WorldWideScience

Sample records for previous lifespan studies

  1. Landfill Lifespan Estimation: A Case Study

    African Journals Online (AJOL)

    Michael

    2017-12-02

    Dec 2, 2017 ... site selection, design, construction, operation and management. For this reason, it ... This research used the future value of money equation to estimate the lifespan of the ..... Geomatic Engineering, UMaT, Tarkwa, Ghana, pp.

  2. Life-span studies of inhaled plutonium in beagle dogs

    International Nuclear Information System (INIS)

    Bair, W.J.

    1990-04-01

    In 1970 a life-span study with over 300 beagle dogs was begun to gain an understanding of long-term health effects resulting from respiratory tract intakes of plutonium and to derive risk estimates that might be applied to plutonium and other transuranic elements. Groups of beagle dogs were given single exposures to 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 to obtain graded levels of initial lung burdens ranging from 1 to 1800 Bq lung. The objective of this paper is to give you a progress report on the current life-span studies of inhaled plutonium in beagle dogs at the Pacific Northwest Laboratory. I will describe the biokinetics of inhaled plutonium in dogs and the resulting health effects. I will also mention some studies directed towards understanding the mechanism leading to these effects. Finally, I will discuss the current risk estimates derived from these studies and how they might relate to plutonium exposures in humans. 5 refs., 13 figs., 4 tabs

  3. Life-span studies of inhaled plutonium in beagle dogs

    International Nuclear Information System (INIS)

    Bair, W.J.

    1991-01-01

    In 1970 a life-span study with over 300 beagle dogs was begun. Groups of beagle dogs were given single exposures to 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 to obtain graded levels of initial lung burdens ranging from 1 to 1800 Bq lung. After 16 years, the lungs contained about 2% of the initial lung burden of 239 PuO 2 , the thoracic lymph nodes 20%, skeleton 1% and liver 10%. After 15 years the lungs contained about 0.2% of the initial lung burden of 238 PuO 2 , thoracic lymph nodes 5%, skeleton 10%, and liver 10%. After 10 years the lungs contained about 0.29% of the initial lung burden of 239 Pu(NO 3 ) 4 , thoracic lymph nodes 0.17%, skeleton 18% and liver 13%. Chronic lymphopenia has been one of the earliest biological effects observed. Other effects associated with plutonium exposure included sclerosis of the tracheobronchial lymph nodes, focal radiation pneumonitis, adenomatous hyperplasia of the liver and dystrophic osteolytic lesions in the skeleton. In 16 years, mortality due to radiation pneumonitis and/or lung tumor increased with deposition of 24 Bq of 239 PuO 2 . In 15 years, mortality due to lung and/or bone tumors increased with deposition of 96 Bq of 238 PuO 2 . In 11 years, after exposure, mortality due to lung and/or bone tumors increased with deposition of 18 Bq of 239 Pu(NO 3 ) 4 . Lung cancers appeared to originate in the parenchymal regions of the lungs and were of several types; bronchiolar alveolar carcinoma, papillary adenocarcinomas, adenosquamous carcinoma, and epidermoid carcinoma. Metastases were primarily to the thoracic lymph nodes. Sites of osteosarcomas in the 238 PuO 2 and 239 Pu(NO 3 ) 4 dogs were in the lumbar cervical and thoracic vertebrae, humerus, pelvis, facial bones, ribs and nasal turbinates. The risk of lung cancer, based on cumulative dose to the lungs, was about 12 times higher for 239 Pu(NO 3 ) 4 than from inhaled 239 PuO 2 , and 50 times higher than for inhaled 238 PuO 2 . (J.P.N.)

  4. Menstruation during a lifespan: A qualitative study of women's experiences.

    Science.gov (United States)

    Brantelid, Ida Emilie; Nilvér, Helena; Alehagen, Siw

    2014-01-01

    Menstruation is a natural phenomenon for women during their reproductive years. Our aim was to describe women's experiences of menstruation across the lifespan. Qualitative interviews with a narrative approach were conducted with 12 women between 18 and 48 years of age in Sweden. Using thematic analysis, we found menstruation to be a complex phenomenon that binds women together. It is perceived as an intimate and private matter, which makes women want to conceal the occurrence of menstrual bleeding. Over time, menstruation becomes a natural part of women's lives and gender identity. Health professionals play a central role supporting women to deal with menstruation.

  5. On the Tengiz petroleum deposit previous study

    International Nuclear Information System (INIS)

    Nysangaliev, A.N.; Kuspangaliev, T.K.

    1997-01-01

    Tengiz petroleum deposit previous study is described. Some consideration about structure of productive formation, specific characteristic properties of petroleum-bearing collectors are presented. Recommendation on their detail study and using of experience on exploration and development of petroleum deposit which have analogy on most important geological and industrial parameters are given. (author)

  6. Regional and longitudinal estimation of product lifespan distribution: a case study for automobiles and a simplified estimation method.

    Science.gov (United States)

    Oguchi, Masahiro; Fuse, Masaaki

    2015-02-03

    Product lifespan estimates are important information for understanding progress toward sustainable consumption and estimating the stocks and end-of-life flows of products. Publications reported actual lifespan of products; however, quantitative data are still limited for many countries and years. This study presents regional and longitudinal estimation of lifespan distribution of consumer durables, taking passenger cars as an example, and proposes a simplified method for estimating product lifespan distribution. We estimated lifespan distribution parameters for 17 countries based on the age profile of in-use cars. Sensitivity analysis demonstrated that the shape parameter of the lifespan distribution can be replaced by a constant value for all the countries and years. This enabled a simplified estimation that does not require detailed data on the age profile. Applying the simplified method, we estimated the trend in average lifespans of passenger cars from 2000 to 2009 for 20 countries. Average lifespan differed greatly between countries (9-23 years) and was increasing in many countries. This suggests consumer behavior differs greatly among countries and has changed over time, even in developed countries. The results suggest that inappropriate assumptions of average lifespan may cause significant inaccuracy in estimating the stocks and end-of-life flows of products.

  7. Life-span radiation effects studies in animals: what can they tell us

    International Nuclear Information System (INIS)

    Thompson, R.C.

    1984-05-01

    Results from life-span studies in a variety of animal species have found relatively little application in the development of radiation risk factors for various organs of man. This paper discusses possible reasons for this situation and presents recommendations to correct it

  8. Evolution of product lifespan and implications for environmental assessment and management: a case study of personal computers in higher education.

    Science.gov (United States)

    Babbitt, Callie W; Kahhat, Ramzy; Williams, Eric; Babbitt, Gregory A

    2009-07-01

    Product lifespan is a fundamental variable in understanding the environmental impacts associated with the life cycle of products. Existing life cycle and materials flow studies of products, almost without exception, consider lifespan to be constant over time. To determine the validity of this assumption, this study provides an empirical documentation of the long-term evolution of personal computer lifespan, using a major U.S. university as a case study. Results indicate that over the period 1985-2000, computer lifespan (purchase to "disposal") decreased steadily from a mean of 10.7 years in 1985 to 5.5 years in 2000. The distribution of lifespan also evolved, becoming narrower over time. Overall, however, lifespan distribution was broader than normally considered in life cycle assessments or materials flow forecasts of electronic waste management for policy. We argue that these results suggest that at least for computers, the assumption of constant lifespan is problematic and that it is important to work toward understanding the dynamics of use patterns. We modify an age-structured model of population dynamics from biology as a modeling approach to describe product life cycles. Lastly, the purchase share and generation of obsolete computers from the higher education sector is estimated using different scenarios for the dynamics of product lifespan.

  9. Injuries can prolong lifespan in Drosophila melanogaster males

    DEFF Research Database (Denmark)

    Henten, Anne Marie Vestergaard; Loeschcke, Volker; Pedersen, Jørgen Granfeldt

    2016-01-01

    Previous studies have shown that a range of different stresses can increase mean lifespan. Here we investigated the effect of injuries and bacterial inoculation on mean lifespan in lines selected for increased longevity and their controls. The three lines from each selection regime were subjected...

  10. Overview of osseous tissue findings from the lifespan carcinogenesis studies: From whole animals to molecules

    International Nuclear Information System (INIS)

    Miller, S.C.; Jee, W.S.S.; Bruenger, F.B.; Lloyd, R.D.; Taylor, G.N.

    1991-01-01

    This summary presents some of the findings from the 226 Ra and 239 Pu lifespan carcinogenesis studies in Beagle dogs and discusses these findings relative to the tissue, cellular and molecular biology of osseous tissues. This report attempts to integrate some of the dosimetric and pathological findings with current understanding of the factors that may influence carcinogenesis (and non-carcinogenic pathologies) at the various levels of biological organization. Emphasis is placed on the findings from the 226 Ra study, as this study has recently been completely reviewed and verified

  11. DOE life-span radiation effects studies at Pacific Northwest Laboratory

    International Nuclear Information System (INIS)

    Thompson, R.C.; Cross, F.T.; Dagle, G.E.; Park, J.F.; Sanders, C.L.

    1986-01-01

    Major life-span radiation effects studies at Pacific Northwest Laboratory fall into three categories: (1) studies with beagle dogs exposed to plutonium compounds via a single inhalation; (2) studies with dogs and rats exposed chronically via inhalation to various combinations and concentrations of radon, radon daughters, and other components of uranium mine atmospheres; and (3) a study in which rats are exposed via single inhalation, in very large numbers, to very low concentrations of 239 PuO 2 . Exposure of beagles currently on study was initiated in 1970 with 239 PuO 2 , in 1973 with 238 PuO 2 , and in 1976 with 239 Pu(NO 3 ) 4 . These experiments involve more than 500 animals, many of them still alive. Experiments seeking to explain the increased incidence of lung cancer in uranium miners have been in progress since 1966. Present emphasis is on studies with rats, in an attempt to define dose-effect relationships at the lowest feasible radon-daughter exposure levels. Our very-low-level experiment with inhaled 239 PuO 2 in rats, with exposures still under way, includes 1000 rats in the control group and 1000 rats in the lowest-exposure group, where life-span lung doses of <5 rads are anticipated

  12. A Cross-Sectional Study of Ageing and Cardiovascular Function over the Baboon Lifespan.

    Directory of Open Access Journals (Sweden)

    Kristen R Yeung

    Full Text Available Ageing is associated with changes at the molecular and cellular level that can alter cardiovascular function and ultimately lead to disease. The baboon is an ideal model for studying ageing due to the similarities in genetic, anatomical, physiological and biochemical characteristics with humans. The aim of this cross-sectional study was to investigate the changes in cardiovascular profile of baboons over the course of their lifespan.Data were collected from 109 healthy baboons (Papio hamadryas at the Australian National Baboon Colony. A linear regression model, adjusting for sex, was used to analyse the association between age and markers of ageing with P 12 years had significantly shorter telomeres when compared to younger (<3 years baboons (P = 0.001.This study is the first to demonstrate that cardiovascular function alters with age in the baboon. This research identifies similarities within cardiovascular parameters between humans and baboon even though the length of life differs between the two species.

  13. On personality stability and change: main results of Brno longitudinal study on life-span development

    Czech Academy of Sciences Publication Activity Database

    Blatný, Marek

    2007-01-01

    Roč. 51, Supplement (2007), s. 37-49 ISSN 0009-062X R&D Projects: GA ČR(CZ) GA406/06/1408 Institutional research plan: CEZ:AV0Z70250504 Keywords : life-span development * personality stability and change Subject RIV: AN - Psychology Impact factor: 0.133, year: 2007

  14. Personality disorders in previously detained adolescent females: a prospective study

    NARCIS (Netherlands)

    Krabbendam, A.; Colins, O.F.; Doreleijers, T.A.H.; van der Molen, E.; Beekman, A.T.F.; Vermeiren, R.R.J.M.

    2015-01-01

    This longitudinal study investigated the predictive value of trauma and mental health problems for the development of antisocial personality disorder (ASPD) and borderline personality disorder (BPD) in previously detained women. The participants were 229 detained adolescent females who were assessed

  15. Different neural processes accompany self-recognition in photographs across the lifespan: an ERP study using dizygotic twins.

    Science.gov (United States)

    Butler, David L; Mattingley, Jason B; Cunnington, Ross; Suddendorf, Thomas

    2013-01-01

    Our appearance changes over time, yet we can recognize ourselves in photographs from across the lifespan. Researchers have extensively studied self-recognition in photographs and have proposed that specific neural correlates are involved, but few studies have examined self-recognition using images from different periods of life. Here we compared ERP responses to photographs of participants when they were 5-15, 16-25, and 26-45 years old. We found marked differences between the responses to photographs from these time periods in terms of the neural markers generally assumed to reflect (i) the configural processing of faces (i.e., the N170), (ii) the matching of the currently perceived face to a representation already stored in memory (i.e., the P250), and (iii) the retrieval of information about the person being recognized (i.e., the N400). There was no uniform neural signature of visual self-recognition. To test whether there was anything specific to self-recognition in these brain responses, we also asked participants to identify photographs of their dizygotic twins taken from the same time periods. Critically, this allowed us to minimize the confounding effects of exposure, for it is likely that participants have been similarly exposed to each other's faces over the lifespan. The same pattern of neural response emerged with only one exception: the neural marker reflecting the retrieval of mnemonic information (N400) differed across the lifespan for self but not for twin. These results, as well as our novel approach using twins and photographs from across the lifespan, have wide-ranging consequences for the study of self-recognition and the nature of our personal identity through time.

  16. Different neural processes accompany self-recognition in photographs across the lifespan: an ERP study using dizygotic twins.

    Directory of Open Access Journals (Sweden)

    David L Butler

    Full Text Available Our appearance changes over time, yet we can recognize ourselves in photographs from across the lifespan. Researchers have extensively studied self-recognition in photographs and have proposed that specific neural correlates are involved, but few studies have examined self-recognition using images from different periods of life. Here we compared ERP responses to photographs of participants when they were 5-15, 16-25, and 26-45 years old. We found marked differences between the responses to photographs from these time periods in terms of the neural markers generally assumed to reflect (i the configural processing of faces (i.e., the N170, (ii the matching of the currently perceived face to a representation already stored in memory (i.e., the P250, and (iii the retrieval of information about the person being recognized (i.e., the N400. There was no uniform neural signature of visual self-recognition. To test whether there was anything specific to self-recognition in these brain responses, we also asked participants to identify photographs of their dizygotic twins taken from the same time periods. Critically, this allowed us to minimize the confounding effects of exposure, for it is likely that participants have been similarly exposed to each other's faces over the lifespan. The same pattern of neural response emerged with only one exception: the neural marker reflecting the retrieval of mnemonic information (N400 differed across the lifespan for self but not for twin. These results, as well as our novel approach using twins and photographs from across the lifespan, have wide-ranging consequences for the study of self-recognition and the nature of our personal identity through time.

  17. Materialism across the lifespan : An age-period-cohort analysis

    NARCIS (Netherlands)

    Jaspers, Esther; Pieters, Rik

    This research examined the development of materialism across the lifespan. Two initial studies revealed that: 1) lay beliefs were that materialism declines with age; and 2) previous research findings also implied a modest, negative relationship between age and materialism. Yet, previous research has

  18. Life-span studies in 226Ra-injected animals: Effect of low doses, effect of a decorporative treatment

    International Nuclear Information System (INIS)

    Schoeters, G.E.R.; Vanderborght, O.L.J.

    1986-01-01

    A life-span radiation effects study was performed in mice injected with several doses of 226 Ra. The study included 788 male C57Bl mice. For the removal of the 226 Ra, half the mice were treated daily with a diet 5% of which was sodium-alginate. The experiment revealed that mice that received the lowest dose of 226 Ra lived significantly longer than controls, and, despite appreciable skeletal removal of 226 Ra as a result of decorporative treatment, no biological benefit was observed in treated animals. 19 refs., 4 figs., 3 tabs

  19. No influence of Indy on lifespan in Drosophila after correction for genetic and cytoplasmic background effects.

    Directory of Open Access Journals (Sweden)

    Janne M Toivonen

    2007-06-01

    Full Text Available To investigate whether alterations in mitochondrial metabolism affect longevity in Drosophila melanogaster, we studied lifespan in various single gene mutants, using inbred and outbred genetic backgrounds. As positive controls we included the two most intensively studied mutants of Indy, which encodes a Drosophila Krebs cycle intermediate transporter. It has been reported that flies heterozygous for these Indy mutations, which lie outside the coding region, show almost a doubling of lifespan. We report that only one of the two mutants lowers mRNA levels, implying that the lifespan extension observed is not attributable to the Indy mutations themselves. Moreover, neither Indy mutation extended lifespan in female flies in any genetic background tested. In the original genetic background, only the Indy mutation associated with altered RNA expression extended lifespan in male flies. However, this effect was abolished by backcrossing into standard outbred genetic backgrounds, and was associated with an unidentified locus on the X chromosome. The original Indy line with long-lived males is infected by the cytoplasmic symbiont Wolbachia, and the longevity of Indy males disappeared after tetracycline clearance of this endosymbiont. These findings underscore the critical importance of standardisation of genetic background and of cytoplasm in genetic studies of lifespan, and show that the lifespan extension previously claimed for Indy mutants was entirely attributable to confounding variation from these two sources. In addition, we saw no effects on lifespan of expression knockdown of the Indy orthologues nac-2 and nac-3 in the nematode Caenorhabditis elegans.

  20. Radon anomalies prior to earthquakes (1). Review of previous studies

    International Nuclear Information System (INIS)

    Ishikawa, Tetsuo; Tokonami, Shinji; Yasuoka, Yumi; Shinogi, Masaki; Nagahama, Hiroyuki; Omori, Yasutaka; Kawada, Yusuke

    2008-01-01

    The relationship between radon anomalies and earthquakes has been studied for more than 30 years. However, most of the studies dealt with radon in soil gas or in groundwater. Before the 1995 Hyogoken-Nanbu earthquake, an anomalous increase of atmospheric radon was observed at Kobe Pharmaceutical University. The increase was well fitted with a mathematical model related to earthquake fault dynamics. This paper reports the significance of this observation, reviewing previous studies on radon anomaly before earthquakes. Groundwater/soil radon measurements for earthquake prediction began in 1970's in Japan as well as foreign countries. One of the most famous studies in Japan is groundwater radon anomaly before the 1978 Izu-Oshima-kinkai earthquake. We have recognized the significance of radon in earthquake prediction research, but recently its limitation was also pointed out. Some researchers are looking for a better indicator for precursors; simultaneous measurements of radon and other gases are new trials in recent studies. Contrary to soil/groundwater radon, we have not paid much attention to atmospheric radon before earthquakes. However, it might be possible to detect precursors in atmospheric radon before a large earthquake. In the next issues, we will discuss the details of the anomalous atmospheric radon data observed before the Hyogoken-Nanbu earthquake. (author)

  1. Exploring the fitness hypothesis in ALS: a population-based case-control study of parental cause of death and lifespan

    NARCIS (Netherlands)

    Visser, A.E.; Seelen, M.; Hulsbergen, A.; Graaf, Joris de; Kooi, A.J. van der; Raaphorst, J.; Veldink, J.H.; Berg, L.H. van den

    2017-01-01

    OBJECTIVE: To investigate the theory of premorbid fitness in amyotrophic lateral sclerosis (ALS), we studied whether a common genetic profile for physical or cardiovascular fitness was manifest in progenitors leading to less cardiovascular death and a longer lifespan in parents of patients with ALS

  2. Listening comprehension across the adult lifespan.

    Science.gov (United States)

    Sommers, Mitchell S; Hale, Sandra; Myerson, Joel; Rose, Nathan; Tye-Murray, Nancy; Spehar, Brent

    2011-01-01

    Although age-related declines in perceiving spoken language are well established, the primary focus of research has been on perception of phonemes, words, and sentences. In contrast, relatively few investigations have been directed at establishing the effects of age on the comprehension of extended spoken passages. Moreover, most previous work has used extreme-group designs in which the performance of a group of young adults is contrasted with that of a group of older adults and little if any information is available regarding changes in listening comprehension across the adult lifespan. Accordingly, the goals of the current investigation were to determine whether there are age differences in listening comprehension across the adult lifespan and, if so, whether similar trajectories are observed for age-related changes in auditory sensitivity and listening comprehension. This study used a cross-sectional lifespan design in which approximately 60 individuals in each of 7 decades, from age 20 to 89 yr (a total of 433 participants), were tested on three different measures of listening comprehension. In addition, we obtained measures of auditory sensitivity from all participants. Changes in auditory sensitivity across the adult lifespan exhibited the progressive high-frequency loss typical of age-related hearing impairment. Performance on the listening comprehension measures, however, demonstrated a very different pattern, with scores on all measures remaining relatively stable until age 65 to 70 yr, after which significant declines were observed. Follow-up analyses indicated that this same general pattern was observed across three different types of passages (lectures, interviews, and narratives) and three different question types (information, integration, and inference). Multiple regression analyses indicated that low-frequency pure-tone average was the single largest contributor to age-related variance in listening comprehension for individuals older than 65 yr, but

  3. Autism through the Lifespan

    Science.gov (United States)

    ... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Donate Home What is Autism? What is Autism? ... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Autism through the Lifespan Home / Living with Autism / ...

  4. 10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling

    Directory of Open Access Journals (Sweden)

    Yoko Honda

    2015-01-01

    Full Text Available Royal jelly (RJ produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA, the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS, indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.

  5. 10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling.

    Science.gov (United States)

    Honda, Yoko; Araki, Yoko; Hata, Taketoshi; Ichihara, Kenji; Ito, Masafumi; Tanaka, Masashi; Honda, Shuji

    2015-01-01

    Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS), indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR) components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.

  6. Starving for life: what animal studies can and cannot tell us about the use of caloric restriction to prolong human lifespan.

    Science.gov (United States)

    Speakman, John R; Hambly, Catherine

    2007-04-01

    Caloric restriction (CR) is the only experimental nongenetic paradigm known to increase lifespan. It has broad applicability and extends the life of most species through a retardation of aging. There is considerable interest in the use of CR in humans, and animal studies can potentially tell us about the impacts. In this article we highlight some of the things that animal studies can tell us about CR in humans. Rodent studies indicate that the benefits of CR on lifespan extension are related to the extent of restriction. The benefits of CR, however, decline as the age of onset of treatment is delayed. Modeling these impacts suggests that if a 48-y-old man engaged in 30% CR until his normal life expectancy of 78, he might increase his life expectancy by 2.8 y. Exercise and cold exposure induce similar energy deficits, but animals respond to these energy deficits in different ways that have a minor impact on lifespan. Measurements of animal responses when they cease restriction indicate that prolonged CR does not diminish hunger, even though the animals may have been in long-term energy balance. Neuroendocrine profiles support the idea that animals under CR are continuously hungry. The feasibility of restricting intake in humans for many decades without long-term support is questionable. However, what is unclear from animal studies is whether taking drugs that suppress appetite will generate the same impact on longevity or whether the neuroendocrine correlates of hunger play an integral role in mediating CRs effects.

  7. Gengnianchun Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1 Signalling Pathway

    Directory of Open Access Journals (Sweden)

    Fanhui Meng

    2018-01-01

    Full Text Available Gengnianchun (GNC, a traditional Chinese medicine (TCM, is believed to have beneficial effects on ageing-related diseases, such as antioxidant properties and effects against Aβ-induced toxicity. We previously found that GNC extended the lifespan of Caenorhabditis elegans. However, the mechanism underlying this effect was unclear. In this study, we further explored the mechanisms of GNC using a C. elegans model. GNC significantly increased the lifespan of C. elegans and enhanced oxidative and thermal stress resistance. Moreover, chemotaxis increased after GNC treatment. RNA-seq analysis showed that GNC regulated genes associated with longevity. We also conducted lifespan assays with a series of worm mutants. The results showed that GNC significantly extended the lifespan of several mutant strains, including eat-2 (ad465, rsks-1 (ok1255, and glp-1 (e2144, suggesting that the prolongevity effect of GNC is independent of the function of these genes. However, GNC failed to extend the lifespan of daf-2 (e1370, age-1 (hx546, and daf-16 (mu86 mutant strains. Our findings suggest that GNC extends the lifespan of C. elegans via the insulin/IGF-1 signalling pathway and may be a potential antiageing agent.

  8. Characterizing lifespan development of three aspects of coherence in life narratives: a cohort-sequential study.

    Science.gov (United States)

    Köber, Christin; Schmiedek, Florian; Habermas, Tilmann

    2015-02-01

    The ability to narrate stories and a synchronic self-concept develop in the pre- and primary school years. Life story theory proposes that both developments extend to an even later developmental stage, that is, to adolescents' acquisition of a coherent life story. Cross-sectional evidence supports the emergence of a life story in adolescence, but is mixed in terms of later life span development. The present study examines longitudinally the development of global coherence in life narratives across almost the entire life span. Starting in 2003, a total of 172 participants narrated their lives over the course of 8 years (aged 16, 20, 24, 28, 44, and 69 when last tested) resulting in up to 4 life narratives per person. Three aspects of global life narrative coherence--temporal, causal-motivational, and thematic coherence--were measured with global ratings and predicted by their respective textual indicators. Children lacked most aspects of global coherence. Almost all indicators of temporal and causal-motivational coherence increased substantially across adolescence up to early adulthood, as did thematic coherence, which continued to develop throughout middle adulthood. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  9. Low-level inhaled-239PuO2 life-span studies in rats

    International Nuclear Information System (INIS)

    Sanders, C.L.; McDonald, K.E.; Killand, B.W.; Mahaffey, J.A.; Cannon, W.C.

    1986-01-01

    This study determined the dose-response curve for lung tumor incidence in rats after inhalation of high-fired 239 PuO 2 , which gave radiation doses to the lung of from ∼5 to >1000 rads. Exposed rats were given a single, nose-only, inhalation exposure to 169 Yb- 239 PuO 2 aerosol (AMAD, 1.6 +- 0.11 μm). The effective half-time for 169 Yb in the lung was 14 days, whereas ∼76% of 239 Pu was cleared with a half-time of 20 days and 24%, with a half-time of 180 days. Whole-body counting for 169 Yb at 14 days after exposure was an accurate method for determining 239 Pu IAD in individual rats, even at IAD's as low as 0.60 nCi of 239 Pu. The 239 Pu lung-clearance curve and an equation describing changes in lung weight with body weight and age were used to determine lung radiation doses. The IAD's of exposure groups were 0.60 +- 0.15 nCi of 239 Pu (1000 rats), 0.98 +- 0.25 (531 rats), 2.4 +- 0.69 (209 rats), 5.7 +- 1.2 (98 rats), and 7.5 +- 2.0 to 150 +- 37 nCi (300 rats); corresponding radiation doses to the lung estimated at 3 years after exposure were 8.3, 14, 33, 79, and 100 to 2100 rads, respectively. 71 refs., 5 figs., 4 tabs

  10. Choosing a proper working length can improve the lifespan of locked plates. A biomechanical study.

    Science.gov (United States)

    Hoffmeier, Konrad L; Hofmann, Gunther O; Mückley, Thomas

    2011-05-01

    It is hypothesized that the working length influences the implants fatigue behavior. However, few studies addressing this issue came to contrary results. Therefore, we tested systematically the influence of working length and implant material on the plate's endurance. We used an artificial model providing the substantial angle and length conditions of a human femur. A fracture gap of 10mm was bridged with identical shaped plate implants made of stainless steel and grade-2 titanium. The fatigue strength was tested for a short, medium and long working length. Aiming at an implant failure within 80,000 loading cycles the upper load threshold was set to 265N for the titanium plates and to 420N for the steel plates. The lower load threshold was -20N for both plates. For the steel plates there was no correlation between fatigue strength and working length. The construct stiffness did not differ at short and medium working length and was reduced by 10% (P=0.047) at long working length. For the titanium plates the fatigue strength tends to increase with the working length but this correlation was not significant (τ=0.417, P=0.051). Further there was a negative correlation between working length and construct stiffness (τ=0.552; P=0.01). The working length has no appreciable effect on the endurance of the steel plates. Compared to the grade 2-titanium plates the stainless steel plates sustain a larger amount of cyclic load. However, for the titanium plates a larger working length tends to improve the endurance. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. The Lifespan of Ornaments

    DEFF Research Database (Denmark)

    Munch, Anders V.; Riisberg, Vibeke

    ? In this paper we will look at contemporary use of ornament in different scales and contexts – from fashion textiles and interior objects to architecture. The lifespan of a building is different from that of a fashion dress or a plate, but with the digital era it seems like the concern of appropriateness...

  12. Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster.

    Science.gov (United States)

    Mason, Janet S; Wileman, Tom; Chapman, Tracey

    2018-01-01

    Autophagy is a highly conserved mechanism for cellular repair that becomes progressively down-regulated during normal ageing. Hence, manipulations that activate autophagy could increase lifespan. Previous reports show that manipulations to the autophagy pathway can result in longevity extension in yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore, manipulations of TOR that increase autophagy may offer a mechanism for extending lifespan. Ideally, such manipulations should be specific and minimise off-target effects, and it is important to discover additional methods for 'clean' lifespan manipulation. Here we report an initial study into the effect of up-regulating autophagy on lifespan and fertility in Drosophila melanogaster by dietary addition of Torin1. Activation of autophagy using this selective TOR inhibitor was associated with significantly increased lifespan in both sexes. Torin1 induced a dose-dependent increase in lifespan in once-mated females. There was no evidence of a trade-off between longevity and fecundity or fertility. Torin1-fed females exhibited significantly elevated fecundity, but also elevated egg infertility, resulting in no net change in overall fertility. This supports the idea that lifespan can be extended without trade-offs in fertility and suggest that Torin1 may be a useful tool with which to pursue anti-ageing research.

  13. Drug synergy drives conserved pathways to increase fission yeast lifespan.

    Directory of Open Access Journals (Sweden)

    Xinhe Huang

    Full Text Available Aging occurs over time with gradual and progressive loss of physiological function. Strategies to reduce the rate of functional loss and mitigate the subsequent onset of deadly age-related diseases are being sought. We demonstrated previously that a combination of rapamycin and myriocin reduces age-related functional loss in the Baker's yeast Saccharomyces cerevisiae and produces a synergistic increase in lifespan. Here we show that the same drug combination also produces a synergistic increase in the lifespan of the fission yeast Schizosaccharomyces pombe and does so by controlling signal transduction pathways conserved across a wide evolutionary time span ranging from yeasts to mammals. Pathways include the target of rapamycin complex 1 (TORC1 protein kinase, the protein kinase A (PKA and a stress response pathway, which in fission yeasts contains the Sty1 protein kinase, an ortholog of the mammalian p38 MAP kinase, a type of Stress Activated Protein Kinase (SAPK. These results along with previous studies in S. cerevisiae support the premise that the combination of rapamycin and myriocin enhances lifespan by regulating signaling pathways that couple nutrient and environmental conditions to cellular processes that fine-tune growth and stress protection in ways that foster long term survival. The molecular mechanisms for fine-tuning are probably species-specific, but since they are driven by conserved nutrient and stress sensing pathways, the drug combination may enhance survival in other organisms.

  14. A cross-cultural study of the lifespan distributions of life script events and autobiographical memories of life story events

    DEFF Research Database (Denmark)

    Zaragoza Scherman, Alejandra; Salgado, Sinué; Shao, Zhifang

    Cultural Life Script Theory provides a cultural explanation of the reminiscence bump: adults older than 40 years remember more life events happening between 15 - 30 years of age. The cultural life script represents semantic knowledge about commonly shared expectations regarding the order and timing...... of major transitional life events in an idealized life course. By comparing the lifespan distribution of life scripts events and memories of life story events, we can determine the degree to which the cultural life script serves as a recall template for autobiographical memories, especially of positive...

  15. GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Yuka; Tamura, Takayuki [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Yoshida, Ryo [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ohta, Shinji [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Fukusaki, Eiichiro [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan)

    2011-04-01

    Highlights: {yields}We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. {yields} Deletion of the UGA1 or GAD1 genes extends replicative lifespan. {yields} Addition of GABA to wild-type cultures has no effect on lifespan. {yields} Intracellular GABA levels do not differ in longevity mutants and wild-type cells. {yields} Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for {gamma}-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The {Delta}uga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for {Delta}uga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of {sup 1}H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan

  16. GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

    International Nuclear Information System (INIS)

    Kamei, Yuka; Tamura, Takayuki; Yoshida, Ryo; Ohta, Shinji; Fukusaki, Eiichiro; Mukai, Yukio

    2011-01-01

    Highlights: →We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. → Deletion of the UGA1 or GAD1 genes extends replicative lifespan. → Addition of GABA to wild-type cultures has no effect on lifespan. → Intracellular GABA levels do not differ in longevity mutants and wild-type cells. → Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for γ-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The Δuga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for Δuga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of 1 H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan extension. These results strongly suggest

  17. 10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling

    OpenAIRE

    Honda, Yoko; Araki, Yoko; Hata, Taketoshi; Ichihara, Kenji; Ito, Masafumi; Tanaka, Masashi; Honda, Shuji

    2015-01-01

    Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA f...

  18. Worker lifespan is an adaptive trait during colony establishment in the long-lived ant Lasius niger

    NARCIS (Netherlands)

    Kramer, Boris H.; Schaible, Ralf; Scheuerlein, Alexander

    2016-01-01

    Eusociality has been recognized as a strong driver of lifespan evolution. While queens show extraordinary lifespans of 20 years and more, worker lifespan is short and variable. A recent comparative study found that in eusocial species with larger average colony sizes the disparities in the lifespans

  19. 40 CFR 152.93 - Citation of a previously submitted valid study.

    Science.gov (United States)

    2010-07-01

    ... Data Submitters' Rights § 152.93 Citation of a previously submitted valid study. An applicant may demonstrate compliance for a data requirement by citing a valid study previously submitted to the Agency. The... the original data submitter, the applicant may cite the study only in accordance with paragraphs (b...

  20. Survival and death of seeds during liquid nitrogen storage: a case study on seeds with short lifespans.

    Science.gov (United States)

    Ballesteros, D; Pence, V C

    The low temperature of liquid nitrogen is assumed to stop ageing and preserve viability indefinitely, however there are few validating data sets. The use of seeds to test these assumptions is important because other cryopreserved systems lack quantitative measures of viability to allow comparisons among timed points. To evaluate survival of a collection of seeds with short lifespans stored 12-20 years in liquid nitrogen. Seeds from 11 species (26 accessions) were removed from cryostorage and evaluated for germination and normal growth. Germination of Plantago cordata and Betula spp. seeds did not decrease significantly during cryostorage. However, Populus deltoides and most Salix spp. accessions showed a significant decrease in germination, with further loss observed when P. deltoides seedlings were followed to the young plant stage. Seeds of initial low quality showed greater deterioration during cryostorage. Cryostorage maintained viability of Salix and Populus seeds longer than other temperatures. However, ageing was not completely stopped and seed longevity was shorter than that predicted for many other species. A high initial seed quality is important in order to obtain the maximum benefit of cryostorage.

  1. Summary of Previous Chamber or Controlled Anthrax Studies and Recommendations for Possible Additional Studies

    Energy Technology Data Exchange (ETDEWEB)

    Piepel, Gregory F.; Amidan, Brett G.; Morrow, Jayne B.

    2010-12-29

    This report and an associated Excel file(a) summarizes the investigations and results of previous chamber and controlled studies(b) to characterize the performance of methods for collecting, storing and/or transporting, extracting, and analyzing samples from surfaces contaminated by Bacillus anthracis (BA) or related simulants. This report and the Excel are the joint work of the Pacific Northwest National Laboratory (PNNL) and the National Institute of Standards and Technology (NIST) for the Department of Homeland Security, Science and Technology Directorate. The report was originally released as PNNL-SA-69338, Rev. 0 in November 2009 with limited distribution, but was subsequently cleared for release with unlimited distribution in this Rev. 1. Only minor changes were made to Rev. 0 to yield Rev. 1. A more substantial update (including summarizing data from other studies and more condensed summary tables of data) is underway

  2. Animal lifespan and human influence

    Science.gov (United States)

    Guo, Q.; Yang, S.

    2002-01-01

    Lifespan differs radically among organisms ever lived on earth, even among those roughly similar in size, shape, form, and physiology; Yet, in general, there exists a strong positive relationship between lifespan and body size. Although lifespans of humans and human-related (domestic) animals are becoming increasingly longer than that of other animals of similar sizes, the slope of the regression (lifespan-body size) line and the intercepts have been surprisingly stable over the course of the dramatic human population growth, indicating substantial depression in lifespans of many other animals probably due to shrunk and fragmented natural habitats. This article addresses two questions related to the lifespan-size relationship: (1) what caused the exceptions (e.g., a few remote human-related animals are also located above the regression line with great residuals) and why (e.g., could brain size or intelligence be a covariate in addition to body size in predicting lifespan?), and (2) whether continued human activities can eventually alter the ' natural' regression line in the future, and if so, how much. We also suggest similar research efforts to be extended to the plant world as well.

  3. Visual Word Recognition Across the Adult Lifespan

    Science.gov (United States)

    Cohen-Shikora, Emily R.; Balota, David A.

    2016-01-01

    The current study examines visual word recognition in a large sample (N = 148) across the adult lifespan and across a large set of stimuli (N = 1187) in three different lexical processing tasks (pronunciation, lexical decision, and animacy judgments). Although the focus of the present study is on the influence of word frequency, a diverse set of other variables are examined as the system ages and acquires more experience with language. Computational models and conceptual theories of visual word recognition and aging make differing predictions for age-related changes in the system. However, these have been difficult to assess because prior studies have produced inconsistent results, possibly due to sample differences, analytic procedures, and/or task-specific processes. The current study confronts these potential differences by using three different tasks, treating age and word variables as continuous, and exploring the influence of individual differences such as vocabulary, vision, and working memory. The primary finding is remarkable stability in the influence of a diverse set of variables on visual word recognition across the adult age spectrum. This pattern is discussed in reference to previous inconsistent findings in the literature and implications for current models of visual word recognition. PMID:27336629

  4. Lower Doses of Fructose Extend Lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Zheng, Jolene; Gao, Chenfei; Wang, Mingming; Tran, Phuongmai; Mai, Nancy; Finley, John W; Heymsfield, Steven B; Greenway, Frank L; Li, Zhaoping; Heber, David; Burton, Jeffrey H; Johnson, William D; Laine, Roger A

    2017-05-04

    Epidemiological studies indicate that the increased consumption of sugars including sucrose and fructose in beverages correlate with the prevalence of obesity, type-2 diabetes, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension in humans. A few reports suggest that fructose extends lifespan in Saccharomyces cerevisiae. In Anopheles gambiae, fructose, glucose, or glucose plus fructose also extended lifespan. New results presented here suggest that fructose extends lifespan in Caenorhabditis elegans (C. elegans) wild type (N2). C. elegans were fed standard laboratory food source (E. coli OP50), maintained in liquid culture. Experimental groups received additional glucose (111 mM), fructose (55 mM, 111 mM, or 555 mM), sucrose (55 mM, 111 mM, or 555 mM), glucose (167 mM) plus fructose (167 mM) (G&F), or high fructose corn syrup (HFCS, 333 mM). In four replicate experiments, fructose dose-dependently increased mean lifespan at 55 mM or 111 m Min N2, but decreased lifespan at 555 mM (P Glucose reduced lifespan (P fructose (555 mM), glucose (111 mM), and sucrose (55 mM, 111 mM, and 555 mM). Here we report a biphasic effect of fructose increasing lifespan at lower doses and shortening lifespan at higher doses with an inverse effect on IFD. In view of reports that fructose increases lifespan in yeast, mosquitoes and now nematodes, while decreasing fat deposition (in nematodes) at lower concentrations, further research into the relationship of fructose to lifespan and fat accumulation in vertebrates and mammals is indicated.

  5. Matched cohort study of external cephalic version in women with previous cesarean delivery.

    Science.gov (United States)

    Keepanasseril, Anish; Anand, Keerthana; Soundara Raghavan, Subrahmanian

    2017-07-01

    To evaluate the efficacy and safety of external cephalic version (ECV) among women with previous cesarean delivery. A retrospective study was conducted using data for women with previous cesarean delivery and breech presentation who underwent ECV at or after 36 weeks of pregnancy during 2011-2016. For every case, two multiparous women without previous cesarean delivery who underwent ECV and were matched for age and pregnancy duration were included. Characteristics and outcomes were compared between groups. ECV was successful for 32 (84.2%) of 38 women with previous cesarean delivery and 62 (81.6%) in the control group (P=0.728). Multivariate regression analysis confirmed that previous cesarean was not associated with ECV success (odds ratio 1.89, 95% confidence interval 0.19-18.47; P=0.244). Successful vaginal delivery after successful ECV was reported for 19 (59.4%) women in the previous cesarean delivery group and 52 (83.9%) in the control group (P<0.001). No ECV-associated complications occurred in women with previous cesarean delivery. To avoid a repeat cesarean delivery, ECV can be offered to women with breech presentation and previous cesarean delivery who are otherwise eligible for a trial of labor. © 2017 International Federation of Gynecology and Obstetrics.

  6. Measurement of lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Linford, Nancy J; Bilgir, Ceyda; Ro, Jennifer; Pletcher, Scott D

    2013-01-07

    Aging is a phenomenon that results in steady physiological deterioration in nearly all organisms in which it has been examined, leading to reduced physical performance and increased risk of disease. Individual aging is manifest at the population level as an increase in age-dependent mortality, which is often measured in the laboratory by observing lifespan in large cohorts of age-matched individuals. Experiments that seek to quantify the extent to which genetic or environmental manipulations impact lifespan in simple model organisms have been remarkably successful for understanding the aspects of aging that are conserved across taxa and for inspiring new strategies for extending lifespan and preventing age-associated disease in mammals. The vinegar fly, Drosophila melanogaster, is an attractive model organism for studying the mechanisms of aging due to its relatively short lifespan, convenient husbandry, and facile genetics. However, demographic measures of aging, including age-specific survival and mortality, are extraordinarily susceptible to even minor variations in experimental design and environment, and the maintenance of strict laboratory practices for the duration of aging experiments is required. These considerations, together with the need to practice careful control of genetic background, are essential for generating robust measurements. Indeed, there are many notable controversies surrounding inference from longevity experiments in yeast, worms, flies and mice that have been traced to environmental or genetic artifacts(1-4). In this protocol, we describe a set of procedures that have been optimized over many years of measuring longevity in Drosophila using laboratory vials. We also describe the use of the dLife software, which was developed by our laboratory and is available for download (http://sitemaker.umich.edu/pletcherlab/software). dLife accelerates throughput and promotes good practices by incorporating optimal experimental design, simplifying

  7. Study of some physical aspects previous to design of an exponential experiment

    International Nuclear Information System (INIS)

    Caro, R.; Francisco, J. L. de

    1961-01-01

    This report presents the theoretical study of some physical aspects previous to the design of an exponential facility. The are: Fast and slow flux distribution in the multiplicative medium and in the thermal column, slowing down in the thermal column, geometrical distribution and minimum needed intensity of sources access channels and perturbations produced by possible variations in its position and intensity. (Author) 4 refs

  8. Study of functional-performance deficits in athletes with previous ankle sprains

    Directory of Open Access Journals (Sweden)

    hamid Babaee

    2008-04-01

    Full Text Available Abstract Background: Despite the importance of functional-performance deficits in athletes with history of ankle sprain few, studies have been carried out in this area. The aim of this research was to study relationship between previous ankle sprains and functional-performance deficits in athletes. Materials and methods: The subjects were 40 professional athletes selected through random sampling among volunteer participants in soccer, basketball, volleyball and handball teams of Lorestan province. The subjects were divided into 2 groups: Injured group (athletes with previous ankle sprains and healthy group (athletes without previous ankle sprains. In this descriptive study we used Functional-performance tests (figure 8 hop test and side hop test to determine ankle deficits and limitations. They participated in figure 8 hop test including hopping in 8 shape course with the length of 5 meters and side hop test including 10 side hop repetitions in course with the length of 30 centimeters. Time were recorded via stopwatch. Results: After data gathering and assessing information distributions, Pearson correlation was used to assess relationships, and independent T test to assess differences between variables. Finally the results showed that there is a significant relationship between previous ankle sprains and functional-performance deficits in the athletes. Conclusion: The athletes who had previous ankle sprains indicated functional-performance deficits more than healthy athletes in completion of mentioned functional-performance tests. The functional-performance tests (figure 8 hop test and side hop test are sensitive and suitable to assess and detect functional-performance deficits in athletes. Therefore we can use the figure 8 hop and side hop tests for goals such as prevention, assessment and rehabilitation of ankle sprains without spending too much money and time.

  9. Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

    Science.gov (United States)

    Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka; Uddin, Lucina Q; Heller, Aaron S

    2017-05-31

    Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation. SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan. Copyright © 2017 the authors 0270-6474/17/375539-10$15.00/0.

  10. The Eyring-Stover theory of survival applied to life-span radiation effects studies in animals

    International Nuclear Information System (INIS)

    Stover, B.J.; Wrenn, M.E.; Jee, W.S.S.; Atherton, D.R.

    1986-01-01

    The Eyring-Stover theory of survival describes the observed biological phenomena of damage and repair as steady-state processes that can be expressed in the formalism of absolute reaction rate theory. The steady-state formulation, rather than that of dynamic equilibrium, is invoked since biological phenomena, in contrast with most chemical and physical phenemena, are time irreversible. The theory is appropriate for calculating life shortening that results from environmental factors such as irradiation since it does not require universality and intrinsicality as to some theories of aging. The theory gives not only midrange mortality rate values but also end-range values, which are difficult to predict empirically. The previously calculated life shortening of mice after external x-irradiation and of beagles after internal irradiation from 239 Pu or 226 Ra is reviewed; life shortening at low dose levels of 226 Ra is presented. 21 refs., 1 tab

  11. Data from studies of previous radioactive waste disposal in Massachusetts Bay

    International Nuclear Information System (INIS)

    Curtis, W.R.; Mardis, H.M.

    1984-12-01

    This report presents the results of studies conducted in Massachusetts Bay during 1981 and 1982. Included are data from: (1) a side scan sonar survey of disposal areas in the Bay that was carried out by the National Oceanic and Atmospheric Administration (NOAA) for EPA; (2) Collections of sediment and biota by NOAA for radiochemical analysis by EPA; (3) collections of marketplace seafood samples by the Food and Drug Administration (FDA) for radioanalysis by both FDA and EPA; and (4) a radiological monitoring survey of LLW disposal areas by EPA to determine whether there should be any concern for public health resulting from previous LLW disposals in the Bay

  12. DOE life-span radiation effects studies in experimental animals at University of Utah Division of Radiobiology

    International Nuclear Information System (INIS)

    Wrenn, M.E.; Taylor, G.N.; Stevens, W.

    1986-01-01

    The Radiobiology Laboratory at the University of Utah compared the long-term biological effects of 226 Ra and 239 Pu in adult beagles. The program includes the investigation of other radionuclides. More recently, groups of juvenile and aged beagles were added to the study to investigate the influence of age at exposure. These studies involved single intravenous injection of radionuclides to small groups of beagles, in graded doses from levels at which no effects were expected up to levels where a 100% incidence of bone tumors was sometimes found. Some of the principal effects were bone tumors, fractures, and other skeletal alterations observed radiographically and histologically; emphasis was placed on the detection of precancerous changes, hematological changes, and changes related to aging. Emphasis was also placed on metabolic and autoradiographic studies necessary for good radiation dosimetry

  13. Telomerase levels control the lifespan of human T lymphocytes

    NARCIS (Netherlands)

    Roth, Alexander; Yssel, Hans; Pene, Jerome; Chavez, Elizabeth A.; Schertzer, Mike; Lansdorp, Peter M.; Spits, Hergen; Luiten, Rosalie M.

    2003-01-01

    The loss of telomeric DNA with each cell division contributes to the limited replicative lifespan of human T lymphocytes. Although telomerase is transiently expressed in T lymphocytes upon activation, it is insufficient to confer immortality. We have previously shown that immortalization of human

  14. From flexibility human resource management to employee engagement and perceived job performance across the lifespan: A multisample study

    NARCIS (Netherlands)

    Bal, P.M.; Lange, A.H. de

    2015-01-01

    This study investigated the effects of flexibility human resource management (HRM) on employee outcomes over time, as well as the role of age in these relations. Based on work adjustment theory and AMO theory, it was predicted that availability and use of flexibility HRM would be positively related

  15. Life-span radiation effects studies in prenatally and postnatally exposed beagle dogs at Colorado State University

    International Nuclear Information System (INIS)

    Benjamin, S.A.; Lee, A.C.; Angleton, G.M.; Jaenke, R.S.; Saunders, W.J.; Miller, G.K.; Brewster, R.D.

    1986-01-01

    The lifetime hazards associated with exposure to ionizing radiation during development are studied in 1680 beagle dogs given whole-body exposures to 60 Co gamma radiation. Eight groups of 120 dogs each received 20-R or 100-R exposures at 8, 28, or 55 days postcoitus (dpc) or at 2 days postpartum (dpp). In addition, exposures of 100 R were given to 120 dogs at 70 dpp and to 240 dogs at 365 dpp. An additional 360 dogs were sham exposed. Smaller groups of dogs were used to identify organs and tissues of particular sensitivity to radiation injury during development and to evaluate mechanisms of radiation injury. The research is concerned primarily with evaluating the role of age at exposure as a factor influencing response to radiation injury. As of December 31, 1982, of the 1680 dogs, 1058 were dead. Survivors ranged from 9.9 to 15 years of age. Through 10 years of age, no differences in survival were evident in any exposure groups. A variety of clinical, pathophysiologic, and pathologic responses have been studied. Irradiation during development has been found to be associated with abnormalities of skeletal, dental, and central nervous system development. Irradiation during ocular development has induced dysplastic and atrophic retinal lesions. Perinatal irradiation of the kidney has resulted in dysplasia, and, in animals receiving higher doses, significant chronic renal disease. The thymus gland, particularly thymic epithelium, has been found to be highly radiosensitive during fetal development

  16. Ontogenetic patterns in the dreams of women across the lifespan.

    Science.gov (United States)

    Dale, Allyson; Lortie-Lussier, Monique; De Koninck, Joseph

    2015-12-01

    The present study supports and extends previous research on the developmental differences in women's dreams across the lifespan. The participants included 75 Canadian women in each of 5 age groups from adolescence to old age including 12-17, 18-24, 25-39, 40-64, and 65-85, totaling 375 women. One dream per participant was scored by two independent judges using the method of content analysis. Trend analysis was used to determine the ontogenetic pattern of the dream content categories. Results demonstrated significant ontogenetic decreases (linear trends) for female and familiar characters, activities, aggression, and friendliness. These patterns of dream imagery reflect the waking developmental patterns as proposed by social theories and recognized features of aging as postulated by the continuity hypothesis. Limitations and suggestions for future research including the examining of developmental patterns in the dreams of males are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. A longitudinal study of plasma insulin and glucagon in women with previous gestational diabetes

    DEFF Research Database (Denmark)

    Damm, P; Kühl, C; Hornnes, P

    1995-01-01

    OBJECTIVE: To investigate whether plasma insulin or glucagon predicts later development of diabetes in women with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The subjects studied were 91 women with diet-treated GDM and 33 healthy women. Plasma insulin and glucagon during a 50...... at follow-up (2 had insulin-dependent diabetes mellitus, 13 had non-insulin-dependent diabetes mellitus, and 12 had impaired glucose tolerance). Compared with the control subjects, women with previous GDM had relatively impaired insulin secretion (decreased insulinogenic index and delayed peak insulin...... for subsequent development of overt diabetes (logistic regression analysis). CONCLUSIONS: Women who develop GDM have a relative insulin secretion deficiency, the severity of which is predictive for later development of diabetes. Furthermore, our data indicate that their relatively reduced beta-cell function may...

  18. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    Directory of Open Access Journals (Sweden)

    Moreno Victor

    2011-08-01

    Full Text Available Abstract Background Colorectal cancer (CRC is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. Methods CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. Results None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive, rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive, rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant, and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive. In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1

  19. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    International Nuclear Information System (INIS)

    Abulí, Anna; Morillas, Juan D; Rigau, Joaquim; Latorre, Mercedes; Fernández-Bañares, Fernando; Peña, Elena; Riestra, Sabino; Payá, Artemio; Jover, Rodrigo; Xicola, Rosa M; Llor, Xavier; Fernández-Rozadilla, Ceres; Carvajal-Carmona, Luis; Villanueva, Cristina M; Moreno, Victor; Piqué, Josep M; Carracedo, Angel; Castells, Antoni; Andreu, Montserrat; Ruiz-Ponte, Clara; Castellví-Bel, Sergi; Alonso-Espinaco, Virginia; Muñoz, Jenifer; Gonzalo, Victoria; Bessa, Xavier; González, Dolors; Clofent, Joan; Cubiella, Joaquin

    2011-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1

  20. Workplace flexibility across the lifespan

    OpenAIRE

    Bal, Pieter; Jansen, Paul G W

    2016-01-01

    As demographic changes impact the workplace, governments, organizations and workers arelooking for ways to sustain optimal working lives at higher ages. Workplace flexibility has beenintroduced as a potential way workers can have more satisfying working lives until theirretirement ages. This paper presents a critical review of the literature on workplace flexibilityacross the lifespan. It discusses how flexibility has been conceptualized across differentdisciplines, and postulates a definitio...

  1. A study about the interest and previous contact of high school students with Astronomy

    Science.gov (United States)

    Carvalho, C. L.; Zanitti, M. H. R.; Felicidade, B. L.; Gomes, A. D. T.; Dias, E. W.; Coelho, F. O.

    2016-04-01

    The currently problems in Astronomy teaching in Brazilian Basic Education contrast with the space, and the popularity that astronomical themes have in various media in the country. In this work, we present the results of a study about the interest, and previous contact of high school students from a public school in the city of "São João del-Rei"/MG with topics related to Astronomy. The study and the pedagogical intervention were carried out by students of the PIBID/CAPES/UFSJ. The intervention was performed through an oral exposition with the students' participation, followed by the use of the Stellarium program. The results suggest the majority of students surveyed are interested in Astronomy, and have had some contact with the area. However, some inconsistencies in their responses were identified and examined. The implications for research and for Astronomy Education are discussed. We also make some considerations about relationship between the lack of specific knowledge and the misinformation as one possible reason for the little interest of students in various areas of Science.

  2. Sex-specific lifespan and its evolution in nematodes.

    Science.gov (United States)

    Ancell, Henry; Pires-daSilva, Andre

    2017-10-01

    Differences between sexes of the same species in lifespan and aging rate are widespread. While the proximal and evolutionary causes of aging are well researched, the factors that contribute to sex differences in these traits have been less studied. The striking diversity of nematodes provides ample opportunity to study variation in sex-specific lifespan patterns associated with shifts in life history and mating strategy. Although the plasticity of these sex differences will make it challenging to generalize from invertebrate to vertebrate systems, studies in nematodes have enabled empirical evaluation of predictions regarding the evolution of lifespan. These studies have highlighted how natural and sexual selection can generate divergent patterns of lifespan if the sexes are subject to different rates or sources of mortality, or if trade-offs between complex traits and longevity are resolved differently in each sex. Here, we integrate evidence derived mainly from nematodes that addresses the molecular and evolutionary basis of sex-specific aging and lifespan. Ultimately, we hope to generate a clearer picture of current knowledge in this area, and also highlight the limitations of our understanding. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Fire Risk Scoping Study: Investigation of nuclear power plant fire risk, including previously unaddressed issues

    International Nuclear Information System (INIS)

    Lambright, J.A.; Nowlen, S.P.; Nicolette, V.F.; Bohn, M.P.

    1989-01-01

    An investigation of nuclear power plant fire risk issues raised as a result of the USNRC sponsored Fire Protection Research Program at Sandia National Laboratories has been performed. The specific objectives of this study were (1) to review and requantify fire risk scenarios from four fire probabilistic risk assessments (PRAs) in light of updated data bases made available as a result of USNRC sponsored Fire Protection Research Program and updated computer fire modeling capabilities, (2) to identify potentially significant fire risk issues that have not been previously addressed in a fire risk context and to quantify the potential impact of those identified fire risk issues where possible, and (3) to review current fire regulations and plant implementation practices for relevance to the identified unaddressed fire risk issues. In performance of the fire risk scenario requantifications several important insights were gained. It was found that utilization of a more extensive operational experience base resulted in both fire occurrence frequencies and fire duration times (i.e., time required for fire suppression) increasing significantly over those assumed in the original works. Additionally, some thermal damage threshold limits assumed in the original works were identified as being nonconservative based on more recent experimental data. Finally, application of the COMPBRN III fire growth model resulted in calculation of considerably longer fire damage times than those calculated in the original works using COMPBRN I. 14 refs., 2 figs., 16 tabs

  4. The Lifespan Self-Esteem Scale: Initial Validation of a New Measure of Global Self-Esteem.

    Science.gov (United States)

    Harris, Michelle A; Donnellan, M Brent; Trzesniewski, Kali H

    2018-01-01

    This article introduces the Lifespan Self-Esteem Scale (LSE), a short measure of global self-esteem suitable for populations drawn from across the lifespan. Many existing measures of global self-esteem cannot be used across multiple developmental periods due to changes in item content, response formats, and other scale characteristics. This creates a need for a new lifespan scale so that changes in global self-esteem over time can be studied without confounding maturational changes with alterations in the measure. The LSE is a 4-item measure with a 5-point response format using items inspired by established self-esteem scales. The scale is essentially unidimensional and internally consistent, and it converges with existing self-esteem measures across ages 5 to 93 (N = 2,714). Thus, the LSE appears to be a useful measure of global self-esteem suitable for use across the lifespan as well as contexts where a short measure is desirable, such as populations with short attention spans or large projects assessing multiple constructs. Moreover, the LSE is one of the first global self-esteem scales to be validated for children younger than age 8, which provides the opportunity to broaden the field to include research on early formation and development of global self-esteem, an area that has previously been limited.

  5. Cortical Changes Across the Autism Lifespan.

    Science.gov (United States)

    Osipowicz, Karol; Bosenbark, Danielle D; Patrick, Kristina E

    2015-08-01

    Although it is widely accepted that autism spectrum disorder (ASD) involves neuroanatomical abnormalities and atypical neurodevelopmental patterns, there is little consensus regarding the precise pattern of neuroanatomical differences or how these differences relate to autism symptomology. Furthermore, there is limited research related to neuroanatomical correlates of autism symptomology in individuals with ASD and the studies that do exist primarily include small samples. This study was the first to investigate gray matter (GM) changes throughout the ASD lifespan, using voxel-based morphometry to determine whether significant differences exist in the GM volumes of a large sample of individuals with ASD compared to age- and IQ-matched typical controls. We examined GM volume across the lifespan in 531 individuals diagnosed with ASD and 571 neurotypical controls, aged 7-64. We compared groups and correlated GM with age and autism severity in the ASD group. Findings suggest bilateral decreased GM volume for individuals with ASD in regions extending from the thalamus to the cerebellum, anterior medial temporal lobes, and orbitofrontal regions. Higher autism severity was associated with decreased GM volumes in prefrontal cortex, inferior parietal and temporal regions, and temporal poles. Similar relationships were found between GM volume and age. ASD diagnosis and severity were not associated with increased GM volumes in any region. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  6. The biomechanics of running in athletes with previous hamstring injury: A case-control study.

    Science.gov (United States)

    Daly, C; Persson, U McCarthy; Twycross-Lewis, R; Woledge, R C; Morrissey, D

    2016-04-01

    Hamstring injury is prevalent with persistently high reinjury rates. We aim to inform hamstring rehabilitation by exploring the electromyographic and kinematic characteristics of running in athletes with previous hamstring injury. Nine elite male Gaelic games athletes who had returned to sport after hamstring injury and eight closely matched controls sprinted while lower limb kinematics and muscle activity of the previously injured biceps femoris, bilateral gluteus maximus, lumbar erector spinae, rectus femoris, and external oblique were recorded. Intergroup comparisons of muscle activation ratios and kinematics were performed. Previously injured athletes demonstrated significantly reduced biceps femoris muscle activation ratios with respect to ipsilateral gluteus maximus (maximum difference -12.5%, P = 0.03), ipsilateral erector spinae (maximum difference -12.5%, P = 0.01), ipsilateral external oblique (maximum difference -23%, P = 0.01), and contralateral rectus femoris (maximum difference -22%, P = 0.02) in the late swing phase. We also detected sagittal asymmetry in hip flexion (maximum 8°, P = 0.01), pelvic tilt (maximum 4°, P = 0.02), and medial rotation of the knee (maximum 6°, P = 0.03) effectively putting the hamstrings in a lengthened position just before heel strike. Previous hamstring injury is associated with altered biceps femoris associated muscle activity and potentially injurious kinematics. These deficits should be considered and addressed during rehabilitation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Rancidity inhibition study in frozen whole mackerel (scomber scombrus by a previous plant extract treatment.

    Directory of Open Access Journals (Sweden)

    Aubourg, Santiago P.

