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Sample records for early postnatal death

  1. Parental experiences of early postnatal discharge

    DEFF Research Database (Denmark)

    Nilsson, Ingrid; Danbjørg, Dorthe B.; Aagaard, Hanne

    2015-01-01

    and taking responsibility; A time of insecurity; Being together as a family; and Striving to be confident. The mothers׳ and fathers׳ experiences of responsibility, security and confidence in their parental role, were positively influenced by having the opportunity to be together as a family, receiving...... postnatal care that included both parents, having influence on time of discharge, and getting individualised and available support focused on developing and recognising their own experiences of taking care of the baby. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the new parents׳ experiences of early...... discharge and becoming a parent were closely related. Feeling secure and confident in the parental role was positively or negatively influenced by the organisation of early discharge. This underscores the importance of the way health professionals support new mothers and fathers at early postnatal discharge....

  2. Facility Delivery, Postnatal Care and Neonatal Deaths in India: Nationally-Representative Case-Control Studies.

    Directory of Open Access Journals (Sweden)

    Shaza A Fadel

    Full Text Available Clinical studies demonstrate the efficacy of interventions to reduce neonatal deaths, but there are fewer studies of their real-life effectiveness. In India, women often seek facility delivery after complications arise, rather than to avoid complications. Our objective was to quantify the association of facility delivery and postnatal checkups with neonatal mortality while examining the "reverse causality" in which the mothers deliver at a health facility due to adverse perinatal events.We conducted nationally representative case-control studies of about 300,000 live births and 4,000 neonatal deaths to examine the effect of, place of delivery and postnatal checkup on neonatal mortality. We compared neonatal deaths to all live births and to a subset of live births reporting excessive bleeding or obstructed labour that were more comparable to cases in seeking care.In the larger study of 2004-8 births, facility delivery without postnatal checkup was associated with an increased odds of neonatal death (Odds ratio = 2.5; 99% CI 2.2-2.9, especially for early versus late neonatal deaths. However, use of more comparable controls showed marked attenuation (Odds ratio = 0.5; 0.4-0.5. Facility delivery with postnatal checkup was associated with reduced odds of neonatal death. Excess risks were attenuated in the earlier study of 2001-4 births.The combined effect of facility deliveries with postnatal checks ups is substantially higher than just facility delivery alone. Evaluation of the real-life effectiveness of interventions to reduce child and maternal deaths need to consider reverse causality. If these associations are causal, facility delivery with postnatal check up could avoid about 1/3 of all neonatal deaths in India (~100,000/year.

  3. Early postnatal dexamethasone treatment and increased incidence of cerebral palsy

    National Research Council Canada - National Science Library

    Shinwell, E S; Karplus, M; Reich, D; Weintraub, Z; Blazer, S; Bader, D; Yurman, S; Dolfin, T; Kogan, A; Dollberg, S; Arbel, E; Goldberg, M; Gur, I; Naor, N; Sirota, L; Mogilner, S; Zaritsky, A; Barak, M; Gottfried, E

    2000-01-01

    To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease...

  4. Cell proliferation and cell death are disturbed during prenatal and postnatal brain development after uranium exposure.

    Science.gov (United States)

    Legrand, M; Elie, C; Stefani, J; N Florès; Culeux, C; Delissen, O; Ibanez, C; Lestaevel, P; Eriksson, P; Dinocourt, C

    2016-01-01

    The developing brain is more susceptible to neurotoxic compounds than adult brain. It is also well known that disturbances during brain development cause neurological disorders in adulthood. The brain is known to be a target organ of uranium (U) exposure and previous studies have noted that internal U contamination of adult rats induces behavioral disorders as well as affects neurochemistry and neurophysiological properties. In this study, we investigated whether depleted uranium (DU) exposure affects neurogenesis during prenatal and postnatal brain development. We examined the structural morphology of the brain, cell death and finally cell proliferation in animals exposed to DU during gestation and lactation compared to control animals. Our results showed that DU decreases cell death in the cortical neuroepithelium of gestational day (GD) 13 embryos exposed at 40mg/L and 120mg/L and of GD18 fetuses exposed at 120mg/L without modification of the number of apoptotic cells. Cell proliferation analysis showed an increase of BrdU labeling in the dentate neuroepithelium of fetuses from GD18 at 120mg/L. Postnatally, cell death is increased in the dentate gyrus of postnatal day (PND) 0 and PND5 exposed pups at 120mg/L and is associated with an increase of apoptotic cell number only at PND5. Finally, a decrease in dividing cells is observed in the dentate gyrus of PND21 rats developmentally exposed to 120mg/L DU, but not at PND0 and PND5. These results show that DU exposure during brain development causes opposite effects on cell proliferation and cell death processes between prenatal and postnatal development mainly at the highest dose. Although these modifications do not have a major impact in brain morphology, they could affect the next steps of neurogenesis and thus might disrupt the fine organization of the neuronal network.

  5. Gestational and early postnatal exposure to simulated high altitude does not modify postnatal body mass growth trajectory in the rat.

    Science.gov (United States)

    Bozzini, Carlos E; Champin, Graciela M; Bozzini, Clarisa; Alippi, Rosa M

    2014-09-01

    Postnatal hypoxia blunts body mass growth. It is also known that the quality of the fetal environment can influence the subsequent adult phenotype. The main purpose of the study was to determine whether gestational hypoxia and early postnatal hypoxia are able to blunt growth when the offspring is raised under normoxia. Hypobaric hypoxia was induced in simulated high altitude (SHA) chambers in which air was maintained at 380 mmHg (5450 m). Mature Sprague-Dawley rats of both sexes were divided in normoxic (NX) and hypoxic (HX) groups and, in the case of the HX group, maintained for 1 month at 5450 m. Mating was then allowed under NX or HX conditions. Offspring were NX-NX, NX-HX, HX-HX, or HX-NX: the first term indicates NX or HX during both gestation and the first 30 days of life; the second term indicates NX or HX during postnatal life between days 30 and 133. Body mass (g) was measured periodically and body mass growth rate (BMGR, g/d) was estimated between days 33 and 65 of postnatal life. Results can be summarized as follows: 1) BM was significantly higher in NX than in HX rats at weaning; 2) BMGR was not significantly different between NX-NX and HX-NX rats, and between HX-HX and NX-HX animals; and 3) BMGR was significantly higher in rats living under NX conditions than in those living under HX conditions during postnatal life. Data suggest that that hypobaric hypoxia during gestational and early postnatal development of rats does not alter the regulation of body mass growth in rats when compared to that seen under sea-level conditions.

  6. Cell death atlas of the postnatal mouse ventral forebrain and hypothalamus: effects of age and sex.

    Science.gov (United States)

    Ahern, Todd H; Krug, Stefanie; Carr, Audrey V; Murray, Elaine K; Fitzpatrick, Emmett; Bengston, Lynn; McCutcheon, Jill; De Vries, Geert J; Forger, Nancy G

    2013-08-01

    Naturally occurring cell death is essential to the development of the mammalian nervous system. Although the importance of developmental cell death has been appreciated for decades, there is no comprehensive account of cell death across brain areas in the mouse. Moreover, several regional sex differences in cell death have been described for the ventral forebrain and hypothalamus, but it is not known how widespread the phenomenon is. We used immunohistochemical detection of activated caspase-3 to identify dying cells in the brains of male and female mice from postnatal day (P) 1 to P11. Cell death density, total number of dying cells, and regional volume were determined in 16 regions of the hypothalamus and ventral forebrain (the anterior hypothalamus, arcuate nucleus, anteroventral periventricular nucleus, medial preoptic nucleus, paraventricular nucleus, suprachiasmatic nucleus, and ventromedial nucleus of the hypothalamus; the basolateral, central, and medial amygdala; the lateral and principal nuclei of the bed nuclei of the stria terminalis; the caudate-putamen; the globus pallidus; the lateral septum; and the islands of Calleja). All regions showed a significant effect of age on cell death. The timing of peak cell death varied between P1 to P7, and the average rate of cell death varied tenfold among regions. Several significant sex differences in cell death and/or regional volume were detected. These data address large gaps in the developmental literature and suggest interesting region-specific differences in the prevalence and timing of cell death in the hypothalamus and ventral forebrain. Copyright © 2013 Wiley Periodicals, Inc.

  7. Arousal responses in babies at risk of sudden infant death syndrome at different postnatal ages.

    LENUS (Irish Health Repository)

    Dunne, K P

    1992-03-01

    Hypercarbic and hypoxic arousal responses during sleep were measured in healthy term infants, infants where a previous sibling died from sudden infant death syndrome (SIDS) and infants suffering a clearly defined apparent life threatening event (ALTE) requiring vigorous or mouth to mouth resuscitation. Groups of infants were tested at approximately one, six and 13 weeks postnatally. Arousal was defined as gross body movement with eyes opening and moving or crying. Hypercarbic arousal was by step increases in F1 Co2 until arousal occurred or until endtidal (PETCO2) reached 8.7 KpA (65 mm Hg) Hypoxic arousal was by step decreases in FIO2 until arousal occurred or until an FIO2 of 0.15 had been maintained for 20 minutes. There was no difference in hypercaribic arousal threshold with age in any group. Hypercarbic arousal threshold was significantly higher in siblings (mean 53.4, 53.6, 54.7 mmHg. [7.12, 7.14, 7.29 KPA] at 0, 6, 13 postnatal weeks) compared to controls (mean 50.9, 52.3, 53.0mm Hg. [6.78, 6.97, 7.29 KPS respectively). ALTE infants differed only at 12 weeks having a significantly lower threshold (51.0mmHg. [6.80 KPA] V 53.0mm Hg. (7.06 KPA]) compared to controls. There was no difference in hypoxic arousal response with age in any group. An arousal response to hypoxia occurred in only 22% of ALTE infants and 40% of siblings compared to 67% of normal infants. Deficient sleep arousal, especially to hypoxia, is common in infants and especially those considered at increased risk from SIDS. This deficiency is present in the first postnatal week and did not vary overy the first three months of postnatal life.

  8. Impact of Early Postnatal Androgen Exposure on Voice Development

    Science.gov (United States)

    Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

    2012-01-01

    Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

  9. Impact of early postnatal androgen exposure on voice development.

    Directory of Open Access Journals (Sweden)

    Leila Grisa

    Full Text Available BACKGROUND: The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT in childhood. METHODS: The long-term effects of androgen exposure on the fundamental vocal frequency (F0, vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years and 10 adolescent (13.6 to 17.8 years female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. RESULTS: Of the 19 subjects, 17 (89% had been diagnosed with ACT before 4 years of age, 1 (5% at 8.16 years, and 1 (5% at 10.75 years. Androgen exposure (2 to 30 months was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19 of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. CONCLUSIONS: Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors.

  10. Cell death during the postnatal morphogenesis of the normal rabbit kidney and in experimental renal polycystosis.

    Science.gov (United States)

    García-Porrero, J A; Ojeda, J L; Hurlé, J M

    1978-01-01

    We have studied, by means of optic and electron microscopy, the normal and abnormal cell death that takes place during the postnatal morphogenesis of rabbit kidney, and in the experimental renal polycystosis produced by methylprednisolone acetate. In the normal kidney intertubular cell death can be observed during the first 20 days of the postnatal development. However, cell death in the normal metanephric blastema is a very rare event. In the polycystic kidney numerous dead cells can be seen between the third and forty eighth days after injection. The topography and morphology of the dead cells depend on the stage in the evolution of the disease. In the 'stage of renal immaturity', dying and dead cells are present in the nephrogenic tissue, in the dilating collecting tubules and in the intertubular spaces. In this stage the cellular pathology is essentially nuclear. In the stage of tubular cysts, the dead cells are mostly located in the walls of cysts, with some dead cells, but mostly cellular debris in their lumina. At this stage the cellular pathology is basically cytoplasmic. The dead cells are eventually digested by what appear to be phagocytes of tubular epithelial origin. It is suggested that cell death is an important factor in the evolution of the lesions of renal polycystosis induced by corticosteroids, and probably in the initiation of the pathological process as well. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 PMID:670065

  11. Early Postnatal Blood Manganese Levels and Children’s Neurodevelopment

    Science.gov (United States)

    Henn, Birgit Claus; Ettinger, Adrienne S.; Schwartz, Joel; Téllez-Rojo, Martha María; Lamadrid-Figueroa, Héctor; Hernández-Avila, Mauricio; Schnaas, Lourdes; Amarasiriwardena, Chitra; Bellinger, David C.; Hu, Howard; Wright, Robert O.

    2011-01-01

    Background Recent evidence suggests that low-level environmental exposure to manganese adversely affects child growth and neurodevelopment. Previous studies have addressed the effects of prenatal exposure, but little is known about developmental effects of early postnatal exposure. Methods We studied 448 children born in Mexico City from 1997 through 2000, using a longitudinal study to investigate neurotoxic effects of early life manganese exposure. Archived blood samples, collected from children at 12 and 24 months of age, were analyzed for manganese levels using inductively-coupled plasma mass spectrometry. Mental and psychomotor development were scored using Bayley Scales of Infant Development at 6-month intervals between 12 and 36 months of age. Results At 12 months of age, the mean (SD) blood manganese level was 24.3 (4.5) μg/l and the median was 23.7 μg/l; at 24 months, these values were 21.1 (6.2) μg/l and 20.3 μg/l, respectively. Twelve- and 24-month manganese concentrations were correlated (Spearman correlation = 0.55) and levels declined over time (β = −5.7 [95% CI = −6.2 to −5.1]). We observed an inverted U-shaped association between 12-month blood manganese and concurrent mental development scores (compared with the middle 3 manganese quintiles, for the lowest manganese quintile, β = −3.3 [−6.0 to −0.7] and for the highest manganese quintile, β = −2.8 [−5.5 to −0.2]). This 12-month manganese effect was apparent but diminished with mental development scores at later ages. The 24-month manganese levels were not associated with neurodevelopment. Conclusions These results suggest a possible biphasic dose-response relationship between early-life manganese exposure at lower exposure levels and infant neurodevelopment. The data are consistent with manganese as both an essential nutrient and a toxicant. PMID:20549838

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    OBJECTIVE: To investigate the association between exposure to mothers smoking during prenatal and early postnatal life and risk of overweight at age 7 years, while taking birth weight into account. METHODS: From the Danish National Birth Cohort a total of 32,747 families were identified with avai......, and with higher OR if exposed both during pregnancy and in early postnatal life. Clear dose-response relationships were observed, which emphasizes the need for prevention of any tobacco exposure of infants....

  13. Effect of fetal undernutrition and postnatal overfeeding on rat adipose tissue and organ growth at early stages of postnatal development.

    Science.gov (United States)

    Munoz-Valverde, D; Rodríguez-Rodríguez, P; Gutierrez-Arzapalo, P Y; López de Pablo, A L; Carmen González, M; López-Giménez, R; Somoza, B; Arribas, S M

    2015-01-01

    Intrauterine and perinatal life are critical periods for programming of cardiometabolic diseases. However, their relative role remains controversial. We aimed to assess, at weaning, sex-dependent alterations induced by fetal or postnatal nutritional interventions on key organs for metabolic and cardiovascular control. Fetal undernutrition was induced by dam food restriction (50 % from mid-gestation to delivery) returning to ad libitum throughout lactation (Maternal Undernutrition, MUN, 12 pups/litter). Postnatal overfeeding (POF) was induced by litter size reduction from normally fed dams (4 pups/litter). Compared to control, female and male MUN offspring exhibited: 1) low birth weight and accelerated growth, reaching similar weight and tibial length by weaning, 2) increased glycemia, liver and white fat weights; 3) increased ventricular weight and tendency to reduced kidney weight (males only). Female and male POF offspring showed: 1) accelerated growth; 2) increased glycemia, liver and white fat weights; 3) unchanged heart and kidney weights. In conclusion, postnatal accelerated growth, with or without fetal undernutrition, induces early alterations relevant for metabolic disease programming, while fetal undernutrition is required for heart abnormalities. The progression of cardiac alterations and their role on hypertension development needs to be evaluated. The similarities between sexes in pre-pubertal rats suggest a role of sex-hormones in female protection against programming.

  14. Early postnatal testosterone predicts sex-related differences in early expressive vocabulary.

    Science.gov (United States)

    Kung, Karson T F; Browne, Wendy V; Constantinescu, Mihaela; Noorderhaven, Rebecca M; Hines, Melissa

    2016-06-01

    During the first few years of life, girls typically have a larger expressive vocabulary than boys. This sex difference is important since a small vocabulary may predict subsequent language difficulties, which are more prevalent in boys than girls. The masculinizing effects of early androgen exposure on neurobehavioral development are well-documented in nonhuman mammals. The present study conducted the first test of whether early postnatal testosterone concentrations influence sex differences in expressive vocabulary in toddlers. It was found that testosterone measured in saliva samples collected at 1-3 months of age, i.e., during the period called mini-puberty, negatively predicted parent-report expressive vocabulary size at 18-30 months of age in boys and in girls. Testosterone concentrations during mini-puberty also accounted for additional variance in expressive vocabulary after other predictors such as sex, child's age at vocabulary assessment, and paternal education, were taken into account. Furthermore, testosterone concentrations during mini-puberty mediated the sex difference in expressive vocabulary. These results suggest that testosterone during the early postnatal period contributes to early language development and neurobehavioral sexual differentiation in humans.

  15. Repeatability of Maternal Report on Prenatal, Perinatal and Early Postnatal Factors

    DEFF Research Database (Denmark)

    Hermann, Diana; Suling, Marc; Reisch, Lucia

    2011-01-01

    and length, Caesarean (C)-section, week of delivery) and early postnatal factors (exclusive breastfeeding, breastfeeding, introduction of solid food). Intra-class correlation coefficients (ICCs) were calculated to compare maternal reports on prenatal, perinatal and early postnatal factors between the first......To investigate the repeatability of maternal self-reported prenatal, perinatal and early postnatal factors within the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study. Design: Data are from the baseline survey of the longitudinal...... reports showed moderate correlation for the introduction of several types of food (cereals ICC=0.64, Pless than or equal to0.05; fruits ICC=0.70, Pless than or equal to0.05; meat ICC=0.83, Pless than or equal to0.05; vegetables ICC=0.75, Pless than or equal to0.05), and high correlation (ICC=0.88, Pless...

  16. [Effects of early postnatal exposure to dieldrin on synaptic development of striatum in mice].

    Science.gov (United States)

    Gao, Ye; Wang, Qu-nan; Wu, Shan

    2012-02-01

    To investigate the effects of early postnatal exposure to dieldrin on striatum synaptic development in lactation, adolescence and adulthood of mice. The pups were divided into 5 groups randomly. Three groups were exposed to dieldrin (0.01% DMSO solution) at doses of 0.2, 2.0 and 20.0 microg/kg and two control groups were exposed to DMSO or saline by intraperitoneal injection of every other day from postnatal days (PND) 3 to PND13. The striatum were isolated from brain in lactation (PND14), adolescence (PND36) and adulthood (PND98). Western blot assay was used to detect the expression levels of striatal synaptic proteins. The postnatal exposure to dieldrin could reduce the level of growth associated protein (GAP43) of striatum in lactation in a dose-dependent manner. In adolescence, the level of glial fibrillary acidic protein (GFAP) in striatum increased and the levels of tyrosine hydroxylase (TH), GAP43 and post-synaptic density protein 95 (PSD95) decreased with exposure doses. The level of Synapsin I decreased in adolescence male mice. The changes of expression levels of GFAP, TH and PSD95 proteins lasted to adulthood. Early postnatal exposure to dieldrin could affect the expression level of GAP43 protein in striatum. The expression levels of TH and PSD95 proteins in striatum decreased in adolescence and adulthood. These results indicated that the early postnatal exposure to dieldrin may persistently interfere in the striatal synaptic development.

  17. Progress of farrowing and early postnatal pig behavior in relation to genetic merit for pig survival

    NARCIS (Netherlands)

    Leenhouwers, J.L.; Almeida Junior, de C.A.; Knol, E.F.; Lende, van der T.

    2001-01-01

    The objective of this study was to investigate whether pigs with different genetic merit for survival differed in birth weight, progress of farrowing, early postnatal behavior, or rectal temperature within 24 h after birth. On a nucleus farm in Rio Verde, Brazil, information was collected on 280 pig

  18. Daily activity of the rabbit jaw muscles during early postnatal development

    NARCIS (Netherlands)

    van Wessel, T.; Langenbach, G.E.J.; Brugman, P.; Korfage, J.A.M.; van Eijden, T.M.G.J.

    2006-01-01

    Early postnatal development of the jaw muscles is characterized by the transition from suckling to chewing behavior. As chewing develops the jaw closing muscles become more powerful compared with the jaw openers. These changes are likely to affect the amount of daily muscle activity. Therefore, the

  19. Do families after early postnatal discharge need new ways to communicate with the hospital?

    DEFF Research Database (Denmark)

    Danbjørg, Dorthe Boe; Wagner, Lis; Clemensen, Jane

    2014-01-01

    the length of the postnatal hospital stay in Denmark as well as globally has been radically reduced over the past 10-20 years and this raises the challenge of finding new ways of providing observation and support to families discharged early, that they otherwise would be provided as inpatients. A...

  20. Evaluation of a neurodevelopmental model of schizophrenia - Early postnatal PCP treatment in attentional set-shifting

    DEFF Research Database (Denmark)

    Broberg, B.V.; Dias, R.; Olsen, C.K.;

    2008-01-01

    Phencyclidine (PCP) was administered to male and female Lister hooded rats on postnatal days (PND) 7, 9 and 11. All PCP animals tested in adulthood (PND 53-93) showed deficits in cognitive flexibility, specifically in their ability to shift attentional set, compared to controls. This novel findin...... is reminiscent of the impairment observed in schizophrenia patients, and supports the validity of the early postnatal PCP regimen as a disease-like model. (c) 2008 Elsevier B.V. All rights reserved Udgivelsesdato: 2008...

  1. Impaired GABAergic Inhibition in the Prefrontal Cortex of Early Postnatal Phencyclidine (PCP)-Treated Rats

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe

    2014-01-01

    in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction...... in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl...... postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life....

  2. Effect of prenatal cocaine on early postnatal thermoregulation and ultrasonic vocalization production

    Directory of Open Access Journals (Sweden)

    Matthew Stephen McMurray

    2013-11-01

    Full Text Available Prenatal cocaine exposure can alter the postnatal care received by rat pups. Such effects could be caused in part by alterations in pup-produced stimuli that elicit early postnatal maternal care. Pup ultrasonic vocalizations are thought to be a particularly salient stimulus, and when paired with other cues, may elicit maternal attention. Cocaine is known to acutely alter thermoregulatory and cardiac function, thus prenatal cocaine may affect vocalizations through altering these functions. The data presented here determine the impact of full term prenatal cocaine exposure , saline exposure, or no exposure on thermogenic capacity, cardiac function, and the resulting ultrasonic vocalizations across the early postnatal period (days 1-5. Results indicated that while sharing many similar characteristics with saline-exposed and untreated animals, prenatal cocaine exposure was associated with specific alterations in vocalization characteristics on postnatal day 1 (PND 1, including call amplitude. Furthermore, numerous spectral parameters of their vocalizations were found altered on PND 3, including rate, call duration, and frequency, while no alterations were found on PND 5. Additionally, cocaine-exposed pups also showed a reduced thermoregulatory capacity compared to saline animals and reduced cardiac mass compared to untreated animals on PND 5. Together, these findings indicate that prenatal cocaine may be altering the elicitation of maternal care through its impact on vocalizations and thermoregulation, and suggests a potential mechanism for these effects through cocaine’s impact on developing stress systems.

  3. Adult neuropsychological performance following prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water.

    Science.gov (United States)

    Janulewicz, Patricia A; White, Roberta F; Martin, Brett M; Winter, Michael R; Weinberg, Janice M; Vieira, Veronica; Aschengrau, Ann

    2012-01-01

    This population-based retrospective cohort study examined adult performance on a battery of neuropsychological tests in relation to prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using pipe network information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and a Geographic Information System (GIS). Results of crude and multivariate analyses among 35 exposed and 28 unexposed subjects showed no association between prenatal and early postnatal exposure and decrements on tests that assess abilities in the domains of omnibus intelligence, academic achievement or language. The results were suggestive of an association between prenatal and early postnatal PCE exposure and diminished performance on tests that assessed abilities in the domains of visuospatial functioning, learning and memory, motor, attention and mood. Because the sample size was small, most findings were not statistically significant. Future studies with larger sample sizes should be conducted to further define the neuropsychological consequences of early developmental PCE exposure.

  4. Behavioral and cognitive changes after early postnatal lesions of the rat mediodorsal thalamus.

    Science.gov (United States)

    Ouhaz, Zakaria; Ba-M'hamed, Saadia; Mitchell, Anna S; Elidrissi, Abdeslem; Bennis, Mohamed

    2015-10-01

    Early insults to the thalamus result in functional and/or structural abnormalities in the cerebral cortex. However, differences in behavioral and cognitive changes after early insult are not well characterized. The present study assessed whether early postnatal damage to mediodorsal nucleus of the thalamus (MD), reciprocally interconnected with the prefrontal cortex, causes behavioral and cognitive alterations in young adult rats. Rat pups at postnatal day 4 received bilateral electrolytic lesion of MD, or a MD Sham lesion or were anesthetized controls; on recovery they were returned to their mothers until weaning. Seven weeks later, all rats were tested with the following behavioral and cognitive paradigms: T-maze test, open field test, actimetry, elevated plus maze test, social interactions test and passive avoidance test. Rats with bilateral MD damage presented with disrupted recognition memory, deficits in shifting response rules, significant hypoactivity, increased anxiety-like behavior, deficits in learning associations as well as decreased locomotor activity, and reduced social interactions compared to MD Sham lesion and anesthetized Control rats. The lesion also caused significant decreases in pyramidal cell density in three frontal cortex regions: medial infralimbic cortex, dorsolateral anterior cortex, and cingulate Cg1 cortex. The present findings suggest a functional role for MD in the postnatal maturation of affective behavior. Further some of the behavioral and cognitive alterations observed in these young adult rats after early MD lesion are reminiscent of those present in major psycho-affective disorders, such as schizophrenia in humans.

  5. The Yugoslavia Prospective Lead Study: contributions of prenatal and postnatal lead exposure to early intelligence.

    Science.gov (United States)

    Wasserman, G A; Liu, X; Popovac, D; Factor-Litvak, P; Kline, J; Waternaux, C; LoIacono, N; Graziano, J H

    2000-01-01

    To investigate associations between the timing of lead (Pb) exposure on early intelligence, we examined the results of psychometric evaluations at ages 3, 4, 5, and 7 years, from 442 children whose mothers were recruited during pregnancy from a smelter town and a non-lead-exposed town in Yugoslavia. We compared the relative contribution of prenatal blood lead (BPb) with that of relative increases in BPb in either the early (0-2 years) or the later (from 2 years on) postnatal period to child intelligence measured longitudinally at ages 3 and 4 (McCarthy GCI), 5 (Wechsler Preschool and Primary Scale of Intelligence-Revised, WPPSI-R IQ), and 7 (Wechsler Intelligence Scale for Children-version III, WISC-III IQ), controlling for: Home Observation for Measurement of the Environment (HOME) quality; maternal age, intelligence, education, and ethnicity; and birthweight and gender. Elevations in both prenatal and postnatal BPb were associated with small decrements in young children's intelligence.

  6. Early meiotic-specific protein expression in post-natal rat ovaries.

    Science.gov (United States)

    Zhang, P; Lv, L X; Xing, W J

    2010-12-01

    Recent studies in mice challenged the basic doctrine that most mammalian females lose neo-oogenesis in post-natal ovaries. In order to provide more information in other species, we examined post-natal rat ovaries by histological sections and detected the germline cell marker protein RVLG (rat vasa-like gene), BrdU (5-bromodeoxyuridine) incorporation in RVLG-expressing cells, for identification of germline cells undergoing mitosis and meiosis in the ovarian surface epithelium (OSE). We also detected the expression of early meiotic-specific proteins disruption of meiotic control 1 (DMC1), stimulated by retinoic acid gene 8 (STRA8) and synaptonemal complex protein 3 (SCP3) by immunohistochemical analysis and Western blotting, and the transcript of SCP1, SCP3 and Sporulation-specific protein 11 (SPO11) by RT-PCR in the post-natal ovarian cortex. However we failed in detecting large ovoid cells in the OSE, which may represent the putative germline stem cells (GSCs) that are supposed to sustain neo-oogenesis, and the transcription of the meiotic-specific genes SCP1, SCP3 and SPO11 by RT-PCR as well as the translation of DMC1, STRA8 and SCP3 by Western blotting. Our data support the postulation that there is no neo-oogenesis occurring in the OSE of rat post-natal ovary through meiosis of GSCs.

  7. Consequences of early postnatal benzodiazepines exposure in rats. II. Social behavior

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    Anna eMikulecka

    2014-05-01

    Full Text Available Social behavior represents an integral part of behavioral repertoire of rats particularly sensitive to pharmacological and environmental influences. The aim of the present study was to investigate whether early postnatal clonazepam (CZP exposure can induce age-dependent changes related to expression of social behavior. The drug was administered from postnatal day (P 7 until P11 at daily doses of 0.1, 0.5 and 1.0 mg/kg i.p. We designed three experiments to assess whether exposure to CZP affects social behavior in respect to the age of rats and the test circumstances, specifically their familiarity with test conditions during adolescence (P32, social behavior in juveniles and adolescents (P18-P42 and social behavior in a resident-intruder paradigm. The frequency and duration of a various patterns of social behavior related to play and social investigation not related to play were evaluated. The results showed that CZP postnatal exposure decreased social play behavior regardless of age and familiarity or unfamiliarity of experimental environment but did not affect the social investigation per se. When rats were confronted with an intruder in their home cages intense wrestling and inhibition of genital investigation were found. In conclusion, these findings show that short-term CZP postnatal exposure inhibits social play behavior and alters specific patterns of social behavior in an age and environment related manner

  8. Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

    Science.gov (United States)

    Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

    2017-04-01

    Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O2, 6 h; postnatal day 7, P7) at P14. Exposure to hypoxia led to reduced body weight (P treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain.

  9. Early postnatal hyperalimentation impairs renal function via SOCS-3 mediated renal postreceptor leptin resistance.

    Science.gov (United States)

    Alcazar, Miguel Angel Alejandre; Boehler, Eva; Rother, Eva; Amann, Kerstin; Vohlen, Christina; von Hörsten, Stephan; Plank, Christian; Dötsch, Jörg

    2012-03-01

    Early postnatal hyperalimentation has long-term implications for obesity and developing renal disease. Suppressor of cytokine signaling (SOCS) 3 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and ERK1/2 and thereby plays a pivotal role in mediating leptin resistance. In addition, SOCS-3 is induced by both leptin and inflammatory cytokines. However, little is known about the intrinsic-renal leptin synthesis and function. Therefore, this study aimed to elucidate the implications of early postnatal hyperalimentation on renal function and on the intrinsic-renal leptin signaling. Early postnatal hyperalimentation in Wistar rats during lactation was induced by litter size reduction at birth (LSR) either to LSR10 or LSR6, compared with home cage control male rats. Assessment of renal function at postnatal day 70 revealed decreased glomerular filtration rate and proteinuria after LSR6. In line with this impairment of renal function, renal inflammation and expression as well as deposition of extracellular matrix molecules, such as collagen I, were increased. Furthermore, renal expression of leptin and IL-6 was up-regulated subsequent to LSR6. Interestingly, the phosphorylation of Stat3 and ERK1/2 in the kidney, however, was decreased after LSR6, indicating postreceptor leptin resistance. In accordance, neuropeptide Y (NPY) gene expression was down-regulated; moreover, SOCS-3 protein expression, a mediator of postreceptor leptin resistance, was strongly elevated and colocalized with NPY. Thus, our findings not only demonstrate impaired renal function and profibrotic processes but also provide compelling evidence of a SOCS-3-mediated intrinsic renal leptin resistance and concomitant up-regulated NPY expression as an underlying mechanism.

  10. Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

    Science.gov (United States)

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

    2014-09-01

    A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. IGF-1 Induces GHRH Neuronal Axon Elongation during Early Postnatal Life in Mice

    Science.gov (United States)

    Clemessy, Maud; Heurtier, Victor; Ledent, Tatiana; Robinson, Iain C.; Mollard, Patrice; Epelbaum, Jacques; Meaney, Michael J.; Garel, Sonia; Le Bouc, Yves; Kappeler, Laurent

    2017-01-01

    Nutrition during the perinatal period programs body growth. Growth hormone (GH) secretion from the pituitary regulates body growth and is controlled by Growth Hormone Releasing Hormone (GHRH) neurons located in the arcuate nucleus of the hypothalamus. We observed that dietary restriction during the early postnatal period (i.e. lactation) in mice influences postnatal growth by permanently altering the development of the somatotropic axis in the pituitary gland. This alteration may be due to a lack of GHRH signaling during this critical developmental period. Indeed, underfed pups showed decreased insulin-like growth factor I (IGF-I) plasma levels, which are associated with lower innervation of the median eminence by GHRH axons at 10 days of age relative to normally fed pups. IGF-I preferentially stimulated axon elongation of GHRH neurons in in vitro arcuate explant cultures from 7 day-old normally fed pups. This IGF-I stimulating effect was selective since other arcuate neurons visualized concomitantly by neurofilament labeling, or AgRP immunochemistry, did not significantly respond to IGF-I stimulation. Moreover, GHRH neurons in explants from age-matched underfed pups lost the capacity to respond to IGF-I stimulation. Molecular analyses indicated that nutritional restriction was associated with impaired activation of AKT. These results highlight a role for IGF-I in axon elongation that appears to be cell selective and participates in the complex cellular mechanisms that link underfeeding during the early postnatal period with programming of the growth trajectory. PMID:28076448

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

    Directory of Open Access Journals (Sweden)

    Susanne Eifer Møller

    Full Text Available OBJECTIVE: To investigate the association between exposure to mothers smoking during prenatal and early postnatal life and risk of overweight at age 7 years, while taking birth weight into account. METHODS: From the Danish National Birth Cohort a total of 32,747 families were identified with available information on maternal smoking status in child's pre- and postnatal life and child's birth weight, and weight and height at age 7 years. Outcome was overweight according to the International Obesity Task Force gender and age specific body mass index. Smoking exposure was categorized into four groups: no exposure (n = 25,076; exposure only during pregnancy (n = 3,343; exposure only postnatally (n = 140; and exposure during pregnancy and postnatally (n = 4,188. Risk of overweight according to smoking status as well as dose-response relationships were estimated by crude and adjusted odds ratios using logistic regression models. RESULTS: Exposure to smoking only during pregnancy, or both during pregnancy and postnatally were both significantly associated with overweight at 7 years of age (OR: 1.31, 95% CI: 1.15-1.48, and OR: 1.76, 95% CI: 1.58-1.97, respectively. Analyses excluding children with low birth weight (<2,500 gram revealed similar results. A significant prenatal dose-response relationship was found. Per one additional cigarette smoked per day an increase in risk of overweight was observed (OR: 1.02, 95% CI: 1.01-1.03. When adjusting for quantity of smoking during pregnancy, prolonged exposure after birth further increased the risk of later overweight in the children (OR 1.28, 95% CI:1.09-1.50 compared with exposure only in the prenatal period. CONCLUSIONS: Mother's perinatal smoking increased child's OR of overweight at age 7 years irrespective of birth weight, and with higher OR if exposed both during pregnancy and in early postnatal life. Clear dose-response relationships were observed, which emphasizes the need for

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Gestational Medication Use, Birth Conditions, and Early Postnatal Exposures for Childhood Asthma

    Directory of Open Access Journals (Sweden)

    Yang-Ching Chen

    2012-01-01

    Full Text Available Our aim is to explore (1 whether gestational medication use, mode of delivery, and early postnatal exposure correlate with childhood asthma, (2 the dose responsiveness of such exposure, and (3 their links to early- and late-onset asthma. We conducted a matched case-control study based on the Taiwan Children Health Study, which was a nationwide survey that recruited 12-to-14-year-old school children in 14 communities. 579 mothers of the participants were interviewed by telephone. Exclusive breastfeeding protected children from asthma. Notably, childhood asthma was significantly associated with maternal medication use during pregnancy, vacuum use during vaginal delivery, recurrent respiratory tract infections, hospitalization, main caregiver cared for other children, and early daycare attendance. Exposure to these factors led to dose responsiveness in relationships to asthma. Most of the exposures revealed a greater impact on early-onset asthma, except for vacuum use and daycare attendance.

  15. Early experience modifies the postnatal assembly of autonomic emotional motor circuits in rats.

    Science.gov (United States)

    Card, J Patrick; Levitt, Pat; Gluhovsky, Maxim; Rinaman, Linda

    2005-10-01

    Rat pups that are repeatedly handled and separated from their dam exhibit altered adult behavioral, endocrine, and autonomic responses to stress, but the extent to which early handling and/or maternal separation (H/S) alters the development of circuits that underlie these responses is unknown. The present study tested the hypothesis that early H/S alters the postnatal assembly of synapses within preautonomic emotional motor circuits. Circuit development was traced by synapse-dependent retrograde transneuronal transport of pseudorabies virus (PRV) from the stomach wall. Control and H/S rats were analyzed between postnatal day 6 (P6) and P10, a period of rapid synaptic assembly among preautonomic circuit components. Pups in H/S groups were removed from their dam daily for either 15 min or 3 h beginning on P1, and were injected with virus on P8 and perfused on P10. Quantitative analyses of primary and transsynaptic PRV immunolabeling confirmed an age-dependent assembly of hypothalamic, limbic, and cortical inputs to autonomic nuclei. Circuit assembly was significantly altered in H/S pups, in which fewer neurons in the central amygdala, the bed nucleus of the stria terminalis, and visceral cortices were infected compared with age-matched controls. In contrast, H/S did not alter the assembly of paraventricular hypothalamic inputs to gastric autonomic neurons. H/S-related reductions in limbic and cortical transneuronal infection were similar in pups exposed daily to 15 min or 3 h maternal separation. These findings support the view that environmental events during early postnatal life can influence the formation of neural circuits that provide limbic and cortical control over autonomic emotional motor output.

  16. Early Family Deaths May Create 'Grief Gap' for Blacks

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_163190.html Early Family Deaths May Create 'Grief Gap' for Blacks Compared ... Americans, the researchers found that death strikes black families significantly earlier than whites on average. "Blacks were ...

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

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    Takanori Miki

    2011-05-01

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

  18. Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex

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    Hiroshi Ueno

    2015-01-01

    Full Text Available Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28 or P58 on the density of parvalbumin (PV, calbindin (CB, and calretinin (CR neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6. Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity.

  19. Urinary Metabolite Profiles in Premature Infants Show Early Postnatal Metabolic Adaptation and Maturation

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    Sissel J. Moltu

    2014-05-01

    Full Text Available Objectives: Early nutrition influences metabolic programming and long-term health. We explored the urinary metabolite profiles of 48 premature infants (birth weight < 1500 g randomized to an enhanced or a standard diet during neonatal hospitalization. Methods: Metabolomics using nuclear magnetic resonance spectroscopy (NMR was conducted on urine samples obtained during the first week of life and thereafter fortnightly. Results: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group. Enhanced nutrition did not appear to affect the urine profiles to an extent exceeding individual variation. However, in all infants the glucogenic amino acids glycine, threonine, hydroxyproline and tyrosine increased substantially during the early postnatal period, along with metabolites of the tricarboxylic acid cycle (succinate, oxoglutarate, fumarate and citrate. The metabolite changes correlated with postmenstrual age. Moreover, we observed elevated threonine and glycine levels in first-week urine samples of the small for gestational age (SGA; birth weight < 10th percentile for gestational age as compared to the appropriate for gestational age infants. Conclusion: This first nutri-metabolomics study in premature infants demonstrates that the physiological adaptation during the fetal-postnatal transition as well as maturation influences metabolism during the breastfeeding period. Elevated glycine and threonine levels were found in the first week urine samples of the SGA infants and emerged as potential biomarkers of an altered metabolic phenotype.

  20. Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex.

    Science.gov (United States)

    Ueno, Hiroshi; Suemitsu, Shunsuke; Matsumoto, Yosuke; Okamoto, Motoi

    2015-01-01

    Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC) in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28) or P58 on the density of parvalbumin (PV), calbindin (CB), and calretinin (CR) neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6). Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity.

  1. High uptake of exclusive breastfeeding and reduced early post-natal HIV transmission.

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    Louise Kuhn

    Full Text Available BACKGROUND: Empirical data showing the clear benefits of exclusive breastfeeding (EBF for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF. METHODS AND RESULTS: As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004 among EBF (0.040 95% CI: 0.024-0.055 than non-EBF infants (0.102 95% CI: 0.047-0.157; time-dependent Relative Hazard (RH of transmission due to non-EBF = 3.48 (95% CI: 1.71-7.08. There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28-5.62 after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight. CONCLUSIONS: Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their children's lives. TRIAL REGISTRATION: ClinicalTrials.gov NCT00310726.

  2. Molecular and functional heterogeneity of early postnatal porcine satellite cell populations is associated with bioenergetic profile

    Science.gov (United States)

    Miersch, Claudia; Stange, Katja; Hering, Silvio; Kolisek, Martin; Viergutz, Torsten; Röntgen, Monika

    2017-01-01

    During postnatal development, hyperplastic and hypertrophic processes of skeletal muscle growth depend on the activation, proliferation, differentiation, and fusion of satellite cells (SC). Therefore, molecular and functional SC heterogeneity is an important component of muscle plasticity and will greatly affect long-term growth performance and muscle health. However, its regulation by cell intrinsic and extrinsic factors is far from clear. In particular, there is only minor information on the early postnatal period which is critical for muscle maturation and the establishment of adult SC pools. Here, we separated two SC subpopulations (P40/50, P50/70) from muscle of 4-day-old piglets. Our results characterize P40/50 as homogeneous population of committed (high expression of Myf5), fast-proliferating muscle progenitors. P50/70 constituted a slow-proliferating phenotype and contains high numbers of differentiated SC progeny. During culture, P50/70 is transformed to a population with lower differentiation potential that contains 40% Pax7-positive cells. A reversible state of low mitochondrial activity that results from active down-regulation of ATP-synthase is associated with the transition of some of the P50/70 cells to this more primitive fate typical for a reserve cell population. We assume that P40/50 and P50/70 subpopulations contribute unequally in the processes of myofiber growth and maintenance of the SC pool. PMID:28344332

  3. Growth abnormalities in the population exposed in utero and early postnatally to polychlorinated biphenyls and dibenzofurans

    Energy Technology Data Exchange (ETDEWEB)

    Yueliang L. Guo; Chen-Chin Hsu [National Cheng Kung Univ. Medical College, Tainan (Taiwan, Province of China); Lambert, G.H. [UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (United States)

    1995-09-01

    This article reviews the findings in children exposed to various levels of polychlorinated biphenyls (PCBs) and related compounds in utero and early postnatally. Yu-Cheng ({open_quotes}oil-disease{close_quotes}) mothers were Taiwanese women exposed to PCBs and their heat-degradation products form the ingestion of contaminated rice oil in 1979. Children of these mothers were born growth retarded, with dysmorphic physical findings, and delayed cognitive development compared with unexposed children. In this article, findings in Yu-Cheng children born between 1978 and 1985 are summarized and compared with two other well-documented cohorts of children prenatally exposed to different levels of PCBs. Results of the investigation in Yu-Cheng children will provide important information about the toxicities, health effects, and mechanisms of PCB/PCDF exposure and demonstrate that the developing human is more sensitive than the adult to the toxic effects of these chemicals. 53 refs., 2 tabs.

  4. An association of adult personality with prenatal and early postnatal growth

    DEFF Research Database (Denmark)

    Flensborg-Madsen, Trine; Revsbech, Rasmus; Sørensen, Holger Jelling

    2014-01-01

    individuals participated in a follow-up at 20–34 years and was administered the Eysenck Personality Questionnaire (EPQ) which includes a lie-scale (indicating social acquiescence or self-insight). Associations between lie-scale scores and weight, length and head circumference respectively were analysed...... by multiple linear regression adjusting for single-mother status, parity, mother’s age, father’s age, parental social status, age at EPQ measurement, intelligence, and adult size. Results: Male infants with lower weight, length, and head-circumference at birth and the following three years grew up to have...... influence of prenatal and early postnatal development on personality growth and development. Keywords: Eysenck personality questionnaire, Lie-scale, Extraversion, Neuroticism, Psychoticism, Birth weight, Birth length, Birth head-circumference...

  5. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

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    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

    2015-08-07

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.

  6. Early postnatal nociceptive stimulation results in deficits of spatial memory in male rats.

    Science.gov (United States)

    Amaral, Cristiane; Antonio, Bruno; Oliveira, Maria Gabriela Menezes; Hamani, Clement; Guinsburg, Ruth; Covolan, Luciene

    2015-11-01

    Prematurely-born infants are exposed to multiple invasive procedures while in the intensive care unit. Newborn rats and humans have similar behavioral responses to noxious stimulation. Previous studies have shown that early noxious stimuli may alter dentate gyrus neurogenesis and the behavioral repertoire of adult rats. We evaluated the late effects of noxious stimulation administered during different phases of development on two spatial memory tests; object recognition (OR) and Morris water maze (WM) tests. Noxious stimulation was induced by an intra-plantar injection of complete Freund's adjuvant (CFA) on postnatal (P) day 1 (group P1) or 8 (P8). Control animals were not stimulated. Behavioral tests were conducted on P60 in both male and female animals. In the WM, three domains were evaluated: acquisition, probe trial performance and reversal re-acquisition. The number of Nissl stained cells in the dentate granule cell layer was assessed by stereological counting. The OR test revealed that P1 male rats had poor long-term memory compared to the control and P8 groups. In the WM, no short- or long-term memory differences were detected between early postnatal-stimulated male and female rats and their respective controls. However, the ability to find the hidden platform in a new position was reduced in P1 male rats. The number of dentate granule cells in P8 males was higher than in all other groups. This study demonstrates that noxious stimulation on P1 results in spatial learning deficits in male animals, but does not disrupt the development of the hippocampus-dependent strategies of learning and memory. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Antenatal Health Care and Postnatal Dental Check-Ups Prevent Early Childhood Caries.

    Science.gov (United States)

    Nakai, Yukie; Mori, Yukako; Tamaoka, Izumi

    2016-01-01

    The first stage of early childhood caries (ECC) is infection by mutans streptococci, of which the primary infection source is the child's mother. Early intervention programs including antenatal and postnatal phases are effective for reducing ECC. This study was conducted to assess the respective effects of antenatal health care and postnatal care such as regular dental check-ups on reducing ECC among 3-year-old Japanese children. This nested case-control study of 155 three-year-old children (49.0% boys) was conducted at a dental clinic that provides collaborative health services with the Obstetrics and Gynecology Clinic, Okayama. Child characteristics and the mothers' antenatal data were collected retrospectively from the dental charts. They were divided into two groups: caries-free children (n = 77) and children without ECC (n = 78). Most of the children (81.9%) received regular check-ups with topical fluoride application. Most of the mothers reported morning sickness during pregnancy (81.3%), normal delivery (72.9%), and used antenatal health care (80.6%). Over half (55.5%) were primigravida. Adjusted odds ratio (AOR) and 95% confidential interval (95% CI) were computed to assess the strength of association using logistic regression analysis. Receiving antenatal health care (AOR, 3.27; 95% CI, 1.30-8.24) and child's having regular check-ups (AOR, 3.42; 95% CI, 1.35-8.69) were significantly associated with caries-free status among three-year old children. For ECC prevention, antenatal health care is as effective as regular check-ups up to three years of age. The results of this retrospective study demonstrate that maternal health education during pregnancy is effective for ECC prevention.

  8. Chronic early postnatal scream sound stress induces learning deficits and NMDA receptor changes in the hippocampus of adult mice.

    Science.gov (United States)

    Hu, Lili; Han, Bo; Zhao, Xiaoge; Mi, Lihua; Song, Qiang; Wang, Jue; Song, Tusheng; Huang, Chen

    2016-04-13

    Chronic scream sounds during adulthood affect spatial learning and memory, both of which are sexually dimorphic. The long-term effects of chronic early postnatal scream sound stress (SSS) during postnatal days 1-21 (P1-P21) on spatial learning and memory in adult mice as well as whether or not these effects are sexually dimorphic are unknown. Therefore, the present study examines the performance of adult male and female mice in the Morris water maze following exposure to chronic early postnatal SSS. Hippocampal NR2A and NR2B levels as well as NR2A/NR2B subunit ratios were tested using immunohistochemistry. In the Morris water maze, stress males showed greater impairment in spatial learning and memory than background males; by contrast, stress and background females performed equally well. NR2B levels in CA1 and CA3 were upregulated, whereas NR2A/NR2B ratios were downregulated in stressed males, but not in females. These data suggest that chronic early postnatal SSS influences spatial learning and memory ability, levels of hippocampal NR2B, and NR2A/NR2B ratios in adult males. Moreover, chronic early stress-induced alterations exert long-lasting effects and appear to affect performance in a sex-specific manner.

  9. Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

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    Carmen eRey-Santano

    2011-09-01

    Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

  10. Prenatal and Early Postnatal Diagnosis of Congenital Toxoplasmosis in a Setting With No Systematic Screening in Pregnancy.

    Science.gov (United States)

    Stajner, Tijana; Bobic, Branko; Klun, Ivana; Nikolic, Aleksandra; Srbljanovic, Jelena; Uzelac, Aleksandra; Rajnpreht, Irena; Djurkovic-Djakovic, Olgica

    2016-03-01

    To determine the risk of congenital toxoplasmosis (CT) and provide early (pre- or postnatal) identification of cases of CT in the absence of systematic screening in pregnancy.I n the presented cross-sectional study, serological criteria were used to date Toxoplasma gondii infection versus conception in 80 pregnant women with fetal abnormalities or referred to as suspected of acute infection, and in 16 women after delivery of symptomatic neonates. A combination of serological, molecular (qPCR), and biological (bioassay) methods was used for prenatal and/or postnatal diagnosis of CT. Most (77.5%) pregnant women were examined in advanced pregnancy. Of all the examined seropositive women (n = 90), infection could not be ruled out to have occurred during pregnancy in 93.3%, of which the majority (69%) was dated to the periconceptual period. CT was diagnosed in 25 cases, of which 17 prenatally and 8 postnatally. Molecular diagnosis proved superior, but the diagnosis of CT based on bioassay in 7 instances and by Western blot in 2 neonates shows that other methods remain indispensable. In the absence of systematic screening in pregnancy, maternal infection is often diagnosed late, or even only when fetal/neonatal infection is suspected. In such situations, use of a complex algorithm involving a combination of serological, biological, and molecular methods allows for prenatal and/or early postnatal diagnosis of CT, but lacks the preventive capacity provided by early maternal treatment.

  11. Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions.

    Science.gov (United States)

    Meaney, Michael J; Aitken, David H; Bodnoff, Shari R; Iny, Linda J; Tatarewicz, Joseph E; Sapolsky, Robert M

    2013-10-01

    Norway rat pups were either handled (H) or undisturbed (nonhandled, NH) in the period between birth and weaning on Day 21. Following weaning, half of the animals in each group were housed socially (Soc), and half were housed in isolation (Isol). At 120-150 days of age, all animals were sacrificed, and the following regions were dissected and frozen at -70 °C until the time of assay: frontal cortex, hippocampus, hypothalamus, amygdala, septum, and pituitary. [3H]Dexamethasone (3H Dex) binding in each region was examined by an in vitro, cytosol, receptor assay. 3H Dex binding was significantly higher in the hippocampus of both H-Soc and H-Isol than in NH groups. In the frontal cortex, 3H Dex binding was higher in the H-Soc animals than in the H-Isol and NH-Isol animals. There were no significant handling or housing effects found in the amygdala, hypothalamus, septum, or pituitary. Thus, early postnatal handling appears to influence the development of the glucocorticoid receptor system in the hippocampus and frontal cortex. These results are discussed as providing a possible mechanism for some of the previously reported effects of early handling on the development of the pituitary-adrenal response to stress. 2013 APA, all rights reserved

  12. Consequences of early postnatal benzodiazepines exposure in rats. I. Cognitive-like behavior

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    Anna eMikulecka

    2014-03-01

    Full Text Available Clinical and experimental studies suggest possible risks associated with the repeated administration of BZDS during the prenatal or early postnatal period on further development and behavior. In the present study, we assess short- and long-term effects of early exposure to clonazepam (CZP on cognitive tasks. CZP (0.5 or 1.0 mg/kg/day was administered from postnatal day (P7 until P11, and animals were exposed to the following behavioral tests at different developmental stages: (1 a homing response test, which exploits the motivation of a rat pup to reach its home nest, was administered on P12, P15, P18 and P23 rats; (2 passive avoidance was tested in three trials (at 0 h, 2 h and 24 h intervals on P12, P15, P18, P25 and P32 rats; (3 within- and between-session habituation was tested in an open field (OF at P70; and (4 a long-term memory version of the Morris water maze (MWM was tested at P80. A 1.0 mg/kg dose of CZP extended latency in the homing response and decreased the number of correct responses when tested at P12 and P23. In the first trial of the passive avoidance test, latency to enter a dark compartment was shorter in the CZP-exposed rats. Both treated and control animals older than P15 learned the passive-avoidance response at the same rate. Irrespective of the treatments, all adult animals showed within-session habituation. Between-session habituation, however, was found only in the controls. With respect to the MWM test, all animals learned to reach the platform, but animals exposed to higher doses of CZP spent more time swimming in the first acquisition test. No difference between groups was found in a repeated acquisition test (10 and 40 days after the first acquisition test. The results of the present study show that even short-term exposure to CZP alters behavioral responsiveness in pre-weaning, juvenile and adult animals. Not only were changes observed on conventional cognitive tests in our study, but the changes also seem to be

  13. Early Postnatal Blood Pressure in Preterm Infants : Effects of Chorioamnionitis and Timing of Antenatal Steroids

    NARCIS (Netherlands)

    Been, Jasper V.; Kornelisse, Rene F.; Rours, Ingrid G. I. J. G.; Passos, Valeria Lima; De Krijger, Ronald R.; Zimmermann, Luc J. I.

    2009-01-01

    Previous studies suggest postnatal blood pressure in preterm infants to be decreased by chorioamnionitis and increased by antenatal steroids (AS). We examined the adjusted effects of both antenatal modulators on postnatal blood pressure (BP), with separate effects reported for histologic chorioamnio

  14. Cyclooxygenase-2 contributes to elevated renin in the early postnatal period in rats

    DEFF Research Database (Denmark)

    Stubbe, Jane; Jensen, Boye L; Bachmann, Sebastian;

    2003-01-01

    We asked whether cyclooxygenase (COX) activity controls the renin-angiotensin system in the postnatal period. During kidney development, renin peaked at postnatal days 0-1 at the mRNA, tissue protein [renal renin concentration (RRC)], and plasma renin concentration (PRC) levels and was widely...

  15. Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary.

    Science.gov (United States)

    Asadi-Azarbaijani, Babak; Santos, Regiane R; Jahnukainen, Kirsi; Braber, Saskia; van Duursen, Majorie B M; Toppari, Jorma; Saugstad, Ola D; Nurmio, Mirja; Oskam, Irma C

    2017-03-01

    Imatinib mesylate is an anti-cancer agent that competitively inhibits several receptor tyrosine kinases (RTKs). RTKs play important roles in the regulation of primordial follicle formation, the recruitment of primordial follicles into the pool of growing follicles and maturation of the follicles. In the present study, we investigated the effects of the tyrosine kinase inhibitor imatinib on primordial follicle assembly and early folliculogenesis in postnatal rats. Female Sprague-Dawley rats were treated with either imatinib (150mg/kg) or placebo (water) on postnatal days 2-4. Bilateral ovariectomy was performed on postnatal day 2 and 5. Histology, immunohistochemistry, and mRNA analysis were performed. Imatinib treatment was associated with increased density of the multi-oocyte follicles (Pprimordial follicles, increased expression of c-Kit and AMH, and decreased protein expression of Kit-ligand and GDF9 when compared to age-matched controls. In conclusion, imatinib affects folliculogenesis in postnatal rat ovaries by delaying the cluster breakdown, follicular assembly and early activation of the primordial follicle pool. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  16. Distribution features of the rats’ major salivary glands cells glycoproteins during early postnatal period after antenatal antigen action

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    Syrtsov V.K.

    2014-06-01

    Full Text Available Background. Nowadays, in the diseases’ structure, according to literature data, one of the leading place take pathological condition connecting with the salivary glands’ inflammatory and dystrophic disorders. The problem of etiology and pathogenic not enough studied and demanded intent attention of researchers. Objective. The purpose was to determine the features of glycoproteins’ distribution in the structures of rats’ major salivary glands in early postnatal period after intrauterine antigen action. Methods. The object of the research was 224 salivary glands of white laboratory rats. Due to impossible quality materials’ taking in the early periods of postnatal life parotid and sublingual salivary glands, the investigation done at the gl. submaxillaris. The histochemical exposure and differentiation of carbohydrate compounds conducted by means of PAS-staining technic. For fermentative control used diastase. The results of histochemical exposure of glycoproteins stain were done by semi-quantitative. Results. In newborn animals receiving antigen in the antenatal period, in the cells’ cytoplasm indicate the accumulation’ increase of PAS-positive compounds retained until the 14th and offset at the 45th day of postnatal life. The detected changes in the major salivary glands cells’ are the basis for the development of inflammatory and dystrophic processes and can lead to the functional violations formation’ hereinafter. Conclusion. Our findings indicate that at the background of intrauterine antigen action, the glycoproteins’ accumulation intensity in parenchymal and stromal cells’ cytoplasm of the major salivary glands is decrease, but glycogen content is increase compared with intact animals group. Furthermore, we detected cells’ secretory activity reduction from 1st to 14th day of postnatal life with increase glycogen’ accumulation in the cells’ cytoplasm. That revealed changes offset at the 45th day after birth in all

  17. GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex.

    Science.gov (United States)

    Anastasiades, Paul G; Marques-Smith, Andre; Lyngholm, Daniel; Lickiss, Tom; Raffiq, Sayda; Kätzel, Dennis; Miesenböck, Gero; Butt, Simon J B

    2016-02-04

    GABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1-derived interneurons possess functional synaptic connections before emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L) 4 and 5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain.

  18. Patent ductus arteriosus: peculiarities of early neonatal, postnatal diagnostics, clinical manifestations, treatment and prognosis

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    K.A. Kalashnikova

    2017-05-01

    Full Text Available The article presents the published data on the prevalence, the main clinical manifestations, and modern methods of early neonatal and postnatal diagnosis, treatment and prognosis of patent ductus arteriosus — the congenital malformation of cardiovascular system. The International Statistical Classification of Diseases version10 defines it Q25.0 Patent ductus arteriosus. Patent ductus Botalli. Botallo’s duct patency. The pre-valence of the patent ductus arteriosus is from 0.006 to 0.02 % in mature newborns, in premature newborns — from 15 to 80 %. Clinical manifestation of the malformation depends on its size, pulmonary pressure, and proportion of pulmonary and syste-mic circulation. One of the basic clinical signs of patent ductus arteriosus  is permanent eddy murmur  in II–III space along left sternal border. In newborns and infants and if severe pulmonary hypertension diastolic murmur can be absent while systolic and forced second sound on pulmonary artery, collapsing magnus pulse, increased pulse pressure are determined. Open ductus arteriosus is not determined auscultatory in low-weight premature children. The electrocardiograph reveals downloaded left ventricular. Echo-cardiograph images ductus arteriosis, increased left ventriclular, volume overload of left ventricular. Chest roentgenograms may reveal prominent pulmonary arterial markings, increased heart breadth due to hypertrophic left ventricular. Drug obliteration with indometacin is effective in newborns aged 2 weeks. The surgical indication is verified heart disease aged 6–12 months old. The appropriate age for surgical intervention is 2–5 years old.

  19. Neuronal nitric oxide synthase immunoreactivity in ependymal cells during early postnatal development.

    Science.gov (United States)

    Soygüder, Zafer; Karadağ, Hüseyin; Nazli, Mümtaz

    2004-03-01

    Neuronal nitric oxide synthase (nNOS) immunoreactivity was observed in ependymal cell layer of the central canal of spinal cord of neonatal rats (2-20 days old). Neuronal nitric oxide synthase immunoreactivity was present in postnatal day 2 and this immunoreactivity gradually disappeared by postnatal day 16. The progressive decrease in nNOS staining with the increasing postnatal age may suggest that nNOS staining paralleled the maturation of the central canal and may also suggest that nNOS activity plays a role in the development of the ependymal cells.

  20. [Morphofunctional and biochemical properties of erythrocytes in early postnatal ontogenesis in rats in norm and after prenatal stress].

    Science.gov (United States)

    Golubeva, E K; Nazarov, S B; Tomilova, I K

    2011-07-01

    Morphofunctional and biochemical properties of erythrocyte membrane were investigated in early postnatal ontogenesis in rats in norm and after prenatal immobilization stress. The transient decrease of erythrocyte membranes stability was revealed in the control rats. The ability to erythrocyte transformation and the concentration of lipid peroxidation products are increased. It has been shown by an increase of percentage discocytes and lower lipid peroxidation level that the erythrocyte membrane of the rats after prenatal stress is more stable.

  1. Lack of long-term behavioral alterations after early postnatal treatment with tropisetron: implications for developmental psychobiology.

    Science.gov (United States)

    Inta, Dragos; Vogt, Miriam A; Lima-Ojeda, Juan M; Pfeiffer, Natascha; Schneider, Miriam; Gass, Peter

    2011-07-01

    The early postnatal period represents a critical time window for brain development. Transient Cajal-Retzius cells in layer I of the cortex play an important role in cortical lamination by modulating neuronal migration and maturation. Recent data have demonstrated that the 5-HT(3) receptor antagonist and alpha7 nicotinic receptor partial agonist tropisetron, acting via 5-HT(3) receptors expressed on Cajal-Retzius cells, can disturb the formation of cortical columns at perinatal stages. This process is thought to be involved in several neuropsychiatric disorders. Here we investigated the possible long-term behavioral effects of exposure to tropisetron at early postnatal stages in mice. We found that the administration of 1mg/kg, intraperitoneal (i.p.) tropisetron from postnatal days 2-12 (P2-P12) did not induce significant cognitive, schizophrenia-like or emotional alterations in tropisetron-treated animals as compared to controls, when tested in multiple behavioral assays. These results may be of relevance regarding the possible protracted deleterious neuropsychiatric effects of tropisetron during early life.

  2. Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria.

    Science.gov (United States)

    Brace, Lear E; Vose, Sarah C; Vargas, Dorathy F; Zhao, Shuangyun; Wang, Xiu-Ping; Mitchell, James R

    2013-12-01

    Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa(-/-) | Xpa(-/-)). Survival past weaning revealed a number of CS-like symptoms including small size, progressive loss of adiposity, and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS-related progeroid symptoms including lipodystrophy and neurodysfunction.

  3. Selective underexpression of Kv3.2 and Kv3.4 channels in the cortex of rats exposed to ethanol during early postnatal life.

    Science.gov (United States)

    Tavian, Daniela; De Giorgio, Andrea; Granato, Alberto

    2011-08-01

    The expression of voltage-gated potassium channels belonging to the Kv3 family has been studied in the sensori-motor cortex of rats exposed to alcohol inhalation during the first postnatal week (P2-P6). The study was carried out using comparative RT-PCR. At P9, a significant reduction of the expression of Kv3.2 and Kv3.4 subunits occurred in alcohol-treated animals, as compared with controls. The expression of the Kv3.4a splicing variant, which is thought to be critically involved in the high-frequency firing of some cortical interneurons, was also correspondingly reduced. The downregulation of Kv3.2 and Kv3.4a subunits represented a long-lasting effect of alcohol exposure, since it was also observed in P24 animals. The expression of both Kv3.1 and Kv3.3 channels appeared to be not significantly affected by alcohol exposure. An increased susceptibility to apoptotic neuronal death after early postnatal exposure to ethanol was confirmed by the lower bcl-2/bax ratio observed in alcohol-treated animals. Although Kv3.4 subunits are thought to trigger apoptosis, the lack of upregulation in our model argues against their involvement in the mechanism leading to alcohol-induced apoptosis. The possible consequences of the selective downregulation of Kv3 subunits on the cortical function, as well as their relevance for the genesis of fetal alcohol effects, are discussed.

  4. Clean birth and postnatal care practices to reduce neonatal deaths from sepsis and tetanus: a systematic review and Delphi estimation of mortality effect

    Science.gov (United States)

    2011-01-01

    Background Annually over 520,000 newborns die from neonatal sepsis, and 60,000 more from tetanus. Estimates of the effect of clean birth and postnatal care practices are required for evidence-based program planning. Objective To review the evidence for clean birth and postnatal care practices and estimate the effect on neonatal mortality from sepsis and tetanus for the Lives Saved Tool (LiST). Methods We conducted a systematic review of multiple databases. Data were abstracted into standard tables and assessed by GRADE criteria. Where appropriate, meta-analyses were undertaken. For interventions with low quality evidence but a strong GRADE recommendation, a Delphi process was conducted. Results Low quality evidence supports a reduction in all-cause neonatal mortality (19% (95% c.i. 1–34%)), cord infection (30% (95% c.i. 20–39%)) and neonatal tetanus (49% (95% c.i. 35–62%)) with birth attendant handwashing. Very low quality evidence supports a reduction in neonatal tetanus mortality with a clean birth surface (93% (95% c.i. 77-100%)) and no relationship between a clean perineum and tetanus. Low quality evidence supports a reduction of neonatal tetanus with facility birth (68% (95% c.i. 47-88%). No relationship was found between birth place and cord infections or sepsis mortality. For postnatal clean practices, all-cause mortality is reduced with chlorhexidine cord applications in the first 24 hours of life (34% (95% c.i. 5–54%, moderate quality evidence) and antimicrobial cord applications (63% (95% c.i. 41–86%, low quality evidence). One study of postnatal maternal handwashing reported reductions in all-cause mortality (44% (95% c.i. 18–62%)) and cord infection ((24% (95% c.i. 5-40%)). Given the low quality of evidence, a Delphi expert opinion process was undertaken. Thirty experts reached consensus regarding reduction of neonatal sepsis deaths by clean birth practices at home (15% (IQR 10–20)) or in a facility (27% IQR 24–36)), and by clean

  5. Altering the trajectory of early postnatal cortical development can lead to structural and behavioural features of autism

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    Chomiak Taylor

    2010-08-01

    Full Text Available Abstract Background Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking. Results We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA in vivo. Brain sections obtained from postnatal rat pups treated with VPA in vivo revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour. Conclusions The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism.

  6. Lipopolysaccharide exposure during the early postnatal period adversely affects the structure and function of the developing rat carotid body.

