WorldWideScience

Sample records for premature aging phenotype

  1. NRMT1 knockout mice exhibit phenotypes associated with impaired DNA repair and premature aging.

    Science.gov (United States)

    Bonsignore, Lindsay A; Tooley, John G; Van Hoose, Patrick M; Wang, Eugenia; Cheng, Alan; Cole, Marsha P; Schaner Tooley, Christine E

    2015-03-01

    Though defective genome maintenance and DNA repair have long been known to promote phenotypes of premature aging, the role protein methylation plays in these processes is only now emerging. We have recently identified the first N-terminal methyltransferase, NRMT1, which regulates protein-DNA interactions and is necessary for both accurate mitotic division and nucleotide excision repair. To demonstrate if complete loss of NRMT1 subsequently resulted in developmental or aging phenotypes, we constructed the first NRMT1 knockout (Nrmt1(-/-)) mouse. The majority of these mice die shortly after birth. However, the ones that survive, exhibit decreased body size, female-specific infertility, kyphosis, decreased mitochondrial function, and early-onset liver degeneration; phenotypes characteristic of other mouse models deficient in DNA repair. The livers from Nrmt1(-/-) mice produce less reactive oxygen species (ROS) than wild type controls, and Nrmt1(-/-) mouse embryonic fibroblasts show a decreased capacity for handling oxidative damage. This indicates that decreased mitochondrial function may benefit Nrmt1(-/-) mice and protect them from excess internal ROS and subsequent DNA damage. These studies position the NRMT1 knockout mouse as a useful new system for studying the effects of genomic instability and defective DNA damage repair on organismal and tissue-specific aging.

  2. Premature aging syndrome.

    Science.gov (United States)

    Coppedè, Fabio

    2012-01-01

    Hutchinson-Gilford progeria syndrome and Werner syndrome are two of the best characterized human progeroid diseases with clinical features mimicking physiological aging at an early age. Both disorders have been the focus of intense research in recent years since they might provide insights into the pathology of normal human aging. The chapter contains a detailed description of the clinical features of both disorders and then it focuses on the genetics, the resulting biochemical alterations at the protein level and the most recent findings and hypotheses concerning the molecular basis of the premature aging phenotypes. A description of available diagnostic and therapeutic approaches is included.

  3. Phenotype-Dependent Coexpression Gene Clusters: Application to Normal and Premature Ageing.

    Science.gov (United States)

    Wang, Kun; Das, Avinash; Xiong, Zheng-Mei; Cao, Kan; Hannenhalli, Sridhar

    2015-01-01

    Hutchinson Gilford progeria syndrome (HGPS) is a rare genetic disease with symptoms of aging at a very early age. Its molecular basis is not entirely clear, although profound gene expression changes have been reported, and there are some known and other presumed overlaps with normal aging process. Identification of genes with agingor HGPS-associated expression changes is thus an important problem. However, standard regression approaches are currently unsuitable for this task due to limited sample sizes, thus motivating development of alternative approaches. Here, we report a novel iterative multiple regression approach that leverages co-expressed gene clusters to identify gene clusters whose expression co-varies with age and/or HGPS. We have applied our approach to novel RNA-seq profiles in fibroblast cell cultures at three different cellular ages, both from HGPS patients and normal samples. After establishing the robustness of our approach, we perform a comparative investigation of biological processes underlying normal aging and HGPS. Our results recapitulate previously known processes underlying aging as well as suggest numerous unique processes underlying aging and HGPS. The approach could also be useful in detecting phenotype-dependent co-expression gene clusters in other contexts with limited sample sizes.

  4. Premature ovarian failure : from phenotype to genotype

    NARCIS (Netherlands)

    Knauff, A.H.

    2009-01-01

    Postponement of childbearing has led to increased rates of age-related female subfertility. Age-related decreases in ovarian follicle numbers and decay in oocyte quality influence the natural loss of fecundity and ultimately the start of menopause. The rate of ovarian ageing is highly variable among

  5. Cloned Sheep May Age Prematurely

    Institute of Scientific and Technical Information of China (English)

    Joseph; B.Verrengia; 孙颖

    1999-01-01

    1996年的头条科技新闻之一是:多利羊被克隆成功。世人曾为消息雀跃,以为克隆技术马上可以造福人类了,而且科幻作家也开始忙碌起来。而今,当多利羊过3岁生日时,人们却伤感地发现: In Dolly’s case,she is 3,but her genetic material is aging at the rate of the6-year-old sheep from which she was cloned. 这就是所谓aging prematurely。这则消息给人们带来的忧虑有两条。一是:被克隆的动物的预期寿命比人们想象的要短;二是:人们是否能够有效利用克隆的人体细胞去治疗疾病。目前,科学家们的担心还是集中于后者。本书收入的另一篇有关克隆的文章(It’s A Boy!Scientists Clone First Male Mammal)和本篇构成了强烈的对照,可谓一喜一忧。然而,无论喜忧,人类在克隆技术方面正在以坚实的步伐向前迈进。

  6. Progeria: A rare genetic premature ageing disorder

    OpenAIRE

    Jitendra Kumar Sinha; Shampa Ghosh; Manchala Raghunath

    2014-01-01

    Progeria is characterized by clinical features that mimic premature ageing. Although the mutation responsible for this syndrome has been deciphered, the mechanism of its action remains elusive. Progeria research has gained momentum particularly in the last two decades because of the possibility of revealing evidences about the ageing process in normal and other pathophysiological conditions. Various experimental models, both in vivo and in vitro, have been developed in an effort to understand...

  7. Similar phenotype characteristics comparing familial and sporadic premature ovarian failure.

    NARCIS (Netherlands)

    Janse, F.; Knauff, E.A.; Niermeijer, M.F.; Eijkemans, M.J.; Laven, J.S.E.; Lambalk, C.B.; Fauser, B.C.J.M.; Goverde, A.J.

    2010-01-01

    OBJECTIVE: Premature ovarian failure (POF) is characterized by secondary amenorrhea before the age of 40 years, along with repeated increased follicle-stimulating hormone and low estrogen concentrations. POF is considered a complex genetic disease with a familial presentation in 12% to 50% of cases.

  8. Similar phenotype characteristics comparing familial and sporadic premature ovarian failure

    NARCIS (Netherlands)

    Janse, Femi; Knauff, Erik A. H.; Niermeijer, Martinus F.; Eijkemans, Marinus J.; Laven, Joop S. E.; Lambalk, Cornelius B.; Fauser, Bart C. J. M.; Goverde, Angelique J.; Hoek, Annemieke

    2010-01-01

    Objective: Premature ovarian failure (POF) is characterized by secondary amenorrhea before the age of 40 years, along with repeated increased follicle-stimulating hormone and low estrogen concentrations. POF is considered a complex genetic disease with a familial presentation in 12% to 50% of cases.

  9. Premature ovarian failure (POF): discordance between somatic and reproductive aging.

    Science.gov (United States)

    Pal, Lubna; Santoro, Nanette

    2002-06-01

    Premature ovarian failure (POF) is a unique example of isolated organ senescence, with a population prevalence of approximately 1%. Though the phenotypic expression of POF is similar to that of age-appropriate natural menopause, the underlying pathophysiological mechanisms are diverse and not entirely clear. The impact of POF on the patient is profound, with myriad ramifications, ranging from psychological devastation to multi-system implications of estrogen deprivation and its sequelae. The hastening of degenerative changes noted in these patients however, are not entirely ameliorated with estrogen replacement and POF may indeed represent an acceleration of the aging process.

  10. The epidemiology of premature aging and associated comorbidities

    Directory of Open Access Journals (Sweden)

    Coppedè F

    2013-08-01

    Full Text Available Fabio Coppedè Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy Abstract: Hutchinson–Gilford Progeria Syndrome and Werner syndrome, also known as childhood- and adulthood-progeria, respectively, represent two of the best characterized human progeroid diseases with clinical features mimicking physiological aging at an early age. The discovery of their genetic basis has led to the identification of several gene mutations leading to a spectrum of progeroid phenotypes ranging from moderate and mild–severe to very aggressive forms. In parallel, the creation of disease registers and databases provided available data for the design of relatively large-scale epidemiological studies, thereby allowing a better understanding of the nature and frequency of the premature aging-associated signs and symptoms. The aim of this article is to review the most recent findings concerning the epidemiology of premature aging disorders, their genetic basis, and the most recent reports on the frequency of associated diseases. Keywords: Hutchinson–Gilford Progeria Syndrome, Werner syndrome, premature aging disorders, epidemiology, cardiovascular diseases, cancer, atherosclerosis, genetics, sign and symptoms

  11. Premature and accelerated ageing: HIV or HAART?

    Directory of Open Access Journals (Sweden)

    Reuben Luke Smith

    2013-01-01

    Full Text Available Highly Active Anti-Retroviral Therapy (HAART has significantly increased life expectancy of the HIV-positive population. Nevertheless, the average lifespan of HIV patients remains shorter compared to uninfected individuals. Immunosenescence, a current explanation for this difference invokes heavily on viral stimulus despite HAART efficiency in viral suppression. We propose here that the premature and accelerated ageing of HIV patients can also be caused by adverse effects of antiretroviral drugs, specifically those that affect the mitochondria. The Nucleoside Reverse Transcriptase Inhibitor (NRTI antiretroviral drug class for instance, is known to cause depletion of mitochondrial DNA via inhibition of the mitochondrial specific DNA polymerase-ƴ. Besides NRTIs, other antiretroviral drug classes such as Protease Inhibitors also cause severe mitochondrial damage by increasing oxidative stress and diminishing mitochondrial function. We also discuss important areas for future research and argue in favour of the use of C. elegans as a novel model system for studying these effects.

  12. Progeria: a rare genetic premature ageing disorder.

    Science.gov (United States)

    Sinha, Jitendra Kumar; Ghosh, Shampa; Raghunath, Manchala

    2014-05-01

    Progeria is characterized by clinical features that mimic premature ageing. Although the mutation responsible for this syndrome has been deciphered, the mechanism of its action remains elusive. Progeria research has gained momentum particularly in the last two decades because of the possibility of revealing evidences about the ageing process in normal and other pathophysiological conditions. Various experimental models, both in vivo and in vitro, have been developed in an effort to understand the cellular and molecular basis of a number of clinically heterogeneous rare genetic disorders that come under the umbrella of progeroid syndromes (PSs). As per the latest clinical trial reports, Lonafarnib, a farnesyltranferase inhibitor, is a potent 'drug of hope' for Hutchinson-Gilford progeria syndrome (HGPS) and has been successful in facilitating weight gain and improving cardiovascular and skeletal pathologies in progeroid children. This can be considered as the dawn of a new era in progeria research and thus, an apt time to review the research developments in this area highlighting the molecular aspects, experimental models, promising drugs in trial and their implications to gain a better understanding of PSs.

  13. Progeria: A rare genetic premature ageing disorder

    Directory of Open Access Journals (Sweden)

    Jitendra Kumar Sinha

    2014-01-01

    Full Text Available Progeria is characterized by clinical features that mimic premature ageing. Although the mutation responsible for this syndrome has been deciphered, the mechanism of its action remains elusive. Progeria research has gained momentum particularly in the last two decades because of the possibility of revealing evidences about the ageing process in normal and other pathophysiological conditions. Various experimental models, both in vivo and in vitro, have been developed in an effort to understand the cellular and molecular basis of a number of clinically heterogeneous rare genetic disorders that come under the umbrella of progeroid syndromes (PSs. As per the latest clinical trial reports, Lonafarnib, a farnesyltranferase inhibitor, is a potent ′drug of hope′ for Hutchinson-Gilford progeria syndrome (HGPS and has been successful in facilitating weight gain and improving cardiovascular and skeletal pathologies in progeroid children. This can be considered as the dawn of a new era in progeria research and thus, an apt time to review the research developments in this area highlighting the molecular aspects, experimental models, promising drugs in trial and their implications to gain a better understanding of PSs.

  14. Premature aging in telomerase-deficient zebrafish

    Directory of Open Access Journals (Sweden)

    Monique Anchelin

    2013-09-01

    The study of telomere biology is crucial to the understanding of aging and cancer. In the pursuit of greater knowledge in the field of human telomere biology, the mouse has been used extensively as a model. However, there are fundamental differences between mouse and human cells. Therefore, additional models are required. In light of this, we have characterized telomerase-deficient zebrafish (Danio rerio as the second vertebrate model for human telomerase-driven diseases. We found that telomerase-deficient zebrafish show p53-dependent premature aging and reduced lifespan in the first generation, as occurs in humans but not in mice, probably reflecting the similar telomere length in fish and humans. Among these aging symptoms, spinal curvature, liver and retina degeneration, and infertility were the most remarkable. Although the second-generation embryos died in early developmental stages, restoration of telomerase activity rescued telomere length and survival, indicating that telomerase dosage is crucial. Importantly, this model also reproduces the disease anticipation observed in humans with dyskeratosis congenita (DC. Thus, telomerase haploinsufficiency leads to anticipation phenomenon in longevity, which is related to telomere shortening and, specifically, with the proportion of short telomeres. Furthermore, p53 was induced by telomere attrition, leading to growth arrest and apoptosis. Importantly, genetic inhibition of p53 rescued the adverse effects of telomere loss, indicating that the molecular mechanisms induced by telomere shortening are conserved from fish to mammals. The partial rescue of telomere length and longevity by restoration of telomerase activity, together with the feasibility of the zebrafish for high-throughput chemical screening, both point to the usefulness of this model for the discovery of new drugs able to reactivate telomerase in individuals with DC.

  15. Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome

    Science.gov (United States)

    Heyn, Holger; Moran, Sebastian; Esteller, Manel

    2013-01-01

    DNA methylation gradiently changes with age and is likely to be involved in aging-related processes with subsequent phenotype changes and increased susceptibility to certain diseases. The Hutchinson-Gilford Progeria (HGP) and Werner Syndrome (WS) are two premature aging diseases showing features of common natural aging early in life. Mutations in the LMNA and WRN genes were associated to disease onset; however, for a subset of patients the underlying causative mechanisms remain elusive. We aimed to evaluate the role of epigenetic alteration on premature aging diseases by performing comprehensive DNA methylation profiling of HGP and WS patients. We observed profound changes in the DNA methylation landscapes of WRN and LMNA mutant patients, which were narrowed down to a set of aging related genes and processes. Although of low overall variance, non-mutant patients revealed differential DNA methylation at distinct loci. Hence, we propose DNA methylation to have an impact on premature aging diseases. PMID:23257959

  16. Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome.

    Science.gov (United States)

    Heyn, Holger; Moran, Sebastian; Esteller, Manel

    2013-01-01

    DNA methylation gradiently changes with age and is likely to be involved in aging-related processes with subsequent phenotype changes and increased susceptibility to certain diseases. The Hutchinson-Gilford Progeria (HGP) and Werner Syndrome (WS) are two premature aging diseases showing features of common natural aging early in life. Mutations in the LMNA and WRN genes were associated to disease onset; however, for a subset of patients the underlying causative mechanisms remain elusive. We aimed to evaluate the role of epigenetic alteration on premature aging diseases by performing comprehensive DNA methylation profiling of HGP and WS patients. We observed profound changes in the DNA methylation landscapes of WRN and LMNA mutant patients, which were narrowed down to a set of aging related genes and processes. Although of low overall variance, non-mutant patients revealed differential DNA methylation at distinct loci. Hence, we propose DNA methylation to have an impact on premature aging diseases.

  17. Premature birth and age at onset of puberty.

    Science.gov (United States)

    Hui, Lai Ling; Leung, Gabriel M; Lam, Tai Hing; Schooling, C Mary

    2012-05-01

    Premature birth is associated with poor metabolic health in both sexes, potentially via earlier pubertal timing. We examined the associations of gestational age and premature birth (Premature girls reached puberty about 4 months later than girls with ≥ 41 weeks' gestation (time ratio = 1.04 [95% confidence interval = 1.01-1.06]), adjusted for mother' age of menarche, mother's place of birth, and smoking during pregnancy. Gestational age was not associated with onset of puberty in boys (test for interaction by sex, P Premature birth was not related to earlier onset of puberty; instead, premature girls had later onset of puberty. Thus, the association between premature birth and subsequent cardiovascular risk is probably not mediated through the timing of pubertal onset. It is unclear whether onset, duration, or tempo of puberty is more relevant to the detrimental consequences of early puberty. Further studies investigating intrauterine, infant, and childhood influences on the duration and tempo of puberty may help unravel the early origins of cardiovascular diseases.

  18. Median age at death as an indicator of premature mortality

    OpenAIRE

    Jannerfeldt, Eric; Hörte, Lars-Gunnar

    1988-01-01

    The median age at death from certain diseases was calculated for each year for 1969-85 and compared with that at death from all causes. The results indicated the impact of these diseases in terms of premature mortality and changes over time. Cancer was a more important cause of premature mortality among women than among men. For cancer of the cervix the median age at death increased appreciably whereas for cancer of the lung in women it slightly decreased. The median age at death is easy to c...

  19. Specific premature epigenetic aging of cartilage in osteoarthritis

    Science.gov (United States)

    Vidal-Bralo, Laura; Lopez-Golan, Yolanda; Mera-Varela, Antonio; Rego-Perez, Ignacio; Horvath, Steve; Zhang, Yuhua; del Real, Álvaro; Zhai, Guangju; Blanco, Francisco J; Riancho, Jose A.; Gomez-Reino, Juan J; Gonzalez, Antonio

    2016-01-01

    Osteoarthritis (OA) is a disease affecting multiple tissues of the joints in the elderly, but most notably articular cartilage. Premature biological aging has been described in this tissue and in blood cells, suggesting a systemic component of premature aging in the pathogenesis of OA. Here, we have explored epigenetic aging in OA at the local (cartilage and bone) and systemic (blood) levels. Two DNA methylation age-measures (DmAM) were used: the multi-tissue age estimator for cartilage and bone; and a blood-specific biomarker for blood. Differences in DmAM between OA patients and controls showed an accelerated aging of 3.7 years in articular cartilage (95 % CI = 1.1 to 6.3, P = 0.008) of OA patients. By contrast, no difference in epigenetic aging was observed in bone (0.04 years; 95 % CI = −1.8 to 1.9, P = 0.3) and in blood (−0.6 years; 95 % CI = −1.5 to 0.3, P = 0.2) between OA patients and controls. Therefore, premature epigenetic aging according to DNA methylation changes was specific of OA cartilage, adding further evidence and insight on premature aging of cartilage as a component of OA pathogenesis that reflects damage and vulnerability. PMID:27689435

  20. Premature aging and cancer in nucleotide excision repair-disorders

    NARCIS (Netherlands)

    K.E.M. Diderich (Karin); M. Alanazi; J.H.J. Hoeijmakers (Jan)

    2011-01-01

    textabstractDuring the past decades, the major impact of DNA damage on cancer as 'disease of the genes' has become abundantly apparent. In addition to cancer, recent years have also uncovered a very strong association of DNA damage with many features of (premature) aging. The notion that DNA repair

  1. Impact of prematurity on language skills at school age.

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    Smith, Jamie Mahurin; DeThorne, Laura Segebart; Logan, Jessica A R; Channell, Ron W; Petrill, Stephen A

    2014-06-01

    The existing literature on language outcomes in children born prematurely focuses almost exclusively on standardized test scores rather than discourse-level abilities. The authors of this study looked longitudinally at school-age language outcomes and potential moderating variables for a group of twins born prematurely versus a control group of twins born at full term, analyzing both standardized test results and language sample data from the population-based Western Reserve Reading Project (WRRP; Petrill, Deater-Deckard, Thompson, DeThorne, & Schatschneider, 2006). Fifty-seven children born prematurely, at ≤32 weeks or children born at full term and were matched for age, gender, race, and parental education. Data included discourse-level language samples and standardized test results, collected at average ages 7, 8, and 10 years. The language samples were analyzed to yield a number of semantic and syntactic measures that were consolidated via factor analysis. Regression models showed significant differences between the 2 groups for standardized test results, although the mean score for both groups fell in the normal range. For the discourse-level language measures, however, differences never reached statistical significance. Parental education was significantly associated with improved standardized test scores. These findings suggest that in the absence of frank neurological impairment, sophisticated semantic and syntactic skills may be relatively intact in the discourse-level language of children born prematurely. Implications for assessment, particularly the potential role of attention and executive function in standardized testing tasks, are reviewed.

  2. Reprogramming suppresses premature senescence phenotypes of Werner syndrome cells and maintains chromosomal stability over long-term culture.

    Directory of Open Access Journals (Sweden)

    Akira Shimamoto

    Full Text Available Werner syndrome (WS is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. Recent studies have revealed that cells from WS patients can be successfully reprogrammed into induced pluripotent stem cells (iPSCs. In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency. WS iPSCs also showed recapitulation of the phenotypes during differentiation. Furthermore, karyotype analysis indicated that WS iPSCs were stable, and half of the descendant clones had chromosomal profiles that were similar to those of parental cells. These unexpected properties might be achieved by induced expression of endogenous telomerase gene during reprogramming, which trigger telomerase reactivation leading to suppression of both replicative senescence and telomere dysfunction in WS cells. These findings demonstrated that reprogramming suppressed premature senescence phenotypes in WS cells and WS iPSCs could lead to chromosomal stability over the long term. WS iPSCs will provide opportunities to identify affected lineages in WS and to develop a new strategy for the treatment of WS.

  3. Stress-Induced Premature Senescence or Stress-Induced Senescence-Like Phenotype: One In Vivo Reality, Two Possible Definitions?

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    Olivier Toussaint

    2002-01-01

    Full Text Available No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1. Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2. As stress increases, the proportion of cells in “stress-induced premature senescence-like phenotype” according to definition 1 or “stress-induced premature senescence,” according to definition 2, should increase when a culture reaches growth arrest, and the proportion of cells that reached telomere-dependent replicative senescence due to the end-replication problem should decrease. Stress-induced premature senescence-like phenotype and telomere-dependent replicatively senescent cells share basic similarities such as irreversible growth arrest and resistance to apoptosis, which may appear through different pathways. Irreversible growth arrest after exposure to oxidative stress and generation of DNA damage could be as efficient in avoiding immortalisation as “telomere-dependent” replicative senescence. Probabilities are higher that the senescent cells (according to definition 2 appearing in vivo are in stress-induced premature senescence rather than in telomere-dependent replicative senescence. Examples are given suggesting these cells affect in vivo tissue (pathophysiology and aging.

  4. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging Xpd mice.

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    Park, Jung Yoon; Cho, Mi-Ook; Leonard, Shanique; Calder, Brent; Mian, I Saira; Kim, Woo Ho; Wijnhoven, Susan; van Steeg, Harry; Mitchell, James; van der Horst, Gijsbertus T J; Hoeijmakers, Jan; Cohen, Pinchas; Vijg, Jan; Suh, Yousin

    2008-06-11

    Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. Xpd(TTD) mice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a reduced incidence of cancer. To gain further insight into the molecular basis of the mutant-specific manifestation of age-related phenotypes, we used comparative microarray analysis of young and old female livers to discover gene expression signatures distinguishing Xpd(TTD) mice from their age-matched wild type controls. We found a transcription signature of increased apoptosis in the Xpd(TTD) mice, which was confirmed by in situ immunohistochemical analysis and found to be accompanied by increased proliferation. However, apoptosis rate exceeded the rate of proliferation, resulting in homeostatic imbalance. Interestingly, a metabolic response signature was observed involving decreased energy metabolism and reduced IGF-1 signaling, a major modulator of life span. We conclude that while the increased apoptotic response to endogenous DNA damage contributes to the accelerated aging phenotypes and the reduced cancer incidence observed in the Xpd(TTD) mice, the signature of reduced energy metabolism is likely to reflect a compensatory adjustment to limit the increased genotoxic stress in these mutants. These results support a general model for premature aging in DNA repair deficient mice based on cellular responses to DNA damage that impair normal tissue homeostasis.

  5. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging Xpd mice.

    Directory of Open Access Journals (Sweden)

    Jung Yoon Park

    Full Text Available Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. Xpd(TTD mice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W, display severe symptoms of premature aging but have a reduced incidence of cancer. To gain further insight into the molecular basis of the mutant-specific manifestation of age-related phenotypes, we used comparative microarray analysis of young and old female livers to discover gene expression signatures distinguishing Xpd(TTD mice from their age-matched wild type controls. We found a transcription signature of increased apoptosis in the Xpd(TTD mice, which was confirmed by in situ immunohistochemical analysis and found to be accompanied by increased proliferation. However, apoptosis rate exceeded the rate of proliferation, resulting in homeostatic imbalance. Interestingly, a metabolic response signature was observed involving decreased energy metabolism and reduced IGF-1 signaling, a major modulator of life span. We conclude that while the increased apoptotic response to endogenous DNA damage contributes to the accelerated aging phenotypes and the reduced cancer incidence observed in the Xpd(TTD mice, the signature of reduced energy metabolism is likely to reflect a compensatory adjustment to limit the increased genotoxic stress in these mutants. These results support a general model for premature aging in DNA repair deficient mice based on cellular responses to DNA damage that impair normal tissue homeostasis.

  6. Risk factors for premature death in middle aged men

    OpenAIRE

    Petersson, Bo; Trell, Erik; Henningsen, Nels-Christian; Hood, Bertil

    1984-01-01

    The causes of premature death and the associated risk factors were analysed in a cohort of 7935 middle aged men participating in a preventive population programme in Malmö. They were screened when aged 46-48 and then followed up for 3½-8 years. Two hundred and eighteen died, of whom 181 (83%) underwent necropsy. Three major causes of death were established: cancer in 61 (28%), deaths related to consumption of alcohol in 55 (25%), and coronary heart disease in 50 (23%).

  7. Premature ageing prevention: limitations and perspectives of pharmacological interventions.

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    Anisimov, Vladimir N

    2006-11-01

    A significant increase of the elderly in populations of developed countries is followed by increase morbidity and mortality from main age-related diseases--cardiovascular and neuro-degenerative, cancer, diabetes mellitus, declining in a resistance to infections. Obviously, the development of means of the prevention of the premature ageing and these diseases in humans are crucial at present. However, data on such type means rather scarce, contradictory and often not reliable from the points of view of the adequacy of the experiments to current scientific requirements, as well as the interpretation of the results and safety. Available data on the life span extension and adverse effects of chemical compounds and drugs suggested as geroprotectors are critically analyzed: antidiabetic drugs, growth and thyroid hormones, glucocorticoids, DHEA, sex steroids and contraceptives, melatonin and peptide preparations modulating the pineal gland, antioxidants, chelate agents and lathyrogens, adaptogens and herbs, neurotropic drugs, inhibitors of monoamine oxidase, immunomodulators and some other. Most of the results could not convincingly evidence the life span extension and safety of the suggested geroprotectors. We believe that it is necessary to establish an international program for the expert evaluation of the life span extension potential of pharmacological interventions for humans. The scope of the program should be to evaluate chemical, immunological, dietary and behavioural interventions that may lead to life span extension or retard premature ageing and the objective--preparation of critical reviews and evaluations on evidence of the life span extending properties of a wide range of potential geroprotectors and strategies by international groups of working experts. The program may assist national and international authorities in devising programs of health promotion and premature ageing prevention.

  8. Cellular senescence in normal and premature lung aging.

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    Bartling, B

    2013-10-01

    The incidence of chronic respiratory diseases (e.g., chronic obstructive pulmonary disease, COPD) and interstitial lung diseases (e.g., pneumonia and lung fibrosis) increases with age. In addition to immune senescence, the accumulation of senescent cells directly in lung tissue might play a critical role in the increased prevalence of these pulmonary diseases. In the last couple of years, detailed studies have identified the presence of senescent cells in the aging lung and in diseased lungs of patients with COPD and lung fibrosis. Cellular senescence has been shown for epithelial cells of bronchi and alveoli as well as mesenchymal and vascular cells. Known risk factors for pulmonary diseases (cigarette smoke, air pollutions, bacterial infections, etc.) were identified in experimental studies as being possible mediators in the development of cellular senescence. The present findings indicate the importance of cellular senescence in normal lung aging and in premature aging of the lung in patients with COPD, lung fibrosis, and probably other respiratory diseases.

  9. Molecular insights into the premature aging disease progeria.

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    Vidak, Sandra; Foisner, Roland

    2016-04-01

    Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare premature aging disease presenting many features resembling the normal aging process. HGPS patients die before the age of 20 years due to cardiovascular problems and heart failure. HGPS is linked to mutations in the LMNA gene encoding the intermediate filament protein lamin A. Lamin A is a major component of the nuclear lamina, a scaffold structure at the nuclear envelope that defines mechanochemical properties of the nucleus and is involved in chromatin organization and epigenetic regulation. Lamin A is also present in the nuclear interior where it fulfills lamina-independent functions in cell signaling and gene regulation. The most common LMNA mutation linked to HGPS leads to mis-splicing of the LMNA mRNA and produces a mutant lamin A protein called progerin that tightly associates with the inner nuclear membrane and affects the dynamic properties of lamins. Progerin expression impairs many important cellular processes providing insight into potential disease mechanisms. These include changes in mechanosignaling, altered chromatin organization and impaired genome stability, and changes in signaling pathways, leading to impaired regulation of adult stem cells, defective extracellular matrix production and premature cell senescence. In this review, we discuss these pathways and their potential contribution to the disease pathologies as well as therapeutic approaches used in preclinical and clinical tests.

  10. Loss of HtrA2/Omi activity in non-neuronal tissues of adult mice causes premature aging.

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    Kang, S; Louboutin, J-P; Datta, P; Landel, C P; Martinez, D; Zervos, A S; Strayer, D S; Fernandes-Alnemri, T; Alnemri, E S

    2013-02-01

    mnd2 mice die prematurely as a result of neurodegeneration 30-40 days after birth due to loss of the enzymatic activity of the mitochondrial quality control protease HtrA2/Omi. Here, we show that transgenic expression of human HtrA2/Omi in the central nervous system of mnd2 mice rescues them from neurodegeneration and prevents their premature death. Interestingly, adult transgenic mnd2 mice develop accelerated aging phenotypes, such as premature weight loss, hair loss, reduced fertility, curvature of the spine, heart enlargement, increased autophagy, and death by 12-17 months of age. These mice also have elevated levels of clonally expanded mitochondrial DNA (mtDNA) deletions in their tissues. Our results provide direct genetic evidence linking mitochondrial protein quality control to mtDNA deletions and aging in mammals.

  11. Familial aggregation of phenotypic expression of premature hair hypopigmentation in the craniofacial region

    Directory of Open Access Journals (Sweden)

    Corey Black

    2015-04-01

    Full Text Available There are many patients who experience premature hypopigmentation of hair, but do not understand the underlying causes and potential dangers associated with them. The causes range from genetic predisposition to environmental influences such as tobacco use. Premature hypopigmentation of the hair shaft can also be associated with many syndromes; some which cause dental anomalies. Today, treatment options are limited for patients, although various studies are being done on mice to target the underlying mechanism of action. Understanding the differences between all of the possible causes of this particular phenotype can help clinicians better identify the symptoms, educate patients, and possibly modify treatment to suit the needs of each patient on an individual basis.

  12. Ataxia-telangiectasia (A-T): An emerging dimension of premature ageing.

    Science.gov (United States)

    Shiloh, Yosef; Lederman, Howard M

    2017-01-01

    A-T is a prototype genome instability syndrome and a multifaceted disease. A-T leads to neurodegeneration - primarily cerebellar atrophy, immunodeficiency, oculocutaneous telangiectasia (dilated blood vessels), vestigial thymus and gonads, endocrine abnormalities, cancer predisposition and varying sensitivity to DNA damaging agents, particularly those that induce DNA double-strand breaks. With the recent increase in life expectancy of A-T patients, the premature ageing component of this disease is gaining greater awareness. The complex A-T phenotype reflects the ever growing number of functions assigned to the protein encoded by the responsible gene - the homeostatic protein kinase, ATM. The quest to thoroughly understand the complex A-T phenotype may reveal yet elusive ATM functions. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Blood cell mitochondrial DNA content and premature ovarian aging.

    Directory of Open Access Journals (Sweden)

    Marco Bonomi

    Full Text Available Primary ovarian insufficiency (POI is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA content in a group of women undergoing ovarian hyperstimulation (OH, and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF and 42 poor responders (PR to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001 in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction.

  14. Blood Cell Mitochondrial DNA Content and Premature Ovarian Aging

    Science.gov (United States)

    Cacciatore, Chiara; Busnelli, Marta; Rossetti, Raffaella; Bonetti, Silvia; Paffoni, Alessio; Mari, Daniela; Ragni, Guido; Persani, Luca; Arosio, M.; Beck-Peccoz, P.; Biondi, M.; Bione, S.; Bruni, V.; Brigante, C.; Cannavo`, S.; Cavallo, L.; Cisternino, M.; Colombo, I.; Corbetta, S.; Crosignani, P.G.; D'Avanzo, M.G.; Dalpra, L.; Danesino, C.; Di Battista, E.; Di Prospero, F.; Donti, E.; Einaudi, S.; Falorni, A.; Foresta, C.; Fusi, F.; Garofalo, N.; Giotti, I.; Lanzi, R.; Larizza, D.; Locatelli, N.; Loli, P.; Madaschi, S.; Maghnie, M.; Maiore, S.; Mantero, F.; Marozzi, A.; Marzotti, S.; Migone, N.; Nappi, R.; Palli, D.; Patricelli, M.G.; Pisani, C.; Prontera, P.; Petraglia, F.; Radetti, G.; Renieri, A.; Ricca, I.; Ripamonti, A.; Rossetti, R.; Russo, G.; Russo, S.; Tonacchera, M.; Toniolo, D.; Torricelli, F.; Vegetti, W.; Villa, N.; Vineis, P.; Wasniewsk, M.; Zuffardi, O.

    2012-01-01

    Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction. PMID:22879975

  15. Premature aging in skeletal muscle lacking serum response factor.

    Directory of Open Access Journals (Sweden)

    Charlotte Lahoute

    Full Text Available Aging is associated with a progressive loss of muscle mass, increased adiposity and fibrosis that leads to sarcopenia. At the molecular level, muscle aging is known to alter the expression of a variety of genes but very little is known about the molecular effectors involved. SRF (Serum Response Factor is a crucial transcription factor for muscle-specific gene expression and for post-natal skeletal muscle growth. To assess its role in adult skeletal muscle physiology, we developed a post-mitotic myofiber-specific and tamoxifen-inducible SRF knockout model. Five months after SRF loss, no obvious muscle phenotype was observed suggesting that SRF is not crucial for myofiber maintenance. However, mutant mice progressively developed IIB myofiber-specific atrophy accompanied by a metabolic switch towards a more oxidative phenotype, muscular lipid accumulation, sarcomere disorganization and fibrosis. After injury, mutant muscles exhibited an altered regeneration process, showing smaller regenerated fibers and persistent fibrosis. All of these features are strongly reminiscent of abnormalities encountered in aging skeletal muscle. Interestingly, we also observed an important age associated decrease in SRF expression in mice and human muscles. Altogether, these results suggest that a naturally occurring SRF down-regulation precedes and contributes to the muscle aging process. Indeed, triggering SRF loss in the muscles of mutant mice results in an accelerated aging process.

  16. [Gait characteristics of women with fibromyalgia: a premature aging pattern].

    Science.gov (United States)

    Góes, Suelen M; Leite, Neiva; de Souza, Ricardo M; Homann, Diogo; Osiecki, Ana C V; Stefanello, Joice M F; Rodacki, André L F

    2014-01-01

    Fibromyalgia is a condition which involves chronic pain. Middle-aged individuals with fibromyalgia seem to exhibit changes in gait pattern, which may prematurely expose them to a gait pattern which resembles that found in the elderly population. To determine the 3D spatial (linear and angular) gait parameters of middle-aged women with fibromyalgia and compare to elderly women without this condition. 25 women (10 in the fibromyalgia group and 15 in the elderly group) volunteered to participate in the study. Kinematics was performed using an optoelectronic system, and linear and angular kinematic variables were determined. There was no difference in walking speed, stride length, cadence, hip, knee and ankle joints range of motion between groups, except the pelvic rotation, in which the fibromyalgia group showed greater rotation (P<0.05) compared to the elderly group. Also, there was a negative correlation with pelvic rotation and gluteus pain (r = -0.69; P<0.05), and between pelvic obliquity and greater trochanter pain (r = -0.69; P<0.05) in the fibromyalgia group. Middle-aged women with fibromyalgia showed gait pattern resemblances to elderly, women, which is characterized by reduced lower limb ROM, stride length and walking speed. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  17. Prelamin A accumulation and stress conditions induce impaired Oct-1 activity and autophagy in prematurely aged human mesenchymal stem cell.

    Science.gov (United States)

    Infante, Arantza; Gago, Andrea; de Eguino, Garbiñe Ruiz; Calvo-Fernández, Teresa; Gómez-Vallejo, Vanessa; Llop, Jordi; Schlangen, Karin; Fullaondo, Ane; Aransay, Ana M; Martín, Abraham; Rodríguez, Clara I

    2014-04-01

    Aging, a time-dependent functional decline of biological processes, is the primary risk factor in developing diseases such as cancer, cardiovascular or degenerative diseases. There is a real need to understand the human aging process in order to increase the length of disease-free life, also known as "health span". Accumulation of progerin and prelamin A are the hallmark of a group of premature aging diseases but have also been found during normal cellular aging strongly suggesting similar mechanisms between healthy aging and LMNA-linked progeroid syndromes. How this toxic accumulation contributes to aging (physiological or pathological) remains unclear. Since affected tissues in age-associated disorders and in pathological aging are mainly of mesenchymal origin we propose a model of human aging based on mesenchymal stem cells (hMSCs) which accumulate prelamin A. We demonstrate that prelamin A-accumulating hMSCs have a premature aging phenotype which affects their functional competence in vivo. The combination of prelamin A accumulation and stress conditions enhance the aging phenotype by dysregulating the activity of the octamer binding protein Oct-1This experimental model has been fundamental to identify a new role for Oct-1 in hMSCs aging.

  18. Aging Phenotypes of Common Marmosets (Callithrix jacchus

    Directory of Open Access Journals (Sweden)

    Corinna N. Ross

    2012-01-01

    Full Text Available Characterizing the phenotypic changes associated with aging in a short-lived primate is necessary in order to develop better translational models for human health, aging, and disease research. A population of conventionally housed marmoset monkeys was assessed to determine if phenotypes of body composition, hematology, and morphometrical measures were associated with age or risk of death. We found that the cause of mortality in older marmosets was more likely to be due to cardiac and chronic kidney disease than in younger marmosets. Older marmosets have decreased fat mass, morphometric measures, and serum albumin. Older marmosets are more likely to show a modified posture while at rest and this modified posture was significantly associated with an increased risk of imminent death. These assessments provide an initial definition of aged health in marmosets and a base for future translational aging research with this species.

  19. Homeostatic Imbalance between Apoptosis and Cell Renewal in the Liver of Premature Aging XpdTTD Mice

    Science.gov (United States)

    Park, Jung Yoon; Cho, Mi-Ook; Leonard, Shanique; Calder, Brent; Mian, I. Saira; Kim, Woo Ho; Wijnhoven, Susan; van Steeg, Harry; Mitchell, James; van der Horst, Gijsbertus T. J.; Hoeijmakers, Jan; Cohen, Pinchas; Vijg, Jan; Suh, Yousin

    2008-01-01

    Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. XpdTTD mice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a reduced incidence of cancer. To gain further insight into the molecular basis of the mutant-specific manifestation of age-related phenotypes, we used comparative microarray analysis of young and old female livers to discover gene expression signatures distinguishing XpdTTD mice from their age-matched wild type controls. We found a transcription signature of increased apoptosis in the XpdTTD mice, which was confirmed by in situ immunohistochemical analysis and found to be accompanied by increased proliferation. However, apoptosis rate exceeded the rate of proliferation, resulting in homeostatic imbalance. Interestingly, a metabolic response signature was observed involving decreased energy metabolism and reduced IGF-1 signaling, a major modulator of life span. We conclude that while the increased apoptotic response to endogenous DNA damage contributes to the accelerated aging phenotypes and the reduced cancer incidence observed in the XpdTTD mice, the signature of reduced energy metabolism is likely to reflect a compensatory adjustment to limit the increased genotoxic stress in these mutants. These results support a general model for premature aging in DNA repair deficient mice based on cellular responses to DNA damage that impair normal tissue homeostasis. PMID:18545656

  20. LMNA-Associated Cardiocutaneous Progeria: a Novel Autosomal Dominant Premature Aging Syndrome with Late Onset

    Science.gov (United States)

    Kane, Megan S.; Lindsay, Mark E.; Judge, Daniel P.; Barrowman, Jemima; Rhys, Colette Ap; Simonson, Lisa; Dietz, Harry C.; Michaelis, Susan

    2013-01-01

    Hutchinson-Gilford Progeria Syndrome (HGPS) is a well-characterized premature aging disorder caused by mutations in LMNA, the gene encoding the nuclear scaffold proteins lamin A and C. In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24. Emerging evidence indicates that LMNA-linked progerias can be grouped into two classes: 1) the processing-deficient, early onset “typical” progerias (e.g. HGPS), and 2) the processing-proficient “atypical” progeria syndromes (APS) that are later in onset. Here we describe a novel progeria syndrome with prominent cutaneous and cardiovascular manifestations belonging to the second class. We suggest the name LMNA-associated cardiocutaneous progeria syndrome (LCPS) for this disorder. Affected patients are normal at birth but undergo progressive cutaneous changes in childhood and die in middle age of cardiovascular complications, including accelerated atherosclerosis, calcific valve disease, and cardiomyopathy. In addition, the proband demonstrated cancer susceptibility, a phenotype rarely described for LMNA-based progeria disorders. The LMNA mutation that causes LCPS is a heterozygous missense mutation resulting in an amino acid substitution (D300G) in the coiled-coil domain of lamin A/C. In skin fibroblasts isolated from the proband, the processing and levels of lamin A and C are normal. However, nuclear morphology is aberrant and rescued by treatment with farnesyltransferase inhibitors (FTIs), as is also the case for HGPS and other laminopathies. Our findings advance knowledge of human LMNA progeria syndromes, and raise the possibility that typical and atypical progerias may converge upon a common mechanism to cause premature aging disease. PMID:23666920

  1. LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.

    Science.gov (United States)

    Kane, Megan S; Lindsay, Mark E; Judge, Daniel P; Barrowman, Jemima; Ap Rhys, Colette; Simonson, Lisa; Dietz, Harry C; Michaelis, Susan

    2013-07-01

    Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disorder caused by mutations in LMNA, which encodes the nuclear scaffold proteins lamin A and C. In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24. LMNA-linked progerias can be grouped into two classes: (1) the processing-deficient, early onset "typical" progerias (e.g., HGPS), and (2) the processing-proficient "atypical" progeria syndromes (APS) that are later in onset. Here we describe a previously unrecognized progeria syndrome with prominent cutaneous and cardiovascular manifestations belonging to the second class. We suggest the name LMNA-associated cardiocutaneous progeria syndrome (LCPS) for this disorder. Affected patients are normal at birth but undergo progressive cutaneous changes in childhood and die in middle age of cardiovascular complications, including accelerated atherosclerosis, calcific valve disease, and cardiomyopathy. In addition, the proband demonstrated cancer susceptibility, a phenotype rarely described for LMNA-based progeria disorders. The LMNA mutation that caused LCPS in this family is a heterozygous c.899A>G (p.D300G) mutation predicted to alter the coiled-coil domain of lamin A/C. In skin fibroblasts isolated from the proband, the processing and levels of lamin A and C are normal. However, nuclear morphology is aberrant and rescued by treatment with farnesyltransferase inhibitors, as is also the case for HGPS and other laminopathies. Our findings advance knowledge of human LMNA progeria syndromes, and raise the possibility that typical and atypical progerias may converge upon a common mechanism to cause premature aging disease.

  2. Congenital Heart Disease in Premature Infants 25-32 Weeks' Gestational Age.

    Science.gov (United States)

    Chu, Patricia Y; Li, Jennifer S; Kosinski, Andrzej S; Hornik, Christoph P; Hill, Kevin D

    2017-02-01

    To determine the birth prevalence of congenital heart defects (CHDs) across the spectrum of common defects in very/extremely premature infants and to compare mortality rates between premature infants with and without CHDs. The Kids' Inpatient Databases (2003-2012) were used to estimate the birth prevalence of CHDs (excluding patent ductus arteriosus) in very/extremely premature infants born between 25 and 32 weeks' gestational age. Birth prevalence was compared with term infants for a subset of "severe" defects expected to be near universally diagnosed in the neonatal period. Weighted multivariable logistic regression was used to calculate aORs of mortality comparing very and extremely premature infants with vs without CHDs. We identified 249 011 very/extremely premature infants, including 28 806 with CHDs. The overall birth prevalence of CHDs was 116 per 1000 very/extremely premature births. Severe CHDs had significantly higher birth prevalence in very/extremely premature infants when compared with term infants (7.4 per 1000 very/premature births vs 1.5 per 1000 term births; P premature infants with severe CHDs had an overall 26.3% in-hospital mortality and a 7.5-fold increased adjusted odds of death compared with those without CHDs. Mortality varied widely by defect in very/extremely premature infants, ranging from 12% for interrupted aortic arch to 67% for truncus arteriosus. Given the increased birth prevalence of severe CHDs in very/extremely premature infants, and significantly higher mortality, there is justification for intensive interventions aimed at decreasing the likelihood of premature delivery for patients where CHD is diagnosed in utero. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Air Pollution Stress and the Aging Phenotype: The Telomere Connection.

    Science.gov (United States)

    Martens, Dries S; Nawrot, Tim S

    2016-09-01

    Aging is a complex physiological phenomenon. The question why some subjects grow old while remaining free from disease whereas others prematurely die remains largely unanswered. We focus here on the role of air pollution in biological aging. Hallmarks of aging can be grouped into three main categories: genomic instability, telomere attrition, and epigenetic alterations leading to altered mitochondrial function and cellular senescence. At birth, the initial telomere length of a person is largely determined by environmental factors. Telomere length shortens with each cell division and exposure to air pollution as well as low residential greens space exposure is associated with shorter telomere length. Recent studies show that the estimated effects of particulate air pollution exposure on the telomere mitochondrial axis of aging may play an important role in chronic health effects of air pollution. The exposome encompasses all exposures over an entire life. As telomeres can be considered as the cellular memories of exposure to oxidative stress and inflammation, telomere maintenance may be a proxy for assessing the "exposome". If telomeres are causally related to the aging phenotype and environmental air pollution is an important determinant of telomere length, this might provide new avenues for future preventive strategies.

  4. Prematurity, smallness-for-gestational age and later hospital admissions

    DEFF Research Database (Denmark)

    Á Rogvi, Rasmus; Forman, Julie Lyng; Greisen, Gorm

    2015-01-01

    hospital admissions later in life. METHODS: Using Danish nation-wide registries we created a cohort of 1,348,106 persons born 1974-1996 and assessed all unique diagnoses registered in the Danish Patient Registry (DPR) for hospital admissions in the period 1994-2007 (n=27,910,558). We determined the odds...... in life. CONCLUSION: Being born premature or SGA was associated with significantly altered risks of being admitted to a hospital with a wide range of diseases later in life, affecting almost all organ systems throughout childhood and early adulthood. Our findings may motivate testing in other cohorts...

  5. Changing course in ageing research: The healthy ageing phenotype.

    Science.gov (United States)

    Franco, Oscar H; Karnik, Kavita; Osborne, Gabrielle; Ordovas, Jose M; Catt, Michael; van der Ouderaa, Frans

    2009-05-20

    Ageing is often associated with the aged and the diseased, nevertheless ageing is a process that starts in-uterus and is characterised by a progressive functional loss but not necessarily by the presence of disease and poor quality of life. How to meander through life without crossing the confines of major chronic disease and cognitive and physical impairment remains one of the most relevant challenges for science and humankind. Delimiting that 'immaculate' trajectory - that we dub as the 'Healthy Ageing Phenotype' - and exploring solutions to help the population to stay or return to this trajectory should constitute the core focus of scientific research. Nevertheless, current efforts on ageing research are mainly focused on developing animal models to disentangle the human ageing process, and on age-related disorders often providing merely palliative solutions. Therefore, to identify alternative perspectives in ageing research, Unilever and the Medical Research Council (MRC) UK convened a Spark workshop entitled 'The Healthy Ageing Phenotype'. In this meeting, international specialists from complementary areas related to ageing research, gathered to find clear attributes and definitions of the 'Healthy Ageing Phenotype', to identify potential mechanisms and interventions to improve healthy life expectancy of the population; and to highlight areas within ageing research that should be prioritised in the future. General agreement was reached in recognising ageing research as a disaggregated field with little communication between basic, epidemiological and clinical areas of research and limited translation to society. A more holistic, multi-disciplinary approach emanating from a better understanding of healthy ageing trajectories and centred along human biological resilience, its maintenance and the reversibility from early deviations into pathological trajectories, is urgently required. Future research should concentrate on understanding the mechanisms that permit

  6. Maternal age as risk factor of prematurity in Spain: Mediterranean area

    Directory of Open Access Journals (Sweden)

    E. Cortés Castell

    2013-10-01

    Full Text Available Background: Maternal age is a preponderant variable in the epidemiological analysis of the premature birth. Studies show that in the extreme ages of the maternal life there is a risk of premature birth that generates a high rate of neonatal morbidity. Objetives: Determine the effect on the extreme ages of women residents in the province of Alicante on the total of the premature births. Method: An explanatory, retrospective case-control study was conducted during the period from January 1st, 2008 to December 31st, 2011. The study was based on the revision of the newborn registers from the Neonatal Screening Center of the province of Alicante. All the preterm were included, this means between 22 & 36 complete weeks of pregnancy (5,295 out of 78,391 newborn which represents 6.75% of prematurity, and a random sample of the deliveries with 37 weeks or more of pregnancy (control group. The age of the mother was studied as independent variable and the prematurity as dependent variable. Results: Clearly shows an increased risk of prematurity among teenage mothers compared to the age group nearest to them, which is confirmed by a squared Chi test which gives a significantly different distribution (p < 0,0001 and an OD for very preterm of 2,41 (1,51-3,24 and of preterm of 1,71 (1,32-2,19. This probability is also higher among mothers over 40 years old with an OD of 1,86 (1,39-2,48 and 1,66 (1,44-1,91 for very preterm newborns and preterm newborns respectively. Discussion: The results clearly manifest that teenagers and older pregnant mothers are at higher prematurity and low birth weight risk, therefore imposes the need to trace educational interventions to minimize this problem from the results in this research.

  7. Cardiovascular Risk in Women With Premature Ovarian Insufficiency Compared to Premenopausal Women at Middle Age

    NARCIS (Netherlands)

    Daan, Nadine M P; Muka, Taulant; Koster, Maria P H; Roeters van Lennep, Jaenine E; Lambalk, Cornelis B; Laven, Joop S E; Fauser, Clemens G K M; Meun, Cindy; de Rijke, Yolanda B; Boersma, Eric; Franco, Oscar H; Kavousi, Maryam; Fauser, Bart C J M

    2016-01-01

    CONTEXT: A young age at menopause has been associated with increased cardiovascular disease (CVD) risk. OBJECTIVE: To compare the cardiovascular risk profile between women with premature ovarian insufficiency (POI) and premenopausal controls of comparable age. DESIGN: Cross-sectional case control st

  8. The Premature Aging Hypothesis: Old Before Its Time?

    Science.gov (United States)

    Kramer, Joel H.; And Others

    1989-01-01

    Administered California Verbal Learning Test to young and old alcoholics and controls. Alcoholism and aging produced similar levels of immediate and delayed free recall. However, poor recognition memory and more frequent intrusion and false positive errors were associated with alcoholism but not with aging. Results suggest that alcoholism and…

  9. Uremia causes premature ageing of the T cell compartment in end-stage renal disease patients

    Directory of Open Access Journals (Sweden)

    Meijers Ruud WJ

    2012-09-01

    Full Text Available Abstract Background End-stage renal disease (ESRD patients treated with renal replacement therapy (RRT have premature immunologically aged T cells which may underlie uremia-associated immune dysfunction. The aim of this study was to investigate whether uremia was able to induce premature ageing of the T cell compartment. For this purpose, we examined the degree of premature immunological T cell ageing by examining the T cell differentiation status, thymic output via T cell receptor excision circle (TREC content and proliferative history via relative telomere length in ESRD patients not on RRT. Results Compared to healthy controls, these patients already had a lower TREC content and an increased T cell differentiation accompanied by shorter telomeres. RRT was able to enhance CD8+ T cell differentiation and to reduce CD8+ T cell telomere length in young dialysis patients. An increased differentiation status of memory CD4+ T cells was also noted in young dialysis patients. Conclusion Based on these results we can conclude that uremia already causes premature immunological ageing of the T cell system and RRT further increases immunological ageing of the CD8+ T cell compartment in particular in young ESRD patients.

  10. Leaving College Prematurely: The Experiences of Nontraditional-Age College Students With Depression

    Science.gov (United States)

    Thompson-Ebanks, Valerie

    2017-01-01

    This qualitative study examines the experiences of former nontraditional-age students with depression and reasons that led them to leave college prematurely. Constant comparative methods were used to illuminate themes within and across participants' stories. The findings showcase eight complex interlocking factors that these former students…

  11. Leaving College Prematurely: The Experiences of Nontraditional-Age College Students With Depression

    Science.gov (United States)

    Thompson-Ebanks, Valerie

    2017-01-01

    This qualitative study examines the experiences of former nontraditional-age students with depression and reasons that led them to leave college prematurely. Constant comparative methods were used to illuminate themes within and across participants' stories. The findings showcase eight complex interlocking factors that these former students…

  12. Muscle wasting in myotonic dystrophies: a model of premature aging.

    Science.gov (United States)

    Mateos-Aierdi, Alba Judith; Goicoechea, Maria; Aiastui, Ana; Fernández-Torrón, Roberto; Garcia-Puga, Mikel; Matheu, Ander; López de Munain, Adolfo

    2015-01-01

    Myotonic dystrophy type 1 (DM1 or Steinert's disease) and type 2 (DM2) are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, while other clinical manifestations such as cardiomyopathy, insulin resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTG) triplet expansion in the 3' untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9 (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and (CCUG)n-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular

  13. Muscle wasting in myotonic dystrophies: a model of premature aging.

    Directory of Open Access Journals (Sweden)

    Alba Judith eMateos-Aierdi

    2015-07-01

    Full Text Available Myotonic dystrophy type I (DM1 or Steinert’s disease and type II (DM2 are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, and other clinical manifestations such as cardiomyopathy, insulin-resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc., including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTGn triplet expansion in the 3’ untranslated region of the DMPK gene, whereas (CCTGn repeats in the first intron of the CNBP/ZNF9 gene cause DM2. The expansions are transcribed into (CUGn and (CCUGn-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL, forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular degeneration seen in DM patients, highlighting the similarities found with muscle aging.

  14. Metformin Alleviates Aging Cellular Phenotypes in Hutchinson-Gilford Progeria Syndrome Dermal Fibroblasts.

    Science.gov (United States)

    Park, Seul-Ki; Shin, Ok Sarah

    2017-02-13

    Metformin is a popular antidiabetic biguanide, which has been considered as a candidate drug for cancer treatment and aging prevention. Hutchinson-Gilford progeria syndrome (HGPS) is a devastating disease characterized by premature aging and severe age-associated complications leading to death. The effects of metformin on HGPS dermal fibroblasts remain largely undefined. In this study, we investigated whether metformin could exert a beneficial effect on nuclear abnormalities and delay senescence in fibroblasts derived from HGPS patients. Metformin treatment partially restored normal nuclear phenotypes, delayed senescence, activated the phosphorylation of AMP-activated protein kinase, and decreased reactive oxygen species formation in HGPS dermal fibroblasts. Interestingly, metformin reduced the number of phosphorylated histone variant H2AX-positive DNA damage foci and suppressed progerin protein expression, compared to the control. Furthermore, metformin-supplemented aged mice showed higher splenocyte proliferation and mRNA expression of the antioxidant enzyme, superoxide dismutase 2 than the control mice. Collectively, our results show that metformin treatment alleviates the nuclear defects and premature aging phenotypes in HGPS fibroblasts. Thus, metformin can be considered a promising therapeutic approach for life extension in HGPS. This article is protected by copyright. All rights reserved.

  15. Spotted phenotypes in horses lost attractiveness in the Middle Ages

    DEFF Research Database (Denmark)

    Wutke, Saskia; Benecke, Norbert; Sandoval-Castellanos, Edson

    2016-01-01

    were influenced by humans. Our results from genotype analyses show a significant increase in spotted coats in early domestic horses (Copper Age to Iron Age). In contrast, medieval horses carried significantly fewer alleles for these phenotypes, whereas solid phenotypes (i.e., chestnut) became dominant...

  16. GDF11 administration does not extend lifespan in a mouse model of premature aging

    Science.gov (United States)

    Freitas-Rodríguez, Sandra; Rodríguez, Francisco; Folgueras, Alicia R.

    2016-01-01

    GDF11 has recently emerged as a powerful anti-aging candidate, found in young blood, capable of rejuvenating a number of aged tissues, such as heart, skeletal muscle and brain. However, recent reports have shown contradictory data questioning its capacity to reverse age-related tissue dysfunction. The availability of a mouse model of accelerated aging, which shares most of the features occurring in physiological aging, gives us an excellent opportunity to test in vivo therapies aimed at extending lifespan both in pathological and normal aging. On this basis, we wondered whether the proposed anti-aging functions of GDF11 would have an overall effect on longevity. We first confirmed the existence of a reduction in GDF11/8 levels in our mouse model of accelerated aging compared with wild-type littermates. However, we show herein that GDF11 daily administration does not extend lifespan of premature-aged mice. PMID:27507054

  17. Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia.

    Science.gov (United States)

    Exley, Andrew Robert; Buckenham, Samantha; Hodges, Elizabeth; Hallam, Robert; Byrd, Phil; Last, James; Trinder, Claire; Harris, Susan; Screaton, Nicholas; Williams, Anthony P; Taylor, A Malcolm R; Shneerson, John M

    2011-07-01

    ATM kinase modulates pathways implicated in premature ageing and ATM genotype predicts survival, yet immunodeficiency in ataxia telangiectasia is regarded as mild and unrelated to age. We address this paradox in a molecularly characterised sequential adult cohort with classical and mild variant ataxia telangiectasia. Immunodeficiency has the characteristics of premature ageing across multiple cellular and molecular immune parameters. This immune ageing occurs without previous CMV infection. Age predicts immunodeficiency in genetically homogeneous ataxia telangiectasia, and in comparison with controls, calendar age is exceeded by immunological age defined by thymic naïve CD4+ T cell levels. Applying ataxia telangiectasia as a model of immune ageing, pneumococcal vaccine responses, characteristically deficient in physiological ageing, are predicted by thymic naïve CD4+ T cell levels. These data suggest inherited defects of DNA repair may provide valuable insight into physiological ageing. Thymic naïve CD4+ T cells may provide a biomarker for vaccine responsiveness in elderly cohorts. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Inhibition of the K+ channel K(Ca3.1 reduces TGF-β1-induced premature senescence, myofibroblast phenotype transition and proliferation of mesangial cells.

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    Rong-Guo Fu

    Full Text Available OBJECTIVE: K(Ca3.1 channel participates in many important cellular functions. This study planned to investigate the potential involvement of K(Ca3.1 channel in premature senescence, myofibroblast phenotype transition and proliferation of mesangial cells. METHODS & MATERIALS: Rat mesangial cells were cultured together with TGF-β1 (2 ng/ml and TGF-β1 (2 ng/ml + TRAM-34 (16 nM separately for specified times from 0 min to 60 min. The cells without treatment served as controls. The location of K(Ca3.1 channels in mesangial cells was determined with Confocal laser microscope, the cell cycle of mesangial cells was assessed with flow cytometry, the protein and mRNA expression of K(Ca3.1, α-smooth muscle actin (α-SMA and fibroblast-specific protein-1 (FSP-1 were detected with Western blot and RT-PCR. One-way analysis of variance (ANOVA and Student-Newman-Keuls-q test (SNK-q were used to do statistical analysis. Statistical significance was considered at P<0.05. RESULTS: Kca3.1 channels were located in the cell membranes and/or in the cytoplasm of mesangial cells. The percentage of cells in G0-G1 phase and the expression of K(ca3.1, α-SMA and FSP-1 were elevated under the induction of TGF-β1 when compared to the control and decreased under the induction of TGF-β1+TRAM-34 when compared to the TGF-β1 induced (P<0.05 or P<0.01. CONCLUSION: Targeted disruption of K(Ca3.1 inhibits TGF-β1-induced premature aging, myofibroblast-like phenotype transdifferentiation and proliferation of mesangial cells.

  19. The Effect of Gestational Age on Axial Length of the Eyes of Premature Infants

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    Mehmet Ali Sekeroglu

    2016-01-01

    Full Text Available Aim: The aim of the present study is to evaluate the axial length of the eyes of premature infants without retinopathy of prematurity and to document the relationship with gestational age and changes as infants grew-up. Material and Method: The axial length of the eyes were measured by using a mobile A-scan ultrasonographic biometry device just before the first retinopathy of prematurity screening examination and 4-weeks thereafter. Results: One-hundred and thirty-six infants with a mean gestational age of 31,7±2,7 weeks and a birth-weight of 1561.0±379.3 g were included in the study. Axial length measurements were done at a mean postconceptional age of 35.8 ±2.6 (31-40 and 39.8±2.7 (35-44 weeks, consecutively. The mean axial length at first and second visits were 16.43±0.42 mm (15.28-17.13 and 16.69±0.41 mm (15.60-17.70, consecutively (p

  20. Association of Maternal Age to Development and Progression of Retinopathy of Prematurity in Infants of Gestational Age under 33 Weeks

    Directory of Open Access Journals (Sweden)

    Atsuro Uchida

    2014-01-01

    Full Text Available Aim. To find predictive and indicative markers of risk for development of retinopathy of prematurity (ROP and its progression to the stage requiring laser treatment, in premature infants whose gestational age (GA was under 33 weeks. Methods. We retrospectively reviewed medical records of 197 premature infants born in 2005–2010 whose GA<33 weeks and underwent eye screening at Keio University Hospital. The association between candidate risk factors and development or progression of ROP was assessed. Results. Among the 182 eligible infants (median GA, 29.1 weeks; median birth weight (BW, 1028 g, 84 (46% developed any stage of ROP, of which 45 (25% required laser treatment. Multivariate analysis using a stepwise method showed that GA (P=0.002; 95% confidence interval (CI, 0.508–0.858, BW (P<0.001; 95% CI, 0.994–0.998, and lower maternal age (P=0.032; 95% CI, 0.819–0.991 were the risk factors for ROP development and GA (P<0.001; 95% CI, 0.387–0.609 and lower maternal age (P=0.012; 95% CI, 0.795–0.973 were for laser treatment. The odds ratio of requiring laser treatment was 3.3 when the maternal age was <33 years. Conclusion. ROP was more likely to be developed and progressed in infants born from younger mother and low GA.

  1. Prognostic value of neonatal electroencephalography in premature newborns less than 33 weeks of gestational age.

    Science.gov (United States)

    Marret, S; Parain, D; Ménard, J F; Blanc, T; Devaux, A M; Ensel, P; Fessard, C; Samson-Dollfus, D

    1997-03-01

    In a prospective study of 417 premature neonates born before 33 weeks' gestational age, neonatal tracings were reviewed to evaluate the use of EEG in prognosis of neurological injuries. The population was divided into two groups: Group 1, infants who died before the age of 1, and Group 2, survivors in which two categories of motor development were considered. Category A, were abnormal, and Category B, were always normal. Positive rolandic sharp waves (PRSW), which reflect white matter injury, occurred equally in both groups, indicating a similar incidence of white matter damage in Groups 1 and 2. In Group 2, there was a significant correlation of PRSW with developmental motor sequelae (Category A). A frequency of PRSW above 2/min (suggesting more severe periventricular white matter injury) and seizures were significantly more prevalent in Group 1 than in Group 2 and in Category A of Group 2 than in Category B. Background abnormalities occurred equally in both subgroups of extremely premature infants ( 28 weeks' gestation) and extremely (< or = 28 weeks' gestation) premature newborns.

  2. Diet-induced phenotypic plasticity during aging

    NARCIS (Netherlands)

    Rusli, Fenni

    2016-01-01

    Increasing life expectancy in the past decades has led to the emergence of age-related chronic diseases and disabilities. A deeper understanding in the molecular events of the aging process is essential to provide evidence-based guidance how lifestyle interventions will be more efficient in delaying

  3. Microglia phenotypes in aging-associated diseases

    NARCIS (Netherlands)

    Yin, Zhuoran

    2017-01-01

    Due to the improvement in the public health and medical care, the life span of human beings has elongated considerably over the last decades. Consequently, the occurrence of aging-associated diseases has also increased. Inflammation of the brain increases during aging and could be an important facto

  4. Diet-induced phenotypic plasticity during aging

    NARCIS (Netherlands)

    Rusli, Fenni

    2016-01-01

    Increasing life expectancy in the past decades has led to the emergence of age-related chronic diseases and disabilities. A deeper understanding in the molecular events of the aging process is essential to provide evidence-based guidance how lifestyle interventions will be more efficient in delaying

  5. Factors influencing the motor development of prematurely born school-aged children in Brazil.

    Science.gov (United States)

    Moreira, Rafaela S; Magalhães, Lívia C; Dourado, Jordana S; Lemos, Stela M A; Alves, Claudia R L

    2014-09-01

    Despite technological advances in neonatology, premature children are still susceptible to disruptions in neurological development. The current study aimed to analyze the factors that influence motor development in prematurely born school-aged children in Brazil. This cross-sectional study involved 100 "apparently normal" children, aged 8-10 years, born at less than 35 weeks of gestation or with birth weightmotor development was assessed using the Movement Assessment Battery for Children (MABC-2). The children's neuropsychological and academic performance was assessed with the Token Test (TT) and Teste de Desempenho Escolar (TDE), respectively. Parents answered questions regarding the child's clinical history and behavior using the Strengths and Difficulties Questionnaire (SDQ) and family environment resources (RAF). Hierarchical multivariate analyses revealed that 39% of the children scored lower on the MABC-2, as compared to that expected for their age (manual dexterity: 49%; balance: 35%; throwing/catching a ball: 26%). Multivariate analysis indicated that the lower the birth weight, the maternal age at childbirth, and the RAF score, the greater was the chance of impairment on the MABC-2 scores. The probability of having an impairment MABC-2 scores was four times higher when the mother was not employed. We also found associations between MABC-2 scores and the tasks of tying shoes and opening/closing zippers and buttons. Factors related to children's home environments and birth weight are associated with deficient motor performance in prematurely born Brazilian school-aged children. Deficient motor skills were also associated with difficulty in performing functional tasks requiring greater manual dexterity.

  6. Hypertriglyceridemic Waist Phenotype in Adolescents Aged 15 to 18 Years

    OpenAIRE

    Caridad Hernández Gutiérrez; Elodia Rivas Alpízar; Teresita Rodríguez Izaguirre; Alain Francisco Morejón Giraldoni

    2015-01-01

    Background: presence of the hypertriglyceridemic waist phenotype is a predictor of cardiometabolic deterioration, increased type 2 diabetes mellitus and coronary heart disease. Objective: to determine the hypertriglyceridemic waist phenotype in adolescents aged 15 to 18 years from the Area III of Cienfuegos. Method: a case series study was conducted in a universe of 198 adolescents aged 15 to 18 years who attended a consultation created for this study at the Octavio de la Concepción y de la P...