    2005-09-01

    Full Text Available The effect of flaxseeds (Linum usitatissimum on rancidity development in frozen whole mackerel (Scomber scombrus was studied. For it, fresh mackerel were dipped in flaxseeds aqueous extract during 60 min, frozen at –80 ºC during 24 hours and kept frozen (–20 ºC up to 12 months. Sampling was carried out on the initial material and at months 1, 3, 5, 7, 9 and 12 of frozen storage at –20 ºC. A parallel experiment with non treated fish was carried out in the same conditions. Rancidity development was measured by several biochemical indices (free fatty acids, peroxides, conjugated dienes and trienes, secondary oxidation products and lipoxygenase activity and complemented by the sensory analysis (skin, flesh odour, consistency and flesh appearance. As a result of the previous antioxidant treatment, peroxides showed to breakdown faster (pSe ha estudiado el efecto del lino (Linum usitatissimum en el desarrollo de rancidez en caballa entera congelada (Scomber scombrus. Para ello, caballas frescas fueron sumergidas en extractos acuosos de semillas de lino durante 60 min, congeladas a -80 ºC durante 24 h y mantenidas congeladas ( -20 ºC durante 12 meses. Se tomaron muestras del material inicial y tras 1, 3, 5, 7, 9 y 12 meses de congelación a -20 ºC . Un experimento paralelo con pescado no tratado fue llevado acabo en las mismas condiciones. El desarrollo de la rancidez fue medido por varios índices bioquímicos (ácidos grasos libres, peróxidos, dienos y trienos conjugados, productos secundarios de oxidación y actividad lipoxigenasa y completado con análisis sensorial (piel, olor de la carne, consistencia y apariencia de la carne. Como resultado del tratamiento antioxidante, los peróxidos se degradaron más rápidos (p < 0.05 después del mes 7, y por tanto, contenidos mayores (p < 0.05 de dienos y trienos conjugados pudieron ser detectados en el pescado tratado. El tratamiento antioxidante también condujo a un

  8. Effect of Previous Irradiation on Vascular Thrombosis of Microsurgical Anastomosis: A Preclinical Study in Rats

    Science.gov (United States)

    Gallardo-Calero, Irene; López-Fernández, Alba; Romagosa, Cleofe; Vergés, Ramona; Aguirre-Canyadell, Marius; Soldado, Francisco; Velez, Roberto

    2016-01-01

    Background: The objective of the present investigation was to compare the effect of neoadjuvant irradiation on the microvascular anastomosis in cervical bundle using an experimental model in rats. Methods: One hundred forty male Sprague–Dawley rats were allocated into 4 groups: group I, control, arterial microanastomosis; group II, control, venous microanastomosis; group III, arterial microanastomosis with previous irradiation (20 Gy); and group IV, venous microanastomosis with previous irradiation (20 Gy). Clinical parameters, technical values of anastomosis, patency, and histopathological parameters were evaluated. Results: Irradiated groups (III and IV) and vein anastomosis groups (II and IV) showed significantly increased technical difficulties. Group IV showed significantly reduced patency rates (7/35) when compared with the control group (0/35). Radiotherapy significantly decreased the patency rates of the vein (7/35) when compared with the artery (1/35). Groups III and IV showed significantly reduced number of endothelial cells and also showed the presence of intimal thickening and adventitial fibrosis as compared with the control group. Conclusion: Neoadjuvant radiotherapy reduces the viability of the venous anastomosis in a preclinical rat model with a significant increase in the incidence of vein thrombosis. PMID:27975009

  9. Effects of fluctuating temperature and food availability on reproduction and lifespan.

    Science.gov (United States)

    Schwartz, Tonia S; Pearson, Phillip; Dawson, John; Allison, David B; Gohlke, Julia M

    2016-12-15

    Experimental studies on energetics and aging often remove two major factors that in part regulate the energy budget in a normal healthy individual: reproduction and fluctuating environmental conditions that challenge homeostasis. Here we use the cyclical parthenogenetic Daphnia pulex to evaluate the role of a fluctuating thermal environment on both reproduction and lifespan across six food concentrations. We test the hypotheses that (1) caloric restriction extends lifespan; (2) maximal reproduction will come with a cost of shortened lifespan; and (3) at a given food concentration, relative to a metabolically equivalent constant temperature environment a diel fluctuating thermal environment will alter the allocation of energy to reproduction and lifespan to maintain homeostasis. We did not identify a level of food concentration that extended lifespan in response to caloric restriction, and we found no cost of reproduction in terms of lifespan. Rather, the individuals at the highest food levels generally had the highest reproductive output and the longest lifespans, the individuals at the intermediate food level decreased reproduction and maintained lifespan, and the individuals at the three lower food concentrations had a decrease in reproduction and lifespan as would be predicted with increasing levels of starvation. Fluctuating temperature had no effect on lifespan at any food concentration, but delayed time to reproductive maturity and decreased early reproductive output at all food concentrations. This suggests that a fluctuating temperature regimen activates molecular pathways that alter energy allocation. The costs of fluctuating temperature on reproduction were not consistent across the lifespan. Statistical interactions for age of peak reproduction and lifetime fecundity suggest that senescence of the reproductive system may vary between temperature regimens at the different food concentrations. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Late preterm birth and previous cesarean section: a population-based cohort study.

    Science.gov (United States)

    Yasseen Iii, Abdool S; Bassil, Kate; Sprague, Ann; Urquia, Marcelo; Maguire, Jonathon L

    2018-02-21

    Late preterm birth (LPB) is increasingly common and associated with higher morbidity and mortality than term birth. Yet, little is known about the influence of previous cesarean section (PCS) and the occurrence of LPB in subsequent pregnancies. We aim to evaluate this association along with the potential mediation by cesarean sections in the current pregnancy. We use population-based birth registry data (2005-2012) to establish a cohort of live born singleton infants born between 34 and 41 gestational weeks to multiparous mothers. PCS was the primary exposure, LPB (34-36 weeks) was the primary outcome, and an unplanned or emergency cesarean section in the current pregnancy was the potential mediator. Associations were quantified using propensity weighted multivariable Poisson regression, and mediating associations were explored using the Baron-Kenny approach. The cohort included 481,531 births, 21,893 (4.5%) were LPB, and 119,983 (24.9%) were predated by at least one PCS. Among mothers with at least one PCS, 6307 (5.26%) were LPB. There was increased risk of LPB among women with at least one PCS (adjusted Relative Risk (aRR): 1.20 (95%CI [1.16, 1.23]). Unplanned or emergency cesarean section in the current pregnancy was identified as a strong mediator to this relationship (mediation ratio = 97%). PCS was associated with higher risk of LPB in subsequent pregnancies. This may be due to an increased risk of subsequent unplanned or emergency preterm cesarean sections. Efforts to minimize index cesarean sections may reduce the risk of LPB in subsequent pregnancies.

  11. What happens when we compare the lifespan distributions of life script events and autobiographical memories of life story events? A cross-cultural study

    DEFF Research Database (Denmark)

    Zaragoza Scherman, Alejandra; Salgado, Sinué; Shao, Zhifang

    Cultural Life Script Theory (Berntsen and Rubin, 2004), provides a cultural explanation of the reminiscence bump: adults older than 40 years remember a significantly greater amount of life events happening between 15 - 30 years of age (Rubin, Rahal, & Poon, 1998), compared to other lifetime periods....... Most of these memories are rated as emotionally positive (Rubin & Berntsen, 2003). The cultural life script represents culturally shared expectations about the order and timing of life events in an typical, idealised life course. By comparing the lifespan distribution of the life scripts events...... and memories of life story events, we can determine the degree to which the cultural life script serves as a recall template for autobiographical memories, especially of positive life events from adolescence and early adulthood, also known as the reminiscence bump period....

  12. Modality Differences in Timing and Temporal Memory throughout the Lifespan

    Science.gov (United States)

    Lustig, Cindy; Meck, Warren H.

    2011-01-01

    The perception of time is heavily influenced by attention and memory, both of which change over the lifespan. In the current study, children (8 yrs), young adults (18-25 yrs), and older adults (60-75 yrs) were tested on a duration bisection procedure using 3 and 6-s auditory and visual signals as anchor durations. During test, participants were…

  13. Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1.

    Science.gov (United States)

    Smith, Matthew; De Bono, Johann; Sternberg, Cora; Le Moulec, Sylvestre; Oudard, Stéphane; De Giorgi, Ugo; Krainer, Michael; Bergman, Andries; Hoelzer, Wolfgang; De Wit, Ronald; Bögemann, Martin; Saad, Fred; Cruciani, Giorgio; Thiery-Vuillemin, Antoine; Feyerabend, Susan; Miller, Kurt; Houédé, Nadine; Hussain, Syed; Lam, Elaine; Polikoff, Jonathan; Stenzl, Arnulf; Mainwaring, Paul; Ramies, David; Hessel, Colin; Weitzman, Aaron; Fizazi, Karim

    2016-09-01

    Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments. A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post-random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively). Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes. © 2016 by

  14. Radon diffusion coefficients for soils. Previous studies and their application to uranium-bearing wastes

    International Nuclear Information System (INIS)

    Sasaki, Tomozo; Gunji, Yasuyoshi; Iida, Takao

    2008-01-01

    Radon diffusion in soils has been studied over the years by many researchers. The application of such studies to the evaluation of radiation exposure caused by radon from uranium-bearing wastes disposed in a shallow land site is very important. The present paper surveyed closely relevant studies and elucidated the inherent nature of radon diffusion in terms of the definition of radon diffusion coefficients. Then, basic features of measurement methods for determining radon diffusion coefficients in soils were explained. Furthermore, theoretical aspects of radon diffusion in soils were discussed in terms of microscopic radon diffusion in soils and large-scale radon diffusion through cover soil defects for uranium mill tailings. Finally, in order to apply the radon diffusion studies to uranium-bearing waste disposal in shallow land sites, new challenges were presented: elucidation of radon diffusion in uranium-bearing wastes and cover-soil cracks, and demonstration of the validity of applying only radon diffusion in the evaluation of radiation exposure caused by radon, which would come through Japanese cover soils for uranium-bearing waste disposal. (author)

  15. Interbirth interval and history of previous preeclampsia: a case–control study among multiparous women

    OpenAIRE

    Harutyunyan, Arusyak; Armenian, Haroutune; Petrosyan, Varduhi

    2013-01-01

    Abstract Background Preeclampsia is a disorder with a reported incidence of 2%-8% among all pregnancies, accounting for more than 50,000 deaths worldwide each year. In low- and middle- income countries maternal/perinatal morbidity and mortality associated with preeclampsia are high due to the lack of proper prenatal and hospital care and limited access to neonatal intensive care. The objectives of our study were to determine the association of long in...

  16. A Review of Previous Studies on Information Processing in Career Decision Making among University Students

    OpenAIRE

    池田, 智子; Satoko, Ikeda

    2018-01-01

    This review of the researches of career choice of Japanese university students focused the studies on decision-making theory conducted in Japan. The present review suggested the necessity of examination of the effect of self-efficacy about career information search on the process of career choice. It is also needed to examine the relationship between specific self-efficacy about career information search and career decision-making self-efficacy, moreover, general self-efficacy.

  17. A Comment Upon Previous Studies on 3-D Boundary Layer Transition

    OpenAIRE

    ÇARPINLIOĞLU, Melda Özdinç

    2014-01-01

    The common feature of the experimental studies upon 3-D boundary layer development on swept flat plates cited in the available literature is the application of streamwise and/or spanwise pressure gradients. In fact; presence of the pressure gradients was suggested to be vital for having crossflow effective in 3-D boundary layer transition. In the presented paper here, this idea is questioned evaluating the results of an experimental investigation conducted on swept flat plates under the ab...

  18. Neuropsychiatric and cardiometabolic comorbidities in patients with previously diagnosed Cushing's disease: a longitudinal observational study

    OpenAIRE

    Dimopoulou, C; Geraedts, V; Stalla, G K; Sievers, C

    2015-01-01

    INTRODUCTION: Only few studies have systematically investigated neuropsychiatric aspects in patients with Cushing's disease (CD). Pain syndromes have been described in patients with pituitary adenomas, but so far no systematical investigation has been conducted in patients with CD. Additionally, CD has an association with cardiometabolic comorbidities which ultimately leads to increased morbidity and mortality. Long-term treatment of the hypercortisolic state cannot prevent the persistence of...

  19. A New Zealand based cohort study of anaesthetic trainees' career outcomes compared with previously expressed intentions.

    Science.gov (United States)

    Moran, E M L; French, R A; Kennedy, R R

    2011-09-01

    Predicting workforce requirements is a difficult but necessary part of health resource planning. A 'snapshot' workforce survey undertaken in 2002 examined issues that New Zealand anaesthesia trainees expected would influence their choice of future workplace. We have restudied the same cohort to see if that workforce survey was a good predictor of outcome. Seventy (51%) of 138 surveys were completed in 2009 compared with 100 (80%) of 138 in the 2002 survey. Eighty percent of the 2002 respondents planned consultant positions in New Zealand. We found 64% of respondents were working in New Zealand (P New Zealand based respondents but only 40% of those living outside New Zealand agreed or strongly agreed with this statement (P New Zealand but was important for only 2% of those resident in New Zealand (P New Zealand were predominantly between NZ$150,000 and $200,000 while those overseas received between NZ$300,000 and $400,000. Of those that are resident in New Zealand, 84% had studied in a New Zealand medical school compared with 52% of those currently working overseas (P < 0.01). Our study shows that stated career intentions in a group do not predict the actual group outcomes. We suggest that 'snapshot' studies examining workforce intentions are of little value for workforce planning. However we believe an ongoing program matching career aspirations against career outcomes would be a useful tool in workforce planning.

  20. Towards a unified analysis of brain maturation and aging across the entire lifespan: A MRI analysis.

    Science.gov (United States)

    Coupé, Pierrick; Catheline, Gwenaelle; Lanuza, Enrique; Manjón, José Vicente

    2017-11-01

    There is no consensus in literature about lifespan brain maturation and senescence, mainly because previous lifespan studies have been performed on restricted age periods and/or with a limited number of scans, making results instable and their comparison very difficult. Moreover, the use of nonharmonized tools and different volumetric measurements lead to a great discrepancy in reported results. Thanks to the new paradigm of BigData sharing in neuroimaging and the last advances in image processing enabling to process baby as well as elderly scans with the same tool, new insights on brain maturation and aging can be obtained. This study presents brain volume trajectory over the entire lifespan using the largest age range to date (from few months of life to elderly) and one of the largest number of subjects (N = 2,944). First, we found that white matter trajectory based on absolute and normalized volumes follows an inverted U-shape with a maturation peak around middle life. Second, we found that from 1 to 8-10 y there is an absolute gray matter (GM) increase related to body growth followed by a GM decrease. However, when normalized volumes were considered, GM continuously decreases all along the life. Finally, we found that this observation holds for almost all the considered subcortical structures except for amygdala which is rather stable and hippocampus which exhibits an inverted U-shape with a longer maturation period. By revealing the entire brain trajectory picture, a consensus can be drawn since most of the previously discussed discrepancies can be explained. Hum Brain Mapp 38:5501-5518, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Life cycle impact assessment of ammonia production in Algeria: A comparison with previous studies

    Energy Technology Data Exchange (ETDEWEB)

    Makhlouf, Ali, E-mail: almakhsme@gmail.com; Serradj, Tayeb; Cheniti, Hamza

    2015-01-15

    In this paper, a Life Cycle Analysis (LCA) from “cradle to gate” of one anhydrous ton of ammonia with a purity of 99% was achieved. Particularly, the energy and environmental performance of the product (ammonia) were evaluated. The eco-profile of the product and the share of each stage of the Life Cycle on the whole environmental impacts have been evaluated. The flows of material and energy for each phase of the life cycle were counted and the associated environmental problems were identified. Evaluation of the impact was achieved using GEMIS 4.7 software. The primary data collection was executed at the production installations located in Algeria (Annaba locality). The analysis was conducted according to the LCA standards ISO 14040 series. The results show that Cumulative Energy Requirement (CER) is of 51.945 × 10{sup 3} MJ/t of ammonia, which is higher than the global average. Global Warming Potential (GWP) is of 1.44 t CO{sub 2} eq/t of ammonia; this value is lower than the world average. Tropospheric ozone precursor and Acidification are also studied in this article, their values are: 549.3 × 10{sup −6} t NMVOC eq and 259.3 × 10{sup −6} t SO{sub 2} eq respectively.

  2. Life cycle impact assessment of ammonia production in Algeria: A comparison with previous studies

    International Nuclear Information System (INIS)

    Makhlouf, Ali; Serradj, Tayeb; Cheniti, Hamza

    2015-01-01

    In this paper, a Life Cycle Analysis (LCA) from “cradle to gate” of one anhydrous ton of ammonia with a purity of 99% was achieved. Particularly, the energy and environmental performance of the product (ammonia) were evaluated. The eco-profile of the product and the share of each stage of the Life Cycle on the whole environmental impacts have been evaluated. The flows of material and energy for each phase of the life cycle were counted and the associated environmental problems were identified. Evaluation of the impact was achieved using GEMIS 4.7 software. The primary data collection was executed at the production installations located in Algeria (Annaba locality). The analysis was conducted according to the LCA standards ISO 14040 series. The results show that Cumulative Energy Requirement (CER) is of 51.945 × 10 3 MJ/t of ammonia, which is higher than the global average. Global Warming Potential (GWP) is of 1.44 t CO 2 eq/t of ammonia; this value is lower than the world average. Tropospheric ozone precursor and Acidification are also studied in this article, their values are: 549.3 × 10 −6 t NMVOC eq and 259.3 × 10 −6 t SO 2 eq respectively

  3. Nitrogen Ion Form and Spatio-temporal Variation in Root Distribution Mediate Nitrogen Effects on Lifespan of Ectomycorrhizal Roots

    Science.gov (United States)

    Kou, L.; McCormack, M. L.; Chen, W.; Guo, D.; Wang, H.; Li, S.; Gao, W.; Yang, H.

    2017-12-01

    Background and Aims Absorptive roots active in soil resource uptake are often intimately associated with mycorrhizal fungi, yet it remains unclear how nitrogen (N) loading affects lifespan of absorptive roots associating with ectomycorrhizal (ECM) fungi. Methods Through a three-year minirhizotron experiment, we investigated the responses of ECM lifespan to different rates of N addition and examined the roles of N ion form, rooting depth, seasonal root cohort, and ECM morphotype in mediating the N effects on ECM lifespan in a slash pine (Pinus elliottii) forest in subtropical China. Results High rates of NH4Cl significantly decreased foliar P concentrations and increased foliar N: P ratios, and mean ECM lifespan was negatively correlated to foliar P concentration. N additions generally increased the lifespan of most ectomycorrhizas, but the specific differences were context dependent. N rates and forms exerted significant positive effects on ECM lifespan with stronger effects occurring at high N rates and under ammonium N addition. N additions extended lifespan of ectomycorrhizas in shallower soil and born in spring and autumn, but shortened lifespan of ectomycorrhizas in deeper soil and born in summer and winter. N additions reduced lifespan of dichotomous ectomycorrhizas, but increased lifespan of coralloid ectomycorrhizas. Conclusions The increased ECM lifespan in response to N additions may primarily be driven by the persistent and aggravated P limitation to plants. Our findings highlight the importance of environmental contexts in controlling ECM lifespan and the need to consider potential differences among mycorrhizal morphotypes when studying N—lifespan relationships of absorptive roots in the context of N deposition.

  4. Ifosfamide in previously untreated disseminated neuroblastoma. Results of Study 3A of the European Neuroblastoma Study Group.

    Science.gov (United States)

    Kellie, S J; De Kraker, J; Lilleyman, J S; Bowman, A; Pritchard, J

    1988-05-01

    A prospective study of the effectiveness of ifosfamide as a single agent in the management of previously untreated patients with Evans stage IV neuroblastoma was undertaken. Eighteen children aged more than 1 year were treated with ifosfamide (IFX) 3 g/m2 daily for 2 days immediately after diagnosis and 3 weeks later. Treatment was continued with combination chemotherapy using vincristine, cyclophosphamide, cisplatinum and etoposide (OPEC) or a variant. Mesna (2-mercaptoethane sulphonate) was given to all patients during IFX treatment to prevent urotoxicity. Eight of the 18 patients (44%) responded to IFX. Nine had greater than 66% reduction in baseline tumor volume. Of 15 evaluable patients with raised pre-treatment urinary catecholamine excretion, six (40%) achieved greater than 50% reduction in pretreatment levels. Two of 10 patients evaluable for bone marrow response had complete clearance. Toxicity was mild in all patients. Upon completing 'first line' therapy, only four patients (22%) achieved a good partial remission (GPR) or complete response (CR). Median survival was 11 months. There was a lower rate of attaining GPR and shortened median survival in patients receiving phase II IFX before OPEC or variant, compared to patients with similar pre-treatment characteristics treated with OPEC from diagnosis in an earlier study.

  5. Lifespan development of attentiveness in domestic dogs: drawing parallels with humans

    Directory of Open Access Journals (Sweden)

    Lisa Jessica Wallis

    2014-02-01

    Full Text Available Attention is pivotal to consciousness, perception, cognition, and working memory in all mammals, and therefore changes in attention over the lifespan are likely to influence development and aging of all of these functions. Due to their evolutionary and developmental history, the dog is being recognised as an important species for modelling human healthspan, aging and associated diseases. In this study, we investigated the normal lifespan development of attentiveness of pet dogs in naturalistic situations, and compared the resulting cross-sectional developmental trajectories with data from previous studies in humans. We tested a sample of 145 Border collies (six months to 14 years with humans and objects or food as attention attractors, in order to assess their attentional capture, sustained and selective attention and sensorimotor abilities. Our results reveal differences in task relevance in sustained attentional performance when watching a human or a moving object, which may be explained by life-long learning processes involving such stimuli. During task-switching we found that dogs’ selective attention and sensorimotor abilities showed differences between age groups, with performance peaking at middle age. Dogs’ sensorimotor abilities showed a quadratic distribution with age and were correlated with selective attention performance. Our results support the hypothesis that the development and senescence of sensorimotor and attentional control may be fundamentally interrelated. Additionally, attentional capture, sustained attention and sensorimotor control developmental trajectories paralleled those found in humans. Given that the development of attention is similar across humans and dogs, we propose that the same regulatory mechanisms are likely to be present in both species. Finally, this cross-sectional study provides the first description of age group changes in attention over the lifespan of pet dogs.

  6. Obesity and Lifespan Health—Importance of the Fetal Environment

    Directory of Open Access Journals (Sweden)

    Alice F. Tarantal

    2014-04-01

    Full Text Available A marked increase in the frequency of obesity at the population level has resulted in an increasing number of obese women entering pregnancy. The increasing realization of the importance of the fetal environment in relation to chronic disease across the lifespan has focused attention on the role of maternal obesity in fetal development. Previous studies have demonstrated that obesity during adolescence and adulthood can be traced back to fetal and early childhood exposures. This review focuses on factors that contribute to early developmental events, such as epigenetic modifications, the potential for an increase in inflammatory burden, early developmental programming changes such as the variable development of white versus brown adipose tissue, and alterations in organ ontogeny. We hypothesize that these mechanisms promote an unfavorable fetal environment and can have a long-standing impact, with early manifestations of chronic disease that can result in an increased demand for future health care. In order to identify appropriate preventive measures, attention needs to be placed both on reducing maternal obesity as well as understanding the molecular, cellular, and epigenetic mechanisms that may be responsible for the prenatal onset of chronic disease.

  7. The LIFEspan model of transitional rehabilitative care for youth with disabilities: healthcare professionals' perspectives on service delivery.

    Science.gov (United States)

    Hamdani, Yani; Proulx, Meghann; Kingsnorth, Shauna; Lindsay, Sally; Maxwell, Joanne; Colantonio, Angela; Macarthur, Colin; Bayley, Mark

    2014-01-01

    LIFEspan is a service delivery model of continuous coordinated care developed and implemented by a cross-organization partnership between a pediatric and an adult rehabilitation hospital. Previous work explored enablers and barriers to establishing the partnership service. This paper examines healthcare professionals' (HCPs') experiences of 'real world' service delivery aimed at supporting transitional rehabilitative care for youth with disabilities. This qualitative study - part of an ongoing mixed method longitudinal study - elicited HCPs' perspectives on their experiences of LIFEspan service delivery through in-depth interviews. Data were categorized into themes of service delivery activities, then interpreted from the lens of a service integration/coordination framework. Five main service delivery themes were identified: 1) addressing youth's transition readiness and capacities; 2) shifting responsibility for healthcare management from parents to youth; 3) determining services based on organizational resources; 4) linking between pediatric and adult rehabilitation services; and, 5) linking with multi-sector services. LIFEspan contributed to service delivery activities that coordinated care for youth and families and integrated inter-hospital services. However, gaps in service integration with primary care, education, social, and community services limited coordinated care to the rehabilitation sector. Recommendations are made to enhance service delivery using a systems/sector-based approach.

  8. Sorbitol treatment extends lifespan and induces the osmotic stress response in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Devon eChandler-Brown

    2015-10-01

    Full Text Available The response to osmotic stress is a highly conserved process for adapting to changing environmental conditions. Prior studies have shown that hyperosmolarity by addition of sorbitol to the growth medium is sufficient to increase both chronological and replicative lifespan in the budding yeast, Saccharomyces cerevisiae. Here we report a similar phenomenon in the nematode Caenorhabditis elegans. Addition of sorbitol to the nematode growth medium induces an adaptive osmotic response and increases C. elegans lifespan by about 35%. Lifespan extension from 5% sorbitol behaves similarly to dietary restriction in a variety of genetic backgrounds, increasing lifespan additively with mutation of daf-2(e1370 and independently of daf-16(mu86, sir-2.1(ok434, aak-2(ok524, and hif-1(ia04. Dietary restriction by bacterial deprivation or mutation of eat-2(ad1113 fails to further extend lifespan in the presence of 5% sorbitol. Two mutants with constitutive activation of the osmotic response, osm-5(p813 and osm-7(n1515, were found to be long-lived, and lifespan extension from sorbitol required the glycerol biosynthetic enzymes GPDH-1 and GPDH-2. Taken together, these observations demonstrate that exposure to sorbitol at levels sufficient to induce an adaptive osmotic response extends lifespan in worms and define the osmotic stress response pathway as a longevity pathway conserved between yeast and nematodes.

  9. Estimating the effect of current, previous and never use of drugs in studies based on prescription registries

    DEFF Research Database (Denmark)

    Nielsen, Lars Hougaard; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    of this misclassification for analysing the risk of breast cancer. MATERIALS AND METHODS: Prescription data were obtained from Danish Registry of Medicinal Products Statistics and we applied various methods to approximate treatment episodes. We analysed the duration of HT episodes to study the ability to identify......PURPOSE: Many studies which investigate the effect of drugs categorize the exposure variable into never, current, and previous use of the study drug. When prescription registries are used to make this categorization, the exposure variable possibly gets misclassified since the registries do...... not carry any information on the time of discontinuation of treatment.In this study, we investigated the amount of misclassification of exposure (never, current, previous use) to hormone therapy (HT) when the exposure variable was based on prescription data. Furthermore, we evaluated the significance...

  10. An fMRI study of neuronal activation in schizophrenia patients with and without previous cannabis use

    Directory of Open Access Journals (Sweden)

    Else-Marie eLøberg

    2012-10-01

    Full Text Available Previous studies have mostly shown positive effects of cannabis use on cognition in patients with schizophrenia, which could reflect lower neurocognitive vulnerability. There are however no studies comparing whether such cognitive differences have neuronal correlates. Thus, the aim of the present study was to compare whether patients with previous cannabis use differ in brain activation from patients who has never used cannabis. The patients groups were compared on the ability to up-regulate an effort mode network during a cognitive task and down-regulate activation in the same network during a task-absent condition. Task-present and task-absent brain activation was measured by functional magnetic resonance neuroimaging (fMRI. Twenty-six patients with a DSM-IV and ICD-10 diagnosis of schizophrenia were grouped into a previous cannabis user group and a no-cannabis group. An auditory dichotic listening task with instructions of attention focus on either the right or left ear stimulus was used to tap verbal processing, attention and cognitive control, calculated as an aggregate score. When comparing the two groups, there were remaining activations in the task-present condition for the cannabis group, not seen in the no-cannabis group, while there was remaining activation in the task-absent condition for the no-cannabis group, not seen in the cannabis group. Thus, the patients with previous cannabis use showed increased activation in an effort mode network and decreased activation in the default mode network as compared to the no-cannabis group. It is concluded that the present study show some differences in brain activation to a cognitively challenging task between previous cannabis and no-cannabis schizophrenia patients.

  11. Shortened Lifespan and Lethal Hemorrhage in a Hemophilia A Mouse Model.

    Science.gov (United States)

    Staber, Janice M; Pollpeter, Molly J

    2016-01-01

    Hemophilia A animal models have helped advance our understanding of factor VIII deficiency. Previously, factor VIII deficient mouse models were reported to have a normal life span without spontaneous bleeds. However, the bleeding frequency and survival in these animals has not been thoroughly evaluated. To investigate the survival and lethal bleeding frequency in two strains of E-16 hemophilia A mice. We prospectively studied factor VIII deficient hemizygous affected males (n = 83) and homozygous affected females (n = 55) for survival and bleeding frequency. Animals were evaluated for presence and location of bleeds as potential cause of death. Hemophilia A mice had a median survival of 254 days, which is significantly shortened compared to wild type controls (p hemophilia A mice experienced hemorrhage in several tissues. This previously-underappreciated shortened survival in the hemophilia A murine model provides new outcomes for investigation of therapeutics and also reflects the shortened lifespan of patients if left untreated.

  12. Piceatannol extends the lifespan of Caenorhabditis elegans via DAF-16.

    Science.gov (United States)

    Shen, Peiyi; Yue, Yiren; Sun, Quancai; Kasireddy, Nandita; Kim, Kee-Hong; Park, Yeonhwa

    2017-05-06

    Piceatannol is a natural stilbene with many beneficial effects, such as antioxidative, anti-inflammatory, antiatherogenic activities; however, its role on aging is not known. In this study, we used Caenorhabditis elegans as an animal model to study the effect of piceatannol on its lifespan and investigated the underlying mechanisms. The results showed that 50 and 100 µM piceatannol significantly extended the lifespan of C. elegans without altering the growth rate, worm size and progeny production. Piceatannol delayed the age-related decline of pumping rate and locomotive activity, and protected the worms from heat and oxidative stress. This study further indicated that lifespan extension and enhanced stress resistance induced by piceatannol requires DAF-16. Since DAF-16 is conserved from nematodes to mammals, our study may have important implications in utilizing piceatannol to promote healthy aging and combat age-related disease in humans. © 2016 BioFactors, 43(3):379-387, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  13. Epigenetic variation during the adult lifespan

    DEFF Research Database (Denmark)

    Talens, Rudolf P; Christensen, Kaare; Putter, Hein

    2012-01-01

    The accumulation of epigenetic changes was proposed to contribute to the age-related increase in the risk of most common diseases. In this study on 230 monozygotic twin pairs (MZ pairs), aged 18-89 years, we investigated the occurrence of epigenetic changes over the adult lifespan. Using mass...... individuals, ranging from 1.2-fold larger at ABCA1 (P = 0.010) to 1.6-fold larger at INS (P = 3.7 × 10(-07) ). Similarly, there was more within-MZ-pair discordance in old as compared with young MZ pairs, except for GNASAS, ranging from an 8% increase in discordance each decade at CRH (P = 8.9 × 10...... spectrometry, we investigated variation in global (LINE1) DNA methylation and in DNA methylation at INS, KCNQ1OT1, IGF2, GNASAS, ABCA1, LEP, and CRH, candidate loci for common diseases. Except for KCNQ1OT1, interindividual variation in locus-specific DNA methylation was larger in old individuals than in young...

  14. Effect of gamma irradiation on lifespan and offspring physiology of male drosophila melanogaster

    International Nuclear Information System (INIS)

    Hou Jiangyu; Gu Wei; Jiang Fangping; Han Hetong

    2010-01-01

    This study aimed to investigate the effects of γ-rays irradiation on adult longevity and physiological changes in F 1 generation.Male Drosophila melanogaster at 1 ∼ 2 days old were irradiated by γ-rays with doses of 5, 10, 15 and 30 Gy. In all experimental groups, mean lifespan, maximum lifespan and 90% of lethaldeath irradiated flies were reduced(at P 1 generation of irradiated group, body weight increased, but the capacity of physiological stress declined. (authors)

  15. Effects of fluctuating temperature and food availability on reproduction and lifespan

    OpenAIRE

    Schwartz, Tonia S.; Pearson, Phillip; Dawson, John; Allison, David B.; Gohlke, Julia M.

    2016-01-01

    Experimental studies on energetics and aging often remove two major factors that in part regulate the energy budget in a normal healthy individual: reproduction and fluctuating environmental conditions that challenge homeostasis. Here we use the cyclical parthenogenetic Daphnia pulex to evaluate the role of a fluctuating thermal environment on both reproduction and lifespan across six food concentrations. We test the hypotheses that (1) caloric restriction extends lifespan; (2) maximal reprod...

  16. Parametric and non-parametric models for lifespan modeling of insulation systems in electrical machines

    OpenAIRE

    Salameh , Farah; Picot , Antoine; Chabert , Marie; Maussion , Pascal

    2017-01-01

    International audience; This paper describes an original statistical approach for the lifespan modeling of electric machine insulation materials. The presented models aim to study the effect of three main stress factors (voltage, frequency and temperature) and their interactions on the insulation lifespan. The proposed methodology is applied to two different insulation materials tested in partial discharge regime. Accelerated ageing tests are organized according to experimental optimization m...

  17. Beat Synchronization across the Lifespan: Intersection of Development and Musical Experience.

    Directory of Open Access Journals (Sweden)

    Elaine C Thompson

    Full Text Available Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance of synchronization in childhood through older adulthood in a large cohort of participants (N = 145, and also ask how it may be altered by musical experience. We employed a uniform assessment of beat synchronization for all participants and compared performance developmentally and between individuals with and without musical experience. We show that the ability to consistently tap along to a beat improves with age into adulthood, yet in older adulthood tapping performance becomes more variable. Also, from childhood into young adulthood, individuals are able to tap increasingly close to the beat (i.e., asynchronies decline with age, however, this trend reverses from younger into older adulthood. There is a positive association between proportion of life spent playing music and tapping performance, which suggests a link between musical experience and auditory-motor integration. These results are broadly consistent with previous investigations into the development of beat synchronization across the lifespan, and thus complement existing studies and present new insights offered by a different, large cross-sectional sample.

  18. Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

    OpenAIRE

    Augustin, A.J.; Kuppermann, B.D.; Lanzetta, P.; Loewenstein, A.; Li, X.; Cui, H.; Hashad, Y.; Whitcup, S.M.; Abujamra, S.; Acton, J.; Ali, F.; Antoszyk, A.; Awh, C.C.; Barak, A.; Bartz-Schmidt, K.U.

    2015-01-01

    Background Dexamethasone intravitreal implant 0.7?mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34?68 Early Treatment...

  19. Pomegranate juice enhances healthy lifespan in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Padmavathy eVenkatasubramanian

    2014-12-01

    Full Text Available Exploring innovative ways to ensure healthy ageing of populations is a pre-requisite to contain rising healthcare costs. Scientific research into the principles and practices of traditional medicines can provide new insights and simple solutions to lead a healthy life. Rasayana is a dedicated branch of Ayurveda (an Indian medicine that deals with methods to increase vitality and delay aging through the use of diet, herbal supplements and other lifestyle practices. The life-span and health-span enhancing actions of the fruits of Pomegranate (Punica granatum L., a well-known Rasayana, were tested on Drosophila melanogaster (fruitfly model. Supplementation of standard corn meal with 10% (v/v pomegranate juice (PJ extended the life-span of male and female flies by 18% and 8% respectively. When male and female flies were mixed and reared together, there was 19% increase in the longevity of PJ fed flies, as assessed by MSD, the median survival day (24.8. MSD for control and resveratrol (RV groups was at 20.8 and 23.1 days respectively. A two-fold enhancement in fecundity, improved resistance to oxidative stress (H2O2 and paraquat induced and to Candida albicans infection were observed in PJ fed flies. Further, the flies in the PJ fed group were physically active over an extended period of time, as assessed by the climbing assay. PJ thus outperformed both control and RV groups in the life-span and health-span parameters tested. This study provides the scope to explore the potential of PJ as a nutraceutical to improve health span and lifespan in humans.

  20. Association between duration of reproductive lifespan and Framingham risk score in postmenopausal women.

    Science.gov (United States)

    Kim, Soo Hyun; Sim, Mu Yul; Park, Sat Byul

    2015-12-01

    The benefit of estrogen therapy in postmenopausal women is still uncertain. Based upon extensive observational data, it was believed that estrogen was cardioprotective. The relationship between the period of exposure to endogenous estrogens and the risk of cardiovascular disease (CVD) has not been studied in Korean women. To assess associations between reproductive lifespan and CVD by using the Framingham risk score (FRS) in postmenopausal Korean women. This cross-sectional, population-based study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) for the five years 2008-2012,after adjustment for relevant variables using complex sample analysis and data weighting. Among 25,534 women, 1973 women were enrolled, after excluding those 80 years of age (n=6194), those with diabetes, CVD or cancer (n=491), those with unrecorded physical measurements (n=7335), those with menarche age ≤8 years or ≥20 years (n=6194), and premenopausal women (n=3347). The FRS tended to show a significant negative correlation with the reproductive lifespan (preproductive lifespan and FRS (adjusted relative risk [RR] for reproductive years [shortest lifespan group] compared with 28-33 reproductive years [moderate lifespan group], 1.2, p33 reproductive years [longest lifespan group] compared with 28-33 reproductive years [moderate lifespan group], -0.42, p=0.011). A longer reproductive lifespan is associated with a lower estimated risk of CVD in the next 10 years in postmenopausal women. This result suggests that estrogen has a long-term protective effect against CVD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Youth suicide: an insight into previous hospitalisation for injury and sociodemographic conditions from a nationwide cohort study.

    Science.gov (United States)

    Zambon, Francesco; Laflamme, Lucie; Spolaore, Paolo; Visentin, Cristiana; Hasselberg, Marie

    2011-06-01

    This study investigates the degree to which a previous hospitalisation for injury of any intent is a risk of subsequent youth suicide and whether this association is influenced by family socioeconomic status or economic stress. A nationwide register-based cohort study was conducted covering all Swedish subjects born between January 1977 and December 1991 (N=1,616,342, male/female ratio=1.05). The cohort subjects were followed-up from January 1998 to December 2003, when aged 7-26 years. Poisson regression and the likelihood ratio test (95% CI) were used to assess the age-adjusted effect of hospitalisation for injuries of various intent on youth suicide and its effect once adjusted for family sociodemographic and social circumstances. Each set of exposures was associated independently and significantly with suicide mortality. Being hospitalised for self-inflicted injuries or injuries of undetermined intent was associated with a risk of suicide 36 to 47 times, respectively, that of subjects never hospitalised in the period under study (95% CI 28.36 to 45.58 and 26.67 to 83.87 for self-inflicted injuries and for events of undetermined intent, respectively; overall psuicide (RR 3.08; 95% CI 2.26 to 4.19). These effects were solid and not substantially altered after adjustment for family demographic and socioeconomic circumstances. A strong association exists between previous hospitalisation for injury of any intent and youth suicide. The association is robust and unaltered by family socioeconomic circumstances.

  2. COCOA (Theobroma cacao) Polyphenol-Rich Extract Increases the Chronological Lifespan of Saccharomyces cerevisiae.

    Science.gov (United States)

    Baiges, I; Arola, L

    2016-01-01

    BACKGROUND: Saccharomyces cerevisiae is a model organism with conserved aging pathways. Yeast chronological lifespan experiments mimic the processes involved in human non-dividing tissues, such as the nervous system or skeletal muscle, and can speed up the search for biomolecules with potential anti-aging effects before proceeding to animal studies. OBJECTIVE: To test the effectiveness of a cocoa polyphenol-rich extract (CPE) in expanding the S. cerevisiae chronological lifespan in two conditions: in the stationary phase reached after glucose depletion and under severe caloric restriction. MEASUREMENTS: Using a high-throughput method, wild-type S. cerevisiae and its mitochondrial manganese-dependent superoxide dismutase null mutant (sod2Δ) were cultured in synthetic complete dextrose medium. After 2 days, 0, 5 and 20 mg/ml of CPE were added, and viability was measured throughout the stationary phase. The effects of the major components of CPE were also evaluated. To determine yeast lifespan under severe caloric restriction conditions, cultures were washed with water 24 h after the addition of 0 and 20 mg/ml of CPE, and viability was followed over time. RESULTS : CPE increased the chronological lifespan of S. cerevisiae during the stationary phase in a dose-dependent manner. A similar increase was also observed in (sod2Δ). None of the major CPE components (theobromine, caffeine, maltodextrin, (-)-epicatechin, (+)-catechin and procyanidin B2) was able to increase the yeast lifespan. CPE further increased the yeast lifespan under severe caloric restriction. CONCLUSION: CPE increases the chronological lifespan of S. cerevisiae through a SOD2-independent mechanism. The extract also extends yeast lifespan under severe caloric restriction conditions. The high-throughput assay used makes it possible to simply and rapidly test the efficacy of a large number of compounds on yeast aging, requiring only small amounts, and is thus a convenient screening assay to accelerate

  3. Previous Fractures at Multiple Sites Increase the Risk for Subsequent Fractures: The Global Longitudinal Study of Osteoporosis in Women

    Science.gov (United States)

    Gehlbach, Stephen; Saag, Kenneth G.; Adachi, Jonathan D.; Hooven, Fred H.; Flahive, Julie; Boonen, Steven; Chapurlat, Roland D.; Compston, Juliet E.; Cooper, Cyrus; Díez-Perez, Adolfo; Greenspan, Susan L.; LaCroix, Andrea Z.; Netelenbos, J. Coen; Pfeilschifter, Johannes; Rossini, Maurizio; Roux, Christian; Sambrook, Philip N.; Silverman, Stuart; Siris, Ethel S.; Watts, Nelson B.; Lindsay, Robert

    2016-01-01

    Previous fractures of the hip, spine, or wrist are well-recognized predictors of future fracture, but the role of other fracture sites is less clear. We sought to assess the relationship between prior fracture at 10 skeletal locations and incident fracture. The Global Longitudinal Study of Osteoporosis in Women (GLOW) is an observational cohort study being conducted in 17 physician practices in 10 countries. Women ≥ 55 years answered questionnaires at baseline and at 1 and/or 2 years (fractures in previous year). Of 60,393 women enrolled, follow-up data were available for 51,762. Of these, 17.6%, 4.0%, and 1.6% had suffered 1, 2, or ≥3 fractures since age 45. During the first 2 years of follow-up, 3149 women suffered 3683 incident fractures. Compared with women with no prior fractures, women with 1, 2, or ≥ 3 prior fractures were 1.8-, 3.0-, and 4.8-fold more likely to have any incident fracture; those with ≥3 prior fractures were 9.1-fold more likely to sustain a new vertebral fracture. Nine of 10 prior fracture locations were associated with an incident fracture. The strongest predictors of incident spine and hip fractures were prior spine fracture (hazard ratio 7.3) and hip (hazard ratio 3.5). Prior rib fractures were associated with a 2.3-fold risk of subsequent vertebral fracture, previous upper leg fracture predicted a 2.2-fold increased risk of hip fracture; women with a history of ankle fracture were at 1.8-fold risk of future fracture of a weight-bearing bone. Our findings suggest that a broad range of prior fracture sites are associated with an increased risk of incident fractures, with important implications for clinical assessments and risk model development. PMID:22113888

  4. Previous experiences and emotional baggage as barriers to lifestyle change - a qualitative study of Norwegian Healthy Life Centre participants.

    Science.gov (United States)

    Følling, Ingrid S; Solbjør, Marit; Helvik, Anne-S

    2015-06-23

    Changing lifestyle is challenging and difficult. The Norwegian Directorate of Health recommends that all municipalities establish Healthy Life Centres targeted to people with lifestyle issues. Little is known about the background, experiences and reflections of participants. More information is needed about participants to shape effective lifestyle interventions with lasting effect. This study explores how participants in a lifestyle intervention programme describe previous life experiences in relation to changing lifestyle. Semi-structured qualitative in-depth interviews were performed with 23 participants (16 women and 7 men) aged 18 - 70 years. The data were analysed using systematic text condensation searching for issues describing participants' responses, and looking for the essence, aiming to share the basis of life-world experiences as valid knowledge. Participants identified two main themes: being stuck in old habits, and being burdened with emotional baggage from their previous negative experiences. Participants expressed a wish to change their lifestyles, but were unable to act in accordance with the health knowledge they possessed. Previous experiences with lifestyle change kept them from initiating attempts without professional assistance. Participants also described being burdened by an emotional baggage with problems from childhood and/or with family, work and social life issues. Respondents said that they felt that emotional baggage was an important explanation for why they were stuck in old habits and that conversely, being stuck in old habits added load to their already emotional baggage and made it heavier. Behavioural change can be hard to perform as psychological distress from life baggage can influence the ability to change. The study participants' experience of being stuck in old habits and having substantial emotional baggage raises questions as to whether or not Healthy Life Centres are able to help participants who need to make a lifestyle

  5. Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

    Science.gov (United States)

    Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

    2013-01-01

    Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

  6. Personality and Obesity across the Adult Lifespan

    Science.gov (United States)

    Sutin, Angelina R.; Ferrucci, Luigi; Zonderman, Alan B.; Terracciano, Antonio

    2011-01-01

    Personality traits contribute to health outcomes, in part through their association with major controllable risk factors, such as obesity. Body weight, in turn, reflects our behaviors and lifestyle and contributes to the way we perceive ourselves and others. In this study, we use data from a large (N=1,988) longitudinal study that spanned more than 50 years to examine how personality traits are associated with multiple measures of adiposity and with fluctuations in body mass index (BMI). Using 14,531 anthropometric assessments, we modeled the trajectory of BMI across adulthood and tested whether personality predicted its rate of change. Measured concurrently, participants higher on Neuroticism or Extraversion or lower on Conscientiousness had higher BMI; these associations replicated across body fat, waist, and hip circumference. The strongest association was found for the impulsivity facet: Participants who scored in the top 10% of impulsivity weighed, on average, 11Kg more than those in the bottom 10%. Longitudinally, high Neuroticism and low Conscientiousness, and the facets of these traits related to difficulty with impulse control, were associated with weight fluctuations, measured as the variability in weight over time. Finally, low Agreeableness and impulsivity-related traits predicted a greater increase in BMI across the adult lifespan. BMI was mostly unrelated to change in personality traits. Personality traits are defined by cognitive, emotional, and behavioral patterns that likely contribute to unhealthy weight and difficulties with weight management. Such associations may elucidate the role of personality traits in disease progression and may help to design more effective interventions. PMID:21744974

  7. Doxorubicin and ifosfamide combination chemotherapy in previously treated acute leukemia in adults: a Southwest Oncology Group pilot study.

    Science.gov (United States)

    Ryan, D H; Bickers, J N; Vial, R H; Hussein, K; Bottomley, R; Hewlett, J S; Wilson, H E; Stuckey, W J

    1980-01-01

    The Southwest Oncology Group did a limited institutional pilot study of the combination of doxorubicin and ifosfamide in the treatment of previously treated adult patients with acute leukemia. Thirty-four patients received one or two courses of the combination. All patients had received prior chemotherapy and 32 had received prior anthracycline chemotherapy. Three patients died before their responses could be fully evaluated. Fourteen patients achieved complete remission (41%) and one patient achieved partial remission. The complete remission rate was 27% for patients with acute myeloblastic leukemia (myelomonoblastic leukemia, monoblastic leukemia, and erythroleukemia) and 89% for patients with acute lymphocytic and undifferentiated leukemia (ALL). Toxic effects included severe hematologic reactions in 33 of 34 patients, hematuria in six patients, altered sensorium in one patient, and congestive heart failure in one patient. The safety of the combination was established and toxic side effects of this therapy were tolerable. The 89% complete remission rate for previously treated patients with ALL suggests that the combination of doxorubicin and ifosfamide may be particularly effective in ALL.

  8. The suitability of XRF analysis for compositional classification of archaeological ceramic fabric: A comparison with a previous NAA study

    International Nuclear Information System (INIS)

    Padilla, R.; Espen, P. van; Torres, P.P. Godo

    2006-01-01

    The main drawbacks of EDXRF techniques, restricting its more frequent use for the specific purpose of compositional analysis of archaeological ceramic fabric, have been the insufficient sensitivity to determine some important elements (like Cr, REE, among others), a somewhat worse precision and the inability to perform standard-less quantitative procedures in the absence of suitable certified reference materials (CRM) for ceramic fabric. This paper presents the advantages of combining two energy dispersive X-ray fluorescence methods for fast and non-destructive analysis of ceramic fabric with increased sensitivity. Selective polarized excitation using secondary targets (EDPXRF) and radioisotope excitation (R-XRF) using a 241 Am source. The analytical performance of the methods was evaluated by analyzing several CRM of sediment type, and the fitness for the purpose of compositional classification was compared with that obtained by using Instrumental Neutron Activation Analysis in a previous study of Cuban aborigine pottery

  9. The suitability of XRF analysis for compositional classification of archaeological ceramic fabric: A comparison with a previous NAA study

    Energy Technology Data Exchange (ETDEWEB)

    Padilla, R. [Centro de Aplicaciones Tecnologicas y Desarrollo Nuclear (CEADEN), Laboratorio de Analisis Quimico, Calle 30 no. 502, Playa, Ciudad Habana (Cuba)]. E-mail: roman.padilla@infomed.sld.cu; Espen, P. van [University of Antwerp (Belgium); Torres, P.P. Godo [Centro de Antropologia, Havana (Cuba)

    2006-02-03

    The main drawbacks of EDXRF techniques, restricting its more frequent use for the specific purpose of compositional analysis of archaeological ceramic fabric, have been the insufficient sensitivity to determine some important elements (like Cr, REE, among others), a somewhat worse precision and the inability to perform standard-less quantitative procedures in the absence of suitable certified reference materials (CRM) for ceramic fabric. This paper presents the advantages of combining two energy dispersive X-ray fluorescence methods for fast and non-destructive analysis of ceramic fabric with increased sensitivity. Selective polarized excitation using secondary targets (EDPXRF) and radioisotope excitation (R-XRF) using a {sup 241}Am source. The analytical performance of the methods was evaluated by analyzing several CRM of sediment type, and the fitness for the purpose of compositional classification was compared with that obtained by using Instrumental Neutron Activation Analysis in a previous study of Cuban aborigine pottery.

  10. Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication

    Directory of Open Access Journals (Sweden)

    Yang FD

    2017-04-01

    Full Text Available Fu De Yang,1 Juan Li,1 Yun Long Tan,1 Wei Ye Liang,1 Rongzhen Zhang,1 Ning Wang,1 Wei Feng,1 Shangli Cai,2 Jian Min Zhuo,2 Li Li Zhang2 1Beijing Hui-Long-Guan Hospital, 2Department of Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China Objective: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.Methods: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S and Personal and Social Performance (PSP scores.Results: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55] to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set. The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001 improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20] and PSP score (25.5 [15.0]. A total of 174 (10.28% patients experienced adverse events (AEs. The most common (>10 patients events were extrapyramidal disorder (n=84, 4.96%, poor quality sleep (n=18, 1.06% and akathisia (n=13, 0.77%. The majority of AEs were mild to moderate in severity. No deaths occurred.Conclusion: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia. Keywords: atypical antipsychotics, open label

  11. Study protocol of the ASD-Net, the German research consortium for the study of Autism Spectrum Disorder across the lifespan: from a better etiological understanding, through valid diagnosis, to more effective health care.

    Science.gov (United States)

    Kamp-Becker, Inge; Poustka, Luise; Bachmann, Christian; Ehrlich, Stefan; Hoffmann, Falk; Kanske, Philipp; Kirsch, Peter; Krach, Sören; Paulus, Frieder Michel; Rietschel, Marcella; Roepke, Stefan; Roessner, Veit; Schad-Hansjosten, Tanja; Singer, Tania; Stroth, Sanna; Witt, Stephanie; Wermter, Anne-Kathrin

    2017-06-02

    Autism Spectrum Disorder (ASD) is a severe, lifelong neurodevelopmental disorder with early onset that places a heavy burden on affected individuals and their families. Due to the need for highly specialized health, educational and vocational services, ASD is a cost-intensive disorder, and strain on health care systems increases with increasing age of the affected individual. The ASD-Net will study Germany's largest cohort of patients with ASD over the lifespan. By combining methodological expertise from all levels of clinical research, the ASD-Net will follow a translational approach necessary to identify neurobiological pathways of different phenotypes and their appropriate identification and treatment. The work of the ASD-Net will be organized into three clusters concentrating on diagnostics, therapy and health economics. In the diagnostic cluster, data from a large, well-characterized sample (N = 2568) will be analyzed to improve the efficiency of diagnostic procedures. Pattern classification methods (machine learning) will be used to identify algorithms for screening purposes. In a second step, the developed algorithm will be tested in an independent sample. In the therapy cluster, we will unravel how an ASD-specific social skills training with concomitant oxytocin administration can modulate behavior through neurobiological pathways. For the first time, we will characterize long-term effects of a social skills training combined with oxytocin treatment on behavioral and neurobiological phenotypes. Also acute effects of oxytocin will be investigated to delineate general and specific effects of additional oxytocin treatment in order to develop biologically plausible models for symptoms and successful therapeutic interventions in ASD. Finally, in the health economics cluster, we will assess service utilization and ASD-related costs in order to identify potential needs and cost savings specifically tailored to Germany. The ASD-Net has been established as part of

  12. Development of Glutamatergic Proteins in Human Visual Cortex across the Lifespan.

    Science.gov (United States)

    Siu, Caitlin R; Beshara, Simon P; Jones, David G; Murphy, Kathryn M

    2017-06-21

    Traditionally, human primary visual cortex (V1) has been thought to mature within the first few years of life, based on anatomical studies of synapse formation, and establishment of intracortical and intercortical connections. Human vision, however, develops well beyond the first few years. Previously, we found prolonged development of some GABAergic proteins in human V1 (Pinto et al., 2010). Yet as >80% of synapses in V1 are excitatory, it remains unanswered whether the majority of synapses regulating experience-dependent plasticity and receptive field properties develop late, like their inhibitory counterparts. To address this question, we used Western blotting of postmortem tissue from human V1 (12 female, 18 male) covering a range of ages. Then we quantified a set of postsynaptic glutamatergic proteins (PSD-95, GluA2, GluN1, GluN2A, GluN2B), calculated indices for functional pairs that are developmentally regulated (GluA2:GluN1; GluN2A:GluN2B), and determined interindividual variability. We found early loss of GluN1, prolonged development of PSD-95 and GluA2 into late childhood, protracted development of GluN2A until ∼40 years, and dramatic loss of GluN2A in aging. The GluA2:GluN1 index switched at ∼1 year, but the GluN2A:GluN2B index continued to shift until ∼40 year before changing back to GluN2B in aging. We also identified young childhood as a stage of heightened interindividual variability. The changes show that human V1 develops gradually through a series of five orchestrated stages, making it likely that V1 participates in visual development and plasticity across the lifespan. SIGNIFICANCE STATEMENT Anatomical structure of human V1 appears to mature early, but vision changes across the lifespan. This discrepancy has fostered two hypotheses: either other aspects of V1 continue changing, or later changes in visual perception depend on extrastriate areas. Previously, we showed that some GABAergic synaptic proteins change across the lifespan, but most

  13. Value and reliability of findings from previous epidemiologic studies in the assessment of radiation-related cancer risks. Pt. 3

    International Nuclear Information System (INIS)

    Frasch, G.; Martignoni, K.

    1990-01-01

    The theories put forward here are predominantly based on pooled data from previous studies in a number of cohorts made up by mostly non-average individuals. These studies were carried out by various researchers and differed in procedures and aims. Factors of major importance to the validity and reliability of the conclusions drawn from this study are pointed out. In one chapter some light is thrown on factors known to bear a relation to the incidence of radiation-induced cancer of the breast, even though at present this can only very vaguely be described on a quantitative basis. These factors include fractionated dose regimens, pregnancies and parturitions, menarche, menopause, synergisms as well as secondary cancer of the breast. The available body of evidence suggests that exposure of each of 1 million women to a dose of 10 mGy (rad) can be linked with approx. 3 additional cases of mammary cancer reported on an average per year after the latency period. The fact that there is some statistical scatter around this value is chiefly attributable to age-related causes at the beginning of exposure. Differences in ethnic and cultural characteristics between the populations investigated appeared to be less important here. (orig./MG) [de

  14. Barriers to postpartum screening for type 2 diabetes: a qualitative study of women with previous gestational diabetes.

    Science.gov (United States)

    Rafii, Forough; Rahimparvar, Seyedeh Fatemeh Vasegh; Mehrdad, Neda; Keramat, Afsaneh

    2017-01-01

    Risk of developing type 2 diabetes is increased in women with previous gestational diabetes mellitus (GDM). Postpartum glycemic screening is recommended in women with recent GDM. But this screening rate is low and the reasons are unclear. The aim of this study was to explore the experiences of Iranian women with recent GDM on barriers of postpartum screening for diabetes. This qualitative study was conducted in Tehran, Iran in 2016. Semi-structured interview was used for data collection. 22 women with recent GDM were interviewed. These women gave birth in Tehran hospitals at a minimum of 6 months before interview. The missed screening defined as not attending to laboratory for Fasting Blood Sugar and/or Oral Glucose Tolerance Test, 6 week to 6 month after their child birthing. The data was analyzed by content analysis method. Themes and sub-themes that illustrated the barriers to postpartum diabetes screening were: inadequate education (about developing diabetes in the future, implementation of the screening, and glucometer validity in diagnosis of diabetes), perceiving the screening as difficult (feeling comfortable with the glucometer, poor laboratory conditions, issues related to the baby/babies, and financial problems), improper attitudes toward the screening (unwilling to get diagnosed, not giving priority to oneself, having false beliefs) and procrastination (gap to intention and action, self-deception and self-regulation failure). Women with recent GDM reported several barriers for postpartum diabetes screening. This study help to develop the evidence-based interventions for improving this screening rate.

  15. A Flexible-Dose Study of Paliperidone ER in Patients With Nonacute Schizophrenia Previously Treated Unsuccessfully With Oral Olanzapine.

    Science.gov (United States)

    Kotler, Moshe; Dilbaz, Nesrin; Rosa, Fernanda; Paterakis, Periklis; Milanova, Vihra; Smulevich, Anatoly B; Lahaye, Marjolein; Schreiner, Andreas

    2016-01-01

    The goal of this study was to explore the tolerability, safety, and treatment response of switching from oral olanzapine to paliperidone extended release (ER). Adult patients with nonacute schizophrenia who had been treated unsuccessfully with oral olanzapine were switched to flexible doses of paliperidone ER (3 to 12 mg/d). The primary efficacy outcome was a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint for patients who switched medications because of lack of efficacy with olanzapine and noninferiority versus previous olanzapine treatment (mean endpoint change in PANSS total scores vs. baseline of ≤ 5 points) for patients who switched for reasons other than lack of efficacy. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms, and weight change. Of 396 patients, 65.2% were men, mean age was 40.0 ± 12.0 years, and 75.5% had paranoid schizophrenia. Among the patients whose main reason for switching was lack of efficacy, an improvement in the PANSS total score of ≥ 20% occurred in 57.4% of patients. Noninferiority was confirmed for each subgroup of patients whose main reason for switching was something other than lack of efficacy. Paliperidone ER was generally well tolerated. Extrapyramidal symptoms as measured by total Extrapyramidal Symptom Rating Scale scores showed statistically significant and clinically relevant improvements at endpoint, the average weight decreased by 0.8 ± 5.2 kg at endpoint, and a clinically relevant weight gain of ≥ 7% occurred in 8.0% of patients. Paliperidone ER flexibly-dosed over 6 months was well tolerated and associated with a meaningful clinical response in patients with nonacute schizophrenia who had previously been unsuccessfully treated with oral olanzapine.

  16. Sex differences and stress across the lifespan

    Science.gov (United States)

    Bale, Tracy L; Epperson, C Neill

    2015-01-01

    Sex differences in stress responses can be found at all stages of life and are related to both the organizational and activational effects of gonadal hormones and to genes on the sex chromosomes. As stress dysregulation is the most common feature across neuropsychiatric diseases, sex differences in how these pathways develop and mature may predict sex-specific periods of vulnerability to disruption and increased disease risk or resilience across the lifespan. The aging brain is also at risk to the effects of stress, where the rapid decline of gonadal hormones in women combined with cellular aging processes promote sex biases in stress dysregulation. In this Review, we discuss potential underlying mechanisms driving sex differences in stress responses and their relevance to disease. Although stress is involved in a much broader range of diseases than neuropsychiatric ones, we highlight here this area and its examples across the lifespan. PMID:26404716

  17. Sex differences and stress across the lifespan.

    Science.gov (United States)

    Bale, Tracy L; Epperson, C Neill

    2015-10-01

    Sex differences in stress responses can be found at all stages of life and are related to both the organizational and activational effects of gonadal hormones and to genes on the sex chromosomes. As stress dysregulation is the most common feature across neuropsychiatric diseases, sex differences in how these pathways develop and mature may predict sex-specific periods of vulnerability to disruption and increased disease risk or resilience across the lifespan. The aging brain is also at risk to the effects of stress, where the rapid decline of gonadal hormones in women combined with cellular aging processes promote sex biases in stress dysregulation. In this Review, we discuss potential underlying mechanisms driving sex differences in stress responses and their relevance to disease. Although stress is involved in a much broader range of diseases than neuropsychiatric ones, we highlight here this area and its examples across the lifespan.

  18. Changes in Regenerative Capacity through Lifespan

    Directory of Open Access Journals (Sweden)

    Maximina H. Yun

    2015-10-01

    Full Text Available Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging.

  19. QUANTIFYING LIFE STYLE IMPACT ON LIFESPAN

    Directory of Open Access Journals (Sweden)

    Antonello Lorenzini

    2012-12-01

    Full Text Available A healthy diet, physical activity and avoiding dangerous habits such as smoking are effective ways of increasing health and lifespan. Although a significant portion of the world's population still suffers from malnutrition, especially children, the most common cause of death in the world today is non-communicable diseases. Overweight and obesity significantly increase the relative risk for the most relevant non communicable diseases: cardiovascular disease, type II diabetes and some cancers. Childhood overweight also seems to increase the likelihood of disease in adulthood through epigenetic mechanisms. This worrisome trend now termed "globesity" will deeply impact society unless preventive strategies are put into effect. Researchers of the basic biology of aging have clearly established that animals with short lifespans live longer when their diet is calorie restricted. Although similar experiments carried on rhesus monkeys, a longer-lived species more closely related to humans, yielded mixed results, overall the available scientific data suggest keeping the body mass index in the "normal" range increases the chances of living a longer, healthier life. This can be successfully achieved both by maintaining a healthy diet and by engaging in physical activity. In this review we will try to quantify the relative impact of life style choices on lifespan.