    Science.gov (United States)

    Master, Zankhana R; Porzionato, Andrea; Kesavan, Kalpashri; Mason, Ariel; Chavez-Valdez, Raul; Shirahata, Machiko; Gauda, Estelle B

    2016-09-01

    The carotid body (CB) substantially influences breathing in premature infants by affecting the frequency of apnea and periodic breathing. In adult animals, inflammation alters the structure and chemosensitivity of the CB, yet it is not known if this pertains to neonates. We hypothesized that early postnatal inflammation leads to morphological and functional changes in the developing rat CB, which persists for 1 wk after the initial provoking insult. To test our hypothesis, we exposed rat pups at postnatal day 2 (P2) to lipopolysaccharide (LPS; 100 μg/kg) or saline (SAL) intraperitoneally. At P9-10 (1 wk after treatment), LPS-exposed animals had significantly more spontaneous intermittent hypoxic (IH) events, attenuated ventilatory responses to changes in oxygen tension (measured by whole body plethysmography), and attenuated hypoxic chemosensitivity of the carotid sinus nerve (measured in vitro), compared with SAL-exposed controls. These functional changes were associated with the following: 1) increased inflammatory cytokine mRNA levels; 2) decreased volume of supportive type II cells; and 3) elevated dopamine levels (a major inhibitory neuromodulator) within the CB. These findings suggest that early postnatal inflammation in newborn rats adversely affects the structure and function of the CB and is associated with increased frequency of intermittent desaturations, similar to the phenomenon observed in premature infants. Furthermore, this is the first newborn model of spontaneous intermittent desaturations that may be used to understand the mechanisms contributing to IH events in newborns.

  7. The early postnatal nonhuman primate neocortex contains self-renewing multipotent neural progenitor cells.

    Directory of Open Access Journals (Sweden)

    Jihane Homman-Ludiye

    Full Text Available The postnatal neocortex has traditionally been considered a non-neurogenic region, under non-pathological conditions. A few studies suggest, however, that a small subpopulation of neural cells born during postnatal life can differentiate into neurons that take up residence within the neocortex, implying that postnatal neurogenesis could occur in this region, albeit at a low level. Evidence to support this hypothesis remains controversial while the source of putative neural progenitors responsible for generating new neurons in the postnatal neocortex is unknown. Here we report the identification of self-renewing multipotent neural progenitor cells (NPCs derived from the postnatal day 14 (PD14 marmoset monkey primary visual cortex (V1, striate cortex. While neuronal maturation within V1 is well advanced by PD14, we observed cells throughout this region that co-expressed Sox2 and Ki67, defining a population of resident proliferating progenitor cells. When cultured at low density in the presence of epidermal growth factor (EGF and/or fibroblast growth factor 2 (FGF-2, dissociated V1 tissue gave rise to multipotent neurospheres that exhibited the ability to differentiate into neurons, oligodendrocytes and astrocytes. While the capacity to generate neurones and oligodendrocytes was not observed beyond the third passage, astrocyte-restricted neurospheres could be maintained for up to 6 passages. This study provides the first direct evidence for the existence of multipotent NPCs within the postnatal neocortex of the nonhuman primate. The potential contribution of neocortical NPCs to neural repair following injury raises exciting new possibilities for the field of regenerative medicine.

  8. The early postnatal nonhuman primate neocortex contains self-renewing multipotent neural progenitor cells.

    Science.gov (United States)

    Homman-Ludiye, Jihane; Merson, Tobias D; Bourne, James A

    2012-01-01

    The postnatal neocortex has traditionally been considered a non-neurogenic region, under non-pathological conditions. A few studies suggest, however, that a small subpopulation of neural cells born during postnatal life can differentiate into neurons that take up residence within the neocortex, implying that postnatal neurogenesis could occur in this region, albeit at a low level. Evidence to support this hypothesis remains controversial while the source of putative neural progenitors responsible for generating new neurons in the postnatal neocortex is unknown. Here we report the identification of self-renewing multipotent neural progenitor cells (NPCs) derived from the postnatal day 14 (PD14) marmoset monkey primary visual cortex (V1, striate cortex). While neuronal maturation within V1 is well advanced by PD14, we observed cells throughout this region that co-expressed Sox2 and Ki67, defining a population of resident proliferating progenitor cells. When cultured at low density in the presence of epidermal growth factor (EGF) and/or fibroblast growth factor 2 (FGF-2), dissociated V1 tissue gave rise to multipotent neurospheres that exhibited the ability to differentiate into neurons, oligodendrocytes and astrocytes. While the capacity to generate neurones and oligodendrocytes was not observed beyond the third passage, astrocyte-restricted neurospheres could be maintained for up to 6 passages. This study provides the first direct evidence for the existence of multipotent NPCs within the postnatal neocortex of the nonhuman primate. The potential contribution of neocortical NPCs to neural repair following injury raises exciting new possibilities for the field of regenerative medicine.

  9. Early cell death detection with digital holographic microscopy.

    Directory of Open Access Journals (Sweden)

    Nicolas Pavillon

    Full Text Available BACKGROUND: Digital holography provides a non-invasive measurement of the quantitative phase shifts induced by cells in culture, which can be related to cell volume changes. It has been shown previously that regulation of cell volume, in particular as it relates to ionic homeostasis, is crucially involved in the activation/inactivation of the cell death processes. We thus present here an application of digital holographic microscopy (DHM dedicated to early and label-free detection of cell death. METHODS AND FINDINGS: We provide quantitative measurements of phase signal obtained on mouse cortical neurons, and caused by early neuronal cell volume regulation triggered by excitotoxic concentrations of L-glutamate. We show that the efficiency of this early regulation of cell volume detected by DHM, is correlated with the occurrence of subsequent neuronal death assessed with the widely accepted trypan blue method for detection of cell viability. CONCLUSIONS: The determination of the phase signal by DHM provides a simple and rapid optical method for the early detection of cell death.

  10. Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia

    NARCIS (Netherlands)

    Benders, MJNL; Bos, AF; Radernaker, CMA; Rijken, M; Torrance, HL; Groenendaal, F; van Bel, F

    2006-01-01

    Objective: To investigate whether postnatal allopurinol would reduce free radical induced reperfusion/reoxygenation injury of the brain in severely asphyxiated neonates. Method: In an interim analysis of a randomised, double blind, placebo controlled study, 32 severely asphyxiated infants were given

  11. Nitrergic neurons during early postnatal development of the prefrontal cortex in the rat: histochemical study.

    Science.gov (United States)

    Hvizdosova, Natalia; Tomasova, Lenka; Bolekova, Adriana; Kolesar, Dalibor; Kluchova, Darina

    2014-06-01

    The presence of nitrergic cells in the prefrontal cortex has been confirmed, however little is known about the postnatal development of these cells. Nitrergic neurons were studied histochemically by using NADPH-diaphorase staining in the prefrontal cortex of male Wistar rats from postnatal day 7-21 (P7-21). Neuronal NADPH-diaphorase is a nitric oxide synthase that provides a specific histochemical marker for neurons producing nitric oxide (NO). NO acts as a neurotransmitter and intracellular signaling molecule in the nervous system. We observed in 7 day old rats NADPH-d containing neurons that were intensely stained. These neurons were bipolar with a short dendrite with average length of 23 μm. During the second postnatal week, the neurons were mainly bipolar and were rarely multipolar. By P14 the cells were located primarily in cortical layers III-VI. Nitrergic neurons of the 21 day old rats were histochemically identified as multipolar cells with long radial extending dendrites. Dendrites of neurons in 14 and 21 day old rats were a similar length with an average of 57 μm. These results suggest that nitrergic neurons differentiate during a relatively short period of time and reach their structural maturity by the end of the second week of postnatal development.

  12. Relation between cognitive impairment and early death in the elderly.

    Science.gov (United States)

    Eagles, J M; Beattie, J A; Restall, D B; Rawlinson, F; Hagen, S; Ashcroft, G W

    1990-01-01

    STUDY OBJECTIVE--To study the association between cognitive impairment and early death in elderly patients living in the community. DESIGN--Case-control study of 410 patients assessed by the mental status questionnaire and followed up after three years. SETTING--A general practice in Inverurie, Aberdeenshire, with 14,000 patients. PATIENTS--205 Patients aged greater than or equal to 65 with cognitive impairment according to the mental status questionnaire (score less than or equal to 8) and 205 patients scoring greater than 8 on the questionnaire matched for age and sex. MAIN OUTCOME MEASURE--Death. RESULTS--The relative risk of death in the cognitively impaired patients overall was 3.5. Those patients who scored less than or equal to 7 on the mental status questionnaire were five times more likely to die than their controls. There was no difference in risk of death between those with severe or moderate cognitive impairment. CONCLUSIONS--Cognitive impairment is associated with early death. PMID:2106935

  13. Early metabolic programming of puberty onset: impact of changes in postnatal feeding and rearing conditions on the timing of puberty and development of the hypothalamic kisspeptin system

    DEFF Research Database (Denmark)

    Castellano, Juan M; Bentsen, Agnete H; Sánchez-Garrido, Miguel A

    2011-01-01

    the timing of puberty; however, the potential underlying mechanisms remain poorly defined. Here we report how changes in the pattern of postnatal feeding affect the onset of puberty and evaluate key hormonal and neuropeptide [Kiss1/kisspeptin (Kp)] alterations linked to these early nutritional manipulations...... of puberty, together with higher levels of leptin and hypothalamic Kiss1 mRNA. Conversely, postnatal underfeeding caused a persistent reduction in body weight, lower ovarian and uterus weights, and delayed vaginal opening, changes that were paralleled by a decrease in leptin and Kiss1 mRNA levels. Kisspeptin...... at puberty were similar in all groups, except for enhanced responsiveness to low doses of Kp-10 in postnatally underfed rats. In conclusion, our data document that the timing of puberty is sensitive to both overfeeding and subnutrition during early (postnatal) periods and suggest that alterations...

  14. Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development

    OpenAIRE

    Waterland, Robert A.; Kellermayer, Richard; Rached, Marie-Therese; Tatevian, Nina; Gomes, Marcus V.; Zhang, Jiexin; Li ZHANG; Chakravarty, Abrita; Zhu, Wei; Laritsky, Eleonora; Zhang, Wenjuan; Wang, Xiaodan; Shen, Lanlan

    2009-01-01

    The question of whether DNA methylation contributes to the stabilization of gene expression patterns in differentiated mammalian tissues remains controversial. Using genome-wide methylation profiling, we screened 3757 gene promoters for changes in methylation during postnatal liver development to test the hypothesis that developmental changes in methylation and expression are temporally correlated. We identified 31 genes that gained methylation and 111 that lost methylation from embryonic day...

  15. Early postnatal hyperglycaemia is a risk factor for treatment-demanding retinopathy of prematurity

    DEFF Research Database (Denmark)

    Slidsborg, Carina; Jensen, Louise Bering; Rasmussen, Steen Christian

    2017-01-01

    BACKGROUND: To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP). METHODS: This is a Danish national, retrospective, case-control study of premature infants (birth period 2003-2006). Three national regis......: An independent association was found between the occurrence of hyperglycaemic events during the first postnatal week and later development of treatment-demanding ROP, when adjusted for known risk factors.......BACKGROUND: To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP). METHODS: This is a Danish national, retrospective, case-control study of premature infants (birth period 2003-2006). Three national...... was borderline significant (t-test; p=0.047). Hyperglycaemic events (indexed value) were statistically significantly different between the two study groups (Mann-Whitney U test; pindependent risk factor (OR: 1.022; 95% CI 1.002 to 1.042; p=0.031). CONCLUSION...

  16. Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep

    OpenAIRE

    Khanal, Prabhat; Johnsen, Lærke; Axel, Anne Marie Dixen; Hansen, Pernille Willert; Kongsted, Anna Hauntoft; Lyckegaard, Nette Brinch; Nielsen, Mette Olaf

    2016-01-01

    We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until ...

  17. [Early death in vascular surgery: an ongoing prognostic problem].

    Science.gov (United States)

    Kazimierczak, Arkadiusz; Sledź, Marcin; Guzicka-Kazimierczak, Renata; Gutowski, Piotr; Cnotliwy, Miłosław

    2010-01-01

    Prediction of complications in surgery is commonly done. There are conflicting reports concerning the usefulness of risk scales (P-POSSUM, APACHE, SAPS, ASA, Goldman, etc.) in vascular surgery. We decided to take a fresh look at preoperative risk factors of early death in the context of the usefulness of some parameters which have not been included in existing risk calculators. The study group consisted of 1270 patients treated at the Department of Vascular Surgery, General Surgery, and Angiology, Pomeranian Medical University in Szczecin, during one year. METHOD This was a prospective non-randomized study. All data recorded at admission and data from P-POSSUM, ASA, Goldman, and ECOG-Zubroda-WHO scales were analyzed. Statistics were done with discriminant, multivariate, and logistic tests. There were 42 early deaths in the group. The following independent risk factors were involved in early death: ASA > 2 (OR = 18.31), persistent atrial fibrillation (OR = 5.75), leukocytosis (OR = 13.31), glomerular filtration rate (GFR) SIRS) (OR = 11.36), emergency admission (OR = 38.62), critical limb ischemia (OR = 4.87), acute limb ischemia (OR = 8,98), abdominal aortic aneurysm (OR = 4.4), and ruptured aortic aneurysm (OR = 10.59). Logistic regression exposed the influence of five factors: ASA III, ASA IV, persistent atrial fibrillation, leukocytosis, GFR surgery need to be "refreshed". Creation of the Polish National Vascular Surgery Register seems to be unavoidable.

  18. Is early tuberculosis death associated with increased tuberculosis transmission?

    Directory of Open Access Journals (Sweden)

    Anu Parhar

    Full Text Available Tuberculosis (TB is now a relatively uncommon disease in high income countries. As such, its diagnosis may be missed or delayed resulting in death before or shortly after the introduction of treatment. Whether early TB death is associated with increased TB transmission is unknown. To determine the transmission risk attributable to early TB death we undertook a case-control study.All adults who were: (1 diagnosed with culture-positive pulmonary TB in the Province of Alberta, Canada between 1996 and 2012, and (2 died a TB-related death before or within the first 60 days of treatment, were identified. For each of these "cases" two sets of "controls" were randomly selected from among culture-positive pulmonary TB cases that survived beyond 60 days of treatment. "Controls" were matched by age, sex, population group, +/- smear status. Secondary cases of "cases" and "controls" were identified using conventional and molecular epidemiologic tools and compared. In addition, new infections were identified and compared in contacts of "cases" that died before treatment and contacts of their smear-matched "controls". Conditional logistic regression was used to find associations in both univariate and multivariate analysis."Cases" were as, but not more, likely than "controls" to transmit. This was so whether transmission was measured in terms of the number of "cases" and smear-unmatched or -matched "controls" that had a secondary case, the number of secondary cases that they had or the number of new infections found in contacts of "cases" that died before treatment and their smear-matched "controls".In a low TB incidence/low HIV prevalence country, pulmonary TB patients that die a TB-related death before or in the initial phase of treatment and pulmonary TB patients that survive beyond the initial phase of treatment are equally likely to transmit.

  19. The effect of colostrum ingestion during the first 24 hours of life on early postnatal development of piglet immune systems.

    Science.gov (United States)

    Ogawa, Shohei; Tsukahara, Takamitsu; Imaoka, Taishi; Nakanishi, Nobuo; Ushida, Kazunari; Inoue, Ryo

    2016-12-01

    It has been suggested that colostrum is important not only for direct protection from pathogens but also for proper development of immune systems in piglets. In this study, we focused on the effect of colostrum ingestion during the first 24 h of life on early postnatal development of piglet immune systems. Thirty-six piglets from five litters were divided into colostrum-fed (CoF) and colostrum-deprived (CoD) groups. The former group was allowed to suckle normally while formula milk was fed to the latter group during the first 24 h of life. At the weaning period, the concentrations of fecal immunoglobulin (Ig) A and plasma IgG as well as the number of blood leukocyte subsets were analyzed. Fecal IgA and plasma IgG concentrations in the CoF group were more than twice as high as those in the CoD group (P colostrum ingestion during the first 24 h plays a significant role in early postnatal development of both mucosal and systemic immunity of piglets.

  20. Causes of early childhood deaths in urban Dhaka, Bangladesh.

    Directory of Open Access Journals (Sweden)

    Amal K Halder

    Full Text Available Data on causes of early childhood death from low-income urban areas are limited. The nationally representative Bangladesh Demographic and Health Survey 2007 estimates 65 children died per 1,000 live births. We investigated rates and causes of under-five deaths in an urban community near two large pediatric hospitals in Dhaka, Bangladesh and evaluated the impact of different recall periods. We conducted a survey in 2006 for 6971 households and a follow up survey in 2007 among eligible remaining households or replacement households. The initial survey collected information for all children under five years old who died in the previous year; the follow up survey on child deaths in the preceding five years. We compared mortality rates based on 1-year recall to the 4 years preceding the most recent 1 year. The initial survey identified 58 deaths among children <5 years in the preceding year. The follow up survey identified a mean 53 deaths per year in the preceding five years (SD+/-7.3. Under-five mortality rate was 34 and neonatal mortality was 15 per thousand live births during 2006-2007. The leading cause of under-five death was respiratory infections (22%. The mortality rates among children under 4 years old for the two time periods (most recent 1-year recall and the 4 years preceding the most recent 1 year were similar (36 versus 32. The child mortality in urban Dhaka was substantially lower than the national rate. Mortality rates were not affected by recall periods between 1 and 5 years.

  1. Designing, developing, and testing an app for parents being discharged early postnatally

    DEFF Research Database (Denmark)

    Danbjørg, Dorthe Boe; Wagner, Lis; Clemensen, Jane

    2014-01-01

    , and testing of an app as a viable information technology solution. The app was tested with 10 new families. The test results suggest that the new families and the nurses found the app to be viable and the app met the new families' needs for follow-up support. However, the app required refinements and wider...... testing. •We designed, developed, and testet an app for the iPad.•The app was viable, but the app requires refinements and wider testing.•The app met the new families' needs for follow-up support.•There is a potential for ensuring postnatal security with the use of technology....

  2. Designing, developing, and testing an app for parents being discharged early postnatally

    DEFF Research Database (Denmark)

    Danbjørg, Dorthe Boe; Wagner, Lis; Clemensen, Jane

    2014-01-01

    , and testing of an app as a viable information technology solution. The app was tested with 10 new families. The test results suggest that the new families and the nurses found the app to be viable and the app met the new families' needs for follow-up support. However, the app required refinements and wider...... testing. •We designed, developed, and testet an app for the iPad.•The app was viable, but the app requires refinements and wider testing.•The app met the new families' needs for follow-up support.•There is a potential for ensuring postnatal security with the use of technology....

  3. Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH

    DEFF Research Database (Denmark)

    Main, Katharina M; Schmidt, Ida M; Toppari, Jorma

    2002-01-01

    postnatally, to mimic the physiological development, would improve testicular growth and fertility potential later in life. DESIGN: Our patient presented with micropenis. Serum hormone concentrations were measured monthly after delivery: LH and testosterone were undetectable, and FSH and inhibin B were below...... to values within normal limits (0.7-1.88 IU/l, 0.17-3.24 IU/l, 121-268 pg/ml and 40-55 pmol/l respectively), whereas serum testosterone remained undetectable. Penile length increased from 1.6 to 2.4 cm and testicular volume, assessed by ultrasound, increased by 170%. No significant adverse events were...

  4. Family history of premature death and risk of early onset cardiovascular disease

    DEFF Research Database (Denmark)

    Ranthe, Mattis Flyvholm; Carstensen, Lisbeth; Oyen, Nina;

    2012-01-01

    The purpose of this study was to examine the effect of a family history of premature death, cardiovascular death in particular, on the risk of early cardiovascular disease.......The purpose of this study was to examine the effect of a family history of premature death, cardiovascular death in particular, on the risk of early cardiovascular disease....

  5. Protective effects of resveratrol on the inhibition of hippocampal neurogenesis induced by ethanol during early postnatal life.

    Science.gov (United States)

    Xu, Le; Yang, Yang; Gao, Lixiong; Zhao, Jinghui; Cai, Yulong; Huang, Jing; Jing, Sheng; Bao, Xiaohang; Wang, Ying; Gao, Junwei; Xu, Haiwei; Fan, Xiaotang

    2015-07-01

    Ethanol (EtOH) exposure during early postnatal life triggers obvious neurotoxic effects on the developing hippocampus and results in long-term effects on hippocampal neurogenesis. Resveratrol (RSV) has been demonstrated to exert potential neuroprotective effects by promoting hippocampal neurogenesis. However, the effects of RSV on the EtOH-mediated impairment of hippocampal neurogenesis remain undetermined. Thus, mice were pretreated with RSV and were later exposed to EtOH to evaluate its protective effects on EtOH-mediated toxicity during hippocampal development. The results indicated that a brief exposure of EtOH on postnatal day 7 resulted in a significant impairment in hippocampal neurogenesis and a depletion of hippocampal neural precursor cells (NPCs). This effect was attenuated by pretreatment with RSV. Furthermore, EtOH exposure resulted in a reduction in spine density on the granular neurons of the dentate gyrus (DG), and the spines exhibited a less mature morphological phenotype characterized by a higher proportion of stubby spines and a lower proportion of mushroom spines. However, RSV treatment effectively reversed these responses. We further confirmed that RSV treatment reversed the EtOH-induced down-regulation of hippocampal pERK and Hes1 protein levels, which may be related to the proliferation and maintenance of NPCs. Furthermore, EtOH exposure in the C17.2 NPCs also diminished cell proliferation and activated apoptosis, which could be reversed by pretreatment of RSV. Overall, our results suggest that RSV pretreatment protects against EtOH-induced defects in neurogenesis in postnatal mice and may thus play a critical role in preventing EtOH-mediated toxicity in the developing hippocampus.

  6. Reduced densities of parvalbumin- and somatostatin-expressing interneurons in experimental cortical dysplasia and heterotopia in early postnatal development.

    Science.gov (United States)

    Akakin, Dilek; Martinez-Diaz, Hildabelis; Chen, Huan-Xin; Roper, Steven N

    2013-05-01

    Cortical dysplasia (CD) is strongly associated with intractable epilepsy, probably due to hyperexcitability of neuronal networks. However, the underlying mechanisms are not completely understood. GABAergic interneurons provide major inhibitory function in the CNS and have different subtypes, but it is not clear how each subtype is affected in CD during early post-natal development. We have examined the developmental alterations of the densities of two major subtypes of interneurons, parvalbumin (PV)- and somatostatin (SS)-expressing interneurons in an animal model of CD, in utero irradiation, using immunocytochemistry. We found that the density of PV- and SS-positive interneurons increases significantly in CD and controls during the first three weeks of postnatal life. However, compared to controls, the densities of both subtypes are significantly decreased in CD and heterotopia at all age groups although the time of onset for both PV and SS expression remained unchanged. Our results indicate that the densities of both PV- and SS-positive interneurons are significantly decreased in CD and heterotopia, which may be one important mechanism leading to hyperexcitability of CD.

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

    Directory of Open Access Journals (Sweden)

    Dani Smith

    Full Text Available Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains.Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not.Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  8. A schizophrenia rat model induced by early postnatal phencyclidine treatment and characterized by Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Broberg, Brian V; Madsen, Kristoffer H; Plath, Niels

    2013-01-01

    administration of phencyclidine (PCP) induces schizophrenia-like symptoms in healthy volunteers and exacerbates symptoms in patients with schizophrenia. In this study, pharmacological Magnetic Resonance Imaging (phMRI) was used to evaluate if rats treated with 20mg/kg PCP on postnatal days 7, 9, and 11 (neoPCP......), compared to saline (neoVeh), were hypersensitive to acute PCP administration in adulthood (acutePCP). Intravenous administration of 0.5mg/kg acutePCP produced robust and sustained relative cerebral blood volume (rCBV) increase in discrete frontal, neocortical, hippocampal, thalamic, and limbic brain...... structures in both neoPCP:acutePCP and neoVeh:acutePCP rats compared to acute saline treatment (Vehicle control group). AcutePCP injection significantly increased the rCBV response in the medial prefrontal cortex and nucleus accumbens compared to the Vehicle control group, without distinguishing neoPCP...

  9. Early death during chemotherapy in patients with small-cell lung cancer

    DEFF Research Database (Denmark)

    Lassen, U N; Osterlind, K; Hirsch, F R

    1999-01-01

    Based on an increased frequency of early death (death within the first treatment cycle) in our two latest randomized trials of combination chemotherapy in small-cell lung cancer (SCLC), we wanted to identify patients at risk of early non-toxic death (ENTD) and early toxic death (ETD). Data were...... stored in a database and logistic regression analyses were performed to identify predictive factors for early death. During the first cycle, 118 out of 937 patients (12.6%) died. In 38 patients (4%), the cause of death was sepsis. Significant risk factors were age, performance status (PS), lactate...

  10. Early postnatal development of the mandible in children with isolated cleft palate and children with nonsyndromic Robin sequence

    DEFF Research Database (Denmark)

    Eriksen, J.; Hermann, N.V.; Darvann, Tron Andre

    2006-01-01

    Objective: Analysis of early postnatal mandibular size and growth velocity in children with untreated isolated cleft palate (ICP), nonsyndromic Robin sequence (RS), and a control group of children with unilateral incomplete cleft lip (UICL). Material: 114 children (66 isolated cleft palate, 7 Robin...... sequence, 41 unilateral incomplete cleft lip) drawn from a group representing all Danish cleft children born from 1976 through 1981. All children were examined at both 2 and 22 months of age. Methods: Cephalometric x-rays and maxillary plaster casts. Mandibular length and height were measured...... at 2 months of age. Conclusion: The children with isolated cleft palate and Robin sequence had small mandibles shortly after birth, but with a relatively normal growth potential. No true mandibular catch-up growth was found up to 22 months of age in either group. No significant correlation was found...

  11. Histology Atlas of the Developing Mouse Hepatobiliary Hemolymphatic Vascular System with Emphasis on Embryonic Days 11.5-18.5 and Early Postnatal Development.

    Science.gov (United States)

    Swartley, Olivia M; Foley, Julie F; Livingston, David P; Cullen, John M; Elmore, Susan A

    2016-07-01

    A critical event in embryo development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has led researchers to use transgenic mice to identify the critical steps involved in developmental disorders associated with the hepatobiliary vascular system. Vascular development is dependent upon normal vasculogenesis, angiogenesis, and the transformation of vessels into their adult counterparts. Any alteration in vascular development has the potential to cause deformities or embryonic death. Numerous publications describe specific stages of vascular development relating to various organs, but a single resource detailing the stage-by-stage development of the vasculature pertaining to the hepatobiliary system has not been available. This comprehensive histology atlas provides hematoxylin & eosin and immunohistochemical-stained sections of the developing mouse blood and lymphatic vasculature with emphasis on the hepatobiliary system between embryonic days (E) 11.5-18.5 and the early postnatal period. Additionally, this atlas includes a 3-dimensional video representation of the E18.5 mouse venous vasculature. One of the most noteworthy findings of this atlas is the identification of the portal sinus within the mouse, which has been erroneously misinterpreted as the ductus venosus in previous publications. Although the primary purpose of this atlas is to identify normal hepatobiliary vascular development, potential embryonic abnormalities are also described. © The Author(s) 2016.

  12. CD44 is a marker for the outer pillar cells in the early postnatal mouse inner ear.

    Science.gov (United States)

    Hertzano, Ronna; Puligilla, Chandrakala; Chan, Siaw-Lin; Timothy, Caroline; Depireux, Didier A; Ahmed, Zubair; Wolf, Jeffrey; Eisenman, David J; Friedman, Thomas B; Riazuddin, Sheikh; Kelley, Matthew W; Strome, Scott E

    2010-09-01

    Cluster of differentiation antigens (CD proteins) are classically used as immune cell markers. However, their expression within the inner ear is still largely undefined. In this study, we explored the possibility that specific CD proteins might be useful for defining inner ear cell populations. mRNA expression profiling of microdissected auditory and vestibular sensory epithelia revealed 107 CD genes as expressed in the early postnatal mouse inner ear. The expression of 68 CD genes was validated with real-time RT-PCR using RNA extracted from microdissected sensory epithelia of cochleae, utricles, saccules, and cristae of newborn mice. Specifically, CD44 was identified as preferentially expressed in the auditory sensory epithelium. Immunohistochemistry revealed that within the early postnatal organ of Corti, the expression of CD44 is restricted to outer pillar cells. In order to confirm and expand this finding, we characterized the expression of CD44 in two different strains of mice with loss- and gain-of-function mutations in Fgfr3 which encodes a receptor for FGF8 that is essential for pillar cell development. We found that the expression of CD44 is abolished from the immature pillar cells in homozygous Fgfr3 knockout mice. In contrast, both the outer pillar cells and the aberrant Deiters' cells in the Fgfr3 ( P244R/ ) (+) mice express CD44. The deafness phenotype segregating in DFNB51 families maps to a linkage interval that includes CD44. To study the potential role of CD44 in hearing, we characterized the auditory system of CD44 knockout mice and sequenced the entire open reading frame of CD44 of affected members of DFNB51 families. Our results suggest that CD44 does not underlie the deafness phenotype of the DFNB51 families. Finally, our study reveals multiple potential new cell type-specific markers in the mouse inner ear and identifies a new marker for outer pillar cells.

  13. Effect of prenatal and postnatal malnutrition on intellectual functioning in early school-aged children in rural western China.

    Science.gov (United States)

    Li, Chao; Zhu, Ni; Zeng, Lingxia; Dang, Shaonong; Zhou, Jing; Yan, Hong

    2016-08-01

    The aim of this study was to evaluate the effect of prenatal and postnatal malnutrition on the intellectual functioning of early school-aged children. We followed the offspring of women who had participated in a trial of prenatal supplementation with different combinations of micronutrients and who remained resident in the study field. We measured their intellectual functioning using the Wechsler intelligence scale for children (WISC-IV). Height-for-age, weight-for-age, and body mass index (BMI)-for-age were used as anthropometric nutritional status indices. Four of the 5 composite scores derived from the WISC-IV, except for working memory index (WMI), were significantly lower in low birth weight children after adjusting for confounds. All 5 composite scores, including full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), WMI, perceptual reasoning index (PRI), and processing speed index (PSI) were significant lower in stunted and underweight children. The differences in the means of WISC-IV test scores were greatest between stunted and nonstunted children. The means for FSIQ, VCI, WMI, PRI, and PSI were as follows: 5.88 (95% confidence interval [CI]: 2.84-8.92), 5.08 (95% CI: 1.12-8.41), 4.71 (95% CI: 1.78-7.66), 6.13 (95% CI: 2.83-9.44), and 5.81 (95% CI: 2.61-9.00). These means were lower in stunted children after adjusting for confounds. Our results suggest the important influences of low birth weight and postnatal malnutrition (stunting, low body weight) on intellectual functioning in early school-aged children.

  14. Impact of birth weight and gender on early postnatal hypothalamic energy balance regulatory gene expression in the young lamb.

    Science.gov (United States)

    Adam, C L; Bake, T; Findlay, P A; Milne, J S; Aitken, R P; Wallace, J M

    2013-11-01

    Intra-uterine growth restriction (IUGR) is involved in developmental metabolic programming and here we test the hypothesis that IUGR affects the developing hypothalamic energy balance regulatory pathways in a sex-specific manner. This experiment investigated early postnatal hypothalamic gene expression for six primary leptin- and insulin-sensitive neuropeptides and receptors in male and female IUGR (n = 8 and 9, respectively) and normal (N) birth weight lambs (n = 8 per gender) gestated and suckled by overnourished mothers. IUGR lambs were smaller at birth, had increased fractional growth rates (FGR), lower final body weight (11 weeks) and similar body fat content compared with N lambs, while males had higher final body weight and insulinemia but lower body fat and leptinemia than females. In situ hybridization revealed greater gene expression in the hypothalamic arcuate nucleus at 11 weeks for anorexigenic genes in females and orexigenic genes in males, with no effect of IUGR. Leptinemia correlated with gene expression for neuropeptide Y (NPY, negatively) in both sexes and pro-opiomelanocortin (POMC, positively) in females but with leptin receptor (negatively) only in males. Current FGR for girth correlated negatively with gene expression for NPY in males and POMC in females. Neither IUGR nor gender affected suckling activity (proxy for appetite) assessed at 3 weeks, but final NPY gene expression correlated with suckling weight gain in males. This study has revealed no effect of IUGR on early postnatal hypothalamic energy balance gene expression but a major effect of gender associated with major sex differences in adiposity and leptinemia. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  15. Early metabolic programming of puberty onset: impact of changes in postnatal feeding and rearing conditions on the timing of puberty and development of the hypothalamic kisspeptin system.

    Science.gov (United States)

    Castellano, Juan M; Bentsen, Agnete H; Sánchez-Garrido, Miguel A; Ruiz-Pino, Francisco; Romero, Magdalena; Garcia-Galiano, David; Aguilar, Enrique; Pinilla, Leonor; Diéguez, Carlos; Mikkelsen, Jens D; Tena-Sempere, Manuel

    2011-09-01

    Kiss1 neurons have recently emerged as a putative conduit for the metabolic gating of reproduction, with leptin being a regulator of hypothalamic Kiss1 expression. Early perturbations of the nutritional status are known to predispose to different metabolic disorders later in life and to alter the timing of puberty; however, the potential underlying mechanisms remain poorly defined. Here we report how changes in the pattern of postnatal feeding affect the onset of puberty and evaluate key hormonal and neuropeptide [Kiss1/kisspeptin (Kp)] alterations linked to these early nutritional manipulations. Female rats were raised in litters of different sizes: small (four pups per dam: overfeeding), normal (12 pups per dam), and large litters (20 pups per litter: underfeeding). Postnatal overfeeding resulted in persistently increased body weight and earlier age of vaginal opening, as an external sign of puberty, together with higher levels of leptin and hypothalamic Kiss1 mRNA. Conversely, postnatal underfeeding caused a persistent reduction in body weight, lower ovarian and uterus weights, and delayed vaginal opening, changes that were paralleled by a decrease in leptin and Kiss1 mRNA levels. Kisspeptin-52 immunoreactivity (Kp-IR) in the hypothalamus displayed similar patterns, with lower numbers of Kp-IR neurons in the arcuate nucleus of postnatally underfed animals, and a trend for increased Kp-positive fibers in the periventricular area of early overfed rats. Yet, gonadotropin responses to Kp at puberty were similar in all groups, except for enhanced responsiveness to low doses of Kp-10 in postnatally underfed rats. In conclusion, our data document that the timing of puberty is sensitive to both overfeeding and subnutrition during early (postnatal) periods and suggest that alterations in hypothalamic expression of Kiss1/kisspeptin may underlie at least part of such programming phenomenon.

  16. Chronic NMDA receptor blockade in early postnatal period, but not in adulthood, impairs methamphetamine-induced conditioned place preference in rats.

    Science.gov (United States)

    Furuie, Hiroki; Yamada, Kazuo; Ichitani, Yukio

    2016-03-15

    Early postnatal glutamatergic N-methyl-d-aspartate (NMDA) receptor blockade in animals is known to produce various behavioral deficits in adulthood. In the present study rats postnatally (day 7-20) treated chronically with MK-801, an NMDA receptor antagonist, were tested later in adulthood in methamphetamine (MAP)-induced conditioned place preference (CPP) using a unbiased procedure in a three-compartment apparatus. Rats with the same chronic treatment in adulthood were also tested. CPP test consisted of a baseline test before conditioning, place conditioning, and a preference test after conditioning. Rats postnatally treated with MK-801 did not show any evidence of preference for MAP-paired compartment compared with that for unpaired one in the preference test that was shown in rats postnatally treated with saline. On the other hand, rats treated with MK-801 in adulthood were not affected by the treatment and showed significant CPP as was shown in saline-treated control animals. Results suggest the possibility that chronic early postnatal, but not adulthood, NMDA receptor blockade induces persistent deficit of subsequent appetitive classical conditioning.

  17. Reduced linoleic acid intake in early postnatal life improves metabolic outcomes in adult rodents following a Western-style diet challenge

    NARCIS (Netherlands)

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

    The global increase in dietary n-6 polyunsaturated fatty acid (PUPA) intake has been suggested to contribute to the rise in obesity incidence. We hypothesized that reduced n-6 PUPA intake during early postnatal life improves adult body composition and metabolic phenotype upon a Western diet

  18. Early postnatal EEG features of perinatal arterial ischaemic stroke with seizures.

    Directory of Open Access Journals (Sweden)

    Evonne Low

    Full Text Available Stroke is the second most common cause of seizures in term neonates and is associated with abnormal long-term neurodevelopmental outcome in some cases.To aid diagnosis earlier in the postnatal period, our aim was to describe the characteristic EEG patterns in term neonates with perinatal arterial ischaemic stroke (PAIS seizures.Retrospective observational study.Neonates >37 weeks born between 2003 and 2011 in two hospitals.Continuous multichannel video-EEG was used to analyze the background patterns and characteristics of seizures. Each EEG was assessed for continuity, symmetry, characteristic features and sleep cycling; morphology of electrographic seizures was also examined. Each seizure was categorized as electrographic-only or electroclinical; the percentage of seizure events for each seizure type was also summarized.Nine neonates with PAIS seizures and EEG monitoring were identified. While EEG continuity was present in all cases, the background pattern showed suppression over the infarcted side; this was quite marked (>50% amplitude reduction when the lesion was large. Characteristic unilateral bursts of theta activity with sharp or spike waves intermixed were seen in all cases. Sleep cycling was generally present but was more disturbed over the infarcted side. Seizures demonstrated a characteristic pattern; focal sharp waves/spike-polyspikes were seen at frequency of 1-2 Hz and phase reversal over the central region was common. Electrographic-only seizure events were more frequent compared to electroclinical seizure events (78 vs 22%.Focal electrographic and electroclinical seizures with ipsilateral suppression of the background activity and focal sharp waves are strong indicators of PAIS. Approximately 80% of seizure events were the result of clinically unsuspected seizures in neonates with PAIS. Prolonged and continuous multichannel video-EEG monitoring is advocated for adequate seizure surveillance.

  19. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

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    Wei Ling Lim

    2016-08-01

    Full Text Available Maternal dexamethasone (DEX; a glucocorticoid receptor agonist exposure delays pubertal onset and alters reproductive behaviour in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP under the control of GnRH promoter. Pregnant females were administered with DEX (0.1mg/kg or vehicle (VEH, water daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0 males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the post synaptic marker molecule, post-synaptic density 95 was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

  20. Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood.

    Science.gov (United States)

    Oosting, Annemarie; van Vlies, Naomi; Kegler, Diane; Schipper, Lidewij; Abrahamse-Berkeveld, Marieke; Ringler, Silvia; Verkade, Henkjan J; van der Beek, Eline M

    2014-01-28

    Obese individuals have more (hyperplastic) and larger (hypertrophic) adipocytes in their white adipose tissue (WAT) than normal-weight individuals. The difference in cell number emerges early in childhood, suggesting that this is a critical period for being susceptible to obesity. Breast-feeding has been shown to be protective against obesity, and we have previously shown in mice that the physical structure of lipids in human milk may contribute to this protective effect. In the present study, we investigated how differences in the physical structure of lipids in the early diet may modulate adipose tissue development. Male mice were fed a diet containing control infant milk formula (Control IMF; Danone Research) or Nuturis® (Concept IMF with large phospholipid-coated lipid droplets; Danone Research) from postnatal day (PN)16 to 42. Subsequently, mice were challenged with a moderate Western-style diet (WSD) until PN98, and body composition was monitored by dual-energy X-ray absorptiometry. Epididymal WAT was analysed for adipocyte size, number and gene expression of metabolic transcription factors. Early Concept IMF exposure reduced fat accumulation during the WSD challenge by 30 % compared with the Control IMF. It reduced adipocyte size without affecting adipocyte number in adult mice. The Concept IMF decreased the expression of PPARγ, CCAAT/enhancer-binding protein and retinoid X receptor α in WAT in adulthood, key regulators of metabolic activity. In conclusion, Concept IMF exposure in early life reduced susceptibility to obesity in adult life, by preventing adipocyte hypertrophia upon adult dietary challenge without affecting adipogenesis. These data emphasise the importance of the physical properties of dietary lipids in early life in obesity risk later in life.

  1. Transient overexposure of neuregulin 3 during early postnatal development impacts selective behaviors in adulthood.

    Directory of Open Access Journals (Sweden)

    Clare Paterson

    Full Text Available Neuregulin 3 (NRG3, a specific ligand for ErbB4 and a neuronal-enriched neurotrophin is implicated in the genetic predisposition to a broad spectrum of neurodevelopmental, neurocognitive and neuropsychiatric disorders, including Alzheimer's disease, autism and schizophrenia. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, accompanied by increased expression of prefrontal cortical NRG3. Despite our expanding knowledge of genetic involvement of NRG3 in neurological disorders, little is known about the neurodevelopmental mechanisms of risk. Here we exploited the fact that a paralog of NRG3, NRG1, readily penetrates the murine blood brain barrier (BBB. In this study we synthesized the bioactive epidermal growth factor (EGF domain of NRG3, and using previously validated in-vivo peripheral injection methodologies in neonatal mice, demonstrate that NRG3 successfully crosses the BBB, where it activates its receptor ErbB4 and downstream Akt signaling at levels of bioactivity comparable to NRG1. To determine the impact of NRG3 overexpression during one critical developmental window, C57BL/6 male mice were subcutaneously injected daily with NRG1-EGF, NRG3-EGF or vehicle from postnatal days 2-10. Mice were tested in adulthood using a comprehensive battery of behavioral tasks relevant to neurocognitive and psychiatric disorders. In agreement with previous studies, developmental overexposure to NRG1 induced multiple non-CNS mediated peripheral effects as well as severely disrupting performance of prepulse inhibition of the startle response. In contrast, NRG3 had no effect on any peripheral measures investigated or sensorimotor gating. Specifically, developmental NRG3 overexposure produced an anxiogenic-like phenotype and deficits in social behavior in adulthood. These results provide primary data to support a role for NRG3 in brain development and function, which appears to

  2. Antipsychotic Drugs May Up Risk of Early Death in Alzheimer's Patients

    Science.gov (United States)

    ... Drugs May Up Risk of Early Death in Alzheimer's Patients Increased odds were nearly doubled if two ... significantly increases the risk of premature death among Alzheimer's patients, a new study indicates. Researchers analyzed data ...

  3. Early postnatal respiratory viral infection alters hippocampal neurogenesis, cell fate, and neuron morphology in the neonatal piglet.

    Science.gov (United States)

    Conrad, Matthew S; Harasim, Samantha; Rhodes, Justin S; Van Alstine, William G; Johnson, Rodney W

    2015-02-01

    Respiratory viral infections are common during the neonatal period in humans, but little is known about how early-life infection impacts brain development. The current study used a neonatal piglet model as piglets have a gyrencephalic brain with growth and development similar to human infants. Piglets were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) to evaluate how chronic neuroinflammation affects hippocampal neurogenesis and neuron morphology. Piglets in the neurogenesis study received one bromodeoxyuridine injection on postnatal day (PD) 7 and then were inoculated with PRRSV. Piglets were sacrificed at PD 28 and the number of BrdU+ cells and cell fate were quantified in the dentate gyrus. PRRSV piglets showed a 24% reduction in the number of newly divided cells forming neurons. Approximately 15% of newly divided cells formed microglia, but this was not affected by sex or PRRSV. Additionally, there was a sexual dimorphism of new cell survival in the dentate gyrus where males had more cells than females, and PRRSV infection caused a decreased survival in males only. Golgi impregnation was used to characterize dentate granule cell morphology. Sholl analysis revealed that PRRSV caused a change in inner granule cell morphology where the first branch point was extended further from the cell body. Males had more complex dendritic arbors than females in the outer granule cell layer, but this was not affected by PRRSV. There were no changes to dendritic spine density or morphology distribution. These findings suggest that early-life viral infection can impact brain development.

  4. Early repolarization syndrome: A cause of sudden cardiac death

    Institute of Scientific and Technical Information of China (English)

    Abdi; Ali; Nida; Butt; Azeem; S; Sheikh

    2015-01-01

    Early repolarization syndrome(ERS), demonstrated as J-point elevation on an electrocardiograph, was formerly thought to be a benign entity, but the recent studies have demonstrated that it can be linked to a considerable risk of life- threatening arrhythmias and sudden cardiac death(SCD). Early repolarization characteristics associated with SCD include high-amplitude J-point elevation, horizontal and/or downslopping ST segments, and inferior and/or lateral leads location. The prevalence of ERS varies between 3% and 24%, depending on age, sex and J-point elevation(0.05 m V vs 0.1 m V) being the main determinants.ERS patients are sporadic and they are at a higher risk of having recurrent cardiac events. Implantable cardioverter-defibrillator implantation and isoproterenol are the suggested therapies in this set of patients. On the other hand, asymptomatic patients with ERS are common and have a better prognosis. The risk stratification in asymptomatic patients with ERS still remains a grey area. This review provides an outline of the up-to-date evidence associated with ERS and the risk of life- threatening arrhythmias. Further prospective studies are required to elucidate the mechanisms of ventricular arrhythmogenesis in patients with ERS.

  5. Postnatal interleukin-1β enhances adulthood seizure susceptibility and neuronal cell death after prolonged experimental febrile seizures in infantile rats.

    Science.gov (United States)

    Fukuda, Mitsumasa; Hino, Hitomi; Suzuki, Yuka; Takahashi, Hisaaki; Morimoto, Takehiko; Ishii, Eiichi

    2014-09-01

    Febrile seizures (FS) are recognized as an antecedent to the development of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), but it is unclear whether prolonged FS are a direct cause of TLE-HS. Here, we used a rat model of infantile FS to study the effects of inflammatory cytokines on seizure susceptibility and neuronal death in adults. Prolonged hyperthermia-induced seizures (pHS) were induced in male Lewis rats at post natal day (P) 10. Cytokines were administered twice intranasally, once immediately after pHS and once the following day. The effects of intranasal interleukin (IL)-1β or tumor necrosis factor (TNF) α were tested in rats undergoing a single episode of pHS (P10) and in rats undergoing repeated pHS (P10 and P12). Seizure susceptibility was tested at P70-73 by quantifying the seizure onset time (SOT) after kainic acid administration, and neuronal cell injury and gliosis in adulthood. SOT significantly reduced in rats receiving IL-1β together with repeated pHS, whereas no significant effects were seen in rats receiving IL-1β after a single pHS episode, or in rats receiving TNFα. Hippocampal neuronal cell loss was observed in the CA3 region of rats receiving IL-1β together with repeated pHS; however, there was no significant change in gliosis among each group. Our results are consistent with the hypothesis that excessive production of IL-1β after repeated prolonged FS can enhance adult seizure susceptibility and neuronal cell death, and might contribute to the development of TLE-HS.

  6. Early postnatal methoxychlor exposure inhibits folliculogenesis and stimulates anti-Mullerian hormone production in the rat ovary.

    Science.gov (United States)

    Uzumcu, Mehmet; Kuhn, Peter E; Marano, Jason E; Armenti, AnnMarie E; Passantino, Lisa

    2006-12-01

    Methoxychlor [1,1,1-trichloro-2,2-bis(4-methoxyphenyl) ethane; MXC] is a chlorinated hydrocarbon pesticide commonly used in the United States as a replacement for DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane]. While MXC is a weak estrogenic compound, its more active, major metabolite [2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane; HPTE] shows estrogenic, anti-estrogenic, or anti-androgenic properties depending on the receptor subtype with which it interacts. Anti-Mullerian hormone (AMH) is a paracrine factor that suppresses initial follicle recruitment in the ovary. Studies have shown the effects of exposure to MXC on adult ovarian morphology and function. However, the effect of exposure to MXC at an early postnatal stage on pre-pubertal follicular development and ovarian AMH production has not been studied. Around postnatal day (P) 4, most of the primordial follicular assembly in rats is complete, and a large number of primordial follicles transition into the primary follicle stage, a process that is inhibited by estrogen. The objective of this study was to examine the effect of early postnatal (P3-P10) MXC exposure on ovarian morphology and size, follicle number, and AMH production in the pre-pubertal (P20) rat ovary and to investigate the effect of HPTE on AMH production in immature rat granulosa cells in vitro. Female rats were injected (s.c.) daily with vehicle (control) or 1, 10, 50, 100, or 500 mg MXC/kg per day (referred to here as 1MXC, 10MXC, and so forth.) between P3 and P10. On P20, uterine and ovarian weights were determined, ovarian histology was examined, and follicles were counted and classified into primordial, primary, secondary, pre-antral, or antral stages using the two largest serial sections at the center of the ovary. Ovarian AMH production was examined using immunohistochemistry and western blot analysis. The effect of HPTE (0.5-25 microM) on AMH production in cultured immature rat granulosa cells was determined by western blot

  7. Role of tonic GABAergic currents during pre- and early postnatal rodent development

    Directory of Open Access Journals (Sweden)

    Werner eKilb

    2013-09-01

    Full Text Available In the last three decades it became evident that the GABAergic system plays an essential role for the development of the central nervous system, by influencing the proliferation of neuronal precursors, neuronal migration and differentiation, as well as by controlling early activity patterns and thus formation of neuronal networks. GABA controls neuronal development via depolarizing membrane responses upon activation of ionotropic GABA receptors. However, many of these effects occur before the onset of synaptic GABAergic activity and thus require the presence of extrasynaptic tonic currents in neuronal precursors and immature neurons. This review summarizes our current knowledge about the role of tonic GABAergic currents during early brain development. In this review we compare the temporal sequence of the expression and functional relevance of different GABA receptor subunits, GABA synthesizing enzymes and GABA transporters. We also refer to other possible endogenous agonists of GABAA receptors. In addition, we describe functional consequences mediated by the GABAergic system during early developmental periods and discuss current models about the origin of extrasynaptic GABA and/or other endogenous GABAergic agonists during early developmental states. Finally, we present evidence that tonic GABAergic activity is also critically involved in the generation of physiological as well as pathophysiological activity patterns before and after the establishment of functional GABAergic synaptic connections.

  8. Role of tonic GABAergic currents during pre- and early postnatal rodent development.

    Science.gov (United States)

    Kilb, Werner; Kirischuk, Sergei; Luhmann, Heiko J

    2013-01-01

    In the last three decades it became evident that the GABAergic system plays an essential role for the development of the central nervous system, by influencing the proliferation of neuronal precursors, neuronal migration and differentiation, as well as by controlling early activity patterns and thus formation of neuronal networks. GABA controls neuronal development via depolarizing membrane responses upon activation of ionotropic GABA receptors. However, many of these effects occur before the onset of synaptic GABAergic activity and thus require the presence of extrasynaptic tonic currents in neuronal precursors and immature neurons. This review summarizes our current knowledge about the role of tonic GABAergic currents during early brain development. In this review we compare the temporal sequence of the expression and functional relevance of different GABA receptor subunits, GABA synthesizing enzymes and GABA transporters. We also refer to other possible endogenous agonists of GABAA receptors. In addition, we describe functional consequences mediated by the GABAergic system during early developmental periods and discuss current models about the origin of extrasynaptic GABA and/or other endogenous GABAergic agonists during early developmental states. Finally, we present evidence that tonic GABAergic activity is also critically involved in the generation of physiological as well as pathophysiological activity patterns before and after the establishment of functional GABAergic synaptic connections.

  9. L-Carnitine supplementation during suckling intensifies the early postnatal skeletal myofiber formation in piglets of low birth weight.

    Science.gov (United States)

    Lösel, D; Kalbe, C; Rehfeldt, C

    2009-07-01

    Piglets of low birth weight exhibit a reduced total number of skeletal myofibers at birth and throughout life compared with piglets of middle and heavy birth weight, which is associated with impaired (lean) growth and quality of carcass and meat at market weight. We investigated the effect of L-carnitine supplementation to suckling piglets of different birth weights on early postnatal myofiber formation, muscle growth, and body composition. A total of 48 piglets of low (LW) and middle (MDW) birth weight from 9 German Landrace gilts received 400 mg of L-carnitine (carnitine, n = 25) or a placebo (control, n = 23) once daily from d 7 to 27 of age and were slaughtered on d 28 of age (weaning). Carnitine-supplemented piglets deposited less fat as indicated by a reduced proportion of perirenal (P = 0.1) and intramuscular fat (P = 0.05). Circulating glucose concentrations tended to be greater in supplemented LW piglets (P = 0.13). The concentration of carnitine in semitendinosus (STN) muscle was approximately doubled (P supplementation, with emphasis on the proportion of esterified carnitine. The ratio of lactate dehydrogenase to isocitrate dehydrogenase tended (P = 0.12) to be smaller in STN muscle of supplemented piglets, indicating a more oxidative muscle metabolism. The total number of STN myofibers was increased by 13% (P = 0.02) in supplemented LW piglets, thereby reaching the unchanged level of MDW littermates. In addition, supplemented LW piglets displayed a 2.4-fold mRNA expression of the gene encoding the embryonic isoform of the myosin heavy chain in STN muscle than control piglets (P = 0.05), but there were no differences in the proportion of fibers positively staining for the embryonic myosin isoform. L-carnitine-supplemented piglets exhibited a greater DNA:protein ratio (P = 0.02) in STN muscle, which resulted from a greater DNA concentration (P = 0.04). However, the STN muscle of L-carnitine-supplemented piglets was not less mature as indicated by

  10. Survival of offspring who experience early parental death: early life conditions and later-life mortality.

    Science.gov (United States)

    Smith, Ken R; Hanson, Heidi A; Norton, Maria C; Hollingshaus, Michael S; Mineau, Geraldine P

    2014-10-01

    We examine the influences of a set of early life conditions (ELCs) on all-cause and cause-specific mortality among elderly individuals, with special attention to one of the most dramatic early events in a child's, adolescent's, or even young adult's life, the death of a parent. The foremost question is, once controlling for prevailing (and potentially confounding) conditions early in life (family history of longevity, paternal characteristics (SES, age at time of birth, sibship size, and religious affiliation)), is a parental death associated with enduring mortality risks after age 65? The years following parental death may initiate new circumstances through which the adverse effects of paternal death operate. Here we consider the offspring's marital status (whether married; whether and when widowed), adult socioeconomic status, fertility, and later life health status. Adult health status is based on the Charlson Co-Morbidity Index, a construct that summarizes nearly all serious illnesses afflicting older individuals that relies on Medicare data. The data are based on linkages between the Utah Population Database and Medicare claims that hold medical diagnoses data. We show that offspring whose parents died when they were children, but especially when they were adolescents/young adults, have modest but significant mortality risks after age 65. What are striking are the weak mediating influences of later-life comorbidities, marital status, fertility and adult socioeconomic status since controls for these do little to alter the overall association. No beneficial effects of the surviving parent's remarriage were detected. Overall, we show the persistence of the effects of early life loss on later-life mortality and indicate the difficulties in addressing challenges at young ages.

  11. A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats

    DEFF Research Database (Denmark)

    Alexanderson, Camilla; Stener-Victorin, Elisabet; Kullberg, Joel

    2010-01-01

    of estrogen receptor a was decreased, and expression of leptin, lipoprotein lipase, and hormone-sensitive lipase was unaffected. These findings suggest that early postnatal estradiol exposure of female rats result in long-lasting effects on the ovary and parametrial adipose tissue at adult age.......Events during early life can affect reproductive and metabolic functions in adulthood. We evaluated the programming effects of a single early postnatal estradiol injection (within 3h after birth) in female rats. We assessed ovarian and parametrial adipose tissue morphology, evaluated gene...... expression related to follicular development and adipose tissue metabolism, and developed a non-invasive volumetric estimation of parametrial adipose tissue by magnetic resonance imaging. Estradiol reduced ovarian weight, increased antral follicle size and number of atretic antral follicles, and decreased...

  12. Rates of Early Deaths Rise for Whites, Drop for Blacks

    Science.gov (United States)

    ... 26, 2017 WEDNESDAY, Jan. 25, 2017 (HealthDay News) -- Premature death rates in the United States have fallen for ... 1999 to 2014. They found that rates of premature death (between ages 25 to 64) declined among blacks, ...

  13. Using quality improvement methods to test and scale up a new national policy on early post-natal care in Ghana.

    Science.gov (United States)

    Twum-Danso, Nana Ay; Dasoberi, Ireneous N; Amenga-Etego, Isaac A; Adondiwo, Ane; Kanyoke, Ernest; Boadu, Richard O; Atinbire, Solomon; Balagumyetime, Phoebe; Bagni, Francisca; Kubio, Chrysanthus; Sagoe-Moses, Isabella; Barker, Pierre M

    2014-08-01

    The first week of life presents the greatest risk of dying for a young infant. Yet, due to the sociocultural, financial, geographical and health system barriers found in many resource-poor settings, infants do not access health care until much later. To reduce neonatal mortality, the Ghana Health Service proposed a new policy that promotes skilled care during the first week of life. We report the results of an initiative that uses quality improvement (QI) methods to test the feasibility and effectiveness of the new early post-natal care (PNC) policy and its subsequent scale-up throughout northern Ghana. Over a 10-month period, 30 networked QI teams from 27 rural health facilities developed and tested both facility-based and community-based changes to their processes of maternal and neonatal care. Coverage and outcome data were analysed using an interrupted time-series design. Over 24 months, early PNC increased from a mean of 15% to 71% for visits within the first 48 h, and from 0% to 53% for visits on Day 6 or 7. We observed a slower increase in skilled delivery (mean of 56% to 82%) over a longer period of time (35 months). Facility-based neonatal mortality remained unchanged: mean of 5.1 deaths per 1000 deliveries. Using the most effective change ideas developed in the 27 test facilities, the early PNC policy was scaled up over the subsequent 2 years to 576 health facilities in all 38 districts of northern Ghana. This initiative demonstrates the utility of a QI approach in testing, implementing and subsequent scaling up a national policy for early PNC in a resource-constrained setting. This approach provides a model for improving the implementation of other national health policies to accelerate the achievement of the Millennium Development Goals in Ghana and other resource-poor countries. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2013; all rights reserved.

  14. SOHLH2 is essential for synaptonemal complex formation during spermatogenesis in early postnatal mouse testes.

    Science.gov (United States)

    Park, Miree; Lee, Youngeun; Jang, Hoon; Lee, Ok-Hee; Park, Sung-Won; Kim, Jae-Hwan; Hong, Kwonho; Song, Hyuk; Park, Se-Pill; Park, Yun-Yong; Ko, Jung Jae; Choi, Youngsok

    2016-02-12

    Spermatogenesis- and oogenesis-specific helix-loop-helix transcription factor 2 (SOHLH2) is exclusively expressed in germ cells of the gonads. Previous studies show that SOHLH2 is critical for spermatogenesis in mouse. However, the regulatory mechanism of SOHLH2 during early spermatogenesis is poorly understood. In the present study, we analyzed the gene expression profile of the Sohlh2-deficient testis and examined the role of SOHLH2 during spermatogenesis. We found 513 genes increased in abundance, while 492 genes decreased in abundance in 14-day-old Sohlh2-deficient mouse testes compared to wildtype mice. Gene ontology analysis revealed that Sohlh2 disruption effects the relative abundance of various meiotic genes during early spermatogenesis, including Spo11, Dmc1, Msh4, Prdm9, Sycp1, Sycp2, Sycp3, Hormad1, and Hormad2. Western blot analysis and immunostaining showed that SYCP3, a component of synaptonemal complex, was significantly less abundant in Sohlh2-deficient spermatocytes. We observed a lack of synaptonemal complex formation during meiosis in Sohlh2-deficient spermatocytes. Furthermore, we found that SOHLH2 interacted with two E-boxes on the mouse Sycp1 promoter and Sycp1 promoter activity increased with ectopically expressed SOHLH2. Taken together, our data suggest that SOHLH2 is critical for the formation of synaptonemal complexes via its regulation of Sycp1 expression during mouse spermatogonial differentiation.

  15. Early postnatal diagnosis of hereditary spherocytosis by combining light microscopy, acidified glycerol lysis test and eosin-5'-maleimide binding assay.

    Science.gov (United States)

    Andres, Oliver; Eber, Stefan; Speer, Christian P

    2015-12-01

    Exact diagnosis of hereditary spherocytosis (HS) is widely considered unreliable around birth. However, early postnatal diagnosis at the beginning of congenital hemolysis may be essential for managing neonatal anemia and hemolytic icterus, identifying those at high risk for severe hyperbilirubinemia, irreversible kernicterus, or sudden need for red cell transfusion. We analyzed 37 blood samples from neonates or infants up to six weeks of life that had been collected in-house or shipped to our laboratory due to suspected red cell membrane disorder. By combining assessment of red cell morphology, acidified glycerol lysis test (AGLT), and eosin-5'-maleimide (EMA) binding assay, we were able to clearly exclude HS in 22 and confirm HS in 10 patients, of which one had undergone red cell transfusion prior to blood sampling. Assessment of red cell morphology and normal test results allowed diagnosis of infantile pyknocytosis or Heinz body anemia in three neonates. Re-evaluation of five patients with inconsistent results of AGLT and EMA binding led to confirmation of HS in two cases. Automated analysis of hematologic parameters revealed elevated proportion of hyperdense cells to be a highly significant indicator for HS in neonatal infants. We showed that assessment of red cell morphology in combination with AGLT and EMA binding assay is a reliable basis for confirming or rejecting suspected diagnosis of HS even in neonates. Our data underline the necessity for blood sampling and laboratory exploration in suspected red cell membrane or enzyme defects at the earliest occasion.

  16. Effects of the kainate receptor agonist ATPA on glutamatergic synaptic transmission and plasticity during early postnatal development.

    Science.gov (United States)

    Sallert, Marko; Malkki, Hemi; Segerstråle, Mikael; Taira, Tomi; Lauri, Sari E

    2007-05-01

    Kainate type of glutamate receptors (KARs) modulate synaptic transmission in a developmentally regulated manner at several synapses in the brain. Previous studies have shown that KARs depress glutamatergic transmission at CA3-CA1 synapses in the hippocampus and these receptors are tonically active during early postnatal development. Here we use the GluR5 subunit specific agonist ATPA to further characterize the role of KARs in the modulation of synaptic transmission and plasticity in area CA1 during the first two weeks of life. We find that the depressant effect of ATPA on evoked fEPSPs/EPSCs is smaller in the neonate (P3-P6) than in the juvenile (P14-P18) rat CA1, due to endogenous activity of KAR in the neonate. Further, in the neonate but not juvenile CA1, ATPA downregulates action-potential independent transmission (mEPSCs) and its effects are dependent on protein kinase C activity. ATPA-induced depression of fEPSPs in the neonate occludes the presynaptic component of long-term depression (LTD). In contrast, at P14-P18, ATPA prevents LTD indirectly via GABAergic mechanisms. These data show that GluR5 signaling mechanisms are developmentally regulated and suggest distinct functional role for KARs in the modulation of synaptic transmission and plasticity at different stages of development.

  17. The factors affecting early death after the initial therapy of acute myeloid leukemia

    Science.gov (United States)

    Malkan, Umit Yavuz; Gunes, Gursel; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin; Etgul, Sezgin; Aslan, Tuncay; Yayar, Okan; Aydin, Seda; Demiroglu, Haluk; Ozcebe, Osman Ilhami; Sayinalp, Nilgun; Goker, Hakan; Aksu, Salih; Buyukasik, Yahya

    2015-01-01

    There are some improvements in management of acute myeloid leukemia (AML). However, induction-induced deaths still remain as a major problem. The aim of this study is to assess clinical parameters affecting early death in patients with AML. 199 AML patients, who were treated with intensive, non-intensive or supportive treatment between 2002 and 2014 in Hacettepe Hematology Department, were analyzed retrospectively. In our study early death rate for elderly was found to be lower than previous reports whereas it was similar for those who were under age of 60. Better ECOG performance (ECOG performance score 0 and 1) and non-intensive treatment associated with lower early death rates, however APL-type disease associated with higher early death rates. ECOG performance score at diagnosis was found to be the most related independent factor with higher rate of early death in 15 days after treatment (P<0.001). Therefore we decided to understand the factors which were related with ECOG. WBC count at diagnosis was found to be the only related parameter with ECOG performance score. Leucocyte count at diagnosis appears like to have an indirect effect on early death in AML patients. It maybe suggested that in recent years there is an improvement in early death rates of elderly AML patients. The currently reported findings require prospective validation and would encourage the incorporation of other next generation genomics for the prediction of early death and overall risk status of AML. PMID:26885243

  18. Phospholipase D family member 4, a transmembrane glycoprotein with no phospholipase D activity, expression in spleen and early postnatal microglia.

    Directory of Open Access Journals (Sweden)

    Fumio Yoshikawa

    -PLD, HKD motif-carrying, transmembrane glycoprotein localized in the endoplasmic reticulum and Golgi apparatus. The spatiotemporally restricted expression patterns suggested that PLD4 might play a role in common function(s among microglia during early postnatal brain development and splenic marginal zone cells.

  19. Early postnatal development of the mandibular permanent first molar in infants with isolated cleft palate

    DEFF Research Database (Denmark)

    Hermann, Nuno V.; Zargham, Mostafa; Darvann, Tron Andre

    2012-01-01

    International Journal of Paediatric Dentistry 2012; 22: 280–285 Background. Based on measurements on dental casts, smaller permanent teeth in children with cleft palate have previously been reported in the literature; however, the early maturation of teeth and the size of the follicles and crowns...... have not been investigated. Hypothesis. The maturation of the mandibular permanent first molar (M1inf) is delayed, and the mesiodistal diameters of the follicle and crown of M1inf, respectively, are reduced in children with isolated cleft palate (ICP). Design. Retrospective, longitudinal. Cephalometric...... X‐rays were available for 2 and 22 months old children with clefts (64 children with ICP, and a control group of 38 children with unilateral incomplete cleft lip). The width of the follicle and the crown of M1inf, and the maturation of M1inf were assessed. Intra‐observer error was acceptable...

  20. Infant adiposity at birth and early postnatal weight gain predict increased aortic intima-media thickness at 6 weeks of age: a population-derived cohort study.

    Science.gov (United States)

    McCloskey, Kate; Burgner, David; Carlin, John B; Skilton, Michael R; Cheung, Michael; Dwyer, Terence; Vuillermin, Peter; Ponsonby, Anne-Louise

    2016-03-01

    Infant body composition and postnatal weight gain have been implicated in the development of adult obesity and cardiovascular disease, but there are limited prospective data regarding the association between infant adiposity, postnatal growth and early cardiovascular parameters. Increased aortic intima-media thickness (aortic IMT) is an intermediate phenotype of early atherosclerosis. The aim of the present study was to investigate the relationship between weight and adiposity at birth, postnatal growth and aortic IMT. The Barwon Infant Study (n=1074 mother-infant pairs) is a population-derived birth cohort. Infant weight and other anthropometry were measured at birth and 6 weeks of age. Aortic IMT was measured by trans-abdominal ultrasound at 6 weeks of age (n=835). After adjustment for aortic size and other factors, markers of adiposity including increased birth weight (β=19.9 μm/kg, 95%CI 11.1, 28.6; Pinfant weight and adiposity at birth, as well as increased early weight gain, were positively associated with aortic IMT. Excessive accumulation of adiposity during gestation and early infancy may have adverse effects on cardiovascular risk.

