Chen, Qi; Wang, Yao; Zhao, Min; Hyett, Jonathan; da Silva Costa, Fabricio; Nie, Guiying
2016-07-01
Preeclampsia is a pregnancy specific disorder affecting 3-5% of pregnancies worldwide. It is clinically divided into early-onset and late-onset subtypes. Placental factors are involved in the pathogenesis of preeclampsia. Growth differentiation factor 15 (GDF15), a protein of the transforming growth factor beta superfamily, is highly expressed in the placenta. However, it is unclear whether the circulating levels of GDF15 are altered in preeclampsia at the time of or prior to disease presentation. Serum samples across three trimesters from 29 healthy pregnancies, third trimester sera from 34 women presenting with preeclampsia (early-onset n=16, late-onset n=18) and 66 gestation-age-matched controls, and sera at 11-13weeks of pregnancy from women who later did (n=36) or did not (n=33) develop late-onset preeclampsia, were examined for GDF15 by ELISA. Serum GDF15 levels increased significantly with gestation in normal pregnancy. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia compared to their gestation-age-matched controls. This reduction was apparent in both early-onset and late-onset subtypes, but it was more profound in late-onset cases. At 11-13weeks of gestation, however, serum levels of GDF15 were similar between women who subsequently did and did not develop late-onset preeclampsia. Serum GDF15 increased with gestation age, reaching the highest level in the third trimester. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia, especially in late-onset cases. However, serum GDF15 was not altered in the first trimester in women destined to develop late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.
Hodyl, Nicolette A; Crawford, Tara M; McKerracher, Lorna; Lawrence, Andrew; Pitcher, Julia B; Stark, Michael J
2016-10-01
Neurotrophins are proteins critically involved in neural growth, survival and differentiation, and therefore important for fetal brain development. Reduced cord blood neurotrophins have been observed in very preterm infants (<32weeks gestation) who subsequently develop brain injury. Antenatal steroid exposure can alter neurotrophin concentrations, yet studies to date have not examined whether this occurs in the late preterm infant (33-36weeks gestation), despite increasing recognition of subtle neurodevelopmental deficits in this population. To assess the impact of antenatal steroids on cord blood neurotrophins in late preterm infants following antenatal steroid exposure. Retrospective analysis. Late preterm infants (33-36weeks; n=119) and term infants (37-41weeks; n=129) born at the Women's and Children's Hospital, Adelaide. Cord blood neurotrophin-3 (NT-3), NT-4, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) concentrations measured by ELISA. Cord blood NT-4 and NGF were increased at term compared to the late preterm period (p<0.001), while BDNF and NT-3 were not different. In the late preterm period, cord blood NT-3 was reduced when antenatal steroids were administered >24h prior to delivery (p<0.01). This study identified an association between reduced cord blood NT-3 and antenatal steroid exposure in the late preterm period. The reduced NT-3 may be a consequence of steroids inducing neuronal apoptosis, thereby reducing endogenous neuronal NT3 production, or be an action of steroids on other maternal or fetal NT-3 producing cells, which may then affect neuronal growth, differentiation and survival. Regardless of the specific mechanism, a reduction in NT-3 may have long term implications for child neurodevelopment, and emphasizes the ongoing vulnerability of the fetal brain across the full preterm period. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
What are the causes of late-life depression?
Aziz, Rehan; Steffens, David C
2013-12-01
Although depression in old age is less common than depression in younger populations, it still affects more than 1 million community-living older adults. Depression in late life has been associated with reduced quality of life and increased mortality from both suicide and illness. Its causes are multifactorial but are prominently related to both biologic and social factors. Psychological factors, although less studied in elders, are also important in understanding its cause. In this article, multiple facets of late-life depression are reviewed, including its clinical presentation, epidemiology, and biopsychosocial causes. Copyright © 2013 Elsevier Inc. All rights reserved.
Van Orden, Kimberly; Conwell, Yeates
2011-01-01
Suicide in late life is an enormous public health problem that will likely increase in severity as adults of the baby boom generation age. Data from psychological autopsy studies supplemented with recent studies of suicidal ideation and attempts point to a consistent set of risk factors for the spectrum of suicidal behaviors in late life (suicide ideation, attempts, and deaths). Clinicians should be vigilant for psychiatric illness (especially depression), physical illness, pain, functional impairment, and social disconnectedness. Recent advances in late-life suicide prevention have in common collaborative, multifaceted intervention designs. We suggest that one mechanism shared by all preventive interventions shown to reduce the incidence of late-life suicide is the promotion of connectedness. For the clinician working with older adults, our recommendation is to not only consider risk factors, such as depression, and implement appropriate treatments but to enhance social connectedness as well. PMID:21369952
[Late-onset Group B Streptococcus disease in twins delivered by caesarean section].
Escolano Serrano, S; Ruiz Alcántara, I; Alfonso Diego, J; González Muñoz, A; Gastaldo Simeón, E
2015-01-01
Group B Streptococcus (GBS) is a commensal pathogen of the gut microflora with a well-established role in the aetiology of early and late onset GBS infections in the newborn. The incidence of early onset infections by vertical transmission has been drastically reduced in recent decades with the use of intravenous intrapartum prophylaxis. Progress in risk factor detection and prophylaxis of late-onset infection has however remained static. The ongoing modifications and improvements of the guidelines regarding prophylaxis, risk factors and prevention of the early-onset GBS disease have not addressed late-onset GBS infection in detail. The following cases illustrate the presence of grey areas in current guidelines and in the knowledge of the pathogenesis of late-onset disease. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Gross, Alden L.; Shih, Regina A.; Sachs, Bonnie C.; Glymour, M. Maria; Bangen, Katherine J.; Benitez, Andreana; Skinner, Jeannine; Schneider, Brooke C.; Manly, Jennifer J.
2015-01-01
Objectives. Racial disparities in late-life cognition persist even after accounting for educational attainment. We examined whether early-life educational quality and literacy in later life help explain these disparities. Method. We used longitudinal data from the Washington Heights-Inwood Columbia Aging Project (WHICAP). Educational quality (percent white students; urban/rural school; combined grades in classroom) was operationalized using canonical correlation analysis. Late-life literacy (reading comprehension and ability, writing) was operationalized using confirmatory factor analysis. We examined whether these factors attenuated race-related differences in late-life cognition. Results. The sample consisted of 1,679U.S.-born, non-Hispanic, community-living adults aged 65–102 (71% black, 29% white; 70% women). Accounting for educational quality and literacy reduced disparities by 29% for general cognitive functioning, 26% for memory, and 32% for executive functioning but did not predict differences in rate of cognitive change. Discussion. Early-life educational quality and literacy in late life explain a substantial portion of race-related disparities in late-life cognitive function. PMID:24584038
Einsele, H; Hebart, H; Kauffmann-Schneider, C; Sinzger, C; Jahn, G; Bader, P; Klingebiel, T; Dietz, K; Löffler, J; Bokemeyer, C; Müller, C A; Kanz, L
2000-04-01
PCR-based preemptive therapy with ganciclovir has been shown to reduce the incidence of CMV disease after BMT. Failures of this treatment strategy are CMV disease and secondary non-viral infections. Eighty-six consecutive patients at high risk for CMV disease who received PCR-based preemptive therapy with ganciclovir were assessed for treatment failures and possible risk factors. Ganciclovir was initiated in 57 of 86 patients (66%). Only 28 of 86 (32%) patients received 4 or more weeks of ganciclovir. Recurrence of CMV infection after successful treatment was more frequent among recipients of a BMT from an unrelated compared to a sibling donor (P = 0.004). Three (3.5%) patients developed non-fatal early onset CMV disease and seven of 68 (10.3 %) late onset CMV disease (>100 days post transplant). Risk factors for late onset CMV disease were cGVHD (P = 0.0017) and duration of prior antiviral therapy >4 weeks (P = 0. 0073). The incidence of secondary non-viral infections was 28% with the duration of antiviral treatment being a significant risk factor for secondary bacterial (P = 0.0045) and invasive fungal infections (P = 0.006). Thus, PCR-based preemptive treatment with ganciclovir reduces early onset CMV disease, but the duration of antiviral therapy prior to day +100 is a significant risk factor for late onset CMV disease as well as secondary non-viral infections.
Wang, Minghui; Liu, Shanying; Ouyang, Nengtai; Song, Erwei; Lutz, Jens; Heemann, Uwe
2004-09-01
Lymphocytic infiltration is obvious throughout early and late stages of chronic allograft nephropathy. Early infiltrating lymphocytes are involved in initial insults to kidney allografts, but the contribution of late infiltration to long-term allograft attrition is still controversial. Early application of FTY720 reduced the number of graft infiltrating lymphocytes, and inhibited acute rejection. The present study investigated the potential of FTY720 to reduce the number of infiltrating lymphocytes even at a late stage, and, thus, slow the pace of chronic allograft nephropathy. Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients with an initial 10-day course of cyclosporine A (1.5 mg/kg/day). FTY720, at a dose of 0.5 mg/kg/day, or vehicle was administered to recipients either from weeks 12 to 24 or from 20 to 24 after transplantation. Animals were harvested 24 weeks after transplantation for histologic, immunohistologic, and molecular analysis. FTY720, either initiated at 12 or 20 weeks after transplantation, reduced urinary protein excretion, and significantly ameliorated glomerulosclerosis, interstitial fibrosis, tubular atrophy, and intimal proliferation of graft arteries at 24 weeks after transplantation. Furthermore FTY720 markedly suppressed lymphocyte infiltration and decreased mRNA levels of interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and platelet-derived growth factor-B (PDGF-B) but enhanced the number of apoptotic cells in grafts. FTY720 ameliorated chronic allograft nephropathy even at advanced stages. Furthermore, our data suggest that this effect was achieved by a reduction of graft infiltrating lymphocytes.
Shah, Dilip; Romero, Freddy; Stafstrom, William; Duong, Michelle; Summer, Ross
2014-01-01
Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is irrevocably linked to neutrophil emigration to the lung. Activation and recruitment of neutrophils to the lung is mostly attributable to local production of the chemokines. However, much of our understanding of neutrophil recruitment to the lung is based on studies focusing on early time points after initiation of injury. In this study, we sought to evaluate the extended temporal relationship between neutrophil chemotactic factor expression and influx of neutrophils into the lung after intratracheal administration of either LPS or bleomycin. In both models, results demonstrated two phases of neutrophil chemotactic factor expression; first, an early phase characterized by high levels of CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by increases in extracellular ATP. Furthermore, we show that strategies aimed at either enhancing ATP catabolism (ip ecto-5'-nucleotidase administration) or inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce extracellular ATP accumulation, limit vascular leakage, and effectively block the late, but not the early, stages of neutrophil recruitment to the lung after LPS instillation. In conclusion, this study illustrates that neutrophil recruitment to the lung is mediated by the time-dependent expression of chemotactic factors and suggests that novel strategies, which reduce extracellular ATP accumulation, may attenuate late neutrophil recruitment and limit lung injury during ALI.
Shah, Dilip; Romero, Freddy; Stafstrom, William; Duong, Michelle
2013-01-01
Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is irrevocably linked to neutrophil emigration to the lung. Activation and recruitment of neutrophils to the lung is mostly attributable to local production of the chemokines. However, much of our understanding of neutrophil recruitment to the lung is based on studies focusing on early time points after initiation of injury. In this study, we sought to evaluate the extended temporal relationship between neutrophil chemotactic factor expression and influx of neutrophils into the lung after intratracheal administration of either LPS or bleomycin. In both models, results demonstrated two phases of neutrophil chemotactic factor expression; first, an early phase characterized by high levels of CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by increases in extracellular ATP. Furthermore, we show that strategies aimed at either enhancing ATP catabolism (ip ecto-5′-nucleotidase administration) or inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce extracellular ATP accumulation, limit vascular leakage, and effectively block the late, but not the early, stages of neutrophil recruitment to the lung after LPS instillation. In conclusion, this study illustrates that neutrophil recruitment to the lung is mediated by the time-dependent expression of chemotactic factors and suggests that novel strategies, which reduce extracellular ATP accumulation, may attenuate late neutrophil recruitment and limit lung injury during ALI. PMID:24285266
Sisco, Shannon; Gross, Alden L; Shih, Regina A; Sachs, Bonnie C; Glymour, M Maria; Bangen, Katherine J; Benitez, Andreana; Skinner, Jeannine; Schneider, Brooke C; Manly, Jennifer J
2015-07-01
Racial disparities in late-life cognition persist even after accounting for educational attainment. We examined whether early-life educational quality and literacy in later life help explain these disparities. We used longitudinal data from the Washington Heights-Inwood Columbia Aging Project (WHICAP). Educational quality (percent white students; urban/rural school; combined grades in classroom) was operationalized using canonical correlation analysis. Late-life literacy (reading comprehension and ability, writing) was operationalized using confirmatory factor analysis. We examined whether these factors attenuated race-related differences in late-life cognition. The sample consisted of 1,679 U.S.-born, non-Hispanic, community-living adults aged 65-102 (71% black, 29% white; 70% women). Accounting for educational quality and literacy reduced disparities by 29% for general cognitive functioning, 26% for memory, and 32% for executive functioning but did not predict differences in rate of cognitive change. Early-life educational quality and literacy in late life explain a substantial portion of race-related disparities in late-life cognitive function. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Zheng, Zhe; Chen, Peng; Fu, Weiming; Zhu, Junming; Zhang, Hong; Shi, Jian; Zhang, Jianmin
2013-08-01
We identified factors associated with early and late postoperative seizure control in patients with supratentorial meningioma plus preoperative seizures. In this retrospective study, univariate analysis and multivariate logistic regression analysis compared 24 clinical variables according to the occurrence of early (≤1 week) or late (>1 week) postoperative seizures. Sixty-two of 97 patients (63.9 %) were seizure free for the entire postoperative follow-up period (29.5 ± 11.8 months), while 13 patients (13.4 %) still had frequent seizures at the end of follow-up. Fourteen of 97 patients (14.4 %) experienced early postoperative seizures, and emergence of new postoperative neurological deficits was the only significant risk factor (odds ratio = 7.377). Thirty-three patients (34.0 %) experienced late postoperative seizures at some time during follow-up, including 12 of 14 patients with early postoperative seizures. Associated risk factors for late postoperative seizures included tumor progression (odds ratio = 7.012) and new permanent postoperative neurological deficits (odds ratio = 4.327). Occurrence of postoperative seizures in patients with supratentorial meningioma and preoperative seizure was associated with new postoperative neurological deficits. Reduced cerebral or vascular injury during surgery may lead to fewer postoperative neurological deficits and better seizure outcome.
Ferrucci, Luigi; Costa, Paul T.; Faulkner, Kimberly; Rosano, Caterina; Satterfield, Suzanne; Ayonayon, Hilsa N.; Simonsick, Eleanor M.
2012-01-01
Objectives. To examine the association between openness to experience and conscientiousness and incident reported walking limitation. Method. The study population consisted of 786 men and women aged 71–81 years (M = 75 years, SD = 2.7) participating in the Health, Aging, and Body Composition—Cognitive Vitality Substudy. Results. Nearly 20% of participants (155/786) developed walking limitation during 6 years of follow-up. High openness was associated with a reduced risk of walking limitation (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.69–0.98), independent of sociodemographic factors, health conditions, and conscientiousness. This association was not mediated by lifestyle factors and was not substantially modified by other risk factors for functional disability. Conscientiousness was not associated with risk of walking limitation (HR = 0.91, 95% CI = 0.77–1.07). Discussion. Findings suggest that personality dimensions, specifically higher openness to experience, may contribute to functional resilience in late life. PMID:22437204
Female Adolescents: Factors Differentiating Early-, Middle-, Late-, and Never-Contraceptors.
ERIC Educational Resources Information Center
Rogel, Mary J.; And Others
Identification of factors contributing to the timing of first contraceptive use by girls is an important consideration in structuring primary prevention programs to reduce teenage pregnancies. Interviews with 120 girls aged 12-19 in a study of sexual, contraceptive, and pregnancy decision making covered six areas: (1) demographic information; (2)…
Drain, Paul K; Losina, Elena; Parker, Gary; Giddy, Janet; Ross, Douglas; Katz, Jeffrey N; Coleman, Sharon M; Bogart, Laura M; Freedberg, Kenneth A; Walensky, Rochelle P; Bassett, Ingrid V
2013-01-01
After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults. We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count <100 cells/mm(3). We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing ("competing needs to healthcare") on presentation with late-stage HIV disease. Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6%) presented with late-stage HIV disease. In multivariate analyses, participants who lived ≥5 kilometers from the test site [adjusted odds ratio (AOR) 2.8, 95% CI 1.7-4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2-2.4), were male (AOR 1.7, 95% CI 1.2-2.3), worked outside the home (AOR 1.5, 95% CI 1.1-2.1), perceived health service delivery barriers (AOR 1.5, 95% CI 1.1-2.1), and/or had poor emotional health (AOR 1.4, 95% CI 1.0-1.9) had higher odds of late-stage HIV disease presentation. Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease.
Modifiable Midlife Risk Factors for Late-Life Cognitive Impairment and Dementia
Hughes, Tiffany F.; Ganguli, Mary
2009-01-01
The baby boom generation is approaching the age of greatest risk for cognitive impairment and dementia. There is growing interest in strategies to modify the environment in midlife to increase the probability of maintaining cognitive health in late life. Several potentially modifiable risk factors have been studied in relation to cognitive impairment and dementia in late life, but methodological limitations of observational research have resulted in some inconsistencies across studies. The most promising strategies are maintaining cardiovascular health, engagement in mental, physical, and social activities, using alcohol in moderation, abstaining from tobacco use, and following a heart-healthy diet. Other factors that may influence cognitive health are occupational attainment, depression, personality, exposure to general anesthesia, head injury, postmenopausal hormone therapy, non-steroidal anti-inflammatory medications, and nutritional supplements such as antioxidants. Some long-term observational studies initiated in midlife or earlier, and some randomized controlled trials, have examined the effects of specific cognitive health promotion behaviors in midlife on the risk of cognitive impairment in late life. Overall, these studies provide limited support for risk reduction at this time. Recommendations and challenges for developing effective strategies to reduce the burden of cognitive impairment and dementia in the future are discussed. PMID:19946443
Li, S; Sloboda, D M; Moss, T J M; Nitsos, I; Polglase, G R; Doherty, D A; Newnham, J P; Challis, J R G; Braun, T
2013-04-01
Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40-42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.
Thompson, John M. D.; Cronin, Robin S.; Li, Minglan; Stacey, Tomasina; Stone, Peter R.; Lawton, Beverley A.; Ekeroma, Alec J.; Mitchell, Edwin A.
2017-01-01
Objective Our objective was to test the primary hypothesis that maternal non-left, in particular supine going-to-sleep position, would be a risk factor for late stillbirth (≥28 weeks of gestation). Methods A multicentre case-control study was conducted in seven New Zealand health regions, between February 2012 and December 2015. Cases (n = 164) were women with singleton pregnancies and late stillbirth, without congenital abnormality. Controls (n = 569) were women with on-going singleton pregnancies, randomly selected and frequency matched for health region and gestation. The primary outcome was adjusted odds of late stillbirth associated with self-reported going-to-sleep position, on the last night. The last night was the night before the late stillbirth was thought to have occurred or the night before interview for controls. Going-to-sleep position on the last night was categorised as: supine, left-side, right-side, propped or restless. Multivariable logistic regression adjusted for known confounders. Results Supine going-to-sleep position on the last night was associated with increased late stillbirth risk (adjusted odds ratios (aOR) 3.67, 95% confidence interval (CI) 1.74 to 7.78) with a population attributable risk of 9.4%. Other independent risk factors for late stillbirth (aOR, 95% CI) were: BMI (1.04, 1.01 to 1.08) per unit, maternal age ≥40 (2.88, 1.31 to 6.32), birthweight <10th customised centile (2.76, 1.59 to 4.80), and <6 hours sleep on the last night (1.81, 1.14 to 2.88). The risk associated with supine-going-to-sleep position was greater for term (aOR 10.26, 3.00 to 35.04) than preterm stillbirths (aOR 3.12, 0.97 to 10.05). Conclusions Supine going-to-sleep position is associated with a 3.7 fold increase in overall late stillbirth risk, independent of other common risk factors. A public health campaign encouraging women not to go-to-sleep supine in the third trimester has potential to reduce late stillbirth by approximately 9%. PMID:28609468
Liu, Tie Fu; Vachharajani, Vidula T; Yoza, Barbara K; McCall, Charles E
2012-07-27
The early initiation phase of acute inflammation is anabolic and primarily requires glycolysis with reduced mitochondrial glucose oxidation for energy, whereas the later adaptation phase is catabolic and primarily requires fatty acid oxidation for energy. We reported previously that switching from the early to the late acute inflammatory response following TLR4 stimulation depends on NAD(+) activation of deacetylase sirtuin 1 (SirT1). Here, we tested whether NAD(+) sensing by sirtuins couples metabolic polarity with the acute inflammatory response. We found in TLR4-stimulated THP-1 promonocytes that SirT1 and SirT 6 support a switch from increased glycolysis to increased fatty acid oxidation as early inflammation converts to late inflammation. Glycolysis enhancement required hypoxia-inducing factor-1α to up-regulate glucose transporter Glut1, phospho-fructose kinase, and pyruvate dehydrogenase kinase 1, which interrupted pyruvate dehydrogenase and reduced mitochondrial glucose oxidation. The shift to late acute inflammation and elevated fatty acid oxidation required peroxisome proliferator-activated receptor γ coactivators PGC-1α and β to increase external membrane CD36 and fatty acid mitochondrial transporter carnitine palmitoyl transferase 1. Metabolic coupling between early and late responses also required NAD(+) production from nicotinamide phosphoryltransferase (Nampt) and activation of SirT6 to reduce glycolysis and SirT1 to increase fatty oxidation. We confirmed similar shifts in metabolic polarity during the late immunosuppressed stage of human sepsis blood leukocytes and murine sepsis splenocytes. We conclude that NAD(+)-dependent bioenergy shifts link metabolism with the early and late stages of acute inflammation.
ERIC Educational Resources Information Center
Wilksch, Simon M.; Durbridge, Mitchell R.; Wade, Tracey D.
2008-01-01
The study aims to find out whether programs targeting perfectionism and media literacy are more effective than control classes in reducing eating disorder risk factors. Finding reveals that perfectionism programs are well suited to individuals of mid- to late adolescent age and shows the importune of making prevention programs developmentally…
Horizontal transmission of group B streptococcus in a neonatal intensive care unit
Morinis, Julia; Shah, Jay; Murthy, Prashanth; Fulford, Martha
2011-01-01
The incidence of early-onset group B streptococcal (GBS) sepsis in the neonatal population has decreased substantially since the introduction of maternal intrapartum antibiotic prophylaxis and routine prenatal screening. However, these strategies have not reduced the incidence of late-onset GBS infections. Additional research pertaining to the transmission of late-onset GBS infections is required to develop effective preventive methods. The present report describes probable horizontal transmission of late-onset GBS infection among three infants in a neonatal intensive care unit. GBS strain confirmation was based on the microbiological picture, antibiogram and pulsed-field gel electrophoresis. These cases highlight the morbidity associated with late-onset GBS disease and the importance of considering horizontal transmission as an etiological factor in GBS infection in the newborn period. Further studies assessing horizontal transmission in late-onset GBS disease may improve prevention and early intervention. PMID:22654550
Horizontal transmission of group B streptococcus in a neonatal intensive care unit.
Morinis, Julia; Shah, Jay; Murthy, Prashanth; Fulford, Martha
2011-06-01
The incidence of early-onset group B streptococcal (GBS) sepsis in the neonatal population has decreased substantially since the introduction of maternal intrapartum antibiotic prophylaxis and routine prenatal screening. However, these strategies have not reduced the incidence of late-onset GBS infections. Additional research pertaining to the transmission of late-onset GBS infections is required to develop effective preventive methods. The present report describes probable horizontal transmission of late-onset GBS infection among three infants in a neonatal intensive care unit. GBS strain confirmation was based on the microbiological picture, antibiogram and pulsed-field gel electrophoresis. These cases highlight the morbidity associated with late-onset GBS disease and the importance of considering horizontal transmission as an etiological factor in GBS infection in the newborn period. Further studies assessing horizontal transmission in late-onset GBS disease may improve prevention and early intervention.
Predictors of Cigarette Smoking Initiation in Early, Middle, and Late Adolescence.
O'Loughlin, Jennifer; O'Loughlin, Erin K; Wellman, Robert J; Sylvestre, Marie-Pierre; Dugas, Erika N; Chagnon, Miguel; Dutczak, Hartley; Laguë, Johanne; McGrath, Jennifer J
2017-09-01
Little is known about age-related differences in risk factors for cigarette smoking initiation. We identified predictors of initiation in early, middle, and late adolescence from among sociodemographic factors, indicators of smoking in the social environment, psychological characteristics, lifestyle indicators, and perceived need for cigarettes. Data were drawn from a longitudinal study of 1,801 children recruited at age 10-11 years from 29 elementary schools in Montreal, Canada. Multivariable logistic regression within a generalized estimating equations framework was used to identify predictors among never smokers across three 2-year windows: age 11-13 years (n = 1,221); age 13-15 years (n = 737); and age 15-17 years (n = 690). Among the 18 risk factors investigated, two differed across age. Friends' smoking, a strong risk factor in early adolescence (odds ratio [95% confidence interval] = 5.78 [3.90-8.58]), lost potency in late adolescence (1.83 [1.31-2.57]). Depressive symptoms, a risk factor in early and middle adolescence (1.60 [1.26-2.02] and 1.92 [1.45-2.54], respectively), were inversely associated in late adolescence (.76 [.58-1.00]). Sex, TV viewing, and weight-related goals were not associated with initiation at any age. All other factors were significant in two or three age groups. Most risk factors for smoking initiation were stable across age. Tobacco control interventions may be robust for risk factors across age groups and may not need adjustment. At all ages, interventions should focus on eliminating smoking in the social environment and on reducing the availability of tobacco products. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Late adolescent female smoking.
Seguire, M; Chalmers, K I
2000-06-01
Although there have been intense efforts to reduce the prevalence of cigarette smoking in the past three decades, smoking continues to be a critical public health problem. An area of particular concern is the increasing number of young women who are smoking. Gender specific research usually does not examine factors affecting smoking behaviours. Information on late adolescent female smoking is not readily found in the literature. The aims of this study were to explore the smoking patterns and processes of late adolescent females and to explore factors which may or may not be helpful in assisting them to stop smoking. A qualitative ethnographic approach was used to uncover the perceptions of 25 adolescent girls of their behaviour. Data were collected using tape-recorded semi-structured interviews and a questionnaire. Items for the questionnaire were derived from the Manitoba Youth Smoking Survey and from the Fagerstrorn Nicotine Tolerance Scale. Qualitative analysis resulted in four stories about smoking: the start story, the smoking story, the quit story, and the looking to the future story. Although many of the findings are congruent with the existing literature, much of the data reflected the purposive nature of smoking in late adolescent girls. Study findings support the need for holistic approaches to health promotion to ameliorate factors affecting smoking behaviour.
Op de Coul, Eline L M; van Sighem, Ard; Brinkman, Kees; van Benthem, Birgit H; van der Ende, Marchina E; Geerlings, Suzanne; Reiss, Peter
2016-01-01
Objectives Early testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with late or advanced disease in HIV-infected patients in the Netherlands. Methods HIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort. Risk factors for late presentation and advanced disease were analysed by multivariable logistic regression. Furthermore, geographical differences and time trends were examined. Results Of 20 965 patients, 53% presented with late-stage HIV infection, and 35% had advanced disease. Late presentation decreased from 62% (1996) to 42% (2013), while advanced disease decreased from 46% to 26%. Late presentation only declined significantly among men having sex with men (MSM; p <0.001), but not among heterosexual males (p=0.08) and females (p=0.73). Factors associated with late presentation were: heterosexual male (adjusted OR (aOR), 1.59; 95% CI 1.44 to 1.75 vs MSM), injecting drug use (2.00; CI 1.69 to 2.38), age ≥50 years (1.46; CI 1.33 to 1.60 vs 30–49 years), region of origin (South-East Asia 2.14; 1.80 to 2.54, sub-Saharan Africa 2.11; 1.88 to 2.36, Surinam 1.59; 1.37 to 1.84, Caribbean 1.31; 1.13 to 1.53, Latin America 1.23; 1.04 to 1.46 vs the Netherlands), and location of HIV diagnosis (hospital 3.27; 2.94 to 3.63, general practitioner 1.66; 1.50 to 1.83, antenatal screening 1.76; 1.38 to 2.34 vs sexually transmitted infection clinic). No association was found for socioeconomic status or level of urbanisation. Compared with Amsterdam, 2 regions had higher adjusted odds and 2 regions had lower odds of late presentation. Results were highly similar for advanced disease. Conclusions Although the overall rate of late presentation is declining in the Netherlands, targeted programmes to reduce late HIV diagnoses remain needed for all risk groups, but should be prioritised for heterosexual males, migrant populations, people aged ≥50 years and certain regions in the Netherlands. PMID:26729389
Mandrup, Camilla M; Egelund, Jon; Nyberg, Michael; Lundberg Slingsby, Martina H; Andersen, Caroline B; Løgstrup, Sofie; Bangsbo, Jens; Suetta, Charlotte; Stallknecht, Bente; Hellsten, Ylva
2017-04-01
Menopause is associated with increased risk of cardiovascular disease and the causal factors have been proposed to be the loss of estrogen and the subsequent alterations of the hormonal milieu. However, which factors contribute to the deterioration of cardiometabolic health in postmenopausal women is debated as the menopausal transition is also associated with increased age and fat mass. Furthermore, indications of reduced cardiometabolic adaptations to exercise in postmenopausal women add to the adverse health profile. We sought to evaluate risk factors for type 2 diabetes and cardiovascular disease in late premenopausal and early postmenopausal women, matched by age and body composition, and investigate the effect of high-intensity training. A 3-month high-intensity aerobic training intervention, involving healthy, nonobese, late premenopausal (n = 40) and early postmenopausal (n = 39) women was conducted and anthropometrics, body composition, blood pressure, lipid profile, glucose tolerance, and maximal oxygen consumption were determined at baseline and after the intervention. At baseline, the groups matched in anthropometrics and body composition, and only differed by 4.2 years in age (mean [95% confidence limits] 49.2 [48.5-49.9] vs 53.4 [52.4-54.4] years). Time since last menstrual period for the postmenopausal women was (mean [95% confidence limits] 3.1 [2.6-3.7] years). Hormonal levels (estrogen, follicle stimulation hormone, luteinizing hormone) confirmed menopausal status. At baseline the postmenopausal women had higher total cholesterol (P < .001), low-density lipoprotein-cholesterol (P < .05), and high-density lipoprotein-cholesterol (P < .001) than the premenopausal women. The training intervention reduced body weight (P < .01), waist circumference (P < .01), and improved body composition by increasing lean body mass (P < .001) and decreasing fat mass (P < .001) similarly in both groups. Moreover, training resulted in lower diastolic blood pressure (P < .05), resting heart rate (P < .001), total cholesterol (P < .01), low-density lipoprotein-cholesterol (P < .01), total cholesterol/high-density lipoprotein-cholesterol index (P < .01), and improved plasma insulin concentration during the oral glucose tolerance test (P < .05) in both groups. Cardiovascular risk factors are similar in late premenopausal and early postmenopausal women, matched by age and body composition, with the exception that postmenopausal women have higher high- and low-density lipoprotein-cholesterol levels. A 3-month intervention of high-intensity aerobic training reduces risk factors for type 2 diabetes and cardiovascular disease to a similar extent in late premenopausal and early postmenopausal women. Copyright © 2016 Elsevier Inc. All rights reserved.
Giorgio, Marco; Stendardo, Massimo; Migliaccio, Enrica; Pelicci, Pier Giuseppe
2016-06-01
Oxidative stress and telomere attrition are considered the driving factors of aging. As oxidative damage to telomeric DNA favors the erosion of chromosome ends and, in turn, telomere shortening increases the sensitivity to pro-oxidants, these two factors may trigger a detrimental vicious cycle. To check whether limiting oxidative stress slows down telomere shortening and related progeria, we have investigated the effect of p66SHC deletion, which has been shown to reduce oxidative stress and mitochondrial apoptosis, on late-generation TERC (telomerase RNA component)-deficient mice having short telomeres and reduced lifespan. Double mutant (TERC(-/-) p66SHC(-/-) ) mice were generated, and their telomere length, fertility, and lifespan investigated in different generations. Results revealed that p66SHC deletion partially rescues sterility and weight loss, as well as organ atrophy, of TERC-deficient mice, but not their short lifespan and telomere erosion. Therefore, our data suggest that p66SHC-mediated oxidative stress and telomere shortening synergize in some tissues (including testes) to accelerate aging; however, early mortality of late-generation mice seems to be independent of any link between p66SHC-mediated oxidative stress and telomere attrition. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Acquisition of English word stress patterns in early and late bilinguals
NASA Astrophysics Data System (ADS)
Guion, Susan G.
2004-05-01
Given early acquisition of prosodic knowledge as demonstrated by infants' sensitivity to native language accentual patterns, the question of whether learners can acquire new prosodic patterns across the life span arises. Acquisition of English stress by early and late Spanish-English and Korean-English bilinguals was investigated. In a production task, two-syllable nonwords were produced in noun and verb sentence frames. In a perception task, preference for first or last syllable stress on the nonwords was indicated. Also, real words that were phonologically similar to the nonwords were collected. Logistic regression analyses and ANOVAs were conducted to determine the effect of three factors (syllable structure, lexical class, and stress patterns of phonologically similar words) on the production and perception responses. In all three groups, stress patterns of phonologically similar real words predicted stress on nonwords. For the two other factors, early bilinguals patterned similarly to the native-English participants. Late Spanish-English bilinguals demonstrated less learning of stress patterns based on syllabic structure, and late Korean-English bilinguals demonstrated less learning of stress patterns based on lexical class than native-English speakers. Thus, compared to native speakers, late bilinguals' ability to abstract stress patterns is reduced and affected by the first language. [Work supported by NIH.
Zara, Georgia; Farrington, David P
2010-10-01
Late-onset offending, at the age of 21 or thereafter, is an underexplored dimension of the criminal career. Our aims were to explore which factors are precursors of late-onset offending, and the extent to which adult criminality can be predicted in childhood and adolescence. This is the first study that defines late-onset offending based on a combination of official records and self-reports. Longitudinal data from the Cambridge Study in Delinquent Development (CSDD) were used. Four hundred and three South London men, followed from ages 8-10 to ages 48-50, were divided into late-starters (LS, n = 51), early-starters (ES, n = 140) and non-offenders (NO, n = 212). LS men were more likely than NO men to have been neurotic, truants or in poor housing at ages 8-10. At ages 12-14, they tended to be neurotic, and at ages 16-18, they had high unemployment and spent time hanging about on the streets. Compared with ES, LS were nervous at ages 8-10, and at age 18 they were more likely to be sexual virgins. Overall, LS men were more similar to NO men before age 21, but more similar to ES men by age 32. Our hypotheses that late-onset offenders would be particularly characterised by neuroticism or nervousness, but that this would buffer rather than fully protect over the life course, were sustained. Intervention to increase the resilience of children and adolescents who are rated as high on neurotic characteristics may lessen the burden that these factors impose in adult life and reduce the risk of a deteriorating quality of life and late onset criminal careers. © 2010 John Wiley & Sons, Ltd.
Angiogenic profile and smoking in the Finnish Genetics of Pre-Eclampsia Consortium (FINNPEC) cohort.
Jääskeläinen, Tiina; Suomalainen-König, Sanna; Hämäläinen, Esa; Pulkki, Kari; Romppanen, Jarkko; Heinonen, Seppo; Laivuori, Hannele
2017-11-01
The biological mechanism by which smoking reduces the risk of pre-eclampsia (PE) is unresolved. We studied serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and their ratio, in addition to soluble endoglin (sEng) in early and late pregnancy to ascertain whether these factors are altered in women who smoke. First trimester serum samples were available from 217 women who later developed PE and 238 women who did not develop PE. Second/third trimester serum samples were available from 174 PE and 54 non-PE women. PE women who smoked during pregnancy had elevated first trimester concentrations of serum PlGF [geometric mean (95% CI): 39.8 (32.6-48.5) pg/ml, p = .001] and reduced sEng concentration [5.0 (4.6-5.6) ng/ml, p = .047] compared to PE non-smokers [30.0 (28.1-32.1) pg/ml and 6.1 (5.9-6.4) ng/ml, respectively]. Non-smoking women in the PE group had the highest sFlt-1/PlGF ratio in early and late pregnancy. The protective effect of smoking in reducing the risk of PE may be due to the early pregnancy change towards pro-angiogenic marker profile. Also, in late pregnancy, smoking exerted effect in sFlt-1/PlGF ratio in PE pregnancies, and may complicate its use as a prognostic and diagnostic marker. Key messages Smoking appears to have angiogenic effects in early pregnancy with reduced sEng concentrations and elevated PlGF concentrations in both normal and PE pregnancies. Throughout pregnancy, smoking exerted effect in PlGF concentration and sFlt-1/PlGF ratio in PE pregnancies, and thus may complicate its use as a prognostic and diagnostic marker.
HCN Production via Impact Ejecta Reentry During the Late Heavy Bombardment
NASA Astrophysics Data System (ADS)
Parkos, Devon; Pikus, Aaron; Alexeenko, Alina; Melosh, H. Jay
2018-04-01
Major impact events have shaped the Earth as we know it. The Late Heavy Bombardment is of particular interest because it immediately precedes the first evidence of life. The reentry of impact ejecta creates numerous chemical by-products, including biotic precursors such as HCN. This work examines the production of HCN during the Late Heavy Bombardment in more detail. We stochastically simulate the range of impacts on the early Earth and use models developed from existing studies to predict the corresponding ejecta properties. Using multiphase flow methods and finite-rate equilibrium chemistry, we then find the HCN production due to the resulting atmospheric heating. We use Direct Simulation Monte Carlo to develop a correction factor to account for increased yields due to thermochemical nonequilibrium. We then model 1-D atmospheric turbulent diffusion to find the time accurate transport of HCN to lower altitudes and ultimately surface water. Existing works estimate the necessary HCN molarity threshold to promote polymerization that is 0.01 M. For a mixing depth of 100 m, we find that the Late Heavy Bombardment will produce at least one impact event above this threshold with probability 24.1% for an oxidized atmosphere and 56.3% for a partially reduced atmosphere. For a mixing depth of 10 m, the probability is 79.5% for an oxidized atmosphere and 96.9% for a partially reduced atmosphere. Therefore, Late Heavy Bombardment impact ejecta is likely an HCN source sufficient for polymerization in shallow bodies of water, particularly if the atmosphere were in a partially reduced state.
Waters, L; Fisher, M; Anderson, J; Wood, C; Delpech, V; Hill, T; Walsh, J; Orkin, C; Bansi, L; Gompels, M; Phillips, A; Johnson, M; Gilson, R; Easterbrook, P; Leen, C; Porter, K; Gazzard, B; Sabin, C
2011-05-01
We investigated whether adverse responses to highly active antiretroviral therapy (HAART) associated with late HIV presentation are secondary to low CD4 cell count per se or other confounding factors. A longitudinal analysis of the UK Collaborative HIV Cohort (CHIC) Study of individuals starting HAART in 1998-2007 was carried out, comparing late presenters (presenting/starting HAART at a CD4 count <200 cells/μL) with late starters (presenting at a CD4 count>350 cells/μL; starting HAART at a CD4 count<200 cells/μL), using 'ideal starters' (presenting at a CD4 count>350 cells/μL; starting HAART at a CD4 count of 200-350 cells/μL) as a comparator. Virological, immunological and clinical (new AIDS event/death) outcomes at 48 and 96 weeks were analysed, with the analysis being limited to those remaining on HAART for>3 months. A total of 4978 of 9095 individuals starting first-line HAART with HIV RNA>500 HIV-1 RNA copies/mL were included in the analysis: 2741 late presenters, 947 late starters and 1290 ideal starters. Late presenters were more commonly female, heterosexual and Black African. Most started nonnucleoside reverse transcriptase inhibitors (NNRTIs); 48-week virological suppression was similar in late presenters and starters (and marginally lower than in ideal starters); by week 96 differences were reduced and nonsignificant. The median CD4 cell count increase in late presenters was significantly lower than that in late starters (weeks 48 and 96). During year 1, new clinical events were more frequent for late presenters [odds ratio (OR) 2.04; 95% confidence interval (CI) 1.19-3.51; P=0.01]; by year 2, event rates were similar in all groups. Amongst patients who initiate, and remain on, HAART, late presentation is associated with lower rates of virological suppression, blunted CD4 cell count increases and more clinical events compared with late starters in year 1, but similar clinical and immunological outcomes by year 2 to those of both late and ideal starters. Differences between late presenters and late starters suggest that factors other than CD4 cell count alone may be driving adverse treatment outcomes in late-presenting individuals.
All washed out? Foliar nutrient resorption and leaching in senescing switchgrass
USDA-ARS?s Scientific Manuscript database
Ideal bioenergy feedstocks are low in nutrients that act as anti-quality factors during conversion processes. Research has shown that delaying harvest of temperate perennial grasses until late winter reduces nutrient content, primarily due to end-season resorption, but also indicates a role for foli...
A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts.
Fox, Hannah L; Dembowski, Jill A; DeLuca, Neal A
2017-06-13
Herpes simplex virus 1 (HSV-1) genes are transcribed by cellular RNA polymerase II (RNA Pol II). While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22) function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16) was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes. We further demonstrated that the FACT complex interacts with ICP22 throughout infection. We therefore hypothesized that ICP22 recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes. We reevaluated the phenotype of an ICP22 mutant virus by determining the abundance of all viral mRNAs throughout infection by transcriptome sequencing (RNA-seq). The accumulation of almost all viral mRNAs late in infection was reduced compared to the wild type, regardless of kinetic class. Using chromatin immunoprecipitation sequencing (ChIP-seq), we mapped the location of RNA Pol II on viral genes and found that RNA Pol II levels on the bodies of viral genes were reduced in the ICP22 mutant compared to wild-type virus. In contrast, the association of RNA Pol II with transcription start sites in the mutant was not reduced. Taken together, our results indicate that ICP22 plays a role in recruiting elongation factors like the FACT complex to the HSV-1 genome to allow for efficient viral transcription elongation late in viral infection and ultimately infectious virion production. IMPORTANCE HSV-1 interacts with many cellular proteins throughout productive infection. Here, we demonstrate the interaction of a viral protein, ICP22, with a subset of cellular proteins known to be involved in transcription elongation. We determined that ICP22 is required to recruit the FACT complex and other transcription elongation factors to viral genomes and that in the absence of ICP22 viral transcription is globally reduced late in productive infection, due to an elongation defect. This insight defines a fundamental role of ICP22 in HSV-1 infection and elucidates the involvement of cellular factors in HSV-1 transcription. Copyright © 2017 Fox et al.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zawawi, M.S.F.; Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005; Dharmapatni, A.A.S.S.K.
2012-10-19
Highlights: Black-Right-Pointing-Pointer Calcineurin/NFAT inhibitors FK506 and VIVIT treated human PBMC derived osteoclasts in vitro. Black-Right-Pointing-Pointer Differential regulation of ITAM receptors and adaptor molecules by calcineurin/NFAT inhibitors. Black-Right-Pointing-Pointer FK506 and VIVIT suppress ITAM factors during late phase osteoclast differentiation. -- Abstract: Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway inmore » osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcR{gamma}) and DNAX-activating protein 12 kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin ({beta}3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10 days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that FK506 treatment significantly (p < 0.05) reduced the expression of NFATc1, CathK, OSCAR, FcR{gamma}, TREM2 and DAP12 during the terminal stage of osteoclast formation. VIVIT treatment significantly (p < 0.05) decreased CathK, OSCAR, FcR{gamma}, and AnnVIII, gene expression. This data suggest FK506 and VIVIT act differently in targeting the calcineurin-NFAT signalling cascade to suppress key mediators of the ITAM pathway during late stage osteoclast differentiation and this is associated with a reduction in both osteoclast differentiation and activity.« less
Op de Coul, Eline L M; van Sighem, Ard; Brinkman, Kees; van Benthem, Birgit H; van der Ende, Marchina E; Geerlings, Suzanne; Reiss, Peter
2016-01-04
Early testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with late or advanced disease in HIV-infected patients in the Netherlands. HIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort. Risk factors for late presentation and advanced disease were analysed by multivariable logistic regression. Furthermore, geographical differences and time trends were examined. Of 20,965 patients, 53% presented with late-stage HIV infection, and 35% had advanced disease. Late presentation decreased from 62% (1996) to 42% (2013), while advanced disease decreased from 46% to 26%. Late presentation only declined significantly among men having sex with men (MSM; p <0.001), but not among heterosexual males (p=0.08) and females (p=0.73). Factors associated with late presentation were: heterosexual male (adjusted OR (aOR), 1.59; 95% CI 1.44 to 1.75 vs MSM), injecting drug use (2.00; CI 1.69 to 2.38), age ≥ 50 years (1.46; CI 1.33 to 1.60 vs 30-49 years), region of origin (South-East Asia 2.14; 1.80 to 2.54, sub-Saharan Africa 2.11; 1.88 to 2.36, Surinam 1.59; 1.37 to 1.84, Caribbean 1.31; 1.13 to 1.53, Latin America 1.23; 1.04 to 1.46 vs the Netherlands), and location of HIV diagnosis (hospital 3.27; 2.94 to 3.63, general practitioner 1.66; 1.50 to 1.83, antenatal screening 1.76; 1.38 to 2.34 vs sexually transmitted infection clinic). No association was found for socioeconomic status or level of urbanisation. Compared with Amsterdam, 2 regions had higher adjusted odds and 2 regions had lower odds of late presentation. Results were highly similar for advanced disease. Although the overall rate of late presentation is declining in the Netherlands, targeted programmes to reduce late HIV diagnoses remain needed for all risk groups, but should be prioritised for heterosexual males, migrant populations, people aged ≥ 50 years and certain regions in the Netherlands. 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/
Baer, Rebecca J; Altman, Molly R; Oltman, Scott P; Ryckman, Kelli K; Chambers, Christina D; Rand, Larry; Jelliffe-Pawlowski, Laura L
2018-04-22
Examine factors influencing late (> sixth month of gestation) entry into prenatal care by race/ethnicity and insurance payer. The study population was drawn from singleton live births in California from 2007 to 2012 in the birth cohort file maintained by the California Office of Statewide Health Planning and Development, which includes linked birth certificate and mother and infant hospital discharge records. The sample was restricted to infants delivered between 20 and 44 weeks gestation. Logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI) for factors influencing late entry into prenatal care. Maternal age, education, smoking, drug or alcohol abuse/dependence, mental illness, participation in the Women, Infants and Children's program and rural residence were evaluated for women entering prenatal care > sixth month of gestation compared with women entering < fourth month. Backwards stepwise logistic regression was used to create final multivariable models of risk and protective factors for late prenatal care entry for each race or ethnicity and insurance payer. The sample included 2,963,888 women. The percent of women with late entry into prenatal care was consistently higher among women with public versus private insurance. Less than 1% of white non-Hispanic and Asian women with private insurance entered prenatal care late versus more than 4% of white non-Hispanic and black women with public insurance. After stratifying by race or ethnicity and insurance status, women less than 18 years of age were more likely to enter prenatal care late, with young Asian women with private insurance at the highest risk (15.6%; adjusted RR 7.4, 95%CI 5.3-10.5). Among all women with private insurance, > 12-year education or age >34 years at term reduced the likelihood of late prenatal care entry (adjusted RRs 0.5-0.7). Drugs and alcohol abuse/dependence and residing in a rural county were associated with increased risk of late prenatal care across all subgroups (adjusted RRs 1.3-3.8). Participation in the Women, Infants, and Children's program was associated with decreased risk of late prenatal care for women with public insurance (adjusted RRs 0.6-0.7), but increased risk for women with private insurance (adjusted RRs 1.4-2.1). The percent of women with late entry into prenatal care was consistently higher among women with public insurance. Younger women, women with <12-year education, those who used drugs or alcohol or resided in rural counties were more likely to enter prenatal care late, with Asian women <18 years at especially high risk. Participation in the Women, Infants, and Children's program and maternal age >34 years at delivery increased the likelihood of late prenatal care for some subgroups of women and decreased the likelihood for others. These findings can inform institutional factors influencing late prenatal care, especially among lower income women, and may assist efforts aimed at encouraging earlier entry into prenatal care. Optimal prenatal care includes initiation before the 14th week of gestation. Beginning care in the first trimester provides an opportunity for sonographic pregnancy dating or confirmation with best accuracy, which can later prove critical for management of preterm labor, maternal or fetal complications, or prolonged pregnancy. In order to improve maternal and infant health by increasing the number of women seeking prenatal care in the first trimester, it is important to examine the drivers for late entry. Here, we examine factors influencing late (> sixth month of gestation) entry into prenatal care by race/ethnicity and insurance payer. We found the percent of women with late entry into prenatal care was consistently higher among women with public insurance. Younger women, women with <12-year education, those who used drugs or alcohol or resided in rural counties were more likely to enter prenatal care late, with Asian women <18 years at especially high risk. These findings can inform institutional factors influencing late prenatal care, especially among lower income women, and may assist efforts aimed at encouraging earlier entry into prenatal care.
Factors influencing young adults' attitudes and knowledge of late-life sexuality among older women.
Allen, Rebecca S; Petro, Kathryn N; Phillips, Laura L
2009-03-01
Although sexuality is valued throughout the lifespan, older women's sexual expression can be influenced by physical, mental and social factors, including attitudes and stereotypes held by younger generations. By gaining an understanding of what influences negative attitudes toward sexuality and beliefs about sexual consent capacity, the stigma associated with sexuality in late life may be reduced. Using vignette methodology in an online survey, we examined older women's health and young adults' (N = 606; mean age = 18.86, SD = 1.42, range 17-36) general knowledge and attitudes toward aging and sexuality, personal sexual behavior, religious beliefs and perceived closeness with an older adult on attitudes towards sexual behavior and perceptions of consent capacity among older women. The health status of older women proved important in determining young adults' acceptance and perception of sexual consent capacity regarding late-life heterosexual/autoerotic and homosexual behaviors. Specifically, young adults expressed lower acceptance and more doubt regarding capacity to consent to sexual expression when the older woman was described as cognitively impaired. Additionally, young adults' personal attitudes toward late-life sexuality, but not knowledge, predicted acceptance toward sexual expression and belief in sexual consent capacity. Attention toward the influence of older women's cognitive health and young adults' attitudes toward late-life sexuality may prove beneficial in designing interventions to decrease the stigma associated with sexual activity in later life.
Online assessment of risk factors for dementia and cognitive function in healthy adults.
Huntley, J; Corbett, A; Wesnes, K; Brooker, H; Stenton, R; Hampshire, A; Ballard, C
2018-02-01
Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation. Managing these risk factors in late midlife and older age may help reduce the risk of dementia; however, it is unclear whether these factors also relate to cognitive performance in older individuals without dementia. Data from 14 201 non-demented individuals aged >50 years who enrolled in the online PROTECT study were used to examine the relationship between cognitive function and known modifiable risk factors for dementia. Multivariate regression analyses were conducted on 4 cognitive outcomes assessing verbal and spatial working memory, visual episodic memory, and verbal reasoning. Increasing age was associated with reduced performance across all tasks. Higher educational achievement, the presence of a close confiding relationship, and moderate alcohol intake were associated with benefits across all 4 cognitive tasks, and exercise was associated with better performance on verbal reasoning and verbal working memory tasks. A diagnosis of depression was negatively associated with performance on visual episodic memory and working memory tasks, whereas being underweight negatively affected performance on all tasks apart from verbal working memory. A history of stroke was negatively associated with verbal reasoning and working memory performance. Known modifiable risk factors for dementia are associated with cognitive performance in non-demented individuals in late midlife and older age. This provides further support for public health interventions that seek to manage these risk factors across the lifespan. Copyright © 2017 John Wiley & Sons, Ltd.
Sindhwani, Aastha; Kaur, Harmeet; Tuli, Amit
2017-01-01
Salmonella enterica serovar typhimurium extensively remodels the host late endocytic compartments to establish its vacuolar niche within the host cells conducive for its replication, also known as the Salmonella-containing vacuole (SCV). By maintaining a prolonged interaction with late endosomes and lysosomes of the host cells in the form of interconnected network of tubules (Salmonella-induced filaments or SIFs), Salmonella gains access to both membrane and fluid-phase cargo from these compartments. This is essential for maintaining SCV membrane integrity and for bacterial intravacuolar nutrition. Here, we have identified the multisubunit lysosomal tethering factor—HOPS (HOmotypic fusion and Protein Sorting) complex as a crucial host factor facilitating delivery of late endosomal and lysosomal content to SCVs, providing membrane for SIF formation, and nutrients for intravacuolar bacterial replication. Accordingly, depletion of HOPS subunits significantly reduced the bacterial load in non-phagocytic and phagocytic cells as well as in a mouse model of Salmonella infection. We found that Salmonella effector SifA in complex with its binding partner; SKIP, interacts with HOPS subunit Vps39 and mediates recruitment of this tethering factor to SCV compartments. The lysosomal small GTPase Arl8b that binds to, and promotes membrane localization of Vps41 (and other HOPS subunits) was also required for HOPS recruitment to SCVs and SIFs. Our findings suggest that Salmonella recruits the host late endosomal and lysosomal membrane fusion machinery to its vacuolar niche for access to host membrane and nutrients, ensuring its intracellular survival and replication. PMID:29084291
Green, Dale E; Hamory, Bruce H; Terrell, Grace E; O'Connell, Jasmine
2017-08-01
Over the course of a single year, Cornerstone Health Care, a multispecialty group practice in North Carolina, redesigned the underlying care models for 5 of its highest-risk populations-late-stage congestive heart failure, oncology, Medicare-Medicaid dual eligibles, those with 5 or more chronic conditions, and the most complex patients with multiple late-stage chronic conditions. At the 1-year mark, the results of the program were analyzed. Overall costs for the patients studied were reduced by 12.7% compared to the year before enrollment. All fully implemented programs delivered between 10% and 16% cost savings. The key area for savings factor was hospitalization, which was reduced by 30% across all programs. The greatest area of cost increase was "other," a category that consisted in large part of hospice services. Full implementation was key; 2 primary care sites that reverted to more traditional models failed to show the same pattern of savings.
Influence of physical activity on vertebral strength during late adolescence.
Junno, Juho-Antti; Paananen, Markus; Karppinen, Jaro; Tammelin, Tuija; Niinimäki, Jaakko; Lammentausta, Eveliina; Niskanen, Markku; Nieminen, Miika T; Järvelin, Marjo-Riitta; Takatalo, Jani; Tervonen, Osmo; Tuukkanen, Juha
2013-02-01
Reduced vertebral strength is a clear risk factor for vertebral fractures. Men and women with vertebral fractures often have reduced vertebral size and bone mineral density (BMD). Vertebral strength is controlled by both genetic and developmental factors. Malnutrition and low levels of physical activity are commonly considered to result in reduced bone size during growth. Several studies have also demonstrated the general relationship between BMD and physical activity in the appendicular skeleton. In this study, we wanted to clarify the role of physical activity on vertebral bodies. Vertebral dimensions appear to generally be less pliant than long bones when lifetime changes occur. We wanted to explore the association between physical activity during late adolescence and vertebral strength parameters such as cross-sectional size and BMD. The association between physical activity and vertebral strength was explored by measuring vertebral strength parameters and defining the level of physical activity during adolescence. The study population consisted of 6,928 males and females who, at 15 to 16 and 19 years of age, responded to a mailed questionnaire inquiring about their physical activity. A total of 558 individuals at the mean age of 21 years underwent magnetic resonance imaging (MRI) scans. We measured the dimensions of the fourth lumbar vertebra from the MRI scans of the Northern Finland Birth Cohort 1986 and performed T2* relaxation time mapping, reflective of BMD. Vertebral strength was based on these two parameters. We analyzed the association of physical activity on vertebral strength using the analysis of variance. We observed no association between the level of physical activity during late adolescence and vertebral strength at 21 years. Copyright © 2013 Elsevier Inc. All rights reserved.
Dörffel, W; Riepenhausen, M; Lüders, H; Brämswig, J
2016-11-01
Survival rates have been excellent in patients treated for Hodgkin lymphoma (HL) during childhood and adolescence. Unfortunately, severe treatment related late effects have been observed. It was therefore an important aim of the cooperative pediatric HL therapy studies in Germany to reduce the number of late effects without jeopardizing the excellent treatment results. Progress and relapses of HL were analyzed to obtain important information for the future salvage therapy. All late effects were documented and their etiologies analyzed. Information obtained from bacterial infections and late deaths following splenectomy were used to inform patients at risk and their local physicians about necessary preventive measurements. Procarbazine was recognized as major gonadotoxic agent in boys and eliminated successively from the treatment regimens. Parenthood was normal in female patients when compared to the German female population documenting normal ovarian function except in patients with pelvic radiation. Radiation was the most important risk factor for thyroid diseases, cardiac late effects and subsequent malignant neoplasms, especially thyroid and breast cancer. A special screening program was initiated for women with chest radiotherapy, since they had a high risk of breast cancer already at a young age. The results of the HL Late Effects Research Project are important for the aftercare of patients and for the design of future HL treatment regimens. © Georg Thieme Verlag KG Stuttgart · New York.
USDA-ARS?s Scientific Manuscript database
Enteral formula feeding is a risk factor for necrotizing enterocolitis (NEC) in premature infants, yet studies are conflicting regarding the safest timing for introduction and advancement of feeds. Our aim was to test the effects of early vs. late initiation and abrupt vs. gradual advancement of ent...
Presence and process of fear of birth during pregnancy-Findings from a longitudinal cohort study.
Hildingsson, Ingegerd; Haines, Helen; Karlström, Annika; Nystedt, Astrid
2017-10-01
The prevalence of fear of birth has been estimated between 8-30%, but there is considerable heterogeneity in research design, definitions, measurement tools used and populations. There are some inconclusive findings about the stability of childbirth fear. to assess the prevalence and characteristics of women presenting with scores ≥60 on FOBS-The Fear of Birth Scale, in mid and late pregnancy, and to study change in fear of birth and associated factors. A prospective longitudinal cohort study of a one-year cohort of 1212 pregnant women from a northern part of Sweden, recruited in mid pregnancy and followed up in late pregnancy. Fear of birth was assessed using FOBS-The fear of birth scale, with the cut off at ≥60. The prevalence of fear of birth was 22% in mid pregnancy and 19% in late pregnancy, a statistically significant decrease. Different patterns were found where some women presented with increased fear and some with decreased fear. The women who experienced more fear or less fear later in pregnancy could not be differentiated by background factors. More research is needed to explore factors important to reduce fear of childbirth and the optimal time to measure it. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.
Ortiz-Ortiz, Karen J; Ríos-Motta, Ruth; Marín-Centeno, Heriberto; Cruz-Correa, Marcia; Ortiz, Ana Patricia
2016-08-03
Late stage at diagnosis of cancer is considered a key predictor factor for a lower survival rate. Knowing and understanding the barriers to an early diagnosis of colorectal cancer is critical in the fight to reduce the social and economic burden caused by cancer in Puerto Rico. This study evaluates factors associated to colorectal cancer stage at diagnosis among Puerto Rico's Government Health Plan (GHP) patients. We conducted a cross-sectional study based on a secondary data analysis using information from the Puerto Rico Central Cancer Registry (PRCCR) and the Puerto Rico Health Insurance Administration (PRHIA). Logistic regression models were used to estimate the unadjusted odds ratio (ORs) and adjusted odds ratio (AORs), and their 95 % confidence intervals (CIs). Colorectal cancer cases diagnosed between January 1, 2012 and December 31, 2012, among persons 50 to 64 years of age, participants of the GHP and with a cancer diagnosis reported to the PRCCR were included in the study. There were 68 (35.79 %) colorectal cancer patients diagnosed at early stage while 122 (64.21 %) where diagnosed at late stage. In the multivariate analysis having a diagnostic delay of more than 59 days (AOR 2.94, 95 % CI: 1.32 to 6.52) and having the first visit through the emergency room (AOR 3.48, 95 % CI: 1.60 to 7.60) were strong predictors of being diagnosed with colorectal cancer at a late stage. These results are relevant to understand the factors that influence the outcomes of colorectal cancer patients in the GHP. Therefore, it is important to continue developing studies to understand the Government Health Plan patient's pathways to a cancer diagnosis, in order to promote assertive decisions to improve patient outcomes.
Risk factors for early miscarriage among Chinese: a hospital-based case-control study.
Xu, Guangli; Wu, Yiming; Yang, Liming; Yuan, Lu; Guo, Huafeng; Zhang, Fuqing; Guan, Yichun; Yao, Wu
2014-06-01
To investigate the risk factors for early miscarriage among Chinese women. Hospital-based matched case-control study. Academic medical center and maternal health hospital. 620 women with early miscarriage (less than 13 weeks of gestation) and 1,240 normal pregnant women. Face-to-face questionnaire. Multivariable conditional odds ratio (OR) and 95% confidence interval (CI) to measure risk factors. After adjustment for confounding factors, the following were independently associated with increased risk: history of miscarriage, repeated induced abortion, working night shifts, and frequent staying up late. Vitamin supplementation and regular physical activity reduced the risk of miscarriage. We did not find paternal age, alcohol consumption, or smoking status to be linked with early miscarriage. Our findings suggest that a healthy diet, regular physical activity, and planned pregnancy may be advantageous for women in pre-pregnancy or early pregnancy. Induced abortion, working night shifts, and frequent staying up late were associated with an increased risk of miscarriage. Further work in larger populations is warranted. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Morrow, Lindsey A; Wagner, Brandie D; Ingram, David A; Poindexter, Brenda B; Schibler, Kurt; Cotten, C Michael; Dagle, John; Sontag, Marci K; Mourani, Peter M; Abman, Steven H
2017-08-01
Mechanisms contributing to chronic lung disease after preterm birth are incompletely understood. To identify antenatal risk factors associated with increased risk for bronchopulmonary dysplasia (BPD) and respiratory disease during early childhood after preterm birth, we performed a prospective, longitudinal study of 587 preterm infants with gestational age less than 34 weeks and birth weights between 500 and 1,250 g. Data collected included perinatal information and assessments during the neonatal intensive care unit admission and longitudinal follow-up by questionnaire until 2 years of age. After adjusting for covariates, we found that maternal smoking prior to preterm birth increased the odds of having an infant with BPD by twofold (P = 0.02). Maternal smoking was associated with prolonged mechanical ventilation and respiratory support during the neonatal intensive care unit admission. Preexisting hypertension was associated with a twofold (P = 0.04) increase in odds for BPD. Lower gestational age and birth weight z-scores were associated with BPD. Preterm infants who were exposed to maternal smoking had higher rates of late respiratory disease during childhood. Twenty-two percent of infants diagnosed with BPD and 34% of preterm infants without BPD had no clinical signs of late respiratory disease during early childhood. We conclude that maternal smoking and hypertension increase the odds for developing BPD after preterm birth, and that maternal smoking is strongly associated with increased odds for late respiratory morbidities during early childhood. These findings suggest that in addition to the BPD diagnosis at 36 weeks, other factors modulate late respiratory outcomes during childhood. We speculate that measures to reduce maternal smoking not only will lower the risk for preterm birth but also will improve late respiratory morbidities after preterm birth.
78 FR 23948 - Endangered and Threatened Wildlife and Plants; Black-Footed Ferret Draft Recovery Plan
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-23
... America wherever prairie dogs occurred. The species was listed as endangered in 1967 (32 FR 4001; March 11... prairie dogs was an important factor in the ferret's decline. From the late 1800s to approximately the 1960s, prairie dog-occupied habitat and prairie dog numbers were dramatically reduced by the effects of...
Zhu, Yan; Zhang, Ke; Hu, Lan; Xiao, Mi-Li; Li, Zhi-Hua; Chen, Chao
2017-05-01
To investigate the risk factors, clinical features, and magnetic resonance imaging (MRI) changes of encephalopathy in high-risk late preterm infants. Head MRI scan was performed for late preterm infants with high-risk factors for brain injury who were hospitalized between January 2009 and December 2014. The risk factors, clinical features, and head MRI features of encephalopathy in late preterm infants were analyzed. A total of 1 007 late preterm infants underwent MRI scan, among whom 313 (31.1%) had imaging features in accordance with the features of encephalopathy of prematurity. Of all infants, 76.7% had white matter damage. There was no association between the development of encephalopathy and gestational age in late preterm infants, but the detection rate of encephalopathy gradually increased with the increasing birth weight (P<0.05). The logistic regression analysis showed that a history of resuscitation was an independent risk factor for encephalopathy of prematurity (P<0.01). Encephalopathy of prematurity is commonly seen in high-risk late preterm infants, especially white matter damage. A history of resuscitation is an independent risk factor for encephalopathy in late preterm infants.
McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J
2015-01-15
Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights reserved.
Vowel reduction in word-final position by early and late Spanish-English bilinguals.
Byers, Emily; Yavas, Mehmet
2017-01-01
Vowel reduction is a prominent feature of American English, as well as other stress-timed languages. As a phonological process, vowel reduction neutralizes multiple vowel quality contrasts in unstressed syllables. For bilinguals whose native language is not characterized by large spectral and durational differences between tonic and atonic vowels, systematically reducing unstressed vowels to the central vowel space can be problematic. Failure to maintain this pattern of stressed-unstressed syllables in American English is one key element that contributes to a "foreign accent" in second language speakers. Reduced vowels, or "schwas," have also been identified as particularly vulnerable to the co-articulatory effects of adjacent consonants. The current study examined the effects of adjacent sounds on the spectral and temporal qualities of schwa in word-final position. Three groups of English-speaking adults were tested: Miami-based monolingual English speakers, early Spanish-English bilinguals, and late Spanish-English bilinguals. Subjects performed a reading task to examine their schwa productions in fluent speech when schwas were preceded by consonants from various points of articulation. Results indicated that monolingual English and late Spanish-English bilingual groups produced targeted vowel qualities for schwa, whereas early Spanish-English bilinguals lacked homogeneity in their vowel productions. This extends prior claims that schwa is targetless for F2 position for native speakers to highly-proficient bilingual speakers. Though spectral qualities lacked homogeneity for early Spanish-English bilinguals, early bilinguals produced schwas with near native-like vowel duration. In contrast, late bilinguals produced schwas with significantly longer durations than English monolinguals or early Spanish-English bilinguals. Our results suggest that the temporal properties of a language are better integrated into second language phonologies than spectral qualities. Finally, we examined the role of nonstructural variables (e.g. linguistic history measures) in predicting native-like vowel duration. These factors included: Age of L2 learning, amount of L1 use, and self-reported bilingual dominance. Our results suggested that different sociolinguistic factors predicted native-like reduced vowel duration than predicted native-like vowel qualities across multiple phonetic environments.
Vowel reduction in word-final position by early and late Spanish-English bilinguals
2017-01-01
Vowel reduction is a prominent feature of American English, as well as other stress-timed languages. As a phonological process, vowel reduction neutralizes multiple vowel quality contrasts in unstressed syllables. For bilinguals whose native language is not characterized by large spectral and durational differences between tonic and atonic vowels, systematically reducing unstressed vowels to the central vowel space can be problematic. Failure to maintain this pattern of stressed-unstressed syllables in American English is one key element that contributes to a “foreign accent” in second language speakers. Reduced vowels, or “schwas,” have also been identified as particularly vulnerable to the co-articulatory effects of adjacent consonants. The current study examined the effects of adjacent sounds on the spectral and temporal qualities of schwa in word-final position. Three groups of English-speaking adults were tested: Miami-based monolingual English speakers, early Spanish-English bilinguals, and late Spanish-English bilinguals. Subjects performed a reading task to examine their schwa productions in fluent speech when schwas were preceded by consonants from various points of articulation. Results indicated that monolingual English and late Spanish-English bilingual groups produced targeted vowel qualities for schwa, whereas early Spanish-English bilinguals lacked homogeneity in their vowel productions. This extends prior claims that schwa is targetless for F2 position for native speakers to highly-proficient bilingual speakers. Though spectral qualities lacked homogeneity for early Spanish-English bilinguals, early bilinguals produced schwas with near native-like vowel duration. In contrast, late bilinguals produced schwas with significantly longer durations than English monolinguals or early Spanish-English bilinguals. Our results suggest that the temporal properties of a language are better integrated into second language phonologies than spectral qualities. Finally, we examined the role of nonstructural variables (e.g. linguistic history measures) in predicting native-like vowel duration. These factors included: Age of L2 learning, amount of L1 use, and self-reported bilingual dominance. Our results suggested that different sociolinguistic factors predicted native-like reduced vowel duration than predicted native-like vowel qualities across multiple phonetic environments. PMID:28384234
Carmona, Francisco; Lázaro, Isabel; Reverter, Juan C; Tàssies, Dolors; Font, Josep; Cervera, Ricard; Balasch, Juan
2006-02-01
The objective of the study was to investigate the potential role of impaired factor XII-dependent activation of fibrinolysis in treated antiphospholipid syndrome gestations developing late-pregnancy complications. This was a prospective study in a third-level teaching hospital, including 75 patients: 25 pregnant patients having the antiphospholipid syndrome and carrying their pregnancies until 26 weeks' gestation or later (group 1); 25 pregnant patients having normal term pregnancies and delivery and no previous miscarriage (group 2); and 25 pregnant patients being diagnosed as having severe pre-eclampsia and/or intrauterine growth restriction but testing negative for antiphospholipid antibodies (group 3). Hemostatic evaluation was carried out from patients in groups 1 and 2 between 6 and 10 weeks, between 18 and 22 weeks, and between 28 and 32 weeks' gestation. Patients in group 3 were sampled between 28 and 32 weeks. An additional blood sample was obtained 4 to 6 months after delivery (baseline). The Mann-Whitney U test, the Friedman test, and the chi2 test were used. Patients in group 1 were characterized by increased factor VIIa levels, increased prothrombin fragment 1+2 levels, reduced factor XIIa levels, diminished functional urokinase-type plasminogen activator levels, and decreased levels of plasmin/alpha-2-plasmin inhibitor complexes. These abnormalities were more evident in patients in group 1 developing pre-eclampsia and/or intrauterine growth restriction. Impaired factor XIIa-dependent activation of fibrinolysis seems to be a key mechanism related to late-pregnancy complications in patients with the antiphospholipid syndrome.
