hit cells. The model calculations successfully predict the results of cell survival in an irradiated conditioned medium. The model predicts the shape of dose-effect relationship for cell survival and oncogenic transformation induced by broad-beam and micro-beam irradiation by alpha-particles. (author)

  5. ATR-dependent bystander effects in non-targeted cells

    International Nuclear Information System (INIS)

    Burdak-Rothkamm, S.

    2007-01-01

    Complete text of publication follows. Radiation induced non-targeted bystander effects have been reported for a range of endpoints including the induction of γH2AX foci which serve as a marker for DNA double strand breaks. We have recently reported the induction of γH2AX foci in non-targeted bystander cells up to 48 hours after irradiation and the involvement of reactive oxygen species (ROS) and TGF-beta 1 in the induction of γH2AX foci (Oncogene (2007) 26:993-1002). Here, we wanted to determine the role of the PI3-like kinases ATM, ATR and DNA-PK in DNA damage signalling in bystander cells. Conditioned medium from T98G cells irradiated with 2 Gy of X-rays was transferred onto non-irradiated cells that were subsequently analysed for the induction of γH2AX, ATR and 53BP1 foci as well as clonogenic survival. Irradiated T98G glioma cells generated signals that induced γH2AX and 53BP1 foci in cells treated with the conditioned medium from irradiated cells. These foci co-localised with ATR foci. Inhibition of ATM and DNA-PK could not suppress the induction of bystander γH2AX foci whereas the mutation of ATR in Seckel cells abrogated bystander foci induction. A restriction of bystander foci to the S-phase of the cell cycle both in T98G cells and in ATR- proficient fibroblasts was observed. These results identify ATR as a central player within the bystander signalling cascade leading to γH2AX and 53BP1 foci formation, and suggest a mechanism of DNA damage induction in non-targeted cells. Further investigations have shown decreased clonogenic cell survival in bystander T98G and ATR wild-type fibroblasts. ATR mutated Seckel cells and also ATM-/- fibroblasts were resistant to this effect suggesting a role for both ATR and ATM in the bystander signalling cascade with regard to cell survival. Taken together, these observations support a hypothesis of DNA damage-induced accumulation of stalled replication forks in bystander cells which are subsequently processed by

  6. Diagnóstico Prenatal

    OpenAIRE

    López, Jaime Octavio; Saldarriaga, Wilmar; Fundación Valle de Lili

    2010-01-01

    Diagnóstico Prenatal/ propósitos del diagnóstico prenatal/ Tamizaje a partir del Control Prenatal/ Pacientes de bajo riesgo/ Tamizaje bioquímico/ Pacientes de alto riesgo/ Pruebas invasivas y no invasivas

  7. Preconception Care and Prenatal Care

    Science.gov (United States)

    ... Twitter Pinterest Email Print About Preconception Care and Prenatal Care What is preconception care? Preconception care is the ... improve the health of your child. What is prenatal care? Prenatal care is the health care a woman ...

  8. Guidelines for Bystander First Aid 2016.

    Science.gov (United States)

    Pek, Jen Heng

    2017-07-01

    Cardiac life support is a form of first aid for cardiac emergencies. However, research and evidence in this field is lacking compared with other forms of first aid. Having identified the common emergencies that are encountered in the hospital, based on the available evidence, we have put together what could be an evidence-based approach to the first aid management of some of these common emergencies, viz. breathlessness, chest pain, allergies, stroke, heat injury, poisoning, unconsciousness, seizures, and trauma situations such as bleeding, wounds, contusions, head injury, burns and fractures. Educating the public is the key to developing a first responder bystander. These guidelines could become the basis for training of the public. Copyright: © Singapore Medical Association.

  9. Public Knowledge and Attitudes towards Bystander Cardiopulmonary Resuscitation in China

    Directory of Open Access Journals (Sweden)

    Meng Chen

    2017-01-01

    Full Text Available The rate of bystander CPR is much lower in China than in developed countries. This survey was implemented to assess the current status of layperson CPR training, to analyze the willingness of bystanders to perform CPR, and to identify barriers to improving bystander CPR rates. The questionnaire included individual information, current status of bystander CPR training, and individual’s willingness and attitude towards performing CPR. There were 25.6% laypersons who took CPR training. The majority (98.6% of laypersons would perform CPR on their family members, but fewer laypersons (76.3% were willing to perform CPR on strangers. Most respondents (53.2% were worried about legal issues. If laws were implemented to protect bystanders who give aid, the number of laypersons who were not willing to perform CPR on strangers dropped from 23.7% to 2.4%. An increasing number of people in China know CPR compared with the situation in the past. CPR training in China is much less common than in many developed countries. The barriers are that laypersons are not well-trained and they fear being prosecuted for unsuccessful CPR. More accredited CPR training courses are needed in China. The laws should be passed to protect bystanders who provide assistance.

  10. Significance of radiation-induced bystander effects in radiation therapy

    International Nuclear Information System (INIS)

    Suzuki, Masao

    2014-01-01

    Since 1994, a Phase I/II clinical study and radiotherapy have carried out using carbon-ion beams produced with the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences. Now we constructed the new treatment facility for the advanced carbon-ion therapy at HIMAC applying a 3D fast spot scanning system with pencil beams. In the field of fundamental biological studies for high-LET heavy ions, there are some reports regarding bystander effects after exposure to alpha particles derived from 238 Pu or He-ion microbeams. However, only limited sets of studies have examined bystander effects after exposure to different ion species heavier than helium, such as carbon ions. We have been investigating bystander cellular responses in both normal human and human tumor cells irradiated with the HIMAC carbon ions. Bystander cell-killing effect was observed in the cells harboring wild-type P53 gene, but not in the P53-mutated cells. Moreover, observed bystander effect was suppressed by treating with a specific inhibitor of gap-junction mediated cell-cell communication. There is clear evidence that the carbon-ion irradiation enables the enhanced cell killing in cells with wild-type P53 gene via gap-junction mediated bystander effect. (author)

  11. Genetic changes in progeny of bystander human fibroblasts after microbeam irradiation with X-rays, protons or carbon ions: the relevance to cancer risk.

    Science.gov (United States)

    Autsavapromporn, Narongchai; Plante, Ianik; Liu, Cuihua; Konishi, Teruaki; Usami, Noriko; Funayama, Tomoo; Azzam, Edouard I; Murakami, Takeshi; Suzuki, Masao

    2015-01-01

    Radiation-induced bystander effects have important implications in radiotherapy. Their persistence in normal cells may contribute to risk of health hazards, including cancer. This study investigates the role of radiation quality and gap junction intercellular communication (GJIC) in the propagation of harmful effects in progeny of bystander cells. Confluent human skin fibroblasts were exposed to microbeam radiations with different linear energy transfer (LET) at mean absorbed doses of 0.4 Gy by which 0.036-0.4% of the cells were directly targeted by radiation. Following 20 population doublings, the cells were harvested and assayed for micronucleus formation, gene mutation and protein oxidation. Our results showed that expression of stressful effects in the progeny of bystander cells is dependent on LET. The progeny of bystander cells exposed to X-rays (LET ∼6 keV/μm) or protons (LET ∼11 keV/μm) showed persistent oxidative stress, which correlated with increased micronucleus formation and mutation at the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) locus. Such effects were not observed after irradiation by carbon ions (LET ∼103 keV/μm). Interestingly, progeny of bystander cells from cultures exposed to protons or carbon ions under conditions where GJIC was inhibited harbored reduced oxidative and genetic damage. This mitigating effect was not detected when the cultures were exposed to X-rays. These findings suggest that cellular exposure to proton and heavy charged particle with LET properties similar to those used here can reduce the risk of lesions associated with cancer. The ability of cells to communicate via gap junctions at the time of irradiation appears to impact residual damage in progeny of bystander cells.

  12. The positive bystander effect: passive bystanders increase helping in situations with high expected negative consequences for the helper.

    Science.gov (United States)

    Fischer, Peter; Greitemeyer, Tobias

    2013-01-01

    The present field study investigated the interplay between the presence of a passive bystander (not present versus present) in a simulated bike theft and expected negative consequences (low versus high) in predicting intervention behavior when no physical victim is present. It was found that an additional bystander increases individual intervention in situations where the expected negative consequences for the helper in case of intervention were high (i.e., when the bike thief looks fierce) compared to situations where the expected negative consequences for the helper were low (i.e., when the bike thief does not look fierce). In contrast, no such effect for high vs. low expected negative consequences was observed when no additional bystander observed the critical situation. The results are discussed in light of previous laboratory findings on expected negative consequences and bystander intervention.

  13. Bystander effects and biota: implications of radiation-induced bystander effects for protection of the environment from ionising radiation

    International Nuclear Information System (INIS)

    Mothersill, C.E.; Seymour, C.B.

    2003-01-01

    Bystander effects are now known to be induced by both high and low LET in a variety of cells in culture. They have been proven to occur in vivo in mice following 0.5Gy total body irradiation and in blood from humans being treated for cancer by radiotherapy. Effects have also been detected in fish, crustacea and molluscs. The important questions now are not whether bystander effects occur but why and what implications they have, if any, for radiation protection. Different species and different genetic backgrounds within a species produce different types of bystander effect, different organs also produce different effects. This paper will review the data in this field and will discuss likely implications for protection of man and non-human biota. In particular it will look at the potential long-term outcomes for different organisational levels, from cell to ecosystem, of bystander mechanisms. In view of new concerns about the effects of low level radiation on non-human biota, emphasis will be placed on considering how bystander effects might operate at chronic low doses versus acute accidental low doses. Problems of radiation interaction with chemicals, whether chemicals can also induce 'bystander effects' , and how regulators might handle these situations which occur all the time in real environments, will be presented for discussion. Finally the paper will discuss likely implications of these mechanisms for evolutionary biology

  14. The Significance of the Bystander Effect: Modeling, Experiments, and More Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, David J.

    2009-07-22

    Non-targeted (bystander) effects of ionizing radiation are caused by intercellular signaling; they include production of DNA damage and alterations in cell fate (i.e. apoptosis, differentiation, senescence or proliferation). Biophysical models capable of quantifying these effects may improve cancer risk estimation at radiation doses below the epidemiological detection threshold. Understanding the spatial patterns of bystander responses is important, because it provides estimates of how many bystander cells are affected per irradiated cell. In a first approach to modeling of bystander spatial effects in a three-dimensional artificial tissue, we assumed the following: (1) The bystander phenomenon results from signaling molecules (S) that rapidly propagate from irradiated cells and decrease in concentration (exponentially in the case of planar symmetry) as distance increases. (2) These signals can convert cells to a long-lived epigenetically activated state, e.g. a state of oxidative stress; cells in this state are more prone to DNA damage and behavior alterations than normal and therefore exhibit an increased response (R) for many end points (e.g. apoptosis, differentiation, micronucleation). These assumptions were implemented by a mathematical formalism and computational algorithms. The model adequately described data on bystander responses in the 3D system using a small number of adjustable parameters. Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track pre-malignant cell numbers throughout an entire lifetime but treat initial radiation dose-response simplistically and (2) short-term formalisms that provide a detailed initial dose-response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long

  15. Psychological impact on dispatched local lay rescuers performing bystander cardiopulmonary resuscitation.

    Science.gov (United States)

    Zijlstra, Jolande A; Beesems, Stefanie G; De Haan, Rob J; Koster, Rudolph W

    2015-07-01

    We studied the short-term psychological impact and post-traumatic stress disorder (PTSD)-related symptoms in lay rescuers performing cardiopulmonary resuscitation (CPR) after a text message (TM)-alert for out-of-hospital-cardiac arrest, and assessed which factors contribute to a higher level of PTSD-related symptoms. The lay rescuers received a TM-alert and simultaneously an email with a link to an online questionnaire. We analyzed all questionnaires from February 2013 until October 2014 measuring the short-term psychological impact. We interviewed by telephone all first arriving lay rescuers performing bystander CPR and assessed PTSD-related symptoms with the Impact of Event Scale (IES) 4-6 weeks after the resuscitation. IES-scores 0-8 reflected no stress, 9-25 mild, 26-43 moderate, and 44-75 severe stress. A score ≥ 26 indicated PTSD symptomatology. Of all alerted lay rescuers, 6572 completed the online questionnaire. Of these, 1955 responded to the alert and 507 assisted in the resuscitation. We interviewed 203 first arriving rescuers of whom 189 completed the IES. Of these, 41% perceived no/mild short-term impact, 46% bearable impact and 13% severe impact. On the IES, 81% scored no stress and 19% scored mild stress. None scored moderate or severe stress. Using a multivariable logistic regression model we identified three factors with an independent impact on mild stress level: no automated external defibrillator connected by the lay rescuer, severe short-term impact, and no (very) positive experience. Lay rescuers alerted by text messages, do not show PTSD-related symptoms 4-6 weeks after performing bystander CPR, even if they perceive severe short-term psychological impact. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. The comparative effects of group prenatal care on psychosocial outcomes.

    Science.gov (United States)

    Heberlein, Emily C; Picklesimer, Amy H; Billings, Deborah L; Covington-Kolb, Sarah; Farber, Naomi; Frongillo, Edward A

    2016-04-01

    To compare the psychosocial outcomes of the CenteringPregnancy (CP) model of group prenatal care to individual prenatal care, we conducted a prospective cohort study of women who chose CP group (N = 124) or individual prenatal care (N = 124). Study participants completed the first survey at study recruitment (mean gestational age 12.5 weeks), with 89% completing the second survey (mean gestational age 32.7 weeks) and 84% completing the third survey (6 weeks' postpartum). Multiple linear regression models compared changes by prenatal care model in pregnancy-specific distress, prenatal planning-preparation and avoidance coping, perceived stress, affect and depressive symptoms, pregnancy-related empowerment, and postpartum maternal-infant attachment and maternal functioning. Using intention-to-treat models, group prenatal care participants demonstrated a 3.2 point greater increase (p prenatal planning-preparation coping strategies. While group participants did not demonstrate significantly greater positive outcomes in other measures, women who were at greater psychosocial risk benefitted from participation in group prenatal care. Among women reporting inadequate social support in early pregnancy, group participants demonstrated a 2.9 point greater decrease (p = 0.03) in pregnancy-specific distress in late pregnancy and 5.6 point higher mean maternal functioning scores postpartum (p = 0.03). Among women with high pregnancy-specific distress in early pregnancy, group participants had an 8.3 point greater increase (p prenatal planning-preparation coping strategies in late pregnancy and a 4.9 point greater decrease (p = 0.02) in postpartum depressive symptom scores. This study provides further evidence that group prenatal care positively impacts the psychosocial well-being of women with greater stress or lower personal coping resources. Large randomized studies are needed to establish conclusively the biological and psychosocial benefits of group

  17. The role of TGF-β1–miR-21–ROS pathway in bystander responses induced by irradiated non-small-cell lung cancer cells

    Science.gov (United States)

    Jiang, Y; Chen, X; Tian, W; Yin, X; Wang, J; Yang, H

    2014-01-01

    Background: Many studies have indicated an important implication of radiation-induced bystander effects (RIBEs) in cancer radiotherapy, but the detailed signalling remains unclear. Methods: The roles of tumour growth factor-beta1 (TGF-β1) and miR-21 in medium-mediated RIBEs in H1299 non-small-cell lung cancer cells were investigated using DNA damage, changes in proliferation and levels of reactive oxygen species (ROS) as end points. SB431542, a specific inhibitor of TGF-β type 1 receptor kinases, was used to inhibit TGF-β1 pathways in irradiated and bystander cells. Exogenous miR-21 regulation was achieved through inhibitor or mimic transfection. Results: Compared with relative sham-radiation-conditioned medium, radiation-conditioned medium (RCM) from irradiated cells 1 h post radiation (1-h RCM) caused an increase in ROS levels and DNA damage in bystander cells, while 18-h RCM induced cell cycle delay and proliferation inhibition. All these effects were eliminated by TGF-βR1 inhibition. One-hour RCM upregulated miR-21 expression in bystander cells, and miR-21 inhibitor abolished bystander oxidative stress and DNA damage. Eighteen-hour RCM downregulated miR-21 of bystander cells, and miR-21 mimic eliminated bystander proliferation inhibition. Furthermore, the dysregulation of miR-21 was attenuated by TGF-βR1 inhibition. Conclusions: The TGF-β1–miR-21–ROS pathway of bystander cells has an important mediating role in RIBEs in H1299 cells. PMID:24992582

  18. Radioprotection of targeted and bystander cells by methylproamine

    International Nuclear Information System (INIS)

    Burdak-Rothkamm, Susanne; Smith, Andrea; Lobachevsky, Pavel; Martin, Roger; Prise, Kevin M.

    2015-01-01

    Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells. T98G glioma cells were treated with 15 μM methylproamine and exposed to 137 Cs γ-ray/X-ray irradiation and He 2+ microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay. Radioprotection of directly targeted T98G cells by methylproamine was observed for 137 Cs γ-rays and X-rays but not for He 2+ charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He 2+ ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed. Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He 2+ ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received. (orig.) [de

  19. Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects

    International Nuclear Information System (INIS)

    Chen Shaopeng; Zhao Ye; Zhao Guoping; Han Wei; Bao Lingzhi; Yu, K.N.; Wu Lijun

    2009-01-01

    Genomic instability can be observed in bystander cells. However, the underlying mechanism(s) is still relatively unclear. In a previous study, we found that irradiated cells released mitochondria-dependent intracellular factor(s) which could lead to bystander γ-H2AX induction. In this paper, we used normal (ρ + ) and mtDNA-depleted (ρ 0 ) human-hamster hybrid cells to investigate mitochondrial effects on the genotoxicity in bystander effect through medium transfer experiments. Through the detection of DNA double-strand breaks with γ-H2AX, we found that the fraction of γ-H2AX positive cells changed with time when irradiation conditioned cell medium (ICCM) were harvested. ICCM harvested from irradiated ρ + cells at 10 min post-irradiation (ρ + ICCM 10min ) caused larger increases of bystander γ-H2AX induction comparing to ρ 0 ICCM 10min , which only caused a slight increase of bystander γ-H2AX induction. The ρ + ICCM 10min could also result in the up-regulation of ROS production (increased by 35% at 10 min), while there was no significant increase in cells treated with ρ 0 ICCM 10min . We treated cells with dimethyl sulfoxide (DMSO), the scavenger of ROS, and quenched γ-H2AX induction by ρ + ICCM. Furthermore, after the medium had been transferred and the cells were continuously cultured for 7 days, we found significantly increased CD59 - gene loci mutation (increased by 45.9%) and delayed cell death in the progeny of ρ + ICCM-treated bystander cells. In conclusion, the work presented here suggested that up-regulation of the mitochondria-dependent ROS might be very important in mediating genotoxicity of bystander effects.

  20. Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects

    Energy Technology Data Exchange (ETDEWEB)

    Chen Shaopeng [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Zhao Ye; Zhao Guoping [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Han Wei [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Bao Lingzhi [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Wu Lijun, E-mail: ljw@ipp.ac.cn [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China)

    2009-06-18

    Genomic instability can be observed in bystander cells. However, the underlying mechanism(s) is still relatively unclear. In a previous study, we found that irradiated cells released mitochondria-dependent intracellular factor(s) which could lead to bystander {gamma}-H2AX induction. In this paper, we used normal ({rho}{sup +}) and mtDNA-depleted ({rho}{sup 0}) human-hamster hybrid cells to investigate mitochondrial effects on the genotoxicity in bystander effect through medium transfer experiments. Through the detection of DNA double-strand breaks with {gamma}-H2AX, we found that the fraction of {gamma}-H2AX positive cells changed with time when irradiation conditioned cell medium (ICCM) were harvested. ICCM harvested from irradiated {rho}{sup +} cells at 10 min post-irradiation ({rho}{sup +} ICCM{sub 10min}) caused larger increases of bystander {gamma}-H2AX induction comparing to {rho}{sup 0} ICCM{sub 10min}, which only caused a slight increase of bystander {gamma}-H2AX induction. The {rho}{sup +} ICCM{sub 10min} could also result in the up-regulation of ROS production (increased by 35% at 10 min), while there was no significant increase in cells treated with {rho}{sup 0} ICCM{sub 10min}. We treated cells with dimethyl sulfoxide (DMSO), the scavenger of ROS, and quenched {gamma}-H2AX induction by {rho}{sup +} ICCM. Furthermore, after the medium had been transferred and the cells were continuously cultured for 7 days, we found significantly increased CD59{sup -} gene loci mutation (increased by 45.9%) and delayed cell death in the progeny of {rho}{sup +} ICCM-treated bystander cells. In conclusion, the work presented here suggested that up-regulation of the mitochondria-dependent ROS might be very important in mediating genotoxicity of bystander effects.

  1. Radioprotection of targeted and bystander cells by methylproamine

    Energy Technology Data Exchange (ETDEWEB)

    Burdak-Rothkamm, Susanne [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast (United Kingdom); Oxford University Hospitals, Cellular Pathology, Oxford (United Kingdom); Smith, Andrea; Lobachevsky, Pavel; Martin, Roger [Peter MacCallum Cancer Centre, Molecular Radiation Biology Laboratory, Melbourne (Australia); University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); Prise, Kevin M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast (United Kingdom)

    2014-09-23

    Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells. T98G glioma cells were treated with 15 μM methylproamine and exposed to {sup 137}Cs γ-ray/X-ray irradiation and He{sup 2+} microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay. Radioprotection of directly targeted T98G cells by methylproamine was observed for {sup 137}Cs γ-rays and X-rays but not for He{sup 2+} charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He{sup 2+} ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed. Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He{sup 2+} ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received. (orig.) [German] Radioprotektive Agenzien sind sowohl in der Strahlentherapie von Krebserkrankungen als auch im Strahlenschutz im Zusammenhang mit akzidenteller Exposition von Bedeutung. Methylproamine ist die Leitsubstanz einer Klasse von

  2. A Randomized Controlled Trial of a Multi-Dose Bystander Intervention Program Using Peer Education Theater

    Science.gov (United States)

    McMahon, Sarah; Winter, Samantha C.; Palmer, Jane E.; Postmus, Judy L.; Peterson, N. Andrew; Zucker, Sharon; Koenick, RuthAnne

    2015-01-01

    This article reports findings from a longitudinal, experimental evaluation of a peer education theater program, Students Challenging Realities and Educating Against Myths (SCREAM) Theater. This study examines the impact of SCREAM Theater on a range of bystander-related outcomes (i.e. bystander intentions, bystander efficacy, perception of friend…

  3. Promoting Prosocial Behaviors to Prevent Dating Violence among College Students: Evaluation of a Bystander Intervention

    Science.gov (United States)

    Borsky, Amanda E.