  1. Early parental death and risk of hospitalization for affective disorder in adulthood

    DEFF Research Database (Denmark)

    Appel, Charlotte Welling; Johansen, Christoffer; Deltour, Isabelle

    2013-01-01

    Early parental death is one of the most stressful childhood life events and may influence subsequent psychological health. We investigated the association between early parental loss and risk of hospitalization for an affective disorder in adulthood.......Early parental death is one of the most stressful childhood life events and may influence subsequent psychological health. We investigated the association between early parental loss and risk of hospitalization for an affective disorder in adulthood....

  2. Effects of dust, formaldehyde and delayed feeding on early postnatal development of broiler chickens.

    Science.gov (United States)

    de Gouw, Pieter; van de Ven, Lotte J F; Lourens, Sander; Kemp, Bas; van den Brand, Henry

    2017-06-01

    We investigated effects of perinatal exposure to dust or formaldehyde and the moment of first feed intake after hatching on broiler chicken development during the first week of life. Four environmental treatments were used from 468 until 512h of incubation: control (CONT), heat treated dust (HTD), untreated dust (UTD) or formaldehyde disinfection (FORM). After hatching, all chickens were assigned to 1 of 2 feeding treatments: early feeding (EF; feed and water available in the hatcher) or delayed feeding (DF). After 512h of incubation (day 0), chickens were reared until day 7 of age. In DF chickens, body weight (BW), yolk free body mass (YFBM) and relative liver weight did not differ among environmental treatments at day 0. However, in EF chickens BW at day 0 was greater in HTD chickens than in UTD and FORM chickens. YFBM in EF chickens at day 0 was greater when chickens were exposed to HTD compared to the other environmental treatments. In EF chickens, relative liver weight was greater in HTD chickens than in FORM. In DF chickens, BW at day 0 was positively related with hatching time (HT). In EF chickens, YFBM was positively related to HT. Residual yolk weight at day 0 was positively related with HT, whereas relative liver weight and microbicidal capacity were negatively related with HT. This study demonstrated that formaldehyde and dust during the hatching phase affect broiler chicken development at pulling from the incubator, but not at day 7. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Type I TARPs promote dendritic growth of early postnatal neocortical pyramidal cells in organotypic cultures.

    Science.gov (United States)

    Hamad, Mohammad I K; Jack, Alexander; Klatt, Oliver; Lorkowski, Markus; Strasdeit, Tobias; Kott, Sabine; Sager, Charlotte; Hollmann, Michael; Wahle, Petra

    2014-04-01

    The ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate receptors (AMPARs) have been implicated in the establishment of dendritic architecture. The transmembrane AMPA receptor regulatory proteins (TARPs) regulate AMPAR function and trafficking into synaptic membranes. In the current study, we employ type I and type II TARPs to modulate expression levels and function of endogenous AMPARs and investigate in organotypic cultures (OTCs) of rat occipital cortex whether this influences neuronal differentiation. Our results show that in early development [5-10 days in vitro (DIV)] only the type I TARP γ-8 promotes pyramidal cell dendritic growth by increasing spontaneous calcium amplitude and GluA2/3 expression in soma and dendrites. Later in development (10-15 DIV), the type I TARPs γ-2, γ-3 and γ-8 promote dendritic growth, whereas γ-4 reduced dendritic growth. The type II TARPs failed to alter dendritic morphology. The TARP-induced dendritic growth was restricted to the apical dendrites of pyramidal cells and it did not affect interneurons. Moreover, we studied the effects of short hairpin RNA-induced knockdown of endogenous γ-8 and showed a reduction of dendritic complexity and amplitudes of spontaneous calcium transients. In addition, the cytoplasmic tail (CT) of γ-8 was required for dendritic growth. Single-cell calcium imaging showed that the γ-8 CT domain increases amplitude but not frequency of calcium transients, suggesting a regulatory mechanism involving the γ-8 CT domain in the postsynaptic compartment. Indeed, the effect of γ-8 overexpression was reversed by APV, indicating a contribution of NMDA receptors. Our results suggest that selected type I TARPs influence activity-dependent dendritogenesis of immature pyramidal neurons.

  4. Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.

    Science.gov (United States)

    Lu, Pei-Chen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Lin, Yu-Ju; Chen, Chih-Cheng; Tiao, Mao-Meng; Tsai, Ching-Chou; Huang, Li-Tung; Tain, You-Lin

    2016-07-01

    Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake.

  5. Death is swallowed up in victory : scenes of death in early Christian art and the emergence of crucifixion iconography

    Directory of Open Access Journals (Sweden)

    McGowan, Felicity Harley

    2011-01-01

    Full Text Available Christianity, and the instrument of Jesus’ death, the cross, remains the pivotal, and universally recognised, symbol of the Christian Church. Yet pictorial representations of the death of Jesus are conspicuously rare in the earliest Christian art. Moreover, the earliest surviving images of Jesus’ Crucifixion do not depict him dead on the cross, but defiantly alive – a visual interpretation of the event that incorporates both the means of his execution and his subsequent victory over death in the Resurrection. This article examines the iconography of a small ivory plaque, carved in Rome in the early fifth century, whereon the Crucifixion is juxtaposed with the suicide of Jesus’ betrayer, Judas Iscariot (Matthew 27 3:5 to effect a powerful visual interpretation of Jesus’ death. As the earliest surviving visual narration of Jesus’ Crucifixion and Resurrection, the ivory will be shown to preserve critical information regarding the interpretation of Christ’s death in the early Christian church - incorporating symbols and visual motifs from pagan funerary sculpture, while illustrating the development of a specifically Christian visual language for the representation of Jesus’ death.

  6. Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies

    Science.gov (United States)

    Yu, Grace Z.; Aye, Christina Y.L.; Lewandowski, Adam J.; Davis, Esther F.; Khoo, Cheen P.; Newton, Laura; Yang, Cheng T.; Al Haj Zen, Ayman; Simpson, Lisa J.; O’Brien, Kathryn; Cook, David A.; Granne, Ingrid; Kyriakou, Theodosios; Channon, Keith M.; Watt, Suzanne M.

    2016-01-01

    Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (−17.7±16.4% versus −9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth. PMID:27456522

  7. Gestational and early postnatal hypothyroidism alters VGluT1 and VGAT bouton distribution in the neocortex and hippocampus, and behavior in rats

    Directory of Open Access Journals (Sweden)

    Daniela eNavarro

    2015-02-01

    Full Text Available Thyroid hormones are fundamental for the expression of genes involved in the development of the CNS and their deficiency is associated with a wide spectrum of neurological diseases including mental retardation, attention deficit-hyperactivity disorder and autism spectrum disorders. We examined in rat whether developmental and early postnatal hypothyroidism affects the distribution of vesicular glutamate transporter-1 (VGluT1; glutamatergic and vesicular inhibitory amino acid transporter (VGAT; GABAergic immunoreactive (ir boutons in the hippocampus and somatosensory cortex, and the behavior of the pups. Hypothyroidism was induced by adding 0.02% methimazole (MMI and 1% KClO4 to the drinking water starting at embryonic day 10 (E10; developmental hypothyroidism and E21 (early postnatal hypothyroidism until day of sacrifice at postnatal day 50. Behavior was studied using the acoustic prepulse inhibition (somatosensory attention and the elevated plus-maze (anxiety-like assessment tests. The distribution, density and size of VGlut1-ir and VGAT-ir boutons in the hippocampus and somatosensory cortex was abnormal in MMI pups and these changes correlate with behavioral changes, as prepulse inhibition of the startle response amplitude was reduced, and the percentage of time spent in open arms increased. In conclusion, both developmental and early postnatal hypothyroidism significantly decreases the ratio of GABAergic to glutamatergic boutons in dentate gyrus leading to an abnormal flow of information to the hippocampus and infragranular layers of the somatosensory cortex, and alter behavior in rats. Our data show cytoarchitectonic alterations in the basic excitatory hippocampal loop, and in local inhibitory circuits of the somatosensory cortex and hippocampus that might contribute to the delayed neurocognitive outcome observed in thyroid hormone deficient children born in iodine deficient areas, or suffering from congenital hypothyroidism.

  8. Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: Association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP.

    Science.gov (United States)

    Nakauchi, Sakura; Malvaez, Melissa; Su, Hailing; Kleeman, Elise; Dang, Richard; Wood, Marcelo A; Sumikawa, Katumi

    2015-02-01

    Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-D-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity.

  9. Early experience with lung transplantation using donors after cardiac death.

    Science.gov (United States)

    Mason, David P; Murthy, Sudish C; Gonzalez-Stawinski, Gonzalo V; Budev, Marie M; Mehta, Atul C; McNeill, Ann M; Pettersson, Gösta B

    2008-05-01

    Lung transplantations that utilize donor organs after cardiac death (DCD) can substantially increase the number of available allografts for waiting recipients. Unfortunately, reported clinical outcomes are limited and widespread acceptance is slow. To further examine the potential of this modality, the results of 4 patients transplanted with DCD organs, implementing a protocol of controlled organ retrieval (Maastricht Classification III), were reviewed. There were no operative deaths; extracorporeal membrane oxygenation was required in 1 patient secondary to severe primary graft dysfunction. Three patients are alive and well at 4, 15 and 21 months; 1 patient died at 34 months with bronchiolitis obliterans syndrome, in part attributable to medication non-compliance.

  10. Evaluation of a neurodevelopmental model of schizophrenia--early postnatal PCP treatment in attentional set-shifting

    DEFF Research Database (Denmark)

    Broberg, Brian Villumsen; Dias, Rebecca; Glenthøj, Birte Yding;

    2008-01-01

    Phencyclidine (PCP) was administered to male and female Lister hooded rats on postnatal days (PND) 7, 9 and 11. All PCP animals tested in adulthood (PND 53-93) showed deficits in cognitive flexibility, specifically in their ability to shift attentional set, compared to controls. This novel finding...

  11. Evaluation of a neurodevelopmental model of schizophrenia--early postnatal PCP treatment in attentional set-shifting

    DEFF Research Database (Denmark)

    Broberg, Brian Villumsen; Dias, Rebecca; Glenthøj, Birte Yding

    2008-01-01

    Phencyclidine (PCP) was administered to male and female Lister hooded rats on postnatal days (PND) 7, 9 and 11. All PCP animals tested in adulthood (PND 53-93) showed deficits in cognitive flexibility, specifically in their ability to shift attentional set, compared to controls. This novel findin...

  12. 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.

  13. Early death in active professional athletes: Trends and causes.

    Science.gov (United States)

    Lemez, S; Wattie, N; Baker, J

    2016-05-01

    The objective of the study was to examine mortality trends and causes of death among professional athletes from the four major sports in North America who died during their playing careers. 205 deceased athletes who were registered as active when they died from the National Basketball Association (NBA), National Football League (NFL), National Hockey League (NHL), and Major League Baseball (MLB) were examined. Results were compared with the Canadian and U.S. general population. The leading causes of death in players reflected the leading causes of death in the Canadian and U.S. general population (i.e., car accidents). Descriptively, NFL and NBA players had a higher likelihood of dying in a car accident (OR 1.75, 95% CI: 0.91-3.36) compared with NHL and MLB players. In addition, NFL and NBA players had a significantly higher likelihood of dying from a cardiac-related illness (OR 4.44, 95% CI: 1.59-12.43). Mortality trends were disproportionate to team size. Overall, death in active athletes is low. Out of 53 400 athletes who have historically played in the four leagues, only 205 died while active (0.38%). Future examinations into the trends and causes of mortality in elite athlete populations will create a better understanding of health-related risks in elite sport. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Learning about Life and Death in Early Childhood

    Science.gov (United States)

    Slaughter, Virginia; Lyons, Michelle

    2003-01-01

    Inagaki and Hatano (2002) have argued that young children initially understand biological phenomena in terms of vitalism, a mode of construal in which "life" or "life-force" is the central causal-explanatory concept. This study investigated the development of vitalistic reasoning in young children's concepts of life, the human body and death.…

  15. Parental death and bipolar disorder: a robust association was found in early maternal suicide

    DEFF Research Database (Denmark)

    Tsuchiya, Kenji; Agerbo, Esben; Mortensen, Preben Bo

    2005-01-01

    , 3.44 [1.97 to 6.00] for maternal suicide), whereas the non-suicidal death of parents showed no such association. Those having experienced maternal suicide at some point before reaching 10 years of age were seven times as likely to develop bipolar disorder. LIMITATIONS: The cohort members were......BACKGROUND: Previous studies have suggested that early parental death may be associated with the emergence of bipolar disorder in later life. However, it remains unknown whether this association applies specifically to parental death due to suicide or only to early parental death. The present study...... aimed to explore whether suicide as well as the non-suicidal death of father, mother, or siblings are associated with an increased risk for bipolar disorder, and whether the possible association is modified by the age at which the subject experiences such a death in the family. METHODS: The subjects...

  16. Early clinical manifestations associated with death from visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Valdelaine Etelvina Miranda de Araújo

    Full Text Available BACKGROUND: In Brazil, lethality from visceral leishmaniasis (VL is high and few studies have addressed prognostic factors. This historical cohort study was designed to investigate the prognostic factors for death from VL in Belo Horizonte (Brazil. METHODOLOGY: The analysis was based on data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health relating to the clinical manifestations of the disease. During the study period (2002-2009, the SINAN changed platform from a Windows to a Net-version that differed with respect to some of the parameters collected. Multivariate logistic regression models were performed to identify variables associated with death from VL, and these were included in prognostic score. PRINCIPAL FINDINGS: Model 1 (period 2002-2009; 111 deaths from VL and 777 cured patients included the variables present in both SINAN versions, whereas Model 2 (period 2007-2009; 49 deaths from VL and 327 cured patients included variables common to both SINAN versions plus the additional variables included in the Net version. In Model 1, the variables significantly associated with a greater risk of death from VL were weakness (OR 2.9; 95%CI 1.3-6.4, Leishmania-HIV co-infection (OR 2.4; 95%CI 1.2-4.8 and age ≥60 years (OR 2.5; 95%CI 1.5-4.3. In Model 2, the variables were bleeding (OR 3.5; 95%CI 1.2-10.3, other associated infections (OR 3.2; 95%CI 1.3-7.8, jaundice (OR 10.1; 95%CI 3.7-27.2 and age ≥60 years (OR 3.1; 95%CI 1.4-7.1. The prognosis score was developed using the variables associated with death from VL of the latest version of the SINAN (Model 2. The predictive performance of which was evaluated by sensitivity (71.4%, specificity (73.7%, positive and negative predictive values (28.9% and 94.5% and area under the receiver operating characteristic curve (75.6%. CONCLUSIONS: Knowledge regarding the factors associated with death from VL may improve clinical management of patients and contribute to lower

  17. Parental death and bipolar disorder: a robust association was found in early maternal suicide

    DEFF Research Database (Denmark)

    Tsuchiya, Kenji; Agerbo, Esben; Mortensen, Preben Bo

    2005-01-01

    aimed to explore whether suicide as well as the non-suicidal death of father, mother, or siblings are associated with an increased risk for bipolar disorder, and whether the possible association is modified by the age at which the subject experiences such a death in the family. METHODS: The subjects...... followed until, but not exceeding, the age of 38. CONCLUSION: Early parental, particularly maternal, suicide increases the risk for bipolar disorder in the offspring. Possible explanations include a family history of mental disorders as well as psychosocial factors.......BACKGROUND: Previous studies have suggested that early parental death may be associated with the emergence of bipolar disorder in later life. However, it remains unknown whether this association applies specifically to parental death due to suicide or only to early parental death. The present study...

  18. Sports and Marfan Syndrome: Awareness and Early Diagnosis Can Prevent Sudden Death.

    Science.gov (United States)

    Salim, Mubadda A.; Alpert, Bruce S.

    2001-01-01

    Physicians who work with athletes play an important role in preventing sudden death related to physical activity in people who have Marfan syndrome. Flagging those who have the physical stigmata and listening for certain cardiac auscultation sounds are early diagnostic keys that can help prevent deaths. People with Marfan syndrome should be…

  19. Parental socioeconomic status and unintentional injury deaths in early childhood: consideration of injury mechanisms, age at death, and gender.

    Science.gov (United States)

    Hong, Juhee; Lee, Boeun; Ha, Eun Hee; Park, Hyesook

    2010-01-01

    The aim of this study was to determine whether the socioeconomic status (SES) of parents influences early childhood unintentional injury deaths for different injury mechanisms and the gender and age at death of the child. Study design is a population-based retrospective study. Death certificate data from 1995 to 2004 were linked to birth certificate data from 1995 to 1996 for each child who died when aged Parental age, birth order, marital status, residence area, educational level, and occupation were used as indices for SES. Cox proportional-hazards analysis was employed. Our results indicate that nonmetropolitan residence, low parental education level, and a father working in a nonadministrative job or as a farmer were associated with a higher risk of death from injury for both boys and girls. A mother aged younger than 20 years and parents working in manual jobs were associated with a higher risk in boys only. The risks of some socioeconomic factors (low parental education and a father working in a manual job or as a farmer) were evident for children aged 1-4 years. The risks of rural residency tended to increase in older children, and the risk of injury from having a mother aged younger than 20 years increased for younger children. The risks of childhood injury deaths from traffic accidents, falls, and fire/burns were associated with the SES of the parents. Younger parents were associated with higher risks of injury deaths from traffic accidents (hazard ratio [HR]: father, 7.9; mother, 1.9) and falls (HR: father, 2.0; mother, 2.5). A father working as a farmer was associated with a higher risk of childhood injury death from fire/burns (HR = 4.0). In conclusion, the parental SES risk profiles of childhood injury deaths varied with the age and gender of the child, and with the injury mechanism. Therefore, reducing excess injury deaths during early childhood requires preventive efforts targeted at high-risk parents, and based on injury mechanism and on the gender

  20. Increased Excitatory Synaptic Transmission of Dentate Granule Neurons in Mice Lacking PSD-95-Interacting Adhesion Molecule Neph2/Kirrel3 during the Early Postnatal Period

    Science.gov (United States)

    Roh, Junyeop D.; Choi, Su-Yeon; Cho, Yi Sul; Choi, Tae-Yong; Park, Jong-Sil; Cutforth, Tyler; Chung, Woosuk; Park, Hanwool; Lee, Dongsoo; Kim, Myeong-Heui; Lee, Yeunkum; Mo, Seojung; Rhee, Jeong-Seop; Kim, Hyun; Ko, Jaewon; Choi, Se-Young; Bae, Yong Chul; Shen, Kang; Kim, Eunjoon; Han, Kihoon

    2017-01-01

    Copy number variants and point mutations of NEPH2 (also called KIRREL3) gene encoding an immunoglobulin (Ig) superfamily adhesion molecule have been linked to autism spectrum disorders, intellectual disability and neurocognitive delay associated with Jacobsen syndrome, but the physiological roles of Neph2 in the mammalian brain remain largely unknown. Neph2 is highly expressed in the dentate granule (DG) neurons of the hippocampus and is localized in both dendrites and axons. It was recently shown that Neph2 is required for the formation of mossy fiber filopodia, the axon terminal structure of DG neurons forming synapses with GABAergic neurons of CA3. In contrast, however, it is unknown whether Neph2 also has any roles in the postsynaptic compartments of DG neurons. We here report that, through its C-terminal PDZ domain-binding motif, Neph2 directly interacts with postsynaptic density (PSD)-95, an abundant excitatory postsynaptic scaffolding protein. Moreover, Neph2 protein is detected in the brain PSD fraction and interacts with PSD-95 in synaptosomal lysates. Functionally, loss of Neph2 in mice leads to age-specific defects in the synaptic connectivity of DG neurons. Specifically, Neph2−/− mice show significantly increased spontaneous excitatory synaptic events in DG neurons at postnatal week 2 when the endogenous Neph2 protein expression peaks, but show normal excitatory synaptic transmission at postnatal week 3. The evoked excitatory synaptic transmission and synaptic plasticity of medial perforant pathway (MPP)-DG synapses are also normal in Neph2−/− mice at postnatal week 3, further confirming the age-specific synaptic defects. Together, our results provide some evidence for the postsynaptic function of Neph2 in DG neurons during the early postnatal period, which might be implicated in neurodevelopmental and cognitive disorders caused by NEPH2 mutations. PMID:28381988

  1. Increased Excitatory Synaptic Transmission of Dentate Granule Neurons in Mice Lacking PSD-95-Interacting Adhesion Molecule Neph2/Kirrel3 during the Early Postnatal Period.

    Science.gov (United States)

    Roh, Junyeop D; Choi, Su-Yeon; Cho, Yi Sul; Choi, Tae-Yong; Park, Jong-Sil; Cutforth, Tyler; Chung, Woosuk; Park, Hanwool; Lee, Dongsoo; Kim, Myeong-Heui; Lee, Yeunkum; Mo, Seojung; Rhee, Jeong-Seop; Kim, Hyun; Ko, Jaewon; Choi, Se-Young; Bae, Yong Chul; Shen, Kang; Kim, Eunjoon; Han, Kihoon

    2017-01-01

    Copy number variants and point mutations of NEPH2 (also called KIRREL3) gene encoding an immunoglobulin (Ig) superfamily adhesion molecule have been linked to autism spectrum disorders, intellectual disability and neurocognitive delay associated with Jacobsen syndrome, but the physiological roles of Neph2 in the mammalian brain remain largely unknown. Neph2 is highly expressed in the dentate granule (DG) neurons of the hippocampus and is localized in both dendrites and axons. It was recently shown that Neph2 is required for the formation of mossy fiber filopodia, the axon terminal structure of DG neurons forming synapses with GABAergic neurons of CA3. In contrast, however, it is unknown whether Neph2 also has any roles in the postsynaptic compartments of DG neurons. We here report that, through its C-terminal PDZ domain-binding motif, Neph2 directly interacts with postsynaptic density (PSD)-95, an abundant excitatory postsynaptic scaffolding protein. Moreover, Neph2 protein is detected in the brain PSD fraction and interacts with PSD-95 in synaptosomal lysates. Functionally, loss of Neph2 in mice leads to age-specific defects in the synaptic connectivity of DG neurons. Specifically, Neph2(-/-) mice show significantly increased spontaneous excitatory synaptic events in DG neurons at postnatal week 2 when the endogenous Neph2 protein expression peaks, but show normal excitatory synaptic transmission at postnatal week 3. The evoked excitatory synaptic transmission and synaptic plasticity of medial perforant pathway (MPP)-DG synapses are also normal in Neph2(-/-) mice at postnatal week 3, further confirming the age-specific synaptic defects. Together, our results provide some evidence for the postsynaptic function of Neph2 in DG neurons during the early postnatal period, which might be implicated in neurodevelopmental and cognitive disorders caused by NEPH2 mutations.

  2. Life and death in the family: early parental death, parental remarriage, and offspring suicide risk in adulthood.

    Science.gov (United States)

    Hollingshaus, Michael S; Smith, Ken R

    2015-04-01

    Early-life parental death (PD) may increase suicide and other mortality risk in adulthood. The potential implications of subsequent remarriage of the widowed parent (RWP) for suicide have not been well examined. Data came from the Utah Population Database for birth cohorts between 1886 and 1960, yielding a sample of N = 663,729 individuals, including 4533 suicides. Cox models showed PD was associated with increased adult suicide risk before age 50, and with increased risk of cardiovascular disease deaths (CVD) for adults of all ages. For females, RWP attenuated the suicide relationship before age 50 (though not statistically significant), but significantly exacerbated it after age 50. RWP had no significant impact for males. Further, for females, PD's positive association with suicide was stronger than with CVD before age 50. These findings reinforce the importance of biological and social mechanisms in linking early-life stressors to adult mental and physical health.

  3. Treasure bequest: death and gift in the early middle ages

    OpenAIRE

    Janes, Dominic

    1998-01-01

    Book synopsis: This collection of twenty-two original essays investigates the organising forces of social identity and power in early Medieval Europe, spanning literary and historical texts, artefacts and archeological evidence.

  4. Developmental programming of somatic growth, behavior and endocannabinoid metabolism by variation of early postnatal nutrition in a cross-fostering mouse model.

    Science.gov (United States)

    Schreiner, Felix; Ackermann, Merle; Michalik, Michael; Hucklenbruch-Rother, Eva; Bilkei-Gorzo, Andras; Racz, Ildiko; Bindila, Laura; Lutz, Beat; Dötsch, Jörg; Zimmer, Andreas; Woelfle, Joachim

    2017-01-01

    Nutrient deprivation during early development has been associated with the predisposition to metabolic disorders in adulthood. Considering its interaction with metabolism, appetite and behavior, the endocannabinoid (eCB) system represents a promising target of developmental programming. By cross-fostering and variation of litter size, early postnatal nutrition of CB6F1-hybrid mice was controlled during the lactation period (3, 6, or 10 pups/mother). After weaning and redistribution at P21, all pups received standard chow ad libitum. Gene expression analyses (liver, visceral fat, hypothalamus) were performed at P50, eCB concentrations were determined in liver and visceral fat. Locomotor activity and social behavior were analyzed by means of computer-assisted videotracking. Body growth was permanently altered, with differences for length, weight, body mass index and fat mass persisting beyond P100 (all 3>6>10,peCB system were observed in fat (eCB-synthesis: 3>6>10 (DAGLα peCB-degradation: 3>6>10 (FAAH peCB-receptor transcripts (CB1R peCB system, with long-lasting impact of early postnatal nutrition. Developmental programming of the eCB system in metabolically active tissues, as shown here for liver and fat, may play a role in the formation of the adult cardiometabolic risk profile following perinatal malnutrition in humans.

  5. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN.

    Science.gov (United States)

    Foust, Kevin D; Wang, Xueyong; McGovern, Vicki L; Braun, Lyndsey; Bevan, Adam K; Haidet, Amanda M; Le, Thanh T; Morales, Pablo R; Rich, Mark M; Burghes, Arthur H M; Kaspar, Brian K

    2010-03-01

    Spinal muscular atrophy (SMA), the most common autosomal recessive neurodegenerative disease affecting children, results in impaired motor neuron function. Despite knowledge of the pathogenic role of decreased survival motor neuron (SMN) protein levels, efforts to increase SMN have not resulted in a treatment for patients. We recently demonstrated that self-complementary adeno-associated virus 9 (scAAV9) can infect approximately 60% of motor neurons when injected intravenously into neonatal mice. Here we use scAAV9-mediated postnatal day 1 vascular gene delivery to replace SMN in SMA pups and rescue motor function, neuromuscular physiology and life span. Treatment on postnatal day 5 results in partial correction, whereas postnatal day 10 treatment has little effect, suggesting a developmental period in which scAAV9 therapy has maximal benefit. Notably, we also show extensive scAAV9-mediated motor neuron transduction after injection into a newborn cynomolgus macaque. This demonstration that scAAV9 traverses the blood-brain barrier in a nonhuman primate emphasizes the clinical potential of scAAV9 gene therapy for SMA.

  6. The activation of cannabinoid receptors during early postnatal development reduces the expression of cell adhesion molecule L1 in the rat brain.

    Science.gov (United States)

    Gómez, María; Hernández, Mariluz; Fernández-Ruiz, Javier

    2007-05-11

    Cannabinoid CB(1) receptors and their ligands emerge early in brain development and are abundantly expressed in certain brain regions that play key roles in processes related to cell proliferation and migration, neuritic elongation and guidance, and synaptogenesis. This would support the notion that the cannabinoid system might play a modulatory role in the regulation of these processes. We have recently presented preliminary in vivo evidence showing that this modulatory action might be exerted, among others, through regulating the levels of several key elements in these processes, such as the L1 protein. This was observed in various white matter areas of the rat forebrain. Because these preliminary in vivo experiments focused only in fetal ages, we concentrated now in the period of early postnatal development. To this end, we analyzed the effects of the cannabinoid agonist Delta(9)-tetrahydrocannabinol (Delta(9)-THC) daily administered since the 5th day of gestation on mRNA levels for L1 in different brain structures of rat neonates at different postnatal ages (PND1, PND5 and PND12). Our results revealed that Delta(9)-THC exposure affected the levels of L1 transcripts in specific brain structures only in PND1, these effects disappearing during further days. Thus, we found reduced L1-mRNA levels in grey matter regions, such as the cerebral cortex, septum nuclei, striatum, dentate gyrus and CA3 subfield of the Ammon horn. White matter areas and subventricular zones were, however, more resistant to Delta(9)-THC exposure at this postnatal age in contrast with the previous data obtained in the fetal brain. Importantly, the effects were influenced by gender of animals, since the reductions were always more marked in females than males, also in contrast with the data reported for the fetal brain. In summary, the cannabinoid system seems to modulate the levels of L1 in several brain structures during specific periods of development [late gestation (previous data) and very

  7. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    Energy Technology Data Exchange (ETDEWEB)

    Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  8. The Impact of the in utero and Early Postnatal Environments on Grey and White Matter Volume: A Study with Adolescent Monozygotic Twins.

    Science.gov (United States)

    Levesque, Melissa L; Fahim, Cherine; Ismaylova, Elmira; Verner, Marie-Pier; Casey, Kevin F; Vitaro, Frank; Brendgen, Mara; Dionne, Ginette; Boivin, Michel; Tremblay, Richard E; Booij, Linda

    2015-01-01

    Prenatal and early postnatal adversities have been shown to be associated with brain development. However, we do not know how much of this association is confounded by genetics, nor whether the postnatal environment can moderate the impact of in utero adversity. This study used a monozygotic (MZ) twin design to assess (1) the association between birth weight (BW) and brain volume in adolescence, (2) the association between within-twin-pair BW discordance and brain volume discordance in adolescence, and (3) whether the association between BW and brain volume in adolescence is mediated or moderated by early negative maternal parenting behaviours. These associations were assessed in a sample of 108 MZ twins followed longitudinally since birth and scanned at age 15. The total grey matter (GM) and white matter (WM) volumes were obtained using the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) toolbox in the Statistical Parametric Mapping version 8 (SPM8). We found that the BW was significantly associated with the total GM and WM volumes, particularly in the superior frontal gyrus and thalamus. Within-twin-pair discordance in BW was also significantly associated with within-pair discordance in both the GM and the WM volumes, supporting the hypothesis that the specific in utero environment is associated with brain development independently of genetics. Early maternal hostile parenting behaviours and depressive symptoms were associated with total GM volume but not WM volume. Finally, greater early maternal hostility may moderate the association between the BW and GM volume in adolescence, since the positive association between the BW and total GM volume appeared stronger at higher levels of maternal hostility (trend). Together, these findings support the importance of the in utero and early environments for brain development. © 2015 S. Karger AG, Basel.

  9. Early postnatal amylin treatment enhances hypothalamic leptin signaling and neural development in the selectively bred diet-induced obese rat.

    Science.gov (United States)

    Johnson, Miranda D; Bouret, Sebastien G; Dunn-Meynell, Ambrose A; Boyle, Christina N; Lutz, Thomas A; Levin, Barry E

    2016-12-01

    Selectively bred diet-induced obese (DIO) rats become obese on a high-fat diet and are leptin resistant before becoming obese. Compared with diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y/agouti-related peptide (NPY/AgRP) and α-melanocyte-stimulating hormone (α-MSH; from proopiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC but not NPY/AgRP neurons. Since amylin increases leptin signaling in adult rats, we treated DIO neonates with amylin during postnatal hypothalamic development and assessed leptin signaling, leptin-dependent ARC-PVN pathway development, and metabolic changes. DIO neonates treated with amylin from P0-6 and from P0-16 increased ARC leptin signaling and both AgRP and α-MSH ARC-PVN pathway development, but increased only POMC neuron number. Despite ARC-PVN pathway correction, P0-16 amylin-induced reductions in body weight did not persist beyond treatment cessation. Since amylin enhances adult DIO ARC signaling via an IL-6-dependent mechanism, we assessed ARC-PVN pathway competency in IL-6 knockout mice and found that the AgRP, but not the α-MSH, ARC-PVN pathway was reduced. These results suggest that both leptin and amylin are important neurotrophic factors for the postnatal development of the ARC-PVN pathway. Amylin might act as a direct neurotrophic factor in DIO rats to enhance both the number of POMC neurons and their α-MSH ARC-PVN pathway development. This suggests important and selective roles for amylin during ARC hypothalamic development.

  10. Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep.

    Science.gov (United States)

    Khanal, Prabhat; Johnsen, Lærke; Axel, Anne Marie Dixen; Hansen, Pernille Willert; Kongsted, Anna Hauntoft; Lyckegaard, Nette Brinch; Nielsen, Mette Olaf

    2016-01-01

    We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 2½ years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights.

  11. Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep.

    Directory of Open Access Journals (Sweden)

    Prabhat Khanal

    Full Text Available We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements, LOW (50% of NORM or HIGH (150%/110% of energy/protein requirements diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF or moderate (CONV diets until 6 months of age, and a moderate (obesity correcting diet thereafter. At 2½ years of age (adulthood, plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights.

  12. Effects on transcriptional regulation and lipid droplet characteristics in the liver of female juvenile pigs after early postnatal feed restriction and refeeding are dependent on birth weight.

    Directory of Open Access Journals (Sweden)

    Constance Nebendahl

    Full Text Available Epidemiological and experimental data indicate that caloric restriction in early postnatal life may improve liver lipid metabolism in low birth weight individuals. The present study investigated transcriptional and metabolic responses to low (U and normal (N birth weight (d 75, T1 and postnatal feed restriction (R, 60% of controls, d 98, T2 followed by subsequent refeeding until d 131 of age (T3. Liver tissue studies were performed with a total of 42 female pigs which were born by multiparous German landrace sows. Overall, 194 genes were differentially expressed in the liver of U vs. N (T1 animals with roles in lipid metabolism. The total mean area and number of lipid droplets (LD was about 4.6- and 3.7 times higher in U compared to N. In U, the mean LD size (µm(2 was 24.9% higher. 3-week feed restriction reduced total mean area of LDs by 58.3 and 72.7% in U and N, respectively. A functional role of the affected genes in amino acid metabolism was additionally indicated. This was reflected by a 17.0% higher arginine concentration in the liver of UR animals (vs. NR. To evaluate persistency of effects, analyses were also done after refeeding period at T3. Overall, 4 and 22 genes show persistent regulation in U and N animals after 5 weeks of refeeding, respectively. These genes are involved in e.g. processes of lipid and protein metabolism and glucose homeostasis. Moreover, the recovery of total mean LD area in U and N animals back to the previous T1 level was observed. However, when compared to controls, the mean LD size was still reduced by 23.3% in UR, whereas it was increased in NR (+24.7%. The present results suggest that short-term postnatal feed restriction period programmed juvenile U animals for an increased rate of hepatic lipolysis in later life.

  13. Effects on transcriptional regulation and lipid droplet characteristics in the liver of female juvenile pigs after early postnatal feed restriction and refeeding are dependent on birth weight.

    Science.gov (United States)

    Nebendahl, Constance; Krüger, Ricarda; Görs, Solvig; Albrecht, Elke; Martens, Karen; Hennig, Steffen; Storm, Niels; Höppner, Wolfgang; Pfuhl, Ralf; Metzler-Zebeli, Barbara U; Hammon, Harald M; Metges, Cornelia C

    2013-01-01

    Epidemiological and experimental data indicate that caloric restriction in early postnatal life may improve liver lipid metabolism in low birth weight individuals. The present study investigated transcriptional and metabolic responses to low (U) and normal (N) birth weight (d 75, T1) and postnatal feed restriction (R, 60% of controls, d 98, T2) followed by subsequent refeeding until d 131 of age (T3). Liver tissue studies were performed with a total of 42 female pigs which were born by multiparous German landrace sows. Overall, 194 genes were differentially expressed in the liver of U vs. N (T1) animals with roles in lipid metabolism. The total mean area and number of lipid droplets (LD) was about 4.6- and 3.7 times higher in U compared to N. In U, the mean LD size (µm(2)) was 24.9% higher. 3-week feed restriction reduced total mean area of LDs by 58.3 and 72.7% in U and N, respectively. A functional role of the affected genes in amino acid metabolism was additionally indicated. This was reflected by a 17.0% higher arginine concentration in the liver of UR animals (vs. NR). To evaluate persistency of effects, analyses were also done after refeeding period at T3. Overall, 4 and 22 genes show persistent regulation in U and N animals after 5 weeks of refeeding, respectively. These genes are involved in e.g. processes of lipid and protein metabolism and glucose homeostasis. Moreover, the recovery of total mean LD area in U and N animals back to the previous T1 level was observed. However, when compared to controls, the mean LD size was still reduced by 23.3% in UR, whereas it was increased in NR (+24.7%). The present results suggest that short-term postnatal feed restriction period programmed juvenile U animals for an increased rate of hepatic lipolysis in later life.

  14. gamma-Aminobutyric acid (GABA): a fast excitatory transmitter which may regulate the development of hippocampal neurones in early postnatal life.

    Science.gov (United States)

    Ben-Ari, Y; Tseeb, V; Raggozzino, D; Khazipov, R; Gaiarsa, J L

    1994-01-01

    The properties of neonatal GABAergic synapses were investigated in neurones of the hippocampal CA3 region. GABA, acting on GABAA receptors, provides most of the excitatory drive on immature CA3 pyramidal neurones at an early stage of development, whereas glutamatergic synapses (in particular, those mediated by AMPA receptors) are mostly quiescent. Thus, during the first postnatal week of life, bicuculline fully blocked spontaneous and evoked depolarising potentials, and GABAA receptor agonists depolarised CA3 pyramidal neurones. GABAA mediated currents also had a reduced sensitivity to benzodiazepines. In the presence of bicuculline, between P0 and P4, increasing the stimulus strength reveals an excitatory postsynaptic potential which is mostly mediated by NMDA receptors. During the same developmental period, pre- (but not post) synaptic GABAB inhibition is present. Intracellular injections of biocytin showed that the axonal network of the GABAergic interneurones is well developed at birth, whereas the pyramidal recurrent collaterals are only beginning to develop. Finally, chronic bicuculline treatment of hippocampal neurones in culture reduced the extent of neuritic arborisation, suggesting that GABA acts as a trophic factor in that period. In conclusion, it is suggested that during the first postnatal week of life, when excitatory inputs are still poorly developed, GABAA receptors provide the excitatory drive necessary for pyramidal cell outgrowth. Starting from the end of the first postnatal week of life, when excitatory inputs are well developed, GABA (acting on both GABAA and GABAB receptors) will hyperpolarise the CA3 pyramidal neurones and, as in the adult, will prevent excessive neuronal discharges. Our electrophysiological and morphological studies have shown that hippocampal GABAergic interneurones are in a unique position to modulate the development of CA3 pyramidal neurones. Developing neurones require a certain degree of membrane depolarisation, and a

  15. TOTAL NUMBER: A BRIEF REVIEW OF ITS IMPORTANCE AND ITS USE IN ASSESSING CEREBELLAR DAMAGE IN THE RAT FOLLOWING EARLY POSTNATAL ALCOHOL EXPOSURE

    Directory of Open Access Journals (Sweden)

    Ruth MA Napper

    2011-05-01

    Full Text Available Knowledge of the total number of structural components that make up the various neural networks within the central nervous system is fundamental to our understanding of its normal function and of dysfunction that may accompany injury and disease. This paper briefly reviews the methodology currently used to estimate number and discusses the importance of unbiased estimates of total number in determining changes in brain structure that may underlie dysfunction. An example from the olfactory bulb is used to demonstrate the potential invalidity of using estimates of total number of objects per single section. Exposure to alcohol during the early postnatal period results in motor dysfunction in adult rats. This paper presents data on the extent and magnitude of cell loss within the cerebellar network of the rat following alcohol exposure during postnatal days 4 to 9. High transient blood alcohol concentrations result in a Purkinje cell of 27% across the entire cerebellum but with regional variabiltiy, vermal lobule X has a 43% Purkinje cell deficit. This alcohol regimen also results in a neuronal loss of 28% and 25% within the deep cerebellar nucleus and inferior olivary nucleus respectively. Consistency of overall neuronal loss across diverse neuronal populations within the cerebellar network is discussed in the context of the maintenance of cerebellar connectivity.

  16. Relations between desire for early death, depressive symptoms and antidepressant prescribing in terminally ill patients with cancer.

    Science.gov (United States)

    Tiernan, E; Casey, P; O'Boyle, C; Birkbeck, G; Mangan, M; O'Siorain, L; Kearney, M

    2002-08-01

    Some patients with advanced cancer express the wish for an early death. This may be associated with depression. We examined the relations between depressive symptoms and desire for early death (natural or by euthanasia or physician-assisted suicide) in 142 terminally ill patients with cancer being cared for by a specialist palliative care team. They completed the Hospital Anxiety and Depression Scale questionnaire and answered four supplementary questions on desire for early death. Only 2 patients expressed a strong wish for death by some form of suicide or euthanasia. 120 denied that they ever wished for early release. The desire for early death correlated with depression scores. Depressive symptoms were common in the whole group but few were on antidepressant therapy. Better recognition and treatment of depression might improve the lives of people with terminal illness and so lessen desire for early death, whether natural or by suicide.

  17. 1H magnetic resonance spectroscopy metabolite profiles of neonatal rat hippocampus and brainstem regions following early postnatal exposure to intermittent hypoxia

    Science.gov (United States)

    Darnall, Robert A.; Chen, Xi; Nemani, Krishnamurthy V.; Sirieix, Chrystelle M.; Gimi, Barjor

    2017-03-01

    Most premature infants born at less than 30 weeks gestation are exposed to periods of mild intermittent hypoxia (IH) associated with apnea of prematurity and periodic breathing. In adults, IH associated with sleep apnea causes neurochemical and structural alterations in the brain. However, it is unknown whether IH in the premature infant leads to neurodevelopmental impairment. Quantification of biochemical markers that can precisely identify infants at risk of adverse neurodevelopmental outcome is essential. In vivo 1H magnetic resonance spectroscopy (1H MRS) facilitates the quantification of metabolites from distinct regions of the developing brain. We report the changes in metabolite profiles in the brainstem and hippocampal regions of developing rat brains, resulting from exposure to IH. Rat pups were chosen for study because there is rapid postnatal hippocampal development that occurs during the first 4 weeks in the developing rat brain, which corresponds to the first 2-3 postnatal years of development in humans. The brainstem was examined because of our interest in respiratory control disorders in the newborn and because of brainstem gliosis described in infants who succumb to Sudden Infant Death Syndrome (SIDS). Metabolite profiles were compared between hypoxia treated rat pups (n = 9) and normoxic controls (n = 6). Metabolite profiles were acquired using the Point-RESolved spectroscopy (PRESS) MRS sequence and were quantified using the TARQUIN software. There was a significant difference in the concentrations of creatine (p = 0.031), total creatine (creatine + phosphocreatine) (p = 0.028), and total choline (p = 0.001) in the brainstem, and glycine (p = 0.031) in the hippocampal region. The changes are consistent with altered cellular bioenergetics and metabolism associated with hypoxic insult.

  18. Fetal and early-postnatal developmental patterns of obese-genotype piglets exposed to prenatal programming by maternal over- and undernutrition.

    Science.gov (United States)

    Gonzalez-Bulnes, Antonio; Ovilo, Cristina; Lopez-Bote, Clemente J; Astiz, Susana; Ayuso, Miriam; Perez-Solana, Maria L; Sanchez-Sanchez, Raul; Torres-Rovira, Laura

    2013-09-01

    The present study evaluated the effect of nutritional imbalances during pregnancy, either by excess or deficiency, on fertility and conceptus development in obese-genotype swine (Iberian pig). Twenty-five multiparous sows were fed, from mating to farrowing, with a standard diet fulfilling either 1.6 folds their daily maintenance requirements for pregnancy (overfed group, n = 12) or only the 50% of such requirements (underfed group, n = 13). Ten out of 12 overfed but only two out of 13 underfed sows became pregnant (Pdevelopmental patterns of fetuses. Thus, weight and size of the offspring from both nutritional treatments were finally similar at delivery; the same was found at weaning. There was thereafter a sex-related effect on the growth during the early-postnatal period, with male piglets of both nutritional origins being significantly heavier and more corpulent at weaning that their sisters (Porigin, with male piglets growing faster than females.

  19. Lactoferrin up-regulates intestinal gene expression of brain-derived neurotrophic factors BDNF, UCHL1 and alkaline phosphatase activity to alleviate early weaning diarrhea in postnatal piglets.

    Science.gov (United States)

    Yang, Changwei; Zhu, Xi; Liu, Ni; Chen, Yue; Gan, Hexia; Troy, Frederic A; Wang, Bing

    2014-08-01

    The molecular mechanisms underlying how dietary lactoferrin (Lf) impacts gut development and maturation and protects against early weaning diarrhea are not well understood. In this study, we supplemented postnatal piglets with an Lf at a dose level of 155 and 285 mg/kg/day from 3 to 38 days following birth. Our findings show that the high dose of Lf up-regulated messenger RNA expression levels of genes encoding brain-derived neurotrophic factor (BDNF) and ubiquitin carboxy-terminal hydrolase L1 (ubiquitin thiolesterase (UCHL1) and, to a lesser extent, glial cell line-derived neurotrophic factor, in the duodenum (Pintestinal alkaline phosphatase activity (Pbrain-microbe axis that has not been previously reported.

  20. Photobiomodulation reduces photoreceptor death and regulates cytoprotection in early states of P23H retinal dystrophy

    Science.gov (United States)

    Kirk, Diana K.; Gopalakrishnan, Sandeep; Schmitt, Heather; Abroe, Betsy; Stoehr, Michele; Dubis, Adam; Carroll, Joseph; Stone, Jonathan; Valter, Krisztina; Eells, Janis

    2013-03-01

    Irradiation by light in the far-red to near-infrared (NIR) region of the spectrum (photobiomodulation, PBM) has been demonstrated to attenuate the severity of neurodegenerative disease in experimental and clinical studies. The purpose of this study was to test the hypothesis that 670 nm PBM would protect against the loss of retinal function and improve photoreceptor survival in a rodent model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated once per day with a 670 nm LED array (180 sec treatments at 50 mW/cm2; fluence 9 joules/cm2) (Quantum Devices Inc., Barneveld WI) from postnatal day (p) 16-20 or from p10-20. Sham-treated rats were restrained, but not exposed to NIR light. The status of the retina was determined at p22 by assessment of mitochondrial function, oxidative stress and cell death. In a second series of studies, retinal status was assessed at p30 by measuring photoreceptor function by ERG and retinal morphology by Spectral Domain Optical Coherence Tomography (SD-OCT). 670 nm PBM increased retinal mitochondrial cytochrome oxidase activity and upregulated the retina's production of the key mitochondrial antioxidant enzyme, MnSOD. PBM also attenuated photoreceptor cell loss and improved photoreceptor function. PBM protects photoreceptors in the developing P23H retina, by augmenting mitochondrial function and stimulating antioxidant protective pathways. Photobiomodulation may have therapeutic potential, where mitochondrial damage is a step in the death of photoreceptors.

  1. Impact of leukapheresis on early death rate in adult acute myeloid leukemia presenting with hyperleukocytosis.

    Science.gov (United States)

    Bug, Gesine; Anargyrou, Konstantinos; Tonn, Torsten; Bialleck, Heike; Seifried, Erhard; Hoelzer, Dieter; Ottmann, Oliver G

    2007-10-01

    Patients with acute myeloid leukemia (AML) with hyperleukocytosis of at least 100 x 10(9) per L are at high risk of early death due to pulmonary or cerebral leukostasis. Although the efficacy of leukapheresis in terms of prompt cytoreduction is generally accepted, published data regarding the clinical value of immediate therapeutic leukapheresis are limited and conflicting. To determine whether leukapheresis has a favorable impact on early mortality, the clinical course of 53 newly diagnosed patients with AML and hyperleukocytosis admitted between 1995 and 2005 was analyzed retrospectively. Before August 2001, 28 patients received chemotherapy without leukoreduction (Cohort A). Thereafter, all AML patients with hyperleukocytosis were scheduled to receive leukapheresis, which was performed in 25 patients (Cohort B). There were no procedure-related adverse events. By Day 21 of therapy, 13 of 53 patients had died, resulting in an overall early death rate of 25 percent. In a multivariate logistic regression model, patients in Cohort B had a significantly lower risk of early death than patients in Cohort A (16% vs. 32%, respectively; p = 0.015). Dyspnea (p = 0.005), elevated creatinine (p = 0.028), and higher lactate dehydrogenase serum levels (p = 0.021) were independent risk factors for early death. With a median follow-up of 24.2 months, the overall survival was similar in both cohorts (Cohort A, 7.5; Cohort B, 6.5 months). Thus, leukapheresis had no impact on patients' long-term survivals. Our experience suggests that AML patients with hyperleukocytosis receiving leukapheresis had a significantly lower risk for early death by Day 21 than patients treated without leukapheresis. We therefore have adopted leukapheresis as a standard procedure in our department.

  2. Short Telomere Length, Myocardial Infarction, Ischemic Heart Disease, and Early Death

    DEFF Research Database (Denmark)

    Weischer, Maren; Bojesen, Stig E; Cawthon, Richard M;

    2012-01-01

    OBJECTIVE: We tested the hypothesis that short telomere length is associated with increased risk of myocardial infarction, ischemic heart disease, and early death. METHODS AND RESULTS: We measured leukocyte telomere length in 2 prospective studies of 19 838 Danish general population participants...... from the Copenhagen City Heart Study and the Copenhagen General Population Study. Participants were followed for up to 19 years for incident myocardial infarction (n=929), ischemic heart disease (n=2038), and death (n=4342). Follow-up was 100% complete. Telomere length decreased linearly...... with increasing age in women and men in both studies (P=7×10(-74) to P=3×10(-125)). Multifactorially adjusted hazard ratios were 1.10 (95% CI 1.01-1.19) for myocardial infarction, 1.06 (1.00-1.11) for ischemic heart disease, and 1.09 (1.05-1.13) for early death per 1000-base pair decrease in telomere length...

  3. Death by unnatural causes during childhood and early adulthood in offspring of psychiatric inpatients

    DEFF Research Database (Denmark)

    Webb, Roger; Pickles, Andrew R.; Appleby, Louis

    2007-01-01

    MEASURES: Deaths from all natural causes and all unnatural causes, specifically, accidents, homicides, suicides, and undetermined causes. RESULTS: The highest observed relative risk (RR) was for homicide in young and older children with affected mothers or fathers. Homicides were between 5 and 10 times......-verdict deaths by poisoning were higher than for such deaths occurring by other means. CONCLUSIONS: Almost 99% of children studied survived to their mid-20s. However, they were more vulnerable to death from unnatural causes, notably, homicide during childhood and suicide in early adulthood. Further research......-fold to 3-fold higher risk of suicide. In almost one fourth of the suicides, there was a history of parental admission. Young adults with 2 previously admitted parents were 6 times more likely to kill themselves than were their peers in the general population. Relative risk of suicide or open...

  4. Early immature neuronal death initiates cerebral ischemia-induced neurogenesis in the dentate gyrus.

    Science.gov (United States)

    Kim, D H; Lee, H E; Kwon, K J; Park, S J; Heo, H; Lee, Y; Choi, J W; Shin, C Y; Ryu, J H

    2015-01-22

    Throughout adulthood, neurons are continuously replaced by new cells in the dentate gyrus (DG) of the hippocampus, and this neurogenesis is increased by various neuronal injuries including ischemic stroke and seizure. While several mechanisms of this injury-induced neurogenesis have been elucidated, the initiation factor remains unclear. Here, we investigated which signal(s) trigger(s) ischemia-induced cell proliferation and neurogenesis in the hippocampal DG region. We found that early apoptotic cell death of the immature neurons occurred in the DG region following transient forebrain ischemia/reperfusion in mice. Moreover, early immature neuronal death in the DG initiated transient forebrain ischemia/reperfusion-induced neurogenesis through glycogen synthase kinase-3β/β-catenin signaling, which was mediated by microglia-derived insulin-like growth factor-1 (IGF-1). Additionally, we observed that the blockade of immature neuronal cell death, early microglial activation, or IGF-1 signaling attenuated ischemia-induced neurogenesis. These results suggest that early immature neuronal cell death initiates ischemia-induced neurogenesis through microglial IGF-1 in mice.

  5. Postoperative medical complications are the main cause of early death after emergency surgery for colonic cancer

    DEFF Research Database (Denmark)

    Iversen, L.H.; Bulow, S.; Christensen, Ib Jarle

    2008-01-01

    . The strongest risk factor for early death was postoperative medical complications (cardiopulmonary, renal, thromboembolic and infectious), with an odds ratio of 11.7 (95 percent confidence interval 8.8 to 15.5). Such complications occurred in 24.4 per cent of patients, of whom 57.8 per cent died. Other...

  6. The effect of maternal undernutrition in early gestation on gestation length and fetal and postnatal growth in sheep.

    Science.gov (United States)

    Cleal, Jane K; Poore, Kirsten R; Newman, James P; Noakes, David E; Hanson, Mark A; Green, Lucy R

    2007-10-01

    In utero undernutrition in humans may result in cardiovascular (CV), metabolic, and growth adaptations. In sheep, maternal nutrient restriction during pregnancy, without effects on fetal or birth weight, results in altered CV control in the offspring. Adjustment of gestation length after undernutrition could be a strategy to enhance postnatal health/survival. The aim of this study was to determine in sheep the effect of a 50% reduction in maternal nutrient intake [undernutrition group (U) versus 100%, control group (C)] during 1-31 d of gestation (dGA) on gestation length and offspring size. By 28 dGA, U ewes had gained less weight than C, and twin-bearing ewes had gained less weight than singleton-bearing ewes regardless of group (p<0.05). In different-sex twin pairs, maternal undernutrition resulted in longer gestation compared with C (146.5+/-0.6 versus 144.6+/-0.6 d, p<0.05). Increased weight gain by weaning (20.8+/-0.8 versus 17.9+/-0.8 kg, p<0.05) was observed in U male twins. These findings suggest that the strategy (i.e. growth rate or length of time in utero) adopted by the fetus to enhance immediate survival depends on offspring number and sex. This is likely to reflect the degree of constraint imposed on the fetus.

  7. Prenatal, but not early postnatal, exposure to a Western diet improves spatial memory of pigs later in life and is paired with changes in maternal prepartum blood lipid levels

    NARCIS (Netherlands)

    Clouard, Caroline; Kemp, Bas; Val-Laillet, David; Gerrits, Walter J.J.; Bartels, Andrea C.; Bolhuis, J.E.

    2016-01-01

    Maternal obesity and perinatal high-fat diets are known to affect cognitive development. We examined the effects of late prenatal and/or early postnatal exposure to a Western-type diet, high in both fat and refined sugar, on the cognition of pigs (Sus scrofa) in the absence of obesity. Thirty-six

  8. Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

    Science.gov (United States)

    Goodfellow, Molly J; Lindquist, Derick H

    2014-09-01

    In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock.

  9. Up-regulation of the transient A-type K+ current (IA) in the differentiation of neural stem cells of the early postnatal rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    GUO Hong-bo; HUANG Lian-yan; ZOU Yu-xi; ZOU Fei

    2010-01-01

    Background Neural stem cells (NSCs) not only are essential to cell replacement therapy and transplantation in clinical settings, but also provide a unique model for the research into neurogenesis and epigenesis. However, little attention has been paid to the electrophysiological characterization of NSC development. This work aimed to identify whether the morphological neuronal differentiation process in NSCs included changes in the electrophysiological properties of transient A-type K+ currents (IA).Methods NSCs were isolated from early postnatal rat hippocampus and were multiplied in basic serum-free medium containing basic fibroblast growth factor. Potassium currents were investigated and compared using whole-cell patch-clamp techniques and one-way analysis of variance (ANOVA), respectively.Results Compared with NSC-derived neurons, cloned NSCs (cNSCs) had a more positive resting membrane potential, a higher input resistance, and a lower membrane capacitance. Part of cNSCs and NSC-derived neurons possessed both delayed-rectifier K+ currents (IDR) and IA, steady-state activation of IA in cNSCs (half-maximal activation at (21.34±4.37) mV) occurred at a more positive voltage than in NSC-derived neurons at 1-6 days in vitro (half-maximal activation at (12.85±4.19) mV).Conclusions Our research revealed a developmental up-regulation of the IA component during differentiation of postnatal NSCs. Together with the marked developmental up-regulation of IDR in vitro neuronal differentiation we have previously found, the voltage-gated potassium channels may participate in neuronal maturation process.

  10. [Felix Mendelssohn Bartholdy (1809 - 1847): the mystery of his early death].

    Science.gov (United States)

    Schmideler, S; Somburg, O; Steinberg, H; Splett, T

    2006-09-01

    Composer and director of music at Leipzig's Gewandhaus Felix Mendelssohn Bartholdy died remarkably young, on 4 November 1847, at the age of 38. The cause of his early death has been a mystery ever since. Three contemporary doctors diagnosed Nervenschlag ("nervous stroke"). Starting with a short outline of Mendelssohn's pathography, this paper includes and quotes for the first time all the contemporary accounts of his death. After considering the older medical interpretations, the paper considers these reports from the point of view of present-day neurological and psychiatric expertise. It reveals that all the accounts had been filed by medical laymen, so their personal impressions had played a major role in their reports. However, it is indisputable that it was pathologic brain alterations that lead to Mendelssohn's death. Weighing up and carefully considering the sources, the authors regard subarachnoidal hemorrhage (SAH) as a likely cause of death. There may even have been some kind of genetic predisposition, since what is reported in this paper regarding Mendelssohn's death also applies to the very similar symptoms and circumstances surrounding his sister Fanny's death.

  11. Structural Magnetic Resonance Imaging in an adult cohort following prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water.

    Science.gov (United States)

    Janulewicz, Patricia A; Killiany, Ronald J; White, Roberta F; Martin, Brett M; Winter, Michael R; Weinberg, Janice M; Aschengrau, Ann

    2013-01-01

    This population-based retrospective cohort study examined Structural Magnetic Resonance Imaging (MRI) of the brain in relation to prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using pipe network information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and Geographic Information System (GIS) methodology. Brain imaging was performed on 26 exposed and 16 unexposed subjects. Scans were acquired on a Philips 3T whole body scanner using the ADNI T1-weighted MP-RAGE scan. The scans were processed by FreeSurfer version 4.3.1 software to obtain measurements of specific brain regions. There were no statistically significant differences between exposed and unexposed subjects on the measures of white matter hypointensities (β: 127.5mm(3), 95% CI: -259.1, 1514.0), white matter volumes (e.g. total cerebral white matter: β: 21230.0mm(3), 95% CI: -4512.6, 46971.7) or gray matter volumes (e.g. total cerebral gray matter: β: 11976.0mm(3), 95% CI: -13657.2, 37609.3). The results of this study suggest that exposure to PCE during gestation and early childhood, at the levels observed in this population, is not associated with alterations in the brain structures studied.

  12. Early postnatal hypotension is not associated with indicators of white matter damage or cerebral palsy in extremely low gestational age newborns.

    Science.gov (United States)

    Logan, J W; O'Shea, T M; Allred, E N; Laughon, M M; Bose, C L; Dammann, O; Batton, D G; Kuban, K C; Paneth, N; Leviton, A

    2011-08-01

    To evaluate, in extremely low gestational age newborns (ELGANs), relationships between indicators of early postnatal hypotension and cranial ultrasound indicators of cerebral white matter damage imaged in the nursery and cerebral palsy diagnoses at 24 months follow-up. The 1041 infants in this prospective study were born at treatment with a vasopressor; and (3) blood pressure lability, defined as the upper quartile of the difference between each infant's lowest and highest MAP. Outcomes included indicators of cerebral white matter damage, that is, moderate/severe ventriculomegaly or an echolucent lesion on cranial ultrasound and cerebral palsy diagnoses at 24 months gestation. Logistic regression was used to evaluate relationships among hypotension indicators and outcomes, adjusting for potential confounders. Twenty-one percent of surviving infants had a lowest blood pressure in the lowest quartile for gestational age, 24% were treated with vasopressors and 24% had labile blood pressure. Among infants with these hypotension indicators, 10% percent developed ventriculomegaly and 7% developed an echolucent lesion. At 24 months follow-up, 6% had developed quadriparesis, 4% diparesis and 2% hemiparesis. After adjusting for confounders, we found no association between indicators of hypotension, and indicators of cerebral white matter damage or a cerebral palsy diagnosis. The absence of an association between indicators of hypotension and cerebral white matter damage and or cerebral palsy suggests that early hypotension may not be important in the pathogenesis of brain injury in ELGANs.

  13. Neonatal immune activation during early and late postnatal brain development differently influences depression-related behaviors in adolescent and adult C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Jafar Majidi-Zolbanin

    2014-06-01

    Full Text Available Aim: Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions, resulting in greater risk for the development of neuropsychiatric disorders, such as anxiety and depression, later in life. In addition, previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents. This study aimed to investigate for the first time whether immune challenge with a viral mimic, synthetic double-stranded ribonucleic acid (Poly I: C during different neonatal periods can differently affect depression-related behaviors in adolescent and adult mice. Methods: Male C57BL/6 mice were treated with either saline or Poly I:C (1 mg/kg and 4 mg/kg on postnatal days (PND 3-5 (early neonatal phase or PND 14-16 (late neonatal phase, and then subjected to behavioral tests, including tail suspension test and forced swimming test, during adolescence (PND 35 or 40 and adulthood (PND 85 or 90. Results: The results demonstrated that early neonatal immune activation increases depression-related behaviors in both adolescent and adult mice, but late neonatal immune activation only increases depression in adult mice. In other words, these findings indicated that the nature of the offspring's neuropathology can depend on the severity of the insult, the pup's age at the time of the insult, and offspring age at the time of behavioral testing. Conclusion: These findings suggest that dose and timing of neonatal insult and offspring age may be important factors for evaluating neuropsychiatric disorders in adults who experienced early life infection.

  14. Dwarfism and early death in mice lacking C-type natriuretic peptide

    Science.gov (United States)

    Chusho, Hideki; Tamura, Naohisa; Ogawa, Yoshihiro; Yasoda, Akihiro; Suda, Michio; Miyazawa, Takashi; Nakamura, Kenji; Nakao, Kazuki; Kurihara, Tatsuya; Komatsu, Yasato; Itoh, Hiroshi; Tanaka, Kiyoshi; Saito, Yoshihiko; Katsuki, Motoya; Nakao, Kazuwa

    2001-01-01

    Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc−/− mice). The Nppc−/− mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc−/− mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia. PMID:11259675

  15. Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood

    NARCIS (Netherlands)

    Oosting, Annemarie; van Vlies, Naomi; Kegler, Diane; Schipper, Lidewij; Abrahamse-Berkeveld, Marieke; Ringler, Silvia; Verkade, Henkjan J.; van der Beek, Eline M.

    2014-01-01

    Obese individuals have more (hyperplastic) and larger (hypertrophic) adipocytes in their white adipose tissue (WAT) than normal-weight individuals. The difference in cell number emerges early in childhood, suggesting that this is a critical period for being susceptible to obesity. Breast-feeding has

  16. Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood

    NARCIS (Netherlands)

    Oosting, Annemarie; van Vlies, Naomi; Kegler, Diane; Schipper, Lidewij; Abrahamse-Berkeveld, Marieke; Ringler, Silvia; Verkade, Henkjan J.; van der Beek, Eline M.

    2014-01-01

    Obese individuals have more (hyperplastic) and larger (hypertrophic) adipocytes in their white adipose tissue (WAT) than normal-weight individuals. The difference in cell number emerges early in childhood, suggesting that this is a critical period for being susceptible to obesity. Breast-feeding has

  17. Early European attitudes towards "good death": Eugenios Voulgaris, Treatise on euthanasia, St Petersburg, 1804.

    Science.gov (United States)

    Galanakis, E; Dimoliatis, I D K

    2007-06-01

    Eugenios Voulgaris (Corfu, Greece, 1716; St Petersburg, Russia, 1806) was an eminent theologian and scholar, and bishop of Kherson, Ukraine. He copiously wrote treatises in theology, philosophy and sciences, greatly influenced the development of modern Greek thought, and contributed to the perception of Western thought throughout the Eastern Christian world. In his Treatise on euthanasia (1804), Voulgaris tried to moderate the fear of death by exalting the power of faith and trust in the divine providence, and by presenting death as a universal necessity, a curative physician and a safe harbour. Voulgaris presented his views in the form of a consoling sermon, abundantly enriched with references to classical texts, the Bible and the Church Fathers, as well as to secular sources, including vital statistics from his contemporary England and France. Besides euthanasia, he introduced terms such as dysthanasia, etoimothanasia and prothanasia. The Treatise on euthanasia is one of the first books, if not the very first, devoted to euthanasia in modern European thought and a remarkable text for the study of the very early European attitudes towards "good death". In the Treatise, euthanasia is clearly meant as a spiritual preparation and reconciliation with dying rather than a physician-related mercy killing, as the term progressed to mean during the 19th and the 20th centuries. This early text is worthy of study not only for the historian of medical ethics or of religious ethics, but for everybody who is trying to courageously confront death, either in private or in professional settings.

  18. Reduced heart rate volatility: an early predictor of death in trauma patients.

    Science.gov (United States)

    Grogan, Eric L; Morris, John A; Norris, Patrick R; France, Daniel J; Ozdas, Asli; Stiles, Renée A; Harris, Paul A; Dawant, Benoit M; Speroff, Theodore

    2004-09-01

    To determine if using dense data capture to measure heart rate volatility (standard deviation) measured in 5-minute intervals predicts death. Fundamental approaches to assessing vital signs in the critically ill have changed little since the early 1900s. Our prior work in this area has demonstrated the utility of densely sampled data and, in particular, heart rate volatility over the entire patient stay, for predicting death and prolonged ventilation. Approximately 120 million heart rate data points were prospectively collected and archived from 1316 trauma ICU patients over 30 months. Data were sampled every 1 to 4 seconds, stored in a relational database, linked to outcome data, and de-identified. HR standard deviation was continuously computed over 5-minute intervals (CVRD, cardiac volatility-related dysfunction). Logistic regression models incorporating age and injury severity score were developed on a test set of patients (N = 923), and prospectively analyzed in a distinct validation set (N = 393) for the first 24 hours of ICU data. Distribution of CVRD varied by survival in the test set. Prospective evaluation of the model in the validation set gave an area in the receiver operating curve of 0.81 with a sensitivity and specificity of 70.1 and 80.0, respectively. CVRD predict death as early as 24 hours in the validation set. CVRD identifies a subgroup of patients with a high probability of dying. Death is predicted within first 24 hours of stay. We hypothesize CVRD is a surrogate for autonomic nervous system dysfunction.