Reduced mandibular range of motion in Duchenne Muscular Dystrophy: predictive factors.
van Bruggen, H W; Van Den Engel-Hoek, L; Steenks, M H; Bronkhorst, E M; Creugers, N H J; de Groot, I J M; Kalaykova, S I
2015-06-01
Patients with Duchenne muscular dystrophy (DMD) experience negative effects upon feeding and oral health. We aimed to determine whether the mandibular range of motion in DMD is impaired and to explore predictive factors for the active maximum mouth opening (aMMO). 23 patients with DMD (mean age 16.7 ± 7.7 years) and 23 controls were assessed using a questionnaire about mandibular function and impairments. All participants underwent a clinical examination of the masticatory system, including measurement of mandibular range of motion and variables related to mandibular movements. In all patients, quantitative ultrasound of the digastric muscle and the geniohyoid muscle and the motor function measure (MFM) scale were performed. The patients were divided into early and late ambulatory stage (AS), early non-ambulatory stage (ENAS) and late non-ambulatory stage (LNAS). All mandibular movements were reduced in the patient group (P < 0.001) compared to the controls. Reduction in the aMMO (<40 mm) was found in 26% of the total patient group. LNAS patients had significantly smaller mandibular movements compared to AS and ENAS (P < 0.05). Multiple linear regression analysis for aMMO revealed a positive correlation with the body height and disease progression, with MFM total score as the strongest independent risk factor (R(2) = 0.71). Mandibular movements in DMD are significantly reduced and become more hampered with loss of motor function, including the sitting position, arm function, and neck and head control. We suggest that measurement of the aMMO becomes a part of routine care of patients with DMD. © 2015 John Wiley & Sons Ltd.
Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression
Landry, Benjamin D; Mapa, Claudine E; Arsenault, Heather E; Poti, Kristin E; Benanti, Jennifer A
2014-01-01
To maintain genome stability, regulators of chromosome segregation must be expressed in coordination with mitotic events. Expression of these late cell cycle genes is regulated by cyclin-dependent kinase (Cdk1), which phosphorylates a network of conserved transcription factors (TFs). However, the effects of Cdk1 phosphorylation on many key TFs are not known. We find that elimination of Cdk1-mediated phosphorylation of four S-phase TFs decreases expression of many late cell cycle genes, delays mitotic progression, and reduces fitness in budding yeast. Blocking phosphorylation impairs degradation of all four TFs. Consequently, phosphorylation-deficient mutants of the repressors Yox1 and Yhp1 exhibit increased promoter occupancy and decreased expression of their target genes. Interestingly, although phosphorylation of the transcriptional activator Hcm1 on its N-terminus promotes its degradation, phosphorylation on its C-terminus is required for its activity, indicating that Cdk1 both activates and inhibits a single TF. We conclude that Cdk1 promotes gene expression by both activating transcriptional activators and inactivating transcriptional repressors. Furthermore, our data suggest that coordinated regulation of the TF network by Cdk1 is necessary for faithful cell division. PMID:24714560
Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression.
Landry, Benjamin D; Mapa, Claudine E; Arsenault, Heather E; Poti, Kristin E; Benanti, Jennifer A
2014-05-02
To maintain genome stability, regulators of chromosome segregation must be expressed in coordination with mitotic events. Expression of these late cell cycle genes is regulated by cyclin-dependent kinase (Cdk1), which phosphorylates a network of conserved transcription factors (TFs). However, the effects of Cdk1 phosphorylation on many key TFs are not known. We find that elimination of Cdk1-mediated phosphorylation of four S-phase TFs decreases expression of many late cell cycle genes, delays mitotic progression, and reduces fitness in budding yeast. Blocking phosphorylation impairs degradation of all four TFs. Consequently, phosphorylation-deficient mutants of the repressors Yox1 and Yhp1 exhibit increased promoter occupancy and decreased expression of their target genes. Interestingly, although phosphorylation of the transcriptional activator Hcm1 on its N-terminus promotes its degradation, phosphorylation on its C-terminus is required for its activity, indicating that Cdk1 both activates and inhibits a single TF. We conclude that Cdk1 promotes gene expression by both activating transcriptional activators and inactivating transcriptional repressors. Furthermore, our data suggest that coordinated regulation of the TF network by Cdk1 is necessary for faithful cell division.
Hoenderboom, B M; van Oeffelen, A A M; van Benthem, B H B; van Bergen, J E A M; Dukers-Muijrers, N H T M; Götz, H M; Hoebe, C J P A; Hogewoning, A A; van der Klis, F R M; van Baarle, D; Land, J A; van der Sande, M A B; van Veen, M G; de Vries, F; Morré, S A; van den Broek, I V F
2017-04-11
Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection (STI) among young women, can result in serious sequelae. Although the course of infection is often asymptomatic, CT may cause pelvic inflammatory disease (PID), leading to severe complications, such as prolonged time to pregnancy, ectopic pregnancy, and tubal factor subfertility. The risk of and risk factors for complications following CT-infection have not been assessed in a long-term prospective cohort study, the preferred design to define infections and complications adequately. In the Netherlands Chlamydia Cohort Study (NECCST), a cohort of women of reproductive age with and without a history of CT-infection is followed over a minimum of ten years to investigate (CT-related) reproductive tract complications. This study is a follow-up of the Chlamydia Screening Implementation (CSI) study, executed between 2008 and 2011 in the Netherlands. For NECCST, female CSI participants who consented to be approached for follow-up studies (n = 14,685) are invited, and prospectively followed until 2022. Four data collection moments are foreseen every two consecutive years. Questionnaire data and blood samples for CT-Immunoglobulin G (IgG) measurement are obtained as well as host DNA to determine specific genetic biomarkers related to susceptibility and severity of infection. CT-history will be based on CSI test outcomes, self-reported infections and CT-IgG presence. Information on (time to) pregnancies and the potential long-term complications (i.e. PID, ectopic pregnancy and (tubal factor) subfertility), will be acquired by questionnaires. Reported subfertility will be verified in medical registers. Occurrence of these late complications and prolonged time to pregnancy, as a proxy for reduced fertility due to a previous CT-infection, or other risk factors, will be investigated using longitudinal statistical procedures. In the proposed study, the occurrence of late complications following CT-infection and its risk factors will be assessed. Ultimately, provided reliable risk factors and/or markers can be identified for such late complications. This will contribute to the development of a prognostic tool to estimate the risk of CT-related complications at an early time point, enabling targeted prevention and care towards women at risk for late complications. Dutch Trial Register NTR-5597 . Retrospectively registered 14 February 2016.
Sini, Carla; Fiorino, Claudio; Perna, Lucia; Noris Chiorda, Barbara; Deantoni, Chiara Lucrezia; Bianchi, Marco; Sacco, Vincenzo; Briganti, Alberto; Montorsi, Francesco; Calandrino, Riccardo; Di Muzio, Nadia; Cozzarini, Cesare
2016-01-01
To prospectively identify clinical/dosimetric predictors of acute/late hematologic toxicity (HT) in chemo-naÏve patients treated with whole-pelvis radiotherapy (WPRT) for prostate cancer. Data of 121 patients treated with adjuvant/salvage WPRT were analyzed (static-field IMRT n=19; VMAT/Rapidarc n=57; Tomotherapy n=45). Pelvic bone marrow (BM) was delineated as ilium (IL), lumbosacral, lower and whole pelvis (WP), and the relative DVHs were calculated. HT was graded both according to CTCAE v4.03 and as variation in percentage relative to baseline. Logistic regression was used to analyze association between HT and clinical/DVHs factors. Significant differences (p<0.005) in the DVH of BM volumes between different techniques were found: Tomotherapy was associated with larger volumes receiving low doses (3-20 Gy) and smaller receiving 40-50 Gy. Lower baseline absolute values of WBC, neutrophils and lymphocytes (ALC) predicted acute/late HT (p ⩽ 0.001). Higher BM V40 was associated with higher risk of acute Grade3 (OR=1.018) or late Grade2 lymphopenia (OR=1.005). Two models predicting lymphopenia were developed, both including baseline ALC, and BM WP-V40 (AUC=0.73) and IL-V40+smoking (AUC=0.904) for acute/late respectively. Specific regions of pelvic BM predicting acute/late lymphopenia, a risk factor for viral infections, were identified. The 2-variable models including specific constraints to BM may help reduce HT. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Factors influencing the response to postal questionnaire surveys about respiratory symptoms.
Hazell, Michelle L; Morris, Julie A; Linehan, Mary F; Frank, Peter I; Frank, Timothy L
2009-09-01
Response rates to postal questionnaires have been falling in recent years. To examine factors affecting the response to five postal respiratory questionnaire surveys. Cross sectional study. General practice. Five surveys were conducted in all adults registered with two UK general practices using an ECRHQ-based questionnaire, with two reminders at 4-week intervals. Response rates declined over time (1993 - 71.2%; 1995 - 70.5%; 1999 - 65.5%; 2001 - 65.3%; 2004 - 46.9%). Age and gender of non-responders were available for 2001 and 2004: responders were older (mean 48.8 years vs 37.6, p<0.001; 50.5 vs 38.8, p<0.001) and more likely to be female (54.9% vs 44.9%, p<0.001; 55.3% vs 48.5%, p<0.001). The response rate was increased by 18% (2004) and 23% (2001) by the use of two reminders. Early responders were older and more likely to be females, but were less likely to smoke than late responders after reminders. There was no important association between respiratory symptoms and associated feature prevalence and stage of response. Declining response rates may represent reduced motivation and reluctance to share personal information. Qualitative exploration of late/non-response could help reduce bias when planning and analysing such surveys. The use of two reminders is an important factor in improving response.
ERIC Educational Resources Information Center
Rodriguez, Gustavo A.; Burns, Mark P.; Weeber, Edwin J.; Rebeck, G. William
2013-01-01
The apolipoprotein E4 ("APOE-[epsilon]4") allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, and may predispose individuals to Alzheimer's-related cognitive decline by affecting normal brain function early in life. To investigate the impact of human APOE alleles on cognitive performance in mice, we trained…
Reduced corticomotor excitability and motor skills development in children born preterm
Pitcher, Julia B; Schneider, Luke A; Burns, Nicholas R; Drysdale, John L; Higgins, Ryan D; Ridding, Michael C; Nettelbeck, Theodore J; Haslam, Ross R; Robinson, Jeffrey S
2012-01-01
The mechanisms underlying the altered neurodevelopment commonly experienced by children born preterm, but without brain lesions, remain unknown. While individuals born the earliest are at most risk, late preterm children also experience significant motor, cognitive and behavioural dysfunction from school age, and reduced income and educational attainment in adulthood. We used transcranial magnetic stimulation and functional assessments to examine corticomotor development in 151 children without cerebral palsy, aged 10–13 years and born after gestations of 25–41 completed weeks. We hypothesized that motor cortex and corticospinal development are altered in preterm children, which underpins at least some of their motor dysfunction. We report for the first time that every week of reduced gestation is associated with a reduction in corticomotor excitability that remains evident in late childhood. This reduced excitability was associated with poorer motor skill development, particularly manual dexterity. However, child adiposity, sex and socio-economic factors regarding the child's home environment soon after birth were also powerful influences on development of motor skills. Preterm birth was also associated with reduced left hemisphere lateralization, but without increasing the likelihood of being left handed per se. These corticomotor findings have implications for normal motor development, but also raise questions regarding possible longer term consequences of preterm birth on motor function. PMID:22966161
Al-Hinai, Mohab A.; Jones, Shawn W.
2014-01-01
Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σH (early), σF, σE, σG, and σK (late). Here we show that the Clostridium acetobutylicum σK acts both early, prior to Spo0A expression, and late, past σG activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σG proteins were not detectable by Western analysis, while σF protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σK is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σF, σE, and σG, but not sporulation, which was blocked past the σG stage of development, thus demonstrating that σK is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles. PMID:24187083
Al-Hinai, Mohab A; Jones, Shawn W; Papoutsakis, Eleftherios T
2014-01-01
Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σ(H) (early), σ(F), σ(E), σ(G), and σ(K) (late). Here we show that the Clostridium acetobutylicum σ(K) acts both early, prior to Spo0A expression, and late, past σ(G) activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σ(G) proteins were not detectable by Western analysis, while σ(F) protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σ(K) is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σ(F), σ(E), and σ(G), but not sporulation, which was blocked past the σ(G) stage of development, thus demonstrating that σ(K) is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles.
Frontera, Jennifer A; Starling, Randall; Cho, Sung-Min; Nowacki, Amy S; Uchino, Ken; Hussain, M Shazam; Mountis, Maria; Moazami, Nader
2017-06-01
Stroke is a major cause of mortality after left ventricular assist device (LVAD) placement. Prospectively collected data of patients with HeartMate II (n = 332) and HeartWare (n = 70) LVADs from October 21, 2004, to May 19, 2015, were reviewed. Predictors of early (during index hospitalization) and late (post-discharge) ischemic and hemorrhagic stroke and association of stroke subtypes with mortality were assessed. Of 402 patients, 83 strokes occurred in 69 patients (17%; 0.14 events per patient-year [EPPY]): early ischemic stroke in 18/402 (4%; 0.03 EPPY), early hemorrhagic stroke in 11/402 (3%; 0.02 EPPY), late ischemic stroke in 25/402 (6%; 0.04 EPPY) and late hemorrhagic stroke in 29/402 (7%; 0.05 EPPY). Risk of stroke and death among patients with stroke was bimodal with highest risks immediately post-implant and increasing again 9-12 months later. Risk of death declined over time in patients without stroke. Modifiable stroke risk factors varied according to timing and stroke type, including tobacco use, bacteremia, pump thrombosis, pump infection, and hypertension (all p < 0.05). In multivariable analysis, early hemorrhagic stroke (adjusted odds ratio [aOR] 4.3, 95% confidence interval [CI] 1.0-17.8, p = 0.04), late ischemic stroke (aOR 3.2, 95% CI 1.1-9.0, p = 0.03), and late hemorrhagic stroke (aOR 3.7, 95% CI 1.5-9.2, p = 0.005) predicted death, whereas early ischemic stroke did not. Stroke is a leading cause and predictor of death in patients with LVADs. Risk of stroke and death among patients with stroke is bimodal, with highest risk at time of implant and increasing risk again after 9-12 months. Management of modifiable risk factors may reduce stroke and mortality rates. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Late Talkers: A Population-Based Study of Risk Factors and School Readiness Consequences
ERIC Educational Resources Information Center
Hammer, Carol Scheffner; Morgan, Paul; Farkas, George; Hillemeier, Marianne; Bitetti, Dana; Maczuga, Steve
2017-01-01
Purpose: This study was designed to (a) identify sociodemographic, pregnancy and birth, family health, and parenting and child care risk factors for being a late talker at 24 months of age; (b) determine whether late talkers continue to have low vocabulary at 48 months; and (c) investigate whether being a late talker plays a unique role in…
Late-life factors associated with healthy aging in older men.
Bell, Christina L; Chen, Randi; Masaki, Kamal; Yee, Priscilla; He, Qimei; Grove, John; Donlon, Timothy; Curb, J David; Willcox, D Craig; Poon, Leonard W; Willcox, Bradley J
2014-05-01
To identify potentially modifiable late-life biological, lifestyle, and sociodemographic factors associated with overall and healthy survival to age 85. Prospective longitudinal cohort study with 21 years of follow-up (1991-2012). Hawaii Lifespan Study. American men of Japanese ancestry (mean age 75.7, range 71-82) without baseline major clinical morbidity and functional impairments (N = 1,292). Overall survival and healthy survival (free from six major chronic diseases and without physical or cognitive impairment) to age 85. Factors were measured at late-life baseline examinations (1991-1993). Of 1,292 participants, 1,000 (77%) survived to 85 (34% healthy) and 309 (24%) to 95 (<1% healthy). Late-life factors associated with survival and healthy survival included biological (body mass index, ankle-brachial index, cognitive score, blood pressure, inflammatory markers), lifestyle (smoking, alcohol use, physical activity), and sociodemographic factors (education, marital status). Cumulative late-life baseline risk factor models demonstrated that age-standardized (at 70) probability of survival to 95 ranged from 27% (no factors) to 7% (≥ 5 factors); probability of survival to 100 ranged from 4% (no factors) to 0.1% (≥ 5 factors). Age-standardized (at 70) probability of healthy survival to 90 ranged from 4% (no factors) to 0.01% (≥ 5 factors). There were nine healthy survivors at 95 and one healthy survivor at 100. Several potentially modifiable risk factors in men in late life (mean age 75.7) were associated with markedly greater probability of subsequent healthy survival and longevity. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-14
... Requirements on Valencia and Other Late Type Oranges AGENCY: Agricultural Marketing Service, USDA. ACTION...). This rule reduces the minimum size requirement for Valencia and other late type oranges shipped to... also reduces the minimum grade requirement for Valencia and other late type oranges shipped to...
Samuelsson, A; Isaksson, B; Hanberger, H; Olhager, E
2014-01-01
Between 2006 and 2011, 11 patients with Serratia marcescens sepsis and 47 patients colonized due to the spread of various clones were observed. These recurrent clusters brought about interventions to reduce spread between patients. To evaluate the effect of stepwise interventions to prevent S. marcescens colonization/sepsis and to analyse risk factors for late-onset sepsis (LOS). An open retrospective observational study was performed to evaluate the interventions. A retrospective case-control study was performed to analyse the risk factors for LOS. S. marcescens sepsis and colonization decreased after the stepwise adoption of hygiene interventions. Low gestational age, low birth weight, indwelling central venous or umbilical catheter, and ventilator treatment were identified as risk factors for LOS. Compliance with basic hygiene guidelines was the only intervention monitored continuously from late 2007. Compliance increased gradually to a steady high level in early 2009. There was a decrease in S. marcescens LOS, clustering after the second quarter of 2008. After the first quarter of 2009, S. marcescens colonization decreased. It was not possible to identify the specific effects of each intervention, but it is likely that an update of the hospital's antibiotic policy affected the occurrence of S. marcescens LOS. The delayed effect of interventions on S. marcescens colonization was probably due to the time it takes for new routines to have an effect, illustrated by the gradual increase in compliance with basic hygiene guidelines. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Tadokoro, Rieko; Okumura, Akihisa; Nakazawa, Tomoyuki; Hara, Satoshi; Yamakawa, Yoko; Kamata, Ayako; Kinoshita, Keiji; Obinata, Kaoru; Shimizu, Toshiaki
2010-06-01
We reported a girl with HHV-6 infection associated with both acute encephalopathy with biphasic seizures and late reduced diffusion, and hemophagocytic syndrome. She had a prolonged convulsion after a one-day history of febrile illness. Cerebrospinal fluid or brain CT showed no abnormalities on admission and her consciousness was recovered on the next day. However, a prolonged seizure and deterioration of consciousness appeared on the sixth day of illness. Diffusion-weighted images revealed marked reduction of water diffusion in the bilateral frontal areas. HHV-6 infection was virologically proven by polymerase chain reaction. She was treated with gamma-globulin, steroid pulse therapy, and brain hypothermia. In addition, decrease in white blood cells and platelet counts, and elevation of liver enzymes and ferritin were noted on the fourth day of illness. Hemophagocytic macrophages were revealed by bone marrow aspiration on the sixth day. Her hematological and blood chemistry abnormalities recovered gradually after steroid pulse therapy. An elevation of interleukin-6, -8, and -10, and tumor necrosis factor in the serum and that of interleukin-4, -6, and-8 in the cerebrospinal fluid were observed at the onset of a late seizure. These facts suggested that hypercytokinemia will be related to the pathogenesis of acute encephalopathy of our patient. Copyright (c) 2009 Elsevier B.V. All rights reserved.
Crabbe, Helen; Saavedra-Campos, María; Verlander, Neville Q; Leonard, Anusha; Morris, Jill; Wright, Amanda; Balasegaram, Sooria
2017-01-01
In the United Kingdom, pertussis guidance recommends prophylaxis for household contacts within 21 days of case symptom onset if the household includes a vulnerable contact. The aim of our study was to identify characteristics associated with cases reported late for public health action. We reviewed the epidemiology of cases reported in London and South East England for the period 2010 to 2015. We characterised risk factors associated with late reporting of cases and described public health actions taken on timely reported cases. From 2010 to 2015, 9,163 cases of pertussis were reported to health protection teams. Only 11% of cases were reported within 21 days of onset, limiting opportunities for secondary prevention. Timely reporting was associated with younger age groups, pregnancy, being a healthcare worker and being reported by schools or hospital clinicians. Late reporting was associated with older age groups and general practitioner or laboratory reporting. Delays, such as those due to insidious onset and late presentation to healthcare, may be unavoidable; however, delay in reporting once a patient presents can be reduced since cases can be reported before laboratory confirmation. Thus we recommend working with clinicians and laboratories to determine causes and improve early reporting to public health. PMID:28749334
Paracha, Noman; Thuresson, Per-Olof; Moreno, Santiago G; MacGilchrist, Katherine S
2016-10-01
For patients with late-stage (metastatic) breast cancer, the impact of treatment on health-related quality of life is a key factor in decision-making. A systematic review was conducted to identify health state utility values (HSUVs) for late-stage breast cancer, derived using methods preferred by health technology assessment (HTA) agencies, by treatment line. The aim was to generate a list of HSUVs, that could help to justify the values used to populate cost-utility models. Areas covered: Ten electronic databases, international congress websites and online HSUV databases were searched (January 1995-May 2014) for HSUVs for adults with late-stage breast cancer that had been derived from methods favoured by HTA agencies. Publications were included only if they reported studies that originated HSUVs. Expert commentary: Large numbers of HSUVs are available for late-stage breast cancer in the published literature. Contrary to expectations, the HSUVs reported in the literature vary greatly for some health states. As a result, the choice of HSUV can have considerable implications for the outcomes of economic evaluations. Standardization of HSUV methodology is expected to reduce variability; however, further research is recommended for assessing the sensitivity of generic preference-based measures in late-stage (metastatic) breast cancer.
Plant controls on Late Quaternary whole ecosystem structure and function.
Jeffers, Elizabeth S; Whitehouse, Nicki J; Lister, Adrian; Plunkett, Gill; Barratt, Phil; Smyth, Emma; Lamb, Philip; Dee, Michael W; Brooks, Stephen J; Willis, Katherine J; Froyd, Cynthia A; Watson, Jenny E; Bonsall, Michael B
2018-06-01
Plants and animals influence biomass production and nutrient cycling in terrestrial ecosystems; however, their relative importance remains unclear. We assessed the extent to which mega-herbivore species controlled plant community composition and nutrient cycling, relative to other factors during and after the Late Quaternary extinction event in Britain and Ireland, when two-thirds of the region's mega-herbivore species went extinct. Warmer temperatures, plant-soil and plant-plant interactions, and reduced burning contributed to the expansion of woody plants and declining nitrogen availability in our five study ecosystems. Shrub biomass was consistently one of the strongest predictors of ecosystem change, equalling or exceeding the effects of other biotic and abiotic factors. In contrast, there was relatively little evidence for mega-herbivore control on plant community composition and nitrogen availability. The ability of plants to determine the fate of terrestrial ecosystems during periods of global environmental change may therefore be greater than previously thought. © 2018 John Wiley & Sons Ltd/CNRS.
Cheung, Zelda H
2009-01-01
Endophilin B1 is a member of the endophilin family that is localized predominantly to intracellular membranes. Also known as Bax-interacting factor-1 (Bif-1), this protein has been observed to regulate the membrane dynamics of various intracellular compartments, such as the control of mitochondrial morphology and autophagosome formation in fibroblast. Endophilin B1 is expressed in the brain, but its functions in neurons had remained unknown. Recently, we have observed a novel role of endophilin B1 in neurons where it controls the trafficking of TrkA, cognate receptor for the prototypic neurotrophin nerve growth factor (NGF). Knock-down of endophilin B1 expression induces precocious targeting of NGF/TrkA to late endosomes and lysosomes, thereby leading to reduced TrkA levels. This is accompanied by marked attenuation of NGF-induced gene transcription and neurite outgrowth. Our observations suggest that endophilin B1 regulates TrkA level and downstream functions by controlling the movement of TrkA to late endosomes/lysosomes, possibly acting at the level of early endosomes. PMID:19704909
MacCarthy, Sarah; Brignol, Sandra; Reddy, Manasa; Nunn, Amy; Dourado, Ines
2014-12-22
Late presentation to testing, treatment and continued care has detrimental impacts on the health of HIV-positive individuals as well as their sexual partners' health. Men who have sex with men (MSM) experience disproportionately high rates of HIV both globally and in Brazil. However, the factors that inhibit linkage to care among MSM remain unclear. We conducted a cross-sectional study of HIV-positive MSM (n = 740) enrolled in HIV/AIDS services in a large urban center of Brazil from August 2010 to June 2011. Descriptive, bivariate and multivariate statistics were conducted using STATA 12 to examine the relationship between a range of variables and late presentation, defined as having a first CD4 count <350 cells/mm3. Within the sample, the prevalence of LP was 63.1%. Men who self-identified as heterosexual (AOR 1.54 and 95% CI 1.08 - 2.20) compared to men who self-identified as homosexual and bisexual were at increased odds of late presentation. Additionally, men age 30 and older (AOR 1.56, 95% CI 1.01 - 2.43) compared to individuals age 18-29 experienced increased odds of late presentation among MSM. The prevalence of LP in this population was higher than noted in the global literature on LP among MSM. Heterosexual men and older age individuals experienced substantial barriers to HIV care. The stigma around same-sex behaviors and the current focus of HIV prevention and treatment campaigns on younger age individuals may limit patients' and providers' awareness of the risk for HIV and access to available services. In addition to addressing HIV-specific barriers to care, developing effective strategies to reduce late presentation in Brazil will require addressing social factors - such as stigma against diverse sexualities - to concretely identify and eliminate barriers to available services. Only in so doing can we make currently invisible people, visible.
Gebrekidan, Kahasse; Worku, Alemayehu
2017-01-01
Although Ethiopia has shown remarkable achievements in reducing maternal mortality in the last 10 years, the prevalence of late antenatal care (ANC) initiation is still high in the country. The primary purpose of this study was to identify the factors related to late ANC initiation among pregnant women in selected public health centers in Addis Ababa, Ethiopia. A total of 402 pregnant women (cases=134, controls=268) were recruited using multistage sampling. The design selected for the study was unmatched case-control. EpiData version 3.02 and SPSS version 20.0 were used for data entry and statistical analysis, respectively. Binary logistic regression model was used to model the odds of late ANC initiation. The odds of attending ANC late were significantly higher for mothers with a monthly household income of
Gebrekidan, Kahasse; Worku, Alemayehu
2017-01-01
Background Although Ethiopia has shown remarkable achievements in reducing maternal mortality in the last 10 years, the prevalence of late antenatal care (ANC) initiation is still high in the country. Objective The primary purpose of this study was to identify the factors related to late ANC initiation among pregnant women in selected public health centers in Addis Ababa, Ethiopia. Subjects and methods A total of 402 pregnant women (cases=134, controls=268) were recruited using multistage sampling. The design selected for the study was unmatched case–control. EpiData version 3.02 and SPSS version 20.0 were used for data entry and statistical analysis, respectively. Binary logistic regression model was used to model the odds of late ANC initiation. Results The odds of attending ANC late were significantly higher for mothers with a monthly household income of
Domanski, Michael J; Farkouh, Michael E; Zak, Victor; Feske, Steven; Easton, Donald; Weinberger, Jesse; Hamon, Martial; Escobedo, Jorge; Shrader, Peter; Siami, Flora S; Fuster, Valentin
2015-05-15
This study assesses demographic and clinical variables associated with perioperative and late stroke in diabetes mellitus patients after multivessel coronary artery bypass grafting (CABG). Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) is the largest randomized trial of diabetic patients undergoing multivessel CABG. FREEDOM patients had improved survival free of death, myocardial infarction, or stroke and increased overall survival after CABG compared to percutaneous intervention. However, the stroke rate was greater following CABG than percutaneous intervention. We studied predictors of stroke in CABG-treated patients analyzing separately overall, perioperative (≤30 days after surgery), and late (>30 days after surgery) stroke. For long-term outcomes (overall stroke and late stroke), Cox proportional hazards regression was used, accounting for time to event, and logistic regression was used for perioperative stroke. Independent perioperative stroke predictors were previous stroke (odds ratio [OR] 6.96, 95% confidence interval [CI] 1.43 to 33.96; p = 0.02), warfarin use (OR 10.26, 95% CI 1.10 to 96.03; p = 0.02), and surgery outside the United States or Canada (OR 9.81, 95% CI 1.28 to 75.40; p = 0.03). Independent late stroke predictors: renal insufficiency (hazard ratio [HR] 3.57, 95% CI 1.01 to 12.64; p = 0.048), baseline low-density lipoprotein ≥105 mg/dl (HR 3.28, 95% CI 1.19 to 9.02; p = 0.02), and baseline diastolic blood pressure (each 1 mm Hg increase reduces stroke hazard by 5%; HR 0.95, 95% CI 0.91 to 0.99; p = 0.03). There was no overlap between predictors of perioperative versus late stroke. In conclusion, late post-CABG strokes were associated with well-described risk factors. Nearly half of the strokes were perioperative. Independent risk factors for perioperative stroke: previous stroke, previous warfarin use, and CABG performed outside the United States or Canada. Copyright © 2015 Elsevier Inc. All rights reserved.
Diabetes mellitus is associated with late-onset post-stroke depression.
Zhang, Yu; He, Ji-Rong; Liang, Huai-Bin; Lu, Wen-Jing; Yang, Guo-Yuan; Liu, Jian-Rong; Zeng, Li-Li
2017-10-15
To explore the associated factors of late-onset post-stroke depression (PSD). A total of 251 patients with acute ischemic stroke were recruited. The evaluation of depression was performed 2 weeks after ischemia. 206 patients showing no depression in 2 weeks were followed up. They were divided into late-onset PSD group and non-depressed group by clinical interview with Hamilton depression scale score 3 months after stroke. On the first day following hospitalization, the clinical data including age, gender, educational level and vascular risk factors were recorded. The severity, etiological subtype and location of stroke were evaluated. The inflammatory mediators, glucose and lipid levels were recorded on the day of admission. The association between clinical factors and late-onset PSD was explored by logistic regression analysis. The ROC analysis was performed to evaluate the predicting power of the clinical factors. 187 of 206 patients completed the assessment 3 months after stroke. 19 (10.16%) patients were diagnosed as late onset PSD. Diabetes mellitus was an independent risk factor for late-onset PSD (OR 2.675, p = 0.047). ROC analysis demonstrated that glucose and HbA1C could predict late-onset PSD with specificity of 84.4%. The sample of our study was small. The results should be further confirmed in a larger cohort of patients with acute ischemic stroke. The acute ischemic stroke patients with diabetes mellitus were more tendered to suffer late-onset PSD. Copyright © 2017 Elsevier B.V. All rights reserved.
Viñas, O; Giralt, M; Obregón, M J; Iglesias, R; Villarroya, F; Mampel, T
1988-01-01
Brown adipose tissue iodothyronine 5'-deiodinase activity is significantly lower in 17-day pregnant rats compared with virgin controls and remains low during late pregnancy and lactation. It fully recovers with abrupt weaning, but only partially with spontaneous weaning. Even though this profile of changes is remarkably in step with the known pattern of modifications in brown fat thermogenesis during the breeding cycle, the lowered iodothyronine 5'-deiodinase activity appearing between days 15 and 17 of pregnancy occurs earlier than the reduction in brown adipose tissue thermogenesis. Brown fat 3,3',5-tri-iodothyronine content is also reduced in late pregnant, early and mid-lactating rats, most probably as a consequence of the lowered 5'-deiodination of thyroxine in situ. Acute insulin treatment increases brown fat iodothyronine 5'-deiodinase activity in virgin animals as well as in late-pregnant and lactating rats, despite the lowered basal enzyme activity levels in the latter groups. Thus an impaired response to insulin in brown fat does not appear to be a factor leading to the lowered iodothyronine 5'-deiodinase activity during late pregnancy and lactation. PMID:3060112
Meloche, S; Seuwen, K; Pagès, G; Pouysségur, J
1992-05-01
We have examined the phosphorylation and protein kinase activity of p44 mitogen-activated protein kinase (p44mapk) in growth factor-stimulated hamster fibroblasts using a specific antiserum. The activity of p44mapk was stimulated both by receptor tyrosine kinases and G protein-coupled receptors. Detailed kinetics revealed that alpha-thrombin induces a biphasic activation of p44mapk in CCL39 cells: a rapid phase appearing at 5-10 min was followed by a late and sustained phase still elevated after 4 h. Inactivation of alpha-thrombin with hirudin after 30 sec, which prevented DNA synthesis, did not alter the early p44mapk response but completely abolished the late phase. Pretreatment of the cells with pertussis toxin, which inhibits by more than 95% alpha-thrombin-induced mitogenicity, resulted in the complete loss of late phase activity, while the early peak was partially attenuated. Treatment of CCL39 cells with basic fibroblast growth factor also induced a strong activation of p44mapk. Serotonin, which is not a mitogen by its own, had no effect on late phase p44mapk activity, but synergized with basic fibroblast growth factor to induce late kinase response and DNA synthesis. Both early and late phase activation of p44mapk were accompanied by tyrosine phosphorylation of the enzyme. Together, the results indicate that there is a very close correlation between the ability of a growth factor to induce late and sustained p44mapk activation and its mitogenic potential. Therefore, we propose that sustained p44mapk activation is an obligatory event for growth factor-induced cell cycle progression.
Auditory sensory memory and language abilities in former late talkers: a mismatch negativity study.
Grossheinrich, Nicola; Kademann, Stefanie; Bruder, Jennifer; Bartling, Juergen; Von Suchodoletz, Waldemar
2010-09-01
The present study investigated whether (a) a reduced duration of auditory sensory memory is found in late talking children and (b) whether deficits of sensory memory are linked to persistent difficulties in language acquisition. Former late talkers and children without delayed language development were examined at the age of 4 years and 7 months using mismatch negativity (MMN) with interstimulus intervals (ISIs) of 500 ms and 2000 ms. Additionally, short-term memory, language skills, and nonverbal intelligence were assessed. MMN mean amplitude was reduced for the ISI of 2000 ms in former late talking children both with and without persistent language deficits. In summary, our findings suggest that late talkers are characterized by a reduced duration of auditory sensory memory. However, deficits in auditory sensory memory are not sufficient for persistent language difficulties and may be compensated for by some children.
Parcesepe, Angela M; Tymejczyk, Olga; Remien, Robert; Gadisa, Tsigereda; Kulkarni, Sarah Gorrell; Hoffman, Susie; Melaku, Zenebe; Elul, Batya; Nash, Denis
2018-03-01
HIV diagnosis may be a source of psychological distress. Late initiation of antiretroviral therapy (ART) and treatment-related beliefs may intensify psychological distress among those recently diagnosed. This analysis describes the prevalence of psychological distress among people living with HIV (PLWH) and examines the association of recent HIV diagnosis, late ART initiation and treatment-related beliefs with psychological distress. The sample includes 1175 PLWH aged 18 or older initiating ART at six HIV clinics in Ethiopia. Psychological distress was assessed with Kessler Psychological Distress Scale. Scores ≥ 29 were categorized as severe psychological distress. Individuals who received their first HIV diagnosis in the past 90 days were categorized as recently diagnosed. Multivariable logistic regression modeled the association of recent diagnosis, late ART initiation and treatment-related beliefs on severe psychological distress, controlling for age, sex, education, area of residence, relationship status, and health facility. Among respondents, 29.5% reported severe psychological distress, 46.6% were recently diagnosed and 31.0% initiated ART late. In multivariable models, relative to those who did not initiate ART late and had longer time since diagnosis, odds of severe psychological distress was significantly greater among those with recent diagnosis and late ART initiation (adjusted OR [aOR]: 1.9 [95% CI 1.4, 2.8]). Treatment-related beliefs were not associated with severe psychological distress in multivariable models. Severe psychological distress was highly prevalent, particularly among those who were recently diagnosed and initiated ART late. Greater understanding of the relationship between psychological distress, recent diagnosis, and late ART initiation can inform interventions to reduce psychological distress among this population. Mental health screening and interventions should be incorporated into routine HIV clinical care from diagnosis through treatment.
Hellwig, Birte; Madjar, Katrin; Edlund, Karolina; Marchan, Rosemarie; Cadenas, Cristina; Heimes, Anne-Sophie; Almstedt, Katrin; Lebrecht, Antje; Sicking, Isabel; Battista, Marco J; Micke, Patrick; Schmidt, Marcus; Hengstler, Jan G; Rahnenführer, Jörg
2016-01-01
In breast cancer, gene signatures that predict the risk of metastasis after surgical tumor resection are mainly indicative of early events. The purpose of this study was to identify genes linked to metastatic recurrence more than three years after surgery. Affymetrix HG U133A and Plus 2.0 array datasets with information on metastasis-free, disease-free or overall survival were accessed via public repositories. Time restricted Cox regression models were used to identify genes associated with metastasis during or after the first three years post-surgery (early- and late-type genes). A sequential validation study design, with two non-adjuvantly treated discovery cohorts (n = 409) and one validation cohort (n = 169) was applied and identified genes were further evaluated in tamoxifen-treated breast cancer patients (n = 923), as well as in patients with non-small cell lung (n = 1779), colon (n = 893) and ovarian (n = 922) cancer. Ten late- and 243 early-type genes were identified in adjuvantly untreated breast cancer. Adjustment to clinicopathological factors and an established proliferation-related signature markedly reduced the number of early-type genes to 16, whereas nine late-type genes still remained significant. These nine genes were associated with metastasis-free survival (MFS) also in a non-time restricted model, but not in the early period alone, stressing that their prognostic impact was primarily based on MFS more than three years after surgery. Four of the ten late-type genes, the ribosome-related factors EIF4B, RPL5, RPL3, and the tumor angiogenesis modifier EPN3 were significantly associated with MFS in the late period also in a meta-analysis of tamoxifen-treated breast cancer cohorts. In contrast, only one late-type gene (EPN3) showed consistent survival associations in more than one cohort in the other cancer types, being associated with worse outcome in two non-small cell lung cancer cohorts. No late-type gene was validated in ovarian and colon cancer. Ribosome-related genes were associated with decreased risk of late metastasis in both adjuvantly untreated and tamoxifen-treated breast cancer patients. In contrast, high expression of epsin (EPN3) was associated with increased risk of late metastasis. This is of clinical relevance considering the well-understood role of epsins in tumor angiogenesis and the ongoing development of epsin antagonizing therapies.
Berardi, Alberto; Cattelani, Chiara; Creti, Roberta; Berner, Reinhard; Pietrangiolillo, Zaira; Margarit, Immaculada; Maione, Domenico; Ferrari, Fabrizio
2015-01-01
Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections in developed countries. Early-onset disease (EOD) occurs at day 0-6 and late-onset disease occurs at day 7-89. Currently, the prevention of EOD relies upon intrapartum antibiotic prophylaxis (IAP) given to women who are GBS positive at prenatal screening or women with risk factors for EOD. Although successfully implemented, IAP has not fully eradicated EOD, and incidence rates of late-onset disease remain unchanged. Furthermore, antibiotic resistance may result from widespread antibiotic use. New prophylactic strategies are therefore of critical importance. A vaccine active against GBS, administered during pregnancy and combined with targeted IAP, could overcome these problems and reduce the mortality and morbidity associated with invasive diseases.
Sun, Jianjun; Liu, Li; Shen, Jiayin; Chen, Panpan; Lu, Hongzhou
2017-04-19
There are few studies focus on the factors underlying the late initiation of ART in China. We analyzed the trends in the median CD4 cell counts among different patient groups over time and the risk factors for the late initiation of ART in Shanghai, China. A retrospective cross-sectional survey was made in the Department of Infectious Disease of Shanghai Public Health Clinical Center which is a designated diagnosis and treatment center for HIV-positive patients in Shanghai during the period of January 1st, 2008--June 30th, 2014. Late ART initiation was defined as a CD4 cell count <200 cells/mm 3 or having a clinical AIDS diagnosis prior to ART initiation. Trends in the median CD4 cell count at ART initiation and the proportion of late ART initiation by year were evaluated using Spearman's correlations and Chi-squared methods, respectively. We used a logistic regression model to analyze the risk factors for late ART initiation. The related factors collected in the multivariate model were the patient's age, gender, infection routes and marital status. A total of 3796 patients were analyzed in this study, with a median baseline CD4 cell count of 205 cells/mm 3 [interquartile range: 75-287]. The median CD4 cell counts of patients initiating ART late increased from 76 cells/mm 3 in 2008 to 103 cells/mm 3 in 2014 (p < 0.001), and the proportion of late ART initiation decreased from 80% to 45% (p < 0.001). The risk factors for late ART initiation were male gender, heterosexual transmission and older age (>30 years) (p < 0.001). Notable improvements were made in the median CD4 cell count at ART initiation and the proportion of late ART initiation from 2008 to 2014. However, persons with high risk of HIV exposure who are male, older even heterosexual orientation should be given more opportunities to receive frequently screening, earlier diagnoses and timely treatment.
Kurichi, Jibby E.; Xie, Dawei; Kwong, Pui L.; Bates, Barbara E.; Vogel, W. Bruce; Stineman, Margaret G.
2011-01-01
Objective To determine what patient- and facility-level characteristics drive late specialized rehabilitation among veterans who already received immediate postoperative services. Design Data were obtained from 8 administrative databases for 2,453 patients who underwent lower extremity amputation in Veterans Affairs Medical Centers in 2002-2004. A Cox proportional hazards model was used to determine the hazards ratios and 95% confidence intervals of the factors associated with days to readmission for late services after discharge from the surgical hospitalization. Results There were 2,304 patients who received only immediate postoperative services, while 152 also received late specialized rehabilitation. After adjustment, veterans who were less disabled physically, residing in the South Central compared to the Southeast region, and had their surgeries in CARF accredited facilities were all more likely to receive late services. The hazards ratios for type of immediate postoperative rehabilitation were not constant over time. At hospital discharge, there was no difference in receipt, however, after 3 months, those who received early specialized rehabilitation were significantly less likely to receive late services. Conclusion The factors associated with late specialized rehabilitation were due mainly to facility-level characteristics and care process variables. Knowledge of these factors may help with decision-making policies regarding CARF accredited units. PMID:21389847
Jang, Gun Ja; Lee, Sang Lak; Kim, Hyeon Mi
2012-04-01
This study was done to compare breast feeding rates and factors influencing feeding practice between late preterm (34 ≤ GA < 37) and preterm infants (GA<34). A survey was done of 207 late preterm and 117 preterm infants in neonatal intensive care units (NICU) of 4 university hospitals in D city. Data were collected from July 2009 to June 2010 from 324 medical records in the NICU. Breast-feeding at home was checked either by telephone survey or questioning during hospital visits. Rate of breast feeding for late preterm infants was significantly lower than for preterm infants. There was no significant difference in breast-feeding at home. We found differences in factors influencing breast feeding between the two groups. Factors influencing feeding for late preterm infants were type of delivery, mothers' occupation, feeding type during hospitalization, time elapse from hospital discharge, total admission days, infant's body weight at first feeding and length of NPO (nothing by mouth). Factors influencing feeding for preterm infants were birth order, maternal disease and obstetric complications, and one-minute Apgar score. Results of the study show low rates of breast-feeding for late preterm infants indicating a need for breast-feeding education for mothers of these infants.
Early and Late Recurrent Epistaxis Admissions: Patterns of Incidence and Risk Factors.
Cohen, Oded; Shoffel-Havakuk, Hagit; Warman, Meir; Tzelnick, Sharon; Haimovich, Yaara; Kohlberg, Gavriel D; Halperin, Doron; Lahav, Yonatan
2017-09-01
Objective Epistaxis is a common complaint, yet few studies have focused on the incidence and risk factors of recurrent epistaxis. Our objective was to determine the patterns of incidence and risk factors for recurrent epistaxis admission (REA). Study Design Case series with chart review. Settings Single academic center. Subjects and Methods The medical records of patients admitted for epistaxis between 1999 and 2015 were reviewed. The follow-up period was defined as 3 years following initial admission. REAs were categorized as early (30 days) and late (31 days to 3 years) following initial admission. Logistic regression was used to identify potential predictors of REAs. Results A total of 653 patients were included. Eighty-six patients (14%) had REAs: 48 (7.5%) early and 38 (6.5%) late. Nonlinear incidence curve was demonstrated for both early and late REAs. Based on logistic regression, prior nasal surgery and anemia were independent risk factors for early REAs. According to multivariate analysis, thrombocytopenia was significantly associated with late REAs. Conclusion Early and late REAs demonstrate different risk predictors. Knowledge of such risk factors may help in risk stratification for this selected group of patients. All patients at risk should be advised on possible preventive measures. Patients at risk for early REA may benefit from a more proactive approach.
IFPA Senior Award Lecture: making sense of pre-eclampsia - two placental causes of preeclampsia?
Redman, C W; Sargent, I L; Staff, A C
2014-02-01
Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as chronic hypertension affect early and late sub-types of the syndrome. It also implies that all pregnant women may be destined to get pre-eclampsia but spontaneous or induced delivery averts this outcome in most instances. Copyright © 2013 IFPA and Elsevier Ltd. All rights reserved.
Factors Associated with Late Engagement to HIV Care in Western Kenya: A Cross-Sectional Study.
Kwobah, Charles Meja; Braitstein, Paula; Koech, Julius K; Simiyu, Gilbert; Mwangi, Ann W; Wools-Kaloustian, Kara; Siika, Abraham M
2016-11-01
Late presentation of patients contributes significantly to the high mortality reported in HIV -care and treatment programs in sub-Saharan Africa. A cross-sectional study was conducted to assess factors associated with late engagement to HIV care at the Academic Model Providing Access to Healthcare in western Kenya. Late engagement was defined as baseline CD4 ≤100 cells/mm 3 . Of the 10 533 participants included in the analysis, 67% were female and mean age was 36.7 years. Overall, 23% of the participants presented late. Factors associated with late engagement included male gender (adjusted odds ratio [AOR]: 1.54, 95% confidence interval [CI]: 1.35-1.75), older age (AOR: 1.62, 95% CI: 1.02-2.56), and longer travel time to clinic (AOR: 1.18, 95% CI: 1.04-1.34). Nearly one-quarter of HIV-infected patients in our setting present with advanced immune suppression at initial encounter. Being male, older age, and living further away from clinic are associated with late engagement to care. © The Author(s) 2015.
Preventing group B streptococcal infections in newborns.
Porta, Kelly; Rizzolo, Denise
2015-03-01
Despite advances in intrapartum antibiotic prophylaxis (IAP), group B streptococcal infection continues to be a predominant cause of early-onset disease in neonates. About 2% of neonates exposed to group B Streptococcus develop clinical manifestations including sepsis, pneumonia, and meningitis. Screening in late pregnancy reduces the incidence of early-onset sepsis by more than 80%. Clinicians must be able to identify the risk factors and clinical manifestations of group B streptococcal infection and to understand management and prevention guidelines.
Teixeira, Antonio L.; Machado-Vieira, Rodrigo; Talib, Leda L.; Radanovic, Marcia; Gattaz, Wagner F.; Forlenza, Orestes V.
2014-01-01
Objectives. Late-life depression (LLD) is associated with reduced neurotrophic support and abnormalities in neurodegenerative cascades. The aim of the present study is to determine the concentrations of brain-derived neurotrophic factor (BDNF), amyloid-β42, total Tau, and phosphorylated Tau in the cerebrospinal fluid (CSF) of patients with LLD and cognitive impairment compared to healthy older adults. Method. We included 25 antidepressant-free patients with LLD (10 with mild cognitive impairment [LLD + MCI] and 15 with no cognitive decline [LLD + NCD]) and 25 healthy older adults as a comparison group. Depressive symptoms were assessed by the 21-item Hamilton Depression Rating Scale (HDRS-21) and cognitive performance by a comprehensive cognitive battery. Results. Patients with LLD + MCI showed significantly lower CSF BDNF levels compared to LLD + NCD and healthy controls (p = .003). There were no significant differences in Alzheimer’s disease–related CSF biomarkers between groups. CSF BDNF concentrations were positively correlated with Cambridge Cognitive Test (CAMCOG) scores (r = .36, p = .02). Discussion. The present study adds to the growing body of evidence that abnormalities in the BDNF system are involved in the pathophysiology of LLD. The reduction of the availability of BDNF in the central nervous system may indicate increased vulnerability to the development of several age-related neuropsychiatric disorders as well as to adverse cognitive outcomes. PMID:25149921
Appetite and Weight Loss Symptoms in Late-Life Depression Predict Dementia Outcomes.
Saha, Sayoni; Hatch, Daniel J; Hayden, Kathleen M; Steffens, David C; Potter, Guy G
2016-10-01
Identify depression symptoms during active late-life depression (LLD) that predict conversion to dementia. The authors followed a cohort of 290 participants from the Neurocognitive Outcomes of Depression in the Elderly study. All participants were actively depressed and cognitively normal at enrollment. Depression symptom factors were derived from prior factor analysis: anhedonia and sadness, suicidality and guilt, appetite and weight loss, sleep disturbance, and anxiety and tension. Cox regression analysis modeled time to Alzheimer disease (AD) and non-AD dementia onset on depression symptom factors, along with age, education, sex, and race. Significant dementia predictors were tested for interaction with age at depression onset. Higher scores on the appetite and weight loss symptom factor were associated with an increased hazard of both AD and non-AD dementia. This factor was moderated by age at first depression onset, such that higher scores were associated with higher risk of non-AD dementia when depression first occurred earlier in life. Other depression symptom factors and overall depression severity were not related to risk of AD or non-AD dementia. Results suggest greater appetite/weight loss symptoms in active episodes of LLD are associated with increased likelihood of AD and non-AD dementia, but possibly via different pathways moderated by age at first depression onset. Results may help clinicians identify individuals with LLD at higher risk of developing AD and non-AD dementia and design interventions that reduce this risk. Copyright © 2016. Published by Elsevier Inc.
Zhao, Yang; Zheng, Zhi-Nan; Pi, Yan-Na; Liang, Xue; Jin, San-Qing
2017-01-01
A previous study in our laboratory demonstrated that transfusion of plasma collected at the late phase of remote ischemic preconditioning (RIPC) could reduce myocardial infarct size. Here, we tested whether the reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways are involved in transferring protection. In a two-part study, donor rats ( n = 3) donated plasma 48 hours after RIPC (preconditioned plasma) or control (nonpreconditioned plasma). Normal (part 1) or ischemic (part 2) myocardia were collected from recipients ( n = 6) 24 hours after receiving normal saline, nonpreconditioned plasma, and preconditioned plasma or after further suffering ischemia reperfusion. Western blot was performed to analyze STAT3, Akt, and Erk1/2 phosphorylation in normal and ischemic myocardium (central area and border area). In normal myocardia, preconditioned plasma increased Akt and Erk1/2 phosphorylation significantly compared to nonpreconditioned plasma and normal saline; no STAT3 phosphorylation was detected. In ischemic myocardia, preconditioned plasma increased Akt and Erk1/2 phosphorylation significantly in both central and border areas compared to other fluids; no significant difference in STAT3 phosphorylation occurred among groups. Transfusion of preconditioned plasma collected at the late phase of RIPC could activate the RISK but not SAFE pathway, suggesting that RISK pathway may be involved in transferring protection.
2013-01-01
Background HIV positive patients are at risk of infectious and non-infectious complications that may necessitate intensive care unit (ICU) admission. While the characteristics of patients requiring ICU admission have been described previously, these studies did not include information on the denominator population from which these cases arose. Methods We conducted an observational cohort study of ICU admissions among 2751 HIV positive patients attending King’s College Hospital, South London, UK. Poisson regression models were used to identify factors associated with ICU admission. Results The overall incidence rate of ICU admission was 1.0 [95% CI 0.8, 1.2] per 100 person-years of follow up, and particularly high early (during the first 3 months) following HIV diagnosis (12.4 [8.7, 17.3] per 100 person-years compared to 0.37 [0.27, 0.50] per 100 person-years thereafter; incidence rate ratio 33.5 [23.4, 48.1], p < 0.001). In time-updated analyses, AIDS and current CD4 cell counts of less than 200 cells/mm3 were associated with an increased incidence of ICU admission while receipt of combination antiretroviral therapy (cART) was associated with a reduced incidence of ICU admission. Late HIV diagnosis (initial CD4 cell count <350 or AIDS within 3 months of HIV diagnosis) applied to 81% of patients who were first diagnosed HIV positive during the study period and who required ICU admission. Late HIV diagnosis was significantly associated with ICU admission in the first 3 months following HIV diagnosis (adjusted incidence rate ratio 8.72, 95% CI 2.76, 27.5). Conclusions Late HIV diagnosis was a major risk factor for early ICU admission in our cohort. Earlier HIV diagnosis allowing cART initiation at CD4 cell counts of 350 cells/mm3 is likely to have a significant impact on the need for ICU care. PMID:23331544
Hepple, Russell T; Ross, Karen D; Rempfer, Amanda B
2004-02-01
We examined young adult and late middle-aged male rats to test the hypothesis that gastrocnemius (a locomotor muscle) demonstrates reduced fiber size with aging, whereas soleus (a postural muscle) demonstrates atrophy of some fibers and compensatory hypertrophy in other fibers. Although body mass was greater in late middle-aged animals, mass was reduced in gastrocnemius but not soleus muscle. In another group of animals, physical activity was reduced by 34% in late middle-aged animals. Whereas mean fiber size was lower in gastrocnemius of late middle-aged animals, it was not different in soleus. Histograms revealed atrophied fibers (=1000 micro m(2)) in soleus and gastrocnemius and hypertrophied fibers (>/=8000 micro m(2)) in soleus with aging. Atrophied fibers often demonstrated no subsarcolemmal mitochondrial staining, suggesting denervation, whereas hypertrophied fibers often demonstrated cytochrome oxidase deficiency, suggesting mitochondrial dysfunction. These results underscore the divergent influences (e.g., physical inactivity, denervation, mitochondrial dysfunction) affecting fiber size with aging.
Lifetime hormonal factors may predict late-life depression in women
Ryan, Joanne; Carrière, Isabelle; Scali, Jacqueline; Ritchie, Karen; Ancelin, Marie-Laure
2008-01-01
Background Fluctuating hormone levels are known to influence a woman’s mood and well-being. This study aimed to determine whether lifetime hormonal markers are associated with late-life depression symptoms among elderly community-dwelling women. Method Detailed reproductive histories of 1013 women aged 65 years and over were obtained using questionnaires and depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale. Multivariate logistic regression models were generated to determine whether any lifetime endogenous or exogenous hormonal factors were associated with late-life depression. Results The prevalence of depressive symptoms was 17%. Age at menopause was associated with depressive symptoms, but only among women with a lower education level. For these women, an earlier age at menopause increased their risk of late-life depression (linear effect, OR=0.95, 95%CI: 0.91–0.99). The odds of late-life depression were also increased for women who were past (OR=1.6, 95%CI: 1.1–2.5), but not current hormonal replacement users. On the other hand, long-term oral contraceptive use (≥10 years) was protective against depression (OR=0.3, 95%CI: 0.1–0.9). These associations remained significant even after extensive adjustment for a range of potential confounding factors, including socio-demographic factors, mental and physical incapacities, antidepressant use and past depression. The other factors examined, including age at first menses, parity, age at childbirth and surgical menopause, were not associated with late-life depressive symptoms. Conclusions Lifetime hormonal factors that are significantly associated with depression symptoms in later life have been identified. Further work is needed to determine how potential hormonal interventions could be used in the treatment of late-life depression in certain sub-groups of women. PMID:18533067
Schaafsma, Wandert; Basterra, Laura Bozal; Jacobs, Sabrina; Brouwer, Nieske; Meerlo, Peter; Schaafsma, Anne; Boddeke, Erik W G M; Eggen, Bart J L
2017-10-01
Maternal inflammation during pregnancy can have detrimental effects on embryonic development that persist during adulthood. However, the underlying mechanisms and insights in the responsible cell types are still largely unknown. Here we report the effect of maternal inflammation on fetal microglia, the innate immune cells of the central nervous system (CNS). In mice, a challenge with LPS during late gestation stages (days 15-16-17) induced a pro-inflammatory response in fetal microglia. Adult whole brain microglia of mice that were exposed to LPS during embryonic development displayed a persistent reduction in pro-inflammatory activation in response to a re-challenge with LPS. In contrast, hippocampal microglia of these mice displayed an increased inflammatory response to an LPS re-challenge. In addition, a reduced expression of brain-derived neurotrophic factor (BDNF) was observed in hippocampal microglia of LPS-offspring. Microglia-derived BDNF has been shown to be important for learning and memory processes. In line with these observations, behavioral- and learning tasks with mice that were exposed to maternal inflammation revealed reduced home cage activity, reduced anxiety and reduced learning performance in a T-maze. These data show that exposure to maternal inflammation during late gestation results in long term changes in microglia responsiveness during adulthood, which is different in nature in hippocampus compared to total brain microglia. Copyright © 2017 Elsevier Inc. All rights reserved.
Hoffman, Susie; Wu, Yingfeng; Lahuerta, Maria; Kulkarni, Sarah Gorrell; Nuwagaba-Biribonwoha, Harriet; Sadr, Wafaa El; Remien, Robert H.; Mugisha, Veronicah; Hawken, Mark; Chuva, Ema; Nash, Denis; Elul, Batya
2015-01-01
Objectives To examine changes between 2006 and 2011 in the proportion of HIV-positive patients newly-enrolled in HIV care with advanced disease and the median CD4+ cell count at enrollment; and identify patient-, facility-, and contextual-level factors associated with late enrollment in care in 2011. Design Cross sectional over time. Methods For time trends analyses, routinely-collected patient-level data (307,110 adults newly-enrolled in 138 HIV clinical care facilities) in Kenya, Mozambique, Rwanda and Tanzania; and for analyses of correlates, patient-level data (46,201 in 195 facilities), and facility- and population-level survey data were used. Late enrollment was defined as CD4+ count ≤350 cells/μl and/or WHO clinical stage 3/4. Results Late enrollment declined from 69.9% to 57.2%, (p<0.0001); median CD4+ count increased from 242 to 292 cells/μL (ptrend<0.0001). In 2011, risk of late enrollment was significantly higher for men and non-pregnant women vs. pregnant women; patients aged >25 vs. 15-25 years; non-married vs. married; and those entering from sites other than prevention of mother to child transmission (PMTCT). More extensive HIV testing coverage in the region of a facility was significantly associated with lower risk of late enrollment. Conclusions Despite improvement, in 2011, 57% of patients entered HIV care already ART-eligible. The lower risk of late enrollment among those referred from PMTCT and in regions where HIV testing coverage was higher suggests that innovative approaches to rapidly increase testing uptake among people living with HIV prior to the development of symptoms have the potential to reduce late enrollment in care. PMID:25136842
Update on causes of premature death in people with convulsive epilepsy in rural West China.
Si, Yang; Chen, Deng; Tian, Linyu; Mu, Jie; Chen, Tao; Liu, Ling; Deng, Ying; He, Jun; Li, You; He, Li; Zhou, Dong
2016-06-01
This longitudinal prospective study updated a previous report on premature mortality and focused on the risk factors among patients with convulsive epilepsy in resource-poor settings. The present cohort size (7,231) and follow-up (mean 33.4 months) were expanded. The basic epidemiologic aspects of this cohort were similar to the original report (case fatality: 3.26% vs. 2.97%, respectively; injury contributed more than half of the deaths). Cox regression analysis suggested that male patients, late ages of onset (>45 years old), short duration of epilepsy (<10 years), and high convulsive seizure frequency (>2 per month) were independent risk factors for overall premature death. Male patients with late ages of onset and high seizure frequency had a higher risk of injury-specific death. This study emphasizes the preventable nature of injuries that are leading putative causes of death among people with convulsive epilepsy in rural West China. Education on specific populations and efficient seizure control are of paramount importance in reducing the risk of premature mortality. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Lin, Yan; Wimberly, Michael C
2017-04-01
The purpose of this study was to examine the geographic variations of late-stage diagnosis in colorectal cancer (CRC) and breast cancer as well as to investigate the effects of 3 neighborhood-level factors-socioeconomic deprivation, urban/rural residence, and spatial accessibility to health care-on the late-stage risks. This study used population-based South Dakota cancer registry data from 2001 to 2012. A total of 4,878 CRC cases and 6,418 breast cancer cases were included in the analyses. Two-level logistic regression models were used to analyze the risk of late-stage CRC and breast cancer. For CRC, there was a small geographic variation across census tracts in late-stage diagnosis, and residing in isolated small rural areas was significantly associated with late-stage risk. However, this association became nonsignificant after adjusting for census-tract level socioeconomic deprivation. Socioeconomic deprivation was an independent predictor of CRC late-stage risk, and it explained the elevated risk among American Indians. No relationship was found between spatial accessibility and CRC late-stage risk. For breast cancer, no geographic variation in the late-stage diagnosis was observed across census tracts, and none of the 3 neighborhood-level factors was significantly associated with late-stage risk. Results suggested that socioeconomic deprivation, rather than spatial accessibility, contributed to CRC late-stage risks in South Dakota as a rural state. CRC intervention programs could be developed to target isolated small rural areas, socioeconomically disadvantaged areas, as well as American Indians residing in these areas. © 2016 National Rural Health Association.
Role of familial factors in late-onset Alzheimer disease as a function of age.
Wu, Z; Kinslow, C; Pettigrew, K D; Rapoport, S I; Schapiro, M B
1998-09-01
Whereas early-onset Alzheimer disease (AD; usually onset at age < 50 years) has been defined with genetic mutation on chromosomes 1, 14, and 21, the degree of familial contribution to late-onset AD is unclear. Further, it is uncertain if subgroups of late-onset AD exist. To examine the influence of familial factors as a function of age in late-onset AD we investigated lifetime risks and age-specific hazard rates of AD-like illness among late-onset AD probands' and controls' first-degree relatives, using questionnaires and medical records. As part of a longitudinal study on aging and AD, we studied 78 AD probands with age of onset > or =50 years (28 "definite" and 50 "probable" AD according to NINCDS/ADRDA criteria) and 101 healthy old controls seen since 1981. Both probands and controls were screened rigorously with medical tests and brain imaging and seen regularly until autopsy. Multiple informants and medical records were used for first-degree relatives. Among first-degree relatives, 49 secondary cases of AD-like illness were found for the AD probands' relatives (391 relatives 40 years old or older) compared with 20 cases among controls' relatives (456 relatives 40 years old or older). Relatives of AD probands had a significantly increased lifetime risk of AD-like illness of 52.8+/-11.4% by age 94 years compared with a lifetime risk in relatives of controls of 22.1+/-5.8% by age 90 years. Age-specific hazard rates in relatives of AD probands increased until the 75-79-year age interval and then decreased; in contrast the age-specific hazard rates increased in relatives of controls after the 80-84-year age interval. To determine if a dividing line exist among late-onset AD, several cutoff ages were used in our study to compare cumulative risk curves of AD-like illness between relatives of late-onset probands and relatives of late-late-onset probands. Differences in the pattern of cumulative incidence of AD in relatives showed that 67-71 years is the range for a dividing line between late- and late-late-onset AD. Age-specific hazard rates of AD in relatives supported a difference between late- and late-late-onset. Whereas these rates increased until the 75-79-year age interval and then decreased in late-onset AD, the rates began increasing after the 65-69-year age interval and through the oldest age interval in both late-late-onset AD and control groups. Our results support the concept that familial factors exist in late-onset AD and that different familial factors may exist in late-onset AD subgroups.
Cai, Qian; Lu, Li; Tian, Jin-Hua; Zhu, Yi-Bing; Qiao, Haifa; Sheng, Zu-Hang
2010-10-06
Neuron maintenance and survival require late endocytic transport from distal processes to the soma where lysosomes are predominantly localized. Here, we report a role for Snapin in attaching dynein to late endosomes through its intermediate chain (DIC). snapin(-/-) neurons exhibit aberrant accumulation of immature lysosomes, clustering and impaired retrograde transport of late endosomes along processes, reduced lysosomal proteolysis due to impaired delivery of internalized proteins and hydrolase precursors from late endosomes to lysosomes, and impaired clearance of autolysosomes, combined with reduced neuron viability and neurodegeneration. The phenotypes are rescued by expressing the snapin transgene, but not the DIC-binding-defective Snapin-L99K mutant. Snapin overexpression in wild-type neurons enhances late endocytic transport and lysosomal function, whereas expressing the mutant defective in Snapin-DIC coupling shows a dominant-negative effect. Altogether, our study highlights new mechanistic insights into how Snapin-DIC coordinates retrograde transport and late endosomal-lysosomal trafficking critical for autophagy-lysosomal function, and thus neuronal homeostasis. Copyright © 2010 Elsevier Inc. All rights reserved.
Integrated crop/livestock systems reduce late-fall livestock feeding costs
USDA-ARS?s Scientific Manuscript database
Feed costs during the late-fall and winter periods represent the greatest cost to cow-calf production in the northern Great Plains. Integration of crop and livestock enterprises may improve sustainability through synergisms among enterprises reducing waste and improving productivity, and providing b...
Environmental Correlates of Abundances of Mosquito Species and Stages in Discarded Vehicle Tires
YEE, DONALD A.; KNEITEL, JAMIE M.; JULIANO, STEVEN A.
2012-01-01
Discarded vehicle tires are a common habitat for container mosquito larvae, although the environmental factors that may control their presence or abundance within a tire are largely unknown. We sampled discarded vehicle tires in six sites located within four counties of central Illinois during the spring and summer of 2006 to determine associations between a suite of environmental factors and community composition of container mosquitoes. Our goal was to find patterns of association between environmental factors and abundances of early and late instars. We hypothesized that environmental factors correlated with early instars would be indicative of oviposition cues, whereas environmental factors correlated with late instars would be those important for larval survival. We collected 13 species of mosquitoes, with six species (Culex restuans, Cx. pipiens, Aedes albopictus, Cx. salinarius, Ae. atropalpus, and Ae. triseriatus) accounting for ≈95% of all larvae. There were similar associations between congenerics and environmental factors, with Aedes associated with detritus type (fine detritus, leaves, seeds) and Culex associated with factors related to the surrounding habitat (human population density, canopy cover, tire size) or microorganisms (bacteria, protozoans). Although there was some consistency in factors that were important for early and late instar abundance, there were few significant associations between early and late instars for individual species. Lack of correspondence between factors that explain variation in early versus late instars, most notable for Culex, suggests a difference between environmental determinants of oviposition and survival within tires. Environmental factors associated with discarded tires are important for accurate predictions of mosquito occurrence at the generic level. PMID:20180308
Wu, Haibin; Guo, Zhengtang; Guiot, Joël; Hatté, Christine; Peng, Changhui; Yu, Yanyan; Ge, Junyi; Li, Qin; Sun, Aizhi; Zhao, Deai
2014-05-01
During the late Miocene, a dramatic global expansion of C4 plant distribution occurred with broad spatial and temporal variations. Although the event is well documented, whether subsequent expansions were caused by a decreased atmospheric CO2 concentration or climate change is a contentious issue. In this study, we used an improved inverse vegetation modeling approach that accounts for the physiological responses of C3 and C4 plants to quantitatively reconstruct the paleoclimate in the Siwalik of Nepal based on pollen and carbon isotope data. We also studied the sensitivity of the C3 and C4 plants to changes in the climate and the atmospheric CO2 concentration. We suggest that the expansion of the C4 plant distribution during the late Miocene may have been primarily triggered by regional aridification and temperature increases. The expansion was unlikely caused by reduced CO2 levels alone. Our findings suggest that this abrupt ecological shift mainly resulted from climate changes related to the decreased elevation of the Himalayan foreland. © 2013 John Wiley & Sons Ltd.
Daffner, Kirk R.; Alperin, Brittany R.; Mott, Katherine K.; Tusch, Erich; Holcomb, Phillip J.
2015-01-01
Previous work demonstrated age-associated increases in the anterior P2 and age-related decreases in the anterior N2 in response to novel stimuli. Principal component analysis (PCA) was used to determine if the inverse relationship between these components was due to their temporal and spatial overlap. PCA revealed an early anterior P2, sensitive to task relevance, and a late anterior P2, responsive to novelty, both exhibiting age-related amplitude increases. A PCA factor representing the anterior N2, sensitive to novelty, exhibited age-related amplitude decreases. The late P2 and N2 to novels inversely correlated. Larger late P2 amplitude to novels was associated with better behavioral performance. Age-related differences in the anterior P2 and N2 to novel stimuli likely represent age-associated changes in independent cognitive operations. Enhanced anterior P2 activity (indexing augmentation in motivational salience) may be a compensatory mechanism for diminished anterior N2 activity (indexing reduced ability of older adults to process ambiguous representations). PMID:25596483
Brand, C; Sundararajan, V; Jones, C; Hutchinson, A; Campbell, D
2005-05-01
Comprehensive disease management programmes for chronic disease aim to improve patient outcomes and reduce health-care utilization. Readmission rates are often used as an outcome measure of effectiveness. This study aimed to document readmission rates, and risk for early and late readmission, for patients discharged from the Royal Melbourne Hospital with a disease diagnosis of chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) or diabetes mellitus compared to those with other general medical conditions. Eighty five (8.6%) of patients were readmitted within 28 days and 183 (20.8%) were readmitted between 29 and 180 days. No risk factors for early readmission were identified. Patients with a primary disease diagnosis of CHF and COPD are at increased risk of late readmissions (29-180 days).