    2014-01-01

    The objective of this dissertation was to evaluate a bystander behavior program at the Jefferson College of Health Sciences (JCHS) in Roanoke, Virginia. Specifically, this dissertation examined the: (1) preliminary measurement properties of a newly developed bystander behavior intention scale; (2) impact of the bystander intervention at JCHS; and…

  4. LGBT Discrimination on Campus and Heterosexual Bystanders: Understanding Intentions to Intervene

    Science.gov (United States)

    Dessel, Adrienne B.; Goodman, Kevin D.; Woodford, Michael R.

    2017-01-01

    Discrimination targeting lesbian, gay, bisexual, and transgender (LGBT) students on college campuses occurs. Bystander intervention is important in supporting targeted students and improving campus climate for LGBT students. Peer-familiarity context (i.e., who the bystander knows in the situation) can play a role in bystander intervention, but…

  5. Adolescent Bystander Behavior in the School and Online Environments and the Implications for Interventions Targeting Cyberbullying

    Science.gov (United States)

    Patterson, Lisa J.; Allan, Alfred; Cross, Donna

    2017-01-01

    The aim of this study was to add to the emerging knowledge about the role of bystanders in cyberbullying. To differentiate online versus offline bystander behaviors, 292 Australian children (mean age = 15.2; female = 54.4%) reviewed hypothetical scenarios experimentally manipulated by bystander sex, relationship to target and perpetrator, and…

  6. Nitric oxide mediated bystander responses induced by microbeam targeted cells

    International Nuclear Information System (INIS)

    Shao, C.; Prise, K.M.; Folkard, M.; Michael, B.D.

    2003-01-01

    Considerable evidence has recently been accumulated in support of the existence of a 'bystander effect', which cells having received no irradiation show biological consequences from their vicinal irradiated cells. The application of microbeams is providing new insights into the radiation-induced bystander effect. The present study found that when a fraction of radioresistant human glioblastoma cells were individually targeted with a precise number of helium ions generated from the Gray Cancer Institute Charged Particle Microbeam, micronucleus (MN) induction significantly exceeded the expected value that was calculated from the number of MN observed when all of the cells were targeted assuming no bystander effect occurring. Even when only a single cell within a population was hit by one helium ion, the MN induction in the population could be increased by 16%. These results provide direct evidence of radiation-induced bystander effect. Moreover, MN was effectively induced in the unirradiated primary human fibroblasts and glioblastoma cells either co-cultured with irradiated cells or treated with the medium harvested from irradiated cells, indicating a signal molecule was produced from the irradiated cells. However, when c-PTIO, a nitric oxide (NO)-specific scavenger, was present in the medium during and after irradiation until MN analysis, the production of MN in all of the above cases was reduced to low levels. Consequently, NO plays an important role in the radiation-induced bystander effect

  7. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    Science.gov (United States)

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  8. Novel features of radiation-induced bystander signaling in Arabidopsis thaliana demonstrated using root micro-grafting

    Science.gov (United States)

    Wang, Ting; Li, Fanghua; Xu, Wei; Bian, Po; Wu, Yuejin; Wu, Lijun

    2012-01-01

    Radiation-induced bystander effects (RIBE) have been well demonstrated in whole organisms, as well as in single-cell culture models in vitro and multi-cellular tissues models in vitro, however, the underlying mechanisms remain unclear, including the temporal and spatial course of bystander signaling. The RIBE in vivo has been shown to exist in the model plant Arabidopsis thaliana (A. thaliana). Importantly, the unique plant grafting provides a delicate approach for studying the temporal and spatial course of bystander signaling in the context of whole plants. In our previous study, the time course of bystander signaling in plants has been well demonstrated using the root micro-grafting technique. In this study, we further investigated the temporal cooperation pattern of multiple bystander signals, the directionality of bystander signaling, and the effect of bystander tissues on the bystander signaling. The results showed that the bystander response could also be induced efficiently when the asynchronously generated bystander signals reached the bystander tissues in the same period, but not when they entered into the bystander tissues in an inversed sequence. The absence of bystander response in root-inversed grafting indicated that the bystander signaling along roots might be of directionality. The bystander signaling was shown to be independent of the bystander tissues. PMID:23072991

  9. Workplace mobbing: How the victim's coping behavior influences bystander responses.

    Science.gov (United States)

    Mulder, Roelie; Bos, Arjan E R; Pouwelse, Mieneke; van Dam, Karen

    2017-01-01

    Victims of workplace mobbing show diverse coping behavior. We investigated the impact of this behavior on bystander cognitions, emotions, and helping toward the victim, integrating coping literature with attribution theory. Adult part-time university students (N = 161) working at various organizations participated in a study with a 3(Coping: approach/avoidance/neutral) × 2(Gender Victim: male/female) × 2(Gender Bystander: male/female) design. Victims showing approach (vs. avoidance) coping were considered to be more self-reliant and less responsible for the continuation of the mobbing, and they elicited less anger. Continuation responsibility and self-reliance mediated the relationship between the victim's coping behavior and bystanders' helping intentions. Female (vs. male) participants reported more sympathy for the victim and greater willingness to help, and female (vs. male) victims elicited less anger. Theoretical and practical implications of the findings are discussed.

  10. Prenatal screening and genetics

    DEFF Research Database (Denmark)

    Alderson, P; Aro, A R; Dragonas, T

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...

  11. The association of maternal prenatal psychosocial stress with vascular function in the child at age 10-11 years: findings from the Avon longitudinal study of parents and children.

    Science.gov (United States)

    van Dijk, Aimée E; Dawe, Karen; Deanfield, John; Stronks, Karien; Gemke, Reinoud J B J; Vrijkotte, Tanja G M; Lawlor, Debbie A

    2014-09-01

    To investigate whether (1) maternal psychosocial stress (depression/anxiety) during pregnancy is associated with offspring vascular function and (2) whether any association differs depending on the gestational timing of exposure to stress. We also investigated whether any association is likely to be due to intrauterine mechanisms by (3) comparing with the association of paternal stress with offspring vascular function and (4) examining whether any prenatal association is explained by maternal postnatal stress. Associations were examined in a UK birth cohort, with offspring outcomes (systolic and diastolic blood pressure, SBP and DBP, endothelial function assessed by brachial artery flow-mediated dilatation (FMD); arterial stiffness assessed by carotid to radial pulse wave velocity (PWV), brachial artery distensibility (DC), and brachial artery diameter (BD) assessed at age 10-11 years (n = 4,318). Maternal depressive symptoms and anxiety were assessed at 18 and 32 weeks gestation and 8 months postnatally. Paternal symptoms were assessed at week 19. With the exception of DBP and BD, there were no associations of maternal depressive symptoms with any of the vascular outcomes. Maternal depressive and anxiety symptoms were associated with lower offspring DBP and wider BD, though the latter attenuated to the null with adjustment for confounding factors. Paternal symptoms were not associated with offspring outcomes. Maternal postnatal depressive symptoms were associated with lower offspring SBP. We found no evidence to support the hypothesis that maternal stress during pregnancy adversely affects offspring vascular function at age 10-12 years via intrauterine mechanisms. © Authors 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Role of connexin43 and ATP in long-range bystander radiation damage and oncogenesis in vivo.

    Science.gov (United States)

    Mancuso, M; Pasquali, E; Leonardi, S; Rebessi, S; Tanori, M; Giardullo, P; Borra, F; Pazzaglia, S; Naus, C C; Di Majo, V; Saran, A

    2011-11-10

    Ionizing radiation is a genotoxic agent and human carcinogen. Recent work has questioned long-held dogmas by showing that cancer-associated genetic alterations occur in cells and tissues not directly exposed to radiation, questioning the robustness of the current system of radiation risk assessment. In vitro, diverse mechanisms involving secreted soluble factors, gap junction intercellular communication (GJIC) and oxidative metabolism are proposed to mediate these indirect effects. In vivo, the mechanisms behind long-range 'bystander' responses remain largely unknown. Here, we investigate the role of GJIC in propagating radiation stress signals in vivo, and in mediating radiation-associated bystander tumorigenesis in mouse central nervous system using a mouse model in which intercellular communication is downregulated by targeted deletion of the connexin43 (Cx43) gene. We show that GJIC is critical for transmission of oncogenic radiation damage to the non-targeted cerebellum, and that a mechanism involving adenosine triphosphate release and upregulation of Cx43, the major GJIC constituent, regulates transduction of oncogenic damage to unirradiated tissues in vivo. Our data provide a novel hypothesis for transduction of distant bystander effects and suggest that the highly branched nervous system, similar to the vascular network, has an important role.

  13. Distance distribution of bystander effects in alpha-particle irradiated cell populations using a CR-39-based culture dish

    International Nuclear Information System (INIS)

    Gaillard, S.; Pusset, D.; Toledo, S.M. de; Azzam, E.I.; Fromm, M.

    2008-01-01

    Propagation of induced biological effects from irradiated to non-irradiated cells is known to occur in cell cultures exposed to low fluences of charged particles. These bystander effects are currently investigated using microbeam or non-microbeam (broad beams) irradiation techniques. Identification of the targeted and non-targeted bystander cells is critical to our understanding of mechanisms underlying such effects. We developed a novel cell culture dish where the base consists of a thin CR-39 sheet grafted on a thin polyethylene terephthalate (PET) foil. The validity of this device in identifying not only irradiated cells, but also the cellular compartment traversed by the particle track is described. We have optimized track etch parameters that do not interfere with measurement of induced biological endpoints under normal incident irradiation. Thus the culture dishes can be used to determine distance distributions for the propagation of induced biological effects from a hit cell to bystander cells. We describe the computer code developed to determine the distance distributions of propagated biological stress responses in normal human fibroblast cells exposed to very low fluences of alpha particles

  14. Childhood Maltreatment History, Posttraumatic Relational Sequelae, and Prenatal Care Utilization

    Science.gov (United States)

    Bell, Sue Anne; Seng, Julia

    2015-01-01

    Objective To test the hypothesis that childhood maltreatment history would be associated with inadequate prenatal care utilization. Design A post-hoc analysis of a prospective cohort study of the effects of post traumatic stress disorder (PTSD) on pregnancy outcomes. Setting Recruitment took place via prenatal clinics from three academic health systems in southeast Michigan. Participants This analysis included 467 diverse, nulliparous, English-speaking adult women expecting their first infants. Methods Data were gathered from structured telephone interviews at two time points in pregnancy and from prenatal medical records. Results Contrary to our hypothesis, history of childhood maltreatment was associated with better likelihood of using adequate prenatal care. Risk for inadequate prenatal care occurred in association with the posttraumatic stress and interpersonal sensitivity that can result from maltreatment, with low alliance with the maternity care provider, and with public insurance coverage. Prior mental health treatment was associated with using adequate prenatal care. Conclusion When childhood maltreatment survivors were resilient or have used mental health treatment, they were more likely to utilize adequate prenatal care. The maternity care relationship or service delivery model (e.g., no continuity of care) as well as structural factors may adversely affect utilization among PTSD-affected survivors. Since inadequate care was associated with adverse outcomes, further studies of these modifiable factors are warranted. PMID:23772546

  15. Blood pressure response to psychological stressors in adults after prenatal exposure to the Dutch famine

    NARCIS (Netherlands)

    Painter, Rebecca C.; de Rooij, Susanne R.; Bossuyt, Patrick M.; Phillips, David I.; Osmond, Clive; Barker, David J.; Bleker, Otto P.; Roseboom, Tessa J.

    2006-01-01

    OBJECTIVE: There is increasing evidence that restricted prenatal growth is associated with exaggerated blood pressure responses to stress. We investigated the effect of maternal undernutrition on the adult offspring's stress response. DESIGN: A historical cohort study. METHODS: We performed

  16. Ionizing radiation-induced bystander mutagenesis and adaptation: Quantitative and temporal aspects

    International Nuclear Information System (INIS)

    Zhang Ying; Zhou Junqing; Baldwin, Joseph; Held, Kathryn D.; Prise, Kevin M.; Redmond, Robert W.; Liber, Howard L.

    2009-01-01

    This work explores several quantitative aspects of radiation-induced bystander mutagenesis in WTK1 human lymphoblast cells. Gamma-irradiation of cells was used to generate conditioned medium containing bystander signals, and that medium was transferred onto naive recipient cells. Kinetic studies revealed that it required up to 1 h to generate sufficient signal to induce the maximal level of mutations at the thymidine kinase locus in the bystander cells receiving the conditioned medium. Furthermore, it required at least 1 h of exposure to the signal in the bystander cells to induce mutations. Bystander signal was fairly stable in the medium, requiring 12-24 h to diminish. Medium that contained bystander signal was rendered ineffective by a 4-fold dilution; in contrast a greater than 20-fold decrease in the cell number irradiated to generate a bystander signal was needed to eliminate bystander-induced mutagenesis. This suggested some sort of feedback inhibition by bystander signal that prevented the signaling cells from releasing more signal. Finally, an ionizing radiation-induced adaptive response was shown to be effective in reducing bystander mutagenesis; in addition, low levels of exposure to bystander signal in the transferred medium induced adaptation that was effective in reducing mutations induced by subsequent γ-ray exposures.

  17. Bystander Effects During Synchrotron Imaging Procedures?

    International Nuclear Information System (INIS)

    Schueltke, Elisabeth; Nikkhah, Guido; Bewer, Brian; Wysokinski, Tomasz; Chapman, Dean

    2010-01-01

    Using monochromatic beam and synchrotron phase-contrast technique at the biomedical beamline of the Italian synchrotron facility Elettra (SYRMEP), we have shown in a small animal model of malignant brain tumor that it is possible to obtain high-resolution images of very small tumors when they have developed from implanted tumor cells loaded with colloidal gold nanoparticles (GNP). All previous experiments were conducted in post-mortem samples. We have now designed a cell culture experiment to investigate the effects of synchrotron radiation with an energy and dose profile similar to that expected in our first in vivo imaging studies according to the protocol developed at SYRMEP.Materials and Methods: Culture flasks containing either gold-loaded or naieve C6 glioma cells were exposed to a dose of 0.5 Gy at 24 keV. The irradiated medium was aspirated and replaced with fresh growth medium. Twenty-four hours later this non-irradiated medium exposed to irradiated cells was aspirated, then added to non-irradiated C6 cells in order to investigate whether bystander effects are seen under the conditions of our image acquisition protocol. The irradiated medium was added to a number of other non-irradiated cell cultures. Cell counts were followed until 72 hrs after irradiation. Western blots were conducted with H2AX antibodies. This experiment was one of the first biomedical experiments conducted at BMIT, the new biomedical imaging and therapy beamline of the Canadian Light Source.Results: No significant differences in proliferation were seen between cells that were directly irradiated, exposed to irradiated medium or exposed to the non-irradiated 24-hr-medium from the irradiated cells. However, there was a tendency towards a higher number of double strand breaks in previously irradiated cells when they were exposed to non-irradiated medium that had been in contact with irradiated cells for 24 hrs.

  18. Bystander defibrillation for out-of-hospital cardiac arrest in Public vs Residential Locations

    DEFF Research Database (Denmark)

    Hansen, Steen Møller; Hansen, Carolina Malta; Folke, Fredrik

    2017-01-01

    Importance: Bystander-delivered defibrillation (hereinafter referred to as bystander defibrillation) of patients with out-of-hospital cardiac arrests (OHCAs) remains limited despite the widespread dissemination of automated external defibrillators (AEDs). Objective: To examine calendar changes...... in bystander defibrillation and subsequent survival according to a public or a residential location of the cardiac arrest after nationwide initiatives in Denmark to facilitate bystander-mediated resuscitative efforts, including bystander defibrillation. Design, Setting, and Participants: This nationwide study......, 2016. Exposures: Nationwide initiatives to facilitate bystander resuscitative efforts, including bystander defibrillation, consisted of resuscitation training of Danish citizens, dissemination of on-site AEDs, foundation of an AED registry linked to emergency medical dispatch centers, and dispatcher...

  19. Mechanism of bystander-blaming: defensive attribution, counterfactual thinking, and gender.

    Science.gov (United States)

    Levy, Inna; Ben-David, Sarah

    2015-01-01

    Contemporary victimology recognizes that an understanding of the mechanism of blaming requires a comprehensive approach that includes the victim, the offender, and the bystander. However, most of the existing research on blaming focuses on the victim and the offender, ignoring the issue of bystander-blaming. This study highlights the bystander and investigates bystander-blaming by exploring some theoretical explanations, including counterfactual thinking, defensive attribution, and gender differences. The study included 363 young male and female participants, who read vignettes describing the behavior of the victim and the bystander in a rape scenario and answered questions regarding bystander-blaming. The results show that both counterfactual thinking and defensive attribution play a role in bystander-blaming. This article addresses the theoretical and practical implications of these findings. © The Author(s) 2013.

  20. Predicting Improvement After a Bystander Program for the Prevention of Sexual and Dating Violence.

    Science.gov (United States)

    Hines, Denise A; Palm Reed, Kathleen M

    2015-07-01

    Although evidence suggests that bystander prevention programs are promising interventions for decreasing sexual violence and dating violence on college campuses, there have been no studies to date evaluating moderators of bystander program effectiveness. The current study evaluates whether different demographic characteristics, attitudes, knowledge, and behaviors at pretest predict change over a 6-month follow-up for students who participated in a bystander prevention program. Participants in the three assessments (pretest, posttest, 6-month follow-up) included 296 college students who were mandated to attend a bystander program during their first year orientation. Analyses showed that with few exceptions, the bystander program worked best for students who were most at risk given their pretest demographics and levels of attitudes condoning dating violence and sexual violence, bystander efficacy, and bystander behaviors. Results are discussed in terms of suggestions for future research. © 2014 Society for Public Health Education.

  1. Incoming College Students' Bystander Behaviors to Prevent Sexual Violence

    Science.gov (United States)

    McMahon, Sarah; Banyard, Victoria L.; McMahon, Sheila M.

    2015-01-01

    Evaluations of bystander intervention education programs demonstrate that this approach results in students' increased willingness to intervene in prosocial ways to prevent sexual violence (e.g., Moynihan, Banyard, Arnold, Eckstein, & Stapleton, 2010). These programs often focus on first-year college students, though theories and research on…

  2. A Qualitative Exploration of Cyber-Bystanders and Moral Engagement

    Science.gov (United States)

    Price, Deborah; Green, Deborah; Spears, Barbara; Scrimgeour, Margaret; Barnes, Alan; Geer, Ruth; Johnson, Bruce

    2014-01-01

    Studies have found that moral disengagement plays a significant role in the continuation of bullying situations (Bonanno, 2005); however, the moral stance of cyber-bystanders--those who witness online bullying--is not yet clear. While research into traditional face-to-face bullying reported that peers would probably or certainly intervene to…

  3. Delayed innocent bystander cell death following hypoxia in Caenorhabditis elegans.

    Science.gov (United States)

    Sun, C-L; Kim, E; Crowder, C M

    2014-04-01

    After hypoxia, cells may die immediately or have a protracted course, living or dying depending on an incompletely understood set of cell autonomous and nonautonomous factors. In stroke, for example, some neurons are thought to die from direct hypoxic injury by cell autonomous primary mechanisms, whereas other so called innocent bystander neurons die from factors released from the primarily injured cells. A major limitation in identifying these factors is the inability of current in vivo models to selectively target a set of cells for hypoxic injury so that the primarily injured cells and the innocent bystanders are clearly delineated. In order to develop such a model, we generated transgenic Caenorhabditis elegans strains where 2-3% of somatic cells were made selectively sensitive to hypoxia. This was accomplished by cell type-specific wild-type rescue in either pharyngeal myocytes or GABAergic neurons of a hypoxia resistance-producing translation factor mutation. Surprisingly, hypoxic targeting of these relatively small subsets of non-essential cells produced widespread innocent bystander cell injury, behavioral dysfunction and eventual organismal death. The hypoxic injury phenotypes of the myocyte or neuron sensitized strains were virtually identical. Using this model, we show that the C. elegans insulin receptor/FOXO transcription factor pathway improves survival when activated only after hypoxic injury and blocks innocent bystander death.

  4. Friends, strangers, and bystanders: Informal practices of sexual assault intervention.

    Science.gov (United States)

    Wamboldt, Alexander; Khan, Shamus R; Mellins, Claude Ann; Hirsch, Jennifer S

    2018-05-07

    Sexual assault is a part of many students' experiences in higher education. In U.S. universities, one in four women and one in ten men report being sexually assaulted before graduation. Bystander training programmes have been shown to modestly reduce campus sexual assault. Like all public health interventions, however, they have unintended social consequences; this research examines how undergraduate men on one campus understand bystander interventions and how those understandings shape their actual practices. We draw on ethnographic data collected between August 2015 and January 2017 at Columbia University and Barnard College. Our findings show that university training and an earnest desire to be responsible lead many men to intervene in possible sexual assaults. However, students' gendered methods target more socially vulnerable and socially distant men while protecting popular men and those to whom they are socially connected. Students' actual bystander practices thus reproduce social hierarchies in which low prestige may or may not be connected to actual risks of sexual assault. These results suggest that understanding intragroup dynamics and social hierarchies is essential to assault prevention in universities and that students' actions as bystanders may be effective at preventing assaults in some circumstances but may lead to new risks of sexual assault.