  19. Determining the effects of early gestation in utero heat stress on postnatal fasting heat production and circulating biomarkers associated with metabolism in growing pigs

    Science.gov (United States)

    The study objective was to determine the effects of in utero heat stress (IUHS) on postnatal fasting heat production (FHP) in growing pigs. Based on our previous observation of increased postnatal core body temperature ‘set-point’ in IUHS pigs, we hypothesized that FHP would be greater during postna...

  20. Predictors of early death in female patients with breast cancer in the UK: a cohort study.

    Science.gov (United States)

    Stapelkamp, Ceilidh; Holmberg, Lars; Tataru, Daniela; Møller, Henrik; Robinson, David

    2011-01-01

    Objective To identify factors predicting early death in women with breast cancer. Design Cohort study. Setting 29 trusts across seven cancer networks in the North Thames area. Participants 15 037 women with primary breast cancer diagnosed between January 1996 and December 2005. Methods Logistic regression analyses to determine predictors of early death and factors associated with lack of surgical treatment. Main exposures Age at diagnosis, mode of presentation, ethnicity, disease severity, comorbidities, treatment and period of diagnosis in relation to the Cancer Plan (the NHS's strategy in 2000 for investment in and reform of cancer services). Main outcome measures Death from any cause within 1 year of diagnosis, and receipt of surgical treatment. Results By 31 December 2006, 4765 women had died, 980 in the year after diagnosis. Older age and disease severity independently predicted early death. Women over 80 were more likely to die early than women under 50 (OR 8.05, 95% CI 5.96 to 10.88). Presence of distant metastases on diagnosis increased the odds of early death more than eightfold (OR 8.41, 95% CI 6.49 to 10.89). Two or more recorded comorbidities were associated with a nearly fourfold increase. There was a significant decrease in odds associated with surgery (OR 0.29, 95% CI 0.24 to 0.35). Independently of disease severity and comorbidities, women over 70 were less likely than those under 50 to be treated surgically and this was even more pronounced in those aged over 80 (OR 0.09, 95% CI 0.07 to 0.10). Other factors independently associated with a reduced likelihood of surgery included a non-screening presentation, non-white ethnicity and additional comorbidities. Conclusions These findings may partially explain the survival discrepancies between the UK and other European countries in female patients with breast cancer. The study identifies a group of women with a particularly poor prognosis for whom interventions aiming at early detection may be targeted.

  1. Tobacco Smoke Exposure as Risk Factor in Early Neonatal Death in Mataram, Nusa Tenggara Barat (NTB

    Directory of Open Access Journals (Sweden)

    Musrifa .

    2014-08-01

    Full Text Available Objective: To investigate tobacco smoke exposure as risk factor of early neonatal death in Mataram, NTB.Method: The study design was case control with a total sample of 87 consisting of 29 cases and 58 controls (1:2.Dependent variable was early neonatal death, independent variable was tobacco smoke exposure. Frequency ofantenatal visit, family income, delivery complications, anemia and low birth weight were confounding variables. Datawere collected through interview and registered cohort data from nine health centres during the period of 1 January-31December 2013. Data were analyzed by using bivariate and multivariate (logistic regression to calculate crude OR andadjusted OR.Result: Results of bivariate analysis indicated that tobacco smoke exposure during pregnancy, extent of exposure ?3cigarettes/days during pregnancy, and amount of exposure ?6 cigarettes/days last 24 hours were 2.75 (95%CI: 0.72-10.50; 2.34 (95%CI: 0.77-7.08; and 2.18 (95%CI: 0.65-7.29 respectively, increasing neonatal death but was notstatistically significant. Multivariate analysis indicated that tobacco smoke exposure during pregnancy was 1.32 (95%CI:0.03-69.90. OR of other variables: low birth weight, family income under Rp. 1,100,000,- and delivery complicationswere 204.39 (95%CI: 20.37-2050.07; 7.86 (95%CI: 1.45-42.83 and 7.55 (95%CI: 1.01-56.38 respectively.Conclusion: Tobacco smoke exposure was not statistically significant risk factor, specifically the smoking habits of thehusband. Study discovered that low birth weight, family income under Rp. 1,100,000,- and delivery complication duringbirth were statistically significant factors. Further study is needed to confirm these findings.Key words: tobacco smoke exposure, early neonatal death, risk factors, Nusa Tenggara Barat

  2. 出生24h内新生儿肺出血病因与死因分析%Pathogenesis and death cause of neonatal pulmonary hemorrhage within postnatal 24h

    Institute of Scientific and Technical Information of China (English)

    刘绍基; 陈克正

    2010-01-01

    Objective To investigate the pathogenesis and death cause of neonatal pulmonary hem orrhage (NPH) within postnatal 24 h and speculate their relation to fetal pulmonary hemorrhage. Methods To select the 114 cases of NPH within postnatal 24 h confirmed by pathological examination. According to the pathologic and clinic diagnosis materials, the pathogenesis and death cause of NPH within postnatal 24 h and their relation to fetal pulmonary hemorrhage were analyzed. Results Of the 114 cases with NPH,there were 6 cases of petechial pulmonary hemorrhage,60 cases of focal pulmonary hemorrhage and 48 cases of diffuse pulmonary hemorrhage. The discovery time of NPH were 28 cases at 0~6 h ,71 cases at 7~12 h and 15 cases at 13~24 h after birth. The pathogenesis in 114 cases of NPH could be divided into identical 2 major factors: 110 cases of the oxygen deficient factor consisting of amniotic fluid aspiration pneumonia( 62 cases) .hyaline membrane disease(24 cases) .complexity cyanotic congenital heart disease(7 cases),congenital pulmonary a-genesis(7 cases),neonatal asphyxia (7 cases),intracranial hemorrhage(2 cases) and hypoxic ischemic en-cephalopathy(1 cases) .respectively. Four cases were due to infection including sepsis which was caused by intrauterine infection. The death causes in 114 cases of NPH included hypoxia (113 cases) which consisted of pulmonary hemorrhage (74 cases) .amniotic fluid aspiration pneumonia(15 cases) .hyaline membrane dis-ease(12 cases),complexity cyanotic congenital heart disease(7 cases),congenital pulmonary agenesis(2 ca-ses) ,intracranial hemorrhage(2 cases) .neonatal asphyxia (1 cases) .and infectious factor(1 case) of sepsis which was caused by intrauterine infection. In 114 cases,82 cases had fetal distress,74 cases died from NPH directly including 3 cases with fetal distress died within a few minutes after birth. Conclusion Oxygen defi-cient is an important factor in pathogenesis and death cause of NPH within postnatal 24 h. The

  3. Fetal and Early Post-Natal Mineralization of the Tympanic Bulla in Fin Whales May Reveal a Hitherto Undiscovered Evolutionary Trait

    Science.gov (United States)

    Cozzi, Bruno; Podestà, Michela; Mazzariol, Sandro; Zotti, Alessandro

    2012-01-01

    The evolution of the cetacean skeleton followed a path that differentiated this group from other terrestrial mammals about 50 million years ago [1], and debate is still going on about the relationships between Cetacea and Artiodactyla [2], [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of Archaeocetes), such as the expansion of the peribullary air sinuses, dental modification and vertebral size uniformity [5] are maintained and further emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X-Ray Absorptiometry here we report that the deposition of bone mineral in fetal and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher in the bulla tympanica than in the adjacent basal skull or in the rest of the skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine, hippopotamus) is minimal, becomes sensible after birth and then progresses during growth, contrarily to the precocious mineralization that we observed in fin whales. Given the importance of the ear bones for the precise identification of phylogenetic relationship in therian evolution [6], this feature may indicate a specific evolutionary trait of fin whales and possibly other cetacean species or families. Early mineralization of the tympanic bulla allows immediate sound conduction in the aquatic medium and consequently holds potential importance for mother-calf relationship and postnatal survival. PMID:22615912

  4. Fetal and early post-natal mineralization of the tympanic bulla in fin whales may reveal a Hitherto undiscovered evolutionary trait.

    Directory of Open Access Journals (Sweden)

    Bruno Cozzi

    Full Text Available The evolution of the cetacean skeleton followed a path that differentiated this group from other terrestrial mammals about 50 million years ago [1], and debate is still going on about the relationships between Cetacea and Artiodactyla [2], [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of Archaeocetes, such as the expansion of the peribullary air sinuses, dental modification and vertebral size uniformity [5] are maintained and further emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X-Ray Absorptiometry here we report that the deposition of bone mineral in fetal and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher in the bulla tympanica than in the adjacent basal skull or in the rest of the skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine, hippopotamus is minimal, becomes sensible after birth and then progresses during growth, contrarily to the precocious mineralization that we observed in fin whales. Given the importance of the ear bones for the precise identification of phylogenetic relationship in therian evolution [6], this feature may indicate a specific evolutionary trait of fin whales and possibly other cetacean species or families. Early mineralization of the tympanic bulla allows immediate sound conduction in the aquatic medium and consequently holds potential importance for mother-calf relationship and postnatal survival.

  5. Fetal and early post-natal mineralization of the tympanic bulla in fin whales may reveal a Hitherto undiscovered evolutionary trait.

    Science.gov (United States)

    Cozzi, Bruno; Podestà, Michela; Mazzariol, Sandro; Zotti, Alessandro

    2012-01-01

    The evolution of the cetacean skeleton followed a path that differentiated this group from other terrestrial mammals about 50 million years ago [1], and debate is still going on about the relationships between Cetacea and Artiodactyla [2], [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of Archaeocetes), such as the expansion of the peribullary air sinuses, dental modification and vertebral size uniformity [5] are maintained and further emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X-Ray Absorptiometry here we report that the deposition of bone mineral in fetal and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher in the bulla tympanica than in the adjacent basal skull or in the rest of the skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine, hippopotamus) is minimal, becomes sensible after birth and then progresses during growth, contrarily to the precocious mineralization that we observed in fin whales. Given the importance of the ear bones for the precise identification of phylogenetic relationship in therian evolution [6], this feature may indicate a specific evolutionary trait of fin whales and possibly other cetacean species or families. Early mineralization of the tympanic bulla allows immediate sound conduction in the aquatic medium and consequently holds potential importance for mother-calf relationship and postnatal survival.

  6. Defining the optimal time to the operating room may salvage early trauma deaths.

    Science.gov (United States)

    Remick, Kyle N; Schwab, C William; Smith, Brian P; Monshizadeh, Amir; Kim, Patrick K; Reilly, Patrick M

    2014-05-01

    Early trauma deaths have the potential for salvage with immediate surgery. We studied time from injury to death in this group to qualify characteristics and quantify time to the operating room, yielding the greatest opportunity for salvage. The Pennsylvania Trauma Outcomes Study (PTOS) is a comprehensive registry including all Pennsylvania trauma centers. PTOS was queried for adult trauma patients from 1999 to 2010 dying within 4 hours of injury. The distribution of time to death (TD) was examined for subgroups according to mechanism of injury, hypotension (defined as systolic blood pressure ≤ 90 mm Hg), and operation required. The 5th percentile (TD5) and the 50th percentile (TD50) were calculated from the distributions and compared using the Mann-Whitney U-test. The PTOS yielded 6,547 deaths within 4 hours of injury. The overall TD5 and TD50 were 0:23 (hour:minute) and 0:59, respectively. Median penetrating injury times were significantly shorter than blunt injury times (TD5/TD50, 0:19/0:43 vs. 0:29/1:10). Median time was significantly shorter for hypotensive versus normotensive patients (TD5/TD50, 0:22/0:52 vs. 0:43/2:18). Operative subgroups had different TD5/TD50 (abdominal surgery [n = 607], 1:07/2:26; thoracic surgery [n = 756] 0:25/1:25; vascular surgery [n = 156], 0:35/2:15; and cranial surgery [n = 18], 1:20/2:42). Early trauma deaths have the potential for salvage with immediate surgery. We found TD to vary based on mechanism of injury, presence of hypotension, and type of surgery needed. With the use of TD5 and TD50 benchmarks in these subgroups, a trauma system may determine if decreased time to the operating room decreases mortality. Trauma systems can use these data to further improve prehospital and initial hospital phases of care for this subset of early death trauma patients. Epidemiologic study, level III.

  7. Immunosuppression in early postnatal days induces persistent and allergen-specific immune tolerance to asthma in adult mice.

    Directory of Open Access Journals (Sweden)

    Yan Chen

    Full Text Available Bronchial asthma is a chronic airway inflammatory condition with high morbidity, and effective treatments for asthma are limited. Allergen-specific immunotherapy can only induce peripheral immune tolerance and is not sustainable. Exploring new therapeutic strategies is of great clinical importance. Recombinant adenovirus (rAdV was used as a vector to make cells expressing cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig a soluble CTLA4 immunoglobulin fusion protein. Dendritic cells (DCs were modified using the rAdVs together with allergens. Then these modified DCs were transplanted to mice before allergen sensitization. The persistence and specificity of immune tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell stimulation in vitro. Mice treated with these DCs in the early neonatal period developed tolerance against the allergens that were used to induce asthma in the adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory response all improved. Humoral immunity indices showed that this therapeutic strategy strongly suppressed mice immune responses and was maintained for as long as 7 months. Furthermore, allergen cross-sensitization and challenge experiments demonstrated that this immune tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early neonatal period, inducing persistent and allergen-specific immune tolerance to asthma in adult mice. Our results suggest that it may be possible to develop a vaccine for asthma.

  8. 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

  9. Aliskiren administration during early postnatal life sex-specifically alleviates hypertension programmed by maternal high fructose consumption

    Directory of Open Access Journals (Sweden)

    You-Lin Tain

    2016-07-01

    Full Text Available Background: Maternal high fructose (HF intake induced renal programming and hypertension in male adult offspring. We examined whether maternal HF intake causes programmed hypertension and whether aliskiren administration confers protection against the process in a sex-specific manner, with a focus on the transcriptome changes in the kidney using next-generation RNA sequencing (NGS technology and renin-angiotensin system (RAS. Methods: Pregnant Sprague–Dawley rats received regular chow or chow supplemented with 60% fructose throughout pregnancy and lactation. Offspring were assigned to six groups: male control, male HF (MHF, MHF+Aliskiren, female control, female HF (FHF, and FHF+Aliskiren. Oral aliskiren 10 mg/kg/day was administered via gastric gavage between 2–4 weeks of age. Rats were sacrificed at 12 weeks of age. Results: Maternal HF intake induced programmed hypertension in 12-week-old offspring of both sexes. HF regulated renal transcriptome and RAS components in the offspring kidney in a sex-specific manner. Aliskiren administration prevented HF-induced programmed hypertension in both sexes of adult offspring. Aliskiren administration increased ACE2 and MAS protein levels in female kidneys exposed to maternal HF intake. Conclusion: Maternal HF induced programmed hypertension in both sexes of adult offspring, which was sex-specifically mitigated by early aliskiren administration. Better understanding of the sex-dependent mechanisms that underlie maternal HF-induced renal programming will help develop a novel sex-specific strategy to prevent programmed hypertension.

  10. Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants.

    Science.gov (United States)

    Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A; Löfqvist, Chatarina; Smith, Lois E H; Hård, Anna-Lena

    2016-09-01

    The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities.

  11. Early death after discharge from emergency departments: analysis of national US insurance claims data.

    Science.gov (United States)

    Obermeyer, Ziad; Cohn, Brent; Wilson, Michael; Jena, Anupam B; Cutler, David M

    2017-02-01

     To measure incidence of early death after discharge from emergency departments, and explore potential sources of variation in risk by measurable aspects of hospitals and patients.  Retrospective cohort study.  Claims data from the US Medicare program, covering visits to an emergency department, 2007-12.  Nationally representative 20% sample of Medicare fee for service beneficiaries. As the focus was on generally healthy people living in the community, patients in nursing facilities, aged ≥90, receiving palliative or hospice care, or with a diagnosis of a life limiting illnesses, either during emergency department visits (for example, myocardial infarction) or in the year before (for example, malignancy) were excluded.  Death within seven days after discharge from the emergency department, excluding patients transferred or admitted as inpatients.  Among discharged patients, 0.12% (12 375/10 093 678, in the 20% sample over 2007-12) died within seven days, or 10 093 per year nationally. Mean age at death was 69. Leading causes of death on death certificates were atherosclerotic heart disease (13.6%), myocardial infarction (10.3%), and chronic obstructive pulmonary disease (9.6%). Some 2.3% died of narcotic overdose, largely after visits for musculoskeletal problems. Hospitals in the lowest fifth of rates of inpatient admission from the emergency department had the highest rates of early death (0.27%)-3.4 times higher than hospitals in the highest fifth (0.08%)-despite the fact that hospitals with low admission rates served healthier populations, as measured by overall seven day mortality among all comers to the emergency department. Small increases in admission rate were linked to large decreases in risk. In multivariate analysis, emergency departments that saw higher volumes of patients (odds ratio 0.84, 95% confidence interval 0.81 to 0.86) and those with higher charges for visits (0.75, 0.74 to 0.77) had significantly fewer deaths. Certain

  12. Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid fatty acid composition in a muscle type specific manner in sheep

    DEFF Research Database (Denmark)

    Hou, Lei; Kongsted, Alice; Ghoreishi, S. M.

    2013-01-01

    , these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1 1/2 years. In conclusion, early postnatal, but not late gestation......We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle...... determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein...

  13. Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life.

    Science.gov (United States)

    Wang, Kimberley C W; Brooks, Doug A; Summers-Pearce, Brooke; Bobrovskaya, Larisa; Tosh, Darran N; Duffield, Jaime A; Botting, Kimberley J; Zhang, Song; Caroline McMillen, I; Morrison, Janna L

    2015-02-01

    Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin-angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  14. Low birth weight activates the renin–angiotensin system, but limits cardiac angiogenesis in early postnatal life

    Science.gov (United States)

    Wang, Kimberley C W; Brooks, Doug A; Summers-Pearce, Brooke; Bobrovskaya, Larisa; Tosh, Darran N; Duffield, Jaime A; Botting, Kimberley J; Zhang, Song; Caroline McMillen, I; Morrison, Janna L

    2015-01-01

    Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin–angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life. PMID:25649246

  15. Relations between desire for early death, depressive symptoms and antidepressant prescribing in terminally ill patients with cancer

    OpenAIRE

    Tiernan, E; Casey, P; O'Boyle, C; Birkbeck, G; Mangan, M; O'Siorain, L; Kearney, M.

    2002-01-01

    Some patients with advanced cancer express the wish for an early death. This may be associated with depression. We examined the relations between depressive symptoms and desire for early death (natural or by euthanasia or physician-assisted suicide) in 142 terminally ill patients with cancer being cared for by a specialist palliative care team. They completed the Hospital Anxiety and Depression Scale questionnaire and answered four supplementary questions on desire for...

  16. Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats.

    Science.gov (United States)

    Redrobe, John P; Elster, Lisbeth; Frederiksen, Kristen; Bundgaard, Christoffer; de Jong, Inge E M; Smith, Garrick P; Bruun, Anne Techau; Larsen, Peter H; Didriksen, Michael

    2012-06-01

    A growing body of evidence suggests that negative modulation of γ-aminobutyric acid (GABA) GABA(A) α5 receptors may be a promising strategy for the treatment of certain facets of cognitive impairment; however, selective modulators of GABA(A) α5 receptors have not yet been tested in "schizophrenia-relevant" cognitive assay/model systems in animals. The objectives of this study were to investigate the potential of RO4938581, a negative modulator of GABA(A) α5 receptors, and to attenuate cognitive impairments induced following sub-chronic (sub-PCP) and early postnatal PCP (neo-PCP) administration in the novel object recognition (NOR) and intra-extradimensional shift (ID/ED) paradigms in rats. Complementary in vitro, ex vivo and in vivo studies were performed to confirm negative modulatory activity of RO4938581 and to investigate animal model validity, concept validity and potential side effect issues, respectively. In vitro studies confirmed the reported negative modulatory activity of RO4938581, whilst immunohistochemical analyses revealed significantly reduced parvalbumin-positive cells in the prefrontal cortex of sub-PCP- and neo-PCP-treated rats. RO4938581 (1 mg/kg) ameliorated both sub-PCP- and neo-PCP-induced cognitive deficits in NOR and ID/ED performance, respectively. In contrast, QH-II-066 (1 and 3 mg/kg), a GABA(A) α5 receptor positive modulator, impaired cognitive performance in the NOR task when administered to vehicle-treated animals. Additional studies revealed that both RO4938581 (1 mg/kg) and QH-II-066 (1 and 3 mg/kg) attenuated amphetamine-induced hyperactivity in rats. Taken together, these novel findings suggest that negative modulation of GABA(A) α5 receptors may represent an attractive treatment option for the cognitive impairments, and potentially positive symptoms, associated with schizophrenia.

  17. Searching for early-warning signals of impending dieback and death in Mediterranean oaks

    Science.gov (United States)

    Colangelo, Michele; Ripullone, Francesco; Julio Camarero, Jesus; De Micco, Veronica; Gazol, Antonio; Gentilesca, Tiziana; Borghetti, Marco

    2017-04-01

    In recent decades, forest dieback episodes have been recorded worldwide affecting different tree species. In particular, several cases of widespread dieback and increased mortality rates have been described for Mediterranean oak (Quercus spp.) species. These dieback cases are revealing the high vulnerability of Mediterranean oaks, manifested as a loss in tree vigour (leaf shedding, canopy and shoot dieback), growth decline and sometimes tree death, as a consequence of temperatures rising at unprecedented rates and drying trends. However, in the wake of the so-called 'oak decline phenomenon', the attention on these species has generally been limited, perhaps because they are often regarded as well-adapted to the dry conditions typical of Mediterranean areas. Indeed, according to recent studies, the reduced size, the ability to sprout and the anisohydric behavior of Mediterranean oak species (reduced control of water loss and high stomatal conductance rates) would make them better adapted to withstand heat and drought stress then taller and non-sprouting isohydric species (e.g. conifer, with strict control of water loss by closing stomata). Here, we investigated the vulnerability of Mediterranean oaks by comparing neighboring living and recently dead trees in species with low (Q. pubescens), intermediate (Q. cerris, Q. frainetto) and high (Q. robur) sensitivity to water shortage. We analysed changes in tree vigour using tree-ring width and functional wood anatomical traits as proxies to search for early-warning signals of dieback, in connection with the main proposed dieback mechanisms (hydraulic failure and/or carbon starvation). We also modeled the probability of tree death as a function of tree size (diameter, height) by quantifying recent changes in growth and wood anatomy along tree-ring series. Contrary to the general concept that trees tend to experience increasing cavitation risk with increasing height, our studies show that smaller oaks are more prone to die

  18. Hypermutator Salmonella Heidelberg induces an early cell death in epithelial cells.

    Science.gov (United States)

    Le Gall-David, Sandrine; Zenbaa, Neila; Bouchard, Damien; Lavault, Marie-Thérèse; Bonnaure-Mallet, Martine; Jolivet-Gougeon, Anne; Bousarghin, Latifa

    2015-10-22

    We have previously described that a strain of Salmonella Heidelberg with a hypermutator phenotype, B182, adhered strongly to HeLa cells. In this work, we showed that this hypermutator Salmonella strain invaded HeLa epithelial cells and induced cytoskeleton alteration. Those changes lead to HeLa cell death which was characteristic of apoptosis. For the first time, we showed that this hypermutator strain induced apoptosis associated with the activation of caspases 2, 9 and 3. Complementation of B182 strain showed a decrease in cells death induction. In the presence of other Salmonella Heidelberg with a normomutator phenotype, such as WT and SL486, cell death and caspase 3 were undetectable. These results suggested that early apoptosis and caspase 3 activation were specific to B182. Besides, B182 induced LDH release and caspase 3 activation in CaCo-2 and HCT116 cells. Heat-treated B182 and diffusible products failed to induce this phenotype. Epithelial cells treatment with cytochalasin D caused the inhibition of B182 internalisation and caspase 3 activation. These results showed that this cell death required active S. Heidelberg B182 protein synthesis and bacterial internalisation. However sipB and sopB, usually involved in apoptosis induced by Salmonella were not overexpressed in B182, contrary to fimA and fliC. Comparative genome analysis showed numerous mutations as in rpoS which would be more investigated. The role of the hypermutator phenotype might be suspected to be implicated in these specific features. This result expands our knowledge about strong mutators frequently found in bacterial organisms isolated from clinical specimens.

  19. Understanding the information needs of women with rheumatoid arthritis concerning pregnancy, post-natal care and early parenting: A mixed-methods study.

    Science.gov (United States)

    Ackerman, Ilana N; Jordan, Joanne E; Van Doornum, Sharon; Ricardo, Margaret; Briggs, Andrew M

    2015-08-19

    Although women with rheumatoid arthritis (RA) face a number of challenges in negotiating the journey to parenthood, no studies have explored the information needs of women with RA in relation to their childbearing years. This study aimed to determine the need for (and preferred mode/s of delivery of) information regarding pregnancy, post-natal care and early parenting among women with RA. Interviews and focus groups were conducted with 27 women with RA who were pregnant in the last 5 years, currently pregnant or planning pregnancy. Verbatim transcripts were analysed using both inductive and deductive approaches. Two validated instruments were used to quantify information needs and preferences: the Educational Needs Assessment Tool (ENAT, range 0-156, higher scores indicate higher educational needs) and the Autonomy Preference Index (API, range 0-100, higher scores indicate stronger preferences). Lack of information about medication safety, access to physical/emotional support services and practical strategies for coping with daily challenges related to parenting were the most prominent of the six key themes identified. Rheumatologists were the primary source for information regarding treatment decisions while arthritis consumer organisations were perceived as critical 'resource hubs'. There was strong preference for information delivered electronically, especially among rural participants. Quantitative outcomes supported the qualitative findings; on average, participants reported high educational needs (mean ENAT score 97.2, SD 30.8) and API scores indicated that desire for information (mean 89.8, SD 5.6) was greater than the need for involvement in treatment decision-making (mean 68.4, SD 8.2). Many women with RA struggle to find adequate information on pregnancy planning, pregnancy and early parenting in relation to their chronic condition, and there is a clear need to develop accessible information that is consumer-focused and evidence-based. Although most

  20. Unbiased cell quantification reveals a continued increase in the number of neocortical neurones during early post-natal development in mice

    DEFF Research Database (Denmark)

    Lyck, Lise; Krøigård, Thomas; Finsen, Bente

    2007-01-01

    was delayed until P16. The number of glia reached its maximum at P16, whereas the number of oligodendroglia, identified using a transgenic marker, increased until P55, the latest time of observation. Neurones continued to accumulate in the developing neocortex during the first 2 weeks of post......-natal development, underscoring fundamental differences in brain development in the mouse compared with human and non-human primates. Further, delayed acquisition of NeuN by neurones in the deepest neocortical layers and continued addition of oligodendroglia to the neocortex suggested that neocortical maturation...... the number of neurones and glia in the neocortex during post-natal development in two separate strains of mice. Cell counting by the optical fractionator revealed that the number of neurones increased 80-100% from the time of birth to post-natal day (P)16, followed by a reduction by approximately 25...

  1. Sire effect on early and late embryonic death in French Holstein cattle.

    Science.gov (United States)

    Ledoux, D; Ponsart, C; Grimard, B; Gatien, J; Deloche, M C; Fritz, S; Lefebvre, R; Humblot, P

    2015-05-01

    We investigated the effect of maternal sire on early pregnancy failure (between D0, day of insemination and D90) in their progeny during the first and second lactations (n=3508) in the Holstein breed. The estimated breeding value (EBV) for cow fertility of 12 bulls (reliability⩾0.95) was used to create the following three groups: low, medium and high EBV (EBV from -0.7 to 1 expressed as genetic standard deviation relative to the mean of the breed). In their daughters (93 to 516 per bull), progesterone measurement was carried out on the day of artificial insemination (AI; D0) to check whether the cows were in the follicular phase and on D18 to 25 to assess non-fertilisation-early embryonic mortality (NF-EEM). Late embryonic mortality (LEM) and early foetal death (FD) were determined by ultrasonography on D45 and D90 and by the return to oestrus after the first AI. Frequencies of NF-EEM, LEM, FD and pregnancy were 33.3%, 11.7%, 1.4% and 48.5% and incidences were 35.1, 19.0, 2.7 and 51.1, respectively. Sire EBV was significantly related to the incidences of pregnancy failure between D0 and D90, fertilisation failure-early embryonic mortality (FF-EEM) and LEM but not to the incidence of FD between D45 and D90 of pregnancy. The relative risk (RR) of FF-EEM was significantly higher (RR=1.2; P<0.05) for the progeny group of low EBV bulls when compared with high EBV bulls. The same effect was observed when comparing LEM of the progeny groups from the low EBV bulls to those from moderate and high EBV bulls (RR, respectively, of 1.3 and 1.4; P<005). The incidence of FF-EEM was significantly higher when cows were inseminated before 80 days postpartum compared with later, and for the extreme values of the difference between milk fat and protein content measured during the first 3 months of lactation. FF-EEM was also significantly related to the year of observation. The incidence of LEM was higher for the highest producing cows and was influenced by interaction between milk

  2. Mid-pregnancy genetic terminations of pregnancy - postnatal ...

    African Journals Online (AJOL)

    photographs only. Conclusions. ... The postnatal investigation of stillbirths and neonatal deaths, using a ... of the condition in a future pregnancy, and parents need to be able to ..... fetus, in all multiple congenital anomaly syndromes in which.

  3. Universal HIV screening at postnatal points of care: which public health approach for early infant diagnosis in Cote d'Ivoire?

    Directory of Open Access Journals (Sweden)

    Camille Ndondoki

    Full Text Available BACKGROUND: Universal HIV pediatric screening offered at postnatal points of care (PPOC is an entry point for early infant diagnosis (EID. We assessed the parents' acceptability of this approach in Abidjan, Côte d'Ivoire. METHODS: In this cross-sectional study, trained counselors offered systematic HIV screening to all children aged 6-26 weeks attending PPOC in three community health centers with existing access to HAART during 2008, as well as their parents/caregivers. HIV-testing acceptability was measured for parents and children; rapid HIV tests were used for parents. Both parents' consent was required according to the Ivorian Ethical Committee to perform a HIV test on HIV-exposed children. Free HIV care was offered to those who were diagnosed HIV-infected. FINDINGS: We provided 3,013 HIV tests for infants and their 2,986 mothers. While 1,731 mothers (58% accepted the principle of EID, only 447 infants had formal parental consent 15%; 95% confidence interval (CI: [14%-16%]. Overall, 1,817 mothers (61% accepted to test for HIV, of whom 81 were HIV-infected (4.5%; 95% CI: [3.5%-5.4%]. Among the 81 HIV-exposed children, 42 (52% had provided parental consent and were tested: five were HIV-infected (11.9%; 95% CI: [2.1%-21.7%]. Only 46 fathers (2% came to diagnose their child. Parental acceptance of EID was strongly correlated with prenatal self-reported HIV status: HIV-infected mothers were six times more likely to provide EID parental acceptance than mothers reporting unknown or negative prenatal HIV status (aOR: 5.9; 95% CI: [3.3-10.6], p = 0.0001. CONCLUSIONS: Although the principle of EID was moderately accepted by mothers, fathers' acceptance rate remained very low. Routine HIV screening of all infants was inefficient for EID at a community level in Abidjan in 2008. Our results suggest the need of focusing on increasing the PMTCT coverage, involving fathers and tracing children issued from PMTCT programs in low HIV prevalence countries.

  4. Florfenicol induces early embryonic death in eggs collected from treated hens.

    Science.gov (United States)

    Al-Shahrani, S; Naidoo, V

    2015-08-18

    Florfenicol, a commonly used veterinary antibiotic, was reported to have caused a severe drop in egg hatchability following its off-label use on a broiler breeder farm in South Africa. According to the pharmacovigilance report, hatchability dropped by 80 % for up to a week following a five day course at 10 mg/kg (both males and females treated metaphylactically) to manage an Escherichia coli infection. While mammalian toxicity studies indicate the potential for early embryonic death in utero or testicular damage, no literature is available on the avian toxicity of florfenicol. For this study we investigated the effects of florfenicol at various doses from 10 to 90 mg/kg on the egg hatchability in a breeder flock we kept and established under controlled conditions, with the same cockerels and hens being exposed in a phased manner. Following five days of oral exposure, no toxic signs were evident in any of the cockerels or hens treated at doses up to 90 mg/kg. Treatment of only the cockerels had no effect on egg hatchability, while treatment of only the hens at doses of 60 and 90 mg/kg resulted in decreased hatchability of 0 % in comparison to 70 % of the control as early 24 h after treatment. In all cases, decreased hatchability was associated with embryonic death at 5 days of development. The toxic effects of florfenicol were completely reversible with comparable hatchability being present by day 4 post-treatment withdrawal. Toxicity correlated with total egg florfenicol concentrations with an LC50 of 1.07 μg/g. Florfenicol appears to be toxic to the developing chick embryo at around day 5 of incubation, in the absence of related toxicity in the hen or cockerel.

  5. Early heart failure in the SMNDelta7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery.

    Science.gov (United States)

    Bevan, Adam K; Hutchinson, Kirk R; Foust, Kevin D; Braun, Lyndsey; McGovern, Vicki L; Schmelzer, Leah; Ward, Jennifer G; Petruska, Jeffrey C; Lucchesi, Pamela A; Burghes, Arthur H M; Kaspar, Brian K

    2010-10-15

    Proximal spinal muscular atrophy (SMA) is a debilitating neurological disease marked by isolated lower motor neuron death and subsequent atrophy of skeletal muscle. Historically, SMA pathology was thought to be limited to lower motor neurons and the skeletal muscles they control, yet there are several reports describing the coincidence of cardiovascular abnormalities in SMA patients. As new therapies for SMA emerge, it is necessary to determine whether these non-neuromuscular systems need to be targeted. Therefore, we have characterized left ventricular (LV) function of SMA mice (SMN2+/+; SMNΔ7+/+; Smn-/-) and compared it with that of their unaffected littermates at 7 and 14 days of age. Anatomical and physiological measurements made by electrocardiogram and echocardiography show that affected mouse pups have a dramatic decrease in cardiac function. At 14 days of age, SMA mice have bradycardia and develop a marked dilated cardiomyopathy with a concomitant decrease in contractility. Signs of decreased cardiac function are also apparent as early as 7 days of age in SMA animals. Delivery of a survival motor neuron-1 transgene using a self-complementary adeno-associated virus serotype 9 abolished the symptom of bradycardia and significantly decreased the severity of the heart defect. We conclude that severe SMA animals have compromised cardiac function resulting at least partially from early bradycardia, which is likely attributable to aberrant autonomic signaling. Further cardiographic studies of human SMA patients are needed to clarify the clinical relevance of these findings from this SMA mouse.

  6. Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid Fatty Acid composition in a muscle type specific manner in sheep.

    Directory of Open Access Journals (Sweden)

    Lei Hou

    Full Text Available We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD and biceps femoris (BF and in the cardiac muscle (ventriculus sinister cordis (VSC of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM or 50% (LOW of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty, twin offspring received a high-carbohydrate-high-fat (HCHF or a moderate-conventional (CONV diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults. The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4 protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced

  7. Air pollution and early deaths in the United States. Part I: Quantifying the impact of major sectors in 2005

    Science.gov (United States)

    Caiazzo, Fabio; Ashok, Akshay; Waitz, Ian A.; Yim, Steve H. L.; Barrett, Steven R. H.

    2013-11-01

    Combustion emissions adversely impact air quality and human health. A multiscale air quality model is applied to assess the health impacts of major emissions sectors in United States. Emissions are classified according to six different sources: electric power generation, industry, commercial and residential sources, road transportation, marine transportation and rail transportation. Epidemiological evidence is used to relate long-term population exposure to sector-induced changes in the concentrations of PM2.5 and ozone to incidences of premature death. Total combustion emissions in the U.S. account for about 200,000 (90% CI: 90,000-362,000) premature deaths per year in the U.S. due to changes in PM2.5 concentrations, and about 10,000 (90% CI: -1000 to 21,000) deaths due to changes in ozone concentrations. The largest contributors for both pollutant-related mortalities are road transportation, causing ∼53,000 (90% CI: 24,000-95,000) PM2.5-related deaths and ∼5000 (90% CI: -900 to 11,000) ozone-related early deaths per year, and power generation, causing ∼52,000 (90% CI: 23,000-94,000) PM2.5-related and ∼2000 (90% CI: -300 to 4000) ozone-related premature mortalities per year. Industrial emissions contribute to ∼41,000 (90% CI: 18,000-74,000) early deaths from PM2.5 and ∼2000 (90% CI: 0-4000) early deaths from ozone. The results are indicative of the extent to which policy measures could be undertaken in order to mitigate the impact of specific emissions from different sectors - in particular black carbon emissions from road transportation and sulfur dioxide emissions from power generation.

  8. 早期咖啡因暴露对成年小鼠苦味适应的影响%The Influence of Bitter Adaptation in Adulthood Induced by Early Postnatal Exposure to Caffeine

    Institute of Scientific and Technical Information of China (English)

    刘斯斯; 李伟丽; 李国梁; 陈梦玲; 张根华

    2013-01-01

    咖啡因是一种典型的苦味刺激物,常作为一种心理刺激药物被广泛应用.通常而言,人们对咖啡因的感知是厌恶的,但这种感知可以被后天的经历所影响.我们的实验结果表明,在小鼠出生后早期阶段对其进行慢性咖啡因暴露,可以影响其成年阶段对咖啡因的感知模式,并提高其对咖啡因的厌恶阈值,即早期咖啡因暴露使成年小鼠对咖啡因的苦味适应性增强.%Caffeine is a prototypic bitter stimulus and is consumed as psychoactive stimulant widely. Customarily, people present aversion to caffeine. But the taste preferences can be affected by postnatal experience. Our research indicates that chronic administration of caffeine for mice at early developmental stage may influence the adult caffeine sensory. According to the behavioral test, we observed that the avoid thresholds for caffeine had been increased. Early postnatal exposure to caffeine increases the bitter adaptation in adulthood of ICR mice.

  9. Fate of Cajal-Retzius neurons in the postnatal mouse neocortex

    Directory of Open Access Journals (Sweden)

    Tara G Chowdhury

    2010-03-01

    Full Text Available Cajal-Retzius (CR neurons play a critical role in cortical neuronal migration, but their exact fate after the completion of neocortical lamination remains a mystery. Histological evidence has been unable to unequivocally determine whether these cells die or undergo a phenotypic transformation to become resident interneurons of Layer 1 in the adult neocortex. To determine their ultimate fate, we performed chronic in vivo two-photon imaging of identified CR neurons during postnatal development in mice that express the green fluorescent protein (GFP under the control of the early B-cell factor 2 (Ebf2 promoter. We find that, after birth, virtually all CR neurons in mouse neocortex express Ebf2. Although postnatal CR neurons undergo dramatic morphological transformations, they do not migrate to deeper layers. Instead, their gradual disappearance from the cortex is due to apoptotic death during the second postnatal week. A small fraction of CR neurons present at birth survive into adulthood. We conclude that, in addition to orchestrating cortical layering, a subset of CR neurons must play other roles beyond the third postnatal week.

  10. Redefining Death

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The results of 20 years of research on brain death will be released to the public, the Chinese Ministry of Health reported in early April. A special ministry team has drafted the criteria for brain death in Criteria for the Diagnosis of Brain Death in Adults (Revised Edition) and Technical Specifications for the Diagnosis

  11. Early postnatal handling and environmental enrichment improve the behavioral responses of 17-month-old 3xTg-AD and non-transgenic mice in the Forced Swim Test in a gender-dependent manner.

    Science.gov (United States)

    Torres-Lista, Virginia; Giménez-Llort, Lydia

    2015-11-01

    Forced Swimming Test (FST) models behavioural despair in animals by loss of motivation to respond or the refusal to escape. The present study was aimed at characterizing genetic (genotype and gender) and environmental factors (age/stage of disease and rearing conditions: C, standard; H, early postnatal handling; EE, environmental enrichment consisting in physical exercise as well as social and object enrichment) that may modulate the poor behavioural and cognitive flexibility response we have recently described in 12-month-old male 3xTg-AD mice in the FST. The comprehensive analysis of the ethogram shown in the FST considered the intervals of the test (0-2 and 2-6min), all the elicited behavioural responses (immobility, swimming and climbing) and their features (total duration and frequency of episodes). The long persistence of behaviours found in 17-month-old (late-stages of disease) 3xTg-AD mice was comparable to that recently described in males at 12 months of age (beginning of advanced stages) but also suggested increased age-dependent frailty in both genotypes. The poor behavioral flexibility of 3xTg-AD mice to elicit the behavioural despair shown by the NTg mice, was also found in the female gender. Finally, the present work demonstrates that early-life interventions were able to improve the time and frequency of episodes of immobility, being more evident in the female gender of both old NTg and 3xTg-AD mice. Ontogenic modulation by early-postnatal handling resulted in a more effective long-term improvement of the elicited behaviours in the FST than that achieved by environmental enrichment. The results talk in favor of the beneficence of early-life interventions on ageing in both healthy and disease conditions.

  12. Fetal urinary peptides to predict postnatal outcome of renal disease in fetuses with posterior urethral valves (PUV).

    Science.gov (United States)

    Klein, Julie; Lacroix, Chrystelle; Caubet, Cécile; Siwy, Justyna; Zürbig, Petra; Dakna, Mohammed; Muller, Françoise; Breuil, Benjamin; Stalmach, Angelique; Mullen, William; Mischak, Harald; Bandin, Flavio; Monsarrat, Bernard; Bascands, Jean-Loup; Decramer, Stéphane; Schanstra, Joost P

    2013-08-14

    Bilateral congenital abnormalities of the kidney and urinary tract (CAKUT), although are individually rare diseases, remain the main cause of chronic kidney disease in infants worldwide. Bilateral CAKUT display a wide spectrum of pre- and postnatal outcomes ranging from death in utero to normal postnatal renal function. Methods to predict these outcomes in utero are controversial and, in several cases, lead to unjustified termination of pregnancy. Using capillary electrophoresis coupled with mass spectrometry, we have analyzed the urinary proteome of fetuses with posterior urethral valves (PUV), the prototypic bilateral CAKUT, for the presence of biomarkers predicting postnatal renal function. Among more than 4000 fetal urinary peptide candidates, 26 peptides were identified that were specifically associated with PUV in 13 patients with early end-stage renal disease (ESRD) compared to 15 patients with absence of ESRD before the age of 2. A classifier based on these peptides correctly predicted postnatal renal function with 88% sensitivity and 95% specificity in an independent blinded validation cohort of 38 PUV patients, outperforming classical methods, including fetal urine biochemistry and fetal ultrasound. This study demonstrates that fetal urine is an important pool of peptides that can predict postnatal renal function and thus be used to make clinical decisions regarding pregnancy.

  13. Deletion of Munc18-1 in 5-HT Neurons Results in Rapid Degeneration of the 5-HT System and Early Postnatal Lethality

    Science.gov (United States)

    Dudok, Jacobus J.; Groffen, Alexander J. A.; Toonen, Ruud F. T.; Verhage, Matthijs

    2011-01-01

    The serotonin (5-HT) system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT) promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival. PMID:22140524

  14. Deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and early postnatal lethality.

    Directory of Open Access Journals (Sweden)

    Jacobus J Dudok

    Full Text Available The serotonin (5-HT system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival.

  15. Dietary supplementation with β-hydroxy-β-methylbutyrate calcium during the early postnatal period accelerates skeletal muscle fibre growth and maturity in intra-uterine growth-retarded and normal-birth-weight piglets.

    Science.gov (United States)

    Wan, Haifeng; Zhu, Jiatao; Su, Guoqi; Liu, Yan; Hua, Lun; Hu, Liang; Wu, Caimei; Zhang, Ruinan; Zhou, Pan; Shen, Yong; Lin, Yan; Xu, Shengyu; Fang, Zhengfeng; Che, Lianqiang; Feng, Bin; Wu, De

    2016-04-01

    Intra-uterine growth restriction (IUGR) impairs postnatal growth and skeletal muscle development in neonatal infants. This study evaluated whether dietary β-hydroxy-β-methylbutyrate Ca (HMB-Ca) supplementation during the early postnatal period could improve muscle growth in IUGR neonates using piglets as a model. A total of twelve pairs of IUGR and normal-birth-weight (NBW) male piglets with average initial weights (1·85 (sem 0·36) and 2·51 (sem 0·39) kg, respectively) were randomly allotted to groups that received milk-based diets (CON) or milk-based diets supplemented with 800 mg/kg HMB-Ca (HMB) during days 7-28 after birth. Blood and longissimus dorsi (LD) samples were collected and analysed for plasma amino acid content, fibre morphology and the expression of genes related to muscle development. The results indicate that, regardless of diet, IUGR piglets had a significantly decreased average daily weight gain (ADG) compared with that of NBW piglets (Pgrowth factor-1 and myosin heavy-chain isoform IIb in the LD of piglets (Pmuscle growth and maturity by accelerating fast-twitch glycolytic fibre development in piglets.

  16. Postnatal Cardiovascular Adaptation

    Directory of Open Access Journals (Sweden)

    Ferda Ozlu

    2016-06-01

    Full Text Available Fetus depends on placental circulation in utero. A successful transition from intrauterin to extrauterine life depends on succesful physiological changes during labor. During delivery, fetus transfers from a liquid environment where oxygen comes via umbilical vein to air environement where oxygenation is supported via air breathing. Endocrinological changes are important for fetus to adapt to extrauterine life. In addition to these, cord clemping plays a crucial role in postnatal adaptation. Establishment of neonatal postnatal life and succesful overcome, the fetal cardiovascular transition period are important to stay on. [Archives Medical Review Journal 2016; 25(2.000: 181-190

  17. [Memento mori: what can be learned from early paintings and woodcuts about death and dying in former times?].

    Science.gov (United States)

    Lucke, C; Lucke, M; Gogol, M; Rademacher, U

    2012-06-01

    What was the impression on death and dying from people living in the 15th century? To answer this question written information is rare on this topic, as few people were able to read at that time, but paintings and early woodcuts may be helpful. Danses macabres (Totentänze) could be seen in Tallinn (formerly Reval), Lübeck, Bern and other places: parts of the original dance macabre still exist in Tallinn, but those in Bern and Lübeck are destroyed; copies however may give a decent impression of their former appearance. At all these dances macabre the death invites persons for a dance: the pope, the Kaiser, the king, the queen, various noblemen and citizens, even young women and small children; to dance with the death meant to die. The death does not dance with any old person. At the time of these dances macabre epidemics and famines were frequent causes of untimely early death.--A booklet Ars moriendi was published about 1470 and taught people how to behave at their hour of death; various devils appear at the deathbed haggling for the soul of the dying person. Thereafter an angel convinces him to trust in god and to resist those false promises of the devil.Nowadays dying is quite different. Usually persons die at very old age and are frequently demented, they die in hospitals, even in intensive care units and possibly without attendance of family members. They may have suffered for a long time and have spent years in nursing homes. Today dying may be just a release from very long suffering.

  18. Early Risk stratification for Arrhythmic death in Patients with ST-Elevation Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Sadr-Ameli

    2007-01-01

    Full Text Available Background: Sudden cardiac death is a leading cause of death in patients with ST-elevation myocardial infarction (MI. According to high cost of modern therapeutic modalities it is of paramount importance to define protocols for risk stratification of post-MI patients before considering expensive devices such as implantable cardioverter-defibrillator.Methods: One hundred and thirty seven patients with acute ST-elevation MI were selected and underwent echocardiographic study, holter monitoring and signal-averaged electrocardiography (SAECG. Then, the patients were followed for 12 ±3 months.Results: During follow-up, 13 deaths (9.5% occurred; nine cases happened as sudden cardiac death (6.6%. The effect of ejection fraction (EF less than 40% on occurrence of arrhythmic events was significant (P<0.001. Sensitivity and positive predictive value of EF<40% was 100% and 76.95% respectively. Although with lesser sensitivity and predictive power than EF<40%, abnormal heart rate variability (HRV and SAECG had also significant effects on occurrence of sudden death (P=0.02 and P=0.003 respectively. Nonsustained ventricular tachycardia was not significantly related to risk of sudden death in this study (P=0.20.Conclusions: This study indicated that EF less than 40% is the most powerful predictor of sudden cardiac death in post MI patients. Abnormal HRV and SAECG are also important predictors and can be added to EF for better risk stratification.

  19. Postnatal Testosterone Concentrations and Male Social Development

    Directory of Open Access Journals (Sweden)

    Gerianne M Alexander

    2014-02-01

    Full Text Available Converging evidence from over 40 years of behavioral research indicates that higher testicular androgens in prenatal life and at puberty contribute to the masculinization of human behavior. However, the behavioral significance of the transient activation of the hypothalamic-pituitary-gonadal (HPG axis in early postnatal life remains largely unknown. Although early research on nonhuman primates indicated suppression of the postnatal surge in testicular androgens had no measurable effects on the later expression of the male behavioral phenotype, recent research from our laboratory suggests that postnatal testosterone concentrations influence male infant preferences for larger social groups and temperament characteristics associated with the later development of aggression. In later assessment of gender-linked behavior in the second year of life, concentrations of testosterone at 3-4 months of age were unrelated to toy choices and activity levels during toy play. However, higher concentrations of testosterone predicted less vocalization in toddlers and higher parental ratings on an established screening measure for autism spectrum disorder. These findings suggest a role of the transient activation of the HPG axis in the development of typical and atypical male social relations and suggest that it may be useful in future research on the exaggerated rise in testosterone secretion in preterm infants or exposure to hormone disruptors in early postnatal life to include assessment of gender-relevant behavioral outcomes, including childhood disorders with sex-biased prevalence rates.

  20. CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

    DEFF Research Database (Denmark)

    Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul

    2012-01-01

    PURPOSE We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS From 22 studies participating in the Breast Cancer Assoc...

  1. CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer

    NARCIS (Netherlands)

    M. Weischer (Maren); B.G. Nordestgaard (Børge); P.D.P. Pharoah (Paul); M.K. Bolla (Manjeet); H. Nevanlinna (Heli); L.J. van 't Veer (Laura); M. García-Closas (Montserrat); J.L. Hopper (John); P. Hall (Per); I.L. Andrulis (Irene); P. Devilee (Peter); P.A. Fasching (Peter); H. Anton-Culver (Hoda); D. Lambrechts (Diether); M.J. Hooning (Maartje); A. Cox (Angela); G.G. Giles (Graham); B. Burwinkel (Barbara); A. Lindblom (Annika); F.J. Couch (Fergus); A. Mannermaa (Arto); G.G. Alnæs (Grethe); E.M. John (Esther); T. Dörk (Thilo); H. Flyger (Henrik); A.M. Dunning (Alison); Q. Wang (Qing); T.A. Muranen (Taru); R.R. van Hien (Richard); J.D. Figueroa (Jonine); M.C. Southey (Melissa); K. Czene (Kamila); J.A. Knight (Julia); R.A.E.M. Tollenaar (Rob); M.W. Beckmann (Matthias); A. Ziogas (Argyrios); M.R. Christiaens (Marie Rose); J.M. Collee (Margriet); M.W.R. Reed (Malcolm); G. Severi (Gianluca); F. Marme (Federick); S. Margolin (Sara); J.E. Olson (Janet); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); A. Miron (Alexander); N.V. Bogdanova (Natalia); M. Shah (Mitul); C. Blomqvist (Carl); A. Broeks (Annegien); M.E. Sherman (Mark); K. Phillips (Kelly); J. Li (Jingmei); J. Liu (Jianjun); G. Glendon (Gord); C.M. Seynaeve (Caroline); A.B. Ekici (Arif); K. Leunen; M. Kriege (Mieke); S.S. Cross (Simon); L. Baglietto (Laura); C. Sohn (Christof); X. Wang (Xing); V. Kataja (Vesa); A.L. Børresen-Dale (Anne Lise); A. Meyer (Andreas); D.F. Easton (Douglas); M.K. Schmidt (Marjanka); S.E. Bojesen (Stig)

    2012-01-01

    textabstractPurpose: We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. Patients and Methods: From 22 studies participating in the Breast C

  2. CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer

    NARCIS (Netherlands)

    M. Weischer (Maren); B.G. Nordestgaard (Børge); P.D.P. Pharoah (Paul); M.K. Bolla (Manjeet); H. Nevanlinna (Heli); L.J. van 't Veer (Laura); M. García-Closas (Montserrat); J.L. Hopper (John); P. Hall (Per); I.L. Andrulis (Irene); P. Devilee (Peter); P.A. Fasching (Peter); H. Anton-Culver (Hoda); D. Lambrechts (Diether); M.J. Hooning (Maartje); A. Cox (Angela); G.G. Giles (Graham); B. Burwinkel (Barbara); A. Lindblom (Annika); F.J. Couch (Fergus); A. Mannermaa (Arto); G.G. Alnæs (Grethe); E.M. John (Esther); T. Dörk (Thilo); H. Flyger (Henrik); A.M. Dunning (Alison); Q. Wang (Qing); T.A. Muranen (Taru); R.R. van Hien (Richard); J.D. Figueroa (Jonine); M.C. Southey (Melissa); K. Czene (Kamila); J.A. Knight (Julia); R.A.E.M. Tollenaar (Rob); M.W. Beckmann (Matthias); A. Ziogas (Argyrios); M.R. Christiaens (Marie Rose); J.M. Collee (Margriet); M.W.R. Reed (Malcolm); G. Severi (Gianluca); F. Marme (Federick); S. Margolin (Sara); J.E. Olson (Janet); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); A. Miron (Alexander); N.V. Bogdanova (Natalia); M. Shah (Mitul); C. Blomqvist (Carl); A. Broeks (Annegien); M.E. Sherman (Mark); K. Phillips (Kelly); J. Li (Jingmei); J. Liu (Jianjun); G. Glendon (Gord); C.M. Seynaeve (Caroline); A.B. Ekici (Arif); K. Leunen; M. Kriege (Mieke); S.S. Cross (Simon); L. Baglietto (Laura); C. Sohn (Christof); X. Wang (Xing); V. Kataja (Vesa); A.L. Børresen-Dale (Anne Lise); A. Meyer (Andreas); D.F. Easton (Douglas); M.K. Schmidt (Marjanka); S.E. Bojesen (Stig)

    2012-01-01

    textabstractPurpose: We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. Patients and Methods: From 22 studies participating in the Breast

  3. Between postnationality and postcoloniality

    DEFF Research Database (Denmark)

    Zhang, Chenchen

    2014-01-01

    This paper brings together the project of human rights and that of the European Union under examination vis-à-vis the rights of non-citizens, and in particular the rights of undocumented migrants. In so doing, it attempts to grasp the tension between the postnational articulations of membership, ...

  4. B-Amyloid Precursor Protein Staining of the Brain in Sudden Infant and Early Childhood Death

    DEFF Research Database (Denmark)

    Jensen, Lisbeth Lund; Banner, Jytte; Ulhøi, Benedicte Parm

    2013-01-01

    To develop and validate a scoring method for assessing β-amyloid precursor protein (APP) staining in cerebral white matter and to investigate the occurrence, amount and deposition pattern based on the cause of death in infants and young children.......To develop and validate a scoring method for assessing β-amyloid precursor protein (APP) staining in cerebral white matter and to investigate the occurrence, amount and deposition pattern based on the cause of death in infants and young children....

  5. Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid fatty acid composition in a muscle type specific manner in sheep

    DEFF Research Database (Denmark)

    Hou, Lei; Kongsted, Alice; Ghoreishi, S. M.;

    2013-01-01

    requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet...... determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein......, but increased PGC1a expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes...

  6. 出生后早期营养过度导致成年期胰岛素抵抗%Early postnatal overnutrition results in insulin resistance in adulthood

    Institute of Scientific and Technical Information of China (English)

    贝斐; 蔡威

    2014-01-01

    出生后早期是生长发育的关键期,如营养过度会导致成年期持续性和永久性的体重过重/肥胖和胰岛素抵抗等代谢综合征表现,胰岛素作用的重要靶器官如肝脏、脂肪组织、骨骼肌和中枢神经系统均可出现胰岛素抵抗.涉及的主要机制包括胰岛素信号通路异常、游离脂肪酸和部分脂肪因子分泌增加、氧化应激、摄食/厌食神经调节失衡、下丘脑-垂体-肾上腺轴/糖皮质激素调节失常以及表观遗传的作用等.建议出生后早期避免营养过度,以减少成年期胰岛素抵抗发生的危险.%Overnutrition during the early postnatal life,a critical time window for growth and development,may induce metabolic syndrome later in life,including overweight/obesity and insulin resistance.The important target organs of insulin,such as liver,adipose tissue,skeletal muscle,and central nervous systems show insulin resistance.The involved mechanisms include abnormality of insulin signal pathway,increment of free fatty acid and some adipocytokines,oxidative stress,maladjustment of orexigenic and anorexigenic neuron,modifications of the hypothalamic-pituitary-adrenal glucocorticoid axis as well as epigenetic,etc.Hence,overnutrition should be avoided during the early postnatal life,so as to decrease the risk of developing long-term insulin resistance.

  7. Children who acquire HIV infection perinatally are at higher risk of early death than those acquiring infection through breastmilk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Renaud Becquet

    Full Text Available BACKGROUND: Assumptions about survival of HIV-infected children in Africa without antiretroviral therapy need to be updated to inform ongoing UNAIDS modelling of paediatric HIV epidemics among children. Improved estimates of infant survival by timing of HIV-infection (perinatally or postnatally are thus needed. METHODOLOGY/PRINCIPAL FINDINGS: A pooled analysis was conducted of individual data of all available intervention cohorts and randomized trials on prevention of HIV mother-to-child transmission in Africa. Studies were right-censored at the time of infant antiretroviral initiation. Overall mortality rate per 1000 child-years of follow-up was calculated by selected maternal and infant characteristics. The Kaplan-Meier method was used to estimate survival curves by child's HIV infection status and timing of HIV infection. Individual data from 12 studies were pooled, with 12,112 children of HIV-infected women. Mortality rates per 1,000 child-years follow-up were 39.3 and 381.6 for HIV-uninfected and infected children respectively. One year after acquisition of HIV infection, an estimated 26% postnatally and 52% perinatally infected children would have died; and 4% uninfected children by age 1 year. Mortality was independently associated with maternal death (adjusted hazard ratio 2.2, 95%CI 1.6-3.0, maternal CD4<350 cells/ml (1.4, 1.1-1.7, postnatal (3.1, 2.1-4.1 or peri-partum HIV-infection (12.4, 10.1-15.3. CONCLUSIONS/RESULTS: These results update previous work and inform future UNAIDS modelling by providing survival estimates for HIV-infected untreated African children by timing of infection. We highlight the urgent need for the prevention of peri-partum and postnatal transmission and timely assessment of HIV infection in infants to initiate antiretroviral care and support for HIV-infected children.

  8. The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

    Science.gov (United States)

    Vardavas, C I; Hohmann, C; Patelarou, E; Martinez, D; Henderson, A J; Granell, R; Sunyer, J; Torrent, M; Fantini, M P; Gori, D; Annesi-Maesano, I; Slama, R; Duijts, L; de Jongste, J C; Aurrekoetxea, J J; Basterrechea, M; Morales, E; Ballester, F; Murcia, M; Thijs, C; Mommers, M; Kuehni, C E; Gaillard, E A; Tischer, C; Heinrich, J; Pizzi, C; Zugna, D; Gehring, U; Wijga, A; Chatzi, L; Vassilaki, M; Bergström, A; Eller, E; Lau, S; Keil, T; Nieuwenhuijsen, M; Kogevinas, M

    2016-07-01

    Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

  9. Wnt signaling activates Shh signaling in early postnatal intervertebral discs, and re-activates Shh signaling in old discs in the mouse.

    Science.gov (United States)

    Winkler, Tamara; Mahoney, Eric J; Sinner, Debora; Wylie, Christopher C; Dahia, Chitra Lekha

    2014-01-01

    Intervertebral discs (IVDs) are strong fibrocartilaginous joints that connect adjacent vertebrae of the spine. As discs age they become prone to failure, with neurological consequences that are often severe. Surgical repair of discs treats the result of the disease, which affects as many as one in seven people, rather than its cause. An ideal solution would be to repair degenerating discs using the mechanisms of their normal differentiation. However, these mechanisms are poorly understood. Using the mouse as a model, we previously showed that Shh signaling produced by nucleus pulposus cells activates the expression of differentiation markers, and cell proliferation, in the postnatal IVD. In the present study, we show that canonical Wnt signaling is required for the expression of Shh signaling targets in the IVD. We also show that Shh and canonical Wnt signaling pathways are down-regulated in adult IVDs. Furthermore, this down-regulation is reversible, since re-activation of the Wnt or Shh pathways in older discs can re-activate molecular markers of the IVD that are lost with age. These data suggest that biological treatments targeting Wnt and Shh signaling pathways may be feasible as a therapeutic for degenerative disc disease.

  10. Metabolic trajectories based on 1H NMR spectra of urines from sheep exposed to nutritional challenges during prenatal and early postnatal life

    DEFF Research Database (Denmark)

    Nyberg, Nils; Nielsen, Mette Benedicte Olaf; Jaroszewski, Jerzy W.

    2010-01-01

    1H NMR metabolic profiles of urine from sheep exposed to prenatal nutritional restriction (n = 19) and a control group with normal prenatal nutritional requirements (n = 19), followed by either conventional (n = 10 + 10) or high carbohydrate high fat postnatal diet (n = 9 + 9), were studied. Urine...... was sampled from 2, 6, 19 and 24-month-old animals receiving differential dietary treatments during the first 6 months and the same normal diet later. Principal component analysis of 1H NMR spectra (n = 164) showed a V-shaped metabolic trajectory as a function of age and diet, starting with urines with a high...... amount of glucose, indicative of monogastric-like metabolism, and exhibiting concomitant increase of metabolites related to rumen microflora (mainly glycine conjugates of benzoic and phenylacetic acid) as the ruminal metabolism developed. Urines from young (2-month-old) animals exposed to prenatal...

  11. Post-natal myogenic and adipogenic developmental: defects and metabolic impairment upon loss of A-type lamins.

    Science.gov (United States)

    Kubben, Nard; Voncken, Jan Willem; Konings, Gonda; van Weeghel, Michel; van den Hoogenhof, Maarten Mg; Gijbels, Marion; van Erk, Arie; Schoonderwoerd, Kees; van den Bosch, Bianca; Dahlmans, Vivian; Calis, Chantal; Houten, Sander M; Misteli, Tom; Pinto, Yigal M

    2011-01-01

    A-type lamins are a major component of the nuclear lamina. Mutations in the LMNA gene, which encodes the A-type lamins A and C, cause a set of phenotypically diverse diseases collectively called laminopathies. While adult LMNA null mice show various symptoms typically associated with laminopathies, the effect of loss of lamin A/C on early post-natal development is poorly understood. Here we developed a novel LMNA null mouse (LMNA(GT-/-)) based on genetrap technology and analyzed its early post-natal development. We detect LMNA transcripts in heart, the outflow tract, dorsal aorta, liver and somites during early embryonic development. Loss of A-type lamins results in severe growth retardation and developmental defects of the heart, including impaired myocyte hypertrophy, skeletal muscle hypotrophy, decreased amounts of subcutaneous adipose tissue and impaired ex vivo adipogenic differentiation. These defects cause death at 2 to 3 weeks post partum associated with muscle weakness and metabolic complications, but without the occurrence of dilated cardiomyopathy or an obvious progeroid phenotype. Our results indicate that defective early post-natal development critically contributes to the disease phenotypes in adult laminopathies.

  12. Mapping the risk of sudden oak death in Oregon: prioritizing locations for early detection and eradication

    Science.gov (United States)

    V& aacute; clavík Tom& aacute; & scaron; Alan Kanaskie; Ellen Goheen; Janet Ohmann; Everett Hansen; Ross Meentemeyer

    2010-01-01

    Phytophthora ramorum was first discovered in forests of southwestern Oregon in 2001. Despite intense eradication efforts, disease continues to spread from initially infested sites because of the late discovery of disease outbreaks and incomplete detection. Here we present two GIS predictive models of sudden oak death (SOD) establishment and spread...

  13. A tragic early death has stopped potential revealing knowledge on doping in Russia

    DEFF Research Database (Denmark)

    Christiansen, Ask Vest; Gleaves, John

    2016-01-01

    On 14 February 2016, Nikita Kamaev died of a “massive heart attack”. Kamaev was the executive director of Russia's anti-doping agency, RUSADA, from 2011 to 2015. His death came 10 weeks after he stepped down as head of RUSADA since he knew that he could not continue on the post after WADA on 18 N...

  14. Treatment with garlic restores membrane thiol content and ameliorates lead induced early death of erythrocytes in mice.

    Science.gov (United States)

    Sarkar, Avik; Sengupta, Dipanwita; Mandal, Samir; Sen, Gargi; Dutta Chowdhury, Kaustav; Chandra Sadhukhan, Gobinda

    2015-04-01

    Sequelae of chronic lead (Pb(2+) ) toxicity includes anemia that is partially due to early death of erythrocytes characterized by excess accumulation of ROS and downregulation of antioxidant system causing oxidative stress and externalization of phosphatidylserine. In this study, pathophysiological based therapeutic application of garlic was evaluated against erythrocyte death. Results suggest that garlic administration prevents oxidative stress, restored the antioxidant balance in erythrocytes of Pb(2+) exposed mice. Moreover, in vitro studies revealed that activity of both scramblase and aminophospholipid translocase could be changed by modifying the critical sulfhydryl groups in presence of dithiothreitol during Pb(2+) exposure. Data also indicated that garlic treatment in Pb(2+) exposed mice exhibited sharp decline in PS exposure and increase in erythrocyte membrane thiol group followed by increase in aminophospholipid translocase activity and decline in scramblase activity. Findings indicated that garlic has the ability to restore the lifespan of erythrocytes during Pb(2+) exposure.

  15. Differentiation of expression proifles of two calcineurin subunit genes in chicken skeletal muscles during early postnatal growth depending on anatomical location of muscles and breed

    Institute of Scientific and Technical Information of China (English)

    SHAN Yan-ju; XU Wen-juan; SHU Jing-ting; ZHANG Ming; SONG Wei-tao; TAO Zhi-yun; ZHU Chun-hong; LI Hui-fang

    2016-01-01

    Calcineurin (Cn or CaN) is implicated in the control of skeletal muscle ifber phenotype and hypertrophy. However, little information is available concerning the expression of Cn in chickens. In the present study, the expression of two Cn subunit genes (CnAα andCnB1) was quantiifed by qPCR in the lateral gastrocnemius (LG, mainly composing of red fast-twitch myoifbers), the soleus (mainly composing of red slow-twitch myoifbers) and the extensor digitorum longus (EDL, mainly composing of white fast-twitch myoifbers) from Qingyuan partridge chickens (QY, slow-growing chicken breed) and Recessive White chickens (RW, fast-growing chicken breed) on different days (1, 8, 22, 36, 50 and 64 days post-hatching). Although CnAα andCnB1 gene expressions were variable with different trends in different skeletal muscles in the two chicken breeds during postnatal growth, it is highly muscle phenotype and breed speciifc. In general, the levels ofCnAαandCnB1gene expressions of the soleus were lower than those of EDL and LG in both chicken breeds at the same stages. Compared be-tween the two chicken breeds, the levels ofCnAα gene expression of the three skeletal muscles in QY chickens were higher than those in RW chickens on days 1 and 22. However, on day 64, the levels of bothCnAα andCnB1 gene expressions of the three skeletal muscles were lower in QY chickens than those in RW chickens. Correlation analysis of the levels of CnAα andCnB1 gene expressions of the same skeletal muscle showed that there were positive correlations for al three skeletal muscle tissues in two chicken breeds. These results provide some valuable clues to understand the role of Cn in the development of chicken skeletal muscles, with a function that may be related to meat quality.