Bruce, Martha L; Ten Have, Thomas R; Reynolds, Charles F; Katz, Ira I; Schulberg, Herbert C; Mulsant, Benoit H; Brown, Gregory K; McAvay, Gail J; Pearson, Jane L; Alexopoulos, George S
2004-03-03
Suicide rates are highest in late life; the majority of older adults who die by suicide have seen a primary care physician in preceding months. Depression is the strongest risk factor for late-life suicide and for suicide's precursor, suicidal ideation. To determine the effect of a primary care intervention on suicidal ideation and depression in older patients. Randomized controlled trial known as PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial) with patient recruitment from 20 primary care practices in New York City, Philadelphia, and Pittsburgh regions, May 1999 through August 2001. Two-stage, age-stratified (60-74, > or =75 years) depression screening of randomly sampled patients; enrollment included patients who screened positive and a random sample of screened negative patients. This analysis included patients with a depression diagnosis (N = 598). Treatment guidelines tailored for the elderly with care management compared with usual care. Assessment of suicidal ideation and depression severity at baseline, 4 months, 8 months, and 12 months. Rates of suicidal ideation declined faster (P =.01) in intervention patients compared with usual care patients; at 4 months, in the intervention group, raw rates of suicidal ideation declined 12.9% points (29.4% to 16.5%) compared with 3.0% points (20.1% to 17.1% in usual care [P =.01]). Among patients reporting suicidal ideation, resolution of ideation was faster among intervention patients (P =.03); differences peaked at 8 months (70.7% vs 43.9% resolution; P =.005). Intervention patients had a more favorable course of depression in both degree and speed of symptom reduction; group difference peaked at 4 months. The effects on depression were not significant among patients with minor depression unless suicidal ideation was present. Evidence of the intervention's effectiveness in community-based primary care with a heterogeneous sample of depressed patients introduces new challenges related to its sustainability and dissemination. The intervention's effectiveness in reducing suicidal ideation, regardless of depression severity, reinforces its role as a prevention strategy to reduce risk factors for suicide in late life.
Late-life suicide prevention strategies: current status and future directions.
Van Orden, Kim; Deming, Charlene
2017-09-08
Late life suicide prevention differs from suicide prevention for other age groups: first, the number of older adults worldwide is on the rise; second, late-life suicide receives much less attention in all societal spheres, from the media, to federal funding agencies, to healthcare initiatives. Recent findings indicate an association between internalized ageist stereotypes and reduced will to live. Recent research also addresses the role of cognitive control as a contributor to risk and as an intervention target (e.g., through psychotherapies such as problem solving therapy) as well as firearm safety as a promising, though a politicized and challenging strategy to implement. Another strategy that may prove feasible is an approach on upstream prevention strategies in healthcare. One strategy we believe holds great promise is the promotion of high quality geriatric medicine. Geriatricians are trained to work with patients to prioritize the promotion of physical and cognitive functioning (rather than solely absence of disease) and to focus on well-being as a goal. Thus, geriatricians routinely target numerous late-life suicide risk factors-physical illness, functioning, pain, and (dis)satisfaction with life. However, efficacious strategies will not prevent suicide deaths if they are not implemented-addressing ageism as a universal prevention strategy is essential. Copyright © 2017 Elsevier Ltd. All rights reserved.
Rare-earth metal prices in the USA ca. 1960 to 1994
Hedrick, James B.
1997-01-01
Rare-earth metal prices were compiled from the late 1950s and early 1960s through 1994. Although commercial demand for rare-earth metals began in 1908, as the alloy mischmetal, commercial quantities of a wide range of individual rare-earth metals were not available until the late 1950s. The discovery of a large, high-grade rare-earth deposit at Mountain Pass. CA, USA, in 1949, was significant because it led to the production of commercial quantities or rare-earth elements that reduced prices and encouraged wider application of the materials. The availability of ore from Mountain Pass, and other large rare-earth deposits, especially those in Australia and China, has provided the world with abundant resources for rare-earth metal production. This availability, coupled with improved technology from Government and private-sector metallurgical research, has resulted in substantial decreases in rare-earth metal prices since the late 1950s and early 1960s. Price series for the individual rare-earth metals (except promethium) are quoted on a kilogram basis from the late 1950s and early 1960s through 1994. Prices are given in US dollars on an actual and constant dollar basis. Industrial and economic factors affecting prices during this time period are examined.
Rare-earth metal prices in the USA ca. 1960 to 1994
Hedrick, J.B.
1997-01-01
Rare-earth metal prices were compiled from the late 1950s and early 1960s through 1994. Although commercial demand for rare-earth metals began in 1908, as the alloy mischmetal, commercial quantities of a wide range of individual rare-earth metals were not available until the late 1950s. The discovery of a large, high-grade rare-earth deposit at Mountain Pass, CA, USA, in 1949, was significant because it led to the production of commercial quantities of rare-earth elements that reduced prices and encouraged wider application of the materials. The availability of ore from Mountain Pass, and other large rare-earth deposits, especially those in Australia and China, has provided the world with abundant resources for rare-earth metal production. This availability, coupled with improved technology from Government and private-sector metallurgical research, has resulted in substantial decreases in rare-earth metal prices since the late 1950s and early 1960s. Price series for the individual rare-earth metals (except promethium) are quoted on a kilogram basis from the late 1950s and early 1960s through 1994. Prices are given in US dollars on an actual and constant dollar basis. Industrial and economic factors affecting prices during this time period are examined.
Ejeta, Eyasu; Dabsu, Regea; Zewdie, Olifan; Merdassa, Elias
2017-01-01
Antenatal care (ANC) is important for both maternal and fetal health. However, the existing evidence from developing countries indicates that most pregnant women attending ANC in their late pregnancy. Little is known about the factors determining ANC booking and the content of care among pregnant women in West part of Ethiopia. Therefore, the present study was conducted to identify factors determining late ANC booking and the content of care among pregnant mother attending antenatal care services in East Wollega administrative zone, West Ethiopia. Institutional based cross-sectional study was conducted from July to September, 2014 among 421 pregnant women's attending ANC services in purposively selected health facilities, East Wollega zone, Ethiopia. The pretested-structured questionnaires were used to collect socio-demographic data and predictor factors of late initiation of ANC services. Five trained nurse working at ANC clinic at each health institution administered the questionnaire. The collected data was analysed using SPSS version 20. The prevalence of late ANC booking was 81.5% (343/421) in the study area. Being from Oromo ethnic group (AOR 4.27, (95% CI, 1.48-12.33)), maternal age equal or more than 25 year old (AOR 3.09 (95% CI, 1.53-6.27)), second trimester (AOR 6.05(95% CI, 3.08-11.88)) and third trimester (AOR 7.97 (95% CI, 3.92-16.23)) were main factors identified as contributing (favoring factors) for the likely occurrence of late booking for ANC whereas; monthly income more than and/or equal to 15000 Ethiopian birrs (AOR 0.38 (95% CI, 0.18-084)) were factors compromising (decreasing) the chances for late attendance for the services among the pregnant women. Late ANC initiation is high in the study area despite the services is provided free of charge. Hence, it is important to provide health education on the timing of ANC among women with reproductive age. Community's awareness on importance of receiving early ANC also needs to be promoted.
The DNA damage response activates HPV16 late gene expression at the level of RNA processing.
Nilsson, Kersti; Wu, Chengjun; Kajitani, Naoko; Yu, Haoran; Tsimtsirakis, Efthymios; Gong, Lijing; Winquist, Ellenor B; Glahder, Jacob; Ekblad, Lars; Wennerberg, Johan; Schwartz, Stefan
2018-06-01
We show that the alkylating cancer drug melphalan activated the DNA damage response and induced human papillomavirus type 16 (HPV16) late gene expression in an ATM- and Chk1/2-dependent manner. Activation of HPV16 late gene expression included inhibition of the HPV16 early polyadenylation signal that resulted in read-through into the late region of HPV16. This was followed by activation of the exclusively late, HPV16 splice sites SD3632 and SA5639 and production of spliced late L1 mRNAs. Altered HPV16 mRNA processing was paralleled by increased association of phosphorylated BRCA1, BARD1, BCLAF1 and TRAP150 with HPV16 DNA, and increased association of RNA processing factors U2AF65 and hnRNP C with HPV16 mRNAs. These RNA processing factors inhibited HPV16 early polyadenylation and enhanced HPV16 late mRNA splicing, thereby activating HPV16 late gene expression.
Bogg, Tim; Finn, Peter R.
2011-01-01
Two samples with heterogeneous prevalence of externalizing psychopathology were used to investigate the structure of self-regulatory models of behavioral disinhibition and cognitive capacity. Consistent with expectations, structural equation modeling in the first sample (N = 541) showed a hierarchical model with three lower-order factors of impulsive sensation-seeking, anti-sociality/unconventionality, and lifetime externalizing problem counts, with a behavioral disinhibition superfactor best accounted for the pattern of covariation among six disinhibited personality trait indicators and four externalizing problem indicators. The structure was replicated in a second sample (N = 463) and showed that the behavioral disinhibition superfactor, and not the lower-order impulsive sensation-seeking, anti-sociality/unconventionality, and externalizing problem factors, was associated with lower IQ, reduced short-term memory capacity, and reduced working memory capacity. The results provide a systemic and meaningful integration of major self-regulatory influences during a developmentally important stage of life. PMID:20433626
Thin and small form factor cells : simulated behavior.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Clews, Peggy Jane; Pluym, Tammy; Grubbs, Robert K.
Thin and small form factor cells have been researched lately by several research groups around the world due to possible lower assembly costs and reduced material consumption with higher efficiencies. Given the popularity of these devices, it is important to have detailed information about the behavior of these devices. Simulation of fabrication processes and device performance reveals some of the advantages and behavior of solar cells that are thin and small. Three main effects were studied: the effect of surface recombination on the optimum thickness, efficiency, and current density, the effect of contact distance on the efficiency for thin cells,more » and lastly the effect of surface recombination on the grams per Watt-peak. Results show that high efficiency can be obtained in thin devices if they are well-passivated and the distance between contacts is short. Furthermore, the ratio of grams per Watt-peak is greatly reduced as the device is thinned.« less
2009 Samoa tsunami: factors that exacerbated or reduced impacts in Samoa and American Samoa
NASA Astrophysics Data System (ADS)
Dengler, L. A.; Ewing, L.; Brandt, J.; Irish, J. L.; Jones, C.; Long, K.; Lazrus, H.; McCullough, N.
2009-12-01
An interdisciplinary team with expertise in coastal and port engineering, coastal management, environmental science, anthropology, emergency management, and mitigation visited Samoa and American Samoa in late October and November, 2009. The team, sponsored by ASCE/COPRI, EERI, and the NTHMP focused on identifying the factors which effected the impacts of the September 29, 2009 tsunami. The engineering group assessed the value of engineered coastal protection and natural protective features (reefs, mangroves, etc.) in reducing tsunami inundation by comparing protected and unprotected coastlines and examined possible correlations between damage to the built environment and hydrodynamic forcing, namely loading by runup and velocity. The EERI group looked at how coastal land use planning and management, emergency planning and response, and culture, education and awareness of tsunami hazards affected outcomes. The group also looked at public response to the natural warnings of September 29 and the official warnings following the October 7 Vanuatu tsunami warning.
Carotid Artery Stenting, Endarterectomy, or Medical Treatment Alone: The Debate Is Not Over
Kassaian, Seyed Ebrahim; Goodarzynejad, Hamidreza
2011-01-01
The management of carotid artery stenosis reduces the risk of stroke and its related deaths. Management options include risk factor modification and medical therapy, carotid endarterectomy (CEA), and carotid artery stenting (CAS). Although several randomized controlled trials (RCTs), mostly conducted in late-1980s and mid-1990s, have proved CEA to be effective in the prevention of ipsilateral ischemic events in selected patients with carotid artery stenosis, aggressive risk factor modification and medical therapy with recently introduced antiplatelet agents, statins, and more effective antihypertensive medications may have reduced compelling indications for immediate surgery in asymptomatic populations. Also recently, due to improvements in percutaneous techniques and carotid stents, CAS has received wide attention as a potential alternative to CEA. Herein, we review the recent data on the management options of carotid artery stenosis and seek to identify the most appropriate treatment strategy in selected patients with carotid artery stenosis. PMID:23074598
MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2.
Zhou, Yu; Song, Yan; Shaikh, Zahir; Li, Hui; Zhang, Haiju; Caudle, Yi; Zheng, Shouhua; Yan, Hui; Hu, Dan; Stuart, Charles; Yin, Deling
2017-07-18
Cardiac dysfunction is correlated with detrimental prognosis of sepsis and contributes to a high risk of mortality. After an initial hyperinflammatory reaction, most patients enter a protracted state of immunosuppression (late sepsis) that alters both innate and adaptive immunity. The changes of cardiac function in late sepsis are not yet known. MicroRNA-155 (miR-155) is previously found to play important roles in both regulations of immune activation and cardiac function. In this study, C57BL/6 mice were operated to develop into early and late sepsis phases, and miR-155 mimic was injected through the tail vein 48 h after cecal ligation and puncture (CLP). The effect of miR-155 on CLP-induced cardiac dysfunction was explored in late sepsis. We found that increased expression of miR-155 in the myocardium protected against cardiac dysfunction in late sepsis evidenced by attenuating sepsis-reduced cardiac output and enhancing left ventricular systolic function. We also observed that miR-155 markedly reduced the infiltration of macrophages and neutrophils into the myocardium and attenuated the inflammatory response via suppression of JNK signaling pathway. Moreover, overexpression of β-arrestin 2 (Arrb2) exacerbated the mice mortality and immunosuppression in late sepsis. Furthermore, transfection of miR-155 mimic reduced Arrb2 expression, and then restored immunocompetence and improved survival in late septic mice. We conclude that increased miR-155 expression through systemic administration of miR-155 mimic attenuates cardiac dysfunction and improves late sepsis survival by targeting JNK associated inflammatory signaling and Arrb2 mediated immunosuppression.
Involvement of Brain-Derived Neurotrophic Factor in Late-Life Depression
Dwivedi, Yogesh
2013-01-01
Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons, synaptic integrity, and synaptic plasticity. Evidence suggests that BDNF is involved in major depression, such that the level of BDNF is decreased in depressed patients and that antidepressants reverse this decrease. Stress, a major factor in depression, also modulates BDNF expression. These studies have led to the proposal of the neurotrophin hypothesis of depression. Late-life depression is associated with disturbances in structural and neural plasticity as well as impairments in cognitive behavior. Stress and aging also play a crucial role in late-life depression. Many recent studies have suggested that not only expression of BDNF is decreased in the serum/plasma of patients with late-life depression, but structural abnormalities in the brain of these patients may be associated with a polymorphism in the BDNF gene, and that there is a relationship between a BDNF polymorphism and antidepressant remission rates. This review provides a critical review of the involvement of BDNF in major depression, in general, and in late-life depression, in particular. PMID:23570887
DOE Office of Scientific and Technical Information (OSTI.GOV)
Olsen, Jeffrey R., E-mail: Jeffrey.R.Olsen@ucdenver.edu; Moughan, Jennifer; Myerson, Robert
Purpose: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods and Materials: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structuremore » receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). Results: Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P<.05) toward statistically significant associations were observed between grade ≥2 acute GI AEs and small bowel dose (V20-V40), grade ≥2 late GI AEs and APC dose (V60), grade ≥3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.« less
Chapko, Dorota; Staff, Roger T; McNeil, Christopher J; Whalley, Lawrence J; Black, Corri; Murray, Alison D
2016-07-01
the 'triad of impairment' phenomenon describes the co-occurrence of age-related cognitive, emotional and physical functioning deficits. We investigated how occupational profile and childhood intelligence contribute to the triad of impairment in late life. we analysed data of a subsample of the Aberdeen Birth Cohort of 1936 (n = 346). Data were collected on participants' childhood intelligence, late-life cognitive ability, physical functioning, depressive symptoms and main lifetime occupation. We summarised the various occupational and impairment measures into two latent variables, 'occupational profile' and the 'triad of impairment'. We used a series of data reduction approaches and structural equation models (SEMs) of increasing complexity to test both the validity of the models and to understand causal relationships between the life-course risks for the triad of impairment. occupational profile had a significant effect on the triad of impairment independent of childhood intelligence. Childhood intelligence was the predominant influence on the triad of impairment and exerted its effect directly and indirectly via its influence on occupation. The direct effect of childhood intelligence exceeded the independent influence of the occupational profile on impairment by a factor of 1.7-1.8 and was greater by a factor of ∼4 from the indirect pathway (via occupation). childhood intelligence was the predominant influence on the triad of impairment in late life, independently of the occupational profile. Efforts to reduce impairment in older adults should be informed by a life-course approach with special attention to the early-life environment. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Zhu, Ming-Xia; Zhao, Jin-Yuan; Chen, Gui-An; Guan, Li
2011-09-01
hESCs (human embryonic stem cells) can differentiate into tissue derivatives of all three germ layers in vitro and mimic the development of the embryo in vivo. In this study, we have investigated the potential of an hESC-based assay for the detection of toxicity to cardiac differentiation in embryonic development. First of all, we developed the protocol of cardiac induction from hESCs according to our previous work and distinguished cardiac precursor cells and late mature cardiomyocytes from differentiated cells, demonstrated by the Q-PCR (quantitative real-time PCR), immunocytochemistry and flow cytometry analysis. In order to test whether CPA (cyclophosphamide) induces developmental and cellular toxicity in the human embryo, we exposed the differentiating cells from hESCs to CPA (a well-known proteratogen) at different stages. We have found that a high concentration of CPA could inhibit cardiac differentiation of hESCs. Two separate exposure intervals were used to determine the effects of CPA on cardiac precursor cells and late mature cardiomyocytes respectively. The cardiac precursor cells were sensitive to CPA in non-cytotoxic concentrations for the expression of the cardiac-specific mRNA markers Nkx2.5 (NK2 transcription factor related, locus 5), GATA-4 (GATA binding protein 4 transcription factor) and TNNT2 (troponin T type 2). Non-cytotoxic CPA concentrations did not affect the mRNA markers' expression in late mature cardiomyocytes, indicating that cardiac precursors were more sensitive to CPA than late cardiomyocytes in cardiogenesis. We set up the in vitro developmental toxicity test model so as to reduce the number of test animals and expenses without compromising the safety of consumers and patients. Furthermore, such in vitro methods may be possibly suited to test a large number of chemicals than the classical employed in vivo tests.
Retinopathy of prematurity: the need for prevention
Liegl, Raffael; Hellström, Ann; Smith, Lois EH
2016-01-01
More than 450,000 babies are born prematurely in the USA every year. The improved survival of even the most vulnerable low body weight preterm infants has, despite improving health outcomes, led to the resurgence in preterm complications including one of the major causes for blindness in children, retinopathy of prematurity (ROP). The current mainstay in ROP therapy is laser photocoagulation and the injection of vascular endothelial growth factor (VEGF) antibodies in the late stages of the disease after the onset of neovascularization. Both are proven options for ophthalmologists to treat the severe forms of late ROP. However, laser photocoagulation destroys major parts of the retina, and the injection of VEGF antibodies, although rather simple to administer, may cause a systemic suppression of normal vascularization, which has not been studied in sufficient depth. However, the use of neither VEGF antibody nor laser treatment prevents ROP, which should be the long-term goal. It should be possible to prevent ROP by more closely mimicking the intrauterine environment after preterm birth. Such preventive measures include preventing the toxic postbirth influences (eg, oxygen excess) as well as providing the missing intrauterine factors (eg, insulin growth factor 1) and are likely to also reduce other complications of premature birth as well as ROP. This review is meant to summarize the current knowledge on the prevention of ROP with a particular emphasize on the use of insulin growth factor 1 supplementation. PMID:28539804
ERIC Educational Resources Information Center
Milman, Doris H.
Two studies explore the late outcome of minimal brain dysfunction in 73 patients in relation to their initial presentation and predictive factors. Both studies followed the patients for a period of 10 to 20 years. Findings from the first study of initial presentation in relation to adult outcome showed that there was a strong positive correlation…
Andersson, P; Brange, C; von Kogerer, B; Sonmark, B; Stahre, G
1988-01-01
The effect of glucocorticosteroid (GCS) treatment on ovalbumine-induced IgE-mediated immediate and late allergic response was studied in sensitized guinea pigs. The results show that the GCS budesonide (BUD) inhibits the allergen-induced IgE-mediated immediate and late bronchial obstruction. The effect on the early reaction is correlated to the inhibition of leukotrienes and histamine release. The importance of mediator release inhibition for the antianaphylactic effect of GCS is discussed. In examining the effect on the late reaction, it was found that BUD had to be present during the early reaction but did not inhibit the early reaction. Furthermore, the effect on the late reaction was correlated to the inhibition of vascular leakage but not to the infiltration of inflammatory cells as examined in bronchoalveolar lavage. The results indicate that some triggering factors important for the development of the late reaction are released during the early reaction. Inhibition of the release of that factor or the activation of inflammatory cells by that factor might be the mechanism behind the antiinflammatory activities of GCS.
77 FR 46561 - Amendments to Adjudicatory Process Rules and Related Requirements
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-03
... eight late-filed factors, especially not for late-filed hearing requests or intervention petitions. The... current three Sec. 2.309(f)(2) factors. As the NRC explained in the proposed rule, whether filings after... the existence of good cause, not the other factors. The commenter has not supported its assertion that...
Wang, Xiaoyu; Wang, Xianling; Hu, Qingnan; ...
2015-06-17
In Arabidopsis, anthocyanin biosynthesis is controlled by a MYB-bHLH-WD40 (MBW) transcriptional activator complex. The MBW complex activates the transcription of late biosynthesis genes in the flavonoid pathway, leading to the production of anthocyanins. A similar MBW complex regulates epidermal cell fate by activating the transcription of GLABRA2 (GL2), a homeodomain transcription factor required for trichome formation in shoots and non-hair cell formation in roots. Here we provide experimental evidence to show that GL2 also plays a role in regulating anthocyanin biosynthesis in Arabidopsis. From an activation-tagged mutagenized population of Arabidopsis plants, we isolated a dominant, gain-of-function mutant with reduced anthocyanins.more » Molecular cloning revealed that this phenotype is caused by an elevated expression of GL2, thus the mutant was named gl2-1D. Consistent with the view that GL2 acts as a negative regulator of anthocyanin biosynthesis, gl2-1D seedlings accumulated less whereas gl2-3 seedlings accumulated more anthocyanins in response to sucrose. Gene expression analysis indicated that expression of late, but not early, biosynthesis genes in the flavonoid pathway was dramatically reduced in gl2-1D but elevated in gl2-3 mutants. Further analysis showed that expression of some MBW component genes involved in the regulation of late biosynthesis genes was reduced in gl2-1D but elevated in gl2-3 mutants, and chromatin immunoprecipitation results indicated that some MBW component genes are targets of GL2. We also showed that GL2 functions as a transcriptional repressor. Altogether, these results indicate that GL2 negatively regulates anthocyanin biosynthesis in Arabidopsis by directly repressing the expression of some MBW component genes.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Xiaoyu; Wang, Xianling; Hu, Qingnan
In Arabidopsis, anthocyanin biosynthesis is controlled by a MYB-bHLH-WD40 (MBW) transcriptional activator complex. The MBW complex activates the transcription of late biosynthesis genes in the flavonoid pathway, leading to the production of anthocyanins. A similar MBW complex regulates epidermal cell fate by activating the transcription of GLABRA2 (GL2), a homeodomain transcription factor required for trichome formation in shoots and non-hair cell formation in roots. Here we provide experimental evidence to show that GL2 also plays a role in regulating anthocyanin biosynthesis in Arabidopsis. From an activation-tagged mutagenized population of Arabidopsis plants, we isolated a dominant, gain-of-function mutant with reduced anthocyanins.more » Molecular cloning revealed that this phenotype is caused by an elevated expression of GL2, thus the mutant was named gl2-1D. Consistent with the view that GL2 acts as a negative regulator of anthocyanin biosynthesis, gl2-1D seedlings accumulated less whereas gl2-3 seedlings accumulated more anthocyanins in response to sucrose. Gene expression analysis indicated that expression of late, but not early, biosynthesis genes in the flavonoid pathway was dramatically reduced in gl2-1D but elevated in gl2-3 mutants. Further analysis showed that expression of some MBW component genes involved in the regulation of late biosynthesis genes was reduced in gl2-1D but elevated in gl2-3 mutants, and chromatin immunoprecipitation results indicated that some MBW component genes are targets of GL2. We also showed that GL2 functions as a transcriptional repressor. Altogether, these results indicate that GL2 negatively regulates anthocyanin biosynthesis in Arabidopsis by directly repressing the expression of some MBW component genes.« less
Precursors in adolescence of adult-onset bipolar disorder.
Hiyoshi, Ayako; Sabet, Julia A; Sjöqvist, Hugo; Melinder, Carren; Brummer, Robert J; Montgomery, Scott
2017-08-15
Although the estimated contribution of genetic factors is high in bipolar disorder, environmental factors may also play a role. This Swedish register-based cohort study of men examined if physical and psychological characteristics in late adolescence, including factors previously linked with bipolar disorder (body mass index, asthma and allergy), are associated with subsequent bipolar disorder in adulthood. Unipolar depression and anxiety are analysed as additional outcomes to identify bipolar disorder-specific associations. A total of 213,693 men born between 1952 and 1956, who participated in compulsory military conscription assessments in late adolescence were followed up to 2009, excluding men with any psychiatric diagnoses at baseline. Cox regression estimated risk of bipolar disorder, depression and anxiety in adulthood associated with body mass index, asthma, allergy, muscular strength stress resilience and cognitive function in adolescence. BMI, asthma and allergy were not associated with bipolar disorder. Higher grip strength, cognitive function and stress resilience were associated with a reduced risk of bipolar disorder and the other disease outcomes. The sample consisted only of men; even though the characteristics in adolescence pre-dated disease onset, they may have been the consequence of prodromal disease. Associations with body mass index and asthma found by previous studies may be consequences of bipolar disorder or its treatment rather than risk factors. Inverse associations with all the outcome diagnoses for stress resilience, muscular strength and cognitive function may reflect general risks for these psychiatric disorders or intermediary factors. Copyright © 2017 Elsevier B.V. All rights reserved.
METAL-INDUCED LATE PULMONARY INJURY IS REDUCED BY OZONE (O3) COEXPOSURE
METAL-INDUCED LATE PULMONARY INJURY IS REDUCED BY OZONE (O3) COEXPOSURE. UP Kodavanti, MCJ Schladweiler, WP Watkinson, JP Nolan, PA Evansky, ER Lappi, G Ross, JH Richards, and DL Costa. NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC USA.
Ambient ...
Kimura, Takeshi; Morimoto, Takeshi; Nakagawa, Yoshihisa; Kawai, Kazuya; Miyazaki, Shunichi; Muramatsu, Toshiya; Shiode, Nobuo; Namura, Masanobu; Sone, Takahito; Oshima, Shigeru; Nishikawa, Hideo; Hiasa, Yoshikazu; Hayashi, Yasuhiko; Nobuyoshi, Masakiyo; Mitudo, Kazuaki
2012-01-31
There is a scarcity of long-term data from large-scale drug-eluting stent registries with a large enough sample to evaluate low-frequency events such as stent thrombosis (ST). Five-year outcomes were evaluated in 12 812 consecutive patients undergoing sirolimus-eluting stent (SES) implantation in the j-Cypher registry. Cumulative incidence of definite ST was low (30 day, 0.3%; 1 year, 0.6%; and 5 years, 1.6%). However, late and very late ST continued to occur without attenuation up to 5 years after sirolimus-eluting stent implantation (0.26%/y). Cumulative incidence of target lesion revascularization within the first year was low (7.3%). However, late target lesion revascularization beyond 1 year also continued to occur without attenuation up to 5 years (2.2%/y). Independent risk factors of ST were completely different according to the timing of ST onset, suggesting the presence of different pathophysiological mechanisms of ST according to the timing of ST onset: acute coronary syndrome and target of proximal left anterior descending coronary artery for early ST; side-branch stenting, diabetes mellitus, and end-stage renal disease with or without hemodialysis for late ST; and current smoking and total stent length >28 mm for very late ST. Independent risk factors of late target lesion revascularization beyond 1 year were generally similar to those risk factors identified for early target lesion revascularization. Late adverse events such as very late ST and late target lesion revascularization are continuous hazards, lasting at least up to 5 years after implantation of the first-generation drug-eluting stents (sirolimus-eluting stents), which should be the targets for developing improved coronary stents.
Perceptual load corresponds with factors known to influence visual search
Roper, Zachary J. J.; Cosman, Joshua D.; Vecera, Shaun P.
2014-01-01
One account of the early versus late selection debate in attention proposes that perceptual load determines the locus of selection. Attention selects stimuli at a late processing level under low-load conditions but selects stimuli at an early level under high-load conditions. Despite the successes of perceptual load theory, a non-circular definition of perceptual load remains elusive. We investigated the factors that influence perceptual load by using manipulations that have been studied extensively in visual search, namely target-distractor similarity and distractor-distractor similarity. Consistent with previous work, search was most efficient when targets and distractors were dissimilar and the displays contained homogeneous distractors; search became less efficient when target-distractor similarity increased irrespective of display heterogeneity. Importantly, we used these same stimuli in a typical perceptual load task that measured attentional spill-over to a task-irrelevant flanker. We found a strong correspondence between search efficiency and perceptual load; stimuli that generated efficient searches produced flanker interference effects, suggesting that such displays involved low perceptual load. Flanker interference effects were reduced in displays that produced less efficient searches. Furthermore, our results demonstrate that search difficulty, as measured by search intercept, has little bearing on perceptual load. These results suggest that perceptual load might be defined in part by well-characterized, continuous factors that influence visual search. PMID:23398258
DOE Office of Scientific and Technical Information (OSTI.GOV)
Begolly, Sage; Shrager, Peter G.; Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York
Purpose: To determine the late effects of fractionated versus single-dose cranial radiation on murine white matter. Methods and Materials: Mice were exposed to 0 Gy, 6 × 6 Gy, or 1 × 20 Gy cranial irradiation at 10 to 12 weeks of age. Endpoints were assessed through 18 months from exposure using immunohistochemistry, electron microscopy, and electrophysiology. Results: Weight gain was temporarily reduced after irradiation; greater loss was seen after single versus fractionated doses. Oligodendrocyte progenitor cells were reduced early and late after both single and fractionated irradiation. Both protocols also increased myelin g-ratio, reduced the number of nodes of Ranvier, and promoted a shift in the proportion of small, unmyelinatedmore » versus large, myelinated axon fibers. Conclusions: Fractionation does not adequately spare normal white matter from late radiation side effects.« less
The Development of a Questionnaire on Academic Hardiness for Late Elementary School Children
ERIC Educational Resources Information Center
Kamtsios, Spiridon; Karagiannopoulou, Evangelia
2013-01-01
The purpose of the research was to develop a questionnaire to measure dimensions of academic hardiness in late elementary school children. Questionnaires were distributed to 1474 children. After a set of exploratory factor analyses in studies 1 and 2, the confirmatory factor analysis results provided support for the 9-factor solution which…
ERIC Educational Resources Information Center
Mayer, Birgit; Muris, Peter; Meesters, Cor; Zimmermann-van Beuningen, Ritine
2009-01-01
This study explored correlations between risk factors and eating behavior problems in late adolescent, non-clinical females (N = 301). Participants completed questionnaires for assessing eating problems, the closely associated factors of Body Mass Index (BMI) and body dissatisfaction, and a number of other risk variables that are thought to be…
Liew, Steven; Sundaram, Hema; De Boulle, Koenraad L.; Goodman, Greg J.; Monheit, Gary; Wu, Yan; Trindade de Almeida, Ada R.; Swift, Arthur; Vieira Braz, André
2016-01-01
Background: Although the safety profile of hyaluronic acid fillers is favorable, adverse reactions can occur. Clinicians and patients can benefit from ongoing guidance on adverse reactions to hyaluronic acid fillers and their management. Methods: A multinational, multidisciplinary group of experts in cosmetic medicine convened the Global Aesthetics Consensus Group to review the properties and clinical uses of Hylacross and Vycross hyaluronic acid products and develop updated consensus recommendations for early and late complications associated with hyaluronic acid fillers. Results: The consensus panel provided specific recommendations focusing on early and late complications of hyaluronic acid fillers and their management. The impact of patient-, product-, and technique-related factors on such reactions was described. Most of these were noted to be mild and transient. Serious adverse events are rare. Early adverse reactions to hyaluronic acid fillers include vascular infarction and compromise; inflammatory reactions; injection-related events; and inappropriate placement of filler material. Among late reactions are nodules, granulomas, and skin discoloration. Most adverse events can be avoided with proper planning and technique. Detailed understanding of facial anatomy, proper patient and product selection, and appropriate technique can further reduce the risks. Should adverse reactions occur, the clinician must be prepared and have tools available for effective treatment. Conclusions: Adverse reactions with hyaluronic acid fillers are uncommon. Clinicians should take steps to further reduce the risk and be prepared to treat any complications that arise. PMID:27219265
NASA Astrophysics Data System (ADS)
Drury, Anna Joy; John, Cédric M.; Shevenell, Amelia E.
2016-01-01
Orbital-scale climate variability during the latest Miocene-early Pliocene is poorly understood due to a lack of high-resolution records spanning 8.0-3.5 Ma, which resolve all orbital cycles. Assessing this variability improves understanding of how Earth's system sensitivity to insolation evolves and provides insight into the factors driving the Messinian Salinity Crisis (MSC) and the Late Miocene Carbon Isotope Shift (LMCIS). New high-resolution benthic foraminiferal Cibicidoides mundulus δ18O and δ13C records from equatorial Pacific International Ocean Drilling Program Site U1338 are correlated to North Atlantic Ocean Drilling Program Site 982 to obtain a global perspective. Four long-term benthic δ18O variations are identified: the Tortonian-Messinian, Miocene-Pliocene, and Early-Pliocene Oxygen Isotope Lows (8-7, 5.9-4.9, and 4.8-3.5 Ma) and the Messinian Oxygen Isotope High (MOH; 7-5.9 Ma). Obliquity-paced variability dominates throughout, except during the MOH. Eleven new orbital-scale isotopic stages are identified between 7.4 and 7.1 Ma. Cryosphere and carbon cycle sensitivities, estimated from δ18O and δ13C variability, suggest a weak cryosphere-carbon cycle coupling. The MSC termination coincided with moderate cryosphere sensitivity and reduced global ice sheets. The LMCIS coincided with reduced carbon cycle sensitivity, suggesting a driving force independent of insolation changes. The response of the cryosphere and carbon cycle to obliquity forcing is established, defined as Earth System Response (ESR). Observations reveal that two late Miocene-early Pliocene climate states existed. The first is a prevailing dynamic state with moderate ESR and obliquity-driven Antarctic ice variations, associated with reduced global ice volumes. The second is a stable state, which occurred during the MOH, with reduced ESR and lower obliquity-driven variability, associated with expanded global ice volumes.
Modifiable factors associated with changes in postpartum depressive symptoms.
Howell, Elizabeth A; Mora, Pablo A; DiBonaventura, Marco D; Leventhal, Howard
2009-04-01
Up to 50% of mothers report postpartum depressive symptoms yet providers do a poor job predicting and preventing their occurrence. Our goal was to identify modifiable factors (situational triggers and buffers) associated with postpartum depressive symptoms. Observational prospective cohort telephone study of 563 mothers interviewed at 2 weeks and 6 months postpartum. Mothers reported on demographic factors, physical and emotional symptoms, daily function, infant behaviors, social support, and skills in managing infant and household. Mothers were categorized into four groups based on the presence of depressive symptoms at 2 weeks and at 6 months postpartum: never, always, late onset, and remission groups. Fifty-two percent did not have depressive symptoms at 2 weeks or at 6 months (never group), 14% had symptoms at both time points (always group), 10% had late onset, and 24% had early onset of symptoms with remission. As compared with women in the never group, women in the always and late onset groups had high-risk characteristics (e.g., past history of depression), more situational triggers (e.g., physical symptoms), and less robust social and personal buffers (i.e., social support and self-efficacy). As compared with the never group, mothers in the remission group had more situational triggers and fewer buffers initially. Changes in situational triggers and buffers were different for the four groups and were correlated with group membership. Situational triggers such as physical symptoms and infant colic, and low levels of social support and self-efficacy in managing situational demands are associated with postpartum depressive symptoms. Further research is needed to investigate whether providing education about the physical consequences of childbirth, providing social support, and teaching skills to enhance self-efficacy will reduce the incidence of postpartum symptoms of depression.
Yan, Xu; Zhu, Mei J; Xu, Wei; Tong, Jun F; Ford, Stephen P; Nathanielsz, Peter W; Du, Min
2010-01-01
Maternal obesity is increasing at an alarming rate. We previously showed that maternal obesity induces an inflammatory response and enhances adipogenesis in fetal skeletal muscle at midgestation. The objective of this study was to evaluate effects of maternal obesity on adipogenesis, inflammatory signaling, and insulin pathways at late gestation when ovine fetal skeletal muscle matures. Nonpregnant ewes were assigned to a control diet (Con, fed 100% of National Research Council nutrient recommendations, n = 6) or obesogenic diet (OB, fed 150% of National Research Council recommendations, n = 6) from 60 d before to 135 d after conception (term 148 d) when the fetal semitendenosus skeletal muscle was sampled. Expression of the adipogenic marker, peroxisome proliferator-activated receptor-gamma, was increased in OB compared with Con fetal semitendenosus muscle, indicating up-regulation of adipogenesis. More intramuscular adipocytes were observed in OB muscle. Phosphorylation of inhibitor-kappaB kinase-alpha/beta and nuclear factor-kappaB RelA/p65 were both increased in OB fetal muscle, indicating activation of nuclear factor-kappaB pathway. Phosphorylation of c-Jun N-terminal kinase and c-Jun (at Ser 63 and Ser 73) was also elevated. Toll-like receptor 4 expression was higher in OB than Con fetal muscle. Moreover, despite higher insulin concentrations in OB vs. Con fetal plasma (2.89 +/- 0.53 vs. 1.06 +/- 0.52 ng/ml; P < 0.05), phosphorylation of protein kinase B at Ser 473 was reduced, indicating insulin resistance. In conclusion, our data show maternal obesity-induced inflammatory signaling in late gestation fetal muscle, which correlates with increased im adipogenesis and insulin resistance, which may predispose offspring to later-life obesity and diabetes.
Stephen, Atasige Awin-Irigu; Wurapa, Frederick; Afari, Edwin Andrew; Sackey, Samuel Oko; Malm, Keaziah Laurencia; Nyarko, Kofi Mensah
2016-01-01
The coverage of adequate (≥2 doses) IPTp-SP in Ghana is below the national target of 80% and that is a threat to reducing the incidence of malaria in pregnancy. The primary objective of the study was to determine the client and facility related factors associated with adequate uptake of IPTp-SP and suggest approaches for increased uptake. A cross sectional study was conducted among ANC clients and staff in Gushegu, questionnaires was administered to 330 conveniently sampled nursing mothers and all ANC staff present. A checklist and observation were used to collect health facility data. Data was analyzed descriptively and associations between the related factors and adequate uptake of IPTp-SP were determined. A total of 91.5% and 8.5% of respondents took adequate (≥2doses) and inadequate (≤1dose) IPTp-SP respectively. 85.4% respondents were early first ANC attendance and 80% were multiple gravidae. Mean ANC visits was 5.0 (standard deviation = 2.2). The key determinants for inadequate uptake of IPTp were Unemployment [OR= 4.9 95% CI (1.9-13.1], single gravidae [OR= 3.4 95% CI (1.5-7.6)] and late first ANC visit [OR= 6.8 95% CI (3.0-15.4)]. DOT practice, good staff attitude and health talk at the facility were observed and confirmed by ANC clients as satisfactory. adequate uptake of SP among respondents was high. Majorities were unemployed, have had multiple pregnancies and made early first ANC visits. Unemployment and late first ANC visits are significantly associated with taking inadequate SP dose. Adequate uptake of SP among respondents was high. Majorities were unemployed, have had multiple pregnancies and made early first ANC visits. Unemployment and late first ANC visits are significantly associated with taking inadequate SP dose.
Krysiak, Robert; Gilowski, Wojciech; Okopień, Bogusław
2016-02-01
By reducing LDL cholesterol levels, statins may decrease androgen production. This study was aimed at investigating whether testosterone treatment has an impact on cardiometabolic risk factors in statin-treated men with late-onset hypogonadism (LOH). The study included 31 men with LOH who had been treated for at least 6 months with atorvastatin (20-40mg daily). On the basis of patient preference, atorvastatin-treated patients were divided into two matched groups of patients: receiving intramuscular testosterone enanthate (100mg weekly, n=16) and not treated with this hormone (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and after 4 months of therapy. Compared with the control age-, weight, and lipid-matched statin-naïve subjects with LOH (n=12), atorvastatin-treated patients were characterized by decreased levels of testosterone, hsCRP, and homocysteine. In patients not receiving testosterone therapy, plasma lipids, glucose homeostasis markers, as well as plasma levels of the investigated risk factors remained at the similar levels throughout the whole period of atorvastatin treatment. In atorvastatin-naïve patients, testosterone increased its plasma levels and decreased HDL cholesterol. Apart from an increase in testosterone levels, if administered to atorvastatin-treated subjects with LOH, testosterone reduced plasma levels of LDL cholesterol, uric acid, hsCRP, homocysteine, and fibrinogen, as well as improved insulin sensitivity. Our study may suggest the clinical benefits associated with combination therapy with a statin and testosterone in elderly men with LOH. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
Selective Activation of Transcription by a Novel CCAAT Binding Factor
NASA Astrophysics Data System (ADS)
Maity, Sankar N.; Golumbek, Paul T.; Karsenty, Gerard; de Crombrugghe, Benoit
1988-07-01
A novel CCAAT binding factor (CBF) composed of two different subunits has been extensively purified from rat liver. Both subunits are needed for specific binding to DNA. Addition of this purified protein to nuclear extracts of NIH 3T3 fibroblasts stimulates transcription from several promoters including the α 2(I) collagen, the α 1(I) collagen, the Rous sarcoma virus long terminal repeat (RSV-LTR), and the adenovirus major late promoter. Point mutations in the CCAAT motif that show either no binding or a decreased binding of CBF likewise abolish or reduce activation of transcription by CBF. Activation of transcription requires, therefore, the specific binding of CBF to its recognition sites.
Wielaard, Ilse; Hoyer, Mathijs; Rhebergen, Didi; Stek, Max L; Comijs, Hannie C
2018-03-01
Childhood abuse makes people vulnerable to developing depression, even in late life. Psychosocial factors that are common in late life, such as loneliness or lack of a partner, may explain this association. Our aim was to investigate whether the association between childhood abuse and depression in older adults can be explained by psychosocial factors. Cross-sectional data were derived from the Netherlands Study of Depression in Older Persons (aged 60-93), including 132 without lifetime depression, 242 persons with an early-onset depression (<60 years), and 125 with a late-onset (≥60 years) depression. Childhood abuse (yes/no) and a frequency-based childhood abuse index were included. Multinomial regression and multivariable mediation analyses were used to examine the association between childhood abuse and the onset of depression, and the influence of loneliness, social network, and partner status. Multinomial regression analyses showed a significant association between childhood abuse and the childhood abuse index with early- and late-onset depression. Multivariable mediation analyses showed that the association between childhood abuse and early-onset depression was partly mediated by social network size and loneliness. This was particularly present for emotional neglect and psychological abuse, but not for physical and sexual abuse. No psychosocial mediators were found for the association between childhood abuse and late-onset depression. A smaller social network and feelings of loneliness mediate the association between childhood abuse and early-onset depression in older adults. Our findings show the importance of detecting childhood abuse as well as the age at depression onset and mapping of relevant psychosocial factors in the treatment of late-life depression. Copyright © 2018 John Wiley & Sons, Ltd.
ECO fill: automated fill modification to support late-stage design changes
NASA Astrophysics Data System (ADS)
Davis, Greg; Wilson, Jeff; Yu, J. J.; Chiu, Anderson; Chuang, Yao-Jen; Yang, Ricky
2014-03-01
One of the most critical factors in achieving a positive return for a design is ensuring the design not only meets performance specifications, but also produces sufficient yield to meet the market demand. The goal of design for manufacturability (DFM) technology is to enable designers to address manufacturing requirements during the design process. While new cell-based, DP-aware, and net-aware fill technologies have emerged to provide the designer with automated fill engines that support these new fill requirements, design changes that arrive late in the tapeout process (as engineering change orders, or ECOs) can have a disproportionate effect on tapeout schedules, due to the complexity of replacing fill. If not handled effectively, the impacts on file size, run time, and timing closure can significantly extend the tapeout process. In this paper, the authors examine changes to design flow methodology, supported by new fill technology, that enable efficient, fast, and accurate adjustments to metal fill late in the design process. We present an ECO fill methodology coupled with the support of advanced fill tools that can quickly locate the portion of the design affected by the change, remove and replace only the fill in that area, while maintaining the fill hierarchy. This new fill approach effectively reduces run time, contains fill file size, minimizes timing impact, and minimizes mask costs due to ECO-driven fill changes, all of which are critical factors to ensuring time-to-market schedules are maintained.
Extraocular muscle regeneration in zebrafish requires late signals from Insulin-like growth factors.
Saera-Vila, Alfonso; Louie, Ke'ale W; Sha, Cuilee; Kelly, Ryan M; Kish, Phillip E; Kahana, Alon
2018-01-01
Insulin-like growth factors (Igfs) are key regulators of key biological processes such as embryonic development, growth, and tissue repair and regeneration. The role of Igf in myogenesis is well documented and, in zebrafish, promotes fin and heart regeneration. However, the mechanism of action of Igf in muscle repair and regeneration is not well understood. Using adult zebrafish extraocular muscle (EOM) regeneration as an experimental model, we show that Igf1 receptor blockage using either chemical inhibitors (BMS754807 and NVP-AEW541) or translation-blocking morpholino oligonucleotides (MOs) reduced EOM regeneration. Zebrafish EOMs regeneration depends on myocyte dedifferentiation, which is driven by early epigenetic reprogramming and requires autophagy activation and cell cycle reentry. Inhibition of Igf signaling had no effect on either autophagy activation or cell proliferation, indicating that Igf signaling was not involved in the early reprogramming steps of regeneration. Instead, blocking Igf signaling produced hypercellularity of regenerating EOMs and diminished myosin expression, resulting in lack of mature differentiated muscle fibers even many days after injury, indicating that Igf was involved in late re-differentiation steps. Although it is considered the main mediator of myogenic Igf actions, Akt activation decreased in regenerating EOMs, suggesting that alternative signaling pathways mediate Igf activity in muscle regeneration. In conclusion, Igf signaling is critical for re-differentiation of reprogrammed myoblasts during late steps of zebrafish EOM regeneration, suggesting a regulatory mechanism for determining regenerated muscle size and timing of differentiation, and a potential target for regenerative therapy.
Han, Jae Pil; Hong, Su Jin; Kim, Shin Hee; Choi, Jong Hyo; Jung, Hee Jae; Cho, Youn Hee; Ko, Bong Min; Lee, Moon Sung
2014-08-01
Self-expandable metal stents (SEMSs) have been used as palliative treatment or bridge to surgery for obstructions caused by colorectal cancer (CRC). We assessed the long-term outcomes of palliative SEMSs and evaluated the risk factors influencing complications. One hundred and seventy-five patients underwent SEMS placement for acute malignant colorectal obstruction. Of the 72 patients who underwent palliative treatment for primary CRC, 30 patients received chemotherapy (CT) for primary cancer (CT group) and 42 underwent best supportive treatment (BST) without CT (BST group). There was a significant difference in late migration between the CT group and the BST group (20.0% in CT group, 2.4% in BST group, p = 0.018). Response to CT influenced the rate of late obstruction (0% in disease control, 35.7% in disease progression, p = 0.014). However, late obstruction was not associated with stent properties, such as diameter or type (≤22 mm vs. >22 mm, 13.5% vs. 14.3%, p = 1.00; uncovered stent vs. covered stent, 15.5% vs. 7.1%, p = 0.675) and migration (≤22 mm vs. >22 mm, 16.2% vs. 2.9%, p = 0.108; uncovered stent vs. covered stent, 8.6% vs. 14.3%, p = 0.615) in palliative SEMS. The administration of CT increases the rate of stent migration, and disease control by CT can reduce the risk of obstruction by maintaining the luminal patency of palliative SEMSs.
Late Life Depression Detection: An Evidence-Based Guideline
Smith, Marianne; Haedtke, Christine; Shibley, Deborah
2015-01-01
The disability associated with late life depression makes it an important target for screening. Identifying clinically significant depression symptoms in older adults who have known risk factors provides an important opportunity for early evaluation and treatment. Screening that leads to evaluation and treatment is critical to both preventing depression, and reducing the associated disability, symptom burden, and costs of major depressive disorders (MDD). The guideline described here recommends the 9-item Patient Health Questionnaire (PHQ-9) for screening because it is based on diagnostic criteria for MDD and has the advantages of being brief, self-administered, easily scored and interpreted, and reliable and valid in diverse populations and care settings. Nurses and allied health professionals who provide care to older adults across the continuum of care are uniquely positioned to identify at risk older adults, use depression screening scales, make needed referrals for evaluation and treatment, and monitor outcomes across time. PMID:25633861
Alzheimer's Disease and Exercise: A Literature Review.
Cass, Shane P
Alzheimer's disease (AD) is a progressive neurodegenerative disease that impairs memory and cognitive judgment. It is the leading cause of dementia in late adult life and is associated with a significant social burden and increased morbidity and mortality in the elderly. Because of mixed effectiveness of medications, exercise has been considered as a treatment for pre-clinical AD, late stage AD, and as a prevention strategy. Exercise appears to improve brain blood flow, increase hippocampal volume, and improve neurogenesis. Prospective studies indicate that physical inactivity is one of the most common preventable risk factors for developing AD and that higher physical activity levels are associated with a reduced risk of development of disease. Exercise as a treatment for AD shows improvement in cognitive function, decreased neuropsychiatric symptoms, and a slower decline in activities of daily living (ADL). Exercise has been shown to have fewer side effects and better adherence compared to medications.
Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ondoa, Pascale; Ceulemans, Ann; Vereecken, Chris; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc
2015-01-01
Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART. Methods Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies. Results CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p≤0.028). Conclusion Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype. PMID:26208109
Viana, Andres G; Gratz, Kim L; Bierman, Karen L
2013-01-01
Temperamental vulnerabilities (e.g., behavioral inhibition, anxiety sensitivity) and cognitive biases (e.g., interpretive and judgment biases) may exacerbate feelings of stress and anxiety, particularly among late adolescents during the early years of college. The goal of the present study was to apply person-centered analyses to explore possible heterogeneity in the patterns of these four risk factors in late adolescence, and to examine associations with several anxiety outcomes (i.e., worry, anxiety symptoms, and trait anxiety). Cluster analyses in a college sample of 855 late adolescents revealed a Low-Risk group, along with four reliable clusters with distinct profiles of risk factors and anxiety outcomes (Inhibited, Sensitive, Cognitively-Biased, and Multi-Risk). Of the risk profiles, Multi-Risk youth experienced the highest levels of anxiety outcomes, whereas Inhibited youth experienced the lowest levels of anxiety outcomes. Sensitive and Cognitively-Biased youth experienced comparable levels of anxiety-related outcomes, despite different constellations of risk factors. Implications for interventions and future research are discussed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Berretta, Marcelo F.; Deshpande, Mandar; Crouch, Erin A.
2006-04-25
We compared the abilities of late gene transcription and DNA replication machineries of the baculoviruses Autographa californica nucleopolyhedrovirus (AcMNPV) and Bombyx mori NPV (BmNPV) in SF-21 cells, an insect-derived cell line permissive for AcMNPV infection. It has been well established that 19 AcMNPV late expression factors (lefs) stimulate substantial levels of late gene promoter activity in SF-21 cells. Thus, we constructed a set of clones containing the BmNPV homologs of the AcMNPV lefs under control of the constitutive Drosophila heat shock 70 protein promoter and tested their ability to activate an AcMNPV late promoter-reporter gene cassette in SF-21 cells. Wemore » tested the potential of individual or predicted functional groups of BmNPV lefs to successfully replace the corresponding AcMNPV gene(s) in transient late gene expression assays. We found that most, but not all, BmNPV lefs were able to either fully or partially substitute for the corresponding AcMNPV homolog in the context of the remaining AcMNPV lefs with the exception of BmNPV p143, ie-2, and p35. BmNPV p143 was unable to support late gene expression or be imported into the nucleus of cells in the presence of the AcMNPV or the BmNPV LEF-3, a P143 nuclear shuttling factor. Our results suggest that host-specific factors may affect the function of homologous proteins.« less
hnRNP L controls HPV16 RNA polyadenylation and splicing in an Akt kinase-dependent manner
Kajitani, Naoko; Glahder, Jacob; Wu, Chengjun; Yu, Haoran; Nilsson, Kersti
2017-01-01
Abstract Inhibition of the Akt kinase activates HPV16 late gene expression by reducing HPV16 early polyadenylation and by activating HPV16 late L1 mRNA splicing. We identified ‘hot spots’ for RNA binding proteins at the early polyA signal and at splice sites on HPV16 late mRNAs. We observed that hnRNP L was associated with sequences at all HPV16 late splice sites and at the early polyA signal. Akt kinase inhibition resulted in hnRNP L dephosphorylation and reduced association of hnRNP L with HPV16 mRNAs. This was accompanied by an increased binding of U2AF65 and Sam68 to HPV16 mRNAs. Furthermore, siRNA knock-down of hnRNP L or Akt induced HPV16 gene expression. Treatment of HPV16 immortalized keratinocytes with Akt kinase inhibitor reduced hnRNP L binding to HPV16 mRNAs and induced HPV16 L1 mRNA production. Finally, deletion of the hnRNP L binding sites in HPV16 subgenomic expression plasmids resulted in activation of HPV16 late gene expression. In conclusion, the Akt kinase inhibits HPV16 late gene expression at the level of RNA processing by controlling the RNA-binding protein hnRNP L. We speculate that Akt kinase activity upholds an intracellular milieu that favours HPV16 early gene expression and suppresses HPV16 late gene expression. PMID:28934469
NASA Astrophysics Data System (ADS)
Fawzy, Diaa E.; Stȩpień, K.
2018-03-01
In the current study we present ab initio numerical computations of the generation and propagation of longitudinal waves in magnetic flux tubes embedded in the atmospheres of late-type stars. The interaction between convective turbulence and the magnetic structure is computed and the obtained longitudinal wave energy flux is used in a self-consistent manner to excite the small-scale magnetic flux tubes. In the current study we reduce the number of assumptions made in our previous studies by considering the full magnetic wave energy fluxes and spectra as well as time-dependent ionization (TDI) of hydrogen, employing multi-level Ca II atomic models, and taking into account departures from local thermodynamic equilibrium. Our models employ the recently confirmed value of the mixing-length parameter α=1.8. Regions with strong magnetic fields (magnetic filling factors of up to 50%) are also considered in the current study. The computed Ca II emission fluxes show a strong dependence on the magnetic filling factors, and the effect of time-dependent ionization (TDI) turns out to be very important in the atmospheres of late-type stars heated by acoustic and magnetic waves. The emitted Ca II fluxes with TDI included into the model are decreased by factors that range from 1.4 to 5.5 for G0V and M0V stars, respectively, compared to models that do not consider TDI. The results of our computations are compared with observations. Excellent agreement between the observed and predicted basal flux is obtained. The predicted trend of Ca II emission flux with magnetic filling factor and stellar surface temperature also agrees well with the observations but the calculated maximum fluxes for stars of different spectral types are about two times lower than observations. Though the longitudinal MHD waves considered here are important for chromosphere heating in high activity stars, additional heating mechanism(s) are apparently present.
Yinon, Yoav; Kingdom, John C P; Odutayo, Ayodele; Moineddin, Rahim; Drewlo, Sascha; Lai, Vesta; Cherney, David Z I; Hladunewich, Michelle A
2010-11-02
Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate-induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angiogenic factors (vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin). Flow-mediated vasodilatation was significantly reduced in women with previous early-onset preeclampsia and intrauterine growth restriction compared with women with previous late-onset preeclampsia and control subjects (3.2±2.7% and 2.1±1.2% versus 7.9±3.8% and 9.1±3.5%, respectively; P<0.0001). Flow-independent vasodilatation was similar among all groups. Similarly, the radial augmentation index was significantly increased among women with previous early-onset preeclampsia and intrauterine growth restriction, but not among late preeclamptic women and control subjects (P=0.0105). Circulating angiogenic factors were similar in all groups. Only women with a history of early-onset preeclampsia or intrauterine growth restriction without preeclampsia exhibit impaired vascular function, which might explain their predisposition to placental disease and their higher risk of future vascular disease.
Basic consensus document on late-onset hypogonadism.
Becerra Fernández, Antonio; Enríquez Acosta, Luis
2008-01-01
One of the most important elements in men's live is the ability to engage in normal sexual activity; loss of this activity has always been considered especially important. The relationship between sexual activity, as well as other masculine characteristics, and the testicles has been well known since ancient times and has been related to the slow decrease in testosterone secretion with advanced age. Male hypogonadism is one of the most frequent and under-diagnosed endocrine diseases. Several terms have been proposed to refer to clinical situations caused by the age-related decline in male gonadal function; currently, the most widely accepted term is late-onset hypogonadism (LOH). LOH consists of a clinical and biochemical syndrome associated with advanced age (in men), characterized by typical symptoms and reduced serum testosterone concentrations, which can affect multiple organs and systems and reduce quality of life. This syndrome can be treated and the alterations produced can be reversed. To achieve this, a diagnostic protocol that approaches the multiple factors related to the risks and benefits of treatment is required. Copyright © 2008 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.
USDA-ARS?s Scientific Manuscript database
Diet intake in pregnant rats fed a low-protein (LP) diet was significantly reduced during late pregnancy despite elevated plasma levels of ghrelin. In this study, we hypothesized that ghrelin signaling in the hypothalamus is blunted under a low-protein diet condition and therefore, it does not stimu...
Chua, Christelle En Lin; Tang, Bor Luen
2014-05-02
Rab31 is a member of the Rab5 subfamily of Rab GTPases. Although localized largely to the trans-Golgi network, it shares common guanine nucleotide exchange factors and effectors with other Rab5 subfamily members that have been implicated in endocytic membrane traffic. We investigated whether Rab31 also has a role in the trafficking of the ligand-bound EGF receptor (EGFR) internalized through receptor-mediated endocytosis. We found that loss of Rab31 inhibits, but overexpression enhances, EGFR trafficking to the late endosomes and that the effect of Rab31 silencing could be specifically rescued by overexpression of a silencing-resistant form of Rab31. Rab31 was found to interact with the EGFR by coimmunoprecipitation and affinity pulldown analyses, and the primarily trans-Golgi network-localized Rab31 has increased colocalization with the EGFR in A431 cells 30 min after pulsing with EGF. A glycerol gradient sedimentation assay suggested that Rab31 is sequestered into a high molecular weight complex after stimulation with EGF, as was early endosome antigen 1 (EEA1), a factor responsible for endosomal tethering and fusion events. We found that loss of EEA1 reduced the interaction between Rab31 and the EGFR and abrogated the effect of Rab31 overexpression on the trafficking of the EGFR. Likewise, loss of GAPex5, a Rab31 guanine nucleotide exchange factor that has a role in ubiquitination and degradation of the EGFR, reduced the interaction of Rab31 with the EGFR and its effect on EGFR trafficking. Taken together, our results suggest that Rab31 is an important regulator of endocytic trafficking of the EGFR and functions in an EGFR trafficking complex that includes EEA1 and GAPex5.
Chua, Christelle En Lin; Tang, Bor Luen
2014-01-01
Rab31 is a member of the Rab5 subfamily of Rab GTPases. Although localized largely to the trans-Golgi network, it shares common guanine nucleotide exchange factors and effectors with other Rab5 subfamily members that have been implicated in endocytic membrane traffic. We investigated whether Rab31 also has a role in the trafficking of the ligand-bound EGF receptor (EGFR) internalized through receptor-mediated endocytosis. We found that loss of Rab31 inhibits, but overexpression enhances, EGFR trafficking to the late endosomes and that the effect of Rab31 silencing could be specifically rescued by overexpression of a silencing-resistant form of Rab31. Rab31 was found to interact with the EGFR by coimmunoprecipitation and affinity pulldown analyses, and the primarily trans-Golgi network-localized Rab31 has increased colocalization with the EGFR in A431 cells 30 min after pulsing with EGF. A glycerol gradient sedimentation assay suggested that Rab31 is sequestered into a high molecular weight complex after stimulation with EGF, as was early endosome antigen 1 (EEA1), a factor responsible for endosomal tethering and fusion events. We found that loss of EEA1 reduced the interaction between Rab31 and the EGFR and abrogated the effect of Rab31 overexpression on the trafficking of the EGFR. Likewise, loss of GAPex5, a Rab31 guanine nucleotide exchange factor that has a role in ubiquitination and degradation of the EGFR, reduced the interaction of Rab31 with the EGFR and its effect on EGFR trafficking. Taken together, our results suggest that Rab31 is an important regulator of endocytic trafficking of the EGFR and functions in an EGFR trafficking complex that includes EEA1 and GAPex5. PMID:24644286
NASA Technical Reports Server (NTRS)
Zhang, Ye; Yeshitla, Samrawit; Hada, Megumi; Kadhim, Munira; Wilson, Bobby; Wu, Honglu
2015-01-01
Numerous published studies have reported the Relative Biological Effectiveness (RBE) values for chromosome aberrations induced by charged particles of different LET. The RBE for chromosome aberrations in human lymphocytes exposed ex vivo has been suggested to show a similar relationship as the quality factor for cancer induction. Therefore, increased chromosome aberrations in the astronauts' white blood cells post long-duration missions are used to determine the biological doses from exposures to space radiation. However, the RBE value is known to be very different for different types of cancer. Previously, we reported that, even though the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions, the RBE was significantly reduced after multiple cell divisions post irradiation. To test the hypothesis that RBE values for chromosome aberrations are cell type dependent, and different between early and late damages, we exposed human lymphocytes ex vivo, and human mammary epithelial cells in vitro to various charged particles. Chromosome aberrations were quantified using the samples collected at first mitosis post irradiation for initial damages, and the samples collected after multiple generations for the remaining or late arising aberrations. Results of the study suggested that the effectiveness of high-LET charged particles for late chromosome aberrations may be cell type dependent, even though the RBE values are similar for early damages.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dirix, Piet; Abbeel, Sarah; Vanstraelen, Bianca
2009-10-01
Purpose: To evaluate late dysphagia after chemoradiotherapy for locally advanced head-and-neck squamous cell carcinoma, and to examine its correlation with clinical and dosimetric parameters. Methods and Materials: Consecutive patients, treated with radiotherapy (70-72 Gy) and concomitant chemotherapy (cisplatinum 100 mg/m{sup 2} every 3 weeks) between 2004 and 2007, were examined. Swallowing was evaluated by four quality-of-life questionnaires: EORTC C30 and H and N35, the Performance Status Scale of List, and the MD Anderson Dysphagia Inventory. Clinical and dosimetric parameters were correlated with late dysphagia. Results: A total of 53 disease-free patients were evaluated; mean follow-up was 20.4 months (range, 6-45more » months). The volume of the middle pharyngeal constrictor muscle receiving {>=}50 Gy (p = 0.04), the mean dose to this structure (p = 0.02) and to the supraglottic larynx (p = 0.04) were significantly associated with late swallowing problems at univariate analysis, along with tumor localization (p = 0.008), T-classification (p = 0.02), and pretreatment swallowing problems (p = 0.01). Only this last factor significantly correlated with late dysphagia at multivariate analysis. Conclusion: These findings motivate further efforts to reduce the dose to the swallowing structures, especially to the pharyngeal constrictor muscles and the larynx. However, clinical parameters are also important and should be included in future prospective trials.« less
Outcomes after peritoneal dialysis catheter placement.
Carpenter, Jennifer L; Fallon, Sara C; Swartz, Sarah J; Minifee, Paul K; Cass, Darrell L; Nuchtern, Jed G; Pimpalwar, Ashwin P; Brandt, Mary L
2016-05-01
The purpose of this study was to review surgical outcomes after elective placement of peritoneal dialysis (PD) catheters in children with end-stage renal disease. Children with PD catheters placed between February 2002 and July 2014 were retrospectively reviewed. Outcomes were catheter life, late (>30days post-op) complications (catheter malfunction, catheter malposition, infection), and re-operation rates. Comparison groups included laparoscopic versus open placement, age<2, and weight<10kg. Univariate and multivariate analysis were performed. One hundred sixteen patients had 173 catheters placed (122 open, 51 laparoscopic) with an average patient age of 9.7±6.3years. Mean catheter life was similar in the laparoscopic and open groups (581±539days versus 574±487days, p=0.938). The late complication rate was higher for open procedures (57% versus 37%, p=0.013). Children age<2 or weight<10kg had higher re-operation rates (64% versus 42%, p=0.014 and 73% versus 40%, p=0.001, respectively). Adjusted for age and weight, open technique remained a risk factor for late complications (OR 2.44, 95% CI 1.20-4.95) but not re-operation. Laparoscopic placement appears to reduce the rate of late complications in children who require PD dialysis catheters. Children <2years age or <10kg remain at risk for complications regardless of technique. Copyright © 2016 Elsevier Inc. All rights reserved.
Hasle, Henrik; Kaspers, Gertjan J L
2017-01-01
Over the last four decades the survival of paediatric patients with acute myeloid leukaemia has gradually increased to 70% in high-income countries. The therapy is very intensive and associated with many acute and long-term side effects. The early death rate has been reduced to 1-4%. The acute toxicity is a limiting factor for improving survival in low-income countries. Transplant is associated with more endocrinological late effects while cardiotoxicity is more common after relapse. Reducing the physical costs of therapy without jeopardizing survival may be accomplished by optimal supportive care, less cardiotoxic anthracyclines, less consolidation courses and strict indications for stem cell transplantation. Analysing scenarios with different frequency of transplantation in first complete remission show similar overall survival rates, indicating that almost all patients can be spared the procedure in first remission. Reducing relapse risk is an effective way of reducing toxicity and more targeted therapy and improved risk group stratifications are needed. © 2016 John Wiley & Sons Ltd.
Low cerebral blood flow is associated with lower memory function in metabolic syndrome.
Birdsill, Alex C; Carlsson, Cynthia M; Willette, Auriel A; Okonkwo, Ozioma C; Johnson, Sterling C; Xu, Guofan; Oh, Jennifer M; Gallagher, Catherine L; Koscik, Rebecca L; Jonaitis, Erin M; Hermann, Bruce P; LaRue, Asenath; Rowley, Howard A; Asthana, Sanjay; Sager, Mark A; Bendlin, Barbara B
2013-07-01
Metabolic syndrome (MetS)--a cluster of cardiovascular risk factors--is linked with cognitive decline and dementia. However, the brain changes underlying this link are presently unknown. In this study, we tested the relationship between MetS, cerebral blood flow (CBF), white matter hyperintensity burden, and gray matter (GM) volume in cognitively healthy late middle-aged adults. Additionally, the extent to which MetS was associated with cognitive performance was assessed. Late middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention (N = 69, mean age = 60.4 years) underwent a fasting blood draw, arterial spin labeling perfusion MRI, T1-weighted MRI, T2FLAIR MRI, and neuropsychological testing. MetS was defined as abnormalities on three or more factors, including abdominal obesity, triglycerides, HDL-cholesterol, blood pressure, and fasting glucose. Mean GM CBF was 15% lower in MetS compared to controls. Voxel-wise image analysis indicated that the MetS group had lower CBF across a large portion of the cortical surface, with the exception of medial and inferior parts of the occipital and temporal lobes. The MetS group also had lower immediate memory function; a mediation analysis indicated this relationship was partially mediated by CBF. Among the MetS factors, abdominal obesity and elevated triglycerides were most strongly associated with lower CBF. The results underscore the importance of reducing the number of cardiovascular risk factors for maintaining CBF and cognition in an aging population. Copyright © 2012 The Obesity Society.
[Study on the social factors of patients with genital herpes relapsing].
Liu, Ji-Feng; Xu, Ai-E; Li, Yong-Wei; Zhang, Di-Min
2006-05-01
To investigate the social factors of patients with genital herpes (GH) relapsing and guide GH patients to avoid the related social factors. To select 96 case of patients with recurrent genital herpes of final diagnosis and detailedly record the related social factors before relapsing. The social factors were compared between male and female GH patients, and compared between frequently recurrent (> 6/year) and non-frequently recurrent GH patients (< or = 6/year) too. 65.6% (63/96) of recurrent GH patients have certain social factors before relapsing. The main social factors are overtiredness, mental stress and excessive sexual contact. Staying up late and excessive drinking are common social factors, too. There was no significant difference of social factors between male and female GH patients (P >. 05), and also no significant difference between frequently recurrent and non-frequently recurrent GH patients (P > 0.05), too. Overtiredness, mental stress and excessive sexual are the main social elements during inducing genital herpes relapsing. It is important to reduce GH relapsing and spreading of HIV and syphilis by guiding recurrent genital herpes patients to avoid related social elements.
[Risk factors for anorexia in children].
Liu, Wei-Xiao; Lang, Jun-Feng; Zhang, Qin-Feng
2016-11-01
To investigate the risk factors for anorexia in children, and to reduce the prevalence of anorexia in children. A questionnaire survey and a case-control study were used to collect the general information of 150 children with anorexia (case group) and 150 normal children (control group). Univariate analysis and multivariate logistic stepwise regression analysis were performed to identify the risk factors for anorexia in children. The results of the univariate analysis showed significant differences between the case and control groups in the age in months when supplementary food were added, feeding pattern, whether they liked meat, vegetables and salty food, whether they often took snacks and beverages, whether they liked to play while eating, and whether their parents asked them to eat food on time (P<0.05). The results of the multivariate logistic regression analysis showed that late addition of supplementary food (OR=5.408), high frequency of taking snacks and/or drinks (OR=11.813), and eating while playing (OR=6.654) were major risk factors for anorexia in children. Liking of meat (OR=0.093) and vegetables (OR=0.272) and eating on time required by parents (OR=0.079) were protective factors against anorexia in children. Timely addition of supplementary food, a proper diet, and development of children's proper eating and living habits can reduce the incidence of anorexia in children.