  5. Bystander Obligations at the Domestic and International Level Compared

    NARCIS (Netherlands)

    Spijkers, Otto|info:eu-repo/dai/nl/328454559

    2014-01-01

    This article examines whether States have a legal obligation to assist victims of serious breaches of fundamental obligations owed to the international community as a whole. This so-called ‘bystander State responsibility’ is compared with a similar legal obligation to assist victims at the domestic

  6. Bystander Reaction to Women Fighting: Developing a Theory of Intervention

    Science.gov (United States)

    Lowe, Robert D.; Levine, Mark; Best, Rachel M.; Heim, Derek

    2012-01-01

    This article explores accounts of bystanders to female-on-female public violence. Group interviews with participants in the night-time economy are carried out. Whereas men tend to respond to the discussion topic of female-on-female violence with laughter, this laughter reveals ambivalence and discomfort as much as amusement. Men seem to negotiate…

  7. Bystanders' Supportive and Passive Responses to Cyberaggression

    Science.gov (United States)

    Machackova, Hana; Dedkova, Lenka; Sevcikova, Anna; Cerna, Alena

    2018-01-01

    Bystanders in cyberaggression can support the victim, join the aggressor, or remain passive. We examined how supportive and passive adolescent Czech cyberbystanders (N = 443, ages 12-18) differ in terms of individual characteristics, emotional responses, and contextual factors. The most substantial distinguishing factor between the two groups…

  8. Reactive oxygen species and nitric oxide signaling in bystander cells.

    Science.gov (United States)

    Jella, Kishore Kumar; Moriarty, Roisin; McClean, Brendan; Byrne, Hugh J; Lyng, Fiona M

    2018-01-01

    It is now well accepted that radiation induced bystander effects can occur in cells exposed to media from irradiated cells. The aim of this study was to follow the bystander cells in real time following addition of media from irradiated cells and to determine the effect of inhibiting these signals. A human keratinocyte cell line, HaCaT cells, was irradiated (0.005, 0.05 and 0.5 Gy) with γ irradiation, conditioned medium was harvested after one hour and added to recipient bystander cells. Reactive oxygen species, nitric oxide, Glutathione levels, caspase activation, cytotoxicity and cell viability was measured after the addition of irradiated cell conditioned media to bystander cells. Reactive oxygen species and nitric oxide levels in bystander cells treated with 0.5Gy ICCM were analysed in real time using time lapse fluorescence microscopy. The levels of reactive oxygen species were also measured in real time after the addition of extracellular signal-regulated kinase and c-Jun amino-terminal kinase pathway inhibitors. ROS and glutathione levels were observed to increase after the addition of irradiated cell conditioned media (0.005, 0.05 and 0.5 Gy ICCM). Caspase activation was found to increase 4 hours after irradiated cell conditioned media treatment (0.005, 0.05 and 0.5 Gy ICCM) and this increase was observed up to 8 hours and there after a reduction in caspase activation was observed. A decrease in cell viability was observed but no major change in cytotoxicity was found in HaCaT cells after treatment with irradiated cell conditioned media (0.005, 0.05 and 0.5 Gy ICCM). This study involved the identification of key signaling molecules such as reactive oxygen species, nitric oxide, glutathione and caspases generated in bystander cells. These results suggest a clear connection between reactive oxygen species and cell survival pathways with persistent production of reactive oxygen species and nitric oxide in bystander cells following exposure to irradiated cell

  9. Investigations into the bystander effect: signal versus response

    International Nuclear Information System (INIS)

    Vines, A.M.; Seymour, C.B.; Mothersill, C.E.

    2003-01-01

    The bystander effect is the general term used to describe the effects seen in cells or tissue that have never been directly irradiated, but display similar symptoms to those that have. Some of these symptoms include reduced cell survival, chromosomal aberrations, and increased apoptosis. This investigation aims to explore the signal produced by certain cell and tissue types, and the relationship this has with the subsequent response. The goal is to elucidate whether the reduction in cell survival frequently seen in response to the bystander effect is determined by the signal produced or the response of the cell type. Firstly, a matrix design experiment was set up using 3 cell lines. Each cell line was irradiated to produce ICCM (Irradiated Cell Conditioned Medium), which was in turn used to treat all cell lines in the study. Medium transfer is carried out within cell lines, (ICCM from CHO onto CHO cells) and between cell lines (ICCM from CHO onto HPV-G cells). In the second set of experiments, tissue samples from male Wister rats were used to generate ITCM (Irradiated Tissue Conditioned Medium). This medium was then tested on a cell line with an established response to the bystander effect. As an extension to these two experimental protocols, both ICCM and ITCM were used to investigate if there is calcium flux in the cells as a response to the bystander medium. This has recently been shown to be an early response to the bystander signal. Results indicate that it is the signal produced by the irradiated cells that determine the overall effect of the bystander signal, and not the response of the cells expose to it. CHO-K1 cells treated with autologous ICCM show a 16.2% drop in cell survival. However, when this cell line is treated with HPV-G ICCM, it shows a 36.5% drop in survival. HPV-G cells treated with autologous medium display a similar response to this, with a 41.1% drop in survival, though when treated with CHO-K1 ICCM, the drop in survival is 22.9%. This

  10. Prenatal Care: Second Trimester Visits

    Science.gov (United States)

    ... Pregnancy week by week During the second trimester, prenatal care includes routine lab tests and measurements of your ... too. By Mayo Clinic Staff The goal of prenatal care is to ensure that you and your baby ...

  11. Prenatal Care: Third Trimester Visits

    Science.gov (United States)

    ... Pregnancy week by week During the third trimester, prenatal care might include vaginal exams to check the baby's position. By Mayo Clinic Staff Prenatal care is an important part of a healthy pregnancy, ...

  12. Prenatal Genetic Counseling (For Parents)

    Science.gov (United States)

    ... Videos for Educators Search English Español Prenatal Genetic Counseling KidsHealth / For Parents / Prenatal Genetic Counseling What's in ... can they help your family? What Is Genetic Counseling? Genetic counseling is the process of: evaluating family ...

  13. Multi-College Bystander Intervention Evaluation for Violence Prevention.

    Science.gov (United States)

    Coker, Ann L; Bush, Heather M; Fisher, Bonnie S; Swan, Suzanne C; Williams, Corrine M; Clear, Emily R; DeGue, Sarah

    2016-03-01

    The 2013 Campus Sexual Violence Elimination Act requires U.S. colleges to provide bystander-based training to reduce sexual violence, but little is known about the efficacy of such programs for preventing violent behavior. This study provides the first multiyear evaluation of a bystander intervention's campus-level impact on reducing interpersonal violence victimization and perpetration behavior on college campuses. First-year students attending three similarly sized public university campuses were randomly selected and invited to complete online surveys in the spring terms of 2010-2013. On one campus, the Green Dot bystander intervention was implemented in 2008 (Intervention, n=2,979) and two comparison campuses had no bystander programming at baseline (Comparison, n=4,132). Data analyses conducted in 2014-2015 compared violence rates by condition over the four survey periods. Multivariable logistic regression was used to estimate violence risk on Intervention relative to Comparison campuses, adjusting for demographic factors and time (2010-2013). Interpersonal violence victimization rates (measured in the past academic year) were 17% lower among students attending the Intervention (46.4%) relative to Comparison (55.7%) campuses (adjusted rate ratio=0.83; 95% CI=0.79, 0.88); a similar pattern held for interpersonal violence perpetration (25.5% in Intervention; 32.2% in Comparison; adjusted rate ratio=0.79; 95% CI=0.71, 0.86). Violence rates were lower on Intervention versus Comparison campuses for unwanted sexual victimization, sexual harassment, stalking, and psychological dating violence victimization and perpetration (pSexual Violence Elimination Act bystander training requirements. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

  14. Timely bystander CPR improves outcomes despite longer EMS times.

    Science.gov (United States)

    Park, Gwan Jin; Song, Kyoung Jun; Shin, Sang Do; Lee, Kyung Won; Ahn, Ki Ok; Lee, Eui Jung; Hong, Ki Jeong; Ro, Young Sun

    2017-08-01

    This study aimed to determine the impact of bystander CPR on clinical outcomes in patients with increasing response time from collapse to EMS response. A population-based observational study was conducted in patients with witnessed out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology from 2012 to 2014. The time interval from collapse to CPR by EMS providers was categorized into quartile groups: fastest group (bystander CPR and the time interval from collapse to CPR by EMS providers. A total of 15,354 OHCAs were analyzed. Bystander CPR was performed in 8591 (56.0%). Survival to hospital discharge occurred in 1632 (10.6%) and favorable neurological outcome in 996 (6.5%). In an interaction model of bystander CPR, compared to the fastest group, adjusted odds ratios (AORs) (95% CIs) for survival to discharge were 0.89 (0.66-1.20) in the fast group, 0.76 (0.57-1.02) in the late group, and 0.52 (0.37-0.73) in the latest group. For favorable neurological outcome, AORs were 1.12 (0.77-1.62) in the fast group, 0.90 (0.62-1.30) in the late group, 0.59 (0.38-0.91) in the latest group. The survival from OHCA decreases as the ambulance response time increases. The increase in mortality and worsening neurologic outcomes appear to be mitigated in those patients who receive bystander CPR. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Preventing Interpersonal Violence on College Campuses: The Effect of One Act Training on Bystander Intervention.

    Science.gov (United States)

    Alegría-Flores, Kei; Raker, Kelli; Pleasants, Robert K; Weaver, Mark A; Weinberger, Morris

    2015-05-22

    Sexual assault, stalking, dating violence, and intimate partner violence, herein collectively termed interpersonal violence (IV), are public health problems affecting 20% to 25% of female college students. Currently, One Act is one of the few IV prevention training programs at universities that teach students bystander skills to intervene in low- and high-risk IV situations. The objectives of this study were 1) to evaluate One Act's effects on date rape attitudes and behaviors, and bystanders' confidence, willingness to help, and behavior, and 2) to compare the effects on bystander skills between One Act and Helping Advocates for Violence Ending Now (HAVEN), an IV response training program with similar participants. Data were collected over 2 years, before and after One Act and HAVEN trainings. We measured outcomes with four scales: College Date Rape Attitudes and Behaviors, Bystander Confidence, Willingness to Help, and Bystander Behavior. The analysis compared within- and between-group mean differences in scale scores pre- and post-trainings using linear mixed models. One Act showed improvements for date rape attitudes and behaviors (p trainings' effects on bystander willingness to help and behavior had similar patterns but were not statistically significant. We found a larger positive impact on bystander confidence among students who participated in the bystander prevention training compared with the response training. Further research is needed to improve the measures for bystander behavior and measure the bystander trainings' larger impact on the community. © The Author(s) 2015.

  16. Predicting High-School Students' Bystander Behavior in Simulated Dating Violence Situations.

    Science.gov (United States)

    Jouriles, Ernest N; Rosenfield, David; Yule, Kristen; Sargent, Kelli S; McDonald, Renee

    2016-03-01

    Dating violence among adolescents is associated with a variety of negative health consequences for victims. Bystander programs are being developed and implemented with the intention of preventing such violence, but determinants of high-school students' responsive bystander behavior remain unclear. The present study examines hypothesized determinants of high-school students' bystander behavior in simulated situations of dating violence. Participants were 80 high-school students who completed self-reports of hypothesized determinants of bystander behavior (responsibility, efficacy, and perceived benefits for intervening) at a baseline assessment. A virtual-reality paradigm was used to observationally assess bystander behavior at 1-week and 6-month assessments after baseline. Efficacy for intervening was positively associated with observed bystander behavior at the 1-week and 6-month assessments. Moreover, efficacy predicted bystander behavior over and above feelings of responsibility and perceived benefits for intervening. Contrary to our predictions, neither responsibility nor perceived benefits for intervening were associated with observed bystander behavior. This research advances our understanding of determinants of bystander behavior for high-school students and can inform prevention programming for adolescents. The study also introduces an innovative way to assess high-school students' bystander behavior. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  17. Role of ROS-mediated autophagy in radiation-induced bystander effect of hepatoma cells.

    Science.gov (United States)

    Wang, Xiangdong; Zhang, Jianghong; Fu, Jiamei; Wang, Juan; Ye, Shuang; Liu, Weili; Shao, Chunlin

    2015-05-01

    Autophagy plays a crucial role in cellular response to ionizing radiation, but it is unclear whether autophagy can modulate radiation-induced bystander effect (RIBE). Here, we investigated the relationship between bystander damage and autophagy in human hepatoma cells of HepG2. HepG2 cells were treated with conditioned medium (CM) collected from 3 Gy γ-rays irradiated hepatoma HepG2 cells for 4, 12, or 24 h, followed by the measurement of micronuclei (MN), intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and protein expressions of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 in the bystander HepG2 cells. In some experiments, the bystander HepG2 cells were respectively transfected with LC3 small interfering RNA (siRNA), Beclin-1 siRNA or treated with 1% dimethyl sulfoxide (DMSO). Additional MN and mitochondrial dysfunction coupled with ROS were induced in the bystander cells. The expressions of protein markers of autophagy, LC3-II/LC3-I and Beclin-1, increased in the bystander cells. The inductions of bystander MN and overexpressions of LC3 and Beclin-1 were significantly diminished by DMSO. However, when the bystander cells were transfected with LC3 siRNA or Beclin-1 siRNA, the yield of bystander MN was significantly enhanced. The elevated ROS have bi-functions in balancing the bystander effects. One is to cause MN and the other is to induce protective autophagy.

  18. Bystander Interventions for Sexual Assault and Dating Violence on College Campuses: Are We Putting Bystanders in Harm's Way?

    Science.gov (United States)

    Witte, Tricia H.; Casper, Deborah M.; Hackman, Christine L.; Mulla, Mazheruddin M.

    2017-01-01

    Objective: The present study investigated the well-being of bystanders who witness and intervene in sexual assault and dating violence situations on campus. Participants: Participants were 321 young men and women from a large university in the southeastern United States. Methods: Participants completed a survey at the end of the Spring semester of…

  19. No relationship between risk of schizophrenia and prenatal exposure to stress during the Six-Day War or Yom Kippur War in Israel.

    Science.gov (United States)

    Selten, Jean-Paul; Cantor-Graae, Elizabeth; Nahon, Daniella; Levav, Itzhak; Aleman, André; Kahn, René S

    2003-09-01

    Maternal stress during pregnancy is a possible risk factor for schizophrenia in the offspring. Using data from the Israel Psychiatric Registry we examined the impact of wars in Israel. Retrospective birth cohort study. Relative risks for cohorts exposed to Six-Day War and Yom Kippur War were 0.98 (95% CI: 0.85-1.13) and 1.00 (0.86-1.16). The evidence for maternal stress as a risk factor for schizophrenia remains insufficient.

  20. A pivotal role of the jasmonic acid signal pathway in mediating radiation-induced bystander effects in Arabidopsis thaliana.

    Science.gov (United States)

    Wang, Ting; Xu, Wei; Deng, Chenguang; Xu, Shaoxin; Li, Fanghua; Wu, Yuejin; Wu, Lijun; Bian, Po

    Although radiation-induced bystander effects (RIBE) in Arabidopsis thaliana have been well demonstrated in vivo, little is known about their underlying mechanisms, particularly with regard to the participating signaling molecules and signaling pathways. In higher plants, jasmonic acid (JA) and its bioactive derivatives are well accepted as systemic signal transducers that are produced in response to various environmental stresses. It is therefore speculated that the JA signal pathway might play a potential role in mediating radiation-induced bystander signaling of root-to-shoot. In the present study, pretreatment of seedlings with Salicylhydroxamic acid, an inhibitor of lipoxigenase (LOX) in JA biosynthesis, significantly suppressed RIBE-mediated expression of the AtRAD54 gene. After root irradiation, the aerial parts of A. thaliana mutants deficient in JA biosynthesis (aos) and signaling cascades (jar1-1) showed suppressed induction of the AtRAD54 and AtRAD51 genes and TSI and 180-bp repeats, which have been extensively used as endpoints of bystander genetic and epigenetic effects in plants. These results suggest an involvement of the JA signal pathway in the RIBE of plants. Using the root micro-grafting technique, the JA signal pathway was shown to participate in both the generation of bystander signals in irradiated root cells and radiation responses in the bystander aerial parts of plants. The over-accumulation of endogenous JA in mutant fatty acid oxygenation up-regulated 2 (fou2), in which mutation of the Two Pore Channel 1 (TPC1) gene up-regulates expression of the LOX and allene oxide synthase (AOS) genes, inhibited RIBE-mediated expression of the AtRAD54 gene, but up-regulated expression of the AtKU70 and AtLIG4 genes in the non-homologous end joining (NHEJ) pathway. Considering that NHEJ is employed by plants with increased DNA damage, the switch from HR to NHEJ suggests that over-accumulation of endogenous JA might enhance the radiosensitivity of plants

  1. Space radiation-induced bystander effect: kinetics of biologic responses, mechanisms, and significance of secondary radiations

    International Nuclear Information System (INIS)

    Gonon, Geraldine

    2011-01-01

    Widespread evidence indicates that exposure of cell cultures to a particles results in significant biological changes in both the irradiated and non-irradiated bystander cells in the population. The induction of non-targeted biological responses in cell cultures exposed to low fluences of high charge (Z) and high energy (E) particles is relevant to estimates of the health risks of space radiation and to radiotherapy. Here, we investigated the mechanisms underlying the induction of stressful effects in confluent normal human fibroblast cultures exposed to low fluences of 1000 MeV/u iron ions (linear energy transfer (LET) 151 keV/μm), 600 MeV/u silicon ions (LET 50 keV/μm) or 290 MeV/u carbon ions (LET 13 keV/μm). We compared the results with those obtained in cell cultures exposed, in parallel, to low fluences of 0.92 MeV/u a particles (LET 109 keV/μm). Induction of DNA damage, changes in gene expression, protein carbonylation and lipid peroxidation during 24 h after exposure of confluent cultures to mean doses as low as 0.2 cGy of iron or silicon ions strongly supported the propagation of stressful effects from irradiated to bystander cells. At a mean dose of 0.2 cGy, only 1 and 3 % of the cells would be targeted through the nucleus by an iron or silicon ion, respectively. Within 24 h post-irradiation, immunoblot analyses revealed significant increases in the levels of phospho-TP53 (serine 15), p21Waf1 (also known as CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation. The magnitude of the responses suggested participation of non-targeted cells in the response. Furthermore, when the irradiated cell populations were subcultured in fresh medium shortly after irradiation, greater than expected increases in the levels of these markers were also observed during 24 h. Together, the results imply a rapidly propagated and persistent bystander effect. In situ analyses in confluent cultures showed 53BP1 foci formation, a marker of DNA damage, in

  2. Hatchlings of the Marine Turtle Lepidochelys olivacea Display Signs of Prenatal Stress at Emergence after Being Incubated in Man-Made Nests: A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Ma. A. Herrera-Vargas

    2017-12-01

    Full Text Available Egg translocation and incubation in man-made nests (MMN are common conservation practices through marine turtle hatcheries worldwide. These measures have been associated with reduced hatching rates, altered hatchling sex ratio, fetal dysmorphic anatomical features, and feeble hatchlings health. Previous studies have shown that MMN and natural nests (NN provide different incubatory conditions. Therefore, incubatory challenges imposed by MMN conditions on fetal development could induce stress responses affecting hatchlings functional morphology later on life. There is no evidence of incubatory stress associated with conservation measures in turtle fetuses or hatchlings. Thus, in this paper we tested the hypothesis that MMN incubation exposes turtle fetuses to stressing conditions. Given that the hypothalamic-pituitary-interrenal axis begins functioning by day 11 of incubation in reptiles, our experiments explored the effects of incubatory conditions, rather than those associated with translocation, on fetal stress responses. We showed that Lepidochelys olivacea hatchlings incubated in MMN displayed reduced body weight, hypertrophic inter-renal glands, testicular hypotrophy and hypotrophic dorso-medial cortical pyramidal neurons, when compared with hatchlings emerging from NN. Furthermore, MMN hatchlings had higher serum levels of corticosterone at emergence, and displayed an attenuated acute stress response after traversing the beach. Therefore, the relocation of nests to protect them could negatively impact the health and survival of sea turtles. Thus, this action should only be undertaken when no alternative is available.

  3. Self-protective function of post-conflict bystander affiliation in mandrills.

    Directory of Open Access Journals (Sweden)

    Gabriele Schino

    Full Text Available BACKGROUND: Affiliative interactions exchanged between victims of aggression and individuals not involved in the original aggression (bystanders have been observed in various species. Three hypothetical functions have been proposed for these interactions: consolation, self-protection and substitute reconciliation, but data to test them are scanty. METHODOLOGY/PRINCIPAL FINDINGS: We conducted post-conflict and matched control observations on a captive group of mandrills (Mandrillus sphinx. We found that victims often redirected aggression to bystanders, that they received most affiliation from those bystanders that were frequently the target of redirection, and that bystander affiliation reduced the likelihood of redirection. Bystander affiliation did not reduce the victim's distress (as measured by its scratching rates and was not received primarily from kin/friends. Finally, bystander affiliation did not reduce the likelihood of renewed aggression from the original aggressor. CONCLUSIONS/SIGNIFICANCE: These results provide support for the self-protection hypothesis but not for the consolation and substitute reconciliation hypotheses.

  4. Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

    Science.gov (United States)

    Ghosh, Somnath; Ghosh, Anu; Krishna, Malini

    2015-12-01

    The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. MiR-21 is involved in radiation-induced bystander effects

    Science.gov (United States)

    Xu, Shuai; Ding, Nan; Pei, Hailong; Hu, Wentao; Wei, Wenjun; Zhang, Xurui; Zhou, Guangming; Wang, Jufang

    2014-01-01

    Radiation-induced bystander effects are well-established phenomena, in which DNA damage responses are induced not only in the directly irradiated cells but also in the non-irradiated bystander cells through intercellular signal transmission. Recent studies hint that bystander effects are possibly mediated via small non-coding RNAs, especially microRNAs. Thus, more details about the roles of microRNA in bystander effects are urgently needed to be elucidated. Here we demonstrated that bystander effects were induced in human fetal lung MRC-5 fibroblasts through medium-mediated way by different types of radiation. We identified a set of differentially expressed microRNAs in the cell culture medium after irradiation, among which the up-regulation of miR-21 was further verified with qRT-PCR. In addition, we found significant upregulation of miR-21 in both directly irradiated cells and bystander cells, which was confirmed by the expression of miR-21 precursor and its target genes. Transfection of miR-21 mimics into non-irradiated MRC-5 cells caused bystander-like effects. Taken together, our data reveals that miR-21 is involved in radiation-induced bystander effects. Elucidation of such a miRNA-mediated bystander effect is of utmost importance in understanding the biological processes related to ionizing radiation and cell-to-cell communication. PMID:25483031

  6. Students as Prosocial Bystanders to Sexual Assault: Demographic Correlates of Intervention Norms, Intentions, and Missed Opportunities.