  20. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-01-01

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

  1. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun, E-mail: lijunzhou@tju.edu.cn

    2015-12-25

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

  2. Pilot Study of an Individualised Early Postpartum Intervention to Increase Physical Activity in Women with Previous Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Harold David McIntyre

    2012-01-01

    Full Text Available Optimal strategies to prevent progression towards overt diabetes in women with recent gestational diabetes remain ill defined. We report a pilot study of a convenient, home based exercise program with telephone support, suited to the early post-partum period. Twenty eight women with recent gestational diabetes were enrolled at six weeks post-partum into a 12 week randomised controlled trial of Usual Care (n=13 versus Supported Care (individualised exercise program with regular telephone support; n=15. Baseline characteristics (Mean ± SD were: Age  33±4  years; Weight 80 ± 20 kg and Body Mass Index (BMI 30.0±9.7 kg/m2. The primary outcome, planned physical activity {Median (Range}, increased by 60 (0–540 mins/week in the SC group versus 0 (0–580 mins/week in the UC group (P=0.234. Walking was the predominant physical activity. Body weight, BMI, waist circumference, % body fat, fasting glucose and insulin did not change significantly over time in either group. This intervention designed to increase physical activity in post-partum women with previous gestational diabetes proved feasible. However, no measurable improvement in metabolic or biometric parameters was observed over a three month period.

  3. Patterns and Determinants of Treatment Seeking among Previously Untreated Psychotic Patients in Aceh Province, Indonesia: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Marthoenis Marthoenis

    2016-01-01

    Full Text Available Immediate treatment of first-episode psychosis is essential in order to achieve a positive outcome. However, Indonesian psychiatric patients often delay accessing health services, the reason for which is not yet fully understood. The current study aimed to understand patterns of treatment seeking and to reveal determinants of the delay in accessing psychiatric care among first-time user psychotic patients. Qualitative interviews were conducted with sixteen family members who accompanied the patients to a psychiatric hospital. Many families expressed beliefs that mental illness appertains to village sickness and not hospital sickness; therefore, they usually take the patients to traditional or religious healers before taking them to a health professional. They also identified various factors that potentially delay accessing psychiatric treatment: low literacy and beliefs about the cause of the illness, stigmatisation, the role of extended family, financial problems, and long distance to the psychiatric hospital. On the other hand, the family mentioned various factors related to timely help seeking, including being a well-educated family, living closer to health facilities, previous experience of successful psychotic therapy, and having more positive symptoms of psychosis. The findings call for mental health awareness campaigns in the community.

  4. Development of a Lifespan-Based Novel Composite Person-Reported Outcome Measure Using Data from the CINRG Duchenne Natural History Study

    Science.gov (United States)

    2017-10-01

    Duchenne natural history study PRINCIPAL INVESTIGATOR: McDonald, Craig M. CONTRACTING ORGANIZATION: University of California, Davis Davis, CA 95618...composite person- reported outcome measure using data from the CINRG Duchenne natural history study 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Craig...SUPPLEMENTARY NOTES 14. ABSTRACT Development of novel technologies and therapeutic agents to treat Duchenne muscular dystrophy (DMD) have increased

  5. Acidic Food pH Increases Palatability and Consumption and Extends Drosophila Lifespan.

    Science.gov (United States)

    Deshpande, Sonali A; Yamada, Ryuichi; Mak, Christine M; Hunter, Brooke; Soto Obando, Alina; Hoxha, Sany; Ja, William W

    2015-12-01

    Despite the prevalent use of Drosophila as a model in studies of nutrition, the effects of fundamental food properties, such as pH, on animal health and behavior are not well known. We examined the effect of food pH on adult Drosophila lifespan, feeding behavior, and microbiota composition and tested the hypothesis that pH-mediated changes in palatability and total consumption are required for modulating longevity. We measured the effect of buffered food (pH 5, 7, or 9) on male gustatory responses (proboscis extension), total food intake, and male and female lifespan. The effect of food pH on germfree male lifespan was also assessed. Changes in fly-associated microbial composition as a result of food pH were determined by 16S ribosomal RNA gene sequencing. Male gustatory responses, total consumption, and male and female longevity were additionally measured in the taste-defective Pox neuro (Poxn) mutant and its transgenic rescue control. An acidic diet increased Drosophila gustatory responses (40-230%) and food intake (5-50%) and extended survival (10-160% longer median lifespan) compared with flies on either neutral or alkaline pH food. Alkaline food pH shifted the composition of fly-associated bacteria and resulted in greater lifespan extension (260% longer median survival) after microbes were eliminated compared with flies on an acidic (50%) or neutral (130%) diet. However, germfree flies lived longer on an acidic diet (5-20% longer median lifespan) compared with those on either neutral or alkaline pH food. Gustatory responses, total consumption, and longevity were unaffected by food pH in Poxn mutant flies. Food pH can directly influence palatability and feeding behavior and affect parameters such as microbial growth to ultimately affect Drosophila lifespan. Fundamental food properties altered by dietary or drug interventions may therefore contribute to changes in animal physiology, metabolism, and survival. © 2015 American Society for Nutrition.

  6. A Questionnaire Study on the Attitudes and Previous Experience of Croatian Family Physicians toward their Preparedness for Disaster Management.

    Science.gov (United States)

    Pekez-Pavliško, Tanja; Račić, Maja; Jurišić, Dinka

    2018-04-01

    To explore family physicians' attitudes, previous experience and self-assessed preparedness to respond or to assist in mass casualty incidents in Croatia. The cross-sectional survey was carried out during January 2017. Study participants were recruited through a Facebook group that brings together family physicians from Croatia. They were asked to complete the questionnaire, which was distributed via google.docs. Knowledge and attitudes toward disaster preparedness were evaluated by 18 questions. Analysis of variance, Student t test and Kruskal-Wallis test t were used for statistical analysis. Risk awareness of disasters was high among respondents (M = 4.89, SD=0.450). Only 16.4 of respondents have participated in the management of disaster at the scene. The majority (73.8%) of physicians have not been participating in any educational activity dealing with disaster over the past two years. Family physicians believed they are not well prepared to participate in national (M = 3.02, SD=0.856) and local community emergency response system for disaster (M = 3.16, SD=1.119). Male physicians scored higher preparedness to participate in national emergency response system for disaster ( p =0.012), to carry out accepted triage principles used in the disaster situation ( p =0.003) and recognize differences in health assessments indicating potential exposure to specific agents ( p =0,001) compared to their female colleagues. Croatian primary healthcare system attracts many young physicians, who can be an important part of disaster and emergency management. However, the lack of experience despite a high motivation indicates a need for inclusion of disaster medicine training during undergraduate studies and annual educational activities.

  7. Previous injuries and some training characteristics predict running-related injuries in recreational runners: a prospective cohort study.

    Science.gov (United States)

    Hespanhol Junior, Luiz Carlos; Pena Costa, Leonardo Oliveira; Lopes, Alexandre Dias

    2013-12-01

    What is the incidence of running-related injuries (RRIs) in recreational runners? Which personal and training characteristics predict RRIs in recreational runners? Prospective cohort study. A total of 200 recreational runners answered a fortnightly online survey containing questions about their running routine, races, and presence of RRI. These runners were followed-up for a period of 12 weeks. The primary outcome of this study was running-related injury. The incidence of injuries was calculated taking into account the exposure to running and was expressed by RRI/1000 hours. The association between potential predictive factors and RRIs was estimated using generalised estimating equation models. A total of 84 RRIs were registered in 60 (31%) of the 191 recreational runners who completed all follow-up surveys. Of the injured runners 30% (n=18/60) developed two or more RRIs, with 5/18 (28%) being recurrences. The incidence of RRI was 10 RRI/1000 hours of running exposure. The main type of RRI observed was muscle injuries (30%, n=25/84). The knee was the most commonly affected anatomical region (19%, n=16/84). The variables associated with RRI were: previous RRI (OR 1.88, 95% CI 1.01 to 3.51), duration of training although the effect was very small (OR 1.01, 95% CI 1.00 to 1.02), speed training (OR 1.46, 95% CI 1.02 to 2.10), and interval training (OR 0.61, 95% CI 0.43 to 0.88). Physiotherapists should be aware and advise runners that past RRI and speed training are associated with increased risk of further RRI, while interval training is associated with lower risk, although these associations may not be causative. Copyright © 2013 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

  8. Emotional Egocentricity Bias across the life-span

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    Federica eRiva

    2016-04-01

    Full Text Available In our daily lives, we often have to quickly estimate the emotions of our conspecifics in order to have successful social interactions. While this estimation process seems quite easy when we are ourselves in a neutral or equivalent emotional state, it has recently been shown that in case of incongruent emotional states between ourselves and the others, our judgments can be biased. This phenomenon, introduced to the literature with the term Emotional Egocentricity Bias (EEB, has been found to occur in young adults and, to a greater extent, in children. However, how EEB changes across the life-span from adolescence to old age has been largely unexplored. In this study, we recruited 114 female participants subdivided in four cohorts (adolescents, young adults, middle-aged adults, older adults to examine EEB age-related changes. Participants were administered with a paradigm which, by making use of visuo-tactile stimulation that elicits conflicting feelings in paired participants, allows the valid and reliable exploration of EEB. Results highlighted a U-shaped relation between age and EEB, revealing higher emotional egocentricity in adolescents and older adults compared to young and middle-aged adults. These results are in line with the neuroscientific literature which has recently shown that overcoming EEB is associated with a greater activation of a portion of the parietal lobe, namely the right Supramarginal Gyrus (rSMG. This is an area that reaches full maturation only by the end of adolescence, and displays an early decay in older age. Thus, the age-related changes of the EEB could be possibly due to the life-span development of the rSMG. This study is the first one to show the quadratic relation between age and the EEB and set a milestone for further research exploring the neural correlates of the life-span development of the EEB. Future studies are needed in order to generalize these results to the male population and to explore gender

  9. Factors of positive social functioning in the context of transforming societies: Results of the Brno Longitudinal Study on Life-Span Human Development

    Czech Academy of Sciences Publication Activity Database

    Millová, Katarína; Blatný, Marek; Jelínek, Martin

    2015-01-01

    Roč. 59, Supplement (2015), s. 47-55 ISSN 0009-062X R&D Projects: GA ČR GA15-22474S Institutional support: RVO:68081740 Keywords : social functioning * transforming societies * longitudinal study * personality * socio-economic variables Subject RIV: AN - Psychology Impact factor: 0.236, year: 2015

  10. Phylogenetic relationship and Fourier-transform infrared spectroscopy-derived lipid determinants of lifespan parameters in the Saccharomyces cerevisiae yeast.

    Science.gov (United States)

    Molon, Mateusz; Zebrowski, Jacek

    2017-06-01

    Yeast ageing has been gaining much attention in gerontology research, yet the process itself is still not entirely clear. One of the constraints related to the use of the Saccharomyces cerevisiae yeast in studies is the ambiguity of the results concerning ageing determinants for different genetic backgrounds. In this paper, we compare reproductive potentials and lifespans of seven widely used haploid laboratory strains differing in daughter cells production capabilities and highlight the importance of choosing an appropriate genotype for the studies on ageing. Moreover, we show here links between post-reproductive lifespan and lipid metabolism, as well as between reproductive potential, reproductive lifespan and phylogenetic relationship. Using FTIR spectroscopy that generated a biochemical fingerprint of cells, coupled with chemometrics, we found that the band of carbonyl (C = O) stretching vibration discriminates the strains according to post-reproductive lifespan. The results indicated that prolonged post-reproductive lifespan was associated with relatively lower amount of fatty acids esterified to phospholipids compared to a free acid pool, thus implying phospholipid metabolism for the post-reproductive lifespan of yeast. In addition, phylogenetic analysis showed a correlation between nucleotide similarity and the reproductive potential or reproductive lifespan, but not to the longevity expressed in time units. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure.

    Science.gov (United States)

    Rios, Jorge A; Schlumpf, Karen S; Kakaiya, Ram M; Triulzi, Darrell J; Roback, John D; Kleinman, Steve H; Murphy, Edward L; Gottschall, Jerome L; Carey, Patricia M

    2011-06-01

    Transfusion-related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States. We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type. A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively. A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI. © 2010 American Association of Blood Banks.

  12. PCNL - a comparative study in nonoperated and in previously operated (open nephrolithotomy/pyelolithotomy patients - a single-surgeon experience

    Directory of Open Access Journals (Sweden)

    Rahul Gupta

    2011-12-01

    Full Text Available PURPOSE: Re-procedure in patients with history of open stone surgery is usually challenging due to the alteration in the retroperitoneal anatomy. The aim of this study was to determine the possible impact of open renal surgery on the efficacy and morbidity of subsequent percutaneous nephrolithotomy (PCNL. MATERIALS AND METHODS: From March 2009 until September 2010, 120 patients underwent PCNL. Of these, 20 patients were excluded (tubeless or bilateral simultaneous PCNL. Of the remaining 100, 55 primary patients were categorized as Group 1 and the remaining (previous open nephrolithotomy as Group 2. Standard preoperative evaluation was carried out prior to intervention, Statistical analysis was performed using SPSS v. 11 with the chi-square test, independent samples t-test, and Mann-Whitney U test. A p-value < 0.05 was taken as statistically significant. RESULTS: Both groups were similar in demographic profile and stone burden. Attempts to access the PCS was less in Group 1 compared to Group 2 (1.2 + 1 2 vs 3 + 1.3 respectively and this was statistically significant (p < 0.04. However, the mean operative time between the two groups was not statistically significant (p = 0.44. Blood transfusion rate was comparable in the two groups (p = 0.24. One patient in Group 2 developed hemothorax following a supra-11th puncture. Remaining complications were comparable in both groups. CONCLUSION: Patients with past history of renal stone surgery may need more attempts to access the pelvicaliceal system and have difficulty in tract dilation secondary to retroperitoneal scarring. But overall morbidity and efficacy is same in both groups.

  13. Sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer: a population-based study

    Science.gov (United States)

    Fischer, Alexander H.; Wang, Timothy S.; Yenokyan, Gayane; Kang, Sewon; Chien, Anna L.

    2016-01-01

    Background Individuals with previous nonmelanoma skin cancer (NMSC) are at increased risk for subsequent skin cancer, and should therefore limit UV exposure. Objective To determine whether individuals with previous NMSC engage in better sun protection than those with no skin cancer history. Methods We pooled self-reported data (2005 and 2010 National Health Interview Surveys) from US non-Hispanic white adults (758 with and 34,161 without previous NMSC). We calculated adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (95% CI), taking into account the complex survey design. Results Individuals with previous NMSC versus no history of NMSC had higher rates of frequent use of shade (44.3% versus 27.0%; aPOR=1.41; 1.16–1.71), long sleeves (20.5% versus 7.7%; aPOR=1.55; 1.21–1.98), a wide-brimmed hat (26.1% versus 10.5%; aPOR=1.52; 1.24–1.87), and sunscreen (53.7% versus 33.1%; aPOR=2.11; 95% CI=1.73–2.59), but did not have significantly lower odds of recent sunburn (29.7% versus 40.7%; aPOR=0.95; 0.77–1.17). Among subjects with previous NMSC, recent sunburn was inversely associated with age, sun avoidance, and shade but not sunscreen. Limitations Self-reported cross-sectional data and unavailable information quantifying regular sun exposure. Conclusion Physicians should emphasize sunburn prevention when counseling patients with previous NMSC, especially younger adults, focusing on shade and sun avoidance over sunscreen. PMID:27198078

  14. Community Resilience throughout the Lifespan--The Potential Contribution of Healthy Elders.

    Science.gov (United States)

    Cohen, Odeya; Geva, Diklah; Lahad, Mooli; Bolotin, Arkady; Leykin, Dima; Goldberg, Avishay; Aharonson-Daniel, Limor

    2016-01-01

    An increase in the exposure and predisposition of civilian populations to disasters has been recorded in the last decades. In major disasters, as demonstrated recently in Nepal (2015) and previously in Haiti (2010), external aid is vital, yet in the first hours after a disaster, communities must usually cope alone with the challenge of providing emergent lifesaving care. Communities therefore need to be prepared to handle emergency situations. Mapping the needs of the populations within their purview is a trying task for decision makers and community leaders. In this context, the elderly are traditionally treated as a susceptible population with special needs. The current study aimed to explore variations in the level of community resilience along the lifespan. The study was conducted in nine small to mid-size towns in Israel between August and November 2011 (N = 885). The Conjoint Community Resiliency Assessment Measure (CCRAM), a validated instrument for community resilience assessment, was used to examine the association between age and community resilience score. Statistical analysis included spline and logistic regression models that explored community resiliency over the lifespan in a way that allowed flexible modeling of the curve without prior constraints. This innovative statistical approach facilitated identification of the ages at which trend changes occurred. The study found a significant rise in community resiliency scores in the age groups of 61-75 years as compared with younger age bands, suggesting that older people in good health may contribute positively to building community resiliency for crisis. Rather than focusing on the growing medical needs and years of dependency associated with increased life expectancy and the resulting climb in the proportion of elders in the population, this paper proposes that active "young at heart" older people can be a valuable resource for their community.

  15. Community Resilience throughout the Lifespan--The Potential Contribution of Healthy Elders.

    Directory of Open Access Journals (Sweden)

    Odeya Cohen

    Full Text Available An increase in the exposure and predisposition of civilian populations to disasters has been recorded in the last decades. In major disasters, as demonstrated recently in Nepal (2015 and previously in Haiti (2010, external aid is vital, yet in the first hours after a disaster, communities must usually cope alone with the challenge of providing emergent lifesaving care. Communities therefore need to be prepared to handle emergency situations. Mapping the needs of the populations within their purview is a trying task for decision makers and community leaders. In this context, the elderly are traditionally treated as a susceptible population with special needs. The current study aimed to explore variations in the level of community resilience along the lifespan. The study was conducted in nine small to mid-size towns in Israel between August and November 2011 (N = 885. The Conjoint Community Resiliency Assessment Measure (CCRAM, a validated instrument for community resilience assessment, was used to examine the association between age and community resilience score. Statistical analysis included spline and logistic regression models that explored community resiliency over the lifespan in a way that allowed flexible modeling of the curve without prior constraints. This innovative statistical approach facilitated identification of the ages at which trend changes occurred. The study found a significant rise in community resiliency scores in the age groups of 61-75 years as compared with younger age bands, suggesting that older people in good health may contribute positively to building community resiliency for crisis. Rather than focusing on the growing medical needs and years of dependency associated with increased life expectancy and the resulting climb in the proportion of elders in the population, this paper proposes that active "young at heart" older people can be a valuable resource for their community.

  16. Homeless Aging Veterans in Transition: A Life-Span Perspective

    Directory of Open Access Journals (Sweden)

    Carla J. Thompson

    2013-01-01

    Full Text Available The need for counseling and career/educational services for homeless veterans has captured political and economic venues for more than 25 years. Veterans are three times more likely to become homeless than the general population if veterans live in poverty or are minority veterans. This mixed methods study emphasized a life-span perspective approach for exploring factors influencing normative aging and life-quality of 39 homeless veterans in Alabama and Florida. Seven descriptive quantitative and qualitative research questions framed the investigation. Study participants completed a quantitative survey reflecting their preferences and needs with a subset of the sample (N=12 also participating in individual qualitative interview sessions. Thirty-two service providers and stakeholders completed quantitative surveys. Empirical and qualitative data with appropriate triangulation procedures provided interpretive information relative to a life-span development perspective. Study findings provide evidence of the need for future research efforts to address strategies that focus on the health and economic challenges of veterans before they are threatened with the possibility of homelessness. Implications of the study findings provide important information associated with the premise that human development occurs throughout life with specific characteristics influencing the individual’s passage. Implications for aging/homelessness research are grounded in late-life transitioning and human development intervention considerations.

  17. Cross-sectional relations of race and poverty status to cardiovascular risk factors in the Healthy Aging in Neighborhoods of Diversity across the Lifespan (HANDLS) study.

    Science.gov (United States)

    Waldstein, Shari R; Moody, Danielle L Beatty; McNeely, Jessica M; Allen, Allyssa J; Sprung, Mollie R; Shah, Mauli T; Al'Najjar, Elias; Evans, Michele K; Zonderman, Alan B

    2016-03-14

    Examine interactive relations of race and poverty status with cardiovascular disease (CVD) risk factors in a socioeconomically diverse sample of urban-dwelling African American (AA) and White adults. Participants were 2,270 AAs and Whites (57% AA; 57% female; ages 30-64 years) who completed the first wave of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. CVD risk factors assessed included body mass index (BMI), waist circumference (WC), total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), triglycerides (TG), glycated hemoglobin (HbA1c), high-sensitivity C-reactive protein (CRP), and systolic, diastolic, and pulse pressure (SBP, DBP, PP). Interactive and independent relations of race, poverty status, and sex were examined for each outcome via ordinary least squares regression adjusted for age, education, literacy, substance use, depressive symptoms, perceived health care barriers, medical co-morbidities, and medications. Significant interactions of race and poverty status (p's poverty had lower BMI and WC and higher HDL-C than non-poverty AAs, whereas Whites living in poverty had higher BMI and WC and lower HDL-C than non-poverty Whites. Main effects of race revealed that AAs had higher levels of HbA1c, SBP, and PP, and Whites had higher levels of TC, LDL-C and TG (p's Poverty status moderated race differences for BMI, WC, and HDL-C, conveying increased risk among Whites living in poverty, but reduced risk in their AA counterparts. Race differences for six additional risk factors withstood extensive statistical adjustments including SES indicators.

  18. Laparoscopy After Previous Laparotomy

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    Zulfo Godinjak

    2006-11-01

    Full Text Available Following the abdominal surgery, extensive adhesions often occur and they can cause difficulties during laparoscopic operations. However, previous laparotomy is not considered to be a contraindication for laparoscopy. The aim of this study is to present that an insertion of Veres needle in the region of umbilicus is a safe method for creating a pneumoperitoneum for laparoscopic operations after previous laparotomy. In the last three years, we have performed 144 laparoscopic operations in patients that previously underwent one or two laparotomies. Pathology of digestive system, genital organs, Cesarean Section or abdominal war injuries were the most common causes of previouslaparotomy. During those operations or during entering into abdominal cavity we have not experienced any complications, while in 7 patients we performed conversion to laparotomy following the diagnostic laparoscopy. In all patients an insertion of Veres needle and trocar insertion in the umbilical region was performed, namely a technique of closed laparoscopy. Not even in one patient adhesions in the region of umbilicus were found, and no abdominal organs were injured.

  19. Trade-off between reproduction and lifespan of the rotifer Brachionus plicatilis under different food conditions.

    Science.gov (United States)

    Sun, Yunfei; Hou, Xinying; Xue, Xiaofeng; Zhang, Lu; Zhu, Xuexia; Huang, Yuan; Chen, Yafen; Yang, Zhou

    2017-11-13

    Phaeocystis globosa, one of the most typical red tide-forming species, is usually mixed in the food composition of rotifers. To explore how rotifers respond by adjusting life history strategy when feeding on different quality foods, we exposed the rotifer Brachionus plicatilis to cultures with 100% Chlorella, a mixture of 50% P. globosa and 50% Chlorella, or 100% P. globosa. Results showed that rotifers exposed to 100% Chlorella or to mixed diets produced more total offspring and had higher age-specific fecundity than those exposed to 100% P. globosa. Food combination significantly affected the net reproduction rates of rotifers. By contrast, rotifers that fed on 100% P. globosa or on mixed diets had a longer lifespan than those fed on 100% Chlorella. The overall performances (combining reproduction and lifespan together) of rotifers cultured in 100% Chlorella or mixed diets were significantly higher than those cultured in 100% P. globosa. In general, Chlorella favors rotifers reproduction at the cost of shorter lifespan, whereas P. globosa tends to extend the lifespan of rotifers with lower fecundity, indicating that trade-off exists between reproduction and lifespan under different food conditions. The present study also suggests that rotifers may have the potential to control harmful P. globosa.

  20. A role for autophagy in the extension of lifespan by dietary restriction in C. elegans.

    Directory of Open Access Journals (Sweden)

    Malene Hansen

    2008-02-01

    Full Text Available In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin. TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins.

  1. Caenorhabditis elegans battling starvation stress: low levels of ethanol prolong lifespan in L1 larvae.

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    Paola V Castro

    Full Text Available The nematode Caenorhabditis elegans arrests development at the first larval stage if food is not present upon hatching. Larvae in this stage provide an excellent model for studying stress responses during development. We found that supplementing starved larvae with ethanol markedly extends their lifespan within this L1 diapause. The effects of ethanol-induced lifespan extension can be observed when the ethanol is added to the medium at any time between 0 and 10 days after hatching. The lowest ethanol concentration that extended lifespan was 1 mM (0.005%; higher concentrations to 68 mM (0.4% did not result in increased survival. In spite of their extended survival, larvae did not progress to the L2 stage. Supplementing starved cultures with n-propanol and n-butanol also extended lifespan, but methanol and isopropanol had no measurable effect. Mass spectrometry analysis of nematode fatty acids and amino acids revealed that L1 larvae can incorporate atoms from ethanol into both types of molecules. Based on these data, we suggest that ethanol supplementation may extend the lifespan of L1 larvae by either serving as a carbon and energy source and/or by inducing a stress response.

  2. Reward speeds up and increases consistency of visual selective attention: a lifespan comparison.

    Science.gov (United States)

    Störmer, Viola; Eppinger, Ben; Li, Shu-Chen

    2014-06-01

    Children and older adults often show less favorable reward-based learning and decision making, relative to younger adults. It is unknown, however, whether reward-based processes that influence relatively early perceptual and attentional processes show similar lifespan differences. In this study, we investigated whether stimulus-reward associations affect selective visual attention differently across the human lifespan. Children, adolescents, younger adults, and older adults performed a visual search task in which the target colors were associated with either high or low monetary rewards. We discovered that high reward value speeded up response times across all four age groups, indicating that reward modulates attentional selection across the lifespan. This speed-up in response time was largest in younger adults, relative to the other three age groups. Furthermore, only younger adults benefited from high reward value in increasing response consistency (i.e., reduction of trial-by-trial reaction time variability). Our findings suggest that reward-based modulations of relatively early and implicit perceptual and attentional processes are operative across the lifespan, and the effects appear to be greater in adulthood. The age-specific effect of reward on reducing intraindividual response variability in younger adults likely reflects mechanisms underlying the development and aging of reward processing, such as lifespan age differences in the efficacy of dopaminergic modulation. Overall, the present results indicate that reward shapes visual perception across different age groups by biasing attention to motivationally salient events.

  3. An engineering approach to extending lifespan in C. elegans.

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    Dror Sagi

    Full Text Available We have taken an engineering approach to extending the lifespan of Caenorhabditis elegans. Aging stands out as a complex trait, because events that occur in old animals are not under strong natural selection. As a result, lifespan can be lengthened rationally using bioengineering to modulate gene expression or to add exogenous components. Here, we engineered longer lifespan by expressing genes from zebrafish encoding molecular functions not normally present in worms. Additionally, we extended lifespan by increasing the activity of four endogenous worm aging pathways. Next, we used a modular approach to extend lifespan by combining components. Finally, we used cell- and worm-based assays to analyze changes in cell physiology and as a rapid means to evaluate whether multi-component transgenic lines were likely to have extended longevity. Using engineering to add novel functions and to tune endogenous functions provides a new framework for lifespan extension that goes beyond the constraints of the worm genome.

  4. Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models.

    Science.gov (United States)

    Berryman, Darlene E; Christiansen, Jens Sandahl; Johannsson, Gudmundur; Thorner, Michael O; Kopchick, John J

    2008-12-01

    Animal models are fundamentally important in our quest to understand the genetic, epigenetic, and environmental factors that contribute to human aging. In comparison to humans, relatively short-lived mammals are useful models as they allow for rapid assessment of both genetic manipulation and environmental intervention as related to longevity. These models also allow for the study of clinically relevant pathologies as a function of aging. Data associated with more distant species offers additional insight and critical consideration of the basic physiological processes and molecular mechanisms that influence lifespan. Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages. In this review, we will provide an overview of how the

  5. Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan.

    Science.gov (United States)

    Bansal, Ankita; Kwon, Eun-Soo; Conte, Darryl; Liu, Haibo; Gilchrist, Michael J; MacNeil, Lesley T; Tissenbaum, Heidi A

    2014-01-01

    Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is the primary target of insulin/IGF-1 signaling, and multiple isoforms of DAF-16 (a, b, and d/f) modulate lifespan, metabolism, dauer formation, and stress resistance. Thus far, across phylogeny modulation of mammalian FOXOs and DAF-16 have focused on post-translational regulation with little focus on transcriptional regulation. In C. elegans, we have previously shown that DAF-16d/f cooperates with DAF-16a to promote longevity. In this study, we generated transgenic strains expressing near-endogenous levels of either daf-16a or daf-16d/f, and examined temporal expression of the isoforms to further define how these isoforms contribute to lifespan regulation. Here, we show that DAF-16a is sensitive both to changes in gene dosage and to alterations in the level of insulin/IGF-1 signaling. Interestingly, we find that as worms age, the intestinal expression of daf-16d/f but not daf-16a is dramatically upregulated at the level of transcription. Preventing this transcriptional upregulation shortens lifespan, indicating that transcriptional regulation of daf-16d/f promotes longevity. In an RNAi screen of transcriptional regulators, we identify elt-2 (GATA transcription factor) and swsn-1 (core subunit of SWI/SNF complex) as key modulators of daf-16d/f gene expression. ELT-2 and another GATA factor, ELT-4, promote longevity via both DAF-16a and DAF-16d/f while the components of SWI/SNF complex promote longevity specifically via DAF-16d/f. Our findings indicate that transcriptional control of C. elegans FOXO/daf-16 is an essential regulatory event. Considering the conservation of FOXO across species, our findings identify a new layer of FOXO regulation as a potential determinant of mammalian longevity and age-related diseases such as cancer and diabetes.

  6. Proliferative lifespan is conserved after nuclear transfer.

    Science.gov (United States)

    Clark, A John; Ferrier, Patricia; Aslam, Samena; Burl, Sarah; Denning, Chris; Wylie, Diana; Ross, Arlene; de Sousa, Paul; Wilmut, Ian; Cui, Wei

    2003-06-01

    Cultured primary cells exhibit a finite proliferative lifespan, termed the Hayflick limit. Cloning by nuclear transfer can reverse this cellular ageing process and can be accomplished with cultured cells nearing senescence. Here we describe nuclear transfer experiments in which donor cell lines at different ages and with different proliferative capacities were used to clone foetuses and animals from which new primary cell lines were generated. The rederived lines had the same proliferative capacity and rate of telomere shortening as the donor cell lines, suggesting that these are innate, genetically determined, properties that are conserved by nuclear transfer.

  7. Radioimmunotherapy with Y-90-epratuzumab in patients with previously treated B-cell lymphoma. A fractionated dose-escalation study

    International Nuclear Information System (INIS)

    Linden, O.; Cavallin-Stahl, E.; Tennvall, J.; Hindorf, C.; Olsson, T.; Strand, S.E.; Stenberg, L.; Wingardh, K.

    2002-01-01

    Aim: Fractionated RIT may improve outcome by decreasing heterogeneity in absorbed dose and by increasing therapeutic window. The humanised anti-CD22 antibody, Epratuzumab, (Immunomedics, Inc., Morris Plains, NJ) can be given repeatedly with minimal risk of neutralising Ab (HAHA), making fractionated treatment with 90 Y-labelled epratuzumab possible. Materials and Methods: Patients with previously treated B-cell lymphoma received increasing number (2-4) of weekly infusions of 90 Y-epratuzumab. Patients received either 185 MBq/m 2 per infusion (group A), or, if they had a history of high-dose chemotherapy with stem-cell rescue, 92.5 MBq/m 2 per infusion (group B). The first infusion included 150 MBq of 111 Indium for scintigraphic verification of tumour targeting and dosimetry. 1.5 mg/kg epratuzumab was administered with each infusion. The treatment could be repeated once after 3 m. Results: Of 23 patients, 16 in group A and 6 in group B were evaluable for response. The RR in group A was 62% objective response (OR) and 25% CR/CRu. One patient in group B showed OR. OR was seen in aggressive and indolent lymphoma. Response was also long-lasting and event-free survival of patients showing CR/CRu was 14 to 25+ months. In group A all seven patient, receiving three infusions, showed less than grade 3 platelet and neutrophil toxicity, except for two patients suffering grade 3 neutropenia. Of five patients with 4 weekly infusions there were two patients with dose-limiting haematological toxicity (DLT), both recently treated with high dose cytosar before RIT. With criteria used the maximal tolerated dose was three infusions 185 MBq/m 2 . In group B no patient suffered DLT and one patient exhibited OR. Seven patients were retreated after 3 months with minor toxicity, but improvement in OR in two cases. No patient has developed HAHA. CD22 expression on tumour cells, as assessed by flow cytometry, is available in 18 of 22 patients. In group A, seven of eight patients with

  8. Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.

    Science.gov (United States)

    Morselli, Eugenia; Galluzzi, Lorenzo; Kepp, Oliver; Criollo, Alfredo; Maiuri, Maria Chiara; Tavernarakis, Nektarios; Madeo, Frank; Kroemer, Guido

    2009-12-23

    Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies. Similarly, resveratrol can trigger autophagy in cells from different organisms, extend lifespan in nematodes, and ameliorate the fitness of human cells undergoing metabolic stress. These beneficial effects are lost when essential autophagy modulators are genetically or pharmacologically inactivated, indicating that autophagy is required for the cytoprotective and/or anti-aging effects of spermidine and resveratrol. Genetic and functional studies indicate that spermidine inhibits histone acetylases, while resveratrol activates the histone deacetylase Sirtuin 1 to confer cytoprotection/longevity. Although it remains elusive whether the same histones (or perhaps other nuclear or cytoplasmic proteins) act as the downstream targets of spermidine and resveratrol, these results point to an essential role of protein hypoacetylation in autophagy control and in the regulation of longevity.

  9. Sex differences in facial emotion perception ability across the lifespan.

    Science.gov (United States)

    Olderbak, Sally; Wilhelm, Oliver; Hildebrandt, Andrea; Quoidbach, Jordi

    2018-03-22

    Perception of emotion in the face is a key component of human social cognition and is considered vital for many domains of life; however, little is known about how this ability differs across the lifespan for men and women. We addressed this question with a large community sample (N = 100,257) of persons ranging from younger than 15 to older than 60 years of age. Participants were viewers of the television show "Tout le Monde Joue", and the task was presented on television, with participants responding via their mobile devices. Applying latent variable modeling, and establishing measurement invariance between males and females and across age, we found that, for both males and females, emotion perception abilities peak between the ages of 15 and 30, with poorer performance by younger adults and declining performance after the age of 30. In addition, we show a consistent advantage by females across the lifespan, which decreases in magnitude with increasing age. This large scale study with a wide range of people and testing environments suggests these effects are largely robust. Implications are discussed.

  10. On the challenge of a century lifespan satellite

    Science.gov (United States)

    Gonzalo, Jesús; Domínguez, Diego; López, Deibi

    2014-10-01

    This paper provides a review of the main issues affecting satellite survivability, including a discussion on the technologies to mitigate the risks and to enhance system reliability. The feasibility of a 100-year lifespan space mission is taken as the guiding thread for the discussion. Such a mission, defined with a few preliminary requirements, could be used to deliver messages to our descendants regardless of the on-ground contingencies. After the analysis of the main threats for long endurance in space, including radiation, debris and micrometeoroids, atmospheric drag and thermal environment, the available solutions are investigated. A trade-off study analyses orbital profiles from the point of view of radiation, thermal stability and decay rate, providing best locations to maximize lifespan. Special attention is also paid to on-board power, in terms of energy harvesting and accumulation, highlighting the limitations of current assets, i.e. solar panels and batteries, and revealing possible future solutions. Furthermore, the review includes electronics, non-volatile memories and communication elements, which need extra hardening against radiation and thermal cycling if extra-long endurance is required. As a result of the analysis, a century-lifetime mission is depicted by putting together all the reviewed concepts. The satellite, equipped with reliability enhanced elements and system-level solutions such as smart hibernation policies, could provide limited but still useful performance after a 100-year flight.

  11. Advances in asthma 2015: Across the lifespan.

    Science.gov (United States)

    Liu, Andrew H; Anderson, William C; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

    2016-08-01

    In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened. Predicting and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. Although allergy has long been linked to asthma exacerbations, a mechanism through which IgE impairs rhinovirus immunity and underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy (omalizumab). Other key molecular pathways underlying asthma exacerbations, such as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food and Drug Administration approved for the treatment of patients with severe eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA-specific DNAzyme attenuated early- and late-phase allergic responses to inhaled allergen. These current findings are significant steps toward addressing unmet needs in asthma prevention, severity modification, disparities, and lifespan outcomes. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Male lifespan and the secondary sex ratio.

    Science.gov (United States)

    Catalano, Ralph; Bruckner, Tim

    2006-01-01

    Literature speculating on the fetal origins of later life morbidity often invokes the "damaged cohort" theory, i.e., that maternal responses to exogenous shocks induce "stress reactivity" in fetuses and thereby shorten the lifespan of males in utero during stressful times. A rival, or "culled cohort," theory posits that exogenous shocks to gravid females induce spontaneous abortions of frail male fetuses, leaving relatively hardy survivors who enjoy, on average, lifespans longer than males in less stressed birth cohorts. A recent test based on archival data from Sweden supported the culled cohort theory. Several characteristics of the Swedish data, however, raise questions regarding the external validity of the findings. We repeat the test with data from Denmark, Iceland, and England and Wales. We use time-series methods that control for trends, seasonal cycles, and other forms of autocorrelation that could confound the test. None of the results supports the "damaged cohort" theory. Consistent with the Swedish findings and with evolutionary theory, we find support in Iceland and England and Wales for the "culled cohort" theory. We discuss the implications of our findings for basic research as well as for public health.

  13. Nicotinamide extends replicative lifespan of human cells.

    Science.gov (United States)

    Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong

    2006-10-01

    We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

  14. Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets

    Directory of Open Access Journals (Sweden)

    Adam J. Dobson

    2017-01-01

    Full Text Available Consumption of unhealthy diets is exacerbating the burden of age-related ill health in aging populations. Such diets can program mammalian physiology to cause long-term, detrimental effects. Here, we show that, in Drosophila melanogaster, an unhealthy, high-sugar diet in early adulthood programs lifespan to curtail later-life survival despite subsequent dietary improvement. Excess dietary sugar promotes insulin-like signaling, inhibits dFOXO—the Drosophila homolog of forkhead box O (FOXO transcription factors—and represses expression of dFOXO target genes encoding epigenetic regulators. Crucially, dfoxo is required both for transcriptional changes that mark the fly’s dietary history and for nutritional programming of lifespan by excess dietary sugar, and this mechanism is conserved in Caenorhabditis elegans. Our study implicates FOXO factors, the evolutionarily conserved determinants of animal longevity, in the mechanisms of nutritional programming of animal lifespan.

  15. Availability of Amino Acids Extends Chronological Lifespan by Suppressing Hyper-Acidification of the Environment in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Yo Maruyama

    Full Text Available The chronological lifespan of Saccharomyces cerevisiae represents the duration of cell survival in the postdiauxic and stationary phases. Using a prototrophic strain derived from the standard auxotrophic laboratory strain BY4742, we showed that supplementation of non-essential amino acids to a synthetic defined (SD medium increases maximal cell growth and extends the chronological lifespan. The positive effects of amino acids can be reproduced by modulating the medium pH, indicating that amino acids contribute to chronological longevity in a cell-extrinsic manner by alleviating medium acidification. In addition, we showed that the amino acid-mediated effects on extension of chronological longevity are independent of those achieved through a reduction in the TORC1 pathway, which is mediated in a cell-intrinsic manner. Since previous studies showed that extracellular acidification causes mitochondrial dysfunction and leads to cell death, our results provide a path to premature chronological aging caused by differences in available nitrogen sources. Moreover, acidification of culture medium is generally associated with culture duration and cell density; thus, further studies are required on cell physiology of auxotrophic yeast strains during the stationary phase because an insufficient supply of essential amino acids may cause alterations in environmental conditions.

  16. IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan.

    Science.gov (United States)

    Ashpole, Nicole M; Logan, Sreemathi; Yabluchanskiy, Andriy; Mitschelen, Matthew C; Yan, Han; Farley, Julie A; Hodges, Erik L; Ungvari, Zoltan; Csiszar, Anna; Chen, Sixia; Georgescu, Constantin; Hubbard, Gene B; Ikeno, Yuji; Sonntag, William E

    2017-04-01

    Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf f/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

  17. A Modified Carbon Monoxide Breath Test for Measuring Erythrocyte Lifespan in Small Animals

    Directory of Open Access Journals (Sweden)

    Yong-Jian Ma

    2016-01-01

    Full Text Available This study was to develop a CO breath test for RBC lifespan estimation of small animals. The ribavirin induced hemolysis rabbit models were placed individually in a closed rebreath cage and air samples were collected for measurement of CO concentration. RBC lifespan was calculated from accumulated CO, blood volume, and hemoglobin concentration data. RBC lifespan was determined in the same animals with the standard biotin-labeling method. RBC lifespan data obtained by the CO breath test method for control (CON, 49.0±5.9 d rabbits, rabbits given 10 mg/kg·d−1 of ribavirin (RIB10, 31.0±4.0 d, and rabbits given 20 mg/kg·d−1 of ribavirin (RIB20, 25.0±2.9 d were statistically similar (all p>0.05 to and linearly correlated (r=0.96, p<0.01 with the RBC lifespan data obtained for the same rabbits by the standard biotin-labeling method (CON, 51.0±2.7 d; RIB10, 33.0±1.3 d; and RIB20, 27.0±0.8 d. The CO breath test method takes less than 3 h to complete, whereas the standard method requires at least several weeks. In conclusion, the CO breath test method provides a simple and rapid means of estimating RBC lifespan and is feasible for use with small animal models.

  18. Calorie restriction extends the chronological lifespan of Saccharomyces cerevisiae independently of the Sirtuins.

    Science.gov (United States)

    Smith, Daniel L; McClure, Julie M; Matecic, Mirela; Smith, Jeffrey S

    2007-10-01

    Calorie restriction (CR) extends the mean and maximum lifespan of a wide variety of organisms ranging from yeast to mammals, although the molecular mechanisms of action remain unclear. For the budding yeast Saccharomyces cerevisiae reducing glucose in the growth medium extends both the replicative and chronological lifespans (CLS). The conserved NAD(+)-dependent histone deacetylase, Sir2p, promotes replicative longevity in S. cerevisiae by suppressing recombination within the ribosomal DNA locus and has been proposed to mediate the effects of CR on aging. In this study, we investigated the functional relationships of the yeast Sirtuins (Sir2p, Hst1p, Hst2p, Hst3p and Hst4p) with CLS and CR. SIR2, HST2, and HST4 were not major regulators of CLS and were not required for the lifespan extension caused by shifting the glucose concentration from 2 to 0.5% (CR). Deleting HST1 or HST3 moderately shortened CLS, but did not prevent CR from extending lifespan. CR therefore works through a Sirtuin-independent mechanism in the chronological aging system. We also show that low temperature or high osmolarity additively extends CLS when combined with CR, suggesting that these stresses and CR act through separate pathways. The CR effect on CLS was not specific to glucose. Restricting other simple sugars such as galactose or fructose also extended lifespan. Importantly, growth on nonfermentable carbon sources that force yeast to exclusively utilize respiration extended lifespan at nonrestricted concentrations and provided no additional benefit when restricted, suggesting that elevated respiration capacity is an important determinant of chronological longevity.

  19. Perceptions of love across the lifespan: differences in passion, intimacy, and commitment

    NARCIS (Netherlands)

    Sumter, S.R.; Valkenburg, P.M.; Peter, J.

    2013-01-01

    This study investigated perceptions of love across the lifespan using Sternberg’s triangular theory of love, which distinguishes between passion, intimacy, and commitment. The study aimed to (a) investigate the psychometric properties of the short Triangular Love Scale (TLS-short) in adolescents and

  20. Perceptions of Love across the Lifespan: Differences in Passion, Intimacy, and Commitment

    Science.gov (United States)

    Sumter, Sindy R.; Valkenburg, Patti M.; Peter, Jochen

    2013-01-01

    This study investigated perceptions of love across the lifespan using Sternberg's triangular theory of love, which distinguishes between passion, intimacy, and commitment. The study aimed to (a) investigate the psychometric properties of the short Triangular Love Scale (TLS-short) in adolescents and adults (see Appendix), and (b) track age and…

  1. A Motivational Theory of Life-Span Development

    Science.gov (United States)

    Heckhausen, Jutta; Wrosch, Carsten; Schulz, Richard

    2010-01-01

    This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the…

  2. Minority Stress across the Career-Lifespan Trajectory

    Science.gov (United States)

    Dispenza, Franco; Brown, Colton; Chastain, Taylor E.

    2016-01-01

    Sexual minority persons (e.g., lesbian, gay, bisexual, and queer) are likely to encounter "minority stress", such as discrimination, concealment, expectation of rejection, and internalized heterosexism. Minority stress occurs alongside one's lifespan and has considerable implications in the context of the career lifespan trajectory.…

  3. The Path to Competence: A Lifespan Developmental Perspective on Reading

    Science.gov (United States)

    Alexander, Patricia A.

    2012-01-01

    The purpose of this document is to present a developmental model of reading that encompasses changes across the lifespan. The need for such a lifespan orientation toward reading within our educational institutions is great. Until we adopt this lifelong perspective, we continue to run the risk of turning out undeveloped, unmotivated, and uncritical…

  4. A case study of IMRT planning (Plan B) subsequent to a previously treated IMRT plan (Plan A)

    International Nuclear Information System (INIS)

    2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" data-affiliation=" (Department of Medical Physics and 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" >Cao, F; 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" data-affiliation=" (Department of Medical Physics and 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" >Leong, C; 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" data-affiliation=" (Department of Medical Physics and 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" >Schroeder, J; 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" data-affiliation=" (Department of Medical Physics and 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" >Lee, B

    2014-01-01

    Background and purpose: Treatment of the contralateral neck after previous ipsilateral intensity modulated radiation therapy (IMRT) for head and neck cancer is a challenging problem. We have developed a technique that limits the cumulative dose to the spinal cord and brainstem while maximizing coverage of a planning target volume (PTV) in the contralateral neck. Our case involves a patient with right tonsil carcinoma who was given ipsilateral IMRT with 70Gy in 35 fractions (Plan A). A left neck recurrence was detected 14 months later. The patient underwent a neck dissection followed by postoperative left neck radiation to a dose of 66 Gy in 33 fractions (Plan B). Materials and Methods: The spinal cord-brainstem margin (SCBM) was defined as the spinal cord and brainstem with a 1.0 cm margin. Plan A was recalculated on the postoperative CT scan but the fluence outside of SCBM was deleted. A further modification of Plan A resulted in a base plan that was summed with Plan B to evaluate the cumulative dose received by the spinal cord and brainstem. Plan B alone was used to evaluate for coverage of the contralateral neck PTV. Results: The maximum cumulative doses to the spinal cord with 0.5cm margin and brainstem with 0.5cm margin were 51.96 Gy and 45.60 Gy respectively. For Plan B, 100% of the prescribed dose covered 95% of PTVb1. Conclusion: The use of a modified ipsilateral IMRT plan as a base plan is an effective way to limit the cumulative dose to the spinal cord and brainstem while enabling coverage of a PTV in the contralateral neck.

  5. Evaluation of a rapid dipstick (Crystal VC for the diagnosis of cholera in Zanzibar and a comparison with previous studies.

    Directory of Open Access Journals (Sweden)

    Benedikt Ley

    Full Text Available The gold standard for the diagnosis of cholera is stool culture, but this requires laboratory facilities and takes at least 24 hours. A rapid diagnostic test (RDT that can be used by minimally trained staff at treatment centers could potentially improve the reporting and management of cholera outbreaks.We evaluated the Crystal VC™ RDT under field conditions in Zanzibar in 2009. Patients presenting to treatment centers with watery diarrhea provided a stool sample for rapid diagnostic testing. Results were compared to stool culture performed in a reference laboratory. We assessed the overall performance of the RDT and evaluated whether previous intake of antibiotics, intravenous fluids, location of testing, and skill level of the technician affected the RDT results.We included stool samples from 624 patients. Compared to culture, the overall sensitivity of the RDT was 93.1% (95%CI: 88.7 to 96.2%, specificity was 49.2% (95%CI: 44.3 to 54.1%, the positive predictive value was 47.0% (95%CI: 42.1 to 52.0% and the negative predictive value was 93.6% (95%CI: 89.6 to 96.5%. The overall false positivity rate was 50.8% (213/419; fieldworkers frequently misread very faint test lines as positive.The observed sensitivity of the Crystal VC RDT evaluated was similar compared to earlier versions, while specificity was poorer. The current version of the RDT could potentially be used as a screening tool in the field. Because of the high proportion of false positive results when field workers test stool specimens, positive results will need to be confirmed with stool culture.

  6. Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans.

    Directory of Open Access Journals (Sweden)

    Mai-Britt Mosbech

    Full Text Available Ceramide and its metabolites constitute a diverse group of lipids, which play important roles as structural entities of biological membranes as well as regulators of cellular growth, differentiation, and development. The C. elegans genome comprises three ceramide synthase genes; hyl-1, hyl-2, and lagr-1. HYL-1 function is required for synthesis of ceramides and sphingolipids containing very long acyl-chains (≥C24, while HYL-2 is required for synthesis of ceramides and sphingolipids containing shorter acyl-chains (≤C22. Here we show that functional loss of HYL-2 decreases lifespan, while loss of HYL-1 or LAGR-1 does not affect lifespan. We show that loss of HYL-1 and LAGR-1 functions extend lifespan in an autophagy-dependent manner, as knock down of the autophagy-associated gene ATG-12 abolishes hyl-1;lagr-1 longevity. The transcription factors PHA-4/FOXA, DAF-16/FOXO, and SKN-1 are also required for the observed lifespan extension, as well as the increased number of autophagosomes in hyl-1;lagr-1 animals. Both autophagic events and the transcription factors PHA-4/FOXA, DAF-16, and SKN-1 have previously been associated with dietary restriction-induced longevity. Accordingly, we find that hyl-1;lagr-1 animals display reduced feeding, increased resistance to heat, and reduced reproduction. Collectively, our data suggest that specific sphingolipids produced by different ceramide synthases have opposing roles in determination of C. elegans lifespan. We propose that loss of HYL-1 and LAGR-1 result in dietary restriction-induced autophagy and consequently prolonged longevity.

  7. Contextual Cueing Effects across the Lifespan

    Science.gov (United States)

    Merrill, Edward C.; Conners, Frances A.; Roskos, Beverly; Klinger, Mark R.; Klinger, Laura Grofer

    2013-01-01

    The authors evaluated age-related variations in contextual cueing, which reflects the extent to which visuospatial regularities can facilitate search for a target. Previous research produced inconsistent results regarding contextual cueing effects in young children and in older adults, and no study has investigated the phenomenon across the life…

  8. Studies in iodine metabolism: 33 year summary, 1948-1979 (as previously submitted) with appendix, 1979-1982

    International Nuclear Information System (INIS)

    Middlesworth, L.V.

    1982-01-01

    The results of research into iodine metabolism from 1948 to 1982 are summarized. Study areas included the monitoring of iodine 131 from fallout in the thyroid glands of cattle and humans, the biological functions and metabolism of thyroid hormones, and methods to reduce the retention of radioiodine in the thyroid

  9. The association between intelligence and lifespan is mostly genetic

    DEFF Research Database (Denmark)

    Arden, Rosalind; Luciano, Michelle; Deary, Ian J

    2016-01-01

    BACKGROUND: Several studies in the new field of cognitive epidemiology have shown that higher intelligence predicts longer lifespan. This positive correlation might arise from socioeconomic status influencing both intelligence and health; intelligence leading to better health behaviours; and....../or some shared genetic factors influencing both intelligence and health. Distinguishing among these hypotheses is crucial for medicine and public health, but can only be accomplished by studying a genetically informative sample. METHODS: We analysed data from three genetically informative samples...... containing information on intelligence and mortality: Sample 1, 377 pairs of male veterans from the NAS-NRC US World War II Twin Registry; Sample 2, 246 pairs of twins from the Swedish Twin Registry; and Sample 3, 784 pairs of twins from the Danish Twin Registry. The age at which intelligence was measured...

  10. Lifespan divergence between social insect castes : Challenges and opportunities for evolutionary theories of aging

    NARCIS (Netherlands)

    Kramer, Boris H; van Doorn, G Sander; Weissing, Franz J; Pen, Ido

    The extraordinarily long lifespans of queens (and kings) in eusocial insects and the strikingly large differences in life expectancy between workers and queens challenge our understanding of the evolution of aging and provide unique opportunities for studying the causes underlying adaptive variation

  11. Mental health and illness in relation to physical health across the lifespan

    NARCIS (Netherlands)

    Lamers, S.M.A.; Westerhof, Gerben Johan; Bohlmeijer, Ernst Thomas; Keyes, Corey L.M.; Sinnott, J.D.

    2013-01-01

    This chapter addresses mental health as more than the absence of disease, also approaching it from a positive perspective as the presence of well-being across the lifespan. The study described in the chapter investigated the association of age with psychopathology and positive mental health,

  12. An Adaptation, Validity and Reliability of the Lifespan Sibling Relationship Scale to the Turkish Adolescents

    Science.gov (United States)

    Öz, F. Selda

    2015-01-01

    The purpose of this study is to adapt the Lifespan Sibling Relationship Scale (LSRS) developed by Riggio (2000) to Turkish. The scale with its original form in English consists of 48 items in total. The original scale was translated into Turkish by three instructors who are proficient both in the field and the language. Later, the original and…

  13. Dance Talent Development across the Lifespan: A Review of Current Research

    Science.gov (United States)

    Chua, Joey

    2014-01-01

    The aim of this study is to compile and synthesize empirically based articles published between 2000 and 2012 about the critical issues of developing dance talents across the lifespan of children, adolescents and adults. The present article updates and extends a review article related to the identification and development in dance written by…

  14. Investigating the life-span of cork products through a longitudinal approach with users- Interim results

    NARCIS (Netherlands)

    Da Silva Pereira, A.C.; Brezet, J.C.; Pereira, H.; Vogtlander, J.G.

    2012-01-01

    Products with long life-spans are generally preferred form an environmental perspective. This paper addresses the longevity of cork products, and the respective influencing aspects. This is accomplished through a longitudinal study where several cork products are used, and at different moments in

  15. Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.

    Science.gov (United States)

    Apfeld, Javier; Fontana, Walter

    2017-12-23

    It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinson's disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinson's disease, such a joint distribution is not available, because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinson's disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of individual neurons. Therefore, neuronal loss is age-dependent and aging-independent. We also find that a lifespan-extending intervention into insulin/IGF1 signaling accelerates the loss of specific dopaminergic neurons, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans . Although the human context might well be different, our study calls attention to the need to maintain a rigorous distinction between age-dependence and aging-dependence.

  16. Estimation of adult and neonatal RBC lifespans in anemic neonates using RBCs labeled at several discrete biotin densities.

    Science.gov (United States)

    Kuruvilla, Denison J; Widness, John A; Nalbant, Demet; Schmidt, Robert L; Mock, Donald M; An, Guohua; Veng-Pedersen, Peter

    2017-06-01

    Prior conclusions that autologous neonatal red blood cells (RBC) have substantially shorter lifespans than allogeneic adult RBCs were not based on direct comparison of autologous neonatal vs. allogeneic adult RBCs performed concurrently in the same infant. Biotin labeling of autologous neonatal RBCs and allogeneic adult donor RBCs permits concurrent direct comparison of autologous vs. allogeneic RBC lifespan. RBCs from 15 allogeneic adult donors and from 15 very-low-birth-weight (VLBW) neonates were labeled at separate biotin densities and transfused simultaneously into the 15 neonates. Two mathematical models that account for the RBC differences were employed to estimate lifespans for the two RBC populations. Mean ± SD lifespan for adult allogeneic RBC was 70.1 ± 19.1 d, which is substantially shorter than the 120 d lifespan of both autologous and adult allogeneic RBC in healthy adults. Mean ± SD lifespan for neonatal RBC was 54.2 ± 11.3 d, which is only about 30% shorter than that of the adult allogeneic RBCs. This study provides evidence that extrinsic environmental factors primarily determine RBC survival (e.g., small bore of the capillaries of neonates, rate of oxygenation/deoxygenation cycles) rather than factors intrinsic to RBC.

  17. CHRONOVAC VOYAGEUR: A study of the immune response to yellow fever vaccine among infants previously immunized against measles.

    Science.gov (United States)

    Goujon, Catherine; Gougeon, Marie-Lise; Tondeur, Laura; Poirier, Béatrice; Seffer, Valérie; Desprès, Philippe; Consigny, Paul-Henri; Vray, Muriel

    2017-10-27

    For administration of multiple live attenuated vaccines, the Advisory Committee on Immunization Practices recommends either simultaneous immunization or period of at least 28days between vaccines, due to a possible reduction in the immune response to either vaccine. The main objective of this study was to compare the immune response to measles (alone or combined with mumps and rubella) and yellow fever vaccines among infants aged 6-24months living in a yellow fever non-endemic country who had receivedmeasles and yellow fever vaccines before travelling to a yellow fever endemic area. A retrospective, multicenter case-control study was carried out in 7 travel clinics in the Paris area from February 1st 2011 to march 31, 2015. Cases were defined as infants immunized with the yellow fever vaccine and with the measles vaccine, either alone or in combination with mumps and rubella vaccine, with a period of 1-27days between each immunization. For each case, two controls were matched based on sex and age: a first control group (control 1) was defined as infants having received the measles vaccine and the yellow fever vaccine simultaneously; a second control group (control 2) was defined as infants who had a period of more than 27days between receiving the measles vaccine and yellow fever vaccine. The primary endpoint of the study was the percentage of infants with protective immunity against yellow fever, measured by the titer of neutralizing antibodies in a venous blood sample. One hundred and thirty-one infants were included in the study (62 cases, 50 infants in control 1 and 19 infants in control 2). Of these, 127 (96%) were shown to have a protective titer of yellow fever antibodies. All 4 infants without a protective titer of yellow fever antibodies were part of control group 1. The measles vaccine, alone or combined with mumps and rubella vaccines, appears to have no influence on humoral immune response to the yellow fever vaccine when administered between 1 and 27

  18. Structural Study and Evaluation of Previous Restoration Work of Mohammad 'Ali Pasha Mosque at the Citadel in Cairo

    Directory of Open Access Journals (Sweden)

    dr.Yaser Yehya Amin Abdel-Aty

    2011-01-01

    Full Text Available Mohammad 'Ali Pasha Mosque at the Citadel in Cairo is considered one of the main landmarks in Egypt. It majestically stands at a northwestern bend of the Citadel and it is visible from numerous locations in Cairo. It has become the symbol of the Citadel, to the point that its name is given to the whole complex in the colloquial Egyptian parlance. This paper studies analytically the static and dynamic structural behavior of this great mosque using computer numerical modeling techniques, to reach the main reasons for past cracking and failures in its domed-roof and other structural elements, which occurred by the end of 19th Century. A number of 3D-models are analyzed to study the mosque, in both original and after restoration conditions, under static (i.e. dead and live loads and dynamic (i.e. Eigenvector modal analysis, response-spectrum and time-history cases of loading. Besides, structural evaluation of major restoration project, in 1930s, is conducted to determine the current structural safety status of the mosque

  19. Comparative study of a novel application of automated HR HPV assay and stability in a previously untested Preservative media.

    Science.gov (United States)

    Morel, Mike E; McBride, Simon E; Gomez, Maria P

    2017-12-01

    The suitability and stability of cervical cells in Novaprep media (NHQ) for certain HPV assays is unknown. We evaluated the accuracy of an automated HPV assay (Abbott RealTime HR HPV) for cervical cells prepared in NHQ and NHQ with a pre-treatment to mimic a worst case clinical use, compared to the assay manufacturers media; repeatability and reproducibility of HPV results and the stability of detectable HPV in NHQ over time compared to CE marked liquid based cytology preservatives. Cell lines were used to simulate patient samples. Cells stored in NHQ produced accurate, repeatable and reproducible results. Stability in NHQ was comparable to the best performing LBC, with at least 7 months' stability at 18-25°C, 2-8°C, -20°C and -80°C; and at least 3 months' stability at 40°C. Similar results were obtained for pre-treated NHQ except only 3.5 months' stability at 18-25°C. Cell line samples in all media and concentrations tested were detected appropriately by the assay. Based on this first stage validation analytical study, cervical cells stored in NHQ are suitable for the Realtime HPV assay. There should be no reservations for inclusion of NHQ in any further validation and clinical performance evaluation of this assay. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. No turnover in lens lipids for the entire human lifespan.

    Science.gov (United States)

    Hughes, Jessica R; Levchenko, Vladimir A; Blanksby, Stephen J; Mitchell, Todd W; Williams, Alan; Truscott, Roger J W

    2015-03-11

    Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease (Dawidowicz 1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan. This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable. Such substantial changes in lens cell membranes may play a role in the genesis of age-related eye disorders. Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.