  7. Clinical sonography in premature infant: Sonographic analysis of incidence and grade of germinal metrixhemorrhage according to gestational age,risk

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Hyoung; Kim, I. W.; Yeon, K. M. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1989-12-15

    The authors reviewed 63 premature infants who was born from January 1986 to August 1988 at College of Medicine Seoul National University, to analyze grade of germinal metrixhemorrhage to gestational age, risk.

  8. Telomerase Protects Werner Syndrome Lineage-Specific Stem Cells from Premature Aging

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    Hoi-Hung Cheung

    2014-04-01

    Full Text Available Werner syndrome (WS patients exhibit premature aging predominantly in mesenchyme-derived tissues, but not in neural lineages, a consequence of telomere dysfunction and accelerated senescence. The cause of this lineage-specific aging remains unknown. Here, we document that reprogramming of WS fibroblasts to pluripotency elongated telomere length and prevented telomere dysfunction. To obtain mechanistic insight into the origin of tissue-specific aging, we differentiated iPSCs to mesenchymal stem cells (MSCs and neural stem/progenitor cells (NPCs. We observed recurrence of premature senescence associated with accelerated telomere attrition and defective synthesis of the lagging strand telomeres in MSCs, but not in NPCs. We postulate this “aging” discrepancy is regulated by telomerase. Expression of hTERT or p53 knockdown ameliorated the accelerated aging phenotypein MSC, whereas inhibition of telomerase sensitized NPCs to DNA damage. Our findings unveil a role for telomerase in the protection of accelerated aging in a specific lineage of stem cells.

  9. Kidney aging: from phenotype to genetics.

    Science.gov (United States)

    Buemi, Michele; Nostro, Lorena; Aloisi, Carmela; Cosentini, Vincenzo; Criseo, Manila; Frisina, Nicola

    2005-01-01

    Aging is a physiological process that causes structural and functional changes in human body systems, sometimes leading to various organ failure. As far as the kidney is concerned, both genetic factors and environmental agents may influence the tissues damage in elderly people and the related loss of function. On the other hand, functional adaptations to structural changes appear to be compromised by co-morbid conditions that are frequently found in elderly people, such as atherosclerosis and hypertension. It is not yet known whether physiological aging is inevitably accompanied by a decline in renal function or how rapidly it might happen. The discovery of molecular mechanisms responsible for tissue damage in aging could offer new perspectives on interventions. The role of nitric oxide, oxidative stress, the renin-angiotensin system, changes in length of telomeres, and klotho gene expression are important subjects for further in-depth studies about aging. A better understanding of physiological renal aging could improve the clinical approach to this process and widen the therapeutic possibilities offered by transplantation.

  10. Prematurely aged children: molecular alterations leading to Hutchinson-Gilford progeria and Werner syndromes.

    Science.gov (United States)

    Domínguez-Gerpe, Lourdes; Araújo-Vilar, David

    2008-12-01

    Ageing is thought to be a polygenic and stochastic process in which multiple mechanisms operate at the same time. At the level of the individual organism ageing is associated with a progressive deterioration of health and quality of life, sharing common features such as: alopecia and grey hair, loss of audition, macular degeneration, neurodegeneration, cardiovascular diseases, osteoporosis, cataract formation, type-2 diabetes, lipodystrophies; a generally increased susceptibility to infection, autoimmune disorders and diseases such as cancer; and an impaired ability to cope with stress. Recent studies of mechanisms involved in the ageing process are contributing to the identification of genes involved in longevity. Monogenic heritable disorders causing premature ageing, and animal models have contributed to the understanding of some of the characteristic organism-level features associated with human ageing. Werner syndrome and Hutchinson-Gilford progeria syndrome are the best characterized human disorders. Werner syndrome patients have a median life expectancy of 47 years with clinical conditions from the second decade of life. Hutchinson-Gilford progeria syndrome patients die at a median age of 11-13 years with clinical conditions appearing soon after birth. In both syndromes, alterations in specific genes have been identified, with mutations in the WRN and LMNA genes respectively being the most closely associated with each syndrome. Results from molecular studies strongly suggest an increase in DNA damage and cell senescence as the underlying mechanism of pathological premature ageing in these two human syndromes. The same general mechanism has also been observed in human cells undergoing the normal ageing process. In the present article the molecular mechanisms currently proposed for explaining these two syndromes, which may also partly explain the normal ageing process, are reviewed.

  11. Radiological Diagnosis of a Rare Premature Aging Genetic Disorder: Progeria (Hutchinson-Gilford Syndrome

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    Haji Mohammed Nazir

    2017-01-01

    Full Text Available Hutchinson-Gilford Progeria Syndrome (HGPS is a rare disease with a combination of short stature, bone abnormalities, premature ageing, and skin changes. Though the physical appearance of these patients is characteristic, there is little emphasis on the characteristic radiological features. In this paper, we report a 16-year-old boy with clinical and radiological features of this rare genetic disorder. He had a characteristic facial appearance with a large head, large eyes, thin nose with beaked tip, small chin, protruding ears, prominent scalp veins, and absence of hair.

  12. Characterization of monoaminergic systems in brain regions of prematurely ageing mice.

    Science.gov (United States)

    De la Fuente, Monica; Hernanz, Angel; Medina, Sonia; Guayerbas, Noelia; Fernández, Beatriz; Viveros, Maria Paz

    2003-07-01

    We have previously shown that differences in life span among members of Swiss mouse populations appear to be related to their exploration of a T-maze, with a slow exploration ("slow mice") being linked to increased levels of emotionality/anxiety, an impaired immune function and a shorter life span. Thus, we proposed the slow mice as prematurely ageing mice (PAM). We have now compared the monoaminergic systems of the PAM and of the non-prematurely ageing mice (NPAM), in discrete brain regions. PAM had decreased noradrenaline (NA) levels in all the brain regions analysed, whereas the 3-methoxy-4-hydroxyphenyl glycol (MHPG)/NA ratios were not significantly modified. PAM also showed decreased serotonine (5-HT) levels in hypothalamus, striatum and midbrain, as well as increased 5-hydroxyindol-3-acetic acid (5-HIAA)/5-HT ratios in hypothalamus and hippocampus. The dopamine (DA) content was lower in PAM in most regions, whereas the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA and homovanillic acid (HVA)/DA ratios were either increased or unchanged depending on the region analysed. In most cases, the differences between PAM and NPAM involved both sexes. One exception was the hypothalamus where the differences only affected the male mice. The neurochemical alterations found in PAM resemble some changes reported for aged animals and are related with their behavioural features.

  13. SOX2 redirects the developmental fate of the intestinal epithelium toward a premature gastric phenotype

    Institute of Scientific and Technical Information of China (English)

    Lalini Raghoebir; Dick Tibboel; Ron Smits; Robbert J. Rottier; Elvira RM. Bakker; Jason C. Mills; Sigrid Swagemakers; Marjon Buscop-van Kempen; Anne Boerema-de Munck; Siska Driegen; Dies Meijer; Frank Grosveld

    2012-01-01

    Various factors play an essential role in patterning the digestive tract.During development,Sox2 and Cdx2 are exclusively expressed in the anterior and the posterior parts of the primitive gut,respectively.However,it is unclear whether these transcription factors influence each other in determining specification of the na(i)ve gut endoderm.We therefore investigated whether Sox2 redirects the fate of the prospective intestinal part of the primitive gut.Ectopic expression of Sox2 in the posterior region of the primitive gut caused anteriorization of the gut toward a gastric-like phenotype.Sox2 activated the foregut transcriptional program,in spite of sustained co-expression of endogenous Cdx2.However,binding of Cdx2 to its genomic targets and thus its transcriptional activity was strongly reduced.Recent findings indicate that endodermal Cdx2 is required to initiate the intestinal program and to suppress anterior cell fate.Our findings suggest that reduced Cdx2 expression by itself is not sufficient to cause anteriorization,but that Sox2 expression is also required.Moreover,it indicates that the balance between Sox2 and Cdx2 function is essential for proper specification of the primitive gut and that Sox2 may overrule the initial patterning of the primitive gut,emphasizing the plasticity of the primitive gut.

  14. Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function.

    Directory of Open Access Journals (Sweden)

    Alexandra Vaccaro

    2017-01-01

    Full Text Available Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0 and in wild-type flies under constant light, which stops the clock. In contrast, ClkAR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing than cyc0 and tim0, or than control flies under constant light. Reactive oxygen species accumulated more with age in ClkAR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF-expressing central pacemaker neurons led to similar loss of climbing performance as ClkAR. Conversely, restoring Clk function in these cells was sufficient to rescue the ClkAR locomotor phenotype, independently of behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1 clusters. This neuronal loss was rescued when the ClkAR mutation was placed in an apoptosis-deficient background. Impairing dopamine synthesis in a single pair of PPL1 neurons that innervate the mushroom bodies accelerated locomotor decline in otherwise wild-type flies. Our results therefore reveal a novel circadian-independent requirement for Clk in brain circadian neurons to maintain a subset of dopaminergic cells and avoid premature locomotor aging in Drosophila.

  15. Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function

    Science.gov (United States)

    Issa, Abdul-Raouf; Seugnet, Laurent; Klarsfeld, André

    2017-01-01

    Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0) and in wild-type flies under constant light, which stops the clock. In contrast, ClkAR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing) than cyc0 and tim0, or than control flies under constant light. Reactive oxygen species accumulated more with age in ClkAR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF)-expressing central pacemaker neurons led to similar loss of climbing performance as ClkAR. Conversely, restoring Clk function in these cells was sufficient to rescue the ClkAR locomotor phenotype, independently of behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1) clusters. This neuronal loss was rescued when the ClkAR mutation was placed in an apoptosis-deficient background. Impairing dopamine synthesis in a single pair of PPL1 neurons that innervate the mushroom bodies accelerated locomotor decline in otherwise wild-type flies. Our results therefore reveal a novel circadian-independent requirement for Clk in brain circadian neurons to maintain a subset of dopaminergic cells and avoid premature locomotor aging in Drosophila. PMID:28072817

  16. Determinants of Indices of Cerebral Volume in Former Very Premature Infants at Term Equivalent Age

    Science.gov (United States)

    Wirth, Maelle

    2017-01-01

    Conventional magnetic resonance imaging (MRI) at term equivalent age (TEA) is suggested to be a reliable tool to predict the outcome of very premature infants. The objective of this study was to determine simple reproducible MRI indices, in premature infants and to analyze their neonatal determinants at TEA. A cohort of infants born before 32 weeks gestational age (GA) underwent a MRI at TEA in our center. Two axial images (T2 weighted), were chosen to realize nine measures. We defined 4 linear indices (MAfhlv: thickness of lateral ventricle; CSI: cortex-skull index; VCI: ventricular-cortex index; BOI: bi occipital index) and 1 surface index (VS.A: volume slice area). Perinatal data were recorded. Sixty-nine infants had a GA (median (interquartile range)) of 30.0 weeks GA (27.0; 30.0) and a birth weight of 1240 grams (986; 1477). MRI was done at 41.0 (40.0; 42.0) weeks post menstrual age (PMA). The inter-investigator reproducibility was good. Twenty one MRI (30.5%) were quoted abnormal. We observed an association with retinopathy of prematurity (OR [95CI] = 4.205 [1.231–14.368]; p = 0.017), surgery for patent ductus arteriosus (OR = 4.688 [1.01–21.89]; p = 0.036), early onset infection (OR = 4.688 [1.004–21.889]; p = 0.036) and neonatal treatment by cefotaxime (OR = 3.222 [1.093–9.497]; p = 0.03). There was a difference for VCI between normal and abnormal MRI (0.412 (0.388; 0.429) vs. 0.432 (0.418; 0.449); p = 0,019); BOI was higher when fossa posterior lesions were observed; VS.A seems to be the best surrogate for cerebral volume, 80% of VS.As’ variance being explained by a multiple linear regression model including 7 variables (head circumference at birth and at TEA, PMA, dopamine, ibuprofen treatment, blood and platelets transfusions). These indices, easily and rapidly achievable, seem to be useful but need to be validated in a large population to allow generalization for diagnosis and follow-up of former premature infants. PMID:28125676

  17. The relationship of birth weight, gestational age, and postmenstrual age with ocular biometry parameters in premature infants

    Directory of Open Access Journals (Sweden)

    Ozdemir Ozdemir

    2015-06-01

    Full Text Available ABSTRACT Purpose: To analyze ocular biometry parameters and evaluate their relationship with gestational age, birth weight, and postmenstrual age in prematurely born infants. Methods: The right eyes of 361 premature infants born before the 36th gestational week were evaluated. Birth weight, gestational week, and gender were recorded. An A-scan Biometer was used for obtaining axial measurements, including anterior chamber depth, lens thickness, vitreous length, and total axial length. Results: Gestational age and birth weight values ranged from 23 to 36 weeks and from 560 to 2,670 g, respectively. The mean gestational age and birth weight were 30.8 ± 2.8 weeks and 1,497.9 ± 483.6 g, respectively. During the first examination (4-5 weeks of postnatal age, birth weight and gestational age of the infants correlated significantly and positively with lens thickness, vitreous length, and axial length (r>0.5, p<0.001, but not with anterior chamber depth (r<0.5. Increased vitreous and axial lengths correlated significantly with increasing postmenstrual age of the infants (r=0.669, p<0.001; r=0.845, p<0.001, respectively. Conclusions: Lens thickness, vitreous length, and axial length, but not anterior chamber depth, were significantly correlated with birth weight and gestational age. All four parameters increased with increasing postmenstrual age, with higher correlations for vitreous and axial lengths than for anterior chamber depth and lens thickness. It was concluded that axial elongation resulted primarily from increasing posterior chamber length.

  18. Hypertriglyceridemic Waist Phenotype in Adolescents Aged 15 to 18 Years

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    Caridad Hernández Gutiérrez

    2015-09-01

    Full Text Available Background: presence of the hypertriglyceridemic waist phenotype is a predictor of cardiometabolic deterioration, increased type 2 diabetes mellitus and coronary heart disease. Objective: to determine the hypertriglyceridemic waist phenotype in adolescents aged 15 to 18 years from the Area III of Cienfuegos. Method: a case series study was conducted in a universe of 198 adolescents aged 15 to 18 years who attended a consultation created for this study at the Octavio de la Concepción y de la Pedraja University Polyclinic in Cienfuegos municipality from March to December 2013. Each patient completed a questionnaire including the following variables: age, sex, personal medical history, family medical history, weight, height, body mass index, presence of acanthosis nigricans, triglycerides and perimeter. Results: frequency of the phenotype was determined in 15.1 % of the participants with a slight predominance of the 18 age group (16.3 % and female sex (8.6 %. Twenty-one point six percent of the adolescents with a family history of obesity and 21.7 % of those with first-degree diabetic relatives presented the phenotype, being hypertriglyceridemia the most significant condition. Conclusions: a relationship between a family history of diabetes mellitus, obesity, body mass index above the 90th percentile value and presence of the phenotype was established.

  19. Premature Birth and Large for Gestational Age Are Associated with Risk of Barrett's Esophagus in Adults.

    Science.gov (United States)

    Shiota, Seiji; El-Serag, Hashem B; Thrift, Aaron P

    2016-04-01

    Birth characteristics, including weight and gestational age, may be associated with risk of Barrett's esophagus (BE), the only known precursor for esophageal adenocarcinoma; however, data are limited. To examine associations between various birth characteristics and BE, and whether these associations are mediated by known risk factors for BE. Data were obtained from a cross-sectional study among eligible Veterans Affairs patients scheduled for an upper endoscopy, and a sample identified from primary care clinics. Participants underwent an esophagogastroduodenoscopy and completed a survey that captured information on sociodemographic and clinical factors, as well as birth information. We compared 263 patients with histologically confirmed BE to 1416 controls without BE on endoscopy. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using multivariate logistic regression. Premature birth was independently associated with risk of BE after adjusted by age, sex, race, and other birth characteristics (OR 3.28, 95 % CI 1.22-8.79). On the other hand, large for gestational age was inversely associated with risk of BE (OR 0.46, 95 % CI 0.21-0.98). These effects were stronger for patients with long-segment BE than with short-segment BE. The associations were not mediated by gastroesophageal reflux disease symptoms, use of proton pump inhibitors, Helicobacter Pylori infection, waist-hip-ratio, height or the presence of hiatus hernia. Premature birth and large for gestational age may be associated with risk of BE in adults. These associations do not appear to be mediated through known risk factors for BE; however, additional studies are required to confirm our findings.

  20. Atypical perceptual narrowing in prematurely born infants is associated with compromised language acquisition at 2 years of age.

    Science.gov (United States)

    Jansson-Verkasalo, Eira; Ruusuvirta, Timo; Huotilainen, Minna; Alku, Paavo; Kushnerenko, Elena; Suominen, Kalervo; Rytky, Seppo; Luotonen, Mirja; Kaukola, Tuula; Tolonen, Uolevi; Hallman, Mikko

    2010-07-30

    Early auditory experiences are a prerequisite for speech and language acquisition. In healthy children, phoneme discrimination abilities improve for native and degrade for unfamiliar, socially irrelevant phoneme contrasts between 6 and 12 months of age as the brain tunes itself to, and specializes in the native spoken language. This process is known as perceptual narrowing, and has been found to predict normal native language acquisition. Prematurely born infants are known to be at an elevated risk for later language problems, but it remains unclear whether these problems relate to early perceptual narrowing. To address this question, we investigated early neurophysiological phoneme discrimination abilities and later language skills in prematurely born infants and in healthy, full-term infants. Our follow-up study shows for the first time that perceptual narrowing for non-native phoneme contrasts found in the healthy controls at 12 months was not observed in very prematurely born infants. An electric mismatch response of the brain indicated that whereas full-term infants gradually lost their ability to discriminate non-native phonemes from 6 to 12 months of age, prematurely born infants kept on this ability. Language performance tested at the age of 2 years showed a significant delay in the prematurely born group. Moreover, those infants who did not become specialized in native phonemes at the age of one year, performed worse in the communicative language test (MacArthur Communicative Development Inventories) at the age of two years. Thus, decline in sensitivity to non-native phonemes served as a predictor for further language development. Our data suggest that detrimental effects of prematurity on language skills are based on the low degree of specialization to native language early in development. Moreover, delayed or atypical perceptual narrowing was associated with slower language acquisition. The results hence suggest that language problems related to

  1. Atypical perceptual narrowing in prematurely born infants is associated with compromised language acquisition at 2 years of age

    Directory of Open Access Journals (Sweden)

    Suominen Kalervo

    2010-07-01

    Full Text Available Abstract Background Early auditory experiences are a prerequisite for speech and language acquisition. In healthy children, phoneme discrimination abilities improve for native and degrade for unfamiliar, socially irrelevant phoneme contrasts between 6 and 12 months of age as the brain tunes itself to, and specializes in the native spoken language. This process is known as perceptual narrowing, and has been found to predict normal native language acquisition. Prematurely born infants are known to be at an elevated risk for later language problems, but it remains unclear whether these problems relate to early perceptual narrowing. To address this question, we investigated early neurophysiological phoneme discrimination abilities and later language skills in prematurely born infants and in healthy, full-term infants. Results Our follow-up study shows for the first time that perceptual narrowing for non-native phoneme contrasts found in the healthy controls at 12 months was not observed in very prematurely born infants. An electric mismatch response of the brain indicated that whereas full-term infants gradually lost their ability to discriminate non-native phonemes from 6 to 12 months of age, prematurely born infants kept on this ability. Language performance tested at the age of 2 years showed a significant delay in the prematurely born group. Moreover, those infants who did not become specialized in native phonemes at the age of one year, performed worse in the communicative language test (MacArthur Communicative Development Inventories at the age of two years. Thus, decline in sensitivity to non-native phonemes served as a predictor for further language development. Conclusion Our data suggest that detrimental effects of prematurity on language skills are based on the low degree of specialization to native language early in development. Moreover, delayed or atypical perceptual narrowing was associated with slower language acquisition. The

  2. Premature aging in mice activates a systemic metabolic response involving autophagy induction.

    Science.gov (United States)

    Mariño, Guillermo; Ugalde, Alejandro P; Salvador-Montoliu, Natalia; Varela, Ignacio; Quirós, Pedro M; Cadiñanos, Juan; van der Pluijm, Ingrid; Freije, José M P; López-Otín, Carlos

    2008-07-15

    Autophagy is a highly regulated intracellular process involved in the turnover of most cellular constituents and in the maintenance of cellular homeostasis. It is well-established that the basal autophagic activity of living cells decreases with age, thus contributing to the accumulation of damaged macromolecules during aging. Conversely, the activity of this catabolic pathway is required for lifespan extension in animal models such as Caenorhabditis elegans and Drosophila melanogaster. In this work, we describe the unexpected finding that Zmpste24-null mice, which show accelerated aging and are a reliable model of human Hutchinson-Gilford progeria, exhibit an extensive basal activation of autophagy instead of the characteristic decline in this process occurring during normal aging. We also show that this autophagic increase is associated with a series of changes in lipid and glucose metabolic pathways, which resemble those occurring in diverse situations reported to prolong lifespan. These Zmpste24(-/-) mice metabolic alterations are also linked to substantial changes in circulating blood parameters, such as leptin, glucose, insulin or adiponectin which in turn lead to peripheral LKB1-AMPK activation and mTOR inhibition. On the basis of these results, we propose that nuclear abnormalities causing premature aging in Zmpste24(-/-) mice trigger a metabolic response involving the activation of autophagy. However, the chronic activation of this catabolic pathway may turn an originally intended pro-survival strategy into a pro-aging mechanism and could contribute to the systemic degeneration and weakening observed in these progeroid mice.

  3. The relationship between premature ageing and immune responses in the oral cavity of Down syndrome

    Directory of Open Access Journals (Sweden)

    Yoko Tanaka

    2010-02-01

    Full Text Available Down syndrome (DS is the most common chromosomal disorder resulting in various abnormalities such as mental retardation, immunodeficiency and physical abnormities. Especially, abnormality of the immune function is important pathological features in this syndrome, and leads to increased susceptibility to viral or bacterial infections. Interestingly, several studies have showed that they have high susceptibility of severe periodontal disease, even though they have lower or equal prevalence of dental caries. Many studies have attempted to clarify this phenomenon but it remains unsolved. It is also well known that DS is a premature ageing syndrome. DS has been considered as a model of precocious, abnormal ageing of immune function in human. Age-related declines in immune function cause more susceptibility to infections in the elderly. In addition, it is well known that ageing is related with telomere shortening. Furthermore, DS has an accelerated telomere shortening. However, there are only a few reports that focus on the relations among ageing, telomere length and high susceptibility of oral infectious disease in individuals with DS. Therefore, we summarize our current knowledge on the relations between the oral disease and immunodeficiency in individuals with DS taking account of telomere shortening and ageing.

  4. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging XpdTTD mice

    NARCIS (Netherlands)

    J.Y. Park; M.O. Cho; S. Leonard (Shanique); B. Calder (Brent); I.S. Mian (Saira); W.H. Kim (Woo); S.W.P. Wijnhoven (Susan); H. van Steeg (Harry); J.R. Mitchell (James); G.T.J. van der Horst (Gijsbertus); J.H.J. Hoeijmakers (Jan); P. Cohen (Pinchas); J. Vijg (Jan); Y. Suh (Yousin)

    2008-01-01

    textabstractUnrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. XpdTTDmice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a rduced incidence

  5. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging XpdTTD mice

    NARCIS (Netherlands)

    J.Y. Park; M.O. Cho; S. Leonard (Shanique); B. Calder (Brent); I.S. Mian (Saira); W.H. Kim (Woo); S.W.P. Wijnhoven (Susan); H. van Steeg (Harry); J.R. Mitchell (James); G.T.J. van der Horst (Gijsbertus); J.H.J. Hoeijmakers (Jan); P. Cohen (Pinchas); J. Vijg (Jan); Y. Suh (Yousin)

    2008-01-01

    textabstractUnrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. XpdTTDmice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a rduced incidence

  6. MECHANISMS OF PREMATURE VASCULAR AGING IN CHILDREN WITH HUTCHINSON-GILFORD PROGERIA SYNDROME

    Science.gov (United States)

    Gerhard-Herman, Marie; Smoot, Leslie B.; Wake, Nicole; Kieran, Mark W.; Kleinman, Monica E.; Miller, David T.; Schwartzman, Armin; Giobbie-Hurder, Anita; Neuberg, Donna; Gordon, Leslie B.

    2011-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare, segmental premature aging syndrome of accelerated atherosclerosis and early death from myocardial infarction or stroke. This study sought to establish comprehensive characterization of the fatal vasculopathy in HGPS and its relevance to normal aging. We performed cardiovascular assessments at a single clinical site on the largest prospectively studied cohort to date. Carotid-femoral pulse wave velocity was dramatically elevated (mean 13.00±3.83 m/s). Carotid duplex ultrasound echobrightness, assessed in predefined tissue sites as a measure of arterial wall density, was significantly greater than age- and gender-matched controls in the intima-media (P<0.02), near adventitia (P<0.003) and deep adventitia (P<0.01), as was internal carotid artery mean flow velocity (p<0.0001). Ankle-brachial indices were abnormal in 78% of patients. Effective disease treatments may be heralded by normalizing trends of these noninvasive cardiovascular measures. The data demonstrates that, along with peripheral vascular occlusive disease, accelerated vascular stiffening is an early and pervasive mechanism of vascular disease in HGPS. There is considerable overlap with cardiovascular changes of normal aging, which reinforces the view that defining mechanisms of cardiovascular disease in HGPS provides a unique opportunity to isolate a subset of factors influencing cardiovascular disease in the general aging population. PMID:22083160

  7. Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Gerhard-Herman, Marie; Smoot, Leslie B; Wake, Nicole; Kieran, Mark W; Kleinman, Monica E; Miller, David T; Schwartzman, Armin; Giobbie-Hurder, Anita; Neuberg, Donna; Gordon, Leslie B

    2012-01-01

    Hutchinson-Gilford progeria syndrome is a rare, segmental premature aging syndrome of accelerated atherosclerosis and early death from myocardial infarction or stroke. This study sought to establish comprehensive characterization of the fatal vasculopathy in Hutchinson-Gilford progeria syndrome and its relevance to normal aging. We performed cardiovascular assessments at a single clinical site on the largest prospectively studied cohort to date. Carotid-femoral pulse wave velocity was dramatically elevated (mean: 13.00±3.83 m/s). Carotid duplex ultrasound echobrightness, assessed in predefined tissue sites as a measure of arterial wall density, was significantly greater than age- and sex-matched controls in the intima-media (Pnormalizing trends of these noninvasive cardiovascular measures. The data demonstrate that, along with peripheral vascular occlusive disease, accelerated vascular stiffening is an early and pervasive mechanism of vascular disease in Hutchinson-Gilford progeria syndrome. There is considerable overlap with cardiovascular changes of normal aging, which reinforces the view that defining mechanisms of cardiovascular disease in Hutchinson-Gilford progeria syndrome provides a unique opportunity to isolate a subset of factors influencing cardiovascular disease in the general aging population.

  8. A quantitative neural network approach to understanding aging phenotypes.

    Science.gov (United States)

    Ash, Jessica A; Rapp, Peter R

    2014-05-01

    Basic research on neurocognitive aging has traditionally adopted a reductionist approach in the search for the basis of cognitive preservation versus decline. However, increasing evidence suggests that a network level understanding of the brain can provide additional novel insight into the structural and functional organization from which complex behavior and dysfunction emerge. Using graph theory as a mathematical framework to characterize neural networks, recent data suggest that alterations in structural and functional networks may contribute to individual differences in cognitive phenotypes in advanced aging. This paper reviews literature that defines network changes in healthy and pathological aging phenotypes, while highlighting the substantial overlap in key features and patterns observed across aging phenotypes. Consistent with current efforts in this area, here we outline one analytic strategy that attempts to quantify graph theory metrics more precisely, with the goal of improving diagnostic sensitivity and predictive accuracy for differential trajectories in neurocognitive aging. Ultimately, such an approach may yield useful measures for gauging the efficacy of potential preventative interventions and disease modifying treatments early in the course of aging. Published by Elsevier B.V.

  9. Microglial Aging in the Healthy CNS: Phenotypes, Drivers, and Rejuvenation

    Directory of Open Access Journals (Sweden)

    Wai T Wong

    2013-03-01

    Full Text Available Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and age-related macular degeneration, share two characteristics in common: 1 a disease prevalence that increases markedly with advancing age, and 2 neuroinflammatory changes in which microglia, the primary resident immune cell of the CNS, feature prominently. These characteristics have led to the hypothesis that pathogenic mechanisms underlying age-related neurodegenerative disease involve aging changes in microglia. If correct, targeting features of microglial senescence may constitute a feasible therapeutic strategy. This review explores this hypothesis and its implications by considering the current knowledge on how microglia undergo change during aging and how the emergence of these aging phenotypes relate to significant alterations in microglial function. Evidence and theories on cellular mechanisms implicated in driving senescence in microglia are reviewed, as are rejuvenative measures and strategies that aim to reverse or ameliorate the aging microglial phenotype. Understanding and controlling microglial aging may represent an opportunity for elucidating disease mechanisms and for formulating novel therapies.

  10. Trajectories of the healthy ageing phenotype among middle-aged and older Britons, 2004-2013.

    Science.gov (United States)

    Tampubolon, Gindo

    2016-06-01

    Since the ageing population demands a response to ensure older people remain healthy and active, we studied the dynamics of a recently proposed healthy ageing phenotype. We drew the phenotype's trajectories and tested whether their levels and rates of change are influenced by health behaviours, comorbidities and socioeconomic positions earlier in the life course. The English Longitudinal Ageing Study, a prospective, nationally representative sample of people aged ≥50 years, measured a set of eight biomarkers which make up the outcome of the healthy ageing phenotype three times over nearly a decade (N2004=5009, N2008=5301, N2013=4455). A cluster of health behaviours, comorbidities and socioeconomic positions were also measured repeatedly. We assessed the phenotype's distribution non-parametrically, then fitted linear mixed models to phenotypic change and further examined time interactions with gender and socioeconomic position. We ran additional analyses to test robustness. Women had a wider distribution of the healthy ageing phenotype than men had. The phenotype declined annually by -0.242 (95% confidence interval [CI]: -0.352, -0.131). However, there was considerable heterogeneity in the levels and rates of phenotypic change. Women started at higher levels, then declined more steeply by -0.293 (CI: -0.403, -0.183) annually, leading to crossover in the trajectories. Smoking and physical activity assessed on the Allied Dunbar scale were strongly associated with the trajectories. Though marked by secular decline, the trajectories of the healthy ageing phenotype showed distinct socioeconomic gradients. The trajectories were also susceptible to variations in health behaviours, strengthening the case for serial interventions to attain healthy and active ageing. Copyright © 2016 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.

  11. Transformation Resistance in a Premature Aging Disorder Identifies a Tumor-Protective Function of BRD4

    Directory of Open Access Journals (Sweden)

    Patricia Fernandez

    2014-10-01

    Full Text Available Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis.

  12. Premature Aging of the Microcirculation in Patients with Advanced Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Oanh H.D. Thang

    2012-11-01

    Full Text Available Background: Increasing age and advanced chronic kidney disease (CKD are both associated with an attenuated vasodilator response of the skin microcirculation. In the present study, we investigated the effect of aging on microvascular reactivity in patients with advanced CKD. Methods: Acetylcholine (ACh-mediated endothelium-dependent vasodilation and sodium nitroprusside (SNP-mediated endothelium-independent vasodilation were assessed by iontophoresis combined with laser Doppler flowmetry. Microvascular function was compared between 52 patients with advanced CKD (stage 4–5: n = 16; end-stage renal disease: n = 36 and 33 healthy control subjects. As aging has an important effect on microvascular function, both control subjects and CKD patients were divided in subgroups younger and older than 45 years. Linear regression analysis was applied to assess potential associations between microvascular function and various demographic and clinical parameters. Results: There were three main findings. (1 In young patients with advanced CKD, both ACh- and SNP-mediated vasodilations were impaired if compared to young healthy controls (p = 0.04 and p = 0.056, respectively. (2 In young patients with advanced CKD, microvascular function was similar to old healthy controls and elderly patients with advanced CKD. (3 Whereas age was inversely associated with microvascular function in healthy controls (log ACh-mediated vasodilation R = –0.41; p = 0.02 and log SNP-mediated vasodilation R = –0.38; p = 0.03, no such relation was found in patients with advanced CKD. Conclusions: Our results are consistent with premature aging of the microvascular vasodilatory capacity in patients with advanced CKD.

  13. Modifiable causes of premature death in middle-age in Western Europe : Results from the EPIC cohort study

    NARCIS (Netherlands)

    Muller, David C.; Murphy, Neil; Johansson, Mattias; Ferrari, Pietro; Tsilidis, Konstantinos K.; Boutron-Ruault, Marie Christine; Clavel, Francoise; Dartois, Laureen; Li, Kuanrong; Kaaks, Rudolf; Weikert, Cornelia; Bergmann, Manuela; Boeing, Heiner; Tjønneland, Anne; Overvad, Kim; Redondo, M. Luisa; Agudo, Antonio; Molina-Portillo, Elena; Altzibar, Jone M.; Cirera, Lluís; Ardanaz, Eva; Khaw, Kay Tee; Wareham, Nicholas J.; Key, Timothy J.; Travis, Ruth C.; Bamia, Christina; Orfanos, Philippos; Trichopoulou, Antonia; Palli, Domenico; Pala, Valeria; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Verschuren, W. M Monique; Struijk, Ellen A.; Peeters, Petra H.; Engström, Gunnar; Melander, Olle; Sund, Malin; Weiderpass, Elisabete; Skeie, Guri; Lund, Eiliv; Norat, Teresa; Gunter, Marc; Riboli, Elio; Brennan, Paul

    2016-01-01

    Background: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk

  14. Modifiable causes of premature death in middle-age in Western Europe : results from the EPIC cohort study

    NARCIS (Netherlands)

    Muller, David C.; Murphy, Neil; Johansson, Mattias; Ferrari, Pietro; Tsilidis, Konstantinos K.; Boutron-Ruault, Marie-Christine; Clavel, Francoise; Dartois, Laureen; Li, Kuanrong; Kaaks, Rudolf; Weikert, Cornelia; Bergmann, Manuela; Boeing, Heiner; Tjonneland, Anne; Overvad, Kim; Luisa Redondo, M.; Agudo, Antonio; Molina-Portillo, Elena; Altzibar, Jone M.; Cirera, Lluis; Ardanaz, Eva; Khaw, Kay-Tee; Wareham, Nicholas J.; Key, Timothy J.; Travis, Ruth C.; Bamia, Christina; Orfanos, Philippos; Trichopoulou, Antonia; Palli, Domenico; Pala, Valeria; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Verschuren, W. M. Monique; Struijk, Ellen A.; Peeters, Petra H.; Engstrom, Gunnar; Melander, Olle; Sund, Malin; Weiderpass, Elisabete; Skeie, Guri; Lund, Eiliv; Norat, Teresa; Gunter, Marc; Riboli, Elio; Brennan, Paul

    2016-01-01

    Background: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk

  15. School performance at nine years of age in very premature and very low birth weight infants : Perinatal risk factors and predictors at five years of age

    NARCIS (Netherlands)

    Hille, E.T.M.; Ouden, A.L. den; Bauer, L.; Oudenrijn, C. van den; Brand, R.; Verloove-Vanhorick, S.P.

    1994-01-01

    To assess the impact of both perinatal disorders and developmental problems identified at preschool age on school performance, we followed a virtually complete birth cohort of very premature (<32 completed weeks of gestation) and very low birth weight infants until they were 9 years of age. In 84% o

  16. Attenuation of Replication Stress–Induced Premature Cellular Senescence to Assess Anti-Aging Modalities

    Science.gov (United States)

    Zhao, Hong; Darzynkiewicz, Zbigniew

    2014-01-01

    Described is an in vitro model of premature senescence in pulmonary adenocarcinoma A549 cells induced by persistent DNA replication stress in response to treatment with the DNA damaging drug mitoxantrone (Mxt). The degree of cellular senescence, based on characteristic changes in cell morphology, is measured by laser scanning cytometry. Specifically, the flattening of cells grown on slides (considered the hallmark of cellular senescence) is measured as the decline in local intensity of DNA-associated DAPI fluorescence (represented by maximal pixels). This change is paralleled by an increase in nuclear area. Thus, the ratio of mean intensity of maximal pixels to nuclear area provides a very sensitive morphometric biomarker for the degree of senescence. This analysis is combined with immunocytochemical detection of senescence markers, such as overexpression of cyclin kinase inhibitors (e.g., p21WAF1) and phosphorylation of ribosomal protein S6 (rpS6), a key marker associated with aging/senescence that is detected using a phospho-specific antibody. These biomarker indices are presented in quantitative terms defined as a senescence index (SI), which is the fraction of the marker in test cultures relative to the same marker in exponentially growing control cultures. This system can be used to evaluate the anti-aging potential of test agents by assessing attenuation of maximal senescence. As an example, the inclusion of berberine, a natural alkaloid with reported anti-aging properties and a long history of use in traditional Chinese medicine, is shown to markedly attenuate the Mxt-induced SI and phosphorylation of rpS6. The multivariate analysis of senescence markers by laser scanning cytometry offers a promising tool to explore the potential anti-aging properties of a variety agents. PMID:24984966

  17. Attenuation of replication stress-induced premature cellular senescence to assess anti-aging modalities.

    Science.gov (United States)

    Zhao, Hong; Darzynkiewicz, Zbigniew

    2014-01-01

    Described is an in vitro model of premature senescence in pulmonary adenocarcinoma A549 cells induced by persistent DNA replication stress in response to treatment with the DNA damaging drug mitoxantrone (Mxt). The degree of cellular senescence, based on characteristic changes in cell morphology, is measured by laser scanning cytometry. Specifically, the flattening of cells grown on slides (considered the hallmark of cellular senescence) is measured as the decline in local intensity of DNA-associated DAPI fluorescence (represented by maximal pixels). This change is paralleled by an increase in nuclear area. Thus, the ratio of mean intensity of maximal pixels to nuclear area provides a very sensitive morphometric biomarker for the degree of senescence. This analysis is combined with immunocytochemical detection of senescence markers, such as overexpression of cyclin kinase inhibitors (e.g., p21(WAF1) ) and phosphorylation of ribosomal protein S6 (rpS6), a key marker associated with aging/senescence that is detected using a phospho-specific antibody. These biomarker indices are presented in quantitative terms defined as a senescence index (SI), which is the fraction of the marker in test cultures relative to the same marker in exponentially growing control cultures. This system can be used to evaluate the anti-aging potential of test agents by assessing attenuation of maximal senescence. As an example, the inclusion of berberine, a natural alkaloid with reported anti-aging properties and a long history of use in traditional Chinese medicine, is shown to markedly attenuate the Mxt-induced SI and phosphorylation of rpS6. The multivariate analysis of senescence markers by laser scanning cytometry offers a promising tool to explore the potential anti-aging properties of a variety agents.

  18. Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells.

    Science.gov (United States)

    Guidi, Novella; Sacma, Mehmet; Ständker, Ludger; Soller, Karin; Marka, Gina; Eiwen, Karina; Weiss, Johannes M; Kirchhoff, Frank; Weil, Tanja; Cancelas, Jose A; Florian, Maria Carolina; Geiger, Hartmut

    2017-04-03

    Upon aging, hematopoietic stem cells (HSCs) undergo changes in function and structure, including skewing to myeloid lineages, lower reconstitution potential and loss of protein polarity. While stem cell intrinsic mechanisms are known to contribute to HSC aging, little is known on whether age-related changes in the bone marrow niche regulate HSC aging. Upon aging, the expression of osteopontin (OPN) in the murine bone marrow stroma is reduced. Exposure of young HSCs to an OPN knockout niche results in a decrease in engraftment, an increase in long-term HSC frequency and loss of stem cell polarity. Exposure of aged HSCs to thrombin-cleaved OPN attenuates aging of old HSCs, resulting in increased engraftment, decreased HSC frequency, increased stem cell polarity and a restored balance of lymphoid and myeloid cells in peripheral blood. Thus, our data suggest a critical role for reduced stroma-derived OPN for HSC aging and identify thrombin-cleaved OPN as a novel niche informed therapeutic approach for ameliorating HSC phenotypes associated with aging. © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  19. [The relationship between metabolic disorders and small for gestational age with idiopathic premature adrenarche].

    Science.gov (United States)

    Mejorado Molano, Francisco Javier; Andrés Zallo, Laura; Fornos Rodríguez, Marta; Pérez Segura, Pilar; Gavela Pérez, Teresa; Sanz Calvo, María Luisa; Soriano Guillén, Leandro

    2016-11-09

    There is still controversy on the relationship between idiopathic premature adrenarche (IPA) and a history of small for gestational age, as well as the concomitant presence of obesity and other metabolic disturbances. An attempt is made to study these potential associations in a cohort of girls with IPA from our hospital. A descriptive cross-sectional study was conducted that included girls with a diagnosis of IPA from the Paediatric Department of the Fundación Jiménez Díaz (Madrid, Spain) between January 2007 and May 2015. A record was made of family and personal history with perinatal data, as well as anthropometric data and biochemical values at the time of diagnosis. Out of a total of 76 girls with IPA, 2.7% had a history of small for gestational age. When body mass index was analysed according to modified criteria of WHO 2007/Cole 2000, 11.8% were overweight, and 11.8% were obese at diagnosis. Using the criteria set by the Spanish Ministry of Health, 6.6% were overweight and 18.4% obese, with 21.2% of the girls being insulin resistance, and 13.95% having dyslipidaemia. None of them had hypertension. From a comparative analysis between normal and overweight and obesity IPA girls, the latter had significantly higher levels of triglycerides and insulin, a higher HOMA index, and lower levels of HDL cholesterol. IPA girls included in the study do not have a higher prevalence of small for gestational age compared to the general population. Prevalence of overweight and obesity in girls with IPA is not higher than the prevalence in the normal population. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  20. Younger or older parental age and risk of suicidality, premature death, psychiatric illness, and criminality in offspring

    OpenAIRE

    Mok, Pearl; Antonsen, Sussie; Pedersen, Carsten Bøcker; Webb, Roger

    2017-01-01

    BackgroundYounger or older parental age has been linked with a range of adverse offspring endpoints. We investigated associations between parental age and nine adverse offspring outcomes in three correlated domains: (i) Premature death: suicide, unnatural death, natural death; (ii) Psychiatric morbidity: any mental illness, suicide attempt, substance misuse; (iii) Criminality: violent offending, imprisonment, driving whilst intoxicated.MethodsPersons born in Denmark 1966–1996 were followed fr...

  1. Investigation into the human premature ageing disease, Hutchinson Gilford Progeria syndrome, using hTERT immortalised fibroblasts

    OpenAIRE

    Worthington, Gemma Louise

    2016-01-01

    This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London Hutchinson Gilford Progeria syndrome (HGPS) is a rare premature ageing disease affecting children. 80% of “classic” HGPS patients share the same mutation in the LMNA gene that gives rise to characteristics similar to normal human ageing and they usually die in their teens from heart attacks or strokes. Cells taken from progeria patients have a short replicative lifespan in culture an...

  2. Long-chain saturated and monounsaturated fatty acids associate with development of premature infants up to 18 months of age.

    Science.gov (United States)

    Strandvik, Birgitta; Ntoumani, Eleni; Lundqvist-Persson, Cristina; Sabel, Karl-Göran

    2016-04-01

    Myelination is important perinatally and highly dependent on long-chain saturated and monounsaturated fatty acids. Long-chain polyunsaturated fatty acids, nowadays often supplemented, inhibit oleic acid synthesis. Using data from a premature cohort, we studied if nervonic, lignoceric and oleic acids correlated to growth and early development up to 18 months corrected age. Small for gestational age infants had lower concentrations than infants appropriate for gestational age. Only oleic acid was negatively correlated to long-chain polyunsaturated fatty acids. Oleic and lignoceric acids correlated to social interaction at one month, and nervonic acid to mental, psychomotor and behavioral development at 6, 10 and 18 months, also when adjusted for several confounders. Negative association between oleic acid and long-chain polyunsaturated fatty acids suggests inhibition of delta-9 desaturase, and nervonic acid´s divergent correlation to lignoceric and oleic acids suggests different metabolism in neonatal period. Our results may have implications for the supplementation of premature infants.

  3. The Reasons and Prevention of Ovarian Premature Aging%卵巢早衰的原因与预防

    Institute of Scientific and Technical Information of China (English)

    李莉

    2014-01-01

    Objective To analyze the factors that cause ovarian premature aging so as to provide a basis for clinical prevention and treatment of ovarian premature aging. Methods A questionnaire was used to investigate the 100 cases in the observation group and the control group, and the data was treated by logistic regression analysis. Results 12 variables such as the number of induced abortion, drinking, smoking, marital status, family and social relationship, bean products, mood, taking corticosteroids and so on are related to the occurrence of ovarian premature aging. Multiple factors analysis showed that marital status (OR = 6.03), number of induced abortion (OR = 2.14), smoking (OR =3.26), hair coloring (OR =2.74), mood (OR= 0.16), vegetables (OR = 0.34), mumps (OR = 10.23), and other factors are closely associated with ovarian premature aging. Conclusion Many factors can cause ovarian premature aging, so effective measures should be taken clinically to strengthen the prevention and treatment, thereby reducing the incidence of the disease and promoting the recovery of the patients as early as possible.%目的:分析卵巢早衰发生因素,为临床卵巢早衰的防治提供一定的依据。方法采用问卷调查方式对观察组和健康对照组共100例进行logistic回归分析。结果卵巢早衰发生因素与人工流产次数、饮酒、吸烟、婚姻状况以及家人社会相处关系、豆制品、心情和服用糖皮质激素等12个变量相关。多因素分析表明,婚姻状况(OR=6.03)、人工流产次数(OR=2.14)、吸烟(OR=3.26)、染发(OR=2.74)、心情(OR=0.16)、蔬菜(OR=0.34)、腮腺炎(OR=10.23)等因素与卵巢早衰密切相关。结论卵巢早衰发生因素较多,临床应采取有效的措施加强预防,治疗,以降低发病率,促进患者早日康复。

  4. Néstor-Guillermo progeria syndrome: a novel premature aging condition with early onset and chronic development caused by BANF1 mutations.

    Science.gov (United States)

    Cabanillas, Rubén; Cadiñanos, Juan; Villameytide, José A F; Pérez, Mercedes; Longo, Jesús; Richard, José M; Alvarez, Rebeca; Durán, Noelia S; Illán, Rafael; González, Daniel J; López-Otín, Carlos

    2011-11-01

    Progeria syndromes are rare disorders that involve premature aging. Mutations in BANF1 have been recently reported to cause a new hereditary progeroid syndrome that we now propose to call the Néstor-Guillermo progeria syndrome (NGPS). We describe herein the clinical features of the first two NGPS patients, who phenocopy features of classic progerias (i.e., Hutchinson-Gilford progeria syndrome or mandibuloacral dysplasia), such as aged appearance, growth retardation, decreased subcutaneous fat, thin limbs, and stiff joints. However, these NGPS patients have a distinctive phenotype. In their early adulthood (32 and 24 years of age), they have no signs of cardiovascular impairment, diabetes mellitus, or hypertriglyceridemia. In contrast, they suffer profound skeletal abnormalities that affect their quality of life. The observed differences are of utmost importance to patients and their families and palliation of osseous manifestations is a priority, given their relatively long lifespan. We define NGPS as a chronic progeria because of its slow clinical course and relatively long survival, despite its early onset. Understanding the differences between progeria syndromes might contribute to the development of treatment strategies for common skeletal conditions, as well as aging itself.

  5. Premature Contractions

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Premature Contractions - PACs and PVCs Updated:Dec 15,2016 ... You felt this more-forceful beat. Types of premature contractions Premature atrial contractions (PACs) start in the ...

  6. Attenuation of Replication Stress–Induced Premature Cellular Senescence to Assess Anti-Aging Modalities

    OpenAIRE

    Zhao, Hong; Darzynkiewicz, Zbigniew

    2014-01-01

    Described is an in vitro model of premature senescence in pulmonary adenocarcinoma A549 cells induced by persistent DNA replication stress in response to treatment with the DNA damaging drug mitoxantrone (Mxt). The degree of cellular senescence, based on characteristic changes in cell morphology, is measured by laser scanning cytometry. Specifically, the flattening of cells grown on slides (considered the hallmark of cellular senescence) is measured as the decline in local intensity of DNA-as...

  7. A model of premature aging in mice based on altered stress-related behavioral response and immunosenescence.

    Science.gov (United States)

    Viveros, María-Paz; Arranz, Lorena; Hernanz, Angel; Miquel, Jaime; De la Fuente, Mónica

    2007-01-01

    The intensity of behavioral and neuroendocrine responses to stressful stimuli in rodent strains seems to be inversely related to their life span. We have previously shown that interindividual differences in members of outbred Swiss and inbred BALB/c mouse populations, both male and female, may be related to their behavior in a simple T-maze test. The animals that explore the maze slowly show impaired neuromuscular vigor and coordination, decreased locomotor activity, increased level of emotionality/anxiety, decreased levels of brain biogenic amines as well as immunosenescence and decreased life span, when compared to their control counterparts, which quickly explore the maze. These traits are similar to some of the alterations previously observed in aging animals and therefore we proposed that those 'slow mice' are biologically older than the fast animals and may be a model of prematurely aging mice (PAM). Although most of our work on this model has been performed on chronologically adult-mature animals, we have also shown that certain characteristics of PAM, such as increased anxiety and deficient immune response, are already present in chronologically young animals. Thus, it is tempting to hypothesize that chronic hyperreactivity to stress (trait anxiety) leading to immune dysfunction may have a causal relationship with impaired health and premature aging. In view of the link between oxidative stress and the aging process, the redox state of peritoneal leukocytes from PAM has been studied, showing an oxidative stress situation. In the present work we have determined the levels of a key antioxidant, reduced glutathione (GSH), and the oxidant malondialdehyde (MDA), a marker of lipid peroxidation, both in the spleen and brain of male and female PAM and non-PAM (NPAM). We found that GSH and MDA are decreased and increased, respectively, in PAM with respect to NPAM. Moreover, diet supplementation with antioxidants showed to be an effective strategy for protection

  8. Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema.

    Science.gov (United States)

    Chilosi, Marco; Carloni, Angelo; Rossi, Andrea; Poletti, Venerino

    2013-09-01

    Different anatomic and physiological changes occur in the lung of aging people that can affect pulmonary functions, and different pulmonary diseases, including deadly diseases such as chronic obstructive pulmonary disease (COPD)/emphysema and idiopathic pulmonary fibrosis (IPF), can be related to an acceleration of the aging process. The individual genetic background, as well as exposure to a variety of toxic substances (cigarette smoke in primis) can contribute significantly to accelerating pulmonary senescence. Premature aging can impair lung function by different ways: by interfering specifically with tissue repair mechanisms after damage, thus perturbing the correct crosstalk between mesenchymal and epithelial components; by inducing systemic and/or local alteration of the immune system, thus impairing the complex mechanisms of lung defense against infections; and by stimulating a local and/or systemic inflammatory condition (inflammaging). According to recently proposed pathogenic models in COPD and IPF, premature cellular senescence likely affects distinct progenitors cells (mesenchymal stem cells in COPD, alveolar epithelial precursors in IPF), leading to stem cell exhaustion. In this review, the large amount of data supporting this pathogenic view are discussed, with emphasis on the possible molecular and cellular mechanisms leading to the severe parenchymal remodeling that characterizes, in different ways, these deadly diseases.

  9. Premature infant

    Science.gov (United States)

    There are many support groups for parents of premature babies. Ask the social worker in the neonatal intensive care unit. ... Prematurity used to be a major cause of infant deaths. Improved ... Prematurity can have long-term effects. Many premature infants ...

  10. Patch-based augmentation of Expectation-Maximization for brain MRI tissue segmentation at arbitrary age after premature birth.

    Science.gov (United States)

    Liu, Mengyuan; Kitsch, Averi; Miller, Steven; Chau, Vann; Poskitt, Kenneth; Rousseau, Francois; Shaw, Dennis; Studholme, Colin

    2016-02-15

    Accurate automated tissue segmentation of premature neonatal magnetic resonance images is a crucial task for quantification of brain injury and its impact on early postnatal growth and later cognitive development. In such studies it is common for scans to be acquired shortly after birth or later during the hospital stay and therefore occur at arbitrary gestational ages during a period of rapid developmental change. It is important to be able to segment any of these scans with comparable accuracy. Previous work on brain tissue segmentation in premature neonates has focused on segmentation at specific ages. Here we look at solving the more general problem using adaptations of age specific atlas based methods and evaluate this using a unique manually traced database of high resolution images spanning 20 gestational weeks of development. We examine the complimentary strengths of age specific atlas-based Expectation-Maximization approaches and patch-based methods for this problem and explore the development of two new hybrid techniques, patch-based augmentation of Expectation-Maximization with weighted fusion and a spatial variability constrained patch search. The former approach seeks to combine the advantages of both atlas- and patch-based methods by learning from the performance of the two techniques across the brain anatomy at different developmental ages, while the latter technique aims to use anatomical variability maps learnt from atlas training data to locally constrain the patch-based search range. The proposed approaches were evaluated using leave-one-out cross-validation. Compared with the conventional age specific atlas-based segmentation and direct patch based segmentation, both new approaches demonstrate improved accuracy in the automated labeling of cortical gray matter, white matter, ventricles and sulcal cortical-spinal fluid regions, while maintaining comparable results in deep gray matter.

  11. Premature Birth and Large for Gestational Age Are Associated with Risk of Barrett’s Esophagus in Adults

    Science.gov (United States)

    Shiota, Seiji; El-Serag, Hashem B.; Thrift, Aaron P.

    2015-01-01

    Background Birth characteristics, including weight and gestational age, may be associated with risk of Barrett’s esophagus (BE), the only known precursor for esophageal adenocarcinoma; however, data are limited. Aims To examine associations between various birth characteristics and BE, and whether these associations are mediated by known risk factors for BE. Methods Data were obtained from a cross-sectional study among eligible Veterans Affairs patients scheduled for an upper endoscopy, and a sample identified from primary care clinics. Participants underwent an esophagogastroduodenoscopy and completed a survey that captured information on sociodemographic and clinical factors, as well as birth information. We compared 263 patients with histologically confirmed BE to 1,416 controls without BE on endoscopy. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using multivariate logistic regression. Results Premature birth was independently associated with risk of BE after adjusted by age, sex, race, and other birth characteristics (OR 3.28, 95% CI 1.22–8.79). On the other hand, large for gestational age was inversely associated with risk of BE (OR 0.46, 95% CI 0.21–0.98). These effects were stronger for patients with long-segment BE than short-segment BE. The associations were not mediated by gastroesophageal reflux disease symptoms, use of proton pump inhibitors, Helicobacter Pylori infection, waist-hip-ratio, height or presence of hiatus hernia. Conclusions Premature birth and large for gestational age may be associated with risk of BE in adults. These associations do not appear to be mediated through known risk factors for BE; however, additional studies are required to confirm our findings. PMID:26611860

  12. Age at diagnosis of pheochromocytoma differs according to catecholamine phenotype and tumor location

    NARCIS (Netherlands)

    Eisenhofer, G.; Timmers, H.J.L.M.; Lenders, J.W.M.; Bornstein, S.R.; Tiebel, O.; Mannelli, M.; King, K.S.; Vocke, C.D.; Linehan, W.M.; Bratslavsky, G.; Pacak, K.

    2011-01-01

    CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are diagnosed earlier in patients with hereditary than sporadic disease. Whether other factors influence age at diagnosis is unclear. OBJECTIVE: We examined ages at which PPGLs were diagnosed according to different catecholamine phenotypes and

  13. Inhibition of Mitochondrial Cytochrome c Release and Suppression of Caspases by Gamma-Tocotrienol Prevent Apoptosis and Delay Aging in Stress-Induced Premature Senescence of Skin Fibroblasts

    Directory of Open Access Journals (Sweden)

    Suzana Makpol

    2012-01-01

    Full Text Available In this study, we determined the molecular mechanism of γ-tocotrienol (GTT in preventing cellular aging by focusing on its anti-apoptotic effect in stress-induced premature senescence (SIPS model of human diploid fibroblasts (HDFs. Results obtained showed that SIPS exhibited senescent-phenotypic characteristic, increased expression of senescence-associated β-galactosidase (SA β-gal and promoted G0/G1 cell cycle arrest accompanied by shortening of telomere length with decreased telomerase activity. Both SIPS and senescent HDFs shared similar apoptotic changes such as increased Annexin V-FITC positive cells, increased cytochrome c release and increased activation of caspase-9 and caspase-3 (P<0.05. GTT treatment resulted in a significant reduction of Annexin V-FITC positive cells, inhibited cytochrome c release and decreased activation of caspase-9 and caspase-3 (P<0.05. Gene expression analysis showed that GTT treatment down regulated BAX mRNA, up-regulated BCL2A1 mRNA and decreased the ratio of Bax/Bcl-2 protein expression (P<0.05 in SIPS. These findings suggested that GTT inhibits apoptosis by modulating the upstream apoptosis cascade, causing the inhibition of cytochrome c release from the mitochondria with concomitant suppression of caspase-9 and caspase-3 activation. In conclusion, GTT delays cellular senescence of human diploid fibroblasts through the inhibition of intrinsic mitochondria-mediated pathway which involved the regulation of pro- and anti-apoptotic genes and proteins.

  14. Mutations in EXOSC2 are associated with a novel syndrome characterised by retinitis pigmentosa, progressive hearing loss, premature ageing, short stature, mild intellectual disability and distinctive gestalt.

    Science.gov (United States)

    Di Donato, Nataliya; Neuhann, Teresa; Kahlert, Anne-Karin; Klink, Barbara; Hackmann, Karl; Neuhann, Irmingard; Novotna, Barbora; Schallner, Jens; Krause, Claudia; Glass, Ian A; Parnell, Shawn E; Benet-Pages, Anna; Nissen, Anke M; Berger, Wolfgang; Altmüller, Janine; Thiele, Holger; Weber, Bernhard H F; Schrock, Evelin; Dobyns, William B; Bier, Andrea; Rump, Andreas

    2016-06-01

    Retinitis pigmentosa in combination with hearing loss can be a feature of different Mendelian disorders. We describe a novel syndrome caused by biallelic mutations in the 'exosome component 2' (EXOSC2) gene. Clinical ascertainment of three similar affected patients followed by whole exome sequencing. Three individuals from two unrelated German families presented with a novel Mendelian disorder encompassing childhood myopia, early onset retinitis pigmentosa, progressive sensorineural hearing loss, hypothyroidism, short stature, brachydactyly, recognisable facial gestalt, premature ageing and mild intellectual disability. Whole exome sequencing revealed homozygous or compound heterozygous missense variants in the EXOSC2 gene in all three patients. EXOSC2 encodes the 'ribosomal RNA-processing protein 4' (RRP4)-one of the core components of the RNA exosome. The RNA exosome is a multiprotein complex that plays key roles in RNA processing and degradation. Intriguingly, the EXOSC2-associated phenotype shows only minimal overlap with the previously reported diseases associated with mutations in the RNA exosome core component genes EXOSC3 and EXOSC8. We report a novel condition that is probably caused by altered RNA exosome function and expands the spectrum of clinical consequences of impaired RNA metabolism. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Antenatal betamethasone and fetal growth in prematurely born children: implications for temperament traits at the age of 2 years.

    Science.gov (United States)

    Pesonen, Anu-Katriina; Räikkönen, Katri; Lano, Aulikki; Peltoniemi, Outi; Hallman, Mikko; Kari, M Anneli

    2009-01-01

    We explored whether repeated dose of antenatal betamethasone and variation in intrauterine growth of prematurely born children predict temperament characteristics at the age of 2 years. The patients (n = 142) were prematurely born children (mean gestational age: 31.0 weeks; range: 24.6-35.0 weeks) who participated in a randomized and blinded trial testing the effects of a repeated dose of antenatal betamethasone in imminent preterm birth. Fetal growth was estimated as weight, length, and head circumference in SDs according to Finnish growth charts. Parents assessed their toddlers' temperament with 201 items of the Early Childhood Temperament Questionnaire (mean child corrected age: 2.1 years). No significant main effects of repeated betamethasone on toddler temperament existed. However, a significant interaction between study group and duration of exposure to betamethasone emerged; those exposed to a repeated dose for >24 hours before delivery were more impulsive. One-SD increases in weight, length, and head circumference at birth were associated with 0.14- to 0.19-SD lower levels of negative affectivity (fearfulness, anger proneness, and sadness); 1-SD increases in length, weight, and head circumference at birth were associated with 0.14- to 0.18-SD higher levels of effortful control (self-regulation). Repeated antenatal betamethasone did not induce alterations in toddler temperament. The results, however, suggest that a longer duration of exposure is associated with higher impulsivity scores. Regardless of betamethasone exposure, slower fetal growth exerted influences on temperament. Our findings indicate prenatal programming of psychological development and imply that more attention is needed to support the development of infants born at the lower end of the fetal growth distribution.

  16. Premature ejaculation

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001524.htm Premature ejaculation To use the sharing features on this page, please enable JavaScript. Premature ejaculation is when a man has an orgasm ...

  17. Correlation of serum KL-6 and CC16 levels with neurodevelopmental outcome in premature infants at 12 months corrected age

    Science.gov (United States)

    Zhang, Zhiqun; Lu, Hui; Zhu, Yunxia; Xiang, Junhua; Huang, Xianmei

    2015-01-01

    The aim of this study was to evaluate KL-6 and CC16 levels and their correlation with neurodevelopmental outcome among very low birth weight pre-term infants at 12 months corrected age. This prospective cohort study was performed from 2011 to 2013 by enrolling pre-term neonates of gestational age ≤ 32 weeks and birth weight ≤ 1500 g. Serum KL-6 and CC16 levels were determined 7 days after birth and their correlation with neurodevelopment was evaluated using Gesell Mental Developmental Scales. Of the 86 eligible pre-term infants, 63 completed follow-up, of which 15 had bronchopulmonary dysplasia. At 12 months corrected age, 49 infants had favorable outcomes and 14 infants had poor neurodevelopmental outcome. KL-6 levels were higher and CC16 levels were lower in infants with poor neurodevelopmental outcome compared with those infants who had favourable neurodevelopmental outcome. Serum KL-6 levels less than 90.0 ng/ml and CC16 levels greater than 320.0 pg/ml at 7 days of life were found to be predictive of a favourable outcome at 12 months corrected age. These biological markers could predict neurodevelopmental outcome at 12 months corrected age in very low birth weight premature infants, and help the clinician plan early therapeutic interventions to minimize or avoid poor neurodevelopmental outcome. PMID:25631862

  18. Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

    DEFF Research Database (Denmark)

    Bruun, Camilla S.; Jørgensen, Claus B.; Bay, Lene

    2008-01-01

    Background: A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin...... of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 and ITGAV orthologs map to SSC15. In an experimentall family (n=113), showing segregation of the trait, the candidate region was confirmed by linkage...

  19. Low birthweight and premature birth are both associated with type 2 diabetes in a random sample of middle-aged Danes.

    Science.gov (United States)

    Pilgaard, K; Færch, K; Carstensen, B; Poulsen, P; Pisinger, C; Pedersen, O; Witte, D R; Hansen, T; Jørgensen, T; Vaag, A

    2010-12-01

    We studied the associations of size at birth and prematurity with type 2 diabetes, insulin sensitivity and beta cell function in the Danish population-based Inter99 study (ClinicalTrials.gov NCT00289237). Information about size at birth and prematurity was identified from original midwife records in 4,744 middle-aged Danes. Type 2 diabetes status, insulin sensitivity (Matsuda index) and beta cell function (disposition index) were assessed using a 75 g oral glucose tolerance test. Participants born prematurely were compared with a group of at-term participants born small for gestational age. An increase in birthweight of 1 kg was associated with a 51% (OR 0.49, 95% CI 0.35-0.69) reduced risk of type 2 diabetes. Ponderal index, reflecting thinness at birth, was associated with type 2 diabetes to the same extent as birthweight. The prevalence of type 2 diabetes was increased to a similar degree in participants born prematurely and participants born small for gestational age, although the former had a higher ponderal index at birth. In addition, birthweight z-scores, reflecting fetal growth rate, were unrelated to the risk of type 2 diabetes and to other measures of glucose regulation in participants born prematurely. While low birthweight was inversely associated with insulin sensitivity and beta cell function, prematurity was associated solely with decreased insulin sensitivity. While the association between birthweight and risk of type 2 diabetes is mediated via combined effects on beta cell function and insulin sensitivity, prematurity seems to influence risk of type 2 diabetes via attenuated insulin sensitivity only and independently of fetal growth rates.

  20. Molecular Clues to Physiological and Premature Ageing Revealed | Center for Cancer Research

    Science.gov (United States)

    There are many theories about the molecular basis of ageing. One of the most popular ones postulates that organisms age by accumulating damage to their tissues, cells, and molecules. On the cellular level, ageing is associated with progressive changes in chromatin (a combination of DNA and proteins that makes up chromosomes). These changes include loss of chromatin structure, loss and/or modification of essential proteins, and accumulation of DNA damage.

  1. Defining microglial phenotypic diversity and the impact of ageing

    OpenAIRE

    2015-01-01

    Microglia are the resident macrophages of the central nervous system (CNS) and, as key immune effector cells, form the first line of defence. Microglial cells also provide support for maintaining neuronal homeostasis and more generally normal brain physiology and cognitive function. It has been speculated that in order to support homeostasis, microglia adapt to a variety of brain microenvironments leading to regional phenotypic heterogeneity. To date this hypothesis lacks convi...

  2. Age-dependent heterogeneity of familiar hypertrophic cardiomyopathy phenotype: a role of cardiovascular magnetic resonance.

    Science.gov (United States)

    Glaveckaitė, Sigita; Rudys, Alfredas; Mikštienė, Violeta; Valevičienė, Nomeda; Palionis, Darius; Laucevičius, Aleksandras

    2013-01-01

    In this case report, we present familiar hypertrophic cardiomyopathy with age-dependent heterogeneity of the disease phenotype among the members of one family who carry the same mutation of the myosin-binding protein C gene. Phenotypic heterogeneity is common in patients with familial forms of hypertrophic cardiomyopathy, both in clinical expression and outcome. Compared with other noninvasive cardiac imaging modalities, cardiovascular magnetic resonance provides an opportunity to more accurately characterize the varying phenotypic presentations of hypertrophic cardiomyopathy.

  3. SU5416 induces premature senescence in endothelial progenitor cells from patients with age-related macular degeneration

    Science.gov (United States)

    Berna, Marc J.; Kunst, Frank; Wege, Henning; Strunnikova, Natalya V.; Gordiyenko, Natalya; Grierson, Rebecca; Richard, Gisbert; Csaky, Karl G.