    Science.gov (United States)

    Hoxmeier, Jill C; Acock, Alan C; Flay, Brian R

    2017-01-01

    Sexual assault is a major public health issue. Bystander engagement programs are becoming widely used to combat sexual assault on college campuses. The purpose of this study was to examine students' intervention norms, intentions, opportunities, and behaviors as bystanders to sexual assault. Undergraduate students ( N = 779) completed the Sexual Assault Bystander Behavior Questionnaire in the fall of 2014. The t tests revealed differences in students' intervention norms, intentions, opportunities, and missed opportunities based on sex, race/ethnicity, athletic participation, and fraternity/sorority membership. The findings support the use of additional measures to assess bystander behavior and to identify student subpopulations that may benefit from programs aimed at increasing prosocial intervention.

  7. Influence of catechins on bystander responses in CHO cells induced by alpha-particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Law, Y.L.; Wong, T.P.W. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Yu, K.N. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)], E-mail: peter.yu@cityu.edu.hk

    2010-04-15

    In this work, we studied alpha-particle induced and medium-mediated bystander effects in Chinese hamster ovary (CHO) cells through micronucleus (MN) assay. We showed that signal transduction from irradiated cells to bystander cells occur within a short time after irradiation. We then studied the effects of ROS (reactive oxygen species)-scavenging catechins in the medium before irradiation. We observed decreases in the percentage of bystander cells with MN formation and thus proved the protection effect of catechins on bystander cells from radiation.

  8. Contribution of bystander effects in radiation induced genotoxicity

    International Nuclear Information System (INIS)

    Zhou, H.; Persaud, R.; Gillispie, J.; Randers-Pehrson, G.; Hei, T.K.; Suzuki, Masao

    2005-01-01

    The controversial use of a linear, no threshold extrapolation model for low dose risk assessment is based on the accepted dogma that the deleterious effects of ionizing radiation such as mutagenesis and carcinogenesis are attributable mainly to direct damage to DNA. However, this extrapolation was challenged by the recent reports on the bystander phenomenon. The bystander effect contributes to this debate by implying that the biological effects of low doses, where not all cells are traversed by a charged particle, are amplified by the transfer of factors to un-irradiated neighbors. This interested phenomenon implies that a linear extrapolation of risks from high to low doses may underestimate rather than over estimate low dose risks. Together with some radiation-induced phenomena such as adaptive response and genomic instability, the radiobiological response at low doses is likely to be a complex interplay among many factors. (author)

  9. Bystander effects on mammalian cells induced by carbon ions

    International Nuclear Information System (INIS)

    Wang Jufang; Zhao Jing; Ma Qiufeng; Chinese Academy of Sciences, Beijing; Li Weijian; Zhou Guangming; Dang Bingrong; Mao Limin; Feng Yan

    2004-01-01

    Bystander effects on unirradiated V79 cells were observed by irradiated conditioned medium (ICM) method and co-cultured with carbon-ion-irradiated V79 cells. The results showed that the colony formation efficiency of unirradiated cells is obviously decreased by ICM. After co-culture with carbon-ion-irradiated cells for some time, the colony formation efficiency of co-cultured cells was lower than expected results assuming no bystander effects. The micronucleus frequency and hprt gene mutation rate was almost the same as expected results. Cytotoxic factor(s), which was effective for cell growth but not for micronucleus and mutation on unirradiated cells, might be released by irradiated cells. (authors)

  10. Attitudes toward the performance of bystander cardiopulmonary resuscitation in Japan.

    Science.gov (United States)

    Taniguchi, Takumi; Omi, Wataru; Inaba, Hideo

    2007-10-01

    Early initiation of bystander cardiopulmonary resuscitation (CPR) improves the chances of successful resuscitation and survival. The importance of bystander CPR is attracting more interest, and there has been an increase in attendance at CPR training courses in Japan. However, there have been few reports regarding Japanese attitudes toward the performance of bystander CPR. The present study was performed to identify current Japanese attitudes toward bystander CPR compared to our previous study performed in 1998. Between February and March 2006, participants were asked about their willingness to perform CPR in five varying scenarios, i.e., performing CPR on a stranger, a trauma patient, a child, an elderly person, and a relative, and CPR techniques consisting of chest compression plus mouth-to-mouth ventilation (CC plus MMV) versus chest compression only (CC only). A total of 4223 individuals (male 50%) completed the questionnaire, including high school students, teachers, emergency medical technicians (EMTs), medical nurses, and medical students. About 70% of the subjects had experienced CPR training more than once. Only 10-30% of high school students, teachers, and health care providers reported willingness to perform CC plus MMV, especially on a stranger or trauma victim. In contrast, 70-100% of these subjects reported willingness to perform CC only, which was the same as in our previous study. The reasons for the unwillingness among laypeople to perform CC plus MMV were inadequate knowledge and/or doubt regarding whether they could perform the techniques effectively, while health care providers reported a fear contracting of a disease. Most laypeople and health care providers are unlikely to perform CC plus MMV, especially on a stranger or trauma victim, but are more likely to perform CC only, as also found in our previous study in 1998. These findings suggest that MMV training should be de-emphasised and the awareness of CC alone should be emphasised because

  11. Cytokines shape chemotherapy-induced and 'bystander' senescence

    Czech Academy of Sciences Publication Activity Database

    Hodný, Zdeněk; Hubáčková, Soňa; Bartek, Jiří

    2010-01-01

    Roč. 2, č. 2 (2010), s. 375-376 ISSN 1945-4589 R&D Projects: GA ČR GA204/08/1418; GA ČR GA301/08/0353 Institutional research plan: CEZ:AV0Z50520514 Keywords : bystander cellular senescence * cytokines * PML Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.964, year: 2010

  12. Bystander Helping Behavior in Response to Workplace Bullying

    OpenAIRE

    Hellemans, Catherine; Dal Cason, Davide; Casini, Annalisa

    2017-01-01

    This research examines the role of colleagues in workplace bullying. While colleagues could often intervene to support the victim or stop the situation, passive behaviors and non-intervention are more frequent. The bystander effect highlighted by Latané and Darley (1970) has been studied in the context of school bullying and sexual harassment, but only rarely in the context of workplace bullying. We tested the impact of the belief in a just world for others, self-efficacy, perceived severity,...

  13. The Prenatal Care at School Program

    Science.gov (United States)

    Griswold, Carol H.; Nasso, Jacqueline T.; Swider, Susan; Ellison, Brenda R.; Griswold, Daniel L.; Brooks, Marilyn

    2013-01-01

    School absenteeism and poor compliance with prenatal appointments are concerns for pregnant teens. The Prenatal Care at School (PAS) program is a new model of prenatal care involving local health care providers and school personnel to reduce the need for students to leave school for prenatal care. The program combines prenatal care and education…

  14. Host and Viral Factors in HIV-Mediated Bystander Apoptosis

    Science.gov (United States)

    Garg, Himanshu; Joshi, Anjali

    2017-01-01

    Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis. PMID:28829402

  15. Identifiable images of bystanders extracted from corneal reflections.

    Directory of Open Access Journals (Sweden)

    Rob Jenkins

    Full Text Available Criminal investigations often use photographic evidence to identify suspects. Here we combined robust face perception and high-resolution photography to mine face photographs for hidden information. By zooming in on high-resolution face photographs, we were able to recover images of unseen bystanders from reflections in the subjects' eyes. To establish whether these bystanders could be identified from the reflection images, we presented them as stimuli in a face matching task (Experiment 1. Accuracy in the face matching task was well above chance (50%, despite the unpromising source of the stimuli. Participants who were unfamiliar with the bystanders' faces (n = 16 performed at 71% accuracy [t(15 = 7.64, p<.0001, d = 1.91], and participants who were familiar with the faces (n = 16 performed at 84% accuracy [t(15 = 11.15, p<.0001, d = 2.79]. In a test of spontaneous recognition (Experiment 2, observers could reliably name a familiar face from an eye reflection image. For crimes in which the victims are photographed (e.g., hostage taking, child sex abuse, reflections in the eyes of the photographic subject could help to identify perpetrators.

  16. An investigation of bystander effects in Schizosaccharomyces pombe

    International Nuclear Information System (INIS)

    DeVeaux, L.C.; Wells, D.P.; Durtschi, L.S.; Reda, M.; Frujinoiu, C.; Harmon, F.

    2003-01-01

    Full text: 'Bystander' effects have been documented in various mammalian cell types and appear to act by two distinct mechanisms. One response requires a functional gap-junction. A non gap-junction-mediated response has also been observed in human cell lines, indicating release of a signaling factor. No analogous response has been investigated in unicellular organisms. Given that DNA damage signaling pathways are present in simple eukaryotes, we investigated bystander signaling effects using a single-celled organism, the fission yeast Schizosaccharomyces pombe. This organism may provide a much simpler model system than higher eukaryotic cells for studying these effects. We measured survival and mutation rate in an unirradiated culture after exposure to an irradiated culture. These two cultures were mixed immediately after irradiation, and any signaling factor that was produced had direct and continuous access to the unirradiated cells during subsequent cell divisions. The irradiated culture was from a multiply auxotrophic strain, whereas the unirradiated culture was from a prototrophic strain. Surviving colonies of the unirradiated culture were thus easily distinguished from those arising from irradiated cells. Mutation rates were measured as forward mutation to 2-deoxyglucose resistance. We have investigated bystander effects with electron and gamma dose from 6 to 20 MeV electron linacs. We varied electron beam energies, dose rates and temporal distributions of dose. The importance of this research stems from the fundamental evolutionary significance of cell signaling of any kind in unicellular systems, representing a major step toward the evolution of multi-cellular states

  17. [Prenatal care in Latin America].

    Science.gov (United States)

    Buekens, P; Hernández, P; Infante, C

    1990-01-01

    Available data on the coverage of prenatal care in Latin America were reviewed. In recent years, only Bolivia had a coverage of prenatal care of less than 50 per cent. More than 90 per cent of pregnant women received prenatal care in Chile, Cuba, the Dominican Republic, and Puerto Rico. Prenatal care increased between the 1970 and 1980 in the Dominican Republic, Ecuador, Guatemala, Honduras, Mexico, and Peru. The coverage of prenatal care decreased in Bolivia and Colombia. The mean number of visits increased in Cuba and Puerto Rico. The increase of prenatal care in Guatemala and Honduras is due to increased care by traditional birth attendants, compared to the role of health care institutions. We compared the more recent data on tetanus immunization of pregnant women to the more recent data on prenatal care. The rates of tetanus immunization are always lower than the rates of prenatal care attendance, except in Costa Rica. The rates of tetanus immunization was less than half as compared to the rates of prenatal care in Bolivia, Guatemala, and Peru. To improve the content of prenatal care should be an objective complementary to the increase of the number of attending women.

  18. Bully, Bullied, Bystander...and beyond

    Science.gov (United States)

    Coloroso, Barbara

    2011-01-01

    Bullying is seldom the only factor in a teenager's suicide. Often, mental illness and family stresses are involved. But bullying does plainly play a role in many cases. These students feel that they have no way out of the pain heaped on them by their tormentors so they turn the violence inward with a tragic and final exit. Bullying involves three…

  19. Bystander Defibrillation for Out-of-Hospital Cardiac Arrest in Public vs Residential Locations.

    Science.gov (United States)

    Hansen, Steen Møller; Hansen, Carolina Malta; Folke, Fredrik; Rajan, Shahzleen; Kragholm, Kristian; Ejlskov, Linda; Gislason, Gunnar; Køber, Lars; Gerds, Thomas A; Hjortshøj, Søren; Lippert, Freddy; Torp-Pedersen, Christian; Wissenberg, Mads

    2017-05-01

    Bystander-delivered defibrillation (hereinafter referred to as bystander defibrillation) of patients with out-of-hospital cardiac arrests (OHCAs) remains limited despite the widespread dissemination of automated external defibrillators (AEDs). To examine calendar changes in bystander defibrillation and subsequent survival according to a public or a residential location of the cardiac arrest after nationwide initiatives in Denmark to facilitate bystander-mediated resuscitative efforts, including bystander defibrillation. This nationwide study identified 18 688 patients in Denmark with first-time OHCA from June 1, 2001, to December 31, 2012, using the Danish Cardiac Arrest Registry. Patients had a presumed cardiac cause of arrest that was not witnessed by emergency medical services personnel. Data were analyzed from April 1, 2015, to December 10, 2016. Nationwide initiatives to facilitate bystander resuscitative efforts, including bystander defibrillation, consisted of resuscitation training of Danish citizens, dissemination of on-site AEDs, foundation of an AED registry linked to emergency medical dispatch centers, and dispatcher-assisted guidance of bystander resuscitation efforts. The proportion of patients who received bystander defibrillation according to the location of the cardiac arrest and their subsequent 30-day survival. Of the 18 688 patients with OHCAs (67.8% men and 32.2% women; median [interquartile range] age, 72 [62-80] years), 4783 (25.6%) had a cardiac arrest in a public location and 13 905 (74.4%) in a residential location. The number of registered AEDs increased from 141 in 2007 to 7800 in 2012. The distribution of AED location was consistently skewed in favor of public locations. Bystander defibrillation increased in public locations from 3 of 245 (1.2%; 95% CI, 0.4%-3.5%) in 2001 to 78 of 510 (15.3%; 95% CI, 12.4%-18.7%) in 2012 (P bystander defibrillation increased in public locations from 8.3% (95% CI, 1.5%-35.4%) in 2001/2002 to 57

  20. Radiation-induced bystander effects in cultured human stem cells.

    Directory of Open Access Journals (Sweden)

    Mykyta V Sokolov

    2010-12-01

    Full Text Available The radiation-induced "bystander effect" (RIBE was shown to occur in a number of experimental systems both in vitro and in vivo as a result of exposure to ionizing radiation (IR. RIBE manifests itself by intercellular communication from irradiated cells to non-irradiated cells which may cause DNA damage and eventual death in these bystander cells. It is known that human stem cells (hSC are ultimately involved in numerous crucial biological processes such as embryologic development; maintenance of normal homeostasis; aging; and aging-related pathologies such as cancerogenesis and other diseases. However, very little is known about radiation-induced bystander effect in hSC. To mechanistically interrogate RIBE responses and to gain novel insights into RIBE specifically in hSC compartment, both medium transfer and cell co-culture bystander protocols were employed.Human bone-marrow mesenchymal stem cells (hMSC and embryonic stem cells (hESC were irradiated with doses 0.2 Gy, 2 Gy and 10 Gy of X-rays, allowed to recover either for 1 hr or 24 hr. Then conditioned medium was collected and transferred to non-irradiated hSC for time course studies. In addition, irradiated hMSC were labeled with a vital CMRA dye and co-cultured with non-irradiated bystander hMSC. The medium transfer data showed no evidence for RIBE either in hMSC and hESC by the criteria of induction of DNA damage and for apoptotic cell death compared to non-irradiated cells (p>0.05. A lack of robust RIBE was also demonstrated in hMSC co-cultured with irradiated cells (p>0.05.These data indicate that hSC might not be susceptible to damaging effects of RIBE signaling compared to differentiated adult human somatic cells as shown previously. This finding could have profound implications in a field of radiation biology/oncology, in evaluating radiation risk of IR exposures, and for the safety and efficacy of hSC regenerative-based therapies.

  1. Vincristine-induced bystander effect in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Testi, Serena; Azzarà, Alessia; Giovannini, Caterina; Lombardi, Sara [Unità di Genetica, Dipartimento di Biologia, Pisa University, Via Derna 1, 56126 Pisa (Italy); Piaggi, Simona [Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Pisa University, Via Savi 10, 56126 Pisa (Italy); Facioni, Maria Sole [Unità di Genetica, Dipartimento di Biologia, Pisa University, Via Derna 1, 56126 Pisa (Italy); Scarpato, Roberto, E-mail: roberto.scarpato@unipi.it [Unità di Genetica, Dipartimento di Biologia, Pisa University, Via Derna 1, 56126 Pisa (Italy); Research Center of Nutraceuticals and Food for Health, University of Pisa, Pisa (Italy)

    2016-07-15

    Highlights: • We studied whether or not vincristine induced a bystander response in human lymphocytes. • Vincristine significantly increased MN frequencies in mononucleated recipient cells. • ROS or soluble proteins (IL-32 and TGF-β) may account for the observed response. - Abstract: Bystander effect is a known radiobiological effect, widely described using ionizing radiations and which, more recently, has also been related to chemical mutagens. In this study, we aimed to assess whether or not a bystander response can be induced in cultured human peripheral lymphocytes by vincristine, a chemotherapeutic mutagen acting as spindle poison, and by mitomycin-C, an alkylating agent already known to induce this response in human lymphoblastoid cells. Designing a modified ad hoc protocol for the cytokinesis blocked micronucleus (MN) assay, we detected the presence of a dose-dependent bystander response in untreated cultures receiving the conditioned medium (CM) from mitomycin-C (MMC) or vincristine (VCR) treated cultures. In the case of MMC, MN frequencies, expressed as micronucleated binucleates, were: 13.5 ± 1.41 at 6 μM, 22 ± 2.12 at 12 μM or 28.25 ± 5.13 at 15 μM vs. a control value of 4.75 ± 1.59. MN levels for VCR, expressed as micronucleated mononucleates were: 2.75 ± 0.88 at 0.0 μM, 27.25 ± 2.30 at 0.4 μM, 46.25 ± 1.94 at 0.8 μM, 98.25 ± 7.25 at 1.6 μM. To verify that no mutagen residual was transferred to recipient cultures together with the CM, we evaluated MN levels in cultures receiving the medium immediately after three washings following the chemical treatment (unconditioned medium). We further confirmed these results using a cell-mixing approach where untreated lymphocytes were co-cultured with donor cells treated with an effect-inducing dose of MMC or VCR. A distinct production pattern of both reactive oxygen species and soluble mediator proteins by treated cells may account for the differences observed in the manifestation of the

  2. Vincristine-induced bystander effect in human lymphocytes

    International Nuclear Information System (INIS)

    Testi, Serena; Azzarà, Alessia; Giovannini, Caterina; Lombardi, Sara; Piaggi, Simona; Facioni, Maria Sole; Scarpato, Roberto

    2016-01-01

    Highlights: • We studied whether or not vincristine induced a bystander response in human lymphocytes. • Vincristine significantly increased MN frequencies in mononucleated recipient cells. • ROS or soluble proteins (IL-32 and TGF-β) may account for the observed response. - Abstract: Bystander effect is a known radiobiological effect, widely described using ionizing radiations and which, more recently, has also been related to chemical mutagens. In this study, we aimed to assess whether or not a bystander response can be induced in cultured human peripheral lymphocytes by vincristine, a chemotherapeutic mutagen acting as spindle poison, and by mitomycin-C, an alkylating agent already known to induce this response in human lymphoblastoid cells. Designing a modified ad hoc protocol for the cytokinesis blocked micronucleus (MN) assay, we detected the presence of a dose-dependent bystander response in untreated cultures receiving the conditioned medium (CM) from mitomycin-C (MMC) or vincristine (VCR) treated cultures. In the case of MMC, MN frequencies, expressed as micronucleated binucleates, were: 13.5 ± 1.41 at 6 μM, 22 ± 2.12 at 12 μM or 28.25 ± 5.13 at 15 μM vs. a control value of 4.75 ± 1.59. MN levels for VCR, expressed as micronucleated mononucleates were: 2.75 ± 0.88 at 0.0 μM, 27.25 ± 2.30 at 0.4 μM, 46.25 ± 1.94 at 0.8 μM, 98.25 ± 7.25 at 1.6 μM. To verify that no mutagen residual was transferred to recipient cultures together with the CM, we evaluated MN levels in cultures receiving the medium immediately after three washings following the chemical treatment (unconditioned medium). We further confirmed these results using a cell-mixing approach where untreated lymphocytes were co-cultured with donor cells treated with an effect-inducing dose of MMC or VCR. A distinct production pattern of both reactive oxygen species and soluble mediator proteins by treated cells may account for the differences observed in the manifestation of the

  3. Do Sexual Assault Bystander Interventions Change Men's Intentions? Applying the Theory of Normative Social Behavior to Predicting Bystander Outcomes.

    Science.gov (United States)

    Mabry, Amanda; Turner, Monique Mitchell

    2016-01-01

    The high prevalence of sexual assault on college campuses has led to the implementation of health communication programs to prevent sexual assault. A few novel programs focus on primary prevention by targeting social norms related to gender and masculinity among men through bystander intervention. Guided by the theory of normative social behavior, this study sought to examine the relative effect of campaigns communicating positive versus negative injunctive norms and the interaction between exposure to such campaign messages and perceived descriptive norms and relevant cognitive moderators (e.g., outcome expectations, injunctive norms, group identity, ego involvement) among men. A 2 (high/low descriptive norms) × 2 (high/low moderator) × 3 (public service announcement) independent groups quasi-experimental design (N = 332) was used. Results indicated that messages communicating positive injunctive norms were most effective among men who were least likely to engage in bystander intervention. Furthermore, descriptive norms played a significant role in behavioral intentions, such that those with stronger norms were more likely to report intentions to engage in bystander behaviors in the future. Similarly, the moderators of aspiration, injunctive norms, social approval, and ego involvement had a significant positive effect on behavioral intentions. These findings have important implications for future message design strategy and audience segmentation.