  1. Comparative study of a novel application of automated HR HPV assay and stability in a previously untested Preservative media

    Directory of Open Access Journals (Sweden)

    Mike E. Morel

    2017-12-01

    Full Text Available Background: The suitability and stability of cervical cells in Novaprep media (NHQ for certain HPV assays is unknown. Methods: We evaluated the accuracy of an automated HPV assay (Abbott RealTime HR HPV for cervical cells prepared in NHQ and NHQ with a pre-treatment to mimic a worst case clinical use, compared to the assay manufacturers media; repeatability and reproducibility of HPV results and the stability of detectable HPV in NHQ over time compared to CE marked liquid based cytology preservatives. Cell lines were used to simulate patient samples. Results: Cells stored in NHQ produced accurate, repeatable and reproducible results. Stability in NHQ was comparable to the best performing LBC, with at least 7 months’ stability at 18–25 °C, 2–8 °C, −20 °C and −80 °C; and at least 3 months’ stability at 40 °C. Similar results were obtained for pre-treated NHQ except only 3.5 months’ stability at 18–25 °C. Cell line samples in all media and concentrations tested were detected appropriately by the assay. Conclusions: Based on this first stage validation analytical study, cervical cells stored in NHQ are suitable for the Realtime HPV assay. There should be no reservations for inclusion of NHQ in any further validation and clinical performance evaluation of this assay. Keywords: HPV, Preservative, Sample stability, Automated HR HPV assay

  2. Sexual selection affects the evolution of lifespan and ageing in the decorated cricket Gryllodes sigillatus.

    Science.gov (United States)

    Archer, C R; Zajitschek, F; Sakaluk, S K; Royle, N J; Hunt, J

    2012-10-01

    Recent work suggests that sexual selection can influence the evolution of ageing and lifespan by shaping the optimal timing and relative costliness of reproductive effort in the sexes. We used inbred lines of the decorated cricket, Gryllodes sigillatus, to estimate the genetic (co)variance between age-dependent reproductive effort, lifespan, and ageing within and between the sexes. Sexual selection theory predicts that males should die sooner and age more rapidly than females. However, a reversal of this pattern may be favored if reproductive effort increases with age in males but not in females. We found that male calling effort increased with age, whereas female fecundity decreased, and that males lived longer and aged more slowly than females. These divergent life-history strategies were underpinned by a positive genetic correlation between early-life reproductive effort and ageing rate in both sexes, although this relationship was stronger in females. Despite these sex differences in life-history schedules, age-dependent reproductive effort, lifespan, and ageing exhibited strong positive intersexual genetic correlations. This should, in theory, constrain the independent evolution of these traits in the sexes and may promote intralocus sexual conflict. Our study highlights the importance of sexual selection to the evolution of sex differences in ageing and lifespan in G. sigillatus. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  3. Neoplastic and life-span effects of chronic exposure to tritium. II. Rats exposed in utero

    International Nuclear Information System (INIS)

    Cahill, D.F.; Wright, J.F.; Godbold, J.H.; Ward, J.M.; Laskey, J.W.; Tompkins, E.A.

    1975-01-01

    A study was conducted to determine the effects on neoplasia incidence and life-span of exposure in utero to a major environmental radionuclide. Sprague-Dawley rats were continuously exposed to tritiated water (HTO) from conception through birth in doses of 0, 1, 10, 50, and 100 μCi HTO/ml body water. HTO administration was terminated at birth. Calculated cumulative doses during gestation were approximately 0, 6.6, 66, 330, and 660 rads of total body irradiation. Under these exposure conditions, the two highest doses resulted in sterile offspring. Animals surviving through 30 days postnatally were defined as the study population and observed until their deaths. Intrauterine exposures to doses up to 66 rads had no significant effects on either sex with respect to lifespan, overall neoplasia incidence, incidence rate, or onset of mammary fibroadenomas. Females exposed to 330 or 660 rads were sterile and had lower incidence rates of mammary fibroadenomas than did controls; at 660 rads females had a lower incidence of overall neoplasia and reduced mean lifespans. Sterile male offspring had reduced mean longevity after irradiation at 660 rads. Regardless of dose group, females had significantly higher incidences of neoplasia and longer life-spans than males

  4. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-12-25

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Neurodevelopmental origins of lifespan changes in brain and cognition

    Science.gov (United States)

    Walhovd, Kristine B.; Krogsrud, Stine K.; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J.; Håberg, Asta K.; Kremen, William S.; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S.; Rohani, Darius A.; Skranes, Jon; Storsve, Andreas B.; Sølsnes, Anne Elisabeth; Tamnes, Christian K.; Thompson, Wesley K.; Reuter, Chase; Dale, Anders M.; Fjell, Anders M.

    2016-01-01

    Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4–88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother–Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain–cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course. PMID:27432992

  6. Empirically derived lifespan polytraumatization typologies: A systematic review.

    Science.gov (United States)

    Contractor, Ateka A; Caldas, Stephanie; Fletcher, Shelley; Shea, M Tracie; Armour, Cherie

    2018-07-01

    Polytraumatization classes based on trauma endorsement patterns relate to distinct clinical outcomes. Person-centered approaches robustly evaluate the nature, and construct validity of polytraumatization classes. Our review examined evidence for the nature and construct validity of lifespan polytraumatization typologies. In September 2016, we searched Pubmed, PSYCINFO, PSYC ARTICLES, Academic Search Complete, PILPTS, Web of Science, CINAHL, Medline, PsycEXTRA, and PBSC. Search terms included "latent profile," "latent class," "latent analysis," "person-centered," "polytrauma," "polyvictimization," "traumatization," "lifetime," "cooccurring," "complex," "typology," "multidimensional," "sequential," "multiple," "subtype," "(re)victimization," "cumulative," "maltreatment," "abuse," and "stressor." Inclusionary criteria included: peer-reviewed; latent class/latent profile analyses (LCA/LPA) of lifespan polytrauma classes; adult samples of size greater than 200; only trauma types as LCA/LPA indicators; mental health correlates of typologies; and individual-level trauma assessment. Of 1,397 articles, nine met inclusion criteria. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, research assistants completed a secondary reference search, and independently extracted data with standardized coding forms. Three-class (n = 5) or four-class (n = 4) solutions were found. Seven studies found a class characterized by higher trauma endorsement (high-trauma). All studies found a class characterized by lower trauma endorsement (low-trauma), and predominance of specific traumas (specific-trauma; e.g., childhood maltreatment). High-trauma versus low-trauma classes and specific-trauma versus low-trauma classes differed on mental health correlates. Evidence supports the prevalence of a high-trauma class experiencing poorer mental health, and the detrimental impact of aggregated interpersonal and other traumas. We highlight the clinical

  7. Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model

    Directory of Open Access Journals (Sweden)

    Virk Bhupinder

    2012-07-01

    Full Text Available Abstract Background Gut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live E. coli provides the nematode worm Caenorhabditis elegans with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits C. elegans lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging. Results Serendipitously, we isolated an E. coli mutant that slows C. elegans aging. We identified the disrupted gene to be aroD, which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased C. elegans lifespan was caused by decreased availability of para-aminobenzoic acid, a precursor to folate. Consistent with this result, inhibition of folate synthesis by sulfamethoxazole, a sulfonamide, led to a dose-dependent increase in C. elegans lifespan. As expected, these treatments caused a decrease in bacterial and worm folate levels, as measured by mass spectrometry of intact folates. The folate cycle is essential for cellular biosynthesis. However, bacterial proliferation and C. elegans growth and reproduction were unaffected under the conditions that increased lifespan. Conclusions In this animal:microbe system, folates are in excess of that required for biosynthesis. This study suggests that microbial folate synthesis is a pharmacologically accessible target to slow animal aging without detrimental effects.

  8. Lifespan metabolic potential of the unicellular organisms expressed by Boltzmann constant, absolute temperature and proton mass

    Science.gov (United States)

    Atanasov, Atanas Todorov

    2016-12-01

    The unicellular organisms and phages are the first appeared fundamental living organisms on the Earth. The total metabolic energy (Els, J) of these organisms can be expressed by their lifespan metabolic potential (Als, J/kg) and body mass (M, kg): Els =Als M. In this study we found a different expression - by Boltzmann's constant (k, J/K), nucleon mass (mp+, kg) of protons (and neutrons), body mass (M, kg) of organism or mass (Ms) of biomolecules (proteins, nucleotides, polysaccharides and lipids) building organism, and the absolute temperature (T, K). The found equations are: Els= (M/mp+)kT for phages and Els=(Ms/mp+)kT for the unicellular organisms. From these equations the lifespan metabolic potential can be expressed as: Als=Els/M= (k/mp+)T for phages and Als=Els/M= (k/3.3mp+)T for unicellular organisms. The temperature-normated lifespan metabolic potential (Als/T, J/K.kg) is equals to the ratio between Boltzmann's constant and nucleon mass: Als/T=k/mp+ for phages and Als/T=k/3.3mp+ for unicellular organisms. The numerical value of the k/mp+ ratio is equals to 8.254×103 J/K.kg, and the numerical value of k/3.3mp+ ratio is equal to 2.497×103 J/K.kg. These values of temperature-normated lifespan metabolic potential could be considered fundamental for the unicellular organisms.

  9. Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction.

    Science.gov (United States)

    Luis, Nuno Miguel; Wang, Lifen; Ortega, Mauricio; Deng, Hansong; Katewa, Subhash D; Li, Patrick Wai-Lun; Karpac, Jason; Jasper, Heinrich; Kapahi, Pankaj

    2016-10-25

    Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut. Consistently, IRE1/XBP1 function in ECs is required for increased longevity upon DR. We further identify sugarbabe, a Gli-like zinc-finger transcription factor, as a key mediator of the IRE1/XBP1-regulated induction of de novo lipogenesis in ECs. Overexpression of sugarbabe rescues metabolic and lifespan phenotypes of IRE1 loss-of-function conditions. Our study highlights the critical role of metabolic adaptation of the intestinal epithelium for DR-induced lifespan extension and explores the IRE1/XBP1 signaling pathway regulating this adaptation and influencing lifespan. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yoko Honda

    Full Text Available One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action.We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5. pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS. pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA, which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity.These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse species and may lead to the development of nutraceutical

  11. Docosahexaenoic Acid and Cognition throughout the Lifespan

    Directory of Open Access Journals (Sweden)

    Michael J. Weiser

    2016-02-01

    Full Text Available Docosahexaenoic acid (DHA is the predominant omega-3 (n-3 polyunsaturated fatty acid (PUFA found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action.

  12. Understanding aggressive behaviour across the lifespan.

    Science.gov (United States)

    Liu, J; Lewis, G; Evans, L

    2013-03-01

    Aggressive behaviour is the observable manifestation of aggression and is often associated with developmental transitions and a range of medical and psychiatric diagnoses across the lifespan. As healthcare professionals involved in the medical and psychosocial care of patients from birth through death, nurses frequently encounter - and may serve as - both victims and perpetrators of aggressive behaviour in the workplace. While the nursing literature has continually reported research on prevention and treatment approaches, less emphasis has been given to understanding the aetiology, including contextual precipitants of aggressive behaviour. This paper provides a brief review of the biological, social and environmental risk factors that purportedly give rise to aggressive behaviour. Further, many researchers have focused specifically on aggressive behaviour in adolescence and adulthood. Less attention has been given to understanding the aetiology of such behaviour in young children and older adults. This paper emphasizes the unique risk factors for aggressive behaviour across the developmental spectrum, including childhood, adolescence, adulthood and late life. Appreciation of the risk factors of aggressive behaviour, and, in particular, how they relate to age-specific manifestations, can aid nurses in better design and implementation of prevention and treatment programmes. © 2012 Blackwell Publishing.

  13. Bacterial Respiration and Growth Rates Affect the Feeding Preferences, Brood Size and Lifespan of Caenorhabditis elegans

    Science.gov (United States)

    Yu, Li; Yan, Xiaomei; Ye, Chenglong; Zhao, Haiyan; Chen, Xiaoyun; Hu, Feng; Li, Huixin

    2015-01-01

    Bacteria serve as live food and nutrients for bacterial-feeding nematodes (BFNs) in soils, and influence nematodes behavior and physiology through their metabolism. Five bacterial taxa (Bacillus amyloliquefaciens JX1, Variovorax sp. JX14, Bacillus megaterium JX15, Pseudomonas fluorescens Y1 and Escherichia coli OP50) and the typical BFN Caenorhabditis elegans were selected to study the effects of bacterial respiration and growth rates on the feeding preferences, brood size and lifespan of nematodes. P. fluorescens Y1 and E. coli OP50 were found to be more active, with high respiration and rapid growth, whereas B. amyloliquefaciens JX1 and B. megaterium JX15 were inactive. The nematode C. elegans preferred active P. fluorescens Y1 and E. coli OP50 obviously. Furthermore, worms that fed on these two active bacteria produced more offspring but had shorter lifespan, while inactive and less preferred bacteria had increased nematodes lifespan and decreased the brood size. Based on these results, we propose that the bacterial activity may influence the behavior and life traits of C. elegans in the following ways: (1) active bacteria reproduce rapidly and emit high levels of CO2 attracting C. elegans; (2) these active bacteria use more resources in the nematodes’ gut to sustain their survival and reproduction, thereby reducing the worm's lifespan; (3) inactive bacteria may provide less food for worms than active bacteria, thus increasing nematodes lifespan but decreasing their fertility. Nematodes generally require a balance between their preferred foods and beneficial foods, only preferred food may not be beneficial for nematodes. PMID:26222828

  14. Lifespan and reproduction in brain-specific miR-29-knockdown mouse.

    Science.gov (United States)

    Takeda, Toru; Tanabe, Hiroyuki

    2016-03-18

    The microRNA miR-29 is widely distributed and highly expressed in adult mouse brain during the mouse's lifetime. We recently created conditional mutant mice whose miR-29 was brain-specifically knocked down through overexpression of an antisense RNA transgene against miR-29. To explore a role for brain miR-29 in maximizing organismal fitness, we assessed somatic growth, reproduction, and lifespan in the miR-29-knockdown (KD) mice and their wild-type (WT) littermates. The KD mice were developmentally indistinguishable from WT mice with respect to gross morphology and physical activity. Fertility testing revealed that KD males were subfertile, whereas KD females were hyperfertile, only in terms of reproductive success, when compared to their gender-matched WT correspondents. Another phenotypic difference between KD and WT animals appeared in their lifespan data; KD males displayed an overall increasing tendency in post-reproductive survival relative to WT males. In contrast, KD females were prone to shorter lifespans than WT females. These results clarify that brain-targeted miR-29 knockdown affects both lifespan and reproduction in a gender-dependent manner, and moreover that the reciprocal responsiveness to the miR-29 knockdown between these two phenotypes in both genders closely follow life-course models based on the classical trade-off prediction wherein elaborate early-life energetic investment in reproduction entails accelerated late-life declines in survival, and vice versa. Thus, this study identified miR-29 as the first mammalian miRNA that is directly implicated in the lifetime trade-off between the two major fitness components, lifespan and reproduction. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. An epigenetic biomarker of aging for lifespan and healthspan

    Science.gov (United States)

    Levine, Morgan E.; Lu, Ake T.; Quach, Austin; Chen, Brian H.; Assimes, Themistocles L.; Bandinelli, Stefania; Hou, Lifang; Baccarelli, Andrea A.; Stewart, James D.; Li, Yun; Whitsel, Eric A.; Wilson, James G; Reiner, Alex P; Aviv, Abraham; Lohman, Kurt; Liu, Yongmei; Ferrucci, Luigi

    2018-01-01

    Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging. PMID:29676998

  16. Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis

    Science.gov (United States)

    2015-08-01

    exposure to the HFD or LFD, obese mice weighed significantly greater than lean mice (p=0.003, Table 1). There was no effect of HFD on non- fasted blood...AWARD NUMBER: W81XWH-13-1-0164 TITLE: Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis PRINCIPAL INVESTIGATOR: Victoria Bae...31 May 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis 5b. GRANT NUMBER

  17. Comparing the Developmental Genetics of Cognition and Personality over the Lifespan

    Science.gov (United States)

    Briley, Daniel A.; Tucker-Drob, Elliot M.

    2015-01-01

    Objective Empirical studies of cognitive ability and personality have tended to operate in isolation of one another. We suggest that returning to a unified approach to considering the development of individual differences in both cognition and personality can enrich our understanding of human development. Method We draw on previous meta-analyses of longitudinal, behavior genetic studies of cognition and personality across the lifespan, focusing particular attention on age trends in heritability and differential stability. Results Both cognition and personality are moderately heritable and exhibit large increases in stability with age; however, marked differences are evident. First, the heritability of cognition increases substantially with child age, while the heritability of personality decreases modestly with age. Second, increasing stability of cognition with age is overwhelmingly mediated by genetic factors, whereas increasing stability of personality with age is entirely mediated by environmental factors. Third, the maturational time-course of stability differs: Stability of cognition nears its asymptote by the end of the first decade of life, whereas stability of personality takes three decades to near its asymptote. Conclusions We discuss how proximal gene-environment dynamics, developmental processes, broad social contexts, and evolutionary pressures may intersect to give rise to these divergent patterns. PMID:26045299

  18. A Novel Physiology-Based Mathematical Model to Estimate Red Blood Cell Lifespan in Different Human Age Groups.

    Science.gov (United States)

    An, Guohua; Widness, John A; Mock, Donald M; Veng-Pedersen, Peter

    2016-09-01

    Direct measurement of red blood cell (RBC) survival in humans has improved from the original accurate but limited differential agglutination technique to the current reliable, safe, and accurate biotin method. Despite this, all of these methods are time consuming and require blood sampling over several months to determine the RBC lifespan. For situations in which RBC survival information must be obtained quickly, these methods are not suitable. With the exception of adults and infants, RBC survival has not been extensively investigated in other age groups. To address this need, we developed a novel, physiology-based mathematical model that quickly estimates RBC lifespan in healthy individuals at any age. The model is based on the assumption that the total number of RBC recirculations during the lifespan of each RBC (denoted by N max) is relatively constant for all age groups. The model was initially validated using the data from our prior infant and adult biotin-labeled red blood cell studies and then extended to the other age groups. The model generated the following estimated RBC lifespans in 2-year-old, 5-year-old, 8-year-old, and 10-year-old children: 62, 74, 82, and 86 days, respectively. We speculate that this model has useful clinical applications. For example, HbA1c testing is not reliable in identifying children with diabetes because HbA1c is directly affected by RBC lifespan. Because our model can estimate RBC lifespan in children at any age, corrections to HbA1c values based on the model-generated RBC lifespan could improve diabetes diagnosis as well as therapy in children.

  19. Sex differences in the genetic architecture of lifespan in a seed beetle: extreme inbreeding extends male lifespan

    DEFF Research Database (Denmark)

    Bilde, T.; Maklakov, Alexei A.; Meisner, Katrine

    2009-01-01

    Background Sex differences in lifespan are ubiquitous throughout the animal kingdom but the causes underlying this phenomenon remain poorly understood. Several explanations based on asymmetrical inheritance patterns (sex chromosomes or mitochondrial DNA) have been proposed, but these ideas have...

  20. Polychlorinated biphenyl exposure, diabetes and endogenous hormones: a cross-sectional study in men previously employed at a capacitor manufacturing plant.

    Science.gov (United States)

    Persky, Victoria; Piorkowski, Julie; Turyk, Mary; Freels, Sally; Chatterton, Robert; Dimos, John; Bradlow, H Leon; Chary, Lin Kaatz; Burse, Virlyn; Unterman, Terry; Sepkovic, Daniel W; McCann, Kenneth

    2012-08-29

    Studies have shown associations of diabetes and endogenous hormones with exposure to a wide variety of organochlorines. We have previously reported positive associations of polychlorinated biphenyls (PCBs) and inverse associations of selected steroid hormones with diabetes in postmenopausal women previously employed in a capacitor manufacturing plant. This paper examines associations of PCBs with diabetes and endogenous hormones in 63 men previously employed at the same plant who in 1996 underwent surveys of their exposure and medical history and collection of bloods and urine for measurements of PCBs, lipids, liver function, hematologic markers and endogenous hormones. PCB exposure was positively associated with diabetes and age and inversely associated with thyroid stimulating hormone and triiodothyronine-uptake. History of diabetes was significantly related to total PCBs and all PCB functional groupings, but not to quarters worked and job score, after control for potential confounders. None of the exposures were related to insulin resistance (HOMA-IR) in non-diabetic men. Associations of PCBs with specific endogenous hormones differ in some respects from previous findings in postmenopausal women employed at the capacitor plant. Results from this study, however, do confirm previous reports relating PCB exposure to diabetes and suggest that these associations are not mediated by measured endogenous hormones.

  1. Quantifying the influence of previously burned areas on suppression effectiveness and avoided exposure: A case study of the Las Conchas Fire

    Science.gov (United States)

    Matthew P. Thompson; Patrick Freeborn; Jon D. Rieck; Dave Calkin; Julie W. Gilbertson-Day; Mark A. Cochrane; Michael S. Hand

    2016-01-01

    We present a case study of the Las Conchas Fire (2011) to explore the role of previously burned areas (wildfires and prescribed fires) on suppression effectiveness and avoided exposure. Methodological innovations include characterisation of the joint dynamics of fire growth and suppression activities, development of a fire line effectiveness framework, and...

  2. Study of some physical aspects previous to design of an exponential experiment; Estudio de algunos aspectos fisicos previos al diseno de una experiencia exponencial

    Energy Technology Data Exchange (ETDEWEB)

    Caro, R; Francisco, J L. de

    1961-07-01

    This report presents the theoretical study of some physical aspects previous to the design of an exponential facility. The are: Fast and slow flux distribution in the multiplicative medium and in the thermal column, slowing down in the thermal column, geometrical distribution and minimum needed intensity of sources access channels and perturbations produced by possible variations in its position and intensity. (Author) 4 refs.

  3. Malate and fumarate extend lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Clare B Edwards

    Full Text Available Malate, the tricarboxylic acid (TCA cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1, glyoxylate shunt (gei-7, succinate dehydrogenase flavoprotein (sdha-2, or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.

  4. Running on empty: does mitochondrial DNA mutation limit replicative lifespan in yeast?: Mutations that increase the division rate of cells lacking mitochondrial DNA also extend replicative lifespan in Saccharomyces cerevisiae.

    Science.gov (United States)

    Dunn, Cory D

    2011-10-01

    Mitochondrial DNA (mtDNA) mutations escalate with increasing age in higher organisms. However, it has so far been difficult to experimentally determine whether mtDNA mutation merely correlates with age or directly limits lifespan. A recent study shows that budding yeast can also lose functional mtDNA late in life. Interestingly, independent studies of replicative lifespan (RLS) and of mtDNA-deficient cells show that the same mutations can increase both RLS and the division rate of yeast lacking the mitochondrial genome. These exciting, parallel findings imply a potential causal relationship between mtDNA mutation and replicative senescence. Furthermore, these results suggest more efficient methods for discovering genes that determine lifespan. Copyright © 2011 WILEY Periodicals, Inc.

  5. Visual word recognition across the adult lifespan.

    Science.gov (United States)

    Cohen-Shikora, Emily R; Balota, David A

    2016-08-01

    The current study examines visual word recognition in a large sample (N = 148) across the adult life span and across a large set of stimuli (N = 1,187) in three different lexical processing tasks (pronunciation, lexical decision, and animacy judgment). Although the focus of the present study is on the influence of word frequency, a diverse set of other variables are examined as the word recognition system ages and acquires more experience with language. Computational models and conceptual theories of visual word recognition and aging make differing predictions for age-related changes in the system. However, these have been difficult to assess because prior studies have produced inconsistent results, possibly because of sample differences, analytic procedures, and/or task-specific processes. The current study confronts these potential differences by using 3 different tasks, treating age and word variables as continuous, and exploring the influence of individual differences such as vocabulary, vision, and working memory. The primary finding is remarkable stability in the influence of a diverse set of variables on visual word recognition across the adult age spectrum. This pattern is discussed in reference to previous inconsistent findings in the literature and implications for current models of visual word recognition. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  6. Toward an Integrative Science of Life-Span Development and Aging

    Science.gov (United States)

    Piccinin, Andrea M.

    2010-01-01

    The study of aging demands an integrative life-span developmental framework, involving interdisciplinary collaborations and multiple methodological approaches for understanding how and why individuals change, in both normative and idiosyncratic ways. We highlight and summarize some of the issues encountered when conducting integrative research for understanding aging-related change, including, the integration of results across different levels of analysis; the integration of theory, design, and analysis; and the synthesis of results across studies of aging. We emphasize the necessity of longitudinal designs for understanding development and aging and discuss methodological issues that should be considered for achieving reproducible research on within-person processes. It will be important that current and future studies permit opportunities for quantitative comparison across populations given the extent to which historical shifts and cultural differences influence life-span processes and aging-related outcomes. PMID:20237144

  7. A cross-sectional study of tuberculosis drug resistance among previously treated patients in a tertiary hospital in Accra, Ghana: public health implications of standardized regimens.

    Science.gov (United States)

    Forson, Audrey; Kwara, Awewura; Kudzawu, Samuel; Omari, Michael; Otu, Jacob; Gehre, Florian; de Jong, Bouke; Antonio, Martin

    2018-04-02

    Mycobacterium tuberculosis drug resistance is a major challenge to the use of standardized regimens for tuberculosis (TB) therapy, especially among previously treated patients. We aimed to investigate the frequency and pattern of drug resistance among previously treated patients with smear-positive pulmonary tuberculosis at the Korle-Bu Teaching Hospital Chest Clinic, Accra. This was a cross-sectional survey of mycobacterial isolates from previously treated patients referred to the Chest Clinic Laboratory between October 2010 and October 2013. The Bactec MGIT 960 system for mycobactrerial culture and drug sensitivity testing (DST) was used for sputum culture of AFB smear-positive patients with relapse, treatment failure, failure of smear conversion, or default. Descriptive statistics were used to summarize patient characteristics, and frequency and patterns of drug resistance. A total of 112 isolates were studied out of 155 from previously treated patients. Twenty contaminated (12.9%) and 23 non-viable isolates (14.8%) were excluded. Of the 112 studied isolates, 53 (47.3%) were pan-sensitive to all first-line drugs tested Any resistance (mono and poly resistance) to isoniazid was found in 44 isolates (39.3%) and any resistance to streptomycin in 43 (38.4%). Thirty-one (27.7%) were MDR-TB. Eleven (35.5%) out of 31 MDR-TB isolates were pre-XDR. MDR-TB isolates were more likely than non-MDR isolates to have streptomycin and ethambutol resistance. The main findings of this study were the high prevalence of MDR-TB and streptomycin resistance among previously treated TB patients, as well as a high prevalence of pre-XDR-TB among the MDR-TB patients, which suggest that first-line and second-line DST is essential to aid the design of effective regimens for these groups of patients in Ghana.

  8. Age structure changes and extraordinary lifespan in wild medfly populations.

    Science.gov (United States)

    Carey, James R; Papadopoulos, Nikos T; Müller, Hans-Georg; Katsoyannos, Byron I; Kouloussis, Nikos A; Wang, Jane-Ling; Wachter, Kenneth; Yu, Wei; Liedo, Pablo

    2008-06-01

    The main purpose of this study was to test the hypotheses that major changes in age structure occur in wild populations of the Mediterranean fruit fly (medfly) and that a substantial fraction of individuals survive to middle age and beyond (> 3-4 weeks). We thus brought reference life tables and deconvolution models to bear on medfly mortality data gathered from a 3-year study of field-captured individuals that were monitored in the laboratory. The average time-to-death of captured females differed between sampling dates by 23.9, 22.7, and 37.0 days in the 2003, 2004, and 2005 field seasons, respectively. These shifts in average times-to-death provided evidence of changes in population age structure. Estimates indicated that middle-aged medflies (> 30 days) were common in the population. A surprise in the study was the extraordinary longevity observed in field-captured medflies. For example, 19 captured females but no reference females survived in the laboratory for 140 days or more, and 6 captured but no reference males survived in the laboratory for 170 days or more. This paper advances the study of aging in the wild by introducing a new method for estimating age structure in insect populations, demonstrating that major changes in age structure occur in field populations of insects, showing that middle-aged individuals are common in the wild, and revealing the extraordinary lifespans of wild-caught individuals due to their early life experience in the field.

  9. Cognitive Predictors of Everyday Problem Solving across the Lifespan.

    Science.gov (United States)

    Chen, Xi; Hertzog, Christopher; Park, Denise C

    2017-01-01

    An important aspect of successful aging is maintaining the ability to solve everyday problems encountered in daily life. The limited evidence today suggests that everyday problem solving ability increases from young adulthood to middle age, but decreases in older age. The present study examined age differences in the relative contributions of fluid and crystallized abilities to solving problems on the Everyday Problems Test (EPT). We hypothesized that due to diminishing fluid resources available with advanced age, crystallized knowledge would become increasingly important in predicting everyday problem solving with greater age. Two hundred and twenty-one healthy adults from the Dallas Lifespan Brain Study, aged 24-93 years, completed a cognitive battery that included measures of fluid ability (i.e., processing speed, working memory, inductive reasoning) and crystallized ability (i.e., multiple measures of vocabulary). These measures were used to predict performance on EPT. Everyday problem solving showed an increase in performance from young to early middle age, with performance beginning to decrease at about age of 50 years. As hypothesized, fluid ability was the primary predictor of performance on everyday problem solving for young adults, but with increasing age, crystallized ability became the dominant predictor. This study provides evidence that everyday problem solving ability differs with age, and, more importantly, that the processes underlying it differ with age as well. The findings indicate that older adults increasingly rely on knowledge to support everyday problem solving, whereas young adults rely almost exclusively on fluid intelligence. © 2017 S. Karger AG, Basel.

  10. A methodology for the analysis of differential coexpression across the human lifespan.

    Science.gov (United States)

    Gillis, Jesse; Pavlidis, Paul

    2009-09-22

    Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks. It has previously been hypothesized that such changes might be occurring over time in the lifespan of an organism. While both coexpression and differential expression of genes have been previously studied in life stage change or aging, differential coexpression has not. Generalizing differential coexpression analysis to many time points presents a methodological challenge. Here we introduce a method for analyzing changes in coexpression across multiple ordered groups (e.g., over time) and extensively test its validity and usefulness. Our method is based on the use of the Haar basis set to efficiently represent changes in coexpression at multiple time scales, and thus represents a principled and generalizable extension of the idea of differential coexpression to life stage data. We used published microarray studies categorized by age to test the methodology. We validated the methodology by testing our ability to reconstruct Gene Ontology (GO) categories using our measure of differential coexpression and compared this result to using coexpression alone. Our method allows significant improvement in characterizing these groups of genes. Further, we examine the statistical properties of our measure of differential coexpression and establish that the results are significant both statistically and by an improvement in semantic similarity. In addition, we found that our method finds more significant changes in gene relationships compared to several other methods of expressing temporal relationships between genes, such as coexpression over time. Differential coexpression over age generates significant and biologically relevant information about the genes producing it. Our Haar basis methodology for determining age-related differential coexpression performs better than other tested methods. The Haar basis set also lends itself to ready interpretation

  11. Is email a reliable means of contacting authors of previously published papers? A study of the Emergency Medicine Journal for 2001.

    Science.gov (United States)

    O'Leary, F

    2003-07-01

    To determine whether it is possible to contact authors of previously published papers via email. A cross sectional study of the Emergency Medicine Journal for 2001. 118 articles were included in the study. The response rate from those with valid email addresses was 73%. There was no statistical difference between the type of email address used and the address being invalid (p=0.392) or between the type of article and the likelihood of a reply (p=0.197). More responses were obtained from work addresses when compared with Hotmail addresses (86% v 57%, p=0.02). Email is a valid means of contacting authors of previously published articles, particularly within the emergency medicine specialty. A work based email address may be a more valid means of contact than a Hotmail address.

  12. Modulation of Replicative Lifespan in Cryptococcus neoformans: Implications for Virulence

    Science.gov (United States)

    Bouklas, Tejas; Jain, Neena; Fries, Bettina C.

    2017-01-01

    were used for infection, which confirmed target specificity and ruled out non-specific effects of the drugs on the Galleria host. Thus, this study suggests that RLS modulating drugs, such as Sir2p agonists, shift lifespan and vulnerability of the fungal population, and should be further investigated as a potential class of novel antifungal drug targets that can enhance antifungal efficacy. PMID:28194146

  13. Magpies and mirrors : identity as a mediator of music preferences across the lifespan

    OpenAIRE

    Leadbeater, Richard; Marsden, Alan

    2014-01-01

    This thesis examines the role of identity on the development and trajectory of music preferences across the lifespan. The focus of interest in recent empirical research has been to predict music preferences using adolescent individual differences. It is widely recognized that adolescents use music to help them deal with a number of psychosocial and emotional challenges, which often arise during this critical period of identity development. There has been little study whether adults similarly ...

  14. Immigration, Language Proficiency, and Autobiographical Memories: Lifespan Distribution and Second-Language Access

    OpenAIRE

    Esposito, Alena G.; Baker-Ward, Lynne

    2015-01-01

    This investigation examined two controversies in the autobiographical literature: how cross-language immigration affects the distribution of autobiographical memories across the lifespan and under what circumstances language-dependent recall is observed. Both Spanish/English bilingual immigrants and English monolingual non-immigrants participated in a cue word study, with the bilingual sample taking part in a within-subject language manipulation. The expected bump in the num...

  15. Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults

    OpenAIRE

    Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

    2015-01-01

    This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys (N=847), we confirmed four main uses of tablets: 1) Information Seekin...

  16. Steroids as central regulators of organismal development and lifespan.

    Directory of Open Access Journals (Sweden)

    Siu Sylvia Lee

    Full Text Available Larvae of the nematode Caenorhabditis elegans must choose between reproductive development and dauer diapause. This decision is based on sensing of environmental inputs and dauer pheromone, a small molecule signal that serves to monitor population density. These signals are integrated via conserved neuroendocrine pathways that converge on steroidal ligands of the nuclear receptor DAF-12, a homolog of the mammalian vitamin D receptor and liver X receptor. DAF-12 acts as the main switch between gene expression programs that drive either reproductive development or dauer entry. Extensive studies in the past two decades demonstrated that biosynthesis of two bile acid-like DAF-12 ligands, named dafachronic acids (DA, controls developmental fate. In this issue of PLoS Biology, Wollam et al. showed that a conserved steroid-modifying enzyme, DHS-16, introduces a key feature in the structures of the DAF-12 ligands, closing a major gap in the DA biosynthesis pathway. The emerging picture of DA biosynthesis in C. elegans enables us to address a key question in the field: how are complex environmental signals integrated to enforce binary, organism-wide decisions on developmental fate? Schaedel et al. demonstrated that pheromone and DA serve as competing signals, and that a positive feedback loop based on regulation of DA biosynthesis ensures organism-wide commitment to reproductive development. Considering that many components of DA signaling are highly conserved, ongoing studies in C. elegans may reveal new aspects of bile acid function and lifespan regulation in mammals.

  17. Previous dropout from diabetic care as a predictor of patients' willingness to use mobile applications for self-management: A cross-sectional study.

    Science.gov (United States)

    Yamaguchi, Satoko; Waki, Kayo; Tomizawa, Nobuko; Waki, Hironori; Nannya, Yasuhito; Nangaku, Masaomi; Kadowaki, Takashi; Ohe, Kazuhiko

    2017-07-01

    Preventing dropout is crucial in managing diabetes. Accordingly, we investigated whether patients who had dropped out of diabetic care are suitable candidates for the use of mobile technologies - such as smartphone applications - to support self-management (mHealth), which might help prevent dropout. We carried out a cross-sectional study in Tokyo, Japan. Patients aged 20 years or older who were clinically diagnosed as diabetic and who regularly visited the outpatient unit at the University of Tokyo Hospital were recruited between August 2014 and March 2015. Data were collected through face-to-face structured interviews, physical measurements and medical records. Participants were asked whether they were willing to use mHealth after being shown DialBetics - an mHealth application for diabetics - as an example, and about their history of dropout and previous mHealth experience. Data were analyzed by multivariate logistic regression models. Of 307 patients with type 1 and type 2 diabetes, 34 (11.1%) had previously dropped out from diabetic care. Multivariate analysis identified previous mHealth experience as a negative predictor of dropout (odds ratio 0.211, P = 0.023). Of those 34 patients, 27 (79.4%) expressed willingness to use mHealth, a significantly higher percentage than for those who had never dropped out (51.5%, P = 0.002). After adjusting for confounders, history of dropout remained a strong predictor of willingness (odds ratio 3.870, P = 0.004). Patients who previously dropped out of diabetic care are suitable candidates for mHealth. Future studies must evaluate whether mHealth is effective for preventing repeated dropout and improving glycemic control among this population. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  18. A reduction in age-enhanced gluconeogenesis extends lifespan.

    Science.gov (United States)

    Hachinohe, Mayumi; Yamane, Midori; Akazawa, Daiki; Ohsawa, Kazuhiro; Ohno, Mayumi; Terashita, Yuzu; Masumoto, Hiroshi

    2013-01-01

    The regulation of energy metabolism, such as calorie restriction (CR), is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan.

  19. A reduction in age-enhanced gluconeogenesis extends lifespan.

    Directory of Open Access Journals (Sweden)

    Mayumi Hachinohe

    Full Text Available The regulation of energy metabolism, such as calorie restriction (CR, is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan.

  20. Understanding retirement: the promise of life-span developmental frameworks.

    Science.gov (United States)

    Löckenhoff, Corinna E

    2012-09-01

    The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.

  1. Weight concern across the life-span: relationship to self-esteem and feminist identity.

    Science.gov (United States)

    Tiggemann, M; Stevens, C

    1999-07-01

    The aim of this study was to investigate the correlates of weight concern across the life-span. Questionnaires assessing weight concern, self-esteem, and feminist attitudes were completed in their homes by 180 women aged between 18 and 60 years. It was found that there was a negative relationship between weight concern and self-esteem for 30 to 49-year-old women, but not for younger or older women. A similar pattern held for feminist attitudes. Among 30 to 49-year-old women, a strong feminist orientation related to a lesser concern with weight. It was concluded that the meaning and experience of body weight and size change across the life-span.

  2. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study

    DEFF Research Database (Denmark)

    Schramm, Tina Ken; Gislason, Gunnar Hilmar; Vaag, Allan

    2011-01-01

    Aims The impact of insulin secretagogues (ISs) on long-term major clinical outcomes in type 2 diabetes remains unclear. We examined mortality and cardiovascular risk associated with all available ISs compared with metformin in a nationwide study. Methods and results All Danish residents >20 years......, initiating single-agent ISs or metformin between 1997 and 2006 were followed for up to 9 years (median 3.3 years) by individual-level linkage of nationwide registers. All-cause mortality, cardiovascular mortality, and the composite of myocardial infarction (MI), stroke, and cardiovascular mortality...... associated with individual ISs were investigated in patients with or without previous MI by multivariable Cox proportional-hazard analyses including propensity analyses. A total of 107 806 subjects were included, of whom 9607 had previous MI. Compared with metformin, glimepiride (hazard ratios and 95...

  3. Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults

    Science.gov (United States)

    Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

    2015-01-01

    This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys (N=847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations. PMID:26113769

  4. Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Portal-Celhay Cynthia

    2012-03-01

    Full Text Available Abstract Background A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. Results We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. Conclusions In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.

  5. Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults.

    Science.gov (United States)

    Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

    2015-11-01

    This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys ( N =847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations.

  6. Lifespan extension and the doctrine of double effect.

    Science.gov (United States)

    Capitaine, Laura; Devolder, Katrien; Pennings, Guido

    2013-06-01

    Recent developments in biogerontology--the study of the biology of ageing--suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan--a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the 'double effect argument', has gone unnoticed. This article exposes and critically evaluates this 'double effect argument'. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the 'double effect argument' is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning.

  7. How long do centenarians survive? Life expectancy and maximum lifespan.

    Science.gov (United States)

    Modig, K; Andersson, T; Vaupel, J; Rau, R; Ahlbom, A

    2017-08-01

    The purpose of this study was to explore the pattern of mortality above the age of 100 years. In particular, we aimed to examine whether Scandinavian data support the theory that mortality reaches a plateau at particularly old ages. Whether the maximum length of life increases with time was also investigated. The analyses were based on individual level data on all Swedish and Danish centenarians born from 1870 to 1901; in total 3006 men and 10 963 women were included. Birth cohort-specific probabilities of dying were calculated. Exact ages were used for calculations of maximum length of life. Whether maximum age changed over time was analysed taking into account increases in cohort size. The results confirm that there has not been any improvement in mortality amongst centenarians in the past 30 years and that the current rise in life expectancy is driven by reductions in mortality below the age of 100 years. The death risks seem to reach a plateau of around 50% at the age 103 years for men and 107 years for women. Despite the rising life expectancy, the maximum age does not appear to increase, in particular after accounting for the increasing number of individuals of advanced age. Mortality amongst centenarians is not changing despite improvements at younger ages. An extension of the maximum lifespan and a sizeable extension of life expectancy both require reductions in mortality above the age of 100 years. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  8. Developmental aspects of synaesthesia across the adult lifespan

    Directory of Open Access Journals (Sweden)

    Beat eMeier

    2014-03-01

    Full Text Available In synaesthesia, stimuli such as sounds, words or letters trigger experiences of colours, shapes or tastes and the consistency of these experiences is a hallmark of this condition. In this study we investigate for the first time whether there are age-related changes in the consistency of synaesthetic experiences. We tested a sample of more than 400 grapheme-colour synaesthetes who have colour experiences when they see letters and/or digits with a well-established test of consistency. Our results showed a decline in the number of consistent grapheme-colour associations across the adult lifespan. We also assessed age-related changes in the breadth of the colour spectrum. The results showed that the appearance of primary colours (i.e., red, blue, and green was mainly age-invariant. However, there was a decline in the occurrence of lurid colours while brown and achromatic tones occurred more often as concurrents in older age. These shifts in the colour spectrum suggest that synaesthesia does not simply fade, but rather undergoes more comprehensive changes. We propose that these changes are the result of a combination of both age-related perceptual and memory processing shifts.

  9. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

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    Tricia Hubbard-Turner, Erik A. Wikstrom, Sophie Guderian, Michael J. Turner

    2015-09-01

    Full Text Available We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL group, the transected anterior talofibular ligament (ATFL/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011. Daily duration was different between the three running groups (p = 0.048. The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046 while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028 compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019 and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005. The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately.

  10. Telomeres and the natural lifespan limit in humans

    DEFF Research Database (Denmark)

    Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon

    2017-01-01

    An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal...... natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends...

  11. Sedentary behaviour and diet across the lifespan: an updated systematic review.

    Science.gov (United States)

    Hobbs, Matthew; Pearson, Natalie; Foster, Perry J; Biddle, Stuart J H

    2015-09-01

    Sedentary behaviour and its association with dietary intake in young people and adults are important topics and were systematically reviewed in 2011. There is a need to update this evidence given the changing nature of sedentary behaviour and continued interest in this field. This review aims to assist researchers in better interpreting the diversity of findings concerning sedentary behaviour and weight status. To provide an update of the associations between sedentary behaviour and dietary intake across the lifespan. Electronic databases searched were MEDLINE, PsychInfo, Cochrane Library, Web of Science and Science Direct for publications between January 2010 and October 2013, thus updating a previous review. Included were observational studies assessing an association between at least one sedentary behaviour and at least one aspect of dietary intake in preschool children (18 years). 27 papers met inclusion criteria (preschool k=3, school-aged children k=9, adolescents k=15, adults k=3). For all three groups of young people, trends were evident for higher levels of sedentary behaviour, especially TV viewing, to be associated with a less healthful diet, such as less fruit and vegetable and greater consumption of energy-dense snacks and sugar sweetened beverages. Data for the three studies with adults were less conclusive. Sedentary behaviour continues to be associated with unhealthy diet in young people in mostly cross-sectional studies. More studies utilising a prospective design are needed to corroborate findings and more studies are needed with adults. 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.

  12. EFFECT ON LIFESPAN OF HIGH YIELD NONMYELOABLATING TRANSPLANTATION OF BONE MARROW FROM YOUNG TO OLD MICE

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    Marina eKovina

    2013-08-01

    Full Text Available Tissue renewal is a well-known phenomenon by which old and dying-off cells of various tissues of the body are replaced by progeny of local or circulating stem cells (SC. An interesting question is whether donor stem cells are capable to prolong the lifespan of an ageing organism by tissue renewal.. In this work we investigated the possible use of bone marrow SC for lifespan extension. To this purpose, chimeric C57BL/6 mice were created by transplanting bone marrow from young 1.5-month donors to 21.5-month-old recipients. Transplantation was carried out by means of a recently developed method which allowed to transplant without myeloablation up to 1.5×108 cells, that is, about 25 % of the total BM cells of the mouse. As a result, the mean survival time, counting from the age of 21.5 months, the start of the experiment, was +3.6 and +5.0 (± 0.1 months for the control and experimental groups, respectively, corresponding to a 39% ± 4% increase in the experimental group over the control. In earlier studies on BM transplantation a considerably smaller quantity of donor cells (5×106 was used, about 1 % of the total own BM cells. The recipients before transplantation were exposed to a lethal (for control animals X-ray dose which eliminated the possibility of studying the lifespan extension by this method.

  13. The First International Mini-Symposium on Methionine Restriction and Lifespan

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    Gene eAbles

    2014-05-01

    Full Text Available It has been 20 years since the Orentreich Foundation for the Advancement of Science, under the leadership Dr. Norman Orentreich, first reported that low methionine (Met ingestion by rats extends lifespan [1]. Since then, several studies have replicated the effects of dietary methionine restriction (MR in delaying age-related diseases [2–5]. We report the abstracts from the First International Mini-Symposium on Methionine Restriction and Lifespan held in Tarrytown, NY last September 2013. The goals were 1 to gather researchers with an interest in methionine restriction and lifespan, 2 to exchange knowledge, 3 to generate ideas for future investigations, and 4 to strengthen relationships within this community. The presentations highlighted the importance of research on cysteine, growth hormone (GH, and ATF4 in the paradigm of aging. In addition, the effects of dietary restriction or MR in the kidneys, liver, bones and the adipose tissue were discussed. The symposium also emphasized the value of other species, e.g. the naked mole rat, Brandt’s bat and drosophila in aging research. Overall, the symposium consolidated scientists with similar research interests and provided opportunities to conduct future collaborative studies.

  14. Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice.

    Science.gov (United States)

    Leibrock, Christina B; Voelkl, Jakob; Kohlhofer, Ursula; Quintanilla-Martinez, Leticia; Kuro-O, Makoto; Lang, Florian

    2016-01-01

    Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic (kl/kl) mice, excessive 1,25(OH)2D3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO3 did not significantly affect plasma concentrations of 1,25(OH)2D3 and Ca(2+) but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice. Copyright © 2016 the American Physiological Society.

  15. Catalpol Modulates Lifespan via DAF-16/FOXO and SKN-1/Nrf2 Activation in Caenorhabditis elegans

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    Hyun Won Seo

    2015-01-01

    Full Text Available Catalpol is an effective component of rehmannia root and known to possess various pharmacological properties. The present study was aimed at investigating the potential effects of catalpol on the lifespan and stress tolerance using C. elegans model system. Herein, catalpol showed potent lifespan extension of wild-type nematode under normal culture condition. In addition, survival rate of catalpol-fed nematodes was significantly elevated compared to untreated control under heat and oxidative stress but not under hyperosmolality conditions. We also found that elevated antioxidant enzyme activities and expressions of stress resistance proteins were attributed to catalpol-mediated increased stress tolerance of nematode. We further investigated whether catalpol’s longevity effect is related to aging-related factors including reproduction, food intake, and growth. Interestingly, catalpol exposure could attenuate pharyngeal pumping rate, indicating that catalpol may induce dietary restriction of nematode. Moreover, locomotory ability of aged nematode was significantly improved by catalpol treatment, while lipofuscin levels were attenuated, suggesting that catalpol may affect age-associated changes of nematode. Our mechanistic studies revealed that mek-1, daf-2, age-1, daf-16, and skn-1 are involved in catalpol-mediated longevity. These results indicate that catalpol extends lifespan and increases stress tolerance of C. elegans via DAF-16/FOXO and SKN-1/Nrf activation dependent on insulin/IGF signaling and JNK signaling.

  16. Acceleration and Orientation Jumping Performance Differences Among Elite Professional Male Handball Players With or Without Previous ACL Reconstruction: An Inertial Sensor Unit-Based Study.

    Science.gov (United States)

    Setuain, Igor; González-Izal, Miriam; Alfaro, Jesús; Gorostiaga, Esteban; Izquierdo, Mikel

    2015-12-01

    Handball is one of the most challenging sports for the knee joint. Persistent biomechanical and jumping capacity alterations can be observed in athletes with an anterior cruciate ligament (ACL) injury. Commonly identified jumping biomechanical alterations have been described by the use of laboratory technologies. However, portable and easy-to-handle technologies that enable an evaluation of jumping biomechanics at the training field are lacking. To analyze unilateral/bilateral acceleration and orientation jumping performance differences among elite male handball athletes with or without previous ACL reconstruction via a single inertial sensor unit device. Case control descriptive study. At the athletes' usual training court. Twenty-two elite male (6 ACL-reconstructed and 16 uninjured control players) handball players were evaluated. The participants performed a vertical jump test battery that included a 50-cm vertical bilateral drop jump, a 20-cm vertical unilateral drop jump, and vertical unilateral countermovement jump maneuvers. Peak 3-dimensional (X, Y, Z) acceleration (m·s(-2)), jump phase duration and 3-dimensional orientation values (°) were obtained from the inertial sensor unit device. Two-tailed t-tests and a one-way analysis of variance were performed to compare means. The P value cut-off for significance was set at P handball athletes with previous ACL reconstruction demonstrated a jumping biomechanical profile similar to control players, including similar jumping performance values in both bilateral and unilateral jumping maneuvers, several years after ACL reconstruction. These findings are in agreement with previous research showing full functional restoration of abilities in top-level male athletes after ACL reconstruction, rehabilitation and subsequent return to sports at the previous level. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  17. Differential control of ageing and lifespan by isoforms and splice variants across the mTOR network.

    Science.gov (United States)

    Razquin Navas, Patricia; Thedieck, Kathrin

    2017-07-15

    Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease. The nutrient-sensing kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing. mTOR promotes cell growth and controls central metabolic pathways including protein biosynthesis, autophagy and glucose and lipid homoeostasis. The concept that mTOR has a crucial role in ageing is supported by numerous reports on the lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and vertebrate model organisms. Dietary restriction increases lifespan and delays ageing phenotypes as well and mTOR has been assigned a major role in this process. This may suggest a causal relationship between the lifespan of an organism and its metabolic phenotype. More than 25 years after mTOR's discovery, a wealth of metabolic and ageing-related effects have been reported. In this review, we cover the current view on the contribution of the different elements of the mTOR signalling network to lifespan and age-related metabolic impairment. We specifically focus on distinct roles of isoforms and splice variants across the mTOR network. The comprehensive analysis of mouse knockout studies targeting these variants does not support a tight correlation between lifespan prolongation and improved metabolic phenotypes and questions the strict causal relationship between them. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  18. Calycosin promotes lifespan in Caenorhabditis elegans through insulin signaling pathway via daf-16, age-1 and daf-2.

    Science.gov (United States)

    Lu, Lulu; Zhao, Xuan; Zhang, Jianyong; Li, Miao; Qi, Yonghao; Zhou, Lijun

    2017-07-01

    The naturally occurring calycosin is a known antioxidant that prevents redox imbalance in organisms. However, calycosin's effect on lifespan and its physiological molecular mechanisms are not yet well understood. In this study, we demonstrated that calycosin could prolong the lifespan of Caenorhabditis elegans, and that such extension was associated with its antioxidant capability as well as its ability to enhance stress resistance and reduce ROS (reactive oxygen species) accumulation. To explore mechanisms of this longevity effect, we assessed the impact of calycosin on lifespans of insulin-signaling impaired worms: daf-2, age-1, and daf-16 mutants. We found that calycosin did not alter the lifespan of all three mutants, thereby suggesting that calycosin requires insulin signaling to promote lifespan extension. On the other hand, we observed that calycosin could enhance the nuclear translocation of the core transcription factor DAF-16/FoXO instead of the conserved stress-responsive transcription factor SKN-1/Nrf-2. This observation is consistent with the understanding that the nuclear localized DAF-16 up-regulates its downstream targets sod-3, ctl-1, and hsp-16.2. Lastly, it is also noteworthy that the longevity effect of calycosin is likely not associated with the calorie restriction mechanism. Collectively, our results strongly suggest that calycosin could function as an antioxidant to extend the lifespan of C. elegans by enhancing nucleus translocation of DAF-16 through the insulin-signaling pathway. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  19. Connectivity trajectory across lifespan differentiates the precuneus from the default network.

    Science.gov (United States)

    Yang, Zhi; Chang, Catie; Xu, Ting; Jiang, Lili; Handwerker, Daniel A; Castellanos, F Xavier; Milham, Michael P; Bandettini, Peter A; Zuo, Xi-Nian

    2014-04-01

    The default network of the human brain has drawn much attention due to its relevance to various brain disorders, cognition, and behavior. However, its functional components and boundaries have not been precisely defined. There is no consensus as to whether the precuneus, a hub in the functional connectome, acts as part of the default network. This discrepancy is more critical for brain development and aging studies: it is not clear whether age has a stronger impact on the default network or precuneus, or both. We used Generalized Ranking and Averaging Independent Component Analysis by Reproducibility (gRAICAR) to investigate the lifespan trajectories of intrinsic functional networks. By estimating individual-specific spatial components and aligning them across subjects, gRAICAR measures the spatial variation of component maps across a population without constraining the same components to appear in every subject. In a cross-lifespan fMRI dataset (N=126, 7-85years old), we observed stronger age dependence in the spatial pattern of a precuneus-dorsal posterior cingulate cortex network compared to the default network, despite the fact that the two networks exhibit considerable spatial overlap and temporal correlation. These results remained even when analyses were restricted to a subpopulation with very similar head motion across age. Our analyses further showed that the two networks tend to merge with increasing age. Post-hoc analyses of functional connectivity confirmed the distinguishable cross-lifespan trajectories between the two networks. Based on these observations, we proposed a dynamic model of cross-lifespan functional segregation and integration between the two networks, suggesting that the precuneus network may have a different functional role than the default network, which declines with age. These findings have implications for understanding the functional roles of the default network, gaining insight into its dynamics throughout life, and guiding

  20. De novo adamantinomatous craniopharyngioma presenting anew in an elderly patient with previous normal CT and MRI studies: A case report and implications on pathogenesis

    Directory of Open Access Journals (Sweden)

    Amy Walker, B.S.

    2015-09-01

    Full Text Available Adamantinomatous craniopharyngiomas are histologically benign epithelial tumors which arise from embryonic remnants of the craniopharyngeal duct and Rathke’s pouch. They are thought to have a congenital origin and are histologically unique from papillary craniopharyngioma. We describe the case of an elderly male who presented with symptoms related to a large craniopharyngioma with previously normal brain magnetic resonance and computed tomography imaging studies. These findings dispute the embryogenic theory that craniopharyngiomas observed in adults develop from the persistent slow growth of embryonic remnants.

  1. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

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    Nicole M. Templeman

    2017-07-01

    Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

  2. Tenebrio molitor Extracts Modulate the Response to Environmental Stressors and Extend Lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Won, Seong-Min; Cha, Hye-Uk; Yi, Sun Shin; Kim, Sung-Jo; Park, Sang-Kyu

    2016-09-08

    Tenebrio molitor are large insects and their larvae are consumed as food in many countries. The nutritional composition of T. molitor has been studied and contains high amounts of proteins, unsaturated fatty acids, and valuable minerals. However, the bioactivity of T. molitor has not been fully understood. We examined the effects of T. molitor extracts on resistance to oxidative stress and organism's lifespan using Caenorhabditis elegans as a model system. The response to heat shock and ultraviolet (UV) irradiation was monitored in vivo. The extracts from T. molitor showed significant effects on resistance to oxidative stress and UV irradiation and extend both mean and maximum lifespan of C. elegans. The number of progeny produced significantly increased in animals supplemented with T. molitor extracts. In addition, the expression of hsp-16.2 and sod-3 was markedly upregulated by supplementation with T. molitor extracts. These findings suggest that T. molitor extracts can increase response to stressors and extend lifespan by the induction of longevity assurance genes in C. elegans.

  3. Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan.

    Science.gov (United States)

    Wolkow, Catherine A; Iser, Wendy B

    2006-05-01

    Uncoupling proteins (UCPs), which dissipate the mitochondrial proton gradient, have the ability to decouple mitochodrial respiration from ATP production. Since mitochondrial electron transport is a major source of free radical production, it is possible that UCP activity might impact free radical production. Free radicals can react with and damage cellular proteins, DNA and lipids. Accumulated damage from oxidative stress is believed to be a major contributor to cellular decline during aging. If UCP function were to impact mitochondrial free radical production, then one would expect to find a link between UCP activity and aging. This theory has recently been tested in a handful of organisms whose genomes contain UCP1 homologs. Interestingly, these experiments indicate that UCP homologs can affect lifespan, although they do not support a simple relationship between UCP activity and aging. Instead, UCP-like proteins appear to have a variety of effects on lifespan, and on pathways implicated in lifespan regulation. One possible explanation for this complex picture is that UCP homologs may have tissue-specific effects that complicate their effects on aging. Furthermore, the functional analysis of UCP1 homologs is incomplete. Thus, these proteins may perform functions in addition to, or instead of, mitochondrial uncoupling. Although these studies have not revealed a clear picture of UCP effects on aging, they have contributed to the growing knowledge base for these interesting proteins. Future biochemical and genetic investigation of UCP-like proteins will do much to clarify their functions and to identify the regulatory networks in which they are involved.

  4. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

    Science.gov (United States)

    Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

    2017-07-11

    The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Caloric Restriction-Induced Extension of Chronological Lifespan Requires Intact Respiration in Budding Yeast.

    Science.gov (United States)

    Kwon, Young-Yon; Lee, Sung-Keun; Lee, Cheol-Koo

    2017-04-01

    Caloric restriction (CR) has been shown to extend lifespan and prevent cellular senescence in various species ranging from yeast to humans. Many effects of CR may contribute to extend lifespan. Specifically, CR prevents oxidative damage from reactive oxygen species (ROS) by enhancing mitochondrial function. In this study, we characterized 33 single electron transport chain (ETC) gene-deletion strains to identify CR-induced chronological lifespan (CLS) extension mechanisms. Interestingly, defects in 17 of these 33 ETC gene-deleted strains showed loss of both respiratory function and CR-induced CLS extension. On the contrary, the other 16 respiration-capable mutants showed increased CLS upon CR along with increased mitochondrial membrane potential (MMP) and intracellular adenosine triphosphate (ATP) levels, with decreased mitochondrial superoxide generation. We measured the same parameters in the 17 non-respiratory mutants upon CR. CR simultaneously increased MMP and mitochondrial superoxide generation without altering intracellular ATP levels. In conclusion, respiration is essential for CLS extension by CR and is important for balancing MMP, ROS, and ATP levels.

  6. Topological organization of the human brain functional connectome across the lifespan

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    Miao Cao

    2014-01-01

    Full Text Available Human brain function undergoes complex transformations across the lifespan. We employed resting-state functional MRI and graph-theory approaches to systematically chart the lifespan trajectory of the topological organization of human whole-brain functional networks in 126 healthy individuals ranging in age from 7 to 85 years. Brain networks were constructed by computing Pearson's correlations in blood-oxygenation-level-dependent temporal fluctuations among 1024 parcellation units followed by graph-based network analyses. We observed that the human brain functional connectome exhibited highly preserved non-random modular and rich club organization over the entire age range studied. Further quantitative analyses revealed linear decreases in modularity and inverted-U shaped trajectories of local efficiency and rich club architecture. Regionally heterogeneous age effects were mainly located in several hubs (e.g., default network, dorsal attention regions. Finally, we observed inverse trajectories of long- and short-distance functional connections, indicating that the reorganization of connectivity concentrates and distributes the brain's functional networks. Our results demonstrate topological changes in the whole-brain functional connectome across nearly the entire human lifespan, providing insights into the neural substrates underlying individual variations in behavior and cognition. These results have important implications for disease connectomics because they provide a baseline for evaluating network impairments in age-related neuropsychiatric disorders.

  7. Impact of Availability and Use of ART/PMTCT Services on Fertility Desires of Previously Pregnant Women in Rakai, Uganda: A Retrospective Cohort Study.

    Science.gov (United States)

    Litwin, Lindsay E; Makumbi, Frederick E; Gray, Ronald; Wawer, Maria; Kigozi, Godfrey; Kagaayi, Joseph; Nakigozi, Gertrude; Lutalo, Tom; Serwada, David; Brahmbhatt, Heena

    2015-07-01

    To assess fertility desires by availability and use of antiretroviral therapy and prevention of mother-to-child transmission (ART/PMTCT) services in Rakai, Uganda. Retrospective analyses of longitudinal data from the Rakai Community Cohort Study. Study participants were retrospectively identified and categorized by HIV status. Availability of ART/PMTCT services in Rakai was defined in three periods: (1) pre-ART/PMTCT (ART/PMTCT rollout (2005-2006), and (3) universal ART/PMTCT (>2006); and use of ART/PMTCT was coded as yes if the woman received services. Trends in fertility desires were assessed by χ. "Modified" Poisson regression was performed using generalized linear models with a log link and Poisson family to estimate prevalence rate ratios (PRRs) and 95% confidence intervals (CIs) of desire for another child among previously and currently pregnant women; PRRs were adjusted for demographic and behavioral factors. A total of 4227 sexually active women in Rakai, including 436 HIV+ women, contributed 13,970 observations over 5 survey rounds. Fertility desires increased in the population in the ART/PMTCT rollout [adjusted (adj.) PRR: 1.08, 95% CI: 1.04 to 1.13] and the universal availability periods (adj. PRR: 1.11, 95% CI: 1.08 to 1.14) compared with pre-ART/PMTCT period. A total of 862 woman observations used ART/PMTCT services. Fertility desires were similar among ART/PMTCT service users and nonusers in cross-sectional analysis (adj. PRR: 0.84, 95% CI: 0.62 to 1.14) and 1 year after ART/PMTCT use (adj. PRR: 1.27, 95% CI: 0.83 to 1.94). Availability of ART/PMTCT may increase fertility desires of previously pregnant women in Rakai, Uganda. Use of ART/PMTCT services was not correlated with fertility desires of previously or current pregnant women.