    2011-01-01

    Purpose We recently demonstrated increased frequency and growth potential of late outgrowth endothelial progenitor cells (OECs) in patients with neovascular age-related macular degeneration (nvAMD). This study investigated the effects of short- and long-term in vitro inhibition of vascular endothelial growth factor (VEGF) Receptor-2 (VEGFR-2) signaling by SU5416 and other inhibitors of the VEGF signaling pathway in OECs. Methods OECs, from the peripheral blood of patients with nvAMD, and human umbilical vein endothelial cells were grown in the presence of SU5416, other VEGFR-2 tyrosine kinase inhibitors (TKIs), and inhibitors of phosphatidylinositol 3′-Kinase (PI3K)/protein kinase B (Akt) and protein kinase C (PKC) in complete angiogenic medium. Apotosis was assessed after 48 h using the fluorescein isothiocyanate Annexin V method. Cell counts were performed for 10 days, and features of senescence were analyzed using senescence-associated β-galactosidase staining, the telomeric repeat amplification protocol for telomerase activity, Southern blot analysis for mean telomere length, flow cytometric analysis for cell-cycle arrest, and western blot for p53 and p21. Control OECs, cells treated for 7 days with inhibitors, as well as naturally senescent OECs were analyzed for expression of different endothelial antigens, including VEGFR-2 and the receptor for stromal cell-derived factor 1, chemokine receptor 4 (CXCR-4). Migration in vitro to VEGF and stromal cell-derived factor 1 of OECs was assessed. Results SU5416, other VEGFR-2 TKIs, and inhibitors of PI3K, Akt, and PKC induced apoptosis, inhibited long-term proliferation, reduced telomerase activity, and induced premature senescence and cell-cycle arrest in OECs as well as in human umbilical vein endothelial cells. Naturally senescent cells and cells rendered senescent by VEGFR-2 TKIs had reduced VEGFR-2 and CXCR-4 expression and demonstrated reduced migratory ability to VEGF. Conclusions This study demonstrates

  4. von Willebrand disease and aging : an evolving phenotype

    NARCIS (Netherlands)

    Sanders, Y. V.; Giezenaar, M. A.; Laros-van Gorkom, B. A. P.; Meijer, K.; van der Bom, J. G.; Cnossen, M. H.; Nijziel, M. R.; Ypma, P. F.; Fijnvandraat, K.; Eikenboom, J.; Mauser-Bunschoten, E. P.; Leebeek, F. W. G.

    2014-01-01

    Background: Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. Objectives: To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related diff

  5. Development of the Corticospinal and Callosal Tracts from Extremely Premature Birth up to 2 Years of Age.

    Science.gov (United States)

    Braga, Rodrigo M; Roze, Elise; Ball, Gareth; Merchant, Nazakat; Tusor, Nora; Arichi, Tomoki; Edwards, David; Rueckert, Daniel; Counsell, Serena J

    2015-01-01

    White matter tracts mature asymmetrically during development, and this development can be studied using diffusion magnetic resonance imaging. The aims of this study were i. to generate dynamic population-averaged white matter registration templates covering in detail the period from 25 weeks gestational age to term, and extending to 2 years of age based on DTI and fractional anisotropy, ii. to produce tract-specific probability maps of the corticospinal tracts, forceps major and forceps minor using probabilistic tractography, and iii. to assess the development of these tracts throughout this critical period of neurodevelopment. We found evidence for asymmetric development across the fiber bundles studied, with the corticospinal tracts showing earlier maturation (as measured by fractional anisotropy) but slower volumetric growth compared to the callosal fibers. We also found evidence for an anterior to posterior gradient in white matter microstructure development (as measured by mean diffusivity) in the callosal fibers, with the posterior forceps major developing at a faster rate than the anterior forceps minor in this age range. Finally, we report a protocol for delineating callosal and corticospinal fibers in extremely premature cohorts, and make available population-averaged registration templates and a probabilistic tract atlas which we hope will be useful for future neonatal and infant white-matter imaging studies.

  6. [Development deficit risks in the late premature newborn: Evaluation at 48 months using the Ages & Stages Questionnaires®].

    Science.gov (United States)

    Demestre, X; Schonhaut, L; Morillas, J; Martínez-Nadal, S; Vila, C; Raspall, F; Sala, P

    2016-01-01

    Lack of specific monitoring protocols hinders the knowledge of the impact of late prematurity on delayed psychomotor development. The objective of this study is to evaluate this at 48 months and compare it with those born at term. A retrospective cohort study was conducted on 90 late preterm (PT) and 89 term (AT) healthy children at 48 months, assessed by the Ages & Stages Questionnaires® (ASQ-3). Continuous variables described using mean and standard deviation compared with the t Student t test for independent samples. The categorical variables were described as frequencies and proportions, compared with the Chi-square test of independence. A cut-off was determined for the total score of ASQ-3 able to discriminate the risk of developmental deficit by a ROC analysis. A step-wise logistic regression model identified the associated risk factors. The mean scores for each domain and overall ASQ-3 score showed no differences between groups. However, when analyzing the probability density for the ASQ-3 total score of ≤251 points, 15 PT (16.6%) and 4 AT (4.5%) showed risk of psychomotor deficits, and late prematurity and lack of breastfeeding were significantly associated factors. There is an increased prevalence of risk of development deficit in the PT, which justifies considering this population at risk and establishing effective monitoring programs. It should be further investigated whether this risk corresponds to the entire population, or if there are biological factors or perinatal history that makes them more vulnerable. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  7. Premature Aging-related Peripheral Neuropathy in a Mouse Model of Progeria

    Science.gov (United States)

    Goss, James R.; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D.; Glorioso, Joseph C.; Niedernhofer, Laura J.

    2011-01-01

    Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1−/Δ mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1−/Δ mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. PMID:21596054

  8. Premature aging-related peripheral neuropathy in a mouse model of progeria.

    Science.gov (United States)

    Goss, James R; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D; Glorioso, Joseph C; Niedernhofer, Laura J

    2011-08-01

    Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1(-/Δ) mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1(-/Δ) mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies.

  9. No support for premature central nervous system aging in HIV-1 when measured by cerebrospinal fluid phosphorylated tau (p-tau)

    OpenAIRE

    Krut, J. J.; Price, R W; Zetterberg, H; Fuchs, D.; Hagberg, L.; YILMAZ, A.; Cinque, P.; Nilsson, S; Gisslén, M.

    2016-01-01

    BACKGROUND: The prevalence of neurocognitive deficits are reported to be high in HIV-1 positive patients, even with suppressive antiretroviral treatment, and it has been suggested that HIV can cause accelerated aging of the brain. In this study we measured phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as a potential marker for premature central nervous system (CNS) aging. P-tau increases with normal aging but is not affected by HIV-associated neurocognitive disorders. METHODS: With ...

  10. Premature age-related comorbidities among HIV-infected persons compared with the general population.

    Science.gov (United States)

    Guaraldi, Giovanni; Orlando, Gabriella; Zona, Stefano; Menozzi, Marianna; Carli, Federica; Garlassi, Elisa; Berti, Alessandra; Rossi, Elisa; Roverato, Alberto; Palella, Frank

    2011-12-01

    Human immunodeficiency virus (HIV)-infected patients may have a greater risk of noninfectious comorbidities (NICMs) compared with the general population. We assessed the prevalence and risk factors for NICMs in a large cohort of HIV-infected adults and compared these findings with data from matched control subjects. We performed a case-control study involving antiretroviral therapy (ART)-experienced HIV-infected patients treated at Modena University, Italy, from 2002 through 2009. These patients were compared with age-, sex-, and race-matched adults (control subjects) from the general population included in the CINECA ARNO database. NICMs included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Polypathology (Pp) was defined as the concurrent presence of ≥2 NICMs. Logistic regression models were constructed to evaluate associated predictors of NICMs and Pp. There were 2854 patients and 8562 control subjects. The mean age was 46 years, and 37% were women. Individual NICM and Pp prevalences in each age stratum were higher among patients than among controls (all P <.001). Pp prevalence among patients aged 41-50 years was similar to that among controls aged 51-60 years (P value was not statistically significant); diabetes mellitus, cardiovascular disease, bone fractures, and renal failure were statistically independent after adjustment for sex, age, and hypertension. Logistic regression models showed that independent predictors of Pp in the overall cohort were (all P < .001) age (odds ratio [OR], 1.11), male sex (OR, 1.77), nadir CD4 cell count <200 cells/μL (OR, 4.46), and ART exposure (OR, 1.01). Specific age-related NICMs and Pp were more common among HIV-infected patients than in the general population. The prevalence of Pp in HIV-infected persons anticipated Pp prevalence observed in the general population among persons who were 10 years older, and HIV-specific cofactors (lower nadir CD4 cell count and more prolonged

  11. Inflammation and Oxidative Stress as Biomarkers of Premature Aging in Persons with Intellectual Disability

    Science.gov (United States)

    Carmeli, Eli; Imam, Bita; Bachar, Asad; Merrick, Joav

    2012-01-01

    The decline in cognitive ability and physical performance in older adults with intellectual disabilities (ID) is accompanied by less participation in social activities and a sedentary lifestyle; however the pathogenesis is not clear yet. It was recently suggested that chronic disease, adverse drug reactions, and aging create a cascade of events…

  12. Premature aging in mice activates a systemic metabolic response involving autophagy induction

    NARCIS (Netherlands)

    G. Mariño (Guillermo); A.P. Ugalde (Alejandro); N. Salvador-Montoliu (Natalia); I. Varela (Ignacio); P.M. Quirós (Pedro); J. Cadiñanos (Juan); I. van der Pluijm (Ingrid); J.M.P. Freije (José); C. López-Otín (Carlos)

    2008-01-01

    textabstractAutophagy is a highly regulated intracellular process involved in the turnover of most cellular constituents and in the maintenance of cellular homeostasis. It is well-established that the basal autophagic activity of living cells decreases with age, thus contributing to the accumulation

  13. Inflammation and Oxidative Stress as Biomarkers of Premature Aging in Persons with Intellectual Disability

    Science.gov (United States)

    Carmeli, Eli; Imam, Bita; Bachar, Asad; Merrick, Joav

    2012-01-01

    The decline in cognitive ability and physical performance in older adults with intellectual disabilities (ID) is accompanied by less participation in social activities and a sedentary lifestyle; however the pathogenesis is not clear yet. It was recently suggested that chronic disease, adverse drug reactions, and aging create a cascade of events…

  14. The transverse diameter of the chest on routine radiographs reliably estimates gestational age and weight in premature infants

    Energy Technology Data Exchange (ETDEWEB)

    Dietz, Kelly R. [University of Minnesota, Department of Radiology, Minneapolis, MN (United States); Zhang, Lei [University of Minnesota, Biostatistical Design and Analysis Center, Minneapolis, MN (United States); Seidel, Frank G. [Lucile Packard Children' s Hospital, Department of Radiology, Stanford, CA (United States)

    2015-08-15

    Prior to digital radiography it was possible for a radiologist to easily estimate the size of a patient on an analog film. Because variable magnification may be applied at the time of processing an image, it is now more difficult to visually estimate an infant's size on the monitor. Since gestational age and weight significantly impact the differential diagnosis of neonatal diseases and determine the expected size of kidneys or appearance of the brain by MRI or US, this information is useful to a pediatric radiologist. Although this information may be present in the electronic medical record, it is frequently not readily available to the pediatric radiologist at the time of image interpretation. To determine if there was a correlation between gestational age and weight of a premature infant with their transverse chest diameter (rib to rib) on admission chest radiographs. This retrospective study was approved by the institutional review board, which waived informed consent. The maximum transverse chest diameter outer rib to outer rib was measured on admission portable chest radiographs of 464 patients admitted to the neonatal intensive care unit (NICU) during the 2010 calendar year. Regression analysis was used to investigate the association between chest diameter and gestational age/birth weight. Quadratic term of chest diameter was used in the regression model. Chest diameter was statistically significantly associated with both gestational age (P < 0.0001) and birth weight (P < 0.0001). An infant's gestational age and birth weight can be reliably estimated by comparing a simple measurement of the transverse chest diameter on digital chest radiograph with the tables and graphs in our study. (orig.)

  15. Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency.

    Science.gov (United States)

    Griffith, Ann V; Venables, Thomas; Shi, Jianjun; Farr, Andrew; van Remmen, Holly; Szweda, Luke; Fallahi, Mohammad; Rabinovitch, Peter; Petrie, Howard T

    2015-08-18

    T lymphocytes are essential mediators of immunity that are produced by the thymus in proportion to its size. The thymus atrophies rapidly with age, resulting in progressive diminution of new T cell production. This decreased output is compensated by duplication of existing T cells, but it results in gradual dominance by memory T cells and decreased ability to respond to new pathogens or vaccines. Here, we show that accelerated and irreversible thymic atrophy results from stromal deficiency in the reducing enzyme catalase, leading to increased damage by hydrogen peroxide generated by aerobic metabolism. Genetic complementation of catalase in stromal cells diminished atrophy, as did chemical antioxidants, thus providing a mechanistic link between antioxidants, metabolism, and normal immune function. We propose that irreversible thymic atrophy represents a conventional aging process that is accelerated by stromal catalase deficiency in the context of an intensely anabolic (lymphoid) environment.

  16. Effect of Infant Prematurity on Auditory Brainstem Response at Preschool Age

    Directory of Open Access Journals (Sweden)

    Sara Hasani

    2013-03-01

    Full Text Available Introduction: Preterm birth is a risk factor for a number of conditions that requires comprehensive examination. Our study was designed to investigate the impact of preterm birth on the processing of auditory stimuli and brain structures at the brainstem level at a preschool age.   Materials and Methods: An auditory brainstem response (ABR test was performed with low rates of stimuli in 60 children aged 4 to 6 years. Thirty subjects had been born following a very preterm labor or late-preterm labor and 30 control subjects had been born following a full-term labor.   Results: Significant differences in the ABR test result were observed in terms of the inter-peak intervals of the I–III and III–V waves, and the absolute latency of the III wave (P

  17. Sporadic premature aging in a Japanese monkey: a primate model for progeria.

    Directory of Open Access Journals (Sweden)

    Takao Oishi

    Full Text Available In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes.

  18. Sporadic premature aging in a Japanese monkey: a primate model for progeria.

    Science.gov (United States)

    Oishi, Takao; Imai, Hiroo; Go, Yasuhiro; Imamura, Masanori; Hirai, Hirohisa; Takada, Masahiko

    2014-01-01

    In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged) monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes.

  19. Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective.

    Science.gov (United States)

    Cau, Pierre; Navarro, Claire; Harhouri, Karim; Roll, Patrice; Sigaudy, Sabine; Kaspi, Elise; Perrin, Sophie; De Sandre-Giovannoli, Annachiara; Lévy, Nicolas

    2014-05-01

    Lamin A-related progeroid syndromes are genetically determined, extremely rare and severe. In the past ten years, our knowledge and perspectives for these diseases has widely progressed, through the progressive dissection of their pathophysiological mechanisms leading to precocious and accelerated aging, from the genes mutations discovery until therapeutic trials in affected children. A-type lamins are major actors in several structural and functional activities at the nuclear periphery, as they are major components of the nuclear lamina. However, while this is usually poorly considered, they also play a key role within the rest of the nucleoplasm, whose defects are related to cell senescence. Although nuclear shape and nuclear envelope deformities are obvious and visible events, nuclear matrix disorganization and abnormal composition certainly represent the most important causes of cell defects with dramatic pathological consequences. Therefore, lamin-associated diseases should be better referred as laminopathies instead of envelopathies, this later being too restrictive, considering neither the key structural and functional roles of soluble lamins in the entire nucleoplasm, nor the nuclear matrix contribution to the pathophysiology of lamin-associated disorders and in particular in defective lamin A processing-associated aging diseases. Based on both our understanding of pathophysiological mechanisms and the biological and clinical consequences of progeria and related diseases, therapeutic trials have been conducted in patients and were terminated less than 10 years after the gene discovery, a quite fast issue for a genetic disease. Pharmacological drugs have been repurposed and used to decrease the toxicity of the accumulated, unprocessed and truncated prelaminA in progeria. To date, none of them may be considered as a cure for progeria and these clinical strategies were essentially designed toward reducing a subset of the most dramatic and morbid features

  20. Reading, Mathematics and Fine Motor Skills at 5 Years of Age in US Children who were Extremely Premature at Birth.

    Science.gov (United States)

    Lee, Miryoung; Pascoe, John M; McNicholas, Caroline I

    2017-01-01

    Objectives The prevalence of extreme prematurity at birth has increased, but little research has examined its impact on developmental outcomes in large representative samples within the United States. This study examined the association of extreme prematurity with kindergarteners' reading skills, mathematics skills and fine motor skills. Methods The early childhood longitudinal study-birth cohort, a representative sample of the US children born in 2001 was analyzed for this study. Early reading and mathematics skills and fine motor skills were compared among 200 extremely premature children (EPC) (gestational age sampling weights, children's age, race, sex, and general health status, and parental marital status and education among singleton children. Results At age 5 years, EPC were 2.6(95 % CI 1.7-3.8) times more likely to fail build a gate and were 3.1(95 % CI 1.6-5.8) times more likely to fail all four drawing tasks compared to TC (p values gate, 1.3[95 % CI 1.0-1.7]; failed to draw all four shapes, 1.1[95 % CI 0.8-1.6]) was not significantly different from TC. Mean early reading scale score (36.8[SE:1.3]) of EPC was 4.0 points lower than TC (p value sample of infants, the biological risk of extreme prematurity persists after adjusting for other factors related to development.

  1. Vanishing honey bees: Is the dying of adult worker bees a consequence of short telomeres and premature aging?

    Science.gov (United States)

    Stindl, Reinhard; Stindl, Wolfgang

    2010-10-01

    Einstein is often quoted to have said that without the bee, mankind would have but 4years to live. It is highly unlikely that he made this comment, which was even mentioned in a Lancet article on honey bees. However, the current vanishing of the bees can have serious consequences for human health, because 35% of the human diet is thought to benefit from pollination. Colony collapse disorder (CCD) in honey bees is characterized by the rapid decline of the adult bee population, leaving the brood and the queen poorly or completely unattended, with no dead bodies in or around the hive. A large study found no evidence that the presence or amount of any individual pesticide or infectious agent occurred more frequently or abundantly in CCD-affected colonies. The growing consensus is that honey bees are suffering from comprised immune systems, which allow various infectious pathogens to invade. The question remains, what causes immunosuppression in many colonies of Apis mellifera in North America and Europe? Telomeres are protective DNA structures located at eukaryotic chromosome tips that shorten in the somatic tissues of animals with age. Lifelong tissue regeneration takes place in Apis mellifera, and worker bees have been shown to senesce. In humans, a vast amount of literature has accumulated on exhausted telomere reserves causing impaired tissue regeneration and age-associated diseases, specifically cancer and immunosuppression. Therefore, we propose a new causative mechanism for the vanishing of the bees: critically short telomeres in long-lived winter bees. We term this the telomere premature aging syndrome. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. The phenotype of polycystic ovary syndrome ameliorates with aging

    NARCIS (Netherlands)

    Brown, Zoe A.; Louwers, Yvonne V.; Fong, Sharon Lie; Valkenburg, Olivier; Birnie, Erwin; de Jong, Frank H.; Fauser, Bart C. J. M.; Laven, Joop S. E.

    2011-01-01

    Objective: To assess the effects of aging on the features of polycystic ovary syndrome (PCOS). Design: Retrospective longitudinal follow-up study. Setting: Tertiary care center. Patient(s): Patients with PCOS, diagnosed according to the 2003 Rotterdam criteria, who visited the outpatient clinic on c

  3. The phenotype of polycystic ovary syndrome ameliorates with aging

    NARCIS (Netherlands)

    Brown, Zoe A.; Louwers, Yvonne V.; Fong, Sharon Lie; Valkenburg, Olivier; Birnie, Erwin; de Jong, Frank H.; Fauser, Bart C. J. M.; Laven, Joop S. E.

    2011-01-01

    Objective: To assess the effects of aging on the features of polycystic ovary syndrome (PCOS). Design: Retrospective longitudinal follow-up study. Setting: Tertiary care center. Patient(s): Patients with PCOS, diagnosed according to the 2003 Rotterdam criteria, who visited the outpatient clinic on

  4. Impact of Oxidative Stress in Premature Aging and Iron Overload in Hemodialysis Patients

    Science.gov (United States)

    Hernández Vázquez, Wendy Ivett; Solorio-Meza, Sergio; Albarrán-Tamayo, Froylán; Ramos-Rodríguez, Edna; Benítez- Bribiesca, Luis

    2016-01-01

    Background. Increased oxidative stress is a well described feature of patients in hemodialysis. Their need for multiple blood transfusions and supplemental iron causes a significant iron overload that has recently been associated with increased oxidation of polyunsaturated lipids and accelerated aging due to DNA damage caused by telomere shortening. Methods. A total of 70 patients were evaluated concomitantly, 35 volunteers with ferritin levels below 500 ng/mL (Group A) and 35 volunteers with ferritin levels higher than 500 ng/mL (Group B). A sample of venous blood was taken to extract DNA from leukocytes and to measure relative telomere length by real-time PCR. Results. Patients in Group B had significantly higher plasma TBARS (p = 0.008), carbonyls (p = 0.0004), and urea (p = 0.02) compared with those in Group A. Telomeres were significantly shorter in Group B, 0.66 (SD, 0.051), compared with 0.75 (SD, 0.155) in Group A (p = 0.0017). We observed a statistically significant association between relative telomere length and ferritin levels (r = −0.37, p = 0.001). Relative telomere length was inversely related to time on hemodialysis (r = −0.27, p = 0.02). Conclusions. Our findings demonstrate that iron overload was associated with increased levels of oxidative stress and shorter relative telomere length. PMID:27800120

  5. Prematurely delivered rats show improved motor coordination during sensory-evoked motor responses compared to age-matched controls.

    Science.gov (United States)

    Roberto, Megan E; Brumley, Michele R

    2014-05-10

    The amount of postnatal experience for perinatal rats was manipulated by delivering pups one day early (postconception day 21; PC21) by cesarean delivery and comparing their motor behavior to age-matched controls on PC22 (the typical day of birth). On PC22, pups were tested on multiple measures of motor coordination: leg extension response (LER), facial wiping, contact righting, and fore- and hindlimb stepping. The LER and facial wiping provided measures of synchronous hind- and forelimb coordination, respectively, and were sensory-evoked. Contact righting also was sensory-evoked and provided a measure of axial coordination. Stepping provided a measure of alternated forelimb and hindlimb coordination and was induced with the serotonin receptor agonist quipazine. Pups that were delivered prematurely and spent an additional day in the postnatal environment showed more bilateral limb coordination during expression of the LER and facial wiping, as well as a more mature righting strategy, compared to controls. These findings suggest that experience around the time of birth shapes motor coordination and the expression of species-typical behavior in the developing rat.

  6. Helicobacter pylori colonization and pregnancies complicated by preeclampsia, spontaneous prematurity, and small for gestational age birth.

    Science.gov (United States)

    den Hollander, Wouter J; Schalekamp-Timmermans, Sarah; Holster, I Lisanne; Jaddoe, Vincent W; Hofman, Albert; Moll, Henriëtte A; Perez-Perez, Guillermo I; Blaser, Martin J; Steegers, Eric A P; Kuipers, Ernst J

    2017-04-01

    Preeclampsia (PE), small for gestational age (SGA), and spontaneous preterm birth (PTB) each may be complications of impaired placental function in pregnancy. Although their exact pathogenesis is still unknown, certain infectious agents seem to play a role. Helicobacter pylori (H. pylori) colonization has been associated with increased risk for PE. Our aim was to assess the association between H. pylori colonization and PE, SGA, and PTB. We measured IgG anti-H. pylori and CagA antibodies in serum of pregnant women (median 20.5 weeks, range 16.5-29.4) who participated in a population-based prospective cohort study. Delivery and medical records were assessed. Information on demographics, education, and maternal risk factors was collected by questionnaire. We used multivariate logistic regression analyses to assess associations between H. pylori colonization and PE, SGA, and PTB. In total, 6348 pregnant women were assessed. H. pylori positivity was found in 2915 (46%) women, of whom 1023 (35%) also were CagA-positive. Pregnancy was complicated by PE, SGA, or PTB in 927 (15%) women. H. pylori colonization was associated with PE (aOR 1.51; 95%CI 1.03-2.25). Differentiation according to CagA status revealed the same risk. H. pylori was positively related with SGA, mainly explained by CagA-positive strains (aOR 1.34; 1.04-1.71). No association was observed between H. pylori and PTB. Our data suggest that H. pylori colonization may be a risk factor for PE and SGA. If these associations are confirmed by future studies and shown to be causal, H. pylori eradication may reduce related perinatal morbidity and mortality. © 2016 John Wiley & Sons Ltd.

  7. Influence of age, irradiation and humanization on NSG mouse phenotypes

    Directory of Open Access Journals (Sweden)

    Jaclyn S. Knibbe-Hollinger

    2015-10-01

    Full Text Available Humanized mice are frequently utilized in bench to bedside therapeutic tests to combat human infectious, cancerous and degenerative diseases. For the fields of hematology-oncology, regenerative medicine, and infectious diseases, the immune deficient mice have been used commonly in basic research efforts. Obstacles in true translational efforts abound, as the relationship between mouse and human cells in disease pathogenesis and therapeutic studies requires lengthy investigations. The interplay between human immunity and mouse biology proves ever more complicated when aging, irradiation, and human immune reconstitution are considered. All can affect a range of biochemical and behavioral functions. To such ends, we show age- and irradiation-dependent influences for the development of macrocytic hyper chromic anemia, myelodysplasia, blood protein reductions and body composition changes. Humanization contributes to hematologic abnormalities. Home cage behavior revealed day and dark cycle locomotion also influenced by human cell reconstitutions. Significant age-related day-to-day variability in movement, feeding and drinking behaviors were observed. We posit that this data serves to enable researchers to better design translational studies in this rapidly emerging field of mouse humanization.

  8. Associations of menstrual cycle irregularities with age, obesity and phenotype in patients with polycystic ovary syndrome.

    Science.gov (United States)

    Panidis, Dimitrios; Tziomalos, Konstantinos; Papadakis, Efstathios; Chatzis, Panagiotis; Kandaraki, Eleni A; Tsourdi, Elena A; Macut, Djuro; Bjekic-Macut, Jelica; Marthopoulos, Apostolos; Katsikis, Ilias

    2015-01-01

    Limited data suggest that menstrual cycle abnormalities are more pronounced in younger and more obese patients with polycystic ovary syndrome (PCOS). We aimed to evaluate the association between menstrual cycle pattern and age, obesity and PCOS phenotype in a large population of women with PCOS. We studied 1,297 women with PCOS and divided them according to: a) age in ≤ 20, 21-30 and > 30 years old, b) body mass index in normal weight, overweight and obese and c) PCOS phenotype in phenotype 1 (anovulation, hyperandrogenemia and polycystic ovaries), 2 (anovulation and hyperandrogenemia without polycystic ovaries), 3 (hyperandrogenemia and polycystic ovaries without anovulation) and 4 (anovulation and polycystic ovaries without hyperandrogenemia). The proportion of women with regular menstrual cycles progressively increased in the older age groups, being 8.1, 10.5 and 12.7% in women ≤ 20, 21-30 and > 30 years old, respectively (p = 0.037). The proportion of women with regular menstrual cycles did not differ between normal weight and obese women but was higher in overweight women (9.3, 9.4 and 13%, respectively; p = 0.020). The proportion of women with regular cycles alternating with irregular cycles was highest in women with phenotype 4, intermediate in women with phenotype 2 and lowest in women with phenotype 1 (74.3, 69.4 and 61.7%, respectively; p = 0.027). Menstrual cycle pattern is more irregular in women with the "classic" PCOS phenotypes than in phenotype 4 but appears to normalize with ageing. On the other hand, obesity does not appear to have an important effect on menstrual cycle pattern in PCOS.

  9. Classifying human audiometric phenotypes of age-related hearing loss from animal models.

    Science.gov (United States)

    Dubno, Judy R; Eckert, Mark A; Lee, Fu-Shing; Matthews, Lois J; Schmiedt, Richard A

    2013-10-01

    Age-related hearing loss (presbyacusis) has a complex etiology. Results from animal models detailing the effects of specific cochlear injuries on audiometric profiles may be used to understand the mechanisms underlying hearing loss in older humans and predict cochlear pathologies associated with certain audiometric configurations ("audiometric phenotypes"). Patterns of hearing loss associated with cochlear pathology in animal models were used to define schematic boundaries of human audiograms. Pathologies included evidence for metabolic, sensory, and a mixed metabolic + sensory phenotype; an older normal phenotype without threshold elevation was also defined. Audiograms from a large sample of older adults were then searched by a human expert for "exemplars" (best examples) of these phenotypes, without knowledge of the human subject demographic information. Mean thresholds and slopes of higher frequency thresholds of the audiograms assigned to the four phenotypes were consistent with the predefined schematic boundaries and differed significantly from each other. Significant differences in age, gender, and noise exposure history provided external validity for the four phenotypes. Three supervised machine learning classifiers were then used to assess reliability of the exemplar training set to estimate the probability that newly obtained audiograms exhibited one of the four phenotypes. These procedures classified the exemplars with a high degree of accuracy; classifications of the remaining cases were consistent with the exemplars with respect to average thresholds and demographic information. These results suggest that animal models of age-related hearing loss can be used to predict human cochlear pathology by classifying audiograms into phenotypic classifications that reflect probable etiologies for hearing loss in older humans.

  10. An Influence of Birth Weight, Gestational Age, and Apgar Score on Pattern Visual Evoked Potentials in Children with History of Prematurity

    Directory of Open Access Journals (Sweden)

    Marta Michalczuk

    2015-01-01

    Full Text Available Purpose. The objective of our study was to examine a possible influence of gestational age, birth weight, and Apgar score on amplitudes and latencies of P100 wave in preterm born school-age children. Materials and Methods. We examined the following group of school-age children: 28 with history of prematurity (mean age 10.56 ± 1.66 years and 25 born at term (mean age 11.2 ± 1.94 years. The monocular PVEP was performed in all children. Results. The P100 wave amplitudes and latencies significantly differ between preterm born school-age children and those born at term. There was an essential positive linear correlation of the P100 wave amplitudes with birth weight, gestational age, and Apgar score. There were the negative linear correlations of P100 latencies in 15-minute stimulation from O1 and Oz electrode with Apgar score and O1 and O2 electrode with gestational age. Conclusions. PVEP responses vary in preterm born children in comparison to term. Low birth weight, early gestational age, and poor baseline output seem to be the predicting factors for the developmental rate of a brain function in children with history of prematurity. Further investigations are necessary to determine perinatal factors that can affect the modified visual system function in preterm born children.

  11. Agreement between grating acuity at age 1 year and Snellen acuity at age 5.5 years in the preterm child. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

    Science.gov (United States)

    Dobson, V; Quinn, G E; Siatkowski, R M; Baker, J D; Hardy, R J; Reynolds, J D; Trese, M T; Tung, B

    1999-02-01

    To examine the relation between grating acuity at age 1 year and Snellen acuity and grating acuity at 5.5 years, in preterm children with birth weights less than 1251 g. Subjects were participants in the multicenter study of Cryotherapy for Retinopathy of Prematurity. The Teller acuity card (TAC; Vistech Consultants, Dayton, OH) procedure was used to measure monocular grating acuity in children at ages 1 and 5.5 years. Early-treatment diabetic retinopathy study (ETDRS) charts were used to measure the childrens' monocular recognition (Snellen) acuity at age 5.5 years. Data are presented for 575 eyes with measurable TAC grating acuity at 1 year and 111 eyes that had no measurable acuity at 1 year. Among eyes with normal acuity at 1 year, 86.8% showed normal Snellen acuity, and 94.3% showed normal grating acuity at 5.5 years. Among eyes that were blind (i.e., had no measurable TAC grating acuity) at 1 year, 96.8% showed no quantifiable Snellen acuity, and 89.2% showed no quantifiable grating acuity at 5.5 years. Only 2.4% of eyes had acuity in the range between normal and blind at 1 year (i.e., measurable grating acuity Snellen and grating acuity at age 5.5 years, and eyes that had no quantifiable acuity at 1 year remained blind at 5.5 years. Relative position of an eye's acuity score within the normal range was not predictive of the relative position of that eye's later acuity score.

  12. Your Premature Baby

    Science.gov (United States)

    ... birth defects, premature birth and infant mortality. Solving premature birth Featured articles Accomplishments and lessons learned since ... Complications & Loss > Preterm labor & premature birth > Premature babies Premature babies E-mail to a friend Please fill ...

  13. Dietary restriction ameliorates haematopoietic ageing independent of telomerase, whilst lack of telomerase and short telomeres exacerbates the ageing phenotype.

    Science.gov (United States)

    Al-Ajmi, Nouf; Saretzki, Gabriele; Miles, Colin; Spyridopoulos, Ioakim

    2014-10-01

    Ageing is associated with an overall decline in the functional capacity of tissues and stem cells, including haematopoietic stem and progenitor cells (HSPCs), as well as telomere dysfunction. Dietary restriction (DR) is a recognised anti-ageing intervention that extends lifespan and improves health in several organisms. To investigate the role of telomeres and telomerase in haematopoietic ageing, we compared the HSPC profile and clonogenic capacity of bone marrow cells from wild type with telomerase-deficient mice and the effect of DR on these parameters. Compared with young mice, aged wild type mice demonstrated a significant accumulation of HSPCs (1.3% vs 0.2%, P=0.002) and elevated numbers of granulocyte/macrophage colony forming units (CFU-GM, 26.4 vs 17.3, P=0.0037) consistent with myeloid "skewing" of haematopoiesis. DR was able to restrict the increase in HSPC number as well as the myeloid "skewing" in aged wild type mice. In order to analyse the influence of short telomeres on the ageing phenotype we examined mice lacking the RNA template for telomerase, TERC(-/-). Telomere shortening resulted in a similar bone marrow phenotype to that seen in aged mice, with significantly increased HSPC numbers and an increased formation of all myeloid colony types but at a younger age than wild type mice. However, an additional increase in erythroid colonies (BFU-E) was also evident. Mice lacking telomerase reverse transcriptase without shortened telomeres, TERT(-/-), also presented with augmented haematopoietic ageing which was ameliorated by DR, demonstrating that the effect of DR was not dependent on the presence of telomerase in HSPCs. We conclude that whilst shortened telomeres mimic some aspects of haematopoietic ageing, both shortened telomeres and the lack of telomerase produce specific phenotypes, some of which can be prevented by dietary restriction. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Reversible Age-Related Phenotypes Induced during Larval Quiescence in C. elegans.

    Science.gov (United States)

    Roux, Antoine E; Langhans, Kelley; Huynh, Walter; Kenyon, Cynthia

    2016-06-14

    Cells can enter quiescent states in which cell cycling and growth are suspended. We find that during a long developmental arrest (quiescence) induced by starvation, newly hatched C. elegans acquire features associated with impaired proteostasis and aging: mitochondrial fission, ROS production, protein aggregation, decreased proteotoxic-stress resistance, and at the organismal level, decline of mobility and high mortality. All signs of aging but one, the presence of protein aggregates, were reversed upon return to development induced by feeding. The endoplasmic reticulum receptor IRE-1 is completely required for recovery, and the downstream transcription factor XBP-1, as well as a protein kinase, KGB-1, are partially required. Interestingly, kgb-1(-) mutants that do recover fail to reverse aging-like mitochondrial phenotypes and have a short adult lifespan. Our study describes the first pathway that reverses phenotypes of aging at the exit of prolonged quiescence.

  15. Ovarian Aging-Like Phenotype in the Hyperandrogenism-Induced Murine Model of Polycystic Ovary

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    Mohammad Amin Rezvanfar

    2014-01-01

    Full Text Available There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS. Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO and reactive oxygen species (ROS and decrease in total antioxidant capacity (TAC in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF-α levels, and ovarian matrix metalloproteinase-2 (MMP-2 were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO.

  16. Osteopenia - premature infants

    Science.gov (United States)

    Neonatal rickets; Brittle bones - premature infants; Weak bones - premature infants; Osteopenia of prematurity ... the baby. This helps the baby grow. A premature infant may not receive the proper amount of ...

  17. Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

    DEFF Research Database (Denmark)

    Bruun, Camilla S.; Jørgensen, Claus B.; Bay, Lene

    2008-01-01

    ß6-/- knockout phenotype seen in mice, the two genes encoding the two subunits of integrin avß6, i.e. ITGB6 and ITGAV, were considered candidate genes for this trait. Results: The mutated pig phenotype is characterized by hairlessness until puberty, thin skin with few hair follicles and absence...... resembling the integrin ß6-/- knockout phenotype seen in mice has been characterized in the pig. The candidate region on SSC15 has been confirmed by linkage analysis but molecular and functional analyses have excluded that the mutated phenotype is caused by structural mutations in or ablation of any...

  18. Examining genotypic variation in autism spectrum disorder and its relationship to parental age and phenotype

    Directory of Open Access Journals (Sweden)

    Geier DA

    2016-07-01

    Full Text Available David A Geier,1,2 Janet K Kern,1,3 Lisa K Sykes,2 Mark R Geier1,2 1Research Department, The Institute of Chronic Illnesses, Inc, 2Research Department, CoMeD, Inc, Silver Spring, MD, 3Research Department, CONEM US Autism Research Group, Allen, TX, USA Background: Previous studies on genetic testing of chromosomal abnormalities in individuals diagnosed with autism spectrum disorder (ASD found that ~80% have negative genetic test results (NGTRs and ~20% have positive genetic test results (PGTRs, of which ~7% were probable de novo mutations (PDNMs. Research suggests that parental age is a risk factor for an ASD diagnosis. This study examined genotypic variation in ASD and its relationship to parental age and phenotype.Methods: Phenotype was derived from detailed clinical information, and genotype was derived from high-resolution blood chromosome and blood whole-genome copy number variant genetic testing on a consecutive cohort (born: 1983–2009 of subjects diagnosed with ASD (N=218.Results: Among the subjects examined, 80.3% had NGTRs and 19.7% had PGTRs, of which 6.9% had PDNMs. NGTR subjects were born more recently (the risk of PDNMs decreasing by 12% per more recent birth year and tended to have an increased male–female ratio compared to PDNM subjects. PDNM subjects had significantly increased mean parental age and paternal age at subject’s birth (the risk of a PDNM increasing by 7%–8% per year of parental or paternal age compared to NGTR subjects. PGTR and NGTR subjects showed significant improvements in speech/language/communication with increasing age. PGTR subjects showed significant improvements in sociability, a core feature of an ASD diagnosis, with increasing age, whereas NGTR subjects showed significant worsening in sociability with increasing age.Conclusion: This study helps to elucidate different phenotypic ASD subtypes and may even indicate the need for differential diagnostic classifications. Keywords: genotype, phenotype

  19. Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study

    DEFF Research Database (Denmark)

    Druley, Todd E; Wang, Lihua; Lin, Shiow J

    2016-01-01

    that was significantly associated with three phenotypes (GSK3B with the Healthy Aging Index, NOTCH1 with diastolic blood pressure and TP53 with serum HDL). CONCLUSIONS: Sequencing analysis of family-based associations for age-related phenotypes can identify rare or novel variants.......BACKGROUND: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. METHODS...... or as a group across an entire gene for association to aging phenotypes using family based tests. RESULTS: We found significant associations to three genes and nine single variants. Most notably, we found a novel variant significantly associated with exceptional survival in the 3' UTR OBFC1 in 13 individuals...

  20. Cardiovascular follow-up at school age after perinatal glucocorticoid exposure in prematurely born children: perinatal glucocorticoid therapy and cardiovascular follow-up.

    Science.gov (United States)

    de Vries, Willem B; Karemaker, Rosa; Mooy, Nicole F; Strengers, Jan L M; Kemperman, Hans; Baerts, Wim; Veen, Sylvia; Visser, Gerard H A; Heijnen, Cobi J; van Bel, Frank

    2008-08-01

    To study whether antenatal or neonatal glucocorticoid therapy to reduce the incidence and severity of chronic lung disease in preterm infants is associated with long-term adverse cardiac effects and hypertension. Retrospective matched-cohort study. Outpatient clinic of a tertiary care hospital. One hundred ninety-three children aged 7 to 10 years who had been born prematurely between December 2, 1993, and September 15, 1997. Main Exposure Neonatal treatment with dexamethasone disodium phosphate(n = 48) or the clinically equally effective glucocorticoid hydrocortisone (n = 51), or only antenatal treatment with betamethasone disodium phosphate and betamethasone acetate (n = 51). These 3 groups were compared with a reference group of prematurely born children who had not been exposed to perinatal glucocorticoid therapy (n = 43). General hemodynamic data (heart rate and blood pressure), cardiovascular function as assessed at echocardiography, intima-media thickness of the carotid arteries, and cardiac biochemical features as early markers of expansion and volume overload of the cardiac left ventricle (B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide). No significant group differences were found for heart rate, blood pressure, biochemical features, intima-media thickness, or systolic or diastolic left ventricular function. Although no differences were found in blood pressure and cardiovascular function at school age in children antenatally or neonatally treated with glucocorticoids, further cardiovascular follow-up may be advisable because cardiovascular dysfunction may become apparent only later in life.

  1. Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta

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    Mark Asquith

    2012-06-01

    Full Text Available Aged individuals are more susceptible to infections due to a general decline in immune function broadly referred to as immune senescence. While age-related changes in the adaptive immune system are well documented, aging of the innate immune system remains less well understood, particularly in nonhuman primates. A more robust understanding of age-related changes in innate immune function would provide mechanistic insight into the increased susceptibility of the elderly to infection. Rhesus macaques have proved a critical translational model for aging research, and present a unique opportunity to dissect age-dependent modulation of the innate immune system. We examined age-related changes in: (i innate immune cell frequencies; (ii expression of pattern recognition receptors (PRRs and innate signaling molecules; (iii cytokine responses of monocytes and dendritic cells (DC following stimulation with PRR agonists; and (iv plasma cytokine levels in this model. We found marked changes in both the phenotype and function of innate immune cells. This included an age-associated increased frequency of myeloid DC (mDC. Moreover, we found toll-like receptor (TLR agonists lipopolysaccharide (TLR4, fibroblast stimulating ligand-1 (TLR2/6, and ODN2006 (TLR7/9 induced reduced cytokine responses in aged mDC. Interestingly, with the exception of the monocyte-derived TNFα response to LPS, which increased with age, TNFα, IL-6, and IFNα responses declined with age. We also found that TLR4, TLR5, and innate negative regulator, sterile alpha and TIR motif containing protein (SARM, were all expressed at lower levels in young animals. By contrast, absent in melanoma 2 and retinoic acid-inducible gene I expression was lowest in aged animals. Together, these observations indicate that several parameters of innate immunity are significantly modulated by age and contribute to differential immune function in aged macaques.

  2. Methods for diagnosing perceived age on the basis of an ensemble of phenotypic features.

    Science.gov (United States)

    Coma, Mireia; Valls, Raquel; Mas, José Manuel; Pujol, Albert; Herranz, Miquel Angel; Alonso, Vicente; Naval, Jordi

    2014-01-01

    Perceived age has been defined as the age that a person is visually estimated to be on the basis of physical appearance. In a society where a youthful appearance are an object of desire for consumers, and a source of commercial profit for cosmetic companies, this concept has a prominent role. In addition, perceived age is also an indicator of overall health status in elderly people, since old-looking people tend to show higher rates of morbidity and mortality. However, there is a lack of objective methods for quantifying perceived age. In order to satisfy the need of objective approaches for estimating perceived age, a novel algorithm was created. The novel algorithm uses supervised mathematical learning techniques and error retropropagation for the creation of an artificial neural network able to learn biophysical and clinically assessed parameters of subjects. The algorithm provides a consistent estimation of an individual's perceived age, taking into account a defined set of facial skin phenotypic traits, such as wrinkles and roughness, number of wrinkles, depth of wrinkles, and pigmentation. A nonintervention, epidemiological cross-sectional study of cases and controls was conducted in 120 female volunteers for the diagnosis of perceived age using this novel algorithm. Data collection was performed by clinical assessment of an expert panel and biophysical assessment using the ANTERA 3D(®) device. Employing phenotype data as variables and expert assignments as objective data, the algorithm was found to correctly classify the samples with an accuracy of 92.04%. Therefore, we have developed a method for determining the perceived age of a subject in a standardized, consistent manner. Further application of this algorithm is thus a promising approach for the testing and validation of cosmetic treatments and aesthetic surgery, and it also could be used as a screening method for general health status in the population.

  3. Microglia change from a reactive to an age-like phenotype with the time in culture

    Directory of Open Access Journals (Sweden)

    Claudia eCaldeira

    2014-06-01

    Full Text Available Age-related neurodegenerative diseases have been associated with chronic neuroinflammation and microglia activation. However, cumulative evidence supports that inflammation only occurs at an early stage once microglia change the endogenous characteristics with ageing and switch to irresponsive/senescent and dystrophic phenotypes with disease progression. Thus, it will be important to have the means to assess the role of reactive and aged microglia when studying advanced brain neurodegeneration processes and age-associated related disorders. Yet, most studies are done with microglia from neonates since there are no adequate means to isolate degenerating microglia for experimentation. Indeed, only a few studies report microglia isolation from aged animals, using either short-term cultures or high concentrations of mitogens in the medium, which trigger microglia reactivity. The purpose of this study was to develop an experimental process to naturally age microglia after isolation from neonatal mice and to characterize the cultured cells at 2 days in vitro (DIV, 10 DIV and 16 DIV. We found that 2 DIV (young microglia had predominant amoeboid morphology and markers of stressed/reactive phenotype. In contrast, 16 DIV (aged microglia evidenced ramified morphology and increased metalloproteinase (MMP-2 activation, as well as reduced MMP-9, glutamate release and nuclear factor kappa-B activation, in parallel with decreased expression of Toll-like receptor (TLR-2 and TLR-4, capacity to migrate and phagocytose. These findings together with the reduced expression of microRNA (miR-124, and miR-155, decreased autophagy, enhanced senescence associated beta-galactosidase activity and elevated miR-146a expression, are suggestive that 16 DIV cells mainly correspond to irresponsive/senescent microglia. Data indicate that the model represent an opportunity to understand and control microglial aging, as well as to explore strategies to recover microglia surveillance

  4. Premature delivery

    Directory of Open Access Journals (Sweden)

    Bernardita Donoso Bernales

    2012-09-01

    Full Text Available Preterm delivery is the single most important cause of perinatal morbidity and mortality. In Chile, preterm births have increased in the past decade, although neonatal morbidity and mortality attributable to it shows a downward trend, thanks to improvements in neonatal care of premature babies, rather than the success of obstetric preventive and therapeutic strategies. This article describes clinical entities, disease processes and conditions that constitute predisposing factors of preterm birth, as well as an outline for the prevention and clinical management of women at risk of preterm birth.

  5. Distinctive Risk Factors and Phenotype of Younger Patients With Resistant Hypertension: Age Is Relevant.

    Science.gov (United States)

    Ghazi, Lama; Oparil, Suzanne; Calhoun, David A; Lin, Chee Paul; Dudenbostel, Tanja

    2017-05-01

    Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ≤40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ≤40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; Phypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone, and high dietary sodium intake compared with elderly. © 2017 American Heart Association, Inc.

  6. Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.

    Directory of Open Access Journals (Sweden)

    Tamuno Alfred

    Full Text Available The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP rs1260326 (P446L in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported.As part of the Healthy Ageing across the Life Course (HALCyon collaborative research programme, men and women from five UK cohorts aged between 44 and 90+ years were genotyped for rs1260326. Meta-analysis was used to pool within-study genotypic associations between the SNP and several age-related phenotypes, including body mass index (BMI, blood lipid levels, lung function, and cognitive and physical capability.We confirm the associations between the minor allele of the SNP and higher triglycerides and lower glucose levels. We also observed a triglyceride-independent association between the minor allele and lower BMI (pooled beta on z-score= -0.04, p-value=0.0001, n=16,251. Furthermore, there was some evidence for gene-environment interactions, including physical activity attenuating the effects on triglycerides. However, no associations were observed with measures of cognitive and physical capability.Findings from middle-aged to older adults confirm associations between rs1260326 GCKR and triglycerides and glucose, suggest possible gene-environment interactions, but do not provide evidence that its relevance extends to cognitive and physical capability.

  7. [The age and sex indicators of mortality of population and years of life lost as a result of premature mortality in the Russian Federation in 2012].

    Science.gov (United States)

    Boiytsov, S A; Samorodskaya, I V

    2014-01-01

    The age-specific mortality coefficients and years of life lost as a result of premature mortality are among important medical demographic characteristics of population health. The study analyzed age and sex indicators of mortality of population in the Russian Federation. The number of years of life lost as a result of premature mortality is calculated. The comparison of values of years of life lost in various subjects of the Russian Federation was carried out. The data of Rosstat concerning population size and number of the deceased in year age groups in the Russian Federation and subjects of the Russian Federation in 2012 was used. The indicator was calculated on the basis of technique included into "The global burden of diseases report" (2010). The minimal indicators of mortality of males are noted at the age of 11 years (25.4 per 100 000 of population) and females at the age of 10 years (18.2 per 100 000 of population). The maximal differences in indicators of mortality of males and females are marked in the age group 20-29 years (314.5 of males and 92.3 of females per 100 000 of population). The percentage of deceased prior 70 years consists 63.2% among males and 29.9% among females. The total number of years of life lost in the Russian Federation consisted 36 864 309 and out of them 24 321 992 (65.9%) as a result of death of males and 12 542 317 (34.1%) as a result of death of females. The maximum percentage of years of life lost among males is marked in the age group of 51-60 years (24.61%) and among females in the age group of 71-80 years (22.38%). The indicator of years of life lost per 100 000 of population consisted 25769 for total population, 36 753 for male population and 16 314 for female population. The highest rate of indicator of years of life lost is marked in the Chukchi Autonomous Okrug and the lowest rate in the Republics of the Northern Caucasus and Moscow. However, in all subjects of the Russian Federation indicator of years of life lost is

  8. Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals

    DEFF Research Database (Denmark)

    Soerensen, Mette; Nygaard, Marianne; Dato, Serena

    2015-01-01

    -old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease......, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3A variation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture...

  9. Genotype-phenotype correlations in Cornelia de Lange syndrome: Behavioral characteristics and changes with age.

    Science.gov (United States)

    Moss, Joanna; Penhallow, Jessica; Ansari, Morad; Barton, Stephanie; Bourn, David; FitzPatrick, David R; Goodship, Judith; Hammond, Peter; Roberts, Catherine; Welham, Alice; Oliver, Chris

    2017-06-01

    Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder associated with unusual facial features, limb abnormalities, a wide range of health conditions, and intellectual disability. Mutations in five genes that encode (SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex have been identified in up to 70% of individuals. Genetic cause remains unknown for a proportion of individuals. There is substantial heterogeneity in all aspects of CdLS but very little is known about what predicts phenotypic heterogeneity. In this study, we evaluated genotype-phenotype associations in 34 individuals with CdLS. Participants with NIPBL mutations had significantly lower self help skills and were less likely to have verbal skills relative to those who were negative for the NIPBL mutation. No significant differences were identified between the groups in relation to repetitive behavior, mood, interest and pleasure, challenging behavior, activity, impulsivity, and characteristics of autism spectrum disorder whilst controlling differences in self help skills. Significant correlations indicating lower mood, interest and pleasure, and increased insistence on sameness with older age were identified for those who were NIPBL mutation positive. The findings suggest similarities in the behavioral phenotype between those with and without the NIPBL mutation once differences in self help skills are controlled for. However, there may be subtle differences in the developmental trajectory of these behaviors according to genetic mutation status in CdLS. © 2017 Wiley Periodicals, Inc.

  10. Phenotypic plasticity in age at first reproduction of female northern sea otters (Enhydra lutris kenyoni)

    Science.gov (United States)

    Von Biela, V.R.; Gill, V.A.; Bodkin, J.L.; Burns, Jennifer M.

    2009-01-01

    Life-history theory predicts that within a species, reproduction and survival rates will differ among populations that differ in resource availability or predation rates through phenotypic plasticity. When populations are near carrying capacity (K) or when they are declining due to reduced prey resources, the average age at 1st reproduction (average AFR) is predicted to be older than in populations below K. Differences between the trajectories of northern sea otter (Enhydra lutris kenyoni) populations in Alaska provides an opportunity to examine phenotypic plasticity. Using premolar teeth or reproductive tracts, we estimated average AFR from demographically distinct populations of sea otters in Alaska. We obtained samples from 2 populations near K, Prince William Sound (PWS) and the Aleutian Archipelago (archived samples), and from 2populations below K, the Kodiak Archipelago and Sitka. The average AFR was lower in populations below K (3.60 years ??0.16 SD)compared to those near K (4.21 ?? 0.13 years, P phenotypic plasticity in sea otters. Our findings highlight the value of using average AFR as a tool for monitoring mammalian populations. ?? 2009 American Society of Mammalogists.

  11. A high-fat diet and NAD+ activate sirt1 to rescue premature aging in cockayne syndrome

    DEFF Research Database (Denmark)

    Scheibye-Knudsen, Morten; Mitchell, Sarah J.; Fang, Evandro F.;

    2014-01-01

    SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high-fat diet, and β-hydroxybutyrate, PARP inhibition, or NAD+ supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB can displace activated PARP1 from damaged DNA...... to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD+, through the deacetylase SIRT1 and suggests possible interventions for CS....

  12. Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study

    DEFF Research Database (Denmark)

    Druley, Todd E; Wang, Lihua; Lin, Shiow J;

    2016-01-01

    BACKGROUND: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. METHODS......: We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually...... that was significantly associated with three phenotypes (GSK3B with the Healthy Aging Index, NOTCH1 with diastolic blood pressure and TP53 with serum HDL). CONCLUSIONS: Sequencing analysis of family-based associations for age-related phenotypes can identify rare or novel variants....

  13. Ablations of ghrelin and ghrelin receptor exhibit differential metabolic phenotypes and thermogenic capacity during aging.

    Directory of Open Access Journals (Sweden)

    Xiaojun Ma

    Full Text Available BACKGROUND: Obesity is a hallmark of aging in many Western societies, and is a precursor to numerous serious age-related diseases. Ghrelin (Ghrl, via its receptor (growth hormone secretagogue receptor, GHS-R, is shown to stimulate GH secretion and appetite. Surprisingly, our previous studies showed that Ghrl(-/- mice have impaired thermoregulatory responses to cold and fasting stresses, while Ghsr(-/- mice are adaptive. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the mechanism, we analyzed the complete metabolic profiles of younger (3-4 months and older (10-12 months Ghrl(-/- and Ghsr(-/- mice. Food intake and locomotor activity were comparable for both null mice and their wild-type (WT counterparts, regardless of age. There was also no difference in body composition between younger null mice and their WT counterparts. As the WT mice aged, as expected, the fat/lean ratio increased and energy expenditure (EE decreased. Remarkably, however, older Ghsr(-/- mice exhibited reduced fat/lean ratio and increased EE when compared to older WT mice, thus retaining a youthful lean and high EE phenotype; in comparison, there was no significant difference with EE in Ghrl(-/- mice. In line with the EE data, the thermogenic regulator, uncoupling protein 1 (UCP1, was significantly up-regulated in brown adipose tissue (BAT of Ghsr(-/- mice, but not in Ghrl(-/- mice. CONCLUSIONS: Our data therefore suggest that GHS-R ablation activates adaptive thermogenic function(s in BAT and increases EE, thereby enabling the retention of a lean phenotype. This is the first direct evidence that the ghrelin signaling pathway regulates fat-burning BAT to affect energy balance during aging. This regulation is likely mediated through an as-yet-unidentified new ligand of GHS-R.

  14. Towards measurement of the Healthy Ageing Phenotype in lifestyle-based intervention studies.

    Science.gov (United States)

    Lara, Jose; Godfrey, Alan; Evans, Elizabeth; Heaven, Ben; Brown, Laura J E; Barron, Evelyn; Rochester, Lynn; Meyer, Thomas D; Mathers, John C

    2013-10-01

    Given the biological complexity of the ageing process, there is no single, simple and reliable measure of how healthily someone is ageing. Intervention studies need a panel of measures which capture key features of healthy ageing. To help guide our research in this area, we have adopted the concept of the "Healthy Ageing Phenotype" (HAP) and this study aimed to (i) identify the most important features of the HAP and (ii) identify/develop tools for measurement of those features. After a comprehensive assessment of the literature we selected the following domains: physiological and metabolic health, physical capability, cognitive function, social wellbeing, and psychological wellbeing which we hoped would provide a reasonably holistic characterisation of the HAP. We reviewed the literature and identified systematic reviews and/or meta-analysis of cohort studies, and clinical guidelines on outcome measures of these domains relevant to the HAP. Selection criteria for these measures included: frequent use in longitudinal studies of ageing; expected to change with age; evidence for strong association with/prediction of ageing-related phenotypes such as morbidity, mortality and lifespan; whenever possible, focus on studies measuring these outcomes in populations rather than on individuals selected on the basis of a particular disease; (bio)markers that respond to (lifestyle-based) intervention. Proposed markers were exposed to critique in a Workshop held in Newcastle, UK in October 2012. We have selected a tentative panel of (bio)markers of physiological and metabolic health, physical capability, cognitive function, social wellbeing, and psychological wellbeing which we propose may be useful in characterising the HAP and which may have utility as outcome measures in intervention studies. In addition, we have identified a number of tools which could be applied in community-based intervention studies designed to enhance healthy ageing. We have proposed, tentatively, a panel

  15. A 3-month age difference profoundly alters the primary rat stromal vascular fraction phenotype

    DEFF Research Database (Denmark)

    Quaade, Marlene Louise; Jensen, Charlotte Harken; Andersen, Ditte Caroline;

    2016-01-01

    The stromal vascular fraction (SVF) is a heterogeneous population obtained from collagenase digestion of adipose tissue. When cultured the population becomes more homogeneous and the cells are then termed adipose stromal/stem cells (ASCs). Both the freshly isolated primary SVF population...... and the cultured ASC population possess regenerative abilities suggested to be mediated by paracrine mechanisms mainly. The use of ASCs and SVF cells, both in animal studies and human clinical studies, has dramatically increased during recent years. However, more knowledge regarding optimal donor characteristics...... such as age is demanded. Here we report that even a short age difference has an impact on the phenotype of primary SVF cells. We observed that a 3-month difference in relatively young adult rats affects the expression pattern of several mesenchymal stem cell markers in their primary SVF. The younger animals...

  16. A hyperoxic lung injury model in premature rabbits: the influence of different gestational ages and oxygen concentrations.

    Directory of Open Access Journals (Sweden)

    Roberta Munhoz Manzano

    Full Text Available BACKGROUND: Many animal models have been developed to study bronchopulmonary dysplasia (BPD. The preterm rabbit is a low-cost, easy-to-handle model, but it has a high mortality rate in response to the high oxygen concentrations used to induce lung injury. The aim of this study was to compare the mortality rates of two models of hyperoxia-induced lung injury in preterm rabbits. METHODS: Pregnant New Zealand white rabbits were subjected to caesarean section on gestational day 28 or 29 (full term  = 31 days. The premature rabbits in the 28-day gestation group were exposed to room air or FiO₂ ≥95%, and the rabbits in the 29-day gestation group were exposed to room air or FiO₂  = 80% for 11 days. The mean linear intercept (Lm, internal surface area (ISA, number of alveoli, septal thickness and proportion of elastic and collagen fibers were quantified. RESULTS: The survival rates in the 29-day groups were improved compared with the 28-day groups. Hyperoxia impaired the normal development of the lung, as demonstrated by an increase in the Lm, the septal thickness and the proportion of elastic fibers. Hyperoxia also decreased the ISA, the number of alveoli and the proportion of collagen fibers in the 28-day oxygen-exposed group compared with the control 28-day group. A reduced number of alveoli was found in the 29-day oxygen exposed animals compared with the control 29-day group. CONCLUSIONS: The 29-day preterm rabbits had a reduced mortality rate compared with the 28-day preterm rabbits and maintained a reduction in the alveoli number, which is comparable to BPD in humans.

  17. Premature Ventricular Contractions (PVCs)

    Science.gov (United States)

    Diseases and Conditions Premature ventricular contractions (PVCs) By Mayo Clinic Staff Premature ventricular contractions (PVCs) are extra, abnormal heartbeats that begin in one of your heart's two ...

  18. Inactivation of RAD52 and HDF1 DNA repair genes leads to premature chronological aging and cellular instability

    Indian Academy of Sciences (India)

    SILVIA MERCADO-SÁENZ; BEATRIZ LÓPEZ-DÍAZ; FRANCISCO SENDRA-PORTERO; MANUEL MARTÍNEZ-MORILLO; MIGUEL J RUIZ-GÓMEZ

    2017-06-01

    The present study aims to investigate the role of radiation sensitive 52 (RAD52) and high-affinity DNA binding factor1 (HDF1) DNA repair genes on the life span of budding yeasts during chronological aging. Wild type (wt) and rad52,hdf1, and rad52 hdf1 mutant Saccharomyces cerevisiae strains were used. Chronological aging and survival assayswere studied by clonogenic assay and drop test. DNA damage was analyzed by electrophoresis after phenol extraction.Mutant analysis, colony forming units and the index of respiratory competence were studied by growing on dextroseand glycerol plates as a carbon source. Rad52 and rad52 hdf1 mutants showed a gradual decrease in surviving fractionin relation to wt and hdf1 mutant during aging. Genomic DNA was spontaneously more degraded during aging,mainly in rad52 mutants. This strain showed an increased percentage of revertant colonies. Moreover, all mutantsshowed a decrease in the index of respiratory competence during aging. The inactivation of RAD52 leads to prematurechronological aging with an increase in DNA degradation and mutation frequency. In addition, RAD52 and HDF1contribute to maintain the metabolic state, in a different way, during chronological aging. The results obtained couldhave important implications in the chronobiology of aging.

  19. Premature ejaculation

    Directory of Open Access Journals (Sweden)

    Chris G McMahon

    2007-01-01

    Full Text Available Premature ejaculation (PE is a common male sexual disorder. Recent normative data suggests that men with an intravaginal ejaculatory latency time (IELT of less than 1 minute have "definite" PE, while men with IELTs between 1 and 1.5 minutes have "probable" PE. Although there is insufficient empirical evidence to identify the etiology of PE, there is limited correlational evidence to suggest that men with PE have high levels of sexual anxiety and inherited altered sensitivity of central 5-HT (5-hydroxytryptamine, serotonin receptors. Pharmacological modulation of the ejaculatory threshold using off-label daily or on-demand selective serotonin re-uptake inhibitors is well tolerated and offers patients a high likelihood of achieving improved ejaculatory control within a few days of initiating treatment, consequential improvements in sexual desire and other sexual domains. Investigational drugs such as the ejaculo-selective serotonin transport inhibitor, dapoxetine represent a major development in sexual medicine. These drugs offer patients the convenience of on-demand dosing, significant improvements in IELT, ejaculatory control and sexual satisfaction with minimal adverse effects.

  20. Premature ejaculation.

    Science.gov (United States)

    McMahon, Chris G

    2007-04-01

    Premature ejaculation (PE) is a common male sexual disorder. Recent normative data suggests that men with an intravaginal ejaculatory latency time (IELT) of less than 1 minute have "definite" PE, while men with IELTs between 1 and 1.5 minutes have "probable" PE. Although there is insufficient empirical evidence to identify the etiology of PE, there is limited correlational evidence to suggest that men with PE have high levels of sexual anxiety and inherited altered sensitivity of central 5-HT (5-hydroxytryptamine, serotonin) receptors. Pharmacological modulation of the ejaculatory threshold using off-label daily or on-demand selective serotonin re-uptake inhibitors is well tolerated and offers patients a high likelihood of achieving improved ejaculatory control within a few days of initiating treatment, consequential improvements in sexual desire and other sexual domains. Investigational drugs such as the ejaculo-selective serotonin transport inhibitor, dapoxetine represent a major development in sexual medicine. These drugs offer patients the convenience of on-demand dosing, significant improvements in IELT, ejaculatory control and sexual satisfaction with minimal adverse effects.

  1. Reversible cell cycle inhibition and premature aging features imposed by conditional expression of p16Ink4a

    Science.gov (United States)

    Boquoi, Amelie; Arora, Sanjeevani; Chen, Tina; Litwin, Sam; Koh, James; Enders, Greg H

    2015-01-01

    The cyclin-dependent kinase (Cdk) inhibitor p16Ink4a (p16) is a canonical mediator of cellular senescence and accumulates in aging tissues, where it constrains proliferation of some progenitor cells. However, whether p16 induction in tissues is sufficient to inhibit cell proliferation, mediate senescence, and/or impose aging features has remained unclear. To address these issues, we generated transgenic mice that permit conditional p16 expression. Broad induction at weaning inhibited proliferation of intestinal transit-amplifying and Lgr5+ stem cells and rapidly imposed features of aging, including hair loss, skin wrinkling, reduced body weight and subcutaneous fat, an increased myeloid fraction in peripheral blood, poor dentition, and cataracts. Aging features were observed with multiple combinations of p16 transgenes and transactivators and were largely abrogated by a germline Cdk4 R24C mutation, confirming that they reflect Cdk inhibition. Senescence markers were not found, and de-induction of p16, even after weeks of sustained expression, allowed rapid recovery of intestinal cell proliferation and reversal of aging features in most mice. These results suggest that p16-mediated inhibition of Cdk activity is sufficient to inhibit cell proliferation and impose aging features in somatic tissues of mammals and that at least some of these aging features are reversible. PMID:25481981

  2. Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals.

    Science.gov (United States)

    Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Stevnsner, Tinna; Bohr, Vilhelm A; Christensen, Kaare; Christiansen, Lene

    2015-02-01

    FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 oldest-old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3A variation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture risk for carriers of the minor alleles of 8 and 10 SNPs, respectively. These positive directions of effects are in agreement with the positive effects on longevity previously reported for these SNPs. However, when correcting for the test of 9 phenotypes by Bonferroni correction, bone fracture showed borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94-100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis of both study populations displayed similar or decreased sized P-values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed.

  3. Association study of FOXO3ASNPs and aging phenotypes in Danish oldest-old individuals

    Science.gov (United States)

    Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Stevnsner, Tinna; Bohr, Vilhelm A; Christensen, Kaare; Christiansen, Lene

    2015-01-01

    FOXO3Avariation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3Avariation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3Atagging single nucleotide polymorphisms (SNPs) in 1088 oldest-old Danes (age 92–93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3Avariation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture risk for carriers of the minor alleles of 8 and 10 SNPs, respectively. These positive directions of effects are in agreement with the positive effects on longevity previously reported for these SNPs. However, when correcting for the test of 9 phenotypes by Bonferroni correction, bone fracture showed borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94–100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis of both study populations displayed similar or decreased sized P-values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed. PMID:25470651

  4. A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells

    Science.gov (United States)

    Lo Cicero, Alessandra; Jaskowiak, Anne-Laure; Egesipe, Anne-Laure; Tournois, Johana; Brinon, Benjamin; Pitrez, Patricia R.; Ferreira, Lino; de Sandre-Giovannoli, Annachiara; Levy, Nicolas; Nissan, Xavier

    2016-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process and, among these, all-trans retinoic acid and 13-cis-retinoic acid, that also decreased progerin expression. This study highlights the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders. PMID:27739443

  5. No Association between Variation in Longevity Candidate Genes and Aging-related Phenotypes in Oldest-old Danes.

    Science.gov (United States)

    Soerensen, Mette; Nygaard, Marianne; Debrabant, Birgit; Mengel-From, Jonas; Dato, Serena; Thinggaard, Mikael; Christensen, Kaare; Christiansen, Lene

    2016-06-01

    In this study we explored the association between aging-related phenotypes previously reported to predict survival in old age and variation in 77 genes from the DNA repair pathway, 32 genes from the growth hormone 1/ insulin-like growth factor 1/insulin (GH/IGF-1/INS) signalling pathway and 16 additional genes repeatedly considered as candidates for human longevity: APOE, APOA4, APOC3, ACE, CETP, HFE, IL6, IL6R, MTHFR, TGFB1, SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. Altogether, 1,049 single nucleotide polymorphisms (SNPs) were genotyped in 1,088 oldest-old (age 92-93 years) Danes and analysed with phenotype data on physical functioning (hand grip strength), cognitive functioning (mini mental state examination and a cognitive composite score), activity of daily living and self-rated health. Five SNPs showed association to one of the phenotypes; however, none of these SNPs were associated with a change in the relevant phenotype over time (7 years of follow-up) and none of the SNPs could be confirmed in a replication sample of 1,281 oldest-old Danes (age 94-100). Hence, our study does not support association between common variation in the investigated longevity candidate genes and aging-related phenotypes consistently shown to predict survival. It is possible that larger sample sizes are needed to robustly reveal associations with small effect sizes.