  16. Over half the hair cells in the mouse utricle first appear after birth, with significant numbers originating from early postnatal mitotic production in peripheral and striolar growth zones.

    Science.gov (United States)

    Burns, Joseph C; On, Doan; Baker, Wendy; Collado, M Sol; Corwin, Jeffrey T

    2012-10-01

    Many non-mammalian vertebrates produce hair cells throughout life and recover from hearing and balance deficits through regeneration. In contrast, embryonic production of hair cells declines sharply in mammals where deficits from hair cell losses are typically permanent. Hair cell density estimates recently suggested that the vestibular organs of mice continue to add hair cells after birth, so we undertook comprehensive counting in murine utricles at different ages. The counts show that 51% of the hair cells in adults arise during the 2 weeks after birth. Immature hair cells are most common near the neonatal macula's peripheral edge and striola, where anti-Ki-67 labels cycling nuclei in zones that appear to contain niches for supporting-cell-like stem cells. In vivo lineage tracing in a novel reporter mouse where tamoxifen-inducible supporting cell-specific Cre expression switched tdTomato fluorescence to eGFP fluorescence showed that proteolipid-protein-1-expressing supporting cells are an important source of the new hair cells. To assess the contributions of postnatal cell divisions, we gave mice an injection of BrdU or EdU on the day of birth. The labels were restricted to supporting cells 1 day later, but by 12 days, 31% of the labeled nuclei were in myosin-VIIA-positive hair cells. Thus, hair cell populations in neonatal mouse utricles grow appreciably through two processes: the progressive differentiation of cells generated before birth and the differentiation of new cells arising from divisions of progenitors that progress through S phase soon after birth. Subsequent declines in these processes coincide with maturational changes that appear unique to mammalian supporting cells.

  17. Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells.

    Science.gov (United States)

    Monetti, Emanuela; Kadono, Takashi; Tran, Daniel; Azzarello, Elisa; Arbelet-Bonnin, Delphine; Biligui, Bernadette; Briand, Joël; Kawano, Tomonori; Mancuso, Stefano; Bouteau, François

    2014-03-01

    Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·(-)) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·(-) generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca(2+)]cyt increase and singlet oxygen production, do not seem to be involved in PCD.

  18. Creatinine, eGFR and association with myocardial infarction, ischemic heart disease and early death in the general population

    DEFF Research Database (Denmark)

    Sibilitz, Kirstine L; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    OBJECTIVE: We tested the hypothesis that moderately elevated plasma creatinine levels and decreased levels of estimated glomerular filtration rate (eGFR) are associated with increased risk of myocardial infarction, ischemic heart disease, and early death in the general population. METHODS: We...... studied 10,489 individuals with a plasma creatinine measurement and calculated eGFR from the Danish general population, of which 1498 developed myocardial infarction, 3001 ischemic heart disease, and 7573 died during 32 years follow-up. RESULTS: Cumulative incidences of myocardial infarction and ischemic...... heart disease as a function of age increased with increasing levels of creatinine, and survival decreased (log-rank trends: creatinine levels

  19. IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients

    Energy Technology Data Exchange (ETDEWEB)

    Bacci, M.R.; Leme, R.C.P.; Zing, N.P.C. [Departamento de Cliníca Médica, Faculdade de Medicina do ABC, Santo André, SP (Brazil); Murad, N. [Departamento de Cardiologia, Faculdade de Medicina do ABC, Santo André, SP (Brazil); Adami, F.; Hinnig, P.F. [Departamento de Cliníca Médica, Faculdade de Medicina do ABC, Santo André, SP (Brazil); Feder, D. [Departamento de Farmacologia, Faculdade de Medicina do ABC, Santo André, SP (Brazil); Chagas, A.C.P. [Departamento de Cardiologia, Faculdade de Medicina do ABC, Santo André, SP (Brazil); Fonseca, F.L.A. [Departamento de Cliníca Médica, Faculdade de Medicina do ABC, Santo André, SP (Brazil)

    2015-02-24

    Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.

  20. AGPAT2 is essential for postnatal development and maintenance of white and brown adipose tissue

    Directory of Open Access Journals (Sweden)

    Kelly M. Cautivo

    2016-07-01

    Conclusion: We conclude that lipodystrophy in Agpat2−/− mice results from postnatal cell death of adipose tissue in association with acute local inflammation. It is possible that AGPAT2 deficient adipocytes have an altered lipid filling or a reduced capacity to adapt the massive lipid availability associated with postnatal feeding.

  1. Risk factors for antenatal depression, postnatal depression and parenting stress

    OpenAIRE

    Leigh, Bronwyn; Milgrom, Jeannette

    2008-01-01

    Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the stro...

  2. Risk factors for antenatal depression, postnatal depression and parenting stress

    OpenAIRE

    Milgrom Jeannette; Leigh Bronwyn

    2008-01-01

    Abstract Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite...

  3. Risk factors for antenatal depression, postnatal depression and parenting stress

    OpenAIRE

    Milgrom Jeannette; Leigh Bronwyn

    2008-01-01

    Abstract Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite...

  4. Risk factors for antenatal depression, postnatal depression and parenting stress

    OpenAIRE

    Leigh, Bronwyn; Milgrom, Jeannette

    2008-01-01

    Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the stro...

  5. High CD10 expression in lymph node metastases from surgically treated prostate cancer independently predicts early death.

    Science.gov (United States)

    Fleischmann, Achim; Rocha, Carla; Saxer-Sekulic, Nikolina; Zlobec, Inti; Sauter, Guido; Thalmann, George N

    2011-06-01

    Patients with nodal positive prostate cancers are an important cohort with poorly defined risk factors. CD10 is a cell surface metallopeptidase that has been suggested to play a role in prostate cancer progression. CD10 expression was evaluated in 119 nodal positive prostate cancer patients using tissue microarrays constructed from primary tumors and lymph node metastases. All patients underwent radical prostatectomy and standardized extended lymphadenectomy. They had no neoadjuvant therapy and received deferred androgen deprivation. In the primary tumor, high CD10 expression was significantly associated with earlier death from disease when compared with low CD10 expression (5-year survival 73.7% vs. 91.8%; p = 0.043). In the metastases, a high CD10 expression was significantly associated with larger total size of metastases (median 11.4 vs. 6.5 mm; p = 0.015), earlier death of disease (5-year survival 71.5% vs. 87.3%; p = 0.017), and death of any cause (5-year survival 70.0% vs. 87.2%; p = 0.001) when compared with low CD10 expression. CD10 expression in the metastases added independent prognostic information for overall survival (p = 0.029) after adjustment for Gleason score of the primary tumor, nodal tumor burden, and resection margins. In conclusion, a high CD10 expression in prostate cancer predicts early death. This information is inherent in the primary tumors and in the lymph node metastases and might help to personalize patient management.

  6. The long-term impact of early parental death: lessons from a narrative study.

    Science.gov (United States)

    Ellis, Jackie; Dowrick, Chris; Lloyd-Williams, Mari

    2013-02-01

    To explore the individual experiences of those who had experienced the death of a parent(s) before the age of 18, and investigate how such experiences were perceived to impact on adult life. An exploratory qualitative design using written (n = 5) and oral (n = 28) narratives and narrative analysis was adopted to explore the experiences 33 adults (7 men and 26 women) who had experienced parental death during childhood. UK participants: Individuals living in the North West of England who had lost a parent(s) before the age of 18. Views of adults bereaved of a parent before the age of 18 of impact of parental loss in adult life. While individual experiences of bereavement in childhood were unique and context bound, the narratives were organized around three common themes: disruptions and continuity, the role of social networks and affiliations and communication and the extent to which these dynamics mediated the bereavement experience and the subsequent impact on adult life. Specifically they illustrate how discontinuity (or continuity that does not meet the child's needs), a lack of appropriate social support for both the child and surviving parent and a failure to provide clear and honest information at appropriate time points relevant to the child's level of understanding was perceived to have a negative impact in adulthood with regards to trust, relationships, self-esteem, feeling of self-worth loneliness and isolation and the ability to express feelings. A model is suggested for identifying and supporting those that may be more vulnerable to less favourable outcomes in adult life. The findings suggest that if the negative consequences are to be minimized it is crucial that guidelines for 'best practice' that recognize the complex nature of the bereavement experience are followed.

  7. Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish

    Science.gov (United States)

    Mishra, Shikha; Guan, Jian; Plovie, Eva; Seldin, David C.; Connors, Lawreen H.; Merlini, Giampaolo; Falk, Rodney H.; MacRae, Calum A.

    2013-01-01

    Systemic amyloid light-chain (AL) amyloidosis is associated with rapidly progressive and fatal cardiomyopathy resulting from the direct cardiotoxic effects of circulating AL light chain (AL-LC) proteins and the indirect effects of AL fibril tissue infiltration. Cardiac amyloidosis is resistant to standard heart failure therapies, and, to date, there are limited treatment options for these patients. The mechanisms underlying the development of cardiac amyloidosis and AL-LC cardiotoxicity are largely unknown, and their study has been limited by the lack of a suitable in vivo model system. Here, we establish an in vivo zebrafish model of human AL-LC-induced cardiotoxicity. AL-LC isolated from AL cardiomyopathy patients or control nonamyloidogenic LC protein isolated from multiple myeloma patients (Con-LC) was directly injected into the circulation of zebrafish at 48 h postfertilization. AL-LC injection resulted in impaired cardiac function, pericardial edema, and increased cell death relative to Con-LC, culminating in compromised survival with 100% mortality within 2 wk, independent of AL fibril deposition. Prior work has implicated noncanonical p38 MAPK activation in the pathogenesis of AL-LC-induced cardiotoxicity, and p38 MAPK inhibition via SB-203580 rescued AL-LC-induced cardiac dysfunction and cell death and attenuated mortality in zebrafish. This in vivo zebrafish model of AL-LC cardiotoxicity demonstrates that antagonism of p38 MAPK within the AL-LC cardiotoxic signaling response may serve to improve cardiac function and mortality in AL cardiomyopathy. Furthermore, this in vivo model system will allow for further study of the molecular underpinnings of AL cardiotoxicity and identification of novel therapeutic strategies. PMID:23624626

  8. Infant cynomolgus monkeys exposed to denosumab in utero exhibit an osteoclast-poor osteopetrotic-like skeletal phenotype at birth and in the early postnatal period.

    Science.gov (United States)

    Boyce, Rogely W; Varela, Aurore; Chouinard, Luc; Bussiere, Jeanine L; Chellman, Gary J; Ominsky, Michael S; Pyrah, Ian T

    2014-07-01

    RANKL is a key regulator of bone resorption and osteoclastogenesis. Denosumab is a fully human IgG2 monoclonal antibody that inhibits bone resorption by binding and inhibiting the activity of RANKL. To determine the effects of denosumab on pre- and postnatal skeletal growth and development, subcutaneous injections of 0 (control) or 50 mg/kg/month denosumab were given to pregnant cynomolgus monkeys from approximately gestation day (GD) 20 until parturition (up to 6 doses). For up to 6 months postpartum (birth day [BD] 180/181), evaluation of the infants included skeletal radiographs, bone biomarkers, and oral examinations for assessment of tooth eruption. Infant bones were collected at necropsy for densitometry, biomechanical testing, and histopathologic evaluation from control and denosumab-exposed infants on BD1 (or within 2 weeks of birth) and BD181, and from infants that died or were euthanized moribund from BD5 to BD69. In all denosumab-exposed infants, biomarkers of bone resorption and formation were markedly decreased at BD1 and BD14 and slightly greater at BD91 vs. control, then similar to control values by BD181. Spontaneous long bone fractures were detected clinically or radiographically in 4 denosumab-exposed infants at BD28 and BD60, with evidence of radiographic healing at ≥BD60. In BD1 infants exposed to denosumab in utero, radiographic evaluations of the skeleton revealed decreased long bone length; a generalized increased radio-opacity of the axial and appendicular skeleton and bones at the base of the skull with decreased or absent marrow cavities, widened growth plates, flared/club-shaped metaphysis, altered jaw/skull shape, and reduced jaw length; and delayed development of secondary ossification centers. Densitometric evaluations in these infants demonstrated a marked increase in bone mineral density at trabecular sites, but cortical bone mineral density was decreased. Histologically, long bone cortices were attenuated and there was an absence

  9. Noninvasive indocyanine green plasma disappearance rate predicts early complications, graft failure or death after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Lutz Schneider; Martin Spiegel; Sebastian Latanowicz; Markus A Weigand; Jan Schmidt; Jens Werner; Wolfgang Stremmel; Christoph Eisenbach

    2011-01-01

    BACKGROUND: Early  detection  of  graft  malfunction  or postoperative  complications  is  essential  to  save  patients  and organs after orthotopic liver transplantation (OLT). Predictive tests  for  graft  dysfunction  are  needed  to  enable  earlier implementation  of  organ-saving  interventions  following transplantation. This study was undertaken to assess the value of indocyanine green plasma disappearance rates (ICG-PDRs) for predicting postoperative complications, graft dysfunction, and patient survival following OLT. METHODS: Eighty-six patients undergoing OLT were included in this single-centre trial. ICG-PDR was assessed daily for the first 7 days following OLT. Endpoints were graft loss or death within 30 days and postoperative complications, graft loss, or death within 30 days. RESULTS: Postoperative complications of 31 patients included deaths (12 patients) or graft losses. ICG-PDR was significantly different in patients whose endpoints were graft loss or death beginning from day 3 and in those whose endpoints were graft-loss,  death,  or  postoperative  complications  beginning  from day  4  after  OLT.  For  day  7  measurements,  receiver  operating characteristic  curve  analysis  revealed  an  ICG-PDR  cut-off  for predicting  death  or  graft  loss  of  9.6%  per  min  (a  sensitivity of 75.0%, a specificity of 72.6%, positive predictive value 0.35, negative predictive value 0.94). For prediction of graft loss, death, or postoperative complications, the ICG-PDR cut-off was 12.3% per min (a sensitivity of 68.9%,

  10. Comorbidity, Use of Common Medications, and Risk of Early Death in Patients with Localized or Locally Advanced Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Carsten Nieder

    2011-01-01

    Full Text Available In this paper, we analyze predictive factors for early death from comorbidity (defined as death within 3 years from diagnosis and unrelated to prostate cancer in patients with localized or locally advanced prostate cancer. Such information may guide individually tailored treatment or observation strategies, and help to avoid overtreatment. We retrospectively analyzed baseline parameters including information on comorbidity and medication use among 177 patients (median age at diagnosis 70 years. Actuarial survival analyses were performed. During the first 3 years, two patients (1.1% died from progressive prostate cancer after they had developed distant metastases. The risk of dying from other causes (3.4% was numerically higher, although not to a statistically significant degree. Six patients who died from other causes had age-adjusted Charlson comorbidity index (CCI scores ≥5 (CCI is a sum score where each comorbid condition is assigned with a score depending on the risk of dying associated with this condition. The main comorbidity was cardiovascular disease. The two statistically significant predictive factors were medication use and age-adjusted CCI score ≥5 (univariate analysis. However, medication use was not an independent factor as all patients with age-adjusted CCI score ≥5 also used at least one class of medication. Median survival was 30 months in patients with age-adjusted CCI score ≥5. Prediction of non-prostate cancer death may be important to prevent overtreatment in patients who are more threatened by comorbidity. Our data suggest that simple parameters such as use of medications vs. none, or presence of serious cardiac disease vs. none, are not sufficient, and that age-adjusted CCI scores outperform the other factors included in our analysis.

  11. Confounding factors for early death in incident end-stage renal disease patients: Role of emergency dialysis start.

    Science.gov (United States)

    Descamps, Chrystèle; Labeeuw, Michel; Trolliet, Pierre; Cahen, Rémi; Ecochard, René; Pouteil-Noble, Claire; Villar, Emmanuel

    2011-01-01

    Hemodialysis (HD) has been associated with higher 1-year mortality than peritoneal dialysis (PD) after dialysis start. Confounding effects of late referral, emergency dialysis start, or start with central venous catheter on this association have never been studied concomitantly. Survival was studied among the 495 incident dialysed patients in our department from 1995 to 2006 and followed at least 1 year until December 31, 2007. Nested Cox models adjusted on patient characteristics explored factors associated with 1-year and ≥1-year mortality. Hemodialysis patients were 332 (67.1%), 104 (21.0%) were late referred (dialysis in emergency, and 144 (29.1%) started with central venous catheter. When adjusted only on age, sex, and comorbidities, HD was associated with poor 1-year outcome: adjusted hazard ratio (aHR) for death in HD vs. PD was 1.77, P=0.02. In fully adjusted model, among first dialysis feature variables, only emergency dialysis start was significantly associated with 1-year mortality: aHR 1.53, P=0.02. Dialysis modality was not associated with 1-year mortality rates in this fully adjusted model: aHR in HD vs. PD became 1.03, P=0.91. In ≥1-year period, HD was associated with lower mortality than PD (aHR 0.61, P=0.004), whereas other first dialysis features were not associated with death. Other factors associated with death were age, type 2 diabetes, peripheral vascular disease, heart failure, and hepatic failure. Negative association between HD and 1-year survival on dialysis was explained by confounders. Emergency dialysis start was strongly associated with early mortality on dialysis. Its prevention may improve patient survival. © 2011 The Authors. Hemodialysis International © 2011 International Society for Hemodialysis.

  12. Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols. EORTC Lymphoma Cooperative Group.

    Science.gov (United States)

    Henry-Amar, M; Hayat, M; Meerwaldt, J H; Burgers, M; Carde, P; Somers, R; Noordijk, E M; Monconduit, M; Thomas, J; Cosset, J M

    1990-11-01

    The risk of dying from different causes after Hodgkin's disease (HD) therapy has been quantified from a series of 1,449 patients with early stages included in four successive clinical trials conducted by the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Cooperative Group since 1963. Overall, 240 patients died and the 15-year survival rate was 69% whereas the expected rate was 95%. The standardized mortality ratio (SMR) technique was used to quantify excess deaths as a function of time since first therapy. At each interval, SMR was significantly increased, giving: 0-3 year, 8.86 (p less than 0.001); 4-6 year, 9.25 (p less than 0.001); 7-9 year, 7.08 (p less than 0.001); 10-12 year, 9.53 (p less than 0.001); 13-15 year, 4.37 (p less than 0.01); and 16+ years, 3.80 (p less than 0.05). While the proportion of deaths as a consequence of HD progression, treatment side-effect, and intercurrent disease decreased with time, that of second cancer and cardiac failure peaked during the 10-12 year post-treatment interval. After 15 years of follow-up, the risk of dying from causes other than HD continued to increase. These findings indicate that although probably cured from HD, patients are at higher risk for death than expected, a risk that might be a consequence of therapy.

  13. Lanthanum Prevents Salt Stress-induced Programmed Cell Death in Rice Root Tip Cells by Controlling Early Induction Events

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In a previous study, a salt stress-induced programmed cell death (PCD) model was established in rice root tip cells. Here,by using Wuyunjing 8th rice seedlings, the effects of lanthanum on salt stress-induced PCD early events were studied. The peroxidase (APX). Imidazole (20 mmol/L), the inhibitor of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), could alleviate the occurrence of PCD obviously, and such alleviation could be enhanced by the addition of La3+,indicating the involvement of NADPH oxidase in the salt stress-induced PCD process. Taken together, lanthanum could prevent salt stress-induced PCD occurrence in the rice root tip cells by blocking the calcium influx under stress, which was followed by inhibiting calcium-dependent NADPH oxidase activity to prevent O2·-production and, enhancing the cytosolic antioxidative enzyme activities to scavenge the reactive oxygen species.

  14. Dissecting the proteome dynamics of the early heat stress response leading to plant survival or death in Arabidopsis.

    Science.gov (United States)

    Echevarría-Zomeño, Sira; Fernández-Calvino, Lourdes; Castro-Sanz, Ana B; López, Juan Antonio; Vázquez, Jesús; Castellano, M Mar

    2016-06-01

    In many plant species, an exposure to a sublethal temperature triggers an adaptative response called acclimation. This response involves an extensive molecular reprogramming that allows the plant to further survive to an otherwise lethal increase of temperature. A related response is also launched under an abrupt and lethal heat stress that, in this case, is unable to successfully promote thermotolerance and therefore ends up in plant death. Although these molecular programmes are expected to have common players, the overlapping degree and the specific regulators of each process are currently unknown. We have carried out a high-throughput comparative proteomics analysis during acclimation and during the early stages of the plant response to a severe heat stress that lead Arabidopsis seedlings either to survival or death. This analysis dissects these responses, unravels the common players and identifies the specific proteins associated with these different fates. Thermotolerance assays of mutants in genes with an uncharacterized role in heat stress demonstrate the relevance of this study to uncover both positive and negative heat regulators and pinpoint a pivotal role of JR1 and BAG6 in heat tolerance.

  15. Parvalbumin expression in visual cortical interneurons depends on neuronal activity and TrkB ligands during an Early period of postnatal development.

    Science.gov (United States)

    Patz, Silke; Grabert, Jochen; Gorba, Thorsten; Wirth, Marcus J; Wahle, Petra

    2004-03-01

    The differentiation of cortical interneurons is controlled by environmental factors. Here, we describe the role of activity and neurotrophins in regulating parvalbumin (PARV) expression using organotypic cultures (OTC) of rat visual cortex as model system. In OTC, PARV expression was dramatically delayed. The organotypic proportion of approximately 6% PARV neurons was not established before 50-70 DIV, whereas in vivo all neurons are present until P20. Thalamic afferents increased cortical PARV mRNA in OTC, but not to the age-matched in vivo level. During the first 10 DIV, BDNF and NT-4 accelerated PARV mRNA expression in a Trk receptor and MEK2 dependent manner. The BDNF action required PI3 kinase signalling. PARV expression required activity. The proportion of neurons which managed to up-regulate PARV was inversely related to the duration of early transient periods of activity deprivation. Long-term activity-deprived OTC completely failed to up-regulate PARV mRNA. Both TrkB ligands failed to promote PARV expression in activity-deprived OTC. However, a few basket and chandelier neurons were observed, suggesting that the development of class-specific morphological features is activity-independent. Once established, PARV expression became resistant to late-onset activity deprivation. In conclusion, PARV expression depended on activity and TrkB ligands which appear to prime the PARV expression already before its developmental onset.

  16. Origination and death of petroleum systems along the Late Jurassic/Early Cretaceous northern Tethyan margin

    Energy Technology Data Exchange (ETDEWEB)

    Golonka, J. [Mobil Research and Development Corp., Dallas, TX (United States); Kiessling, W. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Geologie und Mineralogie; Krobicki, M. [Academy of Mining and Metallurgy, Cracow (Poland). Inst. of Petroleum Engineering; Bocharova, N.Y. [Russian Academy of Sciences, Moscow (Russian Federation). Center for Program Studies

    1997-09-01

    Breakup of Pangea during Jurassic and Cretaceous times created a system of rifts along the northern Tethyan margin. Some of these rifts developed into oceanic basins while others developed on continental crust and turned into aulacogenes. The basins were separated from the main Tethys ocean by several plates and ridges. Partial uplift of the main European plate and late Kimmerian orogeny resulted in the establishment of restricted conditions in the marginal Tethyan basins. The paleogeographic and paleoclimatic setting favoured upwelling along the ridges and continental margins. Source rock prediction value modelling placed Tethyan marginal basins among the best Jurassic source rocks of the world. Self-contained petroleum systems consisting of source rocks, carbonate reservoirs and evaporitic seals occur in the area east of Poland. Actual hydrocarbon production is ongoing in Afghanistan and the Amu-Daria province. Some of Carpathian oils might also be sourced by Late Jurassic/Early Cretaceous rocks. In the western area, petroleum systems were destroyed during the Alpine orogeny.

  17. Risk factors for antenatal depression, postnatal depression and parenting stress

    Directory of Open Access Journals (Sweden)

    Milgrom Jeannette

    2008-04-01

    Full Text Available Abstract Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Methods Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program 1. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26–32 weeks gestation. A subsample of these women (N = 161 also completed questionnaires at 10–12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI. Results Regression analyses identified significant risk factors for the three outcome measures. (1. Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2. Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3. Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator

  18. Risk factors for antenatal depression, postnatal depression and parenting stress.

    Science.gov (United States)

    Leigh, Bronwyn; Milgrom, Jeannette

    2008-04-16

    Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program 1. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26-32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10-12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI). Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors. Risk factor profiles for

  19. Kennedy, the early sixties, and visitation by the angel of death.

    Science.gov (United States)

    O'Toole, D; Chase, C C L; Miller, M M; Campen, H Van

    2014-11-01

    The inaugural issue of Pathologia Veterinaria in 1964 contained the first detailed account of lesions in aborted fetuses following natural, experimental, and postvaccinal infection with bovine herpesvirus 1 (BoHV-1). The article, written by pathologists Kennedy and Richards, described diagnostic gross and histologic features in 13 bovine fetuses. The authors provided clinical and epidemiologic features of 1 postvaccination outbreak, including the absence of clinical signs in infected dams and the propensity for abortions to occur after 6 months' gestation. Subsequent field and experimental studies corroborated and expanded these observations. As a result of this and later reports, veterinarians became alert to the association between infectious bovine rhinotracheitis and abortion, including the risks of exposing pregnant cattle to live vaccinal BoHV-1. Methods were developed to corroborate a morphologic diagnosis of herpetic abortion in cattle, including immunofluorescence, immunohistochemistry, and polymerase chain reaction methods. Outbreaks of postvaccinal BoHV-1 abortion in the United States began to be reported with apparently increased frequency in the early 2000s. This coincided with licensure in 2003 of modified live BoHV-1 vaccines intended for use in pregnant cattle, which are now sold by 3 manufacturers. Ten recent herd episodes of postvaccinal BoHV-1 abortion are reported. All 10 BoHV-1 isolates had single-nucleotide polymorphism (SNPs) profiles previously identified in a group of BoHV-1 isolates that contains vaccine strains, based on a BoHV-1 SNP classification system. They lacked SNP features typical of those in characterized field-type strains of BoHV-1. © The Author(s) 2014.

  20. Programmed Death Ligand 1 Promotes Early-Life Chlamydia Respiratory Infection-Induced Severe Allergic Airway Disease.

    Science.gov (United States)

    Starkey, Malcolm R; Nguyen, Duc H; Brown, Alexandra C; Essilfie, Ama-Tawiah; Kim, Richard Y; Yagita, Hideo; Horvat, Jay C; Hansbro, Philip M

    2016-04-01

    Chlamydia infections are frequent causes of respiratory illness, particularly pneumonia in infants, and are linked to permanent reductions in lung function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. In the current study, we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease in later life. Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4(+), and CD8(+) T cells as major sources of PD-1 and PD-L1. Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. Given that PD-L1 was the most highly up-regulated and its targeting prevented infection-induced AHR, subsequent analyses focused on this ligand. Inhibition of PD-L1 had no effect on Chlamydia load but suppressed infection-induced pulmonary inflammation. Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later life by decreasing IL-13 levels, Gob-5 expression, mucus production, and AHR. Thus, early-life Chlamydia respiratory infection-induced PD-L1 promotes severe inflammation during infection, permanent reductions in lung function, and the development of more severe allergic airway disease in later life.

  1. 分娩预演对初产妇自我效能和产后抑郁情绪的影响%Effect of early maternal childbirth rehearsal on self-efficacy and post-natal depression for primipara

    Institute of Scientific and Technical Information of China (English)

    吕连玉; 孙莉娟

    2015-01-01

    目的:研究分娩预演健康教育对初产妇自我效能和产后抑郁情绪的影响,以期降低临床剖宫产率,提高初产妇的生活质量。方法选取2013年1—12月入院定期产检,且无剖宫产指征的初产妇120名。根据随机数字表法随机分为观察组60名和对照组60名。对照组初产妇接受常规产前健康教育培训,观察组在其基础上应用分娩预演健康教育培训。比较两组初产妇培训前后的自我效能感(GSES)评分、分娩方式及产后抑郁情况。结果两组初产妇培训前GSES评分差异无统计学意义(P>0.05),培训后观察组为(30.13±4.10)分,高于对照组的(26.18±5.69)分,差异有统计学意义( t=2.978,P<0.05)。观察组自然分娩50名占83.33%,剖宫产10名占16.67%;与对照组比较差异有统计学意义(χ2值分别为2.316,2.334;P<0.05)。产前1个月两组产后抑郁评分差异无统计学意义( P>0.05),观察组产后1个月为(12.1±2.4)分,产后6个月为(9.7±1.6)分,分别低于对照组,差异有统计学意义( t值分别为2.297,5.497;P<0.05)。结论分娩预演健康教育可提高初产妇的自我效能感,提高自然分娩率、降低社会因素剖宫产率,并可有效改善产后抑郁,可为临床指导初产妇生产提供一定参考。%Objective To study the impact of early maternal childbirth rehearsal on self-efficacy and post-natal depression , in order to reduce the rate of cesarean section and improve the quality of life in primipara . Methods From January to December in 2013, totals of 120 cases without the evidence of maternal cesarean section were selected as the research subjects .They were randomly divided into experimental group (60 cases) and control group (60 cases) according to the random table method .The control group received routine prenatal maternal health education

  2. A comparative study between Marshall and Rotterdam CT scores in predicting early deaths in patients with traumatic brain injury in a major tertiary care hospital in Nepal

    Institute of Scientific and Technical Information of China (English)

    Sunil Munakomi

    2016-01-01

    Purpose:CT plays a crucial role in the early assessment of patients with traumatic brain injury (TBI).Marshall and Rotterdam are the mostly used scoring systems,in which CT findings are grouped differently.We sought to determine the values of the scoring system and initial CT findings in predicting the death at hospital discharge (early death) in patients with TBI.Methods:There were consecutive 634 traumatic neurosurgical patients with mild-to-severe TBI admitted to the emergency department of College of Medical Sciences.Their initial CT and status at hospital discharge (dead or alive) were reviewed,and both CT scores were calculated.We examined whether each score is related to early death;compared the two scoring systems' performance in predicting early death,and identified the CT findings that are independent predictors for early death.Results:Both imaging score (Marshall) and clinical score (Rotterdam) can be used to reliably predict mortality in patients with acute traumatic brain injury with high prognostic accuracy.Other specific CT characteristics that can be used to predict early mortality are traumatic subarachnoid hemorrhage,midline shift and status of the peri-mesencephalic cisterns.Conclusions:Marshall CT classification has strong predictive power,but greater discrimination can be obtained if the individual CT parameters underlying the CT classification are included in a prognostic model as in Rotterdam score.Consequently,for prognostic purposes,we recommend the use of individual characteristics rather than the CT classification.Performance of CT models for predicting outcome in TBI can be significantly improved by including more details of variables and by adding other variables to the models.

  3. Apoptotic neurons induce proliferative responses of progenitor cells in the postnatal neocortex.

    Science.gov (United States)

    Petrenko, Volodymyr; Mihhailova, Jevgenia; Salmon, Patrick; Kiss, Jozsef Z

    2015-11-01

    Apoptotic cell death is the leading cause of neuronal loss after neonatal brain injury. Little is known about the intrinsic capacity of the immature cerebral cortex for replacing dead cells. Here we test the hypothesis that neuronal apoptosis is able to trigger compensatory proliferation in surrounding cells. In order to establish a "pure" apoptotic cell death model and to avoid the confounding effects of broken blood-brain barrier and inflammatory reactions, we used a diphtheria toxin (DT) and diphtheria toxin receptor (DTR) system to induce ablation of layer IV neurons in the rodent somatosensory cortex during the early postnatal period. We found that DT-triggered apoptosis is a slowly progressing event lasting about for 7 days. While dying cells expressed the morphological features of apoptosis, we could not detect immunoreactivity for activated caspase-3 in these cells. Microglia activation and proliferation represented the earliest cellular responses to apoptotic cell death. In addition, we found that induced apoptosis triggered a massive proliferation of undifferentiated progenitor cell pool including Sox2 as well as NG2 cells. The default differentiation pattern of proliferating progenitors appears to be the glial phenotype; we could not find evidence for newly generated neurons in response to apoptotic neuronal death. These results suggest that mitotically active progenitor populations are intrinsically capable to contribute to the repair process of injured cortical tissue and may represent a potential target for neuronal replacement strategies.

  4. An early ethylene up-regulated gene encoding a calmodulin-binding protein involved in plant senescence and death

    Science.gov (United States)

    Yang, T.; Poovaiah, B. W.

    2000-01-01

    35S-Labeled calmodulin (CaM) was used to screen a tobacco anther cDNA library. A positive clone (NtER1) with high homology to an early ethylene-up-regulated gene (ER66) in tomato, and an Arabidopsis homolog was isolated and characterized. Based on the helical wheel projection, a 25-mer peptide corresponding to the predicted CaM-binding region of NtER1 (amino acids 796-820) was synthesized. The gel-mobility shift assay showed that the peptide formed a stable complex with CaM only in the presence of Ca(2+). CaM binds to NtER1 with high affinity (K(d) approximately 12 nm) in a calcium-dependent manner. Tobacco flowers at different stages of development were treated with ethylene or with 1-methylcyclopropene for 2 h before treating with ethylene. Northern analysis showed that the NtER1 was rapidly induced after 15 min of exposure to ethylene. However, the 2-h 1-methylcyclopropene treatment totally blocked NtER1 expression in flowers at all stages of development, suggesting that NtER1 is an early ethylene-up-regulated gene. The senescing leaves and petals had significantly increased NtER1 induction as compared with young leaves and petals, implying that NtER1 is developmentally regulated and acts as a trigger for senescence and death. This is the first documented evidence for the involvement of Ca(2+)/CaM-mediated signaling in ethylene action.

  5. An early ethylene up-regulated gene encoding a calmodulin-binding protein involved in plant senescence and death

    Science.gov (United States)

    Yang, T.; Poovaiah, B. W.

    2000-01-01

    35S-Labeled calmodulin (CaM) was used to screen a tobacco anther cDNA library. A positive clone (NtER1) with high homology to an early ethylene-up-regulated gene (ER66) in tomato, and an Arabidopsis homolog was isolated and characterized. Based on the helical wheel projection, a 25-mer peptide corresponding to the predicted CaM-binding region of NtER1 (amino acids 796-820) was synthesized. The gel-mobility shift assay showed that the peptide formed a stable complex with CaM only in the presence of Ca(2+). CaM binds to NtER1 with high affinity (K(d) approximately 12 nm) in a calcium-dependent manner. Tobacco flowers at different stages of development were treated with ethylene or with 1-methylcyclopropene for 2 h before treating with ethylene. Northern analysis showed that the NtER1 was rapidly induced after 15 min of exposure to ethylene. However, the 2-h 1-methylcyclopropene treatment totally blocked NtER1 expression in flowers at all stages of development, suggesting that NtER1 is an early ethylene-up-regulated gene. The senescing leaves and petals had significantly increased NtER1 induction as compared with young leaves and petals, implying that NtER1 is developmentally regulated and acts as a trigger for senescence and death. This is the first documented evidence for the involvement of Ca(2+)/CaM-mediated signaling in ethylene action.

  6. The Effects of Death Education.

    Science.gov (United States)

    Freitag, Carl B.; Hassler, Shawn David

    Although fear of death is recorded in the writings of the oldest major religions, the study of death and the fear of death have only occurred for the last few decades. Death education courses have grown in number since the early 1970's. College students participated in an investigation of the effects of death education on death anxiety by…

  7. Sir James Reid and the Death of Queen Victoria: An Early Model for End-of-Life Care.

    Science.gov (United States)

    Abrams, Robert C

    2015-12-01

    An appraisal of the last ten days of Queen Victoria's life, viewed primarily from the perspective of her personal physician, Sir James Reid, is presented. Sir James' clinical encounters with his patient and the Royal Family are examined to reveal his strategic and medical thinking and gauge his level of success in basic palliative aims. It was found that the lack of effective medical interventions, tensions within the Royal Family, the importance of his post to Sir James' professional career, and the political ramifications unavoidably connected with the illness of a head of state, all presented challenges to Reid's efforts to ease the physical and emotional pain of Queen Victoria's dying. Key features of Sir James' approach included reliance on physician-patient and physician-family relationships, emphasis on emotional support for the patient, and the careful selection of interventions for the family. In the first years of the 20th century, an era when the contemporary concepts of palliative care, hospice, and family dynamics did not exist, Sir James' management of the Queen's final illness suggested an early model for end-of-life care. By the end of Queen Victoria's life, Sir James was seen to have preserved his patient's comfort and dignity, at the same time advancing family and societal acceptance of the death of this matriarchal figure. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Determination of the Early Time of Death by Computerized Image Analysis of DNA Degradation: Which Is the Best Quantitative Indicator of DNA Degradation?

    Institute of Scientific and Technical Information of China (English)

    LIU Lijiang; SHU Xiji; REN Liang; ZHOU Hongyan; LI Yan; LIU Wei; ZHU Cheng; LIU Liang

    2007-01-01

    This study evaluated the correlation between DNA degradation of the splenic lymphocytes and the early time of death, examined the early time of death by computerized image analysis technique (CIAT) and identified the best parameter that quantitatively reflects the DNA degradation.The spleen tissues from 34 SD rats were collected, subjected to cell smearing every 2 h within the first 36 h after death, stained by Feulgen-Van's staining, three indices reflecting DNA content in splenic lymphocytes, including integral optical density (IOD), average optical density (AOD), average gray scale (AG) were measured by the image analysis. Our results showed that IOD and AOD decreased and AG increased over time within the first 36 h. A stepwise linear regression analysis showed that only AG was fitted. A correlation between the postmortem interval (PMI) and AG was identified and the corresponding regression equation was obtained. Our study suggests that CIAT is a useful and promising tool for the estimation of early PMI with good objectivity and reproducibility,and AG is a more effective and better quantitative indicator for the estimation of PMI within the first 36 h after death in rats.

  9. Early detection of brain death using the Bispectral Index (BIS) in patients treated by extracorporeal cardiopulmonary resuscitation (E-CPR) for refractory cardiac arrest.

    Science.gov (United States)

    Jouffroy, Romain; Lamhaut, Lionel; Guyard, Alexandra; Philippe, Pascal; An, Kim; Spaulding, Christian; Baud, Frédéric; Carli, Pierre; Vivien, Benoît

    2017-08-24

    Despite increasing use of extracorporeal cardiopulmonary resuscitation (E-CPR) for treatment of refractory cardiac arrest patients, prognosis remains dismal, often resulting in brain-death. However, clinical assessment of brain-death occurence is difficult in post-cardiac arrest patients, sedated, paralyzed, under mild therapeutic hypothermia (MTH). Our objective was to assess the usefulness of Bispectral-Index (BIS) monitoring at bedside for an early detection of brain-death occurrence in refractory cardiac arrest patients treated by E-CPR. This prospective study was performed in an intensive care unit of an university hospital. Forty-six patients suffering from refractory cardiac arrest treated by E-CPR were included. BIS was continuously recorded during ICU hospitalization. Clinical brain-death was confirmed when appropriate by EEG and/or cerebral CT angiography. Twenty-nine patients evolved into brain-death and had average BIS values under MTH and after rewarming (temperature ≥35°C) of 4 (0-47) and 0 (0-82), respectively. Among these, 11 (38%) entered into a procedure of organs donation. Among the 17 non-brain-dead patients, the average BIS values at admission and after rewarming were 39 (0-65) and 59 (22-82), respectively. Two patients had on admission a BIS value equal to zero and evolved to a poor prognostic (CPC 4) and died after care limitations. BIS values were significantly different between patients who developed brain death and those who did not. In both groups, no differences were observed between the AUCs of ROC curves for BIS values under MTH and after rewarming (respectively 0.86 vs 0.83, NS). Initial values of BIS could be used as an assessment tool for early detection of brain-death in refractory cardiac arrest patients treated by mild therapeutic hypothermia and E-CPR. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Postnatal ontogenesis of molecular clock in mouse striatum.

    Science.gov (United States)

    Cai, Yanning; Liu, Shu; Li, Ning; Xu, Shengli; Zhang, Yanli; Chan, Piu

    2009-04-01

    Striatum is an important brain area whose function is related to motor, emotion and motivation. Interestingly, biological and physiological circadian rhythms have been found in the striatum extensively, suggesting molecular clock machinery works efficiently therein. However, the striatal expression profiles of clock genes have not been characterized systematically. In addition, little is known about when the expression rhythms start during postnatal ontogenesis. In the present study, 24 h mRNA oscillations of 6 principle clock genes (Bmal1, Clock, Npas2, Cry1, Per1 and Rev-erb alpha) were examined in mouse striatum, at early postnatal stage (postnatal day 3), pre-weaning stage (postnatal day 14) and in adult (postnatal day 60). At P3, no daily oscillation was found for all clock genes. At P14, a significant time effect was identified only for Rev-erb alpha and Npas2. At P60, the daily oscillations of these clock genes were at least borderline significant, with peak time at Circadian time (CT) 01 for Bmal1, Clock, Npas2 and Cry1; at CT 13 for Per1; and at CT 07 for Rev-erb alpha. In addition, the overall mean mRNA levels of these clock genes also underwent a dynamic change postnatally. For Bmal1, Clock, Npas2, Per1 and Rev-erb alpha, the expression level increased throughout the postnatal ontogenesis from P3, P14 to P60. For Cry1, however, the abundance at P3 and P60 were similar while that at P14 was much lower. In conclusion, the striatal molecular clock machinery, although works efficiently in adult, develops gradually after birth in mice.

  11. Topiramate attenuates early brain injury following subarachnoid haemorrhage in rats via duplex protection against inflammation and neuronal cell death.

    Science.gov (United States)

    Tian, Yong; Guo, Song-Xue; Li, Jian-Ru; Du, Hang-Gen; Wang, Chao-Hui; Zhang, Jian-Min; Wu, Qun

    2015-10-05

    Early brain injury (EBI) following aneurysmal subarachnoid haemorrhage (SAH) insults contributes to the poor prognosis and high mortality observed in SAH patients. Topiramate (TPM) is a novel, broad-spectrum, antiepileptic drug with a reported protective effect against several brain injuries. The current study aimed to investigate the potential of TPM for neuroprotection against EBI after SAH and the possible dose-dependency of this effect. An endovascular perforation SAH model was established in rats, and TPM was administered by intraperitoneal injection after surgery at three different doses (20mg/kg, 40mg/kg, and 80mg/kg). The animals' neurological scores and brain water content were evaluated, and ELISA, Western blotting and immunostaining assays were conducted to assess the effect of TPM. The results revealed that TPM lowers the elevated levels of myeloperoxidase and proinflammatory mediators observed after SAH in a dose-related fashion, and the nuclear factor-kappa B (NF-κB) signalling pathway is the target of neuroinflammation regulation. In addition, TPM ameliorated SAH-induced cortical neuronal apoptosis by influencing Bax, Bcl-2 and cleaved caspase-3 protein expression, and the effect of TPM was enhanced in a dose-dependent manner. Various dosages of TPM also upregulated the protein expression of the γ-aminobutyric acid (GABA)-ergic signalling molecules, GABAA receptor (GABAAR) α1, GABAAR γ2, and K(+)-Cl(-) co-transporter 2 (KCC2) together and downregulated Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1) expression. Thus, TPM may be an effective neuroprotectant in EBI after SAH by regulating neuroinflammation and neuronal cell death.

  12. PRognostic factor of Early Death In phase II Trials or the end of 'sufficient life expectancy' as an inclusion criterion? (PREDIT model).

    Science.gov (United States)

    Grellety, Thomas; Cousin, Sophie; Letinier, Louis; Bosco-Lévy, Pauline; Hoppe, Stéphanie; Joly, Damien; Penel, Nicolas; Mathoulin-Pelissier, Simone; Italiano, Antoine

    2016-10-04

    Optimizing patient selection is a necessary step to design better clinical trials. 'Life expectancy' is a frequent inclusion criterion in phase II trial protocols, a measure that is subjective and often difficult to estimate. The aim of this study was to identify factors associated with early death in patients included in phase II studies. We retrospectively collected medical records of patients with advanced solid tumors included in phase II trials in two French Comprehensive Cancer Centers (Bordeaux, Center 1 set; Lille, Center 2 set). We analyzed patients' baseline characteristics. Predictive factors associated with early death (mortality at 3 months) were identified by logistic regression. We built a model (PREDIT, PRognostic factor of Early Death In phase II Trials) based on prognostic factors isolated from the final multivariate model. Center 1 and 2 sets included 303 and 227 patients, respectively. Patients from Center 1 and 2 sets differed in tumor site, urological (26 % vs 15 %) and gastrointestinal (18 % vs 28 %) and in lung metastasis incidence (10 % vs 49 %). Overall survival (OS) at 3 months was 88 % (95 % CI [83.5; 91.0], Center 1 set) and 91 % (95 % CI [86.7; 94.2], Center 2 set). Presence of a 'life expectancy' inclusion criterion did not improve the 3-month OS (HR 0.6, 95 % CI [0.2; 1.2], p = 0.2325). Independent factors of early death were an ECOG score of 2 (OR 13.3, 95%CI [4.1; 43.4]), hyperleukocytosis (OR 5.5, 95 % CI [1.9; 16.3]) and anemia (OR 2.8, 95 % CI [1.1; 7.1]). Same predictive factors but with different association levels were found in the Center 2 set. Using the Center 1 set, ROC analysis shows a good discrimination to predict early death (AUC: 0.89 at 3 months and 0.86 at 6 months). Risk modeling in two independent cancer populations based on simple clinical parameters showed that baseline ECOG of 2, hyperleukocytosis and anemia are strong early-death predictive factors. This model allows identifying patients who may

  13. Kidney Injury Molecule-1 is an Early Noninvasive Indicator for Donor Brain Death-Induced Injury Prior to Kidney Transplantation

    NARCIS (Netherlands)

    Nijboer, W. N.; Schuurs, T. A.; Damman, J.; van Goor, H.; Vaidya, V. S.; van der Heide, J. J. Homan; Leuvenink, H. G. D.; Bonventre, J. V.; Ploeg, R. J.

    2009-01-01

    In rat kidney, real-time PCR revealed a 46-fold Kim-1 gene upregulation after 4 h of brain death. In situ hybridization showed proximal tubular Kim-1 localization, which was confirmed by immunohistochemistry. Also, Luminex assay showed a 6.6-fold Kim-1 rise in urine after 4 h of brain death. In huma

  14. Competing risks of death in women treated with adjuvant aromatase inhibitors for early breast cancer on NCIC CTG MA.27.

    Science.gov (United States)

    Chapman, Judith-Anne W; Shepherd, Lois E; Ingle, James N; Muss, Hyman B; Pritchard, Kathleen I; Gelmon, Karen A; Whelan, Timothy J; Elliott, Catherine; Goss, Paul E

    2016-04-01

    Baseline patient and tumor characteristics differentially affected type of death in the MA.17 placebo-controlled letrozole trial where cardiovascular death was not separately identified. The MA.27 trial allowed competing risks analysis of breast cancer (BC), cardiovascular, and other type (OT) of death. MA.27 was a phase III adjuvant breast cancer trial of exemestane versus anastrozole. Effects of baseline patient and tumor characteristics were tested for whether factors were associated with (1) all cause mortality and (2) cause-specific mortality. We also fit step-wise forward cause-specific-adjusted models. 7576 women (median age 64 years; 5417 (72 %) breast cancer related. Baseline patient and tumor characteristics differentially affected type of death with women 70 or older experiencing more non-breast cancer death.

  15. Dacryocystocele on prenatal ultrasonography: diagnosis and postnatal outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Hwa; Lee, Yu Jin; Song, Mi Jin; Han, Byoung Hee; Lee, Young Ho; Lee, Kyung Sang [Dept. of Radiology, Cheil General Hospital and Women' s Healthcare Center, Catholic Kwandong University College of Medicine, Seoul (Korea, Republic of)

    2015-01-15

    To report the incidence of dacryocystoceles detected by prenatal ultrasonography (US) and their postnatal outcomes and to determine the factors associated with the postnatal persistence of dacryocystoceles at birth. We retrospectively reviewed the prenatal US database at our institution for the period between January 2012 and December 2013. The medical records of women who had fetuses diagnosed with dacryocystocel larger than 5 mm were reviewed for maternal age, gestational age (GA) at detection, size and side of the dacryocystoceles, delivery, and postnatal information, such as GA at delivery, delivery mode, and gender of the neonate. A total of 49 singletons were diagnosed with a dacryocystocele on prenatal US, yielding an overall incidence of 0.43%. The incidence of dacryocystoceles was the highest at the GA of 27 weeks and decreased toward term. Of the 49 fetuses including three of undeter mined gender, 25 (54%) were female. The mean GA at first detection was 31.2 weeks. The dacryocystocele was unilateral in 29 cases, with a mean maximum diameter of 7 mm. Spontaneous resolution at birth was documented in 35 out of 46 neonates (76%), including six with prenatal resolution. Multivariate analysis demonstrated that GA at delivery was a significant predictor of the postnatal persistence of dacryocystoceles (P=0.045). The overall incidence of prenatal dacryocystoceles was 0.43%; the incidence was higher in the early third trimester and decreased thereafter. Prenatal dacryocystoceles resolved in 76% of the patients at birth, and the GA at delivery was a significant predictor of postnatal persistence.

  16. Postnatal Growth and Psychomotor Development in Small for Gestational Age Brazilian Infants.

    Science.gov (United States)

    Paine, Patricia Ann; Pasquali, Luiz

    1984-01-01

    The early psychomotor development (DQ) of 29 term small-for-gestational-age Brazilian infants was shown to be more dependent on postnatal growth than the DQ of 51 term appropriate-for-gestational-age infants. (Author/RH)

  17. Major epigenetic development distinguishing neuronal and non-neuronal cells occurs postnatally in the murine hypothalamus

    Science.gov (United States)

    Prenatal and early postnatal environment can persistently alter one's risk of obesity. Environmental effects on hypothalamic developmental epigenetics constitute a likely mechanism underlying such 'developmental programming' of energy balance regulation. To advance our understanding of these process...

  18. Postnatal effects of prenatal insult

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, E.M.; Newman, L.M.; Schmidt, R.R.

    1988-03-01

    Exogenous agents may perturb development during the embryonic period and adversely affect the formation of organs. However, adverse effects on development are not limited to the embryonic period nor are the manifestations restricted solely to outright gross structural malformation, but may instead be expressed as a decrement or abberration of postnatal function. Susceptibility to altered development may extend well into the postnatal period. Studies of functional parameters in several organ systems have demonstrated the broad-based susceptibility, subtlety of expression and potential of long-lasting effects of altered development assessed by physiologic assays. Adverse effects on functional development, whether in the CNS, reproductive, gastrointestinal, genitourinary, respiratory, or immune systems, etc., merit continuing investigation. From the viewpoint of risk estimation and hazard detection, evaluations of postnatal functional parameters may be relevant for several reasons. First, such parameters may serve as low-dose triggers. Second, they may be useful as a focal point for epidemiological studies. Finally, a more thorough understanding of the degree and magnitude of such postnatal functional deficits is needed since an adverse maternal effect may be transient, considered acceptable, or unperceived, but the effect on the conceptus may be permanent and severe. The immune and respiratory systems are discussed as two examples of how subtle and protean adverse effects on functional development may be.

  19. Intestinal absorption and renal reabsorption of calcium throughout postnatal development.

    Science.gov (United States)

    Beggs, Megan R; Alexander, R Todd

    2017-04-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

  20. Differential Activation of Mitogen-Activated Protein Kinases, ERK 1/2, p38(MAPK) and JNK p54/p46 During Postnatal Development of Rat Hippocampus.

    Science.gov (United States)

    Costa, Ana Paula; Lopes, Mark William; Rieger, Débora K; Barbosa, Sabrina Giovana Rocha; Gonçalves, Filipe Marques; Xikota, João Carlos; Walz, Roger; Leal, Rodrigo B

    2016-05-01

    Mitogen-activated protein kinases (MAPKs) are a group of serine-threonine kinases, including p38(MAPK), ERK 1/2 and JNK p54/p46, activated by phosphorylation in response to extracellular stimuli. The early postnatal period is characterized by significant changes in brain structure as well as intracellular signaling. In the hippocampus MAPKs have been involved in the modulation of development and neural plasticity. However, the temporal profile of MAPK activation throughout the early postnatal development is incomplete. An understanding of this profile is important since slight changes in the activity of these enzymes, in response to environmental stress in specific developmental windows, might alter the course of development. The present study was undertaken to investigate the hippocampal differential activation of MAPK during postnatal period. MAPK activation and total content were evaluated by Western blotting of hippocampal tissue obtained from male Wistar rats at postnatal days (P) 1, 4, 7, 10, 14, 21, 30 and 60. The total content and phosphorylation of each MAPK was expressed as mean ± SEM and then calculates as a percentile compared to P1 (set at 100 %). The results showed: (1) phosphorylation peaks of p38(MAPK) at PN4 (p = 0.036) and PN10 to PN60; (2) phosphorylation of ERK1 and ERK2 were increased with age (ERK1 p = 0.0000005 and ERK2 p = 0.003); (3) phosphorylation profile of JNK p54/p46 was not changed during the period analyzed (JNKp56 p = 0.716 and JNKp46 p = 0.192). Therefore, the activity profile of ERK 1/2 and p38(MAPK) during postnatal development of rat hippocampus are differentially regulated. Our results demonstrate that ERK 1/2 and p38(MAPK) are dynamically regulated during postnatal neurodevelopment, suggesting temporal correlation of MAPK activity with critical periods when programmed cell death and synaptogenesis are occurring. This suggests an important role for these MAPKs in postnatal development of rat hippocampus.

  1. Postnatal brain development

    DEFF Research Database (Denmark)

    Jernigan, Terry L; Baaré, William F C; Stiles, Joan

    2011-01-01

    After birth, there is striking biological and functional development of the brain's fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact...... constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes...... in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain-behavior associations in children, including genetic variation, behavioral interventions...

  2. Postnatal brain development

    DEFF Research Database (Denmark)

    Jernigan, Terry L; Baaré, William F C; Stiles, Joan;

    2011-01-01

    constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes......After birth, there is striking biological and functional development of the brain's fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact...... in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain-behavior associations in children, including genetic variation, behavioral interventions...

  3. Predictors of early death and survival among children, adolescents and young adults with acute myeloid leukaemia in California, 1988-2011: a population-based study.

    Science.gov (United States)

    Abrahão, Renata; Keogh, Ruth H; Lichtensztajn, Daphne Y; Marcos-Gragera, Rafael; Medeiros, Bruno C; Coleman, Michel P; Ribeiro, Raul C; Keegan, Theresa H M

    2016-04-01

    A better understanding of factors associated with early death and survival among children, adolescents and young adults with acute myeloid leukaemia (AML) may guide health policy aimed at improving outcomes in these patients. We examined trends in early death and survival among 3935 patients aged 0-39 years with de novo AML in California during 1988-2011 and investigated the associations between sociodemographic and selected clinical factors and outcomes. Early death declined from 9·7% in 1988-1995 to 7·1% in 2004-2011 (P = 0·062), and survival improved substantially over time. However, 5-year survival was still only 50% (95% confidence interval 47-53%) even in the most recent treatment period (2004-2011). Overall, the main factors associated with poor outcomes were older age at diagnosis, treatment at hospitals not affiliated with National Cancer Institute-designated cancer centres, and black race/ethnicity. For patients diagnosed during 1996-2011, survival was lower among those who lacked health insurance compared to those with public or private insurance. We conclude that mortality after AML remained strikingly high in California and increased with age. Possible strategies to improve outcomes include wider insurance coverage and treatment at specialized cancer centres.

  4. Early apoptosis and cell death induced by ATX-S10Na ( Ⅱ)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Makoto Mitsunaga; Akihito Tsubota; Kohichi Nariai; Yoshihisa Namiki; Makoto Sumi; Tetsuya Yoshikawa; Kiyotaka Fujise

    2007-01-01

    AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (Ⅱ).METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin V assays, transmission electron microscopy assays, caspase assays and western blotting.RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-XL,were decreased in Bax- and p53-independent manner.CONCLUSION: Our results indicate that early apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizingphotosensitizer ATX-S10Na (Ⅱ) are mediated by p53-Bax network and Iow levels of Bcl-2 and Bcl-XL proteins.Our results might help in formulating new therapeutic approaches in photedynamic therapy.

  5. A mutation in the cytosolic O-acetylserine (thiol lyase induces a genome-dependent early leaf death phenotype in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Schippers Jos HM

    2010-04-01

    Full Text Available Abstract Background Cysteine is a component in organic compounds including glutathione that have been implicated in the adaptation of plants to stresses. O-acetylserine (thiol lyase (OAS-TL catalyses the final step of cysteine biosynthesis. OAS-TL enzyme isoforms are localised in the cytoplasm, the plastids and mitochondria but the contribution of individual OAS-TL isoforms to plant sulphur metabolism has not yet been fully clarified. Results The seedling lethal phenotype of the Arabidopsis onset of leaf death3-1 (old3-1 mutant is due to a point mutation in the OAS-A1 gene, encoding the cytosolic OAS-TL. The mutation causes a single amino acid substitution from Gly162 to Glu162, abolishing old3-1 OAS-TL activity in vitro. The old3-1 mutation segregates as a monogenic semi-dominant trait when backcrossed to its wild type accession Landsberg erecta (Ler-0 and the Di-2 accession. Consistent with its semi-dominant behaviour, wild type Ler-0 plants transformed with the mutated old3-1 gene, displayed the early leaf death phenotype. However, the old3-1 mutation segregates in an 11:4:1 (wild type: semi-dominant: mutant ratio when backcrossed to the Colombia-0 and Wassilewskija accessions. Thus, the early leaf death phenotype depends on two semi-dominant loci. The second locus that determines the old3-1 early leaf death phenotype is referred to as odd-ler (for old3 determinant in the Ler accession and is located on chromosome 3. The early leaf death phenotype is temperature dependent and is associated with increased expression of defence-response and oxidative-stress marker genes. Independent of the presence of the odd-ler gene, OAS-A1 is involved in maintaining sulphur and thiol levels and is required for resistance against cadmium stress. Conclusions The cytosolic OAS-TL is involved in maintaining organic sulphur levels. The old3-1 mutation causes genome-dependent and independent phenotypes and uncovers a novel function for the mutated OAS-TL in cell

  6. Usefulness of Serum Unbound Free Fatty Acid Levels to Predict Death Early in Patients with ST Segment Elevation Myocardial Infarction[From the TIMI II Trial

    Science.gov (United States)

    Huber, Andrew H.; Kampf, J. Patrick; Kwan, Thomas; Zhu, Baolong; Adams, Jesse; Kleinfeld, Alan M.

    2013-01-01

    Circulating total free fatty acids (FFA) are elevated early in myocardial infarction (MI) and are associated with an increase in mortality. We investigated the association of serum unbound free fatty acids (FFAu) levels with mortality,in patients presenting with ST elevation myocardial infarction (STEMI) in the Thrombolysis in Myocardial Infarction (TIMI) II trial.TIMI II enrolled patients within 4 hours of chest pain. Patients were treated with recombinant tissue plasminogen activator within 1 hour of enrollment. The concentration of FFAu was evaluated in serum samplesfrom 1834 patients obtained at baseline, before therapy.FFAu was an independent risk factor for death as early as one day of hospitalization and continued to be an independent risk factor for the more than 3·8 years of follow up. When adjusted for other cardiovascular risk factors FFAu levels in the fourth as compared to the first quartile remained an independent risk factor for death due to MI (hazard ratio, 5.0; 95 % confidence interval, 1.9-13.0), to all cardiac death (hazard ratio, 2.4; confidence interval, 1.3-4.4) and to all cause death (hazard ratio, 1.9, confidence interval, 1.2-3.1).Females were twice as likely to be in the upper two FFAu quartiles and had approximately twice the rate of death as males. In conclusion, increased levels of FFAu are one of the earliest molecular biomarkers of mortality in STEMI and are independent of other risk factors known to affect outcomes in STEMI. PMID:24176067

  7. Postnatal depression and its associated factors among Northeastern Nigerian women

    Directory of Open Access Journals (Sweden)

    Dauda Sulyman

    2016-01-01

    Full Text Available Background: Postnatal depression is a serious psychiatric condition that occurs in puerperium. It is associated with increased morbidity and can overwhelm new mothers and interfere with the care of their babies. This study aimed to determine the prevalence rate of postnatal depression and assess factors that are associated with its development among northeastern Nigerian women. Materials and Methods: Edinburgh Postnatal Depression Scale (EPDS questionnaire was administered to four hundred and eighty-three women who delivered at the maternity unit of a tertiary health institution in northeastern Nigeria. Their sociodemographic and clinical variables were also obtained using pro forma questionnaire designed by the researchers. Results: One hundred and eight respondents scored 13 or more points on EPNDS, making the prevalence rate of postnatal depression 22.4%. Factors that are associated with the development of postnatal depression are unemployment [odds ratio (OR = 0.49, 95% (CI = 0.27-0.86, P value = 0.018, lack of support from the husband (OR = 0.34, 95% CI = 0.19-0.60, P value = 0.000, and primiparity (OR = 0.56, 95% CI = 0.35-0.88, P value = 0.013; others are unplanned pregnancy (OR = 0.56, 95% CI = 0.35-0.88, P value = 0.013 and physical illness in the mother (OR = 1.81, 95% CI = 1.77-2.79, P value = 0.007. Conclusion: The study showed that a significant proportion of new mothers have postnatal depression. This may negatively affect their parenting skills and may have adverse effects on them and their children. Early detection and effective management, together with an efficient collaboration among psychiatrists, obstetricians, and other health workers who are involved in the care of new mothers, will go a long way in reducing the negative consequences that may result from this condition.

  8. Role of sensory-motor cortex activity in postnatal development of corticospinal axon terminals in the cat.

    Science.gov (United States)

    Friel, Kathleen M; Martin, John H

    2005-04-25

    The initial pattern of corticospinal (CS) terminations, as axons grow into the spinal gray matter, bears little resemblance to the pattern later in development and in maturity. This is because of extensive axon pruning and local axon terminal growth during early postnatal development. Pruning is driven by activity-dependent competition between the CS systems on each side during postnatal weeks (PW) 3-7. It is not known whether CS axon terminal growth and final topography are activity dependent. We examined the activity dependence of CS axon terminal growth and topography at different postnatal times. We inactivated sensory-motor cortex by infusion of the gamma-aminobutyric acid type A (GABA(A)) agonist muscimol and traced CS axons from the inactivated side. Inactivation between PW5 and PW7 produced permanent changes in projection topography, reduced local axon branching, and prevented development of dense clusters of presynaptic sites, which are normally characteristic of CS terminals. Inactivation at younger (PW3-5) and older (PW8-12) ages did not affect projection topography but impeded development of local axon branching and presynaptic site clusters. These effects were not due to increased cortical cell death during inactivation. Neural activity plays an important role in determining the morphology of CS terminals during the entire period of development, but, for the projection topography, the role of activity is exercised during a very brief period. This points to a complex, and possibly independent, regulation of termination topography and terminal morphology. Surprisingly, when a CS neuron's activity is blocked during early development, it does not recover lost connections later in development once activity resumes.

  9. Serum neutrophil gelatinase associated lipocalin during the early postoperative period predicts the recovery of graft function after kidney transplantation from donors after cardiac death.

    Science.gov (United States)

    Kusaka, Mamoru; Iwamatsu, Fumi; Kuroyanagi, Yoko; Nakaya, Miho; Ichino, Manabu; Marubashi, Shigeru; Nagano, Hiroaki; Shiroki, Ryoichi; Kurahashi, Hiroki; Hoshinaga, Kiyotaka

    2012-06-01

    Kidneys procured from donors after cardiac death hold great potential to expand the donor pool. However, they have not yet been fully used, in part due to the high incidence of delayed graft function. Although urine neutrophil gelatinase-associated lipocalin is a well-known early biomarker for renal injury after kidney transplantation, its usefulness is limited in cases with delayed graft function because of the unavailability of a urine sample. We evaluated serum neutrophil gelatinase-associated lipocalin as a potential biomarker to predict the functional recovery of kidneys transplanted from donors after cardiac death. Consecutive patients transplanted with a kidney from a living related (39), brain dead (1) or post-cardiac death (27) donor were retrospectively enrolled in the study. Serum samples were collected serially before and after kidney transplantation. Serum neutrophil gelatinase-associated lipocalin was measured using the ARCHITECT® assay. Average serum neutrophil gelatinase-associated lipocalin was markedly high during the pre transplantation period. It decreased rapidly after transplantation. The slope of the decrease correlated well with the recovery period. By analyzing ROC curves we determined cutoffs to predict immediate, slow or delayed graft function requiring hemodialysis for longer than 1 week with high sensitivity and specificity. These data suggest that serial monitoring of serum neutrophil gelatinase-associated lipocalin may allow us to predict graft recovery and the need for hemodialysis after kidney transplantation from a donor after cardiac death. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Myelin-associated glycoprotein modulates apoptosis of motoneurons during early postnatal development via NgR/p75(NTR) receptor-mediated activation of RhoA signaling pathways.

    Science.gov (United States)

    Palandri, A; Salvador, V R; Wojnacki, J; Vivinetto, A L; Schnaar, R L; Lopez, P H H

    2015-09-03

    Myelin-associated glycoprotein (MAG) is a minor constituent of nervous system myelin, selectively expressed on the periaxonal myelin wrap. By engaging multiple axonal receptors, including Nogo-receptors (NgRs), MAG exerts a nurturing and protective effect the axons it ensheaths. Pharmacological activation of NgRs has a modulatory role on p75(NTR)-dependent postnatal apoptosis of motoneurons (MNs). However, it is not clear whether this reflects a physiological role of NgRs in MN development. NgRs are part of a multimeric receptor complex, which includes p75(NTR), Lingo-1 and gangliosides. Upon ligand binding, this multimeric complex activates RhoA/ROCK signaling in a p75(NTR)-dependent manner. The aim of this study was to analyze a possible modulatory role of MAG on MN apoptosis during postnatal development. A time course study showed that Mag-null mice suffer a loss of MNs during the first postnatal week. Also, these mice exhibited increased susceptibility in an animal model of p75(NTR)-dependent MN apoptosis induced by nerve-crush injury, which was prevented by treatment with a soluble form of MAG (MAG-Fc). The protective role of MAG was confirmed in in vitro models of p75(NTR)-dependent MN apoptosis using the MN1 cell line and primary cultures. Lentiviral expression of shRNA sequences targeting NgRs on these cells abolished protection by MAG-Fc. Analysis of RhoA activity using a FRET-based RhoA biosensor showed that MAG-Fc activates RhoA. Pharmacological inhibition of p75(NTR)/RhoA/ROCK pathway, or overexpression of a p75(NTR) mutant unable to activate RhoA, completely blocked MAG-Fc protection against apoptosis. The role of RhoA/ROCK signaling was further confirmed in the nerve-crush model, where pretreatment with ROCK inhibitor Y-27632 blocked the pro-survival effect of MAG-Fc. These findings identify a new protective role of MAG as a modulator of apoptosis of MNs during postnatal development by a mechanism involving the p75(NTR)/RhoA/ROCK signaling pathway

  11. Early activation of lipoxygenase in lentil (Lens culinaris) root protoplasts by oxidative stress induces programmed cell death

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Maccarrone, M.; Zadelhoff, G. van; Veldink, G.A.; Finazzi Agrò, A.