Perioperative Modulating Factors on Astigmatism in Sutured Cataract Surgery
Cho, Yang Kyeung
2009-01-01
Purpose To evaluate the factors that affect postoperative astigmatism and post-suture removal astigmatism, and to evaluate the risk factors associated with astigmatism axis shift. Methods We performed a retrospective chart review of 130 eyes that had undergone uneventful phacoemulsification cataract surgery. Preoperative astigmatism was divided into four groups (Groups I, II, III, and IV) according to the differences between the axis of preoperative astigmatism (flattest axis) and the incision axis (105 degrees). We analyzed the magnitude and axis of the induced astigmatism after the operation and after suture removal in each group. We also analyzed the factors which affected the postoperative astigmatism and post-suture removal astigmatism in each sub-group of Groups I, II, III, and IV, excluding postoperative or post-suture removal axis shift (specifically, Group IWAS, IIWAS, IIIWAS, and IVWAS). We identified the variables associated with the prevalence of postoperative astigmatism axis shift and those associated with the prevalence of post-suture removal axis shift. Results An increase in the magnitude of postoperative astigmatism was associated with an increase in the preoperative magnitude of astigmatism in Groups IWAS, IIWAS, and IIIWAS (p<0.05), and with an increase in the corneal tunnel length in Group IWAS. A decrease in the magnitude of postoperative astigmatism was associated with an increase in the corneal tunnel length in Groups IIIWAS and IVWAS (p<0.05). An increase in the magnitude of post-suture removal astigmatism was associated with an increase in the magnitude of postoperative astigmatism in Groups IWAS and IVWAS (p<0.05), and with late suture removal in Group IVWAS (p<0.05). A decrease in the magnitude of post-suture removal astigmatism was associated with late suture removal in Groups IWAS and IIWAS. A logistic regression analysis showed that the prevalence of post-suture removal astigmatism axis shift was associated with increased corneal tunnel length, decreased magnitude of postoperative astigmatism, and early suture removal. Conclusions In order to reduce postoperative and post-suture removal astigmatism, we recommend a short corneal tunnel length and late suture removal in patients with Group IWAS characteristics, late suture removal in Group IIWAS-like patients, long corneal tunnel length in Group IIIWAS-like patients, and long corneal tunnel length and early suture removal in patients with characteristics of Group IVWAS. PMID:20046682
Evaluating the causes of photovoltaics cost reduction: Why is PV different?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Trancik, Jessika; McNerney, James; Kavlak, Goksin
The goals of this project were to quantify sources of cost reduction in photovoltaics (PV), improve theories of technological evolution, develop new analytical methods, and formu- late guidelines for continued cost reduction in photovoltaics. A number of explanations have been suggested for why photovoltaics have come down in cost rapidly over time, including increased production rates, significant R&D expenditures, heavy patenting ac- tivity, decreasing material and input costs, scale economies, reduced plant construction costs, and higher conversion efficiencies. We classified these proposed causes into low- level factors and high-level drivers. Low-level factors include technical characteristics, such as module efficiency ormore » wafer area, which are easily posed in terms of variables of a cost equation. High-level factors include scale economies, research and development (R&D), and learning-by-doing.« less
Lifetime romantic attachment style and social adaptation in late-onset depression.
Paradiso, Sergio; Naridze, Rachelle; Holm-Brown, Erika
2012-10-01
Measuring social adjustment (including attachment style and current social adaptation) in late-life depression may support planning secondary prevention, rehabilitation, and treatment. Insecure attachment style is a risk factor for developing new depression, and social adjustment may constitute a problem after symptoms abatement. Few studies have examined attachment style and social adjustment in late-onset depression. Subjects 50 years of age and older with early-onset (n = 35), late-onset DSM-IV unipolar depression (n = 38), and never-depressed volunteers (n = 47) were assessed with a widely used measure of attachment style (the Experiences in Close Relationship Scale). Social adjustment was measured using the Social Adjustment Scale. Both early-onset and late-onset patients with depression showed greater insecure attachment and poorer social adaptation compared with never-depressed volunteers. No difference was found between early-onset and late-onset patients with depression on attachment style or social adjustment. There were no significant differences between late-life depression in remission or current on attachment or social adaptation. Insecure attachment style may be a risk factor for late-life depression irrespective of the age of onset. Social maladaptation may persist among individuals with late-life depression in remission. Copyright © 2011 John Wiley & Sons, Ltd.
Morel, Nathalie; Lévesque, Kateri; Maltret, Alice; Baron, Gabriel; Hamidou, Mohamed; Orquevaux, Pauline; Piette, Jean-Charles; Barriere, François; Le Bidois, Jérôme; Fermont, Laurent; Fain, Olivier; Theulin, Arnaud; Sassolas, François; Hauet, Quentin; Guettrot-Imbert, Gaëlle; Georgin-Lavialle, Sophie; Deligny, Christophe; Hachulla, Eric; Mouthon, Luc; Le Jeunne, Claire; Ravaud, Philippe; Le Mercier, Delphine; Romefort, Bénédicte; Villain, Elisabeth; Bonnet, Damien; Costedoat-Chalumeau, Nathalie
2017-12-01
Dilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear. We analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies. Among 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth-36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM (P=0.0199; HR=3.13 [95% CI: 1.20-8.16]), non-European origin (P=0.0052; HR=4.10 [95% CI: 1.81-9.28]) and pacemaker implantation (P=0.0013; HR=5.48 [95% CI: 1.94-15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth-4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months-22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM (P=0.27; HR=1.65 [95% CI: 0.63-4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM. Neonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB. Copyright © 2017 Elsevier B.V. All rights reserved.
Late Ordovician Reefs and the Biological Crisis at the Ordovician-Silurian Boundary
NASA Astrophysics Data System (ADS)
Kuznetsov, V. G.
2018-05-01
Reef formation in the Late Ordovician was relatively widespread in the Sandbian and Katian times. In the late Katian, it gradually reduced and ended in the Hirnantian, before the end of the Ordovician. In parallel, reef-building skeleton frame-building biota disappeared and was replaced with algae and calcimicrobes.
Pragmatic Functions of Toddlers Who Are Late Talkers
ERIC Educational Resources Information Center
MacRoy-Higgins, Michelle; Kaufman, Ilana
2012-01-01
Toddlers who are "late talkers" demonstrate reduced expressive vocabulary in the absence of physical, social, cognitive, or sensory impairment; they are usually identified at age 2, when they produce fewer than 50 words and do not combine words (Rescorla, 1989). This study analyzed spontaneous language samples of 10 late talking toddlers and 11…
Federal Register 2010, 2011, 2012, 2013, 2014
2013-08-22
... Requirements on Valencia and Other Late Type Oranges AGENCY: Agricultural Marketing Service, USDA. ACTION...). The interim rule reduced the minimum size for Valencia and other late type oranges shipped to... interim rule also lowered the minimum grade for Valencia and other late type oranges shipped to interstate...
Santos Tavares Silva, I; Sunnerhagen, K S; Willén, C; Ottenvall Hammar, I
2016-11-18
Fatigue is reported as one of the most disabling symptoms and is common among persons living with late effects of polio. Although fatigue has been studied in the context of people living with late effects of polio, there is a lack of knowledge concerning the association of fatigue and variables of importance for participation in daily life. Therefore, the aim of this study was to explore possible factors associated with fatigue among persons with late effects of polio in Sweden. This retrospective registry study consisted of 89 persons with late effects of polio living in Sweden. Fatigue was measured with the Multidimensional Fatigue Inventory (MFI-20) scale, Swedish version. Pearson's correlation coefficient was used to analyse the correlation between the factors and fatigue, and a multiple linear regression was carried out to explore factors for fatigue. Fatigue statistically significantly correlated with age (r = 0.234, p < 0.05) and the use of mobility assistive devices (r = 0.255, p < 0.05). The multiple linear regression model showed that the factors age (β = 0.304, p < 0.019) and mobility assistive devices (β = 0.262, p < 0.017) were associated with fatigue among persons living with late effects of polio, and the model partly explained 14% of the variation of fatigue. Fatigue could partly be explained by the extent of using mobility assistive devices and age. Healthcare professionals should provide and demonstrate the importance of assistive devices to ensure management of fatigue in persons living with late effects of polio.
Perceptual load corresponds with factors known to influence visual search.
Roper, Zachary J J; Cosman, Joshua D; Vecera, Shaun P
2013-10-01
One account of the early versus late selection debate in attention proposes that perceptual load determines the locus of selection. Attention selects stimuli at a late processing level under low-load conditions but selects stimuli at an early level under high-load conditions. Despite the successes of perceptual load theory, a noncircular definition of perceptual load remains elusive. We investigated the factors that influence perceptual load by using manipulations that have been studied extensively in visual search, namely target-distractor similarity and distractor-distractor similarity. Consistent with previous work, search was most efficient when targets and distractors were dissimilar and the displays contained homogeneous distractors; search became less efficient when target-distractor similarity increased irrespective of display heterogeneity. Importantly, we used these same stimuli in a typical perceptual load task that measured attentional spillover to a task-irrelevant flanker. We found a strong correspondence between search efficiency and perceptual load; stimuli that generated efficient searches produced flanker interference effects, suggesting that such displays involved low perceptual load. Flanker interference effects were reduced in displays that produced less efficient searches. Furthermore, our results demonstrate that search difficulty, as measured by search intercept, has little bearing on perceptual load. We conclude that rather than be arbitrarily defined, perceptual load might be defined by well-characterized, continuous factors that influence visual search. PsycINFO Database Record (c) 2013 APA, all rights reserved.
Jansson, T; Kristiansson, B; Qirbi, A
1988-01-01
Khat chewing is a widespread male social habit in countries around the southern shore of the Red Sea and in eastern Africa and is also practiced by women, even during pregnancy and lactation. In order to study the potentially adverse effects of khat chewing during pregnancy, guinea pigs were fed 2.2 g/kg of khat leaves daily throughout the third trimester. Control animals were given aspen leaves. Maternal daily food intake was significantly reduced during the first 10 days of feeding and maternal weight gain was slightly lower in the khat group. Khat feeding of the mother significantly reduced the mean birth weight of the offspring by 7% without any effect on litter size or length of gestational period. Since low birth weight is a well-established risk factor for both perinatal and young infant death, khat chewing during pregnancy may be one of the factors contributing to infant mortality.
A meta-analytic review on social relationships and suicidal ideation among older adults.
Chang, Qingsong; Chan, Chee Hon; Yip, Paul S F
2017-10-01
Social relationships play an important role in mental health as well as suicidal ideation in later life. In contrast with the other well-established risk factors, despite an increasing number of related studies, no meta-analyses focusing on social relationships and late-life suicidal ideation have been published. Synthesis of data across the studies using different measurements of social relationships would allow for comparison of the effects on late-life suicidal ideation that have not been studied before. Therefore, we conducted a meta-analysis on the studies published between January 1, 2000 and November 31, 2016 extracted from 7 medical and social science databases. 31 studies with 83 estimates of Odds Ratios ("ORs") on the associations between social relationships and late-life suicidal ideation were identified to compute effect sizes using a random-effect model. Sensitivity analyses were also performed to evaluate their heterogeneity and bias. Moderator analyses were further conducted to determine moderating factors of the associations. Eventually, across the 31 studies (203,152 participants), the overall random effect size was OR = 1.57(95% CI [1.40, 1.76]), indicating a 57% likelihood increase of suicidal ideation for elderly participants with discordant social relationships. The functional measures (OR = 1.77; 95%CI [1.48, 2.10]) of social relationships, however, were more predictive than structural measures (OR = 1.37; 95%CI [1.25, 1.51]). Among all the measures of social relationships, elderly mistreatment (OR = 2.31; 95%CI [1.81, 2.94]) had the strongest effect size, followed by perceived loneliness (OR = 2.24; 95%CI [1.73, 2.90]) and poorly perceived social support (OR = 1.59; 95% CI [1.37, 1.83]). The associations between social relationships and late-life suicidal ideation were moderated by country income levels, social-cultural context, study types, and various measurements of social relationships. More importantly, our study is the first meta-analysis to provide significant evidence for improving social relationships, especially in perceived bonds, is a promising strategy in reducing late-life suicide risks. Copyright © 2017 Elsevier Ltd. All rights reserved.
Yu, Naichang; Xia, Ping; Mastroianni, Anthony; Kolar, Matthew D; Chao, Samuel T; Greskovich, John F; Suh, John H
Process consistency in planning and delivery of radiation therapy is essential to maintain patient safety and treatment quality and efficiency. Ensuring the timely completion of each critical clinical task is one aspect of process consistency. The purpose of this work is to report our experience in implementing a quantitative metric and automatic auditing program (QMAP) with a goal of improving the timely completion of critical clinical tasks. Based on our clinical electronic medical records system, we developed a software program to automatically capture the completion timestamp of each critical clinical task while providing frequent alerts of potential delinquency. These alerts were directed to designated triage teams within a time window that would offer an opportunity to mitigate the potential for late completion. Since July 2011, 18 metrics were introduced in our clinical workflow. We compared the delinquency rates for 4 selected metrics before the implementation of the metric with the delinquency rate of 2016. One-tailed Student t test was used for statistical analysis RESULTS: With an average of 150 daily patients on treatment at our main campus, the late treatment plan completion rate and late weekly physics check were reduced from 18.2% and 8.9% in 2011 to 4.2% and 0.1% in 2016, respectively (P < .01). The late weekly on-treatment physician visit rate was reduced from 7.2% in 2012 to <1.6% in 2016. The yearly late cone beam computed tomography review rate was reduced from 1.6% in 2011 to <0.1% in 2016. QMAP is effective in reducing late completions of critical tasks, which can positively impact treatment quality and patient safety by reducing the potential for errors resulting from distractions, interruptions, and rush in completion of critical tasks. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
O’Sullivan, Therese A.; Bremner, Alexandra P.; Mori, Trevor A.; Beilin, Lawrence J.; Wilson, Charlotte; Hafekost, Katherine; Ambrosini, Gina L.; Huang, Rae Chi; Oddy, Wendy H.
2016-01-01
Reduced fat dairy products are generally recommended for adults and children over the age of two years. However, emerging evidence suggests that dairy fat may not have detrimental health effects. We aimed to investigate prospective associations between consumption of regular versus reduced fat dairy products and cardiometabolic risk factors from early to late adolescence. In the West Australian Raine Study, dairy intake was assessed using semi-quantitative food frequency questionnaires in 860 adolescents at 14 and 17-year follow-ups; 582 of these also had blood biochemistry at both points. Using generalized estimating equations, we examined associations with cardiometabolic risk factors. Models incorporated reduced fat and regular fat dairy together (in serves/day) and were adjusted for a range of factors including overall dietary pattern. In boys, there was a mean reduction in diastolic blood pressure of 0.66 mmHg (95% CI 0.23–1.09) per serve of reduced fat dairy and an independent, additional reduction of 0.47 mmHg (95% CI 0.04–0.90) per serve of regular fat dairy. Each additional serve of reduced fat dairy was associated with a 2% reduction in HDL-cholesterol (95% CI 0.97–0.995) and a 2% increase in total: HDL-cholesterol ratio (95% CI 1.002–1.03); these associations were not observed with regular fat products. In girls, there were no significant independent associations observed in fully adjusted models. Although regular fat dairy was associated with a slightly better cholesterol profile in boys, overall, intakes of both regular fat and reduced fat dairy products were associated with similar cardiometabolic associations in adolescents. PMID:26729163
Ma, Qiu-Lan; Teter, Bruce; Ubeda, Oliver J.; Morihara, Takashi; Dhoot, Dilsher; Nyby, Michael D.; Tuck, Michael L.; Frautschy, Sally A.; Cole, Greg M.
2008-01-01
Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer’s disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate β-amyloid (Aβ). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential ω-3 fatty acid related to reduced AD risk and reduced Aβ accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Aβ production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD. PMID:18160637
ERIC Educational Resources Information Center
Jumare, Abubakare M.; Maina, Bashir A.; Ankoma-Sey, Vera Rosemary
2015-01-01
This study attempted to answer the following research questions among others: Has gender any relation with students' late-coming to school? Has age any relation with students' late-coming to school? Do senior students come to school later than juniors? Four secondary schools were selected for the study. A sample of sixty students late comers were…
Zepeda, Rodrigo; Contreras, Valentina; Pissani, Claudia; Stack, Katherine; Vargas, Macarena; Owen, Gareth I; Lazo, Oscar M; Bronfman, Francisca C
2016-08-01
Neuromodulators, such as antidepressants, may contribute to neuroprotection by modulating growth factor expression to exert anti-inflammatory effects and to support neuronal plasticity after stroke. Our objective was to study whether early treatment with venlafaxine, a serotonin-norepinephrine reuptake inhibitor, modulates growth factor expression and positively contributes to reducing the volume of infarcted brain tissue resulting in increased functional recovery. We studied the expression of BDNF, FGF2 and TGF-β1 by examining their mRNA and protein levels and cellular distribution using quantitative confocal microscopy at 5 days after venlafaxine treatment in control and infarcted brains. Venlafaxine treatment did not change the expression of these growth factors in sham rats. In infarcted rats, BDNF mRNA and protein levels were reduced, while the mRNA and protein levels of FGF2 and TGF-β1 were increased. Venlafaxine treatment potentiated all of the changes that were induced by cortical stroke alone. In particular, increased levels of FGF2 and TGF-β1 were observed in astrocytes at 5 days after stroke induction, and these increases were correlated with decreased astrogliosis (measured by GFAP) and increased synaptophysin immunostaining at twenty-one days after stroke in venlafaxine-treated rats. Finally, we show that venlafaxine reduced infarct volume after stroke resulting in increased functional recovery, which was measured using ladder rung motor tests, at 21 days after stroke. Our results indicate that the early oral administration of venlafaxine positively contributes to neuroprotection during the acute and late events that follow stroke. Copyright © 2016 Elsevier Ltd. All rights reserved.
Chen, Ben; Zhong, Xiaomei; Mai, Naikeng; Peng, Qi; Wu, Zhangying; Ouyang, Cong; Zhang, Weiru; Liang, Wanyuan; Wu, Yujie; Liu, Sha; Chen, Lijian; Ning, Yuping
2018-03-15
Late-life depression patients are at a high risk of developing Alzheimer's disease, and diminished olfactory identification is an indicator in early screening for Alzheimer's disease in the elderly. However, whether diminished olfactory identification is associated with risk of developing Alzheimer's disease in late-life depression patients remains unclear. One hundred and twenty-five late-life depression patients, 50 Alzheimer's disease patients, and 60 normal controls were continuously recruited. The participants underwent a clinical evaluation, olfactory test, neuropsychological assessment, and neuroimaging assessment. The olfactory identification impairment in late-life depression patients was milder than that in Alzheimer's disease patients. Diminished olfactory identification was significantly correlated with worse cognitive performance (global function, memory language, executive function, and attention) and reduced grey matter volume (olfactory bulb and hippocampus) in the late-life depression patients. According to a multiple linear regression analysis, olfactory identification was significantly associated with the memory scores in late-life depression group (B=1.623, P<.001). The late-life depression with olfactory identification impairment group had worse cognitive performance (global, memory, language, and executive function) and more structural abnormalities in Alzheimer's disease-related regions than the late-life depression without olfactory identification impairment group, and global cognitive function and logical memory in the late-life depression without olfactory identification impairment group was intact. Reduced volume observed in many areas (hippocampus, precuneus, etc.) in the Alzheimer's disease group was also observed in late-life depression with olfactory identification impairment group but not in the late-life depression without olfactory identification impairment group. The patterns of cognitive impairment and structural abnormalities in late-life depression with olfactory identification impairment patients were similar to those in Alzheimer's disease; olfactory identification may help identify late-life depression patients who are at a high risk of developing Alzheimer's disease.
HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION.
Schick, Tina; Ersoy, Lebriz; Lechanteur, Yara T E; Saksens, Nicole T M; Hoyng, Carel B; den Hollander, Anneke I; Kirchhof, Bernd; Fauser, Sascha
2016-04-01
To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). Of 3,701 individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179 (31.9%) late AMD, and 1,770 (47.8%) were controls. Information about current and past sunlight exposure, former occupation type, subdivided in indoor working and outdoor working, and iris color were obtained by standardized interviewer-assisted questionnaires. Associations between environmental factors adjusted for age, gender, and smoking and early and late AMD were performed by multivariate regression analysis. Current sunlight exposure showed no association with early AMD or late AMD, but past sunlight exposure (≥8 hours outside daily) was significantly associated with early AMD (odds ratio: 5.54, 95% confidence interval 1.25-24.58, P = 0.02) and late AMD (odds ratio: 2.77, 95% confidence interval 1.25-6.16, P = 0.01). Outside working was found to be associated with late AMD (odds ratio: 2.57, 95% confidence interval 1.89-3.48, P = 1.58 × 10). No association was observed between iris color and early or late AMD. Sunlight exposure during working life is an important risk factor for AMD, whereas sunlight exposure after retirement seems to have less influence on the disease development. Therefore, preventive measures, for example, wearing sunglasses to minimize sunlight exposure, should start early to prevent development of AMD later in life.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Guyda, H.J.
1991-03-01
The metabolic effects of epidermal growth factor (EGF), insulin, insulin-like growth factor-I (IGF-I), and IGF-II were determined on human placental cells in monolayer culture obtained from early gestation (less than 20 weeks) and late gestation (38-42 weeks). Parameters studied were uptake of aminoisobutyric acid (AIB), uptake of 3-O-methylglucose and (3H)thymidine incorporation into cell protein. Since benzo(alpha)pyrene (BP) inhibits EGF binding and autophosphorylation in cultured human placental cells, particularly in early gestation, we also studied the effect of benzo(alpha)pyrene and other polycyclic aromatic hydrocarbons (PAHs) on EGF-mediated AIB uptake. The metabolic effects of EGF, insulin, and the IGFs in cultured humanmore » placental cells varied with gestational age and the growth factor studied. All three classes of growth factors stimulated AIB uptake in both early and late gestation at concentrations from 10-100 micrograms/L, well within a physiological range. However, insulin stimulation of AIB uptake was maximal at a high concentration in both early and late gestation cells, suggesting an action via type 1 IGF receptors rather than via insulin receptors. EGF stimulated 3-O-methylglucose uptake only in term placental cells. No significant stimulation of (3H)thymidine incorporation by any of the growth factors tested was seen with either early or late gestation cells. The effect of PAHs on AIB uptake by cultured placental cells was variable. BP alone stimulated AIB uptake by both very early and late gestation cells and enhanced EGF-stimulated AIB uptake. alpha-naphthoflavone alone inhibited AIB uptake at all gestational ages and inhibited EGF-stimulated AIB uptake. beta-Naphthoflavone and 3-methylcholanthrene minimally inhibited AIB uptake by early gestation cells and did not modify EGF-stimulated uptake at any gestational period.« less
Järbrink-Sehgal, M Ellionore; Schmidt, Peter T; Sköldberg, Filip; Hemmingsson, Tomas; Hagström, Hannes; Andreasson, Anna
2018-04-12
The burden of diverticular disease on society is high and is increasing with an aging population. It is therefore important to identify risk factors for disease development or progression. Many lifestyle behaviors during adolescence affect risk for later disease. We searched for adolescent lifestyle factors that affect risk of diverticular disease later in life. We performed a retrospective analysis of data from 43,772 men (age, 18-20 y) conscripted to military service in Sweden from 1969 through 1970, with a follow-up period of 39 years. All conscripts underwent an extensive mental and physical health examination and completed questionnaires covering alcohol consumption, smoking, and use of recreational drugs; cardiovascular fitness was assessed using an ergometer cycle at the time of conscription. Outcome data were collected from national registers to identify discharge diagnoses of diverticular disease until the end of 2009. We performed Cox regression analysis to determine whether body mass index, cardiovascular fitness, smoking, use of recreational drugs, alcohol consumption, and risky use of alcohol, at time of conscription are independent risk factors for development of diverticular disease. Overweight and obese men had a 2-fold increased risk of diverticular disease compared to normal-weight men (hazard ratio, 2.00; P < .001). A high level of cardiovascular fitness was associated with a reduced risk of diverticular disease requiring hospitalization (P = .009). Smoking (P = .003), but not use of recreational drugs (P = .11), was associated with an increased risk of diverticular disease requiring hospitalization. Risky use of alcohol, but not alcohol consumption per se, was associated with a 43% increase in risk of diverticular disease requiring hospitalization (P = .007). In a retrospective analysis of data from 43,772 men in Sweden, we associated being overweight or obese, a smoker, a high-risk user of alcohol, and/or having a low level of cardiovascular fitness in late adolescence with an increased risk of developing diverticular disease requiring hospitalization later in life. Improving lifestyle factors among adolescents might reduce the economic burden of diverticular disease decades later. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
Associations of insulin resistance later in lactation on fertility of dairy cows.
Baruselli, P S; Vieira, L M; Sá Filho, M F; Mingoti, R D; Ferreira, R M; Chiaratti, M R; Oliveira, L H; Sales, J N; Sartori, R
2016-07-01
The challenge of getting dairy cows pregnant during early lactation is a well-described, worldwide problem. However, specifically in farms with poor reproductive, nutritional, and environmental conditions/management, a low pregnancy rate during early lactation is followed inevitably by an increased number of nonpregnant cows after 150 days in milk, with even more difficulties to achieve pregnancy. Therefore, several studies were designed to understand and develop strategies to mitigate reduced fertility of cows during late lactation. Experiments were performed under tropical regions to determine metabolic status during lactation and association of stage of lactation on oocyte quality and fertility. Lactating cows with extended days not pregnant (e.g.,>150 days in milk) often had systemic metabolic alterations, including development of peripheral insulin resistance and various oocyte alterations, including reduced expression of genes encoding glucose transport proteins, reduced amounts of mtDNA, increased expression of mitochondria-related genes, and increased expression of apoptosis-related genes. Additionally, in vitro embryo production and pregnancy per AI were lower in late- versus early-lactation cows in some but not all studies. Notwithstanding, when a normal embryo was transferred to a cow in late lactation, the pregnancy per transfer was reasonable, reinforcing the assertion that fertility problems in late-lactation cows may be associated with oocyte quality, fertilization, and/or failure of early embryo development. In conclusion, insulin resistance may reduce oocyte competence and consequently fertility in late-lactation dairy cows. Copyright © 2016 Elsevier Inc. All rights reserved.
Cdc7 is required throughout the yeast S phase to activate replication origins.
Donaldson, A D; Fangman, W L; Brewer, B J
1998-02-15
The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.
Richard, Erin Morris; Thiyagarajan, Thirumagal; Bunni, Marlene A.; Basher, Fahmin; Roddy, Patrick O.; Siskind, Leah J.; Nietert, Paul J.; Nowling, Tamara K.
2013-01-01
Systemic Lupus erythematosus (SLE) is an autoimmune disease caused, in part, by abnormalities in cells of the immune system including B and T cells. Genetically reducing globally the expression of the ETS transcription factor FLI1 by 50% in two lupus mouse models significantly improves disease measures and survival through an unknown mechanism. In this study we analyze the effects of reducing FLI1 in the MRL/lpr lupus prone model on T cell function. We demonstrate that adoptive transfer of MRL/lpr Fli1 +/+ or Fli1 +/- T cells and B cells into Rag1-deficient mice results in significantly decreased serum immunoglobulin levels in animals receiving Fli1 +/- lupus T cells compared to animals receiving Fli1 +/+ lupus T cells regardless of the genotype of co-transferred lupus B cells. Ex vivo analyses of MRL/lpr T cells demonstrated that Fli1 +/- T cells produce significantly less IL-4 during early and late disease and exhibited significantly decreased TCR-specific activation during early disease compared to Fli1 +/+ T cells. Moreover, the Fli1 +/- T cells expressed significantly less neuraminidase 1 (Neu1) message and decreased NEU activity during early disease and significantly decreased levels of glycosphingolipids during late disease compared to Fli1 +/+ T cells. FLI1 dose-dependently activated the Neu1 promoter in mouse and human T cell lines. Together, our results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by decreasing TCR-specific activation and IL-4 production in part through the modulation of glycosphingolipid metabolism. Reducing the expression of FLI1 or targeting the glycosphingolipid metabolic pathway in lupus may serve as a therapeutic approach to treating lupus. PMID:24040398
Richard, Erin Morris; Thiyagarajan, Thirumagal; Bunni, Marlene A; Basher, Fahmin; Roddy, Patrick O; Siskind, Leah J; Nietert, Paul J; Nowling, Tamara K
2013-01-01
Systemic Lupus erythematosus (SLE) is an autoimmune disease caused, in part, by abnormalities in cells of the immune system including B and T cells. Genetically reducing globally the expression of the ETS transcription factor FLI1 by 50% in two lupus mouse models significantly improves disease measures and survival through an unknown mechanism. In this study we analyze the effects of reducing FLI1 in the MRL/lpr lupus prone model on T cell function. We demonstrate that adoptive transfer of MRL/lpr Fli1(+/+) or Fli1(+/-) T cells and B cells into Rag1-deficient mice results in significantly decreased serum immunoglobulin levels in animals receiving Fli1(+/-) lupus T cells compared to animals receiving Fli1(+/+) lupus T cells regardless of the genotype of co-transferred lupus B cells. Ex vivo analyses of MRL/lpr T cells demonstrated that Fli1(+/-) T cells produce significantly less IL-4 during early and late disease and exhibited significantly decreased TCR-specific activation during early disease compared to Fli1(+/+) T cells. Moreover, the Fli1(+/-) T cells expressed significantly less neuraminidase 1 (Neu1) message and decreased NEU activity during early disease and significantly decreased levels of glycosphingolipids during late disease compared to Fli1(+/+) T cells. FLI1 dose-dependently activated the Neu1 promoter in mouse and human T cell lines. Together, our results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by decreasing TCR-specific activation and IL-4 production in part through the modulation of glycosphingolipid metabolism. Reducing the expression of FLI1 or targeting the glycosphingolipid metabolic pathway in lupus may serve as a therapeutic approach to treating lupus.
Bauer, P; Barthelmes, D; Kurz, M; Fleischhauer, J C; Sutter, F K
2008-05-01
Due to the predicted age shift of the population an increase in the number of patients with late AMD is expected. At present smoking represents the only modifiable risk factor. Supplementation of antioxidants in patients at risk is the sole effective pharmacological prevention. The aim of this study is to estimate the future epidemiological development of late AMD in Switzerland and to quantify the potential effects of smoking and antioxidants supplementation. The modelling of the future development of late AMD cases in Switzerland was based on a meta-analysis of the published data on AMD-prevalence and on published Swiss population development scenarios until 2050. Three different scenarios were compared: low, mean and high. The late AMD cases caused by smoking were calculated using the "population attributable fraction" formula and data on the current smoking habits of the Swiss population. The number of potentially preventable cases was estimated using the data of the Age-Related Eye Disease Study (AREDS). According to the mean population development scenario, late AMD cases in Switzerland will rise from 37 200 cases in 2005 to 52 500 cases in 2020 and to 93 200 cases in 2050. Using the "low" and the "high" scenarios the late AMD cases may range from 49 500 to 56 000 in 2020 and from 73 700 to 118 400 in 2050, respectively. Smoking is responsible for approximately 7 % of all late AMD cases, i. e., 2600 cases in 2005, 3800 cases in 2020, 6600 cases in 2050 ("mean scenario"). With future antioxidant supplementation to all patients at risk another 3100 cases would be preventable until 2020 and possibly 23 500 cases until 2050. Due to age shift in the population a 2.5-fold increase in late AMD cases until 2050 is expected, representing a socioeconomic challenge. Cessation of smoking and supplementation of antioxidants to all patients at risk has the potential to reduce this number. Unfortunately, public awareness is low. These data may support health-care providers and public opinion leaders when developing public education and prevention strategies.
Immediate, early and late seizures after primary intracerebral hemorrhage.
Qian, Cheng; Löppönen, Pekka; Tetri, Sami; Huhtakangas, Juha; Juvela, Seppo; Turtiainen, Hanna-Maria E; Bode, Michaela K; Hillbom, Matti
2014-05-01
Seizures after primary intracerebral hemorrhage (PICH) are significant and treatable complications, but the factors predicting immediate, early and late seizures are poorly known. We investigated characteristics and outcome with special reference to occurrence and timing of a first seizure among consecutive subjects with PICH. A population-based study was conducted in Northern Ostrobothnia, Finland, in 1993-2008 that included all patients with a first-ever primary ICH without any prior diagnosis of epilepsy. Immediate (<24h after admission), early (1-14 days) and late (>2 weeks) seizures were considered separately. Out of a total of 935 ICH patients, 51 had immediate, 21 early and 58 late seizures. The patients with seizures were significantly younger than the others and more often had a subcortical hematoma location (p<0.05). Lifestyle factors did not differ between the groups. The risk factors for immediate seizures in multivariable analysis were a low Glasgow coma scale score (GCS) on admission, subcortical location and age inversely (p<0.01). The only independent risk factor for early seizures was subcortical location (p<0.001), whereas subcortical location (p<0.001), age inversely (p<0.01) and hematoma evacuation (p<0.05) independently predicted late seizures. Immediate and early seizures predicted infectious complications (p<0.05). Patients with subcortical hematoma and of younger age are at risk for immediate seizures after primary ICH irrespective of hematoma size. Patients with immediate and early seizures more often had infectious complications. Surgery increases the risk of a late seizure after ICH. Copyright © 2014 Elsevier B.V. All rights reserved.
Development of the Computer-Adaptive Version of the Late-Life Function and Disability Instrument
Tian, Feng; Kopits, Ilona M.; Moed, Richard; Pardasaney, Poonam K.; Jette, Alan M.
2012-01-01
Background. Having psychometrically strong disability measures that minimize response burden is important in assessing of older adults. Methods. Using the original 48 items from the Late-Life Function and Disability Instrument and newly developed items, a 158-item Activity Limitation and a 62-item Participation Restriction item pool were developed. The item pools were administered to a convenience sample of 520 community-dwelling adults 60 years or older. Confirmatory factor analysis and item response theory were employed to identify content structure, calibrate items, and build the computer-adaptive testings (CATs). We evaluated real-data simulations of 10-item CAT subscales. We collected data from 102 older adults to validate the 10-item CATs against the Veteran’s Short Form-36 and assessed test–retest reliability in a subsample of 57 subjects. Results. Confirmatory factor analysis revealed a bifactor structure, and multi-dimensional item response theory was used to calibrate an overall Activity Limitation Scale (141 items) and an overall Participation Restriction Scale (55 items). Fit statistics were acceptable (Activity Limitation: comparative fit index = 0.95, Tucker Lewis Index = 0.95, root mean square error approximation = 0.03; Participation Restriction: comparative fit index = 0.95, Tucker Lewis Index = 0.95, root mean square error approximation = 0.05). Correlation of 10-item CATs with full item banks were substantial (Activity Limitation: r = .90; Participation Restriction: r = .95). Test–retest reliability estimates were high (Activity Limitation: r = .85; Participation Restriction r = .80). Strength and pattern of correlations with Veteran’s Short Form-36 subscales were as hypothesized. Each CAT, on average, took 3.56 minutes to administer. Conclusions. The Late-Life Function and Disability Instrument CATs demonstrated strong reliability, validity, accuracy, and precision. The Late-Life Function and Disability Instrument CAT can achieve psychometrically sound disability assessment in older persons while reducing respondent burden. Further research is needed to assess their ability to measure change in older adults. PMID:22546960
Lowered Insulin Signalling Ameliorates Age-Related Sleep Fragmentation in Drosophila
Hendrich, Oliver; Hinze, Yvonne; Birras, Ulrike; Partridge, Linda
2014-01-01
Sleep fragmentation, particularly reduced and interrupted night sleep, impairs the quality of life of older people. Strikingly similar declines in sleep quality are seen during ageing in laboratory animals, including the fruit fly Drosophila. We investigated whether reduced activity of the nutrient- and stress-sensing insulin/insulin-like growth factor (IIS)/TOR signalling network, which ameliorates ageing in diverse organisms, could rescue the sleep fragmentation of ageing Drosophila. Lowered IIS/TOR network activity improved sleep quality, with increased night sleep and day activity and reduced sleep fragmentation. Reduced TOR activity, even when started for the first time late in life, improved sleep quality. The effects of reduced IIS/TOR network activity on day and night phenotypes were mediated through distinct mechanisms: Day activity was induced by adipokinetic hormone, dFOXO, and enhanced octopaminergic signalling. In contrast, night sleep duration and consolidation were dependent on reduced S6K and dopaminergic signalling. Our findings highlight the importance of different IIS/TOR components as potential therapeutic targets for pharmacological treatment of age-related sleep fragmentation in humans. PMID:24690889
Evolution of CAM and C4 carbon-concentrating mechanisms
Keeley, Jon E.; Rundel, Philip W.
2003-01-01
Mechanisms for concentrating carbon around the Rubisco enzyme, which drives the carbon-reducing steps in photosynthesis, are widespread in plants; in vascular plants they are known as crassulacean acid metabolism (CAM) and C4 photosynthesis. CAM is common in desert succulents, tropical epiphytes, and aquatic plants and is characterized by nighttime fixation of CO2. The proximal selective factor driving the evolution of this CO2-concentrating pathway is low daytime CO2, which results from the unusual reverse stomatal behavior of terrestrial CAM species or from patterns of ambient CO2 availability for aquatic CAM species. In terrestrials the ultimate selective factor is water stress that has selected for increased water use efficiency. In aquatics the ultimate selective factor is diel fluctuations in CO2 availability for palustrine species and extreme oligotrophic conditions for lacustrine species. C4 photosynthesis is based on similar biochemistry but carboxylation steps are spatially separated in the leaf rather than temporally as in CAM. This biochemical pathway is most commonly associated with a specialized leaf anatomy known as Kranz anatomy; however, there are exceptions. The ultimate selective factor driving the evolution of this pathway is excessively high photorespiration that inhibits normal C3 photosynthesis under high light and high temperature in both terrestrial and aquatic habitats. CAM is an ancient pathway that likely has been present since the Paleozoic era in aquatic species from shallow-water palustrine habitats. While atmospheric CO2 levels have undoubtedly affected the evolution of terrestrial plant carbon-concentrating mechanisms, there is reason to believe that past atmospheric changes have not played as important a selective role in the aquatic milieu since palustrine habitats today are not generally carbon sinks, and the selective factors driving aquatic CAM are autogenic. Terrestrial CAM, in contrast, is of increasing selective value under extreme water deficits, and undoubtedly, high Mesozoic CO2 levels reduced the amount of landscape perceived by plants as water limited. Late Tertiary and Quaternary reductions in atmospheric CO2, coupled with increasing seasonality, were probably times of substantial species radiation and ecological expansion for CAM plants. C4 photosynthesis occurs in only about half as many families as CAM, and three-fourths of C4 species are either grasses or sedges. Molecular phylogenies indicate C4 is a more recent innovation than CAM and that it originated in the mid-Tertiary, 20–30 Ma, although some data support an earlier origin. While the timing of the origin of C4 remains controversial, the nearly explosive increase in C4 species is clearly documented in the late Miocene, 4–7 Ma. Increasing seasonality has been widely suggested as an important climatic stimulus for this C4 expansion. Alternatively, based on models of photosynthetic quantum yield at different temperatures and CO2 concentration, it has been hypothesized that the late Miocene C4 expansion resulted from declining atmospheric CO2 levels. This model is most appropriate for explaining the transition from C3 grasslands to C4 grasslands but by itself may not be sufficient to explain the more likely scenario of a late Miocene transition from C3 woodland/ savanna to C4 grasslands. A largely unexplored hypothesis is that climatic changes in late Miocene altered disturbance regimes, in particular the incidence of fires, which today are often associated with maintenance of C4 grasslands. Oceanic charcoal sediments that appear to represent Aeolian deposits from continental wildfires follow a strikingly similar pattern of explosive increase in late Miocene. Climate, CO2, and disturbance are not mutually exclusive explanations and probably all acted in concert to promote the expansion of C4 grasslands. More recently, late Quaternary changes in CO2 may have been responsible for driving major changes in the landscape distribution of C4 species. The theory is sound; however, many of the studies cited in support of this model are open to alternative interpretations, and none has eliminated climatic factors as important selective agents. CAM and C4 evolution required coupling of biochemical pathways with structural changes in photosynthetic tissues, succulence in CAM and Kranz in C4. This was apparently accomplished by piecemeal evolution beginning with mechanisms for recapturing respiratory CO2, although this need not have been so in aquatic CAM species. It has been proposed that the extreme rarity of both pathways in the same plant results from biochemical and structural incompatibilities (Sage 2002). Equally important is the fact that the selective environments are quite different, with CAM evolution thriving on stressful sites inhospitable to C3 species whereas C4 evolution has selected for rapid growth capable of outcompeting associated C3 plants.
Factors Influencing Adjustment to Late-Life Divorce.
ERIC Educational Resources Information Center
Wilson, Keren Brown; DeShane, Michael R.
Although the rate of divorce among older Americans has increased steadily, little attention has been paid to late life divorce. To describe the role of age and other factors which might influence adjustment to divorce in later life, data from a larger pilot study were used: 81 divorced persons over the age of 60 completed in-depth, structured…
Thermal Transgressions and Phanerozoic Extinctions
NASA Astrophysics Data System (ADS)
Worsley, T. R.; Kidder, D. L.
2007-12-01
A number of significant Phanerozoic extinctions are associated with marine transgressions that were probably driven by rapid ocean warming. The conditions associated with what we call thermal transgressions are extremely stressful to life on Earth. The Earth system setting associated with end-Permian extinction exemplifies an end-member case of our model. The conditions favoring extreme warmth and sea-level increases driven by thermal expansion are also conducive to changes in ocean circulation that foster widespread anoxia and sulfidic subsurface ocean waters. Equable climates are characterized by reduced wind shear and weak surface ocean circulation. Late Permian and Early Triassic thermohaline circulation differs considerably from today's world, with minimal polar sinking and intensified mid-latitude sinking that delivers sulfate from shallow evaporative areas to deeper water where it is reduced to sulfide. Reduced nutrient input to oceans from land at many of the extinction intervals results from diminished silicate weathering and weakened delivery of iron via eolian dust. The falloff in iron-bearing dust leads to minimal nitrate production, weakening food webs and rendering faunas and floras more susceptible to extinction when stressed. Factors such as heat, anoxia, ocean acidification, hypercapnia, and hydrogen sulfide poisoning would significantly affect these biotas. Intervals of tectonic quiescence set up preconditions favoring extinctions. Reductions in chemical silicate weathering lead to carbon dioxide buildup, oxygen drawdown, nutrient depletion, wind and ocean current abatement, long-term global warming, and ocean acidification. The effects of extinction triggers such as large igneous provinces, bolide impacts, and episodes of sudden methane release are more potent against the backdrop of our proposed preconditions. Extinctions that have characteristics we call for in the thermal transgressions include the Early Cambrian Sinsk event, as well as extinction events at the Frasnian-Famennian, end-Devonian, end Permian, Early Toarcian, Cenomanian-Turonian, and end Cretaceous. The Late Paleocene and end Triassic extinctions are still under evaluation. The extinctions associated with the glacio-eustatic sea-level change in the Late Ordovician are not consistent with the conditions of our model.
Nagasaka, Hironori; Yorifuji, Tohru; Murayama, Kei; Kubota, Mitsuru; Kurokawa, Keiji; Murakami, Tomoko; Kanazawa, Masaki; Takatani, Tomozumi; Ogawa, Atsushi; Ogawa, Emi; Yamamoto, Shigenori; Adachi, Masanori; Kobayashi, Kunihiko; Takayanagi, Masaki
2006-09-01
The aim of this study was to investigate the effects of arginine on nutrition, growth and urea cycle function in boys with late-onset ornithine transcarbamylase deficiency (OTCD). Seven Japanese boys with late-onset OTCD enrolled in this study resumed arginine treatment after the cessation of this therapy for a few years. Clinical presentations such as vomiting and unconsciousness, plasma amino acids and urinary orotate excretion were followed chronologically to evaluate urea cycle function and protein synthesis with and without this therapy. In addition to height and body weight, blood levels of proteins, lipids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein -3 (IGFBP-3) were monitored. The frequency of hyperammonemic attacks and urinary orotate excretion decreased significantly following the resumption of arginine treatment. Despite showing no marked change in body weight, height increased gradually. Extremely low plasma arginine increased to normal levels, while plasma glutamine and alanine levels decreased considerably. Except for a slight increase in high-density lipoprotein cholesterol level, blood levels of markers for nutrition did not change. In contrast, low serum IGF-I and IGFBP-3 levels increased to age-matched control levels, and normal urinary GH secretion became greater than the level observed in the controls. Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth.
de Pedro-Cuesta, Jesús; Martínez-Martín, Pablo; Rábano, Alberto; Alcalde-Cabero, Enrique; José García López, Fernando; Almazán-Isla, Javier; Ruiz-Tovar, María; Medrano, Maria-José; Avellanal, Fuencisla; Calero, Olga; Calero, Miguel
2016-01-01
Background: Sutherland et al. (2011) suggested that, instead of risk factors for single neurodegenerative disorders (NDDs), there was a need to identify specific “drivers”, i.e., risk factors with impact on specific deposits, such as amyloid-β, tau, or α-synuclein, acting across entities. Objectives and Methods: Redefining drivers as “neither protein/gene- nor entity-specific features identifiable in the clinical and general epidemiology of conformational NDDs (CNDDs) as potential footprints of templating/spread/transfer mechanisms”, we conducted an analysis of the epidemiology of ten CNDDs, searching for patterns. Results: We identified seven potential drivers, each of which was shared by at least two CNDDs: 1) an age-at-exposure-related susceptibility to Creutzfeldt-Jakob disease (CJD) and several late-life CNDDs; 2) a relationship between age at onset, survival, and incidence; 3) shared genetic risk factors for CJD and late-life CNNDs; 4) partly shared personal (diagnostic, educational, behavioral, and social risk factors) predating clinical onset of late-life CNDDs; 5) two environmental risk factors, namely, surgery for sporadic CJD and amyotrophic lateral sclerosis, and Bordetella pertussis infection for Parkinson’s disease; 6) reticulo-endothelial system stressors or general drivers (andropause or premenopausal estrogen deficiency, APOEɛ4, and vascular risk factors) for late-life CNDDs such as dementia/Alzheimer’s disease, type-2 diabetes mellitus, and some sporadic cardiac and vascular degenerative diseases; and 7) a high, invariant incidence ratio of sporadic to genetic forms of mid- and late-life CNDDs, and type-2 diabetes mellitus. Conclusion: There might be a systematic epidemiologic pattern induced by specific proteins (PrP, TDP-43, SOD1, α-synuclein, amyloid-β, tau, Langerhans islet peptide, and transthyretin) or established combinations of these. PMID:26923014
USDA-ARS?s Scientific Manuscript database
Foliar late blight, caused by Phytophthora infestans, is an important disease problem worldwide. Foliar resistance to late blight was found in a hybrid population of the cultivated diploid species Solanum phureja-S. stenotomum (phu-stn). The objective of this study was to determine if resistance t...
Patterns of late embryonic and fetal mortality and association with several factors in sheep.
Dixon, A B; Knights, M; Winkler, J L; Marsh, D J; Pate, J L; Wilson, M E; Dailey, R A; Seidel, G; Inskeep, E K
2007-05-01
Embryonic and fetal mortality reduce lambing rates and litter sizes, thus contributing to economic losses in the sheep industry. In the current study, the timing of late embryonic and fetal loss in ewes and the factors with which these losses were associated were examined. Ewes lambing and lambs born were compared with pregnancy diagnosis and counts of embryos by ultrasonography near d 25, 45, 65, or 85 of gestation. Approximately 19.9% of the ewes experienced late embryonic loss, fetal loss, or both; and 21.2% of the embryos or fetuses were lost from d 25 to term. Potential offspring were lost throughout gestation; 3.7% of embryos from d 25 to 45, 4.3% of fetuses from d 45 to 65, 3.3% from d 65 to 85, and 11.5% from d 85 to parturition; thus, approximately 3 to 4% of the potential offspring were lost for each 20-d period of pregnancy beyond d 25. A greater proportion of ewes lost one (36.7%) rather than all (20.5% single; 3.8% multiple) embryos or fetuses. The patterns of loss were similar in ewes mated during the anestrous season and the transitional period and did not vary with service period within breeding season or method of synchronization of estrus. Late embryonic or fetal losses were not related to the temperature-humidity index. Maternal serum collected near d 25, 45, 65, or 85 of gestation was assayed for concentrations of progesterone, estradiol-17beta , and vascular endothelial growth factor (VEGF). The proportions of embryos or fetuses lost were associated with breed type (P < 0.05), as were concentrations of progesterone (P < 0.01), estradiol (P < 0.05), and VEGF (P < 0.01). The relationships of loss or retention of pregnancy to hormonal variables at the 4 stages studied were limited. Complete and partial losses increased rapidly as maternal progesterone at d 25 decreased below 2 ng/mL (P < 0.05). Survival of fetuses within a litter from d 25 to 65 was greater for ewes with medium concentrations of VEGF near d 25 and from d 65 to parturition was greater for ewes with high concentrations of VEGF near d 45 (P < 0.05). In summary, late embryonic or fetal losses occurred from d 25 throughout gestation and varied with breed type and with concentrations of progesterone in maternal serum on d 25.
Latest Jurassic ammonoid provinces: Paleoecological implications using a general circulation model
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ross, C.A.; Moore, G.T.; Hayashida, D.N.
1992-01-01
The Lake Permian-early Mesozoic megacontinent Pangea was progressively fragmented by two rift systems that propagated westward out of the Tethys Sea and a third more persistent rift system that connected the Boreal and Tethys seas. By the late Tithonian, these major rift systems produced interconnected oceanic seaways that divided Pangea into four continental segments: North America, Eur-Asia, and northern and southern Gondwana. Increased rates of sea-floor spreading during the Jurassic reduced the volumetric capacity of ocean basins and produced a sea level rise through the period that culminated in the Lake Jurassic. The extensive marine shelf margins and epeiric seasmore » hosted a widely distributed and diverse ammonoid fauna. By the early Tithonian, faunal communication existed between the northwestern Tethys Sea and the eastern Panthalassa Ocean through the proto-Gulf of Mexico. By the late Tithonian, faunal similarities indicate the opening of the proto-Indian Ocean so that northern and southern Gondwana had become separate continents. A region of the equatorial Tethys that includes most of the present Arabian Peninsular contains neuritic platform facies but lacks ammonoids. In high northern latitudes, cool to cold water faunas formed a Boreal Realm which extended westward across northern North America, Europe, and Siberia during middle and late Tithonian. Late Kimmeridgian and Tithonian ammonoid distributions when compared with Late Jurassic paleoclimate simulations show likely causal relationships with sea surface water temperatures and upwelling, and possibly shed light on the temperature limitations of ammonoids. Results from modeled seasonal sea surface temperature, sea ice distribution, precipitation-evaporation, and wind-driven upwelling permit the evaluation and quantification of paleoenvironmental factors favorable as well as pernicious for ammonoid distribution.« less
[A project to ameliorate nurses working overtime in psychiatry ward].
Feng, Yuen-Hsiang; Li, Hsiu-Chen; Fang, Mao-So
2009-12-01
The authors found nurses working in psychiatry wards were frequently required to work overtime, with average overtime measuring 85 minutes. After analysis, we found main factors leading to overtime to be late new patient admissions, tardy ward inspections by attending physicians, failure to implement workplace regulations, failure by nurses to implement proper shift transfer procedures, and meeting-related delays. This paper proposes an approach by which average overtime for psychiatry ward nurses may be reduced from 85 to 30 minutes. Based on findings, the researchers adjusted the schedule for ward visits by attending physicians, updated and streamlined workplace regulations, ensured administrative procedures were precisely followed, and updated and streamlined standing orders. Average overtime was reduced from 85 to 25 minutes. This research facilitated a reduction in the amount of overtime registered by nurses.
Otitis Media and Speech/Language Development in Late-Talkers.
ERIC Educational Resources Information Center
Paul, Rhea; And Others
This study examines otitis media as a possible factor associated with increased risk for communicative handicap in a group of children with a possible vulnerability for language delay: "late-talkers." Speech and language outcomes at ages 3 and 4 were examined in 28 late talkers and 24 children with normal language development. Late…
Influence of Phonotactic Probability/Neighbourhood Density on Lexical Learning in Late Talkers
ERIC Educational Resources Information Center
MacRoy-Higgins, Michelle; Schwartz, Richard G.; Shafer, Valerie L.; Marton, Klara
2013-01-01
Background: Toddlers who are late talkers demonstrate delays in phonological and lexical skills. However, the influence of phonological factors on lexical acquisition in toddlers who are late talkers has not been examined directly. Aims: To examine the influence of phonotactic probability/neighbourhood density on word learning in toddlers who were…
Gender differences in predictors of late-life health insurance knowledge.
Jacobs-Lawson, Joy M; Schumacher, Mitzi M; Webb, Alicia
2007-01-01
For many older adults having access to affordable health care is a major concern. The present study's goal was to examine what factors were related to individuals' knowledge of late-life health insurance. A total of 131 women and 116 men (all aged 55-71) answered questions about private, Medicare, Medigap, and long-term care insurances. In addition, they answered demographic, personality, and health status questions. Results revealed that different factors are related to men's and women's knowledge of late-life health insurance options implying genderspecific educational interventions would be more effective than current educational interventions.
Wang, Erica T; Sundheimer, Lauren W; Spades, Carla; Quant, Cara; Simmons, Charles F; Pisarska, Margareta D
2017-08-01
Late preterm infants are at risk for short-term morbidities. We report that late preterm singletons conceived with fertility treatment have increased risk for admission to the neonatal intensive care unit and respiratory support compared with spontaneously conceived infants. Fertility treatment may be a risk factor to consider in managing late preterm infants. Copyright © 2017 Elsevier Inc. All rights reserved.
Koch, Franziska; Lamp, Ole; Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn
2016-01-01
Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production simultaneously reducing endogenous heat production.
Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn
2016-01-01
Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production simultaneously reducing endogenous heat production. PMID:27513961
Role of the DNA Damage Response in Human Papillomavirus RNA Splicing and Polyadenylation.
Nilsson, Kersti; Wu, Chengjun; Schwartz, Stefan
2018-06-12
Human papillomaviruses (HPVs) have evolved to use the DNA repair machinery to replicate its DNA genome in differentiated cells. HPV activates the DNA damage response (DDR) in infected cells. Cellular DDR factors are recruited to the HPV DNA genome and position the cellular DNA polymerase on the HPV DNA and progeny genomes are synthesized. Following HPV DNA replication, HPV late gene expression is activated. Recent research has shown that the DDR factors also interact with RNA binding proteins and affects RNA processing. DDR factors activated by DNA damage and that associate with HPV DNA can recruit splicing factors and RNA binding proteins to the HPV DNA and induce HPV late gene expression. This induction is the result of altered alternative polyadenylation and splicing of HPV messenger RNA (mRNA). HPV uses the DDR machinery to replicate its DNA genome and to activate HPV late gene expression at the level of RNA processing.
Neuroinflammatory and morphological changes in late-life depression: the NIMROD study.
Su, L; Faluyi, Y O; Hong, Y T; Fryer, T D; Mak, E; Gabel, S; Hayes, L; Soteriades, S; Williams, G B; Arnold, R; Passamonti, L; Rodríguez, P Vázquez; Surendranathan, A; Bevan-Jones, R W; Coles, J; Aigbirhio, F; Rowe, J B; O'Brien, J T
2016-12-01
We studied neuroinflammation in individuals with late-life depression, as a risk factor for dementia, using [ 11 C]PK11195 positron emission tomography (PET). Five older participants with major depression and 13 controls underwent PET and multimodal 3T magnetic resonance imaging (MRI), with blood taken to measure C-reactive protein (CRP). We found significantly higher CRP levels in those with late-life depression and raised [ 11 C]PK11195 binding compared with controls in brain regions associated with depression, including subgenual anterior cingulate cortex, and significant hippocampal subfield atrophy in cornu ammonis 1 and subiculum. Our findings suggest neuroinflammation requires further investigation in late-life depression, both as a possible aetiological factor and a potential therapeutic target. © The Royal College of Psychiatrists 2016.
Levchenkova, O S; Novikov, V E; Parfenov, E A; Kulagin, K N
2016-12-01
We studied combined effect of moderate hypoxia and compounds pQ-4, pQ-915, pQ-1032, and pQ-1104 on neurological deficit and survival of rats after bilateral ligation of common carotid arteries. Preconditioning including moderate hypoxia and treatment with compound pQ-4 produced a neuroprotective effect and increased animal survival during the early (by 51%) and late (by 33.5%) periods of modeled ischemia and reduced neurological deficit (by 50% and 41%, respectively). Moreover, this combination of preconditioning factors prevented postischemic excessive activation of free radical oxidation in brain hemispheres and blood serum.
NASA Astrophysics Data System (ADS)
Adelman, Saul J.
1991-09-01
This paper presents elemental abundance analyses of sharp-lined normal late B stars. These stars exhibit mostly near-solar abundances, but each star also shows a few abundances which are a factor of 2 less than solar. The coadded photographic spectrograms are supplemented with Reticon data. A comparison of 261 equivalent widths on 2.4 A/mm spectra of sharp-lined B and A stars shows that the Reticon equivalent widths are about 95 percent of the coadded equivalent mean. The H-gamma profiles of the coadded and Reticon spectra for eight sharp-lined stars show generally good agreement. The generally high quality of the coadded data produced from 10 or more spectrograms is confirmed using the REDUCE graphics-oriented computed reduction code. For five stars, metal lines which fall in the gap between the U and V plates are analyzed using Reticon data.
NASA Technical Reports Server (NTRS)
Adelman, Saul J.
1991-01-01
This paper presents elemental abundance analyses of sharp-lined normal late B stars. These stars exhibit mostly near-solar abundances, but each star also shows a few abundances which are a factor of 2 less than solar. The coadded photographic spectrograms are supplemented with Reticon data. A comparison of 261 equivalent widths on 2.4 A/mm spectra of sharp-lined B and A stars shows that the Reticon equivalent widths are about 95 percent of the coadded equivalent mean. The H-gamma profiles of the coadded and Reticon spectra for eight sharp-lined stars show generally good agreement. The generally high quality of the coadded data produced from 10 or more spectrograms is confirmed using the REDUCE graphics-oriented computed reduction code. For five stars, metal lines which fall in the gap between the U and V plates are analyzed using Reticon data.
Taking the brakes off the learning curve.
Gheysen, Freja; Lasne, Gabriel; Pélégrini-Issac, Mélanie; Albouy, Genevieve; Meunier, Sabine; Benali, Habib; Doyon, Julien; Popa, Traian
2017-03-01
Motor learning is characterized by patterns of cerebello-striato-cortical activations shifting in time, yet the early dynamic and function of these activations remains unclear. Five groups of subjects underwent either continuous or intermittent theta-burst stimulation of one cerebellar hemisphere, or no stimulation just before learning a new motor sequence during fMRI scanning. We identified three phases during initial learning: one rapid, one slow, and one quasi-asymptotic performance phase. These phases were not changed by left cerebellar stimulation. Right cerebellar inhibition, however, accelerated learning and enhanced brain activation in critical motor learning-related areas during the first phase, continuing with reduced brain activation but high-performance in late phase. Right cerebellar excitation did not affect the early learning process, but slowed learning significantly in late phase, along with increased brain activation. We conclude that the right cerebellum is a key factor coordinating other neuronal loops in the early acquisition of an explicit motor sequential skill. Hum Brain Mapp 38:1676-1691, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Bryce, Yolanda; Kim, Wonho; Katzen, Barry; Benenati, James; Samuels, Shaun
2018-07-01
To assess differences in outcome in an early and later time period in patients with hostile neck anatomy who underwent endovascular aneurysm repair (EVAR). This single-center, institutional review board-approved retrospective study assessed patients who underwent EVAR between 2004 and 2013, divided into 2 time periods: 2004-2008 and 2009-2013. One hundred twenty-five patients had at least 1 hostile neck parameter that met inclusion criteria: 61 of 216 (28%) patients in the early period and 64 of 144 (44%) patients in the late period. Patients in the late group were younger compared to patients in the early group (late group, 74.5 ± 8.8 years vs early group, 77.5 ± 7.5 years; P = .046). No significant differences were observed in hostile neck anatomic factors between the early and late periods. No statistical difference was observed in periprocedural factors or outcome measures, except for abdominal aortic aneurysm (AAA) sac regression in the late period compared to the early period (late period, 73.5% vs early period, 55.7%; P = .038). A statistically significant increase was observed in type 1a endoleaks in patients in the late group with suprarenal fixation compared to patients with infrarenal fixation (suprarenal, 27.0% vs infrarenal, 7.9%; P = .025) and in the overall time studied (suprarenal, 20.3% vs infrarenal, 7.6%; P = .045). Except for AAA sac regression, no changes were observed in periprocedural factors and outcome measures over time in patients with hostile neck who underwent EVAR. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.
Preclinical and clinical data for factor Xa and “universal” reversal agents☆,☆☆,★
Milling, Truman J.; Kaatz, Scott
2017-01-01
Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoymolecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development. This review summarizes the published data to date on both drugs, which have the potential to change the management approach to patients with FXa inhibitoreassociated major hemorrhage. PMID:27697443
Preclinical and Clinical Data for Factor Xa and “Universal” Reversal Agents
Milling, Truman J.; Kaatz, Scott
2017-01-01
Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoy molecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development. This review summarizes the published data to date on both drugs, which have the potential to change the management approach to patients with FXa inhibitor–associated major hemorrhage. PMID:27575436
Stephen, Atasige Awin-irigu; Wurapa, Frederick; Afari, Edwin Andrew; Sackey, Samuel Oko; Malm, Keaziah Laurencia; Nyarko, Kofi Mensah
2016-01-01
Introduction The coverage of adequate (≥2 doses) IPTp-SP in Ghana is below the national target of 80% and that is a threat to reducing the incidence of malaria in pregnancy. The primary objective of the study was to determine the client and facility related factors associated with adequate uptake of IPTp-SP and suggest approaches for increased uptake. Methods A cross sectional study was conducted among ANC clients and staff in Gushegu, questionnaires was administered to 330 conveniently sampled nursing mothers and all ANC staff present. A checklist and observation were used to collect health facility data. Data was analyzed descriptively and associations between the related factors and adequate uptake of IPTp-SP were determined. Results A total of 91.5% and 8.5% of respondents took adequate (≥2doses) and inadequate (≤1dose) IPTp-SP respectively. 85.4% respondents were early first ANC attendance and 80% were multiple gravidae. Mean ANC visits was 5.0 (standard deviation = 2.2). The key determinants for inadequate uptake of IPTp were Unemployment [OR= 4.9 95% CI (1.9-13.1], single gravidae [OR= 3.4 95% CI (1.5-7.6)] and late first ANC visit [OR= 6.8 95% CI (3.0-15.4)]. DOT practice, good staff attitude and health talk at the facility were observed and confirmed by ANC clients as satisfactory. adequate uptake of SP among respondents was high. Majorities were unemployed, have had multiple pregnancies and made early first ANC visits. Unemployment and late first ANC visits are significantly associated with taking inadequate SP dose. Conclusion Adequate uptake of SP among respondents was high. Majorities were unemployed, have had multiple pregnancies and made early first ANC visits. Unemployment and late first ANC visits are significantly associated with taking inadequate SP dose. PMID:28149434
The Influence of Social Determinants on Late Stage Breast Cancer for Women in Mississippi.
Fortune, Melody L
2017-02-01
Breast cancer is the most common diagnosed cancer in women exacting an emotional and economic hardship for them and their families. There are no known causes of breast cancer, but there are certain genetic, social, and environment risk factors that pre-dispose women to this disease. Also, diagnosis at later stages of disease has been shown to have adverse outcomes for many as compared to early stages. The social determinants researched to examine their influence on breast cancer outcomes were race, health insurance, and income. The results of this study confirmed that race and health insurance were the two major factors that negatively impacted stages of breast cancer diagnoses. The purpose of this study was to investigate the influence that social determinants have on stage of breast cancer diagnoses. This research focused on three social determinants that research demonstrated had an influence on stages of breast cancer diagnoses (race, income, and lack of health insurance). Bivariate analyses were conducted to examine the relationships between race and income, race and health insurance, and race and stage of diagnosis. The findings confirmed what was suspected for Mississippians; more African Americans had lower incomes, had less health insurance coverage, and were diagnosed at later stages of breast cancer disease. Only race and health insurance directly affected late stage diagnosis in analyses for this study. The influence of income on stage of breast cancer diagnosis was not statistically significant. The results of these analyses demonstrated that African American women in Mississippi were disproportionately diagnosed at late stage breast cancer as opposed to early stage. An individual cannot alter the genetic factor of race, but some of the disparate health outcomes that appear to be associated with race may be behavioral or socio-economically based and can be addressed, which could impact health outcomes. Adequate health insurance could positively impact stage of breast cancer diagnoses, ultimately reducing health disparities and premature death.
Smith, Amanda L.; Rosenkrantz, Ted S.; Fitch, R. Holly
2016-01-01
Hypoxia ischemia (HI) is a recognized risk factor among late-preterm infants, with HI events leading to varied neuropathology and cognitive/behavioral deficits. Studies suggest a sex difference in the incidence of HI and in the severity of subsequent behavioral deficits (with better outcomes in females). Mechanisms of a female advantage remain unknown but could involve sex-specific patterns of compensation to injury. Neuroprotective hypothermia is also used to ameliorate HI damage and attenuate behavioral deficits. Though currently prescribed only for HI in term infants, cooling has potential intrainsult applications to high-risk late-preterm infants as well. To address this important clinical issue, we conducted a study using male and female rats with a postnatal (P) day 7 HI injury induced under normothermic and hypothermic conditions. The current study reports patterns of neuropathology evident in postmortem tissue. Results showed a potent benefit of intrainsult hypothermia that was comparable for both sexes. Findings also show surprisingly different patterns of compensation in the contralateral hemisphere, with increases in hippocampal thickness in HI females contrasting reduced thickness in HI males. Findings provide a framework for future research to compare and contrast mechanisms of neuroprotection and postinjury plasticity in both sexes following a late-preterm HI insult. PMID:27042359
Hani, E H; Suaud, L; Boutin, P; Chèvre, J C; Durand, E; Philippi, A; Demenais, F; Vionnet, N; Furuta, H; Velho, G; Bell, G I; Laine, B; Froguel, P
1998-01-01
Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disorder characterized by hyperglycemia resulting from defects in insulin secretion and action. Recent studies have found mutations in the hepatocyte nuclear factor-4 alpha gene (HNF-4alpha) in families with maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes characterized by early age at onset and a defect in glucose-stimulated insulin secretion. During the course of our search for susceptibility genes contributing to the more common late-onset NIDDM forms, we observed nominal evidence for linkage between NIDDM and markers in the region of the HNF-4alpha/MODY1 locus in a subset of French families with NIDDM diagnosed before 45 yr of age. Thus, we screened these families for mutations in the HNF-4alpha gene. We found a missense mutation, resulting in a valine-to-isoleucine substitution at codon 393 in a single family. This mutation cosegregated with diabetes and impaired insulin secretion, and was not present in 119 control subjects. Expression studies showed that this conservative substitution is associated with a marked reduction of transactivation activity, a result consistent with this mutation contributing to the insulin secretory defect observed in this family. PMID:9449683
Suicidal behaviour and suicide prevention in later life.
Draper, Brian M
2014-10-01
Despite a general decline in late life suicide rates over the last 30 years, older people have the highest rates of suicide in most countries. In contrast, non-fatal suicidal behaviour declines with age and more closely resembles suicide than in younger age groups. There are difficulties in the detection and determination of pathological suicidal ideation in older people. Multiple factors increase suicide risk ranging from distal early and mid-life issues such as child abuse, parental death, substance misuse and traumatic life experiences to proximal precipitants in late life such as social isolation and health-related concerns. Clinical depression is the most frequently identified proximal mental health concern and in many cases is a first episode of major depression. Recent studies have identified changes on neuroimaging and neurocognitive factors that might distinguish suicidal from non-suicidal depression in older people. Strategies for suicide prevention need to be 'whole of life' and, as no single prevention strategy is likely to be successful alone, a multi-faceted, multi-layered approach is required. This should include optimal detection and management of depression and of high risk individuals as available evidence indicates that this can reduce suicidal behaviour. How best to improve the quality of depression management in primary and secondary care requires further research. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Sundowning: Late-Day Confusion
... behavior is unknown. Factors that may aggravate late-day confusion include: Fatigue Low lighting Increased shadows Disruption ... for activities and exposure to light during the day to encourage nighttime sleepiness. Limit daytime napping. Limit ...