  8. Outcome of secondary high-grade glioma in children previously treated for a malignant condition: A study of the Canadian Pediatric Brain Tumour Consortium

    International Nuclear Information System (INIS)

    Carret, Anne-Sophie; Tabori, Uri; Crooks, Bruce; Hukin, Juliette; Odame, Isaac; Johnston, Donna L.; Keene, Daniel L.; Freeman, Carolyn; Bouffet, Eric

    2006-01-01

    Background and purpose: Reports of secondary high-grade glioma (HGG) in survivors of childhood cancer are scarce. The aim of this study was to review the pattern of diagnosis, the treatment, and outcome of secondary pediatric HGG. Patients and methods: We performed a multi-center retrospective study among the 17 paediatric institutions participating in the Canadian Pediatric Brain Tumour Consortium (CPBTC). Results: We report on 18 patients (14 males, 4 females) treated in childhood for a primary cancer, who subsequently developed a HGG as a second malignancy. All patients had previously received radiation therapy +/- chemotherapy for either acute lymphoblastic leukaemia (n = 9) or solid tumour (n = 9). All HGG occurred within the previous radiation fields. At the last follow-up, 17 patients have died and the median survival time is 9.75 months. Conclusion: Although aggressive treatment seems to provide sustained remissions in some patients, the optimal management is still to be defined. Further documentation of such cases is necessary in order to better understand the pathogenesis, the natural history and the prevention of these tumours

  9. Lifespan Differences in the Social Networks of Prison Inmates

    Science.gov (United States)

    Bond, Gary D.; Thompson, Laura A.; Malloy, Daniel M.

    2005-01-01

    Socioemotional Selectivity Theory (SST) (Carstensen, 1992, 1993) accounts for lifespan changes in human social networks and for the motivations which underlie those changes. SST is applied in this research with 256 prison inmates and non-inmates, ages 18-84, from Mississippi, Kansas, and New Mexico. Two research questions sought to identify (a)…

  10. Extension of mouse lifespan by overexpression of catalase.

    Science.gov (United States)

    Schriner, Samuel E; Linford, Nancy J

    2006-06-01

    The free radical theory of aging was originally proposed 50 years ago, and is arguably the most popular mechanism explaining the aging process. According to this theory, aging results from the progressive decline in organ function due to the damage generated by reactive oxygen species (ROS). These chemical species are a normal part of metabolism, and a group of enzymes exists to protect cells against their toxic effects. One of these species is hydrogen peroxide (H(2)O(2)), which can be degraded by catalase. To determine the role of hydrogen peroxide in aging and its importance in different subcellular compartments, transgenic mice were developed with increased catalase activities localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). The largest effect on lifespan was found in MCAT animals, with a 20% increase in median lifespan and a 10% increase in the maximum lifespan. A more modest effect was seen in PCAT animals, and no significant change was found in NCAT animals. Upon further examination of the MCAT mice, it was found that H(2)O(2) production and H(2)O(2)-induced aconitase inactivation were attenuated, oxidative damage and the development of mitochondrial deletions were reduced, and cardiac pathology and cataract development were delayed. These results are consistent with a role of H(2)O(2) in the development of pathology and in the limitation of mouse lifespan. They also demonstrate the importance of mitochondria as a source, and possible target, of ROS.

  11. Lifespan extension by preserving proliferative homeostasis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Benoît Biteau

    2010-10-01

    Full Text Available Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan.

  12. Implications of Methodist clergies' average lifespan and missional ...

    African Journals Online (AJOL)

    2015-06-09

    Jun 9, 2015 ... The author of Genesis 5 paid meticulous attention to the lifespan of several people ... of Southern Africa (MCSA), and to argue that memories of the ... average ages at death were added up and the sum was divided by 12 (which represents the 12 ..... not explicit in how the departed Methodist ministers were.

  13. Engineering Substantially Prolonged Human Lifespans: Biotechnological Enhancement and Ethics

    NARCIS (Netherlands)

    Derkx, P.H.J.M.

    2006-01-01

    Substantial extension of the human lifespan has recently become a subject of lively debate. One reason for this is the completion in 2001 of the Human Genome Project and the experimental avenues for biogerontological research it has opened. Another is recent theoretical progress in biogerontology.

  14. The reproductive lifespan of Onchocerca volvulus in West African savanna

    NARCIS (Netherlands)

    A.P. Plaisier (Anton); G.J. van Oortmarssen (Gerrit); J.H.F. Remme (Jan); J.D.F. Habbema (Dik)

    1991-01-01

    markdownabstractAbstract The epidemiological model ONCHOSIM — a model and computer simulation program for the transmission and control of onchocerciasis — has been used to determine the range of plausible values for the reproductive lifespan of Onchocerca volvulus. Model predictions based on

  15. Vitamin D deficiency in medical patients at a central hospital in Malawi: a comparison with TB patients from a previous study.

    Directory of Open Access Journals (Sweden)

    Yamikani Mastala

    Full Text Available OBJECTIVES: To determine the prevalence of vitamin D deficiency (VDD in adult medical, non-tuberculous (non-TB patients. To investigate associations with VDD. To compare the results with a similar study in TB patients at the same hospital. DESIGN: Cross-sectional sample. SETTING: Central hospital in Malawi. PARTICIPANTS: Adult non-TB patients (n = 157, inpatients and outpatients. OUTCOME MEASURES: The primary outcome was the prevalence of VDD. Potentially causal associations sought included nutritional status, in/outpatient status, HIV status, anti-retroviral therapy (ART and, by comparison with a previous study, a diagnosis of tuberculosis (TB. RESULTS: Hypovitaminosis D (≤75 nmol/L occurred in 47.8% (75/157 of patients, 16.6% (26/157 of whom had VDD (≤50 nmol/L. None had severe VDD (≤25 nmol/L. VDD was found in 22.8% (23/101 of in-patients and 5.4% (3/56 of out-patients. In univariable analysis in-patient status, ART use and low dietary vitamin D were significant predictors of VDD. VDD was less prevalent than in previously studied TB patients in the same hospital (68/161 = 42%. In multivariate analysis of the combined data set from both studies, having TB (OR 3.61, 95%CI 2.02-6.43 and being an in-patient (OR 2.70, 95%CI 1.46-5.01 were significant independent predictors of VDD. CONCLUSIONS: About half of adult medical patients without TB have suboptimal vitamin D status, which is more common in in-patients. VDD is much more common in TB patients than non-TB patients, even when other variables are controlled for, suggesting that vitamin D deficiency is associated with TB.

  16. How changes in subjective general health predict future time perspective, and development and generativity motives over the lifespan

    NARCIS (Netherlands)

    Kooij, D.T.A.M.; Voorde, F.C. van de

    2011-01-01

    In this study, we used the lifespan theories of selection optimization and compensation (SOC) and the socio-emotional selectivity theory (SST) to integrate the disengagement and activity perspectives on aging and to explain intra-individual changes in work motivation. A two-wave longitudinal survey

  17. Plantar pressure in diabetic peripheral neuropathy patients with active foot ulceration, previous ulceration and no history of ulceration: a meta-analysis of observational studies.

    Science.gov (United States)

    Fernando, Malindu Eranga; Crowther, Robert George; Pappas, Elise; Lazzarini, Peter Anthony; Cunningham, Margaret; Sangla, Kunwarjit Singh; Buttner, Petra; Golledge, Jonathan

    2014-01-01

    Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP) and pressure time integral (PTI) were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310). Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290-0.811, pdiabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More homogenous data is needed to confirm these findings.

  18. Phase II study of a 3-day schedule with topotecan and cisplatin in patients with previously untreated small cell lung cancer and extensive disease

    DEFF Research Database (Denmark)

    Sorensen, M.; Lassen, Ulrik Niels; Jensen, Peter Buhl

    2008-01-01

    INTRODUCTION: Treatment with a topoisomerase I inhibitor in combination with a platinum results in superior or equal survival compared with etoposide-based treatment in extensive disease small cell lung cancer (SCLC). Five-day topotecan is inconvenient and therefore shorter schedules of topotecan...... and cisplatin are needed. The aim of this phase II study was to establish the response rate and response duration in chemo-naive patients with SCLC receiving a 3-day topotecan and cisplatin schedule. METHODS: Simons optimal two-stage design was used. Patients with previously untreated extensive disease SCLC...... age was 59 (range 44-74), 79% had performance status 0 or 1. Thirty-one patients completed all six cycles. Grade 3/4 anemia, neutrocytopenia, and thrombocytopenia were recorded in 9.5%, 66.7%, and 21.4% of patients, respectively. Fourteen percent of patients experienced neutropenic fever. No episodes...

  19. EXPERIMENTAL CHALLENGE STUDY OF FV3-LIKE RANAVIRUS INFECTION IN PREVIOUSLY FV3-LIKE RANAVIRUS INFECTED EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) TO ASSESS INFECTION AND SURVIVAL.

    Science.gov (United States)

    Hausmann, Jennifer C; Wack, Allison N; Allender, Matthew C; Cranfield, Mike R; Murphy, Kevin J; Barrett, Kevin; Romero, Jennell L; Wellehan, James F X; Blum, Stella A; Zink, M Christine; Bronson, Ellen

    2015-12-01

    The Maryland Zoo in Baltimore experienced an outbreak of Frog virus-3 (FV3)-like ranavirus during the summer of 2011, during which 14 of 27 (52%) of its captive eastern box turtles (Terrapene carolina carolina) survived. To assess survival, immunity, and viral shedding, an experimental challenge study was performed in which the surviving, previously infected turtles were reinfected with the outbreak strain of FV3-like ranavirus. Seven turtles were inoculated with virus intramuscularly and four control turtles received saline intramuscularly. The turtles were monitored for 8 wk with blood and oral swabs collected for quantitative polymerase chain reaction (qPCR). During that time, one of seven (14%) inoculated turtles and none of the controls (0%) died; there was no significant difference in survival. Clinical signs of the inoculated turtles, except for the turtle that died, were mild compared to the original outbreak. Quantitative PCR for FV3-like ranavirus on blood and oral swabs was positive for all inoculated turtles and negative for all controls. The turtle that died had intracytoplasmic inclusion bodies in multiple organs. Three inoculated and two control turtles were euthanized at the end of the study. No inclusion bodies were present in any of the organs. Quantitative PCR detected FV3-like ranavirus in the spleen of a control turtle, which suggested persistence of the virus. The surviving five turtles were qPCR-negative for FV3-like ranavirus from blood and oral swabs after brumation. Quantitative PCR for Terrapene herpesvirus 1 found no association between ranavirus infection and herpesvirus loads. In conclusion, previously infected eastern box turtles can be reinfected with the same strain of FV3-like ranavirus and show mild to no clinical signs but can shed the virus from the oral cavity.

  20. Trial of labour and vaginal birth after previous caesarean section: A population based study of Eastern African immigrants in Victoria, Australia.

    Science.gov (United States)

    Belihu, Fetene B; Small, Rhonda; Davey, Mary-Ann

    2017-03-01

    Variations in caesarean section (CS) between some immigrant groups and receiving country populations have been widely reported. Often, African immigrant women are at higher risk of CS than the receiving population in developed countries. However, evidence about subsequent mode of birth following CS for African women post-migration is lacking. The objective of this study was to examine differences in attempted and successful vaginal birth after previous caesarean (VBAC) for Eastern African immigrants (Eritrea, Ethiopia, Somalia and Sudan) compared with Australian-born women. A population-based observational study was conducted using the Victorian Perinatal Data Collection. Pearson's chi-square test and logistic regression analysis were performed to generate adjusted odds ratios for attempted and successful VBAC. Victoria, Australia. 554 Eastern African immigrants and 24,587 Australian-born eligible women with previous CS having singleton births in public care. 41.5% of Eastern African immigrant women and 26.1% Australian-born women attempted a VBAC with 50.9% of Eastern African immigrants and 60.5% of Australian-born women being successful. After adjusting for maternal demographic characteristics and available clinical confounding factors, Eastern African immigrants were more likely to attempt (OR adj 1.94, 95% CI 1.57-2.47) but less likely to succeed (OR adj 0.54 95% CI 0.41-0.71) in having a VBAC. There are disparities in attempted and successful VBAC between Eastern African origin and Australian-born women. Unsuccessful VBAC attempt is more common among Eastern African immigrants, suggesting the need for improved strategies to select and support potential candidates for vaginal birth among these immigrants to enhance success and reduce potential complications associated with failed VBAC attempt. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  1. Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer

    International Nuclear Information System (INIS)

    Arcaroli, John; Quackenbush, Kevin; Dasari, Arvind; Powell, Rebecca; McManus, Martine; Tan, Aik-Choon; Foster, Nathan R; Picus, Joel; Wright, John; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A

    2012-01-01

    Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] “top scoring pairs” polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3′ untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible

  2. DhHP-6 extends lifespan of Caenorhabditis elegans by enhancing nuclear translocation and transcriptional activity of DAF-16.

    Science.gov (United States)

    Huang, Lei; Li, Pengfei; Wang, Guan; Guan, Shuwen; Sun, Xiaoli; Wang, Liping

    2013-04-01

    Earlier studies have demonstrated that Deuterohaemin-AlaHisThrValGluLys (DhHP-6), a novel porphyrin-peptide, increases lifespan and enhances stress resistance of Caenorhabditis elegans. To explore the possible mechanisms, in this study we investigated the roles of SIR-2.1 and DAF-16 in DhHP-6's function using wild-type and various other mutant strains of C. elegans. DhHP-6's effect was dependent upon DAF-16, and it did not extend the lifespan of the loss-of-function daf-16 mutant strain (daf-16(mu86) I). DhHP-6 enhanced DAF-16 translocation from cytoplasm to nuclei; and it increased DAF-16's transcriptional activity, likely by activating the SIR-2.1/DAF-16 complex. DhHP-6's effect was also dependent upon SIR-2.1, and it did not increase the lifespan of the worms with SIR-2.1 deacetylase activity inhibited by niacin amide (SIR-2.1 inhibitor) and SIR-2.1 RNA interference (RNAi). Niacin amide and RNAi increased DAF-16's nuclear localization; but they decreased DAF-16's transcriptional activity, likely by preventing the formation of the SIR-2.1/DAF-16 complex. These results suggest that DhHP-6 extends the lifespan of C. elegans via SIR 2.1 and DAF-16, and they provide new insights into the molecular mechanisms of aging.

  3. Women's decision-making processes and the influences on their mode of birth following a previous caesarean section in Taiwan: a qualitative study.

    Science.gov (United States)

    Chen, Shu-Wen; Hutchinson, Alison M; Nagle, Cate; Bucknall, Tracey K

    2018-01-17

    Vaginal birth after caesarean (VBAC) is an alternative option for women who have had a previous caesarean section (CS); however, uptake is limited because of concern about the risks of uterine rupture. The aim of this study was to explore women's decision-making processes and the influences on their mode of birth following a previous CS. A qualitative approach was used. The research comprised three stages. Stage I consisted of naturalistic observation at 33-34 weeks' gestation. Stage II involved interviews with pregnant women at 35-37 weeks' gestation. Stage III consisted of interviews with the same women who were interviewed postnatally, 1 month after birth. The research was conducted in a private medical centre in northern Taiwan. Using a purposive sampling, 21 women and 9 obstetricians were recruited. Data collection involved in-depth interviews, observation and field notes. Constant comparative analysis was employed for data analysis. Ensuring the safety of mother and baby was the focus of women's decisions. Women's decisions-making influences included previous birth experience, concern about the risks of vaginal birth, evaluation of mode of birth, current pregnancy situation, information resources and health insurance. In communicating with obstetricians, some women complied with obstetricians' recommendations for repeat caesarean section (RCS) without being informed of alternatives. Others used four step decision-making processes that included searching for information, listening to obstetricians' professional judgement, evaluating alternatives, and making a decision regarding mode of birth. After birth, women reflected on their decisions in three aspects: reflection on birth choices; reflection on factors influencing decisions; and reflection on outcomes of decisions. The health and wellbeing of mother and baby were the major concerns for women. In response to the decision-making influences, women's interactions with obstetricians regarding birth choices

  4. Four Forensic Entomology Case Studies: Records and Behavioral Observations on Seldom Reported Cadaver Fauna With Notes on Relevant Previous Occurrences and Ecology.

    Science.gov (United States)

    Lindgren, Natalie K; Sisson, Melissa S; Archambeault, Alan D; Rahlwes, Brent C; Willett, James R; Bucheli, Sibyl R

    2015-03-01

    A yearlong survey of insect taxa associated with human decomposition was conducted at the Southeast Texas Applied Forensic Science (STAFS) facility located in the Center for Biological Field Studies of Sam Houston State University in Huntsville, TX. During this study, four insect-cadaver interactions were observed that represent previously poorly documented yet forensically significant interactions: Syrphidae maggots colonized a corpse in an aquatic situation; Psychodidae adults mated and oviposited on an algal film that was present on a corpse that had been recently removed from water; several Panorpidae were the first insects to feed upon a freshly placed corpse in the autumn; and a noctuid caterpillar was found chewing and ingesting dried human skin. Baseline knowledge of insect-cadaver interactions is the foundation of forensic entomology, and unique observations have the potential to expand our understanding of decomposition ecology. © The Author 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Late tamoxifen in patients previously operated for breast cancer without postoperative tamoxifen: 5-year results of a single institution randomised study

    International Nuclear Information System (INIS)

    Veronesi, Andrea; Miolo, GianMaria; Magri, Maria D; Crivellari, Diana; Scalone, Simona; Bidoli, Ettore; Lombardi, Davide

    2010-01-01

    A population of breast cancer patients exists who, for various reasons, never received adjuvant post-operative tamoxifen (TAM). This study was aimed to evaluate the role of late TAM in these patients. From 1997 to 2003, patients aged 35 to 75 years, operated more than 2 years previously for monolateral breast cancer without adjuvant TAM, with no signs of metastases and no contraindication to TAM were randomized to TAM 20 mg/day orally for 2 years or follow-up alone. Events were categorized as locoregional relapse, distant metastases, metachronous breast cancer, tumours other than breast cancer and death from any causes, whichever occurred first. The sample size (197 patients per arm, plus 10% allowance) was based on the assumption of a 30% decrease in the number of events occurring at a rate of 5% annually in the 10 years following randomization. Four hundred and thirty-three patients were randomized in the study (TAM 217, follow-up 216). Patients characteristics (TAM/follow-up) included: median age 55/55 years, median time from surgery 25/25 months (range, 25-288/25-294), in situ carcinoma 18/24, oestrogen receptor (ER) positive in 75/68, negative in 70/57, unknown in 72/91 patients. Previous adjuvant treatment included chemotherapy in 131/120 and an LHRH analogue in 11/13 patients. Thirty-six patients prematurely discontinued TAM after a median of 1 month, mostly because of subjective intolerance. Eighty-three events (TAM 39, follow-up 44) occurred: locoregional relapse in 10/8, distant metastases in 14/16, metachronous breast cancer in 4/10, other tumours in 11/10 patients. Less ER-positive secondary breast cancers occurred in the TAM treated patients than in follow-up patients (1 vs 10, p = 0.005). Event-free survival was similar in both groups of patients. This 5-year analysis revealed significantly less metachronous ER-positive breast cancers in the TAM treated patients. No other statistically significant differences have emerged thus far

  6. Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Prevented Weight Regain in Obese Women with Polycystic Ovary Syndrome Previously Treated with Liraglutide: A Pilot Randomized Study.

    Science.gov (United States)

    Ferjan, Simona; Janez, Andrej; Jensterle, Mojca

    2017-12-01

    Weight loss is often nonsustainable after liraglutide cessation. The present study is the first insight into the potential prevention of weight regain in obese subjects who have been withdrawn from liraglutide. We evaluated whether dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in adjunct to metformin prevents body weight regain more effectively than metformin alone in obese polycystic ovary syndrome (PCOS) previously treated with liraglutide. A 12-week prospective randomized open-label study was conducted with 24 obese women with PCOS who had been pretreated with liraglutide 3.0 mg due to antiobesity management (aged 34.3 ± 6.8 years, body mass index [BMI] 36.3 ± 5.2 kg/m 2 , mean ± standard deviation). They were randomized to combined treatment (COMBO) with sitagliptin 100 mg per day (QD) and metformin (MET) 1000 mg twice daily (BID) (n = 12) or MET 1000 mg BID (n = 12). Lifestyle intervention was promoted in both groups. The primary outcome was change in anthropometric measures of obesity. Women treated with MET regain 4.7 ± 2.7 kg (P = 0.002) compared with a 0.9 ± 2.5 kg in COMBO (P = 0.147). BMI increased for 1.7 ± 0.9 kg/m 2 in MET (P = 0.002) compared with 0.3 ± 0.8 kg/m 2 increase in COMBO (P = 0.136). MET group regain 4.5% ± 2.5% of body weight as opposed to 0.8% ± 2.6% in COMBO. The between-treatment differences were significant for weight change (P weight change (P weight regain in obese women with PCOS previously treated with liraglutide.

  7. Previously unreported abnormalities in Wolfram Syndrome Type 2.

    Science.gov (United States)

    Akturk, Halis Kaan; Yasa, Seda

    2017-01-01

    Wolfram syndrome (WFS) is a rare autosomal recessive disease with non-autoimmune childhood onset insulin dependent diabetes and optic atrophy. WFS type 2 (WFS2) differs from WFS type 1 (WFS1) with upper intestinal ulcers, bleeding tendency and the lack ofdiabetes insipidus. Li-fespan is short due to related comorbidities. Only a few familieshave been reported with this syndrome with the CISD2 mutation. Here we report two siblings with a clinical diagnosis of WFS2, previously misdiagnosed with type 1 diabetes mellitus and diabetic retinopathy-related blindness. We report possible additional clinical and laboratory findings that have not been pre-viously reported, such as asymptomatic hypoparathyroidism, osteomalacia, growth hormone (GH) deficiency and hepatomegaly. Even though not a requirement for the diagnosis of WFS2 currently, our case series confirm hypogonadotropic hypogonadism to be also a feature of this syndrome, as reported before. © Polish Society for Pediatric Endocrinology and Diabetology.

  8. Staphylococcus saprophyticus surface-associated protein (Ssp) is associated with lifespan reduction in Caenorhabditis elegans.

    Science.gov (United States)

    Szabados, Florian; Mohner, Amelie; Kleine, Britta; Gatermann, Sören G

    2013-10-01

    Staphylococcal lipases have been proposed as pathogenicity factors. In Staphylococcus saprophyticus the surface-associated protein (Ssp) has been previously characterized as a cell wall-associated true lipase. A S. saprophyticus Δssp::ermB mutant has been described as less virulent in an in vivo model of urinary tract infection compared with its wild-type. This is the first report showing that S. saprophyticus induced a lifespan reduction in Caenorhabditis elegans similar to that of S. aureus RN4220. In two S. saprophyticus Δssp::ermB mutants lifespan reduction in C. elegans was partly abolished. In order to attribute virulence to the lipase activity itself and distinguish this phenomenon from the presence of the Ssp-protein, the conserved active site of the lipase was modified by site-directed ligase-independent mutagenesis and lipase activity-deficient mutants were constructed. These results indicate that the Ssp is associated with pathogenicity in C. elegans and one could speculate that the lipase activity itself is responsible for this virulence.

  9. Lifespan trends of autobiographical remembering: episodicity and search for meaning.

    Science.gov (United States)

    Habermas, Tilmann; Diel, Verena; Welzer, Harald

    2013-09-01

    Autobiographical memories of older adults show fewer episodic and more non-episodic elements than those of younger adults. This semantization effect is attributed to a loss of episodic memory ability. However the alternative explanation by an increasing proclivity to search for meaning has not been ruled out to date. To test whether a decrease in episodicity and an increase in meaning-making in autobiographical narratives are related across the lifespan, we used different instructions, one focussing on specific episodes, the other on embedding events in life, in two lifespan samples. A continuous decrease of episodic quality of memory (memory specificity, narrative quality) was confirmed. An increase of search for meaning (interpretation, life story integration) was confirmed only up to middle adulthood. This non-inverse development of episodicity and searching for meaning in older age speaks for an autonomous semantization effect that is not merely due to an increase in interpretative preferences. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Myc-dependent genome instability and lifespan in Drosophila.

    Directory of Open Access Journals (Sweden)

    Christina Greer

    Full Text Available The Myc family of transcription factors are key regulators of cell growth and proliferation that are dysregulated in a large number of human cancers. When overexpressed, Myc family proteins also cause genomic instability, a hallmark of both transformed and aging cells. Using an in vivo lacZ mutation reporter, we show that overexpression of Myc in Drosophila increases the frequency of large genome rearrangements associated with erroneous repair of DNA double-strand breaks (DSBs. In addition, we find that overexpression of Myc shortens adult lifespan and, conversely, that Myc haploinsufficiency reduces mutation load and extends lifespan. Our data provide the first evidence that Myc may act as a pro-aging factor, possibly through its ability to greatly increase genome instability.

  11. In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case–control study

    International Nuclear Information System (INIS)

    Rivero, Javier; Luzardo, Octavio P.; Henríquez-Hernández, Luis A.; Machín, Rubén P.; Pestano, José; Zumbado, Manuel; Boada, Luis D.; Camacho, María; Valerón, Pilar F.

    2015-01-01

    Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. However, humans are environmentally exposed to more or less complex mixtures of these organochlorines, and the biological effects of these mixtures must be elucidated. In this work we evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case–control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action. - Highlights: • E-screen and A-screen of two mixtures of organochlorine pesticides (OCP) • Assay concentrations based on a previous breast cancer case–control study • Only non-cytotoxic concentrations assayed • Both OCP mixtures induce proliferation mediated by oestrogen receptor. • OCP mixture of breast cancer patients exhibits additional androgenic activity.

  12. In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case–control study

    Energy Technology Data Exchange (ETDEWEB)

    Rivero, Javier; Luzardo, Octavio P., E-mail: octavio.perez@ulpgc.es; Henríquez-Hernández, Luis A.; Machín, Rubén P.; Pestano, José; Zumbado, Manuel; Boada, Luis D.; Camacho, María; Valerón, Pilar F.

    2015-12-15

    Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. However, humans are environmentally exposed to more or less complex mixtures of these organochlorines, and the biological effects of these mixtures must be elucidated. In this work we evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case–control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action. - Highlights: • E-screen and A-screen of two mixtures of organochlorine pesticides (OCP) • Assay concentrations based on a previous breast cancer case–control study • Only non-cytotoxic concentrations assayed • Both OCP mixtures induce proliferation mediated by oestrogen receptor. • OCP mixture of breast cancer patients exhibits additional androgenic activity.

  13. Carbon dioxide sensing modulates lifespan and physiology in Drosophila.

    Directory of Open Access Journals (Sweden)

    Peter C Poon

    Full Text Available For nearly all life forms, perceptual systems provide access to a host of environmental cues, including the availability of food and mates as well as the presence of disease and predators. Presumably, individuals use this information to assess the current and future states of the environment and to enact appropriate developmental, behavioral, and regulatory decisions. Recent work using the nematode worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, has established that aging is subject to modulation through neurosensory systems and that this regulation is evolutionarily conserved. To date, sensory manipulations shown to impact Drosophila aging have involved general loss of function or manipulation of complex stimuli. We therefore know little about the specific inputs, sensors, or associated neural circuits that affect these life and death decisions. We find that a specialized population of olfactory neurons that express receptor Gr63a (a component of the olfactory receptor for gaseous phase CO(2 affects fly lifespan and physiology. Gr63a loss of function leads to extended lifespan, increased fat deposition, and enhanced resistance to some (but not all environmental stresses. Furthermore, we find that the reduced lifespan that accompanies exposure to odors from live yeast is dependent on Gr63a. Together these data implicate a specific sensory cue (CO(2 and its associated receptor as having the ability to modulate fly lifespan and alter organism stress response and physiology. Because Gr63a is expressed in a well-defined population of neurons, future work may now be directed at dissecting more complex neurosensory and neuroendocrine circuits that modulate aging in Drosophila.

  14. Carbon dioxide sensing modulates lifespan and physiology in Drosophila.

    Science.gov (United States)

    Poon, Peter C; Kuo, Tsung-Han; Linford, Nancy J; Roman, Gregg; Pletcher, Scott D

    2010-04-20

    For nearly all life forms, perceptual systems provide access to a host of environmental cues, including the availability of food and mates as well as the presence of disease and predators. Presumably, individuals use this information to assess the current and future states of the environment and to enact appropriate developmental, behavioral, and regulatory decisions. Recent work using the nematode worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, has established that aging is subject to modulation through neurosensory systems and that this regulation is evolutionarily conserved. To date, sensory manipulations shown to impact Drosophila aging have involved general loss of function or manipulation of complex stimuli. We therefore know little about the specific inputs, sensors, or associated neural circuits that affect these life and death decisions. We find that a specialized population of olfactory neurons that express receptor Gr63a (a component of the olfactory receptor for gaseous phase CO(2)) affects fly lifespan and physiology. Gr63a loss of function leads to extended lifespan, increased fat deposition, and enhanced resistance to some (but not all) environmental stresses. Furthermore, we find that the reduced lifespan that accompanies exposure to odors from live yeast is dependent on Gr63a. Together these data implicate a specific sensory cue (CO(2)) and its associated receptor as having the ability to modulate fly lifespan and alter organism stress response and physiology. Because Gr63a is expressed in a well-defined population of neurons, future work may now be directed at dissecting more complex neurosensory and neuroendocrine circuits that modulate aging in Drosophila.

  15. Evaluation of the Widal tube agglutination test for the diagnosis of typhoid fever among children admitted to a rural hdospital in Tanzania and a comparison with previous studies

    Directory of Open Access Journals (Sweden)

    Malahiyo Rajabu

    2010-06-01

    Full Text Available Abstract Background The diagnosis of typhoid fever is confirmed by culture of Salmonella enterica serotype Typhi (S. typhi. However, a more rapid, simpler, and cheaper diagnostic method would be very useful especially in developing countries. The Widal test is widely used in Africa but little information exists about its reliability. Methods We assessed the performance of the Widal tube agglutination test among febrile hospitalized Tanzanian children. We calculated the sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV of various anti-TH and -TO titers using culture-confirmed typhoid fever cases as the "true positives" and all other febrile children with blood culture negative for S. typhi as the "true negatives." Results We found that 16 (1% of 1,680 children had culture-proven typhoid fever. A single anti-TH titer of 1:80 and higher was the optimal indicator of typhoid fever. This had a sensitivity of 75%, specificity of 98%, NPV of 100%, but PPV was only 26%. We compared our main findings with those from previous studies. Conclusion Among febrile hospitalized Tanzanian children with a low prevalence of typhoid fever, a Widal titer of ≥ 1:80 performed well in terms of sensitivity, specificity, and NPV. However a test with improved PPV that is similarly easy to apply and cost-efficient is desirable.

  16. Caring for women wanting a vaginal birth after previous caesarean section: A qualitative study of the experiences of midwives and obstetricians.

    Science.gov (United States)

    Foureur, Maralyn; Turkmani, Sabera; Clack, Danielle C; Davis, Deborah L; Mollart, Lyndall; Leiser, Bernadette; Homer, Caroline S E

    2017-02-01

    One of the greatest contributors to the overall caesarean section rate is elective repeat caesarean section. Decisions around mode of birth are often complex for women and influenced by the views of the doctors and midwives who care for and counsel women. Women may be more likely to choose a repeat elective caesarean section (CS) if their health care providers lack skills and confidence in supporting vaginal birth after caesarean section (VBAC). To explore the views and experiences of providers in caring for women considering VBAC, in particular the decision-making processes and the communication of risk and safety to women. A descriptive interpretive method was utilised. Four focus groups with doctors and midwives were conducted. The central themes were: 'developing trust', 'navigating the system' and 'optimising support'. The impact of past professional experiences; the critical importance of continuity of carer and positive relationships; the ability to weigh up risks versus benefits; and the language used were all important elements. The role of policy and guidelines on providing standardised care for women who had a previous CS was also highlighted. Midwives and doctors in this study were positively oriented towards assisting and supporting women to attempt a VBAC. Care providers considered that women who have experienced a prior CS need access to midwifery continuity of care with a focus on support, information-sharing and effective communication. Copyright © 2016 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  17. Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: A phase II, randomized, double-blind, placebo-controlled study

    International Nuclear Information System (INIS)

    Gregoire, Vincent; Hamoir, Marc; Chen Changhu; Kane, Madeleine; Kawecki, Andrzej; Julka, Pramod K.; Wang, Hung-Ming; Prasad, Srihari; D'Cruz, Anil K.; Radosevic-Jelic, Ljiljana; Kumar, Rejnish R.; Korzeniowski, Stanislaw; Fijuth, Jacek; Machiels, Jean-Pascal; Sellers, Mark V.; Tchakov, Ilian; Raben, David

    2011-01-01

    Background and purpose: To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN. Materials and methods: In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250 mg/day, 500 mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2 years; secondary endpoints were LDCR at 1 year, objective response rate, progression-free survival, overall survival, and safety and tolerability. Results: Gefitinib (250 and 500 mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p = 0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p = 0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy. Conclusion: Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone.

  18. Prevalence of pain in the head, back and feet in refugees previously exposed to torture: a ten-year follow-up study

    DEFF Research Database (Denmark)

    Olsen, Dorthe Reff; Montgomery, Edith; Bøjholm, Søren

    2007-01-01

    AIM: To estimate change over 10 years concerning the prevalence of pain in the head, back and feet, among previously tortured refugees settled in Denmark, and to compare associations between methods of torture and prevalent pain at baseline and at 10-year follow-up. METHODS: 139 refugees previous...... associated with the type and bodily focus of the torture. This presents a considerable challenge to future evidence-based development of effective treatment programs....

  19. Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

    Science.gov (United States)

    Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis

    2012-09-07

    In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. A phase II study of VP-16-ifosfamide-cisplatin combination chemotherapy plus early concurrent thoracic irradiation for previously untreated limited small cell lung cancer

    International Nuclear Information System (INIS)

    Woo, In Sook; Park, Young Suk; Kwon, Sung Hee

    2000-01-01

    At present the addition of thoracic irradiation to combination chemotherapy is a standard treatment for limited staged small cell ling cancer. However, there is still controversy about the optimum timing of chest irradiation. We conducted a phase II study of etoposide (VP-16)-ifosfamide-cisplatin (VIP) combination chemotherapy plus early concurrent thoracic irradiation for the patients with previously untreated limited small cell lung cancer in order to assess if the treatment modality could improve the response rate and the toxicity. Forty-four patients with limited small cell lung cancer were treated with etoposide-ifosfamide-cisplatin and concurrent thoracic irradiation. Combination chemotherapy consisted of etoposide 100 mg/m 2 (on day 1-3), ifosfamide 1000 mg/m 2 (on days 1 and 2) and cisplatin 100 mg/m 2 (on day 1). Concurrent thoracic irradiation consisted of a total of 4000 cGy over 4 weeks starting on the first day of the first chemotherapy. All patients who showed a complete response were given prophylactic cranial irradiation for 2.5 weeks. Forty-four of the 49 patients who entered the study from May 1994 to August 1998 were evaluable. The median age was 59 years and 40 patients had a performance status of 0 or 1. The median survival time was 22.5 months. Twenty-eight patients (62%) showed a complete response and 16 (38%) a partial response. Twenty-four patients (54%) developed grade 3 or 4 neutropenia; there was a 9% RTOG score 3 or 4 esophagitis. VIP combination chemotherapy and early concurrent thoracic irradiation for patients with limited stage small cell lung cancer revealed excellent antitumor response with tolerable toxicity. (author)

  1. Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs.

    Directory of Open Access Journals (Sweden)

    Susan Broughton

    Full Text Available The insulin/IGF-like signalling (IIS pathway has diverse functions in all multicellular organisms, including determination of lifespan. The seven insulin-like peptides (DILPs in Drosophila are expressed in a stage- and tissue-specific manner. Partial ablation of the median neurosecretory cells (mNSCs in the brain, which produce three DILPs, extends lifespan, reduces fecundity, alters lipid and carbohydrate metabolism and increases oxidative stress resistance. To determine if reduced expression of DILPs is causal in these effects, and to investigate possible functional diversification and redundancy between DILPs, we used RNA interference to lower specifically the transcript and protein levels of dilp2, the most highly expressed of the mNSC-derived DILPs. We found that DILP2 was limiting only for the increased whole-body trehalose content associated with mNSC-ablation. We observed a compensatory increase in dilp3 and 5 mRNA upon dilp2 knock down. By manipulation of dfoxo and dInR, we showed that the increase in dilp3 is regulated via autocrine insulin signaling in the mNSCs. Our study demonstrates that, despite the correlation between reduced dilp2 mRNA levels and lifespan-extension often observed, DILP2 reduction is not sufficient to extend lifespan. Nor is the increased trehalose storage associated with reduced IIS sufficient to extend lifespan. To understand the normal regulation of expression of the dilps and any functional diversification between them will require independent control of the expression of different dilps.

  2. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk.

    Directory of Open Access Journals (Sweden)

    Cathy Slack

    2010-03-01

    Full Text Available Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data. However, a recent study in Drosophila has shown that Lnk is an important regulator of the insulin/insulin-like growth factor (IGF-1 signaling (IIS pathway during growth, functioning in parallel to the insulin receptor substrate, Chico. As this pathway also has an evolutionary conserved role in the determination of organism lifespan, we investigated whether Lnk is required for normal lifespan in Drosophila. Phenotypic analysis of mutants for Lnk revealed that loss of Lnk function results in increased lifespan and improved survival under conditions of oxidative stress and starvation. Starvation resistance was found to be associated with increased metabolic stores of carbohydrates and lipids indicative of impaired metabolism. Biochemical and genetic data suggest that Lnk functions in both the IIS and Ras/Mitogen activated protein Kinase (MapK signaling pathways. Microarray studies support this model, showing transcriptional feedback onto genes in both pathways as well as indicating global changes in both lipid and carbohydrate metabolism. Finally, our data also suggest that Lnk itself may be a direct target of the IIS responsive transcription factor, dFoxo, and that dFoxo may repress Lnk expression. We therefore describe novel functions for a member of the SH2B protein family and provide the first evidence for potential mechanisms of SH2B regulation. Our findings suggest that IIS signaling in Drosophila may require the activity of a second intracellular adaptor, thereby yielding fundamental new insights into the

  3. Socially disparate trends in lifespan variation

    DEFF Research Database (Denmark)

    Brønnum-Hansen, Henrik

    2017-01-01

    BACKGROUND: Social inequality trends in life expectancy are not informative as to changes in social disparity in the age-at-death distribution. The purpose of the study was to investigate social differentials in trends and patterns of adult mortality in Denmark. METHODS: Register data on income...... quartile. The results do not provide support for a uniformly extension of pension age for all....

  4. Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study.

    Science.gov (United States)

    Maréchaux, Sylvestre; Rusinaru, Dan; Jobic, Yannick; Ederhy, Stéphane; Donal, Erwan; Réant, Patricia; Arnalsteen, Elise; Boulanger, Jacques; Garban, Thierry; Ennezat, Pierre-Vladimir; Jeu, Antoine; Szymanski, Catherine; Tribouilloy, Christophe

    2015-02-01

    The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD. This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001). FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  5. SAFETY AND ACTIVITY OF TEMSIROLIMUS AND BEVACIZUMAB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS: A PHASE 2 CONSORTIUM STUDY

    Science.gov (United States)

    Merchan, Jaime R.; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J.; Flynn, Patrick J.; Fruth, Briant F.; Erlichman, Charles

    2015-01-01

    Purpose Bevacizumab or Temsirolimus regimens have clinical activity in the first line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods In the phase I portion, eligible patients were treated with Temsirolimus (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression free rate. Secondary endpoints were response rate, toxicity evaluation, PFS and OS. Results MTD was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (Temsirolimus 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/progressive disease were seen in 23%/63%/14% of patients. Most common grade 3-4 AEs included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions Temsirolimus and Bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. PMID:25556030

  6. Low-calorie energy drink improves physiological response to exercise in previously sedentary men: a placebo-controlled efficacy and safety study.

    Science.gov (United States)

    Lockwood, Christopher M; Moon, Jordan R; Smith, Abbie E; Tobkin, Sarah E; Kendall, Kristina L; Graef, Jennifer L; Cramer, Joel T; Stout, Jeffrey R

    2010-08-01

    Energy drink use has grown despite limited research to support efficacy or safety and amid concerns when combined with exercise. The purpose of this study was to assess the effects of 10 weeks of once-daily energy drink consumption or energy drink consumption with exercise on measures of body composition, cardiorespiratory fitness, strength, mood, and safety in previously sedentary males. Thirty-eight males were randomly assigned to energy drink + exercise (EX-A), energy drink (NEX-A), placebo + exercise (EX-B), or placebo (NEX-B). All participants consumed 1 drink per day for 10 weeks; EX-A and EX-B participated in 10 weeks of resistance and endurance exercise. Testing was performed before (PRE) and after (POST) the 10-week intervention. No significant (p > 0.05) changes were observed for body composition, fitness, or strength in NEX-A; however, significantly greater decreases in fat mass and percentage body fat and increases in VO2peak were observed in EX-A versus EX-B. Ventilatory threshold (VT), minute ventilation, VO2 at VT, and power output at VT improved significantly PRE to POST in EX-A but not in EX-B or nonexercising groups. Clinical markers for hepatic, renal, cardiovascular, and immune function, as determined by PRE and POST blood work revealed no adverse effects in response to the energy drink. Mood was not affected by energy drink use. Absent energy restriction or other dietary controls, chronic ingestion of a once-daily low-calorie energy drink appears ineffective at improving body composition, cardiorespiratory fitness, or strength in sedentary males. However, when combined with exercise, preworkout energy drink consumption may significantly improve some physiological adaptations to combined aerobic and resistance training.

  7. Phase I/II study of gefitinib (Iressa(®)) and vorinostat (IVORI) in previously treated patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Han, Ji-Youn; Lee, Soo Hyun; Lee, Geon Kook; Yun, Tak; Lee, Young Joo; Hwang, Kum Hui; Kim, Jin Young; Kim, Heung Tae

    2015-03-01

    Vorinostat has been shown to overcome resistance to gefitinib. We performed a phase I/II study combining gefitinib with vorinostat in previously treated non-small cell lung cancer (NSCLC). A 3 + 3 dose-escalation design was used to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Three dose levels were tested: 250 mg/day gefitinib on days 1-28 and 200, 300 or 400 mg/day vorinostat on days 1-7, and 15-21 out of every 28 days. The primary endpoint was median progression-free survival (PFS). Fifty-two patients were enrolled and treated (43 in phase II). The median age was 59 years, 28 patients were male, 44 had adenocarcinoma, 29 had never smoked, and 36 had undergone one prior treatment. Twenty-two patients exhibited sensitive EGFR mutations. Planned dose escalation was completed without reaching the MTD. The RP2D was 250 mg gefitinib and 400 mg vorinostat. In 43 assessable patients in phase II, the median PFS was 3.2 months; the overall survival (OS) was 19.0 months. There were 16 partial responses and six cases of stable disease. In EGFR-mutant NSCLC, response rate was 77 %, median PFS was 9.1 months, and median OS was 24.1 months. The most common adverse events were anorexia and diarrhea. Treatment with 250 mg gefitinib daily with biweekly 400 mg/day vorinostat was feasible and well tolerated. In an unselected patient population, this combination dose did not improve PFS. However, this combination showed a potential for improving efficacy of gefitinib in EGFR-mutant NSCLC (NCT01027676).

  8. Effect of donepezil in patients with Alzheimer's disease previously untreated or treated with memantine or nootropic agents in Germany: an observational study.

    Science.gov (United States)

    Klinger, Tatjana; Ibach, Bernd; Schoenknecht, Peter; Kamleiter, Martin; Silver, Gabrielle; Schroeder, Johannes; Mielke, Ruediger

    2005-05-01

    This open-label, prospective, observational, Post-Marketing Surveillance (PMS) study assessed the efficacy and safety of donepezil in patients who had been switched from therapies currently used in Germany to treat Alzheimer's disease (AD), such as memantine and nootropics, due to insufficient efficacy or poor tolerability. A treatment-naive population was included as a comparator. Patients with AD were treated with donepezil and observed for a period of approximately 3 months. A cognitive assessment was made using the Mini-Mental State Examination (MMSE). Quality of life (QoL) was assessed by the investigators who answered the question 'How did therapy with donepezil influence the QoL of the patient and/or his family over the observation period?' and was graded using three ratings: improved/unchanged/worsened. Adverse events (AEs) were also monitored. A total of 913 patients entered the study (mean +/- SD MMSE score 18.03 +/- 5.34). Efficacy assessments were analyzed for three groups: an overall group of patients who had received any form of prior AD drug therapy (N+ group; n = 709); a subgroup of patients from the N+ group who had received prior memantine therapy only (M+ group; n = 111) and patients who were drug treatment naive (N- group; n = 204). In the evaluable population donepezil improved MMSE scores by 2.21 +/- 3.47 points on average, with similar improvements observed in all three groups. QoL was judged to be improved in at least 70% of patients, again with similar results obtained for all three groups. Donepezil was well tolerated, with 85 of 913 (9.3%) patients reporting AEs. The most common AEs were those typically seen with cholinergic therapies (i.e., diarrhoea, vomiting and nausea). In this observational PMS study, donepezil was shown to be efficacious and well tolerated in patients who were being insufficiently treated with memantine or nootropic therapy. The magnitude of response was similar to that observed in patients who were previously

  9. Stability and Change in Risk-Taking Propensity Across the Adult Lifespan

    Science.gov (United States)

    Josef, Anika K.; Richter, David; Samanez-Larkin, Gregory R.; Wagner, Gert G.; Hertwig, Ralph; Mata, Rui

    2016-01-01

    Can risk-taking propensity be thought of as a trait that captures individual differences across domains, measures, and time? Studying stability in risk-taking propensities across the lifespan can help to answer such questions by uncovering parallel, or divergent, trajectories across domains and measures. We contribute to this effort by using data from respondents aged 18 to 85 in the German Socio-Economic Panel Study (SOEP) and by examining (1) differential stability, (2) mean-level differences, and (3) individual-level changes in self-reported general (N = 44,076) and domain-specific (N =11,903) risk-taking propensities across adulthood. In addition, we investigate (4) the correspondence between cross-sectional trajectories of self-report and behavioral measures of social (trust game; N = 646) and nonsocial (monetary gamble; N = 433) risk taking. The results suggest that risk-taking propensity can be understood as a trait with moderate stability. Results show reliable mean-level differences across the lifespan, with risk-taking propensities typically decreasing with age, although significant variation emerges across domains and individuals. Interestingly, the mean-level trajectory for behavioral measures of social and nonsocial risk taking was similar to those obtained from self-reported risk, despite small correlations between task behavior and self-reports. Individual-level analyses suggest a link between changes in risk-taking propensities both across domains and in relation to changes in some of the Big Five personality traits. Overall, these results raise important questions concerning the role of common processes or events that shape the lifespan development of risk-taking across domains as well as other major personality facets. PMID:26820061

  10. Lifespan Development of the Human Brain Revealed by Large-Scale Network Eigen-Entropy

    Directory of Open Access Journals (Sweden)

    Yiming Fan

    2017-09-01

    Full Text Available Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying functional connectivity patterns of the developing and aging brain. Normal brain development is characterized by continuous and significant network evolution through infancy, childhood, and adolescence, following specific maturational patterns. Normal aging is related to some resting state brain networks disruption, which are associated with certain cognitive decline. It is a big challenge to design an integral metric to track connectome evolution patterns across the lifespan, which is to understand the principles of network organization in the human brain. In this study, we first defined a brain network eigen-entropy (NEE based on the energy probability (EP of each brain node. Next, we used the NEE to characterize the lifespan orderness trajectory of the whole-brain functional connectivity of 173 healthy individuals ranging in age from 7 to 85 years. The results revealed that during the lifespan, the whole-brain NEE exhibited a significant non-linear decrease and that the EP distribution shifted from concentration to wide dispersion, implying orderness enhancement of functional connectome over age. Furthermore, brain regions with significant EP changes from the flourishing (7–20 years to the youth period (23–38 years were mainly located in the right prefrontal cortex and basal ganglia, and were involved in emotion regulation and executive function in coordination with the action of the sensory system, implying that self-awareness and voluntary control performance significantly changed during neurodevelopment. However, the changes from the youth period to middle age (40–59 years were located in the mesial temporal lobe and caudate, which are associated with long-term memory, implying that the memory of the human brain begins to decline with age during this period. Overall, the findings suggested that the human connectome

  11. The Influence of Parental Psychopathology on Offspring Suicidal Behavior across the Lifespan.

    Directory of Open Access Journals (Sweden)

    Geilson Lima Santana

    Full Text Available Suicide tends to occur in families, and parental psychopathology has been linked to offspring suicidal behaviors. This study explores the influence of parental mental disorders across the lifespan. Data are from the Sao Paulo Megacity Mental Health Survey, a cross-sectional household study with a representative sample of the adult population living in the Sao Paulo Metropolitan Area, Brazil (N=2,942. Survival models examined bivariate and multivariate associations between a range of parental disorders and offspring suicidality. After controlling for comorbidity, number of mental disorders and offspring psychopathology, we found that parental psychopathology influences suicidal behaviors throughout most part of the life cycle, from childhood until young adult years. Generalized anxiety disorder (GAD and antisocial personality were associated with offspring suicidal ideation (OR 1.8 and 1.9, respectively, panic and GAD predicted suicidal attempts (OR 2.3 and 2.7, respectively, and panic was related to the transition from ideation to attempts (OR 2.7. Although noticed in many different stages of the lifespan, this influence is most evident during adolescence. In this period, depression and antisocial personality increased the odds of suicidal ideation (OR 5.1 and 3.2, respectively, and depression, panic disorder, GAD and substance abuse predicted suicidal attempts (OR varying from 1.7 to 3.8. In short, parental disorders characterized by impulsive-aggression and anxiety-agitation were the main predictors of offspring suicidality across the lifespan. This clinically relevant intergenerational transmission of suicide risk was independent of offspring mental disorders, and this underscores the need for a family approach to psychopathology.

  12. Sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer (NMSC): A population-based study.

    Science.gov (United States)

    Fischer, Alexander H; Wang, Timothy S; Yenokyan, Gayane; Kang, Sewon; Chien, Anna L

    2016-08-01

    Individuals with previous nonmelanoma skin cancer (NMSC) are at increased risk for subsequent skin cancer, and should therefore limit ultraviolet exposure. We sought to determine whether individuals with previous NMSC engage in better sun protection than those with no skin cancer history. We pooled self-reported data (2005 and 2010 National Health Interview Surveys) from US non-Hispanic white adults (758 with and 34,161 without previous NMSC). We calculated adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (CI), taking into account the complex survey design. Individuals with previous NMSC versus no history of NMSC had higher rates of frequent use of shade (44.3% vs 27.0%; aPOR 1.41; 95% CI 1.16-1.71), long sleeves (20.5% vs 7.7%; aPOR 1.55; 95% CI 1.21-1.98), a wide-brimmed hat (26.1% vs 10.5%; aPOR 1.52; 95% CI 1.24-1.87), and sunscreen (53.7% vs 33.1%; aPOR 2.11; 95% CI 1.73-2.59), but did not have significantly lower odds of recent sunburn (29.7% vs 40.7%; aPOR 0.95; 95% CI 0.77-1.17). Among those with previous NMSC, recent sunburn was inversely associated with age, sun avoidance, and shade but not sunscreen. Self-reported cross-sectional data and unavailable information quantifying regular sun exposure are limitations. Physicians should emphasize sunburn prevention when counseling patients with previous NMSC, especially younger adults, focusing on shade and sun avoidance over sunscreen. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  13. Holistic life-span health outcomes among elite intercollegiate student-athletes.

    Science.gov (United States)

    Sorenson, Shawn C; Romano, Russell; Scholefield, Robin M; Martin, Brandon E; Gordon, James E; Azen, Stanley P; Schroeder, E Todd; Salem, George J

    2014-01-01

    Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student-athletes (SAs). Cross-sectional study. A large Division I university. Population-based sample of 496 university students and alumni (age 17-84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. Participants completed anonymous, self-report questionnaires. We measured the Short-Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P students (P 99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P = .006; d = -0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50; pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs. No differences were observed between SAs and NAs in physical component HRQL. The SAs demonstrated significant, clinically meaningful evidence of greater joint health concerns later in life, comparable

  14. Patterns of presentation of chronic ischemic heart disease with and without previous myocardial infarction

    International Nuclear Information System (INIS)

    Ahmad, R.; Rabbani, A.; Awan, Z.A.

    2009-01-01

    The prevalence of Ischemic Heart Disease (IHD) is on the rise, from increasing lifespan of population and availability of better medical facilities. We studied chronic IHD cases with and without previous myocardial infarction, in Hazara, NWFP, Pakistan to evaluate left ventricular (LV) dysfunction, wall motion abnormalities and complications of IHD. All patients presenting with history of chest pain in Medical 'C' Unit, Ayub Teaching Hospital, Abbottabad from June 2004 to May 2005 were included in the study. Patients with non-cardiac chest pain were excluded from the study. Cases with congenital and rheumatic heart disease, cardiomyopathies, unstable angina and acute MI were excluded. Patients with IHD with or without myocardial infarction (MI) were studied for left ventricular dysfunction (ejection fraction, left atrial size, E/A ratio), wall motion abnormalities and complications of IHD (Mitral regurgitation, Ventricular Septal Defect (VSD), LV aneurysm, LV clot). Clinical and echocardiographic evaluation was done in each case. Out of 183 cases of chronic IHD, 123 patients were without previous MI and 60 had had previous MI. Ejection fraction (EF) was 45%+-15 in the group without MI and 35+-11% in cases with MI. Left Atrium (LA) size was 35+-6 mm and 39+-4 mm in the two groups respectively. LV diastolic dysfunction was seen in 17% in the first and 24% in the second group respectively. Global hypokinesia was seen in 8% and 17% in the 2 groups respectively. Regional Wall Motion Abnormality (RWMA) was observed in 12% in patients without MI and in 58% cases with MI. Mitral regurgitation was seen in 10 and 20% in the 2 groups respectively LV clots, VSD, LV and aneurysm were seen in 8.4, 5, and 6.5% respectively, only in cases with previous MI. LV dysfunction, wall motion abnormalities and mitral regurgitation were more common in IHD cases with previous heart attack. (author)

  15. A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control.

    Directory of Open Access Journals (Sweden)

    Rosanna Ghinai

    2015-01-01

    Full Text Available Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5-17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes.

  16. Annual report references to dog longevity studies in which all dogs have died

    Energy Technology Data Exchange (ETDEWEB)

    Boecker, B B

    1988-12-01

    All of the dogs in several of the-lifespan studies with beta-emitting radionuclides are dead. Routine annual summaries of these studies have been discontinued. To aid the reader interested in obtaining further information, this report provides summaries of the final status of each study and lists all previous ITRI Annual Report references for each study. (author)

  17. Annual report references to dog longevity studies in which all dogs have died

    International Nuclear Information System (INIS)

    Boecker, B.B.

    1988-01-01

    All of the dogs in several of the-lifespan studies with beta-emitting radionuclides are dead. Routine annual summaries of these studies have been discontinued. To aid the reader interested in obtaining further information, this report provides summaries of the final status of each study and lists all previous ITRI Annual Report references for each study. (author)

  18. Effect of Spaceflight on the Circadian Rhythm, Lifespan and Gene Expression of Drosophila melanogaster

    Science.gov (United States)

    Xu, Kanyan

    2015-01-01

    Space travelers are reported to experience circadian rhythm disruption during spaceflight. However, how the space environment affects circadian rhythm is yet to be determined. The major focus of this study was to investigate the effect of spaceflight on the Drosophila circadian clock at both the behavioral and molecular level. We used China’s Shenzhou-9 spaceship to carry Drosophila. After 13 days of spaceflight, behavior tests showed that the flies maintained normal locomotor activity rhythm and sleep pattern. The expression level and rhythm of major clock genes were also unaffected. However, expression profiling showed differentially regulated output genes of the circadian clock system between space flown and control flies, suggesting that spaceflight affected the circadian output pathway. We also investigated other physiological effects of spaceflight such as lipid metabolism and lifespan, and searched genes significantly affected by spaceflight using microarray analysis. These results provide new information on the effects of spaceflight on circadian rhythm, lipid metabolism and lifespan. Furthermore, we showed that studying the effect of spaceflight on gene expression using samples collected at different Zeitgeber time could obtain different results, suggesting the importance of appropriate sampling procedures in studies on the effects of spaceflight. PMID:25798821

  19. Effect of spaceflight on the circadian rhythm, lifespan and gene expression of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Lingling Ma

    Full Text Available Space travelers are reported to experience circadian rhythm disruption during spaceflight. However, how the space environment affects circadian rhythm is yet to be determined. The major focus of this study was to investigate the effect of spaceflight on the Drosophila circadian clock at both the behavioral and molecular level. We used China's Shenzhou-9 spaceship to carry Drosophila. After 13 days of spaceflight, behavior tests showed that the flies maintained normal locomotor activity rhythm and sleep pattern. The expression level and rhythm of major clock genes were also unaffected. However, expression profiling showed differentially regulated output genes of the circadian clock system between space flown and control flies, suggesting that spaceflight affected the circadian output pathway. We also investigated other physiological effects of spaceflight such as lipid metabolism and lifespan, and searched genes significantly affected by spaceflight using microarray analysis. These results provide new information on the effects of spaceflight on circadian rhythm, lipid metabolism and lifespan. Furthermore, we showed that studying the effect of spaceflight on gene expression using samples collected at different Zeitgeber time could obtain different results, suggesting the importance of appropriate sampling procedures in studies on the effects of spaceflight.

  20. Radiation effects on lifespan of the fish Oryzias latipes

    International Nuclear Information System (INIS)

    Egami, N.

    1979-01-01

    The mortality rate of adult fish exposed to continuous γ-ray irradiation was examined and the results summarized. Initial results into the effects of low-dose γ-irradiation during early developmental stages (one day embryo - 3 month old young) on lifespan, indicate that in this fish the life-shortening effects of radiation are marked at high doses but not at low doses. Age-related histological changes in various tissues have been observed in both irradiated and non-irradiated fish. (Auth.)

  1. The effects of oral clefts on hospital use throughout the lifespan

    Directory of Open Access Journals (Sweden)

    Wehby George L

    2012-03-01

    Full Text Available Abstract Background Oral clefts are one of the most common birth defects worldwide. They require multiple healthcare interventions and add significant burden on the health and quality of life of affected individuals. However, not much is known about the long term effects of oral clefts on health and healthcare use of affected individuals. In this study, we evaluate the effects of oral clefts on hospital use throughout the lifespan. Methods We estimate two-part regression models for hospital admission and length of stay for several age groups up to 68 years of age. The study employs unique secondary population-based data from several administrative inpatient, civil registration, demographic and labor market databases for 7,670 individuals born with oral clefts between 1936 and 2002 in Denmark, and 220,113 individuals without oral clefts from a 5% random sample of the total birth population from 1936 to 2002. Results Oral clefts significantly increase hospital use for most ages below 60 years by up to 233% for children ages 0-10 years and 16% for middle age adults. The more severe cleft forms (cleft lip with palate have significantly larger effects on hospitalizations than less severe forms. Conclusions The results suggest that individuals with oral clefts have higher hospitalization risks than the general population throughout most of the lifespan.

  2. Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass.

    Science.gov (United States)

    Hirozane, Toru; Tohmonda, Takahide; Yoda, Masaki; Shimoda, Masayuki; Kanai, Yae; Matsumoto, Morio; Morioka, Hideo; Nakamura, Masaya; Horiuchi, Keisuke

    2016-09-28

    Ataxia-telangiectasia mutated (ATM) kinase is a central component involved in the signal transduction of the DNA damage response (DDR) and thus plays a critical role in the maintenance of genomic integrity. Although the primary functions of ATM are associated with the DDR, emerging data suggest that ATM has many additional roles that are not directly related to the DDR, including the regulation of oxidative stress signaling, insulin sensitivity, mitochondrial homeostasis, and lymphocyte development. Patients and mice lacking ATM exhibit growth retardation and lower bone mass; however, the mechanisms underlying the skeletal defects are not fully understood. In the present study, we generated mutant mice in which ATM is specifically inactivated in osteoclasts. The mutant mice did not exhibit apparent developmental defects but showed reduced bone mass due to increased osteoclastic bone resorption. Osteoclasts lacking ATM were more resistant to apoptosis and showed a prolonged lifespan compared to the controls. Notably, the inactivation of ATM in osteoclasts resulted in enhanced NF-κB signaling and an increase in the expression of NF-κB-targeted genes. The present study reveals a novel function for ATM in regulating bone metabolism by suppressing the lifespan of osteoclasts and osteoclast-mediated bone resorption.

  3. The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

    International Nuclear Information System (INIS)

    Khan, Maruf H.; Hart, Matthew J.; Rea, Shane L.

    2012-01-01

    Highlights: ► Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. ► Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. ► Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation – when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that has recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.

  4. The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Maruf H. [Barshop Institute for Longevity and Aging Studies, Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78240 (United States); Hart, Matthew J., E-mail: HartMJ@uthscsa.edu [Barshop Institute for Longevity and Aging Studies, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78240 (United States); Rea, Shane L., E-mail: reas3@uthscsa.edu [Barshop Institute for Longevity and Aging Studies, Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78240 (United States)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. Black-Right-Pointing-Pointer Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. Black-Right-Pointing-Pointer Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation - when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that has recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.

  5. Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

    Directory of Open Access Journals (Sweden)

    Lopez-Saura Pedro

    2009-07-01

    Full Text Available Abstract Background Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC or squamous cell skin carcinomas (SCSC. Methods Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. Results Sixteen elder (median 70 years-old patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination, 40% PR (>30% tumor reduction, and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated. Conclusion The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. Trial registration Current Controlled Trials RPCEC00000052.