  6. Neurodevelopmental sequelae in premature newborns with extremely low weight and with very low weight at two years of age who left the Neonatal Intensive Care Unit of the Hospital Nacional Edgardo Rebagliati Martins 2009-2014

    Directory of Open Access Journals (Sweden)

    Carmen Fernández Sierra

    2017-02-01

    Full Text Available Objective: The purpose of this study is to describe the neurodevelopmental sequelae in premature newborns with extremely low weight and with very low weight at two years of age who left the Neonatal Intensive Care Unit of the Hospital Nacional Edgardo Rebagliati Martins. Materials and methods: A descriptive, retrospective, cross-sectional study in a population of 190 premature newborns with extremely low weight and with very low weight born from January 2009 to June 2014 who left the Neonatal Intensive Care Unit and took part in the follow-up program. The psychomotor development, sensorineural hearing loss, retinopathy of prematurity, presence of cerebral palsy and convulsive syndrome were assessed. Results: The average weight at birth was 1,180.53 ± 212.40 grams with a gestational age of 29.86 ± 2.33 weeks, and 51.58% of the newborns were male. Forty-two point six three percent (42.63% of the premature newborns with very low weight showed retardation of psychomotor development; 25.26%, retinopathy; 13.68%, sensorineural hearing loss; 3.68%, cerebral palsy; and 3.68%, convulsive syndrome. Fifty-two point two seven percent (52.27% of the premature newborns with extremely low weight showed retardation of psychomotor development; 50%, retinopathy; 15.91%, sensorineural hearing loss; and 2.27%, convulsive syndrome. Conclusions: Retardation of psychomotor development and retinopathy were the most important complications shown by premature newborns with extremely low weight and with very low weight at two years of age.

  7. Pathway-Based Factor Analysis of Gene Expression Data Produces Highly Heritable Phenotypes That Associate with Age

    Science.gov (United States)

    Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

    2015-01-01

    Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 “pathway phenotypes” that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold (P<5.38×10−5). These phenotypes are more heritable (h2=0.32) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. PMID:25758824

  8. Increased release and activity of matrix metalloproteinase-9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome.

    Science.gov (United States)

    Lombardi, F; Fasciglione, G F; D'Apice, M R; Vielle, A; D'Adamo, M; Sbraccia, P; Marini, S; Borgiani, P; Coletta, M; Novelli, G

    2008-10-01

    Mandibuloacral dysplasia type A (MADA; OMIM 248370), a rare disorder caused by mutation in the LMNA gene, is characterized by post-natal growth retardation, craniofacial and skeletal anomalies (mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial sutures, low bone mass and joint contractures), cutaneous changes and partial lipodystrophy. Little is known about the molecular mechanisms by which LMNA mutations produce bone alterations. An altered bone extracellular matrix (ECM) remodelling could play a pivotal role in this disorder and influence part of the typical bone phenotype observed in patients. Therefore, we have focused our investigation on matrix metalloproteinases (MMPs), which are degradative enzymes involved in ECM degradation and ECM remodelling, thus likely contributing to the altered bone mineral density and bone metabolism values seen in five MADA patients. We evaluated the serum levels of several MMPs involved in bone development, remodelling and homeostasis, such as MMP-9, -2, -3, -8 and -13, and found that only the 82 kDa active enzyme forms of MMP-9 are significantly higher in MADA sera compared with healthy controls (n = 16). The serum level of MMP-3 was instead lower in all patients. No significant differences were observed between controls and MADA patients for the serum levels of MMP-2, -8 and -13 and of tissue inhibitor of metalloproteinase 2, a natural inhibitor of MMP-9. Similarly, normal serum levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-6 and IL-1beta were detected. These data suggest a possible involvement of MMP-9 in MADA disease, underlying the potential use in diagnosis and therapy.

  9. News of cognitive cure for age-related brain shrinkage is premature: a comment on Burgmans et al. (2009).

    Science.gov (United States)

    Raz, Naftali; Lindenberger, Ulman

    2010-03-01

    The extant longitudinal literature consistently supports the notion of age-related declines in human brain volume. In a report on a longitudinal cognitive follow-up with cross-sectional brain measurements, Burgmans and colleagues (2009) claim that the extant studies overestimate brain volume declines, presumably due to inclusion of participants with preclinical cognitive pathology. Moreover, the authors of the article assert that such declines are absent among optimally healthy adults who maintain cognitive stability for several years. In this comment accompanied by reanalysis of previously published data, we argue that these claims are incorrect on logical, methodological, and empirical grounds.

  10. Whole exome sequencing of extreme age-related macular degeneration phenotypes

    Science.gov (United States)

    Sardell, Rebecca J.; Bailey, Jessica N Cooke; Courtenay, Monique D.; Whitehead, Patrice; Laux, Reneé A.; Adams, Larry D.; Fortun, Jorge A.; Brantley, Milam A.; Kovach, Jaclyn L.; Schwartz, Stephen G.; Agarwal, Anita; Scott, William K.; Haines, Jonathan L.

    2016-01-01

    Purpose Demographic, environmental, and genetic risk factors for age-related macular degeneration (AMD) have been identified; however, a substantial portion of the variance in AMD disease risk and heritability remains unexplained. To identify AMD risk variants and generate hypotheses for future studies, we performed whole exome sequencing for 75 individuals whose phenotype was not well predicted by their genotype at known risk loci. We hypothesized that these phenotypically extreme individuals were more likely to carry rare risk or protective variants with large effect sizes. Methods A genetic risk score was calculated in a case–control set of 864 individuals (467 AMD cases, 397 controls) based on 19 common (≥1% minor allele frequency, MAF) single nucleotide variants previously associated with the risk of advanced AMD in a large meta-analysis of advanced cases and controls. We then selected for sequencing 39 cases with bilateral choroidal neovascularization with the lowest genetic risk scores to detect risk variants and 36 unaffected controls with the highest genetic risk score to detect protective variants. After minimizing the influence of 19 common genetic risk loci on case-control status, we targeted single variants of large effect and the aggregate effect of weaker variants within genes and pathways. Single variant tests were conducted on all variants, while gene-based and pathway analyses were conducted on three subsets of data: 1) rare (≤1% MAF in the European population) stop, splice, or damaging missense variants, 2) all rare variants, and 3) all variants. All analyses controlled for the effects of age and sex. Results No variant, gene, or pathway outside regions known to be associated with risk for advanced AMD reached genome-wide significance. However, we identified several variants with substantial differences in allele frequency between cases and controls with strong additive effects on affection status after controlling for age and sex

  11. Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

    Science.gov (United States)

    Weismüller, Tobias J.; Trivedi, Palak J.; Bergquist, Annika; Imam, Mohamad; Lenzen, Henrike; Ponsioen, Cyriel Y.; Holm, Kristian; Gotthardt, Daniel; Färkkilä, Martti A.; Marschall, Hanns-Ulrich; Thorburn, Douglas; Weersma, Rinse K.; Fevery, Johan; Mueller, Tobias; Chazouillères, Olivier; Schulze, Kornelius; Lazaridis, Konstantinos N.; Almer, Sven; Pereira, Stephen P.; Levy, Cynthia; Mason, Andrew; Naess, Sigrid; Bowlus, Christopher L.; Floreani, Annarosa; Halilbasic, Emina; Yimam, Kidist K.; Milkiewicz, Piotr; Beuers, Ulrich; Huynh, Dep K.; Pares, Albert; Manser, Christine N.; Dalekos, George N.; Eksteen, Bertus; Invernizzi, Pietro; Berg, Christoph P.; Kirchner, Gabi I.; Sarrazin, Christoph; Zimmer, Vincent; Fabris, Luca; Braun, Felix; Marzioni, Marco; Juran, Brian D.; Said, Karouk; Rupp, Christian; Jokelainen, Kalle; Benito de Valle, Maria; Saffioti, Francesca; Cheung, Angela; Trauner, Michael; Schramm, Christoph; Chapman, Roger W.; Karlsen, Tom H.; Schrumpf, Erik; Strassburg, Christian P.; Manns, Michael P.; Lindor, Keith D.; Hirschfield, Gideon M.; Hansen, Bettina E.; Boberg, Kirsten M.

    2017-01-01

    BACKGROUND & AIMS Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21–30 years old, 9.0 per 100 patient-years for patients 31–40 years old, 14.0 per 100 patient-years for patients 41–50 years old, 15.2 per 100 patient-years for patients 51–60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn’s disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P

  12. The I4895T mutation in the type 1 ryanodine receptor induces fiber-type specific alterations in skeletal muscle that mimic premature aging.

    Science.gov (United States)

    Boncompagni, Simona; Loy, Ryan E; Dirksen, Robert T; Franzini-Armstrong, Clara

    2010-12-01

    The I4898T (IT) mutation in type 1 ryanodine receptor (RyR1), the Ca(2+) release channel of the sarcoplasmic reticulum (SR) is linked to a form of central core disease (CCD) in humans and results in a nonleaky channel and excitation-contraction uncoupling. We characterized age-dependent and fiber-type-dependent alterations in muscle ultrastructure, as well as the magnitude and spatiotemporal properties of evoked Ca(2+) release in heterozygous Ryr1(I4895T/WT) (IT/+) knock-in mice on a mixed genetic background. The results indicate a classical but mild CCD phenotype that includes muscle weakness and the presence of mitochondrial-deficient areas in type I fibers. Electrically evoked Ca(2+) release is significantly reduced in single flexor digitorum brevis (FDB) fibers from young and old IT/+ mice. Structural changes are strongly fiber-type specific, affecting type I and IIB/IIX fibers in very distinct ways, and sparing type IIA fibers. Ultrastructural alterations in our IT/+ mice are also present in wild type, but at a lower frequency and older ages, suggesting that the disease mutation on the mixed background promotes an acceleration of normal age-dependent changes. The observed functional and structural alterations and their similarity to age-associated changes are entirely consistent with the known properties of the mutated channel, which result in reduced calcium release as is also observed in normal aging muscle. In strong contrast to these observations, a subset of patients with the analogous human heterozygous mutation and IT/+ mice on an inbred 129S2/SvPasCrl background exhibit a more severe disease phenotype, which is not directly consistent with the mutated channel properties.

  13. Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss.

    Science.gov (United States)

    Iwaniec, U T; Philbrick, K A; Wong, C P; Gordon, J L; Kahler-Quesada, A M; Olson, D A; Branscum, A J; Sargent, J L; DeMambro, V E; Rosen, C J; Turner, R T

    2016-10-01

    Room temperature housing (22 °C) results in premature cancellous bone loss in female mice. The bone loss was prevented by housing mice at thermoneutral temperature (32 °C). Thermogenesis differs markedly between mice and humans and mild cold stress induced by standard room temperature housing may introduce an unrecognized confounding variable into preclinical studies. Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18-23 °C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture. Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 or 32 °C for up to 18 weeks. C57BL/6J mice housed at 22 °C experienced a 62 % cancellous bone loss from the distal femur metaphysis during the interval from 8 to 18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32 °C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption. Housing female mice at 22 °C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies

  14. Low birthweight and premature birth are both associated with type 2 diabetes in a random sample of middle-aged Danes

    DEFF Research Database (Denmark)

    Pilgaard, K; Færch, K; Carstensen, B

    2010-01-01

    We studied the associations of size at birth and prematurity with type 2 diabetes, insulin sensitivity and beta cell function in the Danish population-based Inter99 study (ClinicalTrials.gov NCT00289237)....

  15. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L.; Youssef, S. A.; de Bruin, A.

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of geroscience, wh

  16. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L; Youssef, S A; de Bruin, A|info:eu-repo/dai/nl/304837261

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

  17. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L; Youssef, S A; de Bruin, A

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

  18. XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Tainer, John; Fan, Li; Fuss, Jill O.; Cheng, Quen J.; Arvai, Andrew S.; Hammel, Michal; Roberts, Victoria A.; Cooper, Priscilla K.; Tainer, John A.

    2008-06-02

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  19. XPD Helicase Structures And Activities: Insights Into the Cancer And Aging Phenotypes From XPD Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Fan, L.; Fuss, J.O.; Cheng, Q.J.; Arvai, A.S.; Hammel, M.; Roberts, V.A.; Cooper, P.K.; Tainer, J.A.

    2009-05-18

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  20. A Validated Phenotyping Algorithm for Genetic Association Studies in Age-related Macular Degeneration

    Science.gov (United States)

    Simonett, Joseph M.; Sohrab, Mahsa A.; Pacheco, Jennifer; Armstrong, Loren L.; Rzhetskaya, Margarita; Smith, Maureen; Geoffrey Hayes, M.; Fawzi, Amani A.

    2015-01-01

    Age-related macular degeneration (AMD), a multifactorial, neurodegenerative disease, is a leading cause of vision loss. With the rapid advancement of DNA sequencing technologies, many AMD-associated genetic polymorphisms have been identified. Currently, the most time consuming steps of these studies are patient recruitment and phenotyping. In this study, we describe the development of an automated algorithm to identify neovascular (wet) AMD, non-neovascular (dry) AMD and control subjects using electronic medical record (EMR)-based criteria. Positive predictive value (91.7%) and negative predictive value (97.5%) were calculated using expert chart review as the gold standard to assess algorithm performance. We applied the algorithm to an EMR-linked DNA bio-repository to study previously identified AMD-associated single nucleotide polymorphisms (SNPs), using case/control status determined by the algorithm. Risk alleles of three SNPs, rs1061170 (CFH), rs1410996 (CFH), and rs10490924 (ARMS2) were found to be significantly associated with the AMD case/control status as defined by the algorithm. With the rapid growth of EMR-linked DNA biorepositories, patient selection algorithms can greatly increase the efficiency of genetic association study. We have found that stepwise validation of such an algorithm can result in reliable cohort selection and, when coupled within an EMR-linked DNA biorepository, replicates previously published AMD-associated SNPs. PMID:26255974

  1. Low birthweight and premature birth are both associated with type 2 diabetes in a random sample of middle-aged Danes

    DEFF Research Database (Denmark)

    Pilgaard, K; Færch, K; Carstensen, B;

    2010-01-01

    We studied the associations of size at birth and prematurity with type 2 diabetes, insulin sensitivity and beta cell function in the Danish population-based Inter99 study (ClinicalTrials.gov NCT00289237).......We studied the associations of size at birth and prematurity with type 2 diabetes, insulin sensitivity and beta cell function in the Danish population-based Inter99 study (ClinicalTrials.gov NCT00289237)....

  2. Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes.

    Science.gov (United States)

    Thompson, Cheryl L; Klein, Barbara E K; Klein, Ronald; Xu, Zhiying; Capriotti, Jennifer; Joshi, Tripti; Leontiev, Dmitry; Lee, Kristine E; Elston, Robert C; Iyengar, Sudha K

    2007-09-01

    In this study, we investigated the associations of complement factor H (CFH) and hemicentin-1 (HMCN1) with age-related macular degeneration (AMD) and renal function. Three scales, measuring the course of AMD and drusen development, were examined in two samples: the Family Age-Related Macular degeneration Study (FARMS), consisting of families ascertained through a single individual with severe AMD, and an unascertained population-based family cohort, the Beaver Dam Eye Study (BDES), which was also used to assess longitudinal changes in AMD and associations with renal function. Associations were performed by a regression accounting for known risk factors as well as familial and sibling effects. Strong evidence of the association of rs1061170 (Y402H) variation with AMD was confirmed (P = 9.15 x 10(-5) in BDES, P = 0.016 in FARMS). This association was observed in multiple AMD scales, suggesting that its role is not phenotype-specific. Polymorphisms in both CFH and HMCN1 appeared to influence the longitudinal rate of change of AMD. The rs1061170 polymorphism was also associated with a reduction in estimated glomerular filtration rate (eGFR) (P = 0.046). Another CFH polymorphism, rs800292, was similarly associated with eGFR [beta = -0.90 (P = 0.022)]. Associations between rs743137 (P = 0.05) and rs680638 (P = 0.022) in HMCN1 with calculated creatinine clearance progression were also observed. Both genes appear to play a role in both AMD and renal pathophysiology. These findings support evidence for common pathways influencing ocular and renal function and suggest that further work is required on their common determinants.

  3. Electrical stimulation directs engineered cardiac tissue to an age-matched native phenotype

    Directory of Open Access Journals (Sweden)

    Richard A Lasher

    2012-12-01

    Full Text Available Quantifying structural features of native myocardium in engineered tissue is essential for creating functional tissue that can serve as a surrogate for in vitro testing or the eventual replacement of diseased or injured myocardium. We applied three-dimensional confocal imaging and image analysis to quantitatively describe the features of native and engineered cardiac tissue. Quantitative analysis methods were developed and applied to test the hypothesis that environmental cues direct engineered tissue toward a phenotype resembling that of age-matched native myocardium. The analytical approach was applied to engineered cardiac tissue with and without the application of electrical stimulation as well as to age-matched and adult native tissue. Individual myocytes were segmented from confocal image stacks and assigned a coordinate system from which measures of cell geometry and connexin-43 spatial distribution were calculated. The data were collected from 9 nonstimulated and 12 electrically stimulated engineered tissue constructs and 5 postnatal day 12 and 7 adult hearts. The myocyte volume fraction was nearly double in stimulated engineered tissue compared to nonstimulated engineered tissue (0.34 ± 0.14 vs 0.18 ± 0.06 but less than half of the native postnatal day 12 (0.90 ± 0.06 and adult (0.91 ± 0.04 myocardium. The myocytes under electrical stimulation were more elongated compared to nonstimulated myocytes and exhibited similar lengths, widths, and heights as in age-matched myocardium. Furthermore, the percentage of connexin-43-positive membrane staining was similar in the electrically stimulated, postnatal day 12, and adult myocytes, whereas it was significantly lower in the nonstimulated myocytes. Connexin-43 was found to be primarily located at cell ends for adult myocytes and irregularly but densely clustered over the membranes of nonstimulated, stimulated, and postnatal day 12 myocytes. These findings support our hypothesis and reveal

  4. Retinopathy of Prematurity (ROP)

    Science.gov (United States)

    ... of Prematurity (ROP) Facts About Retinopathy of Prematurity (ROP) This information was developed by the National Eye ... blind from ROP. Are there different stages of ROP? Yes. ROP is classified in five stages, ranging ...

  5. Relation between genotype, phenotype and therapeutic drug concentrations of nortriptyline or venlafaxine users in old age psychiatry

    NARCIS (Netherlands)

    Berm, E.J.J.; Kok, R.M.; Hak, E.; Wilffert, B.

    2015-01-01

    Background The relationship between phenotype and genotype of the polymorphic cytochrome P450 2D6 enzyme (CYP2D6) has been intensively studied, however few studies are conducted among older persons. In a study among 900 relatively young venlafaxine users (mean age 45 years), 83% were genotyped as an

  6. Effects of paternal phenotype and environmental variability on age and size at maturity in a male dimorphic mite

    NARCIS (Netherlands)

    I.M. Smallegange

    2011-01-01

    Investigating how the environment affects age and size at maturity of individuals is crucial to understanding how changes in the environment affect population dynamics through the biology of a species. Paternal phenotype, maternal, and offspring environment may crucially influence these traits, but

  7. Pharmacotherapy for premature ejaculation

    NARCIS (Netherlands)

    Waldinger, Marcel D

    PURPOSE OF REVIEW: As there are various drugs and different treatment strategies to delay ejaculation, a review of the current drug treatments for premature ejaculation is relevant for daily clinical practice. RECENT FINDINGS: There are four premature ejaculation subtypes: lifelong premature

  8. Pharmacotherapy for premature ejaculation

    NARCIS (Netherlands)

    Waldinger, Marcel D

    2014-01-01

    PURPOSE OF REVIEW: As there are various drugs and different treatment strategies to delay ejaculation, a review of the current drug treatments for premature ejaculation is relevant for daily clinical practice. RECENT FINDINGS: There are four premature ejaculation subtypes: lifelong premature ejacula

  9. Health Issues of Premature Babies

    Science.gov (United States)

    ... Text Size Email Print Share Health Issues of Premature Babies Page Content Because premature babies are born before they are physically ready ... associated with prematurity. Because of these health concerns, premature babies are given extra medical attention and assistance ...

  10. Phenotypic and functional characterization of lymphocytes from different age groups of Bolivian squirrel monkeys (Saimiri boliviensis boliviensis.

    Directory of Open Access Journals (Sweden)

    Pramod N Nehete

    Full Text Available Due to many physiological and genetic characteristic similarities to humans, squirrel monkeys provide an ideal animal model specifically for studying malaria, and transmissible spongiform encephalopathies (Creutzfeldt-Jacob disease. While squirrel monkeys three years and older are generally considered adult subjects suitable for use in medical research studies, little is known about the functional properties of lymphocytes in relation to the age of these animals, which could significantly impact the quality and quantity of innate and adaptive immune responses. In this study, we investigated differences in the phenotype and function of lymphocytes subsets of young (3-4 years, adult (8-10 years and aged (16-19 years squirrel monkeys. In general, animals in all three age groups exhibited comparable numbers of different lymphocyte subsets except for CD20+ B cells that were significantly lower in aged relative to young animals and T cells subsets expressing both CD4 and CD8 (double positive were significantly higher in aged relative to young animals. With increasing age, phenotypic differences in central and effector memory T cells subsets were observed, that were more pronounced for the CD8+ T cells. Despite equal proportions of CD3+ T cells among the three age groups, responses of peripheral blood mononuclear cells to T cell mitogens PHA and Con A showed lower IFN-γ producing cells in the aged group than that in the young group. Furthermore, aged animals showed significantly higher plasma levels of inflammatory cytokines IL-6, IFN-γ, TNF-α, IL-10 and IL-12. These findings suggest that while the squirrel monkeys in general share phenotypic and functional similarities of lymphocyte subsets with humans in relation to age, specific differences exist in immune function of lymphocytes between young and old animals that could potentially impact experimental outcomes for which the measurement of immunologic endpoints are critical.

  11. Premature ovarian failure.

    Science.gov (United States)

    Shelling, Andrew N

    2010-11-01

    Premature ovarian failure (POF) is a common cause of infertility in women, and is characterised by amenorrhoea, hypo-oestrogenism and elevated gonadotrophin levels in women under the age of 40. Known causes include iatrogenic agents that cause permanent damage to the ovaries, such as chemotherapy, radiation therapy and surgery, autoimmune conditions, X-chromosome abnormalities and autosomal genetic conditions. However, few genes have been identified that can explain a substantial proportion of cases of POF. Most women with POF are deeply upset by the diagnosis, partly due to the unexpected menopausal symptoms, but also due to infertility. Therefore, early detection would provide better opportunity for early intervention, and furthermore, the identification of specific gene defects will help to direct potential targets for future treatment.

  12. Apnea of prematurity

    Directory of Open Access Journals (Sweden)

    Piermichele Paolillo

    2013-06-01

    Full Text Available Apnea of prematurity (AOP is one of the most frequent pathologies in the Neonatal Intensive Care Unit, with an incidence inversely related to gestational age. Its etiology is often multi factorial and diagnosis of idiopathic forms requires exclusion of other underlying diseases. Despite being a self-limiting condition which regresses with the maturation of the newborn, possible long-term effects of recurring apneas and the degree of desaturation and bradycardia who may lead to abnormal neurological outcome are not yet clarified. Therefore AOP needs careful evaluation of its etiology and adequate therapy that can be both pharmacological and non-pharmacological. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  13. Analysis on effects of fetal age and birth weight on prognosis of premature infants%胎龄和出生体重对早产儿预后影响分析

    Institute of Scientific and Technical Information of China (English)

    卫雅蓉; 章恒; 许兵

    2011-01-01

    目的:探讨胎龄及出生体重对早产儿预后的影响.方法:回顾性分析无锡市妇幼保健院2008年1月~2009年12月间分娩的217例早产儿资料.结果:早产儿并发症的发生率和死亡率分别为43.8%和2.3%.早产儿并发症和死亡主要发生于胎龄<32周或出生体重<1 500 g的极低体重儿.缺氧缺血性脑病、窒息、呼吸窘迫综合症发生率和死亡率随胎龄或出生体重增加均呈下降趋势.结论:出生前加强孕期保健,尽可能延长胎龄,促进肺成熟;出生后防止早产儿窒息和加强低出生体重儿监护,将降低早产儿并发症发生率和死亡率.%Objective: To explore the effects of fetal age and birth weight on prognosis of premature infants. Methods: The clinical data of 217 premature infants born in the hospital from January 2008 to December 2009 were analyzed retrospectively. Results: The incidence of complication and mortality of premature infants were 43.8% and 2. 3%, respectively; the premature infants less than 32 gestational weeks or birth weight < 1 500 g had high incidence of complication and high mortality; the incidences of complications ( including hypoxic ischemic encephalopathy, asphyxia and respiratory distress syndrome) and mortality of premature infants showed a decreasing trend with fetal age and the increase of birth weight. Conclusion: Enhancing pregnant health care before delivery, prolonging fetal age as far as possible,promoting fetal lung maturity, preventing neonatal asphyxia and strengthening the monitoring on low birth weight infants may reduce the incidence of complication and mortality of premature infants.

  14. Mowat-Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature.

    Science.gov (United States)

    Garavelli, L; Zollino, M; Mainardi, P Cerruti; Gurrieri, F; Rivieri, F; Soli, F; Verri, R; Albertini, E; Favaron, E; Zignani, M; Orteschi, D; Bianchi, P; Faravelli, F; Forzano, F; Seri, M; Wischmeijer, A; Turchetti, D; Pompilii, E; Gnoli, M; Cocchi, G; Mazzanti, L; Bergamaschi, R; De Brasi, D; Sperandeo, M P; Mari, F; Uliana, V; Mostardini, R; Cecconi, M; Grasso, M; Sassi, S; Sebastio, G; Renieri, A; Silengo, M; Bernasconi, S; Wakamatsu, N; Neri, G

    2009-03-01

    Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects. Since the first delineation by Mowat et al. [Mowat et al. (1998); J Med Genet 35:617-623], approximately 179 patients with ZEB2 mutations, deletions or cytogenetic abnormalities have been reported primarily from Europe, Australia and the United States. Genetic defects include chromosome 2q21-q23 microdeletions (or different chromosome rearrangements) in few patients, and ZEB2 mutations in most. We report on clinical and genetic data from 19 Italian patients, diagnosed within the last 5 years, including six previously published, and compare them with patients already reported. The main purpose of this review is to underline a highly consistent phenotype and to highlight the phenotypic evolution occurring with age, particularly of the facial characteristics. The prevalence of MWS is likely to be underestimated. Knowledge of the phenotypic spectrum of MWS and of its changing phenotype with age can improve the detection rate of this condition.

  15. Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

    Directory of Open Access Journals (Sweden)

    Johannsson Oskar

    2008-11-01

    Full Text Available Abstract Background Familial adenomatous polyposis (FAP is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations. Methods Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify APC gene mutations, which were correlated to the clinical presentations. Results 10 novel APC gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'APC mutation (c.5030_5031insAA developed colon cancer at age 72 as the first manifestation of attenuated FAP. Conclusion With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel APC mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.

  16. Human milk for the premature infant

    Science.gov (United States)

    Underwood, Mark A.

    2012-01-01

    Synopsis Premature infants are a heterogeneous group with widely differing needs for nutrition and immune protection with risk of growth failure, developmental delays, necrotizing enterocolitis, and late-onset sepsis increasing with decreasing gestational age and birth weight. Human milk from women delivering prematurely has more protein and higher levels of many bioactive molecules compared to milk from women delivering at term. Human milk must be fortified for small premature infants to achieve adequate growth. Mother’s own milk improves growth and neurodevelopment and decreases the risk of necrotizing enterocolitis and late-onset sepsis and should therefore be the primary enteral diet of premature infants. Donor milk is a valuable resource for premature infants whose mothers are unable to provide an adequate supply of milk, but presents significant challenges including the need for pasteurization, nutritional and biochemical deficiencies and a limited supply. PMID:23178065

  17. Size and Composition of the Lexicon in Prematurely Born Very-Low-Birth-Weight and Full-Term Finnish Children at Two Years of Age

    Science.gov (United States)

    Stolt, Suvi; Klippi, Anu; Launonen, Kaisa; Munck, Petriina; Lehtonen, Liisa; Lapinleimu, Helena; Haataja, Leena

    2007-01-01

    This paper focuses on the aspects of the lexicon in 66 prematurely born very-low-birth-weight and 87 full-term Finnish children at 2;0, studied using the Finnish version of the "MacArthur Communicative Developmental Inventory". The groups did not differ in vocabulary size. Furthermore, the female advantage in vocabulary size was not seen…

  18. Proteome oxidative carbonylation during oxidative stress-induced premature senescence of WI-38 human fibroblasts

    DEFF Research Database (Denmark)

    Le Boulch, Marine; Ahmed, Emad K; Rogowska-Wrzesinska, Adelina

    2017-01-01

    Accumulation of oxidatively damaged proteins is a hallmark of cellular and organismal ageing, and is also a phenotypic feature shared by both replicative senescence and stress-induced premature senescence of human fibroblasts. Moreover, proteins that are building up as oxidized (i.e. the "Oxi......-proteome") during ageing and age-related diseases represent a restricted set of cellular proteins, indicating that certain proteins are more prone to oxidative carbonylation and subsequent intracellular accumulation. The occurrence of specific carbonylated proteins upon oxidative stress induced premature senescence...... of WI-38 human fibroblasts and their follow-up identification have been addressed in this study. Indeed, it was expected that the identification of these proteins would give insights into the mechanisms by which oxidatively damaged proteins could affect cellular function. Among these proteins, some...

  19. Premature infants' health at multiple induced pregnancy.

    Directory of Open Access Journals (Sweden)

    Chernenkov Yu.V.

    2015-09-01

    Full Text Available Objective: to define the risk factors adversely influencing prenatal development at premature birth at use of methods of assisted reproductive technology (ART; to estimate premature' infants health from multiple induced pregnancy according to Perinatal Center of Saratov for last 3 years. Material and Methods. Under supervision there were 139 pregnant women with application ART. 202 children (51 twins were born and 5 triplet babies, from them 83 premature infants born from multiple induced pregnancy have been analyzed. Results. The newborns examined by method ART, were distributed as follows: 22-28 weeks — 19 children; 29-32 weeks — 23; 33-36 weeks — 41. Asphyxia at birth was marked at all premature infants. Respiratory insufficiency at birth is revealed in 87,3% of cases. The most frequent pathologies in premature infants are revealed: neurologic infringements and bronchopulmonary pathology occured at all children, developmental anomaly — 33, 8%, retinopathies in premature infants — 26,5%. The mortality causes include: extreme immaturity, cerebral leukomalacia, IVN 3 degrees. Conclusion. The risk factors, premature birth at application of methods ART are revealed: aged primiparas, pharmacological influence, absence of physiological conditions of prenatal development; multifetation. The high percent of birth of children with ELBW and ULBW is revealed. RDCN with further BPD development, retinopathies in premature infants and CNS defeat is more often occured.

  20. Phenotypic and genotypic analysis of age at first calving in Iranian Holstein dairy cows

    Directory of Open Access Journals (Sweden)

    Atefeh Seyeddokht

    2015-12-01

    Full Text Available Introduction: Age at first calving (AFC has an important effect on profitability and reproductive management of dairy cattle. Every month increase in AFC beyond 24 months increases the cost of production. The time between birth and first calving represents a period in which replacement heifers are not generating income. Instead this rearing period requires considerable capital expenditures including feed, housing, and veterinary expenses. These expenses constitute 15% to 20% of the total expenses related to milk production. A basic approach to reduce this cost is to decrease the time between birth and her first freshening. Worldwide recommendations for one particular AFC might be an incorrect management goal for all of the cattle on all of the farms, since the recommendation might not represent the management goals and/or capabilities of a particular production system or farm. We realize that each dairy has its own set of unique management and environmental conditions, which makes a universal AFC and BW after first calving, a difficult goal to achieve. The AFC has a profound influence on the total cost of raising dairy replacements in which older calving heifers are more expensive to raise than younger ones. Materials and methods: A total of 19499 calving records belonged to 96 herd from 1996 to 2008 were used to estimate genetic components and genetic trend for age at first calving in Holstein dairy cows of Iran. Data were analyzed using a univariate model and Wombat software. Linear regression of estimated breeding values on calving year was used to estimate genetic trend. Results and Discussion: Estimated genetic trend was positive for some years and was negative for others and showed that reducing age at first calving has not been considered in the selection strategies; however, the phenotypic trend was decreased. The age at first calving for Yazd, Markazi, and southern Khorasan provinces were the highest and for Kermanshah, East Azarbayjan

  1. Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

    NARCIS (Netherlands)

    Weismueller, Tobias J.; Trivedi, Palak J; Bergquist, Annika; Imam, Mohamad; Lenzen, Henrike; Ponsioen, Cyriel Y.; Holm, Kristian; Gotthardt, Daniel; Faerkkilae, Martti A.; Marschall, Hanns-Ulrich; Thorburn, Douglas; Weersma, Rinse K.; Fevery, Johan; Mueller, Tobias; Chazouilleres, Olivier; Schulze, Kornelius; Lazaridis, Konstantinos N.; Almer, Sven; Pereira, Stephen P.; Levy, Cynthia; Mason, Andrew L.; Naess, Sigrid; Bowlus, Christopher L.; Floreani, Annarosa; Halilbasic, Emina; Yimam, Kidist K.; Milkiewicz, Piotr; Beuers, Ulrich; Huynh, Dep K.; Pares, Albert; Manser, Christine N.; Dalekos, George N.; Eksteen, Bertus; Invernizzi, Pietro; Berg, Christoph P.; Kirchner, Gabi I.; Sarrazin, Christoph; Zimmer, Vincent; Fabris, Luca; Braun, Felix; Marzioni, Marco; Juran, Brian D.; Said, Karouk; Rupp, Christian; Jokelainen, Kalle; de Valle, Maria Benito; Saffioti, Francesca; Cheung, Angela; Trauner, Michael; Schramm, Christoph; Chapman, Roger W.; Karlsen, Tom H.; Schrumpf, Erik; Strassburg, Christian P.; Manns, Michael P.; Lindor, Keith D; Hirschfield, Gideon M.; Hansen, Bettina E.; Boberg, Kirsten M.

    BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We

  2. Genotypes and phenotypes for apolipoprotein E and Alzheimer disease in the Honolulu-Asia aging study

    NARCIS (Netherlands)

    J.W.P.F. Kardaun (Jan); L. White (Lon); H.E. Resnick; H. Petrovitch; S.M. Marcovina; A.M. Saunders (Ann); D.J. Foley (Dan); R.J. Havlik

    2000-01-01

    textabstractBACKGROUND: The utility of apolipoprotein E (ApoE) type as an indicator of genetic susceptibility to Alzheimer disease (AD) depends on the reliability of typing. Although ApoE protein isoform phenotyping is generally assumed equivalent to genotyping from DNA

  3. Phenotype-directed treatment of pre-school-aged children with recurrent wheeze

    NARCIS (Netherlands)

    Schultz, Andre; Brand, Paul L. P.

    2012-01-01

    Wheeze in childhood may comprise different underlying diseases. Disease-specific treatment could potentially improve treatment efficacy. Various attempts have been made to differentiate between pre-school wheeze phenotypes. In this review, the results of clinical trials evaluating treatment of pre-s

  4. Intrauterine infection and prematurity.

    Science.gov (United States)

    Gonçalves, Luís F; Chaiworapongsa, Tinnakorn; Romero, Roberto

    2002-01-01

    Intrauterine infection is a major cause of premature labor with and without intact membranes. Intrauterine infection is present in approximately 25% of all preterm births and the earlier the gestational age at delivery, the higher the frequency of intra-amniotic infection. Microorganisms may also gain access to the fetus before delivery. A fetal inflammatory response syndrome elicited in response to microbial products is associated with the impending onset of preterm labor and also with multi-systemic organ involvement in the human fetus and a higher rate of perinatal morbidity. The most common microorganisms involved in intrauterine infections are Ureaplasma urealyticum, Fusobacterium species and Mycoplasma hominis. The role of Chlamydia trachomatis and viruses in preterm labor remain to be determined. Use of molecular microbiology techniques to diagnose intrauterine infection may uncover the role of fastidious microorganisms that have not yet been discovered. Antibiotic administration to patients with asymptomatic bacteriuria is associated with a significant reduction in the rate of preterm birth. However, such benefit has not been demonstrated for patients with bacterial vaginosis, or women who carry Streptococcus agalactia, Ureaplasma urealyticum or Trichomonas vaginalis. Antibiotic administration to patients with preterm premature rupture of membranes is associated with prolongation of pregnancy and a reduction in the rate of clinical chorioamnionitis and neonatal sepsis. The benefit has not been demonstrated in patients with preterm labor and intact membranes. Major efforts are required to determine why some women develop an ascending intrauterine infection and others do not and also what interventions may reduce the deleterious effect of systemic fetal inflammation. Copyright 2002 Wiley-Liss, Inc.

  5. Increasing incidence of premature thelarche in the Central Region of Denmark - Challenges in differentiating girls less than 7 years of age with premature thelarche from girls with precocious puberty in real-life practice

    DEFF Research Database (Denmark)

    Sømod, Mia Elbek; Vestergaard, Esben Thyssen; Kristensen, Kurt

    2016-01-01

    was the variable which best discriminated PT from PP. Third, stimulated LH in 1-3 years old girls with PT is similar to stimulated LH in 5-7 years old girls with PP. Age, BMISDS, ethnicity, bone age, stimulated gonadotropins and LH/FSH and SHBG are all useful variables for differentiating PP from PT. However...

  6. Acute appendicitis in a premature baby

    Energy Technology Data Exchange (ETDEWEB)

    Beluffi, Giampiero; Alberici, Elisa [Department of Radiodiagnosis, Section of Paediatric Radiology, IRCCS Policlinico S. Matteo, Piazzale Golgi 2, 27100 Pavia PV (Italy)

    2002-07-01

    A case of acute appendicitis in a premature baby in whom diagnosis was suggested on plain films of the abdomen is presented. In this baby air in a hollow viscus suspected of being an enlarged appendix was the clue to diagnosis. The diagnostic dilemma of this rare and life-threatening condition in premature babies and newborns is underlined. The relevance of different imaging modalities and of different findings in this age group is discussed. Awareness of this rare condition and possible differential diagnosis in newborns and premature babies is stressed. (orig.)

  7. [Premature rupture of membranes and chorioamnionitis].

    Science.gov (United States)

    Lopez Garcia, R

    1988-01-01

    , and congenital malformations. Neonatal sepsis occurs in about 5% of live births following premature rupture, but the rate triples after 24 hours, especially in premature infants. The rate of neonatal asphyxia also increases considerable after 24 hours. Congenital malformations, prolapse of the cord, and pelvic presentation are positively associated with premature rupture of membranes. If the decision is made to interrupt the pregnancy, it should be done between 12-24 hours after rupture because the risks of infection and respiratory difficulty are most balanced at that point. Vaginal deliveries should be preferred only if conditions are favorable for a prompt delivery. The gestational age, presence of infection, obstetric condition of the mother, and indication for hysterectomy are the most important points to consider i management of premature rupture.

  8. Proteomic profiling of adipose tissue from Zmpste24-/- mice, a model of lipodystrophy and premature aging, reveals major changes in mitochondrial function and vimentin processing.

    Science.gov (United States)

    Peinado, Juan R; Quirós, Pedro M; Pulido, Marina R; Mariño, Guillermo; Martínez-Chantar, Maria L; Vázquez-Martínez, Rafael; Freije, José M P; López-Otín, Carlos; Malagón, María M

    2011-11-01

    Lipodystrophy is a major disease involving severe alterations of adipose tissue distribution and metabolism. Mutations in genes encoding the nuclear envelope protein lamin A or its processing enzyme, the metalloproteinase Zmpste24, cause diverse human progeroid syndromes that are commonly characterized by a selective loss of adipose tissue. Similarly to humans, mice deficient in Zmpste24 accumulate prelamin A and display phenotypic features of accelerated aging, including lipodystrophy. Herein, we report the proteome and phosphoproteome of adipose tissue as well as serum metabolome in lipodystrophy by using Zmpste24(-/-) mice as experimental model. We show that Zmpste24 deficiency enhanced lipolysis, fatty acid biogenesis and β-oxidation as well as decreased fatty acid re-esterification, thus pointing to an increased partitioning of fatty acid toward β-oxidation and away from storage that likely underlies the observed size reduction of Zmpste24-null adipocytes. Besides the mitochondrial proteins related to lipid metabolism, other protein networks related to mitochondrial function, including those involved in tricarboxylic acid cycle and oxidative phosphorylation, were up-regulated in Zmpste24(-/-) mice. These results, together with the observation of an increased mitochondrial response to oxidative stress, support the relationship between defective prelamin A processing and mitochondrial dysfunction and highlight the relevance of oxidative damage in lipoatrophy and aging. We also show that absence of Zmpste24 profoundly alters the processing of the cytoskeletal protein vimentin and identify a novel protein dysregulated in lipodystrophy, High-Mobility Group Box-1 Protein. Finally, we found several lipid derivates with important roles in energy balance, such as Lysophosphatidylcholine or 2-arachidonoylglycerol, to be dysregulated in Zmpste24(-/-) serum. Together, our findings in Zmpste24(-/-) mice may be useful to unveil the mechanisms underlying adipose tissue

  9. Oxidative stress in oocytes during midprophase induces premature loss of cohesion and chromosome segregation errors.

    Science.gov (United States)

    Perkins, Adrienne T; Das, Thomas M; Panzera, Lauren C; Bickel, Sharon E

    2016-11-01

    In humans, errors in meiotic chromosome segregation that produce aneuploid gametes increase dramatically as women age, a phenomenon termed the "maternal age effect." During meiosis, cohesion between sister chromatids keeps recombinant homologs physically attached and premature loss of cohesion can lead to missegregation of homologs during meiosis I. A growing body of evidence suggests that meiotic cohesion deteriorates as oocytes age and contributes to the maternal age effect. One hallmark of aging cells is an increase in oxidative damage caused by reactive oxygen species (ROS). Therefore, increased oxidative damage in older oocytes may be one of the factors that leads to premature loss of cohesion and segregation errors. To test this hypothesis, we used an RNAi strategy to induce oxidative stress in Drosophila oocytes and measured the fidelity of chromosome segregation during meiosis. Knockdown of either the cytoplasmic or mitochondrial ROS scavenger superoxide dismutase (SOD) caused a significant increase in segregation errors, and heterozygosity for an smc1 deletion enhanced this phenotype. FISH analysis indicated that SOD knockdown moderately increased the percentage of oocytes with arm cohesion defects. Consistent with premature loss of arm cohesion and destabilization of chiasmata, the frequency at which recombinant homologs missegregate during meiosis I is significantly greater in SOD knockdown oocytes than in controls. Together these results provide an in vivo demonstration that oxidative stress during meiotic prophase induces chromosome segregation errors and support the model that accelerated loss of cohesion in aging human oocytes is caused, at least in part, by oxidative damage.

  10. Outcomes for Extremely Premature Infants

    Science.gov (United States)

    Glass, Hannah C.; Costarino, Andrew T.; Stayer, Stephen A.; Brett, Claire; Cladis, Franklyn; Davis, Peter J.

    2015-01-01

    Premature birth is a significant cause of infant and child morbidity and mortality. In the United States, the premature birth rate, which had steadily increased during the 1990s and early 2000s, has decreased annually for four years and is now approximately 11.5%. Human viability, defined as gestational age at which the chance of survival is 50%, is currently approximately 23–24 weeks in developed countries. Infant girls, on average, have better outcomes than infant boys. A relatively uncomplicated course in the intensive care nursery for an extremely premature infant results in a discharge date close to the prenatal EDC. Despite technological advances and efforts of child health experts during the last generation, the extremely premature infant (less than 28 weeks gestation) and extremely low birth weight infant (ELBW) (premature labor improved neonatal mortality and morbidity in the late 1990s. The recognition that chronic postnatal administration of steroids to infants should be avoided may have improved outcomes in the early 2000s. Evidence from recent trials attempting to define the appropriate target for oxygen saturation in preterm infants suggests arterial oxygen saturation between 91–95% (compared to 85–89%) avoids excess mortality. However, final analyses of data from these trials have not been published, so definitive recommendations are still pending The development of neonatal neurocognitive care visits may improve neurocognitive outcomes in this high-risk group. Long-term follow up to detect and address developmental, learning, behavioral, and social problems is critical for children born at these early gestational ages. The striking similarities in response to extreme prematurity in the lung and brain imply that agents and techniques that benefit one organ are likely to also benefit the other. Finally, since therapy and supportive care continue to change, the outcomes of ELBW infants are ever evolving. Efforts to minimize injury, preserve

  11. Outcomes for extremely premature infants.

    Science.gov (United States)

    Glass, Hannah C; Costarino, Andrew T; Stayer, Stephen A; Brett, Claire M; Cladis, Franklyn; Davis, Peter J

    2015-06-01

    Premature birth is a significant cause of infant and child morbidity and mortality. In the United States, the premature birth rate, which had steadily increased during the 1990s and early 2000s, has decreased annually for 7 years and is now approximately 11.39%. Human viability, defined as gestational age at which the chance of survival is 50%, is currently approximately 23 to 24 weeks in developed countries. Infant girls, on average, have better outcomes than infant boys. A relatively uncomplicated course in the intensive care nursery for an extremely premature infant results in a discharge date close to the prenatal estimated date of confinement. Despite technological advances and efforts of child health experts during the last generation, the extremely premature infant (less than 28 weeks gestation) and extremely low birth weight infant (death and disability with 30% to 50% mortality and, in survivors, at least 20% to 50% risk of morbidity. The introduction of continuous positive airway pressure, mechanical ventilation, and exogenous surfactant increased survival and spurred the development of neonatal intensive care in the 1970s through the early 1990s. Routine administration of antenatal steroids during premature labor improved neonatal mortality and morbidity in the late 1990s. The recognition that chronic postnatal administration of steroids to infants should be avoided may have improved outcomes in the early 2000s. Evidence from recent trials attempting to define the appropriate target for oxygen saturation in preterm infants suggests arterial oxygen saturation between 91% and 95% (compared with 85%-89%) avoids excess mortality; however, final analyses of data from these trials have not been published, so definitive recommendations are still pending. The development of neonatal neurocritical intensive care units may improve neurocognitive outcomes in this high-risk group. Long-term follow-up to detect and address developmental, learning, behavioral, and

  12. A case of premature ovarian failure (POF) in a 31-year-old woman with a 47,XXX karyotype.

    Science.gov (United States)

    Skałba, Piotr; Cygal, Anna; Gierzyńska, Zuzanna

    2010-01-01

    A case of POF in a 31-year-old woman with karyotype 47,XXX. The aim of the study was to discuss a case of POF in a 31-year-old patient with polysomy 47,XXX. The described karyotype is not usually associated with this characteristic physical phenotype. In some rare cases, menstrual disorders, sterility, secondary amenorrhoea, premature menopause, and low intelligence are found. Our observations revealed the necessity for cytogenetic examination in all women at reproductive age with symptoms of premature ovarian failure. According to the data found in literature, patients with POF and karyotype disorders belong to the risk group of premature death, mostly for cardiological reasons. Raising patient awareness about the risk may have a positive effect on quality of life and regularity of check-ups.

  13. Premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Vujović Svetlana

    2012-01-01

    Full Text Available Premature ovarian failure (POF is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc. The diagnosis is confirmed by the level of FSH of over 40 IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin, TSH, prolactin, testosterone, karyotype (<30 years of age, ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications. Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc.

  14. Advanced aging phenotype is revealed by epigenetic modifications in rat liver after in utero malnutrition.

    Science.gov (United States)

    Heo, Hye J; Tozour, Jessica N; Delahaye, Fabien; Zhao, Yongmei; Cui, Lingguang; Barzilai, Nir; Einstein, Francine Hughes

    2016-10-01

    Adverse environmental exposures of mothers during fetal period predispose offspring to a range of age-related diseases earlier in life. Here, we set to determine whether a deregulated epigenetic pattern is similar in young animals whose mothers' nutrition was modulated during fetal growth to that acquired during normal aging in animals. Using a rodent model of maternal undernutrition (UN) or overnutrition (ON), we examined cytosine methylation profiles of liver from young female offspring and compared them to age-matched young controls and aged (20-month-old) animals. HELP-tagging, a genomewide restriction enzyme and sequencing assay demonstrates that fetal exposure to two different maternal diets is associated with nonrandom dysregulation of methylation levels with profiles similar to those seen in normal aging animals and occur in regions mapped to genes relevant to metabolic diseases and aging. Functional consequences were assessed by gene expression at 9 weeks old with more significant changes at 6 months of age. Early developmental exposures to unfavorable maternal diets result in altered methylation profiles and transcriptional dysregulation in Prkcb, Pc, Ncor2, and Smad3 that is also seen with normal aging. These Notch pathway and lipogenesis genes may be useful for prediction of later susceptibility to chronic disease.

  15. Natural variation in life history and aging phenotypes is associated with mitochondrial DNA deletion frequency in Caenorhabditis briggsae

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    Smith Samson W

    2011-01-01

    Full Text Available Abstract Background Mutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. A barrier to rigorous tests of the role of mitochondrial dysfunction in aging processes has been the lack of model systems with relevant, naturally occurring mitochondrial genetic variation. Toward the goal of developing such a model system, we studied natural variation in life history, metabolic, and aging phenotypes as it relates to levels of a naturally-occurring heteroplasmic mitochondrial ND5 deletion recently discovered to segregate among wild populations of the soil nematode, Caenorhabditis briggsae. The normal product of ND5 is a central component of the mitochondrial electron transport chain and integral to cellular energy metabolism. Results We quantified significant variation among C. briggsae isolates for all phenotypes measured, only some of which was statistically associated with isolate-specific ND5 deletion frequency. We found that fecundity-related traits and pharyngeal pumping rate were strongly inversely related to ND5 deletion level and that C. briggsae isolates with high ND5 deletion levels experienced a tradeoff between early fecundity and lifespan. Conversely, oxidative stress resistance was only weakly associated with ND5 deletion level while ATP content was unrelated to deletion level. Finally, mean levels of reactive oxygen species measured in vivo showed a significant non-linear relationship with ND5 deletion level, a pattern that may be driven by among-isolate variation in antioxidant or other compensatory mechanisms. Conclusions Our findings suggest that the ND5 deletion may adversely affect fitness and mitochondrial functioning while promoting aging in natural populations, and help to further establish this species as a useful model for explicit tests of hypotheses in aging biology and mitochondrial genetics.

  16. Age-Related Disruption of Steady-State Thymic Medulla Provokes Autoimmune Phenotype via Perturbing Negative Selection.

    Science.gov (United States)

    Xia, Jiangyan; Wang, Hongjun; Guo, Jianfei; Zhang, Zhijie; Coder, Brandon; Su, Dong-Ming

    2012-06-01

    The hymic medulla plays an essential role in the generation of central tolerance by eliminating self-reactive T-cell clones through thymic negative selection and developing natural regulatory T cells. Age-related FoxN1 decline induces disruption of medullary thymic epithelial cells (mTECs). However, it is unknown whether this perturbs central tolerance to increase autoimmune predisposition in the elderly. Using a loxP-floxed-FoxN1 (FoxN1(flox)) mouse model, which exhibits a spontaneous ubiquitous deletion of FoxN1 with age to accelerate thymic aging, we investigated whether disruption of steady-state thymic medulla results in an increase of autoimmune-prone associated with age. We demonstrated age-associated ubiquitous loss of FoxN1(flox)-formed two-dimensional thymic epithelial cysts were primarily located in the medulla. This resulted in disruption of thymic medullary steady state, with evidence of perturbed negative selection, including reduced expression of the autoimmune regulator (Aire) gene and disrupted accumulation of thymic dendritic cells in the medulla, which are required for negative selection. These provoke autoimmune phenotypes, including increased inflammatory cell infiltration in multiple organs in these mice. This finding in an animal model provides a mechanistic explanation of increased susceptibility to autoimmunity in aged humans, although they may not show clinic manifestations without induction.

  17. Apnea of prematurity: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Picone S

    2014-06-01

    Full Text Available Simonetta Picone, Roberto Aufieri, Piermichele PaolilloDivision of Neonatology and Neonatal Intensive Care, Department of Maternal and Child Health, Casilino General Hospital, Rome, ItalyAbstract: Apnea of prematurity is a developmental disorder that frequently affects preterm infants, especially those with lower gestational age. Even if apnea of prematurity is by definition a self-limiting condition, it can cause serious problems during the hospital stay and can potentially have long-term neurological and cognitive consequences depending on the severity and intensity of the episodes. The diagnosis of apnea of prematurity can be made only after excluding a number of diseases of the preterm infant in which apnea may be an epiphenomenon. Etiological diagnosis is essential for selection of appropriate treatment, which may be nonpharmacological or involve use of drugs.Keywords: apnea of prematurity, idiopathic and secondary apnea, caffeine

  18. Acetaminophen developmental pharmacokinetics in premature neonates and infants

    DEFF Research Database (Denmark)

    Anderson, Brian J; van Lingen, Richard A; Hansen, Tom G

    2002-01-01

    The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens.......The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens....

  19. Hydrogen sulfide restores a normal morphological phenotype in Werner syndrome fibroblasts, attenuates oxidative damage and modulates mTOR pathway

    NARCIS (Netherlands)

    Talaei, F.; van Praag, V. M.; Henning, R. H.

    2013-01-01

    Werner syndrome (WS) protein is involved in DNA repair and its truncation causes Werner syndrome, an autosomal recessive genetic disorder with a premature aging phenotype. WRN protein mutation is currently known as the primary cause of WS. In cultured WS fibroblasts, we found an increase in cytosoli

  20. Hydrogen sulfide restores a normal morphological phenotype in Werner syndrome fibroblasts, attenuates oxidative damage and modulates mTOR pathway

    NARCIS (Netherlands)

    Talaei, F.; van Praag, V. M.; Henning, R. H.

    2013-01-01

    Werner syndrome (WS) protein is involved in DNA repair and its truncation causes Werner syndrome, an autosomal recessive genetic disorder with a premature aging phenotype. WRN protein mutation is currently known as the primary cause of WS. In cultured WS fibroblasts, we found an increase in cytosoli

  1. The Phenotype of Spontaneous Preterm Birth: Application of a Clinical Phenotyping Tool

    Science.gov (United States)

    Manuck, Tracy A.; Esplin, M. Sean; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Varner, Michael W.; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John

    2015-01-01

    Objective Spontaneous preterm birth (SPTB) is a complex condition that is likely a final common pathway with multiple possible etiologies. We hypothesized that a comprehensive classification system could appropriately group women with similar STPB etiologies, and provide an explanation, at least in part, for the disparities in SPTB associated with race and gestational age at delivery. Study Design Planned analysis of a multicenter, prospective study of singleton SPTB. Women with SPTB < 34 weeks were included. We defined 9 potential SPTB phenotypes based on clinical data, including infection/inflammation, maternal stress, decidual hemorrhage, uterine distention, cervical insufficiency, placental dysfunction, premature rupture of the membranes, maternal comorbidities, and familial factors. Each woman was evaluated for each phenotype. Delivery gestational age was compared between those with and without each phenotype. Phenotype profiles were also compared between women with very early (20.0–27.9 weeks) SPTB vs. those with early SPTB (28.0–34.0 weeks), and between African-American and Caucasian women. Statistical analysis was by t-test and chi-square as appropriate. Results The phenotyping tool was applied to 1025 women with SPTB who delivered at a mean 30.0 (+/− 3.2) weeks gestation. Of these, 800 (78%) had ≥2 phenotypes. Only 43 (4.2%) had no phenotypes. The 281 women with early SPTB were more likely to have infection/inflammation, decidual hemorrhage, and cervical insufficiency phenotypes (all p≤0.001). African-American women had more maternal stress and cervical insufficiency but less decidual hemorrhage and placental dysfunction compared to Caucasian women (all p<0.05). Gestational age at delivery decreased as the number of phenotypes present increased. Conclusions Precise SPTB phenotyping classifies women with SPTB and identifies specific differences between very early and early SPTB and between African-Americans and Caucasians. PMID:25687564

  2. Premature ovarian failure and ovarian autoimmunity

    NARCIS (Netherlands)

    J.A. Schoemaker (Joop); H.A. Drexhage (Hemmo); A. Hoek (Annemieke)

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a

  3. Premature ovarian failure and ovarian autoimmunity

    NARCIS (Netherlands)

    J.A. Schoemaker (Joop); H.A. Drexhage (Hemmo); A. Hoek (Annemieke)

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a heter

  4. Premature ovarian failure and ovarian autoimmunity

    NARCIS (Netherlands)

    J.A. Schoemaker (Joop); H.A. Drexhage (Hemmo); A. Hoek (Annemieke)

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a heter

  5. Nrf2 Signaling and the Slowed Aging Phenotype: Evidence from Long-Lived Models

    Directory of Open Access Journals (Sweden)

    Danielle R. Bruns

    2015-01-01

    Full Text Available Studying long-lived animals provides novel insight into shared characteristics of aging and represents a unique model to elucidate approaches to prevent chronic disease. Oxidant stress underlies many chronic diseases and resistance to stress is a potential mechanism governing slowed aging. The transcription factor nuclear factor (erythroid-derived 2-like 2 is the “master regulator” of cellular antioxidant defenses. Nrf2 is upregulated by some longevity promoting interventions and may play a role in regulating species longevity. However, Nrf2 expression and activity in long-lived models have not been well described. Here, we review evidence for altered Nrf2 signaling in a variety of slowed aging models that accomplish lifespan extension via pharmacological, nutritional, evolutionary, genetic, and presumably epigenetic means.

  6. During yeast chronological aging resveratrol supplementation results in a short-lived phenotype Sir2-dependent.

    Science.gov (United States)

    Orlandi, Ivan; Stamerra, Giulia; Strippoli, Maurizio; Vai, Marina

    2017-08-01

    Resveratrol (RSV) is a naturally occurring polyphenolic compound endowed with interesting biological properties/functions amongst which are its activity as an antioxidant and as Sirtuin activating compound towards SIRT1 in mammals. Sirtuins comprise a family of NAD(+)-dependent protein deacetylases that are involved in many physiological and pathological processes including aging and age-related diseases. These enzymes are conserved across species and SIRT1 is the closest mammalian orthologue of Sir2 of Saccharomyces cerevisiae. In the field of aging researches, it is well known that Sir2 is a positive regulator of replicative lifespan and, in this context, the RSV effects have been already examined. Here, we analyzed RSV effects during chronological aging, in which Sir2 acts as a negative regulator of chronological lifespan (CLS). Chronological aging refers to quiescent cells in stationary phase; these cells display a survival-based metabolism characterized by an increase in oxidative stress. We found that RSV supplementation at the onset of chronological aging, namely at the diauxic shift, increases oxidative stress and significantly reduces CLS. CLS reduction is dependent on Sir2 presence both in expired medium and in extreme Calorie Restriction. In addition, all data point to an enhancement of Sir2 activity, in particular Sir2-mediated deacetylation of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (Pck1). This leads to a reduction in the amount of the acetylated active form of Pck1, whose enzymatic activity is essential for gluconeogenesis and CLS extension. Copyright © 2017. Published by Elsevier B.V.

  7. Cell surface phenotype of cytolytic T lymphocyte precursors in aged nude mice.

    Science.gov (United States)

    Maryanski, J L; MacDonald, H R; Sordat, B; Cerottini, J C

    1981-12-01

    The cell surface phenotype of cytolytic T lymphocyte precursors (CTL-P) in congenitally athymic C57BL/6 nu/nu mice has been investigated. CTL-P were detected and quantitated in a limited dilution mixed leukocyte microculture assay system supplemented with interleukin 2. Minimal estimates of the frequency of CTL-P among nylon wool passed (NWP) nude spleen cells were obtained following elimination of Thy-1-bearing or Lyt-2-bearing cells with monoclonal antibodies plus complement. Alternatively, NWP spleen cells bearing Thy-1 or Lyt-2 were positively selected on a cell sorter and assayed for CTL-P frequency. Both positive and negative selection techniques demonstrated that essentially all (greater than 98%) CTL-P in NWP nude spleen expressed Thy-1 and that the majority (80-90%) expressed Lyt-2. In control NWP spleen cells from normal C57BL/6 mice, greater than 98% of CTL-P were positive for both Thy-1 and Lyt-2. These data demonstrate that most functional alloreactive CTL-P developing in the apparent absence of thymic influence already express both Thy-1 and Lyt-2 prior to exposure to antigen.

  8. 早产儿胎龄和体重对儿童糖尿病的预测作用%Study on the Prediction Function of Gestational Age and Body Weight of Premature Infants on Diabetes in C hildren

    Institute of Scientific and Technical Information of China (English)

    陈召金; 黎见乐; 姚慧梅; 兰红霞

    2014-01-01

    目的:探究并分析早产儿胎龄和体重对儿童糖尿病的预测作用。方法回顾性分析200例早产儿的临床资料。按照早产儿的胎龄分为A1、A2、A3、A4组,根据出生体重分为B1、B2、B3、B4组,根据喂养方式分为C1、C2、C3组。跟踪随访15年后,记录早产儿儿童糖尿病的发病率。结果28~30周胎龄组早产儿儿童糖尿病发病率为80.0%,明显高于其他胎龄组;出生体重≤999 g早产儿发病率为80.0%,较其他组早产儿高;人工喂养组早产儿发病率为60.8%,明显高于其余两组(P均<0.05),具有统计学意义。结论儿童糖尿病的发病率与早产儿胎龄和出生体重密切相关。%Objective To explore and analyze the prediction function of gestational age and body weight of premature infants on diabetes in children .Methods The retrospective analysis of clinical data was taken ,in-cluding 200 cases of premature infants .According to their gestational age ,they were divided into A1,A2,A3, A4 four groups,with B1 ,B2,B3,B4 four groups according to their birth weight ,C1,C2,C3 three groups accord-ing to the feeding patterns .After a follow-up visit for 15 years,records were written down on the incidences of diabetes in these children .Re sults The incidence of diabetes was 80%in group of premature infants with 28~30 weeks'gestational age ,significantly higher than other age groups .So was the morbidity rate of those with birth weight ≤999g,which accounted for 80.0%.The morbidity rate of premature infants ,who were treated with arti-ficial feeding was 60.8%,significantly higher than the other two groups (P<0.05).Besides,the morbidity rate in group of infants with non-nutritive sucking accounted for 50 .9%.Conclusion The incidence of diabetes in children is closely related to the gestational age and birth weight of these premature infants .

  9. Joint-Attention and the Social Phenotype of School-Aged Children with ASD

    Science.gov (United States)

    Mundy, Peter; Novotny, Stephanie; Swain-Lerro, Lindsey; McIntyre, Nancy; Zajic, Matt; Oswald, Tasha

    2017-01-01

    The validity of joint attention assessment in school-aged children with ASD is unclear (Lord, Jones, "Journal of Child Psychology and Psychiatry" 53(5):490-509, 2012). This study examined the feasibility and validity of a parent-report measure of joint attention related behaviors in verbal children and adolescents with ASD. Fifty-two…

  10. Investigation of the 5q33.3 longevity locus and age-related phenotypes

    DEFF Research Database (Denmark)

    Nygaard, Marianne; Thinggaard, Mikael; Christensen, Kaare

    2017-01-01

    between the rs2149954 minor allele and a decreased risk of heart attack and heart failure as well as increased physical functioning were found in the long-lived individuals. In the middle-aged and elderly individuals, rs2149954 minor allele carriers had a lower risk of hypertension. Our results thereby...

  11. Investigation of the 5q33.3 longevity locus and age-related phenotypes

    DEFF Research Database (Denmark)

    Nygaard, Marianne; Thinggaard, Mikael; Christensen, Kaare

    2017-01-01

    between the rs2149954 minor allele and a decreased risk of heart attack and heart failure as well as increased physical functioning were found in the long-lived individuals. In the middle-aged and elderly individuals, rs2149954 minor allele carriers had a lower risk of hypertension. Our results thereby...

  12. When aging reaches CD4+ T-cells: phenotypic and functional changes

    Directory of Open Access Journals (Sweden)

    Marco Antonio Moro-García

    2013-05-01

    Full Text Available Beyond midlife, the immune system shows aging features and its defensive capability becomes impaired, by a process known as immunosenescence that involves many changes in the innate and adaptive responses. Innate immunity seems to be better preserved globally, while the adaptive immune response exhibits profound age-dependent modifications. Elderly people display a decline in numbers of naïve T-cells in peripheral blood and lymphoid tissues, while, in contrast, their proportion of highly differentiated effector and memory T-cells, such as the CD28null T-cells, increases markedly. Naïve and memory CD4+ T-cells constitute a highly dynamic system with constant homeostatic and antigen-driven proliferation, influx, and loss of T-cells. Thymic activity dwindles with age and essentially ceases in the later decades of life, severely constraining the generation of new T-cells. Homeostatic control mechanisms are very effective at maintaining a large and diverse subset of naïve CD4+ T-cells throughout life, but although later than in CD8+T-cell compartment, these mechanisms ultimately fail with age.

  13. Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Suzana Gispert

    Full Text Available BACKGROUND: Parkinson's disease (PD is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1 cause the recessive PARK6 variant of PD. METHODOLOGY/PRINCIPAL FINDINGS: Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of alpha-synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons. CONCLUSION: Thus, aging Pink1(-/- mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death.

  14. Genetically modified mouse models for premature ovarian failure (POF).

    Science.gov (United States)

    Jagarlamudi, Krishna; Reddy, Pradeep; Adhikari, Deepak; Liu, Kui

    2010-02-01

    Premature ovarian failure (POF) is a complex disorder that affects approximately 1% of women. POF is characterized by the depletion of functional ovarian follicles before the age of 40 years, and clinically, patients may present with primary amenorrhea or secondary amenorrhea. Although some genes have been hypothesized to be candidates responsible for POF, the etiology of most of the cases is idiopathic, with the underlying causes still unidentified because of the heterogeneity of the disease. In this review, we consider some mutant mouse models that exhibit phenotypes which are comparable to human POF, and we suggest that the use of these mouse models may help us to gain a better understanding of the molecular mechanisms underlying POF in humans.

  15. The Effects of Fetal Surgery on Retinopathy of Prematurity Development

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    Sudha Nallasamy

    2009-10-01

    Full Text Available Background: Fetal surgery is selectively offered for severe or life-threatening fetal malformations. These infants are often born prematurely and are thus at risk for retinopathy of prematurity (ROP. It is not known whether fetal surgery confers an increased risk of developing severe ROP relative to published rates in standard premature populations ≤37 weeks of age grouped by birth weight (

  16. A susceptibility gene for premature ovarian failure (POF) maps to proximal Xq28.

    Science.gov (United States)

    Rossetti, Francesca; Rizzolio, Flavio; Pramparo, Tiziano; Sala, Cinzia; Bione, Silvia; Bernardi, Franca; Goegan, Mara; Zuffardi, Orsetta; Toniolo, Daniela

    2004-10-01

    Terminal deletions of the long arm of the human X chromosome have been described in women with premature ovarian failure (POF). We report here the molecular characterization of an inherited deletion in two affected women and in their mother. The two daughters presented secondary amenorrhea at 17 or 22 years respectively, while the mother was fertile. She had four children, but she eventually had premature menopause at 43 years of age. The fine molecular analysis of the deletion showed that the three women carried an identical deletion. We conclude that the phenotypic difference within the family must be attributed to genetic or environmental factors and not to the presence of different extent deletions. By comparison with other deletions in the region, we map a susceptibility gene for POF to 4.5 Mb, in the distal part of Xq.