  4. Human prenatal diagnosis

    International Nuclear Information System (INIS)

    Filkins, K.; Russo, R.J.

    1985-01-01

    The multiauthor text is written as a ''guide to rationalize and clarify certain aspects of diagnosis, general counseling and intervention'' for ''health professionals who provide care to pregnant women.'' The text is not aimed at the ultrasonographer but rather at the physicians who are clinically responsible for patient management. Chapters of relevance to radiologists include an overview of prenatal screening and counseling, diagnosis of neural tube defects, ultrasonographic (US) scanning of fetal disorders in the first and second trimesters of pregnancy, US scanning in the third trimester, multiple gestation and selective termination, fetal echo and Doppler studies, and fetal therapy. Also included are overviews of virtually all currently utilized prenatal diagnostic techniques including amniocentesis, fetal blood sampling, fetoscopy, recombinant DNA detection of hemoglobinopathies, chorionic villus sampling, embryoscopy, legal issues, and diagnosis of Mendelian disorders by DNA analysis

  5. Breaking bad news in prenatal medicine: a literature review.

    Science.gov (United States)

    Luz, Rita; George, Astrid; Spitz, Elisabeth; Vieux, Rachel

    2017-02-01

    The diagnosis of a fetal anomaly in perinatal medicine forces expectant parents and healthcare providers to face the difficult process of breaking bad news. This exploratory literature review was aimed at providing a medical and psychological view of the psychological experience in expectant parents and physicians in the context of prenatal diagnosis of a fetal anomaly. An exploratory search of PubMed and PsycINFO/PsycARTICLES databases performed by an interdisciplinary team composed of a physician and psychologists. Search terms were: prenatal diagnosis AND bad news; prenatal diagnosis AND psychological consequences; prenatal diagnosis AND psychological sequelae; prenatal diagnosis AND fetal abnormality. The processing of selected articles followed a standardised five-step procedure. A total of 860 articles were screened of which 32 were retained for analysis. Four main themes emerged from the explanatory content analysis: (1) parents' subjective experience; (2) physicians' subjective experience; (3) encounters between expectant parents and professionals; and (4) ethical challenges in breaking bad news in prenatal medicine. Expectant parents go through a complex and multidimensional experience when the diagnosis of a fetal anomaly is disclosed. Simultaneously, physicians consider breaking bad news as a very stressful event and are poorly prepared in this regard. A better knowledge of factors underlying psychological adjustment of the parental dyad and on the subjective experience of physicians delivering these diagnoses could enable better adaptation for both patients and professionals.

  6. Prenatal testosterone and stuttering.

    Science.gov (United States)

    Montag, Christian; Bleek, Benjamin; Breuer, Svenja; Prüss, Holger; Richardt, Kirsten; Cook, Susanne; Yaruss, J Scott; Reuter, Martin

    2015-01-01

    The prevalence of stuttering is much higher in males compared to females. The biological underpinnings of this skewed sex-ratio is poorly understood, but it has often been speculated that sex hormones could play an important role. The present study investigated a potential link between prenatal testosterone and stuttering. Here, an indirect indicator of prenatal testosterone levels, the Digit Ratio (2D:4D) of the hand, was used. As numerous studies have shown, hands with more "male" characteristics (putatively representing greater prenatal testosterone levels) are characterized by a longer ring finger compared to the index finger (represented as a lower 2D:4D ratio) in the general population. We searched for differences in the 2D:4D ratios between 38 persons who stutter and 36 persons who do not stutter. In a second step, we investigated potential links between the 2D:4D ratio and the multifaceted symptomatology of stuttering, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES), in a larger sample of 44 adults who stutter. In the first step, no significant differences in the 2D:4D were observed between individuals who stutter and individuals who do not stutter. In the second step, 2D:4D correlated negatively with higher scores of the OASES (representing higher negative experiences due to stuttering), and this effect was more pronounced for female persons who stutter. The findings indicate for the first time that prenatal testosterone may influence individual differences in psychosocial impact of this speech disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Prenatal stressors in rodents: Effects on behavior

    Directory of Open Access Journals (Sweden)

    Marta Weinstock

    2017-02-01

    Full Text Available The current review focuses on studies in rodents published since 2008 and explores possible reasons for any differences they report in the effects of gestational stress on various types of behavior in the offspring. An abundance of experimental data shows that different maternal stressors in rodents can replicate some of the abnormalities in offspring behavior observed in humans. These include, anxiety, in juvenile and adult rats and mice, assessed in the elevated plus maze and open field tests and depression, detected in the forced swim and sucrose-preference tests. Deficits were reported in social interaction that is suggestive of pathology associated with schizophrenia, and in spatial learning and memory in adult rats in the Morris water maze test, but in most studies only males were tested. There were too few studies on the novel object recognition test at different inter-trial intervals to enable a conclusion about the effect of prenatal stress and whether any deficits are more prevalent in males. Among hippocampal glutamate receptors, NR2B was the only subtype consistently reduced in association with learning deficits. However, like in humans with schizophrenia and depression, prenatal stress lowered hippocampal levels of BDNF, which were closely correlated with decreases in hippocampal long-term potentiation. In mice, down-regulation of BDNF appeared to occur through the action of gene-methylating enzymes that are already increased above controls in prenatally-stressed neonates. In conclusion, the data obtained so far from experiments in rodents lend support to a physiological basis for the neurodevelopmental hypothesis of schizophrenia and depression.

  8. Genes Underlying Positive Influence Of Prenatal Environmental ...

    African Journals Online (AJOL)

    Genes Underlying Positive Influence Of Prenatal Environmental Enrichment And ... Prenatal environmental enrichment (EE) has been proven to positively affect but ... Conclusion: The negative-positive prenatal effect could contribute to altered ...

  9. Conceptualizing the Engaging Bystander Approach to Sexual Violence Prevention on College Campuses

    Science.gov (United States)

    McMahon, Sarah; Postmus, Judy L.; Koenick, Ruth Anne

    2011-01-01

    Bystander intervention offers promise as a sexual violence prevention tool for student affairs administrators on college campuses, but the conceptualization and definition of the approach is in its infancy and needs further development. In an effort to emphasize the potential role of bystanders in the primary prevention of sexual violence, we put…

  10. Sorority Women's and Fraternity Men's Rape Myth Acceptance and Bystander Intervention Attitudes

    Science.gov (United States)

    Bannon, R. Sean; Brosi, Matthew W.; Foubert, John D.

    2013-01-01

    Sorority women and fraternity men are more likely than other students to be survivors and perpetrators of sexual assault, respectively. The present study examined sorority and fraternity members' rape myth acceptance, bystander efficacy, and bystander willingness to help in potential sexual assault situations. Sorority women were more rejecting of…

  11. Effects of a Rape Awareness Program on College Women: Increasing Bystander Efficacy and Willingness to Intervene

    Science.gov (United States)

    Foubert, John D.; Langhinrichsen-Rohling, Jennifer; Brasfield, Hope; Hill, Brent

    2010-01-01

    An experimental study evaluated the efficacy of a sexual assault risk-reduction program on 279 college women that focused on learning characteristics of male perpetrators and teaching bystander intervention techniques. After seeing The Women's Program, participants reported significantly greater bystander efficacy and significantly greater…

  12. Role of iNOS in Bystander Signaling Between Macrophages and Lymphoma Cells

    International Nuclear Information System (INIS)

    Ghosh, Somnath; Maurya, Dharmendra Kumar; Krishna, Malini

    2008-01-01

    Purpose: The present report describes the bystander effects of radiation between similar and dissimilar cells and the role of iNOS in such communication. Materials and Methods: EL-4 and RAW 264.7 cells were exposed to 5 Gy γ-irradiation. The medium from irradiated cells was transferred to unirradiated cells. Results: Irradiated EL-4 cells as well as those cultured in the presence of medium from γ-irradiated EL-4 cells showed an upregulation of NF-κB, iNOS, p53, and p21/waf1 genes. The directly irradiated and the bystander EL-4 cells showed an increase in DNA damage, apoptosis, and NO production. Bystander signaling was also found to exist between RAW 264.7 (macrophage) and EL-4 (lymphoma) cells. Unstimulated or irradiated RAW 264.7 cells did not induce bystander effect in unirradiated EL-4 cells, but LPS stimulated and irradiated RAW 264.7 cells induced an upregulation of NF-κB and iNOS genes and increased the DNA damage in bystander EL-4 cells. Treatment of EL-4 or RAW 264.7 cells with L-NAME significantly reduced the induction of gene expression and DNA damage in the bystander EL-4 cells, whereas treatment with cPTIO only partially reduced the induction of gene expression and DNA damage in the bystander EL-4 cells. Conclusions: It was concluded that active iNOS in the irradiated cells was essential for bystander response

  13. Engaging Upstanders: Class-Wide Approach to Promoting Positive Bystander Behavior

    Science.gov (United States)

    Wood, Laura; Smith, Jennifer; Varjas, Kris; Meyers, Joel

    2016-01-01

    Positive and supportive bystander behaviors have been associated with decreases in the frequency and negative impact of bullying. This article addresses the design, implementation, evaluation, and continuation of a classroom-based intervention that promotes positive bystander behaviors. The Engaging Upstanders curriculum was piloted with two…

  14. Individual Motivations and Characteristics Associated with Bystander Intervention during Bullying Episodes among Children and Youth

    Science.gov (United States)

    Cappadocia, M. Catherine; Pepler, Debra; Cummings, Joanne G.; Craig, Wendy

    2012-01-01

    The aim of the current study was to explore bystander experiences during bullying episodes among children and youth attending a residential summer camp by investigating rates of witnessing and intervention, as well as individual motivations and characteristics associated with bystander intervention. The majority of children had witnessed bullying…

  15. What Would You Do? Strategies for Bystander Intervention to Prevent Sexual Violence by College Students

    Science.gov (United States)

    McMahon, Sarah; Hoffman, Melanie Lowe; McMahon, Sheila M.; Zucker, Sharon; Koenick, Ruth Anne

    2013-01-01

    Bystander education is an increasingly utilized strategy for addressing sexual assault prevention and intervention on U.S. college campuses. Given the paramount importance of peers among college students, what types of pro-social bystander interventions do students themselves deem feasible in the campus context? Drawing on self-reports from…

  16. Action Research Evaluation of Bystander Intervention Training Created by Munche, Stern, and O'Brien

    Science.gov (United States)

    Shiflet, Jacqueline H.

    2013-01-01

    This qualitative, appreciative inquiry study was an examination of bystander intervention as related to sexual assault in the military. The purpose of the study was to examine how military personnel and Department of Defense civilian employees reflecting diverse backgrounds perceived the effectiveness of bystander intervention training and sexual…

  17. Susceptibility to bystander DNA damage is influenced by replication and transcriptional activity

    Science.gov (United States)

    Dickey, Jennifer S.; Baird, Brandon J.; Redon, Christophe E.; Avdoshina, Valeriya; Palchik, Guillermo; Wu, Junfang; Kondratyev, Alexei; Bonner, William M.; Martin, Olga A.

    2012-01-01

    Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA. The DNA in transcription complexes also has a more open structure, and hence may be susceptible to bystander DSB formation from single strand lesions. To examine whether transcription predisposes non-replicating cells to bystander effect-induced DNA DSBs, we examined two types of primary cells that exhibit high levels of transcription in the absence of replication, rat neurons and human lymphocytes. We found that non-replicating bystander cells with high transcription rates exhibited substantial levels of DNA DSBs, as monitored by γ-H2AX foci formation. Additionally, as reported in proliferating cells, TGF-β and NO were found to mimic bystander effects in cell populations lacking DNA synthesis. These results indicate that cell vulnerability to bystander DSB damage may result from transcription as well as replication. The findings offer insights into which tissues may be vulnerable to bystander genomic destabilization in vivo. PMID:22941641

  18. Roles of Fatalism and Parental Support in the Relationship between Bullying Victimization and Bystander Behaviors

    Science.gov (United States)

    Li, Yiqiong; Chen, Peter Y.; Chen, Fu-Li; Wu, Wen-Chi

    2015-01-01

    This article examines how past bullied victims engage two types of bystander behaviors (defender and outsider) when they witness bullying situations.We also investigate if fatalism mediates the relationship between past victimization and two bystander behaviors. Finally, we test if parental support moderates the relationship between fatalism and…

  19. Booze, Bars, and Bystander Behavior: People Who Consumed Alcohol Help Faster in the Presence of Others

    NARCIS (Netherlands)

    van Bommel, Marco; van Prooijen, Jan-Willem; Elffers, Henk; van Lange, Paul A.M.

    2016-01-01

    People help each other less often and less quickly when bystanders are present. In this paper, we propose that alcohol consumption could attenuate or reverse this so-called bystander effect. Alcohol impairs people cognitively and perceptually, leading them to think less about the presence of others

  20. Quality of bystander cardiopulmonary resuscitation during real-life out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Gyllenborg, Tore; Granfeldt, Asger; Lippert, Freddy

    2017-01-01

    BACKGROUND: Cardiopulmonary resuscitation (CPR) can increase survival in out-of-hospital cardiac arrest (OHCA). However, little is known about bystander CPR quality in real-life OHCA. AIM: To describe bystander CPR quality based on automated external defibrillator (AED) CPR process data during OH...

  1. On Standby? A Comparison of Online and Offline Witnesses to Bullying and Their Bystander Behaviour

    Science.gov (United States)

    Quirk, Roslynn; Campbell, Marilyn

    2015-01-01

    Given their ubiquitous presence as witnesses to school-yard bullying, the role of the "bystander" has been studied extensively. The prevalence and behaviour of bystanders to "cyberbullying," however, is less understood. In an anonymous, school-based questionnaire, 716 secondary school students from South-East Queensland…

  2. Debriefing bystanders of out-of-hospital cardiac arrest is valuable.

    Science.gov (United States)

    Møller, Thea Palsgaard; Hansen, Carolina Malta; Fjordholt, Martin; Pedersen, Birgitte Dahl; Østergaard, Doris; Lippert, Freddy K

    2014-11-01

    To explore the concept of debriefing bystanders after participating in an out-of-hospital cardiac arrest resuscitation attempt including (1) bystanders' most commonly addressed reactions after participating in a resuscitation attempt when receiving debriefing from medical dispatchers; (2) their perception of effects of receiving debriefing and (3) bystanders' recommendations for a systematic debriefing concept. Qualitative study based on telephone debriefing to bystanders and interviews with bystanders who received debriefing. Data was analyzed using the phenomenological approach. Six themes emerged from analysis of debriefing audio files: (1) identification of OHCA; (2) emotional and perceptual experience with OHCA; (3) collaboration with healthcare professionals; (4) patients outcome; (5) coping with the experience and (6) general reflections. When evaluating the concept, bystanders expressed positive short term effect of receiving debriefing and a retention of this effect after two months. Recommendations for a future debriefing concept were given. Debriefing by emergency medical dispatchers to OHCA bystanders stimulates reflection, positively influencing the ability to cope with the emotional reactions and the cognitive perception of own performance and motivates improvement of CPR skills. Importantly, it increases confidence to provide CPR in the future. Implementation of telephone debriefing to bystanders at Emergency Medical Dispatch Centres is a low complexity and a low cost intervention though the logistic challenges have to be considered. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. Prenatal origins of hypertension induced by gestational undernutrition or environmental chemical exposure

    Science.gov (United States)

    Epidemiological studies have shown that babies of low birth weight have high blood pressure (BP) as children and adults, suggesting prenatal cardiovascular programming. This programming has been attributed to factors including undernutrition and maternal stress during pregnancy. ...

  4. Stress

    Science.gov (United States)

    ... can be life-saving. But chronic stress can cause both physical and mental harm. There are at least three different types of stress: Routine stress related to the pressures of work, family, and other daily responsibilities Stress brought about ...

  5. HSP: bystander antigen in atopic diseases?

    Directory of Open Access Journals (Sweden)

    Joost A Aalberse

    2012-05-01

    Full Text Available Over the last years insight in the complex interactions between innate and adaptive immunity in the regulation of an inflammatory response has increased enormously. This has revived the interest in stress proteins; proteins that are expressed during cell stress. As these proteins can attract and trigger an immunological response they can act as important mediators in this interaction. In this respect, of special interest are proteins that may act as modulators of both innate and adaptive immunity. Heat shock proteins (HSPs are stress proteins that have these, and more, characteristics. More than two decades of studies on HSPs has revealed that they are part of intrinsic, natural mechanisms that steer inflammation. This has provoked comprehensive explorations of the role of HSPs in various human inflammatory diseases.Most studies have focused on classical autoimmune diseases. This has led to the development of clinical studies with HSPs that have shown promise in Phase II/III clinical trials. Remarkably, only very little is yet known of the role of HSPs in atopic diseases. In allergic disease a number of studies have investigated the possibility that allergen-specific regulatory T cell (Treg function is defective in individuals with allergic diseases. This raises the question whether methods can be identified to improve the Treg repertoire. Studies from other inflammatory diseases have suggested HSPs may have such a beneficial effect on the T cell repertoire. Based on the immune mechanisms of atopic diseases, in this review we will argue that, as in other human inflammatory conditions, understanding immunity to HSPs is likely also relevant for atopic diseases. Specifically, we will discuss why certain HSPs such as HSP60 connect the immune response to environmental antigens with regulation of the inflammatory response.Thus they provide a molecular link that may eventually even help to better understand the immune pathological basis of the hygiene

  6. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

    Science.gov (United States)

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-26

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

  7. Getting angry matters: Going beyond perspective taking and empathic concern to understand bystanders' behavior in bullying.

    Science.gov (United States)

    Pozzoli, Tiziana; Gini, Gianluca; Thornberg, Robert

    2017-12-01

    The present study examined the relations between different empathic dimensions and bystanders' behavior in bullying. Specifically, the indirect effects of empathic concern and perspective taking via empathic anger on defending and passive bystanding were tested in a sample of Italian young adolescents (N = 398; M age  = 12 years, 3 months, 47.2% girls). Path analysis confirmed the direct and indirect effects, via empathic anger, of empathic concern and perspective taking on bystanders' behavior, with the exception of the direct association between perspective taking and passive bystanding that was not significant. Our findings suggest that considering empathic anger together with empathic concern and perspective taking could help researchers to better understand the links between empathic dispositions and bystanders' behavior in bullying. Copyright © 2017. Published by Elsevier Ltd.

  8. Temporally distinct response of irradiated normal human fibroblasts and their bystander cells to energetic heavy ions

    International Nuclear Information System (INIS)

    Hamada, Nobuyuki; Ni, Meinan; Funayama, Tomoo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

    2008-01-01

    Ionizing radiation-induced bystander effects have been documented for a multitude of endpoints such as mutations, chromosome aberrations and cell death, which arise in nonirradiated bystander cells having received signals from directly irradiated cells; however, energetic heavy ion-induced bystander response is incompletely characterized. To address this, we employed precise microbeams of carbon and neon ions for targeting only a very small fraction of cells in confluent fibroblast cultures. Conventional broadfield irradiation was conducted in parallel to see the effects in irradiated cells. Exposure of 0.00026% of cells led to nearly 10% reductions in the clonogenic survival and twofold rises in the apoptotic incidence regardless of ion species. Whilst apoptotic frequency increased with time up to 72 h postirradiation in irradiated cells, its frequency escalated up to 24 h postirradiation but declined at 48 h postirradiation in bystander cells, indicating that bystander cells exhibit transient commitment to apoptosis. Carbon- and neon-ion microbeam irradiation similarly caused almost twofold increments in the levels of serine 15-phosphorylated p53 proteins, irrespective of whether 0.00026, 0.0013 or 0.0066% of cells were targeted. Whereas the levels of phosphorylated p53 were elevated and remained unchanged at 2 h and 6 h postirradiation in irradiated cells, its levels rose at 6 h postirradiation but not at 2 h postirradiation in bystander cells, suggesting that bystander cells manifest delayed p53 phosphorylation. Collectively, our results indicate that heavy ions inactivate clonogenic potential of bystander cells, and that the time course of the response to heavy ions differs between irradiated and bystander cells. These induced bystander responses could be a defensive mechanism that minimizes further expansion of aberrant cells

  9. A Role for Bioelectric Effects in the Induction of Bystander Signals by Ionizing Radiation?

    Science.gov (United States)

    Mothersill, C.; Moran, G.; McNeill, F.; Gow, M.D.; Denbeigh, J.; Prestwich, W.; Seymour, C.B.

    2007-01-01

    The induction of “bystander effects” i.e. effects in cells which have not received an ionizing radiation track, is now accepted but the mechanisms are not completely clear. Bystander effects following high and low LET radiation exposure are accepted but mechanisms are still not understood. There is some evidence for a physical component to the signal. This paper tests the hypothesis that bioelectric or biomagnetic phenomena are involved. Human immortalized skin keratinocytes and primary explants of mouse bladder and fish skin, were exposed directly to ionizing radiation or treated in a variety of bystander protocols. Exposure of cells was conducted by shielding one group of flasks using lead, to reduce the dose below the threshold of 2mGy 60Cobalt gamma rays established for the bystander effect. The endpoint for the bystander effect in the reporter system used was reduction in cloning efficiency (RCE). The magnitude of the RCE was similar in shielded and unshielded flasks. When cells were placed in a Faraday cage the magnitude of the RCE was less but not eliminated. The results suggest that liquid media or cell-cell contact transmission of bystander factors may be only part of the bystander mechanism. Bioelectric or bio magnetic fields may have a role to play. To test this further, cells were placed in a Magnetic Resonance Imaging (MRI) machine for 10min using a typical head scan protocol. This treatment also induced a bystander response. Apart from the obvious clinical relevance, the MRI results further suggest that bystander effects may be produced by non-ionizing exposures. It is concluded that bioelectric or magnetic effects may be involved in producing bystander signaling cascades commonly seen following ionizing radiation exposure. PMID:18648606

  10. Lay Bystanders' Perspectives on What Facilitates Cardiopulmonary Resuscitation and Use of Automated External Defibrillators in Real Cardiac Arrests

    DEFF Research Database (Denmark)

    Malta Hansen, Carolina; Rosenkranz, Simone Mørk; Folke, Fredrik

    2017-01-01

    factors encourage lay bystanders to initiate CPR and AED use in a cohort of bystanders previously trained in CPR techniques who were present at an out-of-hospital cardiac arrest. METHODS AND RESULTS: One-hundred and twenty-eight semistructured qualitative interviews with CPR-trained lay bystanders...... obligation to act. CONCLUSIONS: Several factors other than previous hands-on CPR training facilitate lay bystander instigation of CPR and AED use. The recognition and modification of these factors may increase lay bystander CPR rates and patient survival following an out-of-hospital cardiac arrest....