    2000-01-01

    Oxidative stress caused by hydrogen peroxide (H2O2) triggers the hypersensitive response of plants to pathogens. Here, short pulses of H2O2 are shown to cause death of lentil (Lens culinaris) root protoplasts. Dead cells showed DNA fragmentation and ladder formation, typical hallmarks of apoptosis (

  12. Early activation of lipoxygenase in lentil (Lens culinaris) root protoplasts by oxidative stress induces programmed cell death

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Maccarrone, M.; Zadelhoff, G. van; Veldink, G.A.; Finazzi Agrò, A.

    2000-01-01

    Oxidative stress caused by hydrogen peroxide (H2O2) triggers the hypersensitive response of plants to pathogens. Here, short pulses of H2O2 are shown to cause death of lentil (Lens culinaris) root protoplasts. Dead cells showed DNA fragmentation and ladder formation, typical hallmarks of apoptosis (

  13. Early echocardiographic deformation analysis for the prediction of sudden cardiac death and life-threatening arrhythmias after myocardial infarction

    DEFF Research Database (Denmark)

    Ersbøll, Mads; Valeur, Nana; Andersen, Mads Jønsson

    2013-01-01

    This study sought to hypothesize that global longitudinal strain (GLS) as a measure of infarct size, and mechanical dispersion (MD) as a measure of myocardial deformation heterogeneity, would be of incremental importance for the prediction of sudden cardiac death (SCD) or malignant ventricular ar...

  14. 孕早期暴露家装空气污染物及高温对新生鼠神经行为的影响%Effects of early pregnancy exposure to hazardous indoor air pollutants due to interior decoration and hyperthermia on neurobehavioral development of postnatal rats

    Institute of Scientific and Technical Information of China (English)

    张红; 赵聪敏

    2009-01-01

    目的 探讨孕早期暴露家装空气污染物以及联合高温对新生大鼠神经行为的影响.方法 22只孕鼠随机分为4组,每天置于污染物柜、高温柜、高温联合污染物柜以及空染毒柜中2 h时,共10 d,然后对其分娩的新生鼠在不同时间点观察体质量变化和神经行为学改变.同时观察大鼠海马CAI区凋亡和死亡神经元的数量并检测海马组织中NMDA受体NRI亚基的基因表达变化.结果 化学污染物、高温可导致新生鼠海马神经元的死亡和凋亡以及促进海马NMDA受体NRI基因的表达,并对其神经行为、学习记忆能力有显著的影响,二者联合可加重其损伤作用.结论 孕早期暴露家装宅气污染物和高温环境会对新生鼠神经系统的发育产生明显影响.%Objective To investigate the effects of early pregnancy exposure to hazardous indoor air pollu-tants due to interior decoration and hyperthermia on neurobehavioral development of postnatal rats. Methods Twenty-two pregnant rats were randomly divided into 4 groups. Each group was placed in pollutants cabinet,hyperthermia cabinet, hyperthermia + pollutants cabinet and empty cabinet respectively for 2 h per day for 10 d since their pregnancy. The weight and neurobehavioral development of postnatal rats were observed at different time points. The number of apoptotic and dead neurons in the CA1 region of hippocampus was observed in post-natal rats. The expression of the NR1 subunit of NMDA receptor of hippocampal neurons was also detected.Results Indoor pollutants and hyperthermia could accelerate apoptosis and necrosis of hippocampal neurons in CA1 region of postnatal rats and increase the expression of NRI subunit of NMDA receptor. Furthermore, haz-ardous indoor pollutants and hyperthermia could induce remarkable influences on postnatal rats' neurobehavior-al development, learning and memory capability. Indoor pollutants combined with hyporthermia aggravated these effects

  15. Early Death in Two Patients with Acute Promyelocytic Leukemia Presenting the bcr3 Isoform, FLT3-ITD Mutation, and Elevated WT1 Level

    Directory of Open Access Journals (Sweden)

    Marianna Greco

    2013-01-01

    Full Text Available Despite major advances in the treatment of acute promyelocytic leukemia (APL, the problem of early death (ED remains unsolved. Alongside the currently known clinical and hematological risk factors, prognostic significance has been attributed to internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD, hypogranular variant morphology, and the bcr-3 isoform of PML-RARα. We describe premature death of two patients with the hypogranular variant of APL who presented remarkably high expression levels of Wilms' tumor gene (WT1. Our results point to WT1 as an important prognostic factor of ED that needs to be promptly evaluated in all newly diagnosed cases of APL.

  16. ATP Depletion Via Mitochondrial F1F0 Complex by Lethal Factor is an Early Event in B. Anthracis-Induced Sudden Cell Death

    Directory of Open Access Journals (Sweden)

    Mitchell W. Woodberry

    2009-08-01

    Full Text Available Bacillus anthracis’ primary virulence factor is a tripartite anthrax toxin consisting of edema factor (EF, lethal factor (LF and protective antigen (PA. In complex with PA, EF and LF are internalized via receptor-mediated endocytosis. EF is a calmodulin- dependent adenylate cyclase that induces tissue edema. LF is a zinc-metalloprotease that cleaves members of mitogen-activated protein kinase kinases. Lethal toxin (LT: PA plus LF-induced death of macrophages is primarily attributed to expression of the sensitive Nalp1b allele, inflammasome formation and activation of caspase-1, but early events that initiate these processes are unknown. Here we provide evidence that an early essential event in pyroptosis of alveolar macrophages is LF-mediated depletion of cellular ATP. The underlying mechanism involves interaction of LF with F1F0-complex gamma and beta subunits leading to increased ATPase activity in mitochondria. In support, mitochondrial DNA-depleted MH-S cells have decreased F1F0 ATPase activity due to the lack of F06 and F08 polypeptides and show increased resistance to LT. We conclude that ATP depletion is an important early event in LT-induced sudden cell death and its prevention increases survival of toxin-sensitive cells.

  17. IFN-gamma treatment at early stages of influenza virus infection protects mice from death in a NK cell-dependent manner.

    Science.gov (United States)

    Weiss, Ido D; Wald, Ori; Wald, Hanna; Beider, Katia; Abraham, Michal; Galun, Eithan; Nagler, Arnon; Peled, Amnon

    2010-06-01

    Influenza pandemics are imminent and represent a major world health concern. Since vaccinations are expected to be less efficient in the coming years due to newly emerging influenza virus strains, novel antiviral therapies are urgently needed. Here, we show that influenza-infected mice, capable of clearing the virus in the early stages of infection, failed to control inflammation and death. Sequential administration of Interferon-gamma (IFN-gamma) at early stage of the infection protected infected mice from death in a NK cell-dependent manner. IFN-gamma treatment stimulated NK cell proliferation and function and increased their number in the bone marrow, blood, spleen, and infected lungs, keeping viral clearance intact. In parallel, IFN-gamma treatment significantly reduced the number of T cells and NKT cells in the lungs at the inflammatory phase following infection. Thus, rapidly clearing the virus and reducing inflammation by shaping the cellular and cytokine profiles in the early stages of infection may favorably change the fate of influenza pathogenesis.

  18. The Effects of Maternal Postnatal Depression and Child Sex on Academic Performance at Age 16 Years: A Developmental Approach

    Science.gov (United States)

    Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Croudace, Tim; Cooper, Peter

    2010-01-01

    Background: Postnatal depression (PND) is associated with poor cognitive functioning in infancy and the early school years; long-term effects on academic outcome are not known. Method: Children of postnatally depressed (N = 50) and non-depressed mothers (N = 39), studied from infancy, were followed up at 16 years. We examined the effects on…

  19. Analysis of the risk factors for early death due to disease recurrence or progression within 1 year after hepatectomy in patients with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kamiyama Toshiya

    2012-06-01

    Full Text Available Abstract Background Liver resection for hepatocellular carcinoma (HCC has the highest local controllability among all local treatments and results in a good survival rate. However, the recurrence rates of HCC continue to remain high even after curative hepatectomy Moreover, it has been reported that some patients with HCC have an early death due to recurrence. We analyzed the preoperative risk factors for early cancer death. Methods Between 1997 and 2009, 521 consecutive patients who underwent hepatectomy for HCC at our center were assigned to group ED (death due to HCC recurrence or progression within 1 year after hepatectomy and group NED (alive over 1 year after hepatectomy. Risk factors for early cancer death were analyzed. Results Group ED included 48 patients, and group NED included 473 patients. The cause of death included cancer progression (150; 78.1%, operation-related (1; 0.5%, hepatic failure (15; 7.8%, and other (26; 13.5%. Between the ED and NED groups, there were significant differences in albumin levels, Child-Pugh classifications, anatomical resections, curability, tumor numbers, tumor sizes, macroscopic vascular invasion (portal vein and hepatic vein, alpha-fetoprotein (AFP levels, AFP-L3 levels, protein induced by vitamin K absence or antagonism factor II (PIVKA-II levels, differentiation, microscopic portal vein invasion, microscopic hepatic vein invasion, and distant metastasis by univariate analysis. Multivariate analysis identified specific risk factors, such as AFP level > 1,000 ng/ml, tumor number ≥ 4, tumor size ≥ 5 cm, poor differentiation, and portal vein invasion. With respect to the preoperative risk factors such as AFP level, tumor number, and tumor size, 3 (1.1% of 280 patients with no risk factors, 12 (7.8% of 153 patients with 1 risk factor, 24 (32.9% of 73 patients with 2 factors, and 9 (60.0% of 15 patients with 3 risk factors died within 1 year of hepatectomy (p  Conclusions Hepatectomy

  20. Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death.

    Science.gov (United States)

    Ristagno, Giuseppe; Varpula, Tero; Masson, Serge; Greco, Marta; Bottazzi, Barbara; Milani, Valentina; Aleksova, Aneta; Sinagra, Gianfranco; Assandri, Roberto; Tiainen, Marjaana; Vaahersalo, Jukka; Kurola, Jouni; Barlera, Simona; Montanelli, Alessandro; Latini, Roberto; Pettilä, Ville; Bendel, Stepani; Skrifvars, Markus B

    2015-10-01

    A systemic inflammatory response is observed after cardiopulmonary resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3) and soluble suppression of tumorigenicity 2 (sST2), in comparison with the classic high-sensitivity C-reactive protein (hsCRP), for prediction of early multiple organ dysfunction syndrome (MODS), early death, and long-term outcome after out-of-hospital cardiac arrest. PTX3, sST2, and hsCRP were assayed at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non-neurological Sequential Organ Failure Assessment (SOFA) score ≥ 12. Intensive care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were evaluated. In total, 82% of patients survived to ICU discharge and 48% had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission, median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1 ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were also higher in patients who died in ICU and in those with an unfavorable 12-month neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340, (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and 1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were independently associated with ICU death. Higher plasma levels of PTX3 and sST2, but not of hsCRP, at ICU admission were associated with higher risk of MODS and early death.

  1. 利用肉色相关候选基因对肉色性状进行预测%Utilization of meat color candidate genes in early postnatal prediction of pig meat color trait

    Institute of Scientific and Technical Information of China (English)

    佟辉; 赵茹茜

    2009-01-01

    investigate relationships between parameters. Results showed that MB mRNA positively correlated with subjective color scoring (r = 0.426~(**) (~(**); P<0. 01)) , a~* (r = 0. 379~(**)), and MB concentration (r = 0.364**). NFATcl mRNA positively correlated with subjective color scoring (r = 0. 407~(**)), a~* (r = 0. 406~(**)), MB concentration (r = 0.345~* (~*: P<0.05)), and MB mRNA (r = 0.571~(**)). 2) Large White boars, Erhualian boars and Erhualian gilts were employed to investigate the developmental patterns of expression level of four meat color candidate genes in LD muscle at day 3, 20, 45, 90, 120 and 180 respectively. Results indicated that the developmental pattern of Myoglobin, MEF2, and Calcineurin mRNA levels were similar, higher in Erhualian and lower in Large White except day 3. However, NFATcl was on the opposite, higher in Large White. MB, NFATcl and Calcineurin mRNA levels all increased dramatically at day 20 and after no significant changes were abserved. As for gender difference, expressions of MB and MEF2 mRNA were similar, and significant changes happened only at day 180. The expression of Calcineurin and NFATcl mRNA showed no significant changes. So we suggest day 20 be the eligible time of early postnatal selection.

  2. Profound morphological and functional changes of rodent Purkinje cellsbetween the first and the second postnatal weeks: a metamorphosis?

    Directory of Open Access Journals (Sweden)

    Isabelle eDusart

    2012-04-01

    Full Text Available Between the first and the second postnatal week, the development of rodent Purkinje cells is characterized by several profound transitions. Purkinje cells acquire their typical dendritic espalier tree morphology and form distal spines. During the first postnatal week, they are multi-innervated by climbing fibers and numerous collateral branches sprout from their axons, whereas from the second postnatal week, the regression of climbing fiber multi-innervation begins, and Purkinje cells become innervated by parallel fibers and inhibitory molecular layer interneurons. Furthermore, their periods of developmental cell death and ability to regenerate their axon stop and their axons become myelinated. Thus a Purkinje cell during the first postnatal week looks and functions differently from a Purkinje cell during the second postnatal week. These fundamental changes occur in parallel with a peak of circulating thyroid hormone in the mouse. All these features suggest to some extent an interesting analogy with amphibian metamorphosis.

  3. Mind and mood in modern art, II: Depressive disorders, spirituality, and early deaths in the abstract expressionist artists of the New York School.

    Science.gov (United States)

    Schildkraut, J J; Hirshfeld, A J; Murphy, J M

    1994-04-01

    This article documents the high prevalence of mood disorders in a group of 15 of the mid-twentieth-century Abstract Expressionist artists of the New York School. These artists, using the technique of psychic automatism (based on free association) in order to reveal unconscious material, created a psychologically and spiritually significant art that addressed the mythic themes of creation, birth, life, and death. Over 50% of the 15 artists in this group had some form of psychopathology, predominantly mood disorders and preoccupation with death, often compounded by alcohol abuse. At least 40% sought treatment and 20% were hospitalized for psychiatric problems. Two committed suicide; two died in single-vehicle accidents while driving; and two others had fathers who killed themselves. Many of these artists died early deaths, and close to 50% of the group (seven of 15) were dead before the age of 60. The material presented in this article suggests the following formulation and hypothesis. Depression inevitably leads to a turning inward and to the painful reexamination of the purpose of living and the possibility of dying. Thus, by bringing the artist into direct and lonely confrontation with the ultimate existential question, whether to live or to die, depression may have put these artists in touch with the inexplicable mystery that lies at the heart of the "tragic and timeless" art that the Abstract Expressionists aspired to produce.

  4. A new theraphosid spider toxin causes early insect cell death by necrosis when expressed in vitro during recombinant baculovirus infection.

    Directory of Open Access Journals (Sweden)

    Daniel Mendes Pereira Ardisson-Araújo

    Full Text Available Baculoviruses are the most studied insect viruses in the world and are used for biological control of agricultural and forest insect pests. They are also used as versatile vectors for expression of heterologous proteins. One of the major problems of their use as biopesticides is their slow speed to kill insects. Thus, to address this shortcoming, insect-specific neurotoxins from arachnids have been introduced into the baculovirus genome solely aiming to improve its virulence. In this work, an insecticide-like toxin gene was obtained from a cDNA derived from the venom glands of the theraphosid spider Brachypelma albiceps. The mature form of the peptide toxin (called Ba3 has a high content of basic amino acid residues, potential for three possible disulfide bonds, and a predicted three-stranded β-sheetDifferent constructions of the gene were engineered for recombinant baculovirus Autographa californica multiple nuclepolyhedrovirus (AcMNPV expression. Five different forms of Ba3 were assessed; (1 the full-length sequence, (2 the pro-peptide and mature region, (3 only the mature region, and the mature region fused to an (4 insect or a (5 virus-derived signal peptide were inserted separately into the genome of the baculovirus. All the recombinant viruses induced cell death by necrosis earlier in infection relative to a control virus lacking the toxin gene. However, the recombinant virus containing the mature portion of the toxin gene induced a faster cell death than the other recombinants. We found that the toxin construct with the signal peptide and/or pro-peptide regions delayed the necrosis phenotype. When infected cells were subjected to ultrastructural analysis, the cells showed loss of plasma membrane integrity and structural changes in mitochondria before death. Our results suggest this use of baculovirus is a potential tool to help understand or to identify the effect of insect-specific toxic peptides when produced during infection of insect

  5. A New theraphosid Spider Toxin Causes Early Insect Cell Death by Necrosis When Expressed In Vitro during Recombinant Baculovirus Infection

    Science.gov (United States)

    Ardisson-Araújo, Daniel Mendes Pereira; Morgado, Fabrício Da Silva; Schwartz, Elisabeth Ferroni; Corzo, Gerardo; Ribeiro, Bergmann Morais

    2013-01-01

    Baculoviruses are the most studied insect viruses in the world and are used for biological control of agricultural and forest insect pests. They are also used as versatile vectors for expression of heterologous proteins. One of the major problems of their use as biopesticides is their slow speed to kill insects. Thus, to address this shortcoming, insect-specific neurotoxins from arachnids have been introduced into the baculovirus genome solely aiming to improve its virulence. In this work, an insecticide-like toxin gene was obtained from a cDNA derived from the venom glands of the theraphosid spider Brachypelma albiceps. The mature form of the peptide toxin (called Ba3) has a high content of basic amino acid residues, potential for three possible disulfide bonds, and a predicted three-stranded β-sheetDifferent constructions of the gene were engineered for recombinant baculovirus Autographa californica multiple nuclepolyhedrovirus (AcMNPV) expression. Five different forms of Ba3 were assessed; (1) the full-length sequence, (2) the pro-peptide and mature region, (3) only the mature region, and the mature region fused to an (4) insect or a (5) virus-derived signal peptide were inserted separately into the genome of the baculovirus. All the recombinant viruses induced cell death by necrosis earlier in infection relative to a control virus lacking the toxin gene. However, the recombinant virus containing the mature portion of the toxin gene induced a faster cell death than the other recombinants. We found that the toxin construct with the signal peptide and/or pro-peptide regions delayed the necrosis phenotype. When infected cells were subjected to ultrastructural analysis, the cells showed loss of plasma membrane integrity and structural changes in mitochondria before death. Our results suggest this use of baculovirus is a potential tool to help understand or to identify the effect of insect-specific toxic peptides when produced during infection of insect cells. PMID

  6. Postnatal Migration of Cerebellar Interneurons

    Science.gov (United States)

    Galas, Ludovic; Bénard, Magalie; Lebon, Alexis; Komuro, Yutaro; Schapman, Damien; Vaudry, Hubert; Vaudry, David; Komuro, Hitoshi

    2017-01-01

    Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location. In addition, cortical-layer specific regulatory factors such as neuropeptides (pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin) or proteins (tissue-type plasminogen activator (tPA), insulin growth factor-1 (IGF-1)) have been shown to inhibit or stimulate the migratory process of interneurons. These factors show further complexity because somatostatin, PACAP, or tPA have opposite or no effect on interneuron migration depending on which layer or cell type they act upon. External factors originating from environmental conditions (light stimuli, pollutants), nutrients or drug of abuse (alcohol) also alter normal cell migration, leading to cerebellar disorders. PMID:28587295

  7. Clinical characteristics of Japanese candidates for lung transplant for interstitial lung disease and risk factors for early death while on the waiting list.

    Science.gov (United States)

    Higo, Hisao; Kurosaki, Takeshi; Ichihara, Eiki; Kubo, Toshio; Miyoshi, Kentaroh; Otani, Shinji; Sugimoto, Seiichiro; Yamane, Masaomi; Miyahara, Nobuaki; Kiura, Katsuyuki; Miyoshi, Shinichiro; Oto, Takahiro

    2017-07-01

    Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  8. The Long-Term Economic Impact of in Utero and Postnatal Exposure to Malaria

    Science.gov (United States)

    Barreca, Alan I.

    2010-01-01

    I use an instrumental-variables identification strategy and historical data from the United States to estimate the long-term economic impact of in utero and postnatal exposure to malaria. My research design matches adults in the 1960 Decennial Census to the malaria death rate in their respective state and year of birth. To address potential…

  9. The Long-Term Economic Impact of in Utero and Postnatal Exposure to Malaria

    Science.gov (United States)

    Barreca, Alan I.

    2010-01-01

    I use an instrumental-variables identification strategy and historical data from the United States to estimate the long-term economic impact of in utero and postnatal exposure to malaria. My research design matches adults in the 1960 Decennial Census to the malaria death rate in their respective state and year of birth. To address potential…

  10. 早期复极综合征与特发性室颤及猝死%Idiopathic ventricular fibrillation and sudden death associated with early repolarization syndrome.

    Institute of Scientific and Technical Information of China (English)

    陈漠水

    2011-01-01

    Early repolarization syndrome (ERS) is a well-recognized idiopathic electrocardiographic phenomenon characterized by prominent J wave and a positive large T wave and ST-segment elevation, concave to the top, predominantly in left precordial (V3~V6 ) leads. It was generally thought that ERS is benign, but recently a growing number of case reports indicate that in some instances, ERS repeatedly induces idiopathic ventricular fibrillation which causes sudden death, suggesting that ERS is associated with idiopathic ventricular fibrillation and sudden death.However, the mechanism of its arrhythmogenic potential still remains unknown. Therefore, patients with ERS who have chest pain, unexplained syncope or other symptoms and at high risks of family history of sudden death should be automatically transferred implantable cardiac defibrillator (ICD) to improve the prognosis. This review summarizes the current state of knowledge concerning ERS associated with idiopathic ventricular fibrillation and sudden death.%早期复极综合征(ERS)是一种以心电图上表现为J波增大或J点抬高,胸前导联V3-V6弓背向下的ST段抬高和高大而直立的T波的特征性的心电改变,通常认为是一种正常心电图的良性变异,但近来报道早期复极综合征在一些情况下可诱发特发性心室颤动,导致猝死,机制尚未明确.对于有胸痛、晕厥等症状或(和)猝死家族史等的高危ERS患者,应植入型心脏自动转律除颤器(ICD)以改善预后.

  11. Studies on time of death estimation in the early post mortem period -- application of a method based on eyeball temperature measurement to human bodies.

    Science.gov (United States)

    Kaliszan, Michał

    2013-09-01

    This paper presents a verification of the thermodynamic model allowing an estimation of the time of death (TOD) by calculating the post mortem interval (PMI) based on a single eyeball temperature measurement at the death scene. The study was performed on 30 cases with known PMI, ranging from 1h 35min to 5h 15min, using pin probes connected to a high precision electronic thermometer (Dostmann-electronic). The measured eye temperatures ranged from 20.2 to 33.1°C. Rectal temperature was measured at the same time and ranged from 32.8 to 37.4°C. Ambient temperatures which ranged from -1 to 24°C, environmental conditions (still air to light wind) and the amount of hair on the head were also recorded every time. PMI was calculated using a formula based on Newton's law of cooling, previously derived and successfully tested in comprehensive studies on pigs and a few human cases. Thanks to both the significantly faster post mortem decrease of eye temperature and a residual or nonexistent plateau effect in the eye, as well as practically no influence of body mass, TOD in the human death cases could be estimated with good accuracy. The highest TOD estimation error during the post mortem intervals up to around 5h was 1h 16min, 1h 14min and 1h 03min, respectively in three cases among 30, while for the remaining 27 cases it was not more than 47min. The mean error for all 30 cases was ±31min. All that indicates that the proposed method is of quite good precision in the early post mortem period, with an accuracy of ±1h for a 95% confidence interval. On the basis of the presented method, TOD can be also calculated at the death scene with the use of a proposed portable electronic device (TOD-meter).

  12. The longitudinal time course of QTc in early infancy. Preliminary results of a prospective sudden infant death syndrome surveillance program.

    Science.gov (United States)

    Schaffer, M S; Trippel, D L; Buckles, D S; Young, R H; Dolan, P L; Gillette, P C

    1991-03-01

    Eleven hundred one healthy neonates in Charleston County, SC, were enrolled in a prospective, serial measurement sudden infant death syndrome/QT surveillance program. Automated computer-enhanced ECGs were recorded at 1 day of age in the hospital nursery and again at 1 week and 1, 2, and 3 months in the participant's home. At 1 year, the families were contacted by phone or mail and questioned as to the health of the child. Validation studies demonstrated the computer-enhanced ECGs to be 96% accurate, whereas traditional ECG recording and measurement was 94% accurate. No systematic differences in the QTc according to race and sex were observed. There were parallel longitudinal time courses for each race and sex group with a significant (P less than .001) shortening of the QTc at 1 week. There was no evidence of tracking of the QTc during the first 3 months of life. In conclusion, (1) automated, enhanced ECG QTc intervals are superior to traditional electrocardiography while retaining the advantages of automation; (2) there is a significant shortening of the QTc during the first month of life; and (3) a home follow-up sudden infant death syndrome surveillance program is feasible and produces accurate, reliable information.

  13. Identification of proliferative progenitors associated with prominent postnatal growth of the pons

    Science.gov (United States)

    Lindquist, Robert A.; Guinto, Cristina D.; Rodas-Rodriguez, Jose L.; Fuentealba, Luis C.; Tate, Matthew C.; Rowitch, David H.; Alvarez-Buylla, Arturo

    2016-01-01

    The pons controls crucial sensorimotor and autonomic functions. In humans, it grows sixfold postnatally and is a site of paediatric gliomas; however, the mechanisms of pontine growth remain poorly understood. We show that the murine pons quadruples in volume postnatally; growth is fastest during postnatal days 0–4 (P0–P4), preceding most myelination. We identify three postnatal proliferative compartments: ventricular, midline and parenchymal. We find no evidence of postnatal neurogenesis in the pons, but each progenitor compartment produces new astroglia and oligodendroglia; the latter expand 10- to 18-fold postnatally, and are derived mostly from the parenchyma. Nearly all parenchymal progenitors at P4 are Sox2+Olig2+, but by P8 a Sox2− subpopulation emerges, suggesting a lineage progression from Sox2+ ‘early' to Sox2− ‘late' oligodendrocyte progenitor. Fate mapping reveals that >90% of adult oligodendrocytes derive from P2–P3 Sox2+ progenitors. These results demonstrate the importance of postnatal Sox2+Olig2+ progenitors in pontine growth and oligodendrogenesis. PMID:27188978

  14. Lysosomal Membrane Permeabilization is an Early Event in Sigma-2 Receptor Ligand Mediated Cell Death in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Hornick John R

    2012-05-01

    Full Text Available Abstract Background Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden in preclinical models of human pancreatic cancer. Results Fluorescently labeled sigma-2 receptor ligands of two classes (derivatives of SW43 and PB282 localize to cell membrane components in Bxpc3 and Aspc1 pancreatic cancer cells and accumulate in lysosomes. We found that interactions in the lysosome are critical for cell death following sigma-2 ligand treatment because selective inhibition of a protective lysosomal membrane glycoprotein, LAMP1, with shRNA greatly reduced the viability of cells following treatment. Sigma-2 ligands induced lysosomal membrane permeabilization (LMP and protease translocation triggering downstream effectors of apoptosis. Subsequently, cellular oxidative stress was greatly increased following treatment with SW43, and the hydrophilic antioxidant N-acetylcysteine (NAC gave greater protection against this than a lipophilic antioxidant, α-tocopherol (α-toco. Conversely, PB282-mediated cytotoxicity relied less on cellular oxidation, even though α-toco did provide protection from this ligand. In addition, we found that caspase-3 induction was not as significantly inhibited by cathepsin inhibitors as by antioxidants. Both NAC and α-toco protected against caspase-3 induction following PB282 treatment, while only NAC offered protection following SW43 treatment. The caspase-3 inhibitor DEVD-FMK offered significant protection from PB282, but not SW43. Conclusions Sigma-2 ligand SW43 commits pancreatic cancer cells to death by a caspase-independent process involving LMP and oxidative stress which is protected from by NAC. PB282 however undergoes a

  15. Effects of Prenatal Irradiation with an Accelerated Heavy-Ion Beam on Postnatal Development in Rats

    Science.gov (United States)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Fujita, K.; Coffigny, H.; Hayata, I.

    Effects on postnatal neurophysiological development in offspring were studied following exposure of pregnant Wistar rats to accelerated neon-ion beams with a LET value of about 30 keV mu m at a dose range from 0 1 Gy to 2 0Gy on the 15th day of gestation The age at which four physiologic markers appeared and five reflexes were acquired was examined prior to weaning Gain in body weight was monitored until the offspring were 3 months old Male offspring were evaluated as young adults using two behavioral tests The effects of X-rays at 200 kVp measured for the same biological end points were studied for comparison Our previous study on carbon-ion beams with a LET value of about 13 keV mu m was also cited to elucidate a possible LET-related effect For most of the endpoints at early age significant alteration was even observed in offspring prenatally received 0 1 Gy of accelerated neon ions while neither X rays nor carbon-ions under the same dose resulted in such a significant alteration compared to that from the sham-irradiated dams All offspring whose mothers received 2 0 Gy died prior to weaning Offspring from dams irradiated with accelerated neon ions generally showed higher incidences of prenatal death and preweaning mortality markedly delayed accomplishment in their physiological markers and reflexes and gain in body weight compared to those exposed to X-rays or carbon ions at doses of 0 1 to 1 5 Gy Significantly reduced ratios of main organ weight to body weight at postnatal ages of 30 60 and 90 days were also observed

  16. RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice.

    Directory of Open Access Journals (Sweden)

    Enric Mocholí

    Full Text Available Rnd proteins are a subfamily of Rho GTPases involved in the control of actin cytoskeleton dynamics and other cell functions such as motility, proliferation and survival. Unlike other members of the Rho family, Rnd proteins lack GTPase activity and therefore remain constitutively active. We have recently described that RhoE/Rnd3 is expressed in the Central Nervous System and that it has a role in promoting neurite formation. Despite their possible relevance during development, the role of Rnd proteins in vivo is not known. To get insight into the in vivo function of RhoE we have generated mice lacking RhoE expression by an exon trapping cassette. RhoE null mice (RhoE gt/gt are smaller at birth, display growth retardation and early postnatal death since only half of RhoE gt/gt mice survive beyond postnatal day (PD 15 and 100% are dead by PD 29. RhoE gt/gt mice show an abnormal body position with profound motor impairment and impaired performance in most neurobehavioral tests. Null mutant mice are hypoactive, show an immature locomotor pattern and display a significant delay in the appearance of the hindlimb mature responses. Moreover, they perform worse than the control littermates in the wire suspension, vertical climbing and clinging, righting reflex and negative geotaxis tests. Also, RhoE ablation results in a delay of neuromuscular maturation and in a reduction in the number of spinal motor neurons. Finally, RhoE gt/gt mice lack the common peroneal nerve and, consequently, show a complete atrophy of the target muscles. This is the first model to study the in vivo functions of a member of the Rnd subfamily of proteins, revealing the important role of Rnd3/RhoE in the normal development and suggesting the possible involvement of this protein in neurological disorders.

  17. The influence of postnatal handling on adult neuroendocrine and behavioural stress reactivity

    NARCIS (Netherlands)

    Meerlo, P; Horvath, KM; Nagy, GM; Bohus, B; Koolhaas, JM

    1999-01-01

    Environmental stimuli during early stages of life can influence the development of an organism and may result in permanent changes in adult behaviour and physiology. In the present study we investigated the influence of early postnatal handling on adult neuroendocrine and behavioural stress reactivi

  18. Lung fluid during postnatal transition

    Institute of Scientific and Technical Information of China (English)

    Sture Andersson; Olli Pitk(a)nen; Cecilia Janér; Otto Helve

    2010-01-01

    @@ Successful postnatal pulmonary adaptation is dependent on cessation of fetal fluid secretion into the luminal space of the lung and a switch to fluid absorption during the perinatal period. Most infants undergo this transformation rapidly, but some encounter difficulties.Failure in adaptation may result, in preterm infants, in respiratory distress syndrome (RDS) and, in near-term and term infants, in transient tachypnea of the newborn (TTN). In both entities, among other causes, lung liquid clearance, i.e. the inability to clear the lung of perinatal fluid, may be ineffective.1-4 In addition, there are data connecting bronchopulmonary dysplasia (BPD) to decreased ion transport.5-7 However, only limited data are available on the association of lung fluid transport and neonatal respiratory distress in human infants.

  19. Family dynamics and postnatal depression.

    Science.gov (United States)

    Tammentie, T; Tarkka, M-T; Astedt-Kurki, P; Paavilainen, E; Laippala, P

    2004-04-01

    Research has shown that postnatal depression (PND) affects 10-15% of mothers in Western societies. PND is not easily identified and therefore it often remains undetected. Untreated depression has a detrimental effect on the mother and child and the entire family. The purpose of this study was to ascertain the state of family dynamics after delivery and whether the mother's PND was associated with family dynamics. The study used a survey covering the catchment area of one Finnish university hospital. Both primi- and multiparas took part and data were collected using the Edinburgh Postnatal Depression Scale (EPDS) for mothers and the Family Dynamics Measure II (FDM II) for both mothers and fathers. The data were analysed using SPSS statistical programme and frequency and percentage distributions, means and standard deviations were examined. Correlations were analysed using Spearman's correlation coefficients. The significance of any differences between mothers' and fathers' scores was determined with a paired t-test. Of the families participating in the study (373 mothers and 314 partners), 13% of the mothers suffered from PND symptoms (EPDS score of 13 or more). As a whole, family dynamics in the families participating in the study were reported to be rather good. However, mothers having depressive symptoms reported more negative family dynamics compared with other families. With the exception of individuation, mothers having depressive symptoms reported more negative family dynamics than their partners. With the exception of role reciprocity, non-depressed mothers reported more positive family dynamics than their partners. Knowledge of the association of mothers' PND with family dynamics could help to develop nursing care at maternity and child welfare clinics and maternity hospitals. Depressed mothers and their families need support to be able to make family dynamics as good as possible.

  20. Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters

    Energy Technology Data Exchange (ETDEWEB)

    Damodaran, T.V., E-mail: tdamodar@nccu.edu [Dept of Medicine, Duke University Medical Center, Durham, NC (United States); Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC (United States); Dept of Biology, North Carolina Central University, Durham, NC 27707 (United States); Attia, M.K. [Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC (United States); Abou-Donia, M.B., E-mail: donia@mc.duke.edu [Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC (United States)

    2011-11-15

    analysis revealed that the order of severity of damage declines from the spino-cerebellar, ventral, and dorsal tract respectively, suggesting neuroanatomical specificity. Thus, early activation of cell death and cell survival processes may play significant role in the clinical progression and syndromic clinical feature presentation of OPIDN. -- Highlights: Black-Right-Pointing-Pointer Multiple mechanisms of neurodegeneration were indicated in a study on OPIDN model. Black-Right-Pointing-Pointer Altered expressions of BCL2 and GADD45 were recorded in various tissues of CNS. Black-Right-Pointing-Pointer Multiple anomalous cellular (neuronal and astroglial) features were recorded. Black-Right-Pointing-Pointer Anatomical specificity of the neurodegeneration was described.

  1. Pre- and postnatal nutrition in sheep affects β-cell secretion and hypothalamic control

    DEFF Research Database (Denmark)

    Kongsted, Anna H.; Husted, Sanne V.; Thygesen, Malin P.

    2013-01-01

    Maternal undernutrition increases the risk of type 2 diabetes and metabolic syndrome later in life, particularly upon postnatal exposure to a high-energy diet. However, dysfunctions of, for example, the glucose–insulin axis are not readily detectable by conventional tests early in life, making...... it difficult to identify individuals at risk. Thus, other methods are required. We hypothesised that prenatally undernourished individuals (but not postnatally overnourished ones) are adapted to a life with limited food availability, which would be evident under conditions reflecting starvation, stress...... abundance) and adrenalin challenges. At 6 months of age, postnatal HCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic β-cell secretion. Irrespective of postnatal diet, prenatal undernutrition was found to be associated with unexpected endocrine responses...

  2. Influence of shieldings or antioxidants on DNA damage and early and delyed cell death induced in human fibroblasts by accelerated 595 MeV/u Fe ions

    Science.gov (United States)

    Antonelli, Francesca; Esposito, Giuseppe; Dini, Valentina; Belli, Mauro; Campa, Alessandro; Sorrentino, Eugenio; Antonella Tabocchini, Maria; Lobascio, Cesare; Berra, Bruno

    HZE particles from space radiation raise an important protection concern during long-term astronauts' travels. As high charge, high energy particles interact with a shield, both projec-tile and target fragmentation may occurs, so that the biological properties of the emerging radiation field depend on the nature and energy of the incident particles, and on the nature and thickness of the shield. We have studied the influence of PMMA and Kevlar shielding as well as the antioxidant compounds Rosmarinic acid or Resveratrol on DNA damage induction and processing (as evaluated by the g-H2AX phosphorylation assay) and on early and delayed cell death in AG01522 human fibroblasts irradiated with Fe ions of 595 MeV/u at the NASA Space Radiation Laboratory (NSRL), Brookhaven National Laboratory (BNL, Upton, USA). Insertion of PMMA or Kevlar shields (10 g/cm2 thick) gave no substantial change in the bio-logical effect per unit dose on the sample for all the end points studied. When irradiation was performed in the presence of 300 mM Rosmarinic acid or Resveratrol no difference were found for both early and delayed cell death, while a slight protective effect was observed for the initial and residual DNA damage. For both early and delayed cell death, Fe-ions are more effective than g-rays. The number of Fe-ion induced g-H2AX foci is instead lower than that induced by g-rays, due to the presence of multiple DSB within a single focus induced by Fe-ions. From a comparison of the g-H2AX data with the results on DNA fragmentation obtained with 414 MeV/u Fe ions at the Heavy Ions Medical Accelerator (HIMAC, Chiba, Japan) and with 1 GeV/u Fe ions at BNL, in the absence or in the presence of PMMA shields (Esposito et al, Advance in Space Research 2004) we speculate that the overall effect of the shield is a balance between the contributions due to the slowing down of the primary particles and that due to the nuclear fragmentation. Acknowledgment: Financial support from ASI project

  3. Chronic brain hypoperfusion causes early glial activation and neuronal death, and subsequent long-term memory impairment.

    Science.gov (United States)

    Cechetti, Fernanda; Pagnussat, Aline S; Worm, Paulo V; Elsner, Viviane Rostirolla; Ben, Juliana; da Costa, Marcelo Siveira; Mestriner, Régis; Weis, Simone Nardin; Netto, Carlos Alexandre

    2012-01-04

    Reduction of cerebral blood flow is an important risk factor for dementia states and other brain dysfunctions. In present study, the effects of permanent occlusion of common carotid arteries (2VO), a well established experimental model of brain ischemia, on memory function were investigated, as assessed by reference and working spatial memory protocols and the object recognition task; cell damage to the hippocampus, as measured through changes in immunoreactivity for GFAP and the neuronal marker NeuN was also studied. The working hypothesis is that metabolic impairment following hypoperfusion will affect neuron and glial function and result in functional damage. Adult male Wistar rats were submitted to the modified 2VO method, with the right common carotid artery being occluded first and the left one week later, and tested seven days, three and six months after the ischemic event. A significant cognitive deficit was found in both reference and working spatial memory, as well as in the object recognition task, three and six months after surgery. Neuronal death and reactive astrogliosis were already present at 7 days and continued for up to 3 months after the occlusion; interestingly, there was no significant reduction in hippocampal volume. Present data suggests that cognitive impairment caused by brain hypoperfusion is long - lasting and persists beyond the time point of recovery from glial activation and neuronal loss. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Death Cafe.

    Science.gov (United States)

    Miles, Lizzy; Corr, Charles A

    2017-06-01

    This article explains the meaning of the phrase Death Cafe and describes what typically occurs at a Death Cafe gathering. The article traces the history of the Death Cafe movement, explores some reasons why people take part in a Death Cafe gathering, and gives examples of what individuals think they might derive from their participation. In addition, this article notes similarities between the Death Cafe movement and three other developments in the field of death, dying, and bereavement. Finally, this article identifies two provisional lessons that can be drawn from Death Cafe gatherings and the Death Cafe movement itself.

  5. International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation ≥ 6: a new predictor of hemorrhagic early death in acute promyelocytic leukemia.

    Science.gov (United States)

    Mitrovic, Mirjana; Suvajdzic, Nada; Bogdanovic, Andrija; Kurtovic, Nada Kraguljac; Sretenovic, Aleksandra; Elezovic, Ivo; Tomin, Dragica

    2013-03-01

    High-hemorrhagic early death (ED) rate is a major impediment in the managing of acute promyelocytic leukemia (APL). In our group of 56 newly diagnosed APL patients, ED occurred in 12 subjects, due to endocranial bleeding (8/12), differentiation syndrome (2/12), or infection (2/12). Predictors of hemorrhagic ED were as follows: white blood cells count ≥ 20 × 10(9)/L (P = 0.002337), Eastern cooperative oncology group performance status ≥ 3 (P = 0.00173), fibrinogen level disseminated intravascular coagulation (ISTH DIC score) ≥ 6 (P = 0.00741). Multivariate analysis indicated ISTH DIC score ≥ 6 to be the most significant predictor for hemorrhagic ED (P = 0.008). The main finding of this study is that simple coagulation-related tests, performed on hospital admission and combined in the ISTH DIC score, might help to identify patients at high risk for fatal bleeding needing more aggressive supportive measures.

  6. Altered RyR2 regulation by the calmodulin F90L mutation associated with idiopathic ventricular fibrillation and early sudden cardiac death.

    Science.gov (United States)

    Nomikos, Michail; Thanassoulas, Angelos; Beck, Konrad; Vassilakopoulou, Vyronia; Hu, Handan; Calver, Brian L; Theodoridou, Maria; Kashir, Junaid; Blayney, Lynda; Livaniou, Evangelia; Rizkallah, Pierre; Nounesis, George; Lai, F Anthony

    2014-08-25

    Calmodulin (CaM) association with the cardiac muscle ryanodine receptor (RyR2) regulates excitation-contraction coupling. Defective CaM-RyR2 interaction is associated with heart failure. A novel CaM mutation (CaM(F90L)) was recently identified in a family with idiopathic ventricular fibrillation (IVF) and early onset sudden cardiac death. We report the first biochemical characterization of CaM(F90L). F90L confers a deleterious effect on protein stability. Ca(2+)-binding studies reveal reduced Ca(2+)-binding affinity and a loss of co-operativity. Moreover, CaM(F90L) displays reduced RyR2 interaction and defective modulation of [(3)H]ryanodine binding. Hence, dysregulation of RyR2-mediated Ca(2+) release via aberrant CaM(F90L)-RyR2 interaction is a potential mechanism that underlies familial IVF.

  7. A novel transcription factor, ERD15 (Early Responsive to Dehydration 15), connects endoplasmic reticulum stress with an osmotic stress-induced cell death signal.

    Science.gov (United States)

    Alves, Murilo S; Reis, Pedro A B; Dadalto, Silvana P; Faria, Jerusa A Q A; Fontes, Elizabeth P B; Fietto, Luciano G

    2011-06-03

    As in all other eukaryotic organisms, endoplasmic reticulum (ER) stress triggers the evolutionarily conserved unfolded protein response in soybean, but it also communicates with other adaptive signaling responses, such as osmotic stress-induced and ER stress-induced programmed cell death. These two signaling pathways converge at the level of gene transcription to activate an integrated cascade that is mediated by N-rich proteins (NRPs). Here, we describe a novel transcription factor, GmERD15 (Glycine max Early Responsive to Dehydration 15), which is induced by ER stress and osmotic stress to activate the expression of NRP genes. GmERD15 was isolated because of its capacity to stably associate with the NRP-B promoter in yeast. It specifically binds to a 187-bp fragment of the NRP-B promoter in vitro and activates the transcription of a reporter gene in yeast. Furthermore, GmERD15 was found in both the cytoplasm and the nucleus, and a ChIP assay revealed that it binds to the NRP-B promoter in vivo. Expression of GmERD15 in soybean protoplasts activated the NRP-B promoter and induced expression of the NRP-B gene. Collectively, these results support the interpretation that GmERD15 functions as an upstream component of stress-induced NRP-B-mediated signaling to connect stress in the ER to an osmotic stress-induced cell death signal.

  8. Air pollution and early deaths in the United States. Part II: Attribution of PM2.5 exposure to emissions species, time, location and sector

    Science.gov (United States)

    Dedoussi, Irene C.; Barrett, Steven R. H.

    2014-12-01

    Combustion emissions constitute the largest source of anthropogenic emissions in the US, and lead to the degradation of air quality and human health. In Part I we computed the population fine particulate matter (PM2.5) exposure and number of early deaths caused by emissions from six major sectors: electric power generation, industry, commercial and residential activities, road transportation, marine transportation and rail transportation. In Part II we attribute exposure and early deaths to sectors, emissions species, time of emission, and location of emission. We apply a long-term adjoint sensitivity analysis and calculate the four dimensional sensitivities (time and space) of PM2.5 exposure with respect to each emissions species. Epidemiological evidence is used to relate increased population exposure to premature mortalities. This is the first regional application of the adjoint sensitivity analysis method to characterize long-term air pollution exposure. (A global scale application has been undertaken related to intercontinental pollution.) We find that for the electric power generation sector 75% of the attributable PM2.5 exposure is due to SO2 emissions, and 80% of the annual impacts are attributed to emissions from April to September. In the road transportation sector, 29% of PM2.5 exposure is due to NOx emissions and 33% is from ammonia (NH3), which is a result of emissions after-treatment technologies. We estimate that the benefit of reducing NH3 emissions from road transportation is ∼20 times that of NOx per unit mass. 75% of the road transportation ammonia impacts occur during the months October to March. We publicly release the sensitivity matrices computed, noting their potential use as a rapid air quality policy assessment tool.

  9. Not all are lost: interrupted laboratory monitoring, early death, and loss to follow-up (LTFU in a large South African treatment program.

    Directory of Open Access Journals (Sweden)

    Aima A Ahonkhai

    Full Text Available BACKGROUND: Many HIV treatment programs in resource-limited settings are plagued by high rates of loss to follow-up (LTFU. Most studies have not distinguished between those who briefly interrupt, but return to care, and those more chronically lost to follow-up. METHODS: We conducted a retrospective cohort study of 11,397 adults initiating antiretroviral therapy (ART in 71 Southern African Catholic Bishops Conference/Catholic Relief Services HIV treatment clinics between January 2004 and December 2008. We distinguished among patients with early death, within the first 7 months on ART; patients with interruptions in laboratory monitoring (ILM, defined as missing visits in the first 7 months on ART, but returning to care by 12 months; and those LTFU, defined as missing all follow-up visits in the first 12 months on ART. We used multilevel logistic regression models to determine patient and clinic-level characteristics associated with these outcomes. RESULTS: In the first year on ART, 60% of patients remained in care, 30% missed laboratory visits, and 10% suffered early death. Of the 3,194 patients who missed laboratory visits, 40% had ILM, resuming care by 12 months. After 12 months on ART, patients with ILM had a 30% increase in detectable viremia compared to those who remained in care. Risk of LTFU decreased with increasing enrollment year, and was lowest for patients who enrolled in 2008 compared to 2004 [OR 0.49, 95%CI 0.39-0.62]. CONCLUSIONS: In a large community-based cohort in South Africa, nearly 30% of patients miss follow-up visits for CD4 monitoring in the first year after starting ART. Of those, 40% have ILM but return to clinic with worse virologic outcomes than those who remain in care. The risk of chronic LTFU decreased with enrollment year. As ART availability increases, interruptions in care may become more common, and should be accounted for in addressing program LTFU.

  10. Revealing tact within postnatal care.

    Science.gov (United States)

    Smythe, Elizabeth; Payne, Deborah; Wilson, Sally; Paddy, Ann; Heard, Kate

    2014-02-01

    In this article, we explore the nature of good postnatal care through a hermeneutic unpacking of the notion of tact, drawing on the philosophical writings of Heidegger, Gadamer, and van Manen. The tactful encounters considered were from a hermeneutic research study within a small, rural birthing center in New Zealand. Insights drawn from the analysis were as follows: the openness of listening, watching and being attuned that builds a positive mode of engagement, recognizing that the distance the woman needs from her nurse/midwife is a call of tact, that tact is underpinned by a spirit of care, within tact there are moods and tact might require firmness, and that all of these factors come together to build trust. We conclude that the attunement of tact requires that the staff member has time to spend with a woman, enough energy to engage, and a spirit of care. Women know that tactful practice builds their confidence and affects their mothering experience. Tact cannot be assumed; it needs to be nurtured and sheltered.

  11. Quality of life, postnatal depression and baby gender.

    Science.gov (United States)

    de Tychey, Claude; Briançon, Serge; Lighezzolo, Joëlle; Spitz, Elisabeth; Kabuth, Bernard; de Luigi, Valerie; Messembourg, Catherine; Girvan, Françoise; Rosati, Aurore; Thockler, Audrey; Vincent, Stephanie

    2008-02-01

    To study the impact of postnatal depression on the quality of life of young French mothers and to evaluate if the gender of their child influences this. Postnatal depression (PND) constitutes a major public health problem considering its high prevalence and consequences upon quality of life and parental skills. This research is a cross-sectional study during the postnatal period. This study was carried out during a two-month period. Data were collected by interview and questionnaires. The authors compared the prevalence rate of PND and life quality in a cohort of 181 women and measured the short-term impact of the child's birth. Postnatal depression strongly negatively influences all dimensions of life quality explored through the SF36, e.g. physical functioning (PF), physical Role (RP), bodily pain (BP), mental health (MH), emotional role (RE), social functioning (SF), vitality (VT), general health (GH), standardized physical component (PCS) and standardized mental component (MCS). The baby's gender (having a boy) also significantly reduces quality of life, irrespective of depressive state. There is a relationship between baby gender and PND. This research is the first to show that the birth of a boy reduces several dimensions of the mothers' quality of life. The importance of the impairment of quality of life in case of PND, as well as its effects on mother-child interaction, could justify prevention programs and early psychotherapeutic care. Further research needs to explore the effectiveness of programmes targeting the construction of parenting skills as a preventative measure against PND, especially for parents of boys.

  12. Blood constituents trigger brain swelling, tissue death, and reduction of glucose metabolism early after acute subdural hematoma in rats.

    Science.gov (United States)

    Baechli, Heidi; Behzad, Melika; Schreckenberger, Matthias; Buchholz, Hans-Georg; Heimann, Axel; Kempski, Oliver; Alessandri, Beat

    2010-03-01

    Outcome from acute subdural hematoma is often worse than would be expected from the pure increase of intracranial volume by bleeding. The aim was to test whether volume-independent pathomechanisms aggravate damage by comparing the effects of blood infusion with those of an inert fluid, paraffin oil, on intracranial pressure (ICP), cerebral perfusion pressure (CPP), local cerebral blood flow (CBF), edema formation, glucose metabolism ([18F]-deoxyglucose, MicroPET ), and histological outcome. Rats were injured by subdural infusion of 300 muL venous blood or paraffin. ICP, CPP, and CBF changes, assessed during the first 30 mins after injury, were not different between the injury groups at most time points (n=8 per group). Already at 2 h after injury, blood caused a significantly more pronounced decrease in glucose metabolism in the injured cortex when compared with paraffin (P<0.001, n=5 per group). Ipsilateral brain edema did not differ between groups at 2 h, but was significantly more pronounced in the blood-treated groups at 24 and 48 h after injury (n=8 per group). These changes caused a 56.2% larger lesion after blood when compared with paraffin (48.1+/-23.0 versus 21.1+/-11.8 mm(3); P<0.02). Blood constituent-triggered pathomechanisms aggravate the immediate effects due to ICP, CPP, and CBF during hemorrhage and lead to early reduction of glucose metabolism followed by more severe edema and histological damage.

  13. On Death

    Institute of Scientific and Technical Information of China (English)

    Zhangyan

    2016-01-01

    Death is not a terrible word, but a provoking one. Different people have different opinions, but no one can convince others of what death really means. This article made a tentative and superficial analysis on death according to the true feeing and experiences of the author. In her opinion, we needn’t consider more about death; the important for the death is how to live meaningfully.

  14. Differential Vulnerability to Early-Life Parental Death: The Moderating Effects of Family Suicide History on Risks for Major Depression and Substance Abuse in Later Life.

    Science.gov (United States)

    Hollingshaus, Michael S; Coon, Hilary; Crowell, Sheila E; Gray, Douglas D; Hanson, Heidi A; Pimentel, Richard; Smith, Ken R

    2016-01-01

    Only a portion of those individuals exposed to parental death in early life (PDE) develop behavioral health disorders. We utilized demographic pedigree data from the Utah Population Database to test for differential vulnerability to PDE by creating a risk score of familial susceptibility to suicide (FS) at the population level. Using logistic panel regression models, we tested for multiplicative interactions between PDE and FS on the risks of major depressive disorder (MDD) and substance abuse (SA), measured using Medicare claims, after age 65. The final sample included 155,983 individuals (born 1886-1944), yielding 1,431,060 person-years at risk (1992-2009). Net of several potential confounders, including probability of survival to age 65, we found an FS × PDE interaction for females, in which PDE and FS as main effects had no impact but jointly increased MDD risk. No statistically significant main or interactive effects were found for SA among females or for either phenotype among males. Our findings are consistent with a differential vulnerability model for MDD in females, in which early-life stress increases the risk for poor behavioral health only among the vulnerable. Furthermore, we demonstrate how demographic and pedigree data might serve as tools for investigating differential vulnerability hypotheses.

  15. [BREASTFEEDING AND FORMATION OF POSTNATAL ANXIETY].

    Science.gov (United States)

    Klymenko, V A; Lupaltsova, O S

    2015-01-01

    This article has been performed the investigation of psychological characteristics in mothers with the breastfeeding, the mixed feeding, the artificial feeding. There has been identified factors of the unfavourable prognosis for the postnatal anxiety.

  16. Behaviour of postnatally growth-impaired mice during malnutrition and after partial weight recovery

    DEFF Research Database (Denmark)

    Huber, Reinhard C.; Kolb, Andreas F.; Lillico, Simon

    2013-01-01

    Objectives: Early malnutrition is a highly prevalent condition in developing countries. Different rodent models of postnatal early malnutrition have been used to approach the subject experimentally, inducing early malnutrition by maternal malnutrition, temporal maternal separation, manipulation...... of litter size or the surgical nipple ligation to impair lactation. Studies on the behaviour of (previously) malnourished animals using animal models have produced sometimes contradictory results regarding the effects of early postnatal malnutrition and have been criticized for introducing potential...... confounding factors. The present paper is a first report on the behavioural effects of early malnutrition induced by an alternative approach: mice nursed by a-casein-deficient knockout dams showed a severe growth delay during early development and substantial catch-up growth after weaning when compared...

  17. Improved outcomes for newly diagnosed AL amyloidosis over the years 2000-2014: cracking the glass ceiling of early death.

    Science.gov (United States)

    Muchtar, Eli; Gertz, Morie A; Kumar, Shaji K; Lacy, Martha Q; Dingli, David; Buadi, Francis K; Grogan, Martha; Hayman, Suzanne R; Kapoor, Prashant; Leung, Nelson; Fonder, Amie; Hobbs, Miriam; Hwa, Yi Lisa; Gonsalves, Wilson; Warsame, Rahma; Kourelis, Taxiarchis V; Russell, Stephen; Lust, John A; Lin, Yi; Go, Ronald S; Zeldenrust, Steven; Kyle, Robert A; Rajkumar, S Vincent; Dispenzieri, Angela

    2017-01-26

    In light of major advances, we evaluated the trends in presentation, management and outcome among 1551 newly diagnosed AL amyloidosis patients seen in our institution from 2000-2014. As compared to the two intervals 2000-2004 and 2005-2009, patients diagnosed in 2010-2014 were less likely to have >2 involved organs. Utilization of autologous stem cell transplant (ASCT) was similar across all periods, about one-third of patients, but there was an increase in the use of pre-ASCT bortezomib induction and of unattenuated melphalan conditioning in 2010-2014 compared to earlier periods. Non-ASCT first-line regimen changed with 65% of patients in 2010-2014 received bortezomib-based therapy, 79% of patients in 2005-2009 received melphalan-dexamethasone and 64% of patients in 2000-2004 received melphalan-prednisone. The rate of ≥VGPR was higher in more recent periods (66% vs 58% vs 51%, P=0.001), a change largely driven by improved VGPR rates in the non-ASCT population. Overall survival (OS) has improved, with inflection points for improvement differing for the ASCT and non-ASCT groups. In the ASCT population, the greatest gains were after 2010 (4-year OS 91% compared to 73% and 65%). In the non-ASCT group, greatest gains were after 2005 (4-year OS 38%, 32%, and 16%). Fewer patients died within 6 months of diagnosis in the two later periods (24% vs 25% vs 37%; P<0.001). Overall, outcomes among patients with AL amyloidosis have improved with earlier diagnosis, higher rates of VGPR, lower early mortality and improved OS.

  18. Small particles disrupt postnatal airway development

    OpenAIRE

    2010-01-01

    Increasing numbers of epidemiologic studies associate air pollution exposure in children with decreased lung function development. The objective of this study was to examine the effects of exposure to combustion-generated fine [230 and 212 nm number mean aerodynamic particle diameter (NMAD)] to ultrafine (73 nm NMAD) particles differing in elemental (EC) and organic (OC) carbon content on postnatal airway development in rats. Neonatal Sprague-Dawley rats were exposed from postnatal day 7 thro...

  19. Increased soluble programmed death-1 (sPD-1) is associated with disease activity and radiographic progression in early rheumatoid arthritis.

    Science.gov (United States)

    Greisen, S R; Rasmussen, T K; Stengaard-Pedersen, K; Hetland, M L; Hørslev-Petersen, K; Hvid, M; Deleuran, B

    2014-01-01

    Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought to be implicated in disease activity in chronic rheumatoid arthritis (RA). We measured sPD-1 at baseline and 9 months after treatment initiation in plasma from early RA patients (n = 34). We tested for correlations with the Disease Activity Score using 28 joint counts (DAS28), the Health Assessment Questionnaire (HAQ) score, immunoglobulin M rheumatoid factor (IgM-RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, C-reactive protein (CRP), interleukin-21 (IL-21), and total Sharp score (TSS). We also measured sPD-1 in plasma from healthy volunteers (HV) (n = 20) and in plasma and synovial fluid (SF) from patients with chronic RA (> 8 years of disease, n = 30). We further investigated the cellular expression of PD-1 and its ligand PD-L1. sPD-1 concentrations in early [median 0.421 ng/mL, interquartile range (IQR) 0.04-2.560 ng/mL] and chronic (median 0.239 ng/mL, IQR 0.184-0.584 ng/mL) RA were increased compared with HV (median 0.04 ng/mL, IQR 0.04-0.04 ng/mL) (all p anti-CCP antibodies, and IL-21 (all p elevated plasma levels of sPD-1 in early RA, the association with core disease parameters, and the inverse correlation with TSS suggest that sPD-1 is an important mediator in inflammatory and radiographic disease progression.

  20. Postnatal changes in heart mitochondrial calcium and energy metabolism.

    Science.gov (United States)

    Wolf, W J; Rex, K A; Geshi, E; Sordahl, L A

    1991-07-01

    The newborn mammalian heart has less functional capacity compared with the adult, yet newborn myocardial mitochondrial respiratory activity is the same or exceeds that of adult. This study was aimed at determining the temporal changes in newborn rabbit heart mitochondrial energy-linked Ca2+ transport during early postnatal development. At birth, substrate-supported Ca2+ uptake is twice that of adult and declines toward adult rates during the first 14 days. Both NADH- and succinate-linked respiration are equivalent to adult values at birth, increase transiently during the first 7 days, and then decline toward adult. Newborn heart mitochondrial preparations exhibit the same membrane potential (delta psi) values during Ca2+ uptake and have comparable rates of Na(+)-induced Ca2+ efflux as adult. Creatine kinase (CK) activity is very low in 1- to 7-day-old newborn mitochondria and increases rapidly toward adult values after 10 days of age. The decreasing rates of Ca2+ uptake do not appear to be related to respiratory activity, membrane potential, or increased cycling of Ca2+ but rather to a direct effect on the mitochondrial Ca2+ uniporter. Preliminary studies indicate changes in mitochondrial membrane phospholipids during early development that may be related to the increasing CK activity and decreasing Ca2+ uptake and respiration. We postulate that mitochondrial membrane lipid changes in early postnatal development may be the causative factor underlying these changes in functional activity.

  1. DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration.

    Directory of Open Access Journals (Sweden)

    Masako Osada

    Full Text Available BACKGROUND: Thymic epithelial cell (TEC microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+ Foxn1(+ and Aire(+ TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments. CONCLUSIONS/SIGNIFICANCE: Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at

  2. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  3. Deliberating death.

    Science.gov (United States)

    Landes, Scott D

    2010-01-01

    Utilizing a particular case study of a woman attempting to come to terms with her death, this article explores the difficult metaphors of death present within the Christian tradition. Tracing a Christian understanding of death back to the work of Augustine, the case study is utilized to highlight the difficulties presented by past and present theology embracing ideas of punishment within death. Following the trajectory of the case study, alternative understandings of death present in recent Christian theology and within Native American spirituality are presented in an attempt to find room for a fuller meaning of death post-reconciliation, but premortem.

  4. Voltage-dependent anion channels (VDACs) promote mitophagy to protect neuron from death in an early brain injury following a subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Li, Jian; Lu, Jianfei; Mi, Yongjie; Shi, Zhao; Chen, Chunhua; Riley, John; Zhou, Changman

    2014-07-21

    The term mitophagy is coined to describe the selective removal of mitochondria by autophagy but the process itself is still contentious, especially in the early period following subarachnoid hemorrhage (SAH). In the present study, we investigated the role of mitophagy following 48h after SAH injury in rats. Specifically evaluating whether mitophagy, through voltage dependant anion channels (VDACs) interacting with microtubule-associated protein 1 light chain 3, could orchestrate the induction of apoptotic and necrotic cell death in neurons, a VDAC1siRNA and an activitor Rapamycian (RAPA), were engaged. One hundred and twelve male Sprague-Dawley rats were randomly divided into 4 groups: Sham, SAH, SAH+VDAC1siRNA, and SAH+RAPA. Outcomes measured included mortality rate, brain edema, BBB disruption, and neurobehavioral testing. We also used western blotting techniques to analyze the expressions of key mitophagic/autophagic proteins and pro-apoptotic protein such as ROS, VDAC1, LC-3II and Caspase-3. Rapamycin treatment significantly improved the mortality rate, cerebral edema, and neurobehavioral deficits; apoptotic and necrotic cell death in neurons were reduced by Rapamycin following SAH injury. However, VDAC1siRNA worsened the brain injury following SAH. Immunohistochemical staining and western blot analysis demonstrated a decreased expression of VDAC1, LC3II, and an increase of ROS and Caspase-3 followed by VDAC1siRNA administration. In conclusion, mitophagy induced by VDAC1 following SAH injury may in fact play a significant role in neuroprotection, the mechanism which may be through the attenuation of the apoptosic and necrosic molecular pathways. This translates a preservation of functional integrity and an improvement in mortality.

  5. Molecular and Functional Effects of a Splice Site Mutation in the MYL2 Gene Associated with Cardioskeletal Myopathy and Early Cardiac Death in Infants.

    Science.gov (United States)

    Zhou, Zhiqun; Huang, Wenrui; Liang, Jingsheng; Szczesna-Cordary, Danuta

    2016-01-01

    The homozygous appearance of the intronic mutation (IVS6-1) in the MYL2 gene encoding for myosin ventricular/slow-twitch skeletal regulatory light chain (RLC) was recently linked to the development of slow skeletal muscle fiber type I hypotrophy and early cardiac death. The IVS6-1 (c403-1G>C) mutation resulted from a cryptic splice site in MYL2 causing a frameshift and replacement of the last 32 codons by 19 different amino acids in the RLC mutant protein. Infants who were IVS6-1(+∕+)-positive died between 4 and 6 months of age due to cardiomyopathy and heart failure. In this report we have investigated the molecular mechanism and functional consequences associated with the IVS6-1 mutation using recombinant human cardiac IVS6-1 and wild-type (WT) RLC proteins. Recombinant proteins were reconstituted into RLC-depleted porcine cardiac muscle preparations and subjected to enzymatic and functional assays. IVS6-1-RLC showed decreased binding to the myosin heavy chain (MHC) compared with WT, and IVS6-1-reconstituted myosin displayed reduced binding to actin in rigor. The IVS6-1 myosin demonstrated a significantly lower Vmax of the actin-activated myosin ATPase activity compared with WT. In stopped-flow experiments, IVS6-1 myosin showed slower kinetics of the ATP induced dissociation of the acto-myosin complex and a significantly reduced slope of the kobs-[MgATP] relationship compared to WT. In skinned porcine cardiac muscles, RLC-depleted and IVS6-1 reconstituted muscle strips displayed a significant decrease in maximal contractile force and a significantly increased Ca(2+) sensitivity, both hallmarks of hypertrophic cardiomyopathy-associated mutations in MYL2. Our results showed that the amino-acid changes in IVS6-1 were sufficient to impose significant conformational alterations in the RLC protein and trigger a series of abnormal protein-protein interactions in the cardiac muscle sarcomere. Notably, the mutation disrupted the RLC-MHC interaction and the steady

  6. Cot Deaths.

    Science.gov (United States)

    Tyrrell, Shelagh

    1985-01-01

    Addresses the tragedy of crib deaths, giving particular attention to causes, prevention, and medical research on Sudden Infant Death Syndrome (SIDS). Gives anecdotal accounts of coping strategies used by parents and families of SIDS infants. (DT)

  7. Developmental changes in postnatal murine intestinal interstitial cell of Cajal network structure and function.

    Science.gov (United States)

    Gao, Jerry; Sathar, Shameer; O'Grady, Gregory; Han, Juan; Cheng, Leo K

    2014-08-01

    The mammalian gastrointestinal (GI) tract undergoes rapid development during early postnatal life in order to transition from a milk to solid diet. Interstitial cells of Cajal (ICC) are the pacemaker cells that coordinate smooth muscle contractility within the GI tract, and hence we hypothesized that ICC networks undergo significant developmental changes during this early postnatal period. Numerical metrics for quantifying ICC network structural properties were applied on confocal ICC network imaging data obtained from the murine small intestine at various postnatal ages spanning birth to weaning. These imaging data were also coupled to a biophysically-based computational model to simulate pacemaker activity in the networks, to quantify how changes in structure may alter function. The results showed a pruning-like mechanism which occurs during postnatal development, and the temporal course of this phenomenon was defined. There was an initial ICC process overgrowth to optimize network efficiency and increase functional output volume. This was followed by a selective retaining and strengthening of processes, while others were discarded to further elevate functional output volume. Subsequently, new ICC processes were formed and the network was adjusted to its adult morphology. These postnatal ICC network developmental events may be critical in facilitating mature digestive function.