  17. Micafungin in Premature and Non-premature Infants

    Science.gov (United States)

    Wu, Chunzhang; Tweddle, Lorraine; Roilides, Emmanuel

    2014-01-01

    Background: Invasive fungal infections cause excessive morbidity and mortality in premature neonates and severely ill infants. Methods: Safety and efficacy outcomes of micafungin were compared between prematurely and non-prematurely born infants premature [birth weight (BW) premature, received ≥1 dose of micafungin. Among premature patients, 14.5% were low BW (1500–2499 g), 36.4% very low BW (1000–1499 g) and 49.1% extremely low BW (premature)] died. Significantly more non-premature than premature patients discontinued treatment (P = 0.003). Treatment-related adverse events were recorded in 23% of patients with no difference between groups. More extremely low BW (n = 4, 15%) and very low BW (n = 8, 40%) infants experienced treatment-related adverse events than low BW (n = 0) and there was no relation to micafungin dose or duration. For a subgroup of 30 patients with invasive candidiasis, treatment success was achieved in 73% in both premature and non-premature groups. Prophylaxis was successful in 4/5 non-premature hematopoietic stem cell transplant patients. Conclusion: Micafungin has a safe profile in premature and non-premature infants with substantial efficacy. PMID:24892849

  18. Nox-2-mediated phenotype loss of hippocampal parvalbumin interneurons might contribute to postoperative cognitive decline in aging mice

    Directory of Open Access Journals (Sweden)

    lili qiu

    2016-10-01

    Full Text Available Postoperative cognitive decline (POCD is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH oxidase mediated-abnormalities in parvalbumin (PV interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in sixteen-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO. Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide in vitro were used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1β, markers of oxidative stress, and NADPH oxidase 2 (Nox2 in the hippocampus. In addition, lipopolysaccharide exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived ROS production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice.

  19. Premature temporal theta (PT theta).

    Science.gov (United States)

    Hughes, J R; Fino, J J; Hart, L A

    1987-07-01

    A distinctive pattern called premature temporal theta (PT theta) was studied in 436 infants, ranging in age from 24 to 46 weeks. The pattern is seen in early prematurity, maximizes at 29-31 weeks and then diminishes and disappears near term. Usually the pattern is found independently on both temporal areas, but with a right-sided preference. Patients without PT theta or with a significantly low amount had either neurological or non-neurological (medical) conditions. With age there is a tendency for an increase in frequency and a decrease in amplitude. Five different peaks in the amount of this pattern are seen at approximately every month. Unilateral PT theta tends to be seen in older babies, more often on the right side and with an abnormal EEG. An abnormal EEG is usually associated with a delay in both the appearance and disappearance of this wave form. PT theta is also associated mainly with REM or active sleep. A polynomial rather than an exponential or power function best describes these data with changes of age. PT theta may arise from the inferior temporal gyrus and/or especially the transverse gyrus.

  20. Ursolic acid ameliorates aging-metabolic phenotype through promoting of skeletal muscle rejuvenation.

    Science.gov (United States)

    Bakhtiari, Nuredin; Hosseinkhani, Saman; Tashakor, Amin; Hemmati, Roohullah

    2015-07-01

    Ursolic acid (UA) is a lipophilic compound, which highly found in apple peels. UA has some certain features, of the most important is its anabolic effects on skeletal muscles, which in turn plays a prominent role in the aging process, encouraged us to evaluate skeletal muscle rejuvenation. This study seeks to address the two following questions: primarily, we wonder to know if UA increases anti-aging biomarkers (SIRT1 and PGC-1α) in the isolated satellite cells, to pave the way for satellite cells proliferation. The results revealed that UA elevated the expression of SIRT1 (∼ 35 folds) and PGC-1α (∼ 175 folds) genes. The other question that needs to be asked, however, is to understand whether it is possible to generalize the in vitro findings to in vivo. For this, a study was designed to investigate the effects of UA on the cellular energy status in the animal models (C57BL/6 mice). We found that UA decreased cellular energy charges such as ATP (∼ 3 times) and ADP (∼ 18 times). With respect to the role of UA in energy expenditure and as an anti-aging biomarker, one might wonder to elucidate skeletal muscle rejuvenation as well as satellite cells proliferation and neomyogenesis. The results illustrated that UA boosted neomyogenesis through enhancing the number of satellite cells. In addition, rejuvenation effects of UA on the skeletal muscle promptly encouraged us to reexamine the performance of skeletal muscles. The results indicated that UA through increasing myoglobin expression (∼ 2 folds) accompanied with transforming of glycolytic to fast oxidative status chiefly and slow-twitch muscle fibers. To the best of our knowledge, it seems that UA might be considered as a potential candidate for treatment of pathological conditions associated with muscular atrophy and dysfunction, including skeletal muscle atrophy, amyotrophic lateral sclerosis (ALS), sarcopenia and metabolic diseases of the muscles.

  1. Deletion of myosin VI causes slow retinal optic neuropathy and age-related macular degeneration (AMD)-relevant retinal phenotype.

    Science.gov (United States)

    Schubert, Timm; Gleiser, Corinna; Heiduschka, Peter; Franz, Christoph; Nagel-Wolfrum, Kerstin; Sahaboglu, Ayse; Weisschuh, Nicole; Eske, Gordon; Rohbock, Karin; Rieger, Norman; Paquet-Durand, François; Wissinger, Bernd; Wolfrum, Uwe; Hirt, Bernhard; Singer, Wibke; Rüttiger, Lukas; Zimmermann, Ulrike; Knipper, Marlies

    2015-10-01

    The unconventional myosin VI, a member of the actin-based motor protein family of myosins, is expressed in the retina. Its deletion was previously shown to reduce amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type and myosin VI-deficient Snell's Waltzer mice in more detail, the expression pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and outer plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory potentials in the electroretinogram, photoreceptor cell death, retinal microglia infiltration, and formation of basal laminar deposits. A phenotype comprising features of glaucoma (neurodegeneration) and age-related macular degeneration could thus be uncovered that suggests dysfunction of myosin VI and its variable cargo adaptor proteins for membrane sorting and autophagy, as possible candidate mediators for both disease forms.

  2. Theory of Mind Indexes the Broader Autism Phenotype in Siblings of Children with Autism at School Age

    Directory of Open Access Journals (Sweden)

    Tawny Tsang

    2016-01-01

    Full Text Available Subclinical variants of the social-communicative challenges and rigidity that define autism spectrum disorder (ASD are known as the broader autism phenotype (BAP. The BAP has been conceptualized categorically (as specific to a subset of relatives of individuals with ASD and dimensionally (as continuously distributed within the general population. The current study examined the compatibility of these two approaches by assessing associations among autism symptoms and social-communicative skills in young school-age children with ASD, children who have a sibling with ASD, and children without a sibling with ASD. Autism symptoms were associated with reduced Theory of Mind (ToM, adaptive skills, cognitive empathy, and language skills across the full sample. Reduced ToM was a core aspect of the BAP in the current sample regardless of whether the BAP was defined categorically (in terms of siblings of children with ASD who exhibited atypical developmental or dimensionally (in terms of associations with autism symptoms across the entire sample. Early language skills predicted school-age ToM. Findings support the compatibility of categorical and dimensional approaches to the BAP, highlight reduced ToM as a core aspect of the school-age BAP, and suggest that narrative-based approaches to promoting ToM may be beneficial for siblings of children with ASD.

  3. Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Tsuchihashi T

    2014-12-01

    Full Text Available Takashi Tsuchihashi,1 Keisuke Mori,1 Kuniko Horie-Inoue,2 Yasushi Okazaki,3 Takuya Awata,4,5 Satoshi Inoue,2 Shin Yoneya1 1Department of Ophthalmology, 2Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Division of Translational Research, Research Center for Genomic Medicine, 4Division of Endocrinology and Diabetes, Department of Medicine, 5Division of RI Laboratory, Biomedical Research Center, Saitama Medical University, Iruma, Saitama, Japan Background: This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT for age-related macular degeneration (AMD.Methods: The study included 149 patients with exudative AMD treated by PDT. Eight phenotypic factors and ten genotypic factors for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996 in the complement factor H (CFH gene, rs 11200638-SNP in the high temperature requirement A-1 (HTRA1 gene, two SNPs (rs699947, rs2010963 in the vascular endothelial growth factor (VEGF gene, and four SNPs (rs12948385, rs12150053, rs9913583, rs1136287 in the pigment epithelium-derived factor (PEDF gene were evaluated. Results: A significant association with best-corrected visual acuity change was demonstrated in the greatest linear dimension, presence or absence of pigment epithelial detachment, and HTRA1-rs11200638 genotype statistically (P=3.67×10-4, 1.95×10-2, 1.24×10-3, respectively. Best-corrected visual acuity in patients with AA genotype of HTRA1-rs11200638 significantly decreased compared with that in patients with GG genotype (P=1.33×10-3. Logistic regression analyses demonstrated HTRA1-rs11200638 genotype was most strongly associated with best-corrected visual acuity outcome from baseline at 12 months after photodynamic therapy (P=4.60×10-3; odds ratio 2.363; 95% confidence interval 1.303–4.285.Conclusion: The HTRA1

  4. Ellagic acid metabolism by human gut microbiota: consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age, and health status.

    Science.gov (United States)

    Tomás-Barberán, Francisco A; García-Villalba, Rocío; González-Sarrías, Antonio; Selma, María V; Espín, Juan C

    2014-07-16

    Three phenotypes for urolithin production after ellagitannin and ellagic acid intake are consistently observed in different human intervention trials. Subjects can be stratified into three urolithin-producing groups. "Phenotype A" produced only urolithin A conjugates, which included between 25 and 80% of the volunteers in the different trials. "Phenotype B" produced isourolithin A and/or urolithin B in addition to urolithin A, this being the second relevant group (10-50%). "Phenotype 0" (5-25%) was that in which these urolithins were not detected. The three phenotypes were observed independently of the volunteers' health status and demographic characteristics (age, gender, body mass index (BMI)) and of the amount or type of ellagitannin food source ingested (walnuts and other nuts, strawberries, raspberries, and other berries or pomegranates). Interestingly, a higher percentage of phenotype B was observed in those volunteers with chronic illness (metabolic syndrome or colorectal cancer) associated with gut microbial imbalance (dysbiosis). These urolithin phenotypes could show differences in the human gut microbiota and should be considered in intervention trials dealing with health benefits of ellagitannins or ellagic acid. Whether this phenotypic variation could be a biomarker related to differential health benefits or illness predisposition deserves further research.

  5. Predictive factors for neuromotor abnormalities at the corrected age of 12 months in very low birth weight premature infants Fatores preditivos para anormalidades neuromotoras aos 12 meses de idade corrigida em prematuros de muito baixo peso

    Directory of Open Access Journals (Sweden)

    Rosane Reis de Mello

    2009-06-01

    Full Text Available BACKGROUND: The increase in survival of premature newborns has sparked growing interest in the prediction of their long-term neurodevelopment. OBJECTIVE: To estimate the incidence of neuromotor abnormalities at the corrected age of 12 months and to identify the predictive factors associated with altered neuromotor development in very low birth weight premature infants. METHOD: Cohort study. The sample included 100 premature infants. The outcome was neuromotor development at 12 months classified by Bayley Scale (PDI and neurological assessment (tonus, reflexes, posture. A multivariate logistic regression model was constructed. Neonatal variables and neuromotor abnormalities up to 6 months of corrected age were selected by bivariate analysis. RESULTS: Mean birth weight was 1126g (SD: 240. Abnormal neuromotor development was presented in 60 children at 12 months corrected age. CONCLUSION: According to the model, patients with a diagnosis including bronchopulmonary dysplasia, hypertonia of lower extremities, truncal hypotonia showed a 94.0% probability of neuromotor involvement at 12 months.INTRODUÇÃO: O aumento na sobrevida de recém-nascidos prematuros tem suscitado interesse crescente na predição do seu neurodesenvolvimento a longo prazo. OBJETIVO: Estimar a incidência de anormalidades neuromotoras aos 12 meses de idade corrigida e identificar os fatores associados ao desenvolvimento neuromotor alterado em prematuros de muito baixo peso. MÉTODO: Estudo de coorte. A amostra incluiu 100 crianças prematuras.O desfecho foi o desenvolvimento neuromotor aos 12 meses. Modelo de regressão logística multivariado foi construído. Variáveis neonatais e anormalidades neuromotoras até os 6 meses de idade corrigida foram selecionadas por análise bivariada. RESULTADOS: O peso de nascimento médio foi 1126g (DP:240. Aos 12 meses 60% das crianças apresentaram desenvolvimento neuromotor alterado. CONCLUSÃO: De acordo com o modelo, pacientes com diagn

  6. Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy.

    LENUS (Irish Health Repository)

    Horgan, Richard P

    2012-01-31

    Being born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma samples from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.

  7. Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases

    Science.gov (United States)

    Park, Sung-Jun; Ahmad, Faiyaz; Philp, Andrew; Baar, Keith; Williams, Tishan; Luo, Haibin; Ke, Hengming; Rehmann, Holger; Taussig, Ronald; Brown, Alexandra L.; Kim, Myung K.; Beaven, Michael A.; Burgin, Alex B.; Manganiello, Vincent; Chung, Jay H.

    2012-01-01

    SUMMARY Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca2+ levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca2+-release channel. As a consequence, resveratrol increases NAD+ and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging. PMID:22304913

  8. Lithium prevents parkinsonian behavioral and striatal phenotypes in an aged parkin mutant transgenic mouse model.

    Science.gov (United States)

    Lieu, Christopher A; Dewey, Colleen M; Chinta, Shankar J; Rane, Anand; Rajagopalan, Subramanian; Batir, Sean; Kim, Yong-Hwan; Andersen, Julie K

    2014-12-03

    Lithium has long been used as a treatment for the psychiatric disease bipolar disorder. However, previous studies suggest that lithium provides neuroprotective effects in neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease. The exact mechanism by which lithium exerts these effects still remains unclear. In the present study, we evaluated the effects of low-dose lithium treatment in an aged mouse model expressing a parkin mutation within dopaminergic neurons. We found that low-dose lithium treatment prevented motor impairment as demonstrated by the open field test, pole test, and rearing behavior. Furthermore, lithium prevented dopaminergic striatal degeneration in parkin animals. We also found that parkin-induced striatal astrogliosis and microglial activation were prevented by lithium treatment. Our results further corroborate the use of this parkin mutant transgenic mouse line as a model for PD for testing novel therapeutics. The findings of the present study also provide further validation that lithium could be re-purposed as a therapy for PD and suggest that anti-inflammatory effects may contribute to its neuroprotective mechanisms.

  9. [Application of massage therapy in premature infant nursing care].

    Science.gov (United States)

    Chang, Shu-Min; Sung, Huei-Chuan

    2007-02-01

    Massage therapy has been used in the care of premature infants for many years in western countries, and a significant body of research has already shown the effectiveness of massage therapy in significantly increasing body weight, decreasing infant hospital durations, enhancing bone formation, and improving behavior. Key considerations when applying massage therapy on premature infants include gestational age, bodyweight, and physical condition. Nurses can teach parents to administer massage therapy on their premature infants to enhance parent-child attachment and interaction. This article introduces massage therapy principles and methods, the effectiveness of massage therapy in premature infant care, and an approach to teaching parents how to apply massage therapy on their premature infants. Massage therapy can be included in premature infant care programs in the future.

  10. [Developmental change in facial recognition by premature infants during infancy].

    Science.gov (United States)

    Konishi, Yukihiko; Kusaka, Takashi; Nishida, Tomoko; Isobe, Kenichi; Itoh, Susumu

    2014-09-01

    Premature infants are thought to be at increased risk for developmental disorders. We evaluated facial recognition by premature infants during early infancy, as this ability has been reported to be impaired commonly in developmentally disabled children. In premature infants and full-term infants at the age of 4 months (4 corrected months for premature infants), visual behaviors while performing facial recognition tasks were determined and analyzed using an eye-tracking system (Tobii T60 manufactured by Tobii Technologics, Sweden). Both types of infants had a preference towards normal facial expressions; however, no preference towards the upper face was observed in premature infants. Our study suggests that facial recognition ability in premature infants may develop differently from that in full-term infants.

  11. Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

    Science.gov (United States)

    Bousquet, Jean; Jorgensen, Christian; Dauzat, Michel; Cesario, Alfredo; Camuzat, Thierry; Bourret, Rodolphe; Best, Nicolas; Anto, Josep M; Abecassis, Frederic; Aubas, Pierre; Avignon, Antoine; Badin, Melanie; Bedbrook, Anna; Blain, Hubert; Bourdin, Arnaud; Bringer, Jacques; Camu, William; Cayla, Guilhaume; Costa, David J; Courtet, Philippe; Cristol, Jean-Paul; Demoly, Pascal; de la Coussaye, Jean-Emmanuel; Fesler, Pierre; Gouzi, Fares; Gris, Jean-Christophe; Guillot, Bernard; Hayot, Maurice; Jeandel, Claude; Jonquet, Olivier; Journot, Laurent; Lehmann, Sylvain; Mathieu, Gwenaelle; Morel, Jacques; Ninot, Gregory; Pelissier, Jacques; Picot, Marie-Christine; Radier-Pontal, Francoise; Robine, Jean-Marie; Rodier, Michel; Roubille, Francois; Sultan, Ariane; Wojtusciszyn, Anne; Auffray, Charles; Balling, Rudi; Barbara, Cristina; Cambon-Thomsen, Anne; Chavannes, Niels H; Chuchalin, Alexander; Crooks, George; Dedeu, Antoni; Fabbri, Leonardo M; Garcia-Aymerich, Judith; Hajjam, Jawad; Melo Gomes, Elisabete; Palkonen, Susana; Piette, Francois; Pison, Christophe; Price, David; Samolinski, Boleslaw; Schunemann, Holger J; Sterk, Peter J; Yiallouros, Panayiotis; Roca, Josep; Van de Perre, Philippe; Mercier, Jacques

    2014-01-01

    Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

  12. Lipid profile of women with premature ovarian failure

    NARCIS (Netherlands)

    Knauff, Erik A. H.; Westerveld, Hendrika E.; Goverde, Angelique J.; Eijkemans, Marinus J.; Valkenburg, Olivier; van Santbrink, Evert J. P.; Fauser, Bart C. J. M.; van der Schouw, Yvonne T.

    2008-01-01

    Objective: Earlier menopause is associated with a higher incidence of cardiovascular events later in life. Concurrent with the ages of menopausal transition, a shift in lipid profile takes place. Premature ovarian failure (POF) or premature menopause allows LIS to Study the effect of cessation of

  13. A predictive model for respiratory syncytial virus (RSV hospitalisation of premature infants born at 33–35 weeks of gestational age, based on data from the Spanish FLIP study

    Directory of Open Access Journals (Sweden)

    Figueras-Aloy Jose

    2008-12-01

    Full Text Available Abstract Background The aim of this study, conducted in Europe, was to develop a validated risk factor based model to predict RSV-related hospitalisation in premature infants born 33–35 weeks' gestational age (GA. Methods The predictive model was developed using risk factors captured in the Spanish FLIP dataset, a case-control study of 183 premature infants born between 33–35 weeks' GA who were hospitalised with RSV, and 371 age-matched controls. The model was validated internally by 100-fold bootstrapping. Discriminant function analysis was used to analyse combinations of risk factors to predict RSV hospitalisation. Successive models were chosen that had the highest probability for discriminating between hospitalised and non-hospitalised infants. Receiver operating characteristic (ROC curves were plotted. Results An initial 15 variable model was produced with a discriminant function of 72% and an area under the ROC curve of 0.795. A step-wise reduction exercise, alongside recalculations of some variables, produced a final model consisting of 7 variables: birth ± 10 weeks of start of season, birth weight, breast feeding for ≤ 2 months, siblings ≥ 2 years, family members with atopy, family members with wheeze, and gender. The discrimination of this model was 71% and the area under the ROC curve was 0.791. At the 0.75 sensitivity intercept, the false positive fraction was 0.33. The 100-fold bootstrapping resulted in a mean discriminant function of 72% (standard deviation: 2.18 and a median area under the ROC curve of 0.785 (range: 0.768–0.790, indicating a good internal validation. The calculated NNT for intervention to treat all at risk patients with a 75% level of protection was 11.7 (95% confidence interval: 9.5–13.6. Conclusion A robust model based on seven risk factors was developed, which is able to predict which premature infants born between 33–35 weeks' GA are at highest risk of hospitalisation from RSV. The model could be

  14. Laterality in Prematurely-Born Children.

    Science.gov (United States)

    Segalwitz, Sidney J.; Chapman, Jacqueline S.

    The study examined the relationship between perinatal stress and decreased right handedness and decreased left cerebral dominance for speech with 215 children born prematurely, followed from birth, and tested at age 5. Results indicated that neither hand preference nor hand performance correlated with degree of perinatal stress and that eye…

  15. Premature birth and diseases in premature infants: common genetic background?

    Science.gov (United States)

    Hallman, Mikko

    2012-04-01

    It has been proposed that during human evolution, development of obligate bipedalism, narrow birth canal cross-sectional area and the large brain have forced an adjustment in duration of pregnancy (scaling of gestational age; Plunkett 2011). Children compared to other mammals are born with proportionally small brains (compared to adult brains), suggesting shortening of pregnancy duration during recent evolution. Prevalence of both obstructed delivery and premature birth is still exceptionally high. In near term infants, functional maturity and viability is high, and gene variants predisposing to respiratory distress syndrome (RDS) are rare. Advanced antenatal and neonatal treatment practices during the new era of medicine allowed survival of also very preterm infants (gestation premature birth. Specific genes associating with diseases in preterm infants may also contribute to the susceptibility to preterm birth. Understanding and applying the knowledge of genetic interactions in normal and abnormal perinatal-neonatal development requires large, well-structured population cohorts, studies involving the whole genome and international interdisciplinary collaboration.

  16. Serum fructosamine and retinopathy of prematurity.

    Science.gov (United States)

    Bozdag, Senol; Oguz, Serife Suna; Gokmen, Tulin; Tunay, Zuhal; Tok, Levent; Uras, Nurdan; Erdeve, Omer; Dilmen, Ugur

    2011-12-01

    To determine whether serum fructosamine which is a good marker for detecting hyperglycemia during the previous 2 to 3 wk in infants could predict the development of retinopathy of prematurity in very low birth weight infants. One hundred sixty seven premature infants who had a birth weight of < 1500 g and a gestational age of less than 32 wk were investigated in the present study. Blood glucose was measured at the bedside and infants were recorded as hyperglycemic if their mean blood glucose levels were higher than 150 mg/dL. Serum corrected fructosamine level was obtained from the cord blood at birth and after the first month of life. The infants' eyes were examined by ophthalmologists to detect retinopathy of prematurity at the gestational age of 32 wk or at four wk after birth, whichever came first. Corrected fructosamine was 319.6 ± 59.6 and 272.8 ± 50.6 mmol/l for group 1 on 1(st) and 30(th) day respectively; 320 ± 61.7 and 268.2 ± 47.3 mmol/l for groups 2 + 3 on 1(st) and 30(th) day respectively which did not differ between groups (p = 0.766 and p = 0.665), whereas duration of hyperglycemia was 1.69 ± 1.1 day in group 1 compared with 3.05 ± 2.4 day in groups 2 + 3 which was significantly different (p = 0.019). The multivariate regression analysis indicated that the duration of hyperglycemia in days was significantly correlated with the development of retinopathy of prematurity (OR 3.26; 95% CI 1.09-9.80; p = 0.035). Although the duration of hyperglycemia may contribute to the development of retinopathy of prematurity, serum corrected fructosamine does not have a good predictive value in developing retinopathy of prematurity in very-low-birth-weight (VLBW) infants.

  17. Lifestyle influences on prematurity.

    Science.gov (United States)

    Creasy, R K

    1991-01-01

    It is apparent from this review that the lifestyle of an individual gravida can potentially lead to a premature delivery. Some of these adverse behavioral characteristics may be dealt with by education and motivation, and some with actual medical treatment. However, there also appears to be significant need for public policy reorientation if we are to make a significant impact on the problem of preterm delivery.

  18. Genetic, environmental and phenotypic relationships among gestation length, birth weight, growth traits and age at first calving in beef cattle.

    Science.gov (United States)

    Bourdon, R M; Brinks, J S

    1982-09-01

    Data on the Red Angus, Angus and Hereford herds of Pioneer Hi-Bred International, Inc., Des Moines, Iowa, collected from 1968 to 1976, were analyzed for relationships among gestation length, birth weight, prenatal gain (birth weight adjusted for gestation length), growth traits and age at first calving. A total of 5,691 calf records, 1,783 listing gestation length, were included in the study. Paternal half-sib analyses and least-squares procedures were used to compute heritability estimates and genetic, environmental and phenotypic correlations among traits. Genetic correlations among growth traits, including prenatal gain, were high in all cases. Heritability estimates for gestation length and birth weight were .36 and .43, respectively, for bull calves and .37 and .35 for heifer calves. Genetic correlations between these traits were .25 and .22 for bull and heifer calves, respectively. Gestation length was negatively correlated (genetically) with all growth traits except birth weight. This result suggests that faster growing fetuses may trigger parturition earlier than average. Age at first calving was negatively correlated (genetically) with growth traits, indicating a favorable relationship between growth and early reproduction. Analysis of several selection indexes combining either birth weight and yearling weight or gestation length and yearling weight indicated that continued response to selection for growth without excessive increase in birth weight is feasible. Selection for growth and moderate birth weight would be more effective than selection for growth and shorter gestation, suggesting that the former method would both shorten gestation and alter the growth curve. Repeatability estimates for gestation length and birth weight were .20 and .22, respectively. Maternal effects accounted for approximately 10% of the variation in each trait.

  19. Growth in Small-for-Gestational-Age Preterm-Born Children from 0 to 4 Years : The Role of both Prematurity and SGA Status

    NARCIS (Netherlands)

    Bocca-Tjeertes, Inger F. A.; Reijneveld, Sijmen A.; Kerstjens, Jorien M.; de Winter, Andrea F.; Bos, Arend F.

    2013-01-01

    Background: Fullterm small-for-gestational-age children (SGAs) are known for their ability to catch up on growth. Nevertheless, increased risk of growth restriction remains. Evidence on preterm SGA children's growth is lacking. Objective: To determine absolute gains in height and weight, relative gr

  20. Monitoring antioxidant defenses and free radical production in space-flight, aviation and railway engine operators, for the prevention and treatment of oxidative stress, immunological impairment, and pre-mature cell aging.

    Science.gov (United States)

    De Luca, C; Deeva, I; Mariani, S; Maiani, G; Stancato, A; Korkina, L

    2009-01-01

    Degenerative diseases, immune impairment, and premature ageing commonly affect professional categories exposed to severe environmental and psychological stress. Among these, cosmonauts routinely experience extreme conditions due to microgravity, space radiation, altered oxygen supply, physical and mental fatigue during training, spaceflight, and post-flight. Long route aviation pilots display elevated oncogenic risk, connected with cosmic radiation overexposure, and high mortality rates for cardiovascular causes. Engine drivers, like pilots, are affected by health consequences of psycho-emotional stress, and burnout syndrome. The free radical (FR)/antioxidant (AO) imbalance is a common feature in all these pathological conditions. To assess the effective relevance of oxidative stress, we analyzed blood and urine reliable markers of FR production and AO defenses in 12 Russian cosmonauts, 55 airline pilots, 63 train engine drivers, and 50 age-matched controls by measuring the following: (a) lipophilic/hydrophilic low-molecular weight AO and AO enzyme activities, (b) nitric oxide, superoxide anion, hydroperoxide production, and (c) urinary catecholamine/serotonine metabolites and lipoperoxidation markers. Cosmonauts showed elevated granulocyte superoxide and nitric oxide production, increased erythrocyte superoxide dismutase activity and glutathione oxidation, and drastically decreased plasma/leucocyte lipophilic AO levels (P monitoring of clinical biochemistry laboratory markers of AO/FR status, to tailor individually specific AO supplementation and diet regimen, and monitor treatment outcomes.

  1. Premature birth is associated with not fully differentiated contractile smooth muscle cells in human umbilical artery.

    Science.gov (United States)

    Roffino, S; Lamy, E; Foucault-Bertaud, A; Risso, F; Reboul, R; Tellier, E; Chareyre, C; Dignat-George, F; Simeoni, U; Charpiot, P

    2012-06-01

    Smooth muscle cells (SMCs) participate to the regulation of peripheral arterial resistance and blood pressure. To assume their function, SMCs differentiate throughout the normal vascular development from a synthetic phenotype towards a fully differentiated contractile phenotype by acquiring a repertoire of proteins involved in contraction. In human fetal muscular arteries and umbilical arteries (UAs), no data are available regarding the differentiation of SMCs during the last trimester of gestation. The objective of this study was to characterize the phenotype of SMCs during this gestation period in human UAs. We investigated the phenotype of SMCs in human UAs from very preterm (28-31 weeks of gestation), late preterm (32-35 weeks) and term (37-41 weeks) newborns using biochemical and immunohistochemical detection of α-actin, smooth muscle myosin heavy chain, smoothelin, and non-muscle myosin heavy chain. We found that the number of SMCs positive for smoothelin in UAs increased with gestational age. Western blot analysis revealed a higher content of smoothelin in term compared to very preterm UAs. These results show that SMCs in human UAs gradually acquire a fully differentiated contractile phenotype during the last trimester of gestation and thus that premature birth is associated with not fully differentiated contractile SMCs in human UAs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. A spectral phenotype of oncogenic human papillomavirus-infected exfoliative cervical cytology distinguishes women based on age.

    Science.gov (United States)

    Kelly, Jemma G; Cheung, Karen T; Martin, Cara; O'Leary, John J; Prendiville, Walter; Martin-Hirsch, Pierre L; Martin, Francis L

    2010-08-05

    Human papillomavirus (HPV) is a sexually-transmitted infection associated with cervical cancer. Of over 100 HPV types identified, 13 are high-risk oncogenic. In unvaccinated women worldwide, the incidence of cervical cancer from HPV16 and HPV18 will remain. Cervical cytology can be graded from normal (atypia-free) to low-grade to high-grade. Infrared (IR) spectroscopy is a non-destructive technique that allows the acquisition of a biochemical-cell fingerprint based on vibrational states of chemical bonds. Exfoliative cervical cytology specimens (n=147) were retrieved, graded by a cytologist and HPV-tested/genotyped using hybrid capture 2 and the Roche HPV Linear Array. Additionally, the spectral signatures of cervical cell lines C33A, HeLa and SiHa were examined. After washing, cellular material was transferred to low-E glass slides and interrogated using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. Given the complex nature of the dataset consisting of thousands of variables (wavenumbers), we used multivariate analysis for data reduction and information retrieval. Principal component analysis coupled with linear discriminant analysis (PCA-LDA) generated a visual representation of the data (scores plot) and, identification of the wavenumbers and consequent biochemical entities responsible for segregation (loadings plot). Immortalised cell lines were readily distinguishable from each other. It was difficult to segregate categories of cytology associated with HPV infection types. However, in low-grade cytology infected with high-risk oncogenic HPV16 or HPV18, it was possible to segregate women based on whether they were aged 20-29years vs. 30-39years. Our findings suggest a spectral phenotype in exfoliative cervical cytology associated with transient vs. persistent HPV infection. Copyright 2010 Elsevier B.V. All rights reserved.

  3. A simple method for early age phenotype confirmation using toe tissue from a mouse model of MPS IIIA.

    Science.gov (United States)

    Trim, Paul J; Lau, Adeline A; Hopwood, John J; Snel, Marten F

    2014-04-30

    Determination of genotype can be difficult, especially during the early stages of developing an animal model, e.g. when PCR primers are not yet available. An increase or decrease in specific metabolites can be used as a surrogate marker for genotype; for instance, in homozygous MPS IIIA mice heparan sulphate (HS) is increased. A simple method was developed for extracting and depolymerising HS from mouse toe tissue using methanolysis under acidic conditions. The sample was lyophilised and resuspended in methanolic HCl. The reaction products are desulphated disaccharides and readily analysable by liquid chromatography/tandem mass spectrometry (LC/MS/MS) in positive ion multiple reaction monitoring mode. Measurements were normalised to a spiked deuterated HS internal standard and to endogenous chondroitin sulphate (CS). HS was measured in toe tissue taken from 30 mice in three groups of 10 (normal controls, MPS IIIA homozygotes and heterozygotes). A significant difference was observed between the MPS IIIA homozygotes and the other two groups, making it possible to identify mice with the MPS IIIA genotype based on the measurement of HS. Normalisation to CS was shown to correct for sample variability and reaction efficiency. Analysis of toe tissue provides a simple and rapid way of determining a storage phenotype at 5 to 7 days of age. Significantly, this method does not require any additional samples to be taken from animals, as it utilises tissue that is a by-product of toe clipping, a method that is routinely used to permanently identify mice. Copyright © 2014 John Wiley & Sons, Ltd.

  4. The I4895T Mutation in the Type 1 Ryanodine Receptor Induces Fiber-Type Specific Alterations in Skeletal Muscle that Mimic Premature Aging

    OpenAIRE

    2010-01-01

    The I4898T (IT) mutation in type 1 ryanodine receptor (RyR1), the Ca2+ release channel of the sarcoplasmic reticulum (SR) is linked to a form of central core disease (CCD) in humans and results in a non leaky channel and excitation-contraction uncoupling. We characterized age- and fiber type-dependent alterations in muscle ultrastructure, as well as the magnitude and spatiotemporal properties of evoked Ca2+ release in heterozygous Ryr1I4895T/WT (IT/+) knock-in mice on a mixed genetic backgrou...

  5. DYNAMICS OF DISABILITY ADJUSTED LIFE YEARS (DALY AS A RESULT OF PREMATURE MORTALITY OF CHILDREN AT THE AGE OF 0–17 YEARS IN TOMSK REGION IN 2008–2012

    Directory of Open Access Journals (Sweden)

    О. S. Kobyakova

    2014-01-01

    Full Text Available The DALY indicator (Disability Adjusted Life Years is widely used for the assessment of a contribution of various diseases to losses of the population health and of the analysis of activity efficiency of health care systems. Background: Research objective was to evaluate dynamics of the DALY indicator as a result of premature mortality of the child population of Tomsk region during 2008-2012. Patients and methods: DALY calculation as a result of premature mortality of the child population of the region during the period from 2008 to 2012 is made. While calculating the data of Territorial body of Federal service of state statistics for the Tomsk Region (Rosstat which included a sex of the dead, day, month and year of death, place of residence, cause of death, day, month and year of birth of the dead was used. The number and gender and age structure of the population of the Tomsk Region according to Rosstat data were also considered. Results: The DALY decrease by 16,5% in child population at the age of 0–17 years is observed in the Tomsk region during the period from 2008 to 2012. Following the results of 2012, DALY in studied population made 833.1 (82.3 ± 5.4 years for 10 thousand of corresponding population that is 1,1 times lower than totally in the Russian Federation, and 3.4 times lower than the universal indicator of 2010. Conclusion: The received result reflects the activity of health care system of the region, directed on integration of synthesis of theoretical and practical knowledge. Decrease in DALY among the child population in the territory of the region is promoted by a number of factors: continuous quality improvement of the medical care rendered to children, target programs on motherhood and childhood health protection realized in the territory of the region, and also functioning of the federal scientific and educational institutions promoting introduction of modern techniques of medical care delivery in practical health care

  6. [A neonate with anaemia of prematurity: zinc protoporphyrin identifies iron deficiency anaemia without iron deficiency].

    Science.gov (United States)

    van der Feen, Diederik E; van Hillegersberg, Jacqueline L A M; Schippers, Johannes A

    2015-01-01

    Anaemia is a common problem in premature infants and is generally easy to treat with iron supplementation. If the anaemia persists despite appropriate correction of deficiencies, more extensive evaluation is required. We describe a case of a premature male infant with a production-deficient anaemia without metabolic deficiencies, eventually identified as anaemia of prematurity. This type of anaemia is commonly diagnosed but its highly variable and complex aetiology and phenotype are often poorly understood. A probable explanation for the anaemia of prematurity in this case was a transient iron incorporation defect, identifiable by high levels of zinc protoporphyrin.

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

    Directory of Open Access Journals (Sweden)

    Sissel J. Moltu

    2014-05-01

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

  8. Parent behaviors moderate the relationship between neonatal pain and internalizing behaviors at 18 months corrected age in children born very prematurely.

    Science.gov (United States)

    Vinall, Jillian; Miller, Steven P; Synnes, Anne R; Grunau, Ruth E

    2013-09-01

    Children born very preterm (≤ 32 weeks gestation) exhibit greater internalizing (anxious/depressed) behaviors compared to term-born peers as early as 2 years corrected age (CA); however, the role of early stress in the etiology of internalizing problems in preterm children remains unknown. Therefore, we examined the relationship between neonatal pain and internalizing behavior at 18 months CA in children born very preterm and examined whether parent behavior and stress moderated this relationship. Participants were 145 children (96 very preterm, 49 full term) assessed at 18 months CA. Neonatal data were obtained from medical and nursing chart review. Neonatal pain was defined as the number of skin-breaking procedures. Cognitive ability was measured with the Bayley Scales of Infant Development II. Parents completed the Parenting Stress Index III, Child Behavior Checklist 1.5-5, and participated in a videotaped play session with their child, which was coded using the Emotional Availability Scale IV. Very preterm children displayed greater Internalizing behaviors compared to full-term control children (P=.02). Parent Sensitivity and Nonhostility moderated the relationship between neonatal pain and Internalizing behavior (all Pneonatal medical confounders, gender, and child cognitive ability (all P>.05). Parent Emotional Availability and stress were not associated with Internalizing behaviors in full-term control children. Positive parent interaction and lower stress appears to ameliorate negative effects of neonatal pain on stress-sensitive behaviors in this vulnerable population.

  9. The pathophysiology of lifelong premature ejaculation.

    Science.gov (United States)

    Waldinger, Marcel D

    2016-08-01

    For many decades it has been thought that lifelong premature ejaculation (PE) is only characterized by persistent early ejaculations. Despite enormous progress of in vivo animal research, and neurobiological, genetic and pharmacological research in men with lifelong PE, our current understanding of the mechanisms behind early ejaculations is far from complete. The new classification of PE into four PE subtypes has shown that the symptomatology of lifelong PE strongly differs from acquired PE, subjective PE and variable PE. The phenotype of lifelong PE and therefore also the pathophysiology of lifelong PE is much more complex. A substantial number of men with lifelong PE not only have PE, but also premature erection and premature penile detumescence as part of an acute hypertonic or hypererotic state when engaged in an erotic situation or when making love. As both erectio praecox, ejaculatio praecox, detumescentia praecox, and the hypererotic state are part of the phenotype lifelong PE, it is argued that lifelong PE is not only a disturbance of the timing of ejaculation but also a disturbance of the timing of erection, detumescence and arousal. Since 1998, the pathophysiology of lifelong PE was thought to be mainly mediated by the central serotonergic system in line with genetic polymorphisms of specific serotonergic genes. However, by accepting that lifelong PE is characterized by the reversible hypertonic state the hypothesis of mainly serotonergic dysfunction is no longer tenable. Instead, it has been postulated that the pathophysiology of lifelong PE is mediated by a very complex interplay of central and peripheral serotonergic, dopaminergic, oxytocinergic, endocrinological, genetic and probably also epigenetic factors. Progress in research of lifelong PE can only be accomplished when a stopwatch is used to measure the IELT and the cut-off point of 1 minute for the definition of lifelong PE is maintained. Current use of validated questionnaires, neglect of

  10. The pathophysiology of lifelong premature ejaculation

    Science.gov (United States)

    2016-01-01

    For many decades it has been thought that lifelong premature ejaculation (PE) is only characterized by persistent early ejaculations. Despite enormous progress of in vivo animal research, and neurobiological, genetic and pharmacological research in men with lifelong PE, our current understanding of the mechanisms behind early ejaculations is far from complete. The new classification of PE into four PE subtypes has shown that the symptomatology of lifelong PE strongly differs from acquired PE, subjective PE and variable PE. The phenotype of lifelong PE and therefore also the pathophysiology of lifelong PE is much more complex. A substantial number of men with lifelong PE not only have PE, but also premature erection and premature penile detumescence as part of an acute hypertonic or hypererotic state when engaged in an erotic situation or when making love. As both erectio praecox, ejaculatio praecox, detumescentia praecox, and the hypererotic state are part of the phenotype lifelong PE, it is argued that lifelong PE is not only a disturbance of the timing of ejaculation but also a disturbance of the timing of erection, detumescence and arousal. Since 1998, the pathophysiology of lifelong PE was thought to be mainly mediated by the central serotonergic system in line with genetic polymorphisms of specific serotonergic genes. However, by accepting that lifelong PE is characterized by the reversible hypertonic state the hypothesis of mainly serotonergic dysfunction is no longer tenable. Instead, it has been postulated that the pathophysiology of lifelong PE is mediated by a very complex interplay of central and peripheral serotonergic, dopaminergic, oxytocinergic, endocrinological, genetic and probably also epigenetic factors. Progress in research of lifelong PE can only be accomplished when a stopwatch is used to measure the IELT and the cut-off point of 1 minute for the definition of lifelong PE is maintained. Current use of validated questionnaires, neglect of

  11. The genetic basis of premature ovarian failure.

    Science.gov (United States)

    Woad, Kathryn J; Watkins, Wendy J; Prendergast, Deborah; Shelling, Andrew N

    2006-06-01

    Premature ovarian failure (POF) is a common condition, affecting approximately 1:100 women. It is characterised by amenorrhea, hypoestrogenism, and elevated gonadotrophin levels in women under the age of 40. It is often an unexpected and distressing diagnosis, which coincides with infertility and menopausal symptoms. There is a well recognised genetic basis to the development of POF. Our laboratory has identified several candidate genes associated with POF.

  12. Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency.

    Science.gov (United States)

    Stepensky, Polina; Rensing-Ehl, Anne; Gather, Ruth; Revel-Vilk, Shoshana; Fischer, Ute; Nabhani, Schafiq; Beier, Fabian; Brümmendorf, Tim H; Fuchs, Sebastian; Zenke, Simon; Firat, Elke; Pessach, Vered Molho; Borkhardt, Arndt; Rakhmanov, Mirzokhid; Keller, Bärbel; Warnatz, Klaus; Eibel, Hermann; Niedermann, Gabriele; Elpeleg, Orly; Ehl, Stephan

    2015-01-29

    Autoimmune cytopenia is a frequent manifestation of primary immunodeficiencies. Two siblings presented with Evans syndrome, viral infections, and progressive leukopenia. DNA available from one patient showed a homozygous frameshift mutation in tripeptidyl peptidase II (TPP2) abolishing protein expression. TPP2 is a serine exopeptidase involved in extralysosomal peptide degradation. Its deficiency in mice activates cell death programs and premature senescence. Similar to cells from naïve, uninfected TPP2-deficient mice, patient cells showed increased major histocompatibility complex I expression and most CD8(+) T-cells had a senescent CCR7-CD127(-)CD28(-)CD57(+) phenotype with poor proliferative responses and enhanced staurosporine-induced apoptosis. T-cells showed increased expression of the effector molecules perforin and interferon-γ with high expression of the transcription factor T-bet. Age-associated B-cells with a CD21(-) CD11c(+) phenotype expressing T-bet were increased in humans and mice, combined with antinuclear antibodies. Moreover, markers of senescence were also present in human and murine TPP2-deficient fibroblasts. Telomere lengths were normal in patient fibroblasts and granulocytes, and low normal in lymphocytes, which were compatible with activation of stress-induced rather than replicative senescence programs. TPP2 deficiency is the first primary immunodeficiency linking premature immunosenescence to severe autoimmunity. Determination of senescent lymphocytes should be part of the diagnostic evaluation of children with refractory multilineage cytopenias.

  13. 小胎龄早产儿支气管肺发育不良发生率和危险因素分析%The incidence and risk factors of bronchopulmonary dysplasia in small gestational age premature infants

    Institute of Scientific and Technical Information of China (English)

    郑国方; 武荣; 刘石; 郝小清

    2012-01-01

    Objective To analyse bronchopulmonary dysplasia (BPD) incidence and high risk factor in the small gestational age premature infants. Methods Retrospective analyse the materials of inpatient infants whose gestational age (GA) were =?2 weeks and survived over 28 days in our neonatal intensive care unite ( NICU). The 28 cases as BPD group met the new diagnostic criteria of BPD. The 56 cases as the control group were randomly selected from all the premature infant with no BPD. Results Total of 197 cases of premature infant were included in this study. The incidence of BPD is about 14.2%. There were statistical significance in each GA period group (x2 =32.269,/* =0.000). The incidence increased when the GA decreased; There were statistical significance in each birth weight group (x2 =30. 244, P =0. 000), the incidence increased when birth weight decreased. From the comparison of the 23 risk factors for BPD, we find thai 12 factors have statistical significance (P < 0. 05), those are GA, body weight, oxygen time, maximum oxygen treatment concentration, hospital days, tracheal intubation mechanical ventilation, replacement therapy with pulmonary surfactant, anemia, application of Meropenem, the ratio of tenth day body weight to birth weight, the first blood gas analysis scores after birth and oxygen index < 300. On the basis of Logistic regression analysis of GA, birth weight, the highest inhaled oxygen volume concentration, tracheal intubation mechanical ventilation, anemia, the ratio of tenth day body weight to birth weight, we find that body weight, the highest inhaled oxygen volume concentration, the ratio of tenth body weight to birth weight are high risk factors for BPD. By compared the 18 factors between mild BPD and moderate or severe BPD, we find that asphyxia, application of diuretic, oxygen time and first blood gas analysis scores after birth have statistical significance ( P < 0.05 ) . Conclusions The birth weight, the highest inhaled oxygen volume

  14. Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence

    DEFF Research Database (Denmark)

    Dierick, Jean François; Kalume, Dário E; Wenders, Frédéric

    2002-01-01

    Exposure of human proliferative cells to subcytotoxic stress triggers stress-induced premature senescence (SIPS) which is characterized by many biomarkers of replicative senescence. Proteomic comparison of replicative senescence and stress-induced premature senescence indicates that, at the level....... These changes affect different cell functions, including energy metabolism, defense systems, maintenance of the redox potential, cell morphology and transduction pathways.......Exposure of human proliferative cells to subcytotoxic stress triggers stress-induced premature senescence (SIPS) which is characterized by many biomarkers of replicative senescence. Proteomic comparison of replicative senescence and stress-induced premature senescence indicates that, at the level...... of protein expression, stress-induced premature senescence and replicative senescence are different phenotypes sharing however similarities. In this study, we identified 30 proteins showing changes of expression level specific or common to replicative senescence and/or stress-induced premature senescence...

  15. Premature ejaculation: A review

    Directory of Open Access Journals (Sweden)

    Sukumar Reddy Gajjala

    2014-01-01

    Full Text Available Premature ejaculation (PE is a common male sexual disorder. It is defined by the Diagnostic and statistical manual of mental disorders as "ejaculation occurring, without control, on or shortly after penetration and before the person wishes it, causing marked distress or interpersonal difficulty. [1] Although the timing of intravaginal ejaculatory latency time (IELT (i.e., time from penetration to ejaculation is not included in this definition, an IELT of <2 min, or ejaculation occurring before penetration, has been considered consistent with PE. [2] Management involves both the patient and his partner. Therapeutic options should suit both partners and be appropriate to their habit in planning and frequency of intercourse. Follow-up at appropriate intervals to judge efficacy, titrate dosage of pharmacological treatments and ascertain side effects is mandatory.

  16. Apnea of Prematurity (For Parents)

    Science.gov (United States)

    ... other babies. The apnea of prematurity does not cause brain damage. A healthy baby who is apnea free for a week will probably never have AOP again. Although sudden infant death syndrome (SIDS) does happen more often in premature infants, no relationship between AOP and SIDS has ...

  17. Impact of rotavirus vaccine on premature infants.

    Science.gov (United States)

    Roué, Jean-Michel; Nowak, Emmanuel; Le Gal, Grégoire; Lemaitre, Thomas; Oger, Emmanuel; Poulhazan, Elise; Giroux, Jean-Dominique; Garenne, Armelle; Gagneur, Arnaud

    2014-10-01

    Infants born preterm are at a higher risk of complications and hospitalization in cases of rotavirus diarrhea than children born at term. We evaluated the impact of a rotavirus vaccination campaign (May 2007 to May 2010) on hospitalizations for rotavirus gastroenteritis in a population of children under 3 years old born prematurely (before 37 weeks of gestation) in the Brest University Hospital birth zone. Active surveillance from 2002 to 2006 and a prospective collection of hospitalizations for rotavirus diarrhea were initiated in the pediatric units of Brest University Hospital until May 2010. Numbers of hospitalizations for rotavirus diarrhea among the population of children born prematurely, before and after the start of the vaccination program, were compared using a Poisson regression model controlling for epidemic-to-epidemic variation. A total of 217 premature infants were vaccinated from 2007 to 2010. Vaccine coverage for a complete course of three doses was 41.9%. The vaccine safety in premature infants was similar to that in term infants. The vaccination program led to a division by a factor of 2.6 (95% confidence interval [CI], 1.3 to 5.2) in the number of hospitalizations for rotavirus diarrhea during the first two epidemic seasons following vaccine introduction and by a factor of 11 (95% CI, 3.5 to 34.8) during the third season. We observed significant effectiveness of the pentavalent rotavirus vaccine on the number of hospitalizations in a population of prematurely born infants younger than 3 years of age. A multicenter national study would provide better assessment of this impact. (This study [Impact of Systematic Infants Vaccination Against Rotavirus on Gastroenteritis Hospitalization: a Prospective Study in Brest District, France (IVANHOE)] has been registered at ClinicalTrials.gov under registration no. NCT00740935.).

  18. Acute renal failure in premature neonates

    Directory of Open Access Journals (Sweden)

    Doronjski Aleksandra

    2009-01-01

    Full Text Available Background/Aim. Hemodynamic stress is the leading cause of acute renal failure (ARF in premature neonates. Incidence of ARF in this population is between 8 and 24%. The aim of this study was to determine the frequency of presence of ARF in premature neonates, as well as its impact on their survival. Methods. A retrospective study of 114 premature neonates [(gestational age, GA less than 37 gestation weeks (gw] admitted to the Intensive Care Unit (ICU at the Pediatric Clinic, Institute of Child and Youth Healthcare of Vojvodina in 2007 was conducted. Serum creatinine, urea and bilirubine were determined on the 3rd day of life in 65 newborns who met inclusion criteria. ARF was diagnosed in 16 newborns (n=16/65; 25%. Results. The premature neonates with ARF had significantly lower GA [<28 gw - 8/16 (50% vs. 5/49 (10%; p < 0.05], birth weight (BW (1 265 g vs. 1615 g; p < 0.05 and systolic blood pressure (43.37 mm Hg vs. 52.7 mmHg; p < 0.05 than ones without ARF. Non-olyguric ARF was diagnosed in 62% of newborns with ARF (n=10/16, while the rest had the olyguric type (n = 6/16; 38%. Twenty-five percent of premature neonates with ARF (n = 4/16 died in contrast to 10% of premature neonates without ARF (n = 5/49. ARF was treated conservatively in all but 3 cases when peritoneal dialysis was performed. Renal function has recovered completely in all of the survivors. In order to determine their predictivity in relation to ARF, following parameters were analyzed: GA, BW < 1 500 g, presence of concomitant sepsis and intracranial hemorrhage grade III/IV. BW < 1 500 g demonstrated the highest sensitivity (se 0.75, while GA < 28 gw, sepsis and intracranial hemorrhage grade III/IV showed high specificity (sp = 0.90, 0.89 0.88, respectively. Conclusion. Acute renal failure frequently occurs in population of premature neonates and requires meticulous fluid and electrolyte balance, especially in the case of low birth weight and extreme immaturity.

  19. Circulating hematopoietic stem cell count is a valuable predictor of prematurity complications in preterm newborns

    Directory of Open Access Journals (Sweden)

    Kotowski Maciej

    2012-09-01

    Full Text Available Abstract Background The frequency of preterm labour has risen over the last few years. Hence, there is growing interest in the identification of markers that may facilitate prediction and prevention of premature birth complications. Here, we studied the association of the number of circulating stem cell populations with the incidence of complications typical of prematurity. Methods The study groups consisted of 90 preterm (23–36 weeks of gestational age and 52 full-term (37–41 weeks infants. Non-hematopoietic stem cells (non-HSCs; CD45-lin-CD184+, enriched in very small embryonic-like stem cells (VSELs, expressing pluripotent (Oct-4, Nanog, early neural (β-III-tubulin, and oligodendrocyte lineage (Olig-1 genes as well as hematopoietic stem cells (HSCs; CD45+lin-CD184+, and circulating stem/progenitor cells (CSPCs; CD133+CD34+; CD133-CD34+ in association with characteristics of prematurity and preterm morbidity were analyzed in cord blood (CB and peripheral blood (PB until the sixth week after delivery. Phenotype analysis was performed using flow cytometry methods. Clonogenic assays suitable for detection of human hematopoietic progenitor cells were also applied. The quantitative parameters were compared between groups by the Mann–Whitney test and between time points by the Friedman test. Fisher’s exact test was used for qualitative variables. Results We found that the number of CB non-HSCs/VSELs is inversely associated with the birth weight of preterm infants. More notably, a high number of CB HSCs is strongly associated with a lower risk of prematurity complications including intraventricular hemorrhage, respiratory distress syndrome, infections, and anemia. The number of HSCs remains stable for the first six weeks of postnatal life. Besides, the number of CSPCs in CB is significantly higher in preterm infants than in full-term neonates (p  Conclusion We conclude that CB HSCs are markedly associated with the development of premature

  20. GIT2 acts as a potential keystone protein in functional hypothalamic networks associated with age-related phenotypic changes in rats.

    Directory of Open Access Journals (Sweden)

    Wayne Chadwick

    Full Text Available The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities. The maintenance of good health during the aging process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats. Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process.

  1. Premature and accelerated aging: HIV or HAART?

    NARCIS (Netherlands)

    Smith, R.L.; de Boer, R.; Brul, S.; Budovskaya, Y.; van der Spek, H.

    2013-01-01

    Highly active antiretroviral therapy (HAART) has significantly increased life expectancy of the human immunodeficiency virus (HIV)-positive population. Nevertheless, the average lifespan of HIV-patients remains shorter compared to uninfected individuals. Immunosenescence, a current explanation for

  2. Prenatal Stress, Prematurity, and Asthma.

    Science.gov (United States)

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

    2015-12-01

    Asthma is the most common chronic disease of childhood, affecting millions of children in the United States and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non-Hispanic blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced "premature asthma." Prenatal stress may cause not only abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring TH2 (allergic) immune responses characteristic of atopic asthma: interleukin 6 (IL-6), which has been associated with premature labor, can promote TH2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing "premature asthma." If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common comorbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (eg, from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health.

  3. Premature ovarian insufficiency: Pathogenesis and management

    Directory of Open Access Journals (Sweden)

    Anna J Fenton

    2015-01-01

    Full Text Available The term premature ovarian insufficiency (POI describes a continuum of declining ovarian function in a young woman, resulting in an earlier than average menopause. It is a term that reflects the variable nature of the condition and is substantially less emotive than the formerly used "premature ovarian failure" which signaled a single event in time. Contrary to the decline in the age of menarche seen over the last 3-4 decades there has been no similar change in the age of menopause. In developed nations, the average age for cessation of menstrual cycles is 50-52 years. The age is younger among women from developing nations. Much has been written about POI despite a lack of good data on the incidence of this condition. It is believed that 1% of women under the age of 40 years and 0.1% under the age of 30 years will develop POI. Research is increasingly providing information about the pathogenesis and treatments are being developed to better preserve ovarian function during cancer treatment and to improve fertility options. This narrative review summarizes the current literature to provide an approach to best practice management of POI.

  4. 小于2岁婴幼儿乳房早发育临床随访研究%A clinical follow-up study of premature thelarche in infants under two years of age

    Institute of Scientific and Technical Information of China (English)

    王应旻; 梁黎; 方燕兰; 傅君芬; 董关萍; 王春林

    2013-01-01

    目的 了解小于2岁婴幼儿乳房发育的临床现况及转归,分析影响乳房消退的相关因素.方法 分析2009年10月至2010年9月间因乳房早发育来我院内分泌科就诊的863例2岁以下患儿临床及实验诊断资料并进行纵向随访研究.结果 小于2岁单纯乳房早发育患儿中绝大多数(89.3%)在3周岁内消退,乳房消退平均年龄为17±6月龄;小部分(10.7%)反复或持续增大,3岁后仍不消退,极少数转变为中枢性性早熟.初诊时乳房Tanner分期和基础E2值升高与否是影响乳房消退的独立危险因素.结论 小于2岁婴幼儿乳房早发育在临床并不少见,大多呈自限性病程,3周岁内可消退,但对2岁以上乳房增大持续不消退者要定期随访.%Objective To investigate the clinical status and natural course of premature thelarche (PT) in infants under 2 years of age and to analyze the predictive factors for regression of thelarche. Methods The clinical and laboratory data of 863 infants under 2 years of age, who visited the department of endocrinology in our hospital due to PT between October 2009 and September 2010, were analyzed. A a longitudinal follow-up study was performed. Results Of the infants under 2 years of age with isolated PT, 89. 3% showed a regression before the age of 3 years (mean 17 ± 5. 6 months), 10.7% had recurrent or persistent thelarche, with no regression after the age of 3 years, and some even developed into central precocious puberty. The independent predictive factors for regression of thelarche were Tanner stage at the first visit and whether baseline estradiol level had increased. Conclusions PT in infants under 2 years of age is not rare in the clinical setting, and it usually runs a self-limited course, subsiding before the age of 3 years. However, regular follow-ups should be performed for infants aged over 2 years with persistent thelarche.

  5. [Premature newborn: a case presentation].

    Science.gov (United States)

    Pastor Rodríguez, Jesús David; Pastor Bravo, María Del Mar; López García, Visitación; Cotes Teruel, María Isabel; Mellado, Jesús Eulogio; Cárceles, José Jara

    2010-01-01

    A case is presented of a premature newborn of 27 weeks gestation and weighing 420 grams who was delivered as a result of a maternal pre-eclampsia and retarded intra-uterine growth. During the 125 days of hospitalisation, an individual care plan based on the Virginia Henderson model was devised and applied to both the child and her parents using NANDA diagnostics, interventions according to the NIC classification, and the expected results according to the NOC classification. The Marjory Gordon functional patterns were used for the initial assessment. By applying the pre-term newborn (PTNB) plan, all their needs were provided and were modified throughout the hospital stay, with new needs that were added to the established ones. These required a continuous assessment with the subsequent adapting of the care plan. Likewise, the care required by the parents varied from the initial grief due to the possible loss of their child to learning the alarm signs and the home care that their child would need. The child was finally discharged weighing 2900 grams and with normal neurological and psychomotor development, although with a lower weight appropriate to her age. Currently, at 2 years old, the child has a normal neurological and psychomotor development, but with weight and size lower than the P(3) percentile. She requires speech therapy treatment due to paralysis of the right vocal cord.

  6. Genetics of aging, progeria and lamin disorders.

    Science.gov (United States)

    Ghosh, Shrestha; Zhou, Zhongjun

    2014-06-01

    Premature aging disorders, like Werner syndrome, Bloom's syndrome, and Hutchinson-Gilford Progeria Syndrome (HGPS), have been the subjects of immense interest as they recapitulate many of the phenotypes observed in physiological aging. They, therefore, not only provide model systems to study normal aging processes but also give valuable insights into the intricate mechanisms underlying senescence. Recent works on HGPS have revealed alterations in a spectrum of cellular and molecular pathways involved in the maintenance of genomic integrity, thus suggesting a profound impact of the nuclear lamina in nuclear organization, chromatin dynamics, regulation of gene expression and epigenetics.

  7. Premature thelarche: a follow up study of 40 girls. Natural history and endocrine findings.

    Science.gov (United States)

    Pasquino, A M; Tebaldi, L; Cioschi, L; Cives, C; Finocchi, G; Maciocci, M; Mancuso, G; Boscherini, B

    1985-01-01

    Follow up of 40 girls with premature thelarche showed that where this disorder occurred before age 2 years it usually regressed completely, thus representing a transient and isolated phenomenon. Premature thelarche after age 2 years persisted more frequently, however, and represented the first sign of sexual development, generally leading to simple early puberty. PMID:4091585

  8. 早期蛋白质对不同胎龄早产儿营养评估价值的研究进展%Research Progress of Early Protein’s Nutritional Assessment Value to Premature Infants of Different Gestational Ages

    Institute of Scientific and Technical Information of China (English)

    薛军(综述)

    2014-01-01

    Organs of the premature infants develop immaturely, and infants are usualy pre-delivered because of the changes of intrauterine condition, so complications such as feeding difficulties often appear after birth; protein deficiency and lipid metabolism disorder may easily come along. So the early nutritional status not only decides the survival of the premature infants but also has lasting effects on their future living quality. According to the research findings, the shorter the gestational age of a premature infant is, the lower his ALB, PAB and TP wil be. PAB is the most sensitive index to evaluate the maturity and nutritional status of premature infants so far. Therefore, monitoring the SP level of premature infants has great guiding significance to the clinical reasonable nutritional treatment and disease prevention.%早产儿各脏器发育不成熟,且多因宫内生存条件变化而致早产,生后常有喂养困难等合并症,易发生蛋白质缺乏及血脂代谢紊乱,其早期的营养状况不但决定早产儿存活与否,而且对早产儿远期生活质量也有持久的影响。研究发现,早产儿胎龄越小,白蛋白、前白蛋白、总蛋白水平越低,前白蛋白是目前评价早产儿成熟度及营养状况最敏感的指标。监测早产儿血清蛋白水平变化,对临床合理营养支持治疗及预防疾病具有指导意义。

  9. Premature atherosclerosis: Sounds familial?

    NARCIS (Netherlands)

    Mulders, T.A.

    2013-01-01

    The prevention of cardiovascular disease is an important challenge in current medical practice. Despite higher event rates and cardiovascular burden in individuals at a more advanced age, it represents a greater challenge in individuals who develop cardiovascular disease at a very young age. In

  10. Salidroside protects human fibroblast cells from premature senescence induced by H(2)O(2) partly through modulating oxidative status.

    Science.gov (United States)

    Mao, Gen-xiang; Wang, Yan; Qiu, Qiang; Deng, Hong-bin; Yuan, Long-guo; Li, Rui-guo; Song, Dan-qing; Li, Yi-yang Yvonne; Li, Dian-dong; Wang, Zhen

    2010-01-01

    Although salidroside and salidroside-like compounds are considered as most critical constitutes needed and responsible for multiple therapeutic benefits of Rhodiola rosea L., including anti-aging, direct demonstration regarding the role of salidroside in anti-aging process is still deficient. In this study, we selected the H(2)O(2)-induced premature senescence model in human fetal lung diploid fibroblasts to investigate the protection of salidroside against aging in vitro and associated molecular mechanisms. We found that salidroside considerably reversed senescence-like phenotypes in the oxidant challenged model, including alterations of morphology, cell cycle, SA-β-gal staining, DNA damage, as well as related molecules expression such as p53, p21 and p16. The protection occurred in a dose-dependent manner, with 5μM offering best efficacy. The proposed antioxidant property of the compound was confirmed in this cellular system, and thus at least partially accounted for the protection of the compound against premature senescence. Similar protection of salidroside against replicative senescence was observed as well. Interestingly, the regulation of senescence-related molecules by salidroside involved ROS-irrelevant mechanisms in both models. This finding presents salidroside as an attractive agent with potential to retard aging and attenuate age-related diseases in humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Preterm labor and premature birth: Are you at risk?

    Science.gov (United States)

    ... labor and premature birth: Are you at risk? Preterm labor and premature birth: Are you at risk? ... for preterm labor and premature birth. What are preterm labor and premature birth? Preterm and premature mean ...

  12. Temsirolimus Partially Rescues the Hutchinson-Gilford Progeria Cellular Phenotype

    Science.gov (United States)

    Gabriel, Diana; Gordon, Leslie B.

    2016-01-01

    Hutchinson-Gilford syndrome (HGPS, OMIM 176670, a rare premature aging disorder that leads to death at an average age of 14.7 years due to myocardial infarction or stroke, is caused by mutations in the LMNA gene. Lamins help maintain the shape and stability of the nuclear envelope in addition to regulating DNA replication, DNA transcription, proliferation and differentiation. The LMNA mutation results in the deletion of 50 amino acids from the carboxy-terminal region of prelamin A, producing the truncated, farnesylated protein progerin. The accumulation of progerin in HGPS nuclei causes numerous morphological and functional changes that lead to premature cellular senescence. Attempts to reverse this HGPS phenotype have identified rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), as a drug that is able to rescue the HGPS cellular phenotype by promoting autophagy and reducing progerin accumulation. Rapamycin is an obvious candidate for the treatment of HGPS disease but is difficult to utilize clinically. To further assess rapamycin’s efficacy with regard to proteostasis, mitochondrial function and the degree of DNA damage, we tested temsirolimus, a rapamycin analog with a more favorable pharmacokinetic profile than rapamycin. We report that temsirolimus decreases progerin levels, increases proliferation, reduces misshapen nuclei, and partially ameliorates DNA damage, but does not improve proteasome activity or mitochondrial dysfunction. Our findings suggest that future therapeutic strategies should identify new drug combinations and treatment regimens that target all the dysfunctional hallmarks that characterize HGPS cells. PMID:28033363

  13. Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice.

    Science.gov (United States)

    Roos, Carolyn M; Hagler, Michael; Zhang, Bin; Oehler, Elise A; Arghami, Arman; Miller, Jordan D

    2013-11-15

    The purpose of this study was to characterize changes in antioxidant and age-related gene expression in aorta and aortic valve with aging, and test the hypothesis that increased mitochondrial oxidative stress accelerates age-related endothelial and aortic valve dysfunction. Wild-type (MnSOD(+/+)) and manganese SOD heterozygous haploinsufficient (MnSOD(+/-)) mice were studied at 3 and 18 mo of age. In aorta from wild-type mice, antioxidant expression was preserved, although there were age-associated increases in Nox2 expression. Haploinsufficiency of MnSOD did not alter antioxidant expression in aorta, but increased expression of Nox2. When compared with that of aorta, age-associated reductions in antioxidant expression were larger in aortic valves from wild-type and MnSOD haploinsufficient mice, although Nox2 expression was unchanged. Similarly, sirtuin expression was relatively well-preserved in aorta from both genotypes, whereas expression of SIRT1, SIRT2, SIRT3, SIRT4, and SIRT6 were significantly reduced in the aortic valve. Expression of p16(ink4a), a marker of cellular senescence, was profoundly increased in both aorta and aortic valve from MnSOD(+/+) and MnSOD(+/-) mice. Functionally, we observed comparable age-associated reductions in endothelial function in aorta from both MnSOD(+/+) and MnSOD(+/-) mice. Interestingly, inhibition of NAD(P)H oxidase with apocynin or gp91ds-tat improved endothelial function in MnSOD(+/+) mice but significantly impaired endothelial function in MnSOD(+/-) mice at both ages. Aortic valve function was not impaired by aging or MnSOD haploinsufficiency. Changes in antioxidant and sirtuin gene expression with aging differ dramatically between aorta and aortic valve. Furthermore, although MnSOD does not result in overt cardiovascular dysfunction with aging, compensatory transcriptional responses to MnSOD deficiency appear to be tissue specific.

  14. Genetic and phenotypic correlations between feather pecking and open-field reponse in laying hens at two different ages

    NARCIS (Netherlands)

    Rodenburg, T.B.; Buitenhuis, A.J.; Ask, B.; Uitdehaag, K.A.; Koene, P.; Poel, van der J.J.; Arendonk, van J.A.M.; Bovenhuis, H.