  6. Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

    International Nuclear Information System (INIS)

    Anasagasti-Angulo, Lorenzo; Garcia-Vega, Yanelda; Barcelona-Perez, Silvia; Lopez-Saura, Pedro; Bello-Rivero, Iraldo

    2009-01-01

    Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions) are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN) may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC) or squamous cell skin carcinomas (SCSC). Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. Sixteen elder (median 70 years-old) patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination), 40% PR (>30% tumor reduction), and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated. The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. Current Controlled Trials RPCEC00000052

  7. A Lifespan Perspective on Entrepreneurship: Perceived Opportunities and Skills Explain the Negative Association between Age and Entrepreneurial Activity

    OpenAIRE

    Bohlmann, Clarissa; Rauch, Andreas; Zacher, Hannes

    2017-01-01

    Researchers and practitioners are increasingly interested in entrepreneurship as a means to fight youth unemployment and to improve financial stability at higher ages. However, only few studies so far have examined the association between age and entrepreneurial activity. Based on theories from the lifespan psychology literature and entrepreneurship, we develop and test a model in which perceived opportunities and skills explain the relationship between age and entrepreneurial activity. We an...

  8. Short-term memory predictions across the lifespan: monitoring span before and after conducting a task.

    Science.gov (United States)

    Bertrand, Julie Marilyne; Moulin, Chris John Anthony; Souchay, Céline

    2017-05-01

    Our objective was to explore metamemory in short-term memory across the lifespan. Five age groups participated in this study: 3 groups of children (4-13 years old), and younger and older adults. We used a three-phase task: prediction-span-postdiction. For prediction and postdiction phases, participants reported with a Yes/No response if they could recall in order a series of images. For the span task, they had to actually recall such series. From 4 years old, children have some ability to monitor their short-term memory and are able to adjust their prediction after experiencing the task. However, accuracy still improves significantly until adolescence. Although the older adults had a lower span, they were as accurate as young adults in their evaluation, suggesting that metamemory is unimpaired for short-term memory tasks in older adults. •We investigate metamemory for short-term memory tasks across the lifespan. •We find younger children cannot accurately predict their span length. •Older adults are accurate in predicting their span length. •People's metamemory accuracy was related to their short-term memory span.

  9. Life-span development of self-esteem and its effects on important life outcomes.

    Science.gov (United States)

    Orth, Ulrich; Robins, Richard W; Widaman, Keith F

    2012-06-01

    We examined the life-span development of self-esteem and tested whether self-esteem influences the development of important life outcomes, including relationship satisfaction, job satisfaction, occupational status, salary, positive and negative affect, depression, and physical health. Data came from the Longitudinal Study of Generations. Analyses were based on 5 assessments across a 12-year period of a sample of 1,824 individuals ages 16 to 97 years. First, growth curve analyses indicated that self-esteem increases from adolescence to middle adulthood, reaches a peak at about age 50 years, and then decreases in old age. Second, cross-lagged regression analyses indicated that self-esteem is best modeled as a cause rather than a consequence of life outcomes. Third, growth curve analyses, with self-esteem as a time-varying covariate, suggested that self-esteem has medium-sized effects on life-span trajectories of affect and depression, small to medium-sized effects on trajectories of relationship and job satisfaction, a very small effect on the trajectory of health, and no effect on the trajectory of occupational status. These findings replicated across 4 generations of participants--children, parents, grandparents, and their great-grandparents. Together, the results suggest that self-esteem has a significant prospective impact on real-world life experiences and that high and low self-esteem are not mere epiphenomena of success and failure in important life domains. 2012 APA, all rights reserved

  10. Co-chaperone p23 regulates C. elegans Lifespan in Response to Temperature.

    Directory of Open Access Journals (Sweden)

    Makoto Horikawa

    2015-04-01

    Full Text Available Temperature potently modulates various physiologic processes including organismal motility, growth rate, reproduction, and ageing. In ectotherms, longevity varies inversely with temperature, with animals living shorter at higher temperatures. Thermal effects on lifespan and other processes are ascribed to passive changes in metabolic rate, but recent evidence also suggests a regulated process. Here, we demonstrate that in response to temperature, daf-41/ZC395.10, the C. elegans homolog of p23 co-chaperone/prostaglandin E synthase-3, governs entry into the long-lived dauer diapause and regulates adult lifespan. daf-41 deletion triggers constitutive entry into the dauer diapause at elevated temperature dependent on neurosensory machinery (daf-10/IFT122, insulin/IGF-1 signaling (daf-16/FOXO, and steroidal signaling (daf-12/FXR. Surprisingly, daf-41 mutation alters the longevity response to temperature, living longer than wild-type at 25°C but shorter than wild-type at 15°C. Longevity phenotypes at 25°C work through daf-16/FOXO and heat shock factor hsf-1, while short lived phenotypes converge on daf-16/FOXO and depend on the daf-12/FXR steroid receptor. Correlatively daf-41 affected expression of DAF-16 and HSF-1 target genes at high temperature, and nuclear extracts from daf-41 animals showed increased occupancy of the heat shock response element. Our studies suggest that daf-41/p23 modulates key transcriptional changes in longevity pathways in response to temperature.

  11. C30F12.4 influences oogenesis, fat metabolism, and lifespan in C. elegans

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2016-09-01

    Full Text Available ABSTRACT Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.

  12. A prolonged chronological lifespan is an unexpected benefit of the [PSI+] prion in yeast.

    Science.gov (United States)

    Wang, Kai; Melki, Ronald; Kabani, Mehdi

    2017-01-01

    Self-replicating 'proteinaceous infectious particles' or prions are responsible for complex heritable traits in the yeast Saccharomyces cerevisiae. Our current understanding of the biology of yeast prions stems from studies mostly done in the context of actively dividing cells in optimal laboratory growth conditions. Evidence suggest that fungal prions exist in the wild where most cells are in a non-dividing quiescent state, because of imperfect growth conditions, scarcity of nutrients and competition. We know little about the faithful transmission of yeast prions in such conditions and their physiological consequences throughout the lifespan of yeast cells. We addressed this issue for the [PSI+] prion that results from the self-assembly of the translation release factor Sup35p into insoluble fibrillar aggregates. [PSI+] leads to increased nonsense suppression and confers phenotypic plasticity in response to environmental fluctuations. Here, we report that while [PSI+] had little to no effect on growth per se, it dramatically improved the survival of yeast cells in stationary phase. Remarkably, prolonged chronological lifespan persisted even after [PSI+] was cured from the cells, suggesting that prions may facilitate the acquisition of complex new traits. Such an important selective advantage may contribute to the evolutionary conservation of the prion-forming ability of Sup35p orthologues in distantly related yeast species.

  13. A prolonged chronological lifespan is an unexpected benefit of the [PSI+] prion in yeast.

    Directory of Open Access Journals (Sweden)

    Kai Wang

    Full Text Available Self-replicating 'proteinaceous infectious particles' or prions are responsible for complex heritable traits in the yeast Saccharomyces cerevisiae. Our current understanding of the biology of yeast prions stems from studies mostly done in the context of actively dividing cells in optimal laboratory growth conditions. Evidence suggest that fungal prions exist in the wild where most cells are in a non-dividing quiescent state, because of imperfect growth conditions, scarcity of nutrients and competition. We know little about the faithful transmission of yeast prions in such conditions and their physiological consequences throughout the lifespan of yeast cells. We addressed this issue for the [PSI+] prion that results from the self-assembly of the translation release factor Sup35p into insoluble fibrillar aggregates. [PSI+] leads to increased nonsense suppression and confers phenotypic plasticity in response to environmental fluctuations. Here, we report that while [PSI+] had little to no effect on growth per se, it dramatically improved the survival of yeast cells in stationary phase. Remarkably, prolonged chronological lifespan persisted even after [PSI+] was cured from the cells, suggesting that prions may facilitate the acquisition of complex new traits. Such an important selective advantage may contribute to the evolutionary conservation of the prion-forming ability of Sup35p orthologues in distantly related yeast species.

  14. Metabolome analysis of effect of aspirin on Drosophila lifespan extension.

    Science.gov (United States)

    Song, Chaochun; Zhu, Chenxing; Wu, Qi; Qi, Jiancheng; Gao, Yue; Zhang, Zhichao; Gaur, Uma; Yang, Deying; Fan, Xiaolan; Yang, Mingyao

    2017-09-01

    Effective approaches for drug development involve the repurposing of existing drugs which are already approved by the FDA. Aspirin has been shown to have many health benefits since its discovery as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Recent experiments demonstrated the longevity effects of aspirin in Drosophila, but its mechanism remains to be explored. In order to elucidate the effects of drug on metabolism, we carried out the metabolic analysis of aspirin-treated flies. The results identified 404 active metabolites in addition to the extended lifespan and improved healthspan in fly. There were 28 metabolites having significant changes between aspirin-treated group and the control group, out of which 22 compounds were found to have detailed information. These compounds are reported to have important functions in energy metabolism, amino sugar metabolism, and urea metabolism, indicating that aspirin might be playing positive roles in the fly's lifespan and healthspan improvement. Because of the conservation of major longevity pathways and mechanisms in different species, the health benefits of aspirin administration could be extended to other animals and humans as well. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Why is parental lifespan linked to children's chances of reaching a high age? A transgenerational hypothesis.

    Science.gov (United States)

    Vågerö, Denny; Aronsson, Vanda; Modin, Bitte

    2018-04-01

    Transgenerational determinants of longevity are poorly understood. We used data from four linked generations (G0, G1, G2 and G3) of the Uppsala Birth Cohort Multigeneration Study to address this issue. Mortality in G1 (N = 9565) was followed from 1961-2015 and analysed in relation to tertiles of their parents' (G0) age-at-death using Cox regression. Parental social class and marital status were adjusted for in the analyses, as was G1's birth order and adult social class. For an almost entirely deceased segment of G1 (n = 1149), born 1915-1917, we compared exact age-at-death with G0 parents' age-at-death. Finally, we explored 'resilience' as a potentially important mechanism for intergenerational transmission of longevity, using conscript information from psychological interviews of G2 and G3 men. G0 men's and women's ages-at-death were independently associated with G1 midlife and old age mortality. This association was robust and minimally reduced when G0 and G1 social class were adjusted for. We observed an increased lifespan in all social groups. Median difference in age-at-death for sons compared to fathers was + 3.9 years, and + 6.9 years for daughters compared to mothers.Parents' and maternal grandmother's longevity were associated with resilience in subsequent generations. Resilience scores of G2 men were also associated with those of their G3 sons and with their own mortality in midlife. The chance of reaching a high age is transmitted from parents to children in a modest, but robust way. Longevity inheritance is paralleled by the inheritance of individual resilience. Individual resilience, we propose, develops in the first part of life as a response to adversity and early experience in general. This gives rise to a transgenerational pathway, distinct from social class trajectories. A theory of longevity inheritance should bring together previous thinking around general susceptibility, frailty and resilience with new insights from epigenetics and social

  16. Lifespan decrease in a Caenorhabditis elegans mutant lacking TRX-1, a thioredoxin expressed in ASJ sensory neurons.

    Science.gov (United States)

    Miranda-Vizuete, Antonio; Fierro González, Juan Carlos; Gahmon, Gabriele; Burghoorn, Jan; Navas, Plácido; Swoboda, Peter

    2006-01-23

    Thioredoxins are a class of small proteins that play a key role in regulating many cellular redox processes. We report here the characterization of the first member of the thioredoxin family in metazoans that is mainly associated with neurons. The Caenorhabditis elegans gene B0228.5 encodes a thioredoxin (TRX-1) that is expressed in ASJ ciliated sensory neurons, and to some extent also in the posterior-most intestinal cells. TRX-1 is active at reducing protein disulfides in the presence of a heterologous thioredoxin reductase. A mutant worm strain carrying a null allele of the trx-1 gene displays a reproducible decrease in both mean and maximum lifespan when compared to wild-type. The identification and characterization of TRX-1 paves the way to use C. elegans as an in vivo model to study the role of thioredoxins in lifespan and nervous system physiology and pathology.

  17. The addition of a developmental factor, unc-62, to already long-lived worms increases lifespan and healthspan

    Directory of Open Access Journals (Sweden)

    Dror Sagi

    2017-12-01

    Full Text Available Aging is a complex trait that is affected by multiple genetic pathways. A relatively unexplored approach is to manipulate multiple independent aging pathways simultaneously in order to observe their cumulative effect on lifespan. Here, we report the phenotypic characterization of a strain with changes in five aging pathways: (1 mitochondrial reactive oxygen species (ROS production, (2 innate immunity, (3 stress response, (4 metabolic control and (5 developmental regulation in old age. The quintuply modified strain has a lifespan that is 160% longer than the transgenic control strain. Additionally, the quintuply modified strain maintains several physiological markers of aging for a longer time than the transgenic control. Our results support a modular approach as a general scheme to study how multiple pathways interact to achieve extreme longevity.

  18. Socioeconomic status moderates age-related differences in the brain's functional network organization and anatomy across the adult lifespan.

    Science.gov (United States)

    Chan, Micaela Y; Na, Jinkyung; Agres, Phillip F; Savalia, Neil K; Park, Denise C; Wig, Gagan S

    2018-05-14

    An individual's environmental surroundings interact with the development and maturation of their brain. An important aspect of an individual's environment is his or her socioeconomic status (SES), which estimates access to material resources and social prestige. Previous characterizations of the relation between SES and the brain have primarily focused on earlier or later epochs of the lifespan (i.e., childhood, older age). We broaden this work to examine the relationship between SES and the brain across a wide range of human adulthood (20-89 years), including individuals from the less studied middle-age range. SES, defined by education attainment and occupational socioeconomic characteristics, moderates previously reported age-related differences in the brain's functional network organization and whole-brain cortical structure. Across middle age (35-64 years), lower SES is associated with reduced resting-state system segregation (a measure of effective functional network organization). A similar but less robust relationship exists between SES and age with respect to brain anatomy: Lower SES is associated with reduced cortical gray matter thickness in middle age. Conversely, younger and older adulthood do not exhibit consistent SES-related difference in the brain measures. The SES-brain relationships persist after controlling for measures of physical and mental health, cognitive ability, and participant demographics. Critically, an individual's childhood SES cannot account for the relationship between their current SES and functional network organization. These findings provide evidence that SES relates to the brain's functional network organization and anatomy across adult middle age, and that higher SES may be a protective factor against age-related brain decline. Copyright © 2018 the Author(s). Published by PNAS.

  19. Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

    Science.gov (United States)

    Corrado, C; Santarelli, M T; Pavlovsky, S; Pizzolato, M

    1989-12-01

    Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

  20. Implementation of an electronic medical record system in previously computer-naïve primary care centres: a pilot study from Cyprus.

    Science.gov (United States)

    Samoutis, George; Soteriades, Elpidoforos S; Kounalakis, Dimitris K; Zachariadou, Theodora; Philalithis, Anastasios; Lionis, Christos

    2007-01-01

    The computer-based electronic medical record (EMR) is an essential new technology in health care, contributing to high-quality patient care and efficient patient management. The majority of southern European countries, however, have not yet implemented universal EMR systems and many efforts are still ongoing. We describe the development of an EMR system and its pilot implementation and evaluation in two previously computer-naïve public primary care centres in Cyprus. One urban and one rural primary care centre along with their personnel (physicians and nurses) were selected to participate. Both qualitative and quantitative evaluation tools were used during the implementation phase. Qualitative data analysis was based on the framework approach, whereas quantitative assessment was based on a nine-item questionnaire and EMR usage parameters. Two public primary care centres participated, and a total often health professionals served as EMR system evaluators. Physicians and nurses rated EMR relatively highly, while patients were the most enthusiastic supporters for the new information system. Major implementation impediments were the physicians' perceptions that EMR usage negatively affected their workflow, physicians' legal concerns, lack of incentives, system breakdowns, software design problems, transition difficulties and lack of familiarity with electronic equipment. The importance of combining qualitative and quantitative evaluation tools is highlighted. More efforts are needed for the universal adoption and routine use of EMR in the primary care system of Cyprus as several barriers to adoption exist; however, none is insurmountable. Computerised systems could improve efficiency and quality of care in Cyprus, benefiting the entire population.

  1. Vitellogenin family gene expression does not increase Drosophila lifespan or fecundity [v1; ref status: indexed, http://f1000r.es/3ac

    Directory of Open Access Journals (Sweden)

    Yingxue Ren

    2014-06-01

    Full Text Available One of the most striking patterns in comparative biology is the negative correlation between lifespan and fecundity observed in comparisons among species. This pattern is consistent with the idea that organisms need to allocate a fixed energy budget among competing demands of growth, development, reproduction and somatic maintenance. However, exceptions to this pattern have been observed in many social insects, including ants, bees, and termites.  In honey bees (Apis mellifera, Vitellogenin (Vg, a yolk protein precursor, has been implicated in mediating the long lifespan and high fecundity of queen bees. To determine if Vg-like proteins can regulate lifespan in insects generally, we examined the effects of expression of Apis Vg and Drosophila CG31150 (a Vg-like gene recently identified as cv-d on Drosophila melanogaster lifespan and fecundity using the RU486-inducible GeneSwitch system. For all genotypes tested, overexpression of Vg and CG31150 decreased Drosophila lifespan and did not affect total or age-specific fecundity. We also detected an apparent effect of the GeneSwitch system itself, wherein RU486 exposure (or the GAL4 expression it induces led to a significant increase in longevity and decrease in fecundity in our fly strains. This result is consistent with the pattern reported in a recent meta-analysis of Drosophila aging studies, where transgenic constructs of the UAS/GAL4 expression system that should have no effect (e.g. an uninduced GeneSwitch significantly extended lifespan in some genetic backgrounds. Our results suggest that Vg-family genes are not major regulators of Drosophila life history traits, and highlight the importance of using appropriate controls in aging studies.

  2. Prospective monitoring and self-report of previous falls among older women at high risk of falls and fractures: a study of comparison and agreement.

    Science.gov (United States)

    Garcia, Patrícia A; Dias, João M D; Silva, Silvia L A; Dias, Rosângela C

    2015-01-01

    The identification of the occurrence of falls is an important step for screening and for rehabilitation processes for the elderly. The methods of monitoring these events are susceptible to recording biases, and the choice of the most accurate method remains challenging. (i) To investigate the agreement between retrospective self-reporting and prospective monitoring of methods of recording falls, and (ii) to compare the retrospective self-reporting of falls and the prospective monitoring of falls and recurrent falls over a 12-month period among older women at high risk of falls and fractures. A total of 118 community-dwelling older women with low bone density were recruited. The incidence of falls was monitored prospectively in 116 older women (2 losses) via monthly phone calls over the course of a year. At the end of this monitoring period, the older women were asked about their recall of falls in the same 12-month period. The agreement between the two methods was analyzed, and the sensitivity and specificity of self-reported previous falls in relation to the prospective monitoring were calculated. There was moderate agreement between the prospective monitoring and the retrospective self-reporting of falls in classifying fallers (Kappa = 0.595) and recurrent fallers (Kappa = 0.589). The limits of agreement were 0.35 ± 1.66 falls. The self-reporting of prior falls had a 67.2% sensitivity and a 94.2% specificity in classifying fallers among older women and a 50% sensitivity and a 98.9% specificity in classifying recurrent fallers. Self-reporting of falls over a 12-month period underestimated 32.8% of falls and 50% of recurrent falls. The findings recommend caution if one is considering replacing monthly monitoring with annual retrospective questioning.

  3. The importance of continued exercise participation in quality of life and psychological well-being in previously inactive postmenopausal women: a pilot study.

    Science.gov (United States)

    Asbury, Elizabeth A; Chandrruangphen, Pornpat; Collins, Peter

    2006-01-01

    Exercise and physical activity provide a wide range of health benefits for postmenopausal women, although the impact of maintained exercise participation on psychological well-being is unclear. An exploration of continued exercise participation in psychological well-being after a moderate-intensity exercise program in previously inactive postmenopausal women was therefore undertaken. : Twenty-three healthy sedentary postmenopausal women (age 56 +/- 4 years) were randomly assigned to two groups. All participants completed the Short Form-36, Hospital Anxiety and Depression Scale (HADS), and Health Anxiety Questionnaire (HAQ) and then began a 6-week walking program at 50% heart rate reserve defined by (.-)V(O(2)) treadmill testing. Post-intervention, all participants underwent (.-)V(O(2)) treadmill testing and questionnaires. Group 1 was then instructed to continue exercising, whereas group 2 was instructed to desist for an additional 6-week period. On completion of the 6-week follow-up, participants completed a final set of questionnaires. Participants performed 97% of the prescribed 15-hour (900 minute) exercise program (875.1 +/- 177.4 minutes) in an average of 26 +/- 5 sessions. Total HAQ (P = 0.001), health worry (P = 0.001), fear of illness (P = 0.037), reassurance seeking behavior (P = 0.037), SF-36 well-being (P = 0.037), total HADS (P = 0.019), and HADS depression (P = 0.015) improved significantly following the exercise program. At follow-up, group 1 had lower HADS anxiety (P = 0.013), total HADS (P = 0.02), total HAQ (P = 0.03), and HAQ interference with life (P = 0.03) and significantly higher SF-36 energy (P = 0.01) than group 2. Healthy postmenopausal women gain significant psychological benefit from moderate-intensity exercise. However, exercise participation must continue to maintain improvements in psychological well-being and quality of life.

  4. Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals “aging factors” and mechanism of lifespan asymmetry

    Science.gov (United States)

    Yang, Jing; McCormick, Mark A.; Zheng, Jiashun; Xie, Zhengwei; Tsuchiya, Mitsuhiro; Tsuchiyama, Scott; El-Samad, Hana; Ouyang, Qi; Kaeberlein, Matt; Kennedy, Brian K.; Li, Hao

    2015-01-01

    Budding yeast divides asymmetrically, giving rise to a mother cell that progressively ages and a daughter cell with full lifespan. It is generally assumed that mother cells retain damaged, lifespan limiting materials (“aging factors”) through asymmetric division. However, the identity of these aging factors and the mechanisms through which they limit lifespan remain poorly understood. Using a flow cytometry-based, high-throughput approach, we quantified the asymmetric partitioning of the yeast proteome between mother and daughter cells during cell division, discovering 74 mother-enriched and 60 daughter-enriched proteins. While daughter-enriched proteins are biased toward those needed for bud construction and genome maintenance, mother-enriched proteins are biased towards those localized in the plasma membrane and vacuole. Deletion of 23 of the 74 mother-enriched proteins leads to lifespan extension, a fraction that is about six times that of the genes picked randomly from the genome. Among these lifespan-extending genes, three are involved in endosomal sorting/endosome to vacuole transport, and three are nitrogen source transporters. Tracking the dynamic expression of specific mother-enriched proteins revealed that their concentration steadily increases in the mother cells as they age, but is kept relatively low in the daughter cells via asymmetric distribution. Our results suggest that some mother-enriched proteins may increase to a concentration that becomes deleterious and lifespan-limiting in aged cells, possibly by upsetting homeostasis or leading to aberrant signaling. Our study provides a comprehensive resource for analyzing asymmetric cell division and aging in yeast, which should also be valuable for understanding similar phenomena in other organisms. PMID:26351681

  5. Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals "aging factors" and mechanism of lifespan asymmetry.

    Science.gov (United States)

    Yang, Jing; McCormick, Mark A; Zheng, Jiashun; Xie, Zhengwei; Tsuchiya, Mitsuhiro; Tsuchiyama, Scott; El-Samad, Hana; Ouyang, Qi; Kaeberlein, Matt; Kennedy, Brian K; Li, Hao

    2015-09-22

    Budding yeast divides asymmetrically, giving rise to a mother cell that progressively ages and a daughter cell with full lifespan. It is generally assumed that mother cells retain damaged, lifespan limiting materials ("aging factors") through asymmetric division. However, the identity of these aging factors and the mechanisms through which they limit lifespan remain poorly understood. Using a flow cytometry-based, high-throughput approach, we quantified the asymmetric partitioning of the yeast proteome between mother and daughter cells during cell division, discovering 74 mother-enriched and 60 daughter-enriched proteins. While daughter-enriched proteins are biased toward those needed for bud construction and genome maintenance, mother-enriched proteins are biased towards those localized in the plasma membrane and vacuole. Deletion of 23 of the 74 mother-enriched proteins leads to lifespan extension, a fraction that is about six times that of the genes picked randomly from the genome. Among these lifespan-extending genes, three are involved in endosomal sorting/endosome to vacuole transport, and three are nitrogen source transporters. Tracking the dynamic expression of specific mother-enriched proteins revealed that their concentration steadily increases in the mother cells as they age, but is kept relatively low in the daughter cells via asymmetric distribution. Our results suggest that some mother-enriched proteins may increase to a concentration that becomes deleterious and lifespan-limiting in aged cells, possibly by upsetting homeostasis or leading to aberrant signaling. Our study provides a comprehensive resource for analyzing asymmetric cell division and aging in yeast, which should also be valuable for understanding similar phenomena in other organisms.

  6. Vitellogenin-RNAi and ovariectomy each increase lifespan, increase protein storage, and decrease feeding, but are not additive in grasshoppers.

    Science.gov (United States)

    Tetlak, Alicia G; Burnett, Jacob B; Hahn, Daniel A; Hatle, John D

    2015-12-01

    Reduced reproduction has been shown to increase lifespan in many animals, yet the mechanisms behind this trade-off are unclear. We addressed this question by combining two distinct, direct means of life-extension via reduced reproduction, to test whether they were additive. In the lubber grasshopper, Romalea microptera, ovariectomized (OVX) individuals had a ~20% increase in lifespan and a doubling of storage relative to controls (Sham operated). Similarly, young female grasshoppers treated with RNAi against vitellogenin (the precursor to egg yolk protein) had increased fat body mass and halted ovarian growth. In this study, we compared VgRNAi to two control groups that do not reduce reproduction, namely buffer injection (Buffer) and injection with RNAi against a hexameric storage protein (Hex90RNAi). Each injection treatment was tested with and without ovariectomy. Hence, we tested feeding, storage, and lifespans in six groups: OVX and Buffer, OVX and Hex90RNAi, OVX and VgRNAi, Sham and Buffer, Sham and Hex90RNAi, and Sham and VgRNAi. Ovariectomized grasshoppers and VgRNAi grasshoppers each had similar reductions in feeding (~40%), increases in protein storage in the hemolymph (150-300%), and extensions in lifespan (13-21%). Ovariectomized grasshoppers had higher vitellogenin protein levels than did VgRNAi grasshoppers. Last but not least, when ovariectomy and VgRNAi were applied together, there was no greater effect on feeding, protein storage, or longevity. Hence, feeding regulation, and protein storage in insects, may be conserved components of life-extension via reduced reproduction.

  7. Lifespan extension and increased resistance to environmental stressors by N-Acetyl-L-Cysteine in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Seung-Il Oh

    2015-05-01

    Full Text Available OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV, was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors.

  8. Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in Drosophila.

    Science.gov (United States)

    Romey-Glüsing, Renja; Li, Yang; Hoffmann, Julia; von Frieling, Jakob; Knop, Mirjam; Pfefferkorn, Roxana; Bruchhaus, Iris; Fink, Christine; Roeder, Thomas

    2018-04-01

    Nutritional interventions such as caloric and dietary restriction increase lifespan in various animal models. To identify alternative and less demanding nutritional interventions that extend lifespan, we subjected fruit flies ( Drosophila melanogaster) to weekly nutritional regimens that involved alternating a conventional diet with dietary restriction. Short periods of dietary restriction (up to 2 d) followed by longer periods of a conventional diet yielded minimal increases in lifespan. We found that 3 or more days of contiguous dietary restriction (DR) was necessary to yield a lifespan extension similar to that observed with persistent DR. Female flies were more responsive to these interventions than males. Physiologic changes known to be associated with prolonged DR, such as reduced metabolic rates, showed the same time course as lifespan extension. Moreover, concurrent transcriptional changes indicative of reduced insulin signaling were identified with DR. These physiologic and transcriptional changes were sustained, as they were detectable several days after switching to conventional diets. Taken together, diets with longer periods of DR extended lifespan concurrently with physiologic and transcriptional changes that may underlie this increase in lifespan.-Romey-Glüsing, R., Li, Y., Hoffmann, J., von Frieling, J., Knop, M., Pfefferkorn, R., Bruchhaus, I., Fink, C., Roeder, T. Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in Drosophila.

  9. Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila

    Science.gov (United States)

    Curcumin is an antioxidant extracted from the root of the turmeric plant. We examined the antioxidant effect and lifespan extension of curcumin in Drosophila. To ascertain the antioxidant effects of curcumin with regard to lifespan extension and the response to reactive oxygen species, female and ma...

  10. Mechanisms of increased lifespan in hypoxia in the alfalfa leafcutting bee, Megachile rotundata

    Science.gov (United States)

    Genetic variation accounts for a small amount of variation in lifespan, while environmental stressors are strong predictors. Hypoxia is an environmental stress that increases longevity in some contexts, but the mechanisms remain poorly understood. In the bee Megachile rotundata, lifespan doubles upo...

  11. Transcription factor genes essential for cell proliferation and replicative lifespan in budding yeast

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Yuka; Tai, Akiko; Dakeyama, Shota; Yamamoto, Kaori; Inoue, Yamato; Kishimoto, Yoshifumi; Ohara, Hiroya; Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp

    2015-07-31

    Many of the lifespan-related genes have been identified in eukaryotes ranging from the yeast to human. However, there is limited information available on the longevity genes that are essential for cell proliferation. Here, we investigated whether the essential genes encoding DNA-binding transcription factors modulated the replicative lifespan of Saccharomyces cerevisiae. Heterozygous diploid knockout strains for FHL1, RAP1, REB1, and MCM1 genes showed significantly short lifespan. {sup 1}H-nuclear magnetic resonance analysis indicated a characteristic metabolic profile in the Δfhl1/FHL1 mutant. These results strongly suggest that FHL1 regulates the transcription of lifespan related metabolic genes. Thus, heterozygous knockout strains could be the potential materials for discovering further novel lifespan genes. - Highlights: • Involvement of yeast TF genes essential for cell growth in lifespan was evaluated. • The essential TF genes, FHL1, RAP1, REB1, and MCM1, regulate replicative lifespan. • Heterozygous deletion of FHL1 changes cellular metabolism related to lifespan.

  12. EEG correlates of visual short-term memory in older age vary with adult lifespan cognitive development.

    Science.gov (United States)

    Wiegand, Iris; Lauritzen, Martin J; Osler, Merete; Mortensen, Erik Lykke; Rostrup, Egill; Rask, Lene; Richard, Nelly; Horwitz, Anna; Benedek, Krisztina; Vangkilde, Signe; Petersen, Anders

    2018-02-01

    Visual short-term memory (vSTM) is a cognitive resource that declines with age. This study investigated whether electroencephalography (EEG) correlates of vSTM vary with cognitive development over individuals' lifespan. We measured vSTM performance and EEG in a lateralized whole-report task in a healthy birth cohort, whose cognitive function (intelligence quotient) was assessed in youth and late-middle age. Higher vSTM capacity (K; measured by Bundesen's theory of visual attention) was associated with higher amplitudes of the contralateral delay activity (CDA) and the central positivity (CP). In addition, rightward hemifield asymmetry of vSTM (K λ ) was associated with lower CDA amplitudes. Furthermore, more severe cognitive decline from young adulthood to late-middle age predicted higher CDA amplitudes, and the relationship between K and the CDA was less reliable in individuals who show higher levels of cognitive decline compared to individuals with preserved abilities. By contrast, there was no significant effect of lifespan cognitive changes on the CP or the relationship between behavioral measures of vSTM and the CP. Neither the CDA, nor the CP, nor the relationships between K or K λ and the event-related potentials were predicted by individuals' current cognitive status. Together, our findings indicate complex age-related changes in processes underlying behavioral and EEG measures of vSTM and suggest that the K-CDA relationship might be a marker of cognitive lifespan trajectories. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The possibility of previous epidemiological data to serve as baseline for future national oral health surveys--a study in Vietnam.

    NARCIS (Netherlands)

    Palenstein Helderman, W.H. van; Truin, G.J.; Can, N.; Khanh, N.D.

    2001-01-01

    AIM: The purpose of this paper is to review the most recent epidemiological data (1985-2000) on dental caries and periodontal diseases in Vietnam in an attempt to obtain a 'baseline' for future national oral health surveys. METHODS: Studies on periodontal diseases and caries were included when CPITN

  14. Alfalfa (Medicago sativa L.) is tolerant to higher levels of salinity than previous guidelines indicated: Implications of field and greenhouse studies

    Science.gov (United States)

    Putnam, Daniel H.; Benes, Sharon; Galdi, Giuliano; Hutmacher, Bob; Grattan, Steve

    2017-04-01

    Alfalfa (Medicago sativa L.) is the most widely grown leguminous forage crop in North America and is valued for high productivity, quality, economic value, and for dairy productivity. Alfalfa has historically been classified as moderately sensitive to saline conditions, with yield declines predicted at >2 dS/m in the saturated soil paste extract. However, greenhouse, sand tank, and field studies over the past five years have confirmed that alfalfa can be grown with limited negative effects at much higher salinity levels. A broad collection of alfalfa varieties has exhibited a range of resistance at irrigation water salinities >5 dS/m ECw in greenhouse trials, with significant variation due to variety. USDA-ARS sand tank studies indicated similar or greater tolerances closer to 8 dS/m in the soil water, in addition to confirmation of significant varietal differences. A three-year field study on clay loam soil with applications of 5-7 dS/m ECw irrigation water indicated normal yields and excellent stand survivability. A second field study in the same soil type with levels from 8-10 dS/m ECw showed yield reductions of 10-15% but economic yields were still achieved at those levels. Field and greenhouse studies were conducted with mixed salt saline sodic waters typical of the San Joaquin Valley of California. Field evaluation of variety performance was subject to greater variation due to secondary salinity-soil interactions including water infiltration and crusting problems, not only salinity per-se. Thus, adequate irrigation water availability to the crop may be as important as salinity in impacting yields under field conditions. Once established, the deep-rooted characteristics of alfalfa enable utilization of deeper subsurface moisture, even at moderate to high salinity levels, as documented by USDA lysimeter studies. Significant advantages to salinity-tolerant varieties have been observed. It will be important to consider specific management factors which may enable

  15. Linguistic Processing of Accented Speech Across the Lifespan

    Directory of Open Access Journals (Sweden)

    Alejandrina eCristia

    2012-11-01

    Full Text Available In most of the world, people have regular exposure to multiple accents. Therefore, learning to quickly process accented speech is a prerequisite to successful communication. In this paper, we examine work on the perception of accented speech across the lifespan, from early infancy to late adulthood. Unfamiliar accents initially impair linguistic processing by infants, children, younger adults, and older adults, but listeners of all ages come to adapt to accented speech. Emergent research also goes beyond these perceptual abilities, by assessing links with production and the relative contributions of linguistic knowledge and general cognitive skills. We conclude by underlining points of convergence across ages, and the gaps left to face in future work.

  16. Social consequences of Garona NPP lifespan extension issue

    International Nuclear Information System (INIS)

    Millan, Miguel A.

    2010-01-01

    On June 3, Spanish Nuclear Safety regulatory body, CSN, declared unanimously 'Santa Maria de Garona' nuclear power plant, a BWR reactor, as entirely compliant with all the safety requirements to extend its operation for the 2009-2019 period. Nevertheless, on July 3, Spanish government allowed Garona Nuclear Power Plant for 4 years more, two years more than the design life, 40 years. From June 3 until July 3 there were several public demonstrations in support of Garona continuity. Every day a lot of debates, interviews and articles, regarding Garona issue took place in TV channels, radio stations and newspapers. This paper shows all the activities that the owner, workers, unions and non-profit associations carried out to show the good state of the facility, also includes a discussion regarding the data showed by the government to shut-down the facility eight years before lifespan. And finally, what to do in those cases is discussed in this paper. (authors)

  17. Effect of benzalkonium chloride?free travoprost on intraocular pressure and ocular surface symptoms in patients with glaucoma previously on latanoprost: an open-label study

    OpenAIRE

    Lopes, Joao F.; Hubatsch, Douglas A.; Amaris, Patricia

    2015-01-01

    Background Prostaglandin analogs reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension; however, these medications may affect the ocular surface and elicit ocular discomfort when preserved with benzalkonium chloride (BAK). Methods This was an open-label, single-arm study conducted in Latin America from February 2012 to May 2013. Patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost 0.005?% were transitioned to recei...

  18. A Lifespan Study of Cooperative Education Graduates: Quantitative Aspects.

    Science.gov (United States)

    Linn, Patricia L.; Ferguson, Jane

    1999-01-01

    Career histories of 73 graduates of Antioch College's liberal arts co-op program, 1946-55, showed an average of 6.5 jobs before retirement and high rates of self-employment. Those with low performance in cooperative education were much more likely to have earned graduate degrees. Self-employed graduates had more varied jobs and retired later. (SK)

  19. Low-level 239PuO2 lifespan studies

    International Nuclear Information System (INIS)

    Sanders, C.L.

    1985-01-01

    This project will produce data to generate a dose-response curve (and to evaluate other statistical methods that also incorporate survival time) for lung-tumor incidence in Wistar rats following inhalation of 239 PuO 2 at levels producing lifetime radiation doses to the lung of 2000 rad. The lung clearance of 239 Pu is best represented by a two-exponential equation, with 78% of the initial alveolar depositions (IAD) cleared with a half-time of 19 days and 22% cleared with a half-time of 180 days. A total of 593 of 2134 exposed and 242 of 1058 sham-exposed rats have died. Among the dead rats, the percent with primary lung tumors was 71% for the 150-nCi group, 70% for the 82-nCi group, and 23% for the 32-nCi group. No lung tumors have been found in controls, and only three have been found at an IAD of < 7.5 nCi. 1 figure, 3 tables

  20. Down syndrome: Cognitive and behavioral functioning across the lifespan.

    Science.gov (United States)

    Grieco, Julie; Pulsifer, Margaret; Seligsohn, Karen; Skotko, Brian; Schwartz, Alison

    2015-06-01

    Individuals with Down syndrome (DS) commonly possess unique neurocognitive and neurobehavioral profiles that emerge within specific developmental periods. These profiles are distinct relative to others with similar intellectual disability (ID) and reflect underlying neuroanatomic findings, providing support for a distinctive phenotypic profile. This review updates what is known about the cognitive and behavioral phenotypes associated with DS across the lifespan. In early childhood, mild deviations from neurotypically developing trajectories emerge. By school-age, delays become pronounced. Nonverbal skills remain on trajectory for mental age, whereas verbal deficits emerge and persist. Nonverbal learning and memory are strengths relative to verbal skills. Expressive language is delayed relative to comprehension. Aspects of language skills continue to develop throughout adolescence, although language skills remain compromised in adulthood. Deficits in attention/executive functions are present in childhood and become more pronounced with age. Characteristic features associated with DS (cheerful, social nature) are personality assets. Children are at a lower risk for psychopathology compared to other children with ID; families report lower levels of stress and a more positive outlook. In youth, externalizing behaviors may be problematic, whereas a shift toward internalizing behaviors emerges with maturity. Changes in emotional/behavioral functioning in adulthood are typically associated with neurodegeneration and individuals with DS are higher risk for dementia of the Alzheimer's type. Individuals with DS possess many unique strengths and weaknesses that should be appreciated as they develop across the lifespan. Awareness of this profile by professionals and caregivers can promote early detection and support cognitive and behavioral development. © 2015 Wiley Periodicals, Inc.

  1. Effect of benzalkonium chloride-free travoprost on intraocular pressure and ocular surface symptoms in patients with glaucoma previously on latanoprost: an open-label study.

    Science.gov (United States)

    Lopes, Joao F; Hubatsch, Douglas A; Amaris, Patricia

    2015-11-12

    Prostaglandin analogs reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension; however, these medications may affect the ocular surface and elicit ocular discomfort when preserved with benzalkonium chloride (BAK). This was an open-label, single-arm study conducted in Latin America from February 2012 to May 2013. Patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost 0.005 % were transitioned to receive once-daily BAK-free travoprost 0.004 % containing polyquaternium-1 (Travatan® preserved with POLYQUAD® [PQ], Alcon Laboratories, Inc; Fort Worth, TX) for 12 weeks. Mean change in IOP from baseline (primary efficacy endpoint) and the percentage of patients who achieved a target IOP of ≤18 mmHg were evaluated at all on-therapy visits. Ocular hyperemia, patient preference, and self-projected adherence were assessed at week 12. Adverse events (AEs) were monitored throughout the study. All enrolled patients were included in the analysis (n = 191); the majority of patients (90.6 %, n = 173/191) completed the study. Mean (SD) patient age was 67.5 (11.3) years, and mean baseline IOP was 14.8 mmHg. Mean IOP was reduced by 0.94 mmHg at week 6 and by 1.09 mmHg at week 12 (P glaucoma or ocular hypertension who were intolerant of latanoprost. BAK-free travoprost 0.004 % is a viable alternative for patients who require switching their IOP-lowering medications because of tolerability issues. ClinicalTrials.gov identifier, NCT01510145.

  2. Does hyperbaric oxygen treatment have the potential to increase salivary flow rate and reduce xerostomia in previously irradiated head and neck cancer patients? A pilot study

    DEFF Research Database (Denmark)

    Forner, Lone; Hansen, Ole Hyldegaard; von Brockdorff, Annet Schack

    2011-01-01

    in irradiated head and neck cancer patients. Eighty patients eligible for HBO treatment on the indication of prevention/treatment of osteoradionecrosis or soft tissue radiation injury were consecutively sampled, of whom 45 had hyposalivation (i.e. unstimulated whole saliva (UWS) flow rate......Irradiated head and neck cancer survivors treated in the Hyperbaric Oxygen (HBO) Unit, Copenhagen University Hospital, spontaneously reported improvement of radiation-induced dry mouth feeling. The aim of this pilot study was to evaluate salivary flow rate and xerostomia before and after HBO...

  3. Previous study for the setting up and optimization of detection of ZnS(Ag) scintillation applied to the measure of alpha radioactivity index

    International Nuclear Information System (INIS)

    Pujol, L.; Suarez-Navarro, J.A.; Montero, M.

    1998-01-01

    The determination of radiological water quality is useful for a wide range of environmental studies. In these cases, the gross alpha activity is one of the parameters to determine. This parameter permits to decide if further radiological analyses are necessary in order to identify and quantify the presence of alpha emitters in water. The usual method for monitoring the gross alpha activity includes sample evaporation to dryness on a disk and counting using ZnS(Ag) scintillation detector. Detector electronics is provided with two components which are adjustable by the user the high-voltage applied to the photomultiplier tubes and the low level discriminator that is used to eliminate the electronic noise. The high-voltage and low level discriminator optimization are convenient in order to reach the best counting conditions. This paper is a preliminary study of the procedure followed for the setting up and optimization of the detector electronics in the laboratories of CEDEX for the measurement of gross alpha activity. (Author)

  4. [Mutations of resistance of HIV-1 in previously untreated patients at penitentiary centers of the Autonomous Community of Valencia, Spain. REPRICOVA study].

    Science.gov (United States)

    García-Guerrero, Julio; Herrero, Agustín; Vera, Enrique; Almenara, José M; Araújo, Rosa; Saurí, Vicente V; Castellano, Juan C; Fernández-Clemente, Luis; Bedia, Miguel; Llorente, María I; González-Morán, Francisco

    2002-03-02

    Our purpose was to determine the prevalence of mutations of resistance to nucleoside inhibitors of reverse transcriptase (NIRT) and protease inhibitors (PI) in the HIV-1 genotype of naïve infected subjects in the prisons of the Autonomous Community of Valencia, Spain. Multicentric, descriptive, cross-sectional study of prevalence including a systematic stratified and randomised sampling by centres. Demographic, clinical, virological and immunological data were collected. The HIV gene of protease and transcriptase was studied in peripheral blood plasma samples by means of double PCR amplification and subsequent automatic sequence. Reference: wild strain HXB2. Plasma was obtained from 133 individuals (119 men and 14 women). 117 samples were selected and the rest did not have enough copies for transcription. With regard to NIRT, 7 samples (5.2% of total) showed some mutation of resistance: M41L, D67N, L210W and K219Q, all them secondary to and associated with resistance to zidovudine, abacavir as well as group B multinucleoside-resistance. With regard to PI, only one sample showed a primary mutation, M46I, which was associated with resistance to indinavir. Moreover, a further 41 samples were found to express some secondary mutation. In our series, there was a low number of primary mutations of resistance. These results allow us to exclude the systematic use of resistance tests before an initiation antiretroviral therapy.

  5. Why do lifespan variability trends for the young and old diverge? A perturbation analysis

    Directory of Open Access Journals (Sweden)

    Michal Engelman

    2014-05-01

    Full Text Available Background: Variation in lifespan has followed strikingly different trends for the young and old: while overall lifespan variability has decreased as life expectancy at birth has risen, the variability conditional on survival to older ages has increased. These diverging trends reflect changes in the underlying demographic parameters determining age-specific mortality. Objective: We ask why the variation in the adult ages at death has followed a different trend than the variation at younger ages, and aim to explain the diverging patterns in terms of historical changes in the age schedule of mortality. Methods: Using simulations, we show that the empirical trends in lifespan variation are well characterized using the Siler model, which describes the mortality hazard across the full lifespan using functions representing early-life, later-life, and background mortality. We then obtain maximum likelihood estimates of the Siler parameters over time. Finally, we express lifespan variation in terms of a Markov chain model, and apply matrix calculus perturbation analysis to compute the sensitivity of age-specific lifespan variance trends to the changing Siler model parameters. Results: Our analysis produces a detailed quantification of the impact of changing demographic parameters on the pattern of lifespan variability at all ages, highlighting the impact of declining childhood mortality on the reduction of lifespan variability and the impact of improved survival in adulthood on the rising variability of lifespans at older ages. Conclusions: These findings provide insight into the dynamic relationship between the age pattern of survival improvements and time trends in lifespan variability.

  6. In Vitro Fertilization Outcomes After Placement of Essure Microinserts in Patients With Hydrosalpinges Who Previously Failed In Vitro Fertilization Treatment: A Multicenter Study.

    Science.gov (United States)

    Cohen, Shlomo B; Bouaziz, Jerome; Schiff, Eyal; Simon, Alexander; Nadjary, Michel; Goldenberg, Mordechai; Orvieto, Raoul; Revel, Ariel

    2016-01-01

    To investigate whether hysteroscopic proximal tubal occlusion with Essure microinserts (Conceptus Inc.; Bayer, AG, North Rhine-Westphalia, Germany) can improve pregnancy rates in patients with hydrosalpinges who had failed in vitro fertilization (IVF) treatment. A prospective cohort study. University-affiliated tertiary centers. Twenty-four consecutive women with hydrosalpinges who had failed IVF treatment were included. Hysteroscopic placement of Essure microinserts for hydrosalpinx blockage followed by IVF treatment. Ongoing pregnancy and live birth rates were recorded. Of the 24 patients undergoing a total of 42 IVF cycles after Essure insertion, 18 (75% of patients and 42.8% of IVF cycle attempts) conceived and 16 delivered live births (66.6% of patients and 38.1% of IVF cycle attempts). Hysteroscopic proximal occlusion of hydrosalpinges with Essure microinserts is a valuable alternative to laparoscopic salpingectomy, resulting in reasonable pregnancy rates. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

  7. Kansas City Cardiomyopathy Questionnaire Score Is Associated With Incident Heart Failure Hospitalization in Patients With Chronic Kidney Disease Without Previously Diagnosed Heart Failure: Chronic Renal Insufficiency Cohort Study.

    Science.gov (United States)

    Mishra, Rakesh K; Yang, Wei; Roy, Jason; Anderson, Amanda H; Bansal, Nisha; Chen, Jing; DeFilippi, Christopher; Delafontaine, Patrice; Feldman, Harold I; Kallem, Radhakrishna; Kusek, John W; Lora, Claudia M; Rosas, Sylvia E; Go, Alan S; Shlipak, Michael G

    2015-07-01

    Chronic kidney disease is a risk factor for heart failure (HF). Patients with chronic kidney disease without diagnosed HF have an increased burden of symptoms characteristic of HF. It is not known whether these symptoms are associated with occurrence of new onset HF. We studied the association of a modified Kansas City Cardiomyopathy Questionnaire with newly identified cases of hospitalized HF among 3093 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study who did not report HF at baseline. The annually updated Kansas City Cardiomyopathy Questionnaire score was categorized into quartiles (Q1-4) with the lower scores representing the worse symptoms. Multivariable-adjusted repeated measure logistic regression models were adjusted for demographic characteristics, clinical risk factors for HF, N-terminal probrain natriuretic peptide level and left ventricular hypertrophy, left ventricular systolic and diastolic dysfunction. Over a mean (±SD) follow-up period of 4.3±1.6 years, there were 211 new cases of HF hospitalizations. The risk of HF hospitalization increased with increasing symptom quartiles; 2.62, 1.85, 1.14, and 0.74 events per 100 person-years, respectively. The median number of annual Kansas City Cardiomyopathy Questionnaire assessments per participant was 5 (interquartile range, 3-6). The annually updated Kansas City Cardiomyopathy Questionnaire score was independently associated with higher risk of incident HF hospitalization in multivariable-adjusted models (odds ratio, 3.30 [1.66-6.52]; P=0.001 for Q1 compared with Q4). Symptoms characteristic of HF are common in patients with chronic kidney disease and are associated with higher short-term risk for new hospitalization for HF, independent of level of kidney function, and other known HF risk factors. © 2015 American Heart Association, Inc.

  8. Influence of phytoecdysteroids and plants steroidal glycosides on the lifespan and stress resistance of drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Mikhail Vyacheslavovich Shaposhnikov

    2014-12-01

    Full Text Available Background. Elucidation of the molecular mechanisms of effects of the active substances of plant adaptogens is a topical area of researches. Materials and methods. We studied the effect of herbal substances containing phytoecdysteroids (20-hydroxyecdysone and inokosterone of Serratula coronata L. or steroidal glycosides (dioscin and protodioscine of Trigonella foenum-graecum L. on the expression level of stress response genes (genes of heat shock proteins, DNA repair, antioxidant defense and apoptosis, stressresistanse (paraquat, starvation, hyperthermia and lifespan of Drosophila melanogaster. Results. The studied herbal substances upregulated genes of antioxidant defense mechanisms (Sod1, but downregulated the DNA repair (XPF and Rad51 and apoptosis (Hid genes. At the same time herbal substances induced weak adaptogenic and antiaging effects. Conclusion. Our results demonstrate that the herbal substances containing phytoecdysteroids and steroidal glycosides change the expression level of stress-response genes and activate mechanisms of hormesis.

  9. The Developmental Lexicon Project: A behavioral database to investigate visual word recognition across the lifespan.

    Science.gov (United States)

    Schröter, Pauline; Schroeder, Sascha

    2017-12-01

    With the Developmental Lexicon Project (DeveL), we present a large-scale study that was conducted to collect data on visual word recognition in German across the lifespan. A total of 800 children from Grades 1 to 6, as well as two groups of younger and older adults, participated in the study and completed a lexical decision and a naming task. We provide a database for 1,152 German words, comprising behavioral data from seven different stages of reading development, along with sublexical and lexical characteristics for all stimuli. The present article describes our motivation for this project, explains the methods we used to collect the data, and reports analyses on the reliability of our results. In addition, we explored developmental changes in three marker effects in psycholinguistic research: word length, word frequency, and orthographic similarity. The database is available online.

  10. Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension

    NARCIS (Netherlands)

    Doroszuk, A.; Jonker, M.J.; Pul, N.; Breit, T.M.; Zwaan, B.J.

    2012-01-01

    Background While studying long-lived mutants has advanced our understanding of the processes involved in ageing, the mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown. Here, we characterise genome-wide expression patterns of a long-lived, natural variant of

  11. Time Trends over 16 Years in Incidence-Rates of Autism Spectrum Disorders across the Lifespan Based on Nationwide Danish Register Data

    Science.gov (United States)

    Jensen, Christina Mohr; Steinhausen, Hans-Christoph; Lauritsen, Marlene Briciet

    2014-01-01

    This study investigated time trends and associated factors of incidence rates of diagnosed autism spectrum disorders (ASD) across the lifespan from 1995 to 2010, using data from the Danish Psychiatric Central Research Registry. First time diagnosis of childhood autism, atypical autism, Asperger's syndrome, or pervasive developmental…

  12. RapidArc, intensity modulated photon and proton techniques for recurrent prostate cancer in previously irradiated patients: a treatment planning comparison study

    International Nuclear Information System (INIS)

    Weber, Damien C; Miralbell, Raymond; Wang, Hui; Cozzi, Luca; Dipasquale, Giovanna; Khan, Haleem G; Ratib, Osman; Rouzaud, Michel; Vees, Hansjoerg; Zaidi, Habib

    2009-01-01

    A study was performed comparing volumetric modulated arcs (RA) and intensity modulation (with photons, IMRT, or protons, IMPT) radiation therapy (RT) for patients with recurrent prostate cancer after RT. Plans for RA, IMRT and IMPT were optimized for 7 patients. Prescribed dose was 56 Gy in 14 fractions. The recurrent gross tumor volume (GTV) was defined on 18 F-fluorocholine PET/CT scans. Plans aimed to cover at least 95% of the planning target volume with a dose > 50.4 Gy. A maximum dose (D Max ) of 61.6 Gy was allowed to 5% of the GTV. For the urethra, D Max was constrained to 37 Gy. Rectal D Median was < 17 Gy. Results were analyzed using Dose-Volume Histogram and conformity index (CI 90 ) parameters. Tumor coverage (GTV and PTV) was improved with RA (V 95% 92.6 ± 7.9 and 83.7 ± 3.3%), when compared to IMRT (V 95% 88.6 ± 10.8 and 77.2 ± 2.2%). The corresponding values for IMPT were intermediate for the GTV (V 95% 88.9 ± 10.5%) and better for the PTV (V 95% 85.6 ± 5.0%). The percentages of rectal and urethral volumes receiving intermediate doses (35 Gy) were significantly decreased with RA (5.1 ± 3.0 and 38.0 ± 25.3%) and IMPT (3.9 ± 2.7 and 25.1 ± 21.1%), when compared to IMRT (9.8 ± 5.3 and 60.7 ± 41.7%). CI 90 was 1.3 ± 0.1 for photons and 1.6 ± 0.2 for protons. Integral Dose was 1.1 ± 0.5 Gy*cm 3 *10 5 for IMPT and about a factor three higher for all photon's techniques. RA and IMPT showed improvements in conformal avoidance relative to fixed beam IMRT for 7 patients with recurrent prostate cancer. IMPT showed further sparing of organs at risk

  13. Phase 2 study of tabalumab, a human anti-B-cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma.

    Science.gov (United States)

    Raje, Noopur S; Moreau, Philippe; Terpos, Evangelos; Benboubker, Lotfi; Grząśko, Norbert; Holstein, Sarah A; Oriol, Albert; Huang, Shang-Yi; Beksac, Meral; Kuliczkowski, Kazimierz; Tai, Datchen F; Wooldridge, James E; Conti, Ilaria; Kaiser, Christopher J; Nguyen, Tuan S; Cronier, Damien M; Palumbo, Antonio

    2017-03-01

    In this double-blind, Phase 2 study, 220 patients with relapsed/refractory multiple myeloma were randomly assigned 1:1:1 to receive placebo (N = 72), tabalumab 100 mg (N = 74), or tabalumab 300 mg (N = 74), each in combination with dexamethasone 20 mg and subcutaneous bortezomib 1·3 mg/m 2 on a 21-day cycle. No significant intergroup differences were observed among primary (median progression-free survival [mPFS]) or secondary efficacy outcomes. The mPFS was 6·6, 7·5 and 7·6 months for the tabalumab 100, 300 mg and placebo groups, respectively (tabalumab 100 mg vs. placebo Hazard ratio (HR) [95% confidence interval (CI)] = 1·13 [0·80-1·59], P = 0·480; tabalumab 300 mg vs. placebo HR [95% CI] = 1·03 [0·72-1·45], P = 0·884). The most commonly-reported treatment-emergent adverse events were thrombocytopenia (37%), fatigue (37%), diarrhoea (35%) and constipation (32%). Across treatments, patients with low baseline BAFF (also termed TNFSF13B) expression (n = 162) had significantly longer mPFS than those with high BAFF expression (n = 55), using the 75th percentile cut-off point (mPFS [95% CI] = 8·3 [7·0-9·3] months vs. 5·8 [3·7-6·6] months; HR [95% CI] = 1·59 [1·11-2·29], P = 0·015). Although generally well tolerated, PFS was not improved during treatment with tabalumab compared to placebo. A higher dose of 300 mg tabalumab did not improve efficacy compared to the 100 mg dose. Nonetheless, BAFF appears to have some prognostic value in patients with multiple myeloma. © 2016 John Wiley & Sons Ltd.

  14. Previously unknown species of Aspergillus.

    Science.gov (United States)

    Gautier, M; Normand, A-C; Ranque, S

    2016-08-01

    The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based identification of Aspergillus remains limited to the section or species-complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care. Copyright © 2016 European Society of Clinical Microbiology and

  15. Effects of transgenic methionine sulfoxide reductase A (MsrA expression on lifespan and age-dependent changes in metabolic function in mice

    Directory of Open Access Journals (Sweden)

    Adam B. Salmon

    2016-12-01

    Full Text Available Mechanisms that preserve and maintain the cellular proteome are associated with long life and healthy aging. Oxidative damage is a significant contributor to perturbation of proteostasis and is dealt with by the cell through regulation of antioxidants, protein degradation, and repair of oxidized amino acids. Methionine sulfoxide reductase A (MsrA repairs oxidation of free- and protein-bound methionine residues through enzymatic reduction and is found in both the cytosol and the mitochondria. Previous studies in Drosophila have shown that increasing expression of MsrA can extend longevity. Here we test the effects of increasing MsrA on longevity and healthy aging in two transgenic mouse models. We show that elevated expression of MsrA targeted specifically to the cytosol reduces the rate of age-related death in female mice when assessed by Gompertz analysis. However, neither cytosolic nor mitochondrial MsrA overexpression extends lifespan when measured by log-rank analysis. In mice with MsrA overexpression targeted to the mitochondria, we see evidence for improved insulin sensitivity in aged female mice. With these and our previous data, we conclude that the increasing MsrA expression in mice has differential effects on aging and healthy aging that are dependent on the target of its subcellular localization.

  16. Changes in Standing and Walking Performance Under Dual-Task Conditions Across the Lifespan.

    Science.gov (United States)

    Ruffieux, Jan; Keller, Martin; Lauber, Benedikt; Taube, Wolfgang

    2015-12-01

    Simultaneous performance of a postural and a concurrent task is rather unproblematic as long as the postural task is executed in an automatic way. However, in situations where postural control requires more central processing, cognitive resources may be exceeded by the addition of an attentionally demanding task. This may lead to interference between the two tasks, manifested in a decreased performance in one or both tasks (dual-task costs). Owing to changes in attentional demands of postural tasks as well as processing capacities across the lifespan, it might be assumed that dual-task costs are particularly pronounced in children and older adults probably leading to a U-shaped pattern for dual-task costs as a function of age. However, these changes in the ability of dual-tasking posture from childhood to old age have not yet been systematically reviewed. Therefore, Web of Science and PubMed databases were searched for studies comparing dual-task performance with one task being standing or walking in healthy groups of young adults and either children or older adults. Seventy-nine studies met inclusion criteria. For older adults, the expected increase in dual-task costs could be confirmed. In contrast, in children there was only feeble evidence for a trend towards enlarged dual-task costs. More good-quality studies comparing dual-task ability in children, young, and, ideally, also older adults within the same paradigm are needed to draw unambiguous conclusions about lifespan development of dual-task performance in postural tasks. There is evidence that, in older adults, dual-task performance can be improved by training. For the other age groups, these effects have yet to be investigated.

  17. P300 development across the lifespan: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Rik van Dinteren

    Full Text Available BACKGROUND: The P300 component of the event-related potential is a large positive waveform that can be extracted from the ongoing electroencephalogram using a two-stimuli oddball paradigm, and has been associated with cognitive information processing (e.g. memory, attention, executive function. This paper reviews the development of the auditory P300 across the lifespan. METHODOLOGY/PRINCIPAL FINDINGS: A systematic review and meta-analysis on the P300 was performed including 75 studies (n = 2,811. Scopus was searched for studies using healthy subjects and that reported means of P300 latency and amplitude measured at Pz and mean age. These findings were validated in an independent, existing cross-sectional dataset including 1,572 participants from ages 6-87. Curve-fitting procedures were applied to obtain a model of P300 development across the lifespan. In both studies logarithmic Gaussian models fitted the latency and amplitude data best. The P300 latency and amplitude follow a maturational path from childhood to adolescence, resulting in a period that marks a plateau, after which degenerative effects begin. We were able to determine ages that mark a maximum (in P300 amplitude or trough (in P300 latency segregating maturational from degenerative stages. We found these points of deflection occurred at different ages. CONCLUSIONS/SIGNIFICANCE: It is hypothesized that latency and amplitude index different aspects of brain maturation. The P300 latency possibly indexes neural speed or brain efficiency. The P300 amplitude might index neural power or cognitive resources, which increase with maturation.

  18. Review of previous geophysical and geological studies

    Digital Repository Service at National Institute of Oceanography (India)

    Levchenko, O.V.; Neprochnov, Y.P; Rao, D.G; Subrahmanyam, C.; Murthy, K.S

    stream_size 5 stream_content_type text/plain stream_name Mem_Geol_Soc_India_39_5.pdf.txt stream_source_info Mem_Geol_Soc_India_39_5.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 ...

  19. Ovarian Reserve Assessment in Users of Oral Contraception Seeking Fertility Advice on their Reproductive Lifespan

    DEFF Research Database (Denmark)

    Petersen, K. Birch; Hvidman, H. W.; Forman, J. L.

    2016-01-01

    aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women...... follicles sized 5-7 mm (P groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, REASON FOR CAUTION......STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti...