  8. The effect of community maternal and newborn health family meetings on type of birth attendant and completeness of maternal and newborn care received during birth and the early postnatal period in rural Ethiopia.

    Science.gov (United States)

    Barry, Danika; Frew, Aynalem Hailemichael; Mohammed, Hajira; Desta, Binyam Fekadu; Tadesse, Lelisse; Aklilu, Yeshiwork; Biadgo, Abera; Buffington, Sandra Tebben; Sibley, Lynn M

    2014-01-01

    Maternal and newborn deaths occur predominantly in low-resource settings. Community-based packages of evidence-based interventions and skilled birth attendance can reduce these deaths. The Maternal and Newborn Health in Ethiopia Partnership (MaNHEP) used community-level health workers to conduct prenatal Community Maternal and Newborn Health family meetings to build skills and care-seeking behaviors among pregnant women and family caregivers. Baseline and endline surveys provided data on a random sample of women with a birth in the prior year. An intention-to-treat analysis, plausible net effect calculation, and dose-response analysis examined increases in completeness of care (mean percentage of 17 maternal and newborn health care elements performed) over time and by meeting participation. Regression models assessed the relationship between meeting participation, completeness of care, and use of skilled providers or health extension workers for birth care-controlling for sociodemographic and health service utilization factors. A 151% increase in care completeness occurred from baseline to endline. At endline, women who participated in 2 or more meetings had more complete care than women who participated in fewer than 2 meetings (89% vs 76% of care elements; P < .001). A positive dose-response relationship existed between the number of meetings attended and greater care completeness (P < .001). Women with any antenatal care were nearly 3 times more likely to have used a skilled provider or health extension worker for birth care. Women who had additionally attended 2 or more meetings with family members were over 5 times as likely to have used these providers, compared to women without antenatal care and who attended fewer than 2 meetings (odds ratio, 5.19; 95% confidence interval, 2.88-9.36; P < .001). MaNHEP's family meetings complemented routine antenatal care by engaging women and family caregivers in self-care and care-seeking, resulting in greater completeness

  9. Programmed cell death 2 protein induces gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis in a p53-dependent manner.

    Science.gov (United States)

    Zhang, Jian; Wei, Wei; Jin, Hui-Cheng; Ying, Rong-Chao; Zhu, A-Kao; Zhang, Fang-Jie

    2015-01-01

    Programmed cell death 2 (PDCD2) is a highly conserved nuclear protein, and aberrant PDCD2 expression alters cell apoptosis. The present study aimed to investigate PDCD2 expression in gastric cancer. Tissue specimens from 34 gastric cancer patients were collected for analysis of PDCD2 expression using immunohistochemistry, western blotting and qRT-PCR. Gastric cancer cell lines (a p53-mutated MKN28 line and a wild-type p53 MKN45 line) were used to assess the effects of PDCD2 overexpression. p53-/- nude mice were used to investigate the effect of PDCD2 on ultraviolet B (UVB)-induced skin carcinogenesis. The data showed that PDCD2 expression was reduced in gastric cancer tissue specimens, and loss of PDCD2 expression was associated with the poor survival of patients. PDCD2 expression induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis. The antitumor effects of PDCD2 expression were dependent on p53 expression in gastric cancer cells. Moreover, PDCD2 expression inhibited activity of the ATM/Chk1/2/p53 signaling pathway. In addition, PDCD2 expression suppressed UVB-induced skin carcinogenesis in p53+/+ nude mice, but not in p53-/- mice. The data from the present study demonstrated that loss of PDCD2 expression could contribute to gastric cancer development and progression and that PDCD2-induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis are p53-dependent.

  10. Prenatal and postnatal residential usage of insecticides in a multicenter birth cohort in Spain.

    NARCIS (Netherlands)

    Llop, S.; Casas, L.; Santa-Marina, L.; Estarlich, M.; Fernández-Somoano, A.; Esplugues, A.; Jimenez, A.; Zock, J.P.; Tardón, A.; Marco, A.; Ballester, F.

    2013-01-01

    This study aimed to describe the residential use of insecticides in a birth cohort in Spain. Study subjects were 2 456 women enrolled into the INMA (Environment and Childhood) birth cohort followed prospectively during pregnancy and in the early postnatal period. The women were recruited at the begi

  11. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry.

    Science.gov (United States)

    Lehmann, S; Ravn, A; Carlsson, L; Antunovic, P; Deneberg, S; Möllgård, L; Derolf, A Rangert; Stockelberg, D; Tidefelt, U; Wahlin, A; Wennström, L; Höglund, M; Juliusson, G

    2011-07-01

    Our knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the population-based Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100,000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients <40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydrogenase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population.

  12. An Immunohistochemical Study of Retinal Collagen IV Expression during Pre- and Postnatal Postnatal Periods in Balb/c Mice

    Directory of Open Access Journals (Sweden)

    Mehdi Jalali

    2011-01-01

    Full Text Available Objective: Basement membranes are specialized extracellular matrices which playimportant roles such as cell regulation, proliferation and migration. Collagen fibers,especially type IV, are the most important basement membrane constituents. As retinais one of the target organs in diabetes mellitus, and nephropathy is a major cause ofend stage renal and retinal diseases resulting in increased morbidity and mortality,early diagnosis leads to better treatment. Hence, in this investigation, the appearanceand distribution of collagen IV during gestational days and early postnatal periodswere observed.Materials and Methods: 24 intact female Balb/c mice were kept under normal conditions.After mating, appearance of a vaginal plug was assumed as day zero of the pregnancy.From days 13-18 of gestation, the pregnant mice were euthanised and theirembryos as well as pups from days 1 to 5 were collected. For histochemichal studies,heads of the specimens were fixed, serially sectioned and immunohistochemicallstudies were performed by using monoclonal antibodies for tracing of collagentype IV.Results: Our findings revealed that the amount of collagen IV in the internal limiting membrane(ILM and extra cellular matrix (ECM of the retina, as well as vessels of the vitreusbody appear on embryonic day 16. Also, a patchy distribution was observed in the pigmentedepithelium which continued to further develop until the end stage of embryoniclife. Strong labeling was observed until postnatal day 3 but did not increase significantlythereafter.Conclusion: These findings establish the importance of collagen IV during the critical periodof retinal development. In addition, this study indicates that high levels of collagen IVare present in the basal membrane (BM of the inner limiting membranes and pigmentedepithelium (3rd post natal on the 3rd postnatal day.

  13. Postnatal development of lateralized motor preference in the African grey parrot (Psittacus erithacus).

    Science.gov (United States)

    Snyder, P J; Bonner, J A

    2001-01-01

    The parrot appears to provide a potentially unique animal model of handedness in humans, but few (if any) observational studies of early postnatal development of postural/motor asymmetries have been published. We studied three African Grey hatchlings, raised without human physical contact, for the first 5 months of life. All three animals failed to show consistent postural and/or motor asymmetries until the end of the 4 postnatal week. These results appear to be comparable to data from prior studies with human infants. Delayed development of lateral motor and/or postural preferences may represent an evolutionarily adaptive strategy for altricial animals.

  14. Germ cell development in the postnatal testis

    DEFF Research Database (Denmark)

    Hutson, John M; Li, Ruili; Southwell, Bridget R;

    2012-01-01

    , which leads to secondary germ cell loss and later infertility and risk of cancer. Recent studies suggest that neonatal gonocytes transform into the putative spermatogenic stem cells between 3 and 9 months, and this initial postnatal step is deranged in cryptorchid testes. In addition, it is thought...... the abnormality high temperature may also impair apoptosis of remaining gonocytes, allowing some to persist to become the possible source of carcinoma in situ and malignancy after puberty. The biology of postnatal germ cell development is of intense interest, as it is likely to be the key to the optimal timing...

  15. Role of postnatal dietary sodium in prenatally programmed hypertension.

    Science.gov (United States)

    Stewart, Tyrus; Ascani, Jeannine; Craver, Randall D; Vehaskari, V Matti

    2009-09-01

    In this study we examined the short- and long-term impact of early life dietary sodium (Na) on prenatally programmed hypertension. Hypertension was induced in rat offspring by a maternal low protein (LP) diet. Control and LP offspring were randomized to a high (HS), standard (SS), or low (LS) Na diet after weaning. On the SS diet, the LP pups developed hypertension by 6 weeks of age. The development of hypertension was prevented by the LS diet and exacerbated by the HS diet. Kidney nitrotyrosine content, a measure of oxidative stress, was reduced by the LS diet compared with the HS diet. The modified diets had no effect on control pups. A group of animals on the SS diet was followed up to 51 weeks of age after an early life 3-week exposure to the HS or LS diet. This brief early exposure of LP animals to the LS diet prevented the later development of hypertension and ameliorated the nephrosclerosis observed after early exposure to the HS diet. The LP offspring with early exposure to LS diet had lost their salt-sensitivity when challenged with the HS diet at the age of 43-49 weeks. No effect of early life dietary Na was observed in control animals. These results show that hypertension in this model is salt sensitive and may, in part, be mediated by salt-induced renal oxidative stress and that there may exist a developmental window which allows postnatal "reprogramming" of the hypertension.

  16. Quantitative analysis of postnatal neurogenesis and neuron number in the macaque monkey dentate gyrus

    Science.gov (United States)

    Jabès, Adeline; Lavenex, Pamela Banta; Amaral, David G.; Lavenex, Pierre

    2010-01-01

    The dentate gyrus is one of only two regions of the mammalian brain where substantial neurogenesis occurs postnatally. However, detailed quantitative information about the postnatal structural maturation of the primate dentate gyrus is meager. We performed design-based, stereological studies of neuron number and size, and volume of the dentate gyrus layers in rhesus macaque monkeys (Macaca mulatta) of different postnatal ages. We found that about 40% of the total number of granule cells observed in mature 5–10-year-old macaque monkeys are added to the granule cell layer postnatally; 25% of these neurons are added within the first three postnatal months. Accordingly, cell proliferation and neurogenesis within the dentate gyrus peak within the first three months after birth and remain at an intermediate level between three months and at least one year of age. Although granule cell bodies undergo their largest increase in size during the first year of life, cell size and the volume of the three layers of the dentate gyrus (i.e., the molecular, granule cell and polymorphic layers) continue to increase beyond one year of age. Moreover, the different layers of the dentate gyrus exhibit distinct volumetric changes during postnatal development. Finally, we observe significant levels of cell proliferation, neurogenesis and cell death in the context of an overall stable number of granule cells in mature 5–10-year-old monkeys. These data identify an extended developmental period during which neurogenesis might be modulated to significantly impact the structure and function of the dentate gyrus in adulthood. PMID:20074220

  17. Maternal forced swimming reduces cell proliferation in the postnatal dentate gyrus of mouse offspring

    Directory of Open Access Journals (Sweden)

    Frederick Wasinski

    2016-08-01

    Full Text Available Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring’s neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring.

  18. Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring.

    Science.gov (United States)

    Wasinski, Frederick; Estrela, Gabriel R; Arakaki, Aline M; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C

    2016-01-01

    Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring.

  19. Reelin, an extracellular matrix protein linked to early onset psychiatric diseases, drives postnatal development of the prefrontal cortex via GluN2B-NMDARs and the mTOR pathway.

    Science.gov (United States)

    Iafrati, J; Orejarena, M J; Lassalle, O; Bouamrane, L; Gonzalez-Campo, C; Chavis, P

    2014-04-01

    Defective brain extracellular matrix (ECM) is a factor of vulnerability in various psychiatric diseases such as schizophrenia, depression and autism. The glycoprotein reelin is an essential building block of the brain ECM that modulates neuronal development and participates to the functions of adult central synapses. The reelin gene (RELN) is a strong candidate in psychiatric diseases of early onset, but its synaptic and behavioral functions in juvenile brain circuits remain unresolved. Here, we found that in juvenile reelin-haploinsufficient heterozygous reeler mice (HRM), abnormal fear memory erasure is concomitant to reduced dendritic spine density and anomalous long-term potentiation in the prefrontal cortex. In juvenile HRM, a single in vivo injection with ketamine or Ro25-6981 to inhibit GluN2B-N-methyl-D-aspartate receptors (NMDARs) restored normal spine density, synaptic plasticity and converted fear memory to an erasure-resilient state typical of adult rodents. The functional and behavioral rescue by ketamine was prevented by rapamycin, an inhibitor of the mammalian target of rapamycin pathway. Finally, we show that fear memory erasure persists until adolescence in HRM and that a single exposure to ketamine during the juvenile period reinstates normal fear memory in adolescent mice. Our results show that reelin is essential for successful structural, functional and behavioral development of juvenile prefrontal circuits and that this developmental period provides a critical window for therapeutic rehabilitation with GluN2B-NMDAR antagonists.

  20. Drebrin regulates neuroblast migration in the postnatal mammalian brain.

    Directory of Open Access Journals (Sweden)

    Martina Sonego

    Full Text Available After birth, stem cells in the subventricular zone (SVZ generate neuroblasts that migrate along the rostral migratory stream (RMS to become interneurons in the olfactory bulb (OB. This migration is crucial for the proper integration of newborn neurons in a pre-existing synaptic network and is believed to play a key role in infant human brain development. Many regulators of neuroblast migration have been identified; however, still very little is known about the intracellular molecular mechanisms controlling this process. Here, we have investigated the function of drebrin, an actin-binding protein highly expressed in the RMS of the postnatal mammalian brain. Neuroblast migration was monitored both in culture and in brain slices obtained from electroporated mice by time-lapse spinning disk confocal microscopy. Depletion of drebrin using distinct RNAi approaches in early postnatal mice affects neuroblast morphology and impairs neuroblast migration and orientation in vitro and in vivo. Overexpression of drebrin also impairs migration along the RMS and affects the distribution of neuroblasts at their final destination, the OB. Drebrin phosphorylation on Ser142 by Cyclin-dependent kinase 5 (Cdk5 has been recently shown to regulate F-actin-microtubule coupling in neuronal growth cones. We also investigated the functional significance of this phosphorylation in RMS neuroblasts using in vivo postnatal electroporation of phosphomimetic (S142D or non-phosphorylatable (S142A drebrin in the SVZ of mouse pups. Preventing or mimicking phosphorylation of S142 in vivo caused similar effects on neuroblast dynamics, leading to aberrant neuroblast branching. We conclude that drebrin is necessary for efficient migration of SVZ-derived neuroblasts and propose that regulated phosphorylation of drebrin on S142 maintains leading process stability for polarized migration along the RMS, thus ensuring proper neurogenesis.

  1. Effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation%宫内发育迟缓早产儿生后生长迟缓对早期神经发育的影响

    Institute of Scientific and Technical Information of China (English)

    蔡岳鞠; 宋燕燕; 黄志坚; 李坚; 齐俊冶; 肖旭文; 王兰秀

    2015-01-01

    目的:探讨宫内发育迟缓(IUGR)早产儿生后生长迟缓对早期神经发育的影响。方法回顾性分析2008年5月至2012年5月出生并定期随访至校正胎龄6个月的171例早产儿的临床资料,其中IUGR早产儿40例,早产适于胎龄儿(AGA)131例。比较两组校正胎龄40周、3个月、6个月的生长迟缓率及校正胎龄3个月、6个月时的神经发育情况。神经发育采用Gesell发育量表评估。结果 IUGR组校正胎龄40周、3个月、6个月的生长迟缓率均明显高于AGA组;校正胎龄3个月时Gesell各项发育商(大运动、精细动作、语言、适应性及个人社交)均低于AGA组;校正胎龄6个月时,IUGR组精细动作及语言发育商低于AGA组,但两组大运动、适应性及个人社交发育商比较差异已无统计学意义。IUGR组6月龄时体重追赶落后的患儿各项发育商均明显低于追赶理想的IUGR和AGA患儿。结论 IUGR早产儿生后早期的生长迟缓可对早期神经发育产生不良影响。%Objective To study the effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation (IUGR). Methods A retrospective analysis was performed on the clinical data of 171 premature infants who were born between May 2008 and May 2012 and were followed up until a corrected gestational age of 6 months. These infants were classified into two groups: IUGR group (n=40) and appropriate for gestational age (AGA) group (n=131). The growth retardation rates at the corrected gestational ages of 40 weeks, 3 months, and 6 months, as well as the neurodevelopmental outcome (evaluated by Gesell Developmental Scale) at corrected gestational ages of 3 and 6 months, were compared between the two groups. Results The growth retardation rate in the IUGR group was signiifcantly higher than in the AGA group at the corrected gestational ages of 40 weeks, 3 months, and 6 months. All ifve

  2. Postnatal depression, oxytocin and maternal sensitivity

    NARCIS (Netherlands)

    Mah, Beth Lynette

    2015-01-01

    Intra nasal oxytocin administered to a population of mothers with a diagnosis of postnatal depression: -lowers their current mood -causes mothers to report that their infants are more difficult but their relationship with them is more positive -increases their protective response towards them in the

  3. Recipient twin limb ischemia with postnatal onset.

    Science.gov (United States)

    Broadbent, Roland Spencer

    2007-02-01

    After the occurrence of 3 local cases of limb ischemia in newborn twins, we reviewed the literature to investigate this combination systematically. This review reveals a distinct condition: postnatal onset limb ischemia affecting recipient twins in twin-twin transfusion syndrome.

  4. Paternal postnatal depression – a review

    Directory of Open Access Journals (Sweden)

    Tuszyńska-Bogucka, Wioletta

    2014-06-01

    Full Text Available Objective. Among the factors responsible for the occurrence of paternal postnatal depression, the following are the most frequent: biological factors (mainly hormonal changes, mental pathogens (mainly a specific personal profile, including neuroticism, perfectionism and obsessiveness, mental disorders and problems such as fear, anxiety or mental disorders, marital coincidence of depression, a high level of stress experienced and lower quality of sexual life in the postpartum period, and finally – socioeconomic status (mainly poverty, young age of the spouse, his low level of education and structural problems in the family. However, it should be noticed that the subject of paternal postnatal depression is relatively rarely taken up in research or discussed in specialist magazines. Conclusions. However, due to the fact that postnatal depression, both in mothers and in fathers, greatly impacts the life of the child and the functioning of the family, it seems that this area of research is of crucial importance. The identification of risk factors of depression in new fathers may not only lead to a more profound understanding and description of the ethiology and symptomatology of paternal postnatal depression, but also to distinguishing a risk group in order to provide it with professional prophylactic and therapeutic care

  5. Natural death.

    Science.gov (United States)

    Oehmichen, M; Meissner, C

    2000-01-01

    The increasing age of every human being is the beginning of the end of life, an obviously natural process, but any attempt to define the term 'natural death' soon encounters difficulties in defining what is meant by 'natural'. In the industrialized countries of the West, for example 'natural death' is thought of as the opposite of non-natural types of death such as accidental death, suicide, and homicide. The aim of our present survey is to discuss the meaning of the term 'natural death' under a clinical, a forensic and a scientific point of view with regard to recent developments especially in molecular biology. If there are 'external' physical influences, a medical-technical manipulation, a therapeutic or molecular biological intervention cannot be definitely ruled out as the cause of death, then use of the term 'natural death' in general is open to question. It will only remain meaningful if it can be applied with a specific meaning in definite practical situations. Current research and medical technology, however, do not allow use of the term 'natural death' in its conventional sense: it can thus be stricken from the medical vocabulary. Copyright 2000 S. Karger AG, Basel

  6. N-Terminal Pro-B Type Natriuretic Peptide as a Marker of Bronchopulmonary Dysplasia or Death in Very Preterm Neonates

    DEFF Research Database (Denmark)

    Sellmer, Anna; Hjortdal, Vibeke Elisabeth; Bjerre, Jesper Vandborg

    2015-01-01

    three and bronchopulmonary dysplasia (BPD) or death and further to assess the impact of patent ductus arteriosus (PDA) on this association in neonates born before 32 gestational weeks. METHODS: A cohort study of 183 neonates born before 32 gestational weeks consecutively admitted to the Neonatal......-proBNP to be associated with BPD or death in very preterm neonates. This association was not only explained by the PDA. We speculate that NT-proBNP may help the identification of neonates at risk of BPD as early as postnatal day three....... Intensive Care Unit, Aarhus University Hospital, Denmark. On day three plasma samples were collected and echocardiography carried out. NT-proBNP was measured by routine immunoassays. The combined outcome BPD or death was assessed at 36 weeks of postmenstrual age. Receiver operator characteristic (ROC...

  7. Postnatal changes in fatty acids composition of brown adipose tissue

    Science.gov (United States)

    Ohno, T.; Ogawa, K.; Kuroshima, A.

    1992-03-01

    It has been demonstrated that thermogenic activity of brown adipose tissue (BAT) is higher during the early postnatal period, decreasing towards a low adult level. The present study examined postnatal changes in the lipid composition of BAT. BAT from pre-weaning rats at 4 and 14 days old showed the following differences in lipid composition compared to that from adults of 12 weeks old. (i) Relative weight of interscapular BAT to body weight was markedly greater. (ii) BAT-triglyceride (TG) level was lower, while BAT-phospholipid (PL)level was higher. (iii) In TG fatty acids (FA) polyunsaturated fatty acids (PU; mol %), arachidonate index (AI), unsaturation index (UI) and PU/saturated FA (SA) were higher; rare FA such as eicosadienoate, bishomo- γ-linolenic acid and lignoceric acid in mol % were also higher. (iv) In PL-FA monounsaturated FA (MU) in mol % was lower; PU mol %, AI and UI were higher. These features in BAT of pre-weaning rats resembled those in the cold-acclimated adults, suggesting a close relationship of the PL-FA profile to high activity of BAT.

  8. Mouse models for the study of postnatal cardiac hypertrophy

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    A. Del Olmo-Turrubiarte

    2015-06-01

    Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

  9. Ependymal alterations in sudden intrauterine unexplained death and sudden infant death syndrome: possible primary consequence of prenatal exposure to cigarette smoking

    Directory of Open Access Journals (Sweden)

    Matturri Luigi

    2010-07-01

    Full Text Available Abstract Background The ependyma, the lining providing a protective barrier and filtration system separating brain parenchyma from cerebrospinal fluid, is still inadequately understood in humans. In this study we aimed to define, by morphological and immunohistochemical methods, the sequence of developmental steps of the human ependyma in the brainstem (ventricular ependyma and thoracic spinal cord (central canal ependyma of a large sample of fetal and infant death victims, aged from 17 gestational weeks to 8 postnatal months. Additionally, we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant death and maternal smoking. Results Our results demonstrate that in early fetal life the human ependyma shows a pseudostratified cytoarchitecture including many tanycytes and ciliated cells together with numerous apoptotic and reactive astrocytes in the subependymal layer. The ependyma is fully differentiated, with a monolayer of uniform cells, after 32 to 34 gestational weeks. We observed a wide spectrum of ependymal pathological changes in sudden death victims, such as desquamation, clusters of ependymal cells in the subventricular zone, radial glial cells, and the unusual presence of neurons within and over the ependymal lining. These alterations were significantly related to maternal smoking in pregnancy. Conclusions We conclude that in smoking mothers, nicotine and its derivatives easily reach the cerebrospinal fluid in the fetus, immediately causing ependymal damage. Consequently, we suggest that the ependyma should be examined in-depth first in victims of sudden fetal or infant death with mothers who smoke.

  10. Study on the behavior of rat model of schizophrenia induced by MK-801 in early postnatal period%MK-801诱导出生早期大鼠精神分裂症模型的行为学研究

    Institute of Scientific and Technical Information of China (English)

    蔡菡; 李泽爱; 刘寰忠; 任振华

    2013-01-01

    Objective To study the learning and memory eharaoteristie of rat models of schizophrenia induced by chronic MK-801 treatment in the early postnatal period. Methods 22 SD rats 6 d after birth were divided into MK-801 group and normal saline group of 11 each, and the rats in the two groups accepted intraperitoneal administration of MK-801 ( 0.3 mg/kg ) or saline ( 0. 3 ml/kg ) twice a day for 2 weeks, respectively. Body weights of rats in two groups were measured before and every three days after injection, and continued up to the end of the experiment. After 1 week of injection endpoint, open field and water maze were detected in the rats of two groups. Results Compared with the normal group, body weights of rats in MK-801 group were gradually decreased during the injection process ( P <0. 01 ) and at least continued for 4 weeks after the end of injection. The results of behavior showed that, compared with the normal saline group, the spontaneous activity in rats of MK-801 group significantly reduced ( P < 0. 01 ), and the ability of learn and memory significantly were declined in rats of MK-801 group ( P < 0. 05 ). Conclusion The decrease in the spontaneous activity of rat model of schizophrenia induced by MK-801 in the early postnatal period could partially imitate the negative symptoms of schizophrenia, and the dysfunction in learning and memory is similar to the cognitive impairment of schizophrenia.%目的 建立地卓西平马来酸盐(MK-801)慢性处理的出生早期大鼠精神分裂症(SZ)模型,探讨其神经行为学变化.方法 11只出生后6 d的SD仔鼠,腹腔注射0.3 mg/kg的MK-801(MK-801组),一天2次,连续注射2周;11只同龄的SD仔鼠腹腔注射等体积的生理盐水(NS组).给药前称重1次,给药完毕后每隔2 d称重1次,直至实验结束.给药后1周,检测旷场和水迷宫等行为学的变化.结果 与NS组比较,MK-801组大鼠体重显著降低(P<0.01),并至少持续至注射结束后4周.行为学检测结果

  11. Postnatal toxic and acquired disorders.

    Science.gov (United States)

    Saint-Amour, Dave; Dallaire, Renee; Dulac, Oliver

    2013-01-01

    To develop and function optimally, the brain requires a balanced environment of electrolytes, amino acids, neurotransmitters, and metabolic substrates. As a consequence, organ dysfunction has the potential to induce brain disorders and toxic-metabolic encephalopathies, particularly when occurring during early stages of cerebral maturation. Induced toxicity of three different organ systems that are commonly associated with brain complications are discussed. First, thyroid hormone deficiency caused by intrinsic or extrinsic factors (e.g., environmental toxins) may induce severe adverse effects on child neurological development from reversible impairments to permanent mental retardation. Second, inadequate removal of wastes due to chronic renal failure leads to the accumulation of endogenous toxins that are harmful to brain function. In uremic pediatric patients, the brain becomes more vulnerable to exogenous substances such as aluminum, which can induce aluminum encephalopathy. Following surgical procedures, neurological troubles including focal defects and severe epileptic seizures may result from hypertensive encephalopathy combined with toxicity of immunomodulating substances, or from the delayed consequences of cardiovascular defect. Taken together, this illustrates that organ disorders clearly have an impact on child brain function in various ways. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain

    Directory of Open Access Journals (Sweden)

    Murray Kerren

    2011-02-01

    Full Text Available Abstract From an early postnatal period and throughout life there is a continuous production of olfactory bulb (OB interneurons originating from neuronal precursors in the subventricular zone. To reach the OB circuits, immature neuroblasts migrate along the rostral migratory stream (RMS. In the present study, we employed cultured postnatal mouse forebrain slices and used lentiviral vectors to label neuronal precursors with GFP and to manipulate the expression levels of the Na-K-2Cl cotransporter NKCC1. We investigated the role of this Cl- transporter in different stages of postnatal neurogenesis, including neuroblast migration and integration in the OB networks once they have reached the granule cell layer (GCL. We report that NKCC1 activity is necessary for maintaining normal migratory speed. Both pharmacological and genetic manipulations revealed that NKCC1 maintains high [Cl-]i and regulates the resting membrane potential of migratory neuroblasts whilst its functional expression is strongly reduced at the time cells reach the GCL. As in other developing systems, NKCC1 shapes GABAA-dependent signaling in the RMS neuroblasts. Also, we show that NKCC1 controls the migration of neuroblasts in the RMS. The present study indeed indicates that the latter effect results from a novel action of NKCC1 on the resting membrane potential, which is independent of GABAA-dependent signaling. All in all, our findings show that early stages of the postnatal recruitment of OB interneurons rely on precise, orchestrated mechanisms that depend on multiple actions of NKCC1.

  13. Clonidine treatment delays postnatal motor development and blocks short-term memory in young mice.

    Science.gov (United States)

    Calvino-Núñez, Cristina; Domínguez-del-Toro, Eduardo

    2014-01-01

    During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive.

  14. Neonatal pain in relation to postnatal growth in infants born very preterm.

    Science.gov (United States)

    Vinall, Jillian; Miller, Steven P; Chau, Vann; Brummelte, Susanne; Synnes, Anne R; Grunau, Ruth E

    2012-07-01

    Procedural pain is associated with poorer neurodevelopment in infants born very preterm (≤ 32 weeks gestational age), however, the etiology is unclear. Animal studies have demonstrated that early environmental stress leads to slower postnatal growth; however, it is unknown whether neonatal pain-related stress affects postnatal growth in infants born very preterm. The aim of this study was to examine whether greater neonatal pain (number of skin-breaking procedures adjusted for medical confounders) is related to decreased postnatal growth (weight and head circumference [HC] percentiles) early in life and at term-equivalent age in infants born very preterm. Participants were n=78 preterm infants born ≤ 32 weeks gestational age, followed prospectively since birth. Infants were weighed and HC measured at birth, early in life (median: 32 weeks [interquartile range 30.7-33.6]) and at term-equivalent age (40 weeks [interquartile range 38.6-42.6]). Weight and HC percentiles were computed from sex-specific British Columbia population-based data. Greater neonatal pain predicted lower body weight (Wald χ(2)=7.36, P=0.01) and HC (Wald χ(2)=4.36, P=0.04) percentiles at 32 weeks postconceptional age, after adjusting for birth weight percentile and postnatal risk factors of illness severity, duration of mechanical ventilation, infection, and morphine and corticosteroid exposure. However, later neonatal infection predicted lower weight percentile at term (Wald χ(2)=5.09, P=0.02). Infants born very preterm undergo repetitive procedural pain during a period of physiological immaturity that appears to impact postnatal growth, and may activate a downstream cascade of stress signaling that affects later growth in the neonatal intensive care unit.

  15. Brain-derived neurotrophic factor (BDNF) and TrkB in the piglet brainstem after post-natal nicotine and intermittent hypercapnic hypoxia.

    Science.gov (United States)

    Tang, Samantha; Machaalani, Rita; Waters, Karen A

    2008-09-26

    Brain-derived neurotrophic factor (BDNF) and its receptor TrkB play a significant role in the regulation of cell growth, survival and death during central nervous system development. The expression of BDNF and TrkB is affected by noxious insults. Two insults during the early post-natal period that are of interest to our laboratory are exposure to nicotine and to intermittent hypercapnic hypoxia (IHH). Piglet models were used to mimic the conditions associated with the risk factors for the sudden infant death syndrome (SIDS) including post-natal cigarette smoke exposure (nicotine model) and prone sleeping where the infant is subjected to re-breathing of expired gases (IHH model). We aimed to determine the effects of nicotine and IHH, alone or in combination, on pro- and rhBDNF and TrkB expression in the developing piglet brainstem. Four piglet groups were studied, with equal gender ratios in each: control (n=14), nicotine (n=14), IHH (n=10) and nic+IHH (n=14). Applying immunohistochemistry, and studying six nuclei of the caudal medulla, we found that compared to controls, TrkB was the only protein significantly decreased after nicotine and nic+IHH exposure regardless of gender. For pro-BDNF and rhBDNF however, observed changes were more evident in males than females exposed to nicotine and nic+IHH. The implications of these findings are that a prior nicotine exposure makes the developing brainstem susceptible to greater changes in the neurotrophic effects of BDNF and its receptor TrkB in the face of a hypoxic insult, and that the effects are greater in males than females.

  16. Neonatal Death

    Science.gov (United States)

    ... a premature baby include pneumonia (a lung infection), sepsis (a blood infection) and meningitis (an infection in the fluid around the brain and spinal cord). What birth defects most often cause neonatal death? The most common birth defects that cause ...

  17. Early mortality and primary causes of death in mothers of children with intellectual disability or autism spectrum disorder: a retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    Jenny Fairthorne

    Full Text Available INTRODUCTION: Mothers of children with intellectual disability or autism spectrum disorder (ASD have poorer health than other mothers. Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers. METHODS: The study population comprised all mothers of live-born children in Western Australia from 1983-2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers. RESULTS AND DISCUSSION: During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed. CONCLUSION: Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers' longevity.

  18. Postnatal Treatment in Antenatally Diagnosed Meconium Peritonitis.

    Science.gov (United States)

    Ionescu, S; Andrei, B; Oancea, M; Licsandru, E; Ivanov, M; Marcu, V; Popa-Stanila, R; Mocanu, M

    2015-01-01

    Meconium peritonitis is a rare prenatal disease with an increased rate of morbidity and mortality in the neonatal period. Distinctive features revealed by prenatal and postnatal ultrasoundmay be present: abdominal calcifications, ascites, polyhydramnios, meconium pseudocyst, echogenic mass and dilated bowel or intestinal obstruction. Establishing clear postnatal treatment and prognosis is difficult because of the heterogeneity of the results obtained by ultrasound. The aim of the study is to determine how prenatal diagnosis of meconium peritonitis is associated with perinatal management and further evolution. Clinical results are different depending on the presence of antenatal diagnosis of meconium peritonitis and its form, which can be mild or severe. Surgical treatment and management of meconium peritonitis depend on the clinical presentation of the newborn. Meconium peritonitis diagnosed prenatally differs from that of the newborn, not only concerning the mortality rates but also through reduced morbidity and overall better prognosis. Celsius.

  19. Fibrochondrogenesis, an Antenatal and Postnatal Correlation

    Directory of Open Access Journals (Sweden)

    Nischal G Kundaragi

    2012-01-01

    Full Text Available Fibrochondrogenesis is a rare, neonatally lethal osteochondrodysplasia, with autosomal recessive inheritance. It differs from other lethal dwarfisms in that it leads to broad, long-bone metaphyses (dumb-bell shaped and pear-shaped vertebral bodies. We report a case of fibrochondrogenesis with severe pear-shaped platyspondyly, suspected antenatally, and give a comprehensive pictorial review of the antenatal ultrasound and postnatal radiographic findings. Only few cases of fibrochondrogenesis are diagnosed before the termination of pregnancy.

  20. Factors that affecting mothers’ postnatal comfort

    Directory of Open Access Journals (Sweden)

    Gül Pınar

    2009-01-01

    Full Text Available Aim: The comfort is defined as; “an expected result of a complex conformation of providing peace and help about individual’s needs in a physical, psycho-spiritual, social and environmental entity to overcome the problems”. The aim of this study was to determine the mother’s postnatal comfort and the affecting factors of it.Materials and Methods: This is a sectional and descriptive study. The study was performed on the mothers (n=150 who applied to the delivery service of the Başkent University Ankara Hospital between the date of 30.07.2008 to 31.12.2008. A questionnaire was developed by the investigators to collect data and determine patients’ postnatal comfort scores. Results: The mean age of women was 26.4±3.5 years, the majority of patients had an educational level of high school (68.7% and were multipara (66.0%. It was determined that the mothers had problems and needed help with the fatigue, pain, in standing up, the adverse effect of anesthesia, personal and perineal hygiene that affect their postnatal comfort. The comfort score of the mothers who had spontaneous vaginal birth was higher than those of underwent cesarean delivery (p<0.05.Conclusion: The mothers’ needs and expectations about themselves and their babies were generally supplied by midwifes and the nurses in the postnatal period. Opinion of the mothers about their comfort were influenced to a positive view and the comfort scores increased while the mothers’ satisfaction were augmented (p<0.05.

  1. Clincal research of hyponatremia and early death in cervical spinal cord injury%颈脊髓损伤后低钠血症与早期死亡的临床分析

    Institute of Scientific and Technical Information of China (English)

    尚明富; 赵廷宝; 孟庆溪

    2011-01-01

    目的 分析研究颈脊髓损伤(CSCI)低钠血症的相关因冈素、发病机制及对早期死亡的影响.方法 收集整理2005~2010年入院的131例CSCI患者的临床资料(早期死亡11例),分析CSCI后低钠血症与CSCI节段、损伤程度的关系及对早期死亡的影响.结果 颈脊髓不同损伤程度、不同损伤节段低钠血症发病率的统计分析,相互之间差异有统计学意义(X2值分别为为10.036,19.885,P<0.001);是否存在低钠血症的CSCI患者早期死亡率经统计学分析,差异有统计学意义(X2值为8.285,P<0.001).结论 CSCI程度越重、损伤节段越高,低钠血症的发病率越高,低钠血症是CSCI早期死亡的危险因素.%Objective The research had been launched to analyze the correlated factors mechanism and the influence to the early death of the hyponatremia in cervical spinal cord injury (CSCI).Methods There were totally 131 CSCI cases which had been collected from May 2005 to 2010 (early death 11 cases).The relationship among the hyponatremia and location of spine injury degree of the injury and the influence to the early death was analysed.Result The difference about the frequency of hyponatremia with distinct injury degree and location were statiscally significant (X2 is 15.933,23.443 separately,P<0.001)meanwhile it was statistically significant about early death rate in CSCI with hyponatremia or not (X2 is 8.285,P<0.001).Conclusions The frenquence of hyponatremia increase with the more serious injury and higher location,hyponatremia play a very important role in early death in CSCI.

  2. Thyroid hormone action in postnatal heart development

    Directory of Open Access Journals (Sweden)

    Ming Li

    2014-11-01

    Full Text Available Thyroid hormone is a critical regulator of cardiac growth and development, both in fetal life and postnatally. Here we review the role of thyroid hormone in postnatal cardiac development, given recent insights into its role in stimulating a burst of cardiomyocyte proliferation in the murine heart in preadolescence; a response required to meet the massive increase in circulatory demand predicated by an almost quadrupling of body weight during a period of about 21 days from birth to adolescence. Importantly, thyroid hormone metabolism is altered by chronic diseases, such as heart failure and ischemic heart disease, as well as in very sick children requiring surgery for congenital heart diseases, which results in low T3 syndrome that impairs cardiovascular function and is associated with a poor prognosis. Therapy with T3 or thyroid hormone analogs has been shown to improve cardiac contractility; however, the mechanism is as yet unknown. Given the postnatal cardiomyocyte mitogenic potential of T3, its ability to enhance cardiac function by promoting cardiomyocyte proliferation warrants further consideration.

  3. 早发急性心肌梗死患者院内死亡的临床特点分析%Clinical features of In-hospital death in patients early acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    朱春怀; 许涛; 刘和俊

    2015-01-01

    Objective To investigate the clinical features, risk factors and the death causes of in-hospital death in patients with early acute myocardial infarction in order to provide reference for the specific intervention measures.Methods Retrospectively analyzed the clinical data during the January 2008 to April 2015 of 165 cases of hospital mortality in patients with AMI.The data included the gener-al condition,family history, medical history and the history of surgery, hospital inspection, clinical diagnosis,treatment, in-hospital death and the reasons.According to the age of onset and death, the patients were divided into premature death group ( pre-death group) and no-premature death group(N-pre death group).Results (1)Family history of pre-death group was higher than N-pre death group(P<0.01),the median time from onset to death of pre-death group(2 d) was lower than that in N-pre death group(7 d). (2)The low density lipoprotein cholesterol (LDL), the creatine phosphate kinase (CPK)peak, fibrinogen (Fib) of pre-death group was significantly higher than N-pre death group (P<0.01, P<0.05).(3)Drinking and satiation was the unique cause of AMI in pre-death group.(4) The treatment regimens were not significantly different among the two groups, but emergency percutaneous coro-nary angioplasty ( PTCA) , emergency percutaneous coronary intervention, thrombolytic therapy and percutaneous coronary intervention were less.(5) The inferior wall myocardial infarction of pre-death group was lower than N-pre death group( P<0.01) .AMI was local-ized in 70.59% anterior, anteroseptal, extensive anteriorpartition wall in pre-death group and 56.49% inferior wall in N-pre death group.(6)The death causes included arrhythmia (atrioventricular block, ventricular tachycardia and ventricular fibrillation) were more frequent in pre-death group(24/31,77.42%),while pump failure (including source of heart failure and heart shock) was much more common in N-pre death group(55/131,41.98%).The

  4. 新生儿重症监护室10年早期新生儿死亡分析%Analysis of 10-year early neonatal death in the NICU

    Institute of Scientific and Technical Information of China (English)

    杨燕玲; 蒋裕蕊; 崔兆芳; 崔凤静; 单若冰

    2014-01-01

    目的:对青岛市妇女儿童医院新生儿重症监护室近10年早期新生儿死亡特征进行分析,探索早期新生儿死亡的原因及相应干预措施。方法收集青岛市妇女儿童医院2002年1月至2011年12月10年间新生儿重症监护室死亡新生儿病例资料,对住院早期新生儿死亡病例临床情况及主要死因进行回顾性分析。结果10年间青岛市妇女儿童医院共入院16314例新生儿,共死亡525例,生后1周内早期新生儿死亡408例,包括214例早产儿,194例足月儿,占新生儿死亡的77.71%。前后5年比较,病死率明显下降(P<0.05)。生后1 d内、~3 d、~7 d分别死亡110例(27.00%)、192例(47.06%)、106例(25.98%),多数病例为生后3 d内死亡,且1 d内死亡患儿疾病危重度高于其他两组(P<0.01)。10年内早期新生儿主要死因依次为:早产相关因素(97例,23.78%),重度窒息(91例,22.3%),先天畸形(66例,16.2%)等。2002-2006年早期新生儿死因前3位为重度窒息、先天畸形、呼吸窘迫综合征(RDS),2007-2011年为呼吸窘迫综合征(RDS)、重度窒息、先天畸形。早产儿死亡主要集中在32周以内(26.72%)。结论青岛市妇女儿童医院10年早期新生儿病死率逐年下降,死亡病例以3 d内最多,早产儿死亡主要集中在32周以内;早期新生儿总体死因顺位为早产、重度窒息、先天畸形,且前后五年死因顺位不同。%Objective To analyze the main causes of early neonatal death in Qingdao Women &Children's Hospital in the latest 10 years.Methods The medical records of early neonatal death in the Qingdao Women&Children’s Hospital from January 2002 through December 201 1 were analyzed.Results A total of 16 314 neonates were available to study,and 525 of them died.The mortality of early neonatal death within a week after birth was 77.71% (408 cases),including 214 premature

  5. Determinants of antenatal and postnatal care visits among Indigenous people in Bangladesh: a study of the Mru community.

    Science.gov (United States)

    Islam, M R; Odland, J O

    2011-01-01

    Antenatal and postnatal care services are significant interventions to improve maternal health and prevent maternal and infant deaths. However, these services are poorly developed in Bangladesh, particularly among Indigenous women. This study examined factors associated with antenatal and postnatal care visits among the Mru, the most underprivileged Indigenous people in Bangladesh. This cross-sectional study used both quantitative and qualitative methods. In total, 374 currently married Mru women with at least one child aged 5 years or younger were selected from 3 upazilas (sub-districts) of Bandarban District, Bangladesh for survey. In addition, in-depth interviews were performed with 26 Mru leaders, Mru women, traditional midwives, village 'doctors', school teachers, health and non-government organization workers. Associations between antenatal and postnatal care visits and the women's backgrounds characteristics were assessed by bivariate and multivariate analyses. The traditional Mru prenatal and postnatal practices potentially inhibited women from seeking care. Both antenatal (11.2%) and postnatal (6.4%) care visits among the Mru women were lower than the national level. Most visits were to traditional midwives in their rural villages, rather than to health complexes or hospitals. The main reasons for lack of antenatal and postnatal care were travelling distance to care and transportation problems. Multivariate analysis revealed factors associated with antenatal care were the respondent's place of residence, age, level of education, distance to the service centers and exposure to any mass media. Similar results were obtained with regard to postnatal care visits. This study suggests that cultural issues, distance, infrastructure and socioeconomic status are important determinants of maternal healthcare-seeking behavior. Healthcare delivery systems and appropriate education programs should be developed at the village level to improve the health of mothers and

  6. Postnatal depression and socio-cultural practices among postnatal mothers in Kota Bahru, Kelantan, Malaysia.

    Science.gov (United States)

    Azidah, A K; Shaiful, B I; Rusli, N; Jamil, M Y

    2006-03-01

    This is a cross sectional study to determine the relationship of postnatal depression (PND) and socio-cultural practices post-delivery among women in Kota Bharu, Kelantan. Four hundred and twenty one pregnant women were screened for depression between 36 - 42 weeks of pregnancy, 1 week and 4 - 6 weeks postpartum using Edinburgh Postnatal Depression Scale (EPDS). The women also completed questionnaires on socio-demography, psychosocial support and traditional postnatal care. The prevalence of PND at 4-6 weeks postpartum was 20.7%. Depressive symptoms at the end of pregnancy (p<0.05) and one week postpartum (p<0.05), worry about the baby (p<0.05), use of traditional medication (p<0.05) and traditional massage (p<0.05) were significantly associated with PND.

  7. Surviving death

    DEFF Research Database (Denmark)

    Gerstroem, Anna

    2013-01-01

    such phases. The aim of this paper is to explore how an organization’s identity is re-constructed after organizational death. Based on interviews with members of a bankrupted bank who narrate their bankruptcy experiences, the paper explores how legacy organizational identity is constructed after...... organizational death. The paper shows how members draw on their legacy organizational identity to justify their past interpretations and responses to the intensifying bankruptcy threats. Members refer to their firm belief in the bank’s solid and robust identity claim when they explain how they disregarded...

  8. Patterns of cell death in the perinatal mouse forebrain.

    Science.gov (United States)

    Mosley, Morgan; Shah, Charisma; Morse, Kiriana A; Miloro, Stephen A; Holmes, Melissa M; Ahern, Todd H; Forger, Nancy G

    2017-01-01

    The importance of cell death in brain development has long been appreciated, but many basic questions remain, such as what initiates or terminates the cell death period. One obstacle has been the lack of quantitative data defining exactly when cell death occurs. We recently created a "cell death atlas," using the detection of activated caspase-3 (AC3) to quantify apoptosis in the postnatal mouse ventral forebrain and hypothalamus, and found that the highest rates of cell death were seen at the earliest postnatal ages in most regions. Here we have extended these analyses to prenatal ages and additional brain regions. We quantified cell death in 16 forebrain regions across nine perinatal ages from embryonic day (E) 17 to postnatal day (P) 11 and found that cell death peaks just after birth in most regions. We found greater cell death in several regions in offspring delivered vaginally on the day of parturition compared with those of the same postconception age but still in utero at the time of collection. We also found massive cell death in the oriens layer of the hippocampus on P1 and in regions surrounding the anterior crossing of the corpus callosum on E18 as well as the persistence of large numbers of cells in those regions in adult mice lacking the pro-death Bax gene. Together these findings suggest that birth may be an important trigger of neuronal cell death and identify transient cell groups that may undergo wholesale elimination perinatally. J. Comp. Neurol. 525:47-64, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Maternal forced swimming reduces cell proliferation in the postnatal dentate gyrus of mouse offspring

    OpenAIRE

    Wasinski, Frederick; Estrela, Gabriel R.; Arakaki, Aline M.; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Ronaldo C Araújo

    2016-01-01

    Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mot...

  10. Encountering abuse in health care; lifetime experiences in postnatal women - a qualitative study

    OpenAIRE

    Schroll, Anne-Mette; Kjærgaard, Hanne; Midtgaard, Julie

    2013-01-01

    Background Abuse in health care (AHC) has been associated with potential severe health consequences, and has further been related to maternal morbidity and mortality in childbirth. To improve our understanding of what qualifies as AHC and to support and optimise the health of women with these experiences, the objective of this study was to describe how women, who had previously endured AHC, gave meaning to and managed their experience during pregnancy, childbirth, and in the early postnatal p...

  11. Encountering abuse in health care; lifetime experiences in postnatal women - a qualitative study

    DEFF Research Database (Denmark)

    Schroll, Anne-Mette; Kjærgaard, Hanne; Midtgaard, Julie

    2013-01-01

    Abuse in health care (AHC) has been associated with potential severe health consequences, and has further been related to maternal morbidity and mortality in childbirth. To improve our understanding of what qualifies as AHC and to support and optimise the health of women with these experiences......, the objective of this study was to describe how women, who had previously endured AHC, gave meaning to and managed their experience during pregnancy, childbirth, and in the early postnatal period....

  12. Developmental Profile, Morphology, and Synaptic Connectivity of Cajal-Retzius Cells in the Postnatal Mouse Hippocampus.

    Science.gov (United States)

    Anstötz, Max; Huang, Hao; Marchionni, Ivan; Haumann, Iris; Maccaferri, Gianmaria; Lübke, Joachim H R

    2016-02-01

    Cajal-Retzius (CR) cells are early generated neurons, involved in the assembly of developing neocortical and hippocampal circuits. However, their roles in networks of the postnatal brain remain poorly understood. In order to get insights into these latter functions, we have studied their morphological and synaptic properties in the postnatal hippocampus of the CXCR4-EGFP mouse, where CR cells are easily identifiable. Our data indicate that CR cells are nonuniformly distributed along different subfields of the hippocampal formation, and that their postnatal decline is regulated in a region-specific manner. In fact, CR cells persist in distinct areas of fully mature animals. Subclasses of CR cells project and target either local (molecular layers) or distant regions [subicular complex and entorhinal cortex (EC)] of the hippocampal formation, but have similar firing patterns. Lastly, CR cells are biased toward targeting dendritic shafts compared with spines, and produce large-amplitude glutamatergic unitary postsynaptic potentials on γ-aminobutyric acid (GABA) containing interneurons. Taken together, our results suggest that CR cells are involved in a novel excitatory loop of the postnatal hippocampal formation, which potentially contributes to shaping the flow of information between the hippocampus, parahippocampal regions and entorhinal cortex, and to the low seizure threshold of these brain areas.

  13. Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

    Directory of Open Access Journals (Sweden)

    Adel Jungling

    2017-02-01

    Full Text Available Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD. The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

  14. Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

    Science.gov (United States)

    Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

    2017-01-01

    Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life. PMID:28216584

  15. Effects of Postnatal Enriched Environment in a Model of Parkinson's Disease in Adult Rats.

    Science.gov (United States)

    Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

    2017-02-14

    Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson's disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

  16. Sensory and motor characterization in the postnatal valproate rat model of autism.

    Science.gov (United States)

    Reynolds, Stacey; Millette, Alexandre; Devine, Darragh P

    2012-01-01

    Although autism is diagnosed according to three core features of social deficits, communication impairments, and repetitive or stereotyped behaviors, other behavioral features such as sensory and motor impairments are present in more than 70% of individuals with autism spectrum disorders (ASD). Exposure of rat pups to the teratogen valproate during sensitive periods of brain development has been shown to elicit behavioral features associated with autism diagnosis and has been proposed as a valid animal model of the disorder. The purpose of this study was to characterize sensory and motor performance in rats postnatally treated with valproate. Thirty-four rat pups were injected with either valproate (150 mg/kg) or saline on postnatal days 6-12. Auditory and tactile startle as well as auditory sensory gating was assessed during both the juvenile and adolescent stages of development; motor testing was conducted during late adolescence and included a sunflower seed eating task and a vermicelli handling task. Valproate-treated rats were underresponsive to auditory stimuli, showed deficits in auditory sensory gating, and demonstrated impairments in motor speed and performance. These findings suggest that postnatal valproate treatment elicits sensory and motor features often seen in individuals with ASD. Further, the hyposensitivity seen in postnatally valproate-treated rats contrasted with hypersensitivity previously reported in prenatally valproate-exposed rats. This suggests that timing of teratogenic exposure during early brain development may be important to consider when investigating the neurobiological basis of sensorimotor impairments in ASD.

  17. Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the subventricular zone.

    Science.gov (United States)

    Relucio, Jenne; Menezes, Michael J; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi; Colognato, Holly

    2012-10-01

    The laminin family of extracellular matrix proteins are expressed broadly during embryonic brain development, but are enriched at ventricular and pial surfaces where laminins mediate radial glial attachment during corticogenesis. In the adult brain, however, laminin distribution is restricted, yet is found within the vascular basal lamina and associated fractones of the ventricular zone (VZ)-subventricular zone (SVZ) stem cell niche, where laminins regulate adult neural progenitor cell proliferation. It remains unknown, however, if laminins regulate the wave of oligodendrogenesis that occurs in the neonatal/early postnatal VZ-SVZ. Here we report that Lama2, the gene that encodes the laminin α2-subunit, regulates postnatal oligodendrogenesis. At birth, Lama2-/- mice had significantly higher levels of dying oligodendrocyte progenitor cells (OPCs) in the OPC germinal zone of the dorsal SVZ. This translated into fewer OPCs, both in the dorsal SVZ well as in an adjacent developing white matter tract, the corpus callosum. In addition, intermediate progenitor cells that give rise to OPCs in the Lama2-/- VZ-SVZ were mislocalized and proliferated nearer to the ventricle surface. Later, delays in oligodendrocyte maturation (with accompanying OPC accumulation), were observed in the Lama2-/- corpus callosum, leading to dysmyelination by postnatal day 21. Together these data suggest that prosurvival laminin interactions in the developing postnatal VZ-SVZ germinal zone regulate the ability, or timing, of oligodendrocyte production to occur appropriately.

  18. 2349例心脏瓣膜置换术早期死亡原因分析%Early death causes in 2349 patients who receiving heart valve replacement

    Institute of Scientific and Technical Information of China (English)

    陈海生; 刘盛华; 钟志敏; 谢翠贤; 林秋伟

    2010-01-01

    目的 分析2349例心脏瓣膜置换术病人的死亡原因,以期进一步提高治疗水平.方法 1995年1月至2007年12月,2349例心脏瓣膜病病人接受人工心脏瓣膜置换手术.其中二尖瓣置换术(MVR)1333例,主动脉瓣置换术(AVR)271例,二尖瓣、主动脉瓣同期置换术(DVR)736例,三尖瓣置换术(TVR)9例.结果 早期病死率1995年至1999年6.81%,2000年至2004年3.22%,2005年至2007年2.82%.全组总早期病死率3.40%.结论 心脏瓣膜置换术早期死亡的原因主要是低心排血量综合征、肾功能衰竭、心律失常、肺部感染、脑血管意外、左室破裂和多器官系统功能衰竭等.%Objective The early causes of death were analyze in 2349 patients who had undergone heart valve replacement.Methods Methods From January 1995 to December 2007,2349 patients with heart valve diseases received heart valve replacement.1109 cases were male and 1240 were female.The mean age of the patients was(41±19)years old.1962 cases had rheumatic heart valve disease,308 had congenital heart valve disease,39 had infective endocarditis,29 underwent reintervention by heart valve replacement,11 had Marfan syndrome.34 cases with coronary heart disease underwent heart valve prosthesis implantation and coronary artery bypass grafting.Mitral valve replacement(MVR)was performed in 1333 patients,aortic valve replacement(AVR)in 271,double valves replacement(DVR)in 736 and tricuspid valve replacement(TVR)in 9.There were 3075 mechanical valves and 10 bioprosthetic valves.Results From 1995 to 1999,death occurred in 16 of the 235 cases,early mortality rate was 6.81%.From 2000 to 2004,death occurred in 35 of the 1087 cases,early mortality rate was 3.22%.From 2005 to 2007,there were 29 deaths among 1027 cases,with an early mortality rate of 2.82%.Overall early mortality rate was 3.40%.The early mortality rate was 2.32%(31 in 1333 cases)in patients who underwent MVR,3.32% (9 in 271)in patients who underwent AVR,5.24%(40 in 736)in

  19. Predicting potential and actual distribution of sudden oak death in Oregon: prioritizing landscape contexts for early detection and eradication of disease outbreaks

    Science.gov (United States)

    Tomas Vaclavik; Alan Kanaskie; Everett M. Hansen; Janet L. Ohmann; Ross K. Meentemeyer

    2010-01-01

    An isolated outbreak of the emerging forest disease sudden oak death was discovered in Oregon forests in 2001. Despite considerable control efforts, disease continues to spread from the introduction site due to slow and incomplete detection and eradication. Annual field surveys and laboratory tests between 2001 and 2009 confirmed a total of 802 infested locations. Here...

  20. Death cap

    DEFF Research Database (Denmark)

    Rudbæk, Torsten R; Kofoed, Pernille Bouteloup; Bove, Jeppe

    2014-01-01

    Death cap (Amanita phalloides) is commonly found and is one of the five most toxic fungi in Denmark. Toxicity is due to amatoxin, and poisoning is a serious medical condition, causing organ failure with potential fatal outcome. Acknowledgement and clarification of exposure, symptomatic and focused...

  1. Death Drive

    OpenAIRE

    Stühler, Rebekka Hellstrøm

    2012-01-01

    The aim of this project is to investigate why the Freudian term Death Drive is not acknowledged in modern psychological therapy. On basis of psychoanalytical theory and through a literary analysis, the project will present a discussion of the significance and presence of the term within these practises.

  2. "Spectacular Death"

    DEFF Research Database (Denmark)

    Jacobsen, Michael Hviid

    2016-01-01

    be labelled ‘spectacular death’ in which death, dying and mourning have increasingly become spectacles. Moreover, the author proposes that what is currently happening in contemporary Western society can be interpreted as an expression of a ‘partial re-reversal’ of ‘forbidden death’ to some...

  3. Postnatal handling reverses social anxiety in serotonin receptor 1A knockout mice.

    Science.gov (United States)

    Zanettini, C; Carola, V; Lo Iacono, L; Moles, A; Gross, C; D'Amato, F R

    2010-02-01

    Mice lacking the serotonin receptor 1A (Htr1a knockout, Htr1a(KO)) show increased innate and conditioned anxiety. This phenotype depends on functional receptor activity during the third through fifth weeks of life and thus appears to be the result of long-term changes in brain function as a consequence of an early deficit in serotonin signaling. To evaluate whether this phenotype can be influenced by early environmental factors, we subjected Htr1a knockout mice to postnatal handling, a procedure known to reduce anxiety-like behavior and stress responses in adulthood. Offspring of heterozygous Htr1a knockout mice were separated from their mother and exposed 15 min each day from postnatal day 1 (PD1) to PD14 to clean bedding. Control animals were left undisturbed. Maternal behavior was observed during the first 13 days of life. Adult male offspring were tested in the open field, social approach and resident-intruder tests and assessed for corticosterone response to restraint stress. Knockout mice showed increased anxiety in the open field and in the social approach test as well as an enhanced corticosterone response to stress. However, while no effect of postnatal handling was seen in wild-type mice, handling reduced anxiety-like behavior in the social interaction test and the corticosterone response to stress in knockout mice. These findings extend the anxiety phenotype of Htr1a(KO) mice to include social anxiety and demonstrate that this phenotype can be moderated by early environmental factors.

  4. Lhx8 regulates primordial follicle activation and postnatal folliculogenesis.

    Science.gov (United States)

    Ren, Yu; Suzuki, Hitomi; Jagarlamudi, Krishna; Golnoski, Kayla; McGuire, Megan; Lopes, Rita; Pachnis, Vassilis; Rajkovic, Aleksandar

    2015-06-16

    The early stages of ovarian follicle formation-beginning with the breakdown of germ cell cysts and continuing with the formation of primordial follicles and transition to primary and secondary follicles-are critical in determining reproductive life span and fertility. Previously, we discovered that global knockouts of germ cell-specific transcriptional co-regulators Sohlh1, Sohlh2, Lhx8, and Nobox, cause rapid oocyte loss and ovarian failure. Also factors such as Nobox and Sohlh1 are associated with human premature ovarian failure. In this study, we developed a conditional knockout of Lhx8 to study oocyte-specific pathways in postnatal folliculogenesis. The conditional deficiency of Lhx8 in the oocytes of primordial follicles leads to massive primordial oocyte activation, in part, by indirectly interacting with the PI3K-AKT pathway, as shown by synergistic effects on FOXO3 nucleocytoplasmic translocation and rpS6 activation. However, LHX8 does not directly regulate members of the PI3K-AKT pathway; instead, we show that LHX8 represses Lin28a expression, a known regulator of mammalian metabolism and of the AKT/mTOR pathway. LHX8 can bind to the Lin28a promoter, and the depletion of Lin28a in Lhx8-deficient oocytes partially suppresses primordial oocyte activation. Moreover, unlike the PI3K-AKT pathway, LHX8 is critical beyond primordial follicle activation, and blocks the primary to secondary follicle transition. Our results indicate that the LHX8-LIN28A pathway is essential in the earliest stages of primordial follicle activation, and LHX8 is an important oocyte-specific transcription factor in the ovary for regulating postnatal folliculogenesis.

  5. Innovation:CBT-based support groups for postnatal depression.

    Science.gov (United States)

    Alexander, Pat

    Postnatal depression can have serious implications for mother/child bonding and damage relationships between parents. Approaches to treat it need to overcome barriers that have led to high attrition in some group or clinic-based postnatal depression treatment studies. This retrospective evaluation explored the benefits of offering postnatally depressed mothers group support based on cognitive behavioural therapy. It helped to improve women's self-esteem and self-worth and to make them feel safe and supported.

  6. Induction of enhanced postnatal expression of immunoreactive calbindin-D28k in rat forebrain by the calcium antagonist nimodipine

    NARCIS (Netherlands)

    Luiten, Paul G.M.; Buwalda, Bauke; Traber, Jörg; Nyakas, Csaba

    1994-01-01

    The early postnatal development of immunoreactive calbindin-D28k (CaB-ir) containing neuronal systems in hippocampus and parietal cortex was studied in offspring of Wistar rats chronically treated with either the Ca2+-channel antagonist nimodipine or placebo food. The drug was applied to the mother

  7. Postnatal depression - an examination of psychosocial factors | Mills ...

    African Journals Online (AJOL)

    Postnatal depression - an examination of psychosocial factors. ... South African Medical Journal ... pregnancy, complications after birth, marital relations, relationship with their own mothers, social support and preparation for motherhood.

  8. Increased soluble programmed death-1 (sPD-1) is associated with disease activity and radiographic progression in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Greisen, S. R.; Rasmussen, T. K.; Stengaard-Pedersen, K.

    2014-01-01

    OBJECTIVES: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought to be implica......OBJECTIVES: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought...... Questionnaire (HAQ) score, immunoglobulin M rheumatoid factor (IgM-RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, C-reactive protein (CRP), interleukin-21 (IL-21), and total Sharp score (TSS). We also measured sPD-1 in plasma from healthy volunteers (HV) (n = 20) and in plasma and synovial fluid...

  9. Surviving death

    DEFF Research Database (Denmark)

    Gerstroem, Anna

    2013-01-01

    such phases. The aim of this paper is to explore how an organization’s identity is re-constructed after organizational death. Based on interviews with members of a bankrupted bank who narrate their bankruptcy experiences, the paper explores how legacy organizational identity is constructed after...... organizational death. The paper shows how members draw on their legacy organizational identity to justify their past interpretations and responses to the intensifying bankruptcy threats. Members refer to their firm belief in the bank’s solid and robust identity claim when they explain how they disregarded...... increasing threats and fought to defend and preserve the organization. When the bank was declared bankrupt and the solid and robust identity claim was disconfirmed, members found comfort and guidance in an identity claim of local care and support. After the bankruptcy, part of the bank was acquired...

  10. Patients Hospitalized in General Wards via the Emergency Department: Early Identification of Predisposing Factors for Death or Unexpected Intensive Care Unit Admission—A Historical Prospective

    Directory of Open Access Journals (Sweden)

    Thierry Boulain

    2014-01-01

    Full Text Available Background. To identify, upon emergency department (ED admission, predictors of unexpected death or unplanned intensive care/high dependency units (ICU/HDU admission during the first 15 days of hospitalization on regular wards. Methods. Prospective cohort study in a medical-surgical adult ED in a teaching hospital, including consecutive patients hospitalized on regular wards after ED visit, and identification of predictors by logistic regression and Cox proportional hazards model. Results. Among 4,619 included patients, 77 (1.67% target events were observed: 32 unexpected deaths and 45 unplanned transfers to an ICU/HDU. We identified 9 predictors of the target event including the oxygen administration on the ED, unknown current medications, and use of psychoactive drug(s. All predictors put the patients at risk during the first 15 days of hospitalization. A logistic model for hospital mortality prediction (death of all causes still comprised oxygen administration on the ED, unknown current medications, and the use of psychoactive drug(s as risk factors. Conclusion. The “use of oxygen therapy on the ED,” the “current use of psychoactive drug(s”, and the “lack of knowledge of current medications taken by the patients” were important predisposing factors to severe adverse events during the 15 days of hospitalization on regular wards following the ED visit.

  11. Brain death.

    Science.gov (United States)

    Wijdicks, Eelco F M

    2013-01-01

    The diagnosis of brain death should be based on a simple premise. If every possible confounder has been excluded and all possible treatments have been tried or considered, irreversible loss of brain function is clinically recognized as the absence of brainstem reflexes, verified apnea, loss of vascular tone, invariant heart rate, and, eventually, cardiac standstill. This condition cannot be reversed - not even partly - by medical or surgical intervention, and thus is final. Many countries in the world have introduced laws that acknowledge that a patient can be declared brain-dead by neurologic standards. The U.S. law differs substantially from all other brain death legislation in the world because the U.S. law does not spell out details of the neurologic examination. Evidence-based practice guidelines serve as a standard. In this chapter, I discuss the history of development of the criteria, the current clinical examination, and some of the ethical and legal issues that have emerged. Generally, the concept of brain death has been accepted by all major religions. But patients' families may have different ideas and are mostly influenced by cultural attitudes, traditional customs, and personal beliefs. Suggestions are offered to support these families.