    2004-01-01

    The object of this research was to study the relationship between feather pecking and open-field activity in laying hens at two different ages. A population of 550 birds of a laying hen cross was subjected to an open-field test at 5 and 29 weeks of age and to a social feather pecking test at 6 and 3

  15. The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-α production.

    Science.gov (United States)

    Dimitrijević, Mirjana; Stanojević, Stanislava; Kuštrimović, Nataša; Mitić, Katarina; Vujić, Vesna; Aleksić, Iva; Radojević, Katarina; Leposavić, Gordana

    2013-11-01

    The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-α and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17β-estradiol on LPS-induced macrophage TNF-α and NO production. Results showed that: (a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-α, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-α production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-α and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity.

  16. Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Pauline Rimmelé

    2014-07-01

    Full Text Available Aging hematopoietic stem cells (HSCs exhibit defective lineage specification that is thought to be central to increased incidence of myeloid malignancies and compromised immune competence in the elderly. Mechanisms underlying these age-related defects remain largely unknown. We show that the deacetylase Sirtuin (SIRT1 is required for homeostatic HSC maintenance. Differentiation of young SIRT1-deleted HSCs is skewed toward myeloid lineage associated with a significant decline in the lymphoid compartment, anemia, and altered expression of associated genes. Combined with HSC accumulation of damaged DNA and expression patterns of age-linked molecules, these have striking overlaps with aged HSCs. We further show that SIRT1 controls HSC homeostasis via the longevity transcription factor FOXO3. These findings suggest that SIRT1 is essential for HSC homeostasis and lineage specification. They also indicate that SIRT1 might contribute to delaying HSC aging.

  17. Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans.

    Science.gov (United States)

    Carroll, Judith E; Cole, Steven W; Seeman, Teresa E; Breen, Elizabeth C; Witarama, Tuff; Arevalo, Jesusa M G; Ma, Jeffrey; Irwin, Michael R

    2016-01-01

    Age-related disease risk has been linked to short sleep duration and sleep disturbances; however, the specific molecular pathways linking sleep loss with diseases of aging are poorly defined. Key cellular events seen with aging, which are thought to contribute to disease, may be particularly sensitive to sleep loss. We tested whether one night of partial sleep deprivation (PSD) would increase leukocyte gene expression indicative of DNA damage responses (DDR), the senescence-associated secretory phenotype (SASP), and senescence indicator p16(INK4a) in older adult humans, who are at increased risk for cellular senescence. Community-dwelling older adults aged 61-86years (n=29; 48% male) underwent an experimental partial sleep deprivation (PSD) protocol over 4 nights, including adaptation, an uninterrupted night of sleep, partial sleep deprivation (sleep restricted 3-7AM), and a subsequent full night of sleep. Blood samples were obtained each morning to assess peripheral blood mononuclear cell (PBMC) gene expression using Illumina HT-12 arrays. Analyses of microarray results revealed that SASP (psleep deprivation activates PBMC gene expression patterns consistent with biological aging in this older adult sample. PSD enhanced the SASP and increased the accumulation of damage that initiates cell cycle arrest and promotes cellular senescence. These findings causally link sleep deprivation to the molecular processes associated with biological aging.

  18. Fat and carbohydrate intake over three generations modify growth, metabolism and cardiovascular phenotype in female mice in an age-related manner.

    Directory of Open Access Journals (Sweden)

    Samuel P Hoile

    Full Text Available Environmental challenges such as a high fat diet during pregnancy can induce changes in offspring growth, metabolism and cardiovascular function. However, challenges that are sustained over several generations can induce progressive compensatory metabolic adjustments in young adults. It is not known if such effects persist during ageing. We investigated whether diets with different fat and carbohydrate contents over three generations modifies markers of ageing. Female C57BL/6 F0 mice were fed diets containing 5% or 21% fat (w/w throughout pregnancy and lactation. Female offspring were fed the same diet as their dams until the F3 generation. In each generation, body weight, 24-hour food intake were recorded weekly, and plasma metabolites were measured by colorimetric assays, blood pressure by tail cuff plethysmography and vasoconstriction by myography on postnatal day 90 or 456. There was little effect of diet or generation on phenotypic markers in day 90 adults. There was a significant increase in whole body, liver and heart weight with ageing (d456 in the F3 21% fat group compared to the F1 and F3 5% groups. Fasting plasma glucose concentration was significantly increased with ageing in the 5% group in the F3 generation and in the 21% group in both generations. There was a significant effect of diet and generation on ex-vivo vasoconstriction in ageing females. Differences in dietary fat may induce metabolic compensation in young adults that persist over three generations. However, such compensatory effects decline during ageing.

  19. Premature menopause linked to CVD and osteoporosis.

    Science.gov (United States)

    Park, Claire; Overton, Caroline

    2010-03-01

    Premature menopause affects 1% of women under the age of 40, the usual age of the menopause is 51. Most women will present with irregular periods or no periods at all with or without climacteric symptoms. Around 10% of women present with primary amenorrhoea. A careful history and examination are required. It is important to ask specifically about previous chemotherapy or radiotherapy and to look for signs of androgen excess e.g. polycystic ovarian syndrome, adrenal problems e.g. galactorrhoea and thyroid goitres. Once pregnancy has been excluded, a progestagen challenge test can be performed in primary care. Norethisterone 5 mg tds po for ten days or alternatively medroxyprogesterone acetate 10 mg daily for ten days is prescribed. A withdrawal bleed within a few days of stopping the norethisterone indicates the presence of oestrogen and bleeding more than a few drops is considered a positive withdrawal bleed. The absence of a bleed indicates low levels of oestrogen, putting the woman at risk of CVD and osteoporosis. FSH levels above 30 IU/l are an indicator that the ovaries are failing and the menopause is approaching or has occurred. It should be remembered that FSH levels fluctuate during the month and from one month to the next, so a minimum of two measurements should be made at least four to six weeks apart. The presence of a bleed should not exclude premature menopause as part of the differential diagnosis as there can be varying and unpredictable ovarian function remaining. The progestagen challenge test should not be used alone, but in conjunction with FSH, LH and oestradiol. There is no treatment for premature menopause. Women desiring pregnancy should be referred to a fertility clinic and discussion of egg donation. Women not wishing to become pregnant should be prescribed HRT until the age of 50 to control symptoms of oestrogen deficiency and reduce the risks of osteoporosis and CVD.

  20. Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

    Science.gov (United States)

    Fernandez-Twinn, Denise S.; Chen, Jian Hua; Hargreaves, Iain P.; Neergheen, Viruna; Aiken, Catherine E.; Ozanne, Susan E.

    2016-01-01

    ABSTRACT ‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’) in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb) and an increased frequency of short telomeres (4.2-1.3 kb) in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), and increased xanthine oxidase (XO), p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by

  1. Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

    Directory of Open Access Journals (Sweden)

    Jane L. Tarry-Adkins

    2016-10-01

    Full Text Available ‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’ in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb and an increased frequency of short telomeres (4.2-1.3 kb in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1 in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria, and increased xanthine oxidase (XO, p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB. Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD, copper-zinc superoxide dismutase (CuZnSOD, catalase and heme oxygenase-1 (HO1, all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by

  2. Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis.

    Science.gov (United States)

    Beckervordersandforth, Ruth; Ebert, Birgit; Schäffner, Iris; Moss, Jonathan; Fiebig, Christian; Shin, Jaehoon; Moore, Darcie L; Ghosh, Laboni; Trinchero, Mariela F; Stockburger, Carola; Friedland, Kristina; Steib, Kathrin; von Wittgenstein, Julia; Keiner, Silke; Redecker, Christoph; Hölter, Sabine M; Xiang, Wei; Wurst, Wolfgang; Jagasia, Ravi; Schinder, Alejandro F; Ming, Guo-Li; Toni, Nicolas; Jessberger, Sebastian; Song, Hongjun; Lie, D Chichung

    2017-02-08

    Precise regulation of cellular metabolism is hypothesized to constitute a vital component of the developmental sequence underlying the life-long generation of hippocampal neurons from quiescent neural stem cells (NSCs). The identity of stage-specific metabolic programs and their impact on adult neurogenesis are largely unknown. We show that the adult hippocampal neurogenic lineage is critically dependent on the mitochondrial electron transport chain and oxidative phosphorylation machinery at the stage of the fast proliferating intermediate progenitor cell. Perturbation of mitochondrial complex function by ablation of the mitochondrial transcription factor A (Tfam) reproduces multiple hallmarks of aging in hippocampal neurogenesis, whereas pharmacological enhancement of mitochondrial function ameliorates age-associated neurogenesis defects. Together with the finding of age-associated alterations in mitochondrial function and morphology in NSCs, these data link mitochondrial complex function to efficient lineage progression of adult NSCs and identify mitochondrial function as a potential target to ameliorate neurogenesis-defects in the aging hippocampus.

  3. Phenotypic and Functional Characterization of Peripheral Blood Lymphocytes from Various Age- and Sex-Specific Groups of Owl Monkeys (Aotus nancymaae).

    Science.gov (United States)

    Nehete, Pramod N; Nehete, Bharti P; Chitta, Sriram; Williams, Lawrence E; Abee, Christian R

    2017-02-01

    Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys. We noted age- and sex-dependent changes in CD28+ (an essential T cell costimulatory molecule) and CD95+ (an apoptotic surface marker) T cells and various levels of cytokines in the plasma. In immune assays of freshly isolated peripheral blood mononuclear cells, IFNγ and perforin responses were significantly higher in female than in male monkeys and in young adults than in juvenile and geriatric groups, despite similar lymphocyte (particularly T cell) populations in these groups. Our current findings may be useful in exploring Aotus monkeys as a model system for the study of aging, susceptibility to infectious diseases, and age-associated differences in vaccine efficacy, and other challenges particular to pediatric and geriatric patients.

  4. Geographical variation and sexual differences of body length and age composition in Rana temporaria: the ontogenetic development and phenotypic trends

    Directory of Open Access Journals (Sweden)

    Lyapkov Sergey

    2012-06-01

    Full Text Available The analysis of literature data on the mean values of age and body length of adult individuals of widespread species Rana temporaria from about 70 spatially separated populations, including our published data, was conducted. The evident trend in population mean age increase with the decrease of the of activity season length was revealed as well as the absence of that trend in the mean body length, with the maximal mean value in body length being near central part of the range. Our explanation of non-linear trend in the mean values of body length does not contradict other models of geographic variability explaining the correspondence and discrepance with the Bergman rule. In addition our explanation corresponds to the revealed features of interpopulation variation in growth rate. The revealed trend of variation in the mean body length is resulted from both growth rate decrease and mean age increase with the decrease in the length of activity season. The relatively low mean values of body length in populations from south and southern-west borders of the range are explained not only by low mean age but by lower growth rate despite high length of activity season. The interpopulation variation in body length is determined not only by body length but by age composition differences both between and within population. Therefore, the direction and intensity of sexual differences have not distinct trends, and the correspondence to Rensch rule (in contrast to Bergman rule is rarely observed.

  5. NaDC3 Induces Premature Cellular Senescence by Promoting Transport of Krebs Cycle Intermediates, Increasing NADH, and Exacerbating Oxidative Damage.

    Science.gov (United States)

    Ma, Yuxiang; Bai, Xue-Yuan; Du, Xuan; Fu, Bo; Chen, Xiangmei

    2016-01-01

    High-affinity sodium-dependent dicarboxylate cotransporter 3 (NaDC3) is a key metabolism-regulating membrane protein responsible for transport of Krebs cycle intermediates. NaDC3 is upregulated as organs age, but knowledge regarding the underlying mechanisms by which NaDC3 modulates mammalian aging is limited. In this study, we showed that NaDC3 overexpression accelerated cellular senescence in young human diploid cells (MRC-5 and WI-38) and primary renal tubular cells, leading to cell cycle arrest in G1 phase and increased expression of senescent biomarkers, senescence-associated β-galactosidase and p16. Intracellular levels of reactive oxygen species, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, and carbonyl were significantly enhanced, and activities of respiratory complexes I and III and ATP level were significantly decreased in NaDC3-infected cells. Stressful premature senescent phenotypes induced by NaDC3 were markedly ameliorated via treatment with the antioxidants Tiron and Tempol. High expression of NaDC3 caused a prominent increase in intracellular levels of Krebs cycle intermediates and NADH. Exogenous NADH and NAD(+) may aggravate and attenuate the aging phenotypes induced by NaDC3, respectively. These results suggest that NaDC3 can induce premature cellular senescence by promoting the transport of Krebs cycle intermediates, increasing generation of NADH and reactive oxygen species and leading to oxidative damage. Our results clarify the aging signaling pathway regulated by NaDC3.

  6. Cost-effectiveness of early treatment for retinopathy of prematurity.

    Science.gov (United States)

    Kamholz, Karen L; Cole, Cynthia H; Gray, James E; Zupancic, John A F

    2009-01-01

    The Early Treatment for Retinopathy of Prematurity trial demonstrated that peripheral retinal ablation of eyes with high-risk prethreshold retinopathy of prematurity (early treatment) is associated with improved visual outcomes at 9 months' corrected gestational age compared with treatment at threshold disease (conventional management). However, early treatment increased the frequency of laser therapy, anesthesia with intubation, treatment-related systemic complications, and the need for repeat treatments. To determine the cost-effectiveness of an early treatment strategy for retinopathy of prematurity compared with conventional management. We developed a stochastic decision analytic model to assess the incremental cost of early treatment per eye with severe visual impairment prevented. We derived resource-use and efficacy estimates from the Early Treatment for Retinopathy of Prematurity trial's published outcome data. We used a third-party payer perspective. Our primary analysis focused on outcomes from birth through 9 months' corrected gestational age. A secondary analysis used a lifetime horizon. Parameter uncertainty was quantified by using probabilistic and deterministic sensitivity analyses. The incremental cost-effectiveness of early treatment was $14,200 per eye with severe visual impairment prevented. There was a 90% probability that the cost-effectiveness of early treatment would be less than $40,000 per eye with severe visual impairment prevented and a 0.5% probability that early treatment would be cost-saving (less costly and more effective). Limiting early treatment to more severely affected eyes (eyes with "type 1 retinopathy of prematurity" as defined by the Early Treatment for Retinopathy of Prematurity trial) had a cost-effectiveness of $6,200 per eye with severe visual impairment prevented. Analyses that considered long-term costs and outcomes found that early treatment was cost-saving. Early treatment of retinopathy of prematurity is both

  7. Neurosensory outcome of prematurely born children following intracranial hemorrhage

    Directory of Open Access Journals (Sweden)

    Velisavljev-Filipović Gordana

    2011-01-01

    Full Text Available Introduction. More and more survival of newborns with small or extremely small body mass at birth, as well as increasing percent of prematurely born babies, have emphasized the significance of intracranial haemorrhage problem. Prematurely born infants are under increased risk for strabismus, amblyopia, blinding and hearing loss. Objective. Establishing the frequency of sensory damages (damage of sight and hearing in prematurely born infants with various degrees of intracranial haemorrhage. Methods. The study is prospective, controlled and included 120 prematurely born infants with diagnosed four different grade intracranial haemorrhage on ultrasonic examination of the central nervous system. The study excluded prematurely born children from twin pregnancies with congenital malformations and stoppage of intrauterine growth. Ophthalmological examination was done at 9, 12, and 36 months of postnatal age. Audilogical examination was done after delivery, at 2 months of age. Results. There are statistically significant differences (p<0.01 related to the presence of strabismus among groups of examinees with vairious hemorrhage degrees. Strabismus was present only in one premature infant with 1st and in 10 children (33.3% with the 4th degree. Amblyopia occurred only among examinees with 4th degree hemorrhage. There were statistically significant differences (p<0.01 related to the finding of transitory otoacoustic emission of the left ear and the right ear among the groups. The finding of the right ear was not usual in 7 examinees from the 4th degree hemorrhage. The finding of the left ear was not usual in 1 examinee from the third and in 7 examinees from the fourth group. Conclusion. Prematurely born children with a higher degree intracranial hemorrhage have a greater risk for the loss of hearing and development of visual handicap.

  8. Insight on pathogenesis of lifelong premature ejaculation: inverse relationship between lifelong premature ejaculation and obesity.

    Science.gov (United States)

    Gökçe, A; Ekmekcioglu, O

    2010-01-01

    Although both biological and psychological factors are important in the etiology, the exact pathogenesis of lifelong premature ejaculation (PE) remains to be clarified. Obesity is a worldwide epidemic that contributes to many chronic diseases. Obesity is associated with erectile dysfunction, but the relationship between obesity and PE has not yet been specifically investigated. The aim of this study was to evaluate the relationships of these two conditions. Between January 2008 and December 2009, we evaluated consecutive patients with lifelong PE in the urology outpatient clinic. Control cases without lifelong PE were selected randomly among cases attending the department of internal medicine for a checkup procedure. The age and sex of control group were matched with that of the study group. Body mass index (BMI) of each case was calculated using the World Health Organization criteria by the measurements of the physician instead of relying on verbal expressions. The mean (+/-s.d.) age of the premature ejaculators was 31.7+/-5.7 (range 21-51) years and in the control cases it was 32.3+/-6.7 (range 22-54) years. The comparison of the mean (+/-s.d.) weight between the study (74.1+/-11.2 kg) and control groups (81.9+/-6.4 kg) revealed a significant difference (Pobese cases in the control group (n=26, 24.1%) was three times greater than the obese premature ejaculators (Pobesity, and we found that patients with lifelong PE were leaner than the healthy control cases.

  9. Methylene blue improves sensorimotor phenotype and decreases anxiety in parallel with activating brain mitochondria biogenesis in mid-age mice.

    Science.gov (United States)

    Gureev, Artem P; Syromyatnikov, Mikhail Yu; Gorbacheva, Tatyana M; Starkov, Anatoly A; Popov, Vasily N

    2016-12-01

    Age-related brain dysfunctions are associated with mitochondria malfunctions and increased risk of developing neurodegenerative diseases (ND). Recently, a mitochondria-targeting drug methylene blue has been drawing considerable interest as a potential treatment for ND. We found that aged mice manifested a decrease in physical endurance, spontaneous locomotor activity, and exploration concomitant with an increase in anxiety-related behavior, as compared to adult mice. Treating mice for 60 days with MB slowed down these changes. There were no significant changes in the animals' body weight, oxygen consumption rates, or respiratory quotient index, in adult or aged MB-treated mice. However, MB treatment significantly increased the generation of reactive oxygen species in brain mitochondria. The expression of several genes relevant to mitochondria biogenesis, bioenergetics, and antioxidant defense (NRF1, MTCOX1, TFAM, and SOD2) was greatly suppressed in aged mice; it was restored by MB treatment. It seems plausible that the effects of MB could be mediated by its ability to increase H2O2 production in brain mitochondria, thereby activating Nrf2/ARE signaling pathway and mitochondria biogenesis. Our data and earlier findings support the idea that MB can be an attractive prototype drug for developing safe and efficient gerontoprotective compounds. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  10. No Association between Variation in Longevity Candidate Genes and Aging-related Phenotypes in Oldest-old Danes

    DEFF Research Database (Denmark)

    Sørensen, Mette; Nygaard, Marianne; Debrabant, Birgit;

    2016-01-01

    additional genes repeatedly considered as candidates for human longevity: APOE, APOA4, APOC3, ACE, CETP, HFE, IL6, IL6R, MTHFR, TGFB1, SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. Altogether, 1,049 single nucleotide polymorphisms (SNPs) were genotyped in 1,088 oldest-old (age 92-93 years) Danes and analysed...

  11. Falla ovárica prematura Premature Ovarian Failure

    Directory of Open Access Journals (Sweden)

    J. Scaglia

    2007-12-01

    Full Text Available La Falla Ovárica Prematura (FOP es el cese de la menstruación antes de los 40 años. También fue denominada como Menopausia Precoz. Esta patología afecta al 1 ó 2 % de las mujeres menores de 40 años. Existen distintas causas por las cuales se puede producir una FOP, pero las más frecuentes son las inmunológicas, farmacológicas y genéticas. De las causas farmacológicas, la principal es la quimioterapia. Existen muchos genes candidatos para la FOP, razón por la cual es necesario encontrar para, cada población, que mutaciones o polimorfismos correlacionan mejor con el fenotipo. El tratamiento de la FOP debe estar apuntado a prevenir no sólo las enfermedades a largo plazo sino que, además, debe lograr una buena calidad de vida.Premature Ovarian Failure (POF, also called Precocious Menopause, is the cessation of the ovarian function prior to the age of 40. This pathology affects 1-2 % women below 40 years of age. There are many factors inducing POF, however most frequent are of immunological, pharmacological and genetic origin. Chemotherapy is the most common pharmacological cause. There are many candidate genes for inducing POF, which it makes necessary to find in every population mutations or polymorphisms that best correlate with the phenotype. Treatment of POF must be directed not only to prevent long term pathologies but also to achieve a good quality of life.

  12. Age of onset of RNA toxicity influences phenotypic severity: evidence from an inducible mouse model of myotonic dystrophy (DM1).

    Science.gov (United States)

    Gladman, Jordan T; Mandal, Mahua; Srinivasan, Varadamurthy; Mahadevan, Mani S

    2013-01-01

    Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. It is caused by an expanded (CTG)n tract in the 3' UTR of the Dystrophia Myotonica Protein Kinase (DMPK) gene. This causes nuclear retention of the mutant mRNA into ribonuclear foci and sequestration of interacting RNA-binding proteins (such as muscleblind-like 1 (MBNL1)). More severe congenital and childhood-onset forms of the disease exist but are less understood than the adult disease, due in part to the lack of adequate animal models. To address this, we utilized transgenic mice over-expressing the DMPK 3' UTR as part of an inducible RNA transcript to model early-onset myotonic dystrophy. In mice in which transgene expression was induced during embryogenesis, we found that by two weeks after birth, mice reproduced cardinal features of myotonic dystrophy, including myotonia, cardiac conduction abnormalities, muscle weakness, histopathology and mRNA splicing defects. Notably, these defects were more severe than in adult mice induced for an equivalent period of exposure to RNA toxicity. Additionally, the utility of the model was tested by over-expressing MBNL1, a key therapeutic strategy being actively pursued for treating the disease phenotypes associated with DM1. Significantly, increased MBNL1 in skeletal muscle partially corrected myotonia and splicing defects present in these mice, demonstrating the responsiveness of the model to relevant therapeutic interventions. Furthermore, these results also represent the first murine model for early-onset DM1 and provide a tool to investigate the effects of RNA toxicity at various stages of development.

  13. Age of onset of RNA toxicity influences phenotypic severity: evidence from an inducible mouse model of myotonic dystrophy (DM1.

    Directory of Open Access Journals (Sweden)

    Jordan T Gladman

    Full Text Available Myotonic dystrophy type 1 (DM1 is the most common muscular dystrophy in adults. It is caused by an expanded (CTGn tract in the 3' UTR of the Dystrophia Myotonica Protein Kinase (DMPK gene. This causes nuclear retention of the mutant mRNA into ribonuclear foci and sequestration of interacting RNA-binding proteins (such as muscleblind-like 1 (MBNL1. More severe congenital and childhood-onset forms of the disease exist but are less understood than the adult disease, due in part to the lack of adequate animal models. To address this, we utilized transgenic mice over-expressing the DMPK 3' UTR as part of an inducible RNA transcript to model early-onset myotonic dystrophy. In mice in which transgene expression was induced during embryogenesis, we found that by two weeks after birth, mice reproduced cardinal features of myotonic dystrophy, including myotonia, cardiac conduction abnormalities, muscle weakness, histopathology and mRNA splicing defects. Notably, these defects were more severe than in adult mice induced for an equivalent period of exposure to RNA toxicity. Additionally, the utility of the model was tested by over-expressing MBNL1, a key therapeutic strategy being actively pursued for treating the disease phenotypes associated with DM1. Significantly, increased MBNL1 in skeletal muscle partially corrected myotonia and splicing defects present in these mice, demonstrating the responsiveness of the model to relevant therapeutic interventions. Furthermore, these results also represent the first murine model for early-onset DM1 and provide a tool to investigate the effects of RNA toxicity at various stages of development.

  14. Breastfeeding maintenance of very low weight premature babies: experience of mothers

    Directory of Open Access Journals (Sweden)

    Beatriz de Carvalho Ciaciare

    2015-09-01

    Full Text Available The objectives of this study were to comprehend the breastfeeding process from reports of mothers of premature babies and identify factors facilitating or complicating this process. A descriptive qualitative study regarding the family centered care. We conducted 12 interviews with mothers of six months premature babies of chronological age and we submitted data to content analysis. Four categories emerged: The previous breastfeeding experience in the process of breastfeeding the premature baby; Emotional context versus the breastfeeding process; The ability to manage breastfeeding the premature baby and, Successes and failures. We concluded that family and professional support, adequate management and the welcoming of individualized services in the prematurity context were majorly responsible for the breastfeeding success, being even able to surpass the previous maternal desire. Breastfeeding accompaniment after discharge is indispensable for its success with premature babies.

  15. Pathway-based factor analysis of gene expression data produces highly heritable phenotypes that associate with age

    OpenAIRE

    Brown, Andrew Anand; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

    2015-01-01

    Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to...

  16. The Effects of Age and Latent Cytomegalovirus Infection on NK-Cell Phenotype and Exercise Responsiveness in Man

    Directory of Open Access Journals (Sweden)

    Austin B. Bigley

    2015-01-01

    Full Text Available The redeployment of NK-cells in response to an acute bout of exercise is thought to be an integral component of the “fight-or-flight” response, preparing the body for potential injury or infection. We showed previously that CMV seropositivity impairs the redeployment of NK-cells with exercise in the young. In the current study, we examined the effect of aging on the redeployment of NK-cells with exercise in the context of CMV. We show here that CMV blunts the exercise-induced redeployment of NK-cells in both younger (23–39 yrs and older (50–64 yrs subjects with older CMVneg subjects showing the largest postexercise mobilization and 1 h postexercise egress of NK-cells. The blunted exercise response in CMVpos individuals was associated with a decreased relative redeployment of the CD158a+ and CD57+ NK-cell subsets in younger and older individuals. In addition, we show that aging is associated with a CMV-independent increase in the proportion of NK-cells expressing the terminal differentiation marker CD57, while CMV is associated with an age-dependent decrease in the proportion of NK-cells expressing the inhibitory receptors KLRG1 (in the younger group and CD158a (in the older group. Collectively, these data suggest that CMV may decrease NK-cell mediated immunosurveillance after exercise in both younger and older individuals.

  17. Your Premature Baby: Low Birthweight

    Science.gov (United States)

    ... many low-birthweight babies are born prematurely, many risk factors for having a low-birthweight baby are the same for preterm labor and ... risk for having a low-birthweight baby. Medical risk factors for having a low-birthweight baby Preterm labor . This is labor that starts ...

  18. Music Therapy with Premature Infants

    Science.gov (United States)

    Standley, Jayne

    2003-01-01

    Over 20 years of research and clinical practice in music therapy with premature infants has been compiled into this text designed for Board Certified Music Therapists specializing in Neonatal Intensive Care clinical services, for NICU medical staff incorporating research-based music therapy into developmental care plans, and for parents of…

  19. Music Therapy with Premature Infants

    Science.gov (United States)

    Standley, Jayne

    2003-01-01

    Over 20 years of research and clinical practice in music therapy with premature infants has been compiled into this text designed for Board Certified Music Therapists specializing in Neonatal Intensive Care clinical services, for NICU medical staff incorporating research-based music therapy into developmental care plans, and for parents of…

  20. Aging and photo-aging DNA repair phenotype of skin cells-Evidence toward an effect of chronic sun-exposure

    Energy Technology Data Exchange (ETDEWEB)

    Prunier, Chloe; Masson-Genteuil, Gwenaeelle [Laboratoire Lesions des Acides Nucleiques, CEA, DSM, INAC, SCIB, UMR-E CEA/UJF-Grenoble 1, 17 Rue des Martyrs, F-38054 Grenoble Cedex 9 (France); Ugolin, Nicolas [Laboratoire de Cancerologie Experimentale, CEA, DSV, IRCM, SREIT, BP6, Fontenay-aux-Roses Cedex F-92265 (France); Sarrazy, Fanny [Laboratoire Lesions des Acides Nucleiques, CEA, DSM, INAC, SCIB, UMR-E CEA/UJF-Grenoble 1, 17 Rue des Martyrs, F-38054 Grenoble Cedex 9 (France); Sauvaigo, Sylvie, E-mail: sylvie.sauvaigo@cea.fr [Laboratoire Lesions des Acides Nucleiques, CEA, DSM, INAC, SCIB, UMR-E CEA/UJF-Grenoble 1, 17 Rue des Martyrs, F-38054 Grenoble Cedex 9 (France)

    2012-08-01

    Several studies have demonstrated the deleterious effect of aging on the capacity of cells to repair their DNA. However, current existing assays aimed at measuring DNA repair address only a specific repair step dedicated to the correction of a specific DNA lesion type. Consequently they provide no information regarding the repair pathways that handle other types of lesions. In addition to aging, consequences of photo-exposure on these repair processes remain elusive. In this study we evaluated the consequence of aging and of chronic and/or acute photo-exposure on DNA repair in human skin fibroblasts using a multiplexed approach, which provided detailed information on several repair pathways at the same time. The resulting data were analyzed with adapted statistics/bioinformatics tools. We showed that, irrespective of the repair pathway considered, excision/synthesis was less efficient in non-exposed cells from elderly compared to cells from young adults and that photo-exposure disrupted this very clear pattern. Moreover, it was evidenced that chronic sun-exposure induced changes in DNA repair properties. Finally, the identification of a specific signature at the level of the NER pathway in cells repeatedly exposed to sun revealed a cumulative effect of UVB exposure and chronic sun irradiation. The uses of bioinformatics tools in this study was essential to fully take advantage of the large sum of data obtained with our multiplexed DNA repair assay and unravel the effects of environmental exposure on DNA repair pathways.

  1. [EVALUETION OF THE CLINICAL EFFICACY OF SUSTAINED RELEASE THEOPHILLINE IN A COMPLEX BASIC THERAPY OF EOSINOPHILIC PHENOTYPE OF BRONCHIAL ASTHMA IN SCHOOL AGE CHILDREN].

    Science.gov (United States)

    Ortemenka, Ye P

    2014-01-01

    Based on a complex examination of 11 school age children with eosinophilic phenotype of bronchial asthma, it has been demonstrated that combination of inhaled corticosteroids with oral sustained release theophillines were more effective as a basic anti-inflammatory asthma therapy, in comparison with monotherapy by inhaled corticosteroids. The usage of such combined anti-relapsing asthma treatment has been reduced both the relative risk (RR = 57%) and the attributable risk (AR = 36.3%) of insufficient control of bronchial asthma in children with eosinophilic type of airways inflammation. At the same time, the minimum number of patients, which have to be treated by such method with the object of preventing at least one case of poor asthma control, came to 3 children.

  2. Influence of Perinatal Risk Factors on Premature Labor Outcome

    Directory of Open Access Journals (Sweden)

    Agamurad A. Orazmuradov

    2016-09-01

    Full Text Available In this article, for the first time, the problem of premature labor (PL is considered from the standpoint of the concept of perinatal obstetric risk. The obtained results show that the optimal choice of the mode of delivery must be based on gestational age and perinatal risk (PR factors with calculation of their intrapartum gain (IG.

  3. Early repolarization as a predictor of premature ventricular beats.

    Science.gov (United States)

    Matoshvili, Z T; Petriashvili, Sh G; Archadze, A T; Azaladze, I G

    2015-02-01

    Early repolarization pattern (ERP) is a common ECG variant, characterized by J point elevation manifested either as terminal QRS slurring (the transition from the QRS segment to the ST segment) or notching (a positive deflection inscribed on terminal QRS complex) associated with concave upward ST-segment elevation and prominent T waves in at least two contiguous leads. Aim of this observational study was to compare number of premature ventricular beats in the different groups of patients with early repolarization. The result of this observational study shows that there are: 1,74 fold higher number of premature ventricular beats in 41-74 year subgroup VS 19-40 year subgroup; 1,31 fold higher number of premature ventricular beats in male subgroup VS female subgroup (But this difference is not statistically significant, because t=1,49, p=0,141); 2,85 fold higher number of premature ventricular beats in CAD+ERP subgroup VS ERP without CAD subgroup; 1,74 fold higher number of premature ventricular beats in HF+ERP subgroup VS ERP without HF subgroup; 1,81 fold higher number of premature ventricular beats in CAD+ERP subgroup VS CAD without ERP subgroup; 1,58 fold higher number of premature ventricular beats in HF+ERP subgroup VS HF without ERP subgroup; So, CAD+ERP is very arrhythmogenic condition, after this is HF+ERP, Then Age. This study shows that ERP independently increase number of PVB in different groups (CAD, HF). This is principally new and very important result. Also the number of patients is enough to make this conclusion.

  4. MODERN PRODUCTS FOR FEEDING PREMATURE BABIES

    National Research Council Canada - National Science Library

    A. V. Surzhik

    2012-01-01

    .... Adequate feeding is one of the fundamental factors of premature babies nursing. To ensure a premature baby with all necessary components for power saving in breast milk intake, breast milk fortifiers...

  5. Modern Approach in Premature Ovarian Failure

    Directory of Open Access Journals (Sweden)

    Pacu Irina

    2014-09-01

    Full Text Available Premature ovarian failure (POF is a condition affecting 1-2% of women younger than 40 years of age, characterized by amenorrhea, hypoestrogenism and elevated gonadotropin levels. In the last years it became a problem of social health interest as the frequency increased due to environmental factors and new, efficient methods for cancer treatment in young women. Few genes have beed identified to explain cases of POF but there are also autoimmune associated conditions and an increasing number of iatrogenic cases (chemotherapy, surgery, radiotherapy. Modern approach in POF means not only a precise etiological diagnosis, but also a correct counseling for these patients who often want to become parents, and a chance for a healthy life without the long term consequences of estrogen deprivation from an early age. In vitro fertilization (IVF techniques can be useful for certain cases but research is needed on strategies to improve fertility for women who have follicles remaining in the ovaries.

  6. Premature birth as a risk factor for autism spectrum disorder.

    Science.gov (United States)

    Goldin, Rachel L; Matson, Johnny L

    2016-06-01

    Autism spectrum disorder (ASD) is common, life-long in nature, and can be very debilitating. Thus, an intensive search is on to identify the potential risk factors for the disorder. Premature birth has been identified as one potential factor that could influence potential symptoms of ASD. The sample for this study consisted of 1655 at risk children for developmental delays who were 17-37 months of age. Participants were divided into those diagnosed with ASD (n = 916) and children with atypical development only (n = 739). Premature births were almost twice as common for the atypical development group versus the ASD group. Implications of these data are discussed.

  7. The relationship between premature birth and caregiver first concern in toddlers with autism spectrum disorder: A brief report.

    Science.gov (United States)

    Goldin, Rachel L; Matson, Johnny L; Matheis, Maya; Jang, Jina

    2017-05-01

    The current study examines the relationship between premature birth and the age at which caregivers first become concerned with their child's development in a sample of 84 toddlers with autism spectrum disorder (ASD). The participants were split into two groups: those born prematurely and those born full term. The results indicate that the age of caregiver first concern is significantly younger for those born prematurely than those born full term. The average age caregivers reported first becoming concerned about their child's development was around 7 months for participants born prematurely and around 13 months for participants born full term. Possible explanations for the results and their implications are discussed.

  8. Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age.

    Directory of Open Access Journals (Sweden)

    Adam J Watkins

    Full Text Available Human and animal studies have revealed a strong association between periconceptional environmental factors, such as poor maternal diet, and an increased propensity for cardiovascular and metabolic disease in adult offspring. Previously, we reported cardiovascular and physiological effects of maternal low protein diet (LPD fed during discrete periods of periconceptional development on 6-month-old mouse offspring. Here, we extend the analysis in 1 year aging offspring, evaluating mechanisms regulating growth and adiposity. Isocaloric LPD (9% casein or normal protein diet (18% casein; NPD was fed to female MF-1 mice either exclusively during oocyte maturation (for 3.5 days prior to mating; Egg-LPD, Egg-NPD, respectively, throughout gestation (LPD, NPD or exclusively during preimplantation development (for 3.5 days post mating; Emb-LPD. LPD and Emb-LPD female offspring were significantly lighter and heavier than NPD females respectively for up to 52 weeks. Egg-LPD, LPD and Emb-LPD offspring displayed significantly elevated systolic blood pressure at 52 weeks compared to respective controls (Egg-NPD, NPD. LPD females had significantly reduced inguinal and retroperitoneal fat pad: body weight ratios compared to NPD females. Expression of the insulin receptor (Insr and insulin-like growth factor I receptor (Igf1r in retroperitoneal fat was significantly elevated in Emb-LPD females (P<0.05, whilst Emb-LPD males displayed significantly decreased expression of the mitochondrial uncoupling protein 1 (Ucp1 gene compared to NPD offspring. LPD females displayed significantly increased expression of Ucp1 in interscapular brown adipose tissue when compared to NPD offspring. Our results demonstrate that aging offspring body weight, cardiovascular and adiposity homeostasis can be programmed by maternal periconceptional nutrition. These adverse outcomes further exemplify the criticality of dietary behaviour around the time of conception on long-term offspring

  9. [Preterm premature rupture of membranes: active or expectant management?].

    Science.gov (United States)

    Kayem, G; Maillard, F

    2009-04-01

    Preterm premature rupture of membranes (PPROM) occurs in 3% of pregnancies and is responsible for 30% of preterm births. The management is discussed between active and expectant management. French recommendations let open both possibilities. The risks described in the case of PPROM are those of prematurity, maternofetal infection, acute procidence of the umbilical cord and abruptio placentae. Before 32 weeks of gestation (WG) and even 34 WG, a prolongation of one week of gestational age significantly decreases neonatal mortality and morbidity. Therefore, most of the authors choose expectant management in case of PPROM. Between 34 and 37 WG, the risk of rare severe morbidity associated with prematurity has to be balanced with risks of an acute maternofetal infection and of abruptio placentae. Further randomized trials are required to choose a type of management with a sufficient level of evidence.

  10. Ability to Keep Milk-Ejecting Activity after Premature Birth

    Directory of Open Access Journals (Sweden)

    S. G. Gribakin

    2015-01-01

    Full Text Available The article examines the modern data on the importance of breast milk in nursing premature babies. It is shown that the amount of breast milk in women, who gave birth prematurely, decreases rapidly, especially when it is impossible to get a baby latched on to the breast. There is a negative correlation between gestational age and duration of lactation. According to the opinion of both doctors and the majority of mothers, pumping out breast milk and using it in feeding a premature baby is an important psychological and physiological factor linking a mother and a child at the intensive care unit. Individual breast milk banks are a new safe and effective method for long-term keeping of breast milk.

  11. Risk factors of intracranial hemorrhage in premature neonates.

    Directory of Open Access Journals (Sweden)

    Nasrin Khalessi

    2014-09-01

    Full Text Available Intraventricular hemorrhage (IVH is an important cause of brain injury in premature neonates. Current study tries to define associated risk factors of IVH in preterm neonates in Aliasghar Children Hospital during 2008 to 2011. In this study, the risk factors have been evaluated in premature neonates with IVH, who had at least one brain sonography since their admission in NICU. A total of 63 premature neonates with IVH were assessed. Mean gestational age was 29.81 (24-34 weeks and mean birth weight was 1290.83±382.96 gr. Other risk factors such as sex, mode of delivery, history of using infertility drugs, maternal disease, maternal hypertension and preeclampsia, lumbar puncture, ventilator therapy and pneumothorax were considered. Because no absolute treatment for IVH is available, identifying risk factors is important in prevention and management of IVH.

  12. Evaluation and Treatment of Anemia in Premature Infants

    Science.gov (United States)

    Hasanbegovic, Edo; Cengic, Nermana; Hasanbegovic, Snijezana; Heljic, Jasmina; Lutolli, Ismail; Begic, Edin

    2016-01-01

    Introduction: Anemia in preterm infants is the pathophysiological process with greater and more rapid decline in hemoglobin compared to the physiological anemia in infants. There is a need for transfusions and administration of human recombinant erythropoietin. Aim: To determine the frequency of anemia in premature infants at the Pediatric Clinic, University Clinical Center Sarajevo, as well as parameter values in the blood count of premature infants and to explore a relationship between blood transfusions with the advent of intraventricular hemorrhage (determine treatment outcome in preterm infants). Patients and methods: Research is retrospective study and it included the period of six months in year 2014. Research included 100 patients, gestational age < 37 weeks (premature infants). Data were collected by examining the medical records of patients at the Pediatric Clinic, UCCS. Results: The first group of patients were premature infants of gestational age ≤ 32 weeks (62/100) and the second group were premature infants of gestational age 33-37 weeks (38/100). Among the patients, 5% were boys and 46% girls. There was significant difference in birth weight and APGAR score among the groups. In the first group, there were 27.42% of deaths, while in the second group, there were only 10.53% of deaths. There was a significant difference in the length of treatment. There was a statistically significant difference in the need for transfusion among the groups. 18 patients in the first group required a transfusion, while in the second group only 3 patients. Conclusions: Preterm infants of gestational age ≤ 32 weeks are likely candidates for blood transfusion during treatment. Preterm infants of gestational age ≤ 32 weeks have the risk of intracranial bleeding associated with the application of blood transfusion in the first week of life. PMID:28210010

  13. 过氧化氢诱导的人正常和早老细胞中DNA损伤及其修复研究%The Study of Hydrogen Peroxide Induced DNA Damage and Recovery in Normal Aging and Premature Aging Human Cells

    Institute of Scientific and Technical Information of China (English)

    所起凤; 杜文婷; 杨鸣鸣; 范雪娇; 刘戟

    2011-01-01

    目的 研究人早老细胞和正常衰老细胞在氧化应激条件下的DNA损伤和修复.方法 采用免疫荧光技术和彗星电泳技术,分别检测3组不同群体倍增数(PD)的人正常二倍体成纤维细胞BJ(青年组第14代,成年组第30代,衰老组第45代)和2组不同PD的人赫-吉二氏综合征(HGPS)细胞(青年组第8代,衰老组第17代)的DNA基础损伤程度.研究过氧化氢诱导造成以上细胞组DNA损伤及去除致损因素正常培养后的修复水平,采用免疫荧光和彗星电泳技术检测细胞在沉默DNA损伤修复蛋白着色性干皮病蛋白A(XPA)表达前后的修复能力.结果 BJ细胞衰老组DNA损伤程度较高,与成年组相比,对DNA损伤诱导因子更加敏感(P<0.05);成年组与青年组相比,对损伤诱导因子也更敏感(P<0.05).HGPS细胞青年组的DNA基础损伤程度即已达到衰老BJ细胞类似或更高水平,且与BJ细胞具有一致的DNA损伤年龄变化趋势.经siRNA沉默XPA表达后可部分恢复HGPS细胞的修复能力,对BJ细胞则没有影响.随年龄增长无论正常还是早老细胞,DNA损伤程度增加,修复效率降低.结论 XPA功能异常抑制了HGPS细胞的损伤修复.%Objective To study the DNA damage and recovery induced by hydrogen peroxide in normal aging and premature aging human cells. Methods The immunofluorescent assay and comet assay were used to estimate basal DNA damage in normal aging BJ cells and premature aging Hutchinson-Gilford progeria syndrome (HGPS) cells, which were divided into three and two distinct population doubling (PD) number groups (BJ 14· 30, 45 and HGPS 8, 17) respectively. The DNA damage induced by hydrogen peroxide of these cell populations, as well as their repair activity, was also studied. Finally, the recovery capability before and after the xeroderma pigmentosum group A (XPA ) knocked down in these groups was measured. Results Our results indicated that the normal BJ cells of older PD number

  14. Premature: growth and its relation to oral skills.

    Science.gov (United States)

    Vargas, Camila Lehnhart; Berwig, Luana Cristina; Steidl, Eduardo Matias dos Santos; Prade, Leila Sauer; Bolzan, Geovana; Keske-Soares, Márcia; Weinmann, Angela Regina Maciel

    2015-01-01

    To evaluate the influence of oral motor skills of premature infants on their oral feeding performance and growth, during neonatal hospitalization. Fifty-one newborns hospitalized in the neonatal intensive care unit of a hospital in Southern Brazil, between July 2012 and March 2013, were evaluated. The evaluation of oral feeding skills, according to Lau and Smith, was applied after prescription for starting oral feeding. The oral feeding performance was analyzed using the following variables: days taken to start independent oral feeding and hospital discharge. Growth was measured by weight, length, and head circumference, using the curves of Fenton, at birth, first and independent oral feeding, and hospital discharge. At birth, 71% preterm infants were proper for gestational age, most of them were males (53%), with average of 33.6 (±1.5) weeks of gestational age. The gestational age in the assessment did not influence the oral feeding performance of the premature infant and did not differ between levels. Time of transition from tube feeding to oral feeding and hospital stay was shorter when the oral skills were higher. At birth, there was a tendency of low weight and low oral feeding performance. Level IV premature infants in the release of oral feeding presented higher weights. The level of oral skills of the premature infant interfered positively on time of feeding transition from tube to independent oral feeding and hospital stay. Growth, represented by weight gain, was not affected by the level of oral skill.

  15. Retinopathy of prematurity and risk factors: a prospective cohort study

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    Angell Linda

    2005-06-01

    Full Text Available Abstract Background Increased survival of extremely low birth infants due to advances in antenatal and neonatal care has resulted in a population of infants at high risk of developing retinopathy of prematurity (ROP. Therapeutic interventions include the use of antenatal and postnatal steroids however, their effects on the severity of ROP is in dispute. In addition, it has not been investigated whether severe ROP is due to therapeutic interventions or due to the severity of illness. The aim of the present study was to assess the association between the incidence of severe retinopathy of prematurity (greater than stage 2 – International classification of ROP and mechanical ventilation, oxygen therapy, gestational age, antenatal and postnatal steroids in extremely low birth weight infants. Methods Neonates admitted to the neonatal intensive care unit in Lansing, Michigan, during 1993–2000 were followed to determine factors influencing the development of severe retinopathy of prematurity. Ophthalmologic examinations were started at 6 weeks and followed until resolution. We used logistic regression to estimate the relative risk (odds ratio associated with risk factors of ROP. Results Of the neonates with ≤ 1500 g birth weight, admitted to the neonatal intensive care unit, 85% (616/725 survived. Severe retinopathy of prematurity was detected in 7.8% of 576 neonates who had eye examinations. Neonates of lower gestational age (≤ 25 weeks and 26–28 weeks had an increased odds ratio of 8.49 and 3.19 for the development of severe retinopathy of prematurity, respectively, compared to those 29 weeks and older. Late postnatal steroid treatment starting after 3 weeks of life showed 2.9-fold increased odds ratio, in particular administration for two weeks and more (OR: 4.09, 95% CI: 1.52–11.03. With increasing antenatal steroids courses the risk of severe retinopathy of prematurity decreased, however, it was not significant. Lower gestational age

  16. Prematurity stereotyping and mothers' interactions with their premature and full-term infants during the first year.

    Science.gov (United States)

    Stern, Marilyn; Karraker, Katherine; McIntosh, Bonnie; Moritzen, Sara; Olexa, Michelle

    2006-07-01

    To longitudinally assess stability and correlates of prematurity stereotyping and perceptions of infant vulnerability in mothers of premature (N = 56) and full-term (N = 59) infants. At 5, 9, and 12 months, mothers rated videotapes of unfamiliar infants with a full-term label (FTL) or a preterm label (PL), interacted with their own infant, and completed other questionnaires. A subgroup of infants were administered a developmental assessment at 32 months. Mothers rated PL infants more negatively than FTL infants at each age. Individual differences in stereotyping were not stable. Mothers who negatively rated infants labeled with the same birth status of their own infants exhibited more negative interactive behaviors with their infants. Mothers who viewed their own infant as more vulnerable and who showed more prematurity stereotyping at 5 months had infants with lower 32-month mental scores. The results suggest an association between early maternal cognitions and both contemporaneous maternal behavior and later child developmental outcomes.

  17. Vitamin D receptor signaling improves Hutchinson-Gilford progeria syndrome cellular phenotypes.

    Science.gov (United States)

    Kreienkamp, Ray; Croke, Monica; Neumann, Martin A; Bedia-Diaz, Gonzalo; Graziano, Simona; Dusso, Adriana; Dorsett, Dale; Carlberg, Carsten; Gonzalo, Susana

    2016-05-24

    Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating incurable premature aging disease caused by accumulation of progerin, a toxic lamin A mutant protein. HGPS patient-derived cells exhibit nuclear morphological abnormalities, altered signaling pathways, genomic instability, and premature senescence. Here we uncover new molecular mechanisms contributing to cellular decline in progeria. We demonstrate that HGPS cells reduce expression of vitamin D receptor (VDR) and DNA repair factors BRCA1 and 53BP1 with progerin accumulation, and that reconstituting VDR signaling via 1α,25-dihydroxyvitamin D3 (1,25D) treatment improves HGPS phenotypes, including nuclear morphological abnormalities, DNA repair defects, and premature senescence. Importantly, we discovered that the 1,25D/VDR axis regulates LMNA gene expression, as well as expression of DNA repair factors. 1,25D dramatically reduces progerin production in HGPS cells, while stabilizing BRCA1 and 53BP1, two key factors for genome integrity. Vitamin D/VDR axis emerges as a new target for treatment of HGPS and potentially other lamin-related diseases exhibiting VDR deficiency and genomic instability. Because progerin expression increases with age, maintaining vitamin D/VDR signaling could keep the levels of progerin in check during physiological aging.

  18. Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner.

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    Tommy Noh

    Full Text Available We investigated the role of Lef1, one of the four transcription factors that transmit Wnt signaling to the genome, in the regulation of bone mass. Microcomputed tomographic analysis of 13- and 17-week-old mice revealed significantly reduced trabecular bone mass in Lef1(+/- females compared to littermate wild-type females. This was attributable to decreased osteoblast activity and bone formation as indicated by histomorphometric analysis of bone remodeling. In contrast to females, bone mass was unaffected by Lef1 haploinsufficiency in males. Similarly, females were substantially more responsive than males to haploinsufficiency in Gsk3beta, a negative regulator of the Wnt pathway, displaying in this case a high bone mass phenotype. Lef1 haploinsufficiency also led to low bone mass in males lacking functional androgen receptor (AR (tfm mutants. The protective skeletal effect of AR against Wnt-related low bone mass is not necessarily a result of direct interaction between the AR and Wnt signaling pathways, because Lef1(+/- female mice had normal bone mass at the age of 34 weeks. Thus, our results indicate an age- and gender-dependent role for Lef1 in regulating bone formation and bone mass in vivo. The resistance to Lef1 haploinsufficiency in males with active AR and in old females could be due to the reduced bone turnover in these mice.

  19. MODERN PRODUCTS FOR FEEDING PREMATURE BABIES

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    A. V. Surzhik

    2012-01-01

    Full Text Available In recent decades there has been substantial progress in the technology of premature infants nursing, especially with extremely low birth weight. Adequate feeding is one of the fundamental factors of premature babies nursing. To ensure a premature baby with all necessary components for power saving in breast milk intake, breast milk fortifiers — specifically developed additives that adjust the composition of food for premature babies, are used for more than 20 years (for premature babies receiving breast milk. On the one hand, to preserve all benefits of breastfeeding, on the other — to prevent the deficit development of necessary elements for adequate growth and development of nutrients.

  20. [Forensic importance of premature craniosynostosis].

    Science.gov (United States)

    Fehlow, P

    1991-01-01

    In agreement with Canabis craniosynostosis as a little known organic partial factor of sociopathy is demonstrated. A psychic syndrome of the frontal lobe with increased susceptibility in environmental damages is assumed to be basic disorder. In the criminals of the material sexual offenders were preponderating. Associated craniofacial dysplasias are a risk for psychic maldevelopment. The importance of premature craniosynostocis as a biological risk factor, incidence, diagnostic, indication for an operation, also in the meaning of a neurosurgical "Konflikttherapie" (cosmetical indication) are discussed.

  1. Brain calcification process and phenotypes according to age and sex: Lessons from SLC20A2, PDGFB, and PDGFRB mutation carriers.

    Science.gov (United States)

    Nicolas, Gaël; Charbonnier, Camille; de Lemos, Roberta Rodrigues; Richard, Anne-Claire; Guillin, Olivier; Wallon, David; Legati, Andrea; Geschwind, Daniel; Coppola, Giovanni; Frebourg, Thierry; Campion, Dominique; de Oliveira, João Ricardo Mendes; Hannequin, Didier

    2015-10-01

    Primary Familial Brain Calcification (PFBC) is a dominantly inherited cerebral microvascular calcifying disorder with diverse neuropsychiatric expression. Three causative genes have been identified: SLC20A2, PDGFRB and, recently, PDGFB, whose associated phenotype has not yet been extensively studied. We included in the largest published case series of genetically confirmed PFBC, 19 PDGFB (including three new mutations), 24 SLC20A2 (including 4 new mutations), and 14 PDGFRB mutation carriers, from two countries (France and Brazil). We studied clinical features and applied our visual rating scale on all 49 available CT scans. Among the symptomatic mutation carriers (33/57, 58%), the three most frequently observed categories of clinical features were psychiatric signs (72.7%, 76.5%, and 80% for PDGFB, SLC20A2, and PDGFRB, respectively), movement disorders (45.5%, 76.5%, and 40%), and cognitive impairment (54.6%, 64.7%, and 40%). The median age of clinical onset was 31 years, 25% had an early onset (before 18) and 25% a later onset (after 53). Patients with an early clinical onset exhibited mostly isolated psychiatric or cognitive signs, while patients with a later onset exhibited mostly movement disorders, especially in association with other clinical features. CT scans rating allowed identifying four patterns of calcification. The total calcification score was best predicted by the combined effects of gene (SLC20A2 > PDGFB > PDGFRB mutations), sex (male), and (increasing) age, defining three risk classes, which correlated with the four patterns of calcification. These calcification patterns could reflect the natural history of the calcifying process, with distinct risk classes characterized by different age at onset or rate of progression.

  2. The influence of premature extractions of primary molars on the ultimate root length of their permanent successors.

    Science.gov (United States)

    Brin, I; Koyoumdijsky-Kaye, E

    1981-06-01

    Final root length of lower premolars which succeed prematurely--extracted primary molars is shortened. The proposed explanation focuses on a possible accelerated movement of the permanent tooth bud and undue environmental stress following the premature extraction of its deciduous predecessor. The degree of shortening is different in both sexes and depends on the age at which the premature extraction is performed. Girls are more affected than boys, especially in cases in which the premature extractions are performed before the age of eight yr.

  3. Modeling premature brain injury and recovery

    Science.gov (United States)

    Scafidi, Joey; Fagel, Devon M.; Ment, Laura R.; Vaccarino, Flora M.

    2009-01-01

    Premature birth is a growing and significant public health problem because of the large number of infants that survive with neurodevelopmental sequelae from brain injury. Recent advances in neuroimaging have shown that although some neuroanatomical structures are altered, others improve over time. This review outlines recent insights into brain structure and function in these preterm infants at school age and relevant animal models. These animal models have provided scientists with an opportunity to explore in depth the molecular and cellular mechanisms of injury as well as the potential of the brain for recovery. The endogenous potential that the brain has for neurogenesis and gliogenesis, and how environment contributes to recovery, are also outlined. These preclinical models will provide important insights into the genetic and epigenetic mechanisms responsible for variable degrees of injury and recovery, permitting the exploration of targeted therapies to facilitate recovery in the developing preterm brain. PMID:19482072

  4. Periodic heart rate decelerations in premature infants.

    Science.gov (United States)

    Flower, Abigail A; Moorman, J Randall; Lake, Douglas E; Delos, John B

    2010-04-01

    The pacemaking system of the heart is complex; a healthy heart constantly integrates and responds to extracardiac signals, resulting in highly complex heart rate patterns with a great deal of variability. In the laboratory and in some pathological or age-related states, however, dynamics can show reduced complexity that is more readily described and modeled. Reduced heart rate complexity has both clinical and dynamical significance - it may provide warning of impending illness or clues about the dynamics of the heart's pacemaking system. In this paper, we describe simple and interesting heart rate dynamics that we have observed in premature human infants - reversible transitions to large-amplitude periodic oscillations - and we show that the appearance and disappearance of these periodic oscillations can be described by a simple mathematical model, a Hopf bifurcation.

  5. NEONATAL COMPLICATIONS OF PREMATURE RUPTURE OF MEMBRANES

    Directory of Open Access Journals (Sweden)

    F. Nili AA. Shams Ansari

    2003-07-01

    Full Text Available Premature rupture of membranes (PROM is one of the most common complications of pregnancy that has a major impact on neonatal outcomes. With respect to racial, nutritional and cultural differences between developed and developing countries, this study was conducted to detect the prevalence of neonatal complications following PROM and the role of the duration of rupture of membranes in producing morbidities and mortalities in these neonates in our hospital. Among 2357 pregnant women, we found 163 (6.91% cases of premature rupture of the fetal membranes in Tehran Vali-e-Asr Hospital during April 2001 to April 2002. Route of delivery was cesarean section in 65.6% of women. Urinary tract infection occured in 1.8%, maternal leukocytosis and fever in 20.2% and 5.5%, chorioamnionitis in 6.1%, fetal tachycardia in 1.2% and olygohydramnios in 4.9%. Gestational age in 138 (86% of neonates was less than 37 completed weeks. Thirty five infants (21.47% had respiratory distress syndrome and 33 (20.245% had clinical sepsis. Pneumonia in 6 (3.7% and skeletal deformity in 7 (4.294% were seen. Rupture of membrane of more than 24 hours duration occurred in 71 (43.6% of the patients. Comparison of morbidities between two groups of neonates and their mothers according to the duration of PROM (less and more than 24 hours showed significant differences in NICU admission, olygohydramnios, maternal fever, leukocytosis and chorioamnionitis rates (p24 hr of PROM with an odds ratio of 2.68 and 2.73, respectively. Positive blood and eye cultures were detected in 16 cases during 72 hours of age. Staphylococcus species, klebsiella, E.coli and streptococcus were the predominant organisms among positive blood cultures. Mortality was seen in 18 (11% of neonates because of respiratory failure, disseminated intravascular coagulation, septic shock, and a single case of congenital toxoplasmosis. In this study, the prevalence of prematurity, sepsis and prolonged rupture of membrane

  6. Lamin A, farnesylation and aging

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Sita [Department of Biochemistry and Molecular Biology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Comai, Lucio, E-mail: comai@usc.edu [Department of Molecular Microbiology and Immunology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States)

    2012-01-01

    Lamin A is a component of the nuclear envelope that is synthesized as a precursor prelamin A molecule and then processed into mature lamin A through sequential steps of posttranslational modifications and proteolytic cleavages. Remarkably, over 400 distinct point mutations have been so far identified throughout the LMNA gene, which result in the development of at least ten distinct human disorders, collectively known as laminopathies, among which is the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). The majority of HGPS cases are associated with a single point mutation in the LMNA gene that causes the production of a permanently farnesylated mutant lamin A protein termed progerin. The mechanism by which progerin leads to premature aging and the classical HGPS disease phenotype as well as the relationship between this disorder and the onset of analogous symptoms during the lifespan of a normal individual are not well understood. Yet, recent studies have provided critical insights on the cellular processes that are affected by accumulation of progerin and have suggested that cellular alterations in the lamin A processing pathway leading to the accumulation of farnesylated prelamin A intermediates may play a role in the aging process in the general population. In this review we provide a short background on lamin A and its maturation pathway and discuss the current knowledge of how progerin or alterations in the prelamin A processing pathway are thought to influence cell function and contribute to human aging.

  7. Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.

    Science.gov (United States)

    Aliper, Alexander M; Csoka, Antonei Benjamin; Buzdin, Anton; Jetka, Tomasz; Roumiantsev, Sergey; Moskalev, Alexy; Zhavoronkov, Alex

    2015-01-01

    For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

  8. Chromosome territories, X;Y translocation and Premature Ovarian Failure: is there a relationship?

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    Betri Enrico

    2009-09-01

    Full Text Available Abstract Background Premature ovarian failure (POF is a secondary hypergonadotrophic amenorrhea occurring before the age of 40 and affecting 1-3% of females. Chromosome anomalies account for 6-8% of POF cases, but only few cases are associated with translocations involving X and Y chromosomes. This study shows the cytogenetic and molecular analysis of a POF patient came to our attention as she developed a left ovary choriocarcinoma at the age of 10 and at 14 years of age she presented secondary amenorrhea with elevated levels of gonadotropins. Results Breakpoint position on X and Y chromosomes was investigated using Fluorescent In Situ Hybridisation (FISH with a panel of specific BAC probes, microsatellite analysis and evaluation of copy number changes and loss of heterozigosity by Affymetrix® GeneChip platform (Santa Clara, CA, USA. Patient's karyotype resulted 46, X, der(Yt(X;Y(q13.1;q11.223. X inactivation study was assessed by RBA banding and showed preferential inactivation of derivative chromosome. The reciprocal spatial disposition of sexual chromosome territories was investigated using whole chromosome painting and centromeres probes: patient's results didn't show a significant difference in comparison to normal controls. Conclusion The peculiar clinical case come to our attention highlighted the complexity of POF aetiology and of the translocation event, even if our results seem to exclude any effect on nuclear organisation. POF phenotype could be partially explained by skewed X chromosome inactivation that influences gene expression.

  9. Impact on prognosis of the regional distribution of MGMT methylation with respect to the CpG island methylator phenotype and age in glioma patients.

    Science.gov (United States)

    Mur, Pilar; Rodríguez de Lope, Ángel; Díaz-Crespo, Francisco Javier; Hernández-Iglesias, Teresa; Ribalta, Teresa; Fiaño, Concepción; García, Juan Fernando; Rey, Juan Antonio; Mollejo, Manuela; Meléndez, Bárbara

    2015-05-01

    Clinical and molecular prognostic factors in gliomas include age, IDH mutation, the glioma CpG island methylator phenotype (G-CIMP+) and promoter methylation of the O(6)-methylguanine DNA-methyltransferase (MGMT) gene. Among these markers, a predictive value was reported in glioblastomas (GBM) for MGMT promoter methylation, in particular in elderly GBM patients. In this study, methylation data from 46 glioma samples with the Illumina 450K platform were obtained and extended using external data to include a total of 247 glioma samples. Methylation analysis of the whole MGMT gene with this platform revealed two strongly survival-associated CpG regions within the promoter and the gene body, which were confirmed in a reported dataset of high grade-gliomas. Methylation at the promoter (CpG 25, cg12981137 and the prognostic model MGMT-STP27) and at the gene body CpG 165 (cg07933035), were significantly associated with better overall survival, and strongly correlated with G-CIMP+ status. In this series, the prognostic value of MGMT methylation at the promoter was not observed in G-CIMP- cases, although around 50 % of them were MGMT-methylated. These results were also obtained in an homogeneously-treated series of chemoradiated G-CIMP- GBMs analyzed by MSP and qMSP, and confirmed in a reported pyrosequencing-analyzed series of gliomas. Interestingly, in contrast to the MGMT promoter, gene body methylation was of prognostic value in G-CIMP-patients older than 65 years. Our study highlights the relevance of the prognostic value of the different regions of methylation throughout the MGMT gene that could be affected by specific G-CIMP profiles and age groups.

  10. Nuclear DNA methylation and chromatin condensation phenotypes are distinct between normally proliferating/aging, rapidly growing/immortal, and senescent cells.

    Science.gov (United States)

    Oh, Jin Ho; Gertych, Arkadiusz; Tajbakhsh, Jian

    2013-03-01

    This study reports on probing the utility of in situ chromatin texture features such as nuclear DNA methylation and chromatin condensation patterns - visualized by fluorescent staining and evaluated by dedicated three-dimensional (3D) quantitative and high-throughput cell-by-cell image analysis - in assessing the proliferative capacity, i.e. growth behavior of cells: to provide a more dynamic picture of a cell population with potential implications in basic science, cancer diagnostics/prognostics and therapeutic drug development. Two types of primary cells and four different cancer cell lines were propagated and subjected to cell-counting, flow cytometry, confocal imaging, and 3D image analysis at various points in culture. Additionally a subset of primary and cancer cells was accelerated into senescence by oxidative stress. DNA methylation and chromatin condensation levels decreased with declining doubling times when primary cells aged in culture with the lowest levels reached at the stage of proliferative senescence. In comparison, immortal cancer cells with constant but higher doubling times mostly displayed lower and constant levels of the two in situ-derived features. However, stress-induced senescent primary and cancer cells showed similar levels of these features compared with primary cells that had reached natural growth arrest. With regards to global DNA methylation and chromatin condensation levels, aggressively growing cancer cells seem to take an intermediate level between normally proliferating and senescent cells. Thus, normal cells apparently reach cancer-cell equivalent stages of the two parameters at some point in aging, which might challenge phenotypic distinction between these two types of cells. Companion high-resolution molecular profiling could provide information on possible underlying differences that would explain benign versus malign cell growth behaviors.

  11. Non-Lethal Ionizing Radiation Promotes Aging-Like Phenotypic Changes of Human Hematopoietic Stem and Progenitor Cells in Humanized Mice.

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    Changshan Wang

    Full Text Available Precise understanding of radiation effects is critical to develop new modalities for the prevention and treatment of radiation-induced damage. We previously reported that non-lethal doses of X-ray irradiation induce DNA damage in human hematopoietic stem and progenitor cells (HSPCs reconstituted in NOD/Shi-scid IL2rγnull (NOG immunodeficient mice and severely compromise their repopulating capacity. In this study, we analyzed in detail the functional changes in human HSPCs in NOG mice following non-lethal radiation. We transplanted cord blood CD34+ HSPCs into NOG mice. At 12 weeks post-transplantation, the recipients were irradiated with 0, 0.5, or 1.0 Gy. At 2 weeks post-irradiation, human CD34+ HSPCs recovered from the primary recipient mice were transplanted into secondary recipients. CD34+ HSPCs from irradiated mice showed severely impaired reconstitution capacity in the secondary recipient mice. Of interest, non-lethal radiation compromised contribution of HSPCs to the peripheral blood cells, particularly to CD19+ B lymphocytes, which resulted in myeloid-biased repopulation. Co-culture of limiting numbers of CD34+ HSPCs with stromal cells revealed that the frequency of B cell-producing CD34+ HSPCs at 2 weeks post-irradiation was reduced more than 10-fold. Furthermore, the key B-cell regulator genes such as IL-7R and EBF1 were downregulated in HSPCs upon 0.5 Gy irradiation. Given that compromised repopulating capacity and myeloid-biased differentiation are representative phenotypes of aged HSCs, our findings indicate that non-lethal ionizing radiation is one of the critical external stresses that promote aging of human HSPCs in the bone marrow niche.

  12. Partial correction of the dwarf phenotype by non-viral transfer of the growth hormone gene in mice: Treatment age is critical.

    Science.gov (United States)

    Higuti, Eliza; Cecchi, Cláudia R; Oliveira, Nélio A J; Lima, Eliana R; Vieira, Daniel P; Aagaard, Lars; Jensen, Thomas G; Jorge, Alexander A L; Bartolini, Paolo; Peroni, Cibele N

    2016-02-01

    Non-viral transfer of the growth hormone gene to different muscles of immunodeficient dwarf (lit/scid) mice is under study with the objective of improving phenotypic correction via this particular gene therapy approach. Plasmid DNA was administered into the exposed quadriceps or non-exposed tibialis cranialis muscle of lit/scid mice followed by electroporation, monitoring several growth parameters. In a 6-month bioassay, 50μg DNA were injected three times into the quadriceps muscle of 80-day old mice. A 50% weight increase, with a catch-up growth of 21%, together with a 16% increase for nose-to-tail and tail lengths (catch-up=19-21%) and a 24-28% increase for femur length (catch-up=53-60%), were obtained. mIGF1 serum levels were ~7-fold higher than the basal levels for untreated mice, but still ~2-fold lower than in non-dwarf scid mice. Since treatment age was found to be particularly important in a second bioassay utilizing 40-day old mice, these pubertal mice were compared in a third bioassay with adult (80-day old) mice, all treated twice with 50μg DNA injected into each tibialis cranialis muscle, via a less invasive approach. mIGF1 concentrations at the same level as co-aged scid mice were obtained 15days after administration in pubertal mice. Catch-up growth, based on femur length (77%), nose-to-tail (36%) and tail length (39%) increases was 40 to 95% higher than those obtained upon treating adult mice. These data pave the way for the development of more effective pre-clinical assays in pubertal dwarf mice for the treatment of GH deficiency via plasmid-DNA muscular administration.