  20. Ovarian reserve assessment in users of oral contraception seeking fertility advice on their reproductive lifespan

    DEFF Research Database (Denmark)

    Birch Petersen, K; Hvidman, H W; Forman, J L

    2015-01-01

    aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women...... follicles sized 5-7 mm (P groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, REASON FOR CAUTION......STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti...

  1. Intermittent food restriction initiated late in life prolongs lifespan and retards the onset of age-related markers in the annual fish Nothobranchius guentheri.

    Science.gov (United States)

    Wang, Xia; Du, Xiaoyuan; Zhou, Yang; Wang, Su; Su, Feng; Zhang, Shicui

    2017-06-01

    Two of the most studied and widely accepted conjectures on possible aging mechanisms are the oxidative stress hypothesis and the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway. Intermittent fasting (IF) is known to modulate aging and to prolong lifespan in a variety of organisms, but the mechanisms are still under debate. In this study, we first demonstrated that late-onset two consecutive days a week fasting, a form of IF, termed intermittent food restriction (IFR), exhibited a time-dependent effect, and long-term late-onset IFR extended the mean lifespan and maximum lifespan by approximately 3.5 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We also showed that IFR reduced the accumulation of lipofuscin in the gills and the protein oxidation and lipid peroxidation levels in the muscles. Moreover, IFR was able to enhance the activities of antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase in the fish. Finally, IFR was also able to decelerate the decrease of SirT1 and Foxo3A, but accelerate the decrease of IGF-1. Collectively, our findings suggest that late-onset IFR can retard the onset of age-related markers, and prolong the lifespan of the aging fish, via a synergistic action of an anti-oxidant system and the IIS pathway. It also proposes that the combined assessment of anti-oxidant system and IIS pathway will contribute to providing a more comprehensive view of anti-aging process.

  2. Emodin extends lifespan of Caenorhabditis elegans through insulin/IGF-1 signaling pathway depending on DAF-16 and SIR-2.1.

    Science.gov (United States)

    Zhao, Xuan; Lu, Lulu; Qi, Yonghao; Li, Miao; Zhou, Lijun

    2017-10-01

    The naturally occurring anthraquinone emodin has been serving primarily as an anti-bacterial and anti-inflammatory agent. However, little is known about its potential on anti-aging. This investigation examined the effect of emodin on lifespan and focused on its physiological molecular mechanisms in vivo. Using Caenorhabditis elegans (C. elegans) as an animal model, we found emodin could extend lifespan of worms and improve their antioxidant capacity. Our mechanistic studies revealed that emodin might function via insulin/IGF-1 signaling (IIS) pathway involving, specifically the core transcription factor DAF-16. Quantitative RT-PCR results illustrated that emodin up-regulated transcription of DAF-16 target genes which express antioxidants to promote antioxidant capacity and lifespan of worms. In addition, attenuated effect in sir-2.1 mutants suggests that emodin likely functioned in a SIR-2.1-dependent manner. Our study uncovers a novel role of emodin in prolonging lifespan and supports the understanding of emodin being a beneficial dietary supplement.

  3. Developmental changes in GABAergic mechanisms in human visual cortex across the lifespan

    Directory of Open Access Journals (Sweden)

    Joshua G A Pinto

    2010-06-01

    Full Text Available Functional maturation of visual cortex is linked with dynamic changes in synaptic expression of GABAergic mechanisms. These include setting the excitation-inhibition balance required for experience-dependent plasticity, as well as, intracortical inhibition underlying development and aging of receptive field properties. Animal studies have shown developmental regulation of GABAergic mechanisms in visual cortex. In this study, we show for the first time how these mechanisms develop in the human visual cortex across the lifespan. We used Western blot analysis of postmortem tissue from human primary visual cortex (n=30, range: 20 days to 80 years to quantify expression of 8 pre- and post-synaptic GABAergic markers. We quantified the inhibitory modulating cannabinoid receptor (CB1, GABA vesicular transporter (VGAT, GABA synthesizing enzymes (GAD65/GAD67, GABAA receptor anchoring protein (Gephyrin, and GABAA receptor subunits (GABAA∝1, GABAA∝2, GABAA∝3. We found a complex pattern of changes, many of which were prolonged and continued well into into the teen, young adult, and even older adult years. These included a monotonic increase or decrease (GABAA∝1, GABAA∝2, a biphasic increase then decrease (GAD65, Gephyrin, or multiple increases and decreases (VGAT, CB1 across the lifespan. Comparing the balances between the pre- and post-synaptic markers we found 3 main transitions (early childhood, early teen years, aging when there were rapid switches in the composition of the GABAergic signaling system, indicating that functioning of the GABAergic system must change as the visual cortex develops and ages. Furthermore, these results provide key information for translating therapies developed in animal models into effective treatments for amblyopia in humans.

  4. Eggs hatching and oncomiracidia lifespan of Dawestrema cycloancistrium, a monogenean parasitic on Arapaima gigas.

    Science.gov (United States)

    Maciel, Patricia Oliveira; Muniz, Celli Rodrigues; Alves, Rosiana Rodrigues

    2017-11-30

    Within the production chain of the Arapaima gigas (pirarucu), sanitary issues are still faced at the fingerling phase regarding infestations by the monogenean Dawestrema cycloancistrium. The present study had the objectives of describing the morphology and development phases of this parasite's eggs and oncomiracidia and determining the hatching time and lifespan of the oncomiracidia at different temperatures. D. cycloancistrium eggs were oval and elongated and had a single long appendage at one pole. The egg development was divided into four phases: embryonated egg, developing egg, larva appearance and ecloded egg. They were found in four forms: isolated in gill filaments; grouped in clusters that were anchored in a gill filament; grouped in clusters and entangled in part of a dead adult monogenean; and grouped in clusters in the environment, fixed to a substrate. Eclosion occurred after 72-96h, with faster development at 29°C and 32°C than at 24°C. The morphology of the oncomiracidia were rounded and elongated. They had two pairs of pigmented eye-spots as well as two ciliated areas located on each lateral part of the body and another on the anterior part of the body. The lifespan of the D. cycloancistrium oncomiracidia were 50 and 58h at 24°C and 27°C, respectively. Larvae were found in the mucus, indicating that the oncomiracidia penetrated the host integument. Understanding reproductive aspects of the D. cycloancistrium monogenean is important for developing specific prophylactic management strategies in aquaculture and providing valuable data for further studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. RETENTION OF HIGH TACTILE ACUITY THROUGHOUT THE LIFESPAN IN BLINDNESS

    OpenAIRE

    Legge, Gordon E.; Madison, Cindee; Vaughn, Brenna N.; Cheong, Allen M.Y.; Miller, Joseph C.

    2008-01-01

    Previous studies of tactile acuity on the fingertip using passive touch have demonstrated an age-related decline in spatial resolution for both sighted and blind subjects. We have re-examined this age dependence with two newly designed tactile-acuity charts requiring active exploration of the test symbols. One chart used dot patterns similar to Braille and the other used embossed Landolt rings. Groups of blind Braille readers and sighted subjects, ranging in age from 12 to 85 years, were test...

  6. Preoperative screening: value of previous tests.

    Science.gov (United States)

    Macpherson, D S; Snow, R; Lofgren, R P

    1990-12-15

    To determine the frequency of tests done in the year before elective surgery that might substitute for preoperative screening tests and to determine the frequency of test results that change from a normal value to a value likely to alter perioperative management. Retrospective cohort analysis of computerized laboratory data (complete blood count, sodium, potassium, and creatinine levels, prothrombin time, and partial thromboplastin time). Urban tertiary care Veterans Affairs Hospital. Consecutive sample of 1109 patients who had elective surgery in 1988. At admission, 7549 preoperative tests were done, 47% of which duplicated tests performed in the previous year. Of 3096 previous results that were normal as defined by hospital reference range and done closest to the time of but before admission (median interval, 2 months), 13 (0.4%; 95% CI, 0.2% to 0.7%), repeat values were outside a range considered acceptable for surgery. Most of the abnormalities were predictable from the patient's history, and most were not noted in the medical record. Of 461 previous tests that were abnormal, 78 (17%; CI, 13% to 20%) repeat values at admission were outside a range considered acceptable for surgery (P less than 0.001, frequency of clinically important abnormalities of patients with normal previous results with those with abnormal previous results). Physicians evaluating patients preoperatively could safely substitute the previous test results analyzed in this study for preoperative screening tests if the previous tests are normal and no obvious indication for retesting is present.

  7. Estimation and optimization of flank wear and tool lifespan in finish turning of AISI 304 stainless steel using desirability function approach

    Directory of Open Access Journals (Sweden)

    Lakhdar Bouzid

    2018-10-01

    Full Text Available The wear of cutting tools remains a major obstacle. The effects of wear are not only antagonistic at the lifespan and productivity, but also harmful with the surface quality. The present work deals with some machinability studies on flank wear, surface roughness, and lifespan in finish turning of AISI 304 stainless steel using multilayer Ti(C,N/Al2O3/TiN coated carbide inserts. The machining experiments are conducted based on the response surface methodology (RSM. Combined effects of three cutting parameters, namely cutting speed, feed rate and cutting time on the two performance outputs (i.e. VB and Ra, and combined effects of two cutting parameters, namely cutting speed and feed rate on lifespan (T, are explored employing the analysis of variance (ANOVA. The relationship between the variables and the technological parameters is determined using a quadratic regression model and optimal cutting conditions for each performance level are established through desirability function approach (DFA optimization. The results show that the flank wear is influenced principally by the cutting time and in the second level by the cutting speed. In addition, it is indicated that the cutting time is the dominant factor affecting workpiece surface roughness followed by feed rate, while lifespan is influenced by cutting speed. The optimum level of input parameters for composite desirability was found Vc1-f1-t1 for VB, Ra and Vc1-f1 for T, with a maximum percentage of error 6.38%.

  8. Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Landewé, Robert B. M.; Matteson, Eric L.; Gaylis, Norman; Wollenhaupt, Jurgen; Murphy, Frederick T.; Zhou, Yiying; Hsia, Elizabeth C.; Doyle, Mittie K.

    2012-01-01

    The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason. Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of

  9. Audiovisual Simultaneity Judgment and Rapid Recalibration throughout the Lifespan.

    Science.gov (United States)

    Noel, Jean-Paul; De Niear, Matthew; Van der Burg, Erik; Wallace, Mark T

    2016-01-01

    Multisensory interactions are well established to convey an array of perceptual and behavioral benefits. One of the key features of multisensory interactions is the temporal structure of the stimuli combined. In an effort to better characterize how temporal factors influence multisensory interactions across the lifespan, we examined audiovisual simultaneity judgment and the degree of rapid recalibration to paired audiovisual stimuli (Flash-Beep and Speech) in a sample of 220 participants ranging from 7 to 86 years of age. Results demonstrate a surprisingly protracted developmental time-course for both audiovisual simultaneity judgment and rapid recalibration, with neither reaching maturity until well into adolescence. Interestingly, correlational analyses revealed that audiovisual simultaneity judgments (i.e., the size of the audiovisual temporal window of simultaneity) and rapid recalibration significantly co-varied as a function of age. Together, our results represent the most complete description of age-related changes in audiovisual simultaneity judgments to date, as well as being the first to describe changes in the degree of rapid recalibration as a function of age. We propose that the developmental time-course of rapid recalibration scaffolds the maturation of more durable audiovisual temporal representations.

  10. Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice.

    Science.gov (United States)

    Mitchell, Sarah J; Bernier, Michel; Aon, Miguel A; Cortassa, Sonia; Kim, Eun Young; Fang, Evandro F; Palacios, Hector H; Ali, Ahmed; Navas-Enamorado, Ignacio; Di Francesco, Andrea; Kaiser, Tamzin A; Waltz, Tyler B; Zhang, Ning; Ellis, James L; Elliott, Peter J; Frederick, David W; Bohr, Vilhelm A; Schmidt, Mark S; Brenner, Charles; Sinclair, David A; Sauve, Anthony A; Baur, Joseph A; de Cabo, Rafael

    2018-03-06

    The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD + , is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD + nor NADP + was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects. Published by Elsevier Inc.

  11. Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

    International Nuclear Information System (INIS)

    Yu, Suyeun; Jang, Yeogil; Paik, Donggi; Lee, Eunil; Park, Joong-Jean

    2015-01-01

    NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan. - Highlights: • Ubiquitous Nmdmc overexpression enhanced lifespan and stress tolerance. • Nmdmc overexpression in the fat body extended longevity. • Fat body-specific Nmdmc overexpression increased oxidative stress resistance. • Nmdmc overexpression decreased Hsp22 transcript levels and ROS. • Nmdmc overexpression increased mitochondrial DNA copy number.

  12. Post engineered nanomaterials lifespan: nanowastes classification, legislative development/implementation challenges, and proactive approaches

    CSIR Research Space (South Africa)

    Musee, N

    2012-05-01

    Full Text Available -1 NANOLCA Symposium, "Safety issues and regulatory challenges of nanomaterials", San Sebastian, Spain, 3-4 May 2012 Post engineered nanomaterials lifespan: nanowastes classification, legislative development/implementation challenges, and proactive...

  13. Building lifespan: effect on the environmental impact of building components in a Danish perspective

    DEFF Research Database (Denmark)

    Marsh, Rob

    2017-01-01

    of building lifespan are inadequately addressed. The aim of this research is therefore to explore how environmental impact from building components is affected by building lifespans of 50, 80, 100 and 120 years in a Danish context. LCAs are undertaken for 792 parametric variations of typical construction...... solutions, covering all primary building components and based on contemporary practice. A full statistical analysis is carried out, which shows a significant statistical correlation between changes in building lifespan and environmental impact for all primary building components, except windows......Construction professionals must now integrate environmental concerns with life cycle assessment (LCA) early in the procurement process. Building lifespan is important to LCA, since results must be normalized on an annualized basis for comparison. However, the scientific literature shows that issues...

  14. Alcohol Use and Abuse: Understanding Alcohol Use Across Your Lifespan | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Alcohol Use and Abuse Understanding Alcohol Use Across Your Lifespan Past Issues / Winter 2013 Table of Contents Alcohol use and the risk for alcohol-related problems ...

  15. Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Suyeun [Department of Preventive Medicine, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Jang, Yeogil; Paik, Donggi [Department of Physiology, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Lee, Eunil, E-mail: eunil@korea.ac.kr [Department of Preventive Medicine, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Park, Joong-Jean, E-mail: parkjj@korea.ac.kr [Department of Physiology, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of)

    2015-10-02

    NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan. - Highlights: • Ubiquitous Nmdmc overexpression enhanced lifespan and stress tolerance. • Nmdmc overexpression in the fat body extended longevity. • Fat body-specific Nmdmc overexpression increased oxidative stress resistance. • Nmdmc overexpression decreased Hsp22 transcript levels and ROS. • Nmdmc overexpression increased mitochondrial DNA copy number.

  16. Automatic segmentation of brain MRIs and mapping neuroanatomy across the human lifespan

    Science.gov (United States)

    Keihaninejad, Shiva; Heckemann, Rolf A.; Gousias, Ioannis S.; Rueckert, Daniel; Aljabar, Paul; Hajnal, Joseph V.; Hammers, Alexander

    2009-02-01

    A robust model for the automatic segmentation of human brain images into anatomically defined regions across the human lifespan would be highly desirable, but such structural segmentations of brain MRI are challenging due to age-related changes. We have developed a new method, based on established algorithms for automatic segmentation of young adults' brains. We used prior information from 30 anatomical atlases, which had been manually segmented into 83 anatomical structures. Target MRIs came from 80 subjects (~12 individuals/decade) from 20 to 90 years, with equal numbers of men, women; data from two different scanners (1.5T, 3T), using the IXI database. Each of the adult atlases was registered to each target MR image. By using additional information from segmentation into tissue classes (GM, WM and CSF) to initialise the warping based on label consistency similarity before feeding this into the previous normalised mutual information non-rigid registration, the registration became robust enough to accommodate atrophy and ventricular enlargement with age. The final segmentation was obtained by combination of the 30 propagated atlases using decision fusion. Kernel smoothing was used for modelling the structural volume changes with aging. Example linear correlation coefficients with age were, for lateral ventricular volume, rmale=0.76, rfemale=0.58 and, for hippocampal volume, rmale=-0.6, rfemale=-0.4 (allρ<0.01).

  17. The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans.

    Science.gov (United States)

    Fierro-González, Juan Carlos; González-Barrios, María; Miranda-Vizuete, Antonio; Swoboda, Peter

    2011-03-18

    Dietary restriction (DR) is the only environmental intervention known to extend adult lifespan in a wide variety of animal models. However, the genetic and cellular events that mediate the anti-aging programs induced by DR remain elusive. Here, we used the nematode Caenorhabditis elegans to provide the first in vivo evidence that a thioredoxin (TRX-1) regulates adult lifespan extension induced by DR. We found that deletion of the gene trx-1 completely suppressed the lifespan extension caused by mutation of eat-2, a genetic surrogate of DR in the worm. However, trx-1 deletion only partially suppressed the long lifespan caused by mutation of the insulin-like receptor gene daf-2 or by mutation of the sensory cilia gene osm-5. A trx-1::GFP translational fusion expressed from its own promoter in ASJ neurons (Ptrx-1::trx-1::GFP) rescued the trx-1 deletion-mediated suppression of the lifespan extension caused by mutation of eat-2. This rescue was not observed when trx-1::GFP was expressed from the ges-1 promoter in the intestine. In addition, overexpression of Ptrx-1::trx-1::GFP extended lifespan in wild type, but not in eat-2 mutants. trx-1 deletion almost completely suppressed the lifespan extension induced by dietary deprivation (DD), a non-genetic, nutrient-based model of DR in the worm. Moreover, DD upregulated the expression of a trx-1 promoter-driven GFP reporter gene (Ptrx-1::GFP) in ASJ neurons of aging adults, but not that of control Pgpa-9::GFP (which is also expressed in ASJ neurons). We propose that DR activates TRX-1 in ASJ neurons during aging, which in turn triggers TRX-1-dependent mechanisms to extend adult lifespan in the worm. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Uneven Futures of Human Lifespans: Reckonings from Gompertz Mortality Rates, Climate Change, and Air Pollution

    OpenAIRE

    Finch, Caleb E; Beltrán-Sánchez, Hiram; Crimmins, Eileen M

    2013-01-01

    The past 200 years have enabled remarkable increases in human lifespans through improvements in the living environment that have nearly eliminated infections as a cause of death through improved hygiene, public health, medicine, and nutrition. We argue that the limit to lifespan may be approaching. Since 1997, no one has exceeded Jeanne Calment's record of 122.5 years, despite an exponential increase of centenarians. Moreover, the background mortality may be approaching a lower limit. We calc...

  19. Lifespan differences in hematopoietic stem cells are due to imperfect repair and unstable mean-reversion.

    Directory of Open Access Journals (Sweden)

    Hans B Sieburg

    2013-04-01

    Full Text Available The life-long supply of blood cells depends on the long-term function of hematopoietic stem cells (HSCs. HSCs are functionally defined by their multi-potency and self-renewal capacity. Because of their self-renewal capacity, HSCs were thought to have indefinite lifespans. However, there is increasing evidence that genetically identical HSCs differ in lifespan and that the lifespan of a HSC is predetermined and HSC-intrinsic. Lifespan is here defined as the time a HSC gives rise to all mature blood cells. This raises the intriguing question: what controls the lifespan of HSCs within the same animal, exposed to the same environment? We present here a new model based on reliability theory to account for the diversity of lifespans of HSCs. Using clonal repopulation experiments and computational-mathematical modeling, we tested how small-scale, molecular level, failures are dissipated at the HSC population level. We found that the best fit of the experimental data is provided by a model, where the repopulation failure kinetics of each HSC are largely anti-persistent, or mean-reverting, processes. Thus, failure rates repeatedly increase during population-wide division events and are counteracted and decreased by repair processes. In the long-run, a crossover from anti-persistent to persistent behavior occurs. The cross-over is due to a slow increase in the mean failure rate of self-renewal and leads to rapid clonal extinction. This suggests that the repair capacity of HSCs is self-limiting. Furthermore, we show that the lifespan of each HSC depends on the amplitudes and frequencies of fluctuations in the failure rate kinetics. Shorter and longer lived HSCs differ significantly in their pre-programmed ability to dissipate perturbations. A likely interpretation of these findings is that the lifespan of HSCs is determined by preprogrammed differences in repair capacity.

  20. Lifespan and reproduction of isoclonal individual E.coli in different environments

    DEFF Research Database (Denmark)

    Jouvet, Lionel; Steiner, Ulrich

    Lifespan and reproduction are key fitness components, both of which are influences by genetics and the environment. Tracking large numbers of genotypically known individuals throughout their lives in known environments has been challenging. Here we show for isogenic individual E. coli bacteria...... under controlled environments how demographic parameters and distributions in reproduction and survival change across environments. We achieve this by using a microfluidic device that traps thousands of individual E. coli cells and tracks their division (reproduction) over their lifespan. Our results...

  1. Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jitendra Kumar

    Full Text Available Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.

  2. Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms.

    Directory of Open Access Journals (Sweden)

    Piper R Hunt

    Full Text Available Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C. elegans cap'n'collar (CNC transcription factor, SKN-1, mediates protective responses to oxidative stress. Genetic analysis showed that skn-1 activity is required for lifespan extension by low-dose plumbagin in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.

  3. Toward an understanding of late life suicidal behavior: the role of lifespan developmental theory.

    Science.gov (United States)

    Fiske, Amy; O'Riley, Alisa A

    2016-01-01

    Suicidal behavior in late life differs in important ways from suicidal behavior that occurs earlier in the lifespan, suggesting the possibility of developmental differences in the etiology of suicidal behavior. This paper examines late life suicidal behavior within the context of lifespan developmental theory. This paper presents a conceptual framework for using lifespan developmental theory to better understand late life suicidal behavior. We argue that the motivational theory of lifespan development, which focuses on control, is particularly relevant to late life suicide. This theory posits that opportunities to exert control over important aspects of one's life diminish in late life as a result of declines in physical functioning and other factors, and that successful aging is associated with adaptive regulation of this developmental change. Although continued striving to meet goals is normative throughout the lifespan, most individuals also increase the use of compensatory strategies in old age or when faced with a decline in functioning. We propose that individuals who do not adapt to developmental changes by altering their strategies for exerting control will be at risk for suicidal behavior in late life. This paper reviews evidence that supports the importance of control with respect to suicidal outcomes in older adults, as well as findings regarding specific types of control strategies that may be related to suicide risk in older adults with health-related limitations. Although suicidal behavior is not a normal part of aging, the application of lifespan developmental theory may be useful in understanding and potentially preventing suicide among older adults.

  4. Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

    Science.gov (United States)

    Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali; Lithgow, Gordon J.; Killilea, David W.; Kapahi, Pankaj

    2016-01-01

    Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. PMID:27078872

  5. Personality, self-rated health, and subjective age in a life-span sample: the moderating role of chronological age.

    Science.gov (United States)

    Stephan, Yannick; Demulier, Virginie; Terracciano, Antonio

    2012-12-01

    The present study tested whether chronological age moderates the association between subjective age and self-rated health and personality in a community-dwelling life-span sample (N = 1,016; age range: 18-91 years). Self-rated health, extraversion, and openness to experience were associated with a younger subjective age at older ages. Conscientious individuals felt more mature early in life. Conscientiousness, neuroticism, and agreeableness were not related to subjective age at older ages. These findings suggest that with aging self-rated health and personality traits are increasingly important for subjective age. 2013 APA, all rights reserved

  6. Subsequent pregnancy outcome after previous foetal death

    NARCIS (Netherlands)

    Nijkamp, J. W.; Korteweg, F. J.; Holm, J. P.; Timmer, A.; Erwich, J. J. H. M.; van Pampus, M. G.

    Objective: A history of foetal death is a risk factor for complications and foetal death in subsequent pregnancies as most previous risk factors remain present and an underlying cause of death may recur. The purpose of this study was to evaluate subsequent pregnancy outcome after foetal death and to

  7. Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan

    Directory of Open Access Journals (Sweden)

    Tuan Leng Tay

    2018-01-01

    Full Text Available Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance, and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD, hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs, and obsessive-compulsive disorder (OCD or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD, bipolar disorder (BD, schizophrenia, eating disorders and sleep disorders. Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer’s and Parkinson’s. Taking into account the recent identification of

  8. Why men matter: mating patterns drive evolution of human lifespan.

    Directory of Open Access Journals (Sweden)

    Shripad D Tuljapurkar

    2007-08-01

    Full Text Available Evolutionary theory predicts that senescence, a decline in survival rates with age, is the consequence of stronger selection on alleles that affect fertility or mortality earlier rather than later in life. Hamilton quantified this argument by showing that a rare mutation reducing survival is opposed by a selective force that declines with age over reproductive life. He used a female-only demographic model, predicting that female menopause at age ca. 50 yrs should be followed by a sharp increase in mortality, a "wall of death." Human lives obviously do not display such a wall. Explanations of the evolution of lifespan beyond the age of female menopause have proven difficult to describe as explicit genetic models. Here we argue that the inclusion of males and mating patterns extends Hamilton's theory and predicts the pattern of human senescence. We analyze a general two-sex model to show that selection favors survival for as long as men reproduce. Male fertility can only result from matings with fertile females, and we present a range of data showing that males much older than 50 yrs have substantial realized fertility through matings with younger females, a pattern that was likely typical among early humans. Thus old-age male fertility provides a selective force against autosomal deleterious mutations at ages far past female menopause with no sharp upper age limit, eliminating the wall of death. Our findings illustrate the evolutionary importance of males and mating preferences, and show that one-sex demographic models are insufficient to describe the forces that shape human senescence.

  9. Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan.

    Science.gov (United States)

    Tay, Tuan Leng; Béchade, Catherine; D'Andrea, Ivana; St-Pierre, Marie-Kim; Henry, Mathilde S; Roumier, Anne; Tremblay, Marie-Eve

    2017-01-01

    Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS) that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance), and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep disorders). Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer's and Parkinson's). Taking into account the recent identification of microglia

  10. Lifespan anxiety is reflected in human amygdala cortical connectivity

    Science.gov (United States)

    He, Ye; Xu, Ting; Zhang, Wei

    2016-01-01

    Abstract The amygdala plays a pivotal role in processing anxiety and connects to large‐scale brain networks. However, intrinsic functional connectivity (iFC) between amygdala and these networks has rarely been examined in relation to anxiety, especially across the lifespan. We employed resting‐state functional MRI data from 280 healthy adults (18–83.5 yrs) to elucidate the relationship between anxiety and amygdala iFC with common cortical networks including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default network. Global and network‐specific iFC were separately computed as mean iFC of amygdala with the entire cerebral cortex and each cortical network. We detected negative correlation between global positive amygdala iFC and trait anxiety. Network‐specific associations between amygdala iFC and anxiety were also detectable. Specifically, the higher iFC strength between the left amygdala and the limbic network predicted lower state anxiety. For the trait anxiety, left amygdala anxiety–connectivity correlation was observed in both somatomotor and dorsal attention networks, whereas the right amygdala anxiety–connectivity correlation was primarily distributed in the frontoparietal and ventral attention networks. Ventral attention network exhibited significant anxiety–gender interactions on its iFC with amygdala. Together with findings from additional vertex‐wise analysis, these data clearly indicated that both low‐level sensory networks and high‐level associative networks could contribute to detectable predictions of anxiety behaviors by their iFC profiles with the amygdala. This set of systems neuroscience findings could lead to novel functional network models on neural correlates of human anxiety and provide targets for novel treatment strategies on anxiety disorders. Hum Brain Mapp 37:1178–1193, 2016. © 2015 The Authors Human Brain Mapping

  11. Crosstalk between mitochondrial stress signals regulates yeast chronological lifespan.

    Science.gov (United States)

    Schroeder, Elizabeth A; Shadel, Gerald S

    2014-01-01

    Mitochondrial DNA (mtDNA) exists in multiple copies per cell and is essential for oxidative phosphorylation. Depleted or mutated mtDNA promotes numerous human diseases and may contribute to aging. Reduced TORC1 signaling in the budding yeast, Saccharomyces cerevisiae, extends chronological lifespan (CLS) in part by generating a mitochondrial ROS (mtROS) signal that epigenetically alters nuclear gene expression. To address the potential requirement for mtDNA maintenance in this response, we analyzed strains lacking the mitochondrial base-excision repair enzyme Ntg1p. Extension of CLS by mtROS signaling and reduced TORC1 activity, but not caloric restriction, was abrogated in ntg1Δ strains that exhibited mtDNA depletion without defects in respiration. The DNA damage response (DDR) kinase Rad53p, which transduces pro-longevity mtROS signals, is also activated in ntg1Δ strains. Restoring mtDNA copy number alleviated Rad53p activation and re-established CLS extension following mtROS signaling, indicating that Rad53p senses mtDNA depletion directly. Finally, DDR kinases regulate nucleus-mitochondria localization dynamics of Ntg1p. From these results, we conclude that the DDR pathway senses and may regulate Ntg1p-dependent mtDNA stability. Furthermore, Rad53p senses multiple mitochondrial stresses in a hierarchical manner to elicit specific physiological outcomes, exemplified by mtDNA depletion overriding the ability of Rad53p to transduce an adaptive mtROS longevity signal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Joint inhibition of TOR and JNK pathways interacts to extend the lifespan of Brachionus manjavacas (Rotifera).

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Rabeneck, Brett; Zipperer, Cody; Teat, Stephanie

    2014-04-01

    The TOR kinase pathway is central in modulating aging in a variety of animal models. The target of rapamycin (TOR) integrates a complex network of signals from growth conditions, nutrient availability, energy status, and physiological stresses and matches an organism's growth rate to the resource environment. Important remaining problems are the identification of the pathways that interact with TOR and their characterization as additive or synergistic. One of the most versatile stress sensors in metazoans is the Jun-N-terminal kinase (JNK) signaling pathway. JNK is an evolutionarily conserved stress-activated protein kinase that is induced by a range of stressors, including UV irradiation, reactive oxygen species, DNA damage, heat, and bacterial antigens. JNK is thought to interact with the TOR pathway, but its effects on TOR are poorly understood. We used the rotifer Brachionus manjavacas as a model animal to probe the regulation of TOR and JNK pathways and explore their interaction. The effect of various chemical inhibitors was examined in life table and stressor challenge experiments. A survey of 12 inhibitors revealed two, rapamycin and JNK inhibitor, that significantly extended lifespan of B. manjavacas. At 1 μM concentration, exposure to rapamycin or JNK inhibitor extended mean rotifer lifespan by 35% and maximum lifespan by 37%. Exposure to both rapamycin and JNK inhibitor simultaneously extended mean rotifer lifespan by 65% more than either alone. Exposure to a combination of rapamycin and JNK inhibitors conveyed greater protection to starvation, UV and osmotic stress than either inhibitor alone. RNAi knockdown of TOR and JNK gene expression was investigated for its ability to extend rotifer lifespan. RNAi knockdown of the TOR gene resulted in 29% extension of the mean lifespan compared to control and knockdown of the JNK gene resulted in 51% mean lifespan extension. In addition to the lifespan, we quantified mitochondria activity using the fluorescent

  13. A potential impact of DNA repair on ageing and lifespan in the ageing model organism Podospora anserina

    DEFF Research Database (Denmark)

    Soerensen, Mette; Gredilla, Ricardo; Müller-Ohldach, Mathis

    2009-01-01

    and hence contribute to ageing and lifespan control in this ageing model. Additionally, we find low DNA glycosylase activities in the long-lived mutants grisea and DeltaPaCox17::ble, which are characterized by low mitochondrial ROS generation. Overall, our data identify a potential role of mtDNA repair......The free radical theory of ageing states that ROS play a key role in age-related decrease in mitochondrial function via the damage of mitochondrial DNA (mtDNA), proteins and lipids. In the sexually reproducing ascomycete Podospora anserina ageing is, as in other eukaryotes, associated with mtDNA...... instability and mitochondrial dysfunction. Part of the mtDNA instabilities may arise due to accumulation of ROS induced mtDNA lesions, which, as previously suggested for mammals, may be caused by an age-related decrease in base excision repair (BER). Alignments of known BER protein sequences with the P...

  14. Positive Social Interactions in a Lifespan Perspective with a Focus on Opioidergic and Oxytocinergic Systems: Implications for Neuroprotection

    Science.gov (United States)

    Colonnello, Valentina; Petrocchi, Nicola; Farinelli, Marina; Ottaviani, Cristina

    2017-01-01

    In recent years, a growing interest has emerged in the beneficial effects of positive social interactions on health. The present work aims to review animal and human studies linking social interactions and health throughout the lifespan, with a focus on current knowledge of the possible mediating role of opioids and oxytocin. During the prenatal period, a positive social environment contributes to regulating maternal stress response and protecting the fetus from exposure to maternal active glucocorticoids. Throughout development, positive social contact with the caregiver acts as a “hidden regulator” and promotes infant neuroaffective development. Postnatal social neuroprotection interventions involving caregiver–infant physical contact seem to be crucial for rescuing preterm infants at risk for neurodevelopmental disorders. Attachment figures and friendships in adulthood continue to have a protective role for health and brain functioning, counteracting brain aging. In humans, implementation of meditative practices that promote compassionate motivation and prosocial behavior appears beneficial for health in adolescents and adults. Human and animal studies suggest the oxytocinergic and opioidergic systems are important mediators of the effects of social interactions. However, most of the studies focus on a specific phase of life (i.e., adulthood). Future studies should focus on the role of opioids and oxytocin in positive social interactions adopting a lifespan perspective. PMID:27538784

  15. In Vivo MRI Mapping of Brain Iron Deposition across the Adult Lifespan.

    Science.gov (United States)

    Acosta-Cabronero, Julio; Betts, Matthew J; Cardenas-Blanco, Arturo; Yang, Shan; Nestor, Peter J

    2016-01-13

    Disruption of iron homeostasis as a consequence of aging is thought to cause iron levels to increase, potentially promoting oxidative cellular damage. Therefore, understanding how this process evolves through the lifespan could offer insights into both the aging process and the development of aging-related neurodegenerative brain diseases. This work aimed to map, in vivo for the first time with an unbiased whole-brain approach, age-related iron changes using quantitative susceptibility mapping (QSM)--a new postprocessed MRI contrast mechanism. To this end, a full QSM standardization routine was devised and a cohort of N = 116 healthy adults (20-79 years of age) was studied. The whole-brain and ROI analyses confirmed that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their exact anatomical location. Whereas only patchy signs of iron scavenging were observed in white matter, strong, bilateral, and confluent QSM-age associations were identified in several deep-brain nuclei--chiefly the striatum and midbrain-and across motor, premotor, posterior insular, superior prefrontal, and cerebellar cortices. The validity of QSM as a suitable in vivo imaging technique with which to monitor iron dysregulation in the human brain was demonstrated by confirming age-related increases in several subcortical nuclei that are known to accumulate iron with age. The study indicated that, in addition to these structures, there is a predilection for iron accumulation in the frontal lobes, which when combined with the subcortical findings, suggests that iron accumulation with age predominantly affects brain regions concerned with motor/output functions. This study used a whole--brain imaging approach known as quantitative susceptibility mapping (QSM) to provide a novel insight into iron accumulation in the brain across the adult lifespan. Validity of the method was demonstrated by showing concordance with ROI analysis and prior knowledge

  16. Columnar modelling of nucleation burst evolution in the convective boundary layer – first results from a feasibility study Part IV: A compilation of previous observations for valuation of simulation results from a columnar modelling study

    Directory of Open Access Journals (Sweden)

    O. Hellmuth

    2006-01-01

    according to the parameterisation of the collision-controlled binary nucleation rate proposed by Weber et al. (1996, H2O vapour does not explicitly affect the particle formation. Since the H2SO4 concentration is overpredicted in the simulations presented in Paper III, the nucleation rates are too high compared to previous estimations. Therefore, the results are not directly comparable to measurements. Especially NPF events, where organics are suspected to play a key role, such as those observed at the boreal forest station in Hyytiälä (Southern Finland or at Hohenpeissenberg (mountain site in Southern Germany, can not be explained by employing simple sulphur/ammonia chemistry. However, some valuable hints regarding the role of CBL turbulence in NPF can be obtained. In the literature a number of observations on the link between turbulence and NPF can be found, whose burst patterns support a strong contribution of CBL turbulence to the NPF burst evolution simulated here. Observations, that do not correspond to the scenarios are discussed with respect to possible reasons for the differences between model and observation. The model simulations support some state-of-the-art hypotheses on the contribution of CBL turbulence to NPF. Considering the application of box models, the present study shows, that CBL turbulence, not explicitly considered in such models, can strongly affect the spatio-temporal NPF burst evolution. The columnar high-order model presented here is a helpful tool to elucidate gas-aerosol-turbulence interactions, especially the genesis of NPF bursts in the CBL. An advanced description of the cluster formation and condensation growth is required as well as a comprehensive verification/validation study using observed high-order moments. Further scenario simulations remain to be performed.

  17. The sensory system acts with a neuromedin U signaling pathway to mediate food type-dependent effects on lifespan

    OpenAIRE

    Adilov, Bakhtiyor

    2010-01-01

    In order to survive, the animal uses its sensory system to interpret the complexity of its environment. Interestingly, a subset of sensory neurons, which function in taste or olfaction, has been found to influence the lifespan of C. elegans and Drosophila. Although the mechanisms by which these neurons affect lifespan are unknown, the nature of these neurons suggest that the sensory influence on lifespan is mediated by food-derived cues. This thesis shows that sensory neurons r...

  18. Association of personality with physical, social, and mental activities across the lifespan: Findings from US and French samples.

    Science.gov (United States)

    Stephan, Yannick; Boiché, Julie; Canada, Brice; Terracciano, Antonio

    2014-11-01

    Despite evidence for its health-related benefits, little is known on the psychological predictors of the participation in leisure activities across the lifespan. Therefore, this study aimed to identify whether personality is associated with a variety of different types of activities, involving physical, cognitive, and social components. The samples included individuals from the second wave of the National Study of Midlife in the United States (N = 3,396) and community-dwelling French individuals (N = 2,917) aged between 30 and 84. Both samples completed measures of the five-factor model of personality. To create an activity index, we combined the physical, social, and cognitive (games and developmental) activities performed at least once a month. In both samples, individuals who scored higher on extraversion and openness were more likely to engage in a variety of activity types. The findings were consistent across two samples from different western societies and suggest that extraversion and openness contribute to social, cognitive, and physical functioning across the lifespan. © 2013 The British Psychological Society.

  19. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.

    Science.gov (United States)

    Anderson, Rozalyn M; Bitterman, Kevin J; Wood, Jason G; Medvedik, Oliver; Sinclair, David A

    2003-05-08

    Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.

  20. Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Markus M.M. Bisschops

    2015-10-01

    Full Text Available Stationary-phase (SP batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of anaerobic batch cultures was already evident during the exponential growth phase and, in contrast to the situation in aerobic cultures, was not substantially increased during transition into SP. A combination of physiological and transcriptome analysis showed that the slow post-diauxic growth phase on ethanol, which precedes SP in aerobic, but not in anaerobic cultures, endowed cells with the time and resources needed for inducing longevity and thermotolerance. When combined with literature data on acquisition of longevity and thermotolerance in retentostat cultures, the present study indicates that the fast transition from glucose excess to SP in anaerobic cultures precludes acquisition of longevity and thermotolerance. Moreover, this study demonstrates the importance of a preceding, calorie-restricted conditioning phase in the acquisition of longevity and stress tolerance in SP yeast cultures, irrespective of oxygen availability.

  1. Essential oil alloaromadendrene from mixed-type Cinnamomum osmophloeum leaves prolongs the lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Yu, Chan-Wei; Li, Wen-Hsuan; Hsu, Fu-Lan; Yen, Pei-Ling; Chang, Shang-Tzen; Liao, Vivian Hsiu-Chuan

    2014-07-02

    Cinnamomum osmophloeum Kaneh. is an indigenous tree species in Taiwan. The present study investigates phytochemical characteristics, antioxidant activities, and longevity of the essential oils from the leaves of the mixed-type C. osmophloeum tree. We demonstrate that the essential oils from leaves of mixed-type C. osmophloeum exerted in vivo antioxidant activities on Caenorhabditis elegans. In addition, minor (alloaromadendrene, 5.0%) but not major chemical components from the leaves of mixed-type C. osmophloeum have a key role against juglone-induced oxidative stress in C. elegans. Additionally, alloaromadendrene not only acts protective against oxidative stress but also prolongs the lifespan of C. elegans. Moreover, mechanistic studies show that DAF-16 is required for alloaromadendrene-mediated oxidative stress resistance and longevity in C. elegans. The results in the present study indicate that the leaves of mixed-type C. osmophloeum and essential oil alloaromadendrene have the potential for use as a source for antioxidants or treatments to delay aging.

  2. Concurrent Chemoradiotherapy Followed by Consolidation Chemotherapy With Bi-Weekly Docetaxel and Carboplatin for Stage III Unresectable, Non-Small-Cell Lung Cancer: Clinical Application of a Protocol Used in a Previous Phase II Study

    Energy Technology Data Exchange (ETDEWEB)

    Saitoh, Jun-Ichi, E-mail: junsaito@sannet.ne.jp [Division of Radiation Oncology, Saitama Cancer Center, Saitama (Japan); Saito, Yoshihiro; Kazumoto, Tomoko; Kudo, Shigehiro; Yoshida, Daisaku; Ichikawa, Akihiro [Division of Radiation Oncology, Saitama Cancer Center, Saitama (Japan); Sakai, Hiroshi; Kurimoto, Futoshi [Division of Respiratory Disease, Saitama Cancer Center, Saitama (Japan); Kato, Shingo [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Shibuya, Kei [Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma (Japan)

    2012-04-01

    Purpose: To assess the clinical applicability of a protocol evaluated in a previously reported phase II study of concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin in patients with stage III, unresectable, non-small-cell lung cancer (NSCLC). Methods and Materials: Between January 2000 and March 2006, 116 previously untreated patients with histologically proven, stage III NSCLC were treated with concurrent chemoradiotherapy. Radiation therapy was administered in 2-Gy daily fractions to a total dose of 60 Gy in combination with docetaxel, 30 mg/m{sup 2}, and carboplatin at an area under the curve value of 3 every 2 weeks during and after radiation therapy. Results: The median survival time for the entire group was 25.5 months. The actuarial 2-year and 5-year overall survival rates were 53% and 31%, respectively. The 3-year cause-specific survival rate was 60% in patients with stage IIIA disease, whereas it was 35% in patients with stage IIIB disease (p = 0.007). The actuarial 2-year and 5-year local control rates were 62% and 55%, respectively. Acute hematologic toxicities of Grade {>=}3 severity were observed in 20.7% of patients, while radiation pneumonitis and esophagitis of Grade {>=}3 severity were observed in 2.6% and 1.7% of patients, respectively. Conclusions: The feasibility of the protocol used in the previous phase II study was reconfirmed in this series, and excellent treatment results were achieved.

  3. Concurrent Chemoradiotherapy Followed by Consolidation Chemotherapy With Bi-Weekly Docetaxel and Carboplatin for Stage III Unresectable, Non-Small-Cell Lung Cancer: Clinical Application of a Protocol Used in a Previous Phase II Study

    International Nuclear Information System (INIS)

    Saitoh, Jun-Ichi; Saito, Yoshihiro; Kazumoto, Tomoko; Kudo, Shigehiro; Yoshida, Daisaku; Ichikawa, Akihiro; Sakai, Hiroshi; Kurimoto, Futoshi; Kato, Shingo; Shibuya, Kei

    2012-01-01

    Purpose: To assess the clinical applicability of a protocol evaluated in a previously reported phase II study of concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin in patients with stage III, unresectable, non-small-cell lung cancer (NSCLC). Methods and Materials: Between January 2000 and March 2006, 116 previously untreated patients with histologically proven, stage III NSCLC were treated with concurrent chemoradiotherapy. Radiation therapy was administered in 2-Gy daily fractions to a total dose of 60 Gy in combination with docetaxel, 30 mg/m 2 , and carboplatin at an area under the curve value of 3 every 2 weeks during and after radiation therapy. Results: The median survival time for the entire group was 25.5 months. The actuarial 2-year and 5-year overall survival rates were 53% and 31%, respectively. The 3-year cause-specific survival rate was 60% in patients with stage IIIA disease, whereas it was 35% in patients with stage IIIB disease (p = 0.007). The actuarial 2-year and 5-year local control rates were 62% and 55%, respectively. Acute hematologic toxicities of Grade ≥3 severity were observed in 20.7% of patients, while radiation pneumonitis and esophagitis of Grade ≥3 severity were observed in 2.6% and 1.7% of patients, respectively. Conclusions: The feasibility of the protocol used in the previous phase II study was reconfirmed in this series, and excellent treatment results were achieved.

  4. Subsequent childbirth after a previous traumatic birth.

    Science.gov (United States)

    Beck, Cheryl Tatano; Watson, Sue

    2010-01-01

    Nine percent of new mothers in the United States who participated in the Listening to Mothers II Postpartum Survey screened positive for meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for posttraumatic stress disorder after childbirth. Women who have had a traumatic birth experience report fewer subsequent children and a longer length of time before their second baby. Childbirth-related posttraumatic stress disorder impacts couples' physical relationship, communication, conflict, emotions, and bonding with their children. The purpose of this study was to describe the meaning of women's experiences of a subsequent childbirth after a previous traumatic birth. Phenomenology was the research design used. An international sample of 35 women participated in this Internet study. Women were asked, "Please describe in as much detail as you can remember your subsequent pregnancy, labor, and delivery following your previous traumatic birth." Colaizzi's phenomenological data analysis approach was used to analyze the stories of the 35 women. Data analysis yielded four themes: (a) riding the turbulent wave of panic during pregnancy; (b) strategizing: attempts to reclaim their body and complete the journey to motherhood; (c) bringing reverence to the birthing process and empowering women; and (d) still elusive: the longed-for healing birth experience. Subsequent childbirth after a previous birth trauma has the potential to either heal or retraumatize women. During pregnancy, women need permission and encouragement to grieve their prior traumatic births to help remove the burden of their invisible pain.

  5. From Children to Adults: Motor Performance across the Life-Span

    Science.gov (United States)

    Leversen, Jonas S. R.; Haga, Monika; Sigmundsson, Hermundur

    2012-01-01

    The life-span approach to development provides a theoretical framework to examine the general principles of life-long development. This study aims to investigate motor performance across the life span. It also aims to investigate if the correlations between motor tasks increase with aging. A cross-sectional design was used to describe the effects of aging on motor performance across age groups representing individuals from childhood to young adult to old age. Five different motor tasks were used to study changes in motor performance within 338 participants (7–79 yrs). Results showed that motor performance increases from childhood (7–9) to young adulthood (19–25) and decreases from young adulthood (19–25) to old age (66–80). These results are mirroring results from cognitive research. Correlation increased with increasing age between two fine motor tasks and two gross motor tasks. We suggest that the findings might be explained, in part, by the structural changes that have been reported to occur in the developing and aging brain and that the theory of Neural Darwinism can be used as a framework to explain why these changes occur. PMID:22719958

  6. Hydrogen peroxide induced loss of heterozygosity correlates with replicative lifespan and mitotic asymmetry in Saccharomyces cerevisiae

    Science.gov (United States)

    Jackson, Erin D.; Parker, Meighan C.; Gupta, Nilin; Rodrigues, Jenny

    2016-01-01

    Cellular aging in Saccharomyces cerevisiae can lead to genomic instability and impaired mitotic asymmetry. To investigate the role of oxidative stress in cellular aging, we examined the effect of exogenous hydrogen peroxide on genomic instability and mitotic asymmetry in a collection of yeast strains with diverse backgrounds. We treated yeast cells with hydrogen peroxide and monitored the changes of viability and the frequencies of loss of heterozygosity (LOH) in response to hydrogen peroxide doses. The mid-transition points of viability and LOH were quantified using sigmoid mathematical functions. We found that the increase of hydrogen peroxide dependent genomic instability often occurs before a drop in viability. We previously observed that elevation of genomic instability generally lags behind the drop in viability during chronological aging. Hence, onset of genomic instability induced by exogenous hydrogen peroxide treatment is opposite to that induced by endogenous oxidative stress during chronological aging, with regards to the midpoint of viability. This contrast argues that the effect of endogenous oxidative stress on genome integrity is well suppressed up to the dying-off phase during chronological aging. We found that the leadoff of exogenous hydrogen peroxide induced genomic instability to viability significantly correlated with replicative lifespan (RLS), indicating that yeast cells’ ability to counter oxidative stress contributes to their replicative longevity. Surprisingly, this leadoff is positively correlated with an inverse measure of endogenous mitotic asymmetry, indicating a trade-off between mitotic asymmetry and cell’s ability to fend off hydrogen peroxide induced oxidative stress. Overall, our results demonstrate strong associations of oxidative stress to genomic instability and mitotic asymmetry at the population level of budding yeast. PMID:27833823

  7. The Effect of Post-Reproductive Lifespan on the Fixation Probability of Beneficial Mutations

    DEFF Research Database (Denmark)

    Giaimo, Stefano; Baudisch, Annette

    2015-01-01

    Post-reproductive lifespan is a common trait among mammals and is usually considered to be neutral; i.e. with no influence on population dynamics. Here, we explore the role of post-reproductive lifespan in the fixation probability of beneficial genetic variation. We compare two separate, stationary...... populations living in a constant environment that are equivalent except for the average time their respective members spend in the post-reproductive stage of life. Using a recently derived approximation, we show that fixation of a beneficial mutation is more likely in the population with greater post......-reproductive longevity. This finding is surprising, as the population with more prolonged post-reproductive lifespan has smaller effective size and the classic population-genetic model would suggest that decreasing effective size reduces fixation chances of beneficial mutations. Yet, as we explain, in the age...

  8. Diosgenin a phytosterol substitute for cholesterol, prolongs the lifespan and mitigates glucose toxicity via DAF-16/FOXO and GST-4 in Caenorhabditis elegans.

    Science.gov (United States)

    Shanmugam, Govindan; Mohankumar, Amirthalingam; Kalaiselvi, Duraisamy; Nivitha, Sundararaj; Murugesh, Easwaran; Shanmughavel, Piramanayagam; Sundararaj, Palanisamy

    2017-11-01

    Caenorhabditis elegans is a sterol auxotroph requires minute amount of exogenous sterol for their growth and development. To culture the C. elegans, cholesterol was given as sterol molecule to maintain the optimum survival of worms. Diosgenin (DG), a plant derived steroidal saponin, structurally similar to cholesterol has been used as a precursor for the synthesis of steroidal hormones. In this study, worms were cultured with cholesterol (Cho + ) and cholesterol-free (Cho - ) medium with DG (5, 10 and 50μg/mL) at 20°C. It was observed that worms cultured in (Cho - ) exhibits late egg production, reduced lipid level and short lifespan, while addition of DG overcomes all defective facts. Combinations of both cholesterol and DG further extend the lifespan (20.8%), hinder lipid level and resistance to oxidative, thermal and high glucose stress. The intracellular ROS quantification was done by flouroscenic probe H2DCF-DA and confirmed that DG had significantly reduced ROS level (35.85%). Increased lifespan of worms were observed in the medium treated with DG which activates the nuclear translocation of DAF-16/FOXO transcription factor, followed by downstream antioxidant gene sod-3 as evidenced by GFP tagged strain. The expression of Phase II detoxification enzyme GST-4 significantly (pdaf-16, skn-1, and eat-2. These studies have proved that DG is a sterol source to worms and modulate the DAF-16, SOD-3 and GST-4 expression levels to extend the lifespan of worms. The present study has also highlighted the use of phytosterols as an alternative to cholesterol. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  10. Multimodal Assessment of Recurrent MTBI across the Lifespan

    Directory of Open Access Journals (Sweden)

    Skadi Wilke

    2018-05-01

    Full Text Available Recurrent mild traumatic brain injuries (mTBI and its neurological sequelae have been the focus of a large number of studies, indicating cognitive, structural, and functional brain alterations. However, studies often focused on single outcome measures in small cohorts of specific populations only. We conducted a multimodal evaluation of the impact of recurrent mTBI on a broad range of cognitive functions, regional brain volume, white matter integrity, and resting state functional connectivity (RSFC in young and older adults in the chronic stage (>6 months after the last mTBI. Seventeen young participants with mTBI (age: 24.2 ± 2.8 (mean ± SD and 21 group-wise matched healthy controls (age: 25.8 ± 5.4 (mean ± SD, as well as 17 older participants with mTBI (age: 62.7 ± 7.7 (mean ± SD and 16 group-wise matched healthy controls (age: 61.7 ± 5.9 (mean ± SD were evaluated. We found significant differences in the verbal fluency between young participants with mTBI and young healthy controls. Furthermore, differences in the regional volume of precuneus and medial orbitofrontal gyrus between participants with mTBI and controls for both age groups were seen. A significant age by group interaction for the right hippocampal volume was noted, indicating an accelerated hippocampal volume loss in older participants with mTBI. Other cognitive parameters, white matter integrity, and RSFC showed no significant differences. We confirmed some of the previously reported detrimental effects of recurrent mTBI, but also demonstrated inconspicuous findings for the majority of parameters.

  11. Immigration, language proficiency, and autobiographical memories: Lifespan distribution and second-language access.

    Science.gov (United States)

    Esposito, Alena G; Baker-Ward, Lynne

    2016-08-01

    This investigation examined two controversies in the autobiographical literature: how cross-language immigration affects the distribution of autobiographical memories across the lifespan and under what circumstances language-dependent recall is observed. Both Spanish/English bilingual immigrants and English monolingual non-immigrants participated in a cue word study, with the bilingual sample taking part in a within-subject language manipulation. The expected bump in the number of memories from early life was observed for non-immigrants but not immigrants, who reported more memories for events surrounding immigration. Aspects of the methodology addressed possible reasons for past discrepant findings. Language-dependent recall was influenced by second-language proficiency. Results were interpreted as evidence that bilinguals with high second-language proficiency, in contrast to those with lower second-language proficiency, access a single conceptual store through either language. The final multi-level model predicting language-dependent recall, including second-language proficiency, age of immigration, internal language, and cue word language, explained ¾ of the between-person variance and (1)/5 of the within-person variance. We arrive at two conclusions. First, major life transitions influence the distribution of memories. Second, concept representation across multiple languages follows a developmental model. In addition, the results underscore the importance of considering language experience in research involving memory reports.

  12. Explaining sex differences in lifespan in terms of optimal energy allocation in the baboon.

    Science.gov (United States)

    King, Annette M; Kirkwood, Thomas B L; Shanley, Daryl P

    2017-10-01

    We provide a quantitative test of the hypothesis that sex role specialization may account for sex differences in lifespan in baboons if such specialization causes the dependency of fitness upon longevity, and consequently the optimal resolution to an energetic trade-off between somatic maintenance and other physiological functions, to differ between males and females. We present a model in which females provide all offspring care and males compete for access to reproductive females and in which the partitioning of available energy between the competing fitness-enhancing functions of growth, maintenance, and reproduction is modeled as a dynamic behavioral game, with the optimal decision for each individual depending upon his/her state and the behavior of other members of the population. Our model replicates the sexual dimorphism in body size and sex differences in longevity and reproductive scheduling seen in natural populations of baboons. We show that this outcome is generally robust to perturbations in model parameters, an important finding given that the same behavior is seen across multiple populations and species in the wild. This supports the idea that sex differences in longevity result from differences in the value of somatic maintenance relative to other fitness-enhancing functions in keeping with the disposable soma theory. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  13. Glial cell morphological and density changes through the lifespan of rhesus macaques.

    Science.gov (United States)

    Robillard, Katelyn N; Lee, Kim M; Chiu, Kevin B; MacLean, Andrew G

    2016-07-01

    How aging impacts the central nervous system (CNS) is an area of intense interest. Glial morphology is known to affect neuronal and immune function as well as metabolic and homeostatic balance. Activation of glia, both astrocytes and microglia, occurs at several stages during development and aging. The present study analyzed changes in glial morphology and density through the entire lifespan of rhesus macaques, which are physiologically and anatomically similar to humans. We observed apparent increases in gray matter astrocytic process length and process complexity as rhesus macaques matured from juveniles through adulthood. These changes were not attributed to cell enlargement because they were not accompanied by proportional changes in soma or process volume. There was a decrease in white matter microglial process length as rhesus macaques aged. Aging was shown to have a significant effect on gray matter microglial density, with a significant increase in aged macaques compared with adults. Overall, we observed significant changes in glial morphology as macaques age indicative of astrocytic activation with subsequent increase in microglial density in aged macaques. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Anticipatory postural adjustment patterns during gait initiation across the adult lifespan.

    Science.gov (United States)

    Lu, Chiahao; Amundsen Huffmaster, Sommer L; Harvey, Jack C; MacKinnon, Colum D

    2017-09-01

    Gait initiation involves a complex sequence of anticipatory postural adjustments (APAs) during the transition from steady state standing to forward locomotion. APAs have four core components that function to accelerate the center of mass forwards and towards the initial single-support stance limb. These components include loading of the initial step leg, unloading of the initial stance leg, and excursion of the center of pressure in the posterior and lateral (towards the stepping leg) directions. This study examined the incidence, magnitude, and timing of these components and how they change across the lifespan (ages 20-79). 157 individuals performed five trials of self-paced, non-cued gait initiation on an instrumented walkway. At least one component of the APA was absent in 24% of all trials. The component most commonly absent was loading of the initial step leg (absent in 10% of all trials in isolation, absent in 10% of trials in conjunction with another missing component). Trials missing all four components were rare (1%) and were observed in both younger and older adults. There was no significant difference across decades in the incidence of trials without an APA, the number or type of APA components absent, or the magnitude or timing of the APA components. These data demonstrate that one or more components of the APA sequence are commonly absent in the general population and the spatiotemporal profile of the APA does not markedly change with ageing. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Lifetime return on investment increases with leaf lifespan among 10 Australian woodland species.

    Science.gov (United States)

    Falster, Daniel S; Reich, Peter B; Ellsworth, David S; Wright, Ian J; Westoby, Mark; Oleksyn, Jacek; Lee, Tali D

    2012-01-01

    • Co-occurring species often differ in their leaf lifespan (LL) and it remains unclear how such variation is maintained in a competitive context. Here we test the hypothesis that leaves of long-LL species yield a greater return in carbon (C) fixed per unit C or nutrient invested by the plant than those of short-LL species. • For 10 sympatric woodland species, we assessed three-dimensional shoot architecture, canopy openness, leaf photosynthetic light response, leaf dark respiration and leaf construction costs across leaf age sequences. We then used the YPLANT model to estimate light interception and C revenue along the measured leaf age sequences. This was done under a series of simulations that incorporated the potential covariates of LL in an additive fashion. • Lifetime return in C fixed per unit C, N or P invested increased with LL in all simulations. • In contrast to other recent studies, our results show that extended LL confers a fundamental economic advantage by increasing a plant's return on investment in leaves. This suggests that time-discounting effects, that is, the compounding of income that arises from quick reinvestment of C revenue, are key in allowing short-LL species to succeed in the face of this economic handicap. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

  16. Gender differences in depression and anxiety across the adult lifespan: the role of psychosocial mediators.

    Science.gov (United States)

    Leach, Liana S; Christensen, Helen; Mackinnon, Andrew J; Windsor, Timothy D; Butterworth, Peter

    2008-12-01

    There is robust epidemiological and clinical evidence that a greater number of women than men experience depression and anxiety. This study investigated a number of socio-demographic, health and lifestyle, psychological and social factors as possible mediators for the gender difference in depression and anxiety in three cohorts (20-24, 40-44, 60-64). Responses were from a representative, community based survey (n = 7,485) conducted in Canberra and Queanbeyan (NSW), in Australia. Depression and anxiety were measured using the self-report Goldberg Anxiety and Depression Scales. The analyses initially identified gender differences in the potential mediators, followed by univariate and multivariate mediation models. The results indicated several shared mediators for depression and anxiety across the three age groups including: childhood adversity, mastery, behavioural inhibition, ruminative style, neuroticism, physical health, physical activity, and perceived interpersonal and employment problems. There was a decrease in the number of social mediators as age increased. The multivariate models accounted for gender differences in both conditions for all age groups, except for anxiety in the 20-24 years old. This suggests further important unmeasured mediators for this age group. These findings add to the literature surrounding gender differences in depression and anxiety, and provide a basis for future research exploring variation in these gender disparities over the adult lifespan.

  17. Types of strain among family members of individuals with autism spectrum disorder across the lifespan.

    Science.gov (United States)

    Shivers, Carolyn M; Krizova, Katarina; Lee, Gloria K

    2017-09-01

    Although increased caregiver strain is often found among family caregivers of individuals with autism spectrum disorder, it is still unclear as to how different types of strain relate to amount and types of caregiving across the lifespan. The present study examined different types of strain (i.e. subjective internalized strain, subjective externalized strain, and objective strain) and how such strain relates to the amount of caregiving responsibilities. Data was collected via online survey from a sample of 193 family caregivers of individuals with ASD from the United States, Canada, and the Republic of Ireland. Participants completed measures of strain and caregiving responsibilities, as well as coping, demographics, and services needed and received by the individual with ASD. Caregivers reported higher levels of objective strain than subjective, and caregiving responsibility was related to objective and subjective internalized strain. Coping style was strongly correlated with all types of strain, and unmet service needs were significantly related to objective and subjective internalized strain. Caregiving behaviors were only related to objective strain. The present results indicate that, although caregiving responsibility is related to objective and subjective internalized strain, the relationship is perhaps not as strong as the relationship between coping mechanisms and strain. Future research is needed to understand different types of strain and develop strategies to help caregivers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Cultivating Composting Culture Activities among Citizens and Its Beneficial to Prolong the Landfill Lifespan

    Science.gov (United States)

    Azura Zakarya, Irnis; Azri Jamial, Khairul; Mat Tanda, Norazlinda

    2018-03-01

    Currently, the Ministry of Housing and Local Government manage solid waste in Malaysia, with the participation of the private sector. Food waste represents almost 60% of the total municipal solid waste disposed in the landfill. Material valorisation of food waste usually conducted by biological processes such as composting. Compost, an organic amendment, is the final product of the composting process. These processes are efficient, low cost and environmentally friendly alternative for managing food waste and are used extensively worldwide. Therefore, organic solid waste management practices program for the communities in Perlis was conducted. The main objective of this program was to instilling environment awareness especially among Perlis citizens. This study was investigated the impact of food waste or kitchen waste composting to the citizens in Perlis State and the beneficial of compost fertilizer to our environment especially in plant growth. Composting method was taught to the food premises owner, individuals, teachers, and students and their responses to the composting practices were then summarized. In future, we can prolong our landfill lifespan by practicing organic waste composting and can preserving our environment.

