Postnatal Acute Famine and Risk of Overweight: The Dutch Hungerwinter Study

Objective. To examine the association between undernutrition during postnatal periods of development and the risk of overweight in adulthood. Methods. We studied 8,091 women from Prospect-EPIC, exposed to the Dutch famine at ages between 0 and 21 years, recruited at ages between 49 and 70 years. We used linear and logistic regression models to explore the effect of famine on BMI, waist circumference, and the risk of overweight. Results. Overall, postnatal famine exposure was associated with increased BMI and waist circumference in a dose-dependent manner (P  for trend < 0.01). Furthermore, risk of overweight was increased following famine exposure (P  for trend = 0.01), with those severely exposed at ages 0–9 years having 25% (95% CI 1.05 to 1.50) higher risk compared to unexposed women. Conclusions. This study is the first to directly show a positive association between short and transient undernutrition during postnatal development and BMI, waist circumference, and overweight in adulthood

Direct Evidence for Termination of Obscured Star Formation by Radiatively Driven Outflows in Reddened QSOs

We present optical to far-infrared photometry of 31 reddened QSOs that show evidence for radiatively driven outflows originating from AGN in their rest-frame UV spectra. We use these data to study the relationships between the AGN-driven outflows, and the AGN and starburst infrared luminosities. We find that FeLoBAL QSOs are invariably IR-luminous, with IR luminosities exceeding 10^{12} Solar luminosities in all cases. The AGN supplies 76% of the total IR emission, on average, but with a range from 20% to 100%. We find no evidence that the absolute luminosity of obscured star formation is affected by the AGN-driven outflows. Conversely, we find an anticorrelation between the strength of AGN-driven outflows, as measured from the range of outflow velocities over which absorption exceeds a minimal threshold, and the contribution from star formation to the total IR luminosity, with a much higher chance of seeing a starburst contribution in excess of 25% in systems with weak outflows than in systems with strong outflows. Moreover, we find no convincing evidence that this effect is driven by the IR luminosity of the AGN. We conclude that radiatively driven outflows from AGN can have a dramatic, negative impact on luminous star formation in their host galaxies. We find that such outflows act to curtail star formation such that star formation contributes less than ~25% of the total IR luminosity. We also propose that the degree to which termination of star formation takes place is not deducible from the IR luminosity of the AGN.Comment: Accepted for publication in Ap

Childhood Atopic Diseases and Early Life Circumstances: An Ecological Study in Cuba

Background: Children are especially vulnerable during periods of resource shortage such as economic embargoes. They are likely to suffer most from poor nutrition, infectious diseases, and other ensuing short-term threats. Moreover, early life circumstances can have important consequences for long-term health. We examined the relationship between early childhood exposure to the Cuban economic situation in the nineties and the occurrence of atopic diseases later in childhood. Methodology/Principal Findings: A cross-sectional study of 1321 primary schoolchildren aged 4-14 was conducted in two Cuban municipalities. Asthma, allergic rhinoconjunctivitis and atopic dermatitis were diagnosed using the International Study of Asthma and Allergies in Childhood questionnaire. Children were divided into three groups of exposure to the economic situation in the nineties according to birth date: (1) unexposed; (2) exposed during infancy; (3) exposed during infancy and early childhood. Associations were assessed using multiple logistic regression models. Exposure during infancy had a significant inverse association with the occurrence of asthma (OR 0.56, 95% CI 0.33-0.94) and allergic rhinoconjunctivitis (OR 0.46, 95% CI 0.25-0.85). The associations were stronger after longer exposure, i.e. during infancy and early childhood, for asthma (OR 0.40, 95% CI 0.17-0.95) and allergic rhinoconjunctivitis (OR 0.29, 95% CI 0.11-0.77). No significant associations were found for atopic dermatitis. Conclusions/Significance: Exposure to the economic situation in the nineties during infancy and early childhood was inversely associated with asthma and allergic rhinoconjunctivitis occurrence later in childhood. We hypothesize that factors related to this period, such as infectious diseases and undernutrition, may have an attenuating effect on atopic disease development. The exact cause and underlying mechanisms need to be further elucidated

Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep

AbstractThe circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep

The effects of in vivo amphetamine treatment on dopamine receptor-coupled adenylate cyclase activities in the rat striatum.