Relationship between obesity, ethnicity and risk of late stillbirth: a case control study
2011-01-01
Background In high income countries there has been little improvement in stillbirth rates over the past two decades. Previous studies have indicated an ethnic disparity in the rate of stillbirths. This study aimed to determine whether maternal ethnicity is independently associated with late stillbirth in New Zealand. Methods Cases were women with a singleton, late stillbirth (≥28 weeks' gestation) without congenital abnormality, born between July 2006 and June 2009 in Auckland, New Zealand. Two controls with ongoing pregnancies were randomly selected at the same gestation at which the stillbirth occurred. Women were interviewed in the first few weeks following stillbirth, or at the equivalent gestation for controls. Detailed demographic data were recorded. The study was powered to detect an odds ratio of 2, with a power of 80% at the 5% level of significance, given a prevalence of the risk factor of 20%. A multivariable regression model was developed which adjusted for known risk factors for stillbirth, as well as significant risk factors identified in the current study, and adjusted odds ratios and 95% confidence intervals were calculated. Results 155/215 (72%) cases and 310/429 (72%) controls consented. Pacific ethnicity, overweight and obesity, grandmultiparity, not being married, not being in paid work, social deprivation, exposure to tobacco smoke and use of recreational drugs were associated with an increased risk of late stillbirth in univariable analysis. Maternal overweight and obesity, nulliparity, grandmultiparity, not being married and not being in paid work were independently associated with late stillbirth in multivariable analysis, whereas Pacific ethnicity was no longer significant (adjusted Odds Ratio 0.99; 0.51-1.91). Conclusions Pacific ethnicity was not found to be an independent risk factor for late stillbirth in this New Zealand study. The disparity in stillbirth rates between Pacific and European women can be attributed to confounding factors such as maternal obesity and high parity. PMID:21226915
ERIC Educational Resources Information Center
Fisher, Evelyn L.
2017-01-01
Purpose: The purpose of this study was to explore the literature on predictors of outcomes among late talkers using systematic review and meta-analysis methods. We sought to answer the question: What factors predict preschool-age expressive-language outcomes among late-talking toddlers? Method: We entered carefully selected search terms into the…
de Britto, Alan A; Moraes, Davi J A
2017-03-15
Hypercapnia or parafacial respiratory group (pFRG) disinhibition at normocapnia evokes active expiration in rats by recruitment of pFRG late-expiratory (late-E) neurons. We show that hypercapnia simultaneously evoked active expiration and exaggerated glottal dilatation by late-E synaptic excitation of abdominal, hypoglossal and laryngeal motoneurons. Simultaneous rhythmic expiratory activity in previously silent pFRG late-E neurons, which did not express the marker of ventral medullary CO 2 -sensitive neurons (transcription factor Phox2b), was also evoked by hypercapnia. Hypercapnia-evoked active expiration, neural and neuronal late-E activities were eliminated by pFRG inhibition, but not after blockade of synaptic excitation. Hypercapnia produces disinhibition of non-chemosensitive pFRG late-E neurons to evoke active expiration and concomitant cranial motor respiratory responses controlling the oropharyngeal and upper airway patency. Hypercapnia produces active expiration in rats and the recruitment of late-expiratory (late-E) neurons located in the parafacial respiratory group (pFRG) of the ventral medullary brainstem. We tested the hypothesis that hypercapnia produces active expiration and concomitant cranial respiratory motor responses controlling the oropharyngeal and upper airway patency by disinhibition of pFRG late-E neurons, but not via synaptic excitation. Phrenic nerve, abdominal nerve (AbN), cranial respiratory motor nerves, subglottal pressure, and medullary and spinal neurons/motoneurons were recorded in in situ preparations of juvenile rats. Hypercapnia evoked AbN active expiration, exaggerated late-E discharges in cranial respiratory motor outflows, and glottal dilatation via late-E synaptic excitation of abdominal, hypoglossal and laryngeal motoneurons. Simultaneous rhythmic late-E activity in previously silent pFRG neurons, which did not express the marker of ventral medullary CO 2 -sensitive neurons (transcription factor Phox2b), was also evoked by hypercapnia. In addition, hypercapnia-evoked AbN active expiration, neural and neuronal late-E activities were eliminated by pFRG inhibition, but not after blockade of synaptic excitation. On the other hand, pFRG inhibition did not affect either hypercapnia-induced inspiratory increases in respiratory motor outflows or CO 2 sensitivity of the more medial Phox2b-positive neurons in the retrotrapezoid nucleus (RTN). Our data suggest that neither RTN Phox2b-positive nor other CO 2 -sensitive brainstem neurons activate Phox2b-negative pFRG late-E neurons under hypercapnia to produce AbN active expiration and concomitant cranial motor respiratory responses controlling the oropharyngeal and upper airway patency. Hypercapnia produces disinhibition of non-chemosensitive pFRG late-E neurons in in situ preparations of juvenile rats to activate abdominal, hypoglossal and laryngeal motoneurons. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Santos, Sérgio Alexandre Alcantara Dos; Porto Amorim, Elaine Manoela; Ribeiro, Larissa Mayume; Rinaldi, Jaqueline Carvalho; Delella, Flávia Karina; Justulin, Luis Antonio; Felisbino, Sérgio Luis
2017-12-02
Puberty is an important period for the growth and maturation of the male reproductive system, and is also a critical window for endocrine or environmental interference. The physiological levels of circulating insulin and hyperglycemic control are important factors for a normal prostate growth. Hyperglycemia during puberty is reported to retard the growth of the prostate gland, with remarkable effects on the epithelial compartment. Here, we investigated the impact of hyperglycemia along with a simultaneous or late insulin replacement on the ventral prostate growth in rats during puberty, paying special attention to the deposition of collagen fibers and activities of gelatinase, matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9). Hyperglycemia was induced by streptozotocin (STZ) administration in 40-day-old male Wistar rats. A subset of hyperglycemic rats underwent an early insulin replacement (three days after the STZ administration), and another subset underwent a late insulin replacement (twenty days after the STZ administration). Animals were euthanized at 60 and/or 80 days of age. The ventral prostatic lobe was processed for picrosirius red staining, type I and III collagen immunohistochemistry, and gelatin zymography. Hyperglycemic animals showed an increased area of collagen fibers in the prostate, which was composed both types of collagens. MMP-2 activity was significantly reduced in the hyperglycemic animals, while MMP-9 activity was very low and showed no alteration. The simultaneous and late insulin administration restored collagen content and MMP-2 activity. In conclusion, puberty is a critical window for prostate maturation and type-1 diabetes-induced hyperglycemia affects the ratio of the prostatic parenchymal and stromal growth, leading to fibrotic tissues by also MMP-2 down regulation. Copyright © 2017 Elsevier Inc. All rights reserved.
Yang, Rui; Zhang, Jianjia; Feng, Min; Wu, Xiaofeng
2016-11-01
Bombyx mori nucleopolyhedrovirus orf58a (bm58a) and its homologues are highly conserved in genomes of all sequenced group I alphabaculoviruses and its function is still unknown. Transcriptional analysis revealed that bm58a is a very late gene initiated from a late transcriptional start motif TAAG. To examine its role in the virus, a bm58a knockout virus (vBmbm-58a-KO-PH-GFP) was generated through homologous recombination in Escherichia coli. Analysis of fluorescence microscopy, titration assays and electron microscopy examination showed that the deletion of bm58a did not affect viral replication and occlusion bodies formation in vitro, indicating that bm58a is not required for viral propagation. However, vBmbm-58a-KO-PH-GFP did not result in cell lysis when wild-type virus infected cells began to lyse, and the vBmbm-58a-KO-PH-GFP infected cells remained intact until 2 weeks post-infection. Quantification of polyhedra release from cells confirmed this observation. Accordingly, though deletion of bm58a did not reduce Bombyx mori nucleopolyhedrovirus infectivity in vivo in bioassays, it did significantly disrupt the larval liquefaction, reducing the level of polyhedra release from infected host. Immunofluorescence analysis demonstrated that Bm58a was predominantly localized on the cellular membrane at the late stage of infection, which may contribute to its function of facilitating cell lysis and larval liquefaction. Our results suggest that although bm58a is not essential for viral propagation as an auxiliary gene, it is a key factor of virus-induced cell lysis and larval liquefaction in vitro and in vivo.
Ross, Joshua C.; Trainor, Jennifer L.; Eppich, Walter J.; Adler, Mark D.
2013-01-01
Background Pediatrics residents have few opportunities to perform cardiopulmonary resuscitation (CPR). Enhancing the quality of CPR is a key factor to improving outcomes for cardiopulmonary arrest in children and requires effective training strategies. Objective To evaluate the effectiveness of a simulation-based intervention to reduce first-year pediatrics residents' time for 3 critical actions in CPR: (1) call for help, (2) initiate bag-mask ventilation, and (3) initiate chest compressions. Methods A prospective study involving 31 first-year pediatrics residents at a children's hospital assigned to an early or late (control) intervention group. Residents underwent baseline assessment followed by repeat evaluations at 3 and 6 months. Time to critical actions was scored by video review. A 90-minute educational intervention focused on skill practice was conducted following baseline evaluation for the early-intervention group and following 3-month evaluation for the late-intervention group. Primary outcome was change in time to initiating the 3 critical actions. Change in time was analyzed by comparison of Kaplan-Meier curves, using the log-rank test. A 10% sample was timed by a second rater. Agreement was assessed using intraclass correlation (ICC). Results There was a statistically significant reduction in time for all 3 critical actions between baseline and 3-month evaluation in the early intervention group; this was not observed in the late (control) group. Rater agreement was excellent (ICC ≥ 0.99). Conclusions A simulation-based educational intervention significantly reduced time to initiation of CPR for first-year pediatrics residents. Simulation training facilitated acquisition of critical CPR skills that have the potential to impact patient outcome. PMID:24455010
BDNF is Associated With Age-Related Decline in Hippocampal Volume
Erickson, Kirk I.; Prakash, Ruchika Shaurya; Voss, Michelle W.; Chaddock, Laura; Heo, Susie; McLaren, Molly; Pence, Brandt D.; Martin, Stephen A.; Vieira, Victoria J.; Woods, Jeffrey A.; Kramer, Arthur F.
2010-01-01
Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood. PMID:20392958
Development of a bioassay system for investigating insulin resistance factors of pregnancy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hausman, D.B.; Singh, R.; Martin, R.J.
1986-03-01
To determine if late-term pregnant serum and/or placenta could induce insulin resistance in normal adipose cells, the authors have developed an insulin sensitive bioassay system. Cells isolated from epididymal fat pads of 250-275 g Sprague Dawley rats are preincubated for 3 hours at 37/sup 0/ in media 199 and serum or placental extract. The cells are washed free of serum and tested for metabolic activity in a 2 hour incubation which measures the conversion of U-/sup 14/C-glucose to /sup 14/CO/sub 2/ and to /sup 14/C-triglyceride fatty acids under basal and insulin stimulated conditions. Maximal insulin responsiveness (350-450% basal for CO/submore » 2/ and 1400-1700% basal for fatty acids) is achieved using Worthington Type II collagenase and a 45-60 minute digestion period for cell isolations and Krebs-Ringer bicarbonate buffer containing 0.5 mM glucose, 2% Armour bovine serum albumin (CRG-7), 1000 ..mu..U/ml insulin and 110,000 to 120,000 cells in the 2 hour incubations. Using this bioasssay system the authors have found that insulin responsiveness, in terms of glucose conversion to fatty acids, is unchanged when cells are preincubated with 5% control pig serum but reduced following preincubation with late pregnant (110 day) pig serum. In future experiments the authors hope to further characterize the factor(s) in pregnant serum responsible for inducing this metabolic effect.« less
Lie, Shervi; Hui, Melisa; McMillen, I. Caroline; Muhlhausler, Beverly S.; Posterino, Giuseppe S.; Dunn, Stacey L.; Wang, Kimberley C.; Botting, Kimberley J.
2014-01-01
It is unknown whether cardiomyocyte hypertrophy and the transition to fatty acid oxidation as the main source of energy after birth is dependent on the maturation of the cardiomyocytes' metabolic system, or on the limitation of substrate availability before birth. This study aimed to investigate whether intrafetal administration of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, during late gestation can stimulate the expression of factors regulating cardiac growth and metabolism in preparation for birth, and the consequences of cardiac contractility in the fetal sheep at ∼140 days gestation. The mRNA expression and protein abundance of key factors regulating growth and metabolism were quantified using quantitative RT-PCR and Western blot analysis, respectively. Cardiac contractility was determined by measuring the Ca2+ sensitivity and maximum Ca2+-activated force of skinned cardiomyocyte bundles. Rosiglitazone-treated fetuses had a lower cardiac abundance of insulin-signaling molecules, including insulin receptor-β, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 (Tyr-895), phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, PI3K catalytic subunit p110α, phospho-3-phosphoinositide-dependent protein kinase 1 (Ser-241), protein kinase B (Akt-1), phospho-Akt (Ser-273), PKCζ, phospho-PKCζ(Thr-410), Akt substrate 160 kDa (AS160), phospho-AS160 (Thr-642), and glucose transporter type-4. Additionally, cardiac abundance of regulators of fatty acid β-oxidation, including adiponectin receptor 1, AMPKα, phospho-AMPKα (Thr-172), phospho-acetyl CoA carboxylase (Ser-79), carnitine palmitoyltransferase-1, and PGC-1α was lower in the rosiglitazone-treated group. Rosiglitazone administration also resulted in a decrease in cardiomyocyte size. Rosiglitazone administration in the late-gestation sheep fetus resulted in a decreased abundance of factors regulating cardiac glucose uptake, fatty acid β-oxidation, and cardiomyocyte size. These findings suggest that activation of PPAR-γ using rosiglitazone does not promote the maturation of cardiomyocytes; rather, it may decrease cardiac metabolism and compromise cardiac health later in life. PMID:24477540
Lie, Shervi; Hui, Melisa; McMillen, I Caroline; Muhlhausler, Beverly S; Posterino, Giuseppe S; Dunn, Stacey L; Wang, Kimberley C; Botting, Kimberley J; Morrison, Janna L
2014-03-15
It is unknown whether cardiomyocyte hypertrophy and the transition to fatty acid oxidation as the main source of energy after birth is dependent on the maturation of the cardiomyocytes' metabolic system, or on the limitation of substrate availability before birth. This study aimed to investigate whether intrafetal administration of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, during late gestation can stimulate the expression of factors regulating cardiac growth and metabolism in preparation for birth, and the consequences of cardiac contractility in the fetal sheep at ∼140 days gestation. The mRNA expression and protein abundance of key factors regulating growth and metabolism were quantified using quantitative RT-PCR and Western blot analysis, respectively. Cardiac contractility was determined by measuring the Ca(2+) sensitivity and maximum Ca(2+)-activated force of skinned cardiomyocyte bundles. Rosiglitazone-treated fetuses had a lower cardiac abundance of insulin-signaling molecules, including insulin receptor-β, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 (Tyr-895), phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, PI3K catalytic subunit p110α, phospho-3-phosphoinositide-dependent protein kinase 1 (Ser-241), protein kinase B (Akt-1), phospho-Akt (Ser-273), PKCζ, phospho-PKCζ(Thr-410), Akt substrate 160 kDa (AS160), phospho-AS160 (Thr-642), and glucose transporter type-4. Additionally, cardiac abundance of regulators of fatty acid β-oxidation, including adiponectin receptor 1, AMPKα, phospho-AMPKα (Thr-172), phospho-acetyl CoA carboxylase (Ser-79), carnitine palmitoyltransferase-1, and PGC-1α was lower in the rosiglitazone-treated group. Rosiglitazone administration also resulted in a decrease in cardiomyocyte size. Rosiglitazone administration in the late-gestation sheep fetus resulted in a decreased abundance of factors regulating cardiac glucose uptake, fatty acid β-oxidation, and cardiomyocyte size. These findings suggest that activation of PPAR-γ using rosiglitazone does not promote the maturation of cardiomyocytes; rather, it may decrease cardiac metabolism and compromise cardiac health later in life.
Triunfo, Stefania; Crovetto, Francesca; Crispi, Fatima; Rodriguez-Sureda, Victor; Dominguez, Carmen; Nadal, Alfons; Peguero, Anna; Gratacos, Eduard; Figueras, Francesc
2016-06-01
To explore in women with late-onset preeclampsia (PE) the association between maternal levels of angiogenic/antiangiogenic factors in the first trimester of pregnancy and histological findings attributable to placental underperfusion (PUP). A nested case-control cohort study was conducted in 73 women with pregnancies complicated by late-onset PE (>34 weeks at delivery) matched with controls. First trimester uterine artery Doppler (UtA); maternal levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were retrieved. Placentas were histologically evaluated using a hierarchical and standardized classification system. One-way ANOVA with linear polynomial contrast or linear-by-linear association test was performed to test the hypothesis of a linear association across study groups (controls, PE without PUP and PE with PUP). In 54 (74%) placentas, 89 placental histological findings qualifying for PUP were found. Across study groups, significant values were observed in maternal levels of decreased PlGF (MoM values: 1.53, 1.41 and 1.37; p < 0.001), increased sFlt-1 (MoM values: 3.11, 3.11 and 3.22; p = 0.002), increased sFlt-1/PlGF ratio (MoM values: 2.3, 2.3 and 2.44; p < 0.001), abnormal UtA Doppler (MoM values: 1, 1.26 and 1.32; p < 0.001), and worse perinatal outcomes in terms of gestational age at delivery, cesarean section for not reassuring fetal status, birth weight and neonatal acidosis. In late-onset PE an imbalance of circulating angiogenic and anti-angiogenic factors already present at 8-10 weeks of pregnancy was associated with histological findings reflecting placental insufficiency. An early first trimester screening by angiogenic factors might help to identify patients with placental involvement among late-onset PE cases. In late-onset preeclampsia, first-trimester uterine Doppler and circulating levels of angiogenic/antiangiogenic factors are associated with placental underperfusion. Copyright © 2016 Elsevier Ltd. All rights reserved.
Paradox of Prescribing Late Chemotherapy: Oncologists Explain.
Bluhm, Minnie; Connell, Cathleen M; De Vries, Raymond G; Janz, Nancy K; Bickel, Kathleen E; Silveira, Maria J
2016-12-01
The value of chemotherapy for patients with cancer in the last weeks of life warrants examination. Late chemotherapy may not improve survival or quality of life but typically precludes hospice enrollment and may result in additional symptoms, increased use of other aggressive treatments, and worsening quality of life. Few studies have explored oncologists' rationales for administering chemotherapy near death. This study examines the self-reported factors that influence oncologists' decisions about late chemotherapy. In-depth individual interviews were conducted with 17 oncologists through a semistructured interview guide. Interviews were audio recorded and transcribed verbatim. Transcripts were coded and analyzed using conventional content analysis, a qualitative method that allows the detection and analysis of patterns in the data. Clinical factors take priority in determining late chemotherapy decisions when clear treatment choices exist. When clinical factors are ambiguous, emotion becomes a highly salient influence. Oncologists view late chemotherapy to be patient driven and use it to palliate emotional distress and maintain patient hope even when physical benefit is unexpected. Oncologists experience unique and difficult challenges when caring for dying patients, including emotionally draining communication, overwhelming responsibility for life/death, limitations of oncology to heal, and prognostic uncertainty. These challenges are also eased by offering late chemotherapy. The findings reveal a nuanced understanding of why oncologists find it difficult to refuse chemotherapy treatment for patients near death. Optimal end-of-life treatment decisions require supportive interventions and system change, both of which must take into account the challenges oncologists face.
Al-Holou, Shaza N; Tucker, William R; Agrón, Elvira; Clemons, Traci E; Cukras, Catherine; Ferris, Frederick L; Chew, Emily Y
2015-12-01
To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the majority of previous studies. Statins have been demonstrated to reduce the risk of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression. Published by Elsevier Inc.
Involvement of Clostridium botulinum ATCC 3502 Sigma Factor K in Early-Stage Sporulation
Kirk, David G.; Dahlsten, Elias; Zhang, Zhen; Korkeala, Hannu
2012-01-01
A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σK is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods. PMID:22544236
Involvement of Clostridium botulinum ATCC 3502 sigma factor K in early-stage sporulation.
Kirk, David G; Dahlsten, Elias; Zhang, Zhen; Korkeala, Hannu; Lindström, Miia
2012-07-01
A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σ(K) is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods.
Hayashi, Kazuhiro; Hirashiki, Akihiro; Kodama, Akio; Kobayashi, Kiyonori; Yasukawa, Yuto; Shimizu, Miho; Kondo, Takahisa; Komori, Kimihiro; Murohara, Toyoaki
2016-04-01
Early ambulation after open abdominal aortic aneurysm (AAA) surgery is assumed to play a key role in preventing postoperative complications and reducing hospital length of stay. However, the factors predicting early ambulation after open AAA surgery have not yet been sufficiently investigated. Here, we investigated which preoperative and intraoperative variables are associated with start time for ambulation in patients after open AAA surgery. A total of 67 consecutive patients undergoing open AAA surgery were included in the study [male, 62 (92 %); mean age, 68 years (range, 47-82 years), mean AAA diameter, 53 mm (range, 28-80 mm)]. Preoperative physical activity was examined by means of 6-min walk distance (6MWD) and a medical interview. Patients were divided into two groups, according to when independence in walking was attained: early group <3 days (n = 36) and late group ≥3 days (n = 31), and the pre-, intra-, and postoperative recovery data were compared. There were no significant differences in patient baseline characteristics or intraoperative data between the two groups. The number of patients engaging in preoperative regular physical activity and 6MWD were significantly greater (p = 0.042 and p = 0.034, respectively) in the early group than in the late group. In addition, time to hospital discharge was significantly shorter in the early group than in the late group (p = 0.031). Binary logistic regression analysis showed that preoperative regular physical activity was the only independent factor for identifying patients in the early group (odds ratio 2.769, 95 % confidence interval 1.024-7.487, p = 0.045). These results suggest that engaging in regular physical activity is an effective predictor of early ambulation after open AAA surgery.
Wang, Xia; Chang, Qingyun; Wang, Yu; Su, Feng; Zhang, Shicui
2014-12-01
Two different mechanisms are considered to be related to aging. Cumulative molecular damage caused by reactive oxygen species (ROS), the by-products of oxidative phosphorylation, is one of these mechanisms (ROS concept). Deregulated nutrient sensing by the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway is the second mechanism (IIS concept). Temperature reduction (TR) is known to modulate aging and prolong life span in a variety of organisms, but the mechanisms remain poorly defined. Here we first demonstrate that late-onset TR from 26 °C to 22 °C extends mean life span and maximum life span by approximately 5.2 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We then show that TR is able to decrease the accumulation of the histological aging markers senescence-associated β-galactosidase (SA-β-Gal) in the epithelium and lipofuscin (LF) in the liver and to reduce protein oxidation and lipid peroxidation levels in the muscle. We also show that TR can enhance the activities of catalase, glutathione peroxidase, and superoxide dismutase, and stimulate the synthesis of SirT1 and FOXO3A/FOXO1A, both of which are the downstream regulators of the IIS pathway. Taken together, our findings suggest that late-onset TR, a simple non-intrusion intervention, can retard the aging process in aged fish, resulting in their life span extension, via a synergistic action of an anti-oxidant system and the IIS pathway. This also suggests that combined assessment of the ROS and IIS concepts will contribute to providing a more comprehensive view of the anti-aging process.
Exposure to dust mite allergen and endotoxin in early life and asthma and atopy in childhood
Celedón, Juan C.; Milton, Donald K.; Ramsey, Clare D.; Litonjua, Augusto A.; Ryan, Louise; Platts-Mills, Thomas A. E.; Gold, Diane R.
2013-01-01
Background There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age. Objectives To examine the relation between exposure to dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and atopy in high-risk children. Methods Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area. Results In multivariate analyses, early exposure to high levels of dust mite allergen (≥10 μg/g) was associated with increased risks of asthma at age 7 years (odds ratio [OR], 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% CI, 1.5-16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3 months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI, 0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure in early life was associated with an increased risk of any wheeze between ages 1 and 7 years that did not change significantly with time (hazard ratio for each quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43). Conclusion Among children at risk of atopy, early exposure to high levels of dust mite allergen is associated with increased risks of asthma and late-onset wheeze. In these children, endotoxin exposure is associated with a reduced risk of atopy but an increased risk of wheeze. Clinical implications Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children. PMID:17507083
Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects
DOE Office of Scientific and Technical Information (OSTI.GOV)
Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh
2016-01-01
Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed themore » dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late RILD are also due to different pathologies. As such, new radiation techniques reducing irradiated volume might change the dose-limiting toxicity of the radiation therapy treatment.« less
EPO improved neurologic outcome in rat pups late after traumatic brain injury.
Schober, Michelle E; Requena, Daniela F; Rodesch, Christopher K
2018-05-01
In adult rats, erythropoietin improved outcomes early and late after traumatic brain injury, associated with increased levels of Brain Derived Neurotrophic Factor. Using our model of pediatric traumatic brain injury, controlled cortical impact in 17-day old rats, we previously showed that erythropoietin increased hippocampal neuronal fraction in the first two days after injury. Erythropoietin also decreased activation of caspase3, an apoptotic enzyme modulated by Brain Derived Neurotrophic Factor, and improved Novel Object Recognition testing 14 days after injury. Data on long-term effects of erythropoietin on Brain Derived Neurotrophic Factor expression, histology and cognitive function after developmental traumatic brain injury are lacking. We hypothesized that erythropoietin would increase Brain Derived Neurotrophic Factor and improve long-term object recognition in rat pups after controlled cortical impact, associated with increased neuronal fraction in the hippocampus. Rats pups received erythropoietin or vehicle at 1, 24, and 48 h and 7 days after injury or sham surgery followed by histology at 35 days, Novel Object Recognition testing at adulthood, and Brain Derived Neurotrophic Factor measurements early and late after injury. Erythropoietin improved Novel Object Recognition performance and preserved hippocampal volume, but not neuronal fraction, late after injury. Improved object recognition in erythropoietin treated rats was associated with preserved hippocampal volume late after traumatic brain injury. Erythropoietin is approved to treat various pediatric conditions. Coupled with exciting experimental and clinical studies suggesting it is beneficial after neonatal hypoxic ischemic brain injury, our preliminary findings support further study of erythropoietin use after developmental traumatic brain injury. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Ha, Christina Y; Newberry, Rodney D; Stone, Christian D; Ciorba, Matthew A
2010-08-01
The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Fan, Tingting; Xu, Shibin; Huang, Fei; Zhao, Jinping
2018-04-01
This study compares the interdecadal variations in tropical cyclone (TC) activities over the western North Pacific (WNP) basin during the peak season (July-September) and late season (October-December) of 1955-2014 and explores the possible physical mechanisms behind the variations. Both the peak- and late-season tropical storm (TS) days show distinct interdecadal variations, while the late-season TS days lead the peak-season TS days by approximately 4 years on an interdecadal time scale. The late-season TC activity is related to the east-west sea surface temperature (SST) gradient across the equatorial Pacific. The westerly winds induced by the SST gradient can reduce the vertical wind shear and increase the low-level vorticity, which favors TC genesis over the TC genesis region. The peak-season TC activity appears to relate to the SST gradient between the Indian Ocean and the Central Pacific. The westerly wind induced by the SST gradient can reduce the vertical wind shear and increase the mid-level relative humidity, thereby enhancing the TC activity. The full picture of the interdecadal variation in the WNP TC activity during the peak and late seasons revealed in this study provides a new perspective on the seasonal TC forecasts and future projections.
Yang, Ya-Hsu; Teng, Hao-Wei; Lai, Yen-Ting; Li, Szu-Yuan; Lin, Chih-Ching; Yang, Albert C; Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Lin, Chiao-Fan; Hsu, Fu-Ying; Liu, Chih-Kuang; Liu, Wen-Sheng
2015-01-01
Patients with late-onset depression (LOD) have been reported to run a higher risk of subsequent dementia. The present study was conducted to assess whether statins can reduce the risk of dementia in these patients. We used the data from National Health Insurance of Taiwan during 1996-2009. Standardized Incidence Ratios (SIRs) were calculated for LOD and subsequent dementia. The criteria for LOD diagnoses included age ≥65 years, diagnosis of depression after 65 years of age, at least three service claims, and treatment with antidepressants. The time-dependent Cox proportional hazards model was applied for multivariate analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matching patients for validation studies. Kaplan-Meier curve estimate was used to measure the group of patients with dementia living after diagnosis of LOD. Totally 45,973 patients aged ≥65 years were enrolled. The prevalence of LOD was 12.9% (5,952/45,973). Patients with LOD showed to have a higher incidence of subsequent dementia compared with those without LOD (Odds Ratio: 2.785; 95% CI 2.619-2.958). Among patients with LOD, lipid lowering agent (LLA) users (for at least 3 months) had lower incidence of subsequent dementia than non-users (Hazard Ratio = 0.781, 95% CI 0.685-0.891). Nevertheless, only statins users showed to have reduced risk of dementia (Hazard Ratio = 0.674, 95% CI 0.547-0.832) while other LLAs did not, which was further validated by Kaplan-Meier estimates after we used the propensity scores with the one-to-one nearest-neighbor matching model to control the confounding factors. Statins may reduce the risk of subsequent dementia in patients with LOD.
Late INa increases diastolic SR-Ca2+-leak in atrial myocardium by activating PKA and CaMKII
Fischer, Thomas H.; Herting, Jonas; Mason, Fleur E.; Hartmann, Nico; Watanabe, Saera; Nikolaev, Viacheslav O.; Sprenger, Julia U.; Fan, Peidong; Yao, Lina; Popov, Aron-Frederik; Danner, Bernhard C.; Schöndube, Friedrich; Belardinelli, Luiz; Hasenfuss, Gerd; Maier, Lars S.; Sossalla, Samuel
2015-01-01
Aims Enhanced cardiac late Na current (late INa) and increased sarcoplasmic reticulum (SR)-Ca2+-leak are both highly arrhythmogenic. This study seeks to identify signalling pathways interconnecting late INa and SR-Ca2+-leak in atrial cardiomyocytes (CMs). Methods and results In murine atrial CMs, SR-Ca2+-leak was increased by the late INa enhancer Anemonia sulcata toxin II (ATX-II). An inhibition of Ca2+/calmodulin-dependent protein kinase II (Autocamide-2-related inhibitory peptide), protein kinase A (H89), or late INa (Ranolazine or Tetrodotoxin) all prevented ATX-II-dependent SR-Ca2+-leak. The SR-Ca2+-leak induction by ATX-II was not detected when either the Na+/Ca2+ exchanger was inhibited (KBR) or in CaMKIIδc-knockout mice. FRET measurements revealed increased cAMP levels upon ATX-II stimulation, which could be prevented by inhibition of adenylyl cyclases (ACs) 5 and 6 (NKY 80) but not by inhibition of phosphodiesterases (IBMX), suggesting PKA activation via an AC-dependent increase of cAMP levels. Western blots showed late INa-dependent hyperphosphorylation of CaMKII as well as PKA target sites at ryanodine receptor type-2 (-S2814 and -S2808) and phospholamban (-Thr17, -S16). Enhancement of late INa did not alter Ca2+-transient amplitude or SR-Ca2+-load. However, upon late INa activation and simultaneous CaMKII inhibition, Ca2+-transient amplitude and SR-Ca2+-load were increased, whereas PKA inhibition reduced Ca2+-transient amplitude and load and additionally slowed Ca2+ elimination. In atrial CMs from patients with atrial fibrillation, inhibition of late INa, CaMKII, or PKA reduced the SR-Ca2+-leak. Conclusion Late INa exerts distinct effects on Ca2+ homeostasis in atrial myocardium through activation of CaMKII and PKA. Inhibition of late INa represents a potential approach to attenuate CaMKII activation and decreases SR-Ca2+-leak in atrial rhythm disorders. The interconnection with the cAMP/PKA system further increases the antiarrhythmic potential of late INa inhibition. PMID:25990311
Ajiro, Masahiko; Tang, Shuang; Doorbar, John; Zheng, Zhi-Ming
2016-10-15
Human papillomavirus 18 (HPV18) is the second most common oncogenic HPV type associated with cervical, anogenital, and oropharyngeal cancers. Like other oncogenic HPVs, HPV18 encodes two major (one early and one late) polycistronic pre-mRNAs that are regulated by alternative RNA splicing to produce a repertoire of viral transcripts for the expression of individual viral genes. However, RNA cis-regulatory elements and trans-acting factors contributing to HPV18 alternative RNA splicing remain unknown. In this study, an exonic splicing enhancer (ESE) in the nucleotide (nt) 3520 to 3550 region in the HPV18 genome was identified and characterized for promotion of HPV18 929^3434 splicing and E1^E4 production through interaction with SRSF3, a host oncogenic splicing factor differentially expressed in epithelial cells and keratinocytes. Introduction of point mutations in the SRSF3-binding site or knockdown of SRSF3 expression in cells reduces 929^3434 splicing and E1^E4 production but activates other, minor 929^3465 and 929^3506 splicing. Knockdown of SRSF3 expression also enhances the expression of E2 and L1 mRNAs. An exonic splicing silencer (ESS) in the HPV18 nt 612 to 639 region was identified as being inhibitory to the 233^416 splicing of HPV18 E6E7 pre-mRNAs via binding to hnRNP A1, a well-characterized, abundantly and ubiquitously expressed RNA-binding protein. Introduction of point mutations into the hnRNP A1-binding site or knockdown of hnRNP A1 expression promoted 233^416 splicing and reduced E6 expression. These data provide the first evidence that the alternative RNA splicing of HPV18 pre-mRNAs is subject to regulation by viral RNA cis elements and host trans-acting splicing factors. Expression of HPV18 genes is regulated by alternative RNA splicing of viral polycistronic pre-mRNAs to produce a repertoire of viral early and late transcripts. RNA cis elements and trans-acting factors contributing to HPV18 alternative RNA splicing have been discovered in this study for the first time. The identified ESS at the E7 open reading frame (ORF) prevents HPV18 233^416 splicing in the E6 ORF through interaction with a host splicing factor, hnRNP A1, and regulates E6 and E7 expression of the early E6E7 polycistronic pre-mRNA. The identified ESE at the E1^E4 ORF promotes HPV18 929^3434 splicing of both viral early and late pre-mRNAs and E1^E4 production through interaction with SRSF3. This study provides important observations on how alternative RNA splicing of HPV18 pre-mRNAs is subject to regulation by viral RNA cis elements and host splicing factors and offers potential therapeutic targets to overcome HPV-related cancer. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Ajiro, Masahiko; Tang, Shuang; Doorbar, John
2016-01-01
ABSTRACT Human papillomavirus 18 (HPV18) is the second most common oncogenic HPV type associated with cervical, anogenital, and oropharyngeal cancers. Like other oncogenic HPVs, HPV18 encodes two major (one early and one late) polycistronic pre-mRNAs that are regulated by alternative RNA splicing to produce a repertoire of viral transcripts for the expression of individual viral genes. However, RNA cis-regulatory elements and trans-acting factors contributing to HPV18 alternative RNA splicing remain unknown. In this study, an exonic splicing enhancer (ESE) in the nucleotide (nt) 3520 to 3550 region in the HPV18 genome was identified and characterized for promotion of HPV18 929^3434 splicing and E1^E4 production through interaction with SRSF3, a host oncogenic splicing factor differentially expressed in epithelial cells and keratinocytes. Introduction of point mutations in the SRSF3-binding site or knockdown of SRSF3 expression in cells reduces 929^3434 splicing and E1^E4 production but activates other, minor 929^3465 and 929^3506 splicing. Knockdown of SRSF3 expression also enhances the expression of E2 and L1 mRNAs. An exonic splicing silencer (ESS) in the HPV18 nt 612 to 639 region was identified as being inhibitory to the 233^416 splicing of HPV18 E6E7 pre-mRNAs via binding to hnRNP A1, a well-characterized, abundantly and ubiquitously expressed RNA-binding protein. Introduction of point mutations into the hnRNP A1-binding site or knockdown of hnRNP A1 expression promoted 233^416 splicing and reduced E6 expression. These data provide the first evidence that the alternative RNA splicing of HPV18 pre-mRNAs is subject to regulation by viral RNA cis elements and host trans-acting splicing factors. IMPORTANCE Expression of HPV18 genes is regulated by alternative RNA splicing of viral polycistronic pre-mRNAs to produce a repertoire of viral early and late transcripts. RNA cis elements and trans-acting factors contributing to HPV18 alternative RNA splicing have been discovered in this study for the first time. The identified ESS at the E7 open reading frame (ORF) prevents HPV18 233^416 splicing in the E6 ORF through interaction with a host splicing factor, hnRNP A1, and regulates E6 and E7 expression of the early E6E7 polycistronic pre-mRNA. The identified ESE at the E1^E4 ORF promotes HPV18 929^3434 splicing of both viral early and late pre-mRNAs and E1^E4 production through interaction with SRSF3. This study provides important observations on how alternative RNA splicing of HPV18 pre-mRNAs is subject to regulation by viral RNA cis elements and host splicing factors and offers potential therapeutic targets to overcome HPV-related cancer. PMID:27489271
Burdwood, Erin N; Simons, Robert F
2016-04-01
The present study employed late ERPs to examine differences in the association between neural responses to romantic partners and relationship quality factors across men and women. Participants passively viewed photos of their romantic partners, celebrities, and strangers during a computerized facial processing task. All participants demonstrated enhanced positivity to partner faces at late ERP components (P3 and LPP), furthering the notion that significant others elicit more motivated and sustained attention than do other familiar or unfamiliar individuals. Neural responses to romantic partner faces were influenced by factors including overall relationship quality, investment, and communication quality, with associations varying by gender. Results highlight the key role that relationship quality factors play in the immediate processing of romantic partners-a finding with implications for couples counseling and research. © 2015 Society for Psychophysiological Research.
Fungal Infections: Their Diagnosis and Treatment in Transplant Recipients
Van Thiel, David H.; George, Magdalena; Moore, Christopher M.
2012-01-01
Systemic fungal infections typically occur in individuals who are seriously ill with recognized risk factors such as those frequently found in transplant recipients. Unfortunately, they are often diagnosed late, when the efficacy of the available treatments is low, often less than 50%, and the cost in terms of lives lost, hospital length of stay, and total hospital costs is substantially increased. The application of antifungal therapies associated with reported efficacy rates greater than 50% are those used prophylactically. When used prophylactically, these infections are reduced in greater than 95% of the expected cases. The choice of a prophylactic agent should be based upon its ease of administration, lack of adverse effects, reduced likelihood of potential drug interactions, and its efficacy in patients with established risk factors and comorbid disease processes that include renal, hepatic, and chronic pulmonary disease. The indications for the use of currently available antifungal agents, their adverse effects, drug interactions, ease of dosing, and applicability in patients with preexisting disease states, and especially in liver transplant recipients, are presented in this paper. PMID:22966464
Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer’s Disease Prevention
Schelke, Matthew W.; Attia, Peter; Palenchar, Daniel J.; Kaplan, Bob; Mureb, Monica; Ganzer, Christine A.; Scheyer, Olivia; Rahman, Aneela; Kachko, Robert; Krikorian, Robert; Mosconi, Lisa; Isaacson, Richard S.
2018-01-01
Alzheimer’s disease (AD) is a neurodegenerative dementia that affects nearly 50 million people worldwide and is a major source of morbidity, mortality, and healthcare expenditure. While there have been many attempts to develop disease-modifying therapies for late-onset AD, none have so far shown efficacy in humans. However, the long latency between the initial neuronal changes and onset of symptoms, the ability to identify patients at risk based on family history and genetic markers, and the emergence of AD biomarkers for preclinical disease suggests that early risk-reducing interventions may be able to decrease the incidence of, delay or prevent AD. In this review, we discuss six mechanisms—dysregulation of glucose metabolism, inflammation, oxidative stress, trophic factor release, amyloid burden, and calcium toxicity—involved in AD pathogenesis that offer promising targets for risk-reducing interventions. In addition, we offer a blueprint for a multi-modality AD risk reduction program that can be clinically implemented with the current state of knowledge. Focused risk reduction aimed at particular pathological factors may transform AD to a preventable disorder in select cases. PMID:29706884
Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer's Disease Prevention.
Schelke, Matthew W; Attia, Peter; Palenchar, Daniel J; Kaplan, Bob; Mureb, Monica; Ganzer, Christine A; Scheyer, Olivia; Rahman, Aneela; Kachko, Robert; Krikorian, Robert; Mosconi, Lisa; Isaacson, Richard S
2018-01-01
Alzheimer's disease (AD) is a neurodegenerative dementia that affects nearly 50 million people worldwide and is a major source of morbidity, mortality, and healthcare expenditure. While there have been many attempts to develop disease-modifying therapies for late-onset AD, none have so far shown efficacy in humans. However, the long latency between the initial neuronal changes and onset of symptoms, the ability to identify patients at risk based on family history and genetic markers, and the emergence of AD biomarkers for preclinical disease suggests that early risk-reducing interventions may be able to decrease the incidence of, delay or prevent AD. In this review, we discuss six mechanisms-dysregulation of glucose metabolism, inflammation, oxidative stress, trophic factor release, amyloid burden, and calcium toxicity-involved in AD pathogenesis that offer promising targets for risk-reducing interventions. In addition, we offer a blueprint for a multi-modality AD risk reduction program that can be clinically implemented with the current state of knowledge. Focused risk reduction aimed at particular pathological factors may transform AD to a preventable disorder in select cases.
How Distinctive Processing Enhances Hits and Reduces False Alarms
Hunt, R. Reed; Smith, Rebekah E.
2015-01-01
Distinctive processing is a concept designed to account for precision in memory, both correct responses and avoidance of errors. The principal question addressed in two experiments is how distinctive processing of studied material reduces false alarms to familiar distractors. Jacoby (Jacoby, Kelley, & McElree, 1999) has used the metaphors early selection and late correction to describe two different types of control processes. Early selection refers to limitations on access whereas late correction describes controlled monitoring of accessed information. The two types of processes are not mutually exclusive, and previous research has provided evidence for the operation of both. The data reported here extend previous work to a criterial recollection paradigm and to a recognition memory test. The results of both experiments show that variables that reduce false memory for highly familiar distracters continue to exert their effect under conditions of minimal post-access monitoring. Level of monitoring was reduced in the first experiment through test instructions and in the second experiment through speeded test responding. The results were consistent with the conclusion that both early selection and late correction operate to control accuracy in memory. PMID:26034343
Zou, Yan; Song, Tao; Yu, Wei; Zhao, Ruping; Wang, Yong; Xie, Ruifei; Chen, Tian; Wu, Bo; Wu, Shixiu
2014-03-01
The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.
Why do pregnant women present late for their first antenatal care consultation in Cameroon?
Tolefac, Paul Nkemtendong; Halle-Ekane, Gregory Edie; Agbor, Valirie Ndip; Sama, Carlson Barbila; Ngwasiri, Calypse; Tebeu, Pierre Marie
2017-01-01
Early initiation of antenatal care visits is an essential component of services to improving maternal and new born health. The Cameroonian Demographic and Health Survey conducted in 2011 indicated that only 34% of pregnant women start antenatal care in the first trimester. However, detailed study to identify factors associated with late initiation of care has not been conducted in Cameroon. The aim of this study was to assess the prevalence of late booking first ANC visit amongst attendance of first ANC and the determinants of late first ANC in Douala general hospital. It was a cross sectional analytic study over the period of 5 months in Douala general hospital. The study subjects were pregnant women visiting the facilities for the first time during the index pregnancy. Data were collected using pre-tested questionnaire. Logistic regression analysis was done to identify factors associated with late first ANC with the level of significance set at 0.05. A total of 293 women participated in the study; 129 (44.0%) of them came for their first ANC visit late, after 12 weeks of gestation. Most common reasons for coming late for first ANC were financial constraints (34.5%, 45) and long distance to the hospital (34.5%, 45). Factors associated with late start of first ANC after logistic regression were: family size greater than 4 (OR = 2, 95% CI = 1.25-3.19, p value = 0.004), long distance to the hospital (OR = 1.84, 95% CI = 1.1-3.07, p value = 0.02) and low monthly income level less than 200US dollars (OR = 3.2, 95% CI = 1.33-3.54, p value = 0.002). About half of pregnant women do not start ANC early in the first trimester largely due to large family size, low monthly income and long distance to the hospital.
Muhamadi, Lubega; Tumwesigye, Nazarius Mbona; Kadobera, Daniel; Marrone, Gaetano; Wabwire-Mangen, Fred; Pariyo, George; Peterson, Stefan; Ekström, Anna Mia
2011-01-01
Although WHO recommends starting antiretroviral treatment at a CD4 count of 350 cells/[µ]L, many Ugandan districts still struggle with large proportions of clients initiating ART very late at CD4<50 cells/[µ]L. This study seeks to establish crucial risk factors for very late ART initiation in eastern Uganda. All adult HIV-infected clients on ART in Iganga who enrolled between 2005 and 2009 were eligible for this case-control study. Clients who started ART at CD4 cell count of <50 cells/[µ]L (very late initiators) were classified as cases and 50-200 cells/[µ]L (late initiators) as control subjects. A total of 152 cases and 202 controls were interviewed. Multivariate analyses were performed to calculate adjusted odds ratios and 95% confidence intervals. Reported health system-related factors associated with very late ART initiation were stock-outs of antiretroviral drugs stock-outs (affecting 70% of the cases and none of the controls), competition from traditional/spiritual healers (AOR 7.8, 95 CI% 3.7-16.4), and lack of pre-ARV care (AOR 4.6, 95% CI: 2.3-9.3). Men were 60% more likely and subsistence farmers six times more likely (AOR 6.3, 95% CI: 3.1-13.0) to initiate ART very late. Lack of family support tripled the risk of initiating ART very late (AOR 3.3, 95% CI: 1.6-6.6). Policy makers should prevent ARV stock-outs though effective ARV procurement and supply chain management. New HIV clients should seek pre-ARV care for routine monitoring and determination of ART eligibility. ART services should be more affordable, accessible and user-friendly to make them more attractive than traditional healers.
Grosheva, Maria; Nohroudi, Klaus; Schwarz, Alisa; Rink, Svenja; Bendella, Habib; Sarikcioglu, Levent; Klimaschewski, Lars; Gordon, Tessa; Angelov, Doychin N
2016-05-01
After peripheral nerve injury, recovery of motor performance negatively correlates with the poly-innervation of neuromuscular junctions (NMJ) due to excessive sprouting of the terminal Schwann cells. Denervated muscles produce short-range diffusible sprouting stimuli, of which some are neurotrophic factors. Based on recent data that vibrissal whisking is restored perfectly during facial nerve regeneration in blind rats from the Sprague Dawley (SD)/RCS strain, we compared the expression of brain derived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF2), insulin growth factors 1 and 2 (IGF1, IGF2) and nerve growth factor (NGF) between SD/RCS and SD-rats with normal vision but poor recovery of whisking function after facial nerve injury. To establish which trophic factors might be responsible for proper NMJ-reinnervation, the transected facial nerve was surgically repaired (facial-facial anastomosis, FFA) for subsequent analysis of mRNA and proteins expressed in the levator labii superioris muscle. A complicated time course of expression included (1) a late rise in BDNF protein that followed earlier elevated gene expression, (2) an early increase in FGF2 and IGF2 protein after 2 days with sustained gene expression, (3) reduced IGF1 protein at 28 days coincident with decline of raised mRNA levels to baseline, and (4) reduced NGF protein between 2 and 14 days with maintained gene expression found in blind rats but not the rats with normal vision. These findings suggest that recovery of motor function after peripheral nerve injury is due, at least in part, to a complex regulation of lesion-associated neurotrophic factors and cytokines in denervated muscles. The increase of FGF-2 protein and concomittant decrease of NGF (with no significant changes in BDNF or IGF levels) during the first week following FFA in SD/RCS blind rats possibly prevents the distal branching of regenerating axons resulting in reduced poly-innervation of motor endplates. Copyright © 2016 Elsevier Inc. All rights reserved.
The role of vitamin D in the prevention of late-life depression.
Okereke, Olivia I; Singh, Ankura
2016-07-01
In this article, we review current evidence regarding potential benefits of vitamin D for improving mood and reducing depression risk in older adults. We summarize gaps in knowledge and describe future efforts that may clarify the role of vitamin D in late-life depression prevention. MEDLINE and PsychINFO databases were searched for all articles on vitamin D and mood that had been published up to and including May 2015. Observational studies and randomized trials with 50 or more participants were included. We excluded studies that involved only younger adults and/or exclusively involved persons with current depression. Twenty observational (cross-sectional and prospective) studies and 10 randomized trials (nine were randomized placebo-controlled trials [RCTs]; one was a randomized blinded comparison trial) were reviewed. Inverse associations of vitamin D blood level or vitamin D intake with depression were found in 13 observational studies; three identified prospective relations. Results from all but one of the RCTs showed no statistically significant differences in depression outcomes between vitamin D and placebo groups. Observational studies were mostly cross-sectional and frequently lacked adequate control of confounding. RCTs often featured low treatment doses, suboptimal post-intervention changes in biochemical levels of vitamin D, and/or short trial durations. Vitamin D level-mood associations were observed in most, but not all, observational studies; results indicated that vitamin D deficiency may be a risk factor for late-life depression. However, additional data from well-designed RCTs are required to determine the impact of vitamin D in late-life depression prevention. Copyright © 2016 Elsevier B.V. All rights reserved.
Educational Progress of Looked-After Children in England: A Study Using Group Trajectory Analysis.
Sutcliffe, Alastair G; Gardiner, Julian; Melhuish, Edward
2017-09-01
Looked-after children in local authority care are among the most disadvantaged, and measures of their well-being, including educational outcomes, are poorer than other children's. The study sample consisted of all children in England born in academic years 1993 to 1994 through 1997 to 1998 who were in local authority care at any point during the academic years 2005 to 2006 through 2012 to 2013 and for whom results of national tests in literacy and numeracy were available at ages 7, 11, and 16 ( N = 47 500). Group trajectory analysis of children's educational progress identified 5 trajectory groups: low achievement, late improvement, late decline, predominant, and high achievement. Being looked after earlier was associated with a higher probability of following a high achievement trajectory and a lower probability of following a late decline trajectory. For children first looked after between ages 7 and 16, having a longer total time looked after by age 16 was associated with a higher probability of following a high achievement trajectory. For children with poor outcomes at ages 7 and 11, being looked after by age 16 was associated with an increased chance of educational improvement by age 16. This study provides evidence that early entry into care can reduce the risk of poor educational outcomes. It also establishes group trajectory analysis as an effective method for analyzing the educational progress of looked-after children, with the particular strength that it allows factors associated with a late decline or improvement in educational progress to be identified. Copyright © 2017 by the American Academy of Pediatrics.
Yoon, D S; Kim, Y H; Jung, H S; Paik, S; Lee, J W
2011-10-01
This study has aimed to repopulate 'primitive' cells from late-passage mesenchymal stem cells (MSCs) of poor multipotentiality and low cell proliferation rate, by simply altering plating density. Effects of low density culture compared t high density culture on late-passage bone marrow (BM)-derived MSCs and pluripotency markers of multipotentiality were investigated. Cell proliferation, gene expression, RNA interference and differentiation potential were assayed. We repopulated 'primitive' cells by replating late-passage MSCs at low density (17 cells/cm(2) ) regardless of donor age. Repopulated MSCs from low-density culture were smaller cells with spindle shaped morphology compared to MSCs from high-density culture. The latter had enhanced colony-forming ability, proliferation rate, and adipogenic and chondrogenic potential. Strong expression of osteogenic-related genes (Cbfa1, Dlx5, alkaline phosphatase and type Ι collagen) in late-passage MSCs was reduced by replating at low density, whereas expression of three pluripotency markers (Sox2, Nanog and Oct-4), Osterix and Msx2 reverted to levels of early-passage MSCs. Knockdown of Sox2 and Msx2 but not Nanog, using RNA interference, showed significant decrease in colony-forming ability. Specifically, knockdown of Sox2 significantly inhibited multipotentiality and cell proliferation. Our data suggest that plating density should be considered to be a critical factor for enrichment of 'primitive' cells from heterogeneous BM and that replicative senescence and multipotentiality of MSCs during in vitro expansion may be predominantly regulated through Sox2. © 2011 Blackwell Publishing Ltd.
Wang, Xia; Du, Xiaoyuan; Zhou, Yang; Wang, Su; Su, Feng; Zhang, Shicui
2017-06-01
Two of the most studied and widely accepted conjectures on possible aging mechanisms are the oxidative stress hypothesis and the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway. Intermittent fasting (IF) is known to modulate aging and to prolong lifespan in a variety of organisms, but the mechanisms are still under debate. In this study, we first demonstrated that late-onset two consecutive days a week fasting, a form of IF, termed intermittent food restriction (IFR), exhibited a time-dependent effect, and long-term late-onset IFR extended the mean lifespan and maximum lifespan by approximately 3.5 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We also showed that IFR reduced the accumulation of lipofuscin in the gills and the protein oxidation and lipid peroxidation levels in the muscles. Moreover, IFR was able to enhance the activities of antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase in the fish. Finally, IFR was also able to decelerate the decrease of SirT1 and Foxo3A, but accelerate the decrease of IGF-1. Collectively, our findings suggest that late-onset IFR can retard the onset of age-related markers, and prolong the lifespan of the aging fish, via a synergistic action of an anti-oxidant system and the IIS pathway. It also proposes that the combined assessment of anti-oxidant system and IIS pathway will contribute to providing a more comprehensive view of anti-aging process.
Smith, T
1988-02-13
The Abortion (Amendment) Bill in the British House of Commons would lower the maximum limit for termination of pregnancy from 28 to 18 weeks. Supporters of the bill assert that Britain allows termination of pregnancy later than any other European country, and that in Britain over 90% of all late abortions are of fetuses without phisical abnormality. The 28-week limit is considered anachronoistic by doctors since neonatal care has made possible survival at 24 weeks. A similar bill in the House of Lords would reduce the limit to 24 weeks. Making early abortions more easily available would help reduce late abortions. Statistics indicate that women who have abortions late in their pregnancies tend to be young. In 1986, 172,286 abortions were performed in England and Wales. Of these, 144,857, or 84%, were performed before the 13th week. A total of 8276 (5%) were performed after 18 weeks. Of these, 3688 (45% of late abortions) were on nonresidents who traveled to Britain because of legal restrictions in their own country. This means that 4594 late abortions were performed on residents of England and Wales in 1986. This was 3% of the total, with 14% of this number on grounds of fetal abnormality. About 40% of the rest were in women under the age of 20, with 6% (239) on girls under 16. A 1984 study concluded that more counseling and information should be provided for young women. Education in contraception for young women is less than ideal and likely to become less available as economic restraints reduce the number of family planning clinics. Postcoital contraception should be taught more as an emergency proceedure. Prompt, dispassionate physician counseling, wider provision of National Health Service facilities, and uniform service in all districts would also be beneficial.
Namazkar, Shahla; Stockmarr, Anders; Frenck, Georg; Egsgaard, Helge; Terkelsen, Thilde; Mikkelsen, Teis; Ingvordsen, Cathrine Heinz; Jørgensen, Rikke Bagger
2016-01-01
Plant oil is an essential dietary and bio-energy resource. Despite this, the effects of climate change on plant oil quality remain to be elucidated. The present study is the first to show changes in oil quality and quantity of four rapeseed cultivars in climate scenarios with elevated [CO2], [O3] and temperature (T) combined and as single factors. The combination of environmental factors resembled IPCC’s ‘business as usual’ emission scenario predicted for late this century. Generally, the climate scenarios reduced the average amounts of the six fatty acids (FAs) analysed, though in some treatments single FAs remained unchanged or even increased. Most reduced was the FA essential for human nutrition, C18:3-ω3, which decreased by 39% and 45% in the combined scenarios with elevated [CO2]+T+[O3] and [CO2]+T, respectively. Average oil content decreased 3–17%. When [CO2] and T were elevated concurrently, the seed biomass was reduced by half, doubling the losses in FAs and oil content. This corresponded to a 58% reduction in the oil yield per hectare, and C18:3-ω3 decreased by 77%. Furthermore, the polyunsaturated FAs were significantly decreased. The results indicate undesirable consequences for production and health benefits of rapeseed oil with future climate change. The results also showed strong interactive effects of CO2, T and O3 on oil quality, demonstrating why prediction of climate effects requires experiments with combined factors and should not be based on extrapolation from single factor experiments. PMID:27222513
Tabuchi, Takahiro; Iso, Hiroyasu; Brunner, Eric
2018-04-05
Previous systematic reviews of population-level tobacco control interventions and their effects on smoking inequality by socioeconomic factors concluded that tobacco taxation reduce smoking inequality by income (although this is not consistent for other socioeconomic factors, such as education). Inconsistent results have been reported for socioeconomic differences, especially for other tobacco control measures, such as smoke-free policies and anti-tobacco media campaigns. To understand smoking inequality itself and to develop strategies to reduce smoking inequality, knowledge of the underlying principles or mechanisms of the inequality over a long time-course may be important. For example, the inverse equity hypothesis recognizes that inequality may evolve in stages. New population-based interventions are initially primarily accessed by the affluent and well-educated, so there is an initial increase in socioeconomic inequality (early stage). These inequalities narrow when the deprived population can access the intervention after the affluent have gained maximum benefit (late stage). Following this hypothesis, all tobacco control measures may have the potential to reduce smoking inequality, if they continue for a long term, covering and reaching all socioeconomic subgroups. Re-evaluation of the impact of the interventions on smoking inequality using a long time-course perspective may lead to a favorable next step in equity effectiveness. Tackling socioeconomic inequality in smoking may be a key public health target for the reduction of inequality in health.
Brunner, Eric
2018-01-01
Previous systematic reviews of population-level tobacco control interventions and their effects on smoking inequality by socioeconomic factors concluded that tobacco taxation reduce smoking inequality by income (although this is not consistent for other socioeconomic factors, such as education). Inconsistent results have been reported for socioeconomic differences, especially for other tobacco control measures, such as smoke-free policies and anti-tobacco media campaigns. To understand smoking inequality itself and to develop strategies to reduce smoking inequality, knowledge of the underlying principles or mechanisms of the inequality over a long time-course may be important. For example, the inverse equity hypothesis recognizes that inequality may evolve in stages. New population-based interventions are initially primarily accessed by the affluent and well-educated, so there is an initial increase in socioeconomic inequality (early stage). These inequalities narrow when the deprived population can access the intervention after the affluent have gained maximum benefit (late stage). Following this hypothesis, all tobacco control measures may have the potential to reduce smoking inequality, if they continue for a long term, covering and reaching all socioeconomic subgroups. Re-evaluation of the impact of the interventions on smoking inequality using a long time-course perspective may lead to a favorable next step in equity effectiveness. Tackling socioeconomic inequality in smoking may be a key public health target for the reduction of inequality in health. PMID:29151476
The late-stage diagnosis of colorectal cancer: demographic and socioeconomic factors.
Mandelblatt, J; Andrews, H; Kao, R; Wallace, R; Kerner, J
1996-01-01
OBJECTIVES: This study described factors related to colorectal cancer stage at diagnosis. METHODS: Logistic regression analyses were used on data from the New York State Tumor Registry and US Census area-level social class indicators. RESULTS: After the effects of other predictors were controlled for, the odds of late-stage cancer increased as age decreased; women and African Americans were significantly more likely to have late stage than men and Whites; and individuals living in areas of low socioeconomic status (SES) were significantly more likely to be diagnosed at late stage than those living in higher SES areas. Stratified analyses showed that living in a low SES area was the most important determinant of stage for all age, race, gender and source-of-care groups. CONCLUSIONS: While all populations would benefit from the systematic use of screening socioeconomically disadvantaged groups may also benefit from targeted screening. PMID:9003140
ERIC Educational Resources Information Center
Huang, Yan-You; Kandel, Eric R.
2006-01-01
Protein synthesis-dependent late phase of LTP (L-LTP) is typically induced by repeated high-frequency stimulation (HFS). This form of L-LTP is reduced in the aged animal and is positively correlated with age-related memory loss. Here we report a novel form of protein synthesis-dependent late phase of LTP in the CA1 region of hippocampus induced by…
van den Berg, Gerrit; van Eijsden, Manon; Galindo-Garre, Francisca; Vrijkotte, Tanja G M; Gemke, Reinoud J B J
2013-07-01
Although there is convincing evidence for the association between small for gestational age (SGA) and socioeconomic status (SES), it is not known to what extent explanatory factors contribute to this association. To examine to what extent risk factors could explain educational inequalities in SGA. In this study fully completed data were available for 3793 pregnant women of Dutch origin from a population-based cohort (ABCD study). Path-analysis was conducted to examine the role of explanatory factors in the relation of maternal education to SGA. Low-educated pregnant women had a higher risk of SGA offspring compared to the high-educated women (OR 1.98, 95% CI 1.35-2.89). In path-analysis, maternal cigarette smoking and maternal height explained this association. Maternal age, hypertension, chronic disease, late entry into antenatal care, neighborhood income, underweight, environmental cigarette smoking, drug abuse, alcohol use, caffeine intake, fish intake, folic acid intake, anxiety, and depressive symptoms did not play a role in the association between maternal education and SGA birth. Among a large array of potential factors, the elevated risk of SGA birth among low-educated women appeared largely attributable to maternal smoking and to a lesser extent to maternal height. To reduce educational inequalities more effort is required to include low-educated women especially in prenatal intervention programs such as smoking cessation programs instead of effort into reducing other SGA-risk factors, though these factors might still be relevant at the individual level. Copyright © 2013 Elsevier Ltd. All rights reserved.
[Non-pharmacological diabetes therapy].
Martin, Stephan; Kolb, Hubert
2008-02-01
Diabetes mellitus type 2 is a life-style disease that is triggered by obesity and lack of physical activity. The pathophysiological basis of the disease is a reduction of insulin sensitivity, that is caused by the trigger factors. Glucose metabolic disorders appear if overproduction of insulin can not compensate the insulin resistance. In early phases postprandial blood glucose is increased, in late phases elevation of fasting blood glucose is noted. In the general awareness manifestation of type 2 diabetes is associated with an initiation of a pharmacological therapy. This is not the case, as described in detail in this review. Next to epidemiological studies, which indicate trigger factors, intervention trials will be discussed that led to a shift in paradigm in the diabetology. Non-pharmacological interventions are a therapeutical alternative in a lot of patients or are able to reduce the amount of antidiabetic agents significantly.
On Analytical Solutions of f(R) Modified Gravity Theories in FLRW Cosmologies
NASA Astrophysics Data System (ADS)
Domazet, Silvije; Radovanović, Voja; Simonović, Marko; Štefančić, Hrvoje
2013-02-01
A novel analytical method for f(R) modified theories without matter in Friedmann-Lemaitre-Robertson-Walker (FLRW) spacetimes is introduced. The equation of motion for the scale factor in terms of cosmic time is reduced to the equation for the evolution of the Ricci scalar R with the Hubble parameter H. The solution of equation of motion for actions of the form of power law in Ricci scalar R is presented with a detailed elaboration of the action quadratic in R. The reverse use of the introduced method is exemplified in finding functional forms f(R), which leads to specified scale factor functions. The analytical solutions are corroborated by numerical calculations with excellent agreement. Possible further applications to the phases of inflationary expansion and late-time acceleration as well as f(R) theories with radiation are outlined.
Ruan, Zhong-Bao; Zhu, Li; Yin, Yi-Gang; Chen, Ge-Cai
2014-07-01
The risk factors associated with death in complicated Stanford B acute aortic dissection (AAD) after thoracic endovascular aortic repair (TEVAR) are poorly understood. The aim of this study was to evaluate the early and late events and mortality of complicated Stanford B AAD associated with TEVAR. Sixty-two patients with complicated Stanford B AAD undergoing TEVAR were included in this study. Primary technical success of TEVAR was achieved in 61 (98.39%) cases. The early mortality rate was 9.68%. Procedural type I endoleak (p = 0.007, OR = 7.71, 95% CI: 1.75-34.01) and cardiac tamponade (p = 0.010, OR = 8.86, 95% CI: 1.70-4 6.14) were the significant predictors of early death in the multivariate model. The late mortality was 16.07%. Cox regression analysis revealed rupture of false lumen (p = 0.001, hazard ratio = 21.96, 95% CI: 3.02-82.12), postoperative myocardial infarction (p = 0.001, hazard ratio = 9.86, 95% CI: 2.12-39.64), and acute renal failure (p = 0.024, hazard ratio = 3.98, 95% CI: 1.26-12.11) to be independent risk factors of late mortality. Type I procedural endoleak and cardiac tamponade were the significant predictors of early death in patients of complicated Stanford B AAD undergoing TEVAR. Rupture of false lumen, postoperative myocardial infarction, and acute renal failure were the independent risk factors for late death after TEVAR. © 2014 Wiley Periodicals, Inc.
Cheung, Chui Ming Gemmy; Li, Xiang; Cheng, Ching-Yu; Zheng, Yingfeng; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Yin
2014-08-01
To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. Population-based cross-sectional study. A total of 10 033 persons (3280 Malay, 3400 Indian, and 3353 Chinese; response rate, 75%) 40 years of age or older residing in Singapore. We performed comprehensive systemic and ocular examinations, retinal photography, and laboratory investigations for all participants. We graded early and late AMD signs from retinal photographs using the modified Wisconsin AMD grading scale. We calculated the age-standardized prevalence of AMD using the 2010 Singapore adult population and analyzed risk factors for AMD using logistic regression models. Early and late AMD. Of the 9799 participants with gradable photographs, 588 had early AMD and 60 had late AMD. The age-standardized prevalence was 5.1% (95% confidence interval [CI], 4.6-5.5) for early AMD and 0.5% (95% CI, 0.4-0.6) for late AMD. The prevalence of early AMD was similar between Chinese (5.7%) and Indian (4.5%; P = 0.27) persons and lower in Malays (3.5%; P = 0.002 compared with Chinese; P = 0.09 compared with Indians); in contrast, the prevalence for late AMD was similar across ethnic groups (Chinese, 0.6%; Indian, 0.3%; and Malay, 0.3%; P = 0.20). Risk factors for early AMD were older age (odds ratio [OR], 1.40 per 5-year increase in age; 95% CI, 1.33-1.47), male gender (OR, 1.81; 95% CI, 1.43-2.29), hypertension (OR, 1.28; 95% CI, 1.02-1.61), and hyperopic refraction (OR, 1.17 per 1-diopter increase in spherical equivalent; 95% CI, 1.11-1.24). Risk factors for late AMD include older age (OR, 1.87 per 5-year increase in age; 95% CI, 1.54-2.19), smoking more than 5 packs per week (OR, 3.63; 95% CI, 1.34-9.80), and presence of chronic kidney disease (OR, 2.17; 95% CI, 1.22-3.88). Early AMD is more common in Chinese and Indians than in Malays, but there were no racial variations in the prevalence of late AMD. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Diniz, Breno S.; Reynolds, Charles F.; Butters, Meryl A.; Dew, Mary Amanda; Firmo, Josélia O. A.; Lima-Costa, Maria Fernanda; Castro-Costa, Erico
2014-01-01
Background Increased mortality risk and its moderators is an important, but still under recognized, negative outcome of Late-Life Depression (LLD). Therefore, we aimed to evaluate whether LLD is a risk factor for all-cause mortality in a population-based study with over ten years of follow-up, and addressed the moderating effect of gender and symptom severity on mortality risk. Methods This analysis used data from the Bambuí Cohort Study of Aging. The study population comprised 1.508 (86.5%) of all eligible 1.742 elderly residents. Depressive symptoms were annually evaluated by the GHQ-12, with scores of 5 or higher indicating clinically significant depression. From 1997 to 2007, 441 participants died during 10,648 person-years of follow-up. We estimated the hazard ratio for mortality risk by Cox regression analyses. Results Depressive symptoms were a risk factor for all-cause mortality after adjusting for confounding lifestyle and clinical factors (adjusted HR=1.24 CI95% [1.00–1.55], p=0.05). Mortality risk was significantly elevated in men (adjusted HR=1.45 CI95% [1.01 – 2.07], p=0.04), but not in women (adjusted HR=1.13 CI95% [0.84 – 1.48], p=0.15). We observed a significant interaction between gender and depressive symptoms on mortality risk ((HR= 1.72 CI95% [1.18 – 2.49], p=0.004). Conclusion The present study provides evidence that LLD is a risk factor for all-cause mortality in the elderly, especially in men. The prevention and adequate treatment of LLD may help to reduce premature disability and death among elders with depressive symptoms. PMID:24353128
Inverse Relationship between Serum VEGF Levels and Late In-Stent Restenosis of Drug-Eluting Stents
Shen, Li; Ji, Meng; Cai, Sishi; Chen, Jiahui; Yao, Zhifeng
2017-01-01
Late in-stent restenosis (ISR) has raised concerns regarding the long-term efficacy of drug-eluting stents (DES). The role of vascular endothelial growth factor (VEGF) in the pathological process of ISR is controversial. This retrospective study aimed to investigate the relationship between serum VEGF levels and late ISR in patients with DES implantation. A total of 158 patients who underwent angiography follow-up beyond 1 year after intervention were included. The study population was classified into ISR and non-ISR groups. The ISR group was further divided according to follow-up duration and Mehran classification. VEGF levels were significantly lower in the ISR group than in the non-ISR group [96.34 (48.18, 174.14) versus 179.14 (93.59, 307.74) pg/mL, p < 0.0001]. Multivariate regression revealed that VEGF level, procedure age, and low-density lipoprotein cholesterol were independent risk factors for late ISR formation. Subgroup analysis demonstrated that VEGF levels were even lower in the very late (≥5 years) and diffuse ISR group (Mehran patterns II, III, and IV) than in the late ISR group (1–4 years) and the focal ISR group (Mehran pattern I), respectively. Furthermore, significant difference was found between diffuse and focal ISR groups. Serum VEGF levels were inversely associated with late ISR after DES implantation. PMID:28373989
Nishiyama, Masahiro; Fujita, Kyoko; Maruyama, Azusa; Nagase, Hiroaki
2014-11-01
Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) presents a distinct clinical course of biphasic seizures and impaired consciousness. These symptoms are followed by reduced diffusion in the subcortical white matter on magnetic resonance imaging that is typically observed between 3 and 9 days after illness onset. Here, we report two cases of traumatic head injury with clinical and radiological features similar to those for AESD. The similarities between our cases and AESD may be useful in understanding the pathogenesis of AESD. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Zhu, Yanbo; Wang, Qi; Dai, Zhaoyu; Origasa, Hideki; Di, Jie; Wang, Yangyang; Lin, Lin; Fan, Chunpok
2014-06-01
To explore the relationships between different lifestyle-behavioral factors and phlegm-wetness type of Traditional Chinese Medicine constitution, so as to provide health management strategies for phlegm-wetness constitution. A case-control study was conducted with the cases selected from the database of Chinese constitution survey in 9 provinces or municipalities of China. 1380 cases met the diagnostic criteria of phlegm-wetness type were taken as the case group, and 1380 cases were randomly selected from gentleness type as the control group. Using Chi-square test to compare the differences of lifestyle-behavior composition in each group; single factor and multiple logistic regression analysis were used to compare the relationships of lifestyle-behavioral factors and phlegm-wetness type. There were statistically significant differences between phlegm-wetness type group and gentleness type group in lifestyle behaviors (dietary habits, tobacco and liquor consumptions, exercise habits, sleeping habits). The results of single factor logistic regression analysis demonstrated that the risk of phlegm-wetness constitution decreased significantly in light diet (odds ratio, OR = 0.68); The risk factors of phlegm-wetness type were fatty food intake (OR = 2.36), sleeping early and getting up late (OR = 1.87), tobacco smoking (OR = 1.83), barbecued food intake (OR = 1.68), alcohol drinking (OR = 1.63), salty food intake (OR = 1.44), sleeping erratically (OR = 1.43), less physical activities (OR = 1.42), sweet food intake (OR = 1.29), sleeping and getting up late (OR = 1.26), and pungent food intake (OR = 1.21), respectively. Regardless of the interaction among lifestyle-behavioral factors, the results of the multiple logistic regression analysis revealed that the risk factors of phlegm-wetness type were sleeping early and getting up late (OR = 1.94), fatty food intake (OR = 1.80), tobacco smoking (OR = 1.50), sleeping erratically (OR = 1.50), barbecued food intake (OR = 1.40), sleeping and getting up late (OR = 1.40), less physical activities (OR = 1.31), sleeping late and getting up early (OR = 1.27), and sweet food intake (OR = 1.27, respectively, and the risk of phlegm-wetness type still decreased significantly in light food intake (OR = 0.79). Light diet can decrease the risk of being phlegm-wetness constitution, and bad lifestyle behaviors such as sleeping early and getting up late, sleeping erratically, fatty food, barbecued food or sweet food intake, tobacco and liquor consumptions, and less physical activities can increase the risks of becoming phlegm-wetness constitution.