  19. Polyhydroxy fullerenes (fullerols or fullerenols: beneficial effects on growth and lifespan in diverse biological models.

    Directory of Open Access Journals (Sweden)

    Jie Gao

    Full Text Available Recent toxicological studies on carbon nanomaterials, including fullerenes, have led to concerns about their safety. Functionalized fullerenes, such as polyhydroxy fullerenes (PHF, fullerols, or fullerenols, have attracted particular attention due to their water solubility and toxicity. Here, we report surprisingly beneficial and/or specific effects of PHF on model organisms representing four kingdoms, including the green algae Pseudokirchneriella subcapitata, the plant Arabidopsis thaliana, the fungus Aspergillus niger, and the invertebrate Ceriodaphnia dubia. The results showed that PHF had no acute or chronic negative effects on the freshwater organisms. Conversely, PHF could surprisingly increase the algal culture density over controls at higher concentrations (i.e., 72% increase by 1 and 5 mg/L of PHF and extend the lifespan and stimulate the reproduction of Daphnia (e.g. about 38% by 20 mg/L of PHF. We also show that at certain PHF concentrations fungal growth can be enhanced and Arabidopsis thaliana seedlings exhibit longer hypocotyls, while other complex physiological processes remain unaffected. These findings may open new research fields in the potential applications of PHF, e.g., in biofuel production and aquaculture. These results will form the basis of further research into the mechanisms of growth stimulation and life extension by PHF.

  20. Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension

    Directory of Open Access Journals (Sweden)

    Doroszuk Agnieszka

    2012-05-01

    Full Text Available Abstract Background While studying long-lived mutants has advanced our understanding of the processes involved in ageing, the mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown. Here, we characterise genome-wide expression patterns of a long-lived, natural variant of Drosophila melanogaster resulting from selection for starvation resistance (SR and compare it with normal-lived control flies (C. We do this at two time points representing middle age (90% survival and old age (10% survival respectively, in three adult diets (malnutrition, optimal food, and overfeeding. Results We found profound differences between Drosophila lines in their age-related expression. Most of the age-associated changes in normal-lived flies were abrogated in long-lived Drosophila. The stress-related genes, including those involved in proteolysis and cytochrome P450, were generally higher expressed in SR flies and showed a smaller increase in expression with age compared to C flies. The genes involved in reproduction showed a lower expression in middle-aged SR than in C flies and, unlike C flies, a lack of their downregulation with age. Further, we found that malnutrition strongly affected age-associated transcript patterns overriding the differences between the lines. However, under less stressful dietary conditions, line and diet affected age-dependent expression similarly. Finally, we present lists of candidate markers of ageing and lifespan extension. Conclusions Our study unveils transcriptional changes associated with lifespan extension in SR Drosophila. The results suggest that natural genetic variation for SR and lifespan can operate through similar transcriptional mechanisms as those of dietary restriction and life-extending mutations.

  1. Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group.

    Science.gov (United States)

    van Rooij, Daan; Anagnostou, Evdokia; Arango, Celso; Auzias, Guillaume; Behrmann, Marlene; Busatto, Geraldo F; Calderoni, Sara; Daly, Eileen; Deruelle, Christine; Di Martino, Adriana; Dinstein, Ilan; Duran, Fabio Luis Souza; Durston, Sarah; Ecker, Christine; Fair, Damien; Fedor, Jennifer; Fitzgerald, Jackie; Freitag, Christine M; Gallagher, Louise; Gori, Ilaria; Haar, Shlomi; Hoekstra, Liesbeth; Jahanshad, Neda; Jalbrzikowski, Maria; Janssen, Joost; Lerch, Jason; Luna, Beatriz; Martinho, Mauricio Moller; McGrath, Jane; Muratori, Filippo; Murphy, Clodagh M; Murphy, Declan G M; O'Hearn, Kirsten; Oranje, Bob; Parellada, Mara; Retico, Alessandra; Rosa, Pedro; Rubia, Katya; Shook, Devon; Taylor, Margot; Thompson, Paul M; Tosetti, Michela; Wallace, Gregory L; Zhou, Fengfeng; Buitelaar, Jan K

    2018-04-01

    Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different

  2. The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Fierro-Gonzalez, Juan Carlos; Gonzalez-Barrios, Maria; Miranda-Vizuete, Antonio; Swoboda, Peter

    2011-01-01

    Highlights: → First in vivo data for thioredoxin in dietary-restriction-(DR)-induced longevity. → Thioredoxin (trx-1) loss suppresses longevity of eat-2 mutant, a genetic DR model. → trx-1 overexpression extends wild-type longevity, but not that of eat-2 mutant. → Longevity by dietary deprivation (DD), a non-genetic DR model, requires trx-1. → trx-1 expression in ASJ neurons of aging adults is increased in response to DD. -- Abstract: Dietary restriction (DR) is the only environmental intervention known to extend adult lifespan in a wide variety of animal models. However, the genetic and cellular events that mediate the anti-aging programs induced by DR remain elusive. Here, we used the nematode Caenorhabditis elegans to provide the first in vivo evidence that a thioredoxin (TRX-1) regulates adult lifespan extension induced by DR. We found that deletion of the gene trx-1 completely suppressed the lifespan extension caused by mutation of eat-2, a genetic surrogate of DR in the worm. However, trx-1 deletion only partially suppressed the long lifespan caused by mutation of the insulin-like receptor gene daf-2 or by mutation of the sensory cilia gene osm-5. A trx-1::GFP translational fusion expressed from its own promoter in ASJ neurons (Ptrx-1::trx-1::GFP) rescued the trx-1 deletion-mediated suppression of the lifespan extension caused by mutation of eat-2. This rescue was not observed when trx-1::GFP was expressed from the ges-1 promoter in the intestine. In addition, overexpression of Ptrx-1::trx-1::GFP extended lifespan in wild type, but not in eat-2 mutants. trx-1 deletion almost completely suppressed the lifespan extension induced by dietary deprivation (DD), a non-genetic, nutrient-based model of DR in the worm. Moreover, DD upregulated the expression of a trx-1 promoter-driven GFP reporter gene (Ptrx-1::GFP) in ASJ neurons of aging adults, but not that of control Pgpa-9::GFP (which is also expressed in ASJ neurons). We propose that DR activates TRX-1

  3. The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Fierro-Gonzalez, Juan Carlos [Karolinska Institute, Center for Biosciences at NOVUM, Department of Biosciences and Nutrition, S-141 83 Huddinge (Sweden); Gonzalez-Barrios, Maria [Centro Andaluz de Biologia del Desarrollo (CABD-CSIC), Departamento de Fisiologia, Anatomia y Biologia Celular, Universidad Pablo de Olavide, E-41013 Sevilla (Spain); Miranda-Vizuete, Antonio, E-mail: amirviz@upo.es [Centro Andaluz de Biologia del Desarrollo (CABD-CSIC), Departamento de Fisiologia, Anatomia y Biologia Celular, Universidad Pablo de Olavide, E-41013 Sevilla (Spain); Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, E-41013 Sevilla (Spain); Swoboda, Peter, E-mail: peter.swoboda@ki.se [Karolinska Institute, Center for Biosciences at NOVUM, Department of Biosciences and Nutrition, S-141 83 Huddinge (Sweden)

    2011-03-18

    Highlights: {yields} First in vivo data for thioredoxin in dietary-restriction-(DR)-induced longevity. {yields} Thioredoxin (trx-1) loss suppresses longevity of eat-2 mutant, a genetic DR model. {yields} trx-1 overexpression extends wild-type longevity, but not that of eat-2 mutant. {yields} Longevity by dietary deprivation (DD), a non-genetic DR model, requires trx-1. {yields} trx-1 expression in ASJ neurons of aging adults is increased in response to DD. -- Abstract: Dietary restriction (DR) is the only environmental intervention known to extend adult lifespan in a wide variety of animal models. However, the genetic and cellular events that mediate the anti-aging programs induced by DR remain elusive. Here, we used the nematode Caenorhabditis elegans to provide the first in vivo evidence that a thioredoxin (TRX-1) regulates adult lifespan extension induced by DR. We found that deletion of the gene trx-1 completely suppressed the lifespan extension caused by mutation of eat-2, a genetic surrogate of DR in the worm. However, trx-1 deletion only partially suppressed the long lifespan caused by mutation of the insulin-like receptor gene daf-2 or by mutation of the sensory cilia gene osm-5. A trx-1::GFP translational fusion expressed from its own promoter in ASJ neurons (Ptrx-1::trx-1::GFP) rescued the trx-1 deletion-mediated suppression of the lifespan extension caused by mutation of eat-2. This rescue was not observed when trx-1::GFP was expressed from the ges-1 promoter in the intestine. In addition, overexpression of Ptrx-1::trx-1::GFP extended lifespan in wild type, but not in eat-2 mutants. trx-1 deletion almost completely suppressed the lifespan extension induced by dietary deprivation (DD), a non-genetic, nutrient-based model of DR in the worm. Moreover, DD upregulated the expression of a trx-1 promoter-driven GFP reporter gene (Ptrx-1::GFP) in ASJ neurons of aging adults, but not that of control Pgpa-9::GFP (which is also expressed in ASJ neurons). We propose

  4. [Russian/German contacts in discussion on cellular mechanisms of aging and lifespan (author's transl)].

    Science.gov (United States)

    Duplenko, J K

    1980-01-01

    This is a brief review of the discussions which took place in natural literature at the end of XIX, and the beginning of XX century concerning the problems of cellular mechanism of aging, animal lifespan, death of metazoa and immortality of protozoa. The participation of German and Russian natural scientists in the discussion of cardinal gerontological questions is specially considered. The close relationship between the gerontological conceptions and the evolutionary ideas is emphasized. The author has established historical continuity of the above conceptions and modern evolutionary approaches to the predetermination of species' lifespan and mechanisms of aging.

  5. The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects

    Directory of Open Access Journals (Sweden)

    C. L. Hughes

    2015-01-01

    Full Text Available In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women’s health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan.

  6. Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study

    Directory of Open Access Journals (Sweden)

    Sachin A Narvekar

    2010-01-01

    Full Text Available Background: Management of repeated implantation failure despite transfer of good-quality embryos still remains a dilemma for ART specialists. Scrapping of endometrium in the nontransfer cycle has been shown to improve the pregnancy rate in the subsequent IVF/ET cycle in recent studies. Aim: The objective of this randomized controlled trial (RCT was to determine whether endometrial injury caused by Pipelle sampling in the nontransfer cycle could improve the probability of pregnancy in the subsequent IVF cycle in patients who had previous failed IVF outcome. Setting: Tertiary assisted conception center. Design: Randomized controlled study. Materials and Methods: 100 eligible patients with previous failed IVF despite transfer of good-quality embryos were randomly allocated to the intervention group and control groups. In the intervention group, Pipelle endometrial sampling was done twice: One in the follicular phase and again in the luteal phase in the cycle preceding the embryo transfer cycle. Outcome Measure: The primary outcome measure was live birth rate. The secondary outcome measures were implantation and clinical pregnancy rates. Results: The live birth rate was significantly higher in the intervention group compared to control group (22.4% and 9.8% P = 0.04. The clinical pregnancy rate in the intervention group was 32.7%, while that in the control group was 13.7%, which was also statistically significant ( P = 0.01. The implantation rate was significantly higher in the intervention group as compared to controls (13.07% vs 7.1% P = 0.04. Conclusions: Endometrial injury in nontransfer cycle improves the live birth rate,clinical pregnancy and implantation rates in the subsequent IVF-ET cycle in patients with previous unsuccessful IVF cycles.

  7. The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study.

    Directory of Open Access Journals (Sweden)

    Xingsheng Hu

    Full Text Available Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC previously treated with platinum-based chemotherapy.Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125 mg tablet, three times per day. The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety.From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9-6.6 m and 5.4 months (95%CI 3.1-7.9 m, respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127, diarrhea (12.6%, 16/127 and elevation of transaminase (15.7%, 20/127.In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy.ClinicalTrials.gov NCT02486354.

  8. The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study.

    Science.gov (United States)

    Hu, Xingsheng; Zhang, Li; Shi, Yuankai; Zhou, Caicun; Liu, Xiaoqing; Wang, Dong; Song, Yong; Li, Qiang; Feng, Jifeng; Qin, Shukui; Xv, Nong; Zhou, Jianying; Zhang, Li; Hu, Chunhong; Zhang, Shucai; Luo, Rongcheng; Wang, Jie; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

    2015-01-01

    Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125 mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9-6.6 m) and 5.4 months (95%CI 3.1-7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. ClinicalTrials.gov NCT02486354.

  9. Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study.

    Science.gov (United States)

    Unfer, Vittorio; Raffone, Emanuela; Rizzo, Piero; Buffo, Silvia

    2011-11-01

    Several factors can affect oocyte quality and therefore pregnancy outcome in assisted reproductive technology (ART) cycles. Recently, a number of studies have shown that the presence of several compounds in the follicular fluid positively correlates with oocyte quality and maturation (i.e., myo-inositol and melatonin). In the present study, we aim to evaluate the pregnancy outcomes after the administration of myo-inositol combined with melatonin in women who failed to conceive in previous in vitro fertilization (IVF) cycles due to poor oocyte quality. Forty-six women were treated with 4 g/day myo-inositol and 3 mg/day melatonin (inofolic® and inofolic® Plus, Lo.Lipharma, Rome) for 3 months and then underwent a new IVF cycle. After treatment, the number of mature oocytes, the fertilization rate, the number of both, total and top-quality embryos transferred were statistically higher compared to the previous IVF cycle, while there was no difference in the number of retrieved oocyte. After treatment, a total of 13 pregnancies occurred, 9 of them were confirmed echographically; four evolved in spontaneous abortion. The treatment with myo-inositol and melatonin improves ovarian stimulation protocols and pregnancy outcomes in infertile women with poor oocyte quality.

  10. Age, gender, and cancer but not neurodegenerative and cardiovascular diseases strongly modulate systemic effect of the Apolipoprotein E4 allele on lifespan

    DEFF Research Database (Denmark)

    Kulminski, Alexander M; Arbeev, Konstantin G; Culminskaya, Irina

    2014-01-01

    cohorts and the Long Life Family Study (LLFS) to investigate gender-specific effects of the ApoE4 allele on human survival in a wide range of ages from midlife to extreme old ages, and the sensitivity of these effects to cardiovascular disease (CVD), cancer, and neurodegenerative disorders (ND.......6 × 10(-6)) in the FHS cohorts. Major human diseases including CVD, ND, and cancer, whose risks can be sensitive to the e4 allele, do not mediate the association of this allele with lifespan in large FHS samples. Non-skin cancer non-additively increases mortality of the FHS women with moderate lifespans...... by 150% (p = 5.3 × 10(-8)) compared to the non-carriers. This risk explains the 4.2 year shorter life expectancy of the e4 carriers compared to the non-carriers in this sample. The analyses suggest the existence of age- and gender-sensitive systemic mechanisms linking the e4 allele to lifespan which can...

  11. Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression

    Directory of Open Access Journals (Sweden)

    Liangping Su

    2018-03-01

    Full Text Available Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3 in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11, attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases.

  12. Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression.

    Science.gov (United States)

    Su, Liangping; Li, Hongyuan; Huang, Cheng; Zhao, Tingting; Zhang, Yongjun; Ba, Xueqing; Li, Zhongwei; Zhang, Yu; Huang, Baiqu; Lu, Jun; Zhao, Yanmei; Li, Xiaoxue

    2018-03-06

    Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a) was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11), attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.

    Science.gov (United States)

    Chanan-Khan, Asher; Cramer, Paula; Demirkan, Fatih; Fraser, Graeme; Silva, Rodrigo Santucci; Grosicki, Sebastian; Pristupa, Aleksander; Janssens, Ann; Mayer, Jiri; Bartlett, Nancy L; Dilhuydy, Marie-Sarah; Pylypenko, Halyna; Loscertales, Javier; Avigdor, Abraham; Rule, Simon; Villa, Diego; Samoilova, Olga; Panagiotidis, Panagiots; Goy, Andre; Mato, Anthony; Pavlovsky, Miguel A; Karlsson, Claes; Mahler, Michelle; Salman, Mariya; Sun, Steven; Phelps, Charles; Balasubramanian, Sriram; Howes, Angela; Hallek, Michael

    2016-02-01

    Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma. The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (>1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m(2) intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m(2) on day 1 of cycle 1, and 500 mg/m(2) on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression

  14. Using the genome aggregation database, computational pathogenicity prediction tools, and patch clamp heterologous expression studies to demote previously published long QT syndrome type 1 mutations from pathogenic to benign.

    Science.gov (United States)

    Clemens, Daniel J; Lentino, Anne R; Kapplinger, Jamie D; Ye, Dan; Zhou, Wei; Tester, David J; Ackerman, Michael J

    2018-04-01

    Mutations in the KCNQ1-encoded Kv7.1 potassium channel cause long QT syndrome (LQTS) type 1 (LQT1). It has been suggested that ∼10%-20% of rare LQTS case-derived variants in the literature may have been published erroneously as LQT1-causative mutations and may be "false positives." The purpose of this study was to determine which previously published KCNQ1 case variants are likely false positives. A list of all published, case-derived KCNQ1 missense variants (MVs) was compiled. The occurrence of each MV within the Genome Aggregation Database (gnomAD) was assessed. Eight in silico tools were used to predict each variant's pathogenicity. Case-derived variants that were either (1) too frequently found in gnomAD or (2) absent in gnomAD but predicted to be pathogenic by ≤2 tools were considered potential false positives. Three of these variants were characterized functionally using whole-cell patch clamp technique. Overall, there were 244 KCNQ1 case-derived MVs. Of these, 29 (12%) were seen in ≥10 individuals in gnomAD and are demotable. However, 157 of 244 MVs (64%) were absent in gnomAD. Of these, 7 (4%) were predicted to be pathogenic by ≤2 tools, 3 of which we characterized functionally. There was no significant difference in current density between heterozygous KCNQ1-F127L, -P477L, or -L619M variant-containing channels compared to KCNQ1-WT. This study offers preliminary evidence for the demotion of 32 (13%) previously published LQT1 MVs. Of these, 29 were demoted because of their frequent sighting in gnomAD. Additionally, in silico analysis and in vitro functional studies have facilitated the demotion of 3 ultra-rare MVs (F127L, P477L, L619M). Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  15. Happiness and health across the lifespan in five major cities: The impact of place and government performance.

    Science.gov (United States)

    Hogan, Michael J; Leyden, Kevin M; Conway, Ronan; Goldberg, Abraham; Walsh, Deirdre; McKenna-Plumley, Phoebe E

    2016-08-01

    A growing body of research suggests that urban design has an effect on health and well-being. There have been very few studies to date, however, that compare these effects across the lifespan. The current study examines the direct and indirect effects of the city environment on happiness. It was hypothesised that citizens' ratings of their city along dimensions of performance (e.g., basic - usually government - services related to education, healthcare, social services, and policing) and place (e.g., the beauty of the city and a built environment that provides access to cultural, sport, park, transport, and shopping amenities) would be significant predictors of happiness but that the nature of these effects would change over the lifespan. 5000 adults aged 25-85 years old living in Berlin, Paris, London, New York, and Toronto completed the Quality of Life Survey in 2007. Respondents reported their happiness levels and evaluated their city along place and performance dimensions. The results of the study demonstrate an interesting, and complex relationship between the city environment and happiness of residents across the lifespan. Findings suggest that the happiness of younger residents is a function of having easy access to cultural, shopping, transport, parks and sport amenities and the attractiveness of their cities (i.e. place variables). The happiness of older residents is associated more with the provision of quality governmental services (i.e., performance variables). Place and performance variables also have an effect on health and social connections, which are strongly linked to happiness for all residents. Younger adults' happiness is more strongly related to the accessibility of amenities that add to the quality of a city's cultural and place characteristics; older adults' happiness is more strongly related to the quality of services provided within a city that enable residents to age in place. These results indicate that, in order to be all things to all

  16. Which HRM practices enhance employee outcomes at work across the life-span?

    NARCIS (Netherlands)

    Veth, Klaske; Korzilius, Hubert P.L.M.; van der Heijden, Beatrice I.J.M.; Emans, Ben; de Lange, Annet H.

    Based on the social exchange theory and on ageing and life-span theories, this paper aims to examine: (1) the relationships between perceived availability and use of HRM practices, and employee outcomes (i.e. work engagement and employability); and (2) how employee age moderates these relationships.

  17. Which HRM practices enhance employee outcomes at work across the life-span?

    NARCIS (Netherlands)

    Veth, K.N.; Korzilius, H.P.L.M.; Heijden, B.I.J.M. van der; Lange, A.H. de; Emans, B.J.M.

    2017-01-01

    Based on the social exchange theory and on ageing and life-span theories, this paper aims to examine: (1) the relationships between perceived availability and use of HRM practices, and employee outcomes (i.e. work engagement and employability); and (2) how employee age moderates these relationships.

  18. Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

    Directory of Open Access Journals (Sweden)

    Laurent Kappeler

    2008-10-01

    Full Text Available Mutations that decrease insulin-like growth factor (IGF and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan.

  19. Differences in Binding and Monitoring Mechanisms Contribute to Lifespan Age Differences in False Memory

    Science.gov (United States)

    Fandakova, Yana; Shing, Yee Lee; Lindenberger, Ulman

    2013-01-01

    Based on a 2-component framework of episodic memory development across the lifespan (Shing & Lindenberger, 2011), we examined the contribution of memory-related binding and monitoring processes to false memory susceptibility in childhood and old age. We administered a repeated continuous recognition task to children (N = 20, 10-12 years),…

  20. The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan.

    Science.gov (United States)

    Mittal, Nitish; Guimaraes, Joao C; Gross, Thomas; Schmidt, Alexander; Vina-Vilaseca, Arnau; Nedialkova, Danny D; Aeschimann, Florian; Leidel, Sebastian A; Spang, Anne; Zavolan, Mihaela

    2017-09-06

    In Saccharomyces cerevisiae, deletion of large ribosomal subunit protein-encoding genes increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the messenger RNA and protein abundance, ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes, some encoding ribosomal proteins, that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations, including ribosomal protein gene deletions, calorie restriction, and rapamycin treatment, and provide an explanation for its role in longevity and stress response.The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.

  1. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan

    Science.gov (United States)

    The relationship between lutein and zeaxanthin and visual and cognitive health throughout the lifespan is compelling. There is a variety of evidence to support a role for lutein and zeaxanthin in vision. Lutein's role in cognition has only recently been considered. Lutein and its isomer, zeaxanthin,...

  2. Lifespan Aging and Belief Reasoning: Influences of Executive Function and Social Cue Decoding

    Science.gov (United States)

    Phillips, Louise H.; Bull, Rebecca; Allen, Roy; Insch, Pauline; Burr, Kirsty; Ogg, Will

    2011-01-01

    Older adults often perform poorly on Theory of Mind (ToM) tests that require understanding of others' beliefs and intentions. The course and specificity of age changes in belief reasoning across the adult lifespan is unclear, as is the cause of the age effects. Cognitive and neuropsychological models predict that two types of processing might…

  3. Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways.

    Directory of Open Access Journals (Sweden)

    David E Shore

    Full Text Available Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60, the ER UPR (hsp-4, ROS response (sod-3, gst-4, and xenobiotic detoxification (gst-4. We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors.

  4. Age-related differences in cognition across the adult lifespan in autism spectrum disorder

    NARCIS (Netherlands)

    Lever, A.G.; Geurts, H.M.

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is

  5. Weak linear degeneracy and lifespan of classical solutions for first order quasilinear hyperbolic systems

    International Nuclear Information System (INIS)

    Li Tatsien

    1994-01-01

    By means of the concept of the weak linear degeneracy, one gets the global existence and the sharp estimate of the lifespan of C 1 solutions to the Cauchy problem for general first order quasilinear hyperbolic systems with small initial data with compact support. (author). 23 refs, 1 fig

  6. Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria.

    Science.gov (United States)

    Qian, Minxian; Liu, Zuojun; Peng, Linyuan; Tang, Xiaolong; Meng, Fanbiao; Ao, Ying; Zhou, Mingyan; Wang, Ming; Cao, Xinyue; Qin, Baoming; Wang, Zimei; Zhou, Zhongjun; Wang, Guangming; Gao, Zhengliang; Xu, Jun; Liu, Baohua

    2018-05-02

    DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans , but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases. © 2018, Qian et al.

  7. Gender separation increases somatic growth in females but does not affect lifespan in Nothobranchius furzeri.

    Directory of Open Access Journals (Sweden)

    Michael Graf

    2010-08-01

    Full Text Available According to life history theory, physiological and ecological traits and parameters influence an individual's life history and thus, ultimately, its lifespan. Mating and reproduction are costly activities, and in a variety of model organisms, a negative correlation of longevity and reproductive effort has been demonstrated. We are employing the annual killifish Nothobranchius furzeri as a vertebrate model for ageing. N. furzeri is the vertebrate displaying the shortest known lifespan in captivity with particular strains living only three to four months under optimal laboratory conditions. The animals show explosive growth, early sexual maturation and age-dependent physiological and behavioural decline. Here, we have used N. furzeri to investigate a potential reproduction-longevity trade-off in both sexes by means of gender separation. Though female reproductive effort and offspring investment were significantly reduced after separation, as investigated by analysis of clutch size, eggs in the ovaries and ovary mass, the energetic surplus was not reallocated towards somatic maintenance. In fact, a significant extension of lifespan could not be observed in either sex. This is despite the fact that separated females, but not males, grew significantly larger and heavier than the respective controls. Therefore, it remains elusive whether lifespan of an annual species evolved in periodically vanishing habitats can be prolonged on the cost of reproduction at all.

  8. Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16

    Directory of Open Access Journals (Sweden)

    Wim Wätjen

    2013-06-01

    Full Text Available Myricetin is a naturally occurring flavonol found in many plant based food sources. It increases the lifespan of Caenorhabditis elegans, but the molecular mechanisms are not yet fully understood. We have investigated the impact of this flavonoid on the transcription factors DAF-16 (C. elegans FoxO homologue and SKN-1 (Nrf2 homologue, which have crucial functions in the regulation of ageing. Myricetin is rapidly assimilated by the nematode, causes a nuclear translocation of DAF-16 but not of SKN-1, and finally prolongs the mean adult lifespan of C. elegans by 32.9%. The lifespan prolongation was associated with a decrease in the accumulation of reactive oxygen species (ROS detected by DCF. Myricetin also decreases the formation of lipofuscin, a pigment consisting of highly oxidized and cross-linked proteins that is considered as a biomarker of ageing in diverse species. The lifespan extension was completely abolished in a daf-16 loss-of-function mutant strain (CF1038. Consistently with this result, myricetin was also not able to diminish stress-induced ROS accumulation in the mutant. These results strongly indicate that the pro-longevity effect of myricetin is dependent on DAF-16 and not on direct anti-oxidative effects of the flavonoid.

  9. Sexuality and Developmental Disability: Obstacles to Healthy Sexuality throughout the Lifespan

    Science.gov (United States)

    Richards, Deborah; Miodrag, Nancy; Watson, Shelley L.

    2006-01-01

    This paper presents a lifespan perspective of sexuality issues for individuals with developmental disabilities. Individuals with developmental disabilities are human beings who have historically been denied the right to express their sexuality or engage in sexual relationships due to misconceptions or negative attitudes. Using a hypothetical case…

  10. Cognitive Creative Abilities and Self-Esteem across the Adult Life-Span.

    Science.gov (United States)

    Jaquish, Gail A.; Ripple, Richard E.

    1981-01-01

    Explored the relationship between divergent thinking and self-esteem across the adult lifespan. Subjects from 18 to 84 years of age responded to a self-esteem inventory and an exercise in divergent thinking. Self-esteem predicted divergent thinking across age groups, whereas age differences accounted for little variance in divergent thinking.…

  11. Qualitative Exploration of Acculturation and Life-Span Issues of Elderly Asian Americans

    Science.gov (United States)

    Lee, Jee Hyang; Heo, Nanseol; Lu, Junfei; Portman, Tarrell Awe Agahe

    2013-01-01

    Awareness of aging issues across diverse populations begins the journey toward counselors becoming culturally competent across client life spans. Understanding the life-span experiences of cultural groups is important for helping professionals. The purpose of this research was to gain insight into the qualitative experiences of Asian American…

  12. On the genetic mechanisms of nutrient-dependent lifespan and reproduction

    NARCIS (Netherlands)

    Zandveld, Jelle

    2017-01-01

    Dietary restriction (DR), a moderate reduction in nutrient intake, improves health or extends lifespan across many species. Moreover, recent insights have shown that also the effects of specific nutrients are of importance for the beneficial effects of DR rather than intake alone. However, we

  13. Beat Synchronization across the Lifespan: Intersection of Development and Musical Experience

    OpenAIRE

    Thompson, Elaine C.; White-Schwoch, Travis; Tierney, Adam; Kraus, Nina

    2015-01-01

    Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance ...

  14. Whole lifespan microscopic observation of budding yeast aging through a microfluidic dissection platform

    NARCIS (Netherlands)

    Lee, Sung Sik; Avalos Vizcarra, Ima; Huberts, Daphne H E W; Lee, Luke P; Heinemann, Matthias

    2012-01-01

    Important insights into aging have been generated with the genetically tractable and short-lived budding yeast. However, it is still impossible today to continuously track cells by high-resolution microscopic imaging (e.g., fluorescent imaging) throughout their entire lifespan. Instead, the field

  15. Mental illness and mental health: The two continua model across the lifespan

    NARCIS (Netherlands)

    Westerhof, Gerben Johan; Keyes, Cory L.M.

    2010-01-01

    Mental health has long been defined as the absence of psychopathologies, such as depression and anxiety. The absence of mental illness, however, is a minimal outcome from a psychological perspective on lifespan development. This article therefore focuses on mental illness as well as on three core

  16. Epigenetic Effects of Diet on Fruit Fly Lifespan: An Investigation to Teach Epigenetics to Biology Students

    Science.gov (United States)

    Billingsley, James; Carlson, Kimberly A.

    2010-01-01

    Do our genes exclusively control us, or are other factors at play? Epigenetics can provide a means for students to use inquiry-based methods to understand a complex biological concept. Students research and design an experiment testing whether dietary supplements affect the lifespan of Drosophila melanogaster over multiple generations.

  17. CAMKII and calcineurin regulate the lifespan of Caenorhabditis elegans through the FOXO transcription factor DAF-16.

    Science.gov (United States)

    Tao, Li; Xie, Qi; Ding, Yue-He; Li, Shang-Tong; Peng, Shengyi; Zhang, Yan-Ping; Tan, Dan; Yuan, Zengqiang; Dong, Meng-Qiu

    2013-06-25

    The insulin-like signaling pathway maintains a relatively short wild-type lifespan in Caenorhabditis elegans by phosphorylating and inactivating DAF-16, the ortholog of the FOXO transcription factors of mammalian cells. DAF-16 is phosphorylated by the AKT kinases, preventing its nuclear translocation. Calcineurin (PP2B phosphatase) also limits the lifespan of C. elegans, but the mechanism through which it does so is unknown. Herein, we show that TAX-6•CNB-1 and UNC-43, the C. elegans Calcineurin and Ca(2+)/calmodulin-dependent kinase type II (CAMKII) orthologs, respectively, also regulate lifespan through DAF-16. Moreover, UNC-43 regulates DAF-16 in response to various stress conditions, including starvation, heat or oxidative stress, and cooperatively contributes to lifespan regulation by insulin signaling. However, unlike insulin signaling, UNC-43 phosphorylates and activates DAF-16, thus promoting its nuclear localization. The phosphorylation of DAF-16 at S286 by UNC-43 is removed by TAX-6•CNB-1, leading to DAF-16 inactivation. Mammalian FOXO3 is also regulated by CAMKIIA and Calcineurin. DOI:http://dx.doi.org/10.7554/eLife.00518.001.

  18. Vocabulary Skills in Adulthood: Longitudinal Relations with Cognitive and Personality Measures Across the Life-Span

    Czech Academy of Sciences Publication Activity Database

    Smolík, Filip; Blatný, Marek; Jelínek, Martin; Millová, Katarína; Sobotková, Veronika

    2016-01-01

    Roč. 60, č. 2 (2016), s. 97-105 ISSN 0009-062X R&D Projects: GA ČR GAP407/10/2410 Institutional support: RVO:68081740 Keywords : vocabulary * personality * life-span development * verbal IQ Subject RIV: AN - Psychology Impact factor: 0.242, year: 2016

  19. The Insulation for Machines Having a High Lifespan Expectancy, Design, Tests and Acceptance Criteria Issues

    Directory of Open Access Journals (Sweden)

    Olivier Barré

    2017-02-01

    Full Text Available The windings insulation of electrical machines will remain a topic that is updated frequently. The criteria severity requested by the electrical machine applications increases continuously. Manufacturers and designers are always confronted with new requirements or new criteria with enhanced performances. The most problematic requirements that will be investigated here are the extremely long lifespan coupled to critical operating conditions (overload, supply grid instabilities, and critical operating environments. Increasing lifespan does not have a considerable benefit because the purchasing price of usual machines has to be compared to the purchasing price and maintenance price of long lifespan machines. A machine having a 40-year lifespan will cost more than twice the usual price of a 20-year lifetime machine. Systems which need a long lifetime are systems which are crucial for a country, and those for which outage costs are exorbitant. Nuclear power stations are such systems. It is certain that the used technologies have evolved since the first nuclear power plant, but they cannot evolve as quickly as in other sectors of activities. No-one wants to use an immature technology in such power plants. Even if the electrical machines have exceeded 100 years of age, their improvements are linked to a patient and continuous work. Nowadays, the windings insulation systems have a well-established structure, especially high voltage windings. Unfortunately, a high life span is not only linked to this result. Several manufacturers’ improvements induced by many years of experiment have led to the writing of standards that help the customers and the manufacturers to regularly enhance the insulation specifications or qualifications. Hence, in this publication, the authors will give a step by step exhaustive review of one insulation layout and will take time to give a detailed report on the standards that are linked to insulation systems. No standard can

  20. Obesity Reduces Cognitive and Motor Functions across the Lifespan

    OpenAIRE

    Wang, Chuanming; Chan, John S. Y.; Ren, Lijie; Yan, Jin H.

    2016-01-01

    Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has ...

  1. Tissue characteristics of high- and low-incidence plutonium-induced osteogenic sarcoma sites in life-span beagles

    International Nuclear Information System (INIS)

    Miller, S.C.; Jee, W.S.S.; Smith, J.M.; Wronski, T.J.

    1986-01-01

    On the basis of information gathered from the 239 Pu life-span study in beagles at the University of Utah, the tissue features were found to be characteristic of high-incidence bone-tumor sites compared to low-incidence sites included more hematopoietic tissues in the bone marrow; greater trabecular bone mass; greater bone remodeling rates; greater mineral apposition rates; greater density and activity of bone surface cells; greater density of putative bone-cell precursors; greater initial uptake of plutonium on bone surfaces; and greater marrow vascular volumes and a venous sinusoidal bed. Although most of these studies are not yet complete, the information being collected should contribute to our understanding of the mechanisms of radiation-induced osteogenic sarcomas. This should aid in predicting the types and characteristics of osseous tissues where radiation-induced osteogenic sarcomas may arise in humans. 25 refs., 4 figs., 3 tabs

  2. Extension of Drosophila lifespan by Rhodiola rosea through a mechanism independent from dietary restriction.

    Directory of Open Access Journals (Sweden)

    Samuel E Schriner

    Full Text Available Rhodiola rosea has been extensively used to improve physical and mental performance and to protect against stress. We, and others, have reported that R. rosea can extend lifespan in flies, worms, and yeast. However, its molecular mechanism is currently unknown. Here, we tested whether R. rosea might act through a pathway related to dietary restriction (DR that can extend lifespan in a range of model organisms. While the mechanism of DR itself is also unknown, three molecular pathways have been associated with it: the silent information regulator 2 (SIR2 proteins, insulin and insulin-like growth factor signaling (IIS, and the target of rapamycin (TOR. In flies, DR is implemented through a reduction in dietary yeast content. We found that R. rosea extract extended lifespan in both sexes independent of the yeast content in the diet. We also found that the extract extended lifespan when the SIR2, IIS, or TOR pathways were genetically perturbed. Upon examination of water and fat content, we found that R. rosea decreased water content and elevated fat content in both sexes, but did not sensitize flies to desiccation or protect them against starvation. There were some sex-specific differences in response to R. rosea. In female flies, the expression levels of glycolytic genes and dSir2 were down-regulated, and NADH levels were decreased. In males however, R. rosea provided no protection against heat stress and had no effect on the major heat shock protein HSP70 and actually down-regulated the mitochondrial HSP22. Our findings largely rule out an elevated general resistance to stress and DR-related pathways as mechanistic candidates. The latter conclusion is especially relevant given the limited potential for DR to improve human health and lifespan, and presents R. rosea as a potential viable candidate to treat aging and age-related diseases in humans.

  3. Which surgery should be offered for carpal tunnel syndrome in a patient who was previously treated for recurrence on the contralateral side? Preliminary study of 13 patients with the Canaletto® implant.

    Science.gov (United States)

    Illuminati, I; Seigle-Murandi, F; Gouzou, S; Fabacher, T; Facca, S; Hidalgo Diaz, J J; Liverneaux, P

    2017-12-01

    There are no published studies on the management of carpal tunnel syndrome (CTS) patients who have already been operated for recurrent CTS on the contralateral side. The aim of this study was to evaluate 13 patients with CTS who underwent primary release using a Canaletto ® implant. The 13 patients had all been operated for recurrent CTS previously. On the contralateral side, they all had subjective signs, and two of them already had complications. All were operated with the Canaletto ® implant according to Duché's technique, in a mean of 20minutes. After a mean 19.3-month follow-up, paresthesia, pain, and QuickDASH scores were significantly improved, even in one patient who underwent revision at another facility. This preliminary study suggests that use of a Canaletto ® implant as first-line treatment for CTS in patients who already underwent revision surgery on the other side is a simple and safe technique, without worsening of symptoms. These findings should be assessed with a prospective randomized controlled trial. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

  4. Physical activity, sleep quality, and self-reported fatigue across the adult lifespan.

    Science.gov (United States)

    Christie, Anita D; Seery, Emily; Kent, Jane A

    2016-05-01

    Deteriorating sleep quality and increased fatigue are common complaints of old age, and poor sleep is associated with decreased quality of life and increased mortality rates. To date, little attention has been given to the potential effects of physical activity on sleep quality and fatigue in aging. The purpose of this study was to examine the relationships between activity, sleep and fatigue across the adult lifespan. Sixty community-dwelling adults were studied; 22 younger (21-29 years), 16 middle-aged (36-64 years), and 22 older (65-81 years). Physical activity was measured by accelerometer. Sleep quality was assessed using the Pittsburg Sleep Quality Index. Self-reported fatigue was evaluated with the Patient-Reported Outcomes Measurement Information System (PROMIS). Regression analysis revealed a positive relationship between activity and sleep quality in the older (r(2)=0.18, p=0.05), but not the younger (r(2) = 0.041, p = 0.35) or middle-aged (r(2) = 0.001, p = 0.93) groups. This association was mainly established by the relationship between moderate-vigorous activity and sleep quality (r(2)=0.37, p=0.003) in older adults. No association was observed between physical activity and self-reported fatigue in any of the groups (r(2) ≤ 0.14, p ≥ 0.15). However, an inverse relationship was found between sleep quality and fatigue in the older (r(2) = 0.29, p = 0.05), but not the younger or middle-aged (r(2) ≤ 0.13, p ≥ 0.10) groups. These results support the hypothesis that physical activity may be associated with sleep quality in older adults, and suggest that improved sleep may mitigate self-reported fatigue in older adults in a manner that is independent of activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases

    Science.gov (United States)

    Tang, Yingzhi; Quan, Zhenzhen; Zhang, Zhe; Oliver, Stephen G.; Zhang, Nianshu

    2016-01-01

    Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding ‘signaling’ proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways. The CLS of these signaling mutants, and those of the single, double and triple mutants of RIM15, YAK1 and MCK1 correlates well with the amount of storage carbohydrates but poorly with transition-phase cell cycle status. Combined removal of the glycogen and trehalose biosynthetic genes, especially GSY2 and TPS1, nearly abolishes the accumulation of storage carbohydrates and severely reduces CLS. Concurrent overexpression of GSY2 and TSL1 or supplementation of trehalose to the growth medium ameliorates the severe CLS defects displayed by the signaling mutants (rim15Δyak1Δ or rim15Δmck1Δ). Furthermore, we reveal that the levels of intracellular reactive oxygen species are cooperatively controlled by Yak1, Rim15 and Mck1, and the three kinases mediate the TOR1-regulated accumulation of storage carbohydrates and CLS extension. Our data support the hypothesis that metabolic reprogramming to accumulate energy stores and the activation of anti-oxidant defence systems are coordinated by Yak1, Rim15 and Mck1 kinases to ensure quiescence entry and lifespan extension in yeast. PMID:27923067

  6. A Lifespan Perspective on Entrepreneurship: Perceived Opportunities and Skills Explain the Negative Association between Age and Entrepreneurial Activity.

    Science.gov (United States)

    Bohlmann, Clarissa; Rauch, Andreas; Zacher, Hannes

    2017-01-01

    Researchers and practitioners are increasingly interested in entrepreneurship as a means to fight youth unemployment and to improve financial stability at higher ages. However, only few studies so far have examined the association between age and entrepreneurial activity. Based on theories from the lifespan psychology literature and entrepreneurship, we develop and test a model in which perceived opportunities and skills explain the relationship between age and entrepreneurial activity. We analyzed data from the 2013 Global Entrepreneurship Monitor (GEM), while controlling for gender and potential variation between countries. Results showed that age related negatively to entrepreneurial activity, and that perceived opportunities and skills for entrepreneurship mediated this relationship. Overall, these findings suggest that entrepreneurship research should treat age as a substantial variable.

  7. EEG correlates of visual short-term memory in older age vary with adult lifespan cognitive development

    DEFF Research Database (Denmark)

    Wiegand, Iris; Lauritzen, Martin J.; Osler, Merete

    2018-01-01

    Visual short-term memory (vSTM) is a cognitive resource that declines with age. This study investigated whether electroencephalography (EEG) correlates of vSTM vary with cognitive development over individuals' lifespan. We measured vSTM performance and EEG in a lateralized whole-report task...... in a healthy birth cohort, whose cognitive function (intelligence quotient) was assessed in youth and late-middle age. Higher vSTM capacity (K; measured by Bundesen's theory of visual attention) was associated with higher amplitudes of the contralateral delay activity (CDA) and the central positivity (CP......). In addition, rightward hemifield asymmetry of vSTM (Kλ) was associated with lower CDA amplitudes. Furthermore, more severe cognitive decline from young adulthood to late-middle age predicted higher CDA amplitudes, and the relationship between K and the CDA was less reliable in individuals who show higher...

  8. Effect of gamma rays on sex ratio, emergence and lifespan of cucurbits fruit fly dacus ciliatus (low) irradiated as pupae

    International Nuclear Information System (INIS)

    Al-Shmmary, A. J. M.; Al-Taweel, A. A.; Ahmed, R. F.

    2012-12-01

    The result showed the pupae at the age 1 or 2 days old was very sensitive to all doses of gamma rays, the percentage of adults emerged was zero at the dose of 45 gray and highest and the gigh percentage of adults emergence was recorded when the pupae irradiated at five days ald and the mean percentage of emerged adults was approximated with that of the control group. This study also showed that there was an effect of gamma radiation on the average percentage of deformed at adult stage and it was about 1:1 (male: female). On the other hand, the mean lifespan of females and mice s adult were decreased as the dose of gamma rays increases and the pupae irradiated at youngest ages. The longest life span of females was recorded when the pipa irradiated at five days old with any of the gamma rays dose. (Author)

  9. A Lifespan Perspective on Entrepreneurship: Perceived Opportunities and Skills Explain the Negative Association between Age and Entrepreneurial Activity

    Directory of Open Access Journals (Sweden)

    Clarissa Bohlmann

    2017-12-01

    Full Text Available Researchers and practitioners are increasingly interested in entrepreneurship as a means to fight youth unemployment and to improve financial stability at higher ages. However, only few studies so far have examined the association between age and entrepreneurial activity. Based on theories from the lifespan psychology literature and entrepreneurship, we develop and test a model in which perceived opportunities and skills explain the relationship between age and entrepreneurial activity. We analyzed data from the 2013 Global Entrepreneurship Monitor (GEM, while controlling for gender and potential variation between countries. Results showed that age related negatively to entrepreneurial activity, and that perceived opportunities and skills for entrepreneurship mediated this relationship. Overall, these findings suggest that entrepreneurship research should treat age as a substantial variable.

  10. A Lifespan Perspective on Entrepreneurship: Perceived Opportunities and Skills Explain the Negative Association between Age and Entrepreneurial Activity

    Science.gov (United States)

    Bohlmann, Clarissa; Rauch, Andreas; Zacher, Hannes

    2017-01-01

    Researchers and practitioners are increasingly interested in entrepreneurship as a means to fight youth unemployment and to improve financial stability at higher ages. However, only few studies so far have examined the association between age and entrepreneurial activity. Based on theories from the lifespan psychology literature and entrepreneurship, we develop and test a model in which perceived opportunities and skills explain the relationship between age and entrepreneurial activity. We analyzed data from the 2013 Global Entrepreneurship Monitor (GEM), while controlling for gender and potential variation between countries. Results showed that age related negatively to entrepreneurial activity, and that perceived opportunities and skills for entrepreneurship mediated this relationship. Overall, these findings suggest that entrepreneurship research should treat age as a substantial variable. PMID:29250004

  11. Usefulness of indirect alcohol biomarkers for predicting recidivism of drunk-driving among previously convicted drunk-driving offenders: results from the recidivism of alcohol-impaired driving (ROAD) study.

    Science.gov (United States)

    Maenhout, Thomas M; Poll, Anneleen; Vermassen, Tijl; De Buyzere, Marc L; Delanghe, Joris R

    2014-01-01

    In several European countries, drivers under the influence (DUI), suspected of chronic alcohol abuse are referred for medical and psychological examination. This study (the ROAD study, or Recidivism Of Alcohol-impaired Driving) investigated the usefulness of indirect alcohol biomarkers for predicting drunk-driving recidivism in previously convicted drunk-driving offenders. The ROAD study is a prospective study (2009-13) that was performed on 517 randomly selected drivers in Belgium. They were convicted for drunk-driving for which their licence was confiscated. The initial post-arrest blood samples were collected and analysed for percentage carbohydrate-deficient transferrin (%CDT), transaminsase activities [alanine amino transferase (ALT), aspartate amino transferase (AST)], gamma-glutamyltransferase (γGT) and red cell mean corpuscular volume (MCV). The observation time for each driver was 3 years and dynamic. A logistic regression analysis revealed that ln(%CDT) (P drunk-driving. The ROAD index (which includes ln(%CDT), ln(γGT), -ln(ALT) and the sex of the driver) was calculated and had a significantly higher area under the receiver operator characteristic curve (0.71) than the individual biomarkers for drunk-driving recidivism. Drivers with a high risk of recidivating (ROAD index ≥ 25%; third tertile) could be distinguished from drivers with an intermediate risk (16% ≤ ROAD index drunk-driving. The association with gamma-glutamyltransferase, alanine amino transferase and the sex of the driver could have additional value for identifying drunk-drivers at intermediate risk of recidivism. Non-specific indirect alcohol markers, such as alanine amino transferase, gamma-glutamyltransferase, aspartate amino transferase and red cell mean corpuscular volume have minimal added value to % carbohydrate-deficient transferrin for distinguishing drunk drivers with a low or high risk of recidivism. © 2013 Society for the Study of Addiction.

  12. Longevity studies in GenomEUtwin

    DEFF Research Database (Denmark)

    Skytthe, Axel; Pedersen, Nancy L; Kaprio, Jaakko

    2003-01-01

    Previous twin studies have indicated that approximately 25% of the variation in life span can be attributed to genetic factors and recent studies have also suggested a moderate clustering of extreme longevity within families. Here we discuss various definitions of extreme longevity and some...... analytical approaches with special attention to the challenges due to censored data. Lexis diagrams are provided for the Danish, Dutch, Finnish, Italian, Norwegian, and Swedish Twin registries hereby outlining possibilities for longevity studies within GenomEUtwin. We extend previous analyses of lifespan...

  13. Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan.

    Science.gov (United States)

    Roshina, Natalia V; Symonenko, Alexander V; Krementsova, Anna V; Trostnikov, Mikhail V; Pasyukova, Elena G

    2014-12-01

    Despite the progress in aging research that highlights the role of the nervous system in longevity, whether genes that control development and consequently structure of the nervous system affect lifespan is unclear. We demonstrated that a mutation inshuttle craft, a gene involved in the nervous system development, increased the lifespan of unmated females and decreased the lifespan of mated females, without affecting males. Precise reversions of the mutation lead to the restoration of the lifespan specific to control females. In mutant unmated females, increased lifespan was associated with elevated locomotion at older ages, indicating slowed aging. In mutant mated females, reproduction was decreased compared to controls, indicating a lack of tradeoff between this trait and lifespan. No differences in shuttle craft transcription were observed between whole bodies, ovaries, and brains of mutant and control females of different ages, either unmated or mated. The amount of shuttle craft transcript appeared to be substantially decreased in mutant embryos. Our results demonstrated that a gene that regulates development of the nervous system might also influence longevity, and thus expanded the spectrum of genes involved in lifespan control. We hypothesize that this "carry-over" effect might be the result of transcription regulation in embryos.

  14. Smoking Habits and Body Weight Over the Adult Lifespan in Postmenopausal Women.

    Science.gov (United States)

    Kabat, Geoffrey C; Heo, Moonseong; Allison, Matthew; Johnson, Karen C; Ho, Gloria Y F; Tindle, Hilary A; Asao, Keiko; LaMonte, Michael J; Giovino, Gary A; Rohan, Thomas E

    2017-03-01

    The inter-relationships between smoking habits and weight gain are complex. However, few studies have examined the association of smoking habits with weight gain over the life course. Major smoking parameters and weight gain over time were examined in a large cohort of postmenopausal women aged 50-79 years at enrollment between 1993 and 1998 (N=161,808) and followed through 2014 (analyses conducted in 2016). Cross-sectional analyses were used to assess the association of smoking and body weight at baseline. Retrospective data were used to correlate smoking status with body weight over a 45-year period prior to enrollment. In addition, the association of smoking with weight gain over 6 years of follow-up was examined. At baseline, women who had quit smoking prior to enrollment weighed 4.7 kg more than current smokers and 2.6 kg more than never smokers. Former, never, and current smokers all gained weight over the 45-year period from age 18 years to time of enrollment (average age, 63 years): 16.8, 16.4, and 14.6 kg, respectively. In prospective analyses, women who were current smokers at baseline but who quit smoking during follow-up gained more than 5 kg by Year 6 compared with current smokers at baseline who continued to smoke. Among long-term quitters, greater intensity of smoking and more recent quitting were associated with greater weight gain. These results suggest that excess weight gain associated with smoking cessation occurs soon after quitting and is modest relative to weight gain in never smokers over the adult lifespan. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Underestimation of Severity of Previous Whiplash Injuries

    Science.gov (United States)

    Naqui, SZH; Lovell, SJ; Lovell, ME

    2008-01-01

    INTRODUCTION We noted a report that more significant symptoms may be expressed after second whiplash injuries by a suggested cumulative effect, including degeneration. We wondered if patients were underestimating the severity of their earlier injury. PATIENTS AND METHODS We studied recent medicolegal reports, to assess subjects with a second whiplash injury. They had been asked whether their earlier injury was worse, the same or lesser in severity. RESULTS From the study cohort, 101 patients (87%) felt that they had fully recovered from their first injury and 15 (13%) had not. Seventy-six subjects considered their first injury of lesser severity, 24 worse and 16 the same. Of the 24 that felt the violence of their first accident was worse, only 8 had worse symptoms, and 16 felt their symptoms were mainly the same or less than their symptoms from their second injury. Statistical analysis of the data revealed that the proportion of those claiming a difference who said the previous injury was lesser was 76% (95% CI 66–84%). The observed proportion with a lesser injury was considerably higher than the 50% anticipated. CONCLUSIONS We feel that subjects may underestimate the severity of an earlier injury and associated symptoms. Reasons for this may include secondary gain rather than any proposed cumulative effect. PMID:18201501

  16. Previous exposure in a high-risk area for travellers' diarrhoea within the past year is associated with a significant protective effect for travellers' diarrhoea: a prospective observational cohort study in travellers to South Asia.

    Science.gov (United States)

    Kuenzli, Esther; Juergensen, David; Kling, Kerstin; Jaeger, Veronika K; DeCrom, Susan; Steffen, Robert; Widmer, Andreas F; Battegay, Manuel; Hatz, Christoph; Neumayr, Andreas

    2017-09-01

    Travellers' diarrhoea is the most common health problem in travellers. Depending on the region visited, up to 40% of travellers develop diarrhoea during a 2-week trip. The aim of this study was to assess risk factors for TD among travellers to the Indian subcontinent. An observational prospective multicentre cohort study investigated travellers to the Indian subcontinent. Participants completed questionnaires assessing the incidence of travellers' diarrhoea and identifying potential risk factors. Covariates were assessed univariately, followed by a multivariate regression. Two-hundred and twenty-six travellers were enrolled into the study, 178 filled in both pre- and post-travel questionnaires. Overall, the attack rate of travellers' diarrhoea was 38.2%. Travel destination is a key risk factor for the occurrence of TD. Travelling to India or Nepal vs Bhutan is associated with an increased risk for TD (OR 6.68 and 6.62, respectively). A length of stay of more than 3 weeks compared to less than 2 weeks is also associated with a significantly increased risk (OR 5.45). Having stayed in a high-risk area for travellers' diarrhoea within the past year before the current trip is associated with a significantly decreased risk (OR 0.19). No association was found between consumption of high risk food (i.e. tap water, ice cream, raw meat and hamburgers) and travellers' diarrhoea. Travellers' diarrhoea is a frequent problem in travellers to the Indian subcontinent. Previous exposure in a high-risk area for travellers' diarrhoea within the past year appears to have a significant protective effect. Furthermore, an association between the occurrence of travellers' diarrhoea and travel destination and length of stay, respectively, was observed. Consumption of risk food did not confer a TD risk in our study. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  17. Myocardial adaption to HI(R)T in previously untrained men with a randomized, longitudinal cardiac MR imaging study (Physical adaptions in Untrained on Strength and Heart trial, PUSH-trial).

    Science.gov (United States)

    Scharf, Michael; Oezdemir, Derya; Schmid, Axel; Kemmler, Wolfgang; von Stengel, Simon; May, Matthias S; Uder, Michael; Lell, Michael M

    2017-01-01

    Although musculoskeletal effects in resistance training are well described, little is known about structural and functional cardiac adaption in formerly untrained subjects. We prospectively evaluated whether short term high intensity (resistance) training (HI(R)T) induces detectable morphologic cardiac changes in previously untrained men in a randomized controlled magnetic resonance imaging (MRI) study. 80 untrained middle-aged men were randomly assigned to a HI(R)T-group (n = 40; 43.5±5.9 years) or an inactive control group (n = 40; 42.0±6.3 years). HI(R)T comprised 22 weeks of training focusing on a single-set to failure protocol in 2-3 sessions/week, each with 10-13 exercises addressing main muscle groups. Repetitions were decreased from 8-10 to 3-5 during study period. Before and after HI(R)T all subjects underwent physiologic examination and cardiac MRI (cine imaging, tagging). Indexed left (LV) and right ventricular (RV) volume (LV: 76.8±15.6 to 78.7±14.8 ml/m2; RV: 77.0±15.5 to 78.7±15.1 ml/m2) and mass (LV: 55.5±9.7 to 57.0±8.8 g/m2; RV: 14.6±3.0 to 15.0±2.9 g/m2) significantly increased with HI(R)T (all pHI(R)T-group did not alter with training (0.73g/mL and 0.19g/mL, respectively [p = 0.96 and p = 0.87]), indicating balanced cardiac adaption. Indexed LV (48.4±11.1 to 50.8±11.0 ml/m2) and RV (48.5±11.0 to 50.6±10.7 ml/m2) stroke volume significantly increased with HI(R)T (pHI(R)T (36.2±7.9 to 37.0±8.4 ml/m2, p = 0.411), the ratio to end-diastolic LV volume at baseline and post-training was unchanged (0.47 vs. 0.47, p = 0.79). 22 weeks of HI(R)T lead to measurable, physiological changes in cardiac atrial and ventricular morphologic characteristics and function in previously untrained men. The PUSH-trial is registered at the US National Institutes of Health (ClinicalTrials.gov), NCT01766791.

  18. Extending the lifespan of nuclear power plant structures

    International Nuclear Information System (INIS)

    Naus, D.J.; Oland, C.B.; Ellingwood, B.

    1995-01-01

    By the end of this decade, 63 of the 111 commercial nuclear power plants in the United States will be more than 20 years old, with some nearing the end of their 40-year operating license term. Faced with the prospect of having to replace lost generating capacity from other sources and substantial shutdown and decommissioning costs, many utilities are expected to apply to continue the service of their plants past the initial licensing period. In support of such applications, evidence should be provided that the capacity of the safety-related systems and structures to mitigate potential extreme events has not deteriorated unacceptably due to either aging or environmental stressor effects during the previous service history

  19. Obesity Reduces Cognitive and Motor Functions across the Lifespan

    Science.gov (United States)

    Wang, Chuanming; Chan, John S. Y.; Ren, Lijie; Yan, Jin H.

    2016-01-01

    Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised. PMID:26881095

  20. Obesity Reduces Cognitive and Motor Functions across the Lifespan.

    Science.gov (United States)

    Wang, Chuanming; Chan, John S Y; Ren, Lijie; Yan, Jin H

    2016-01-01

    Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised.

  1. Obesity Reduces Cognitive and Motor Functions across the Lifespan

    Directory of Open Access Journals (Sweden)

    Chuanming Wang

    2016-01-01

    Full Text Available Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised.

  2. Active Hexose Correlated Compound Extends the Lifespan and Increases the Thermotolerance of Nematodes

    Directory of Open Access Journals (Sweden)

    Tetsuya Okuyama

    2013-06-01

    Full Text Available ABSTRACTBackground: Active hexose correlated compound (AHCC is the extract from cultured mycelia of Lentinula edodes, a species of Basidiomycetes mushroom. AHCC contains various polysaccharides, including partially acylated -1,4-glucan, which is one of its major constituents. The application of AHCC has been markedly increased in complementary and alternative medicine as a functional food because AHCC improved the prognosis of postoperative hepatocellular carcinoma patients. AHCC has anti-inflammatory and antioxidant effects, such as the suppression of nitric oxide production in hepatocytes. AHCC might affect resistance to environmental stress, which is assumed to play a pivotal role in the longevity of many organisms.Objective: To investigate the effect of AHCC on longevity, we measured the lifespan of the nematode Caenorhabditis elegans, a model animal that is widely used to assess longevity. We also examined the effect of AHCC on resistance to heat stress, i.e., thermotolerance.Methods: The lifespan of C. elegans animals grown on media in the absence or presence of AHCC at 20°C was evaluated. Thermotolerance assays were performed at 35°C, the restrictive temperature of the animals. The effects of AHCC on lifespan and thermotolerance were analyzed with longevity mutants. Expression levels of stress-related genes, including heat shock genes, were measured by strand-specific reverse transcription-polymerase chain reaction after heat shock.Results: Wild-type C. elegans animals exhibited a longer mean lifespan by up to 10% in the presence of AHCC in the growth media than animals in the absence of AHCC. Furthermore, AHCC markedly increased thermotolerance at 35°C. Epistasis analyses showed that lifespan extension by AHCC at least partly required two longevity-promoting transcription factors: DAF-16 (C. elegans homolog of FOXO and HSF-1 (C. elegans homolog of heat shock transcription factor 1. After heat shock, AHCC activated the transcription

  3. Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans.

    Science.gov (United States)

    Li, Yan-Hui; Zhang, Gai-Gai

    2016-04-12

    DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation.

  4. Do "big guys" really die younger? An examination of height and lifespan in former professional basketball players.

    Science.gov (United States)

    Lemez, Srdjan; Wattie, Nick; Baker, Joseph

    2017-01-01

    While factors such as genetics may mediate the relationship between height and mortality, evidence suggests that larger body size may be an important risk indicator of reduced lifespan longevity in particular. This study critically examined this relationship in professional basketball players. We examined living and deceased players who have played in the National Basketball Association (debut between 1946-2010) and/or the American Basketball Association (1967-1976) using descriptive and Kaplan-Meier and Cox regression analyses. The cut-off date for death data collection was December 11, 2015. Overall, 3,901 living and deceased players were identified and had a mean height of 197.78 cm (± 9.29, Range: 160.02-231.14), and of those, 787 former players were identified as deceased with a mean height of 193.88 cm (± 8.83, Range: 167.6-228.6). Descriptive findings indicated that the tallest players (top 5%) died younger than the shortest players (bottom 5%) in all but one birth decade (1941-1950). Similarly, survival analyses showed a significant relationship between height and lifespan longevity when both dichotomizing [χ2 (1) = 13.04, p < .05] and trichotomizing [χ2 (2) = 18.05, p < .05] the predictor variable height per birth decade, where taller players had a significantly higher mortality risk compare