D1 receptor-coupled adenylate cyclase in the rat striatum is desensitized 30 min after a single intraperitoneal injection of 2.5 or 7.5 mg/kg amphetamine. The apparent V$\\sb{\\rm max}$ for stimulation of adenylate cyclase by the D1 receptor-selective agonist SKF 38393 (($\\pm$)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol) in rat striatal crude membranes is decreased by 21% as compared with saline-injected controls. The apparent V$\\sb{\\rm max}$ was, 199 $\\pm$ 17 pmol/min/mg of protein for the saline group and 157 $\\pm$ 14 pmol/min/mg of protein for the AMPH group. The desensitization is reversible and is not seen in the mesolimbic forebrain. The goal of the thesis project was to further characterize this desensitization. First, the effects of amphetamine on the components of the D1 receptor-coupled adenylate cyclase were examined to determine the site that contributed to the desensitization. The desensitization was accompanied by a decrease in high affinity agonist binding. There was a statistically significant 44% decrease in the B$\\sb{\\rm max}$ for the binding of ($\\sp3$H) DA in the AMPH group (80 $\\pm$ 24 fmol/mg of protein) as compared with the saline group (143 $\\pm$ 23 fmol/mg of protein), n = 5, p $<$ 0.05, and no detectable change in the K$\\sb{\\rm D}$ between the AMPH group and the saline group. This suggests that the site of modification is the receptor or the coupling between the receptor and G$\\sb{\\rm s}.$ Second, the specificity of the desensitization was assessed by examining the effects of in vivo amphetamine on dopamine D2, adenosine A$\\sb2$, and cholinergic receptor coupling to adenylate cyclase. The results demonstrated that in vivo amphetamine pretreatment produced a desensitization that was specific for D1 and D2 receptor-coupled adenylate cyclase activities, implying that the desensitization is homologous. A second goal of the project was to assess the effect of prior repeated intermittent exposure to amphetamine on the ability of acute amphetamine to desensitize D1 receptor-coupled adenylate cyclase. After chronic amphetamine treatment a challenge injection with 1.0 mg/kg AMPH, a dose which did not produce a desensitization in rats that were chronically injected with saline, resulted in a 40% decrease in the V$\\sb{\\rm max}$ for SKF 38393-stimulated adenylate cyclase. These results suggest that prior exposure to amphetamine can lower the dose of amphetamine necessary to produce a desensitization of D1 receptor-coupled adenylate cyclase.Ph.D.PharmacologyNeurosciencesUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/162243/1/8920607.pd

Adult mortality at age 57 after prenatal exposure to the Dutch famine

Prenatal famine exposure has previously been shown to be associated with cardiovascular disease and type II diabetes in adulthood. In the current study, we could not demonstrate an effect of prenatal exposure to famine in 2254 term singletons born during the 1944–1945 Dutch famine on adult mortality up to the age of 57 years. Follow-up of this cohort will resolve whether famine exposure is linked to increased adult mortality

Early life adversity in primates: Behavioral, endocrine, and neural effects.

BACKGROUND: Evidence suggests that early life adversity is associated with maladaptive behaviors and is commonly an antecedent of stress-related psychopathology. This is particularly relevant to rearing in primate species as infant primates depend on prolonged, nurturant rearing by caregivers for normal development. To further understand the consequences of early life rearing adversity, and the relation among alterations in behavior, physiology and brain function, we assessed young monkeys that had experienced maternal separation followed by peer rearing with behavioral, endocrine and multimodal neuroimaging measures. METHODS: 50 young rhesus monkeys were studied, half of which were rejected by their mothers and peer reared, and the other half were reared by their mothers. Assessments were performed at approximately 1.8 years of age and included: threat related behavioral and cortisol responses, cerebrospinal fluid (CSF) measurements of oxytocin and corticotropin releasing hormone (CRH), and multimodal neuroimaging measures (anatomical scans, resting functional connectivity, diffusion tensor imaging, and threat-related regional glucose metabolism). RESULTS: The results demonstrated alterations across behavioral, endocrine, and neuroimaging measures in young monkeys that were reared without their mothers. At a behavioral level in response to a potential threat, peer reared animals engaged in significantly less freezing behavior (p&nbsp;=&nbsp;0.022) along with increased self-directed behaviors (p&nbsp;&lt;&nbsp;0.012). Levels of oxytocin in the CSF, but not plasma, were significantly reduced in the peer reared animals (p&nbsp;=&nbsp;0.019). No differences in plasma cortisol or CSF CRH were observed. Diffusion tensor imaging revealed significantly decreased white matter density across the brain. Exploratory correlational and permutation analyses suggest that the impact of peer rearing on behavior, endocrine and brain structural alterations are mediated by separate parallel mechanisms. CONCLUSIONS: Taken together, these results demonstrate in NHPs the importance of maternal rearing on the development of brain, behavior and hormonal systems that are linked to social functioning and adaptive responses. The findings suggest that the effects of maternal deprivation are mediated via multiple independent pathways which may account for the heterogeneity in behavioral and biological alterations observed in individuals that have experienced this early life adversity

The metabolic syndrome in adults prenatally exposed to the Dutch famine

BACKGROUND: Epidemiologic studies have shown that the metabolic syndrome may originate in utero. OBJECTIVE: We aimed to determine whether exposure to prenatal famine is associated with a greater prevalence of the metabolic syndrome. DESIGN: We assessed the prevalence of the metabolic syndrome according to the National Cholesterol Education Program definition in 783 members of the Dutch Famine Birth Cohort. Participants were born as term singletons around the time of the 1944-1945 Dutch famine. RESULTS: Exposure to famine during gestation was not significantly associated with the metabolic syndrome (odds ratio: 1.2; 95% CI: 0.9, 1.7). Birth weight also was not significantly associated with the metabolic syndrome (odds ratio: 1.3/1-kg decrease in birth weight; 95% CI: 0.9, 1.8/1-kg decrease in birth weight). Exposure to famine during gestation was associated with significantly higher triacylglycerol concentrations (0.1 g/L; 0.0, 0.2 g/L). Men exposed to famine in early gestation had significantly lower HDL-cholesterol concentrations (-0.08 mmol/L; -0.14, 0.00 mmol/L) than did unexposed men. CONCLUSIONS: Prenatal exposure to famine or reduced birth weight is not associated with a significantly greater prevalence of the metabolic syndrome. Our findings suggest that, although elements of the metabolic syndrome may be programmed by fetal undernutrition, the origin of the syndrome as a whole is not likely to be found in poor nutrition during gestatio