  13. Effects of prematurity on language acquisition and auditory maturation: a systematic review.

    Science.gov (United States)

    Rechia, Inaê Costa; Oliveira, Luciéle Dias; Crestani, Anelise Henrich; Biaggio, Eliara Pinto Vieira; Souza, Ana Paula Ramos de

    2016-01-01

    To verify which damages prematurity causes to hearing and language. We used the decriptors language/linguagem, hearing/audição, prematurity/prematuridade in databases LILACS, MEDLINE, Cochrane Library and Scielo. randomized controlled trials, non-randomized intervention studies and descriptive studies (cross-sectional, cohort, case-control projects). The articles were assessed independently by two authors according to the selection criteria. Twenty-six studies were selected, of which seven were published in Brazil and 19 in international literature. Nineteen studies comparing full-term and preterm infants. Two of the studies made comparisons between premature infants small for gestational age and appropriate for gestational age. In four studies, the sample consisted of children with extreme prematurity, while other studies have been conducted in children with severe and moderate prematurity. To assess hearing, these studies used otoacoustic emissions, brainstem evoked potentials, tympanometry, auditory steady-state response and visual reinforcement audiometry. For language assessment, most of the articles used the Bayley Scale of Infant and Toddler Development. Most studies reviewed observed that prematurity is directly or indirectly related to the acquisition of auditory and language abilities early in life. Thus, it could be seen that prematurity, as well as aspects related to it (gestational age, low weight at birth and complications at birth), affect maturation of the central auditory pathway and may cause negative effects on language acquisition.

  14. [Premature ejaculation: pills or sexology?].

    Science.gov (United States)

    Wisard, M; Audette, N

    2008-03-26

    Premature ejaculation (PE) is a frequent male sexual complaint that affects 20 to 30% of men. The exact aetiology is unknown: psychological/behavioristic and biogenic etiologies have been proposed. The introduction of selective serotonin reuptake inhibitors (SSRI) was revolutionary in the medical treatment of PE. However precautions should be taken because of potential adverse side effects. There is no clear consensus as to whether SSRI may represent an eventual cure of PE or will be required for life. The sexocorporal approach is an other treatment of PE, but convincing scientific treatment data are also lacking.

  15. Positional moulding in premature hydrocephalics.

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    Kumar R

    2002-04-01

    Full Text Available Seven premature hydrocephalics presenting with lambdoid positional moulding (LPM were reviewed. All were treated for hydrocephalus secondary to aqueductal stenosis, Dandy Walker Syndrome and infection. Parenchymal hemorrhage, intraventricular bleed, cortical atrophy, septal agenesis, cortical anomalies and subdural hygroma were the other common associations. These children did not show expected improvement in their higher mental functions at 6 months to 5.4 years of follow-up, following the management of hydrocephalus. It was not the LPM but associated intracranial anomalies, which were most probably responsible for their poor outcome. The differentiation from posterior plagiocephaly is also highlighted.

  16. Metabolic bone disease of prematurity

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    Stacy E. Rustico, MD

    2014-09-01

    Full Text Available Metabolic bone disease (MBD of prematurity remains a significant problem for preterm, chronically ill neonates. The definition and recommendations for screening and treatment of MBD vary in the literature. A recent American Academy of Pediatrics Consensus Statement may help close the gap in institutional variation, but evidence based practice guidelines remain obscure due to lack of normative data and clinical trials for preterm infants. This review highlights mineral homeostasis physiology, current recommendations in screening and monitoring, prevention and treatment strategies, and an added perspective of a bone health team serving a high volume referral neonatal intensive care center.

  17. Current therapies for premature ejaculation.

    Science.gov (United States)

    Gur, Serap; Kadowitz, Philip J; Sikka, Suresh C

    2016-07-01

    Premature ejaculation (PE) subjectively affects 20-30% of men globally. Until recently, understanding of PE was hampered by the absence of a widely accepted definition, paucity of evidence-based clinical studies, and the absence of an appropriate animal model. Here, we elaborate on the current definition of PE, its pathogenesis, currently available therapies, and future treatment prospects. Most treatments for PE are 'off-label' and include selective serotonin reuptake inhibitors (SSRIs), topical anesthetics, tramadol, and phosphodiesterase type 5 (PDE5) inhibitors. Such knowledge of the benefit and limitations of each treatment will help to direct future drug design and formulations.

  18. The burden of premature mortality in Spain using standard expected years of life lost: a population-based study

    OpenAIRE

    Álvarez-Martín Elena; de Larrea-Baz Nerea; Catalá-López Ferrán; Gènova-Maleras Ricard; Morant-Ginestar Consuelo

    2011-01-01

    Abstract Background Measures of premature mortality have been used to guide debates on future health priorities and to monitor the population health status. Standard expected years of life lost (SEYLL) is one of the methods used to assess the time lost due to premature death. This article affords an overview of premature mortality in Spain for the year 2008. Methods A population-based study was conducted estimating SEYLL by sex and age groups. SEYLL, a key component of the disability-adjusted...

  19. Premature ventricular contractions associated with isotretinoin use.

    Science.gov (United States)

    Alan, Sevil; Ünal, Betül; Yildirim, Aytül

    2016-01-01

    Isotretinoin has been considered a unique drug for acne treatment. However, it is associated with numerous adverse effects. Isotretinoin can trigger premature ventricular contractions. This report describes a 33-year-old-woman who presented with palpitations for 1 week while undergoing 1-month isotretinoin treatment for mild-moderate facial acne. An electrocardiogram and Holter monitoring showed premature ventricular contractions during isotretinoin (Roaccutane, Roche) treatment. Isotretinoin-related premature ventricular contractions were strongly suggested in this case due to the existence of documented premature ventricular contractions on electrocardiograms and the disappearance of these premature ventricular contractions two weeks after termination of the treatment To the authors' knowledge, there has been 1 reported case of premature ventricular contractions linked to isotretinoin use; this report describes a second such case.

  20. Premature ventricular contractions associated with isotretinoin use*

    Science.gov (United States)

    Alan, Sevil; Ünal, Betül; Yildirim, Aytül

    2016-01-01

    Isotretinoin has been considered a unique drug for acne treatment. However, it is associated with numerous adverse effects. Isotretinoin can trigger premature ventricular contractions. This report describes a 33-year-old-woman who presented with palpitations for 1 week while undergoing 1-month isotretinoin treatment for mild-moderate facial acne. An electrocardiogram and Holter monitoring showed premature ventricular contractions during isotretinoin (Roaccutane, Roche) treatment. Isotretinoin-related premature ventricular contractions were strongly suggested in this case due to the existence of documented premature ventricular contractions on electrocardiograms and the disappearance of these premature ventricular contractions two weeks after termination of the treatment To the authors' knowledge, there has been 1 reported case of premature ventricular contractions linked to isotretinoin use; this report describes a second such case. PMID:28099609

  1. Comparative study of visual functions in premature pre-school children with and without retinopathy of prematurity

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    Lígia Beatriz Bonotto

    2014-01-01

    Full Text Available Purpose: Observe whether there are differences in visual functions among premature infants with treated retinopathy of prematurity (ROP in relation to preterm infants with ROP and spontaneous regression; and among these two groups with ROP and the control group without ROP. Methods: Crosssectional observational no blind study. Premature infants were born between 06/199206/2006 and were exam between 06/200912/2010; registered in data of Hospital de Olhos Sandalla Amin Ghanem; with gestational age less than or equal to 32 weeks and 1,599 g born weigh; without ROP and ROP stages II or III, in one of the eyes, with spontaneous regression or with treatment; at least three visits during the selection period at maximum 6 months in the first exam and minimum 4 years of age in reassessment (chronological age were include. Premature that did not respond or were not located for reassessment and those that did not have conditions to do the exams were exclude. Study's groups: G1 ROP posttreatment; G2ROP postspontaneous regression; G3 without ROP (control. Visual function evaluated with visual acuity (VA, contrast sensitivity test (CST, color test (CT, eye movement, stereopsis. Results: Overall, there were 24 premature infants and 48 eyes. Normal VA: 64.28% (G1, 87.5% (G2 and 100% (G3; Normal CST: 66.67% (G1, 100% (G2 and 55.56% (G3; Normal Ishihara CT: 100% (G1 and G2 and 86% (G3; Normal Farnsworth CT: 20% (G1, 75% (G2 and 50% (G3. Normal stereoacuity: 0.00% (G1; 25% (G2 and 3.5% (G3. Strabismus: 37% (G2, 0.00% (G1 and G3. The prevalent tendency for lower response in CST and CT between the premature children in group G3 and Farnsworth color test in G1 is a curious result of this work and more study is necessary about these visual functions in older premature children. Conclusion: The visual functions showed no statistically significant difference among the groups studied.

  2. Respiratory Failure in Premature Babies Born from Multiple Pregnancy

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    S. A. Perepelitsa

    2010-01-01

    Full Text Available Objective: to reveal the factors that are responsible for the development of respiratory distress syndrome (RDS and the specific features of its course in preterm twin neonates. Subjects and methods. Twenty-three patients who had had twin pregnancy, including 9 (39.1% and 14 (60% with monochorial and bichorial biamniotic twin pregnancies, respectively, were examined. Their mean age was 28.5±5.4 years. Obstetric and gynecologic histories, conditions at conception, the course of pregnancy, the type of pla-centation, and fetal presentation were considered. The placentas were morphologically examined. In all the patients, pregnancy ended in birth of 46 premature neonates, of them there were 19 (41.3% boys and 27 (58.7% girls. The gestational age of the neonates averaged 31.7±2.3 weeks. The evaluation of the efficiency of performed therapy used clinical assessment of the status of the premature neonates; measurement of partial oxygen tension (pO2 and calculation of alveolar-arterial oxygen gradient (A-a DO2, respiratory index (RI, and oxygenation index (OI; death rates were analyzed. Results. The main cause of respiratory failure (RF was RDS in premature twins. Neonatal blood aspiration-caused pneumonia occurred in one case. The course of RDS was variable. Most neonatal infants needed exogenous surfactant replacement therapy and mechanical ventilation (MV. No signs of RF were present in 7 (15.2% premature neonates. Conclusion. Premature twins are a high RDS risk group. The unfavorable factors that contribute to the development of the disease are multiple pregnancy, a past maternal obstetric history, in-vitro fertilization-induced pregnancy, severe gestosis in the second half of pregnancy, and preterm delivery. The type of placentation affects the fetal status after birth. Fatal outcome occurred in infants from the monochorial bioamniotic twins. In multiple pregnancies, there are pathological changes in the placenta, its membranes, and umbilical

  3. PERINATAL AND MATERNAL OUTCOME IN PREMATURE RUPTURE OF MEMBRANES

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    Mercy Rodrigo

    2016-06-01

    Full Text Available BACKGROUND The objectives of this study are 1 To find out the incidence of premature rupture of membranes, 2 To evaluate the aetiology of premature rupture of membranes, 3 To assess foetal and maternal outcome in premature rupture of membranes. MATERIAL AND METHODS This prospective case control study was conducted in Govt. RSRM Lying In Hospital, Chennai, over a period of 6 months and 100 cases of spontaneous rupture of membranes attending the Department of Obstetrics and Gynaecology were studied. Maternal and neonatal outcome were compared with controls. RESULTS Incidence of PROM was 9.06%. Most of them belonged to low socioeconomic class and in the age group 20-29 years, commonly seen primi gravida and in unbooked cases. Aetiological analysis revealed infection in 15% of cases, which is evident by positive amniotic fluid culture, h/o recent coitus in 20%, mal-presentation in 7%. Cause is unknown in most of the cases. The caesarean section rate is 24% when compared to 12% in control group. The PROM group had higher morbidities like postpartum haemorrhage, postpartum fever, wound infection, neonatal sepsis. CONCLUSION This study showed significantly increased morbidity for both mother and baby. PROM causes major increase in the incidence of prematurity, hence careful screening of high risk factors and treatment of infection promptly is needed to decrease the perinatal morbidity and mortality.

  4. Effect of vocal stimulation on responses of premature infants

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    Zahra Alipour

    2014-03-01

    Full Text Available Background and Objectives: There are studies that support music and singing as appropriate developmental care for premature infants, thus, we conducted this study to investigate the physiological and behavioral responses of premature infants to Quran recitation, lullaby music and silence. Methods: In a randomized controlled trial (2011-2012,120 premature infants in the Neonatal Unit (NNU at Izadi Hospital, were randomly assigned to experimental (holy Quran recitation, lullaby music and silence and control groups. The four groups were surveyed for physiological responses including, oxygen saturation, respiratory rate and heart rate and behavioral states. The data were analyzed using SPSS-PC software and quantitative tests. Results: 66females and 54 male infants with gestational age 28- 36 weeks entered into the study. The fourgroupswere not significantly different in terms of demographic variables (P>0.05. The comparisonofchangesinthe infant’s responsesintheendof the intervention comparedtothebase lines, showedno statistically significant differencesbetweengroups(P>0.05. Repeated measures ANOVA and Friedman test did notindicate any significant differences in the mean ofresponseswithinanyof the four groups during the courseof study (P>0.05. Conclusion: Although fluctuations were observed in the mean of physiological responses and behavioral states in premature infants who listened to the recitation of the holy Quran and lullaby music, but these fluctuations were not significant. Findings of this study demonstrated that the preterm infants did not display any adverse reactions to the carefully designed acoustic intervention.

  5. Delayed umbilical cord clamping in premature neonates.

    Science.gov (United States)

    Kaempf, Joseph W; Tomlinson, Mark W; Kaempf, Andrew J; Wu, YingXing; Wang, Lian; Tipping, Nicole; Grunkemeier, Gary

    2012-08-01

    Delayed umbilical cord clamping is reported to increase neonatal blood volume. We estimated the clinical outcomes in premature neonates who had delayed umbilical cord clamping compared with a similar group who had early umbilical cord clamping. This was a before-after investigation comparing early umbilical cord clamping with delayed umbilical cord clamping (45 seconds) in two groups of singleton neonates, very low birth weight (VLBW) (401-1,500 g) and low birth weight (LBW) (greater than 1,500 g but less than 35 weeks gestation). Neonates were excluded from delayed umbilical cord clamping if they needed immediate major resuscitation. Primary outcomes were provision of delivery room resuscitation, hematocrit, red cell transfusions, and the principle Vermont Oxford Network outcomes. In VLBW neonates (77 delayed umbilical cord clamping, birth weight [mean±standard deviation] 1,099±266 g; 77 early umbilical cord clamping 1,058±289 g), delayed umbilical cord clamping was associated with less delivery room resuscitation, higher Apgar scores at 1 minute, and higher hematocrit. Delayed umbilical cord clamping was not associated with significant differences in the overall transfusion rate, peak bilirubin, any of the principle Vermont Oxford Network outcomes, or mortality. In LBW neonates (172 delayed umbilical cord clamping, birth weight [mean±standard deviation] 2,159±384 g; 172 early umbilical cord clamping 2,203±447 g), delayed umbilical cord clamping was associated with higher hematocrit and was not associated with a change in delivery room resuscitation or Apgar scores or with changes in the transfusion rate or peak bilirubin. Regression analysis showed increasing gestational age and birth weight and delayed umbilical cord clamping were the best predictors of higher hematocrit and less delivery room resuscitation. Delayed umbilical cord clamping can safely be performed in singleton premature neonates and is associated with a higher hematocrit, less delivery room

  6. Temperament analysis of children combined with retinopathy of prematurity aged 3 years old%合并早产儿视网膜病变的儿童学龄前期气质特点

    Institute of Scientific and Technical Information of China (English)

    夏宁; 尹同进; 叶巍岭; 杨代秀

    2014-01-01

    目的 探讨合并不同程度早产儿视网膜病变(retinopathy of prematurity,ROP)幼儿期的气质特征,为临床早期干预提供理论依据.方法 采用Carry儿童气质问卷对46例合并不同程度ROP的早产儿在36月龄时进行测试,并与对照组46例进行比较.结果 合并ROP组患儿气质类型以抚养困难型与中间偏难型为主,在适应性、持久性、反应阈方面分值与对照组比较差异有统计学意义.结论 合并ROP的儿童有其自身的气质特点.

  7. Maternal panic disorder: Infant prematurity and low birth weight.

    Science.gov (United States)

    Warren, Susan L; Racu, Camellia; Gregg, Vanessa; Simmens, Samuel J

    2006-01-01

    The aim of this pilot research was to investigate whether infants of mothers with panic disorder (PD) would be at higher risk for prematurity and low birth weight (corrected for gestational age) than controls. Medical records were reviewed for 25 mothers with PD and 33 mothers without a lifetime history of anxiety disorders or other major psychopathology as determined by diagnostic interview. Mothers also completed questionnaires concerning demographic information and life stresses. Compared to controls, infants with PD mothers were not significantly more likely to be born prematurely or earlier than controls but did show smaller birth weight corrected for gestational age, even after accounting for possible confounding influences. Additional research is needed to confirm these preliminary findings. Studying PD mothers during pregnancy could provide insight concerning mechanisms for the development of low birth weight and psychopathology.

  8. The genetics of premature ovarian failure: current perspectives

    OpenAIRE

    2015-01-01

    Chevy Chapman, Lynsey Cree, Andrew N Shelling Department of Obstetrics and Gynecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand Abstract: Premature ovarian failure (POF) is a common cause of infertility in women, characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women under the age of 40. Many genes have been identified over the past few years that contribute to the development of POF. However, few genes have been ...

  9. Psychosocial determinants of premature cardiovascular mortality differences within Hungary

    Science.gov (United States)

    Kopp, Maria; Skrabski, Árpád; Szántó, Zsuzsa; Siegrist, Johannes

    2006-01-01

    Objectives The life expectancy gap between Central‐Eastern European (CEE) countries, including Hungary, and Western Europe (WE) is mainly attributable to excess cardiovascular (CV) mortality in midlife. This study explores the contribution of socioeconomic, work related, psychosocial, and behavioural variables to explaining variations of middle aged male and female CV mortality across 150 sub‐regions in Hungary. Design Cross sectional, ecological analyses. Setting 150 sub‐regions of Hungary. Participants and methods 12 643 people were interviewed in Hungarostudy 2002 survey, representing the Hungarian population according to sex, age, and sub‐regions. Independent variables were income, education, control in work, job insecurity, weekend working hours, social support, depression, hostility, anomie, smoking, body mass index, and alcohol misuse. Main outcome measures Gender specific standardised premature (45–64 years) total CV, ischaemic heart disease, and cerebrovascular mortality rates in 150 sub‐regions of Hungary. Results Low education and income were the most important determinants of mid‐aged CV mortality differences across sub‐regions. High weekend workload, low social support at work, and low control at work account for a large part of variation in male premature CV mortality rates, whereas job insecurity, high weekend workload, and low control at work contribute most noticeably to variations in premature CV mortality rates among women. Low social support from friends, depression, anomie, hostility, alcohol misuse and cigarette smoking can also explain a considerable part of variations of premature CV mortality differences. Conclusion Variations in middle aged CV mortality rates in a rapidly changing society in CEE are largely accounted for by distinct unfavourable working and other psychosocial stress conditions. PMID:16905723

  10. Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination

    OpenAIRE

    Deirdre Therese Little MBBS, DRANZCOG, FACRRM; Harvey Rodrick Grenville Ward Bsc(Med), MBChB, DMCOG, FCOG(SA), MMed (O&G), FRANZCOG

    2014-01-01

    Three young women who developed premature ovarian insufficiency following quadrivalent human papillomavirus (HPV) vaccination presented to a general practitioner in rural New South Wales, Australia. The unrelated girls were aged 16, 16, and 18 years at diagnosis. Each had received HPV vaccinations prior to the onset of ovarian decline. Vaccinations had been administered in different regions of the state of New South Wales and the 3 girls lived in different towns in that state. Each had been p...

  11. Long Latency Auditory Evoked Potential in Term and Premature Infants

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    Didoné, Dayane Domeneghini

    2014-01-01

    Full Text Available Introduction The research in long latency auditory evokes potentials (LLAEP in newborns is recent because of the cortical structure maturation, but studies note that these potentials may be evidenced at this age and could be considered as indicators of cognitive development. Purpose To research the exogenous potentials in term and premature infants during their first month of life. Materials and Methods The sample consisted of 25 newborns, 15 term and 10 premature infants. The infants with gestational age under 37 weeks were considered premature. To evaluate the cortical potentials, the infants remained in natural sleep. The LLAEPs were researched binaurally, through insertion earphones, with frequent /ba/ and rare /ga/ speech stimuli in the intensity of 80 dB HL (decibel hearing level. The frequent stimuli presented a total of 80% of the presentations, and the rare, 20%. The data were statistically analyzed. Results The average gestational age of the term infants was 38.9 weeks (± 1.3 and for the premature group, 33.9 weeks (± 1.6. It was possible to observe only the potentials P1 and N1 in both groups, but there was no statistically significant difference for the latencies of the components P1 and N1 (p > 0.05 between the groups. Conclusion It was possible to observe the exogenous components P1 and N1 of the cortical potentials in both term and preterm newborns of no more than 1 month of age. However, there was no difference between the groups.

  12. Premature senescence in primary muscle cultures of myotonic dystrophy type 2 is not associated with p16 induction

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    L.V. Renna

    2014-10-01

    Full Text Available Myotonic dystrophy type 1 (DM1 and type 2 (DM2 are multisystemic disorders linked to two different genetic loci and characterized by several features including myotonia, muscle weakness and atrophy, cardiac dysfunctions, cataracts and insulin-resistance. In both forms, expanded nucleotide sequences cause the accumulation of mutant transcripts in the nucleus deregulating the activity of some RNAbinding proteins and providing an explanation for the multisystemic phenotype of DM patients. However this pathogenetic mechanism does not explain some histopathological features of DM skeletal muscle like muscle atrophy. It has been observed that DM muscle shares similarities with the ageing muscle, where the progressive muscle weakness and atrophy is accompanied by a lower regenerative capacity possibly due to the failure in satellite cells activation. The aim of our study is to investigate if DM2 satellite cell derived myoblasts exhibit a premature senescence as reported for DM1 and if alterations in their proliferation potential and differentiation capabilities might contribute to some of the histopathological features observed in DM2 muscles. Our results indicate that DM myoblasts have lower proliferative capability than control myoblasts and reach in vitro senescence earlier than controls. Differentely from DM1, the p16 pathway is not responsible for the premature growth arrest observed in DM2 myoblasts which stop dividing with telomeres shorter than controls. During in vitro senescence, a progressive decrease in fusion index is observable in both DM and control myotubes with no significant differences between groups. Moreover, myotubes obtained from senescent myoblasts appear to be smaller than those from young myoblasts. Taken together, our data indicate a possible role of DM2 premature myoblast senescence in skeletal muscle histopathological alterations i.e., dystrophic changes and type 2 fibre atrophy.

  13. Economic evaluation of caffeine for apnea of prematurity.

    Science.gov (United States)

    Dukhovny, Dmitry; Lorch, Scott A; Schmidt, Barbara; Doyle, Lex W; Kok, Joke H; Roberts, Robin S; Kamholz, Karen L; Wang, Na; Mao, Wenyang; Zupancic, John A F

    2011-01-01

    To determine the cost-effectiveness of treatment with caffeine compared with placebo for apnea of prematurity in infants with birth weights less than 1250 g, from birth through 18 to 21 months' corrected age. We undertook a retrospective economic evaluation of the cost per survivor without neurodevelopmental impairment by using individual-patient data from the Caffeine for Apnea of Prematurity clinical trial (N = 1869). We included direct medical costs either to the insurance payer or the hospital but excluded costs to parents and society, such as lost productivity. We used a price of $0.21/mg of generic caffeine citrate for our base-case analysis. All costs were expressed in 2008 Canadian dollars and discounted at 3%. The time horizon for this analysis extended through 18 to 21 months' corrected age to match the clinical trial. The mean cost per infant was $124 466 in the caffeine group and $133 505 in the placebo group (difference: $9039 [-14 749 to -3375]; adjusted P = .014). Cost-effectiveness analysis showed caffeine to be a dominant or "win-win" therapy: in >99% of 1000 bootstrap replications of the analysis, caffeine-treated infants had simultaneously better outcomes and lower mean costs. These results were robust to a 1000% increase in the individual resource items, including the price of caffeine citrate. In comparison with placebo, caffeine therapy for apnea of prematurity in infants weighing less than 1250 g is economically appealing for infants up to 18 to 21 months' corrected age.

  14. The relation between oxygen saturation level and retionopathy of prematurity

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    Mohammad Gharavi Fard

    2016-03-01

    Full Text Available Introduction: Oxygen therapy used for preterm infant disease might be associated with oxygen toxicity or oxidative stress. The exact oxygen concentration to control and maintain the arterial oxygen saturation balance is not certainly clear. We aimed to compare the efficacy of higher or lower oxygen saturations on the development of severe retinopathy of prematurity which is a major cause of blindness in preterm neonates. Methods: PubMed was searched for obtaining the relevant articles. A total of seven articles were included after studying the titles, abstracts, and the full text of retrieved articles at initial search. Inclusion criteria were all the English language human clinical randomized controlled trials with no time limitation, which studied the efficacy of low versus high oxygen saturation measured by pulse oximetry in preterm infants.Result: It can be suggested that lower limits of oxygen saturations have higher efficacy at postmesetural age of ≤28 weeks in preterm neonates. This relation has been demonstrated in five large clinical trials including three Boost trials, COT, and Support.Discussion: Applying higher concentrations of oxygen supplementations at mesentural age ≥32 weeks reduced the development of retinopathy of prematurity. Lower concentrations of oxygen saturation decreased the incidence and the development of retinopathy of prematurity in preterm neonates while applied soon after the birth.Conclusions: Targeting levels of oxygen saturation in the low or high range should be performed cautiously with attention to the postmesentural age in preterm infants at the time of starting the procedures.

  15. Study on the relationship between retinopathy of prematurity and maternal age,smoking during pregnancy,drugs and pregnancy complications%早产儿视网膜病变与孕妇年龄、孕期吸烟、药物、妊娠并发症的关系研究

    Institute of Scientific and Technical Information of China (English)

    熊永强; 刘生荣; 陈立宇; 吕月娥; 陈美玲; 周俊楠

    2011-01-01

    Objective: To explore the relationship between the occurrence of retinopathy of prematurity (ROP) and hazard factorsduring pregnancy including maternal age, smoking during pregnancy, drugs and pregnancy complications. Methods: 829 premature infants visiting the hospital from January 2008 to April 2010 received fundus examination regularly. International staging system of ROP was used for diagnosis and staging of ROP. The related clinical data of pregnant women were collected. Results: Among 829 premature infants, 97 infants were diagnosed as ROP, the incidence was 11.7%. There was no significant difference in maternal age and drug use during pregnancy, there was significant difference in smoking during pregnancy and pregnancy complicationa, multivariate logistic analysis showed that there was a significant correlation between smoking, pregnancy complications and the occurrence of ROP. Conclusion: Smoking and pregnancy complications are important risk factors of ROP during pregnancy.%目的:探讨早产儿视网膜病变(ROP)的发生与孕妇年龄、孕期吸烟、药物、妊娠并发症等孕期危害因素的关系.方法:对2008年1月~2010年4月在厦门市妇幼保健院收治的829例早产儿定期进行眼底检查,根据ROP国际分期标准进行ROP的诊断和分期,并收集孕妇孕期相关临床资料.结果,829例早产儿中ROP的患儿为97例,患病率为11.70%.孕妇年龄、孕期服用药物无明显差异,而孕期吸烟和妊娠期并发症差异有统计学意义,经进一步多因素Logistic回归分析显示吸烟、妊娠并发症与ROP发生有显著相关性.结论:吸烟和妊娠并发症是孕期导致ROP发病的高危因素.

  16. Developmental Outcomes of Premature and Low Birth Weight Infants

    Directory of Open Access Journals (Sweden)

    Reza Saeidi

    2016-03-01

    Full Text Available Background: Prematurity is the most common cause of death and disability And Preterm infants, are prone to developmental complications. For this reason this study was designed for follow up of these babies until 2 years by modified DDST-2. Methods: This study was a prospective longitudinal descriptive study from March 2009 to March 2011 in clinic of sheikh and Imam Reza Hospitals, mashhad, Iran. Sample size with Confidence coefficient of 95% and power 80%, was determined 100 hundred babies. Infants were seen by a pediatrician at a follow up clinic at 1, 3, 6, 9,12,15,18, 24, months.The developmental assessment was done using Denver-2 Developmental Screening Test. Results: mean age for smiling was 4/6 ± 2/1  months which significantly differed with appropriate age (p = 0.000, mean age for telling two syllables words 11/7±  1/9 months, without significant difference of appropriate age.(p = 0.139. Average age for understanding NO was 10/4±  2/0 months that significantly differed with appropriate age(p = 0.000. The average age for telling 6 word was 17/8±  3/0, without significant difference with appropriate age (p = 0.510. Conclusion: Children with history of prematurity and low birth weight have more disability and developmental delay so they need to developmental screening tests.

  17. Sexual function of premature ejaculation patients assayed with Chinese Index of Premature Ejaculation

    Institute of Scientific and Technical Information of China (English)

    Yi-MingYuan; Zhong-ChengXin; HuiJiang; Yan-JieGuo; Wu-JiangLiu; LongTian; Ji-ChuanZhu

    2004-01-01

    Aim: To assess the psychometric properties of the Chinese Index of Premature Ejaculation (CIPE).Methods: The sexual function of 167 patients with and 114 normal controls without premature ejaculation (PE) were evaluated with CIPE. All subjects were married and had regular sexual activity. The CIPE has 10 questions, focusing on libido, erectile function, ejaculatory latency, sexual satisfaction and difficulty in delaying ejaculation, self-confidence and depression. Each question was responded to on a 5 point Likert-type scale. The individual question score and the total scale score were analyzed between the two groups. Results: There were no significant differences between the age, duration of marriage and educational level (P>0.05) of patients with and without PE and normal controls. The mean latency of patients with PE and normal controls were 1.6±1.2 and 10.2±9.5 minutes,respectively. Significant differences between patients with (26.7±4.6) PE and normal controls (41.9±4.0) were observed on the total score of CIPE (P15 point) 19.8%, moderate (10~14 point) 62.8% and severe (<9point) 16.7%. Conclusion:The CIPE-5 is a useful method for the evaluation of sexual function of patients with PE and can be used as a clinical endpoint for clinical trials studying the efficacy of pharmacological intervention.

  18. The DFNA10 phenotype.

    NARCIS (Netherlands)

    Leenheer, E. de; Huygen, P.L.M.; Wayne, S.; Smith, R.J.H.; Cremers, C.W.R.J.

    2001-01-01

    We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available last-

  19. 7 CFR 29.2290 - Premature primings.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Premature primings. 29.2290 Section 29.2290 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... 21) § 29.2290 Premature primings. Ground leaves harvested before reaching complete growth and...

  20. 28 CFR 51.22 - Premature submissions.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Premature submissions. 51.22 Section 51.22 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF... § 51.22 Premature submissions. The Attorney General will not consider on the merits: (a) Any proposal...

  1. Serbia within the European context: An analysis of premature mortality.

    Science.gov (United States)

    Santric Milicevic, Milena; Bjegovic, Vesna; Terzic, Zorica; Vukovic, Dejana; Kocev, Nikola; Marinkovic, Jelena; Vasic, Vladimir

    2009-08-05

    Based on the global predictions majority of deaths will be collectively caused by cancer, cardiovascular diseases, and traffic accidents over the coming 25 years. In planning future national health policy actions, inter - regional assessments play an important role. The purpose of the study was to analyze similarities and differences in premature mortality between Serbia, EURO A, EURO B, and EURO C regions in 2000. Mortality and premature mortality patterns were analysed according to cause of death, by gender and seven age intervals. The study results are presented in relative (%) and absolute terms (age-specific and age-standardized death rates per 100,000 population, and age-standardized rates of years of life lost - YLL per 1,000). Direct standardization of rates was undertaken using the standard population of Europe. The inter-regional comparison was based on a calculation of differences in YLL structures and with a ratio of age-standardized YLL rates per 1,000. A multivariate generalized linear model was used to explore mortality of Serbia and Europe sub-regions with ln age-specific death rates. The dissimilarity was achieved with a p death case. YLL patterns indicated similarities between Serbia and EURO A, while SRR YLL had similarities between Serbia and EURO B. Compared to all Europe sub-regions, Serbia had a major excess of premature mortality in neoplasms and diabetes mellitus. Serbia had lost more years of life than EURO A due to cardiovascular, genitourinary diseases, and intentional injuries. Yet, Serbia was not as burdened with communicable diseases and injuries as were EURO B and EURO C. With a premature mortality pattern, Serbia is placed in the middle position of the Europe triangle. The main excess of YLL in Serbia was due to cardiovascular, malignant diseases, and diabetes mellitus. The results may be used for assessment of unacceptable social risks resulting from health inequalities. Within intentions to reduce an unfavourable premature

  2. Serbia within the European context: An analysis of premature mortality

    Directory of Open Access Journals (Sweden)

    Marinkovic Jelena

    2009-08-01

    Full Text Available Abstract Background Based on the global predictions majority of deaths will be collectively caused by cancer, cardiovascular diseases, and traffic accidents over the coming 25 years. In planning future national health policy actions, inter – regional assessments play an important role. The purpose of the study was to analyze similarities and differences in premature mortality between Serbia, EURO A, EURO B, and EURO C regions in 2000. Methods Mortality and premature mortality patterns were analysed according to cause of death, by gender and seven age intervals. The study results are presented in relative (% and absolute terms (age-specific and age-standardized death rates per 100,000 population, and age-standardized rates of years of life lost – YLL per 1,000. Direct standardization of rates was undertaken using the standard population of Europe. The inter-regional comparison was based on a calculation of differences in YLL structures and with a ratio of age-standardized YLL rates per 1,000. A multivariate generalized linear model was used to explore mortality of Serbia and Europe sub-regions with ln age-specific death rates. The dissimilarity was achieved with a p ≤ 0.05. Results According to the mortality pattern, Serbia was similar to EURO B, but with a lower average YLL per death case. YLL patterns indicated similarities between Serbia and EURO A, while SRR YLL had similarities between Serbia and EURO B. Compared to all Europe sub-regions, Serbia had a major excess of premature mortality in neoplasms and diabetes mellitus. Serbia had lost more years of life than EURO A due to cardiovascular, genitourinary diseases, and intentional injuries. Yet, Serbia was not as burdened with communicable diseases and injuries as were EURO B and EURO C. Conclusion With a premature mortality pattern, Serbia is placed in the middle position of the Europe triangle. The main excess of YLL in Serbia was due to cardiovascular, malignant diseases, and

  3. Telomeres, telomerase and premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Renata Košir Pogačnik

    2011-11-01

    Full Text Available Telomeres are specialized structures at the ends of chromosomes, consisting of six repeated nucleotides in TTAGGG sequence. Genome stability is partly maintained by the architecture of telomeres and is gradually lost as telomeres progressively shorten with each cell replication. Critically shortened telomeres are recognized by DNA repair mechanisms as DNA damage and the cell replication cycle stops. The cell eventually dies or undergoes cell apoptosis. Telomere represents a cellular marker of biological age and are therefore also called cell mitotic clock. The enzyme that counteracts telomere shortening by adding nucleotides to the 3’ end of DNA strand is called telomerase. It is composed of the RNA subunit (TR, which is special type of messenger RNA (mRNA, the catalytic protein subunit (TERT, which works as a reverse transcriptase and numerous additional proteins. Telomerase is active in some germline, epithelial and haemopoietic cells, but in most somatic cells the activity is undetectable. In literature, the length of telomeres is closely connected with premature ovarian failure (POF. POF is generally defined as the onset of menopause before the age of 40. The causes of disease are genetical, autoimmune, iatrogenic or if we cannot establish the cause – idiopathic. A lot of studies examined correlation between idiopathic POF, length of telomeres and telomerase activity. The studies mostly show that women with POF have shortened telomeres and decreased activity of telomerase as compared to healthy women.

  4. Evolución del riesgo de mortalidad fetal tardía, prematuridad y bajo peso al nacer, asociado a la edad materna avanzada, en España (1996-2005 Trends in the risk of late fetal mortality, prematurity and low birth weight associated with advanced maternal age in Spain (1996-2005

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Luque Fernández

    2008-10-01

    Full Text Available Objetivos: Describir la evolución de la fecundidad, la mortalidad fetal tardía, la prematuridad y el bajo peso al nacer, así como su asociación con la edad materna avanzada, en España, durante el período 1996-2005. Métodos: Estudio ecológico. La prematuridad y el bajo peso en función de la edad materna se analizan mediante tablas de contingencia. La evolución de las tasas de mortalidad fetal tardía se analiza mediante una estandarización directa. El riesgo de mortalidad fetal tardía, ajustado por la edad materna y la prematuridad, se analiza mediante una regresión de Poisson. Resultados: Las tasas de mortalidad fetal tardía y de fecundidad han aumentado en las mujeres de más de 35 años de edad, sobre todo en las mayores de 45 años. El riesgo de mortalidad fetal tardía es 2,7 veces superior para las mujeres a partir de los 45 años (razón de tasas: 2,7; intervalo de confianza del 95% [IC95%]: 1,8-3,0, con una fracción etiológica de la exposición del 69% (IC95%: 55,2-78,6. La prevalencia de prematuridad y de bajo peso para este mismo grupo es 3 veces superior, con una razón de prevalencias de prematuridad de 2,9 (IC95%: 2,7-3,1 y de bajo peso de 3,1 (IC95%: 2,9-3,3. Conclusiones: El elevado riesgo de las mujeres de 45 o más años de edad se explica por el aumento de la proporción de embarazos en este grupo de edad. Se requieren nuevos estudios, en el ámbito de la epidemiología perinatal, que analicen el impacto de las técnicas de reproducción asistida en los embarazos a edades avanzadas, así como la dinamización de la puesta en marcha del registro nacional de técnicas de reproducción asistida.Objectives: To describe trends in fertility, fetal death rate, prematurity and low birth weight, as well as their association with advanced maternal age, in Spain from 1996 to 2005. Methods: We performed an ecological study. The association between low birth weight and prematurity with maternal age was analyzed through

  5. The relationship of the subtypes of preterm birth with retinopathy of prematurity.

    Science.gov (United States)

    Lynch, Anne M; Wagner, Brandie D; Hodges, Jennifer K; Thevarajah, Tamara S; McCourt, Emily A; Cerda, Ashlee M; Mandava, Naresh; Gibbs, Ronald S; Palestine, Alan G

    2017-09-01

    Retinopathy of prematurity is an adverse outcome of preterm birth and is a leading cause of childhood blindness. The relationship between the subtypes of preterm birth with retinopathy of prematurity is understudied. To investigate whether there is a difference in the incidence of type 1 or type 2 retinopathy of prematurity in infants with preterm birth resulting from spontaneous preterm labor, a medical indication of preterm birth, or preterm premature rupture of the membranes. A retrospective cohort study was conducted of 827 infants screened for retinopathy of prematurity who were delivered at a single tertiary care center in Colorado. All infants fulfilled the American Academy of Pediatrics 2013 screening criteria for retinopathy of prematurity defined as "infants with a birth weight of ≤1500 g or gestational age of 30 weeks or less (as defined by the attending neonatologist) and selected infants with a birth weight between 1500 and 2000 g or gestational age of >30 weeks with an unstable clinical course, including those requiring cardiorespiratory support and who are believed by their attending pediatrician or neonatologist to be at high risk for retinopathy of prematurity." Two independent reviewers masked to retinopathy of prematurity outcomes determined whether preterm birth resulted from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes. Discrepancies were resolved by a third reviewer. Data were analyzed with univariate and multivariable logistic regression. In our cohort, the frequency of preterm birth resulting from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes was 34%, 40%, and 26%, respectively. The mean gestational age (weeks, days) ± SD (range) in the cohort and across the preterm birth subtypes was as follows: entire cohort, 28 weeks, 6 days ± 2 weeks, 3 days (23 weeks, 3 days - 36 weeks, 4 days); spontaneous preterm labor

  6. Premature Ventricular Complexes and Premature Ventricular Complex Induced Cardiomyopathy.

    Science.gov (United States)

    Latchamsetty, Rakesh; Bogun, Frank

    2015-09-01

    Presentation, prognosis, and management of premature ventricular complexes (PVCs) vary significantly among patients and depend on PVC characteristics as well as patient comorbidities. Presentation can range from incidental discovery in an asymptomatic patient to debilitating heart failure. Prognosis depends on, among other factors, the presence or absence of structural heart disease, PVC burden and other factors detailed in this review. Our understanding of the clinical significance of frequent PVCs, particularly as it relates to development of cardiomyopathy, has advanced greatly in the past decade. In this article, we explore the mechanisms governing PVC initiation and discuss prevalence and frequency of PVCs in the general population. We also explore prognostic implications based on PVC frequency as well as the presence or absence of underlying heart disease. We then take a focused look at PVC-induced cardiomyopathy and identify predictors for developing cardiomyopathy. Finally, we discuss clinical evaluation and management of patients presenting with frequent PVCs. Management can include clinical observation, addressing reversible causes, lifestyle modification, pharmacotherapy, or catheter ablation.

  7. Inflammatory and oxidative stress airway markers in premature newborns of hypertensive mothers.

    Science.gov (United States)

    Madoglio, R J; Rugolo, L M S S; Kurokawa, C S; Sá, M P A; Lyra, J C; Antunes, L C O

    2016-08-01

    Although oxidative stress and inflammation are important mechanisms in the pathophysiology of preeclampsia and preterm diseases, their contribution to the respiratory prognosis of premature infants of hypertensive mothers is not known. Our objective was to determine the levels of oxidative stress and inflammation markers in the airways of premature infants born to hypertensive and normotensive mothers, in the first 72 h of life, and to investigate whether they are predictors of bronchopulmonary dysplasia (BPD)/death. This was a prospective study with premature infants less than 34 weeks' gestation on respiratory support who were stratified into 2 groups: 32 premature infants of hypertensive mothers and 41 of normotensive women, with a mean gestational age of 29 weeks. Exclusion criteria were as follows: diabetes mellitus, chorioamnionitis, malformation, congenital infection, and death within 24 h after birth. The outcome of interest was BPD/death. Malondialdehyde (MDA), nitric oxide (NO), and interleukin 8 (IL-8) were measured in airway aspirates from the first and third days of life and did not differ between the groups. Univariate and multivariate statistical analyses were performed. The concentrations of MDA, NO, and IL-8 were not predictors of BPD/death. Premature infants who developed BPD/death had higher levels of IL-8 in the first days of life. The gestational age, mechanical ventilation, and a small size for gestational age were risk factors for BPD/death. In conclusion, the biomarkers evaluated were not increased in premature infants of hypertensive mothers and were not predictors of BPD/death.

  8. Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity

    Science.gov (United States)

    Pancham, Krishna; Sami, Iman; Perez, Geovanny F.; Huseni, Shehlanoor; Kurdi, Bassem; Rose, Mary C.; Rodriguez-Martinez, Carlos E.; Nino, Gustavo

    2017-01-01

    Rationale Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same of Respiratory Syncytial Virus (RSV). Premature children are at high risk of severe RSV infections, but it is unclear whether HMPV infection is more severe in hospitalized children with history of severe prematurity. Methods We conducted a retrospective analysis of the clinical respiratory presentation of all PCR-confirmed HMPV infections in preschool age children (≤5 yrs.) with and without history of severe prematurity (<32 weeks gestation). Respiratory distress scores were developed to examine the clinical severity of HMPV infections. Demographic and clinical variables were obtained from reviewing electronic medical records (EMR). Results A total of 571 pre-school children were identified by PCR-confirmed viral respiratory tract infection during the study period. HMPV was identified as a causative organism in 63 cases (11%). Fifty–eight (n=58) preschool age children with HMPV infection were included in this study after excluding those with significant co-morbidities. Our data demonstrated that 32.7% of children admitted with HMPV had history of severe prematurity. Preschool children with history of prematurity had more severe HMPV disease as illustrated by longer hospitalizations, new or increased need for supplemental O2, and higher severity scores independently of age, ethnicity and history of asthma. Conclusion Our study suggests that HMPV infection causes significant disease burden among preschool children with history of prematurity leading to severe respiratory infections and increasing health care resource utilization due to prolonged hospitalizations. PMID:26117550

  9. Mouse phenotyping.

    Science.gov (United States)

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Can prematurity risk in twin pregnancies after in vitro fertilization be predicted? A retrospective study

    Directory of Open Access Journals (Sweden)

    Barad David

    2009-01-01

    Full Text Available Abstract Background Assisted reproduction (ART contributes to world-wide increases of twin pregnancies, in turn raising prematurity risks. Whether characteristics of ART cycles, resulting in twin gestations, can predict prematurity risks was the subject of this study. Methods One-hundred-and-six women, ages 20 to 39 years, with consecutive dichorionic-diamniotic (DC/DA twin gestations were retrospectively investigated. All pregnancies investigated followed fresh ART cycles, with use of autologous gamets, and were delivered at a university-based high-risk, maternal-fetal medicine unit. Only premature deliveries (i.e., <37.0 weeks gestational age, with viable neonate(s of ≥ 500 grams, were considered for analysis. Results After 1.8 +/- 1.2 ART cycles, 11.0 +/- 5.4 oocytes were retrieved and 2.4 +/- 0.9 embryos transferred in 106 women aged 31.6 +/- 4.2 years. Indications for ART treatment were male factor in 51.9%, female infertility in 27.4% and combined infertility in 20.8%. Though maternal age significantly influenced prematurity risk (p < 0.05, paternal age, maternal body mass index, indications for fertility treatment, number of previous ART attempts, oocytes retrieved or embryos transferred, as well as stimulation protocols and previous ART pregnancies, were not associated with gestational duration in twin pregnancies. Summary Except for female age, baseline and ART cycle characteristics do not allow for prediction of prematurity risk in dichorionic twin gestations after assisted reproduction.

  11. Visual and visuocognitive development in children born very prematurely.

    Science.gov (United States)

    Atkinson, Janette; Braddick, Oliver

    2007-01-01

    Preterm birth is a risk factor for deficits of neurological and cognitive development. Four cohort studies are reported investigating the effects of very premature birth (development correlated with the severity of brain abnormality observed on structural MRI at and before term, and were sensitive predictors of neurodevelopmental outcome at 2 years. The second study compared VERP measures for orientation-reversal and direction-reversal (DR) stimuli, from 2 to 5 months post-term age, in healthy very premature infants compared to infants born at term. The groups did not differ on the development of OR-VERP responses, but the development of the DR-VERP motion responses was delayed in the premature group despite the absence of any brain damage visible on ultrasound, consistent with the developmental vulnerability we have identified in the dorsal cortical stream. The third study used the Atkinson Battery of Child Development for Examining Functional Vision (ABCDEFV) to assess sensory, perceptual, cognitive and spatial visual functions, together with preschool tests of attention and executive function. The premature group showed delays on these tests in line with severity of observed perinatal brain damage on structural MRI at term age. Deficits on certain spatial tasks (e.g. block-construction copying) and executive function tests (e.g. the detour box task) were apparent even in children with minimal damage apparent on MRI. The fourth study tested a large cohort of 6- to 7-year old children born before 32 weeks gestation, across a wide range of cognitive domains, including new tests of spatial cognition and memory. The premature group as a whole showed significant deficits on both auditory and visual tests of attention and attentional control from the TEA-Ch battery, on tests of location memory, block construction and on many visuocognitive and visuomotor tests. Development was generally relatively normal on language tests and on WPPSI scores. Factor analysis showed

  12. Premature ovarian failure risk factors in an Iranian population

    Directory of Open Access Journals (Sweden)

    Ghassemzadeh A

    2012-04-01

    Full Text Available Alieh Ghassemzadeh1,2, Laya Farzadi1,2, Elaheh Beyhaghi1,21Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Alzahra University Hospital, Department of Obstetrics and Gynecology, Tabriz University of Medical Sciences, Tabriz, IranBackground: The aim of this study was to determine possible correlates of premature ovarian failure (POF in an Iranian population.Methods: In a case-control study, 80 patients with POF were compared with 80 controls enrolled from the same setting during 2007–2008. A food diary was used to assess food consumption habits.Results: Mean age of starting ovarian failure symptoms was 19.3 ± 5.7 years and mean age of menopause was 22.6 ± 6.3 years. Familial coincidence was observed in 16 POF patients versus no one in the control group (P < 0.05. POF patients had lower frequency of both eating red meat and fish when compared with controls (P < 0.001. POF and control subjects consumed similar amounts of dairy products, being 5.3 ± 3.2 times per week in POF and 5.6 ± 2.1 times in the control groups.Conclusion: In this study, an association between POF and lower red meat or fish consumption was found.Keywords: POF, etiology, case-control, nutrition, premature menopause, premature ovarian dysfunction, primary ovarian insufficiency

  13. Accuracy of Transcutaneous Carbon Dioxide Measurement in Premature Infants.

    Science.gov (United States)

    Janaillac, Marie; Labarinas, Sonia; Pfister, Riccardo E; Karam, Oliver

    2016-01-01

    Background. In premature infants, maintaining blood partial pressure of carbon dioxide (pCO2) value within a narrow range is important to avoid cerebral lesions. The aim of this study was to assess the accuracy of a noninvasive transcutaneous method (TcpCO2), compared to blood partial pressure of carbon dioxide (pCO2). Methods. Retrospective observational study in a tertiary neonatal intensive care unit. We analyzed the correlation between blood pCO2 and transcutaneous values and the accuracy between the trends of blood pCO2 and TcpCO2 in all consecutive premature infants born at <33 weeks' gestational age. Results. 248 infants were included (median gestational age: 29 + 5 weeks and median birth weight: 1250 g), providing 1365 pairs of TcpCO2 and blood pCO2 values. Pearson's R correlation between these values was 0.58. The mean bias was -0.93 kPa with a 95% confidence limit of agreement of -4.05 to +2.16 kPa. Correlation between the trends of TcpCO2 and blood pCO2 values was good in only 39.6%. Conclusions. In premature infants, TcpCO2 was poorly correlated to blood pCO2, with a wide limit of agreement. Furthermore, concordance between trends was equally low. We warn about clinical decision-making on TcpCO2 alone when used as continuous monitoring.

  14. Psychosocial interventions for premature ejaculation

    Directory of Open Access Journals (Sweden)

    Tamara Melnik

    Full Text Available BACKGROUND: Premature ejaculation (PE is a very common sexual dysfunction among patients, and with varying prevalence estimates ranging from 3% to 20%. Although psychological issues are present in most patients with premature PE, as a cause or as a consequence, research on the effects of psychological approaches for PE has in general not been controlled or randomised and is lacking in long-term follow up. OBJECTIVE: To assess the efficacy of psychosocial interventions for PE. CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW: Trials were searched in computerized general and specialized databases, such as: MEDLINE by PubMed (1966 to 2010; PsycINFO (1974 to 2010; EMBASE (1980 to 2010; LILACS (1982 to 2010; the Cochrane Central Register of Controlled Trials (Cochrane Library, 2010; and by checking bibliographies, and contacting manufacturers and researchers. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials evaluating psychosocial interventions compared with different psychosocial interventions, pharmacological interventions, waiting list, or no treatment for PE. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form. The primary outcome measure for comparing the effects of psychosocial interventions to waiting list and standard medications was improvement in IELT (i.e., time from vaginal penetration to ejaculation. The secondary outcome was change in validated PE questionnaires. MAIN RESULTS: In one study behavioral therapy (BT was significantly better than waiting list for duration of intercourse (MD (mean difference 407.90 seconds, 95% CI 302.42 to 513.38, and couples' sexual satisfaction (MD -26.10, CI -50.48 to -1.72. BT was also significantly better for a new functional-sexological treatment (FS (MD 412.00 seconds, 95% CI 305.88 to 518.12, change over time in subjective perception of duration of intercourse (Women: MD 2

  15. EVALUATING THE EFFECTIVENESS OF ELKAR (L-CARNITINE IN PREMATURE INFANTS

    Directory of Open Access Journals (Sweden)

    Svetlana V. Garina

    2016-06-01

    Full Text Available Introduction. Recently in Russia there is a tendency to increase the proportion of premature infants, prolonged postnatal adaptation which may be associated with carnitine deficiency Early diagnosis and correction of carnitine deficiency in premature infants is possible to reserve the prevention of pathological conditions of the prenatal period in these patients. Materials and Methods. 98 newborn infants have been examined with the help of clinical laboratory methods. Results. It has been stated that the overwhelming majority of newborn infants irrespective of their gestational age and body mass at the moment of birth had reference ranges of crude carnitine and higher degree of floating carnitine in their peripheral blood within the first days of their lives. These changes are particularly characteristic for small pre-mature infants. Statistically significant differences between the levels of crude carnitine and floating carnitine depended on the gender of newborn infants have been revealed. Directly correlated dependence of the level of crude carnitine on the body mass at the moment of birth of small premature infants has been stated. Discussion and Conclusions. It has been proved that implementing L-carnitine into the development care plan for premature infants facilitates quick body weight gain, significantly cuts down the period of tube feeding, lowers frequency of anemia development of premature infants and duration of neonatal jaundice. The ability of Elkar to correct functional diseases of cardio vascular system of premature infants has been shown.

  16. Prostaglandin E2 and patent ductus arteriosus in premature infants

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    Mochammading,

    2016-01-01

    Full Text Available Background Patent ductus arteriosus (PDA is a congenital heart disease most commonly occurring in premature infants. Spontaneous ductus arteriosus (DA closure in premature infants has been suggested to be associated with duct lumen maturity and the DA sensitivity to prostaglandin E2 (PGE2. Objective To assess for a possible correlation between serum PGE2 levels and PDA size in premature infants. Methods This observational study using repeated measurements on premature infants with PDA detected at days 2-3 of life was undertaken in Cipto Mangunkusumo Hospital and Fatmawati Hospital, Jakarta, from April to May 2014. The PDA was diagnosed using 2-D echocardiography and PGE2 levels were measured by immunoassay. Pearson’s correlation test was used to evaluate a possible correlation between PGE2 level and DA diameter. Results Thirty-three premature infants of median gestational age 31 (range 28-32 weeks and median birth weight 1,360 (range 1,000-1,500 grams were enrolled. Almost two-thirds of the subjects were male. Almost all (30/33 subjects had spontaneous DA closure before the age of 10 days. Subjects’ mean DA diameter was 2.9 (SD 0.5 mm with maximum flow velocity of 0.2 (SD 0.06 cm/sec, and left atrial-to-aortic root ratio (LA/Ao of 1.5 (SD 0.2. Their mean PGE2 levels at the ages of 2-3, 5-7, and after 10 days were 5,238.6 (SD 1,225.2, 4,178.2 (SD 1,534.5, and 915.2 (SD 151.6 pg/mL, respectively. The PGE2 level at days 2-3 was significantly correlated with DA diameter (r = 0.667; P < 0.001, but not at days 5-7 (r = 0.292; P = 0.105 or at day 10 (r = 0.041; P = 0.941. Conclusion There is a strong, positive correlation between the PGE2 level and DA diameter in preterm infants at 2-3 days of age. However, there is no significant correlation between PGE2 level and persistence of PDA.

  17. Treatment for retinopathy of prematurity in Denmark in a ten-year period (1996-2005): Is the incidence increasing?

    DEFF Research Database (Denmark)

    Slidsborg, C.; Olesen, H.B.; Jensen, Peter Koch

    2008-01-01

    OBJECTIVE. The objective of this study was to analyze the population incidence of retinopathy of prematurity treatment in Denmark in the 10-year period from 1996 to 2005. METHODS. Patient charts of infants treated for retinopathy of prematurity and the national birth registry provide information...... about neonatal parameters. These parameters, along with birth in the latter half of the period (2001-2005), were analyzed as risk factors for retinopathy of prematurity. The national registry for blind and visually impaired children was accessed to obtain information about visual impairment attributable....... The incidence of treated retinopathy of prematurity cases increased significantly from 1.3% in 1996 to 2000 to 3.5% in 2001 to 2005. Significant risk factors for retinopathy of prematurity treatment were low gestational age, small for gestational age, male gender, and multiple birth. Other, yet unknown factors...

  18. Sexuality in pregnancy and premature labour.

    Science.gov (United States)

    Georgakopoulos, P A; Dodos, D; Mechleris, D

    1984-09-01

    The relation of sexual behaviour during pregnancy to the initiation of labour was investigated in 358 patients of whom 58 were delivered after premature labour and 300 were delivered spontaneously at term. In all patients the mean weekly coital frequency and the frequency of orgasm were investigated by means of a retrospective questionnaire. There was no significant difference in coital or orgasmic frequency between the women who had a premature labour and those who had a spontaneous delivery at term. This was also true when those having premature labour were divided into those starting labour with ruptured membranes and those starting with contractions.

  19. Psychosexual therapy for premature ejaculation.

    Science.gov (United States)

    Althof, Stanley E

    2016-08-01

    Premature ejaculation (PE) is a male sexual dysfunction that creates considerable anguish for the man, his partner and their relationship. PE is not one disorder but includes the four subtypes (lifelong, acquired, natural and subjective) each with unique psychological concerns and issues. Psychological treatment for men and couples with PE addresses sexual skills/techniques but also focuses on issues of self-esteem, performance anxiety and interpersonal conflict. The outcome studies for psychotherapy alone are difficult to interpret and compare because of poor methodological design (lack of control groups, small sample size, poor outcome measures and lack of follow-up). However, the few studies that surmount these methodological hurdles suggest that psychological intervention offers men and couples a promising treatment option. Combination pharmaco- and psychotherapy is the most promising intervention for lifelong and acquired PE and offers superior efficacy to drug alone. This is because men and couples learn sexual skills, address the intrapsychic, interpersonal and cognitive issues that precipitate and maintain the dysfunction.

  20. The epidemiology of premature ejaculation.

    Science.gov (United States)

    Saitz, Theodore Robert; Serefoglu, Ege Can

    2016-08-01

    Vast advances have occurred over the past decade with regards to understanding the epidemiology, pathophysiology and management of premature ejaculation (PE); however, we still have much to learn about this common sexual problem. As a standardized evidence-based definition of PE has only recently been established, the reported prevalence rates of PE prior to this definition have been difficult to interpret. As a result, a large range of conflicting prevalence rates have been reported. In addition to the lack of a standardized definition and operational criteria, the method of recruitment for study participation and method of data collection have obviously contributed to the broad range of reported prevalence rates. The new criteria and classification of PE will allow for continued research into the diverse phenomenology, etiology and pathogenesis of the disease to be conducted. While the absolute pathophysiology and true prevalence of PE remains unclear, developing a better understanding of the true prevalence of the disease will allow for the completion of more accurate analysis and treatment of the disease.

  1. [Sexological intervention on premature ejaculation].

    Science.gov (United States)

    San Martín Blanco, C

    2014-07-01

    Strategies, recommendations and techniques proposed by sex therapy for intervention on premature ejaculation, have represented for nearly four decades the most effective model of intervention in this sexual dysfunction, which currently is complemented by the efficacy of dapoxetine drug treatment. Clinical experience and recent studies support that combined intervention offers the best therapeutic results. In addition in sex therapy, etiologic diagnosis is obtained from the analysis of the interrelationship of the couple. Diagnostic and therapeutic intervention has to be always centered in the relationship, so the techniques and resources must be applied with the expectation of being implemented in the sexual interaction. It will therefore be the relationship that receive treatment, even if medication is used for one of the members of the couple. On the other hand, this model of intervention can be implemented by a professional with training, although not necessarily a specialist. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.

  2. Medical therapy for premature ejaculation

    Science.gov (United States)

    Mohee, Amar; Eardley, Ian

    2011-01-01

    Premature ejaculation (PE) is a common male sexual dysfunction. Advances in PE research have been hampered owing to a nonstandardized definition of PE, until the definition by the International Society of Sexual Medicine (ISSM) in 2009. Once the diagnosis of PE is established through a thorough history, a variety of medical therapies is available, including tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), centrally acting opiates, phosphodiesterase 5 inhibitors and topical desensitizing creams. Most of these treatments increase the intravaginal ejaculation latency time (IELT) and patient satisfaction scores, with the most convincing evidence for SSRIs and topical creams. Daily SSRIs such as paroxetine, although efficacious, do have a substantial and prolonged side effect profile. Dapoxetine, which is a on-demand SSRI, is the only licensed drug for the treatment of PE, increasing IELT by a factor of 2.5 to 3 with limited and tolerable side effects. In the near future, the topical aerosol PSD502 is due to be licensed for the treatment of PE, increasing IELT by up to a factor of 6 but having minimal local and negligible systemic side effects. PMID:22046199

  3. Premature birth: An Enigma for the Society?

    Directory of Open Access Journals (Sweden)

    Sribas Goswami

    2014-12-01

    Full Text Available Infants born preterm are at greater risk than infants born at term for mortality and a variety of health and developmental problems. Complications include acute respiratory, gastrointestinal, immunologic, central nervous system, hearing, and vision problems, as well as longer-term motor, cognitive, visual, hearing, behavioral, social-emotional, health, and growth problems. The birth of a preterm infant can also bring considerable emotional and economic costs to families and have implications for public-sector services, such as health insurance, educational, and other social support systems. The greatest risk of mortality and morbidity is for those infants born at the earliest gestational ages. However, those infants born nearer to term represent the greatest number of infants born preterm and also experience more complications than infants born at term. Preterm birth is a complex cluster of problems with a set of overlapping factors of influence. Its causes may include individual-level behavioral and psychosocial factors, neighborhood characteristics, environmental exposures, medical conditions, infertility treatments, biological factors and genetics. Many of these factors occur in combination, particularly in those who are socioeconomically disadvantaged or who are members of racial and ethnic minority groups. The empirical investigation was carried out to draw correlation between preterm birth and eventuality. This paper deals with various issues related to the premature deliveries from socio-biological perspectives.

  4. Salidroside protects against premature senescence induced by ultraviolet B irradiation in human dermal fibroblasts.

    Science.gov (United States)

    Mao, G-X; Xing, W-M; Wen, X-L; Jia, B-B; Yang, Z-X; Wang, Y-Z; Jin, X-Q; Wang, G-F; Yan, J

    2015-06-01

    Salidroside, the predominant component of a Chinese herbal medicine, Rhodiola rosea L., becomes an attractive bio-agent due to its multifunction. Although it is well proposed that this herbal medicine may have photoprotective effect according to the folk hearsay, the direct supportive experimental evidences linking the drug with skin ageing have rarely been reported so far. The study was conducted to investigate the photoprotective role of salidrosdie and its related mechanisms in vitro. First, a premature senescence model induced by UVB irradiation (250 mJ cm(-2)) in human dermal fibroblasts (HDFs) was established, and senescent phenotypes were evaluated by cell morphology, cell proliferation, senescence-associated beta-galactosidase (SA-β-gal) activity and cell cycle distribution. Then the photoprotective effect of salidroside was investigated. Cells were pre-treated with various doses of salidroside (1, 5 and 10 μM) followed by the sublethal dosage of UVB exposure and then were harvested for various detections, including senescence-associated phenotypes and molecules, alteration of oxidative stress, matrix metalloproteinase-1 (MMP-1) secretion and inflammatory response. Pre-treatment of salidroside dose dependently reversed the senescent state of HDFs induced by UVB as evidenced by elevated cell viability, decreased SA-β-gal activity and relieving of G1/G0 cell cycle arrest. UVB-induced increased protein expression of cyclin-dependent kinase (CDK) inhibitors p21(WAF) (1) and p16(INK) (4) was also repressed by salidrosdie treatment in a dose-dependent manner. Meanwhile, the increment of malondialdehyde (MDA) level in UVB-irradiated HDFs was inhibited upon salidroside treatment. Additionally, salidroside significantly attenuated UVB-induced synthesis of MMP-1 as well as the production of IL-6 and TNF-α in HDFs. Our data provided the evidences for the protective role of salidroside against UVB-induced premature senescence in HDFs probably via its anti

  5. Cost estimate of hospital stays for premature newborns in a public tertiary hospital in Brazil

    Directory of Open Access Journals (Sweden)

    Claudia Maria Desgualdo

    2011-01-01

    Full Text Available OBJECTIVES: To estimate the direct costs of hospital stays for premature newborns in the Interlagos Hospital and Maternity Center in São Paulo, Brazil and to assess the difference between the amount reimbursed to the hospital by the Unified Health System and the real cost of care for each premature newborn. METHODS: A cost-estimate study in which hospital and professional costs were estimated for premature infants born at 22 to 36 weeks gestation during the calendar year of 2004 and surviving beyond one hour of age. Direct costs included hospital services, professional care, diagnoses and therapy, orthotics, prosthetics, special materials, and blood products. Costs were estimated using tables published by the Unified Health System and the Brasindice as well as the list of medical procedures provided by the Brazilian Classification of Medical Procedures. RESULTS: The average direct cost of care for initial hospitalization of a premature newborn in 2004 was $2,386 USD. Total hospital expenses and professional services for all premature infants in this hospital were $227,000 and $69,500 USD, respectively. The costs for diagnostic testing and blood products for all premature infants totaled $22,440 and $1,833 USD. The daily average cost of a premature newborn weighing less than 1,000 g was $115 USD, and the daily average cost of a premature newborn weighing more than 2,500 g was $89 USD. Amounts reimbursed to the hospital by the Unified Health System corresponded to only 27.42% of the real cost of care. CONCLUSIONS: The cost of hospital stays for premature newborns was much greater than the amount reimbursed to the hospital by the Unified Health System. The highest costs corresponded to newborns with lower birth weight. Hospital costs progressively and discretely decreased as the newborns' weight increased.

  6. Nutrition of premature infants after hospital discharge. Effect on growth and the risk of allergic disease within the first year of life

    DEFF Research Database (Denmark)

    Zachariassen, Gitte; Færk, Jan; Halken, Susanne

    to continue with fortification or premature formula after hospital discharge. The aim of the study is to describe breast-feeding rate at discharge among very preterm infants, whether it is possible to supply breastfeeding with fortification after discharge, eating habits after discharge, growth...... Background and Aims: Human milk offers many advantages for the premature infant, but the content of macro-nutrients might be inadequate. Fortification of mothers own milk or premature formula have shown to improve growth among premature infants while they are hospitalized. It might be beneficial......-velocity and registration of allergic symptoms within the first year of life among premature infants. Methods: The study is a randomized controlled study where premature infants born with a gestational age (GA) ≤ 32+0 weeks are fed premature formula or (if the mother is breastfeeding) randomized to either breastfeeding...