Neighborhood poverty and suicidal thoughts and attempts in late adolescence.
Dupéré, V; Leventhal, T; Lacourse, E
2009-08-01
Suicide tends to concentrate in disadvantaged neighborhoods, and neighborhood disadvantage is associated with many important risk factors for youth suicide. However, no study has directly investigated the link between neighborhood poverty and youth suicidal behaviors, while controlling for pre-existing vulnerabilities. The objective of this study was to determine whether living in a poor neighborhood is associated with suicidal thoughts and attempts in late adolescence over and above background vulnerabilities, and whether this association can be explained by late-adolescence psychosocial risks: depression, social support, negative life events (NLEs), delinquent activities, substance abuse and exposure to suicide. The potential moderating role of neighborhood poverty was also examined. A subset of 2776 participants was selected from the Canadian National Longitudinal Survey of Children and Youth (NLSCY). Late-adolescence suicidal behaviors and risk factors were self-reported. The 2001 Canadian Census was used to characterize neighborhoods during early and middle adolescence. Late-childhood family and individual controls were assessed through parent-report. At the bivariate level, the odds of reporting suicidal thoughts were about twice as high in poor than non-poor neighborhoods, and the odds of attempting suicide were about four times higher. After controlling for background vulnerabilities, neighborhood poverty remained significantly associated with both suicidal thoughts and attempts. However, these associations were not explained by late-adolescence psychosocial risks. Rather, youth living in poor neighborhoods may be at greater risk through the amplification of other risk factors in disadvantaged neighborhoods. Potential explanations for the increased vulnerability of youth living in poor neighborhoods are discussed.
Johansson, Elin; Leijon, Ola; Falkstedt, Daniel; Farah, Ahmed; Hemmingsson, Tomas
2012-10-01
The association between level of education and disability pension (DP) is well known. Earlier studies have investigated the importance of early life factors and work characteristics but not in combination. The aim of this study was to investigate the association between level of education and DP among Swedish middle-aged working men and to what extent such an association can be explained by factors measured in late adolescence and work characteristics in adulthood. Information about IQ, health-related lifestyle factors, psychiatric and musculoskeletal diagnoses was obtained from the 1969 conscription cohort, consisting of 49,321 Swedish men. Data collected when subjects were 18-20 years of age were combined with national register-based information about level of education, job control and physical strain at work in adulthood, and information about DP between 1991 and 2002. There was a strong graded association between level of education and DP. Those with the lowest level of education had a four times greater probability of having DP as compared with those with the highest level. In multivariable analyses, factors measured in late adolescence, IQ in particular, attenuated the association more than work-related characteristics in adulthood. The authors found an association between level of education and DP among Swedish middle-aged working men. A large part of the association was explained by factors measured in late adolescence, IQ in particular, and somewhat less by work characteristics measured in adulthood. Level of education remained as a significant predictor of DP in middle age after full adjustment.
Joachim, Nichole; Colijn, Johanna Maria; Kifley, Annette; Lee, Kristine E; Buitendijk, Gabriëlle H S; Klein, Barbara E K; Myers, Chelsea E; Meuer, Stacy M; Tan, Ava G; Holliday, Elizabeth G; Attia, John; Liew, Gerald; Iyengar, Sudha K; de Jong, Paulus T V M; Hofman, Albert; Vingerling, Johannes R; Mitchell, Paul; Klaver, Caroline C W; Klein, Ronald; Wang, Jie Jin
2018-01-01
Purpose To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. Design Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. Methods Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors. Results In any 5-year duration, 19–28% of unilateral any AMD cases became bilateral and 27–68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye. Conclusion One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement. PMID:28108569
Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat
2014-01-01
Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221
Rhodes, Emma; Devlin, Kathryn N; Steinberg, Laurence; Giovannetti, Tania
2017-05-01
Various psychological assets have been shown to protect against late-life cognitive impairment by promoting cognitive reserve. While factors such as educational attainment and IQ are well-established contributors to cognitive reserve, noncognitive factors, such as grit, have not been studied in this regard. We examined the contribution of adolescent grit, indexed by high school class rank controlling for IQ, to late-life cognition and its decline among approximately 4000 participants in the Wisconsin Longitudinal Study, a random sample of high school graduates followed from 1957 to 2011. Adolescent grit significantly predicted both immediate and delayed memory at ages 64 and 71, over and above the contribution of IQ. While the relative contributions of IQ and grit to immediate memory were comparable, grit was a stronger predictor of delayed memory. Cognitive reserve has noncognitive, as well as cognitive, components.
Rhodes, Emma; Devlin, Kathryn N.; Steinberg, Laurence
2018-01-01
Various psychological assets have been shown to protect against late-life cognitive impairment by promoting cognitive reserve. While factors such as educational attainment and IQ are well-established contributors to cognitive reserve, non-cognitive factors, such as grit, have not been studied in this regard. We examined the contribution of adolescent grit, indexed by high school class rank controlling for IQ, to late-life cognition and its decline among approximately 4,000 participants in the Wisconsin Longitudinal Study, a random sample of high school graduates followed from 1957 to 2011. Adolescent grit significantly predicted both immediate and delayed memory at ages 64 and 71, over and above the contribution of IQ. While the relative contributions of IQ and grit to immediate memory were comparable, grit was a stronger predictor of delayed memory. Cognitive reserve has non-cognitive, as well as cognitive, components. PMID:27428038
Current State of Bioabsorbable Polymer-Coated Drug-Eluting Stents
Akinapelli, Abhilash; Chen, Jack P.; Roy, Kristine; Donnelly, Joseph; Dawkins, Keith; Huibregtse, Barbara; Hou, Dongming
2017-01-01
Drug-eluting stents (DES) have been shown to significantly reduce clinical and angiograph-ic restenosis compared to bare metal stents (BMS). The polymer coatings on DES elute antiproliferative drugs to inhibit intimal proliferation and prevent restenosis after stent implantation. Permanent poly-mers which do not degrade in vivo may increase the likelihood of stent-related delayed arterial healing or polymer hypersensitivity. In turn, these limitations may contribute to an increased risk of late clinical events. Intuitively, a polymer which degrades after completion of drug release, leaving an inert metal scaffold in place, may improve arterial healing by removing a chronic source of inflammation, neoath-erosclerosis, and/or late thrombosis. In this way, a biodegradable polymer may reduce late ischemic events. Additionally, improved healing after stent implantation could reduce the requirement for long-term dual antiplatelet therapy and the associated risk of bleeding and cost. This review will focus on bioabsorbable polymer-coated DES currently being evaluated in clinical trials.
Goodnight, Jackson A.; D’Onofrio, Brian M.; Cherlin, Andrew J.; Emery, Robert E.; Van Hulle, Carol A.; Lahey, Benjamin B.
2012-01-01
Previous studies of the association between multiple parental relationship transitions (i.e., when a parent begins or terminates an intimate relationship involving cohabitation) and offspring antisocial behavior have varied in their efforts to rule out confounding influences, such as parental antisocial behavior and low income. They also have been limited in the representativeness of their samples. Thus, it remains unclear to what degree parents’ multiple relationship transitions have independent effects on children’s antisocial behavior. Analyses were conducted using data on 8,652 6–9-year-old, 6,911 10–13-year-old, and 6,495 14-17-year-old offspring of a nationally representative sample of U.S. women. Cousin-comparisons were used in combination with statistical covariates to evaluate the associations between maternal relationship transitions and offspring antisocial behavior in childhood and adolescence. Cousin-comparisons suggested that associations between maternal relationship transitions and antisocial behavior in childhood and early adolescence are largely explained by confounding factors. In contrast, the associations between maternal relationship transitions and offspring delinquency in late adolescence were robust to measured and unmeasured confounds. The present findings suggest that interventions aimed at reducing exposure to parental relationship transitions or addressing the psychosocial consequences of exposure to parental relationship transitions could reduce risk for offspring delinquency in late adolescence. PMID:22829173
Prevalence and Risk Factors of Maternal Anxiety in Late Pregnancy in China.
Kang, Yu-Ting; Yao, Yan; Dou, Jing; Guo, Xin; Li, Shu-Yue; Zhao, Cai-Ning; Han, Hong-Zhi; Li, Bo
2016-05-04
A large number of studies have shown the adverse neonatal outcomes of maternal psychological ill health. Given the potentially high prevalence of antenatal anxiety and few studies performed among Chinese people, the authors wanted to investigate the prevalence of antenatal anxiety and associated factors among pregnant women and to provide scientific basis to reduce prenatal anxiety effectively. A cross-sectional study was carried out at the Changchun Gynecology and Obstetrics Hospital from January 2015 to march 2015, with 467 participants of at least 38 weeks' gestation enrolled. Antenatal anxiety was measured using the Self-Rating Anxiety Scale (SAS). χ² test and logistic regression analysis were performed to evaluate the association of related factors of antenatal anxiety. Among the 467 participants, the prevalence of antenatal anxiety was 20.6% (96 of 467). After adjustment for women's socio-demographic characteristics (e.g., area, age, household income), multivariate logistical regression analysis revealed that antenatal anxiety showed significant relationship with education level lower than middle school (years ≤ 9), expected natural delivery, anemia during pregnancy, pregnancy-induced hypertension syndrome, disharmony in family relationship and life satisfaction. It is important to prevent or reduce antenatal anxiety from occurring by improving the health status of pregnant women and strengthening prenatal-related education and mental intervention.
Cachulo, Maria da Luz; Laíns, Inês; Lobo, Conceição; Figueira, João; Ribeiro, Luísa; Marques, João P; Costa, José; Vieira, António; Rodrigues, João; Alves, Dalila; Nunes, Sandrina; Costa, Miguel; Rodrigues, Victor; Cunha-Vaz, José; Delcourt, Cecile; Silva, Rufino
2016-09-01
To determine the age- and sex-specific prevalence of early and late age-related macular degeneration (AMD) in two Portuguese population-based samples and to identify its risk factors. A population of 6023 adults aged ≥55 years was recruited from two Portuguese primary healthcare units in the central region of Portugal - one from a coastal (n = 3000) and another from an inland town (n = 3023). Cross-sectional population-based study. Participants were enrolled in the two locations between August 2009 and October 2013. Responders underwent standardized interviews and ophthalmologic examination, including digital fundus imaging. All fundus photographs were graded according to an International Classification and Grading System. The main outcome measures consisted of age- and sex-adjusted prevalence of early and late AMD. Potential epidemiologic risk factors were also evaluated using logistic regression analysis. Of the 6023 subjects enrolled, 5996 had gradable fundus images and were included in the analysis. The crude prevalence of early and late AMD was 6.99 and 0.67%, respectively, for the coastal town and 15.39 and 1.29% for the inland town. Age- and sex-adjusted prevalence of any AMD for the Portuguese population was 12.48% (95% CI: 11.61-13.33) with late AMD accounting for 1.16% (95% CI: 0.85-1.46). Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.55% (95% CI: 0.36-0.75) and 0.61% (95% CI: 0.37-0.84) of individuals, respectively. After adjusting for possible confounding factors, prevalence of early and late AMD increased with increasing age (OR = 1.35; 95% CI: 1.23-1.49 for early and OR = 3.01; 95% CI: 2.22-4.08 for late AMD, per each decade of age increase, p < 0.001). After adjustment for age, sex, family history, smoking history, hypertension, diabetes and BMI, subjects from the inland town presented a significantly higher OR of early and late AMD than subjects from the coastal town (OR = 2.57, 95% CI: 2.12-3.12, p < 0.001 for early and OR = 2.06, 95% CI: 1.07-3.95, p = 0.029 for late AMD). The prevalence of early and late AMD in this Portuguese population was similar to other large-scale population-based cohorts. After controlling for confounders, age and study site of inclusion were significant independent predictors for both early and late forms of the disease. Further analysis will be needed to completely unravel the underlying reasons for this difference regarding geographic location. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Late-onset agoraphobia: general population incidence and evidence for a clinical subtype.
Ritchie, Karen; Norton, Joanna; Mann, Anthony; Carrière, Isabelle; Ancelin, Marie-Laure
2013-07-01
The purpose of this study was to estimate the general population incidence of late-life agoraphobia and to define its clinical characteristics and risk factors. A total of 1,968 persons ≥65 years old were randomly recruited from the electoral rolls of the district of Montpellier, France. Prevalent and incident agoraphobia diagnosed with a standardized psychiatric examination and validated by a clinical panel were assessed at baseline and over a 4-year follow-up. The 1-month baseline prevalence of agoraphobia was estimated to be 10.4%. Among persons with agoraphobia, 10.9% reported having their first episode at age 65 or above. During the 4-year follow-up, 11.2% of participants without agoraphobia at baseline had a first episode, resulting in an incidence rate of 32 per 1,000 person-years. These 132 incident late-onset cases were associated with higher incidence rates of anxiety disorders and suicidal ideation. Of the incident cases, only two were characterized by past or concurrent panic attacks, a rate that was not significantly different from that of the noncase group. The principal baseline risk factors for incident cases, derived from a multivariate model incorporating all significant risk factors, were younger age at onset (odds ratio=0.94, 95% CI=0.90-0.99), poorer visuospatial memory performance (odds ratio=1.60, 95% CI=1.02-2.49), severe depression (odds ratio=2.62, 95% CI=1.34-5.10), and trait anxiety (odds ratio=1.73, 95% CI=1.03-2.90). No significant association was found with cardiac pathologies. Agoraphobia has a high prevalence in the elderly, and unlike cases in younger populations, late-onset cases are not more common in women and are not associated with panic attacks, suggesting a late-life subtype. Severe depression, trait anxiety, and poor visuospatial memory are the principal risk factors for late-onset agoraphobia.
Valentini, Melissa Bianchetti; Toledo, Maria Luíza Guerra de; Fonseca, Marise Oliveira; Thiersch, Laura Maria Silva; Toledo, Ingrid Silva Bremer de; Machado, Flávia Cristina Jácome; Tupinambás, Unaí
2015-01-01
Since 1996 Brazil has provided universal access to free antiretroviral therapy, and as a consequence, HIV/AIDS patients' survival rate has improved dramatically. However, according to scientific reports, a significant number of patients are still late presenting for HIV treatment, which leads to consequences both for the individual and society. Clinical and immunological characteristics of HIV patients newly diagnosed were accessed and factors associated with late presentation for treatment were evaluated. A cross-sectional study was carried out in an HIV/AIDS reference center in Belo Horizonte, Minas Gerais, in Southeastern Brazil from 2008 to 2010. Operationally, patients with late presentation (LP) for treatment were those whose first CD4 cell count was less than 350 cells/mm(3) or presented an AIDS defining opportunistic infection. Patients with late presentation with advanced disease (LPAD) were those whose first CD4 cell count was less than 200 cells/mm(3) or presented an AIDS defining opportunistic infection. LP and LPAD associated risk factors were evaluated using logistic regression methods. Five hundred and twenty patients were included in the analysis. The median CD4 cell count was 336 cells/mm(3) (IQR: 130-531). Two hundred and seventy-nine patients (53.7%) were classified as LP and 193 (37.1%) as LPAD. On average, 75% of the patients presented with a viral load (VL) >10,000 copies/ml. In multivariate logistic regression analysis the factors associated with LP and LPAD were age, being symptomatic at first visit and VL. Race was a factor associated with LP but not with LPAD. The proportion of patients who were late attending a clinic for HIV treatment is still high, and effective strategies to improve early HIV detection with a special focus on the vulnerable population are urgently needed. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.
Late-Onset Asthma Predicts Cardiovascular Disease Events: The Wisconsin Sleep Cohort.
Tattersall, Matthew C; Barnet, Jodi H; Korcarz, Claudia E; Hagen, Erika W; Peppard, Paul E; Stein, James H
2016-08-24
Asthma is a heterogeneous syndrome with different clinical subtypes that is associated with an increased risk for cardiovascular disease (CVD). We hypothesized that the late-onset subtype of asthma is associated with a higher risk of incident CVD. Participants from the Wisconsin Sleep Cohort free of CVD at baseline were followed for a mean (SD) of 13.9 (5.9) years for development of CVD (myocardial infarction, angina, stroke, coronary revascularization, heart failure, or CVD death). Late-onset asthma was defined as physician-diagnosed asthma at age ≥18 years. Multivariable Cox regression models adjusted for age, sex, and CVD risk factors were used to assess associations of late-onset asthma and incident CVD. The 1269 participants were 47.3 (8.0) years old; 166 participants had asthma (111 late-onset, 55 early-onset). Participants with late-onset asthma compared to nonasthmatics were more likely to be female (67% versus 44%) and to have a higher body-mass index (32.2 versus 29.4 kg/m(2)) (P<0.05). Mean age of asthma diagnosis in the late-onset group was 39.5 (9.6) years versus 8.9 (5.7) years in the early-onset group (P<0.0001). Late-onset asthmatics had a higher adjusted risk of incident CVD than nonasthmatics (hazard ratio 1.57, 95% CI 1.01-2.45, P=0.045). There was no interaction between body-mass index and age of asthma diagnosis on incident CVD (P=0.83). In a large cohort study of adults followed prospectively for over a decade, late-onset asthmatics had an increased risk of incident CVD events that persisted after adjustment for age, sex, and CVD risk factors. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Adherence to peritoneal dialysis training schedule.
Chow, Kai Ming; Szeto, Cheuk Chun; Leung, Chi Bon; Law, Man Ching; Kwan, Bonnie Ching-Ha; Li, Philip Kam-Tao
2007-02-01
Shortening behaviour during peritoneal dialysis training can be easily measured, and likened to the skipping behaviour in haemodialysis subjects, although its effect on peritoneal dialysis outcomes is now well understood. We studied the clinical impact of failing to adhere to a peritoneal dialysis training programme among incident dialysis patients. This study included 159 consecutive inception peritoneal dialysis patients in a single centre from September 1999 through November 2002. We evaluated the effects of behavioural compliance quantified by the per cent time arriving late for scheduled peritoneal dialysis training. The patients were categorized by whether they arrived late in >20% of their peritoneal dialysis training sessions. Of the 159 incident peritoneal dialysis patients (mean age 57 +/- 13 years) who attended peritoneal dialysis training, 70 subjects (44%) arrived late in >20% of the sessions. They were younger by 5 years than patients who arrived late < or =20%. Mean peritonitis-free time for subjects who arrived late for training in >20% the of sessions was 30.9 months, as compared with 41.8 months in subjects with < or =20% late attendance behaviour (log rank test, P = 0.038). Multivariable Cox proportional hazards analysis showed that late attendance behaviour and baseline serum albumin were the only independent risk factors for the time to a first peritonitis after adjustment for diabetes mellitus and relevant coexisting medical factors. Late arrival in >20% of the peritoneal dialysis training sessions was associated with >50% increased likelihood of subsequent peritonitis, with an adjusted risk ratio of 1.56 (95% confidence interval, 1.02-2.39; P = 0.04). These findings show that the behavioural measure of late attendance for peritoneal dialysis training has a crucial role in predicting peritonitis. It may therefore represent a practical strategy for identifying poor adherence or predicting medical outcomes.
Kawaguchi, Y
1992-01-01
A slice preparation of rat frontal agranular cortex preserving commissural inputs has been used for intracellular recording from layer V pyramidal cells, in order to characterize the synaptic potentials induced by stimulation of the corpus callosum and to reveal the subtypes of amino acid receptors involved. Stimulation of the corpus callosum induced EPSPs followed by early IPSPs with a peak latency of 30 +/- 2 ms and late IPSPs with a peak latency of 185 +/- 18 ms. Reversal potentials for early and late IPSPs were -75 +/- 5 mV (early) and -96 +/- 5 mV (late). Late IPSPs were more dependent on extracellular K+ concentration. The early IPSPs were blocked by GABAA antagonists, bicuculline and picrotoxin, whereas the late IPSPs were reduced by the GABAB antagonist, phaclofen. CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), an antagonist of non-NMDA (N-methyl-D-aspartate) receptors, suppressed both EPSPs and late IPSPs at 5 microM. Early IPSPs remained at this concentration but were suppressed by 20 microM CNQX. In Mg(2+)-free solution, EPSPs were larger and more prolonged than in control solution. These enhanced EPSPs persisted after 5 to 20 microM CNQX, but were reduced in amplitude, and their onset was delayed by 3.6 +/- 0.8 ms. The remaining EPSPs were suppressed by 50 microM APV (DL-2-amino-5-phosphono-valeric acid), an antagonist of NMDA receptors. In Mg(2+)-free solution containing 5 to 20 microM CNQX, the late IPSPs were not diminished. The remaining late IPSPs were suppressed by APV or by phaclofen.(ABSTRACT TRUNCATED AT 250 WORDS)
Payette, Serge; Boudreau, Stéphane; Morneau, Claude; Pitre, Nadia
2004-12-01
Barren-ground caribou (Rangifer tarandus) herds in North America may reach considerable size and undertake large-scale seasonal migrations from the Arctic tundra to the boreal forest. To test the caribou decline hypothesis associated with native harvesting and fire, we have documented the long-term trends of caribou activity based on a novel approach which uses tree-ring dated trampling scars produced by caribou hooves in the extensive trails distributed over the summer and winter ranges of the Rivièreaux-Feuilles herd (RAF herd, east of Hudson Bay in northern Quebec). The age structure data of trampling scars from lichen woodlands distributed over the entire RAF range confirmed the overall trends of caribou activity from the late 1700s to present time. Over the last 200 years, the RAF herd has undergone two highs in the late 1700s and 1900s separated by a moderate activity pattern in the late 1800s. Native harvesting was possibly involved in the early 1900s decline, although at a moderate level. The reduced magnitude of caribou activity during this period has not modified the natural cycle of highs and lows, which suggests that other demographic factors were controlling the changing caribou abundance. Our data also show that only exceptionally large fires may have a minor, short-lived impact on caribou migrations but not on caribou numbers.
Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure
NASA Technical Reports Server (NTRS)
Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.
2016-01-01
Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.
Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure
NASA Technical Reports Server (NTRS)
Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.
2015-01-01
Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are a documented concern for human exploration of space. Acute CNS risks include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.
Lin, Yu-Sheng; Chen, Tien-Hsing; Hung, Sheng-Ping; Chen, Dong Yi; Mao, Chun-Tai; Tsai, Ming-Lung; Chang, Shih-Tai; Wang, Chun-Chieh; Wen, Ming-Shien; Chen, Mien-Cheng
2015-01-01
Several risk factors for pacemaker (PM) related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications. Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07-0.80; P = 0.020) or the passive fixation group (OR, 0.26; 95% CI, 0.08-0.83; P = 0.023). There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.
Moughon, Diana L.; He, Huanhuan; Schokrpur, Shiruyeh; Jiang, Ziyue Karen; Yaqoob, Madeeha; David, John; Lin, Crystal; Iruela-Arispe, M. Luisa; Dorigo, Oliver; Wu, Lily
2015-01-01
Malignant ascites is a common complication in the late stages of epithelial ovarian cancer (EOC) that greatly diminishes the quality of life of patients. Malignant ascites is a known consequence of vascular dysfunction, but current approved treatments are not effective in preventing fluid accumulation. In this study, we investigated an alternative strategy of targeting macrophage functions to reverse the vascular pathology of malignant ascites using fluid from human patients and an immunocompetent murine model (ID8) of EOC that mirrors human disease by developing progressive vascular disorganization and leakiness culminating in massive ascites. We demonstrate that the macrophage content in ascites fluid from human patients and the ID8 model directly correlates with vascular permeability. To further substantiate macrophages’ role in the pathogenesis of malignant ascites, we blocked macrophage function in ID8 mice using a colony-stimulating factor 1 receptor kinase inhibitor (GW2580). Administration of GW2580 in the late stages of disease resulted in reduced infiltration of protumorigenic (M2) macrophages and dramatically decreased ascites volume. Moreover, the disorganized peritoneal vasculature became normalized and sera from GW2580-treated ascites protected against endothelial permeability. Therefore, our findings suggest that macrophage-targeted treatment may be a promising strategy toward a safe and effective means to control malignant ascites of EOC. PMID:26471360
Late Talkers: A Population-Based Study of Risk Factors and School Readiness Consequences.
Hammer, Carol Scheffner; Morgan, Paul; Farkas, George; Hillemeier, Marianne; Bitetti, Dana; Maczuga, Steve
2017-03-01
This study was designed to (a) identify sociodemographic, pregnancy and birth, family health, and parenting and child care risk factors for being a late talker at 24 months of age; (b) determine whether late talkers continue to have low vocabulary at 48 months; and (c) investigate whether being a late talker plays a unique role in children's school readiness at 60 months. We analyzed data from the Early Childhood Longitudinal Study, a population-based sample of 9,600 children. Data were gathered when the children were 9, 24, 48, and 60 months old. The risk of being a late talker at 24 months was significantly associated with being a boy, lower socioeconomic status, being a nonsingleton, older maternal age at birth, moderately low birth weight, lower quality parenting, receipt of day care for less than 10 hr/week, and attention problems. Being a late talker increased children's risk of having low vocabulary at 48 months and low school readiness at 60 months. Family socioeconomic status had the largest and most profound effect on children's school readiness. Limited vocabulary knowledge at 24 and 48 months is uniquely predictive of later school readiness. Young children with low vocabularies require additional supports prior to school entry.
Risk and resilience trajectories in war-exposed children across the first decade of life.
Halevi, Galit; Djalovski, Amir; Vengrober, Adva; Feldman, Ruth
2016-10-01
Although the effects of early-onset trauma on susceptibility to psychopathology are well-acknowledged, no study to date has followed risk and resilience trajectories in war-exposed young children over lengthy periods and charted predictors of individual pathways. In this prospective longitudinal study, we followed 232 children, including 148 exposed to repeated wartime trauma and 84 controls, at three time points: early childhood (1.5-5 years), middle childhood (5-8 years), and late childhood (9-11 years). Children were diagnosed at each time point and four trajectories defined: children exhibiting no pathology at any time point, those displaying early pathology that later remitted, those showing initial resilience followed by late pathology, and children presenting chronic pathology across the entire first decade. Maternal behavioral containment during trauma evocation and child social engagement during free play were observed in early childhood and maternal emotional distress self-reported across time. War-exposed children showed significantly higher rates of psychopathology, with 81% exhibiting pathology at some point during childhood. In middle childhood, exposed children displayed more posttraumatic stress disorders (PTSD), anxiety disorders, and attention-deficit/hyperactivity disorders (ADHD), and in late childhood more PTSD, conduct/oppositional defiant disorders, and ADHD. War-exposed children had more comorbid psychopathologies and number of comorbidities increased with age. Notably, war-exposure increased prevalence of chronic pathology by 24-fold. Maternal factors, including mother's uncontained style and emotional distress, increased risk for early and chronic psychopathology, whereas reduced child social engagement augmented risk for late pathology. Early-onset chronic stress does not heal naturally, and its effects appear to exacerbate over time, with trauma-exposed children presenting a more comorbid, chronic, and externalizing profile as they grow older. Our findings demonstrate that responses to trauma are dynamic and variable and pinpoint age-specific effects of maternal and child factors on risk and resilience trajectories. Results highlight the importance of conducting long-term follow-up studies and constructing individually tailored early interventions following trauma exposure. © 2016 Association for Child and Adolescent Mental Health.
Knapp, E.E.; Keeley, J.E.; Ballenger, E.A.; Brennan, T.J.
2005-01-01
Fire exclusion has led to an unnatural accumulation and greater spatial continuity of organic material on the ground in many forests. This material serves both as potential fuel for forest fires and habitat for a large array of forest species. Managers must balance fuel reduction to reduce wildfire hazard with fuel retention targets to maintain other forest functions. This study reports fuel consumption and changes to coarse woody debris attributes with prescribed burns ignited under different fuel moisture conditions. Replicated early season burn, late season burn, and unburned control plots were established in old-growth mixed conifer forest in Sequoia National Park that had not experienced fire for more than 120 years. Early season burns were ignited during June 2002 when fuels were relatively moist, and late season burns were ignited during September/October 2001 when fuels were dry. Fuel loading and coarse woody debris abundance, cover, volume, and mass were evaluated prior to and after the burns. While both types of burns reduced fuel loading, early season burns consumed significantly less of the total dead and down organic matter than late season burns (67% versus 88%). This difference in fuel consumption between burning treatments was significant for most all woody fuel components evaluated, plus the litter and duff layers. Many logs were not entirely consumed - therefore the number of logs was not significantly changed by fire - but burning did reduce log length, cover, volume, and mass. Log cover, volume, and mass were reduced to a lesser extent by early season burns than late season burns, as a result of higher wood moisture levels. Early season burns also spread over less of the ground surface within the burn perimeter (73%) than late season burns (88%), and were significantly patchier. Organic material remaining after a fire can dam sediments and reduce erosion, while unburned patches may help mitigate the impact of fire on fire-sensitive species by creating refugia from which these species can recolonize burned areas. Early season burns may be an effective means of moderating potential ecosystem damage when treating heavy and/or continuous fuels resulting from long periods of fire exclusion, if burning during this season is not detrimental to other forest functions. ?? 2005 Elsevier B.V. All rights reserved.
Manuel, Martine; Price, David J.
2011-01-01
The ventricular zone (VZ) of the embryonic dorsal telencephalon is a major site for generating cortical projection neurons. The transcription factor Pax6 is highly expressed in apical progenitors (APs) residing in the VZ from the earliest stages of corticogenesis. Previous studies mainly focused on Pax6−/− mice have implicated Pax6 in regulating cortical progenitor proliferation, neurogenesis, and formation of superficial cortical layers. We analyzed the developing cortex of PAX77 transgenic mice that overexpress Pax6 in its normal domains of expression. We show that Pax6 overexpression increases cell cycle length of APs and drives the system toward neurogenesis. These effects are specific to late stages of corticogenesis, when superficial layer neurons are normally generated, in cortical regions that express Pax6 at the highest levels. The number of superficial layer neurons is reduced in postnatal PAX77 mice, whereas radial migration and lamina specification of cortical neurons are not affected by Pax6 overexpression. Conditional deletion of Pax6 in cortical progenitors at midstages of corticogenesis, by using a tamoxifen-inducible Emx1-CreER line, affected both numbers and specification of late-born neurons in superficial layers of the mutant cortex. Our analyses suggest that correct levels of Pax6 are essential for normal production of superficial layers of the cortex. PMID:20413449
Wasterlain, Claude G.; Stöhr, Thomas; Matagne, Alain
2011-01-01
The effective management of status epilepticus (SE) continues to be a therapeutic challenge. The aim of this study was to investigate the efficacy of lacosamide treatment in an experimental model of self-sustaining SE. Rats were treated with lacosamide (3, 10, 30 or 50 mg/kg) either 10 minutes (early treatment) or 40 minutes (late treatment) after the initiation of perforant path stimulation. Early lacosamide treatment significantly and dose-dependently reduced acute SE seizure activity; late treatment showed only a non-significant trend towards reduced seizure activity. Early lacosamide treatment also dose-dependently reduced the number of spontaneous recurrent seizures following a 6-week waiting period, with 70% reduction at the highest dose tested (50 mg/kg); there was also a significant reduction in the number of spikes and the cumulative time spent in seizures. Late treatment with high-dose lacosamide (30–50 mg/kg) reduced the number of animals that developed spontaneous recurrent seizures (33% vs 100% in controls, P <0.05), but did not significantly reduce seizure severity or frequency in rats that developed spontaneous recurrent seizures.. The results presented here suggest that lacosamide deserves investigation for the clinical treatment of SE. Potential for disease modification in this rat model of self-sustaining SE will require further studies. PMID:21277168
Uncertainties in estimates of the risks of late effects from space radiation
NASA Astrophysics Data System (ADS)
Cucinotta, F. A.; Schimmerling, W.; Wilson, J. W.; Peterson, L. E.; Saganti, P. B.; Dicello, J. F.
2004-01-01
Methods used to project risks in low-Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Using the linear-additivity model for radiation risks, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain an estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including a deep space outpost and Mars missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative metrics, e.g., the number of days in space without exceeding a given risk level within well-defined confidence limits.
NASA Astrophysics Data System (ADS)
Chambers, S. D.; Hong, S.-B.; Williams, A. G.; Crawford, J.; Griffiths, A. D.; Park, S.-J.
2014-09-01
We report on one year of high-precision direct hourly radon observations at King Sejong Station (King George Island) beginning in February 2013. Findings are compared with historic and ongoing radon measurements from other Antarctic sites. Monthly median concentrations reduced from 72 mBq m-3 in late-summer to 44 mBq m-3 in late winter and early spring. Monthly 10th percentiles, ranging from 29 to 49 mBq m-3, were typical of oceanic baseline values. Diurnal cycles were rarely evident and local influences were minor, consistent with regional radon flux estimates one tenth of the global average for ice-free land. The predominant fetch region for terrestrially influenced air masses was South America (47-53° S), with minor influences also attributed to aged Australian air masses and local sources. Plume dilution factors of 2.8-4.0 were estimated for the most terrestrially influenced (South American) air masses, and a seasonal cycle in terrestrial influence on tropospheric air descending at the pole was identified and characterised.
NASA Astrophysics Data System (ADS)
Chambers, S. D.; Hong, S.-B.; Williams, A. G.; Crawford, J.; Griffiths, A. D.; Park, S.-J.
2014-05-01
We report on one year of high precision direct hourly radon observations at King Sejong Station (King George Island) beginning in February 2013. Findings are compared with historic and ongoing radon measurements from other Antarctic sites. Monthly median concentrations reduced from 72 mBq m-3 in late summer to 44 mBq m-3 in late-winter and early-spring. Monthly 10th percentiles, ranging from 29 to 49 mBq m-3, were typical of oceanic baseline values. Diurnal cycles were rarely evident and local influences were minor, consistent with regional radon flux estimates one tenth of the global average for ice-free land. The predominant fetch region for terrestrially influenced air masses was South America (47-53° S), with minor influences also attributed to aged Australian air masses and local sources. Plume dilution factors of 2.8-4.0 were estimated for the most terrestrially influenced (South American) air masses, and a seasonal cycle in terrestrial influence on tropospheric air descending at the pole was identified and characterised.
Treating schizophrenia during menopause.
Brzezinski, Amnon; Brzezinski-Sinai, Noa A; Seeman, Mary V
2017-05-01
The aim of this review is to examine three questions: What are the risks and benefits of treating women with schizophrenia with hormone therapy (HT) at menopause? Should the antipsychotic regimen be changed at menopause? Do early- and late-onset women with schizophrenia respond differently to HT at menopause? MEDLINE databases for the years 1990 to 2016 were searched using the following interactive terms: schizophrenia, gender, menopause, estrogen, and hormones. The selected articles (62 out of 800 abstracts) were chosen on the basis of their applicability to the objectives of this targeted narrative review. HT during the perimenopause in women with schizophrenia ameliorates psychotic and cognitive symptoms, and may also help affective symptoms. Vasomotor, genitourinary, and sleep symptoms are also reduced. Depending on the woman's age and personal risk factors and antipsychotic side effects, the risk of breast cancer and cardiovascular disease may be increased. Antipsychotic types and doses may need to be adjusted at menopause, as may be the mode of administration. Both HT and changes in antipsychotic management should be considered for women with schizophrenia at menopause. The question about differences in response between early- and late-onset women cannot yet be answered.
Robinson, Kristen E; Gerhardt, Cynthia A; Vannatta, Kathryn; Noll, Robert B
2009-02-01
This prospective study examines family predictors of distress among survivors of childhood cancer and comparison peers during the transition to emerging adulthood. Children with cancer (n = 55), comparison peers (n = 60), and parents completed measures of distress, family environment, social support, and demographic characteristics during initial treatment, as well as follow-up measures of young adult distress and demographic characteristics soon after participants turned 18 years old. Severity of initial treatment and late effects were rated by healthcare providers for participants with cancer. For all participants, mother and father report of initial parent distress was associated with their report of young adult distress at follow-up. Young adult gender moderated this association. For survivors of childhood cancer, severity of initial treatment and late effects also moderated the association between parent and young adult distress. Improving parent distress may help reduce child distress in general. For survivors specifically, ameliorating the impact of initial treatment and long-term physical problems may be beneficial. Copyright 2009 APA, all rights reserved.
Välimäki, Matti J; Farrerons-Minguella, Jordi; Halse, Johan; Kröger, Heikki; Maroni, Marilyn; Mulder, Henk; Muñoz-Torres, Manuel; Sääf, Maria; Snorre Øfjord, Erik
2007-09-01
Randomized clinical trials have shown that risedronate reduces the risk for both ver- tebral and nonvertebral fractures in postmenopausal women with osteoporosis (bone mineral density [BMD] T-score, <-2.5). If left untreated, osteopenia (T-score, between -1 and -2.5) may progress to osteo- porosis. Risedronate sodium, a pyridinyl bisphospho- nate, is an antiresorptive drug approved by the US Food and Drug Administration for the prevention and treatment of osteoporosis in postmenopausal women. Although the effects of risedronate in preventing frac- tures has been established, its effects in maintaining or increasing BMD in osteopenia have not. In this clinical trial, the efficacy and tol- erability of risedronate in improving and maintaining BMD levels in late-postmenopausal women with os- teopenia were assessed. This 24-month, randomized, double- blind, placebo-controlled, parallel-group, Phase III trial was conducted at 14 study centers across Finland, The Netherlands, Norway, Spain, and Sweden. Late- postmenopausal (> or =5 years from menopause) women with lumbar spine (LS) BMD T-score between -1 and -2.5 and the presence of > or =1 additional risk factor for osteo- porosis or proximal femur (Fern) BMD T-score < or = -1 were randomized to receive risedronate 5 mg (n = 114) or placebo (n = 57) PO QD for 24 months. The primary efficacy end point was the percentage change from baseline in LS BMD at study end point (24 months or last observation carried forward). Secondary efficacy end points were the percentage changes from base- line in total proximal Fern BMD and 2 bone turnover markers-urinary type I collagen cross-linked N-telopeptide (uNTx) and serum bone-specific alkaline phosphatase (sBAP)-at 12 months and study end point. Tolerability was assessed using reported adverse events (AEs), laboratory analysis, and physical exami- nation including vital-sign measurements. A total of 171 women were included (mean [SD] age, 65.9 [6.8] years; mean [SD] LS BMD T-score,-1.82 [0.42]; risedronate group, 114 patients; placebo group, 57). At study end point, LS BMD had significantly increased from baseline in the risedronate group (P < 0.05) but remained unchanged in the placebo group (mean [SE] %Delta, +4.49% [0.38%] and +0.05% [0.54%], respectively; P < 0.001). Between- treatment differences in mean (SE) percentage changes from baseline in LS BMD and Fem BMD were signif- icant at 12 months and study end point (LS BMD, both P < 0.001; Fem BMD, P = 0.002 and P < 0.001, respectively). At 12 months and study end point, ris- edronate use was associated with significantly reduced concentrations of uNTx and sBAP compared with placebo (both, P < 0.001). Risedronate treatment was well tolerated with regard to gastrointestinal AEs; the most frequent AEs in the risedronate group were hy- pertension (n = 13), constipation (n = 8), and hyper- cholesterolemia (n = 8). In these late-postmenopausal women with LS osteopenia and > or=1 additional risk factor or hip osteopenia, 24-month treatment with risedronate 5 mg/d was associated with the prevention of bone loss at the spine and hip (based on significant increases in BMD in the LS and total proximal Fem) and reduced bone resorption (based on significantly reduced concen- trations of uNTx and sBAP) and was well tolerated.
Delpech, V; Brown, A E; Croxford, S; Chau, C; Polavarapu, V; Cooper, N; Rooney, G; Yin, Z
2013-10-01
Prompt HIV diagnosis and treatment are associated with increased longevity and reduced transmission. The aim of the study was to examine late diagnoses and to assess the quality of care following diagnosis. National surveillance and cohort data were used to examine late HIV diagnoses and to assess the quality of care received in the 12 months following HIV diagnosis. In 2011, 79% (4910/6219) of persons (15 years and over) diagnosed with HIV infection had CD4 counts reported within 3 months; of these, 49% were diagnosed late (CD4 count < 350 cells/μL). Adults aged 50 years and over were more likely to be diagnosed late (67%) compared with those aged 15-24 years (31%). Sixty-four per cent of heterosexual men were diagnosed late compared with 46% of women and 36% of men who have sex with men (MSM) (P < 0.01). The percentage of late diagnoses was highest among black African adults (66%) compared with other ethnicities; 96% of black African adults diagnosed late were born abroad. Overall, 88% and 97% of patients were linked to care within 1 and 3 months of diagnosis, respectively, with little variation by demographics and exposure category. The crude 1-year mortality rate was 31.6 per 1000 persons diagnosed in 2010. It was highest among adults diagnosed late (40.3/1000 versus 5.2/1000 for prompt diagnoses) and particularly among those aged 50 years and over. Excluding deaths, 85% of the 5833 diagnosed in 2010 were retained in care in 2011; 92% of the 2264 adults diagnosed late in 2010 received antiretroviral therapy by the end of 2011. The National Health Service provides high-quality care to persons newly diagnosed with HIV infection in the UK, with no evidence of health inequalities. Despite excellent care, half of adults are diagnosed late according to the threshold at which national guidelines recommend treatment should begin. Such patients have an 8-fold increased risk of 1-year mortality compared with those diagnosed promptly. Reducing late diagnosis of HIV infection remains a public health priority in the UK. © 2013 British HIV Association.
Venables, Noah C; Hall, Jason R; Yancey, James R; Patrick, Christopher J
2015-05-01
The Two-Process theory of psychopathy posits that distinct etiological mechanisms contribute to the condition: (a) a weakness in defensive (fear) reactivity related to affective-interpersonal features, and (b) impaired cognitive-executive functioning, marked by reductions in brain responses such as P3, related to impulsive-antisocial features. The current study examined relations between psychopathy factors and electrocortical response to emotional and neutral pictures in male offenders (N = 139) assessed using the Psychopathy Checklist-Revised (PCL-R). Impulsive-antisocial features of the PCL-R (Factor 2) were associated with reduced amplitude of earlier P3 brain response to pictures regardless of valence, whereas the affective-interpersonal dimension (Factor 1) was associated specifically with reductions in late positive potential response to aversive pictures. Findings provide further support for the Two-Process theory and add to a growing body of evidence linking the impulsive-antisocial facet of psychopathy to the broader construct of externalizing proneness. Findings are discussed in terms of current initiatives directed at incorporating neuroscientific concepts into psychopathology classification. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
Venables, Noah C.; Hall, Jason R.; Yancey, James R.; Patrick, Christopher J.
2014-01-01
The Two-Process theory of psychopathy posits distinct etiological mechanisms contribute to the disorder: 1) a weakness in defensive (fear) reactivity related to affective-interpersonal features, and 2) impaired cognitive-executive functioning, marked by reductions in brain responses such as P3, related to impulsive-antisocial features. The current study examined relations between psychopathy factors and electrocortical response to emotional and neutral pictures in male offenders (N=139) assessed using the Psychopathy Checklist-Revised (PCL-R). Impulsive-antisocial features of the PCL-R (Factor 2) were associated with reduced amplitude of earlier P3 brain response to pictures regardless of valence, whereas the affective-interpersonal dimension (Factor 1) was associated specifically with reductions in late positive potential response to aversive pictures. Findings provide further support for the Two-Process theory and add to a growing body of evidence linking the impulsive-antisocial facet of psychopathy to the broader construct of externalizing proneness. Findings are discussed in terms of current initiatives directed at incorporating neuroscientific concepts into psychopathology classification. PMID:25603361
The Productivity Costs of Inefficient Hiring Practices: Evidence from Late Teacher Hiring
Papay, John P.; Kraft, Matthew A.
2017-01-01
We use matched employee-employer records from the teacher labor market to explore the effects of late teacher hiring on student achievement. Hiring teachers after the school year starts reduces student achievement by 0.042SD in mathematics and 0.026SD in reading. This reflects, in part, a temporary disruption effect in the first year. In mathematics, but not in reading, late-hired teachers remain persistently less effective, evidence of negative selection in the teacher labor market. Late hiring concentrates in schools that disproportionately serve disadvantaged student populations, contributing to challenges in ensuring an equitable distribution of educational resources across students. PMID:28966429
The Productivity Costs of Inefficient Hiring Practices: Evidence from Late Teacher Hiring.
Papay, John P; Kraft, Matthew A
2016-01-01
We use matched employee-employer records from the teacher labor market to explore the effects of late teacher hiring on student achievement. Hiring teachers after the school year starts reduces student achievement by 0.042SD in mathematics and 0.026SD in reading. This reflects, in part, a temporary disruption effect in the first year. In mathematics, but not in reading, late-hired teachers remain persistently less effective, evidence of negative selection in the teacher labor market. Late hiring concentrates in schools that disproportionately serve disadvantaged student populations, contributing to challenges in ensuring an equitable distribution of educational resources across students.
Lim, Limin; Wong, Hungchew; Yong, Euleong; Singh, Kuldip
2012-02-01
Teenage abortions predispose women to adverse pregnancy outcomes in subsequent pregnancies such as anemia, stillbirths, preterm deliveries and low birth weight babies. We aim to profile the women presenting for abortions in our institution and determine risk factors for late presentation for abortions. In this retrospective cohort study, all women who underwent an abortion at the National University Hospital, Singapore, from 2005 to 2009 were recruited. Data was obtained from a prepared questionnaire during the mandatory pre-abortion counseling sessions. Profiles of women aged <20 years were compared with those ≥ 20 years old using Chi-square test if the assumptions for Chi-square test were met; otherwise, Fisher's exact test was carried out. Logistic regression was used to investigate the risk factors for second trimester termination of pregnancy. 2109 women presented for induced abortions, of which 1998 had single abortion throughout the course of the study. The mean age of women with single abortion was 29.1 years (sd 7). In the group of women with single abortion, 182 (9.1%) were teenage abortions. In contrast to women ≥ 20 years of age, pregnant teenagers were more likely not to have used any contraception (51.1% vs. 25.2%) and more likely to present late for abortions (39.6% vs. 15.9%). Other risk factors for late presentation for abortions include Malay ethnicity, singlehood, nulliparity and lack of prior usage of contraception. Teenagers are more likely to have no prior contraceptive usage and to present late for abortions. Lack of proper sexual education and awareness of contraceptive measures may have a major contributory factor to such a trend in teenage abortions. Recommendations have been made in order to curb this societal problem. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Torres, Irina B; Reisaeter, Anna V; Moreso, Francesc; Âsberg, Anders; Vidal, Marta; Garcia-Carro, Clara; Midtvedt, Karsten; Reinholt, Finn P; Scott, Helge; Castellà, Eva; Salcedo, Maite; Dörje, Christina; Sellarés, Joana; Azancot, Maria A; Perello, Manel; Holdaas, Hallvard; Serón, Daniel
2017-11-01
The aim was to evaluate the relationship between maintenance immunosuppression, subclinical tubulo-interstitial inflammation and interstitial fibrosis/tubular atrophy (IF/TA) in surveillance biopsies performed in low immunological risk renal transplants at two transplant centers. The Barcelona cohort consisted of 109 early and 66 late biopsies in patients receiving high tacrolimus (TAC-C 0 target at 1-year 6-10 ng/ml) and reduced MMF dose (500 mg bid at 1-year). The Oslo cohort consisted of 262 early and 237 late biopsies performed in patients treated with low TAC-C 0 (target 3-7 ng/ml) and standard MMF dose (750 mg bid). Subclinical inflammation, adjusted for confounders, was associated with low TAC-C 0 in the early (OR: 0.75, 95% CI: 0.61-0.92; P = 0.006) and late biopsies (OR: 0.69, 95% CI: 0.50-0.95; P = 0.023) from Barcelona. In the Oslo cohort, it was associated with low MMF in early biopsies (OR: 0.90, 95% CI: 0.83-0.98; P = 0.0101) and with low TAC-C 0 in late biopsies (OR: 0.77, 95% CI: 0.61-0.97; P = 0.0286). MMF dose was significantly reduced in Oslo between early and late biopsies. IF/TA was not associated with TAC-C 0 or MMF dose in the multivariate analysis. Our data suggest that in TAC- and MMF-based regimens, TAC-C 0 levels are associated with subclinical inflammation in patients receiving reduced MMF dose. © 2017 Steunstichting ESOT.
THE EFFECT OF ACTIDIONE ON MITOSIS IN THE SLIME MOLD PHYSARUM POLYCEPHALUM
Cummins, J. E.; Brewer, E. N.; Rusch, H. P.
1965-01-01
Actidione, reportedly a specific inhibitor of protein synthesis, was found to reduce the incorporation of labeled amino acids into proteins of the slime mold Physarum polycephalum without drastically inhibiting the incorporation of nucleic acid precursors into RNA. This inhibitor was found to completely block the ensuing mitosis if it was added at any time between telophase and late prophase. Plasmodia given Actidione in late prophase (about the time of nucleolar dissolution) went on through telophase to reconstruction even though nuclear amino acid incorporation was drastically reduced during that period. PMID:5894452
Somatostatin and the dumping syndrome.
Long, R G; Adrian, T E; Bloom, S R
1985-03-23
Infusion of somatostatin reduced the symptoms of the early dumping syndrome after oral glucose was given and also reduced the associated tachycardia and rise in packed cell volume. It inhibited the secretion of enteroglucagon, neurotensin, and vasoactive intestinal polypeptide, which are raised in patients with the dumping syndrome and may have an aetiological role. It also prevented the reactive hypoglycaemia of late dumping by inhibiting the release of gastric inhibitory polypeptide and insulin. Somatostatin, possibly through its inhibitory effects on hormonal secretion, may have a role in the management of patients with the early and late dumping syndrome.
Where does the Occluded Artery Trial leave the late open artery hypothesis?
Lamas, Gervasio A; Hochman, Judith S
2007-01-01
As of April 2007 the early open artery hypothesis is alive and well, but the late open artery hypothesis is adrift. For the foreseeable future, stable patients with persistent occlusion of the infarct artery late after myocardial infarction, and without severe ischaemia or uncontrollable angina, should be managed initially with optimal medical treatment alone, and not with percutaneous coronary intervention. Efforts should focus on establishing reperfusion earlier, including reducing the time to patient presentation. PMID:17933981
Bioresorbable scaffolds for percutaneous coronary interventions
Gogas, Bill D.
2014-01-01
Innovations in drug-eluting stents (DES) have substantially reduced rates of in-segment restenosis and early stent thrombosis, improving clinical outcomes following percutaneous coronary interventions (PCI). However a fixed metallic implant in a vessel wall with restored patency and residual disease remains a precipitating factor for sustained local inflammation, in-stent neo-atherosclerosis and impaired vasomotor function increasing the risk for late complications attributed to late or very late stent thrombosis and late target lesion revascularization (TLR) (late catch-up). The quest for optimal coronary stenting continues by further innovations in stent design and by using biocompatible materials other than cobalt chromium, platinum chromium or stainless steel for engineering coronary implants. Bioresorbable scaffolds made of biodegradable polymers or biocorrodible metals with properties of transient vessel scaffolding, local drug-elution and future restoration of vessel anatomy, physiology and local hemodynamics have been recently developed. These devices have been utilized in selected clinical applications so far providing preliminary evidence of safety showing comparable performance with current generation drug-eluting stents (DES). Herein we provide a comprehensive overview of the current status of these technologies, we elaborate on the potential benefits of transient coronary scaffolds over permanent stents in the context of vascular reparation therapy, and we further focus on the evolving challenges these devices have to overcome to compete with current generation DES. Condensed Abstract:: The quest for optimizing percutaneous coronary interventions continues by iterative innovations in device materials beyond cobalt chromium, platinum chromium or stainless steel for engineering coronary implants. Bioresorbable scaffolds made of biodegradable polymers or biocorrodible metals with properties of transient vessel scaffolding; local drug-elution and future restoration of vessel anatomy, physiology and local hemodynamics were recently developed. These devices have been utilized in selected clinical applications providing preliminary evidence of safety showing comparable intermediate term clinical outcomes with current generation drug-eluting stents. PMID:25780795
Which women default from follow-up cervical cytology tests? A cohort study within the TOMBOLA trial.
Sharp, L; Cotton, S; Thornton, A; Gray, N; Whynes, D; Smart, L; Waugh, N; Duncan, I; Cruickshank, M; Little, J
2012-06-01
To identify factors associated with default from follow-up cervical cytology tests. A cohort study was conducted involving 2166 women, aged 20-59, with recent low-grade cervical cytology taken within the NHS Cervical Screening Programmes in Scotland and England, and managed by 6-monthly cytology in primary care. For the first (6-month) and second (12-month) surveillance cytology tests separately, women were categorized as 'on-time attendees' (attended ≤6 months of test being due), 'late attendees' (attended greater than 6 months after test was due) or 'non-attendees' (failed to attend). Multivariate odds ratios (ORs) were computed for factors associated with late and non-attendance. For the first surveillance test, risk of non-attendance was significantly higher in younger women, those without post-secondary education, and non-users of prescribed contraception. Factors significantly associated with late attendance for the first test were the same as for non-attendance, plus current smoking and having children. The most important predictor of non-attendance for the second surveillance test was late attendance for the first test (OR = 9.65; 95% CI, 6.60-16.62). Non-attendance for the second test was also significantly higher among women who were younger, smokers and had negative cytology on the first surveillance test. Late attendance for the second surveillance test was higher in women who were younger, smokers, had children and attended late for the first test. Women at highest risk of default from follow-up cytology tend to be young, smoke, lack post-secondary education, and have defaulted from a previous surveillance appointment. Tackling default will require development of targeted strategies to encourage attendance and research to better understand the reasons underpinning default. © 2011 Blackwell Publishing Ltd.
Late whiplash syndrome: a clinical science approach to evidence-based diagnosis and management.
Poorbaugh, Keith; Brismée, Jean-Michel; Phelps, Valerie; Sizer, Phillip S
2008-01-01
The purpose of this article is to narrow the gap that exists in the clinical application of scientific research and empiric evidence for the evaluation and management of late whiplash. Considering that 14% to 42% of patients are left with chronic symptoms following whiplash injury, it is unlikely that only minor self-limiting injuries result from the typical rear-end impact. As psychosocial issues play a role in the development of persistent whiplash symptoms, discerning the organic conditions from the biopsychosocial factors remains a challenge to clinicians. The term "whiplash" represents the multiple factors associated with the event, injury, and clinical syndrome that are the end-result of a sudden acceleration-deceleration trauma to the head and neck. However, contentions surround the nature of soft-tissue injuries that occur with most motor vehicle accidents and whether these injuries are significant enough to result in chronic pain and limitations. The stark contrast in litigation for whiplash that exists among industrialized nations and less developed countries suggests another factor that could influence one's interpretation of symptoms' chronicity associated with Late Whiplash Syndrome. There are no gold standard tests or imaging techniques that can objectify whiplash-associated disorders. A lack of supporting evidence and disparity in medico-legal issues have created distinct camps in the scientific interpretations and clinical management of late whiplash. It is likely that efforts in research and/or clinical practice will begin to explain the disparity between acute and chronic whiplash syndrome. Recent evidence suggests that Late Whiplash Syndrome should be considered from a different context. The purpose of this article is to expound on several of the significant findings in the literature and offer clinical applications for evaluation and management of Late Whiplash Syndrome.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Machtay, Mitchell, E-mail: mitchell.machtay@uhhospitals.org; Moughan, Jennifer; Farach, Andrew
Purpose: Concurrent chemoradiation therapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control but at the expense of increased toxicity. We recently showed that several clinical/pretreatment factors were associated with the occurrence of severe late toxicity. This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods and Materials: This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis asmore » chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube {>=}2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors. Results: A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46% of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving {<=}60 Gy to the inferior hypopharynx had a 40% rate of severe late toxicity compared with 56% for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome. Conclusions: Severe late toxicity following CCRT is common in long-term survivors. Age is the most significant factor, but hypopharyngeal dose also was associated.« less
Sex differences in neonatal mortality in Sarlahi, Nepal: the role of biology and environment.
Rosenstock, Summer; Katz, Joanne; Mullany, Luke C; Khatry, Subarna K; LeClerq, Steven C; Darmstadt, Gary L; Tielsch, James M
2013-12-01
Studies in South Asia have documented increased risk of neonatal mortality among girls, despite evidence of a biological survival advantage. Associations between gender preference and mortality are cited as reasons for excess mortality among girls. This has not, however, been tested in statistical models. A secondary analysis of data from a population-based randomised controlled trial of newborn infection prevention conducted in rural southern Nepal was used to estimate sex differences in early and late neonatal mortality, with girls as the reference group. The analysis investigated which underlying biological factors (immutable factors specific to the newborn or his/her mother) and environmental factors (mutable external factors) might explain observed sex differences in mortality. Neonatal mortality was comparable by sex (Ref=girls; OR 1.06, 95% CI 0.92 to 1.22). When stratified by neonatal period, boys were at 20% (OR 1.20, 95% CI 1.02% to 1.42%) greater risk of early and girls at 43% (OR 0.70, 95% CI 0.51% to 0.94%) greater risk of late neonatal mortality. Biological factors, primarily respiratory depression and unconsciousness at birth, explained excess early neonatal mortality among boys. Increased late neonatal mortality among girls was explained by a three-way environmental interaction between ethnicity, sex and prior sibling composition (categorised as primiparous newborns, infants born to families with prior living boys or boys and girls, and infants born to families with only prior living girls). Risk of neonatal mortality inverted between the early and late neonatal periods. Excess risk of early neonatal death among boys was consistent with biological expectations. Excess risk for late neonatal death among girls was not explained by overarching gender preference or preferential care-seeking for boys as hypothesised, but was driven by increased risk among Madeshi girls born to families with only prior girls.
Nam, So-Hyun; Kim, Dae-Yeon; Kim, Seong-Chul; Kim, In-Koo
2010-04-01
Totally implantable access ports (TIAPs) are widely used in pediatric hematology-oncology patients. We investigated the incidence of complications, causes of TIAP removal, and risk factors for infection. We retrospectively analyzed the clinical, demographic, and surgical characteristics in 225 pediatric hematology-oncology patients implanted with 238 TIAPs between January 2004 and December 2005. Except for 20 patients lost to follow-up, the mean maintenance period was 724.8 +/- 500.6 days (range: 17-2,124). Mechanical complications occurred in seven patients (2.9%). The causes of TIAP removal were termination of use in 130 patients (59.6%), death from primary disease with TIAP in situ in 35 (14.7%), infection in 35 (14.7%), and obstruction in 4 (1.8%). Early infections occurred in nine patients at mean 37.77 +/- 16.44 days (range: 17-56). Late infections occurred in 26 patients at mean 334.5 +/- 257.82 days (range: 68-997). Univariate analysis showed that the risk factors of early infection were re-implantation (P = 0.022) and long operation time (P = 0.045). The risk factors of late infection were ANC <500/mm(3) (P = 0.011) and platelet count <50,000/mm(3) (P < 0.001). In multivariate analysis, re-implantation was a significant risk factor of early infection (P = 0.033, OR 4.528) and low platelet count (<50,000/mm(3)) was the independent risk factor for late infection (P = 0.005, OR 4.24). Correct procedure and careful use decreases the incidence of early infection and leads to the prevention of re-implantation. Initial thrombocytopenia was attributable to bone marrow suppression caused by hematologic malignancies or severe infection. Thus, this condition is of value in predicting late infection.
Women's caregiving and paid work: causal relationships in late midlife.
Pavalko, E K; Artis, J E
1997-07-01
Care of an ill or disabled family member or friend is disproportionately done by women and typically is done in late midlife. Because this is-also a time in the life course when women's labor force participation peaks, many women faced with caregiving demands have to decide how to balance them with their employment. In this study we use the National Longitudinal Survey (NLS) of Mature Women to examine the causal relationship between employment and caring for an ill or disabled friend or relative over a three-year period. We find that employment does not affect whether or not women start caregiving, but that women who do start are more likely to reduce employment hours or stop work. Thus, the causal relationship between employment and caregiving in late midlife is largely unidirectional, with women reducing hours to meet caregiving demands.
Sabin, Keith; Ho, Thi Quynh Trang; Le, Ai Kim Anh; Hayashi, Chika; Kato, Masaya
2017-01-01
Background The prevention of mother-to-child transmission (PMTCT) of HIV program was introduced in Vietnam in 2005. Despite the scaling up of PMTCT programs, the rate of mother-to-child HIV transmission in Vietnam was estimated as high as 20% in 2013. Objective The objective of this study was to assess the outcomes of PMTCT and identified factors associated with mother-to-child transmission and infant survival using survey and program data in a high HIV burden province in Vietnam. Methods This community-based retrospective cohort study observed pregnant women diagnosed with HIV infection in Thai Nguyen province from October 2008 to December 2012. Data were collected through interviews using a structured questionnaire and through reviews of log books and medical charts in antenatal care and HIV clinics. Logistic regression and survival analysis were used to analyze data using Stata (StataCorp). Results A total of 172 pregnant women living with HIV were identified between 2008 and 2012. Most of these women had acquired the HIV infection from their husband (77/119, 64.7%). Significant improvement in the PMTCT program was documented, including reduction in late diagnosis of HIV for pregnant women from 62.5% in 2008 to 30% in 2012. Access to antiretrovirals (ARVs) improved, increasing from a rate of 18.2% (2008) to 70.0% (2011) for mothers and from 36.4% (2008) to 93.3% (2012) for infants. For infants, early diagnosis within 2 months of birth reached 66.7% in 2012 compared with 16.7% in 2009. Transmission rate reduced from 27.3% in 2008 to 6.7% in 2012. Late diagnosis was associated with increased risk for HIV transmission (odds ratio [OR] 14.7, 95% CI 1.8-121.4, P=.01), whereas ARV therapy for mother and infant in combination with infant formula feeding were associated with reduced risk for HIV transmission (OR 0.01, 95% CI 0.001-0.1; P<.001). Overall survival rate for HIV-exposed infants at 12 months was 97.7%. Conclusions A combination of program and survey data measured the impact of prevention of HIV transmission from mother-to-child interventions. Significant improvement in access to the interventions was documented in Thai Nguyen province. However, factors that increased the risk of HIV transmission, such as late diagnosis, remain to be addressed. PMID:29263016
Kim, Girak; Jang, Mi Seon; Son, Young Min; Seo, Min Ji; Ji, Sang Yun; Han, Seung Hyun; Jung, In Duk; Park, Yeong-Min; Jung, Hyun Jung; Yun, Cheol-Heui
2013-01-01
Background Curcumin is a promising candidate for a natural medicinal agent to treat chronic inflammatory diseases. Although CD4+ T cells have been implicated in the pathogenesis of chronic inflammation, whether curcumin directly regulates CD4+ T cells has not been definitively established. Here, we showed curcumin-mediated regulation of CD2/CD3/CD28-initiated CD4+ T cell activation in vitro. Methodology/Principal Findings Primary human CD4+ T cells were stimulated with anti-CD2/CD3/CD28 antibody-coated beads as an in vitro surrogate system for antigen presenting cell-T cell interaction and treated with curcumin. We found that curcumin suppresses CD2/CD3/CD28-initiated CD4+ T cell activation by inhibiting cell proliferation, differentiation and cytokine production. On the other hand, curcumin attenuated the spontaneous decline of CD69 expression and indirectly increased expression of CCR7, L-selectin and Transforming growth factor-β1 (TGF-β1) at the late phase of CD2/CD3/CD28-initiated T cell activation. Curcumin-mediated up-regulation of CD69 at late phase was associated with ERK1/2 signaling. Furthermore, TGF-β1 was involved in curcumin-mediated regulation of T cell activation and late-phase generation of regulatory T cells. Conclusions/Significance Curcumin not merely blocks, but regulates CD2/CD3/CD28-initiated CD4+ T cell activation by augmenting CD69, CCR7, L-selectin and TGF-β1 expression followed by regulatory T cell generation. These results suggest that curcumin could directly reduce T cell-dependent inflammatory stress by modulating CD4+ T cell activation at multiple levels. PMID:23658623
Professional Women and Marriage.
ERIC Educational Resources Information Center
Allen, Suzanne M.; Kalish, Richard A.
1984-01-01
Explored the phenomenon of late marriage in 41 highly educated professional women. Compared with normative marriers, the late-marrying women had higher career goals, a more egalitarian role structure in marriage, and were more accepting of premarital sex and cohabitation. Factors associated with family backgrounds were identified. (JAC)
Recent advances in the management of transient ischemic attacks
Gomez, Camilo R.; Schneck, Michael J.; Biller, Jose
2017-01-01
Significant advances in our understanding of transient ischemic attack (TIA) have taken place since it was first recognized as a major risk factor for stroke during the late 1950's. Recently, numerous studies have consistently shown that patients who have experienced a TIA constitute a heterogeneous population, with multiple causative factors as well as an average 5–10% risk of suffering a stroke during the 30 days that follow the index event. These two attributes have driven the most important changes in the management of TIA patients over the last decade, with particular attention paid to effective stroke risk stratification, efficient and comprehensive diagnostic assessment, and a sound therapeutic approach, destined to reduce the risk of subsequent ischemic stroke. This review is an outline of these changes, including a discussion of their advantages and disadvantages, and references to how new trends are likely to influence the future care of these patients. PMID:29263784
Improvement in spatial imagery following sight onset late in childhood.
Gandhi, Tapan K; Ganesh, Suma; Sinha, Pawan
2014-03-01
The factors contributing to the development of spatial imagery skills are not well understood. Here, we consider whether visual experience shapes these skills. Although differences in spatial imagery between sighted and blind individuals have been reported, it is unclear whether these differences are truly due to visual deprivation or instead are due to extraneous factors, such as reduced opportunities for the blind to interact with their environment. A direct way of assessing vision's contribution to the development of spatial imagery is to determine whether spatial imagery skills change soon after the onset of sight in congenitally blind individuals. We tested 10 children who gained sight after several years of congenital blindness and found significant improvements in their spatial imagery skills following sight-restoring surgeries. These results provide evidence of vision's contribution to spatial imagery and also have implications for the nature of internal spatial representations.
Suicide risk in primary care: identification and management in older adults.
Raue, Patrick J; Ghesquiere, Angela R; Bruce, Martha L
2014-09-01
The National Strategy for Suicide Prevention (2012) has set a goal to reduce suicides by 20% within 5 years. Suicide rates are higher in older adults compared to most other age groups, and the majority of suicide completers have visited their primary care physician in the year before suicide. Primary care is an ideal setting to identify suicide risk and initiate mental health care. We review risk factors for late-life suicide; methods to assess for different levels of suicidality; and recent research developments regarding both effective assessment and management of suicide risk among older primary care patients. We highlight that broader scale screening of suicide risk may be considered in light of findings that suicidality can occur even in the absence of major risk factors like depression. We also highlight collaborative care models targeting suicide risk, and recent innovative interventions that aim to prevent the development of suicidal ideation and suicidal behavior.
Cencioni, Chiara; Spallotta, Francesco; Savoia, Matteo; Kuenne, Carsten; Guenther, Stefan; Re, Agnese; Wingert, Susanne; Rehage, Maike; Sürün, Duran; Siragusa, Mauro; Smith, Jacob G; Schnütgen, Frank; von Melchner, Harald; Rieger, Michael A; Martelli, Fabio; Riccio, Antonella; Fleming, Ingrid; Braun, Thomas; Zeiher, Andreas M; Farsetti, Antonella; Gaetano, Carlo
2018-03-29
Nitric oxide (NO) synthesis is a late event during differentiation of mouse embryonic stem cells (mESC) and occurs after release from serum and leukemia inhibitory factor (LIF). Here we show that after release from pluripotency, a subpopulation of mESC, kept in the naive state by 2i/LIF, expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes NO. This eNOS/NO-positive subpopulation (ESNO+) expresses mesendodermal markers and is more efficient in the generation of cardiovascular precursors than eNOS/NO-negative cells. Mechanistically, production of endogenous NO triggers rapid Hdac2 S-nitrosylation, which reduces association of Hdac2 with the transcriptional repression factor Zeb1, allowing mesendodermal gene expression. In conclusion, our results suggest that the interaction between Zeb1, Hdac2, and eNOS is required for early mesendodermal differentiation of naive mESC.