  12. Properties of persistent postnatal cortical subplate neurons.

    Science.gov (United States)

    Torres-Reveron, Juan; Friedlander, Michael J

    2007-09-12

    Subplate (SP) neurons are important for the proper development of thalamocortical innervation. They are necessary for formation of ocular dominance and orientation columns in visual cortex. During the perinatal period, many SP neurons die. The surviving cohort forms interstitial cells in the white matter (WM) and a band of horizontally oriented cells below layer VI (layer VIb, layer VII, or subplate cells). Although the function of embryonic SP neurons has been well established, the functional roles of WM and postnatal SP cells are not known. We used a combination of anatomical, immunohistochemical, and electrophysiological techniques to explore the dendritic morphology, neurotransmitter phenotype, intrinsic electrophysiological, and synaptic input properties of these surviving cells in the rat visual cortex. The density of SP and WM cells significantly decreases during the first month of life. Both populations express neuronal markers and have extensive dendritic arborizations within the SP, WM, and to the overlying visual cortex. Some intrinsic electrophysiological properties of SP and WM cells are similar: each generates high-frequency slowly adapting trains of action potentials in response to a sustained depolarization. However, SP cells exhibit greater frequency-dependent action potential broadening than WM neurons. Both cell types receive predominantly AMPA/kainate receptor-mediated excitatory synaptic input that undergoes paired-pulse facilitation as well as NMDA receptor and GABAergic input. Synaptic inputs to these cells can also undergo long-term synaptic plasticity. Thus, surviving SP and WM cells are functional electrogenic neurons integrated within the postnatal visual cortical circuit.

  13. Diagnostic accuracy of S100B urinary testing at birth in full-term asphyxiated newborns to predict neonatal death.

    Directory of Open Access Journals (Sweden)

    Diego Gazzolo

    Full Text Available BACKGROUND: Neonatal death in full-term infants who suffer from perinatal asphyxia (PA is a major subject of investigation, since few tools exist to predict patients at risk of ominous outcome. We studied the possibility that urine S100B measurement may identify which PA-affected infants are at risk of early postnatal death. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study between January 1, 2001 and December 1, 2006 we measured S100B protein in urine collected from term infants (n = 132, 60 of whom suffered PA. According to their outcome at 7 days, infants with PA were subsequently classified either as asphyxiated infants complicated by hypoxic ischemic encephalopathy with no ominous outcome (HIE Group; n = 48, or as newborns who died within the first post-natal week (Ominous Outcome Group; n = 12. Routine laboratory variables, cerebral ultrasound, neurological patterns and urine concentrations of S100B protein were determined at first urination and after 24, 48 and 96 hours. The severity of illness in the first 24 hours after birth was measured using the Score for Neonatal Acute Physiology-Perinatal Extension (SNAP-PE. Urine S100B levels were higher from the first urination in the ominous outcome group than in healthy or HIE Groups (p1.0 microg/L S100B had a sensitivity/specificity of 100% for predicting neonatal death. CONCLUSIONS/SIGNIFICANCE: Increased S100B protein urine levels in term newborns suffering PA seem to suggest a higher risk of neonatal death for these infants.

  14. Correction of murine hemoglobinopathies by prenatal tolerance induction and postnatal nonmyeloablative allogeneic BM transplants.

    Science.gov (United States)

    Peranteau, William H; Hayashi, Satoshi; Abdulmalik, Osheiza; Chen, Qiukan; Merchant, Aziz; Asakura, Toshio; Flake, Alan W

    2015-09-03

    Sickle cell disease (SCD) and thalassemias (Thal) are common congenital disorders, which can be diagnosed early in gestation and result in significant morbidity and mortality. Hematopoietic stem cell transplantation, the only curative therapy for SCD and Thal, is limited by the absence of matched donors and treatment-related toxicities. In utero hematopoietic stem cell transplantation (IUHCT) is a novel nonmyeloablative transplant approach that takes advantage of the immunologic immaturity and normal developmental properties of the fetus to achieve mixed allogeneic chimerism and donor-specific tolerance (DST). We hypothesized that a combined strategy of IUHCT to induce DST, followed by postnatal nonmyeloablative same donor "booster" bone marrow (BM) transplants in murine models of SCD and Thal would result in high levels of allogeneic engraftment and donor hemoglobin (Hb) expression with subsequent phenotypic correction of SCD and Thal. Our results show that: (1) IUHCT is associated with DST and low levels of allogeneic engraftment in the murine SCD and Thal models; (2) low-level chimerism following IUHCT can be enhanced to high-level chimerism and near complete Hb replacement with normal donor Hb with this postnatal "boosting" strategy; and (3) high-level chimerism following IUHCT and postnatal "boosting" results in phenotypic correction in the murine Thal and SCD models. This study supports the potential of IUHCT, combined with a postnatal nonmyelablative "boosting" strategy, to cure Thal and SCD without the toxic conditioning currently required for postnatal transplant regimens while expanding the eligible transplant patient population due to the lack of a restricted donor pool.

  15. Expression of Npas4 mRNA in telencephalic areas of adult and postnatal mouse brain

    Directory of Open Access Journals (Sweden)

    Joanne C Damborsky

    2015-11-01

    Full Text Available The transcription factor neuronal PAS domain-containing protein 4 (Npas4 is an inducible immediate early gene which regulates the formation of inhibitory synapses, and could have a significant regulatory role during cortical circuit formation. However, little is known about basal Npas4 mRNA expression during postnatal development. Here, postnatal and adult mouse brain sections were processed for isotopic in situ hybridization using an Npas4 specific cRNA antisense probe. In adults, Npas4 mRNA was found in the telencephalon with very restricted or no expression in diencephalon or mesencephalon. In most telencephalic areas, including the anterior olfactory nucleus (AON, piriform cortex, neocortex, hippocampus, dorsal caudate putamen (CPu, septum and basolateral amygdala nucleus (BLA, basal Npas4 expression was detected in scattered cells which exhibited strong hybridization signal. In embryonic and neonatal brain sections, Npas4 mRNA expression signals were very low. Starting at postnatal day 5 (P5, transcripts for Npas4 were detected in the AON, CPu and piriform cortex. At P8, additional Npas4 hybridization was found in CA1 and CA3 pyramidal layer, and in primary motor cortex. By P13, robust mRNA expression was located in layers IV and VI of all sensory cortices, frontal cortex and cingulate cortex. After onset of expression, postnatal spatial mRNA distribution was similar to that in adults, with the exception of the CPu, where Npas4 transcripts became gradually restricted to the most dorsal part. In conclusion, the spatial distribution of Npas4 mRNA is mostly restricted to telencephalic areas, and the temporal expression increases with developmental age during postnatal development, which seem to correlate with the onset of activity-driven excitatory transmission.

  16. Postnatal dexamethasone-induced programmed hypertension is related to the regulation of melatonin and its receptors.

    Science.gov (United States)

    Chang, Hsin-Yu; Tain, You-Lin

    2016-04-01

    Adulthood hypertension can be programmed by glucocorticoid exposure in early life. We found that maternal melatonin therapy prevents postnatal dexamethasone (DEX)-induced programmed hypertension. Melatonin acts through specific receptors, including MT1 and MT2 membrane receptors, and retinoid related orphan nuclear receptors of the RZR/ROR family. Thus we tested whether postnatal DEX-induced hypertension is related to changes of melatonin receptors in the kidney and heart, which was preserved by maternal melatonin therapy. Male neonates were assigned to four groups (n=6-8/group): control, DEX, control+melatonin (MEL), and DEX+MEL. Male rat pups were injected i.p. with DEX on d 1 (0.5 mg/kg BW), d 2 (0.3 mg/kg BW), and d 3 (0.1 mg/kg BW) after birth. Melatonin was administered in drinking water (0.01%) during the lactation period. We found DEX group developed hypertension at 16 weeks of age, which melatonin therapy prevented. Postnatal DEX treatment increased mRNA expression of MT1 and MT2, while decreased RORα and RZRβ in the kidney. These changes were prevented by melatonin therapy. Postnatal DEX decreased protein level of MT2 in the kidney, which was attenuated by melatonin therapy. Renal protein level of RORα was higher in DEX+MEL group compared to control and DEX group. Renal melatonin level was higher in the MEL and DEX+MEL groups compared to control. We concluded that melatonin therapy has long-term protection on postnatal DEX-induced programmed hypertension, which is associated with regulation on melatonin receptors in the kidney. Our findings would offer potential therapeutic approaches to prevent programmed hypertension in premature baby receiving glucocorticoids.

  17. Association between Prenatal and Postnatal Psychological Distress and Toddler Cognitive Development: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Dawn Kingston

    Full Text Available Maternal psychological distress is one of the most common perinatal complications, affecting up to 25% of pregnant and postpartum women. Research exploring the association between prenatal and postnatal distress and toddler cognitive development has not been systematically compiled. The objective of this systematic review was to determine the association between prenatal and postnatal psychological distress and toddler cognitive development.Articles were included if: a they were observational studies published in English; b the exposure was prenatal or postnatal psychological distress; c cognitive development was assessed from 13 to 36 months; d the sample was recruited in developed countries; and e exposed and unexposed women were included. A university-based librarian conducted a search of electronic databases (Embase, CINAHL, Eric, PsycInfo, Medline (January, 1990-March, 2014. We searched gray literature, reference lists, and relevant journals. Two reviewers independently evaluated titles/abstracts for inclusion, and quality using the Scottish Intercollegiate Guideline Network appraisal tool for observational studies. One reviewer extracted data using a standardized form.Thirteen of 2448 studies were included. There is evidence of an association between prenatal and postnatal distress and cognitive development. While variable effect sizes were reported for postnatal associations, most studies reported medium effect sizes for the association between prenatal psychological distress and cognitive development. Too few studies were available to determine the influence of the timing of prenatal exposure on cognitive outcomes.Findings support the need for early identification and treatment of perinatal mental health problems as a potential strategy for optimizing toddler cognitive development.

  18. Postnatal Innate Immune Development: From Birth to Adulthood

    Directory of Open Access Journals (Sweden)

    Anastasia Georgountzou

    2017-08-01

    Full Text Available It is well established that adaptive immune responses are deficient in early life, contributing to increased mortality and morbidity. The developmental trajectories of different components of innate immunity are only recently being explored. Individual molecules, cells, or pathways of innate recognition and signaling, within different compartments/anatomical sites, demonstrate variable maturation patterns. Despite some discrepancies among published data, valuable information is emerging, showing that the developmental pattern of cytokine responses during early life is age and toll-like receptor specific, and may be modified by genetic and environmental factors. Interestingly, specific environmental exposures have been linked both to innate function modifications and the occurrence of chronic inflammatory disorders, such as respiratory allergies. As these conditions are on the rise, our knowledge on innate immune development and its modulating factors needs to be expanded. Improved understanding of the sequence of events associated with disease onset and persistence will lead toward meaningful interventions. This review describes the state-of-the-art on normal postnatal innate immune ontogeny and highlights research areas that are currently explored or should be further addressed.

  19. 儿童医院住院早期新生儿134例死亡原因分析%Analysis on causes of 134 early neonatal death in children s hospital

    Institute of Scientific and Technical Information of China (English)

    李敏; 沈云琳; 刘万红; 刘霞; 龚小慧

    2011-01-01

    目的:回顾性总结并分析上海市儿童医院住院早期新生儿死亡病例的主要死因.方法:调查上海市儿童医院1997年1月~2009年12月死亡住院新生儿的病历资料,分析住院早期新生儿死亡病例的临床情况及其主要死因.结果:1997年1月~2009年12月共收治住院新生儿18061例,其中死亡201例.医治无效死亡的生后1周内早期新生儿134例,其中早产A 59例,足月儿75例,占新生儿死亡66.67%,多数在出生后3天内死亡,在生后<24 h,24~72 h,4~7天,早产儿和足月儿死亡分别为27例(45.76%)、18例(30.51%)、14例(23.73%);35例(46.67%)、16例(21.33%)、24例(32.00%).早期新生儿主要死因前三位:早产儿为呼吸窘迫综合征、极低或超低出生体重儿并发肺炎和重度围产期窒息,足月儿为先天畸形、重度围产期窒息和败血症.结论:为降低住院新生儿的病死率,新生儿科医生应尽早识别出危重新生儿,按各种疾病的高度危险期积极救治,并提高早产儿的监护和治疗水平.%Objective: To summarize and analyze the main causes of early neonatal death in Shanghai children ' s hospital. Methods; The medical records of early neonatal death in the hospital from January 1997 to December 2009 were investigated, the clinical conditions and the main causes of the early neonatal death were analyzed. Results; 18 061 neonates hospitalized in the hospital from January 1997 to December 2009, and 201 of them died. The proportion of early neonatal death within one week after birth was 66. 67% (134 cases) , including 59 premature infants and 75 mature infants, most of the neonates died within 3 days after birth; the mortalities of prema-ture infants within 24 hours, 24-72 hours and 4-7 days after birth were 45. 76% (27 cases) , 30. 51% ( 18 cases) , 23.73% ( 14 cases) , respectively; and the mortalities of mature infants within 24 hours, 24 ~ 72 hours and 4-7 days after birth were 46. 67% (35 cases) , 21. 33% (16 cases

  20. Mechanisms of Resilience in Children of Mothers Who Self-Report with Depressive Symptoms in the First Postnatal Year.

    Directory of Open Access Journals (Sweden)

    Emily Savage-McGlynn

    Full Text Available Symptoms of maternal postnatal depression are associated with an increased risk of adverse effects on child development. However, some children exposed to postnatal depression have outcomes similar to unexposed children, and can be referred to as resilient. This study aimed to determine the mechanisms of resilience in children exposed to depressive symptoms postnatally.Data are from a prospective cohort study, the Avon Longitudinal Study of Parents and Children. Self-report questionnaire data were collected during pregnancy and the child's first 2 years regarding maternal views of parenting and her perception of the child. The Edinburgh Postnatal Depression Scale (EPDS was completed postnatally at 8 months and the Strengths and Difficulties Questionnaire (SDQ at age 11 years. Exposed children who scored above the median score of non-exposed children were defined as resilient. Structural equation modeling was used to investigate the development of resilience.From the core ALSPAC cohort, 1,009 children (6.9% were exposed to maternal depression at 8 months postnatally. The SDQ total difficulties scores at 11 years of age indicated that 325 (32.2% were resilient, 684 were non-resilient. Maternal positive feelings about parenting and child non-verbal communication at 15 months increased the likelihood of later resilience.In this study, resilience was associated with two factors: the child's nonverbal communication at 15 months and by maternal positive feelings about parenting. Early intervention to support mother-child interaction and foster child development in women identified with postnatal depressive symptoms may benefit later child resilience.

  1. Proteomic identification of putative biomarkers for early detection of sudden cardiac death in a family with a LMNA gene mutation causing dilated cardiomyopathy.

    Science.gov (United States)

    Izquierdo, Irene; Rosa, Isaac; Bravo, Susana Belén; Guitián, Esteban; Pérez-Serra, Alexandra; Campuzano, Oscar; Brugada, Ramon; Mangas, Alipio; García, Ángel; Toro, Rocio

    2016-10-04

    Dilated cardiomyopathy (DCM) is a severe heart disease characterized by progressive ventricular dilation and impaired systolic function of the left ventricle. We recently identified a novel pathogenic mutation in the LMNA gene in a family affected by DCM showing sudden death background. We now aimed to identify potential biomarkers of disease status, as well as sudden death predictors, in members of this family. We analysed plasma samples from 14 family members carrying the mutation, four of which (with relevant clinical symptoms) were chosen for the proteomic analysis. Plasma samples from these four patients and from four sex- and age-matched healthy controls were processed for their enrichment in low- and medium-abundance proteins (ProteoMiner™) prior to proteomic analysis by 2D-DIGE and MS. 111 spots were found to be differentially regulated between mutation carriers and control groups, 83 of which were successfully identified by MS, corresponding to 41 different ORFs. Some proteins of interest were validated either by turbidimetry or western blot in family members and healthy controls. Actin, alpha-1-antytripsin, clusterin, vitamin-D binding protein and antithrombin-III showed increased levels in plasma from the diseased group. We suggest following these proteins as putative biomarkers for the evaluation of DCM status in LMNA mutation carriers. We developed a proteomic analysis of plasma samples from a family showing history of dilated cardiomyopathy caused by a LMNA mutation, which may lead to premature death or cardiac transplant. We identified a number of proteins augmented in mutation carriers that could be followed as potential biomarkers for dilated cardiomyopathy on these patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Postnatal development of hypoplastic thymus in semi-lethal dwarf pet/pet males.

    Science.gov (United States)

    Chiba, Junko; Suzuki, Hiroetsu; Aoyama, Hiroaki; Katayama, Kentaro; Suzuki, Katsushi

    2011-04-01

    The petit rat (pet/pet) is a new semi-lethal dwarf mutant with anomalies in the thymus and testes, defects inherited as a single autosomal recessive trait. At birth, these pet/pet rats show low birth weight and extremely small thymuses; at 140 days of age, their thymuses show abnormal involution. In the present study, we examined early postnatal development of hypoplastic pet/pet thymuses. In addition to being hypoplastic at birth, pet/pet thymus growth was almost completely impaired during the early postnatal period. As shown by cellular incorporation of BrdU, the mitotic activity was lower in pet/pet than in normal thymuses, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that apoptosis occurred more often in pet/pet than in normal thymus cells during the first few days after birth. These results indicate that postnatal development of the hypoplastic pet/pet thymus is defective due to the reduced proliferation and increased apoptosis of thymic cells.

  3. Influence of marital history over two and three generations on early death. A longitudinal study of Danish men born in 1953

    DEFF Research Database (Denmark)

    Lund, Rikke; Christensen, Ulla; Holstein, Bjørn Evald

    2006-01-01

    a random sample of all boys born in the the metropolitan area of Copenhagen with complete data from interviews and registers on two and three generation's marital status, socioeconomic position variables, and last generation's admission to psychiatric hospital, n = 2614. Among these 105 deaths occurred...... with increased mortality among the sons. There was no independent effect of maternal grandparent's experience of divorce on third generation's mortality. Son's marital status was the strongest marital status predictor of mortality. Accumulation of both two and three generations' marital status was significantly...

  4. Determinants of postnatal maternity care service utilization in rural Belgaum of Karnataka, India: A community based cross-sectional study

    Directory of Open Access Journals (Sweden)

    Dillee Prasad Paudel

    2014-01-01

    Full Text Available Background: The postnatal period is critical to the health and survival of a mother and her newborn. Lack of care in this period may result in death or disability as well as missed opportunities to promote healthy behaviors, affecting women and newborn children. Hence, the study was carried out to explore determinants of postnatal maternity service utilization in the rural area of Belgaum. Materials and Methods: Community based cross-sectional study was carried out from August 2012 to January 2013 in rural Belgaum. Total 630 mothers with less than 1 year child were interviewed using pretested questionnaire with her written consent. Analysis was done in Statistical Package for Social Sciences (SPSS version 20 applying appropriate statistics. Results were presented in tabular and narrative forms. Results: Among 630 mothers, 54.6% were 20-24 years of age, 61.6% were having secondary level of education, 89.8% house wives and 91.6% Hindus. About 69.7% were from joint family with low economic status. Regarding postnatal service use; 79.0% use properly. Almost; three-fifth met with nurse/health workers at least three times, four-fifth got advice about breast/nipple care, 92.5% about breast-feeding, 67.9% about post-natal exercise, 89.0% on nutrition education, and 85% got the advice of uterus care. About 29.8% perceived some health problems. Education, income, awareness, and delivery places were found most significant determinants (P < 0.01 of postnatal services use. Conclusion: More than three quarters of mothers had used the proper postnatal maternity services. Education, family income, awareness, and delivery place were found as most significant factors. Sustainable maternal and child healthcare (MCH programs and awareness will support to achieve furthermore better results.

  5. [Two sudden deaths of children with mesenterium commune -- a case report].

    Science.gov (United States)

    Grusová, Kateřina; Votava, Milan; Zeman, Martin

    2015-01-01

    Congenital anomalies of the digestive system represent a complicated topic concerning many medical specializations. The goal of this article is to describe two cases of children with mesenterium commune. First was an infant (5.5 months old female) who died shortly after being admitted to hospital with acute bronchitis, vomiting and diarrhoea. The autopsy revealed the cause of death--volvulus of the entire small intestine and the first portion of the large intestine with haemorrhagic infarsation of the intestinal wall in an infant with congenital anomaly of intestinal fixation--mesenterium commune. Second case was a 2.5 years old female after two heart surgeries, with pulmonary hypertension, who died suddenly at home. The cause of death was volvulus of a portion of the small intestine with haemorrhagic infarsation of the intestinal wall and also mesenterium commune. Congenital malpositions of the intestine originate due to malrotation and malfixation of the intestine during prenatal and early postnatal period. This wide range of the individuals developmental disorders always result in a condition where the topographical findings in the abdominal cavity are not as commonly found. Abnormally positioned intestines cannot develop a normal mesentery and are prone to volvulus, which represents the most serious complication with acute abdominal symptoms and when diagnosed late, it can lead to sudden death. Whilst performing autopsies such cases are rarely seen. However in forensic medicine and also in clinical practice it is important to consider intestinal malposition as a cause of acute abdomen.

  6. Postnatal Hematopoiesis and Gut Microbiota in NOD Mice Deviate from C57BL/6 Mice

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    Dina Silke Malling Damlund

    2016-01-01

    Full Text Available Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn mice of dams housed under the same conditions. A distinct bacteria profile rich in staphylococci was found at postnatal days (PND 1–4 in NOD mice. Furthermore, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface in NOD compared to C57BL/6 mice.

  7. Postnatal hematopoiesis and gut microbiota in NOD mice deviate from C57BL/6 mice

    DEFF Research Database (Denmark)

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss

    2016-01-01

    Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate...... from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn mice of dams housed under the same conditions. A distinct bacteria profile rich in staphylococci was found at postnatal days (PND) 1-4 in NOD mice. Furthermore......, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface...

  8. Postnatal changes of leptin levels in full-term and preterm neonates: their relation to intrauterine growth, gender and testosterone.

    Science.gov (United States)

    Ertl, T; Funke, S; Sárkány, I; Szabó, I; Rascher, W; Blum, W F; Sulyok, E

    1999-03-01

    The present study was carried out to investigate leptin levels in arterial and venous cord serum and in amniotic fluid in full-term infants at birth and on the 5th postnatal day to define the relationship of leptin to intrauterine growth rate, gender and early postnatal life. The relation of weight gain to serum leptin levels in male preterm infants was determined measuring leptin concentration weekly in the first 5 postnatal weeks. Testosterone levels were determined simultaneously to explore a possible relationship between leptin and testosterone concentrations. Fifty-three term newborn infants with mean birth weight and gestational age of 3,419 g (range 2,150-4,480) and 38.9 weeks (range 36-41) and 19 preterm male infants (mean birth weight and gestational age were 1,416 g (770-1,800) and 30.2 weeks (26-35) were enrolled into the study. Leptin and testosterone levels were determined by radioimmunoassay. It was demonstrated that serum leptin levels were markedly elevated in the cord blood without discernible arteriovenous differences. Cord blood leptin was found to correlate with birth weight (r = 0.40, p fall by the 5th postnatal day (p preterm infants at 1 week of age was significantly lower compared with term infants (p preterm male infants serum leptin concentration increases with postnatal weight and testosterone may suppress leptin synthesis.

  9. Maternal postnatal care utilization and associated factors: A community-based study among women of child-bearing age in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    I P Okafor

    2013-01-01

    Full Text Available Background and Objective: Nigeria has one of the highest maternal and child death rates in the world. Postnatal care is one of the major interventions recommended to reduce maternal and newborn deaths globally. The aim of this study is to determine the utilization of postnatal health services and identify the factors which affect this utilization among mothers of under-fives in Lagos. Methods: This was a cross-sectional study among women of child bearing age in Lagos using structured, interviewer-administered questionnaire. Six hundred women selected by multi stage sampling method were interviewed and data analyzed with EPI-info Version 3.5.1. Results: Two thirds (66.2% of the respondents utilized postnatal health services. Factors which significantly influenced postnatal health services utilization were: number of children (p=0.031, maternal education (p=0.001, religion (Fisher′s exact p= 0.004, number of antenatal care visits (p<0.001 and skilled attendance at birth (p<0.001. Maternal occupation and time taken to the health facility were not significant determinants of utilization. Conclusion: Utilization of postnatal care services was high but not optimal. Interventions to increase family planning use and improve maternal educational status should be undertaken as well as increasing use of focused antenatal care and skilled delivery services.

  10. Births and deaths including fetal deaths

    Data.gov (United States)

    U.S. Department of Health & Human Services — Access to a variety of United States birth and death files including fetal deaths: Birth Files, 1968-2009; 1995-2005; Fetal death file, 1982-2005; Mortality files,...

  11. [Human lung connective tissue in postnatal ontogeny].

    Science.gov (United States)

    Kasimtsev, A A; Nikolaev, V G

    1993-01-01

    Changes of the connective tissue structures, appearing during all postnatal ontogenesis stages were studied in 147 human lung specimens of different age groups (from newborns up to 82-year-olds). Qualitative and quantitative composition of connective tissue structures changes with the age which leads to the lateral aggregation of the fibers and growth of the general mass of the connective tissue. Heterochronia of the age variability manifestations in different regions of the lung framework was demonstrated. The original age transformations of connective tissue structures are characteristic for the basal lung regions. With the exception of perivasal connective tissue, similar changes in the region of the lung apexes appear 3-5 years later. This gives an opportunity to distinguish three anatomic zones in the lungs in an apico-basal direction, characterising the local nature of the age changes manifestations.

  12. A comparative study of embryonic development of some bird species with different patterns of postnatal growth.

    Science.gov (United States)

    Blom, Jonas; Lilja, Clas

    2005-01-01

    Some studies show that birds with high postnatal growth rates (e.g. altricial species) are characterized by a rapid early development of "supply" organs, such as digestive organs. Birds with low postnatal growth rates (e.g. precocial species) exhibit a slower early development of these organs and a more rapid early development of other "demand" organs, such as brain, muscles, skeleton and feathers. To test whether these differences can be traced back to early embryonic development and whether they can be associated with changes in developmental timing, i.e. heterochrony, we compared embryos of the precocial quail and the altricial fieldfare, two bird species with low and high postnatal growth rates, respectively. We used classical staging techniques that use developmental landmarks to categorize embryonic maturity as well as morphological measurements. These techniques were combined with immune detection of muscle specific proteins in the somites. Our data showed that the anlagen of the head, brain and eyes develop earlier in the quail than in the fieldfare in contrast to the gut which develops earlier in the fieldfare than in the quail. Our data also showed that the quail and the fieldfare displayed different rates of myotome formation in the somites which contribute to muscle formation in the limbs and thorax. We believe these observations are connected with important differences in neonatal characteristics, such as the size of the brain, eyes, organs for locomotion and digestion. This leads us to the conclusion that selection for late ontogenetic characteristics can alter early embryonic development and that growth rate is of fundamental importance for the patterning of avian embryonic development. It also appears that this comparative system offers excellent opportunities to test hypotheses about heterochrony.

  13. Cell death in genome evolution.

    Science.gov (United States)

    Teng, Xinchen; Hardwick, J Marie

    2015-03-01

    Inappropriate survival of abnormal cells underlies tumorigenesis. Most discoveries about programmed cell death have come from studying model organisms. Revisiting the experimental contexts that inspired these discoveries helps explain confounding biases that inevitably accompany such discoveries. Amending early biases has added a newcomer to the collection of cell death models. Analysis of gene-dependent death in yeast revealed the surprising influence of single gene mutations on subsequent eukaryotic genome evolution. Similar events may influence the selection for mutations during early tumorigenesis. The possibility that any early random mutation might drive the selection for a cancer driver mutation is conceivable but difficult to demonstrate. This was tested in yeast, revealing that mutation of almost any gene appears to specify the selection for a new second mutation. Some human tumors contain pairs of mutant genes homologous to co-occurring mutant genes in yeast. Here we consider how yeast again provide novel insights into tumorigenesis.

  14. Developmental changes in the expression of ATP7A during a critical period in postnatal neurodevelopment.

    Science.gov (United States)

    Niciu, M J; Ma, X-M; El Meskini, R; Ronnett, G V; Mains, R E; Eipper, B A

    2006-01-01

    ATP7A is a P-type ATPase that transports copper from cytosol into the secretory pathway for loading onto cuproproteins or efflux. Mutations in Atp7a cause Menkes disease, a copper-deficiency disorder fatal in the postnatal period due to severe neurodegeneration. Early postnatal copper injections are known to diminish degenerative changes in some human patients and mice bearing mutations in Atp7a. In situ hybridization studies previously demonstrated that ATP7A transcripts are expressed widely in the brain. ATP7A-specific antibody was used to study the neurodevelopmental expression and localization of ATP7A protein in the mouse brain. Based on immunoblot analyses, ATP7A expression is most abundant in the early postnatal period, reaching peak levels at P4 in neocortex and cerebellum. In the developing and adult brain, ATP7A levels are greatest in the choroid plexus/ependymal cells of the lateral and third ventricles. ATP7A expression decreases in most neuronal subpopulations from birth to adulthood. In contrast, ATP7A expression increases in CA2 hippocampal pyramidal and cerebellar Purkinje neurons. ATP7A is expressed in a subset of astrocytes, microglia, oligodendrocytes, tanycytes and endothelial cells. ATP7A is largely localized to the trans-Golgi network, adopting the cell-specific and developmentally-regulated morphology of this organelle. The presence of ATP7A in the axons of postnatal, but not adult, optic nerve suggests stage-specific roles for this enzyme. In sum, the precisely-regulated neurodevelopmental expression of ATP7A correlates well with the limited therapeutic window for effective treatment of Menkes disease.

  15. Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations.

    Science.gov (United States)

    Boullu-Ciocca, S; Tassistro, V; Dutour, A; Grino, M

    2015-12-01

    Immediate postnatal overfeeding in rats, obtained by reducing the litter size, results in early-onset obesity. Such experimental paradigm programs overweight, insulin resistance, dyslipidemia, increased adipose glucocorticoid metabolism [up-regulation of glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPARγ agonist, treatment on the above-mentioned overfeeding-induced alterations. Nine-month-old rats normofed or overfed during the immediate postnatal period were given pioglitazone (3 mg/kg/day) for 6 weeks. Pioglitazone stimulated weight gain and induced a redistribution of adipose tissue toward epididymal location with enhanced plasma adiponectin. Treatment normalized postnatal overfeeding-induced metabolic alterations (increased fasting insulinemia and free fatty acids) and mesenteric overexpression of GR, 11β-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. Mesenteric GR mRNA levels correlated positively with mesenteric proinflammatory cytokines mRNA concentrations. In vitro incubation of MAT obtained from overfed rats demonstrated that pioglitazone induced a down-regulation of GR gene expression and normalized glucocorticoid-induced stimulation of 11β-HSD1 and plasminogen-activator inhibitor type 1 mRNAs. Our data show for the first time that the metabolic, endocrine, and inflammatory alterations induced by early-onset postnatal obesity can be reversed by pioglitazone at the adulthood. They demonstrate that pioglitazone, in addition to its well-established effect on adipose tissue redistribution and adiponectin secretion, reverses programing-induced adipose GR, 11β-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism.

  16. 极低出生体重儿早期死亡的围生期危险因素分析%Analysis of perinatal risk factors for early neonatal death among very low birth weight infants

    Institute of Scientific and Technical Information of China (English)

    李月凤; 周平; 吴香兰; 陈睿; 卢光进

    2012-01-01

    [Objective] To investigate the relationship between perinatal risk factors and early neonatal death among very low birth weight (VLBW) infants. [Methods] A retrospective cohort of 143 VLBW infants admitted to NICU was studied. The dependent variable was the outcome, either survival or death at 7 days of life. The independent variables were assigned into three levels: distal, intermediate and proximal according to hierarchical model. All variables were subjected to univariate analysis and multivariate logistic regression. [Results] Early neonatal mortality was 13. 29% (19/143) in VLBW infants. After the adjustment of variables through multivariate Logistic regression it showed that infants born to mother with cord prolapse had higher risk exposure for early death than those of mother without cord prolapse in the distal level (AOR:8. 69;95%C/:1. 128~67. 002). At the intermediate level,infants with gestational age (GAX28 weeks and 5-min Apgar scores<7 had higher odds of early death than those of GA≥28 weeks and 5-min Apgar scores≥7 (AOR: 11. 47, 13. 55;95%CJ:2. 066~63. 712,3. 156 - 58. 221 respectively). At the proximal level, infants with intracranial hemorrhage (ICH) had higher risk of early death than those without ICH (AORS4. 56,95%C7:1. 088 - 19. 170). [Conclusions] The early neonatal mortality among VLBW infants is still high and continues to be a significant public health problem. Asphyxia at birth is the highest risk factor of early neonatal death. Reducing birth asphyxia through enhancing obstetric quality and strengthening cooperation between obstetric and neonatology department is still the key to decrease early neonatal death of VLBW infants.%[目的]探讨极低出生体重(very low birth weight,VLBW)儿早期死亡的围生期高危因素. [方法]选取在本院新生儿科住院的143例VLBW儿为研究对象.生后7d的结果:生存或死亡作为应变量,根据分层分析模型将围产期高危因素(自变量)分为远端、中间和近端3

  17. Relative importance of prenatal and postnatal androgen action in determining growth of the penis and anogenital distance in the rat before, during and after puberty.

    Science.gov (United States)

    van den Driesche, S; Scott, H M; MacLeod, D J; Fisken, M; Walker, M; Sharpe, R M

    2011-12-01

    Experimental animal studies show that measurement of anogenital distance (AGD) and/or penis length may provide lifelong 'read-outs' of foetal androgen exposure during the masculinization programming window (MPW). However, variation in postnatal androgen exposure may complicate interpretation of such measurements. This is important to clarify if such measurements are to be applied to humans. The present aim was to evaluate effects of prenatal and/or postnatal manipulation of androgen production/action on growth of AGD and the penis in rats. Pregnant rats were treated daily before (e13.5-e21.5) and after birth (postnatal days 1-15) with either vehicle, 500 mg/kg di(n-butyl) phthalate (DBP) or 100 mg/kg flutamide (postnatal only) in prenatal + postnatal treatment combinations (N = 6 treatment combinations); DBP impairs androgen production whereas flutamide impairs androgen action. Male offspring were killed on postnatal day 8 (prepuberty), 25 (early puberty) or 90 (adulthood) when AGD was measured, the penis dissected out and its weight and length measured; plasma testosterone and ventral prostate weight were measured at day 90 to assess endogenous androgen exposure. In controls, penis length, girth and AGD increased 2.2-, 5.3-and 5.9-fold respectively from day 8 to day 90. Significant inhibition of penis growth and final length and girth was induced by treatments that inhibited postnatal androgen action. Conversely, growth and ultimate (adult) AGD was inhibited by prenatal inhibition of androgen production whereas postnatal androgen inhibition had negligible effect. Nevertheless, AGD and penis length were highly correlated at every age (R(2) > 0.33; p penis size reflects both prenatal + postnatal androgen exposure. At the group treatment level, prepubertal measurement of either AGD or penis size accurately predicts their size in adulthood.

  18. Donor Preconditioning After the Onset of Brain Death With Dopamine Derivate n-Octanoyl Dopamine Improves Early Posttransplant Graft Function in the Rat.

    Science.gov (United States)

    Li, S; Korkmaz-Icöz, S; Radovits, T; Ruppert, M; Spindler, R; Loganathan, S; Hegedűs, P; Brlecic, P; Theisinger, B; Theisinger, S; Höger, S; Brune, M; Lasitschka, F; Karck, M; Yard, B; Szabó, G

    2017-07-01

    Heart transplantation is the therapy of choice for end-stage heart failure. However, hemodynamic instability, which has been demonstrated in brain-dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n-octanoyl-dopamine (NOD) improves donor cardiac and graft function after transplantation. Donor rats were given a continuous intravenous infusion of either NOD (0.882 mg/kg/h, BDD+NOD, n = 6) or a physiological saline vehicle (BDD, n = 9) for 5 h after the induction of brain death by inflation of a subdural balloon catheter. Controls were sham-operated (n = 9). In BDD, decreased left-ventricular contractility (ejection fraction; maximum rate of rise of left-ventricular pressure; preload recruitable stroke work), relaxation (maximum rate of fall of left-ventricular pressure; Tau), and increased end-diastolic stiffness were significantly improved after the NOD treatment. Following the transplantation, the NOD-treatment of BDD improved impaired systolic function and ventricular relaxation. Additionally, after transplantation increased interleukin-6, tumor necrosis factor TNF-α, NF-kappaB-p65, and nuclear factor (NF)-kappaB-p105 gene expression, and increased caspase-3, TNF-α and NF-kappaB protein expression could be significantly downregulated by the NOD treatment compared to BDD. BDD postconditioning with NOD through downregulation of the pro-apoptotic factor caspase-3, pro-inflammatory cytokines, and NF-kappaB may protect the heart against the myocardial injuries associated with brain death and ischemia/reperfusion. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Invariant death

    Science.gov (United States)

    Frank, Steven A.

    2016-01-01

    In nematodes, environmental or physiological perturbations alter death’s scaling of time. In human cancer, genetic perturbations alter death’s curvature of time. Those changes in scale and curvature follow the constraining contours of death’s invariant geometry. I show that the constraints arise from a fundamental extension to the theories of randomness, invariance and scale. A generalized Gompertz law follows. The constraints imposed by the invariant Gompertz geometry explain the tendency of perturbations to stretch or bend death’s scaling of time. Variability in death rate arises from a combination of constraining universal laws and particular biological processes.

  20. Evaluation of changes in postnatal care using the "Parents' Postnatal Sense of Security" instrument and an assessment of the instrument's reliability and validity

    Directory of Open Access Journals (Sweden)

    Kvist Linda J

    2009-08-01

    Full Text Available Abstract Background A sense of security is important for experiences of parenthood in the early postpartum period. The objectives of this study were to evaluate two models of postnatal care using a questionnaire incorporating the Parents' Postpartum Sense of Security (PPSS instrument and to test the validity of the PPSS instrument. Methods Postal surveys were sent to 234 mothers who had experienced two different forms of postnatal care (study group and control group and returned by 86.8%. These two groups of mothers were compared for total scores on the PPSS instrument. Demographic variables and mothers' opinions about care interventions were also compared and these variables were tested for correlations with the total PPSS score. A regression analysis was carried out to assess areas of midwifery care which might affect a sense of security. The internal consistency and concurrent validity of the instrument were tested for the total population. Results there were no significant differences between the groups for scores on the PPSS instrument. A total of three variables predicted 26% of the variability on the PPSS scores for the study group and five variables predicted 37% of the variability in the control group. One variable was common to both: "The midwives on the postnatal ward paid attention to the mother as an individual". There were significant correlations between the total PPSS scores and scores for postpartum talks and visits to the breastfeeding clinic. There was also a significant correlation between the single question: "I felt secure during the first postpartum week" and the total PPSS score. Tests for internal consistency and concurrent validity were satisfactory. Conclusion The proposed new model of care neither improved nor impaired mothers' feelings of security the week following birth. Being seen as an individual by the midwife who provides postnatal care may be an important variable for mothers' sense of postnatal security. It

  1. Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration.

    Science.gov (United States)

    Alpdogan, Onder; Hubbard, Vanessa M; Smith, Odette M; Patel, Neel; Lu, Sydney; Goldberg, Gabrielle L; Gray, Daniel H; Feinman, Jared; Kochman, Adam A; Eng, Jeffrey M; Suh, David; Muriglan, Stephanie J; Boyd, Richard L; van den Brink, Marcel R M

    2006-03-15

    Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family that mediates epithelial cell proliferation and differentiation in a variety of tissues, including the thymus. We studied the role of KGF in T-cell development with KGF-/- mice and demonstrated that thymic cellularity and the distribution of thymocyte subsets among KGF-/-, wildtype (WT), and KGF+/- mice were similar. However, KGF-/- mice are more vulnerable to sublethal irradiation (450 cGy), and a significant decrease was found in thymic cellularity after irradiation. Defective thymopoiesis and peripheral T-cell reconstitution were found in KGF-/- recipients of syngeneic or allogeneic bone marrow transplant, but using KGF-/- mice as a donor did not affect T-cell development after transplantation. Despite causing an early developmental block in the thymus, administration of KGF to young and old mice enhanced thymopoiesis. Exogenous KGF also accelerated thymic recovery after irradiation, cyclophosphamide, and dexamethasone treatment. Finally, we found that administering KGF before bone marrow transplantation (BMT) resulted in enhanced thymopoiesis and peripheral T-cell numbers in middle-aged recipients of an allogeneic BM transplant. We conclude that KGF plays a critical role in postnatal thymic regeneration and may be useful in treating immune deficiency conditions.

  2. Rett syndrome: disruption of epigenetic control of postnatal neurological functions.

    Science.gov (United States)

    Pohodich, Amy E; Zoghbi, Huda Y

    2015-10-15

    Loss-of-function mutations in the X-linked gene Methyl-CpG-binding protein 2 (MECP2) cause a devastating pediatric neurological disorder called Rett syndrome. In males, these mutations typically result in severe neonatal encephalopathy and early lethality. On the other hand, owing to expression of the normal allele in ∼50% of cells, females do not suffer encephalopathy but instead develop Rett syndrome. Typically females with Rett syndrome exhibit a delayed onset of neurologic dysfunction that manifests around the child's first birthday and progresses over the next few years. Features of this disorder include loss of acquired language and motor skills, intellectual impairment and hand stereotypies. The developmental regression observed in patients with Rett syndrome arises from altered neuronal function and is not the result of neurodegeneration. Maintenance of an appropriate level of MeCP2 appears integral to the function of healthy neurons as patients with increased levels of MeCP2, owing to duplication of the Xq28 region encompassing the MECP2 locus, also present with intellectual disability and progressive neurologic symptoms. Despite major efforts over the past two decades to elucidate the molecular functions of MeCP2, the mechanisms underlying the delayed appearance of symptoms remain unclear. In this review, we will highlight recent findings that have expanded our knowledge of MeCP2's functions, and we will discuss how epigenetic regulation, chromatin organization and circuit dynamics may contribute to the postnatal onset of Rett syndrome.

  3. Sudden Death of Entanglement

    CERN Document Server

    Yu, Ting

    2009-01-01

    A new development in the dynamical behavior of elementary quantum systems is the surprising discovery that correlation between two quantum units of information called qubits can be degraded by environmental noise in a way not seen previously in studies of dissipation. This new route for dissipation attacks quantum entanglement, the essential resource for quantum information as well as the central feature in the Einstein-Podolsky-Rosen so-called paradox and in discussions of the fate of Schr\\"{o}inger's cat. The effect has been labeled ESD, which stands for early-stage disentanglement or, more frequently, entanglement sudden death. We review recent progress in studies focused on this phenomenon.

  4. A review of longitudinal studies on antenatal and postnatal depression.

    Science.gov (United States)

    Underwood, Lisa; Waldie, Karen; D'Souza, Stephanie; Peterson, Elizabeth R; Morton, Susan

    2016-10-01

    Antenatal depression is a known risk factor for postnatal depression; both are common disorders associated with negative impacts on child development. Few studies have followed up women from pregnancy and through the postnatal period to explore how rates of depression change. This review evaluates recent evidence on depression during pregnancy and after childbirth. A search of Embase, PsychINFO, MEDLINE and Cochrane Reviews was carried out to identify longitudinal studies on antenatal and postnatal depression. Studies that measured depression during pregnancy and up to 1 year after childbirth were evaluated against a set of criteria (e.g. less than 50 % attrition). Of the initial 523 studies identified, 16 studies met the final inclusion criteria with a total of 35,419 women. The average rate of antenatal depression across these studies was 17 and 13 % postnatal depression. The longitudinal nature of the studies revealed that on average 39 % of those who experienced antenatal depression went on to have postnatal depression. Similarly, on average, 47 % of those with postnatal depression had also experienced antenatal depression. On average, almost 7 % of women reported significant depressive symptoms in pregnancy that persisted after childbirth. The review provided evidence that rates of depression tend to be higher during pregnancy than in the first year following childbirth. Furthermore, the longitudinal data show that there is much movement between the groups categorised as depressed or not depressed. There is evidence that postnatal depression is often a continuation of existing antenatal depression.

  5. Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides.

    Science.gov (United States)

    Girard, Beatrice; Peterson, Abbey; Malley, Susan; Vizzard, Margaret A

    2016-11-01

    The mechanisms underlying the postnatal maturation of micturition from a somatovesical to a vesicovesical reflex are not known but may involve neuropeptides in the lower urinary tract. A transgenic mouse model with chronic urothelial overexpression (OE) of NGF exhibited increased voiding frequency, increased number of non-voiding contractions, altered morphology and hyperinnervation of the urinary bladder by peptidergic (e.g., Sub P and CGRP) nerve fibers in the adult. In early postnatal and adult NGF-OE mice we have now examined: (1) micturition onset using filter paper void assays and open-outlet, continuous fill, conscious cystometry; (2) innervation and neurochemical coding of the suburothelial plexus of the urinary bladder using immunohistochemistry and semi-quantitative image analyses; (3) neuropeptide protein and transcript expression in urinary bladder of postnatal and adult NGF-OE mice using Q-PCR and ELISAs and (4) the effects of intravesical instillation of a neurokinin (NK)-1 receptor antagonist on bladder function in postnatal and adult NGF-OE mice using conscious cystometry. Postnatal NGF-OE mice exhibit age-dependent (R(2)=0.996-0.998; p≤0.01) increases in Sub and CGRP expression in the urothelium and significantly (p≤0.01) increased peptidergic hyperinnervation of the suburothelial nerve plexus. By as early as P7, NGF-OE mice exhibit a vesicovesical reflex in response to intravesical instillation of saline whereas littermate WT mice require perigenital stimulation to elicit a micturition reflex until P13 when vesicovesical reflexes are first observed. Intravesical instillation of a NK-1 receptor antagonist, netupitant (0.1μg/ml), significantly (p≤0.01) increased void volume and the interval between micturition events with no effects on bladder pressure (baseline, threshold, peak) in postnatal NGF-OE mice; effects on WT mice were few. NGF-induced pleiotropic effects on neuropeptide (e.g., Sub P) expression in the urinary bladder contribute to

  6. Casting-type calcifications on the mammogram suggest a higher probability of early relapse and death among high-risk breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Palka, Istvan [Dept. of Pathology, Univ. of Szeged, Szeged (Hungary); Ormandi, K atalin [Dept. of Radiology, Univ. of Szeged, Szeged (Hungary); Gaal, Szilvia; Kahan, Zsuzsanna [Dept. of Oncotherapy, Univ. of Szeged, Szeged (Hungary); Boda, Krisztina [Dept. of Medical Informatics, Univ. of Szeged, Szeged (Hungary)

    2007-11-15

    A retrospective analysis of the relation between the presence of casting-type calcifications on the mammogram and the prognosis of breast cancer was performed. The mammographic tumor features and other characteristics (invasive tumor size, histological tumor type, grade, nodal, hormone receptor and HER2 status, presence of lymphovascular invasion) of 55 high-risk breast cancers were studied. After a median follow-up time of 29.1 months, the median relapse-free survival and overall survival times among breast cancer patients with tumors associated with casting calcifications were 26.6 and 29.6 months, respectively. The corresponding parameters among patients with tumors not accompanied by casting calcifications were 54.4 and >58.5 months, respectively. Significant associations were found between the presence of casting calcifications and the risks of relapse (HR = 3.048, 95% CI: 1.116-8.323, p = 0.030) or death (HR = 3.504, 95% CI: 1.074-11.427, p 0.038). Positive associations were found between casting calcifications and ER/PR negativity (p = 0.015 and p = 0.003, respectively) and HER2 overexpression (p = 0.019). Our findings support the theory that breast tumors associated with casting-type calcifications at mammography comprise a disease entity which exhibits significantly more aggressive behavior and a poorer outcome than do cancers with other mammographic tumor features.

  7. Developmental profiling of postnatal dentate gyrus progenitors provides evidence for dynamic cell-autonomous regulation

    Science.gov (United States)

    Gilley, Jennifer A.; Yang, Cui-Ping; Kernie, Steven G.

    2009-01-01

    The dentate gyrus of the hippocampus is one of the most prominent regions in the postnatal mammalian brain where neurogenesis continues throughout life. There is tremendous speculation regarding the potential implications of adult hippocampal neurogenesis, though it remains unclear to what extent this ability becomes attenuated during normal aging, and what genetic changes in the progenitor population ensue over time. Using defined elements of the nestin promoter, we developed a transgenic mouse that reliably labels neural stem and early progenitors with green fluorescent protein (GFP). Using a combination of immunohistochemical and flow cytometry techniques, we characterized the progenitor cells within the dentate gyrus and created a developmental profile from postnatal day 7 (P7) until 6 months of age. In addition, we demonstrate that the proliferative potential of these progenitors is controlled at least in part by cell-autonomous cues. Finally, in order to identify what may underlie these differences, we performed stem cell-specific microarrays on GFP-expressing sorted cells from isolated P7 and postnatal day 28 (P28) dentate gyrus. We identified several differentially expressed genes that may underlie the functional differences that we observe in neurosphere assays from sorted cells and differentiation assays at these different ages. These data suggest that neural progenitors from the dentate gyrus are differentially regulated by cell-autonomous factors that change over time. PMID:20014381

  8. Personality, depressive symptoms during pregnancy and their influence on postnatal depression in Spanish pregnant Spanish women

    Directory of Open Access Journals (Sweden)

    Dolores Marín-Morales

    2014-10-01

    Full Text Available The aim of this study was to analyse the influence of personality factors and antenatal depressive symptomatology in postnatal depression. A prospective ex post facto design was carried out. The sample consisted of 116 women, recruited in their first trimester of pregnancy and followed up until four months postpartum. The measurement instruments used were the Edinburg Postnatal Depression Scale (EPDS to assess postpartum depression, the NEO-Five Factor Inventory (NEO-FFI to analyse personality traits and the depression subscale of the Symptoms Check List 90 (SCL-90-R to assess depressive symptomatology in the first half of pregnancy. Socio-demographic variables (age, parity, educational level, employment status, and planned pregnancy and clinical variables (neonatal Apgar score and mode of delivery were also taken into account. A positive correlation was found between postpartum depression and depressive symptomatology in the first trimester; however after the regression analysis neuroticism was the only factor that predicted postpartum depressive symptoms, explaining 24.8% of the variance. Neuroticism significantly influences psychological health during life events such as motherhood. Due to its stable condition, personality could be assessed from the beginning of pregnancy, contributing to the care of pregnant women with high scores in neuroticism, to prevent, detect and treat early postnatal depression.

  9. Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications.

    Science.gov (United States)

    Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michele; Alfano, Christian

    2016-01-27

    During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features.

  10. Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs.

    Science.gov (United States)

    Muñoz-González, Sara; Perez-Simó, Marta; Muñoz, Marta; Bohorquez, José Alejandro; Rosell, Rosa; Summerfield, Artur; Domingo, Mariano; Ruggli, Nicolas; Ganges, Llilianne

    2015-07-09

    Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.

  11. Early Involvement of Death-Associated Protein Kinase Promoter Hypermethylation in the Carcinogenesis of Barrett's Esophageal Adenocarcinoma and Its Association with Clinical Progression

    Directory of Open Access Journals (Sweden)

    Doerthe Kuester

    2007-03-01

    Full Text Available Esophageal Barrett's adenocarcinoma (BA develops through a multistage process, which is associated with the transcriptional silencing of tumor-suppressor genes by promoter CpG island hypermethylation. In this study, we explored the promoter hypermethylation and protein expression of proapoptotic deathassociated protein kinase (DAPK during the multistep Barrett's carcinogenesis cascade. Early BA and paired samples of premalignant lesions of 61 patients were analyzed by methylation-specific polymerase chain reaction and immunohistochemistry. For the association of clinicopathological markers and protein expression, an immunohistochemical tissue microarray analysis of 66 additional BAs of advanced tumor stages was performed. Hypermethylation of DAPK promoter was detected in 20% of normal mucosa, 50% of Barrett's metaplasia, 53% of dysplasia, and 60% of adenocarcinomas, and resulted in a marked decrease in DAPK protein expression (P < .01. The loss of DAPK protein was significantly associated with advanced depth of tumor invasion and advanced tumor stages (P < .001. Moreover, the severity of reflux esophagitis correlated significantly with the hypermethylation rate of the DAPK promoter (P < .003. Thus, we consider DAPK inactivation by promoter hypermethylation as an early event in Barrett's carcinogenesis and suggest that a decreased protein expression of DAPK likely plays a role in the development and progression of BA.

  12. Risk factors analysis of early death in patients with acute promyelocytic leukemia%急性早幼粒细胞白血病早期死亡危险因素分析

    Institute of Scientific and Technical Information of China (English)

    刘玉玉; 焦玉燕; 李斑斑; 滕清良

    2015-01-01

    Objective To investigate risk factors for early death in acute promyelocytic leukemia patients. Methods The clinical characteristics including leucocyte counts at onset,platelet count and fibrinogen content of 42 patients with APL were evaluated. The factors of immunophenotype, genes fusion as well as gene mutations were compared. Results Among the 42 patients with APL,6 cases were observed early death with the early mortality rate of 14.3%. To be spe-cific,4 deaths were attributable to cerebral hemorrhage,whereas the other two were linked with disseminated intravas-cular coagulation complicated with multiple organ failure and myocardial infarction respectively. The leukocyte counts of dead patients were significantly more than complete remission group. At the same time, the blood platelet counts and the fibrinogen counts were all less than those of complete remission patients. 5 patients were confirmed as CD2+,5 cases were CD34 and/or HLA-DR+,and FLT3-ITD gene mutation was found in 4 subjects. Difference between the two groups was statistically significant(P<0.05). Conclusion Acute promyelocytic leukemia patients with leukocytosis,low platelet count, hypofibrinogenemia, CD2+, CD34 and/or HLA-DR+as well as FLT3-ITD gene mutation are at an increased risk of early death in the risk factor analysis.%目的:探讨急性早幼粒细胞白血病患者早期死亡危险因素。方法分析我院42例APL患者发病时的白细胞计数、血小板计数、纤维蛋白原含量等特点,并比较APL患者的免疫分型、融合基因及基因突变等因素。结果42例APL患者中,6例出现早期死亡,早期死亡率14.3%。其中4例死于脑出血,1例死于弥漫性血管内凝血并多脏器功能衰竭,1例死于心肌梗死。死亡组患者白细胞计数显著高于完全缓解组,血小板及纤维蛋白原计数均较完全缓解组患者低,5例为CD2+,5例为CD34和(或)HLA-DR+,4例存在FT3-ITD基因突变,与完全缓解组比

  13. Postnatal development of the human sternum.

    Science.gov (United States)

    O'Neal, M L; Dwornik, J J; Ganey, T M; Ogden, J A

    1998-01-01

    Postnatal development and maturation of the human sternum are highly variable. Endochondral ossification centers (sternebrae) form within each cartilaginous segment of the sternum, with each center enveloped by a spherical growth plate. Within a cartilaginous center there may be either one or two ossification centers, those with two centers retaining and reflecting features of their bilateral embryonic origin. Malaligned bifid centers are clearly associated with rib articulation asymmetry as well. Expansion of individual ossification centers progresses within the peripheral cartilaginous domains of the sternum. With respect to the rostrocaudal axis, sternebrae form between the costosternal articulations. Consistent with the biology of endochondral transition, cartilage canals are evident throughout unossified regions of the hyaline matrix. Expanding ossification of adjacent sternebrae results in depletion of the common area of cartilage between the two sternebrae, and eventually in physiologic epiphysiodesis. Fusion of the mesosternebrae reciprocates the initial pattern of sternebral ossification site appearance, proceeding in a caudal-to-cranial direction. Union of adjacent sternebrae, initiated through a central osseous bridge, progresses through anterior, lateral, cephalocaudal, and posterior domains to achieve synostosis. Accessory and bifid centers of ossification within the same intercostal space coalesce prior to adjoining adjacent sternebrae. Manubriosternal fusion is rare due to the presence of a fibrocartilaginous joint restricting ossification. The xiphoid process remains connected to the most caudal mesosternum via a common zone of hyaline cartilage that ossifies by middle to late adulthood. A single pattern of development does not appear fundamental to successful growth of the sternum, as morphological variants were common.

  14. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects

    Science.gov (United States)

    Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep

    2016-01-01

    Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR. PMID:27441006

  15. Early to Late Pleistocene history of debris-flow fan evolution in western Death Valley (California) using cosmogenic 10Be and 26Al

    Science.gov (United States)

    Dühnforth, Miriam; Densmore, Alexander L.; Ivy-Ochs, Susan; Allen, Philip; Kubik, Peter W.

    2017-03-01

    Debris-flow fans with depositional records over several 105 years may be useful archives for the understanding of fan construction by debris flows and post-depositional surface modification over long timescales. Reading these archives, however, requires that we establish the temporal and spatial pattern of debris-flow activity over time. We used a combination of geomorphic mapping of fan surface characteristics, digital topographic analysis, and cosmogenic radionuclide dating using 10Be and 26Al to study the evolution of the Warm Springs fan on the west side of southern Death Valley, California. The 10Be concentrations yield dates that vary from 989 ± 43 to 595 ± 17 ka on the proximal fan and between 369 ± 13 and 125 ± 5 ka on distal fan surfaces. The interpretation of these results as true depositional ages though is complicated by high inheritance with a minimum of 65 ka measured at the catchment outlet and of at least 125 ka at the distal fan. Results from the 26Al measurements suggest that most sample locations on the fan surfaces underwent simple exposure and were not affected by complex histories of burial and re-exposure. This implies that Warm Springs fan is a relatively stable landform that underwent several 105 years of fan aggradation before fan head incision caused abandonment of the proximal and central fan surfaces and deposition continued on a younger unit at the distal fan. We show that the primary depositional debris-flow morphology is eliminated over a time scale of less than 105 years, which prevents the delineation of individual debris flows as well as the precise reconstruction of lateral shifts in deposition as we find it on younger debris-flow fans. Secondary post-depositional processes control subsequent evolution of surface morphology with the dissection of planar surfaces while smoothing of convex-up interfluves between incised channels continues through time.

  16. Variation in elemental intensities among teeth and between pre- and postnatal regions of enamel.

    Science.gov (United States)

    Dolphin, Alexis E; Goodman, Alan H; Amarasiriwardena, Dulasiri D

    2005-12-01

    Microspatial analyses of the trace element composition of dental enamel are made possible using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Fine spatial resolution, multielement capabilities, and minimal sample destruction make this technique particularly well-suited for documenting the distribution of elements in sequentially calcifying layers of enamel. Because deciduous enamel forms from week 13 in utero up to 9 months postnatally (thereafter essentially becoming inert), the application of LA-ICP-MS allows for the retrospective measurement of prenatal and early postnatal trace-element uptake during a critical period of child development. In this study, we compared intra- and intertooth intensities of 25Mg, 57Fe, 66Zn, 68Zn, 88Sr, 138Ba, and 208Pb via LA-ICP-MS of 38 exfoliated deciduous incisors and canines donated by 36 participants in the Solís Valley Mexico Nutrition Collaborative Research Support Program (NCRSP). Pre- and postnatal comparisons within teeth showed significant increases (P < 0.001) and greater variation in the abundance of all isotopes in postnatal enamel, with the exception of a decrease in 25Mg (P < 0.001) and constant values for 88Sr (P = 0.681). Conversely, comparisons by tooth type and mouth quadrant revealed few significant differences between teeth of the same individual. We argue that more variation in the trace element composition of teeth occurs across developmental areas within a tooth than among different teeth of the same person. This study further demonstrates that sequentially calcifying areas of enamel have different chemical concentrations. The results support the use of microspatial analyses of enamel for understanding changes in nutrition, pollution, and residence.

  17. Prenatal and postnatal residential usage of insecticides in a multicenter birth cohort in Spain.

    Science.gov (United States)

    Llop, Sabrina; Casas, Lidia; Santa Marina, Loreto; Estarlich, Marisa; Fernández-Somoano, Ana; Esplugues, Ana; Jimenez, Ana; Zock, Jan-Paul; Tardón, Adonina; Marco, Alfredo; Ballester, Ferran

    2013-02-15

    This study aimed to describe the residential use of insecticides in a birth cohort in Spain. Study subjects were 2,456 women enrolled into the INMA (Environment and Childhood) birth cohort followed prospectively during pregnancy and in the early postnatal period. The women were recruited at the beginning of their pregnancy between 2003 and 2008 in four regions of Spain. Socio-demographic, environmental and lifestyle information was obtained at two interviews during pregnancy, one at the first (mean:13.8±2.6 weeks of gestation) and the other at the third trimester (mean: 33.3±2.3 weeks of gestation). Information about prenatal use of indoor and outdoor insecticides (type, timing, place of application, place of storage) was obtained from the second interview. In a 3rd interview (mean: 16.2±6.9 months of age of children), information about postnatal indoor and outdoor insecticide use was obtained. Regression models examined the association between demographic and lifestyle factors and pesticide use to determine which characteristics predicted use prenatally and postnatally. Fifty-four percent of women reported using indoor insecticides during pregnancy, 45% in their bedroom and 47% elsewhere in the house. Plug-in devices were the most frequent application methods used in the pregnant woman's bedroom and insecticide sprays elsewhere in the house. The maternal factors related to prenatal use of indoor insecticides were parity, country of birth, educational level, region of residence, having a garden or yard with plants, and living near an agricultural area. These products continued to be used postnatally, although 20% of the women stopped using them. Foetuses and children are especially vulnerable to pesticide exposure; thus knowing how pesticides are used during pregnancy and infancy may be a starting point for the study of their potential effects on health as well as useful for designing preventive actions.

  18. Postnatal persistent infection with classical Swine Fever virus and its immunological implications.

    Directory of Open Access Journals (Sweden)

    Sara Muñoz-González

    Full Text Available It is well established that trans-placental transmission of classical swine fever virus (CSFV during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs

  19. Postnatal persistent infection with classical Swine Fever virus and its immunological implications.

    Science.gov (United States)

    Muñoz-González, Sara; Ruggli, Nicolas; Rosell, Rosa; Pérez, Lester Josué; Frías-Leuporeau, Maria Teresa; Fraile, Lorenzo; Montoya, Maria; Cordoba, Lorena; Domingo, Mariano; Ehrensperger, Felix; Summerfield, Artur; Ganges, Llilianne

    2015-01-01

    It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed

  20. Substratum preferences of motor and sensory neurons in postnatal and adult rats.

    Science.gov (United States)

    Gonzalez-Perez, Francisco; Alé, Albert; Santos, Daniel; Barwig, Christina; Freier, Thomas; Navarro, Xavier; Udina, Esther

    2016-02-01

    After peripheral nerve injuries, damaged axons can regenerate but functional recovery is limited by the specific reinnervation of targets. In this study we evaluated if motor and sensory neurites have a substrate preference for laminin and fibronectin in postnatal and adult stages. In postnatal dorsal root ganglia (DRG) explants, sensory neurons extended longer neurites on collagen matrices enriched with laminin (~50%) or fibronectin (~35%), whereas motoneurons extended longer neurites (~100%) in organotypic spinal cord slices embedded in fibronectin-enriched matrix. An increased percentage of parvalbumin-positive neurites (presumptive proprioceptive) vs. neurofilament-positive neurites was also found in DRG in fibronectin-enriched matrix. To test if the different preference of neurons for extracellular matrix components was maintained in vivo, these matrices were used to fill a chitosan guide to repair a 6-mm gap in the sciatic nerve of adult rats. However, the number of regenerating motor and sensory neurons after 1 month was similar between groups. Moreover, none of the retrotraced sensory neurons in DRG was positive for parvalbumin, suggesting that presumptive proprioceptive neurons had poor regenerative capabilities compared with other peripheral neurons. Using real-time PCR we evaluated the expression of α5β1 (receptor for fibronectin) and α7β1 integrin (receptor for laminin) in spinal cord and DRG 2 days after injury. Postnatal animals showed a higher increase of α5β1 integrin, whereas both integrins were similarly expressed in adult neurons. Therefore, we conclude that motor and sensory axons have a different substrate preference at early postnatal stages but this difference is lost in the adult. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  1. Time-lapse imaging reveals symmetric neurogenic cell division of GFAP-expressing progenitors for expansion of postnatal dentate granule neurons.

    Directory of Open Access Journals (Sweden)

    Takashi Namba

    Full Text Available Granule cells in the hippocampus, a region critical for memory and learning, are generated mainly during the early postnatal period but neurogenesis continues in adulthood. Postnatal neuronal production is carried out by primary progenitors that express glial fibrillary acidic protein (GFAP and they are assumed to function as stem cells. A central question regarding postnatal dentate neurogenesis is how astrocyte-like progenitors produce neurons. To reveal cell division patterns and the process of neuronal differentiation of astrocyte-like neural progenitors, we performed time-lapse imaging in cultured hippocampal slices from early postnatal transgenic mice with mouse GFAP promoter-controlled enhanced green fluorescent protein (mGFAP-eGFP Tg mice in combination with a retrovirus carrying a red fluorescent protein gene. Our results showed that the majority of GFAP-eGFP+ progenitor cells that express GFAP, Sox2 and nestin divided symmetrically to produce pairs of GFAP+ cells (45% or pairs of neuron-committed cells (45%, whereas a minority divided asymmetrically to generate GFAP+ cells and neuron-committed cells (10%. The present results suggest that a substantial number of GFAP-expressing progenitors functions as transient amplifying progenitors, at least in an early postnatal dentate gyrus, although a small population appears to be stem cell-like progenitors. From the present data, we discuss possible cell division patterns of adult GFAP+ progenitors.

  2. Time-lapse imaging reveals symmetric neurogenic cell division of GFAP-expressing progenitors for expansion of postnatal dentate granule neurons.

    Science.gov (United States)

    Namba, Takashi; Mochizuki, Hideki; Suzuki, Ryusuke; Onodera, Masafumi; Yamaguchi, Masahiro; Namiki, Hideo; Shioda, Seiji; Seki, Tatsunori

    2011-01-01

    Granule cells in the hippocampus, a region critical for memory and learning, are generated mainly during the early postnatal period but neurogenesis continues in adulthood. Postnatal neuronal production is carried out by primary progenitors that express glial fibrillary acidic protein (GFAP) and they are assumed to function as stem cells. A central question regarding postnatal dentate neurogenesis is how astrocyte-like progenitors produce neurons. To reveal cell division patterns and the process of neuronal differentiation of astrocyte-like neural progenitors, we performed time-lapse imaging in cultured hippocampal slices from early postnatal transgenic mice with mouse GFAP promoter-controlled enhanced green fluorescent protein (mGFAP-eGFP Tg mice) in combination with a retrovirus carrying a red fluorescent protein gene. Our results showed that the majority of GFAP-eGFP+ progenitor cells that express GFAP, Sox2 and nestin divided symmetrically to produce pairs of GFAP+ cells (45%) or pairs of neuron-committed cells (45%), whereas a minority divided asymmetrically to generate GFAP+ cells and neuron-committed cells (10%). The present results suggest that a substantial number of GFAP-expressing progenitors functions as transient amplifying progenitors, at least in an early postnatal dentate gyrus, although a small population appears to be stem cell-like progenitors. From the present data, we discuss possible cell division patterns of adult GFAP+ progenitors.

  3. BMP signaling regulates satellite cell-dependent postnatal muscle growth.

    Science.gov (United States)

    Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

    2017-08-01