  7. 晚期早产儿及足月儿与胎龄 <35周早产儿呼吸窘迫综合征临床分析%Comparison of clinical characteristics of respiratory distress syndrome between gestational age <35w premature neonates and term and late-preterm neonates

    Institute of Scientific and Technical Information of China (English)

    王美卿; 宋旸

    2015-01-01

    Objective To compare the clinical characteristics of respiratory distress syndrome ( RDS ) between gestational age <35w premature neonates and term and late-preterm neonates and the differences among them.Methods Eighty-nine cases of RDS admitted in People's Hospital of Lanxi City during the period of December 2011 to December 2013 were divided into two groups:term and late-preterm neonate group (gestational age≥35w, n=32) and gestational age<35w premature neonate group (gestational age<35w, n=57).The risk factors, onset time, treatment and complications of them were analyzed.Results Premature was the main etiology of RDS in gestational age<35w premature neonates, while cesarean section was the major high risk factor in term and late-preterm neonates (59.4%), followed by asphyxia, meconium aspiration and gestational diabetes mellitus (χ2 value was 6.52, 6.47, 9.24 and 4.15, respectively, all P<0.05).The occurrence of RDS was later (t=3.92,P<0.01) and the start time to use CPAP or ventilator was also later (t=4.20, P<0.01) in term and late-preterm neonate group than in gestational age<35w premature neonate group.But the continuous application of ventilator was longer (t=2.27,P<0.05) in term and late-preterm neonates, and they were more likely to suffer pneumothorax (χ2 =5.82,P<0.05) and persistent pulmonary hypertension (PPHN) (χ2 =9.49,P <0.01).Conclusion Cesarean section, meconium aspiration, asphyxia and gestational diabetes mellitus are the risk factors of term and late-preterm neonates with RDS.The onset time for RDS is late and mechanical ventilation is long in term and late-preterm neonates, who are likely to suffer pneumothorax and PPHN. Therefore, active preventing neonates asphyxia and meconium aspiration, and reducing cesarean section rate can significantly reduce the occurrence of RDS among term and late-preterm neonates.Meanwhile, it is important to improve clinician' s awareness on RDS to achieve early diagnosis and early treatment as well as

  8. Polymorphisms in MTHFR, MS and CBS genes and premature acute myocardial infarction in a Pakistani population.

    Science.gov (United States)

    Iqbal, Mohammad Perwaiz; Iqbal, Khalida; Tareen, Asal Khan; Parveen, Siddiqa; Mehboobali, Naseema; Haider, Ghulam; Iqbal, Saleem Perwaiz

    2016-11-01

    High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; cystathionine-β-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients (age CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population.

  9. Functional ontogeny of the proglucagon-derived peptide axis in the premature human neonate

    DEFF Research Database (Denmark)

    Amin, Harish; Holst, Jens Juul; Hartmann, Bolette

    2008-01-01

    assimilation, intestinal growth, and function. OBJECTIVE: Our goal was to investigate the production of glucagon-like peptides 1 and 2 in premature human infants and examine the effects of prematurity and feeding on hormone release. PATIENTS AND METHODS: With informed consent, premature infants who were...... levels of both glucagon-like peptides 1 and 2 were elevated. There was no correlation between gestational age and glucagon-like peptide 2 output. However, both glucagon-like peptide 1 and 2 levels were correlated with the caloric value of feeds. CONCLUSIONS: The premature human neonate has significantly...... higher fasting levels of glucagon-like peptides 1 and 2 compared with adults; feeding increases these levels further. These findings suggest that the proglucagon-derived peptides may have a role in normal intestinal development and nutrient handling....

  10. Premature menopause or early menopause and risk of ischemic stroke

    Science.gov (United States)

    Rocca, Walter A.; Grossardt, Brandon R.; Miller, Virginia M.; Shuster, Lynne T.; Brown, Robert D.

    2011-01-01

    Objective The general consensus has been that estrogen is invariably a risk factor for ischemic stroke (IS). We reviewed new observational studies that challenge this simple conclusion. Methods This was a review of observational studies of the association of premature or early menopause with stroke or IS published in English from 2006 through 2010. Results Three cohort studies showed an increased risk of all stroke in women who underwent bilateral oophorectomy compared with women who conserved their ovaries before age 50 years. The increased risk of stroke was reduced by hormonal therapy (HT) in one of the studies, suggesting that estrogen deprivation is involved in the association. Four additional observational studies showed an association of all stroke or IS with the early onset of menopause or with a shorter lifespan of ovarian activity. In three of the seven studies, the association was restricted to IS. Age at menopause was more important than type of menopause (natural vs induced). Conclusions The findings from seven recent observational studies challenge the consensus that estrogen is invariably a risk factor for IS and can be reconciled by a unifying timing hypothesis. We hypothesize that estrogen is protective for IS before age 50 years and may become a risk factor for IS after age 50 years or, possibly, after age 60 years. These findings are relevant to women who experienced premature or early menopause, or to women considering prophylactic bilateral oophorectomy before the onset of natural menopause. PMID:21993082

  11. Retinopathy of Prematurity in Infants with Late Retinal Examination

    Directory of Open Access Journals (Sweden)

    S. Zeinab Mousavi

    2009-01-01

    Full Text Available

    PURPOSE: To report the incidence, severity and risk factors of retinopathy of prematurity (ROP in premature infants with late ROP examination in Farabi Eye Hospital. METHODS: In a retrospective study from January 2001 to July 2007, hospital records of premature infants who were examined later than 9 weeks after birth were reviewed to determine the incidence, severity and possible risk factors of ROP including gender, singleton or multiple gestations, gestational age (GA, birth weight (BW, oxygen therapy, blood transfusion, phototherapy, respiratory distress syndrome (RDS, mechanical ventilation, intraventricular hemorrhage and sepsis as well as age at initial examination. RESULTS: Out of a total of 797 infants referred for ROP screening during the study period, 216 (27.1% had late examinations at a mean age of 141.7±150.4 (range 64-1,460 days. Of these, 87 (40.3% had different stages of ROP, 65 (30.1% had stage 4 or 5 disease including 34 (16.2% infants with stage 5 ROP in both eyes which was untreatable. Lower GA (P < 0.001, RDS (P=0.041 and blood transfusion (P=0.009 were associated with the development of ROP. CONCLUSION: The overall prevalence of ROP and the incidence

  12. Maternal assessment of pain in premature infants

    Directory of Open Access Journals (Sweden)

    Maria Carolina Correia dos Santos

    2015-12-01

    Full Text Available Objective: to identify mothers' perceptions about the pain in their premature babies in the Neonatal Intensive Care Unit. Methods: evaluative, quantitative study with investigative nature conducted with 19 mothers of hospitalized premature newborns. Data were obtained from closed questions, answered by mothers. Results: from the participants, two (10.5% reported that newborns are unable to feel pain. From the 17 mothers who said that premature babies can feel pain, the majority (94.1% identified crying as a characteristic of pain sensation. Eleven (64.7% stated that uneasiness is a sign of pain in newborns. Conclusion: for the proper management of neonatal pain it is essential that mothers know the signs of pain in premature newborns, and that health professionals instruct this recognition, through the enhancement of the maternal presence and practice of effective communication between professionals and newborns’ families.

  13. Future Applications of Antioxidants in Premature Infants

    Science.gov (United States)

    Lee, Jennifer W.; Davis, Jonathan M.

    2012-01-01

    Purpose of Review This review will examine the unique susceptibility of premature infants to oxidative stress, the role of reactive oxygen species (ROS) in the pathogenesis of common disorders of the preterm infant, and potential for therapeutic interventions using enzymatic and/or non-enzymatic antioxidants. Recent Findings Oxidative stress is caused by an imbalance between the production of ROS and the ability to detoxify them with the help of antioxidants. The premature infant is especially susceptible to ROS-induced damage because of inadequate antioxidant stores at birth, as well as impaired upregulation in response to oxidant stress. Thus, the premature infant is at increased risk for the development of ROS-induced diseases of the newborn, such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and periventricular leukomalacia. Summary Potential therapies for ROS-induced disease include both enzymatic and non-enzymatic antioxidant preparations. More research is required to determine the beneficial effects of supplemental antioxidant therapy. PMID:21150443

  14. Predicting utility of exercise tests based on history/holter in patients with premature ventricular contractions.

    Science.gov (United States)

    Robinson, Brad; Xie, Li; Temple, Joel; Octavio, Jenna; Srayyih, Maytham; Thacker, Deepika; Kharouf, Rami; Davies, Ryan; Gidding, Samuel S

    2015-01-01

    Premature ventricular contractions (PVCs) are considered benign in patients with structurally normal hearts, particularly if they suppress with exercise. Catecholaminergic polymorphic ventricular tachycardia (CPVT) requires exercise testing to unmask the malignant phenotype. We studied risk factors and Holter monitor variables to help predict the necessity of exercise testing in patients with PVCs. We retrospectively reviewed 81 patients with PVCs that suppressed at peak exercise and structurally normal hearts referred to the exercise laboratory in 2011. We reviewed 11 patients from 2003 to 2012 whose PVCs were augmented at peak exercise (mean age 13 ± 4 years; 52 % male, 180 exercise studies). We recorded clinical risk factors and comorbidities (family history of arrhythmia or sudden unexpected death [SUD], presence of syncope) and Holter testing parameters. Family history of VT or SUD (P = 0.011) and presence of VT on Holter (P = 0.011) were significant in predicting failure of PVCs to suppress at peak heart rate on exercise testing. Syncope was not statistically significant in predicting suppression (P = 0.18); however, CPVT was diagnosed in four patients with syncope during exercise. Quantity of PVCs, Lown grade, couplets on Holter, monomorphism, and PVC elimination at peak heart rate on Holter were not predictors of PVC suppression on exercise testing. Patients with syncope during exercise, family history of arrhythmia or SUD, or a Holter monitor showing VT warrant exercise testing to assess for CPVT.

  15. Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women.

    Science.gov (United States)

    Jayachandran, Muthuvel; Litwiller, Robert D; Owen, Whyte G; Heit, John A; Behrenbeck, Thomas; Mulvagh, Sharon L; Araoz, Philip A; Budoff, Matthew J; Harman, S Mitchell; Miller, Virginia M

    2008-09-01

    While the risk for symptomatic atherosclerotic disease increases after menopause, currently recognized risk factors do not identify ongoing disease processes in low-risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by the Framingham risk score. The concentration and phenotype of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry, and coronary artery calcification (CAC) was scored using 64-slice computed tomography scanners. The procoagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, serum lipids, systolic blood pressure (Framingham risk score 50; range, 93-315 Agatston units) CAC compared with women without calcification. The total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. The thrombin-generating capacity of the isolated microparticles correlated with phosphatidylserine expression, which also was greatest in women with high CAC scores. The percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, the characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis.

  16. Premature dental eruption: report of case.

    LENUS (Irish Health Repository)

    McNamara, C M

    2011-08-05

    This case report reviews the variability of dental eruption and the possible sequelae. Dental eruption of the permanent teeth in cleft palate children may be variable, with delayed eruption the most common phenomenon. A case of premature dental eruption of a maxillary left first premolar is demonstrated, however, in a five-year-old male. This localized premature dental eruption anomaly was attributed to early extraction of the primary dentition, due to caries.

  17. Neuro-ophthalmic manifestations of prematurity

    OpenAIRE

    Preeti Patil Chhablani; Ramesh Kekunnaya

    2014-01-01

    Increasing rates of preterm births coupled with better survival of these infants have resulted in higher prevalence of systemic and ocular complications associated with prematurity. In addition to retinopathy of prematurity, infants who are born preterm may suffer from severe visual impairment as a result of hypoxic ischemic encephalopathy, hypoglycemia, and other metabolic imbalances. The effect of these processes on the anterior visual pathway may result in optic atrophy, optic nerve hypopl...

  18. PECULIARITIES OF BREAST FEEDING OF PREMATURE CHILDREN

    Directory of Open Access Journals (Sweden)

    V.К. Kotlukov

    2011-01-01

    Full Text Available The article presents main strategies of breast feeding of prematurely born infants support, such as use of Philips AVENT breast pumpfor lactation formation and feeding of the infant with native breast milk.Key words: premature infants, nursing mother, breast feeding support, modern accessories for breast feeding support. (Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (6: 170–175

  19. The pathophysiology of acquired premature ejaculation

    OpenAIRE

    McMahon, Chris G; Jannini, Emmanuele A.; Serefoglu, Ege C.; Hellstrom, Wayne J.G.

    2016-01-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of ne...

  20. Relationship between premature ejaculation and depression

    Science.gov (United States)

    Xia, Yue; Li, Juanjuan; Shan, Guang; Qian, Huijun; Wang, Tao; Wu, Wei; Chen, Jun; Liu, Luhao

    2016-01-01

    Abstract Background: Premature ejaculation (PE) is the most prevalent male sexual dysfunction. Epidemiologic findings are inconsistent concerning the risk for depression associated with PE. Objective: The aim of this study was to investigate the potential association between between depression and risk of PE. Data sources: We conducted a literature search of PubMed, Embase, and the Cochrane Library from these databases’ inception through June 2014 for observational epidemiological studies examining the association between depression on risk of PE. Study eligibility criteria: Studies were selected if they reported the risk estimates for PE associated with depression. Participants: patients>18 years of age suffering from PE. Interventions: a history of depressive disorder. Study appraisal and synthesis methods: These odds ratios (ORs) were pooled using a random or fixed effects model and were tested for heterogeneity. Subgroup analysis was employed to explore heterogeneity. Results: Eight trials involving 18,035 patients were included in the meta-analysis. Depression were statistically significantly associated with the risk of PE (OR = 1.63, 95% CI:1.42–1.87). There was no evidence of between-study heterogeneity (P = 0.623, I2 = 0.0%). The association was similar when stratified by mean age, geographical area, study design, sample size, publication year, and controlling key confounders. Limitations: The severity of depression and PE could not be identified due to unavailable data of trials. No evidence of publication bias was observed. Conclusions: These findings provide evidence that depression is associated with a significantly increased risk of PE. In addition, more prospective studies are necessary to evaluate the association and identify the ideal treatment. Systematic review registration number: CRD42016041272 PMID:27583879

  1. The impact of pharmaceutical innovation on premature cancer mortality in Switzerland, 1995-2012.

    Science.gov (United States)

    Lichtenberg, Frank R

    2016-09-01

    The premature cancer mortality rate has been declining in Switzerland, but there has been considerable variation in the rate of decline across cancer sites (e.g., breast or digestive organs). I analyze the effect that pharmaceutical innovation had on premature cancer mortality in Switzerland during the period 1995-2012 by investigating whether the cancer sites that experienced more pharmaceutical innovation had larger declines in premature mortality, controlling for the number of people diagnosed and mean age at diagnosis. Premature cancer mortality before ages 75 and 65 is significantly inversely related to the cumulative number of drugs registered 5, 10, and 15 years earlier. The number of drugs registered during 1980-1997 explains 63 % of the variation across cancer sites in the 1995-2012 log change in the premature (before age 75) mortality rate. Controlling for the cumulative number of drugs, the cumulative number of chemical subgroups does not have a statistically significant effect on premature mortality. This suggests that drugs (chemical substances) within the same class (chemical subgroup) are not "therapeutically equivalent". Over 17,000 life-years before age 75 were gained in 2012 due to drugs registered during 1990-2007. The number of life-years before age 75 gained in 2012 from drugs registered during two earlier periods (1985-2002 and 1980-1997) were more than twice as great. Since mean utilization of new drugs is much lower than mean utilization of older drugs, more recent drug registrations may have a smaller effect on premature mortality than earlier drug registrations even if the average quality of newer drugs is higher. Estimates of the cost per life-year gained before ages 75 and 65 in 2012 from drugs registered during 1990-2007 are $21,228 and $28,673, respectively. These figures are below even the lowest estimates from the value-of-life literature of the value of a quality-adjusted life-year. The estimates indicate that the cost per life

  2. Frequency of neonatal complications after premature delivery

    Directory of Open Access Journals (Sweden)

    Gordana Grgić

    2013-04-01

    Full Text Available Introduction: Preterm delivery is the delivery before 37 weeks of gestation are completed. The incidence of preterm birth ranges from 5 to 15%. Aims of the study were to determine the average body weight, Apgar score after one and five minutes, and the frequency of the most common complications in preterminfants.Methods: The study involved a total of 631 newborns, of whom 331 were born prematurely Aims of this study were to (24th-37th gestational weeks-experimental group, while 300 infants were born in time (37-42 weeks of gestation-control group.Results: Average body weight of prematurely born infants was 2382 grams, while the average Apgar score in this group after the fi rst minute was 7.32 and 7.79 after the fifth minute. The incidence of respiratory distress syndrome was 50%, intracranial hemorrhage, 28.1% and 4.8% of sepsis. Respiratory distresssyndrome was more common in infants born before 32 weeks of gestation. Mortality of premature infants is present in 9.1% and is higher than that of infants born at term.Conclusions: Birth body weight and Apgar scores was lower in preterm infants. Respiratory distress syndrome is the most common fetal complication of prematurity. Intracranial hemorrhage is the second most common complication of prematurity. Mortality of premature infants is higher than the mortality of infants born at term birth.

  3. "Assessment of retinopathy of prematurity among 150 premature neonates in Farabi eye hospital "

    Directory of Open Access Journals (Sweden)

    "Riazi Esfahani M

    2001-05-01

    Full Text Available The aim of this study was to estimate the incidence of retinopathy of permaturity (ROP and to evaluate possible neonatal risk factors for ROP. The main study was a cross-sectional study including 150 high-risk neonates born at teaching hospitals of Tehran universities referring to to Farabi Eye Hospital. The chossing critertia were birth weight less than 2500 g or gestational age younger than 37 weeks. ROP was present in 9(6% newborns, all of whom aged less than 32 weeks a birth. There was also strong association between ROP and birth weight, oxygen administration, respiratory distress syndrome and intraventricular hemorrhage. There also seems to be a higher risk for developing ROP in female neoates, those who were born by multiple gestaional pregnancies or were treated by phototherapy or transfusion and those who had suffered from bronchopulmonary dysplasia or seiss.Prematurity per se remains the strongest risk factof for ROP. Suitable criteria for screening of ROP seems to be gestational age younger than 32 weeks or birth weight less than 1500 g

  4. Prematurity and Programming Contribution of neonatal (NICU) interventions

    Science.gov (United States)

    Kalhan, Satish C; Wilson-Costello, Dee

    2014-01-01

    Contemporary clinical practice for the care of the prematurely born babies has markedly improved their rates of survival so that most of these babies are expected to grow up to live a healthy functional life. Since the clinical follow up is of short duration (years), only limited data are available to relate non-communicable diseases in adult life to events and interventions in the neonatal period. The major events that could have a programming effect include (1) Intrauterine growth restriction (2) Interruption of pregnancy with change in redox and reactive oxygen species injury (3) Nutritional and pharmacological protocols for Clinical care (4) Nutritional care in the first two years resulting in accelerated weight gain. The available data are discussed in the context of perturbations in one carbon (methyl transfer) metabolism and its possible programming effects. Although direct evidence for genomic methylation is not available, clinical and experimental data on impact of redox and ROS, of low protein intake, excess methionine load and vitamin A, on methyl transfers are reviewed. The consequences of antenatal and postnatal administration of glucocorticoids are presented. Analysis of the correlates of insulin sensitivity at older age, suggests that premature birth is the major contributor, and is compounded by gain in weight during infancy. We speculate that premature interruption of pregnancy and neonatal interventions by effecting one carbon metabolism may cause programming effects on the immature baby. These can be additive to the effects of intrauterine environment (growth restriction) and are compounded by accelerated growth in early infancy. PMID:25054678

  5. Persistent unexplained congenital clitoromegaly in females born extremely prematurely

    Science.gov (United States)

    Williams, C.E.; Nakhal, R.S.; Achermann, J.C.; Creighton, S.M.

    2013-01-01

    Objective Unexplained clitoromegaly is a rare but well recognised feature in girls born premature. Although detected at birth, girls may re-present during childhood to paediatric urologists and gynaecologists who should be aware of this condition. The aim of the study was to describe the clinical findings and management of a series of girls presenting with persistent congenital clitoromegaly associated with prematurity. Materials and methods This was a retrospective notes review set in a tertiary referral centre for Paediatric and Adolescent Gynaecology (PAG). Results Eight girls with a mean age of 6 years were seen over an eight year period. In all cases a Disorder of Sex Development (DSD) had been previously excluded. The main symptoms were discomfort or concern about appearance. On examination five girls had excess skin over the clitoris and three had enlarged corporal tissue. Management included reassurance and simple measures to ease discomfort. In two cases the parents requested referral to a paediatric urologist to consider clitoral surgery. Conclusion As survival rates for extreme prematurity improve, paediatric urologists and gynaecologists are likely to see more of these cases. Clinicians must be familiar with this condition to ensure children are managed appropriately. PMID:23619354

  6. Prematurity and programming: contribution of neonatal Intensive Care Unit interventions.

    Science.gov (United States)

    Kalhan, S C; Wilson-Costello, D

    2013-04-01

    Contemporary clinical practice for the care of the prematurely born babies has markedly improved their rates of survival so that most of these babies are expected to grow up to live a healthy functional life. Since the clinical follow-up is of short duration (years), only limited data are available to relate non-communicable diseases in adult life to events and interventions in the neonatal period. The major events that could have a programming effect include: (1) intrauterine growth restriction; (2) interruption of pregnancy with change in redox and reactive oxygen species (ROS) injury; (3) nutritional and pharmacological protocols for clinical care; and (4) nutritional care in the first 2 years resulting in accelerated weight gain. The available data are discussed in the context of perturbations in one carbon (methyl transfer) metabolism and its possible programming effects. Although direct evidence for genomic methylation is not available, clinical and experimental data on impact of redox and ROS, of low protein intake, excess methionine load and vitamin A, on methyl transfers are reviewed. The consequences of antenatal and postnatal administration of glucocorticoids are presented. Analysis of the correlates of insulin sensitivity at older age, suggests that premature birth is the major contributor, and is compounded by gain in weight during infancy. We speculate that premature interruption of pregnancy and neonatal interventions by affecting one carbon metabolism may cause programming effects on the immature baby. These can be additive to the effects of intrauterine environment (growth restriction) and are compounded by accelerated growth in early infancy.

  7. Carnitine deficiency in premature infants receiving total parenteral nutrition.

    Science.gov (United States)

    Penn, D; Schmidt-Sommerfeld, E; Wolf, H

    1980-03-01

    Carnitine plays a significant role in fatty acid utilization and ketone body production. Its availability is especially important during the immediate postnatal period. To determine whether low birth weight infants who cannot be orally fed are at risk of developing carnitine deficiency, we compared the carnitine blood levels and urinary excretion of 12 premature infants (Group A) receiving total parenteral nutrition (TPN) with those of 8 infants of similar gestational age and birth weight (Group B) who received carnitine-containing milk formulas. In Group A, serum levels of total and free carnitine fell after 5 days of carnitine-deficient parenteral nutrition, and urinary excretion was significantly reduced. Serum levels and urinary excretion increased after the onset of oral feedings. The control Group B exhibited no significant changes in carnitine blood levels between the first and fifth days of life, but did show a later increase. Children in Group A had lower carnitine blood levels compared to those in Group B on the fifth day of life. These findings suggest that premature infants are not able to synthesize enough carnitine to maintain blood levels, and that carnitine deficiency can occur following TPN. Further investigation of metabolic consequences secondary to deficient carnitine intake in premature infants is necessary before carnitine supplementation should be considered.

  8. Homozygosity for a severe novel medium-chain acyl-CoA dehydrogenase (MCAD) mutation IVS3-1G > C that leads to introduction of a premature termination codon by complete missplicing of the MCAD mRNA and is associated with phenotypic diversity ranging from sudden neonatal death to asymptomatic

    DEFF Research Database (Denmark)

    Korman, Stanley H; Gutman, Alisa; Brooks, Rivka

    2004-01-01

    and the first reported splice mutation in the MCAD gene that has been functionally characterized. The association of homozygosity for a null mutation with lethal neonatal presentation in the index patient and presumably the previous infant suggested a genotype/phenotype correlation. However, a 6-year...

  9. A steroid like phytochemical Antcin M is an anti-aging reagent that eliminates hyperglycemia-accelerated premature senescence in dermal fibroblasts by direct activation of Nrf2 and SIRT-1.

    Science.gov (United States)

    Senthil, Kumar K J; Gokila, Vani M; Mau, Jeng-Leun; Lin, Chin-Chung; Chu, Fang-Hua; Wei, Chia-Cheng; Liao, Vivian Hsiu-Chuan; Wang, Sheng-Yang

    2016-09-27

    The present study revealed the anti-aging properties of antcin M (ANM) and elucidated the molecular mechanism underlying the effects. We found that exposure of human normal dermal fibroblasts (HNDFs) to high-glucose (HG, 30 mM) for 3 days, accelerated G0/G1 phase arrest and senescence. Indeed, co-treatment with ANM (10 µM) significantly attenuated HG-induced growth arrest and promoted cell proliferation. Further molecular analysis revealed that ANM blocked the HG-induced reduction in G1-S transition regulatory proteins such as cyclin D, cyclin E, CDK4, CDK6, CDK2 and protein retinoblastoma (pRb). In addition, treatment with ANM eliminated HG-induced reactive oxygen species (ROS) through the induction of anti-oxidant genes, HO-1 and NQO-1 via transcriptional activation of Nrf2. Moreover, treatment with ANM abolished HG-induced SIPS as evidenced by reduced senescence-associated β-galactosidase (SA-β-gal) activity. This effect was further confirmed by reduction in senescence-associated marker proteins including, p21CIP1, p16INK4A, and p53/FoxO1 acetylation. Also, the HG-induced decline in aging-related marker protein SMP30 was rescued by ANM. Furthermore, treatment with ANM increased SIRT-1 expression, and prevented SIRT-1 depletion. This protection was consistent with inhibition of SIRT-1 phosphorylation at Ser47 followed by blocking its upstream kinases, p38 MAPK and JNK/SAPK. Further analysis revealed that ANM partially protected HG-induced senescence in SIRT-1 silenced cells. A similar effect was also observed in Nrf2 silenced cells. However, a complete loss of protection was observed in both Nrf2 and SIRT-1 knockdown cells suggesting that both induction of Nrf2-mediated anti-oxidant defense and SIRT-1-mediated deacetylation activity contribute to the anti-aging properties of ANM in vitro. Result of in vivo studies shows that ANM-treated C. elegens exhibits an increased survival rate during HG-induced oxidative stress insult. Furthermore, ANM significantly

  10. Determinants and Predictors of School Adaptation and Academic Achievement in Prematurely Born Children.

    Science.gov (United States)

    Kalmar, Magda; Varga, Magdolna Estefan

    The study followed up 30 premature Hungarian infants of low birthweight (less than 2500 grams) but no other major perinatal complications. Subjects were tested at age 6 on the Budapest-Binet IQ test, the Goodenough's "Draw a Person" test, the Bender Gestalt test, and a school entry test battery. Test performances at age 6 found that the…

  11. Determinants and Predictors of School Adaptation and Academic Achievement in Prematurely Born Children.

    Science.gov (United States)

    Kalmar, Magda; Varga, Magdolna Estefan

    The study followed up 30 premature Hungarian infants of low birthweight (less than 2500 grams) but no other major perinatal complications. Subjects were tested at age 6 on the Budapest-Binet IQ test, the Goodenough's "Draw a Person" test, the Bender Gestalt test, and a school entry test battery. Test performances at age 6 found that the…

  12. Iodine content of infant formulas and iodine intake of premature babies: high risk of iodine deficiency.

    Science.gov (United States)

    Ares, S; Quero, J; Durán, S; Presas, M J; Herruzo, R; Morreale de Escobar, G

    1994-11-01

    As part of a study of thyroid function in premature babies, the iodine content of their mothers' breast milk, that of 32 formulas from different brands used in Spain, and that of 127 formulas used in other countries was determined. Breast milk contained more iodine--mean (SEM) 10 (1) microgram/dl--than most of the formulas, especially those for premature babies. Iodine intakes were therefore below the recommended daily amount (RDA) for newborns: babies of 27-30 weeks' gestational age took 3.1 (1.1) micrograms/day at 5 days of age and 29.8 (2.7) micrograms by 2 months of age. This problem is not exclusive to Spanish premature babies as the iodine content of many of the formulas on sale in other countries was also inadequate. It is concluded that preterm infants who are formula fed are at high risk of iodine deficiency.

  13. Treatment-related risk factors for premature menopause following Hodgkin lymphoma

    DEFF Research Database (Denmark)

    De Bruin, Marie L; Huisbrink, Jeannine; Hauptmann, Michael;

    2008-01-01

    We conducted a cohort-study among 518 female 5-year Hodgkin lymphoma (HL) survivors, aged 14 to 40 years (median: 25 years) at treatment (1965-1995). Multivariable Cox regression was used to quantify treatment effects on risk of premature menopause, defined as cessation of menses before age 40...... years. After a median follow up of 9.4 years, 97 women had reached menopause before age 40 years. Chemotherapy was associated with a 12.3-fold increased risk of premature menopause compared with radiotherapy alone. Treatment with MOPP (mechlorethamine, vincristine, procarbazine, prednisone......)/ABV (doxorubicine, bleomycine, vinblastine) significantly increased the risk of premature menopause (hazard ratio [HR]: 2.9), although to a lesser extent than MOPP treatment (HR: 5.7). Alkylating agents, especially procarbazine (HR: 8.1) and cyclophosphamide (HR: 3.5), showed the strongest associations. Ten years...

  14. Mean trombosit volume in patients with retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Harun Yüksel

    2014-06-01

    Full Text Available Objective: We aimed to evaluate the mean platelet volume (MPV in patients with retinopathy of prematurity (ROP with respect to development of type 1 ROP Methods: The medical records of the premature infants were evaluated. Babies with a birth weight under 1500 g and a gestational age under 32 weeks were enrolled to the study. Birth weight, gestational age, onset and grade of retinopathy, presence of plus disease were analyzed. At the time of type 1 ROP diagnosis, blood samples were obtained. In the patients without type 1 ROP the blood samples were also obtained at similar gestational age. Hemoglobin, hematocrit, platelet count, and MPV results were recorded. Results: Sixty-three infants were studied. 22 of them had type 1 ROP and 41 had not developed type 1 ROP. The mean gestational age and the mean birth weight between groups were not statistically significant. The mean MPV values in patients with type 1 ROP and without type 1 ROP was 9,1±2,0 fL and 9,4±1,8 fL, respectively (p=0.61. Conclusion: The results demonstrated that MPV values were not associated with severity of ROP in our study population. J Clin Exp Invest 2014; 5 (2: 443-446

  15. A Case of Premature Ovarian Failure in a 33-Year-Old Woman

    Directory of Open Access Journals (Sweden)

    Emma Colao

    2013-01-01

    Full Text Available Objective. To assess aetiology of a POF in a 33-year-old woman and, if possible, plan a cure. Design. Case report. Setting. medical genetics diagnostic unit in a university hospital. Patient. A 33-year-old woman with premature ovarian failure (POF. Intervention(s. Genetic counseling, karyotyping, FISH study. Result(s. Turner-like diagnosis. Conclusion(s. Most cases of POF remain idiopathic. Turner syndrome can occur in very different phenotypes; cytogenetic and molecular profiling can provide a definitive diagnosis in cases with nonclassical phenotype.

  16. A case of premature ovarian failure in a 33-year-old woman.

    Science.gov (United States)

    Colao, Emma; Granata, Teresa; Vismara, Marco F M; Bombardiere, Francesco; Nocera, Donatella; Luciano, Elisa; Perrotti, Nicola; Malatesta, Paola

    2013-01-01

    Objective. To assess aetiology of a POF in a 33-year-old woman and, if possible, plan a cure. Design. Case report. Setting. medical genetics diagnostic unit in a university hospital. Patient. A 33-year-old woman with premature ovarian failure (POF). Intervention(s). Genetic counseling, karyotyping, FISH study. Result(s). Turner-like diagnosis. Conclusion(s). Most cases of POF remain idiopathic. Turner syndrome can occur in very different phenotypes; cytogenetic and molecular profiling can provide a definitive diagnosis in cases with nonclassical phenotype.

  17. Damage, DNA Repair, Aging, and Neurodegeneration

    Science.gov (United States)

    Maynard, Scott; Fang, Evandro Fei; Scheibye-Knudsen, Morten; Croteau, Deborah L.; Bohr, Vilhelm A.

    2017-01-01

    Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrial DNA damage and the major phenotypes associated with aging. Understanding the mechanistic basis for the association of DNA damage and DNA repair with aging and age-related diseases, such as neurodegeneration, would give insight into contravening age-related diseases and promoting a healthy life span. PMID:26385091

  18. Effect of parenteral glutamine supplementation in premature infants

    Institute of Scientific and Technical Information of China (English)

    LI Zheng-hong; WANG Dan-hua; DONG Mei

    2007-01-01

    Background Glutamine, proposed to be conditionally essential for critically ill patients, is not added routinely to parenteral amino acid formulations for premature infants and is provided in only small quantities by the enteral route when enteral feeding is Iow. Parenteral feeding is the basic way of nutrition in the first days of life of premature infants. In this study, we evaluated the effects of glutamine supplemented parenteral nutrition for premature infants on growth and development, feeding toleration, and infective episodes.Methods From December 2002 to July 2006, 53 premature infants were given either standard or glutamine supplemented parenteral nutrition for more than 2 weeks. Twenty-eight infants were in glutamine supplemented group, whose gestational age (31.4±2.0) weeks, birth weight range (1386±251) g; twenty-five infants were in control group, gestational age (31.1 ± 1.7) weeks, with birth weight range (1346± 199) g. There were no differences between the two groups. Various growth and biochemical indices were monitored throughout the duration of hospital stay. Data between groups were analyzed with Student's t test. Nonparametric data were analyzed using a Chi-square test. A two-tailed P value < 0.05 was considered statistically significant.Results The level of serum albumin was lower in the glutamine groups on the second week (3.0 vs 3.2 g/dl, P=0.028), and blood urea nitrogen was higher in glutamine groups on the fourth week (8.1 vs 4.9 mg/dl, P=0.014), but normal. Glutamine group infants took fewer days to regain birth weight (8.1 vs 10.4 days, P=0.017), required fewer days on parenteral nutrition (24.8 vs 30.8 days, P=0.035), with shorter stays in hospital (32.1 vs 38.6 days, P=0.047). Episodes of hospital acquired infection in glutamine supplemented infants were lower than that in control group (0.96 vs 1.84 times, P=0.000).Conclusion Parenteral glutamine supplementation in premature infants can shorten days on parenteral nutrition and

  19. Chronic Exposure to Particulate Chromate Induces Premature Centrosome Separation and Centriole Disengagement in Human Lung Cells

    Science.gov (United States)

    Martino, Julieta; Holmes, Amie L.; Xie, Hong; Wise, Sandra S.; Wise, John Pierce

    2015-01-01

    Particulate hexavalent chromium (Cr(VI)) is a well-established human lung carcinogen. Lung tumors are characterized by structural and numerical chromosome instability. Centrosome amplification is a phenotype commonly found in solid tumors, including lung tumors, which strongly correlates with chromosome instability. Human lung cells exposed to Cr(VI) exhibit centrosome amplification but the underlying phenotypes and mechanisms remain unknown. In this study, we further characterize the phenotypes of Cr(VI)-induced centrosome abnormalities. We show that Cr(VI)-induced centrosome amplification correlates with numerical chromosome instability. We also show chronic exposure to particulate Cr(VI) induces centrosomes with supernumerary centrioles and acentriolar centrosomes in human lung cells. Moreover, chronic exposure to particulate Cr(VI) affects the timing of important centriolar events. Specifically, chronic exposure to particulate Cr(VI) causes premature centriole disengagement in S and G2 phase cells. It also induces premature centrosome separation in interphase. Altogether, our data suggest that chronic exposure to particulate Cr(VI) targets the protein linkers that hold centrioles together. These centriolar linkers are important for key events of the centrosome cycle and their premature disruption might underlie Cr(VI)-induced centrosome amplification. PMID:26293554

  20. Dietary and nutritional manipulation of the nuclear transcription factors peroxisome proliferator-activated receptor and sterol regulatory element-binding proteins as a tool for reversing the primary diseases of premature death and delaying aging.

    Science.gov (United States)

    Kurtak, Karen A

    2014-04-01

    Evolution over 2.1 billion years has equipped us with a biochemical pathway that has the power to literally reverse the primary disease etiologies that have become the leading causes of death and aging in the developed world. Activation of the peroxisome proliferator-activated receptor (PPAR) pathway arrests inflammatory signaling throughout the body, reverses damage to tissues, reverses insulin resistance, and can even dissolve beta-amyloid plaque in the brain. It has played a critical role in the evolution of the metazoans and the successful migration of humans to all corners of the Earth. For two decades, various pharmaceuticals have been designed to activate the PPAR pathway but have consistently fallen short of expectations. There is nothing wrong with these drugs. The problem has been the standard "healthy" diet creating mixed signals that render the drugs ineffective. This article explores the ongoing dance between the two primary nuclear receptors that mediate gene regulation of fatty acids. It discusses their interaction with sirtuins and telomerase, optimization of their obligate heterodimers, and why manipulation of dietary and nutritional factors, like the ketogenic diet, is the most effective means of activation. These are effective tools that we can start implementing now to slow, and in some cases reverse, the diseases of aging.

  1. The two-faced progeria gene and its implications in aging and metabolism.

    Science.gov (United States)

    Chatzispyrou, Iliana A; Houtkooper, Riekelt H

    2014-05-01

    Premature aging syndromes have gained much attention, not only because of their devastating symptoms but also because they might hold a key to some of the mechanisms underlying aging. The Hutchinson-Gilford progeria syndrome (HGPS) is caused by a mutation in the LMNA gene, which normally produces lamins A and C through alternative splicing. Due to this mutation, HGPS patients express an incompletely processed form of lamin A called progerin. In this issue of EMBO Reports, the Tazi group demonstrates how mice expressing different LMNA isoforms present opposite phenotypes in longevity, fat storage and mitochondrial function.

  2. Correlação entre a idade materna, paridade, gemelaridade, síndrome hipertensiva e ruptura prematura de membranas e a indicação de parto cesáreo The influence of maternal age, parity, twin pregnancy, hypertensive syndrome and premature rupture of membranes on the indication for cesarean section

    Directory of Open Access Journals (Sweden)

    Simone Angélica Leite de Carvalho Silva Cabral

    2003-12-01

    Full Text Available OBJETIVO: verificar a contribuição da idade materna, paridade, gemelaridade, síndrome hipertensiva, ruptura prematura das membranas como fator de risco para cesárea. MÉTODOS: após aprovação do Comitê de Ética em Pesquisa da Maternidade Professor Monteiro de Morais, situada em Recife-PE, realizou-se estudo de caso-controle com 3919 gestantes, sem antecedente de duas ou mais cesáreas, que deram à luz concepto vivo, com idade gestacional igual ou superior a 28 semanas, peso mínimo de 1.000 g, em apresentação cefálica, no período de 1 de setembro de 1999 a 31 de agosto de 2000. No grupo caso foram incluídas mulheres submetidas a operação cesariana e no grupo controle, a parto vaginal. Com os dados constantes dos prontuários neonatais e obstétricos, realizou-se análise multivariada por regressão logística, buscando a equação matemática que relacione a probabilidade de ocorrência de cesárea decorrente de mais de uma variável independente atuando como fator de risco, utilizando odds ratio e intervalo de confiança de 95% (IC 95%, consideradas as variáveis: idade materna, paridade, gemelaridade, síndrome hipertensiva e ruptura prematura das membranas. RESULTADOS: as chances de cesárea foram aumentadas em 8,3 vezes (OR = 8,3; IC 95%: 3,7-19,1 na gemelaridade, 3,4 na síndrome hipertensiva (OR = 3,4; IC 95%: 2,9-4,0, 1,9 na primiparidade (OR = 1,9; IC 95% : 1,8-2,0, 1,5 na idade superior a 34 anos (OR = 1,5; IC 95%: 1,2-1,8 e 1,2 na presença de ruptura prematura das membranas (OR = 1,2; IC 95%: 1,0-1,4. CONCLUSÕES: ruptura prematura das membranas, idade superior a 34 anos, primiparidade, síndrome hipertensiva e gemelaridade constituíram fatores de risco para cesárea.PURPOSE: to verify the contribution of maternal age, parity, twin pregnancy, hypertensive syndrome, and premature rupture of membranes as risk factors for cesarean section. METHODS: after approval by the Ethics in Research Committee of the "Maternidade

  3. Influence of the blood glucose level on the development of retinopathy of prematurity in extremely premature children

    Directory of Open Access Journals (Sweden)

    Galina V. Nicolaeva

    2015-08-01

    Full Text Available ABSTRACTPurpose:To investigate the influence of the blood glucose level on the development of retinopathy of prematurity (ROP in extremely premature infants.Methods:Sixty-four premature infants with a gestational age of less than 30 weeks and a birth weight of less than 1500 g were included in the study. Children without ROP were allocated to Group 1 (n=14, gestational age 28.6 ± 1.4 weeks, birth weight 1162 ± 322 g, and children with spontaneous regression of ROP were allocated to Group 2 (n=32, gestational age 26.5 ± 1.2 weeks, birth weight 905 ± 224 g. Children with progressive ROP who underwent laser treatment were included in Group 3 (n=18, gestational age 25.4 ± 0.7 weeks, birth weight 763 ± 138 g. The glucose level in the capillary blood of the premature infants was monitored daily during the first 3 weeks of life. A complete ophthalmological screening was performed from the age of 1 month. The nonparametric signed-rank Wilcoxon-Mann-Whitney test was used for statistical analysis.Results:The mean blood glucose level was 7.43 ± 2.6 mmol/L in Group 1, 7.8 ± 2.7 mmol/L in Group 2, and 6.7 ± 2.6 mmol/L in Group 3. There were no significant differences in the blood glucose levels between children with and without ROP, and also between children with spontaneously regressing ROP and progressive ROP (p>0.05. Additionally, there were no significant differences in the blood glucose levels measured at the first, second, and third weeks of life (p>0.05.Conclusion:The blood glucose level is not related to the development of ROP nor with its progression or regression. The glycemic level cannot be considered as a risk factor for ROP, but reflects the severity of newborns’ somatic condition and morphofunctional immaturity.

  4. Music and 25% glucose pain relief for the premature infant: a randomized clinical trial

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    Maria Vera Lúcia Moreira Leitão Cardoso

    2014-10-01

    Full Text Available OBJECTIVE: to analyze the total Premature Infant Pain Profile scores of premature infants undergoing arterial puncture during music and 25% glucose interventions, and to assess their association with neonatal and therapeutic variables.METHOD: a randomized clinical trial with 80 premature infants; 24 in the Experimental Group 1 (music, 33 in the Experimental Group 2 (music and 25% glucose, 23 in the Positive Control Group (25% glucose. All premature infants were videotaped and a lullaby was played for ten minutes before puncture in Experimental Groups 1 and 2; 25% glucose administered in Experimental Group 2 and the Positive Control Group two minutes before puncture.RESULTS: 60.0% of premature infants had moderate or maximum pain; pain scores and intervention groups were not statistically significant. Statistically significant variables: Experimental Group 1: head and chest circumference, Apgar scores, corrected gestational age; Experimental Group 2: chest circumference, Apgar scores, oxygen therapy; Positive Control group: birth weight, head circumference.CONCLUSION: neonatal variables are associated with pain in premature infants. Brazilian Registry of Clinical Trials: UTN: U1111-1123-4821.

  5. PSYCHOMOTOR DEVELOPMENT IN PREMATURE INFANTS UNTIL THE END OF THEIR THIRD YEAR OF LIFE

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    Valentina DUKOVSKA

    2009-06-01

    Full Text Available Psychomotor development in premature infants has specific characteristics with increased tendency towards neuro-developmental difficulties, such as the fact that certain percent of the developmentally challenged people belongs in this category of children.Many factors contribute to the neuro-developmental difficulties in premature infants. A large number of studies have shown that the birth weight (BW and gestational age (GA have strong correlation with the neuro-developmental outcome.In order to establish the general developmental outcome and the developmental outcome in specific areas of early development, that is the first three years of life in preemies, we have conducted a research on our own population. We conducted a longitudinal study on 20 premature newborns with very low birth weight (VLBW, with a follow-up period from 4 weeks CGA until 36 weeks GA.The research results showed that the largest difference in developmental areas between the group of premature infants with VLBW and the control group is present at the end of the 36th month of life and the general development quotient (GDQ in the premature group was significantly lower during the whole follow-up period, except at the end of month 4 - in different developmental areas. We also concluded that 20% of the premature infants with VLBW have developmental difficulties and severe difficulties in their motor development.

  6. THE ROLE OF PANCREATIC ENZYMOTHERAPY IN POSTNATAL ADAPTATION OF THE PREMATURE INFANTS UNDER ARTIFICIAL FEEDING

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    V.V. Dashichev

    2007-01-01

    Full Text Available Due to immaturity of the digestive system of the premature children under artificial feeding there may often be effects of gastrointestinal tract dysfunctions, which disturb postnatal adaptation among these newborns. The purpose of this research was to analyze a number of indices, characterizing the dynamics of the body weight and functional status of the gastrointestinal tract among the premature children, who received modern active digestive ferment at different periods of time. The authors presented the findings of the retrospective analysis of the case history among 29 premature children, who were held in the department of the premature children of the perinatal center. Children received pancreatine ferment (Creon 10000, Solvay Pharma, Germany. The ferment was introduced in the dosage of 150mg/day. This dose was orally introduced by minimicrospheres during every feeding and in some cases through the nasogastric probe. The ferment intake started in the early neonatal period among 13 children and in the late neonatal period among 16 children. During the course of the ferment therapy the frequency of the symptoms of the gastrointestinal tract dysfunctions drastically reduced. When the course of the ferment therapy was prescribed at an early age, the body weight increase tended to higher indices among premature children during the first month of their lives.Key words: premature children, pancreatic enzymotherapy, gastrointestinal tract dysfunctions.

  7. Quantitative ultrasound bone measurements of different gestational age premature infants at birth in Guangzhou zone%广州地区不同胎龄早产儿出生时骨定量超声值测定

    Institute of Scientific and Technical Information of China (English)

    瞿柳红; 李思涛; 庄桂英; 徐庆活; 杨文欢; 肖昕

    2013-01-01

    目的 测定广州地区不同胎龄早产儿出生时的骨定量超声值,并与高加索白人种早产儿比较,了解广州地区早产儿骨骼发育的状况,评价定量超声技术的实用性.方法 采用以色列Sunlight公司生产的Omnisense定量超声仪,对2010年6月至2012年6月在广州市花都区妇幼保健院出生的不同胎龄的早产儿进行左侧胫骨声波速度(SOS)测量,并与高加索白人种进行比较.结果 广州地区出生的1039例不同胎龄早产儿根据胎龄分为A、B、C、D组(≤30周、30+1 ~32周、32+1~34周和34+1~ 36+6周4组).4组早产儿出生时所测得的SOS值分别为(2892.05±139.17) m/s、(2936.84±137.87) m/s、(2966.65±116.60) m/s和(2988.63±120.74) m/s,SOS值随胎龄增加而增加,差别有统计学意义(F=15.758,P=0.000),但各组中男女童之间SOS值无明显差异(F =2.665,P =0.103).广州地区不同胎龄的早产儿出生时SOS值的差距(定义为Z值)与高加索白人种比较差异无统计学意义(P=0.117),男女比较差异亦无统计学意义(F=3.494,P=0.062).结论 早产儿SOS值随早产儿成熟度增加而升高;广州地区的不同胎龄早产儿出生时骨强度与高加索白人种无明显差距;骨定量超声技术可用于临床评价早产儿骨发育情况.%Objective To measure the values of quantitative ultrasound(QUS) of different gestational age preterm infants at birth in Guangzhou area,and compare them with the values of Caucasian preterm infants in order to get insight into the bone development status of preterm infants in Guangzhou area and to evaluate the practicability of QUS.Methods The Omnisense quantitative ultrasound produced by Israel Sunlight company was used to measure the bone speed of sound(SOS) of left tibia of preterm infants born between Jun.2010 and Jun.2012 in Maternity and Children Health Hospital of Huadu District in Guangzhou,and the values of SOS of Caucasian preterm infants was compared.Results There were totally

  8. Retinopathy of prematurity: A comprehensive risk analysis for prevention and prediction of disease

    Science.gov (United States)

    Owen, Leah A.; Morrison, Margaux A.; Hoffman, Robert O.; Yoder, Bradley A.; DeAngelis, Margaret M.

    2017-01-01

    Background Retinopathy of prematurity (ROP) is a blinding morbidity of preterm infants. Our current screening criteria have remained unchanged since their inception and lack the ability to identify those at greatest risk. Objectives We sought to comprehensively analyze numerous proposed maternal, infant, and environmental ROP risk variables in a robustly phenotyped population using logistic regression to determine the most predictive model for ROP development and severity. We further sought to determine the statistical interaction between significant ROP risk variables, which has not previously been done in the field of ROP. We hypothesize that our comprehensive analysis will allow for better identification of risk variables that independently correlate with ROP disease. Going forward, this may allow for improved infant risk stratification along a time continuum from prenatal to postnatal development, making prevention more feasible. Methods We performed a retrospective cohort analysis of preterm infants referred for ROP screening in one neonatal intensive care unit from 2010–2015. The primary outcome measure was presence of ROP. Secondary outcome measures were ROP requiring treatment and severe ROP not clearly meeting current treatment criteria. Univariate, stepwise regression and statistical interaction analyses of 57 proposed ROP risk variables was performed to identify variables which were significantly associated with each outcome measure. Results We identified 457 infants meeting our inclusion criteria. Within this cohort, numerous factors showed a significant individual association with our ROP outcome measures; however, stepwise regression analysis found the most predictive model for overall ROP risk included estimated gestational age, birth weight, the need for any surgery, and maternal magnesium prophylaxis. The corresponding Area Under the Curve (AUC) for this model was 0.8641, while the traditional model of gestational age and birth weight predicted

  9. Dynamics of human foveal development after premature birth.

    Science.gov (United States)

    Maldonado, Ramiro S; O'Connell, Rachelle V; Sarin, Neeru; Freedman, Sharon F; Wallace, David K; Cotten, C Michael; Winter, Katrina P; Stinnett, Sandra; Chiu, Stephanie J; Izatt, Joseph A; Farsiu, Sina; Toth, Cynthia A

    2011-12-01

    To determine the dynamic morphologic development of the human fovea in vivo using portable spectral domain-optical coherence tomography (SD-OCT). Prospective, observational case series. Thirty-one prematurely born neonates, 9 children, and 9 adults. Sixty-two neonates were enrolled in this study. After examination for retinopathy of prematurity (ROP), SD-OCT imaging was performed at the bedside in nonsedated infants aged 31 to 41 weeks postmenstrual age (PMA) (= gestational age in weeks + chronologic age) and at outpatient follow-up ophthalmic examinations. Thirty-one neonates met eligibility criteria. Nine children and nine adults without ocular pathology served as control groups. Semiautomatic retinal layer segmentation was performed. Central foveal thickness, foveal to parafoveal (FP) ratio (central foveal thickness divided by thickness 1000 μm from the foveal center), and 3-dimensional thickness maps were analyzed. In vivo determination of foveal morphology, layer segmentation, analysis of subcellular changes, and spatiotemporal layer shifting. In contrast with the adult fovea, several signs of immaturity were observed in the neonates: a shallow foveal pit, persistence of inner retinal layers (IRLs), and a thin photoreceptor layer (PRL) that was thinnest at the foveal center. Three-dimensional mapping showed displacement of retinal layers out of the foveal center as the fovea matured and the progressive formation of the inner/outer segment band in the opposite direction. The FP-IRL ratios decreased as IRL migrated before term and minimally after that, whereas FP-PRL ratios increased as PRL subcellular elements formed closer to term and into childhood. A surprising finding was the presence of cystoid macular edema in 58% of premature neonates that appeared to affect inner foveal maturation. This study provides the first view into the development of living cellular layers of the human retina and of subcellular specialization at the fovea in premature infant eyes

  10. Efficacy of Clomipramine, Sertraline and Terazosin Treatments in Premature Ejaculation

    OpenAIRE

    Tuncel, Altuğ; Aslan, Yılmaz; Başar, M. Murad; Atan, Ali

    2014-01-01

    Aim: To compare the efficacy of oral clomipramine, sertraline and terazosin to placebo in premature ejaculation. Materials and Methods: A total of 90 patients aged from 20 to 58 years were enrolled in this study. Patients were randomized into 4 groups. Group 1 (n: 22) took placebo and served as controls. Group 2 (n: 23) patients took 25 mg clomipramine HCl nightly; Group 3 (n: 20) 50 mg sertraline nightly; and Group 4 (n: 25) 5 mg terazosin nightly. The medications were used for two month...

  11. Rhinovirus-induced Airway Cytokines and Respiratory Morbidity in Severely Premature Children

    Science.gov (United States)

    Perez, Geovanny F.; Pancham, Krishna; Huseni, Shehlanoor; Jain, Amisha; Rodriguez-Martinez, Carlos E.; Preciado, Diego; Rose, Mary C.; Nino, Gustavo

    2017-01-01

    Background Rhinovirus (RV) has been linked to the pathogenesis of asthma. Prematurity is a risk factor for severe RV infection in early life, but is unknown if RV elicits enhanced pro-asthmatic airway cytokine responses in premature infants. This study investigated if young children born severely premature (<32 weeks gestation) exhibit airway secretion of Th2 and Th17 cytokines during natural RV infections and if RV-induced Th2-Th17 responses are linked to more respiratory morbidity in premature children during the first two years of life. Methods We measured Th2 and Th17 nasal airway cytokines in a retrospective cohort of young children aged 0–2 years with PCR-confirmed RV infection or non-detectable virus. Protein levels of IL-4, IL-13, TSLP and IL-17 were determined with multiplex immunoassays. Demographic and clinical variables were obtained by electronic medical record (EMR) review. Results The study comprised 214 children born full term (n=108), pre-term (n=44) or severely premature (n=62). Natural RV infection in severely premature children was associated with elevated airway secretion of Th2 (IL-4 and IL-13) and Th17 (IL-17) cytokines, particularly in subjects with history of bronchopulmonary dysplasia. Severely premature children with high RV-induced airway IL-4 had recurrent respiratory hospitalizations (median 3.65 hosp/year; IQR 2.8–4.8) and were more likely to have at least one pediatric intensive care unit admission during the first two years of life (OR 8.72; 95% CI 1.3–58.7; p=0.02). Conclusions Severely premature children have increased airway secretion of Th2 and Th17 cytokines during RV infections, which is associated with more respiratory morbidity in the first two years of life PMID:25640734

  12. Premature Ejaculation and Utilization of Cognitive Techniques

    Directory of Open Access Journals (Sweden)

    Serkan AKKOYUNLU

    2013-03-01

    Full Text Available Introduction: Premature ejaculation is the most common male sexual dysfunction leading to distress in many couples. Master and Johnson emphasized the concept of early learned experiences and Kaplan emphasized lack of sensory awareness. For treatment sex therapists mainly utilize start-stop and squeeze techniques as homework. Couples enter sex therapy with some cognitive distortions and beliefs about sex and sexuality. These beliefs are also named sexual myths. For some couples using techniques to challenge cognitive distortions and maladaptive beliefs about sex and sexuality can be used. In this paper by presenting a case we discussed how cognitive techniques can be used along with behaviour techniques with couples. Case: Presenting clients are five years married couple who are thirty and twenty nine years old respectively. They attended to the outpatient clinic with the request of the female client. Their main complaint was premature ejaculation. They were diagnosed premature ejaculation using clinical interview. In treatment besides start and stop technique, cognitive techniques were utilized to address dysfunctional beliefs about sexuality. Discussion: Premature ejaculation is a male sexual dysfunction that causes distress and intimacy problems between couples. Stop start and squeeze techniques were accepted as the choice of treatment but their effectiveness is questioned recently. Also cognitive distortions and maladaptive beliefs may hamper therapy progress. Besides that, behavioral techniques utilizing cognitive techniques to lessen the degree of dysfunctional beliefs about sex and sexuality may help the couple to overcome premature ejaculation and enhance sexual satisfaction and intimacy.

  13. Meconium microbiome analysis identifies bacteria correlated with premature birth.

    Science.gov (United States)

    Ardissone, Alexandria N; de la Cruz, Diomel M; Davis-Richardson, Austin G; Rechcigl, Kevin T; Li, Nan; Drew, Jennifer C; Murgas-Torrazza, Roberto; Sharma, Renu; Hudak, Mark L; Triplett, Eric W; Neu, Josef

    2014-01-01

    Preterm birth is the second leading cause of death in children under the age of five years worldwide, but the etiology of many cases remains enigmatic. The dogma that the fetus resides in a sterile environment is being challenged by recent findings and the question has arisen whether microbes that colonize the fetus may be related to preterm birth. It has been posited that meconium reflects the in-utero microbial environment. In this study, correlations between fetal intestinal bacteria from meconium and gestational age were examined in order to suggest underlying mechanisms that may contribute to preterm birth. Meconium from 52 infants ranging in gestational age from 23 to 41 weeks was collected, the DNA extracted, and 16S rRNA analysis performed. Resulting taxa of microbes were correlated to clinical variables and also compared to previous studies of amniotic fluid and other human microbiome niches. Increased detection of bacterial 16S rRNA in meconium of infants of premature birth. This provides the first evidence to support the hypothesis that the fetal intestinal microbiome derived from swallowed amniotic fluid may be involved in the inflammatory response that leads to premature birth.

  14. Smokers′ hair: Does smoking cause premature hair graying?

    Directory of Open Access Journals (Sweden)

    Ayman A Zayed

    2013-01-01

    Full Text Available Aims: To determine if there is a significant association between premature hair graying and cigarette smoking. Materials and Methods: A cross-sectional observational study was conducted in a nonclinical setting on 207 participants on August 24 until 25, 2010. Participants were classified into two groups [premature hair graying (PHG and normal hair graying]. PHG was defined as the first appearance of gray hair before the age of 30. Data were collected using an interview questionnaire and measurements of body mass index, waist circumference, fasting blood glucose and blood pressure. Collected data were statistically analyzed using SPSS 16, Chicago, IL. Results: Of the 207 subjects, 104 (50.2% had first appearance of gray hair before the age of 30 (PHG group while the other 103 (49.8% were considered normal hair graying group. The prevalence of smokers in the "PHG" group was higher (40.2% vs. 24.7%, P = 0.031. Smokers had earlier onset of hair graying (smokers: 31 (7.4 vs. nonsmokers: 34 (8.6, P = 0.034. Using multiple logistic regression with conditional likelihood, smokers were two and half times (95% CI: 1.5-4.6 more prone to develop PHG. Conclusion: This study suggests that there is a significant relation (with adjusted odds ratio of two and half between onset of gray hair before the age of 30 and cigarette smoking.

  15. The prevalence of premature ejaculation in young Turkish men.

    Science.gov (United States)

    Karabakan, M; Bozkurt, A; Hirik, E; Celebi, B; Akdemir, S; Guzel, O; Nuhoglu, B

    2016-11-01

    This study was conducted to investigate the prevalence of premature ejaculation (PE) in young Turkish men and to evaluate PE in a population having good physical and mental health. A total of 1230 healthy university graduates aged between 24 and 30 attending the police academy having no physical or mental problems were included in the study. To identify the presence of PE, the participants were asked to complete the premature ejaculation diagnostic tool (PEDT). The mean ages in the PE and non-PE group were 27.3 and 26.7 respectively. There was no statistically significant difference between the two groups concerning age, body mass index (BMI), smoking status and alcohol consumption (P > 0.05). The PE prevalence was found to be 9.2%. The mean PEDT score was calculated as 6.3. Of the participants, 92 scored 11 and higher (9.2%), 66 scored 9 and 10 (6.6%), and the remaining 842 obtained a score equal to or lower than 8 (84.2%). The lower prevalence of PE in young Turkish men compared to the results of studies in the literature can be attributed to the physical and mental well-being of the participants. This study showed that the prevalence of PE in young men with good physical and mental health is lower than that found in the literature.

  16. Investigation of KIT gene mutations in women with 46,XX spontaneous premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Nelson Lawrence M

    2002-08-01

    Full Text Available Abstract Background Spontaneous premature ovarian failure presents most commonly with secondary amenorrhea. Young women with the disorder are infertile and experience the symptoms and sequelae of estrogen deficiency. The mechanisms that give rise to spontaneous premature ovarian failure are largely unknown, but many reports suggest a genetic mechanism in some cases. The small family size associated with infertility makes genetic linkage analysis studies extremely difficult. Another approach that has proven successful has been to examine candidate genes based on known genetic phenotypes in other species. Studies in mice have demonstrated that c-kit, a transmembrane tyrosine kinase receptor, plays a critical role in gametogenesis. Here we test the hypothesis that human KIT mutations might be a cause of spontaneous premature ovarian failure. Methods and Results We examined 42 women with spontaneous premature ovarian failure and found partial X monosomy in two of them. In the remaining 40 women with known 46,XX spontaneous premature ovarian failure we evaluated the entire coding region of the KIT gene. We did this using polymerase chain reaction based single-stranded conformational polymorphism analysis and DNA sequencing. We did not identify a single mutation that would alter the amino acid sequence of the c-KIT protein in any of 40 patients (upper 95% confidence limit is 7.2%. We found one silent mutation at codon 798 and two intronic polymorphisms. Conclusion Mutations in the coding regions of the KIT gene appear not to be a common cause of 46,XX spontaneous premature ovarian failure in North American women.

  17. The role of serum apelin in retinopathy of prematurity

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    Ali YF

    2017-02-01

    Full Text Available Yasser F Ali,1 Salah El-Morshedy,1 Abdulbasit Abdulhalim Imam,2 Nasser Ismai A Abdelrahman,1 Riad M Elsayed,3 Usama M Alkholy,1 Nermin Abdalmonem,1 Mohammed M Shehab1 1Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, 2Department of Pediatrics, Al-Azhar Faculty of Medicine-Girls, Cairo, 3Pediatric Neurology Unit, Pediatric Department, Mansoura University, Mansoura, Egypt Objective: To evaluate the role of serum apelin as a diagnostic tool in retinopathy of prematurity (ROP disease.Patients and methods: Thirty-eight preterm infants (60% male with gestational age ranging from 30 to 36 weeks admitted to the neonatal intensive care unit, KJO Hospital, Saudi Arabia with proven diagnosis of ROP were included in the study. In addition, 27 preterm infants without ROP served as controls. All newborn infants in the study were subjected to adequate history taking, full clinical examination, and fundus examination by indirect ophthalmoscope (at 4–6 weeks as well as determination of serum apelin at birth and at 4–6 weeks of age.Results: The study revealed that oxygen therapy longer than 7 days’ duration, cesarean section (as a mode of delivery, sepsis, mechanical ventilation, blood transfusion, premature rupture of membranes, pneumothorax, perinatal asphyxia, cardiac problems, and neonatal jaundice were considered as risk factors related to development of ROP. Serum apelin levels were significantly lower in patients than controls (P<0.001 at time of diagnosis of the disease (4–6 weeks while no significant differences were observed in levels at birth.Conclusion: Serum apelin was found to be of significant diagnostic value in the occurrence of ROP. Keywords: retinopathy of prematurity, preterm infants, serum apelin

  18. Accuracy of Transcutaneous Carbon Dioxide Measurement in Premature Infants

    Directory of Open Access Journals (Sweden)

    Marie Janaillac

    2016-01-01

    Full Text Available Background. In premature infants, maintaining blood partial pressure of carbon dioxide (pCO2 value within a narrow range is important to avoid cerebral lesions. The aim of this study was to assess the accuracy of a noninvasive transcutaneous method (TcpCO2, compared to blood partial pressure of carbon dioxide (pCO2. Methods. Retrospective observational study in a tertiary neonatal intensive care unit. We analyzed the correlation between blood pCO2 and transcutaneous values and the accuracy between the trends of blood pCO2 and TcpCO2 in all consecutive premature infants born at <33 weeks’ gestational age. Results. 248 infants were included (median gestational age: 29 + 5 weeks and median birth weight: 1250 g, providing 1365 pairs of TcpCO2 and blood pCO2 values. Pearson’s R correlation between these values was 0.58. The mean bias was −0.93 kPa with a 95% confidence limit of agreement of −4.05 to +2.16 kPa. Correlation between the trends of TcpCO2 and blood pCO2 values was good in only 39.6%. Conclusions. In premature infants, TcpCO2 was poorly correlated to blood pCO2, with a wide limit of agreement. Furthermore, concordance between trends was equally low. We warn about clinical decision-making on TcpCO2 alone when used as continuous monitoring.

  19. The circadian variation of premature atrial contractions

    DEFF Research Database (Denmark)

    Larsen, Bjørn Strøier; Kumarathurai, Preman; Nielsen, Olav W

    2016-01-01

    AIMS: The aim of the study was to assess a possible circadian variation of premature atrial contractions (PACs) in a community-based population and to determine if the daily variation could be used to assess a more vulnerable period of PACs in predicting later incidence of atrial fibrillation (AF...... variation in heart rate. After adjusting for relevant risk factors, the risk of AF was equal in all time intervals throughout the day. CONCLUSION: Premature atrial contractions showed a circadian variation in subjects with frequent PACs. No specific time interval of the day was more predictive of AF than...

  20. Meconium microbiome analysis identifies bacteria correlated with premature birth.

    Directory of Open Access Journals (Sweden)

    Alexandria N Ardissone

    Full Text Available Preterm birth is the second leading cause of death in children under the age of five years worldwide, but the etiology of many cases remains enigmatic. The dogma that the fetus resides in a sterile environment is being challenged by recent findings and the question has arisen whether microbes that colonize the fetus may be related to preterm birth. It has been posited that meconium reflects the in-utero microbial environment. In this study, correlations between fetal intestinal bacteria from meconium and gestational age were examined in order to suggest underlying mechanisms that may contribute to preterm birth.Meconium from 52 infants ranging in gestational age from 23 to 41 weeks was collected, the DNA extracted, and 16S rRNA analysis performed. Resulting taxa of microbes were correlated to clinical variables and also compared to previous studies of amniotic fluid and other human microbiome niches.Increased detection of bacterial 16S rRNA in meconium of infants of <33 weeks gestational age was observed. Approximately 61·1% of reads sequenced were classified to genera that have been reported in amniotic fluid. Gestational age had the largest influence on microbial community structure (R = 0·161; p = 0·029, while mode of delivery (C-section versus vaginal delivery had an effect as well (R = 0·100; p = 0·044. Enterobacter, Enterococcus, Lactobacillus, Photorhabdus, and Tannerella, were negatively correlated with gestational age and have been reported to incite inflammatory responses, suggesting a causative role in premature birth.This provides the first evidence to support the hypothesis that the fetal intestinal microbiome derived from swallowed amniotic fluid may be involved in the inflammatory response that leads to premature birth.

  1. PREMATURITY, NEONATAL HEALTH STATUS, AND LATER CHILD BEHAVIORAL/EMOTIONAL PROBLEMS: A SYSTEMATIC REVIEW.

    Science.gov (United States)

    Cassiano, Rafaela G M; Gaspardo, Claudia M; Linhares, Maria Beatriz M

    2016-05-01

    Preterm birth can impact on child development. As seen previously, children born preterm present more behavioral and/or emotional problems than do full-term counterparts. In addition to gestational age, neonatal clinical status should be examined to better understand the differential impact of premature birth on later developmental outcomes. The aim of the present study was to systematically review empirical studies on the relationship between prematurity, neonatal health status, and behavioral and/or emotional problems in children. A systematic search of the PubMed, PsycINFO, Web of Science, and LILACS databases for articles published from 2009 to 2014 was performed. The inclusion criteria were empirical studies that evaluated behavioral and/or emotional problems that are related to clinical neonatal variables in children born preterm. Twenty-seven studies were reviewed. Results showed that the degree of prematurity and birth weight were associated with emotional and/or behavioral problems in children at different ages. Prematurity that was associated with neonatal clinical conditions (e.g., sepsis, bronchopulmonary dysplasia, and hemorrhage) and such treatments as corticoids and steroids increased the risk for these problems. The volume and abnormalities of specific brain structures also were associated with these outcomes. In conclusion, the neonatal health problems associated with prematurity present a negative impact on later child emotional and adapted behavior. © 2016 Michigan Association for Infant Mental Health.