  11. Mechanism of protection of bystander cells by exogenous carbon monoxide: Impaired response to damage signal of radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Han, W.; Yu, K.N.; Wu, L.J.; Wu, Y.C.; Wang, H.Z.

    2011-01-01

    A protective effect of exogenous carbon monoxide (CO), generated by CO releasing molecule ticarbonyldichlororuthenium (II) dimer (CORM-2), on the bystander cells from the toxicity of radiation-induced bystander effect (RIBE) was revealed in our previous study. In the present work, a possible mechanism of this CO effect was investigated. The results from medium transfer experiments showed that α-particle irradiated Chinese hamster ovary (CHO) cells would release nitric oxide (NO), which was detected with specific NO fluorescence probe, to induce p53 binding protein 1 (BP1) formation in the cell population receiving the medium, and the release peak was found to be at 1 h post irradiation. Treating the irradiated or bystander cells separately with CO (CORM-2) demonstrated that CO was effective in the bystander cells but not the irradiated cells. Measurements of NO production and release with a specific NO fluorescence probe also showed that CO treatment did not affect the production and release of NO by irradiated cells. Protection of CO on cells to peroxynitrite, an oxidizing free radical from NO, suggested that CO might protect bystander cells via impaired response of bystander cells to NO, a RIBE signal in our research system.

  12. Mechanism of protection of bystander cells by exogenous carbon monoxide: Impaired response to damage signal of radiation-induced bystander effect

    Energy Technology Data Exchange (ETDEWEB)

    Han, W. [Department of Physics and Materials Science, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Kowloon (Hong Kong); Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Kowloon (Hong Kong); Wu, L.J. [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Wu, Y.C. [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); School of Nuclear Science and Technology, University of Science and Technology of China, Hefei 230029 (China); Wang, H.Z. [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China)

    2011-05-10

    A protective effect of exogenous carbon monoxide (CO), generated by CO releasing molecule ticarbonyldichlororuthenium (II) dimer (CORM-2), on the bystander cells from the toxicity of radiation-induced bystander effect (RIBE) was revealed in our previous study. In the present work, a possible mechanism of this CO effect was investigated. The results from medium transfer experiments showed that {alpha}-particle irradiated Chinese hamster ovary (CHO) cells would release nitric oxide (NO), which was detected with specific NO fluorescence probe, to induce p53 binding protein 1 (BP1) formation in the cell population receiving the medium, and the release peak was found to be at 1 h post irradiation. Treating the irradiated or bystander cells separately with CO (CORM-2) demonstrated that CO was effective in the bystander cells but not the irradiated cells. Measurements of NO production and release with a specific NO fluorescence probe also showed that CO treatment did not affect the production and release of NO by irradiated cells. Protection of CO on cells to peroxynitrite, an oxidizing free radical from NO, suggested that CO might protect bystander cells via impaired response of bystander cells to NO, a RIBE signal in our research system.

  13. Prenatal Care: First Trimester Visits

    Science.gov (United States)

    ... care provider will discuss the importance of proper nutrition and prenatal vitamins. Your first prenatal visit is a good time to discuss exercise, sex during pregnancy and other lifestyle issues. You might also discuss your work environment and the use of medications during pregnancy. If ...

  14. Response to Commentaries on Bystander Training as Leadership Training.

    Science.gov (United States)

    Katz, Jackson

    2018-03-01

    In this article, the author responds to three commentaries about his article "Bystander Training as Leadership Training: Notes on the Origins, Philosophy, and Pedagogy of the Mentors in Violence Prevention Model," published in this volume. Topics covered in the commentaries and response include questions about evaluation and evidence for program effectiveness; the necessity for gender violence prevention education to be gender transformative and part of a comprehensive, multilevel prevention approach, especially for adolescents; and the degree to which Mentors in Violence Prevention (MVP), as a "social justice"-oriented program, incorporates intersectional and anti-oppression frameworks and perspectives.

  15. Helminthiasis, bystander diseases and vaccines: analysis of interaction.

    Science.gov (United States)

    Markus, Miles B; Fincham, John E

    2007-11-01

    Helminthiasis has assumed a new medical and veterinary significance following the recognition of its immunomodulatory consequences for the severity of bystander conditions and the efficacy of immunization against non-helminthic diseases of humans and livestock. Recent papers by Jackson et al. and Turner et al. have an important bearing on research in these areas. One of the implications of their work is that the parasitological criterion of egg-positivity versus egg-negativity is too simplistic to use in co-infection and related studies unless accompanied by immunological analysis.

  16. Increased mitochondrial mass in cells with functionally compromised mitochondria after exposure to both direct gamma radiation and bystander factors.

    LENUS (Irish Health Repository)

    Nugent, Sharon M E

    2007-07-01

    The bystander effect describes radiation-like damage in unirradiated cells either in the vicinity of irradiated cells or exposed to medium from irradiated cells. This study aimed to further characterize the poorly understood mitochondrial response to both direct irradiation and bystander factor(s) in human keratinocytes (HPV-G) and Chinese hamster ovarian cells (CHO-K1). Oxygen consumption rates were determined during periods of state 4, state 3 and uncoupled respiration. Mitochondrial mass was determined using MitoTracker FM. CHO-K1 cells showed significantly reduced oxygen consumption rates 4 h after exposure to 5 Gy direct radiation and irradiated cell conditioned medium (ICCM) and an apparent recovery 12-24 h later. The apparent recovery was likely due to the substantial increase in mitochondrial mass observed in these cells as soon as 4 h after exposure. HPV-G cells, on the other hand, showed a sustained increase in oxygen consumption rates after ICCM exposure and a transient increase 4 h after exposure to 5 Gy direct radiation. A significant increase in mitochondrial mass per HPV-G cell was observed after exposure to both direct radiation and ICCM. These findings are indicative of a stress response to mitochondrial dysfunction that increases the number of mitochondria per cell.

  17. Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

    Science.gov (United States)

    Matsumoto, H.; Ohnishi, T.

    There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

  18. Prenatal vitamins: what is in the bottle?

    Science.gov (United States)

    Duerbeck, Norman B; Dowling, David D; Duerbeck, Jillinda M

    2014-12-01

    Nearly all obstetricians routinely prescribe prenatal vitamins to their pregnant patients at the time of the first prenatal visit. Many times, patients' understanding of the health benefits of prenatal vitamins differs substantially from that of the prescribing physician. The following is a review of the most common ingredients found in prenatal vitamins and their purported health benefits.

  19. What role for DNA damage and repair in the bystander response?

    International Nuclear Information System (INIS)

    Prise, Kevin M.; Folkard, Melvyn; Kuosaite, Virginija; Tartier, Laurence; Zyuzikov, Nikolai; Shao, Chunlin

    2006-01-01

    The radiation-induced bystander effect challenges the accepted paradigm of direct DNA damage in response to energy deposition driving the biological consequences of radiation exposure. With the bystander response, cells which have not been directly exposed to radiation respond to their neighbours being targeted. In our own studies we have used novel targeted microbeam approaches to specifically irradiate parts of individual cells within a population to quantify the bystander response and obtain mechanistic information. Using this approach it has become clear that energy deposited by radiation in nuclear DNA is not required to trigger the effect, with cytoplasmic irradiation required. Irradiated cells also trigger a bystander response regardless of whether they themselves live or die, suggesting that the phenotype of the targeted cell is not a determining factor. Despite this however, a range of evidence has shown that repair status is important for dealing with the consequences of a bystander signal. Importantly, repair processes involved in the processing of dsb appear to be involved suggesting that the bystander response involves the delayed or indirect production of dsb-type lesions in bystander cells. Whether these are infact true dsb or complexes of oxidised bases in combination with strand breaks and the mechanisms for their formation, remains to be elucidated

  20. The development of bystander intentions and social-moral reasoning about intergroup verbal aggression.

    Science.gov (United States)

    Palmer, Sally B; Rutland, Adam; Cameron, Lindsey

    2015-11-01

    A developmental intergroup approach was taken to examine the development of prosocial bystander intentions among children and adolescents. Participants as bystanders (N = 260) aged 8-10 and 13-15 years were presented with scenarios of direct aggression between individuals from different social groups (i.e., intergroup verbal aggression). These situations involved either an ingroup aggressor and an outgroup victim or an outgroup aggressor and an ingroup victim. This study focussed on the role of intergroup factors (group membership, ingroup identification, group norms, and social-moral reasoning) in the development of prosocial bystander intentions. Findings showed that prosocial bystander intentions declined with age. This effect was partially mediated by the ingroup norm to intervene and perceived severity of the verbal aggression. However, a moderated mediation analysis showed that only when the victim was an ingroup member and the aggressor an outgroup member did participants become more likely with age to report prosocial bystander intentions due to increased ingroup identification. Results also showed that younger children focussed on moral concerns and adolescents focussed more on psychological concerns when reasoning about their bystander intention. These novel findings help explain the developmental decline in prosocial bystander intentions from middle childhood into early adolescence when observing direct intergroup aggression. © 2015 The British Psychological Society.

  1. Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect.

    Science.gov (United States)

    Xu, Shuai; Wang, Jufang; Ding, Nan; Hu, Wentao; Zhang, Xurui; Wang, Bing; Hua, Junrui; Wei, Wenjun; Zhu, Qiyun

    2015-01-01

    Bystander effects can be induced through cellular communication between irradiated cells and non-irradiated cells. The signals that mediate this cellular communication, such as cytokines, reactive oxygen species, nitric oxide and even microRNAs, can be transferred between cells via gap junctions or extracellular medium. We have previously reported that miR-21, a well described DDR (DNA damage response) microRNA, is involved in radiation-induced bystander effects through a medium-mediated way. However, the mechanisms of the microRNA transfer have not been elucidated in details. In the present study, it was found that exosomes isolated from irradiated conditioned medium could induce bystander effects. Furthermore, we demonstrated plenty of evidences that miR-21, which is up-regulated as a result of mimic transfection or irradiation, can be transferred from donor or irradiated cells into extracellular medium and subsequently get access to the recipient or bystander cells through exosomes to induce bystander effects. Inhibiting the miR-21 expression in advance can offset the bystander effects to some extent. From all of these results, it can be concluded that the exosome-mediated microRNA transfer plays an important role in the radiation-induced bystander effects. These findings provide new insights into the functions of microRNAs and the cellular communication between the directly irradiated cells and the non-irradiated cells.

  2. TakeCARE, a Video to Promote Bystander Behavior on College Campuses: Replication and Extension.

    Science.gov (United States)

    Jouriles, Ernest N; Sargent, Kelli S; Salis, Katie Lee; Caiozzo, Christina; Rosenfield, David; Cascardi, Michele; Grych, John H; O'Leary, K Daniel; McDonald, Renee

    2017-08-01

    Previous research has demonstrated that college students who view TakeCARE, a video bystander program designed to encourage students to take action to prevent sexual and relationship violence (i.e., bystander behavior), display more bystander behavior relative to students who view a control video. The current study aimed to replicate and extend these findings by testing two different methods of administering TakeCARE and examining moderators of TakeCARE's effects on bystander behavior. Students at four universities ( n = 557) were randomly assigned to one of three conditions: (a) view TakeCARE in a monitored computer lab, (b) view TakeCARE at their own convenience after receiving an email link to the video, or (c) view a video about study skills (control group). Participants completed measures of bystander behavior at baseline and at a 1-month follow-up. Participants in both TakeCARE conditions reported more bystander behavior at follow-up assessments, compared with participants in the control condition. The beneficial effect of TakeCARE did not differ significantly across administration methods. However, the effects of TakeCARE on bystander behavior were moderated by students' perceptions of campus responsiveness to sexual violence, with more potent effects when students perceived their institution as responsive to reports of sexual violence.

  3. The effect of melanin on the bystander effect in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Mosse, I. [Institute of Genetics and Cytology of the National Academy of Sciences, Academicheskaya Str. 27, Minsk (Belarus)]. E-mail: i.mosse@igc.bas-net.by; Marozik, P. [Institute of Genetics and Cytology of the National Academy of Sciences, Academicheskaya Str. 27, Minsk (Belarus); Radiation and Environmental Science Centre, DIT, Dublin 8 (Ireland); Seymour, C. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ont. (Canada); Mothersill, C. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ont. (Canada)

    2006-05-11

    The influence of melanin on radiation-induced bystander effects has been studied. Melanin is known to be a natural substance with proved radioprotective properties in different organisms and cell lines. It is non-toxic and is effective against acute and chronic irradiation. The lower the radiation dose, the higher the relative impact of melanin protection. In this study influence of melanin on human keratinocytes (HPV-G cells) has been studied using the colony-forming assay. We have shown that bystander donor medium from 0.5 Gy irradiated cells when transferred to unirradiated cells, caused almost the same effect as direct irradiation. Melanin increased the colony-forming ability of bystander recipient cells when it was added into culture medium before irradiation. The effect of melanin added after irradiation was to produce less protection in both the directly irradiated and bystander medium treated groups. The absorption spectrum of the filtered medium is identical to one of the intact culture medium showing that melanin was not present in filtered medium. Thus, it cannot protect recipient cells but reduces the amount of the bystander effect. It is concluded that melanin added before irradiation effectively decreased the radiation dose. The reduction of the impact of the bystander signal on recipient cells when melanin was added to the donor medium after harvest but before filtration, may mean that the bystander signal has a physical component as melanin can absorb all types of physical energy.

  4. Intercellular and intracellular signaling pathways mediating ionizing radiation-induced bystander effects

    International Nuclear Information System (INIS)

    Hamada, Nobuyuki; Hara, Takamitsu; Kobayashi, Yasuhiko; Matsumoto, Hideki

    2007-01-01

    A rapidly growing body of experimental evidence indicates that ionizing radiation induces biological effects in non-irradiated bystander cells that have received signals from adjacent or distant irradiated cells. This phenomenon, which has been termed the ionizing radiation-induced bystander effect, challenges the long-standing paradigm that radiation traversal through the nucleus of a cell is a prerequisite to elicit genetic damage or a biological response. Bystander effects have been observed in a number of experimental systems, and cells whose nucleus or cytoplasm is irradiated exert bystander responses. Bystander cells manifest a multitude of biological consequences, such as genetic and epigenetic changes, alterations in gene expression, activation of signal transduction pathways, and delayed effects in their progeny. Several mediating mechanisms have been proposed. These involve gap junction-mediated intercellular communication, secreted soluble factors, oxidative metabolism, plasma membrane-bound lipid rafts, and calcium fluxes. This paper reviews briefly the current knowledge of the bystander effect with a focus on proposed mechanisms. The potential benefit of bystander effects to cancer radiotherapy will also be discussed. (author)

  5. Bystander Effect Induced by UV Radiation; why should we be interested? 

    Directory of Open Access Journals (Sweden)

    Maria Widel

    2012-11-01

    Full Text Available The bystander effect, whose essence is an interaction of cells directly subjected to radiation with adjacent non-subjected cells, via molecular signals, is an important component of ionizing radiation action. However, knowledge of the bystander effect in the case of ultraviolet (UV radiation is quite limited. Reactive oxygen and nitrogen species generated by UV in exposed cells induce bystander effects in non-exposed cells, such as reduction in clonogenic cell survival and delayed cell death, oxidative DNA damage and gene mutations, induction of micronuclei, lipid peroxidation and apoptosis. Although the bystander effect after UV radiation has been recognized in cell culture systems, its occurrence in vivo has not been studied. However, solar UV radiation, which is the main source of UV in the environment, may induce in human dermal tissue an inflammatory response and immune suppression, events which can be considered as bystander effects of UV radiation. The oxidative damage to DNA, genomic instability and the inflammatory response may lead to carcinogenesis. UV radiation is considered one of the important etiologic factors for skin cancers, basal- and squamous-cell carcinomas and malignant melanoma. Based on the mechanisms of actions it seems that the UV-induced bystander effect can have some impact on skin damage (carcinogenesis?, and probably on cells of other tissues. The paper reviews the existing data about the UV-induced bystander effect and discusses a possible implication of this phenomenon for health risk. 

  6. The effect of melanin on the bystander effect in human keratinocytes

    International Nuclear Information System (INIS)

    Mosse, I.; Marozik, P.; Seymour, C.; Mothersill, C.

    2006-01-01

    The influence of melanin on radiation-induced bystander effects has been studied. Melanin is known to be a natural substance with proved radioprotective properties in different organisms and cell lines. It is non-toxic and is effective against acute and chronic irradiation. The lower the radiation dose, the higher the relative impact of melanin protection. In this study influence of melanin on human keratinocytes (HPV-G cells) has been studied using the colony-forming assay. We have shown that bystander donor medium from 0.5 Gy irradiated cells when transferred to unirradiated cells, caused almost the same effect as direct irradiation. Melanin increased the colony-forming ability of bystander recipient cells when it was added into culture medium before irradiation. The effect of melanin added after irradiation was to produce less protection in both the directly irradiated and bystander medium treated groups. The absorption spectrum of the filtered medium is identical to one of the intact culture medium showing that melanin was not present in filtered medium. Thus, it cannot protect recipient cells but reduces the amount of the bystander effect. It is concluded that melanin added before irradiation effectively decreased the radiation dose. The reduction of the impact of the bystander signal on recipient cells when melanin was added to the donor medium after harvest but before filtration, may mean that the bystander signal has a physical component as melanin can absorb all types of physical energy

  7. Bystanders intervene to impede grooming in Western chimpanzees and sooty mangabeys

    Science.gov (United States)

    Samuni, Liran; Preis, Anna; Wittig, Roman M.

    2017-01-01

    Grooming interactions benefit groomers, but may have negative consequences for bystanders. Grooming limits bystanders' grooming access and ensuing alliances could threaten the bystander's hierarchy rank or their previous investment in the groomers. To gain a competitive advantage, bystanders could intervene into a grooming bout to increase their own grooming access or to prevent the negative impact of others' grooming. We tested the impact of dominance rank and social relationships on grooming intervention likelihood and outcome in two sympatric primate species, Western chimpanzees (Pan troglodytes verus) and sooty mangabeys (Cercocebus atys atys). In both species, rather than increasing their own access to preferred partners, bystanders intervened mainly when an alliance between groomers could have a negative impact on them: when the lower-ranking groomer was close to the bystander in rank, when either groomer was an affiliation partner whose services they could lose, or the groomers were not yet strongly affiliated with each other. Thus, bystanders in both species appear to monitor grooming interactions and intervene based on their own dominance rank and social relationships, as well as triadic awareness of the relationship between groomers. While the motivation to intervene did not differ between species, mangabeys appeared to be more constrained by dominance rank than chimpanzees. PMID:29291114

  8. Comparing CenteringPregnancy® to standard prenatal care plus prenatal education

    Science.gov (United States)

    2013-01-01

    Background There is significant evidence to support the importance of prenatal care in preventing adverse outcomes such as preterm birth and low infant birth weight. Previous studies have indicated that the benefits of prenatal care are not evenly distributed throughout the social strata. In addition, emerging evidence suggests that among particular populations, rates of preterm birth are unchanged or increasing. This suggests that an alternate care model is necessary, one that seeks to addresses some of the myriad of social factors that also contribute to adverse birth outcomes. In previous studies, the group prenatal care model CenteringPregnancy® had been shown to reduce adverse birth outcomes, but to date, no comparison had been made with a model that included prenatal education. This study sought to investigate whether any significant difference remained within the comparison groups when both models accounted for social factors. Methods This analysis was based on survey data collected from a prospective cohort of pregnant women through the All Our Babies Study in Calgary, Alberta. Results At baseline, there were significant differences between the comparison groups in their psychosocial health, with the women in the CenteringPregnancy® group scoring higher levels of depressive symptoms, stress and anxiety. At four months postpartum, the differences between the groups were no longer significant. Conclusions: These results suggest that CenteringPregnancy® can recruit and retain a demographically vulnerable group of women with a constellation of risk factors for poor pregnancy and birth outcomes, including poverty, language barriers and poor mental health. Post program, the rates of stress, anxiety and depression were similar to other women with more social and financial advantage. These findings suggest that CenteringPregnancy® may be a community based care strategy that contributes to improved mental health, knowledge, and behaviours to optimize outcomes

  9. Association of Bystander Interventions With Neurologically Intact Survival Among Patients With Bystander-Witnessed Out-of-Hospital Cardiac Arrest in Japan.