Pathogenesis of osteoporotic hip fractures.
McClung, Michael R
2003-01-01
Osteoporosis is characterized late in the course of the disease by an increased risk of fracture, particularly in the elderly. It occurs in both sexes, affecting approximately 8 million women and 2 million men aged > or = 50 years (1). While low bone density is a predictor of fractures, it is not the only determinant of fracture risk. Other factors include advanced age, altered bone quality, a personal or family history of falls, frailty, poor eyesight, debilitating diseases, and high bone turnover. A diet with sufficient calcium and vitamin D is important to minimize bone loss and, along with regular exercise, to maintain muscle strength. Bisphosphonates have been shown to reduce the risk of hip fracture. For elderly patients, the use of hip protectors may be used as a treatment of last resort. Regardless of the age of the patient, individual patient risk factors must be considered to target appropriate treatment and prevent fracture.
Suicide Risk in Primary Care: Identification and Management in Older Adults
Raue, Patrick J.; Ghesquiere, Angela R.; Bruce, Martha L.
2014-01-01
The National Strategy for Suicide Prevention (2012) has set a goal to reduce suicides by 20% within 5 years. Suicide rates are higher in older adults compared to most other age groups, and the majority of suicide completers have visited their primary care physician in the year before suicide. Primary care is an ideal setting to identify suicide risk and initiate mental health care. We review risk factors for late-life suicide; methods to assess for different levels of suicidality; and recent research developments regarding both effective assessment and management of suicide risk among older primary care patients. We highlight that broader scale screening of suicide risk may be considered in light of findings that suicidality can occur even in the absence of major risk factors like depression. We also highlight collaborative care models targeting suicide risk, and recent innovative interventions that aim to prevent the development of suicidal ideation and suicidal behavior. PMID:25030971
Molina-Hernandez, Miguel; Perez, Julian Garcia; Olivera Lopez, Jorge Ivan
2002-06-01
In a conflict test based on the rat's choice between an immediate punished reinforcer or a delayed nonpunished reinforcer, anxiolytic drugs increase the number of immediate punished reinforcers. In this study, two hypotheses were tested: first, during late proestrus or during midpregnancy, female rats will display an elevated amount of immediate punished reinforcers; second, ovariectomized rats will display an elevated amount of immediate punished reinforcers when they receive anxiolytic doses of neurosteroids. Thus, female rats (n = 15) were tested repeatedly during late proestrus, diestrus, and pregnancy in the aforementioned conflict task. They displayed an elevated amount of immediate punished reinforcers during late proestrus (P < .05) and during the 14th (P < .05) and 17th (P < .05) days of pregnancy compared to diestrus or 3rd, 7th, or 20th days of pregnancy. Likewise, ovariectomized rats (n = 90) displayed an elevated amount of immediate punished reinforcers compared to control rats only when they received anxiolytic doses of progesterone (1.0-2.0 mg/kg, P < .05) or allopregnanolone (1.0-2.0 mg/kg, P < .05). In conclusion, female rats displayed reduced conflict behavior during late proestrus and pregnancy, or after received anxiolytic doses of neurosteroids.
LATE EVALUATION OF PATIENTS UNDERGOING MANIPULATION OF THE KNEE AFTER TOTAL ARTHROPLASTY.
DE Sousa, Pedro Guilme Teixeira; Chisté, Yuri Lubiana; Albuquerque, Rodrigo Sattamini Pires E; Cobra, Hugo Alexandre DE Araújo Barros; Barretto, João Maurício; Cavanellas, Naasson Trindade
2017-01-01
We compared gains in range of motion in patients who underwent manipulation within 12 weeks of total knee arthroplasty (TKA) and after this period. We also evaluated maintenance of the arc obtained from knee manipulation in late follow-up, along with factors associated with poorer outcomes. The study was divided into two groups according to the time after TKA; the surgeries took place between January 2008 and December 2014. When comparing the range of motion between early and late manipulations, the group that underwent manipulation within 12 weeks of the TKA exhibited better outcomes, but these were not statistically significant. We observed that 14.3% of cases retained the same range attained at the time of manipulation. In late evaluation after manipulation, 47.7% of the sample had a range of less than 90 degrees. The significant risk factors for recurrence of knee stiffness in the long term are poor range of motion before TKA and before manipulation, female sex, and secondary arthritis. Women previously diagnosed with secondary osteoarthritis and poor range of motion before TKA or manipulation are at higher risk for late stiffness. Level of Evidence III, Retrospective Comparative Study.
Risk factors for late onset gram-negative infections: a case-control study.
Samanta, Srabani; Farrer, Kate; Breathnach, Aodhan; Heath, Paul T
2011-01-01
To determine the incidence, mortality and risk factors for neonatal late onset gram-negative sepsis and meningitis (LOGNS). Retrospective case-control study. Tertiary neonatal unit in London. Consecutive inborn infants with late onset (>48 h of life) invasive gram-negative infections diagnosed between 1999 and 2005. Controls were healthy infants matched for gestation and time of admission to the neonatal unit. Clinical and risk factor data. 73 cases of LOGNS were identified of which 48 were inborn and included in the study (incidence 1.85/1000 live births). Enterobacter spp. (28%), Escherichia coli (27%) and Klebsiella spp. (21%) were the most common pathogens. The majority of infants were of very low birthweight (VLBW; 79%), and cases and controls were well matched (median gestation 26 weeks). Overall case death was 27% in cases versus 13.5% in controls (p=0.08). There was no significant difference between cases and controls regarding maternal risk factors. Mechanical ventilation, total parenteral nutrition (TPN) and its duration, presence of a central venous line and its duration, use of specific antibiotics and the occurrence of necrotising enterocolitis at or before the first positive culture were all significantly associated with case status in univariate analysis. In multivariate logistic regression analysis, only duration of TPN at or before first positive blood culture remained independently associated with LOGNS (p<0.001). LOGNS occurs predominantly in VLBW infants. When the influence of gestational age is accounted for, the only independent risk factor found for late onset gram-negative neonatal infections is the duration of TPN.
Costs of landscape silviculture for fire and habitat management.
S. Hummel; D.E. Calkin
2005-01-01
In forest reserves of the U.S. Pacific Northwest, management objectives include protecting late-semi habitat structure by reducing the threat of large-scale disturbances like wildfire. We simulated how altering within- and among-stand structure with silvicultural treatments of differing intensity affected late-seral forest (LSF) structure and fire threat (FT) reduction...
Namazkar, Shahla; Stockmarr, Anders; Frenck, Georg; Egsgaard, Helge; Terkelsen, Thilde; Mikkelsen, Teis; Ingvordsen, Cathrine Heinz; Jørgensen, Rikke Bagger
2016-07-01
Plant oil is an essential dietary and bio-energy resource. Despite this, the effects of climate change on plant oil quality remain to be elucidated. The present study is the first to show changes in oil quality and quantity of four rapeseed cultivars in climate scenarios with elevated [CO2], [O3] and temperature (T) combined and as single factors. The combination of environmental factors resembled IPCC's 'business as usual' emission scenario predicted for late this century. Generally, the climate scenarios reduced the average amounts of the six fatty acids (FAs) analysed, though in some treatments single FAs remained unchanged or even increased. Most reduced was the FA essential for human nutrition, C18:3-ω3, which decreased by 39% and 45% in the combined scenarios with elevated [CO2]+T+[O3] and [CO2]+T, respectively. Average oil content decreased 3-17%. When [CO2] and T were elevated concurrently, the seed biomass was reduced by half, doubling the losses in FAs and oil content. This corresponded to a 58% reduction in the oil yield per hectare, and C18:3-ω3 decreased by 77%. Furthermore, the polyunsaturated FAs were significantly decreased. The results indicate undesirable consequences for production and health benefits of rapeseed oil with future climate change. The results also showed strong interactive effects of CO2, T and O3 on oil quality, demonstrating why prediction of climate effects requires experiments with combined factors and should not be based on extrapolation from single factor experiments. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Redekar, Neelam R; Biyashev, Ruslan M; Jensen, Roderick V; Helm, Richard F; Grabau, Elizabeth A; Maroof, M A Saghai
2015-12-18
Low phytic acid (lpa) crops are potentially eco-friendly alternative to conventional normal phytic acid (PA) crops, improving mineral bioavailability in monogastric animals as well as decreasing phosphate pollution. The lpa crops developed to date carry mutations that are directly or indirectly associated with PA biosynthesis and accumulation during seed development. These lpa crops typically exhibit altered carbohydrate profiles, increased free phosphate, and lower seedling emergence, the latter of which reduces overall crop yield, hence limiting their large-scale cultivation. Improving lpa crop yield requires an understanding of the downstream effects of the lpa genotype on seed development. Towards that end, we present a comprehensive comparison of gene-expression profiles between lpa and normal PA soybean lines (Glycine max) at five stages of seed development using RNA-Seq approaches. The lpa line used in this study carries single point mutations in a myo-inositol phosphate synthase gene along with two multidrug-resistance protein ABC transporter genes. RNA sequencing data of lpa and normal PA soybean lines from five seed-developmental stages (total of 30 libraries) were used for differential expression and functional enrichment analyses. A total of 4235 differentially expressed genes, including 512-transcription factor genes were identified. Eighteen biological processes such as apoptosis, glucan metabolism, cellular transport, photosynthesis and 9 transcription factor families including WRKY, CAMTA3 and SNF2 were enriched during seed development. Genes associated with apoptosis, glucan metabolism, and cellular transport showed enhanced expression in early stages of lpa seed development, while those associated with photosynthesis showed decreased expression in late developmental stages. The results suggest that lpa-causing mutations play a role in inducing and suppressing plant defense responses during early and late stages of seed development, respectively. This study provides a global perspective of transcriptomal changes during soybean seed development in an lpa mutant. The mutants are characterized by earlier expression of genes associated with cell wall biosynthesis and a decrease in photosynthetic genes in late stages. The biological processes and transcription factors identified in this study are signatures of lpa-causing mutations.
Al-Holou, Shaza N.; Tucker, William R.; Agrón, Elvira; Clemons, Traci E.; Cukras, Catherine; Ferris, Frederick L.; Chew, Emily Y.
2015-01-01
Objective/purpose To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Design Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Subjects Age-Related Eye Disease Study 2 participants, aged 50 to 85 years. Methods Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke, all known to be associated with statin use, were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses were also performed adjusting for the competing risk of death. Main Outcome Measures Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Results Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratios [HR] of 1.08, 95% confidence intervals [CI] of 0.83–1.41, P=0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant with HR: 0.81, 95% CI: 0.55–1.20, P=0.29. Further subgroup analyses of persons with or without late AMD at baseline to the various components of late AMD (neovascular, central geographic atrophy, or any geographic atrophy) also showed no statistically significant association of statin use with progression to AMD. Conclusions Statin use was not statistically significantly associated with the progression to late AMD in the AREDS2 participants, and these findings are consistent with the findings in the majority of previous studies. Statins have been demonstrated to reduce the risks of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression. PMID:26435335
Metabolic syndrome marks early risk for cognitive decline with APOE4 gene variation: A case study.
Brown, Dawson; Gibas, Kelly J
2018-04-20
A vast amount of research has been done on the APOE4 genetic marker for Alzheimer's disease (AD), but its connection to metabolic processes associated with peripheral insulin resistance and cerebral glucose metabolism is still relatively unknown. The APOE4 allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, particularly in individuals who have inherited two copies of the gene (Zhao et al., 2017). In this case study, a 38 year old male with metabolic syndrome (MetS), the APOE4 gene, early stage memory problems and a family history of Alzheimer's Disease (AD) was placed on a ketogenic diet combined with high intensity interval training (HIIT) for 10 weeks. The primary intervention goal was reduce insulin defect, impaired cerebral and peripheral insulin signaling, associated with metabolic syndrome. Recent research demonstrates that insulin defect competes for space with APOE4 in brain cells, thus exacerbating amyloid pathology (Zhao et al., 2017). Primary biomarkers for metabolic syndrome were measured at baseline and after 10 weeks. The MoCA (Montreal Cognitive Assessment) was administered at baseline and after 10 weeks. The results were statistically significant. The HOMA-IR (homeostatic measure of insulin resistance) decreased by 59% from 4.3 to 1.8. The triglyceride/HDL ratio decreased by 77% from 14.7 to 3.4. Fasting triglycerides were reduced from 573 mg/dL to 167 mg/dL (71% reduction); VLDL decreased from 114.6 mg/dL to 33.4 mg/dL (71% decrease); and fasting insulin was reduced by 55% from 15.6 mU/L to 7.1 mU/L. The baseline MoCA score was 22/30; post treatment score was 30/30. If APOEE4 is the strongest genetic risk factor for developing late-onset Alzheimer's Disease, then implementing a ketogenic diet and high intensity exercise could essentially turn "off" the effects of this APOE4 gene earlier in life for prevention of future neurodegeneration. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Muscatello, Maria Rosaria A; Scimeca, Giuseppe; Pandolfo, Gianluca; Micò, Umberto; Romeo, Vincenzo M; Mallamace, Domenico; Mento, Carmela; Zoccali, Rocco; Bruno, Antonio
2014-04-01
Executive cognitive functions (ECFs) and other cognitive impairments, such as lower IQ and verbal deficits, have been associated with the pattern of antisocial and delinquent behavior starting in childhood (early-onset), but not with late-onset antisocial behavior. Beyond objective measures of ECF, basic symptoms are prodromal, subjectively experienced cognitive, perceptual, affective, and social disturbances, associated with a range of psychiatric disorders, mainly with psychosis. The goal of the present study was to examine ECF and basic symptoms in a sample of late-onset juvenile delinquents. Two-hundred nine male adolescents (aged 15-20 years) characterized by a pattern of late-onset delinquent behavior with no antecedents of Conduct Disorder, were consecutively recruited from the Social Services of the Department of Juvenile Justice of the city of Messina (Italy), and compared with nonantisocial controls matched for age, educational level, and socio-demographic features on measures for ECF dysfunction and basic symptoms. Significant differences between late-onset offenders (completers=147) and control group (n=150) were found on ECF and basic symptoms measures. Chi-square analysis showed that a significantly greater number of late-onset offending participants scored in the clinical range on several ECF measures. Executive cognitive impairment, even subtle and subclinical, along with subjective symptoms of cognitive dysfunction (basic symptom), may be contributing factor in the development and persistence of antisocial behaviors displayed by late-onset adolescent delinquents. The findings also suggest the need for additional research aimed to assess a broader range of cognitive abilities and specific vulnerability and risk factors for late-onset adolescent offenders. Copyright © 2014 Elsevier Inc. All rights reserved.
Leal, Maria do Carmo; Esteves-Pereira, Ana Paula; Nakamura-Pereira, Marcos; Torres, Jacqueline Alves; Domingues, Rosa Maria Soares Madeira; Dias, Marcos Augusto Bastos; Moreira, Maria Elizabeth; Theme-Filha, Mariza; da Gama, Silvana Granado Nogueira
2016-01-01
A large proportion of the rise in prematurity worldwide is owing to late preterm births, which may be due to the expansion of obstetric interventions, especially pre-labour caesarean section. Late preterm births pose similar risks to overall prematurity, making this trend a concern. In this study, we describe factors associated with provider-initiated late preterm birth and verify differences in provider-initiated late preterm birth rates between public and private health services according to obstetric risk. This is a sub-analysis of a national population-based survey of postpartum women entitled "Birth in Brazil", performed between 2011 and 2012. We included 23,472 singleton live births. We performed non-conditional multiple logistic regressions assessing associated factors and analysing differences between public and private health services. Provider-initiated births accounted for 38% of late preterm births; 32% in public health services and 61% in private health services. They were associated with previous preterm birth(s) and maternal pathologies for women receiving both public and private services and with maternal age ≥35 years for women receiving public services. Women receiving private health services had higher rates of provider-initiated late preterm birth (rate of 4.8%) when compared to the ones receiving public services (rate of 2.4%), regardless of obstetric risk-adjusted OR of 2.3 (CI 1.5-3.6) for women of low obstetric risk and adjusted OR of 1.6 (CI 1.1-2.3) for women of high obstetric risk. The high rates of provider-initiated late preterm birth suggests a considerable potential for reduction, as such prematurity can be avoided, especially in women of low obstetric risk. To promote healthy births, we advise introducing policies with incentives for the adoption of new models of birth care.
Ebonwu, Joy; Mumbauer, Alexandra; Uys, Margot; Wainberg, Milton L; Medina-Marino, Andrew
2018-01-01
To investigate and compare determinates for delayed first presentation to antenatal care (ANC) services. A cross-sectional study was conducted amongst pregnant women attending their first ANC visit in rural Capricorn District and peri-urban Tlokwe sub-district communities in South Africa. Data collection included questionnaires and medical record abstraction. Bivariate and multivariate analyses assessed factors associated with late ANC presentation. We recruited 807 pregnant women. Of these, 51% of rural women and 28% of peri-urban women presented late for first ANC. Rural women were more likely to present late for first ANC (AOR = 2.65; 95% CI 1.98-3.55) and report barriers to accessing ANC services (P<0.0001). Late ANC presentation in rural communities was associated with being married (AOR = 2.36; 95% CI 1.33-4.19), employed (AOR = 1.90; 95% CI 1.03-3.50), <20 years of age (AOR = 2.19; 95% CI 1.10-4.37), and reporting an unplanned pregnancy (AOR = 2.21; 95% CI 1.40-3.50). Late presentation in peri-urban communities was associated with unplanned pregnancy (AOR = 1.67; 95% CI 1.01-2.74), being told to come back later to initiate ANC after presenting early (AOR 0.51; 95% CI 0.30-0.89) and being pregnant for the first time (AOR = 0.56; 95% CI 0.34-0.94). Both rural and peri-urban women had high rates of late presentation for first ANC. However, women in the rural communities were more likely to present late. Unplanned pregnancy was an independent risk factor in both rural and peri-urban communities. Interventions around family planning, especially for adolescent girls and young women, are needed to improve early presentation for ANC.
Zhu, Luchang; Lin, Jingjun; Kuang, Zhizhou; Vidal, Jorge E.; Lau, Gee W.
2015-01-01
Summary The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for genetic transformation. During competence development, the alternative sigma factor ComX is activated, which in turn, initiates transcription of 80 “late” competence genes. Interestingly, only 16 late genes are essential for genetic transformation. We hypothesized that these late genes that are dispensable for competence are beneficial to pneumococcal fitness during infection. These late genes were systematically deleted, and the resulting mutants were examined for their fitness during mouse models of bacteremia and acute pneumonia. Among these, 14 late genes were important for fitness in mice. Significantly, deletion of some late genes attenuated pneumococcal fitness to the same level in both wild-type and ComX-null genetic backgrounds, suggesting that the constitutive baseline expression of these genes was important for bacterial fitness. In contrast, some mutants were attenuated only in the wild-type genetic background but not in the ComX-null background, suggesting that specific expression of these genes during competence state contributed to pneumococcal fitness. Increased virulence during competence state was partially caused by the induction of allolytic enzymes that enhanced pneumolysin release. These results distinguish the role of basal expression versus competence induction in virulence functions encoded by ComX-regulated late competence genes. Graphical abstract During genetic transformation of pneumococcus, the alternative sigma factor ComX regulates expression of 14 late competence genes important for virulence. The constitutive baseline expression of some of these genes is important for bacteremia and acute pneumonia infections. In contrast, elevated expression of DprA, CbpD, CibAB, and Cinbox are dependent on competence development, enhancing the release of pneumolysin. These results distinguish the role of basal expression versus competence induction in virulence determinants regulated by ComX. PMID:25846124
Disease evolution in late-onset and early-onset systemic lupus erythematosus.
Aljohani, R; Gladman, D D; Su, J; Urowitz, M B
2017-10-01
Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.
Ayton, Jennifer; Hansen, Emily; Quinn, Stephen; Nelson, Mark
2012-11-26
To investigate and examine the factors associated with initiation of, and exclusive breastfeeding at hospital discharge of, late preterm (34 0/7 - 36 6/7 weeks) compared to 37 week gestation (37 0/7 - 37 6/7 week) mother and baby pairs. A retrospective population-based cohort study using a Perinatal National Minimum Data Set and clinical medical records review, at the Royal Hobart Hospital, Tasmania, Australia in 2006. Late preterm and 37 week gestation infants had low rates of initiation of breastfeeding within one hour of birth, 31 (21.1%) and 61 (41.5%) respectively. After multiple regression analysis, late preterm infants were less likely to initiate breastfeeding within one hour of birth (OR 0.3 95% CI 0.1, 0.7 p = 0.009) and were less likely to be discharged exclusively breastfeeding from hospital (OR 0.4 95% CI 0.1, 1.0 p = 0.04) compared to 37 week gestation infants. A late preterm birth is predictive of breastfeeding failure, with late preterm infants at greater risk of not initiating breastfeeding and/or exclusively breastfeeding at hospital discharge, compared with those infants born at 37 weeks gestation. Stratifying breastfeeding outcomes by gestational age groups may help to identify those sub-populations at greatest risk of premature cessation of breastfeeding.
Corbett, Sarah; Chelimo, Carol; Okesene-Gafa, Kara
2014-10-17
To identify barriers to early initiation of antenatal care amongst pregnant women in South Auckland, New Zealand. Women in late pregnancy (>37 weeks gestation) or who had recently delivered (<6 weeks postnatal) completed a questionnaire about their antenatal care. Logistic regression analysis evaluated whether late booking for antenatal care was associated with demographic factors and potential barriers to accessing care. Of the 826 women who participated, 137 (17%) booked for antenatal care at >18 weeks (late bookers). The ethnic composition of the sample was: 43% Pacific Peoples, 20% Maori, 14% Asian, and 21% European or other ethnicities. The multivariate analysis indicated that women were significantly more likely to book late for antenatal care if they had limited resources (OR=1.86; 95% CI=1.17-2.93), no tertiary education (OR=1.96; 95% CI=1.23-3.15), or were not living with a husband/partner (OR=2.34; 95% CI=1.48-3.71). In addition, the odds of late booking for antenatal care was almost six times higher among Maori (OR=5.70; 95% CI=2.57-12.64) and Pacific (OR=5.90; 95% CI=2.83-12.29) women compared to those of European and other ethnicities. Late booking for antenatal care in the Counties Manukau District Health Board area (South Auckland) is associated with sociodemographic factors, social deprivation, and inadequate social support.
Date fruit consumption at term: Effect on length of gestation, labour and delivery.
Razali, Nuguelis; Mohd Nahwari, Siti Hayati; Sulaiman, Sofiah; Hassan, Jamiyah
2017-07-01
Labour induction and augmentation with Prostaglandin and Oxytocin are well established as standard practice worldwide. They are safe when used judiciously, but may be associated with maternal and neonatal morbidities. Other safer alternatives have been studied including dates consumption during late pregnancy with various outcomes. The aim of this randomised controlled trial was to investigate the effect of date fruit consumption during late pregnancy on the onset of labour and need for induction or augmentation of labour. A total of 154 nulliparous women with an uncomplicated singleton pregnancy were randomly allocated to either dates-consumer (77) or control group (77). The women in the dates-consumer group had significantly less need for augmentation of labour and longer intervention to delivery interval. There was no significant difference in the onset of spontaneous labour. Dates consumption reduces the need for labour augmentation but does not expedite the onset of labour. Impact statement • Dates fruit consumption during late pregnancy has been shown to positively affect the outcome of labour and delivery. In this study, date consumption reduced the need for labour augmentation with oxytocin but did not expedite the onset of labour. Therefore, dates consumption in late pregnancy is a safe supplement to be considered as it reduced the need for labour intervention without any adverse effect on the mother and child. This further supports the finding of earlier studies.
Alpha Oscillatory Dynamics Index Temporal Expectation Benefits in Working Memory.
Wilsch, Anna; Henry, Molly J; Herrmann, Björn; Maess, Burkhard; Obleser, Jonas
2015-07-01
Enhanced alpha power compared with a baseline can reflect states of increased cognitive load, for example, when listening to speech in noise. Can knowledge about "when" to listen (temporal expectations) potentially counteract cognitive load and concomitantly reduce alpha? The current magnetoencephalography (MEG) experiment induced cognitive load using an auditory delayed-matching-to-sample task with 2 syllables S1 and S2 presented in speech-shaped noise. Temporal expectation about the occurrence of S1 was manipulated in 3 different cue conditions: "Neutral" (uninformative about foreperiod), "early-cued" (short foreperiod), and "late-cued" (long foreperiod). Alpha power throughout the trial was highest when the cue was uninformative about the onset time of S1 (neutral) and lowest for the late-cued condition. This alpha-reducing effect of late compared with neutral cues was most evident during memory retention in noise and originated primarily in the right insula. Moreover, individual alpha effects during retention accounted best for observed individual performance differences between late-cued and neutral conditions, indicating a tradeoff between allocation of neural resources and the benefits drawn from temporal cues. Overall, the results indicate that temporal expectations can facilitate the encoding of speech in noise, and concomitantly reduce neural markers of cognitive load. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Morado-Urbina, Carlos Eduardo; Alvarado-Vázquez, Perla Abigail; Montiel-Ruiz, Rosa Mariana; Acosta-González, Rosa Issel; Castañeda-Corral, Gabriela; Jiménez-Andrade, Juan Miguel
2014-11-01
This study was performed to evaluate whether early, middle, or late treatment of zoledronate, an approved bisphosphonate that blocks bone resorption, can reduce nociceptive behaviors in a mouse arthritis model. Arthritis was produced by repeated intra-articular knee injections of complete Freund's adjuvant (CFA). A dose-response curve with zoledronate (3, 30, 100, and 300 μg/kg, i.p., day 4 to day 25, twice weekly for 3 weeks) was performed, and the most effective dose of zoledronate (100 μg/kg, i.p.) was initially administered at different times of disease progression: day 4 (early), day 15 (middle), or day 21 (late) and continued until day 25 after the first CFA injection. Flinching of the injected extremity (spontaneous nociceptive behavior), vertical rearings and horizontal activity (functional outcomes), and knee edema were assessed. Zoledronate improved both functional outcomes and reduced flinching behavior. At day 25, the effect of zoledronate on flinching behavior and vertical rearings was greater in magnitude when it was given early or middle rather than late in the treatment regimen. Chronic zoledronate did not reduce knee edema in CFA-injected mice nor functional outcomes in naïve mice by itself. These results suggest that zoledronate may have a positive effect on arthritis-induced nociception and functional disabilities. © 2014 Wiley Periodicals, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Goda, Jayant Sastri; Le, Lisa W.; Lapperriere, Normand J.
Purpose: To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). Methods and Materials: From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients.more » Results: The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade {>=}2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). Conclusions: POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.« less
Causes of gynaecomastia in young adult males and factors associated with idiopathic gynaecomastia.
Ersöz, Halil önder; Onde, Mehmet Emin; Terekeci, Hakan; Kurtoglu, Soner; Tor, Hayati
2002-10-01
Gynaecomastia is a common clinical condition. Persistent pubertal or late onset idiopathic gynaecomastia is the leading cause of gynaecomastia in different series. The aim of this study was the assessment of the prevalence and characteristics of different causes of gynaecomastia in young adult males, and evaluation of the factors associated with idiopathic gynaecomastia. Fifty-three male patients (mean age 22.04 +/- 2.22, range 19-29), who had been admitted to our outpatient clinics with gynaecomastia as the main presenting symptom were enrolled in the study. Patients were evaluated with breast palpation, breast ultrasonography, anthropometric measurements and sex steroid levels. Secondary causes of gynaecomastia were ruled out. Thirty age-matched healthy individuals were also studied as healthy control group. Idiopathic gynaecomastia was diagnosed in 31 of 53 patients (58%), with 17 (32%) persistent pubertal and 14 (24%) late onset course. Other causes of gynaecomastia were hypogonadism in 13 cases (25%), hyperprolactinaemia in five (9%), chronic liver disease in two (4%), and drug induced (prolonged use of H2 antagonists) in two (4%). Patients with idiopathic gynaecomastia, either pubertal or late onset, were compared with the healthy control group in order to find out associated factors. Anthropometric measurements revealed a significant increase in body weight and body mass index (BMI) in the patient group compared with healthy controls (72.4 +/- 13.3 vs. 63.6 +/- 7.9 kg, p = 0.0086 and 25.2 +/- 4.0 vs. 21.5 +/- 2.7 kg/m2, p = 0.0001). Total skin fold thickness (SFT) of four different regions were also higher in the patient group (50.9 +/- 22.1 vs. 32.6 +/- 10.2 mm, p = 0.0006) indicating a higher body fat percentage. Total serum testosterone (4.76 +/- 1.31 vs. 5.70 +/- 1.06 microg/mL, p = 0.0038) and luteinizing hormone (LH) (4.80 +/- 1.92 vs. 7.32 +/- 1.90 mIU/mL, p < 0.0001) levels were significantly lower in the patient group while oestradiol levels were similar. There was a significant correlation between total testosterone and LH levels (r = 0.27, p = 0.0445). Total testosterone and LH levels were negatively correlated with BMI and total SFT. As a result most common form of gynaecomastia is idiopathic gynaecomastia either as persistent pubertal or late onset forms in young adult males. Idiopathic gynaecomastia is closely correlated with generalized obesity, reduced LH and testosterone levels which may be the result of increased conversion of testosterone to oestradiol in increased adipose tissue mass.
[Initial subretinal localization of acute myeloblastic leukemia (AML5) recurrence].
Le Gall, S; François, S; Urier, N; Genevieve, F; d'Hermies, F; Rachieru, P; Ifrah, N
2001-10-13
Reduced visual acuity in patients with acute leucemia can result from many causes including an ocular localization. A patient previously treated for acute myeloblastic leucemia-5 (AML5) developed bilateral vision impairment related to a subretinal localization of the leucemia. Meningeal and bone marrow relapse followed. The subretinal localization responded only to massive systemic steroid treatment. Although asymptomatic, ocular localizations are frequent in leucemia. Their prognostic impact depends on the ocular structure involved and on the chronology of onset--early or late in the leucemia course. The underlying pathophysiological mechanism of ocular involvement remains unexplained but hyperleucocytosis at presentation may be a risk factor and would justify at least systematic specialized examinations and discussion of prophylactic treatment.
[Perspectives in glaucoma surgery].
Dietlein, T S
2002-02-01
Trabeculectomy is still considered to be the gold standard in the surgical treatment of the open-angle glaucomas. The additional application of local antimetabolites has reduced the rate of early filtering bled fibrosis, but increased the rate of essential late-postoperative complications. Growth factor inhibition and photodynamic therapy may be an alternative local treatment to enhance the results in filtering surgery. Non-penetrating glaucoma surgery and ab-interno trabecular surgery have several conceptual advantages, e.g. the lack of overfiltration or the untouched conjunctiva in the ab-interno approach. Clinical studies of these and other new procedures including antiglaucomatous retinectomy and subchoroidal shunt systems are currently performed in order to evaluate their potential and limits in the clinical management of glaucoma.
[Psychosocial factors associated with late HAART initiation in Mexican patients with HIV].
Nogueda-Orozco, María José; Caro-Vega, Yanink; Crabtree-Ramírez, Brenda; Vázquez-Pineda, Fernando; Sierra-Madero, Juan G
2015-01-01
To explore the association between psychosocial factors and late highly active antiretroviral therapy (HAART) initiation in a sample of Mexican patients with HIV. We conducted a cross-sectional study at the HIV Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), and applied structured questionnaires to 150 patients who initiated HAART between January 2010 and August 2011. Late HAART initiation (LHI) was considered when patients started HAART with CD4 counts of <200+ cells/mm³. By multivariate analysis, the strongest psychosocial risk factor for LHI observed was self-stigma towards HIV/AIDS. In addition, being tested by medical prescription, not by own initiative, as well as having one or more previous medical contacts, were associated with greater risk for LH. Our findings suggest the need to develop psychosocial interventions to decrease negative self-image and stigmatizing attitudes and behaviors in risk groups for HIV in Mexico.
Ushie, Boniface A; Izugbara, Chimaraoke O; Mutua, Michael M; Kabiru, Caroline W
2018-02-17
Complications of unsafe abortion are a leading cause of maternal mortality in sub-Saharan Africa. Adolescents and young women are disproportionately represented among those at risk of these complications. Currently, we know little about the factors associated with young women's timing of abortion. This study examined the timing of abortion as well as factors influencing it among adolescents and young women aged 12-24 years who sought post-abortion care (PAC) in health facilities in Kenya. We draw on data from a cross-sectional study on the magnitude and incidence of induced abortion in Kenya conducted in 2012. The study surveyed women presenting with a diagnosis of incomplete, inevitable, missed, complete, or septic abortion over a one-month data collection period in 328 health facilities (levels 2-6). Survey data, specifically, from adolescents and young women were analyzed to examine their characteristics, the timing of abortion, and the factors associated with the timing of abortion. One thousand one hundred forty-five adolescents and young women presented for PAC during the data collection period. Eight percent of the women reported a previous induced abortion and 78% were not using a modern method of contraception about the time of conception. Thirty-nine percent of the index abortions occurred after 12 weeks of gestation. A greater proportion of women presenting with late abortions (more than 12 weeks gestational age) (46%) than those presenting with early abortions (33%) presented with severe complications. Controlling for socio-demographic and reproductive history, timing of abortion was significantly associated with place of residence (marginal), education, parity, clinical stage of abortion and level of severity. Late-term abortions were substantial, and may have contributed substantially to the high proportion of women with post-abortion complications. Efforts to reduce the severity of abortion-related morbidities and mortality must target young women, particularly those living in rural and other remote areas. Interventions to reduce unintended pregnancies in this population are also urgently needed to improve early pregnancy detection and timely care seeking.
Gil Cuesta, Julita; Cerro, Boyd Roderick; Guha-Sapir, Debarati
2016-01-01
In cases of Dengue fever, late hospital admission can lead to treatment delay and even death. In order to improve early disease notification and management, it is essential to investigate the factors affecting the time of admission of Dengue cases. This study determined the factors associated with the time of admission among notified Dengue cases. The study covered the period between 2008 and 2014 in Region VIII, Philippines. The factors assessed were age, sex, hospital sector, hospital level, disease severity based on the 1997 WHO Dengue classification, and period of admission (distinguishing between the 2010 Dengue epidemic and non-epidemic time). We analysed secondary data from the surveillance of notified Dengue cases. We calculated the association through chi-square test, ordinal logistic regression and linear regression at p value < 0.05. The study included 16,357 admitted Dengue cases. The reported cases included a majority of children (70.09%), mild cases of the disease (64.00%), patients from the public sector (69.82%), and non-tertiary hospitals (62.76%). Only 1.40% of cases had a laboratory confirmation. The epidemic period in 2010 comprised 48.68% of all the admitted cases during this period. Late admission was more likely among adults than children (p<0.05). The severe type of the disease was more likely to be admitted late than the mild type (p<0.05). Late admission was also more likely in public hospitals than in private hospitals (p<0.05); and within tertiary level hospitals than non-tertiary hospitals (p<0.05). Late admission was more likely during the non-epidemic period than the 2010 epidemic period (p<0.05). A case fatality rate of 1 or greater was significantly associated with children, severe diseases, tertiary hospitals and public hospitals when admitted late (p<0.05). Data suggests that early admission among child cases was common in Region VIII. This behavior is encouraging, and should be continued. However, further study is needed on the late admission among tertiary, public hospitals and non-epidemic period with reference to the quality of care, patient volume, out of pocket expense, and accessibility We recommend the consistent use of the 2009 WHO Dengue guidelines in order to standardize the admission criteria and time across hospitals. PMID:27780199
Clinical factors associated with failed trials of labor in late preterm and term twin pregnancies.
Ko, Hyun-Joo; Jun, Jong Kwan
2014-07-01
To evaluate the perinatal outcomes and clinical factors of unsuccessful trials of labor (TOLs) in late preterm and term twin pregnancies. We enrolled 896 consecutive twin pregnancies delivered between 1999 and 2012 in a single center, which met the following inclusion criteria: a vertex first twin, live twins, and attempted TOLs after 34 weeks. Obstetric characteristics and perinatal outcomes were compared between vaginal delivery and cesarean delivery groups. Successful TOLs were carried out in 81% (726/896). Failed TOLs occurred in 15% (37/247) of late preterm twins and 20% (133/649) of term twins. Comparisons of neonatal outcomes between the groups showed no significant differences in NICU admission, ventilator use, and composite morbidity. On univariable analysis, nulliparity, preeclampsia, induced labor, excessive weight gain, and intertwin weight discordance of >30% showed significant associations with failed TOLs. Multivariable analyses revealed nulliparity (adjusted odds ratio 9.89, 95% confidence interval 4.64-21.1) and preeclampsia (adjusted odds ratio 2.17, 95% confidence interval 1.30-3.63) as significantly associated with failed TOLs. In late preterm and term twins, trials of labor can be performed successfully without a significant increase in adverse neonatal outcomes. Nulliparity and preeclampsia are clinical factors associated with failed TOLs in twin pregnancies.
Li, Xue; Xu, Zhen-Rui; Tang, Na; Ye, Cui; Zhu, Xiao-Ling; Zhou, Ting; Zhao, Zhi-He
2016-11-01
This study aims to determine the effectiveness of a messaging app (WeChat) in improving patients' compliance and reducing the duration of orthodontic treatment (DOT). A randomized controlled trial was performed in a dental hospital and a clinic from August 2012 to May 2015. Orthodontic patients were included at the beginning of treatment. Patients with multiphase treatment or braceless technique were excluded. Participants were randomized to WeChat group (received regular reminders and educational messages) or control group (received conventional management) and were followed up until the treatment was completed. Primary outcome measure was DOT. Others were late and failed attendance, bracket bond failure, and oral hygiene condition. One hundred twelve patients in each group participated and completed the trial. DOT in WeChat group were 7.3 weeks shorter (P = 0.007). There were less failed attendance (3.1 vs. 10.9 %, P < 0.001), late attendance (20.1 vs. 29.9 %, P < 0.001), and bracket bond failure (11.8 vs. 16.1 %, P < 0.001) in WeChat group than control. There was no difference in orthodontic plaque index nor modified gingivitis index between the two groups before and after treatment. Number of failed attendances was identified as an independent factor affecting DOT (P = 0.004; HR = 0.89, 95 % CI 0.84 to 0.95). The intervention with WeChat is effective in reducing the treatment duration and bracket bond failure, and improving the attendance in orthodontic patients. DOT can be reduced by improving patient's compliance. The messaging app is useful for outpatient education and management.
Stacey, Tomasina; Thompson, John M D; Mitchell, Edwin A; Ekeroma, Alec; Zuccollo, Jane; McCowan, Lesley M E
2011-12-01
Maternal perception of decreased fetal movements has been associated with adverse pregnancy outcomes, including stillbirth. Little is known about other aspects of perceived fetal activity. The objective of this study was to explore the relationship between maternal perception of fetal activity and late stillbirth (≥28 wk gestation) risk. Participants were women with a singleton, late stillbirth without congenital abnormality, born between July 2006 and June 2009 in Auckland, New Zealand. Two control women with ongoing pregnancies were randomly selected at the same gestation at which the stillbirth occurred. Detailed demographic and fetal movement data were collected by way of interview in the first few weeks after the stillbirth, or at the equivalent gestation for control women. A total of 155/215 (72%) women who experienced a stillbirth and 310/429 (72%) control group women consented to participate in the study. Maternal perception of increased strength and frequency of fetal movements, fetal hiccups, and frequent vigorous fetal activity were all associated with a reduced risk of late stillbirth. In contrast, perception of decreased strength of fetal movement was associated with a more than twofold increased risk of late stillbirth (aOR: 2.37; 95% CI: 1.29-4.35). A single episode of vigorous fetal activity was associated with an almost sevenfold increase in late stillbirth risk (aOR: 6.81; 95% CI: 3.01-15.41) compared with no unusually vigorous activity. Our study suggests that maternal perception of increasing fetal activity throughout the last 3 months of pregnancy is a sign of fetal well-being, whereas perception of reduced fetal movements is associated with increased risk of late stillbirth. © 2011, Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc.
Determinants and prevalence of late HIV testing in Tijuana, Mexico.
Carrizosa, Claudia M; Blumberg, Elaine J; Hovell, Melbourne F; Martinez-Donate, Ana P; Garcia-Gonzalez, Gregorio; Lozada, Remedios; Kelley, Norma J; Hofstetter, C Richard; Sipan, Carol L
2010-05-01
Timely diagnosis of HIV is essential to improve survival rates and reduce transmission of the virus. Insufficient progress has been made in effecting earlier HIV diagnoses. The Mexican border city of Tijuana has one of the highest AIDS incidence and mortality rates in all of Mexico. This study examined the prevalence and potential correlates of late HIV testing in Tijuana, Mexico. Late testers were defined as participants who had at least one of: (1) an AIDS-defining illness within 1 year of first positive HIV test; (2) a date of AIDS diagnosis within 1 year of first positive HIV test; or (3) an initial CD4 cell count below 200 cells per microliter within 1 year of first positive HIV test. Medical charts of 670 HIV-positive patients from two HIV/AIDS public clinics in Tijuana were reviewed and abstracted; 362 of these patients were interviewed using a cross-sectional survey. Using multivariate logistic regression, we explored potential correlates of late HIV testing based on the Behavioral Ecological Model. From 342 participants for whom late testing could be determined, the prevalence of late testing was 43.2%. Multivariate logistic regression results (n = 275) revealed five significant correlates of late testing: "I preferred not to know I had HIV" (adjusted odds ratio [AOR] = 2.78, 1.46-5.31); clinic (AOR = 1.90, 1.06-3.41); exposure to peers engaging in high-risk sexual behavior (AOR = 1.14, 1.02-1.27); stigma regarding HIV-infected individuals (AOR = 0.65, 0.47-0.92); and stigma regarding HIV testing (AOR = 0.66, 0.45-0.97). These findings may inform the design of interventions to increase timely HIV testing and help reduce HIV transmission in the community at large.
Social relations and depression in late life-a systematic review.
Schwarzbach, Michaela; Luppa, Melanie; Forstmeier, Simon; König, Hans-Helmut; Riedel-Heller, Steffi G
2014-01-01
Social relations have become the focus of much research attention when studying depressive symptoms in older adults. Research indicates that social support and being embedded in a network may reduce the risk for depression. The aim of the review was to analyze the association of social relations and depression in older adults. Electronic databases were searched systematically for potentially relevant articles published from January 2000 to December 2012. Thirty-seven studies met the inclusion criteria for this review. Factors of social relations were categorized into 12 domains. Factors regarding the qualitative aspects of social relations seem to be more consistent among studies and therefore provide more explicit results. Thus, social support, quality of relations, and presence of confidants were identified as factors of social relations significantly associated with depression. The quantitative aspects of social relations seem to be more inconsistent. Cultural differences become most obvious in terms of the quantitative aspects of social relations. Despite the inconsistent results and the methodological limitations of the studies, this review identified a number of factors of social relations that are significantly associated with depression. The review indicates that it is needful to investigate social relations in all their complexity and not reduce them to one dimension. Simultaneously, it is important to conduct longitudinal studies because studies with cross-sectional design do not allow us to draw conclusions on causality. Beyond that, cultural differences need to be considered. Copyright © 2013 John Wiley & Sons, Ltd.
Huh, Seung Jae; Lim, Do Hoon; Ahn, Yong Chan; Lee, Jeong Eun; Kang, Min Kyu; Shin, Seong Soo; Shin, Kyung Hwan; Kim, Bokyung; Park, Won; Han, Youngyih
2003-03-01
To investigate the correlation between late rectal complications and rectal dose in cervix cancer patients treated with high-dose-rate intracavitary radiotherapy (HDR ICR) and to analyze factors reducing rectal complications. A total of 136 patients with cervix cancer who were treated with external beam radiotherapy (EBRT) and HDR ICR from 1995 to 1999 were retrospectively analyzed. Radiotherapy (RT) consisted of EBRT plus HDR ICR. The median EBRT dose was 50.4 Gy, and midline block was done after 30-50 Gy of EBRT. A total of six fractions of HDR ICR with 4 Gy fraction size each were applied twice per week to the A point. The rectal dose was calculated at the rectal reference point using the barium contrast criteria. In vivo measurement of the rectal dose was performed with thermoluminescent dosimeter (TLD) during HDR ICR. The median follow-up period was 26 months (range 6-60 months). A total of 16 patients (12%) experienced rectal bleeding, which occurred 4-33 months (median 11 months) after the completion of RT. The calculated rectal doses did not differ in patients with rectal bleeding and those without, but the measured rectal doses were higher in affected patients. The differences of the measured ICR fractional rectal dose, ICR total rectal dose, and total rectal biologically equivalent dose (BED) were statistically significant. When the measured ICR total rectal dose exceeded 16 Gy, the ratio of the measured rectal dose to A point dose was > 70%; when the measured rectal BED exceeded 110 Gy(3), a high possibility of late rectal complications could be found. In vivo dosimetry using TLD during HDR ICR was a good predictor of late rectal complications. Hence, if data from in vivo dosimetry shows any possibility of rectal bleeding, efforts should be made to reduce the rectal dose.
Argyri, Letta; Dafnis, Ioannis; Theodossiou, Theodossis A; Gantz, Donald; Stratikos, Efstratios; Chroni, Angeliki
2014-05-02
The apolipoprotein (apo) E4 isoform has consistently emerged as a susceptibility factor for late-onset Alzheimer disease (AD), although the exact mechanism is not clear. A rare apoE4 mutant, apoE4[L28P] Pittsburgh, burdens carriers with an added risk for late-onset AD and may be a useful tool for gaining insights into the role of apoE4 in disease pathogenesis. Toward this end, we evaluated the effect of the L28P mutation on the structural and functional properties of apoE4. ApoE4[L28P] was found to have significantly perturbed thermodynamic properties, to have reduced helical content, and to expose a larger portion of the hydrophobic surface to the solvent. Furthermore, this mutant is thermodynamically destabilized and more prone to proteolysis. When interacting with lipids, apoE4[L28P] formed populations of lipoprotein particles with structural defects. The structural perturbations brought about by the mutation were accompanied by aberrant functions associated with the pathogenesis of AD. Specifically, apoE4[L28P] promoted the cellular uptake of extracellular amyloid β peptide 42 (Aβ42) by human neuroblastoma SK-N-SH cells as well as by primary mouse neuronal cells and led to increased formation of intracellular reactive oxygen species that persisted for at least 24 h. Furthermore, lipoprotein particles containing apoE4[L28P] induced intracellular reactive oxygen species formation and reduced SK-N-SH cell viability. Overall, our findings suggest that the L28P mutation leads to significant structural and conformational perturbations in apoE4 and can induce functional defects associated with neuronal Aβ42 accumulation and oxidative stress. We propose that these structural and functional changes underlie the observed added risk for AD development in carriers of apoE4[L28P].
NASA Astrophysics Data System (ADS)
Shu, L.; Duffy, C.; French, K. D.; Murtha, T., Jr.; Garcia-Gonzalez, S. E.
2014-12-01
In recent years scientists have been debating the role of climate on the trajectory of Maya culture in the Late Classic period, 600-900 AD. Paleo-climatologists have reconstructed realizations of climate [Haug 2003; Medina-Elizalde 2012; Hodell 1995] that offer evidence for reduced precipitation in the Late Classic period. Recently French et al [2014] proposed that landuse change may also play an important role in the available water supply at Tikal, with the removal of tropical forest and conversion to maize-agriculture and urban landuse leading to extensive development of sophisticated water storage systems and rainfall harvesting for water supply and irrigation. Rapid population growth is a concurrent and compounding factor [Scarborough 2012; Shaw 2003] where landuse impacts the distribution and availability of water storage in the surrounding watershed. Although proposed climate scenarios for the Late Classic offer a quantitative scenario for possible atmospheric conditions at Tikal, the impact of land use change on the distribution and availability of water supply has not been evaluated. In this research we reconstruct the plausible vulnerability of the water supply at Tikal under the combined forces of climatic and land use change. The Penn State Integrated Hydrologic Model (PIHM) [Qu and Duffy 2007] is used to simulate the daily-to-seasonal space and time distribution of soil moisture, groundwater and surface water storage for the period 700-800 AD, the peak of Tikal's population history. The analysis includes a quantitative assessment of the likely changes in available water storage as tropical forest is converted to maize agriculture and urban land. In particular we examine the important control that reduced canopy interception plays in the seasonal availability of water. Preliminary simulations suggest that removing tropical forest increases runoff and available water storage, which may serve to moderate seasonal and long-term drought conditions.
Exploring Career Success of Late Bloomers from the TVET Background
ERIC Educational Resources Information Center
Omar, Zoharah; Krauss, Steven Eric; Sail, Rahim M.; Ismail, Ismi Arif
2011-01-01
Purpose: The purpose of this paper is to explore objective and subjective career success and to identify factors contributing to career success among a sample of technical and vocational education and training (TVET) "late bloomers" working in Malaysia. Design/methodology/approach: Incorporating a mixed method design, the authors…
Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia.
Mourani, Peter M; Sontag, Marci K; Younoszai, Adel; Miller, Joshua I; Kinsella, John P; Baker, Christopher D; Poindexter, Brenda B; Ingram, David A; Abman, Steven H
2015-01-01
Pulmonary hypertension (PH) is associated with poor outcomes among preterm infants with bronchopulmonary dysplasia (BPD), but whether early signs of pulmonary vascular disease are associated with the subsequent development of BPD or PH at 36 weeks post-menstrual age (PMA) is unknown. To prospectively evaluate the relationship of early echocardiogram signs of pulmonary vascular disease in preterm infants to the subsequent development of BPD and late PH (at 36 wk PMA). Prospectively enrolled preterm infants with birthweights 500-1,250 g underwent echocardiogram evaluations at 7 days of age (early) and 36 weeks PMA (late). Clinical and echocardiographic data were analyzed to identify early risk factors for BPD and late PH. A total of 277 preterm infants completed echocardiogram and BPD assessments at 36 weeks PMA. The median gestational age at birth and birthweight of the infants were 27 weeks and 909 g, respectively. Early PH was identified in 42% of infants, and 14% were diagnosed with late PH. Early PH was a risk factor for increased BPD severity (relative risk, 1.12; 95% confidence interval, 1.03-1.23) and late PH (relative risk, 2.85; 95% confidence interval, 1.28-6.33). Infants with late PH had greater duration of oxygen therapy and increased mortality in the first year of life (P < 0.05). Early pulmonary vascular disease is associated with the development of BPD and with late PH in preterm infants. Echocardiograms at 7 days of age may be a useful tool to identify infants at high risk for BPD and PH.
Somatostatin and the dumping syndrome.
Long, R G; Adrian, T E; Bloom, S R
1985-01-01
Infusion of somatostatin reduced the symptoms of the early dumping syndrome after oral glucose was given and also reduced the associated tachycardia and rise in packed cell volume. It inhibited the secretion of enteroglucagon, neurotensin, and vasoactive intestinal polypeptide, which are raised in patients with the dumping syndrome and may have an aetiological role. It also prevented the reactive hypoglycaemia of late dumping by inhibiting the release of gastric inhibitory polypeptide and insulin. Somatostatin, possibly through its inhibitory effects on hormonal secretion, may have a role in the management of patients with the early and late dumping syndrome. PMID:2858244
Liang, Y J; Li, Z L; Wang, L; Liu, B Y; Ding, R Y; Ma, X C
2017-10-01
Objective: To compare risk factors and bacterial etiology in patients with early-onset versus late-onset ventilator-associated pneumonia (VAP) in intensive care unit (ICU). Methods: This prospective cohort study enrolled mechanically ventilated patients hospitalized for more than 48 hours in the first affiliated hospital, China Medical University from Jan 2012 to Jun 2016. Subjects were classified by ventilator status: early-onset VAP (< 5 d ventilation, E-VAP) or late-onset VAP (≥ 5 d ventilation, L-VAP). Potential risk factors and pathogen were evaluated. Results: A total of 4 179 patients in adult ICU were screened, 3 989 (95.5%) of whom were mechanically ventilated, 962 patients with mechanical ventilation time ≥ 48 h. VAP developed in 142 patients. E-VAP and L-VAP had different potential risk factors based on statistical analysis.Independent risk factors for E-VAP included male ( OR =1.825, 95% CI 1.006-3.310), chronic obstructive pulmonary disease (COPD; OR =3.746, 95% CI 1.795-7.818), emergency intubation ( OR =1.932, 95% CI 1.139-3.276), aspiration ( OR =3.324, 95% CI 1.359-8.130). Whereas independent risk factors for L-VAP were coma ( OR =2.335, 95% CI 1.300-4.194), renal dysfunction ( OR =0.524, 95% CI 0.290-0.947), emergency intubation ( OR =2.184, 95% CI 1.334-3.574). Mortality in E-VAP and L-VAP group were both higher than the non-VAP group[30.2%(19/63)vs 19.8%(162/820), P =0.044; 29.1%(23/79) vs 19.8%(162/820), P =0.046]. The pathogens isolated from early-onset versus late-onset VAP were not significantly different between groups, which the most common ones were acinetobacter baumannii, pseudomonas aeruginosa and klebsiella pneumoniae. Conclusion: E-VAP and L-VAP have different risk factors, however related pathogens are similar. Different specific preventive strategies are suggested based on different onset of VAP.
Bacterial stem blight of alfalfa: A disease that increases frost damage
USDA-ARS?s Scientific Manuscript database
Alfalfa producers count on the first harvest in late spring to deliver the highest tonnage and best quality of forage of the year. A late frost can significantly reduce both yield and quality. Losses are due not only to the physical damage from freezing of the alfalfa stem and leaves but also from d...
Older adults' health and late-life drinking patterns: a 20-year perspective.
Moos, Rudolf H; Brennan, Penny L; Schutte, Kathleen K; Moos, Bernice S
2010-01-01
This study focused on the associations between older adults' health-related problems and their late-life alcohol consumption and drinking problems. A sample of 719 late-middle-aged community residents (55-65 years old at baseline) participated in a survey of health and alcohol consumption and this survey was followed 10 years and 20 years later. Health-related problems increased and alcohol consumption and drinking problems declined over the 20-year interval. Medical conditions, depressive symptoms, medication use, and acute health events were associated with a higher likelihood of abstinence; acute health events were also associated with less alcohol consumption. In contrast, reliance on alcohol to reduce pain was linked to more alcohol consumption. Moreover, an individual's overall health burden and reliance on alcohol to reduce pain were associated with more drinking problems. Reliance on alcohol to reduce pain potentiated the association between health burden, alcohol consumption and drinking problems. Older adults who have more health problems and rely on alcohol to manage pain are at elevated risk for drinking problems. Health care providers should target high-risk older adults, such as those who drink to reduce pain, for screening and brief interventions to help them identify new ways to cope with pain and curtail their drinking.
NASA Technical Reports Server (NTRS)
Ortiz, Rudy M.; Houser, Dorian S.; Wade, Charles E.; Ortiz, C. Leo
2003-01-01
To better interpret previously described hormonal changes observed during the natural postweaning fast (2-3 months) endured by pups of the northern elephant seal (Mirounga angustirostris), we compared plasma cortisol, thyroid hormones, and leptin in pups (n=5) measured during nursing and fasting periods. Blood samples were taken at four times; early (9 days postpartum) and late (18-22 days postpartum) nursing, and early (second week postweaning) and late (eighth week postweaning) fasting. Plasma cortisol increased 39% between early and late nursing and almost 4-fold by late fasting. After the early nursing period, cortisol and body mass were negatively correlated (y=28.3-0.19 x; R=0.569; p=0.027). Total thyroxine (tT(4)), free T(4) (fT(4)), total triiodothyronine (tT3) and reverse T(3) (rT(3)) were greatest at early nursing and reduced by late nursing and remained so throughout the fast, with the exception of tT(4), which increased between late nursing (17.7+/-2.1 ng mL(-1)) and late fasting (30.1+/-2.8 ng mL(-1)) periods. Leptin remained unaltered among the four sampling periods and was not correlated with body mass. Pups appear to exhibit a shift in the relationship between cortisol and body mass suggesting a potential role for cortisol in the regulation of body fat. The higher concentrations of tT(3) and tT(4) during early nursing may reflect enhanced growth and development during this period, however the increase late in fasting is likely physiologically insignificant and an artifact of reduced metabolic clearance of these hormones. Transition of the pups from nursing to fasting states is characterized by a striking lack of change in cortisol, thyroid hormones, and leptin suggesting that any metabolic alterations associated with this transition may occur independent of these hormones.
Meyers, Kathrine; Qian, Haoyu; Wu, Yingfeng; Lao, Yunfei; Chen, Qingling; Dong, Xingqi; Li, Huiqin; Yang, Yiqing; Jiang, Chengqin; Zhou, Zengquan
2015-01-01
To identify factors associated with mother-to-child-transmission and late access to prevention of maternal to child transmission (PMTCT) services among HIV-infected women; and risk factors for infant mortality among HIV-exposed infants in order to assess the feasibility of virtual elimination of vertical transmission and pediatric HIV in this setting. Observational study evaluating the impact of a provincial PMTCT program. The intervention was implemented in 26 counties of Yunnan Province, China at municipal and tertiary health care settings. Log linear regression models with generalized estimating equations were used to identify unadjusted and adjusted correlates for late ARV intervention and MTCT. Cox proportional hazard models with robust sandwich estimation were applied to examine correlates of infant mortality. Mother-to-child- transmission rate of HIV was controlled to 2%, with late initiation of maternal ARV showing a strong association with vertical transmission and infant mortality. Risk factors for late initiation of maternal ARV were age, ethnicity, education, and having a husband not tested for HIV. Mortality rate among HIV-exposed infants was 2.9/100 person-years. In addition to late initiation of maternal ARV, ethnicity, low birth weight and preterm birth were associated with infant mortality. This PMTCT program in Yunnan achieved low rates of MTCT. However the infant mortality rate in this cohort of HIV-exposed children was almost three times the provincial rate. Virtual elimination of MTCT of HIV is an achievable goal in China, but more attention needs to be paid to HIV-free survival.
Johnson, Rucker C.; Schoeni, Robert F.; Rogowski, Jeannette A.
2012-01-01
The relationship between neighborhoods of residence in young adulthood and health in mid to late life in the United States are examined using the 1968-2005 waves of the Panel Study of Income Dynamics (PSID). The sample consists of persons who were aged 20-30 in 1968 and are followed for a period of 38 years (N=2,730). Four-level hierarchical random effects models of self-assessed general health status as a function of individual, family, and neighborhood factors are estimated. Using the original sampling design of the PSID, we analyze adult health trajectories of married couples and neighbors followed from young adulthood through elderly ages to assess the magnitudes of the possible causal effects of family and neighborhood characteristics in young adulthood on health in mid to late life. Estimates suggest disparities in neighborhood conditions in young adulthood account for one-quarter of the variation in mid-to-late-life health. Living in poor neighborhoods during young adulthood is strongly associated with negative health outcomes in later life. This result is robust even in the presence of a reasonably large amount of potential unobservable individual and family factors that may significantly affect both neighborhood of residence and subsequent health status. Racial differences in health status in mid to late life are also associated with family and neighborhood socioeconomic conditions earlier in life. Three quarters of the black-white gap in health status at ages over 55 can be accounted for by differences in childhood socioeconomic status and neighborhood and family factors in young adulthood. PMID:22212443
Etiology of Teen Dating Violence among Adolescent Children of Alcoholics.
Livingston, Jennifer A; Eiden, Rina D; Lessard, Jared; Casey, Meghan; Henrie, James; Leonard, Kenneth E
2018-03-01
Family processes in early life have been implicated in adolescent involvement in teen dating violence, yet the developmental pathways through which this occurs are not well understood. In this study, etiological pathways from parental psychopathology and marital conflict in infancy to involvement in dating violence in late adolescence were examined in a sample of children at high-risk due to parental alcohol problems. Families (N = 227) recruited when the child was 12 months of age were assessed at 12-, 24-, 36-months, kindergarten, 6th, 8th, and 12th grades. Slightly more than half of the children were female (51%) and the majority were of European American descent (91%). Parental psychopathology in infancy was indirectly associated with teen dating violence in late adolescence via low maternal warmth and self-regulation in early childhood, externalizing behavior from kindergarten to early adolescence, and sibling problems in middle childhood. Marital conflict was also indirectly associated with teen dating violence via child externalizing behavior. Maternal warmth and sensitivity in early childhood emerged as an important protective factor and was associated with reduced marital conflict and increased child self-regulation in the preschool years as well as increased parental monitoring in middle childhood and early adolescence. Family processes occurring in the preschool years and in middle childhood appear to be critical periods for creating conditions that contribute to dating violence risk in late adolescence. These findings underscore the need for early intervention and prevention with at-risk families.
Lankinen, Åsa; Smith, Henrik G; Andersson, Stefan; Madjidian, Josefin A
2016-03-01
Although much attention has focused on the diversity of plant mating systems, only a few studies have considered the joint effects of mating system and sexual conflict in plant evolution. In mixed-mating Collinsia heterophylla, a sexual conflict over timing of stigma receptivity is proposed: pollen with a capacity to induce early onset of stigma receptivity secures paternity for early-arriving pollen (at the expense of reduced maternal seed set), whereas late onset of stigma receptivity mitigates the negative effects of early-arriving pollen. Here we investigated whether selection on pollen and pistil traits involved in sexual conflict is affected by the presence of both outcross- and self-pollen (mixed mating) during pollen competition. We conducted two-donor crosses at different floral developmental stages to explore male fitness (siring ability) and female fitness (seed set) in relation to male and female identity, pollen and pistil traits, and type of competitor pollen (outcross vs. self). Late-fertilizing pollen rather than rapidly growing pollen tubes was most successful in terms of siring success, especially in competition with self-pollen after pollination at early floral stages. Late stigma receptivity increased seed set after early-stage pollinations, in agreement with selection against antagonistic pollen. Selection on pollen and pistil traits in C. heterophylla is affected by both sexual conflict and mixed mating, suggesting the importance of jointly considering these factors in plant evolution. © 2016 Botanical Society of America.
Ambe, Peter C; Kurz, Nadja Rebecca; Nitschke, Claudia; Odeh, Siad F; Möslein, Gabriela; Zirngibl, Hubert
2018-03-16
About 100 000 ostomy carriers are estimated to live in Germany today. The creation of an ostomy represents a major life event that can be associated with impaired quality of life. Optimal ostomy creation and proper ostomy care are crucially important determinants of the success of treatment and of the patients' quality of life. This article is based on pertinent publications retrieved by a selective search in PubMed, GoogleScholar, and Scopus, and on the authors' experience. Intestinal stomata can be created using either the small or the large bowel. More than 75% of all stomata are placed as part of the treatment of colorectal cancer. The incidence of stoma-related complications is reported to be 10-70%. Skin irritation, erosion, and ulceration are the most common early complications, with a combined incidence of 25-34%, while stoma prolapse is the most common late complication, with an incidence of 8-75%. Most early complications can be managed conservatively, while most late complications require surgical revision. In 19% of cases, an ostomy that was initially planned to be temporary becomes permanent. Inappropriate stoma location and inadequate ostomy care are the most common causes of early complications. Both surgical and patient-related factors influence late complications. Every step from the planning of a stoma to its postoperative care should be discussed with the patient in detail. Preoperative marking is essential for an optimal stoma site. Optimal patient management with the involvement of an ostomy nurse increases ostomy acceptance, reduces ostomy-related complications, and improves the quality of life of ostomy carriers.
Singh-Mallah, Gagandeep; McMahon, Christopher D; Guan, Jian; Singh, Kuljeet
2017-12-01
In rodents, post-lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin-like growth factor-1 (IGF-1). Overexpression of IGF-1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic-glycine-proline (cGP), a metabolite of IGF-1, normalizes IGF-1 function under pathological conditions by regulating the bioavailability of IGF-1. The present study investigated the effect of cGP on the physiological decline in IGF-1 function during post-lactational mammary involution. Rat dams were gavaged with either cGP (3 mg/kg) or saline once per day from post-natal d8-22. Before collecting tissue on post-natal d23, a pair of mammary glands were sealed on d20 (72 hr-engorgement, thus representative of late-involution) and d22 (24 hr-engorgement, thus representative of mid-involution), while the remaining glands were allowed to involute naturally (early-involution). During early-involution, cGP accelerated the loss of mammary cells through apoptosis, resulting in an earlier clearance of intact secretory alveoli compared with the control group. This coincided with an earlier up-regulation of the cell survival factors, Bcl-xl and IGF-1R, in the early-involution cGP glands compared with the control glands. During late-involution, cGP reduced the bioactivity of IGF-1, which was evident through decreased phosphorylation of IGF-1R in the regressed alveoli. Maternal administration of cGP did not alter milk production and composition during early-, peak-, or late-stage of lactation. These data show that cGP accelerates post-lactational involution by promoting apoptosis and the physiological decline in IGF-1 function. © 2017 Wiley Periodicals, Inc.
Nitric oxide and tumour necrosis factor alpha in the process of pseudoexfoliation glaucoma
Sarenac Vulovic, Tatjana S.; Pavlovic, Sladjana M.; Jakovljevic, Vladimir LJ.; Janicijevic, Katarina B.; Zdravkovic, Nemanja S.
2016-01-01
AIM To establish the role of nitric oxide (NO), ascorbic acid and tumour necrosis factor-α (TNF-α) in the pathogenesis of pseudoexfoliation glaucoma (XFG). METHODS Our study included 120 patients who were referred for cataract surgery. All patients were divided into four groups according to clinical findings: XFG, early and late pseudoexfoliation syndrome (XFS), and cataract (without pseudoexfoliation). Serum and aqueous humour levels of the ascorbic acid, NO and TNF-α were measured. The concentrations of the ascorbic acid and NO were measured by an appropriate spectrophotometric method. Enzyme-linked immunosorbent assay (ELISA) was used to determine TNF-α level. RESULTS Aqueous humour concentration of ascorbic acid was significantly lower in patients with late XFS (0.61±0.11 mmol/L) and XFG (0.48±0.15 mmol/L) compared to patients with early XFS (0.9±0.15 mmol/L) and cataract (1.16±0.22 mmol/L), while there was no difference in serum concentration in all examined groups. Aqueous humour concentration of NO was significantly higher in patients with XFG (77.7±11.4 µmol/L) compared to patients with early XFS (50.27±9.34 µmol/L) and cataract (49.77±7.1 µmol/L), while serum concentration was increased in the early stage of XFS (73.26±8.29 µmol/L). Aqueous humour level of proinflammatory cytokine TNF-α was increased in patients with XFS (early 460.04±18.32 pg/mL; late 502.42±53.23 pg/mL) and XFG (510.34±43.07 pg/mL), while there was no difference in serum level in all examined groups of patients. CONCLUSION Reduced ascorbic acid and elevated NO and inflammation related cytokine TNF-α level in aqueous humour of the patients with developed XFG suggest that oxidative stress induces local inflammation. PMID:27588268
Zablocki, Jeff A; Elzein, Elfatih; Li, Xiaofen; Koltun, Dmitry O; Parkhill, Eric Q; Kobayashi, Tetsuya; Martinez, Ruben; Corkey, Britton; Jiang, Haibo; Perry, Thao; Kalla, Rao; Notte, Gregory T; Saunders, Oliver; Graupe, Michael; Lu, Yafan; Venkataramani, Chandru; Guerrero, Juan; Perry, Jason; Osier, Mark; Strickley, Robert; Liu, Gongxin; Wang, Wei-Qun; Hu, Lufei; Li, Xiao-Jun; El-Bizri, Nesrine; Hirakawa, Ryoko; Kahlig, Kris; Xie, Cheng; Li, Cindy Hong; Dhalla, Arvinder K; Rajamani, Sridharan; Mollova, Nevena; Soohoo, Daniel; Lepist, Eve-Irene; Murray, Bernard; Rhodes, Gerry; Belardinelli, Luiz; Desai, Manoj C
2016-10-03
Late sodium current (late I Na ) is enhanced during ischemia by reactive oxygen species (ROS) modifying the Na v 1.5 channel, resulting in incomplete inactivation. Compound 4 (GS-6615, eleclazine) a novel, potent, and selective inhibitor of late I Na , is currently in clinical development for treatment of long QT-3 syndrome (LQT-3), hypertrophic cardiomyopathy (HCM), and ventricular tachycardia-ventricular fibrillation (VT-VF). We will describe structure-activity relationship (SAR) leading to the discovery of 4 that is vastly improved from the first generation late I Na inhibitor 1 (ranolazine). Compound 4 was 42 times more potent than 1 in reducing ischemic burden in vivo (S-T segment elevation, 15 min left anteriorior descending, LAD, occlusion in rabbits) with EC 50 values of 190 and 8000 nM, respectively. Compound 4 represents a new class of potent late I Na inhibitors that will be useful in delineating the role of inhibitors of this current in the treatment of patients.
Haberman, Amnon; Bakhshian, Ortal; Cerezo-Medina, Sergio; Paltiel, Judith; Adler, Chen; Ben-Ari, Giora; Mercado, Jose Angel; Pliego-Alfaro, Fernando; Lavee, Shimon; Samach, Alon
2017-08-01
Olive (Olea europaea L.) inflorescences, formed in lateral buds, flower in spring. However, there is some debate regarding time of flower induction and inflorescence initiation. Olive juvenility and seasonality of flowering were altered by overexpressing genes encoding flowering locus T (FT). OeFT1 and OeFT2 caused early flowering under short days when expressed in Arabidopsis. Expression of OeFT1/2 in olive leaves and OeFT2 in buds increased in winter, while initiation of inflorescences occurred i n late winter. Trees exposed to an artificial warm winter expressed low levels of OeFT1/2 in leaves and did not flower. Olive flower induction thus seems to be mediated by an increase in FT levels in response to cold winters. Olive flowering is dependent on additional internal factors. It was severely reduced in trees that carried a heavy fruit load the previous season (harvested in November) and in trees without fruit to which cold temperatures were artificially applied in summer. Expression analysis suggested that these internal factors work either by reducing the increase in OeFT1/2 expression or through putative flowering repressors such as TFL1. With expected warmer winters, future consumption of olive oil, as part of a healthy Mediterranean diet, should benefit from better understanding these factors. © 2017 John Wiley & Sons Ltd.