    Science.gov (United States)

    Nakahara, Shinji; Tomio, Jun; Ichikawa, Masao; Nakamura, Fumiaki; Nishida, Masamichi; Takahashi, Hideto; Morimura, Naoto; Sakamoto, Tetsuya

    2015-07-21

    Neurologically intact survival after out-of-hospital cardiac arrest (OHCA) has been increasing in Japan. However, associations between increased prehospital care, including bystander interventions and increases in survival, have not been well estimated. To estimate the associations between bystander interventions and changes in neurologically intact survival among patients with OHCA in Japan. Retrospective descriptive study using data from Japan's nationwide OHCA registry, which started in January 2005. The registry includes all patients with OHCA transported to the hospital by emergency medical services (EMS) and recorded patients' characteristics, prehospital interventions, and outcomes. Participants were 167,912 patients with bystander-witnessed OHCA of presumed cardiac origin in the registry between January 2005 and December 2012. Prehospital interventions by bystander, including defibrillation using public-access automated external defibrillators and chest compression. Neurologically intact survival was defined as Glasgow-Pittsburgh cerebral performance category score 1 or 2 and overall performance category scores 1 or 2 at 1 month or at discharge. The association between the interventions and neurologically intact survival was evaluated. From 2005 to 2012, the number of bystander-witnessed OHCAs of presumed cardiac origin increased from 17,882 (14.0 per 100,000 persons [95% CI, 13.8-14.2]) to 23,797 (18.7 per 100,000 persons [95% CI, 18.4-18.9]), and neurologically intact survival increased from 587 cases (age-adjusted proportion, 3.3% [95% CI, 3.0%-3.5%]) to 1710 cases (8.2% [95% CI, 7.8%-8.6%]). The rates of bystander chest compression increased from 38.6% to 50.9%, bystander-only defibrillation increased from 0.1% to 2.3%, bystander defibrillation combined with EMS defibrillation increased from 0.1% to 1.4%, and EMS-only defibrillation decreased from 26.6% to 23.5%. Performance of bystander chest compression, compared with no bystander chest compression

  10. Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

    Science.gov (United States)

    Lam, R. K. K.; Fung, Y. K.; Han, W.; Yu, K. N.

    2015-01-01

    The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

  11. X-ray-induced bystander response reduce spontaneous mutations in V79 cells

    International Nuclear Information System (INIS)

    Maeda, Munetoshi; Kobayashi, Katsumi; Matsumoto, Hideki; Usami, Noriko; Tomiya, Masanori

    2013-01-01

    The potential for carcinogenic risks is increased by radiation-induced bystander responses; these responses are the biological effects in unirradiated cells that receive signals from the neighboring irradiated cells. Bystander responses have attracted attention in modern radiobiology because they are characterized by non-linear responses to low-dose radiation. We used a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, High Energy Accelerator Research Organization, KEK, and showed that nitric oxide (NO)-mediated bystander cell death increased biphasically in a dose-dependent manner. Here, we irradiated five cell nuclei using 10 × 10 µm 2 5.35 keV X-ray beams and then measured the mutation frequency at the hypoxanthine-guanosine phosphoribosyl transferase (HPRT) locus in bystander cells. The mutation frequency with the null radiation dose was 2.6 × 10 -5 (background level), and the frequency decreased to 5.3 × 10 -6 with a dose of approximately 1 Gy (absorbed dose in the nucleus of irradiated cells). At high doses, the mutation frequency returned to the background level. A similar biphasic dose-response effect was observed for bystander cell death. Furthermore, we found that incubation with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a specific scavenger of NO, suppressed not only the biphasic increase in bystander cell death but also the biphasic reduction in mutation frequency of bystander cells. These results indicate that the increase in bystander cell death involves mechanisms that suppress mutagenesis. This study has thus shown that radiation-induced bystander responses could affect processes that protect the cell against naturally occurring alterations such as mutations. (author)

  12. Dispatcher-assisted bystander cardiopulmonary resuscitation and survival in out-of-hospital cardiac arrest.

    Science.gov (United States)

    Hagihara, Akihito; Onozuka, Daisuke; Shibuta, Hidetoshi; Hasegawa, Manabu; Nagata, Takashi

    2018-04-19

    Bystander cardiopulmonary resuscitation (CPR) is critical to the survival of patients with out-of-hospital cardiac arrest (OHCA). However, it is unknown whether bystander CPR with or without dispatcher assistance is more effective or why. Thus, we evaluated the association between dispatcher-assisted bystander CPR (vs. bystander CPR without dispatcher assistance) and survival of patients with OHCA. This is a retrospective, nonrandomized, observational study using national registry data for all OHCAs. We performed a propensity analysis. Patients with OHCA of cardiac origin were 18-100 years of age and received bystander chest compression in Japan between 2005 and 2014. Outcome measures were bystander rescue breathing, return of spontaneous circulation (ROSC) before hospital arrival, and survival and Cerebral Performance Category (CPC) 1 or 2 at 1 month after the event. During the study period, 1,176,351 OHCAs occurred, and 87,400 cases met the inclusion criteria. Among propensity-matched patients, a negative association was observed between dispatcher-assisted bystander CPR and outcome measures in a fully-adjusted model [odds ratio (OR) (95% CI) for ROSC = 0.87 (0.78-0.97), P < 0.05; OR (95% CI) for 1-month survival = 0.81 (0.65-1.00), P < 0.05; OR (95% CI) for CPC 1 or 2 = 0.64 (0.43-0.93), P < 0.05]. OR of survival for dispatcher-assisted bystander CPR tended to decrease as the emergency medical services response time increased. Survival benefit was less for dispatcher-assisted bystander CPR with dispatcher assistance than without dispatcher assistance. Low quality is hypothesized to be the cause of the reduced benefit. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Radiation induced bystander effects: mechanisms and implication for low dose radiation risk assessment

    International Nuclear Information System (INIS)

    Hei, T.L.; Randers-Pehrson, G.; Zhou, H.

    2003-01-01

    Using a precision microbeam to target an exact fraction of cells in a population and irradiated their nuclei with exactly one alpha particle each, we found that the frequencies of induced mutations and chromosomal changes in populations where some known fractions of nuclei were hit are consistent with non-hit cells contributing significantly to the response. In fact, irradiation of 10% of a mammalian cell population with a single alpha particle per cell results in a mutant yield similar to that observed when all of the cells in the population are irradiated. Although the bystander observations have been well established, the underlying mechanism(s) remain largely unknown. There are indications that multiple pathways are involved in the bystander phenomenon and different cell types respond differently to the bystander signaling. In confluent monolayers, there is evident that gap junctional communication is crucial in mediating the bystander effect whereas reactive oxygen and reactive nitrogen species have been implicated as the mediating molecules in sub-confluent cultures. Although p53 is not necessary for the expression of bystander effect, there is evident that repair deficient cells may express a higher bystander response. Using cDNA microarrays, a number of cellular signaling genes have been shown to be differentially expressed among bystander cells. The functional roles of these genes in the bystander effect will be discussed. The bystander observations imply that the relevant target for various radiobiological endpoints is larger than an individual cell and suggest a need to reconsider the validity of the linear extrapolation in making risk estimate for low dose radiation exposure. (Work supported by NIH grants CA 49062 and CA-RR11623)

  14. Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation

    Science.gov (United States)

    Tomita, Masanori; Matsumoto, Hideki; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke; Maeda, Munetoshi; Kobayashi, Yasuhiko

    2015-07-01

    In general, a radiation-induced bystander response is known to be a cellular response induced in non-irradiated cells after receiving bystander signaling factors released from directly irradiated cells within a cell population. Bystander responses induced by high-linear energy transfer (LET) heavy ions at low fluence are an important health problem for astronauts in space. Bystander responses are mediated via physical cell-cell contact, such as gap-junction intercellular communication (GJIC) and/or diffusive factors released into the medium in cell culture conditions. Nitric oxide (NO) is a well-known major initiator/mediator of intercellular signaling within culture medium during bystander responses. In this study, we investigated the NO-mediated bystander signal transduction induced by high-LET argon (Ar)-ion microbeam irradiation of normal human fibroblasts. Foci formation by DNA double-strand break repair proteins was induced in non-irradiated cells, which were co-cultured with those irradiated by high-LET Ar-ion microbeams in the same culture plate. Foci formation was suppressed significantly by pretreatment with an NO scavenger. Furthermore, NO-mediated reproductive cell death was also induced in bystander cells. Phosphorylation of NF-κB and Akt were induced during NO-mediated bystander signaling in the irradiated and bystander cells. However, the activation of these proteins depended on the incubation time after irradiation. The accumulation of cyclooxygenase-2 (COX-2), a downstream target of NO and NF-κB, was observed in the bystander cells 6 h after irradiation but not in the directly irradiated cells. Our findings suggest that Akt- and NF-κB-dependent signaling pathways involving COX-2 play important roles in NO-mediated high-LET heavy-ion-induced bystander responses. In addition, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells to distinguish them from directly irradiated cells, although this may depend on the time

  15. Does Non-Targeted Community CPR Training Increase Bystander CPR Frequency?

    Science.gov (United States)

    Uber, Amy; Sadler, Richard C; Chassee, Todd; Reynolds, Joshua C

    2018-05-01

    Only 37% of out-of-hospital cardiac arrests (OHCA) receive bystander Cardiopulmonary resuscitation (CPR) in Kent County, MI. In May 2014, prehospital providers offered one-time, point-of-contact compression-only CPR training to 2,253 passersby at 7 public locations in Grand Rapids, Michigan. To assess the impact of this intervention, we compared bystander CPR frequency and clinical outcomes in regions surrounding training sites before and after the intervention, adjusting for prehospital covariates. We aimed to assess the effect of this broad, non-targeted intervention on bystander CPR frequency, type of CPR utilized, and clinical outcomes. We also tested for differences in geospatial variation of bystander CPR and clinical outcomes clustered around training sites. Retrospective, observational, before-after study of adult, EMS-treated OHCA in Kent County from January 1, 2010 to December 31, 2015. We generated a 5-kilometer radius surrounding each training site to estimate any geospatial influence that training sites might have on bystander CPR frequency in nearby OHCA cases. Chi-squared, Fisher's exact, and t-tests assessed differences in subject features. Difference-in-differences analysis with generalized estimating equation (GEE) modeling assessed bystander CPR frequency, adjusting for training site, covariates (age, sex, witnessed, shockable rhythm, public location), and clustering around training sites. Similar modeling tested for changes in bystander CPR type, return of spontaneous circulation (ROSC), survival to hospital discharge, and cerebral performance category (CPC) of 1-2 at hospital discharge. We included 899 cases before and 587 cases post-intervention. Overall, we observed no increase in the frequency of bystander CPR or favorable clinical outcomes. We did observe an increase in compression-only CPR, but this was paradoxically restricted to OHCA cases falling outside radii around training sites. In adjusted modeling, the bystander CPR training

  16. DMPD: TLR3 in antiviral immunity: key player or bystander? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16027039 TLR3 in antiviral immunity: key player or bystander? Schroder M, Bowie AG.... Trends Immunol. 2005 Sep;26(9):462-8. (.png) (.svg) (.html) (.csml) Show TLR3 in antiviral immunity: key player... or bystander? PubmedID 16027039 Title TLR3 in antiviral immunity: key player or bystander? Authors Schr... File (.png) SVG File (.svg) HTML File (.html) CSML File (.csml) Open .csml file with CIOPlayer Open .csml file with CIOPlayer... - ※CIO Playerのご利用上の注意 Open .csml file with CIO Open .csml file with CIO - ※CIOのご利用上の注意 ...

  17. Association of bystander interventions and hospital length of stay and admission to intensive care unit in out-of-hospital cardiac arrest survivors.

    Science.gov (United States)

    Riddersholm, Signe; Kragholm, Kristian; Mortensen, Rikke Nørmark; Pape, Marianne; Hansen, Carolina Malta; Lippert, Freddy K; Torp-Pedersen, Christian; Christiansen, Christian F; Rasmussen, Bodil Steen

    2017-10-01

    The impact of bystander interventions on post-arrest hospital course is sparsely studied. We examined the association between bystander interventions and length of hospital stay and admission to intensive care unit (ICU) in one-day survivors after OHCA. This cohort study linked data of 4641 one-day OHCA survivors from 2001 to 2014 to data on hospital length of stay and ICU admission. We examined associations between bystander efforts and outcomes using regression, adjusted for age, sex, comorbidities, calendar year and witnessed status. We divided bystander efforts into three categories: 1. No bystander interventions; 2.Bystander CPR only; 3. Bystander defibrillation with or without bystander CPR. For patients surviving to hospital discharge, hospital length of stay was 20days for patients without bystander interventions, compared to 16 for bystander CPR, and 13 for bystander defibrillation. 82% of patients without bystander interventions were admitted to ICU compared to 77.2% for bystander CPR, and 61.2% for bystander defibrillation. In-hospital mortality was 60% in the first category compared to 40.5% and 21.7% in the two latter categories. In regression models, bystander CPR and bystander defibrillation were associated with a reduction of length of hospital stay of 21% (Estimate: 0.79 [95% CI: 0.72-0.86]) and 32% (Estimate: 0.68 [95% CI: 0.59-0.78]), respectively. Both bystander CPR (OR: 0.94 [95% CI: 0.91-0.97]) and bystander defibrillation (OR: 0.81 [0.76-0.85]), were associated with lower risk of ICU admission. Bystander interventions were associated with reduced hospital length of stay and ICU admission, suggesting that these efforts improve recovery in OHCA survivors. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Qualitative Comparison of Women's Perspectives on the Functions and Benefits of Group and Individual Prenatal Care.

    Science.gov (United States)

    Heberlein, Emily C; Picklesimer, Amy H; Billings, Deborah L; Covington-Kolb, Sarah; Farber, Naomi; Frongillo, Edward A

    2016-01-01

    Women's definitions and experiences of the functions and benefits of their routine prenatal care are largely absent from research and public discourse on prenatal care outcomes. This qualitative study aimed to develop a framework of women's prenatal care experiences by comparing the experiences of women in individual and group prenatal care. We conducted serial qualitative interviews with racially diverse low-income women receiving individual prenatal care (n = 14) or group prenatal care (n = 15) through pregnancy and the early postpartum period. We completed 42 second-trimester, 48 third-trimester, and 44 postpartum interviews. Using grounded theory, the semistructured interviews were coded for themes, and the themes were integrated into an explanatory framework of prenatal care functions and benefits. Individual and group participants described similar benefits in 3 prenatal care functions: confirming health, preventing and monitoring medical complications, and building supportive provider relationships. For the fourth function, educating and preparing, group care participants experienced more benefits and different benefits. The benefits for group participants were enhanced by the supportive group environment. Group participants described greater positive influences on stress, confidence, knowledge, motivation, informed decision making, and health care engagement. Whereas pregnant women want to maximize their probability of having a healthy newborn, other prenatal care outcomes are also important: reducing pregnancy-related stress; developing confidence and knowledge for improving health; preparing for labor, birth, and newborn care; and having supportive relationships. Group prenatal care may be more effective in attaining these outcomes. Achieving these outcomes is increasingly relevant in health care systems prioritizing woman-centered care and improved birth outcomes. How to achieve them should be part of policy development and research. © 2016 by the

  19. Early prenatal syphilis

    Directory of Open Access Journals (Sweden)

    Santosh Rathod

    2010-01-01

    Full Text Available Syphilis in pregnancy still remains a challenge despite the availability of adequate diagnostic tests for serological screening and penicillin therapy. We report a case of 2 month old female infant who presented with runny nose, papulosquamous lesions over both palms and soles and perianal erosions since 1 month after birth. Cutaneous examination revealed moist eroded areas in the perianal region and fine scaly lesions over palms and soles. Radiograph of both upper limbs and limbs revealed early periosteal changes in lower end of humerus and lower end of tibia. Diagnosis of early pre-natal syphilis was confirmed by Child′s Serum Rapid Plasma Reagin Antibody test [S.RPR] being positive with 1:64 dilution while that of mother was 1:8.

  20. Prenatal anxiety effects: A review.

    Science.gov (United States)

    Field, Tiffany

    2017-11-01

    This review is based on literature on prenatal anxiety effects that was found on Pubmed and PsycINFO for the years 2010-2016. Prenatal anxiety is thought to have distinct features, although it has been measured both by specific prenatal anxiety symptoms as well as by standardized anxiety scales. Its prevalence has ranged from 21 to 25% and it has been predicted by a number of pregnancy - related variables such as unintended pregnancy, demographic variables such as low acculturation and income and psychosocial factors including pessimism and partner tension. Prenatal anxiety effects on pregnancy include increased cortisol levels, pro-inflammatory cytokines, obstetric problems and cesarean section. Effects on the neonate include lower gestational age, prematurity, less insulin-like growth factor in cord blood, less exclusive breast-feeding and less self-regulation during the heelstick procedure. Prenatal anxiety effects continue into infancy and childhood both on physiological development and emotional/mental development. Among the physiological effects are lower vagal activity across the first two years, and lower immunity, more illnesses and reduced gray matter in childhood. Prenatal anxiety effects on emotional/mental development include greater negative emotionality and in infants, lower mental development scores and internalizing problems. Anxiety disorders occur during childhood and elevated cortisol and internalizing behaviors occur during adolescence. Interventions for prenatal anxiety are virtually nonexistent, although stroking (massaging) the infant has moderated the pregnancy - specific anxiety effects on internalizing behaviors in the offspring. The limitations of this literature include the homogeneity of samples, the frequent use of anxiety measures that are not specific to pregnancy, and the reliance on self-report. Nonetheless, the literature highlights the negative, long-term effects of prenatal anxiety and the need for screening and early

  1. Empowering public service workers to face bystander conflict : Enhancing resources through a training intervention

    NARCIS (Netherlands)

    van Erp, K.J.P.M.; Gevers, J.M.P.; Rispens, S.; Demerouti, E.

    2018-01-01

    Public service employees work in occupations that are accompanied with high psychosocial risks. Police, firefighters, and paramedics are increasingly being confronted with argumentative, conflicting bystanders that frustrate them in executing their task. We developed a resource-enhancement

  2. Bystander chronic infection negatively impacts development of CD8+ T cell memory

    Science.gov (United States)

    Stelekati, Erietta; Shin, Haina; Doering, Travis A.; Dolfi, Douglas V.; Ziegler, Carly G.; Beiting, Daniel P.; Dawson, Lucas; Liboon, Jennifer; Wolski, David; Ali, Mohammed-Alkhatim A.; Katsikis, Peter D.; Shen, Hao; Roos, David S.; Haining, W. Nicholas; Lauer, Georg M.; Wherry, E. John

    2014-01-01

    Summary Epidemiological evidence suggests that chronic infections impair immune responses to unrelated pathogens and vaccines. The underlying mechanisms, however, are unclear and distinguishing effects on priming versus development of immunological memory has been challenging. We investigated whether bystander chronic infections impact differentiation of memory CD8+ T cells, the hallmark of protective immunity against intracellular pathogens. Chronic bystander infections impaired development of memory CD8+ T cells in several mouse models and humans. These effects were independent of initial priming and were associated with chronic inflammatory signatures. Chronic inflammation negatively impacted the number of bystander CD8+ T cells and their memory development. Distinct underlying mechanisms of altered survival and differentiation were revealed with the latter regulated by the transcription factors T-bet and Blimp-1. Thus, exposure to prolonged bystander inflammation impairs the effector to memory transition. These data have relevance for immunity and vaccination during persisting infections and chronic inflammation. PMID:24837104

  3. The application of microbeam in the research on radiation-induced bystander effects

    International Nuclear Information System (INIS)

    Xiong Jie; Han Ling

    2002-01-01

    There has been more and more attention to the phenomenon known as radiation-induced bystander effects, which will have a tremendous effect on the research in low -dose radiation biological effects. However, due to the stochastic nature of energy deposition and the random position of tracts, direct evidence for bystander effects and exact results of single particle interacts with a cell cannot be provided by using conventional broad-field irradiation. The availability of microbeam, especially the single particle microbeam in the world, whereby individual cells or precise location of cells can be irradiated with either a single or an exact number of particles provides a useful tool for the research on radiation-induced bystander effects. The author describes the radiation -induced bystander effect and the application of microbeam in the research on it

  4. Recognising out-of-hospital cardiac arrest during emergency calls increases bystander cardiopulmonary resuscitation and survival

    DEFF Research Database (Denmark)

    Viereck, Søren; Møller, Thea Palsgaard; Ersbøll, Annette Kjær

    2017-01-01

    BACKGROUND: Initiation of early bystander cardiopulmonary resuscitation (CPR) depends on bystanders' or medical dispatchers' recognition of out-of-hospital cardiac arrest (OHCA). The primary aim of our study was to investigate if OHCA recognition during the emergency call was associated...... with bystander CPR, return of spontaneous circulation (ROSC), and 30-day survival. Our secondary aim was to identify patient-, setting-, and dispatcher-related predictors of OHCA recognition. METHODS: We performed an observational study of all OHCA patients' emergency calls in the Capital Region of Denmark from...... the association between OHCA recognition and bystander CPR, ROSC, and 30-day survival. Univariable logistic regression analyses were applied to identify predictors of OHCA recognition. RESULTS: We included 779 emergency calls in the analyses. During the emergency calls, 70.1% (n=534) of OHCAs were recognised...

  5. BYSTANDER EFFECTS GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIAION AND CHEMICAL EXPOSURES

    Science.gov (United States)

    BYSTANDER EFFECTS, GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIATION AND CHEMICAL EXPOSURESR. Julian PrestonEnvironmental Carcinogenesis Division, U.S. Environmental Protection Agency, Research Triangle Park, N.C. 27711, USAThere ...

  6. Social Capital and Bystander Behavior in Bullying: Internalizing Problems as a Barrier to Prosocial Intervention.

    Science.gov (United States)

    Jenkins, Lyndsay N; Fredrick, Stephanie Secord

    2017-04-01

    Theory and research suggests that individuals with greater social capital (i.e., resources and benefits gained from relationships, experiences, and social interactions) may be more likely to be active, prosocial bystanders in bullying situations. Therefore, the goal of the current study was to examine the association of social capital (social support and social skills) with prosocial bystander behavior, and the role of internalizing problems as a potential barrier to this relation among 299 students (45.8% girls, 95% White) in sixth, seventh, and eighth grades. Results indicate a positive relation between social capital and prosocial bystander behavior. In addition, internalizing problems were a significant risk factor that may hinder youth-particularly girls-from engaging in defending behavior. Prosocial bystanders are an essential component to prevent and reduce bullying and further research is needed to better understand how to foster prosocial behavior in bullying situations, perhaps by utilizing social capital, related to school bullying.

  7. Addressing bystander exposure to agricultural pesticides in life cycle impact assessment

    DEFF Research Database (Denmark)

    Ryberg, Morten Walbech; Rosenbaum, Ralph K.; Mosqueron, Luc

    2018-01-01

    Residents living near agricultural fields may be exposed to pesticides drifting from the fields after application to different field crops. To address this currently missing exposure pathway in life cycle assessment (LCA), we developed a modeling framework for quantifying exposure of bystanders...... magnitude of individual bystanders can be substantially larger than the exposure of populations not living in the proximity to agricultural fields. Our framework for assessing bystander exposure to pesticide applications closes a relevant gap in the exposure assessment included in LCA for agricultural...... to pesticide spray drift from agricultural fields. Our framework consists of three parts addressing: (1) loss of pesticides from an agricultural field via spray drift; (2) environmental fate of pesticide in air outside of the treated field; and (3) exposure of bystanders to pesticides via inhalation...

  8. Lack of Bystander Effects From High LET Radiation For Early Cytogenetic Endpoints.

    Energy Technology Data Exchange (ETDEWEB)

    Groesser, Torsten; Cooper, Brian; Rydberg, Bjorn

    2008-05-07

    The aim of this work was to study radiation-induced bystander effects for early cytogenetic end points in various cell lines using the medium transfer technique after exposure to high- and low-LET radiation. Cells were exposed to 20 MeV/ nucleon nitrogen ions, 968 MeV/nucleon iron ions, or 575 MeV/nucleon iron ions followed by transfer of the conditioned medium from the irradiated cells to unirradiated test cells. The effects studied included DNA double-strand break induction, {gamma}-H2AX focus formation, induction of chromatid breaks in prematurely condensed chromosomes, and micronucleus formation using DNA repair-proficient and -deficient hamster and human cell lines (xrs6, V79, SW48, MO59K and MO59J). Cell survival was also measured in SW48 bystander cells using X rays. Although it was occasionally possible to detect an increase in chromatid break levels using nitrogen ions and to see a higher number of {gamma}-H2AX foci using nitrogen and iron ions in xrs6 bystander cells in single experiments, the results were not reproducible. After we pooled all the data, we could not verify a significant bystander effect for any of these end points. Also, we did not detect a significant bystander effect for DSB induction or micronucleus formation in these cell lines or for clonogenic survival in SW48 cells. The data suggest that DNA damage and cytogenetic changes are not induced in bystander cells. In contrast, data in the literature show pronounced bystander effects in a variety of cell lines, including clonogenic survival in SW48 cells and induction of chromatid breaks and micronuclei in hamster cells. To reconcile these conflicting data, it is possible that the epigenetic status of the specific cell line or the precise culture conditions and medium supplements, such as serum, may be critical for inducing bystander effects.

  9. Lack of Bystander Effects From High-LET Radiation For Early Cytogenetic End Points

    International Nuclear Information System (INIS)

    Groesser, Torsten; Cooper, Brian; Rydberg, Bjorn

    2008-01-01

    The aim of this work was to study radiation-induced bystander effects for early cytogenetic end points in various cell lines using the medium transfer technique after exposure to high- and low-LET radiation. Cells were exposed to 20 MeV/ nucleon nitrogen ions, 968 MeV/nucleon iron ions, or 575 MeV/nucleon iron ions followed by transfer of the conditioned medium from the irradiated cells to unirradiated test cells. The effects studied included DNA double-strand break induction, γ-H2AX focus formation, induction of chromatid breaks in prematurely condensed chromosomes, and micronucleus formation using DNA repair-proficient and -deficient hamster and human cell lines (xrs6, V79, SW48, MO59K and MO59J). Cell survival was also measured in SW48 bystander cells using X rays. Although it was occasionally possible to detect an increase in chromatid break levels using nitrogen ions and to see a higher number of γ-H2AX foci using nitrogen and iron ions in xrs6 bystander cells in single experiments, the results were not reproducible. After we pooled all the data, we could not verify a significant bystander effect for any of these end points. Also, we did not detect a significant bystander effect for DSB induction or micronucleus formation in these cell lines or for clonogenic survival in SW48 cells. The data suggest that DNA damage and cytogenetic changes are not induced in bystander cells. In contrast, data in the literature show pronounced bystander effects in a variety of cell lines, including clonogenic survival in SW48 cells and induction of chromatid breaks and micronuclei in hamster cells. To reconcile these conflicting data, it is possible that the epigenetic status of the specific cell line or the precise culture conditions and medium supplements, such as serum, may be critical for inducing bystander effects.

  10. Temporal variations in dispatcher-assisted and bystander-initiated resuscitation efforts.

    Science.gov (United States)

    Yamashita, Akira; Maeda, Tetsuo; Myojo, Yasuhiro; Wato, Yukihiro; Ohta, Keisuke; Inaba, Hideo

    2018-04-03

    To investigate temporal variations in dispatcher-assisted and bystander-initiated resuscitation efforts and their association with survival after bystander-witnessed out-of-hospital cardiac arrests (OHCAs). We retrospectively analyzed the neurologically favorable 1-month survival and the parameters related to dispatcher assisted cardiopulmonary resuscitation (DA-CPR) and bystander CPR (BCPR) for 227,524 OHCA patients between 2007 and 2013 in Japan. DA-CPR sensitivity for OHCAs, bystander's compliance to DA-CPR assessed by the proportion of bystanders who follow DA-CPR, and performance of BCPR measured by the rate of bystander-initiated CPR in patients without DA-CPR were calculated as indices of resuscitation efforts. Performance of BCPR was only similar to temporal variations in the survival (correlation between hourly paired values, R 2 =0.263, P=0.01): a lower survival rate (3.4% vs 4.2%) and performance of BCPR (23.1% vs 30.8%) during night-time (22:00-5:59) than during non-night-time. In subgroup analyses based on interaction tests, all three indices deteriorated during night-time when OHCAs were witnessed by non-family (adjusted odds ratio, 0.73-0.82), particularly in non-elderly patients. The rate of public access defibrillation for these OHCAs markedly decreased during night-time (adjusted odds ratio, 0.49) with delayed emergency calls and BCPR initiation. Multivariable logistic regression analyses revealed that the survival rate of non-family-witnessed OHCAs was 1.83-fold lower during night-time than during non-night-time. Dispatcher-assisted and bystander-initiated resuscitation efforts are low during night-time in OHCAs witnessed by non-family. A divisional alert system to recruit well-trained individuals is needed in order to improve the outcomes of night-time OHCAs witnessed by non-family bystanders. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Bystander-mediated genomic instability after high LET radiation in murine primary haemopoietic stem cells

    International Nuclear Information System (INIS)

    Bowler, Deborah A.; Moore, Stephen R.; Macdonald, Denise A.; Smyth, Sharon H.; Clapham, Peter; Kadhim, Munira A.

    2006-01-01

    Communication between irradiated and unirradiated (bystander) cells can result in responses in unirradiated cells that are similar to responses in their irradiated counterparts. The purpose of the current experiment was to test the hypothesis that bystander responses will be similarly induced in primary murine stem cells under different cell culture conditions. The experimental systems used here, co-culture and media transfer, are similar in that they both restrict communication between irradiated and bystander cells to media borne factors, but are distinct in that with the media transfer technique, cells can only communicate after irradiation, and with co-culture, cells can communication before, during and after irradiation. In this set of parallel experiments, cell type, biological endpoint, and radiation quality and dose, were kept constant. In both experimental systems, clonogenic survival was significantly decreased in all groups, whether irradiated or bystander, suggesting a substantial contribution of bystander effects (BE) to cell killing. Genomic instability (GI) was induced under all radiation and bystander conditions in both experiments, including a situation where unirradiated cells were incubated with media that had been conditioned for 24 h with irradiated cells. The appearance of delayed aberrations (genomic instability) 10-13 population doublings after irradiation was similar to the level of initial chromosomal damage, suggesting that the bystander factor is able to induce chromosomal alterations soon after irradiation. Whether these early alterations are related to those observed at later timepoints remains unknown. These results suggest that genomic instability may be significantly induced in a bystander cell population whether or not cells communicate during irradiation

  12. Influence of Magnolol on the bystander effect induced by alpha-particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wong, T.P.W.; Law, Y.L. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Tse, A.K.W.; Fong, W.F. [Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road, Kowloon Tong (Hong Kong); Yu, K.N. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)], E-mail: peter.yu@cityu.edu.hk

    2010-04-15

    In this work, the influence of Magnolol on the bystander effect in alpha-particle irradiated Chinese hamster ovary (CHO) cells was examined. The bystander effect was studied through medium transfer experiments. Cytokinesis-block micronucleus (CBMN) assay was performed to quantify the chromosome damage induced by alpha-particle irradiation. Our results showed that the alpha-particle induced micronuclei (MN) frequencies were suppressed with the presence of Magnolol.

  13. Bystander motivation in bullying incidents: to intervene or not to intervene?

    Science.gov (United States)

    Thornberg, Robert; Tenenbaum, Laura; Varjas, Kris; Meyers, Joel; Jungert, Tomas; Vanegas, Gina

    2012-08-01

    This research sought to extend knowledge about bystanders in bullying situations with a focus on the motivations that lead them to different responses. The 2 primary goals of this study were to investigate the reasons for children's decisions to help or not to help a victim when witnessing bullying, and to generate a grounded theory (or conceptual framework) of bystander motivation in bullying situations. Thirty students ranging in age from 9 to 15 years (M = 11.9; SD = 1.7) from an elementary and middle school in the southeastern United States participated in this study. Open- ended, semi-structured interviews were used, and sessions ranged from 30 to 45 minutes. We conducted qualitative methodology and analyses to gain an in-depth understanding of children's perspectives and concerns when witnessing bullying. A key finding was a conceptual framework of bystander motivation to intervene in bullying situations suggesting that deciding whether to help or not help the victim in a bullying situation depends on how bystanders define and evaluate the situation, the social context, and their own agency. Qualitative analysis revealed 5 themes related to bystander motives and included: interpretation of harm in the bullying situation, emotional reactions, social evaluating, moral evaluating, and intervention self-efficacy. Given the themes that emerged surrounding bystanders' motives to intervene or abstain from intervening, respondents reported 3 key elements that need to be confirmed in future research and that may have implications for future work on bullying prevention. These included: first, the potential importance of clear communication to children that adults expect bystanders to intervene when witnessing bullying; second, the potential of direct education about how bystanders can intervene to increase children's self-efficacy as defenders of those who are victims of bullying; and third, the assumption that it may be effective to encourage children's belief that

  14. Stress

    Science.gov (United States)

    ... taking care of an aging parent. With mental stress, the body pumps out hormones to no avail. Neither fighting ... with type 1 diabetes. This difference makes sense. Stress blocks the body from releasing insulin in people with type 2 ...

  15. Bystander apoptosis in human cells mediated by irradiated blood plasma

    Energy Technology Data Exchange (ETDEWEB)

    Vinnikov, Volodymyr, E-mail: vlad.vinnikov@mail.ru [Grigoriev Institute for Medical Radiology of the National Academy of Medical Science of Ukraine (Ukraine); Lloyd, David; Finnon, Paul [Centre for Radiation, Chemical and Environmental Hazards of the Health Protection Agency of the United Kingdom (United Kingdom)

    2012-03-01

    Following exposure to high doses of ionizing radiation, due to an accident or during radiotherapy, bystander signalling poses a potential hazard to unirradiated cells and tissues. This process can be mediated by factors circulating in blood plasma. Thus, we assessed the ability of plasma taken from in vitro irradiated human blood to produce a direct cytotoxic effect, by inducing apoptosis in primary human peripheral blood mononuclear cells (PBM), which mainly comprised G{sub 0}-stage lymphocytes. Plasma was collected from healthy donors' blood irradiated in vitro to 0-40 Gy acute {gamma}-rays. Reporter PBM were separated from unirradiated blood with Histopaque and held in medium with the test plasma for 24 h at 37 Degree-Sign C. Additionally, plasma from in vitro irradiated and unirradiated blood was tested against PBM collected from blood given 4 Gy. Apoptosis in reporter PBM was measured by the Annexin V test using flow cytometry. Plasma collected from unirradiated and irradiated blood did not produce any apoptotic response above the control level in unirradiated reporter PBM. Surprisingly, plasma from irradiated blood caused a dose-dependent reduction of apoptosis in irradiated reporter PBM. The yields of radiation-induced cell death in irradiated reporter PBM (after subtracting the respective values in unirradiated reporter PBM) were 22.2 {+-} 1.8% in plasma-free cultures, 21.6 {+-} 1.1% in cultures treated with plasma from unirradiated blood, 20.2 {+-} 1.4% in cultures with plasma from blood given 2-4 Gy and 16.7 {+-} 3.2% in cultures with plasma from blood given 6-10 Gy. These results suggested that irradiated blood plasma did not cause a radiation-induced bystander cell-killing effect. Instead, a reduction of apoptosis in irradiated reporter cells cultured with irradiated blood plasma has implications concerning oncogenic risk from mutated cells surviving after high dose in vivo irradiation (e.g. radiotherapy) and requires further study.

  16. Ion beam induced luminescence: Relevance to radiation induced bystander effects

    Science.gov (United States)

    Ahmad, S. B.; McNeill, F. E.; Byun, S. H.; Prestwich, W. V.; Seymour, C.; Mothersill, C. E.

    2012-10-01

    The aim of this work is quantify the light emitted as a result of charged particle interaction in materials which may be of relevance to radiation induced "bystander effects" studies. We have developed a system which employs single photon counting to measure the light emitted from samples irradiated under vacuum by a charged particle beam. The system uses a fast photomultiplier tube with a peak cathode response at 420 nm. It has been tested in a proof-of-principle experiment using polystyrene targets. Light output, as a result of irradiation, was measured. The luminescence yield appears to have a non-linear behavior with the incident ion fluence: it rises exponentially to an asymptotic value. The target was irradiated with beam energies varying from 1 to 2 MeV and showed saturation at or before an incident fluence rate of 3 × 1013 H+/cm2 s. The average saturation value for the photon output was found to be 40 × 106 cps. Some measurements were performed using filters to study the emission at specific wavelengths. In the case of filtered light measurements, the photon output was found to saturate at 28 × 103, 10 × 106, and 35 × 106 cps for wavelengths of 280 ± 5 nm, 320 ± 5 nm and 340 ± 5 nm respectively. The light output reaches a maximum value because of damage induced in the polymer. Our measurements indicate a "damage cross section" of the order of 10-14 cm2. The average radiant intensity was found to increase at wavelengths of 280 and 320 nm when the proton energy was increased. This was not found to occur at 340 nm. In conclusion, the light emission at specific wavelengths was found to depend upon the incident proton fluence and the proton energy. The wavelengths of the emitted light measured in this study have significance for the understanding of radiation induced bystander effects.

  17. Bystander apoptosis in human cells mediated by irradiated blood plasma

    International Nuclear Information System (INIS)

    Vinnikov, Volodymyr; Lloyd, David; Finnon, Paul

    2012-01-01

    Following exposure to high doses of ionizing radiation, due to an accident or during radiotherapy, bystander signalling poses a potential hazard to unirradiated cells and tissues. This process can be mediated by factors circulating in blood plasma. Thus, we assessed the ability of plasma taken from in vitro irradiated human blood to produce a direct cytotoxic effect, by inducing apoptosis in primary human peripheral blood mononuclear cells (PBM), which mainly comprised G 0 -stage lymphocytes. Plasma was collected from healthy donors’ blood irradiated in vitro to 0–40 Gy acute γ-rays. Reporter PBM were separated from unirradiated blood with Histopaque and held in medium with the test plasma for 24 h at 37 °C. Additionally, plasma from in vitro irradiated and unirradiated blood was tested against PBM collected from blood given 4 Gy. Apoptosis in reporter PBM was measured by the Annexin V test using flow cytometry. Plasma collected from unirradiated and irradiated blood did not produce any apoptotic response above the control level in unirradiated reporter PBM. Surprisingly, plasma from irradiated blood caused a dose-dependent reduction of apoptosis in irradiated reporter PBM. The yields of radiation-induced cell death in irradiated reporter PBM (after subtracting the respective values in unirradiated reporter PBM) were 22.2 ± 1.8% in plasma-free cultures, 21.6 ± 1.1% in cultures treated with plasma from unirradiated blood, 20.2 ± 1.4% in cultures with plasma from blood given 2–4 Gy and 16.7 ± 3.2% in cultures with plasma from blood given 6–10 Gy. These results suggested that irradiated blood plasma did not cause a radiation-induced bystander cell-killing effect. Instead, a reduction of apoptosis in irradiated reporter cells cultured with irradiated blood plasma has implications concerning oncogenic risk from mutated cells surviving after high dose in vivo irradiation (e.g. radiotherapy) and requires further study.

  18. Bystander's willingness to report theft, physical assault, and sexual assault: the impact of gender, anonymity, and relationship with the offender.

    Science.gov (United States)

    Nicksa, Sarah C

    2014-01-01

    This research examines bystander willingness to report three different crimes to the police or campus authorities among a college student sample (n = 295). Twelve original vignettes varied anonymity when reporting, bystander's relationship with the offender (friend or stranger), and crime type. A factorial analysis of variance showed that main effects were found for crime type, bystander's gender, and bystander's relationship with the offender; anonymity was not significant. The physical assault was the most likely to be reported (4.47), followed by theft (3.26), and sexual assault (2.36). Women were more likely than men to report each crime type, and bystanders who were good friends of the offender were less likely to report than strangers. No two- or three-way interactions were significant, but a significant four-way interaction indicated that anonymity, relationship with the offender, and bystander's gender predicted willingness to report for the sexual assault scenario.

  19. Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury.

    Science.gov (United States)

    Calì, Bianca; Ceolin, Stefano; Ceriani, Federico; Bortolozzi, Mario; Agnellini, Andrielly H R; Zorzi, Veronica; Predonzani, Andrea; Bronte, Vincenzo; Molon, Barbara; Mammano, Fabio

    2015-04-30

    Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding "bystander" cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely defined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxide (NO) that diffuses to bystander cells, in which NO levels are further increased by a mechanism compatible with Ca(2+)-dependent enzymatic production. We detected similar signals in tumors grown in dorsal skinfold chambers applied to live mice. Pharmacological blockade of connexin channels significantly reduced the extent of apoptosis in bystander cells, consistent with a critical role played by intercellular communication, Ca2+ and NO in the bystander effects triggered by photodynamic therapy.

  20. Bystanders' responses to offline bullying and cyberbullying: The role of empathy and normative beliefs about aggression.

    Science.gov (United States)

    Machackova, Hana; Pfetsch, Jan

    2016-04-01

    Cyberbullying often takes place with the virtual presence or knowledge of bystanders. While we have some evidence about the determinants of bystanders' responses to offline bullying, we lack empirical studies concerning the variables that influence bystanders' responses to cyberbullying. The current study examines bystanders' responses to offline bullying and cyberbullying incidents. Two types of responses were captured: support toward the victims and the reinforcement of bullies' actions. Using data from 321 German adolescents (ages 12-18; M = 14.99; 44% girls), the association between bystanders' responses and normative beliefs about verbal aggression and cyberaggression, and affective and cognitive empathy, were tested in a path model. Both types of normative beliefs positively predicted the reinforcement of bullies, and normative belief about verbal aggression also predicted support for the victims of offline bullying. Both types of empathy predicted support in offline bullying, but only affective empathy predicted support in cyberbullying. There was no link between affective or cognitive empathy to the reinforcement of bullies. Moreover, bystanders' tendencies to respond supportively to the victim or to reinforce the bully were rather consistent in both cyber- and offline bullying, but there was no link between support and reinforcement. The findings are discussed with regard to implications for prevention and intervention efforts. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  1. An Online Bystander Intervention Program for the Prevention of Sexual Violence.

    Science.gov (United States)

    Kleinsasser, Anne; Jouriles, Ernest N; McDonald, Renee; Rosenfield, David

    2015-07-01

    Because of its high prevalence and serious consequences for victims, sexual violence is a significant problem on college campuses. Sexual assault prevention programs based on the bystander intervention model have been shown to be effective; however, current programs are limited in terms of ease of distribution. To address this issue, we developed and evaluated "Take Care," an online bystander intervention program. To our knowledge, this is the first empirical evaluation of an online bystander intervention program designed to prevent sexual violence. Ninety-three participants (80.6% female, 19.4% male) recruited from social psychology classes at a mid-size university were randomly assigned to view one of two online programs: Take Care or a control program on study skills. Before viewing the programs, participants completed measures of bystander behaviors and feelings of efficacy for performing such behaviors. Measures were administered again post-intervention and at a two-month follow-up assessment. Participants who viewed Take Care reported greater efficacy for engaging in bystander behaviors at post-treatment and two months following treatment, compared to those who viewed the control program. In addition, participants who viewed Take Care reported performing relatively more bystander behaviors for friends at the two-month follow-up assessment, compared to participants who viewed the control program. These results suggest that sexual violence prevention programs may be effectively adapted to an online format.

  2. Relationship between P53 and bystander effect induced by radiated hepatoma cells

    International Nuclear Information System (INIS)

    Zhao Meijia; Shen Bo; Yuan Dexiao; Cheng Honghong; Shao Chunlin

    2009-01-01

    The role of p53 in bystander responses on normal liver cells were investigated by co-culturing irradiated hepatoma cells with non-irradiated bystander Chang liver cells. It was found that radiosensitivity of the hepatoma cells was relative to p53. HepG2 cells with wtp53 had the highest radiosensitivity followed by PLC/PRF/5 cells with mtp53 and Hep3B cells with null-p53. The induction of bystander micronucleus(MN) was observed only in the Chang liver cells that had been co-cultured with HepG2 cells but not co-cultured with PLC/PRF/5 or Hep3B. Also, this bystander MN was relative to the irradiation dose and the cell co-culture rime. When the hepatoma cells were treated with pifithrin-α, a p53 inhibitor, their radiosensitivities were reduced, and the bystander effect was diminished. The results indicate that p53 could regulate not only the radiosensitivity but also the bystander response. (authors)

  3. Detection of chromosomal instability in α-irradiated and bystander human fibroblasts

    International Nuclear Information System (INIS)

    Ponnaiya, Brian; Jenkins-Baker, Gloria; Bigelow, Alan; Marino, Stephen; Geard, Charles R.

    2004-01-01

    There is increasing evidence biological responses to io