Bobowski, Nina P; Baker, Laurence H
2016-09-01
The Children's Cancer Survivorship Study reports more chronic illnesses in sarcoma survivors than other pediatric cancers. Chemotherapy and radiation put survivors at risk for developing chronic illnesses, including heart disease, diabetes, hypertension, and kidney failure. Sarcoma survivors may have a reduced life expectancy and signs of heart disease in their 30s and 40s. Since these medical problems occur much later in the general population, they often go undetected or misdiagnosed in sarcoma survivors, creating delays in intervention and treatment. The good news is that these chronic illnesses can often be prevented or minimized. The most common adverse effect of chemotherapy and radiation is coronary artery disease (CAD). CAD has a number of risk factors, including hypertension, diabetes, obesity, and dyslipidemia. These risk factors are modifiable with lifestyle changes, including diet and exercise, and/or pharmacological intervention. By identifying and managing risk factors like hypertension early, we in turn reduce the risk for CAD and prolong survival. This is well established in the general population; there is no reason a priori not to apply it to sarcoma survivors. Sarcoma survivors should be followed by physicians who understand the late effects and outcomes of sarcoma treatment. The University of Michigan Sarcoma Survivorship Clinic provides long-term care for sarcoma survivors by preventing, diagnosing, and treating the adverse long-term physical and psychological effects associated with sarcoma survivorship.
Liu, Xiuwei; Sun, Hongyong; Feike, Til; Zhang, Xiying; Shao, Liwei; Chen, Suying
2016-01-01
The major wheat production region of China the North China Plain (NCP) is seriously affected by air pollution. In this study, yield of winter wheat (Triticum aestivum L.) was analyzed with respect to the potential impact of air pollution index under conditions of optimal crop management in the NCP from 2001 to 2012. Results showed that air pollution was especially serious at the early phase of winter wheat growth significantly influencing various weather factors. However, no significant correlations were found between final grain yield and the weather factors during the early growth phase. In contrast, significant correlations were found between grain yield and total solar radiation gap, sunshine hour gap, diurnal temperature range and relative humidity during the late growing phase. To disentangle the confounding effects of various weather factors, and test the isolated effect of air pollution induced changes in incoming global solar radiation on yield under ceteris paribus conditions, crop model based scenario-analysis was conducted. The simulation results of the calibrated Agricultural Production Systems Simulator (APSIM) model indicated that a reduction in radiation by 10% might cause a yield reduction by more than 10%. Increasing incident radiation by 10% would lead to yield increases of (only) 7%, with the effects being much stronger during the late growing phase compared to the early growing phase. However, there is evidence that APSIM overestimates the effect of air pollution induced changes on radiation, as it does not consider the changes in radiative properties of solar insulation, i.e. the relative increase of diffuse over direct radiation, which may partly alleviate the negative effects of reduced total radiation by air pollution. Concluding, the present study could not detect a significantly negative effect of air pollution on wheat yields in the NCP.
Uncertainties in estimates of the risks of late effects from space radiation
NASA Technical Reports Server (NTRS)
Cucinotta, F. A.; Schimmerling, W.; Wilson, J. W.; Peterson, L. E.; Saganti, P. B.; Dicello, J. F.
2004-01-01
Methods used to project risks in low-Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Using the linear-additivity model for radiation risks, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain an estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including a deep space outpost and Mars missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative metrics, e.g., the number of days in space without exceeding a given risk level within well-defined confidence limits. Published by Elsevier Ltd on behalf of COSPAR.
Uncertainties in Estimates of the Risks of Late Effects from Space Radiation
NASA Technical Reports Server (NTRS)
Cucinotta, F. A.; Schimmerling, W.; Wilson, J. W.; Peterson, L. E.; Saganti, P.; Dicelli, J. F.
2002-01-01
The health risks faced by astronauts from space radiation include cancer, cataracts, hereditary effects, and non-cancer morbidity and mortality risks related to the diseases of the old age. Methods used to project risks in low-Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Within the linear-additivity model, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain a Maximum Likelihood estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including ISS, lunar station, deep space outpost, and Mar's missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time, and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative objective's, i.e., the number of days in space without exceeding a given risk level within well defined confidence limits.
Uncertainties in Projecting Risks of Late Effects from Space Radiation
NASA Astrophysics Data System (ADS)
Cucinotta, F.; Schimmerling, W.; Peterson, L.; Wilson, J.; Saganti, P.; Dicello, J.
The health risks faced by astronauts from space radiation include cancer, cataracts, hereditary effects, CNS risks, and non - cancer morbidity and mortality risks related to the diseases of the old age. Methods used to project risks in low -Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Within the linear-additivity model, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain a maximum likelihood estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including ISS, lunar station, deep space outpost, and Mar's missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of the primary factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time, and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative objectives, i.e., number of days in space without exceeding a given risk level within well defined confidence limits
Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis
2010-01-01
Background Age-related macular degeneration (AMD) is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours. Methods A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR) and/or relative risk (RR) outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI) were calculated. Results Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels. Conclusions Smoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD. PMID:21144031
NASA Astrophysics Data System (ADS)
Meyer, C. P.(Mick); Cook, Garry; Reisen, Fabienne; Russell-Smith, Jeremy; Maier, Stefan; Schatz, Jon; Yates, Cameron; Watt, Felicity
2010-05-01
Burning of savannas and grasslands consumes more than one third of the total annual biomass burning globally. In Australia, savanna fires emit annually from 2% to 4% of Australia's greenhouse gas emissions. This has led to efforts to reduce savanna burning emissions through early season prescribed burning. These programs aim to change the fire seasonality from predominantly high intensity late season fires which are characterized by low levels of patchiness and high burning efficiencies to early-season fires characterized by low intensity, a high degree of patchiness and low burning efficiency. The result is a net reduction in fire area and associated carbon emissions. Mitigation of greenhouse gas emissions is predicated on there being little change in methane (CH4) or nitrous oxide (N2O) emission factors (EFs) as the fire season progresses, however, recent analysis of the emission characteristics of African savanna fires by Korontzi et al., indicates CH4-EF, in particular, could decline substantially as the fire season progresses. If this also occurs in Australian savanna woodlands, then the current mitigation strategy could be ineffective. To address the issue a series of field campaigns were undertaken in the savanna woodlands of Western Arnhem land, Australia to quantify the variability in CH4 and N2O EFs throughout the fire season. This study compared CH4 and N2O EFs measured in smoke sampled from prescribed burning in late June/early July with those from late season fires in early October. It concentrated on the two major vegetation classes in Western Arnhemland; eucalypt open woodland, in which the fuel is composed predominantly tree leaf-litter supplemented by senescent native Sorghum, and sandstone heaths which are dominated by Spinifex hummocks. There were no significant differences in CH4 EFs between early or late season fires, however there were substantial differences between vegetation classes. The woodland emitted 0.3% of fuel carbon as CH4 compared to 0.15% in the sandstone heathland and pure Spinifex and Sorghum swords. The lower emission factors from the grasses compared to leaf litter can be entirely explained by higher combustion efficiency of grass fires. Emission of N2O were less dependent on combustion conditions; approximately 0.5% of fuel nitrogen was emitted as N2O, however there were no differences between early and late season fires or between vegetation classes. These results compare favorably with previous studies; the CH4-EF is similar to earlier measurements in open woodland, although the N2O-EF is lower than the value of 0.8% reported in previous work. Therefore we conclude that the proposed mitigation strategy is feasible and but the variation in EF with vegetation class calls for further quantification of EFs across all major vegetation types in the savanna regions.
Karmazyn-Campelli, Céline; Rhayat, Lamya; Carballido-López, Rut; Duperrier, Sandra; Frandsen, Niels; Stragier, Patrick
2008-03-01
Sporulation in Bacillus subtilis is a primitive differentiation process involving two cell types, the forespore and the mother cell. Each cell implements two successive transcription programmes controlled by specific sigma factors. We report that activity of sigma(G), the late forespore sigma factor, is kept in check by Gin, the product of csfB, a gene controlled by sigma(F), the early forespore sigma factor. Gin abolishes sigma(G) transcriptional activity when sigma(G) is artificially synthesized during growth, but has no effect on sigma(F). Gin interacts strongly with sigma(G) but not with sigma(F) in a yeast two-hybrid experiment. The absence of Gin allows sigma(G) to be active during sporulation independently of the mother-cell development to which it is normally coupled. Premature sigma(G) activity leads to the formation of slow-germinating spores, and complete deregulation of sigma(G) synthesis is lethal when combined with gin inactivation. Gin allows sigma(F) to delay the switch to the late forespore transcription programme by preventing sigma(G) to take over before the cell has reached a critical stage of development. A similar strategy, following a completely unrelated route, is used by the mother cell.
Risk factors of infant anemia in the perinatal period.
Hirata, Michio; Kusakawa, Isao; Ohde, Sachiko; Yamanaka, Michiko; Yoda, Hitoshi
2017-04-01
Infants are at particular risk of iron-deficiency anemia. We investigated changes in the blood count of the mother and infant as well as the relationship between them and the relationship between infant nutrition method and infant anemia. This retrospective cohort study included healthy neonates born between August 2011 and July 2014 at St Luke's International Hospital, Tokyo, Japan. Data from maternal blood samples obtained during late pregnancy and those of infants obtained at birth and at the age of 3, 6, and 9 months were analyzed. Using multivariate logistic regression, we investigated nutrition methods, maternal anemia, and other clinically relevant parameters that were potential risk factors for infant anemia. In total, data for 3472 infants and their mothers were analyzed. Nutrition method was the most significant risk factor for infant anemia, with risk of future anemia decreasing in the following order: exclusive breast-feeding, partial breast-feeding, and formula feeding. Furthermore, low umbilical cord blood hemoglobin led to a tendency toward anemia in the child. Infant nutrition method was the most significant factor related to anemia in late infancy. Infants with low umbilical cord blood hemoglobin are more likely to develop anemia in late infancy. © 2016 Japan Pediatric Society.
[Analysis of the factors contributing to diabetes insipidus after surgeries for craniopharyngiomas].
Luo, Shi; Pan, Jun; Qi, Song-Tao; Fang, Lu-Xiong; Fan, Jun; Liu, Bao-Guo
2009-03-01
To analyze the factors contributing to the occurrence of diabetes insipidus after operations for craniopharyngiomas. A total of 121 cases of diabetes insipidus following surgeries for craniopharyngiomas were retrospectively analyzed and the factors associated with postoperative diabetes insipidus were analyzed. The incidence of diabetes insipidus was 27.3% (33/121 cases) before the operation, 89.9% (107/1119) early after the operation and 39.8%(37/93) in later stages after the operation. The occurrence of early postoperative diabetes insipidus showed a significant relation to the classification and calcification of the craniopharyngioma. Patients with supradiaphragmatic and extraventricular tumors had the lowest incidence of postoperative diabetes insipidus. Late postoperative diabetes insipidus was closely correlated to such factors as age, classification of craniopharyngioma, and intraoperative treatment of the pituitary stalk, but not to the scope of tumor resection or tumor calcification. Late diabetes insipidus was more frequent in children and patients with severed pituitary stalk. The incidence of late postoperative diabetes insipidus was significantly higher in patients with supradiaphragmatic and extra-intraventricular tumors than in those with tumors beneath the diaphragma sellae and extraventricular tumors. Postoperative diabetes insipidus following surgeries for craniopharyngiomas is closely related to the tumor classification, calcification and pituitary stalk protection.
On the importance of minimizing "coast-time" in x-ray driven inertially confined fusion implosions
NASA Astrophysics Data System (ADS)
Hurricane, O. A.; Kritcher, A.; Callahan, D. A.; Landen, O.; Patel, P. K.; Springer, P. T.; Casey, D. T.; Dewald, E. L.; Dittrich, T. R.; Döppner, T.; Hinkel, D. E.; Berzak Hopkins, L. F.; Kline, J.; Le Pape, S.; Ma, T.; MacPhee, A. G.; Moore, A.; Pak, A.; Park, H.-S.; Ralph, J.; Salmonson, J. D.; Widmann, K.
2017-09-01
By the time an inertially confined fusion (ICF) implosion has converged a factor of 20, its surface area has shrunk 400 × , making it an inefficient x-ray energy absorber. So, ICF implosions are traditionally designed to have the laser drive shut off at a time, toff, well before bang-time, tBT, for a coast-time of t coast = t B T - t o f f > 1 ns. High-foot implosions on NIF showed a strong dependence of many key ICF performance quantities on reduced coast-time (by extending the duration of laser power after the peak power is first reached), most notably stagnation pressure and fusion yield. Herein we show that the ablation pressure, pabl, which drives high-foot implosions, is essentially triangular in temporal shape, and that reducing tcoast boosts pabl by as much as ˜ 2 × prior to stagnation thus increasing fuel and hot-spot compression and implosion speed. One-dimensional simulations are used to track hydrodynamic characteristics for implosions with various coast-times and various assumed rates of hohlraum cooling after toff to illustrate how the late-time conditions exterior to the implosion can impact the fusion performance. A simple rocket model-like analytic theory demonstrates that reducing coast-time can lead to a ˜ 15 % higher implosion velocity because the reduction in x-ray absorption efficiency at late-time is somewhat compensated by small ( ˜ 5 % - 10 %) ablator mass remaining. Together with the increased ablation pressure, the additional implosion speed for short coast-time implosions can boost the stagnation pressure by ˜ 2 × as compared to a longer coast-time version of the same implosion. Four key dimensionless parameters are identified and we find that reducing coast-time to as little as 500 ps still provides some benefit. Finally, we show how the high-foot implosion data is consistent with the above mentioned picture.
On the importance of minimizing “coast-time” in x-ray driven inertially confined fusion implosions
Hurricane, O. A.; Kritcher, A.; Callahan, D. A.; ...
2017-09-01
By the time an inertially confined fusion (ICF) implosion has converged a factor of 20, its surface area has shrunk 400×, making it an inefficient x-ray energy absorber. So, ICF implosions are traditionally designed to have the laser drive shut off at a time, t off, well before bang-time, t BT, for a coast-time of t coast = t BT – t off > 1 ns. High-foot implosions on NIF showed a strong dependence of many key ICF performance quantities on reduced coast-time (by extending the duration of laser power after the peak power is first reached), most notably stagnationmore » pressure and fusion yield. Herein we show that the ablation pressure, p abl, which drives high-foot implosions, is essentially triangular in temporal shape, and that reducing t coast boosts p abl by as much as ~2× prior to stagnation thus increasing fuel and hot-spot compression and implosion speed. One-dimensional simulations are used to track hydrodynamic characteristics for implosions with various coast-times and various assumed rates of hohlraum cooling after t off to illustrate how the late-time conditions exterior to the implosion can impact the fusion performance. A simple rocket model-like analytic theory demonstrates that reducing coast-time can lead to a ~15% higher implosion velocity because the reduction in x-ray absorption efficiency at late-time is somewhat compensated by small (~5%–10%) ablator mass remaining. Together with the increased ablation pressure, the additional implosion speed for short coast-time implosions can boost the stagnation pressure by ~2× as compared to a longer coast-time version of the same implosion. Four key dimensionless parameters are identified and we find that reducing coast-time to as little as 500 ps still provides some benefit. Lastly, we show how the high-foot implosion data is consistent with the above mentioned picture.« less
On the importance of minimizing “coast-time” in x-ray driven inertially confined fusion implosions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hurricane, O. A.; Kritcher, A.; Callahan, D. A.
By the time an inertially confined fusion (ICF) implosion has converged a factor of 20, its surface area has shrunk 400×, making it an inefficient x-ray energy absorber. So, ICF implosions are traditionally designed to have the laser drive shut off at a time, t off, well before bang-time, t BT, for a coast-time of t coast = t BT – t off > 1 ns. High-foot implosions on NIF showed a strong dependence of many key ICF performance quantities on reduced coast-time (by extending the duration of laser power after the peak power is first reached), most notably stagnationmore » pressure and fusion yield. Herein we show that the ablation pressure, p abl, which drives high-foot implosions, is essentially triangular in temporal shape, and that reducing t coast boosts p abl by as much as ~2× prior to stagnation thus increasing fuel and hot-spot compression and implosion speed. One-dimensional simulations are used to track hydrodynamic characteristics for implosions with various coast-times and various assumed rates of hohlraum cooling after t off to illustrate how the late-time conditions exterior to the implosion can impact the fusion performance. A simple rocket model-like analytic theory demonstrates that reducing coast-time can lead to a ~15% higher implosion velocity because the reduction in x-ray absorption efficiency at late-time is somewhat compensated by small (~5%–10%) ablator mass remaining. Together with the increased ablation pressure, the additional implosion speed for short coast-time implosions can boost the stagnation pressure by ~2× as compared to a longer coast-time version of the same implosion. Four key dimensionless parameters are identified and we find that reducing coast-time to as little as 500 ps still provides some benefit. Lastly, we show how the high-foot implosion data is consistent with the above mentioned picture.« less
BARIUM REDUCTION OF INTUSSUSCEPTION IN INFANCY
Denenholz, Edward J.; Feher, George. S.
1955-01-01
Barium enema reduction was used as the initial routine treatment in 29 infants with intussusception. In 22 of them the intussusception was reduced by this means. In three of eight patients operated upon the intussusception was found to be reduced. Four of the remaining five patients had clinical or x-ray evidence of complications before reduction by barium enema was attempted. Twenty-one of the patients, all of whom were observed in private practice, were treated without admission to the hospital. After reduction, these patients were observed closely by the clinician. None of these patients showed clinical or x-ray signs of complications before reduction. Certain clinical and roentgen criteria must be satisfied before it can be concluded that reduction by barium enema is complete. If there are clinical signs of complications with x-ray evidence of small bowel obstruction, only a very cautious attempt at hydrostatic reduction should be made. As the time factor is generally a reliable clinical guide to reducibility, the late cases should be viewed with greater caution. Long duration of symptoms, however, is not per se a contraindication to an attempt at hydrostatic reduction. PMID:13230908
Zhang, Bing; Tang, Xi Can; Zhang, Hai Yan
2013-05-01
Although many post-mortem studies have found evidence of central insulin resistance in Alzheimer's disease (AD) patients, results on changes of central insulin-like growth factor-1 (IGF-1) signaling in the pathological process of AD remain controversial. In the present study, we observed the activation states of IGF-1 downstream signaling in brain slices of transgenic mice carrying APPswe/PS1dE9 mutations (APP/PS1 mice) at both early and late stages (ex vivo) and further investigated the involvement of oligomeric β-amyloid (Aβ) and Aβ-enriched culture medium (CM) on IGF-1 sensitivity employing neuronal models (in vitro). In 6- and 18-month-old APP/PS1 mice, the phosphorylations of IGF-1 receptor (IGF-1R) and Akt in response to IGF-1 stimulation were significantly reduced in the hippocampal and cortical slices, whereas IGF-1R protein expression and mRNA levels of IGF-1 and IGF-1R in the hippocampal slices were significantly higher than that in wild-type mice. In agreement with these results, reduced IGF-1 sensitivity was verified in APP and PS1 double stably transfected CHO cells; moreover, IGF-1 stimulated phosphorylations of IGF-1R and Akt were also markedly weakened by oligomeric Aβ or Aβ-enriched CM posttreatment in CHO cells without APP/PS1-transfected (K1 cells) and primary hippocampal neurons. These observations indicate that the impaired central IGF-1 sensitivity at early and late stages of APP/PS1 transgenic mice might be attributable, at least partially, to the overproduced Aβ, especially the oligomeric Aβ. These findings may shed new light on the mechanisms underlying the defective IGF-1 signaling in AD pathogenesis and provide important clues for AD drug discovery. Copyright © 2013 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Prada, M.; Watremez, L.; Chen, C.; O'Reilly, B.; Minshull, T. A.; Reston, T. J.; Wagner, G.; Gaw, V.; Klaeschen, D.; Shannon, P.
2015-12-01
The Porcupine Basin is a tongue-shaped basin SW of Ireland formed during the opening of the North Atlantic Ocean. Its history of sedimentation reveals several rifting and subsidence phases during the Late Paleozoic and Cenozoic, with a particular major rift phase occurring in Late Jurassic-Early Cretaceous times. Previous work, focused on seismic and gravity data, suggest the presence of major crustal faulting and uppermost mantle serpentinization in the basin. Serpentinization is a key factor in lithospheric extension since it reduces the strength of mantle rocks, and hence, influences the tectonics of the lithosphere. Besides reducing the seismic velocity of the rock, serpentinization decreases mantle rock density favoring isostatic rebound and basin uplift, thus affecting the tectonic and thermal evolution of the basin. Here we characterize the deep structure of the Porcupine Basin from wide-angle seismic (WAS) and gravity data, with especial emphasis on the nature of the underlying mantle. The WAS data used were acquired along a 300 km long transect across the northern region of the basin. We used a travel time inversion method to model the data and obtain a P-wave velocity (Vp) model of the crust and uppermost mantle, together with the geometry of the main geological interfaces. The crustal structure along the model reveals a maximum stretching factor of ~5-6. These values are well within the range of crustal extension at which the crust becomes entirely brittle allowing the formation of major crustal faulting and serpentinization of the mantle. To further constrain the seismic structure and hence the nature of the mantle we assess the Vp uncertainty of the model by means of a Monte Carlo analysis and perform gravity modeling to test different interpretations regarding mantle rock nature. This project is funded by the Irish Shelf Petroleum Studies Group (ISPSG) of the Irish Petroleum Infrastructure Programme Group 4.
Incidence and risk factors of ventilator associated pneumonia in a tertiary care hospital.
Charles, Mv Pravin; Easow, Joshy M; Joseph, Noyal M; Ravishankar, M; Kumar, Shailesh; Umadevi, Sivaraman
2013-01-01
Ventilator associated pneumonia (VAP) is a type of nosocomial pneumonia associated with increased morbidity and mortality. Knowledge about the incidence and risk factors is necessary to implement preventive measures to reduce mortality in these patients. A prospective study was conducted at a tertiary care teaching hospital for a period of 20 months from November 2009 to July 2011. Patients who were on mechanical ventilation (MV) for more than 48 hours were monitored at frequent intervals for development of VAP using clinical and microbiological criteria until discharge or death. Of the 76 patients, 18 (23.7%) developed VAP during their ICU stay. The incidence of VAP was 53.25 per 1,000 ventilator days. About 94% of VAP cases occurred within the first week of MV. Early-onset and late-onset VAP was observed in 72.2% and 27.8%, respectively. Univariate analysis showed chronic lung failure, H2 blockers usage, and supine head position were significant risk factors for VAP. Logistic regression revealed supine head position as an independent risk factor for VAP. VAP occurred in a sizeable number of patients on MV. Chronic lung failure, H2 blockers usage, and supine head position were the risk factors associated with VAP. Awareness about these risk factors can be used to inform simple and effective preventive measures.
Genetic associations between fibrinogen and cognitive performance in three Scottish cohorts.
Marioni, Riccardo E; Deary, Ian J; Murray, Gordon D; Lowe, Gordon D O; Strachan, Mark W J; Luciano, Michelle; Houlihan, Lorna M; Gow, Alan J; Harris, Sarah E; Rumley, Ann; Stewart, Marlene C; Fowkes, F Gerry R; Price, Jackie F
2011-09-01
There is increasing evidence to suggest that elevated plasma levels of fibrinogen are associated with late-life cognitive performance. This study tested the association of single nucleotide polymorphisms in the fibrinogen α (FGA) and β (FGB) genes with cognitive performance. Data were analysed from three community-dwelling populations of older persons (>50 years) in central Scotland: the Aspirin for Asymptomatic Atherosclerosis (AAA) Trial (n = 2,091), the Edinburgh Type 2 Diabetes Study (ET2DS, n = 1,066), and the Lothian Birth Cohort 1936 (LBC1936, n = 1,091). Cognition was assessed using a battery of five, seven, and four psychometric tests, respectively. This information was used to derive a general cognitive factor. Weakly significant associations were found between the rs4220 (FGB), and rs2227412 (FGB) SNPs and a single test of cognitive performance in the AAA Trial (p < 0.05). These findings did not replicate in the LBC1936 or ET2DS cohorts, except for the rs2227412 SNP, which was significantly associated with the general cognitive factor in the ET2DS (p = 3.3 × 10(-4)). A summary term that combined results from all three studies suggested that the rs2227412 genotype associated with reduced cognitive ability also associated with higher plasma fibrinogen levels. These findings suggest a tentative role for fibrinogen as a determinant of late-life cognitive performance and justify further attempts at replication in older persons.
Henrichs, Jens; Schenk, Jacqueline J; Barendregt, Charlotte S; Schmidt, Henk G; Steegers, Eric Ap; Hofman, Albert; Jaddoe, Vincent W V; Moll, Henriette A; Verhulst, Frank C; Tiemeier, Henning
2010-07-01
The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.
A new perspective on adiposity in a naturally obese mammal
NASA Technical Reports Server (NTRS)
Ortiz, R. M.; Noren, D. P.; Litz, B.; Ortiz, C. L.
2001-01-01
Many mammals seasonally reduce body fat due to inherent periods of fasting, which is associated with decreased leptin concentrations. However, no data exist on the correlation between fat mass (FM) and circulating leptin in marine mammals, which have evolved large fat stores as part of their adaptation to periods of prolonged fasting. Therefore, FM was estimated (by tritiated water dilution), and serum leptin and cortisol were measured in 40 northern elephant seal (Mirounga angustirostris) pups early (<1 wk postweaning) and late (6-8 wk postweaning) during their natural, postweaning fast. Body mass (BM) and FM were reduced late; however, percent FM (early: 43.9 +/- 0.5, late: 45.5 +/- 0.5%) and leptin [early: 2.9 +/- 0.1 ng/ml human equivalents (HE), late: 3.0 +/- 0.1 ng/ml HE] did not change. Cortisol increased between early (9.2 +/- 0.5 microg/dl) and late (16.3 +/- 0.9 microg/dl) periods and was significantly and negatively correlated with BM (r = 0.426; P < 0.0001) and FM (r = 0.328; P = 0.003). FM and percent FM were not correlated (P > 0.10) with leptin at either period. The present study suggests that these naturally obese mammals appear to possess a novel cascade for regulating body fat that includes cortisol. The lack of a correlation between leptin and FM may reflect the different functions of fat between terrestrial and marine mammals.
fMRI response during visual motion stimulation in patients with late whiplash syndrome.
Freitag, P; Greenlee, M W; Wachter, K; Ettlin, T M; Radue, E W
2001-01-01
After whiplash trauma, up to one fourth of patients develop chronic symptoms including head and neck pain and cognitive disturbances. Resting perfusion single-photon-emission computed tomography (SPECT) found decreased temporoparietooccipital tracer uptake among these long-term symptomatic patients with late whiplash syndrome. As MT/MST (V5/V5a) are located in that area, this study addressed the question whether these patients show impairments in visual motion perception. We examined five symptomatic patients with late whiplash syndrome, five asymptomatic patients after whiplash trauma, and a control group of seven volunteers without the history of trauma. Tests for visual motion perception and functional magnetic resonance imaging (fMRI) measurements during visual motion stimulation were performed. Symptomatic patients showed a significant reduction in their ability to perceive coherent visual motion compared with controls, whereas the asymptomatic patients did not show this effect. fMRI activation was similar during random dot motion in all three groups, but was significantly decreased during coherent dot motion in the symptomatic patients compared with the other two groups. Reduced psychophysical motion performance and reduced fMRI responses in symptomatic patients with late whiplash syndrome both point to a functional impairment in cortical areas sensitive to coherent motion. Larger studies are needed to confirm these clinical and functional imaging results to provide a possible additional diagnostic criterion for the evaluation of patients with late whiplash syndrome.
[Risk-adjusted assessment: late-onset infection in neonates].
Gmyrek, Dieter; Koch, Rainer; Vogtmann, Christoph; Kaiser, Annette; Friedrich, Annette
2011-01-01
The weak point of the countrywide perinatal/neonatal quality surveillance is the ignorance of interhospital differences in the case mix of patients. As a result, this approach does not produce reliable benchmarking. The objective of this study was to adjust the result of the late-onset infection incidence of different hospitals according to their risk profile of patients by multivariate analysis. The perinatal/neonatal database of 41,055 newborns of the Saxonian quality surveillance from 1998 to 2004 was analysed. Based on 18 possible risk factors, a logistic regression model was used to develop a specific risk predictor for the quality indicator "late-onset infection". The developed risk predictor for the incidence of late-onset infection could be described by 4 of the 18 analysed risk factors, namely gestational age, admission from home, hypoxic ischemic encephalopathy and B-streptococcal infection. The AUC(ROC) value of this quality indicator was 83.3%, which demonstrates its reliability. The hospital ranking based on the adjusted risk assessment was very different from hospital rankings before this adjustment. The average correction of ranking position was 4.96 for 35 clinics. The application of the risk adjustment method proposed here allows for a more objective comparison of the incidence of the quality indicator "late onset infection" among different hospitals. Copyright © 2011. Published by Elsevier GmbH.
Risk factors for depressive symptoms in adolescent pregnancy in a late-teen subsample.
Koleva, Hristina; Stuart, Scott
2014-04-01
Depression in adolescent pregnancy is common but underrecognized and can be associated with negative medical outcomes. This brief report examines the relationship between depressive symptoms and various demographic and obstetrical risk factors, as well as the use of antidepressants in pregnant adolescents of late teenage years. Data were derived from a relatively large sample (506 women) recruited from university-based and community mental health centers in Iowa. A cross-sectional analysis did not reveal significant statistical associations between the risk factors and depressive symptoms (Beck Depression Inventory). Antidepressant use was very low (3.7 %), and adolescents with higher depression scores were more likely to take medications. In conclusion, screening for depression in pregnant adolescents should be universal, regardless of demographic and obstetrical risk factors, and promptly addressed.
A case of mumps-related acute encephalopathy with biphasic seizures and late reduced diffusion.
Hazama, Kyoko; Shiihara, Takashi; Tsukagoshi, Hiroyuki; Hasegawa, Shunji; Dowa, Yuri; Watanabe, Mio
2017-10-01
Mumps is a common childhood viral disease characterized by fever and swelling of the parotid gland. The prognosis is generally good, although some complications, such as encephalitis (0.1%), exist. Acute encephalopathy with biphasic seizures and late reduced diffusion is the most common type of acute encephalopathy. However, this type of encephalopathy has not been reported in association with mumps infection. A previously healthy 3-year-old Japanese boy had a brief convulsion after fever for 3days, and then had conscious disturbance and parotitis. After several days, he had a second brief convulsion and was admitted. Increased serum amylase levels and presence of anti-mumps immunoglobulin M antibody confirmed mumps parotitis. The patient had another brief seizure later the day of admission. He did not have status or cluster seizures, although the biphasic nature of his seizures, conscious disturbance between the seizures, no pleocytosis in cerebrospinal fluid, and brain magnetic resonance images were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion. In Japan, the mumps vaccine is not administered as a part of routine immunizations. It thus has low coverage (30-40%), and as a result, mumps infections are still common. However, this is the first case of mumps-related acute encephalopathy with biphasic seizures and late reduced diffusion. This case may be representative of only a minority of patients with mumps-associated central nervous system involvement. Nevertheless, this diagnostic possibility may be considered. In order to prevent mumps-related complications, routine mumps vaccination might be warranted. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Johnson, Leigh F.; Stinson, Kathryn; Newell, Marie-Louise; Bland, Ruth M.; Moultrie, Harry; Davies, Mary-Ann; Rehle, Thomas M.; Dorrington, Rob E.; Sherman, Gayle G.
2012-01-01
Background The prevention of mother-to-child transmission (PMTCT) of HIV has been focused mainly on women who are HIV-positive at their first antenatal visit, but there is uncertainty regarding the contribution to overall transmission from mothers who seroconvert after their first antenatal visit and before weaning. Method A mathematical model was developed to simulate changes in mother-to-child transmission of HIV over time, in South Africa. The model allows for changes in infant feeding practices as infants age, temporal changes in the provision of antiretroviral prophylaxis and counselling on infant feeding, as well as temporal changes in maternal HIV prevalence and incidence. Results The proportion of MTCT from mothers who seroconverted after their first antenatal visit was 26% (95% CI: 22-30%) in 2008, or 15 000 out of 57 000 infections. It is estimated that by 2014, total MTCT will reduce to 39 000 per annum, and transmission from mothers seroconverting after their first antenatal visit will reduce to 13 000 per annum, accounting for 34% (95% CI: 29-39%) of MTCT. If maternal HIV incidence during late pregnancy and breastfeeding were reduced by 50% after 2010, and HIV screening were repeated in late pregnancy and at 6-week immunization visits after 2010, the average annual number of MTCT cases over the 2010-15 period would reduce by 28% (95% CI: 25-31%), from 39 000 to 28 000 per annum. Conclusion Maternal seroconversion during late pregnancy and breastfeeding contributes significantly to the paediatric HIV burden, and needs greater attention in the planning of PMTCT programmes. PMID:22193774
Student Bedtimes, Academic Performance, and Health in a Residential High School
ERIC Educational Resources Information Center
Wernette, Maliah J.; Emory, Jan
2017-01-01
Inadequate sleep among adolescents is considered an epidemic in the United States. Late night bedtimes could be an important factor in academic performance and health with consequences continuing throughout adulthood. The purpose of this study was to explore the relationships between late night bedtimes, academic performance (grade point average…
Circulating microRNAs as biomarkers of early embryonic viability in cattle
USDA-ARS?s Scientific Manuscript database
Embryonic mortality (EM) is considered to be the primary factor limiting pregnancy success in cattle and occurs early (< day 28) or late (= day 28) during gestation. The incidence of early EM in cattle is approximately 25% while late EM is approximately 3.2 to 42.7%. In cattle, real time ultrasonog...
School Mobility during Childhood Predicts Psychotic Symptoms in Late Adolescence
ERIC Educational Resources Information Center
Winsper, Catherine; Wolke, Dieter; Bryson, Alex; Thompson, Andrew; Singh, Swaran P.
2016-01-01
Background: Recently, school mobility was identified as a risk factor for psychotic symptoms in early adolescence. The extent to which this risk continues into late adolescence and the trajectories via which this risk manifests remain unexplored. Methods: Psychotic symptoms in 4,720 adolescents aged 18 were ascertained by trained psychologists…
ERIC Educational Resources Information Center
Glanz, Jeffrey
Focusing on factors which shaped and influenced public school supervision, the paper investigates educational developments in the late 19th century. During this period the movement toward centralization in urban public schools gained considerable momentum. Educational historians have largely ignored the role school superintendents played in the…
Occupational Propensity for Training in a Late Industrial Society: Evidence from Russia
ERIC Educational Resources Information Center
Anikin, Vasiliy A.
2017-01-01
What factors best explain the low incidence of skills training in a late industrial society like Russia? This research undertakes a multilevel analysis of the role of occupational structure in the probability of training. The explanatory power of occupation-specific determinants and skills polarization are evaluated, using a representative 2012…
Risk Factor Analysis and the Youth Question
ERIC Educational Resources Information Center
France, Alan
2008-01-01
This paper is concerned with exploring how in late modernity the "youth question" is being addressed by public policy and what impact this is having on understandings of childhood and youth. Historically the youth question has been shaped by adult anxieties over youth delinquency and their problems of social integration. In late modernity, this is…
Childhood and Adolescent Predictors of Late Onset Criminal Careers
ERIC Educational Resources Information Center
Zara, Georgia; Farrington, David P.
2009-01-01
This study explores the emergence of a criminal career in adulthood. The main hypothesis tested is that late criminal onset (at age 21 or later) is influenced by early factors that delay antisocial manifestations. The Cambridge Study in Delinquent Development (CSDD) was used to examine early determinants of criminal behavior. 400 Inner London…
School Entrance Recommendation: A Question of Age or Development?
ERIC Educational Resources Information Center
Horstschräer, Julia; Muehler, Grit
2014-01-01
Fixed cutoff dates regulating school entry create disadvantages for children who are young relative to their classmates. Early and late school enrollment, though, might mitigate these disadvantages. In this paper, we analyze in a first step which factors determine school entry, if entrance screenings allow for early and late enrollment. Second, we…
Wang, Xiaohong; Liu, Haibin; Ge, Hui; Ajiro, Masahiko; Sharma, Nishi R.; Meyers, Craig; Morozov, Pavel; Tuschl, Thomas; Klar, Amar; Court, Donald
2017-01-01
ABSTRACT The life cycle of human papillomaviruses (HPVs) is tightly linked to keratinocyte differentiation. Although expression of viral early genes is initiated immediately upon virus infection of undifferentiated basal cells, viral DNA amplification and late gene expression occur only in the mid to upper strata of the keratinocytes undergoing terminal differentiation. In this report, we show that the relative activity of HPV18 TATA-less late promoter P811 depends on its orientation relative to that of the origin (Ori) of viral DNA replication and is sensitive to the eukaryotic DNA polymerase inhibitor aphidicolin. Additionally, transfected 70-nucleotide (nt)-long single-strand DNA oligonucleotides that are homologous to the region near Ori induce late promoter activity. We also found that promoter activation in raft cultures leads to production of the late promoter-associated, sense-strand transcription initiation RNAs (tiRNAs) and splice-site small RNAs (spliRNAs). Finally, a cis-acting AAGTATGCA core element that functions as a repressor to the promoter was identified. This element interacts with hnRNP D0B and hnRNP A/B factors. Point mutations in the core prevented binding of hnRNPs and increased the promoter activity. Confirming this result, knocking down the expression of both hnRNPs in keratinocytes led to increased promoter activity. Taking the data together, our study revealed the mechanism of how the HPV18 late promoter is regulated by DNA replication and host factors. PMID:28559488
Sweeney, Emma L.; Kallapur, Suhas G.; Gisslen, Tate; Lambers, Donna S.; Chougnet, Claire A.; Stephenson, Sally-Anne; Jobe, Alan H.; Knox, Christine L.
2016-01-01
Objective. The human Ureaplasma species are the microbes most frequently isolated from placentae of women who deliver preterm. The role of Ureaplasma species has been investigated in pregnancies at <32 weeks of gestation, but currently no studies have determined the prevalence of ureaplasmas in moderately preterm and late-preterm (hereafter, “moderate/late preterm”) infants, the largest cohort of preterm infants. Methods. Women delivering moderate/late preterm infants (n = 477) and their infants/placentae (n = 535) were recruited, and swab specimens of chorioamnion tissue, chorioamnion tissue specimens, and cord blood specimens were obtained at delivery. Swab and tissue specimens were cultured and analyzed by 16S ribosomal RNA polymerase chain reaction (PCR) for the presence of microorganisms, while cord blood specimens were analyzed for the presence of cytokines, chemokines, and growth factors. Results. We detected microorganisms in 10.6% of 535 placentae (443 were delivered late preterm and 92 were delivered at term). Significantly, Ureaplasma species were the most prevalent microorganisms, and their presence alone was associated with histologically confirmed chorioamnionitis in moderate/late preterm and term placentae (P < .001). The presence of ureaplasmas in the chorioamnion was also associated with elevated levels of granulocyte colony-stimulating factor (P = .02). Conclusions. These findings have important implications for infection and adverse pregnancy outcomes throughout gestation and should be of major consideration for obstetricians and neonatologists. PMID:26671889
Waldinger, Robert J.; Schulz, Marc S.
2011-01-01
Defenses that keep threatening information out of awareness are posited to reduce anxiety at the cost of longer-term dysfunction. By contrast, socioemotional selectivity theory suggests that preference for positively-valenced information is a late-life manifestation of adaptive emotion regulation. Using longitudinal data on 61 men, we examined links between emotion regulation indices informed by these distinct conceptualizations: defenses in earlier adulthood and selective memory for positively-valenced images in late-life. Use of avoidant defenses in midlife predicted poorer memory for positive, negative, and neutral images nearly 4 decades later. Late-life satisfaction was positively linked with midlife engaging defenses but negatively linked at the trend level with concurrent positive memory bias. PMID:21544264
The late open infarct-related artery hypothesis: evidence-based medicine or not?
Brueck, Martin; Bandorski, Dirk; Kramer, Wilfried; Vogt, Paul R; Heidt, Martin C
2007-11-01
Randomized clinical trials have clearly shown that early reperfusion of coronary arteries is the established treatment of myocardial infarction preserving left ventricular function and reducing mortality. However, late patency of the infarct-related artery is an independent predictor of survival leading to the late open-artery hypothesis. This concept implies restoration of antegrade blood flow of the infarct-related artery in patients with myocardial infarction to improve survival by mechanisms less time-dependent or even time-independent. Possible explanations for this benefit include improved left ventricular function and electrical stability by perfusion of hibernating myocardium, accelerated infarct healing and limitation of ventricular remodeling. This review focuses on the evidence of late recanalization of occluded infarct-related arteries in patients with coronary artery disease.
Morbidity, mortality and economic burden of renal impairment in cardiac intensive care.
Chew, D P; Astley, C; Molloy, D; Vaile, J; De Pasquale, C G; Aylward, P
2006-03-01
Moderate to severe impairment of renal function has emerged as a potent risk factor for adverse short- and long-term outcomes among patients presenting with cardiac disease. We sought to define the clinical, late mortality and economic burden of this risk factor among patients presenting to cardiac intensive care. A clinical audit of patients presenting to cardiac intensive care was undertaken between July 2002 and June 2003. All patients presenting with cardiac diagnoses were included in the study. Baseline creatinine levels were assessed in all patients. Late mortality was assessed by the interrogation of the National Death Register. Renal impairment was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2, as calculated by the Modified Diet in Renal Disease formula. In-hospital and late outcomes were compared by Cox proportional hazards modelling, adjusting for known confounders. A matched analysis and attributable risk calculation were undertaken to assess the proportion of late mortality accounted for by impairment of renal function and other known negative prognostic factors. The in-hospital total cost associated with renal impairment was assessed by linear regression. Glomerular filtration rate <60 mL/min per 1.73 m2 was evident in 33.0% of this population. Among these patients, in-hospital and late mortality were substantially increased: risk ratio 13.2; 95% CI 3.0-58.1; P < 0.001 and hazard ratio 6.2; 95% CI 3.6-10.7; P < 0.001, respectively. In matched analysis, renal impairment to this level was associated with 42.1% of all the late deaths observed. Paradoxically, patients with renal impairment were more conservatively managed, but their hospitalizations were associated with an excess adjusted in-hospital cost of $A1676. Impaired renal function is associated with a striking clinical and economic burden among patients presenting to cardiac intensive care. As a marker for future risk, renal function accounts for a substantial proportion of the burden of late mortality. The burden of risk suggests a greater potential opportunity for improvement of outcomes through optimisation of therapeutic strategies.
Growth of Newly Planted Water Tupelo Seedlings After Flooding and Siltation
H. E. Kennedy
1970-01-01
In central Mississippi, outplanted water tupelo seedlings survived and grew well after shallow flooding (up to 8 cm) from late February through June 1. Submersion of the seedlings, flooding until late in the growing season, reflooding, and moderate siltation reduced growth. Flooding caused changes in certain soil properties, but these changes did not seem to be the...
The Productivity Costs of Inefficient Hiring Practices: Evidence from Late Teacher Hiring
ERIC Educational Resources Information Center
Papay, John P.; Kraft, Matthew A.
2016-01-01
We use matched employee-employer records from the teacher labor market to explore the effects of late teacher hiring on student achievement. Hiring teachers after the school year starts reduces student achievement by 0.042 SD in mathematics and 0.026 SD in reading. This reflects, in part, a temporary disruption effect in the first year. In…
Genetic and Environmental Architecture of Changes in Episodic Memory from Middle to Late Middle Age
Panizzon, Matthew S.; Neale, Michael C.; Docherty, Anna R.; Franz, Carol E.; Jacobson, Kristen C.; Toomey, Rosemary; Xian, Hong; Vasilopoulos, Terrie; Rana, Brinda K.; McKenzie, Ruth M.; Lyons, Michael J.; Kremen, William S.
2015-01-01
Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain. We examined six measures from three episodic memory tests in a narrow age cohort at middle and late middle age. The factor structure was invariant across occasions. At both timepoints two of three test-specific factors (story recall, design recall) had significant genetic influences independent of the general memory factor. Phenotypic stability was moderate to high, and primarily accounted for by genetic influences, except for one test-specific factor (list learning). Mean change over time was nonsignificant for one test-level factor; one declined; one improved. The results highlight the phenotypic and genetic complexity of memory and memory change, and shed light on an understudied period of life. PMID:25938244
Genetic and environmental architecture of changes in episodic memory from middle to late middle age.
Panizzon, Matthew S; Neale, Michael C; Docherty, Anna R; Franz, Carol E; Jacobson, Kristen C; Toomey, Rosemary; Xian, Hong; Vasilopoulos, Terrie; Rana, Brinda K; McKenzie, Ruth; Lyons, Michael J; Kremen, William S
2015-06-01
Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain. We examined 6 measures from 3 episodic memory tests in a narrow age cohort at middle and late middle age. The factor structure was invariant across occasions. At both timepoints 2 of 3 test-specific factors (story recall, design recall) had significant genetic influences independent of the general memory factor. Phenotypic stability was moderate to high, and primarily accounted for by genetic influences, except for 1 test-specific factor (list learning). Mean change over time was nonsignificant for 1 test-level factor; 1 declined; 1 improved. The results highlight the phenotypic and genetic complexity of memory and memory change, and shed light on an understudied period of life. (c) 2015 APA, all rights reserved.
Timing and causes of death in septic shock.
Daviaud, Fabrice; Grimaldi, David; Dechartres, Agnès; Charpentier, Julien; Geri, Guillaume; Marin, Nathalie; Chiche, Jean-Daniel; Cariou, Alain; Mira, Jean-Paul; Pène, Frédéric
2015-12-01
Most studies about septic shock report a crude mortality rate that neither distinguishes between early and late deaths nor addresses the direct causes of death. We herein aimed to determine the modalities of death in septic shock. This was a 6-year (2008-2013) monocenter retrospective study. All consecutive patients diagnosed for septic shock within the first 48 h of intensive care unit (ICU) admission were included. Early and late deaths were defined as occurring within or after 3 days following ICU admission, respectively. The main cause of death in the ICU was determined from medical files. A multinomial logistic regression analysis using the status alive as the reference category was performed to identify the prognostic factors associated with early and late deaths. Five hundred forty-three patients were included, with a mean age of 66 ± 15 years and a high proportion (67 %) of comorbidities. The in-ICU and in-hospital mortality rates were 37.2 and 45 %, respectively. Deaths occurred early for 78 (32 %) and later on for 166 (68 %) patients in the ICU (n = 124) or in the hospital (n = 42). Early deaths were mainly attributable to intractable multiple organ failure related to the primary infection (82 %) and to mesenteric ischemia (6.4 %). In-ICU late deaths were directly related to end-of-life decisions in 29 % of patients and otherwise mostly related to ICU-acquired complications, including nosocomial infections (20.4 %) and mesenteric ischemia (16.6 %). Independent determinants of early death were age, malignancy, diabetes mellitus, no pathogen identification, and initial severity. Among 3-day survivors, independent risk factors for late death were age, cirrhosis, no pathogen identification, and previous corticosteroid treatment. Our study provides a comprehensive assessment of septic shock-related deaths. Identification of risk factors of early and late deaths may determine differential prognostic patterns.
Psychotic states arising in late life (late paraphrenia). The role of risk factors.
Almeida, O P; Howard, R J; Levy, R; David, A S
1995-02-01
This study explored the association between 'late paraphrenia' and various risk factors such as female gender, sensory impairment, marital status, positive family history of psychoses, and the presence of abnormal neurological signs. It was hypothesised that patients would show significantly more abnormal neurological signs than controls. Inclusion criteria for the diagnosis of late paraphrenia were fulfilled by 47 patients, including in-patients, out-patients, day-patients, and those living in the community. Thirty-three age-, sex-, education-, and premorbid IQ-matched elderly controls were recruited from luncheon clubs in Southwark and Lambeth (London, UK). A scale for the assessment of neurological soft and hard signs was developed for this study. The Abnormal Involuntary Movement Scale (AIMS) and the Tardive Dyskinesia Rating Scale (TDRS) were also used. There was a high female-to-male ratio (42:5), and a fourfold increase in the risk of patients having hearing impairment (odds ratio = 4.15, Clodds = 1.36 to 12.63). There was no difference between the two groups in visual difficulties nor in marital status. Patients were approximately ten times more likely to be living on their own (odds ratio = 10.61; Clodds = 3.59 to 31.33) and 16 times more likely to be considered socially isolated (odds ratio = 16.65; Clodds = 5.39 to 51.40). There was no difference between patients and controls in frequency of schizophrenia-like family history. Patients were more likely than controls to exhibit neurological soft signs (z = 4.70; P < 0.001; Cld = 4.61 to 9.63). The presence of abnormal involuntary and tardive dyskinesia movements was associated with the use of antipsychotic medication. Women appear to run a greater risk of developing late paraphrenia, especially those who are socially isolated and present with associated hearing impairment. The increased presence of neurological soft signs among patients indicates that brain disease may be a critical factor in the development of psychotic symptoms in late life.
Garg, Pankaj
2016-06-10
There are several factors which contribute to patients' reporting late to healthcare facility even after detecting the breast lump (patient delay). Amongst these, one of the important factors in low- and middle-income countries is lack of awareness that early cancer lump is painless (ECLIPs). Pain is often taken as a danger sign and absence of pain is often not taken seriously. The studies have shown that up to 98% of women in low-income countries are unaware that a painless lump could be a warning sign of early breast cancer. This fact is significant because this could be one of the prime reasons for the women having discovered a painless lump in the breast, accidentally or by breast self-examination, presume it to be harmless and don't report early to health care facility. Therefore, creating awareness about ECLIPs could be an effective strategy to reduce mortality due to breast cancer in low- and middle-income countries. Moreover, unlike modifying risk factors which requires long term behavior modification, creating awareness about ECLIPs is easy and cost effective.
Radiation protection issues in galactic cosmic ray risk assessment
NASA Technical Reports Server (NTRS)
Sinclair, W. K.
1994-01-01
Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.
Depression and dementia: cause, consequence or coincidence?
Bennett, Sophia; Thomas, Alan J
2014-10-01
The relationship between depression and dementia is complex and still not well understood. A number of different views exist regarding how the two conditions are linked as well as the underlying neurobiological mechanisms at work. This narrative review examined longitudinal and cross sectional studies in the existing literature and determined the evidence supporting depression being a risk factor, a prodrome, a consequence, or an independent comorbidity in dementia. Overall there is convincing evidence to support both the notion that early life depression can act as a risk factor for later life dementia, and that later life depression can be seen as a prodrome to dementia. There is also evidence to support both conditions showing similar neurobiological changes, particularly white matter disease, either indicating shared risk factors or a shared pattern of neuronal damage. These findings highlight the need to examine if effective treatment of depressive episodes has any effect in reducing the prevalence of dementia, as well as clinicians being vigilant for late life depression indicating the incipient development of dementia, and therefore carefully following up these individuals for future cognitive impairment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Maekawa, T; Sudo, T; Kurimoto, M; Ishii, S
1991-09-11
The transcription factor HIV-TF1, which binds to a region about 60 bp upstream from the enhancer of the human immunodeficiency virus-1 (HIV-1), was purified from human B cells. HIV-TF1 had a molecular weight of 39,000. Binding of HIV-TF1 to the HIV long terminal repeat (LTR) activated transcription from the HIV promoter in vitro. The HIV-TF1-binding site in HIV LTR was similar to the site recognized by upstream stimulatory factor (USF) in the adenovirus major late promoter. DNA-binding properties of HIV-TF1 suggested that HIV-TF1 might be identical or related to USF. Interestingly, treatment of purified HIV-TF1 by phosphatase greatly reduced its DNA-binding activity, suggesting that phosphorylation of HIV-TF1 was essential for DNA binding. The disruption of HIV-TF1-binding site induced a 60% decrease in the level of transcription from the HIV promoter in vivo. These results suggest that HIV-TF1 is involved in transcriptional regulation of HIV-1.
Radiation protection issues in galactic cosmic ray risk assessment.
Sinclair, W K
1994-01-01
Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.
Maternal Risk Factors for Preterm Birth in Murmansk County, Russia: A Registry-Based Study.
Usynina, Anna A; Postoev, Vitaly A; Grjibovski, Andrej M; Krettek, Alexandra; Nieboer, Evert; Odland, Jon Øyvind; Anda, Erik Eik
2016-09-01
Globally, about 11% of all liveborn infants are preterm. To date, data on prevalence and risk factors of preterm birth (PTB) in Russia are limited. The aims of this study were to estimate the prevalence of PTB in Murmansk County, Northwestern Russia and to investigate associations between PTB and selected maternal factors using the Murmansk County Birth Registry. We conducted a registry-based study of 52 806 births (2006-2011). In total, 51 156 births were included in the prevalence analysis, of which 3546 were PTBs. Odds ratios with 95% confidence intervals of moderate-to-late PTB, very PTB and extremely PTB for a range of maternal characteristics were estimated using multinomial logistic regression, adjusting for potential confounders. The overall prevalence of PTB in Murmansk County was 6.9%. Unmarried status, prior PTBs, spontaneous and induced abortions were strongly associated with PTB at any gestational age. Maternal low educational level increased the risk of extremely and moderate-to-late PTB. Young (<18 years) or older (≥35 years) mothers, graduates of vocational schools, underweight, overweight/obese mothers, and smokers were at higher risk of moderate-to-late PTB. Secondary education, alcohol abuse, diabetes mellitus, or gestational diabetes were strongly associated with moderate-to-late and very PTB. The observed prevalence of PTB (6.9%) in Murmansk County, Russia was comparable with data on live PTB from European countries. Adverse prior pregnancy outcomes, maternal low educational level, unmarried status, alcohol abuse, and diabetes mellitus or gestational diabetes were the most common risk factors for PTB. © 2016 John Wiley & Sons Ltd.
Suppression of the Febrile Response in Late Gestation: Evidence, Mechanisms and Outcomes
Mouihate, A.; Harré, E.-M.; Martin, S.; Pittman, Q. J.
2012-01-01
Fever is a beneficial host defence response. However, fever caused by the immune stimulant, lipopolysaccharide (LPS), are attenuated in many species during pregnancy, particularly near term. A number of parallel mechanisms may be responsible, and these vary in magnitude according to the time of gestation, type of inflammatory stimulus and species of animal. Some studies report a reduction in the plasma levels of circulating pro-inflammatory cytokines such as tumour necrosis factor-α, interleukin-1β and interleukin-6 along with increased levels of anti-inflammatory cytokines such as interleukin-1 receptor antagonist. Associated with the attenuated febrile response to LPS is a reduction in the activation of the prostaglandin synthesising enzyme, cyclo-oxygenase 2, resulting in reduced levels of the obligatory prostaglandin mediators of the febrile response in the brain. There is also a reduction in the sensitivity of the brain to the pyrogenic action of prostaglandins, which does not appear to be due to a change in the levels of hypothalamic EP3 prostaglandin receptors. The suppression of fever at term may be important for the health of the neonate because fever in pregnant mothers may be harmful to the late-term foetus and neonate. PMID:18266941
Advantages and disadvantages of biodegradable platforms in drug eluting stents.
Rodriguez-Granillo, Agustina; Rubilar, Bibiana; Rodriguez-Granillo, Gaston; Rodriguez, Alfredo E
2011-03-26
Coronary angioplasty with drug-eluting stent (DES) implantation is currently the most common stent procedure worldwide. Since the introduction of DES, coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced. However, the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to bare-metal stent (BMS) implantation. Several factors have been associated with very late stent thrombosis after DES implantation, such as delayed healing, inflammation, stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers, which were essential to allow the elution of the immunosuppressive drug in the first DES designs. The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug, after which a BMS remains in place. Several DES designs with biodegradable (BIO) polymers have been introduced in preclinical and clinical studies, including randomized trials. In this review, we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology.
MacNamara, Annmarie; Jackson, T Bryan; Fitzgerald, Jacklynn M; Hajcak, Greg; Phan, K Luan
2018-04-22
Internalizing disorders such as anxiety may be characterized by an imbalance between bottom-up (stimulus-driven) and top-down (goal-directed) attention. The late positive potential (LPP) can be used to assess these processes when task-irrelevant negative and neutral pictures are presented within a working memory paradigm. Prior work using this paradigm has found that working memory load reduces the picture-elicited LPP across participants; however, anxious individuals showed a reduced effect of working memory load on the LPP, suggesting increased distractibility. The current study assessed transdiagnostic associations between specific symptom dimensions of anxiety, the LPP, and behavior in a clinically representative, heterogeneous group of 76 treatment-seeking patients with internalizing disorders, who performed a working memory task interspersed with negative and neutral pictures. As expected, negative pictures enhanced the LPP, and working memory load reduced the LPP. Participants with higher social anxiety showed increased LPPs to negative stimuli during early and late portions of picture presentation. Panic symptoms were associated with reduced LPPs to negative pictures compared with neutral pictures as well as a reduced effect of working memory load on the LPP during the late time window. Reduced positive affect was associated with greater behavioral interference from negative pictures. Hypervigilance for negative stimuli was uniquely explained by social anxiety symptoms, whereas panic symptoms were associated with the opposing effect-blunted processing/avoidance of these stimuli. Panic symptoms were uniquely associated with reduced top-down control. Results reveal distinct associations between neural reactivity and anxiety symptom dimensions that transcend traditional diagnostic boundaries. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Santoni, Matteo; Buti, Sebastiano; Conti, Alessandro; Porta, Camillo; Procopio, Giuseppe; Sternberg, Cora N; Bracarda, Sergio; Basso, Umberto; De Giorgi, Ugo; Rizzo, Mimma; Derosa, Lisa; Ortega, Cinzia; Massari, Francesco; Milella, Michele; Bersanelli, Melissa; Cerbone, Linda; Muzzonigro, Giovanni; Burattini, Luciano; Montironi, Rodolfo; Santini, Daniele; Cascinu, Stefano
2015-12-01
We aimed to assess the prognostic role of pretreatment neutrophilia, lymphocytopenia, and neutrophil to lymphocyte ratio (NLR) in patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKIs) for late relapsing (>5 years) metastatic renal cell carcinoma (mRCC). Data were collected from 13 Italian centers involved in the treatment of metastatic RCC. Late relapse was defined as >5 years after initial radical nephrectomy. One hundred fifty-one patients were included in this analysis. Among them, MSKCC risk score was favorable in 68 %, intermediate in 29 %, and poor in 3 %. Fifty-six patients (37 %) had NLR ≥3 at the start of VEGFR-TKI therapy (group A), while 95 had lower NLR (63 %, group B). The median overall survival (OS) was 28.8 months in group A and 68.7 months (95 % confidence interval (CI) 45.3-NA) in group B (p < 0.001). The median progression-free survival (PFS) was 15.8 months in group A and 25.1 months in group B (p = 0.03). At multivariate analysis, MSKCC risk group and NLR were independent prognostic factors for both OS and PFS. Pretreatment NLR is an independent prognostic factor for patients with late relapsing mRCC treated with first-line VEGFR-TKIs. A better characterization of baseline immunological impairment may optimize the management of this RCC subpopulation.
Predicting Health Resilience in Pediatric Type 1 Diabetes: A Test of the Resilience Model Framework
Huang, Bin; Pendley, Jennifer Shroff; Delamater, Alan; Dolan, Lawrence; Reeves, Grafton; Drotar, Dennis
2015-01-01
Objectives This research examined whether individual and family-level factors during the transition from late childhood to early adolescence protected individuals from an increased risk of poor glycemic control across time, which is a predictor of future diabetes-related complications (i.e., health resilience). Methods This longitudinal, multisite study included 239 patients with type 1 diabetes and their caregivers. Glycemic control was based on hemoglobin A1c. Individual and family-level factors included: demographic variables, youth behavioral regulation, adherence (frequency of blood glucose monitoring), diabetes self-management, level of parental support for diabetes autonomy, level of youth mastery and responsibility for diabetes management, and diabetes-related family conflict. Results Longitudinal mixed-effects logistic regression indicated that testing blood glucose more frequently, better self-management, and less diabetes-related family conflict were indicators of health resilience. Conclusions Multiple individual and family-level factors predicted risk for future health complications. Future research should develop interventions targeting specific individual and family-level factors to sustain glycemic control within recommended targets, which reduces the risk of developing future health complications during the transition to adolescence and adulthood. PMID:26152400
2012-01-01
Background Neonatal sepsis is a worldwide public health issue in which, depending on the studied population, marked variations concerning its risk and prognostic factors have been reported. The aim of this study was to assess risk and prognostic factors for neonatal sepsis prevailing at a medical unit in southeastern Mexico. Thus, we used a historic cohort design to assess the association between a series of neonates and their mothers, in addition to hospital evolution features and the risk and prognosis of neonatal sepsis (defined by Pediatric Sepsis Consensus [PSC] criteria) in 11,790 newborns consecutively admitted to a Neonatology Service in Mérida, Mexico, between 2004 and 2007. Results Sepsis was found in 514 of 11,790 (4.3 %) newborns; 387 of these cases were categorized as early-onset (<72 h) (75.3 %) and 127, as late-onset (>72 h) (24.7 %). After logistic regression, risk factors for sepsis included the following: low birth weight; prematurity; abnormal amniotic fluid; premature membrane rupture (PMR) at >24 h; respiratory complications, and the requirement of assisted ventilation, O2 Inspiration fraction (IF) >60 %, or a surgical procedure. Some of these factors were differentially associated with early- or late-onset neonatal sepsis. The overall mortality rate of sepsis was 9.5 %. A marked difference in the mortality rate was found between early- and late-onset sepsis (p >0.0001). After Cox analysis, factors associated with mortality in newborns with sepsis comprised the following: prematurity; low birth weight; low Apgar score; perinatal asphyxia, and the requirement of any invasive medical or surgical procedure. Conclusions The incidence of neonatal sepsis in southeastern Mexico was 4.3 %. A different risk and prognostic profile between early- and late-onset neonatal sepsis was found. PMID:22691696
Kuleshova, D K; Davydov, V V
2014-01-01
The study has shown that neuroendocrine obesity in adolescents is associated with the formation of oxidative stress which is more pronounced in early than in late puberty. Obesity with concomitant insulin resistance increases manifestations of oxidative stress accompanied by a compensatory increase in the activity of catabolic enzymes and reduced capacity of the defense antioxidant system in late puberty. These alterations may be caused by age-related changes in hormonal secretion under conditions of insulin resistance in late puberty.
Activated microglia in acute encephalopathy with biphasic seizures and late reduced diffusion.
Fujita, Yuji; Takanashi, Jun-Ichi; Takei, Haruka; Ota, Setsuo; Fujii, Katsunori; Sakuma, Hiroshi; Hayashi, Masaharu
2016-07-15
Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. The exact pathogenesis of and the best therapeutic strategy for AESD are uncertain. We firstly performed a brain biopsy in a 2-year-old boy with AESD associated with RS viral infection, which revealed activated ameoboid microglia accumulation around degenerated neuron, and astrogliosis in the affected cortex. Glutamate released from activated microglia may play an important role in the pathogenesis of AESD, which is compatible with the previous report of magnetic resonance spectroscopy showing elevated glutamate. Copyright © 2016 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Serrano, Francisco; Guerra-Merchán, Antonio; Lozano-Francisco, Carmen; Vera-Peláez, José Luis
1997-09-01
Nerja Cave is a karstic cavity used by humans from Late Paleolithic to post-Chalcolithic times. Remains of molluscan foods in the uppermost Pleistocene and Holocene sediments were studied with cluster analysis and principal components analysis, in both Qand Rmodes. The results from cluster analysis distinguished interval groups mainly in accordance with chronology and distinguished assemblages of species mainly according to habitat. Significant changes in the shellfish diet through time were revealed. In the Late Magdalenian, most molluscs consumed consisted of pulmonate gastropods and species from sandy sea bottoms. The Epipaleolithic diet was more varied and included species from rocky shorelines. From the Neolithic onward most molluscs consumed were from rocky shorelines. From the principal components analysis in Qmode, the first factor reflected mainly changes in the predominant capture environment, probably because of major paleogeographic changes. The second factor may reflect selective capture along rocky coastlines during certain times. The third factor correlated well with the sea-surface temperature curve in the western Mediterranean (Alboran Sea) during the late Quaternary.
Biddinger, Jessica E; Fox, Edward A
2014-07-30
Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF(-/-)) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF(-/-) mice were increased, but stomach IGLEs were normal. INT-BDNF(-/-) mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF(-/-) mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF(-/-) mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF(-/-) mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF(-/-) mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF(-/-) mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation. Copyright © 2014 the authors 0270-6474/14/3410379-15$15.00/0.
Anatomy and physiology of the esophagus.
Gavaghan, M
1999-02-01
Modern diagnosis and treatment of esophageal disease is a result of progress in assessing the anatomy and physiology of the esophagus, as well as refinements in anesthetic and surgical techniques. Esophageal carcinoma spreads rapidly and metastasizes easily. The tendency for early spread and the absence of symptoms result in late diagnosis that reduces treatment options and cure rates. Lifestyle (i.e., use of alcohol and tobacco), nutritional deficiencies, ingestion of nitrosamines, and mutagen-inducing fungi are blamed for cancer of the esophagus. Other pathologic conditions (e.g., achalasia, Barrett's epithelium, gastric reflux, hiatal hernia) are potential contributors to the development of carcinoma. Nurses are in key positions to identify the existence of factors contributing to premalignant or malignant lesions and to educate patients and make the appropriate referrals.
Membrane contactors for CO2 capture processes - critical review
NASA Astrophysics Data System (ADS)
Nogalska, Adrianna; Trojanowska, Anna; Garcia-Valls, Ricard
2017-07-01
The use of membrane contactor in industrial processes is wide, and lately it started to be used in CO2 capture process mainly for gas purification or to reduce the emission. Use of the membrane contactor provides high contact surface area so the size of the absorber unit significantly decreases, which is an important factor for commercialization. The research has been caried out regarding the use of novel materials for the membrane production and absorbent solution improvements. The present review reveals the progress in membrane contactor systems for CO2 capture processes concerning solution for ceramic membrane wetting, comparison study of different polymers used for fabrication and methods of enzyme immobilization for biocomposite membrane. Also information about variety of absorbent solutions is described.
Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis
Reid, Brian J.; Li, Xiaohong; Galipeau, Patricia C.; Vaughan, Thomas
2010-01-01
The public health importance of Barrett’s oesophagus lies in its association with oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma has risen at an alarming rate over the past four decades in many regions of the Western world and there are indications that the incidence of this disease is on the rise in Asian populations where it has been rare. Much has been learned of host and environmental risk factors that affect the incidence of oesophageal adenocarcinoma and data indicate that patients with Barrett’s oesophagus rarely develop oesophageal adenocarcinoma. Given that 95% of oesophageal adenocarcinoma arise in individuals without a prior diagnosis of Barrett’s oesophagus, what strategies can be used to reduce late diagnosis of oesophageal adenocarcinoma? PMID:20094044
Effects of late-gestation heat stress on immunity and performance of calves.
Dahl, G E; Tao, S; Monteiro, A P A
2016-04-01
Lactating cows that experience heat stress will have reduced dry matter intake and milk yield and shift metabolism, which ultimately reduces the efficiency of milk production. Dry cows that are heat stressed similarly experience lower intake, reduced mammary growth, and compromised immune function that ultimately results in a poorer transition into lactation and lower milk yield in the next lactation. A recent focus in our laboratory is on the effects of late gestation, in utero heat stress on calf survival and performance. We have completed a series of studies to examine preweaning growth and health, and later reproductive and productive responses, in an attempt to quantify acute and persistent effects of in utero heat strain. Late gestation heat stress results in calves with lower body weight at birth, shorter stature at weaning, and failure to achieve the same weight or height at 12 mo of age observed in calves from dams that are cooled when dry. A portion of the reduced growth may result from the lower immune status observed in calves heat stressed in utero, which begins with poorer apparent efficiency of immunoglobulin absorption and extends to lower survival rates through puberty. Heat-stressed calves, however, have permanent shifts in metabolism that are consistent with greater peripheral accumulation of energy and less lean growth relative to those from cooled dams. Comparing reproductive performance in calves heat stressed versus those cooled in utero, we observe that the cooled heifers require fewer services to attain pregnancy and become pregnant at an earlier age. Tracking the milk production in calves that were heat stressed in utero versus those cooled in late gestation revealed a significant reduction of yield in the first lactation, approximately 5 kg/d through 35 wk of lactation, despite similar body weight and condition score at calving. These observations indicate that a relatively brief period of heat stress in late gestation dramatically alters the health, growth, and ultimate performance of dairy calves. Thus, it is critical to effectively manage heat stress of dry cows to avoid negative effects on the calf. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Early Risk Factors of Overweight Developmental Trajectories during Middle Childhood
Pryor, Laura E.; Brendgen, Mara; Tremblay, Richard E.; Pingault, Jean-Baptiste; Liu, Xuecheng; Dubois, Lise; Touchette, Evelyne; Falissard, Bruno; Boivin, Michel; Côté, Sylvana M.
2015-01-01
Background Research is needed to identify early life risk factors associated with different developmental paths leading to overweight by adolescence. Objectives To model heterogeneity in overweight development during middle childhood and identify factors associated with differing overweight trajectories. Methods Data was drawn from the Quebec Longitudinal Study of Child Development (QLSCD; 1998-2010). Trained research assistants measured height and weight according to a standardized protocol and conducted yearly home interviews with the child’s caregiver (mother in 98% of cases). Information on several putative early life risk factors for the development of overweight were obtained, including factors related to the child’s perinatal, early behavioral family and social environment. Group-based trajectories of the probability of overweight (6-12 years) were identified with a semiparametric method (n=1678). Logistic regression analyses were used to identify early risk factors (5 months- 5 years) associated with each trajectory. Results Three trajectories of overweight were identified: “early-onset overweight” (11.0 %), “late-onset overweight” (16.6%) and “never overweight” (72.5%). Multinomial analyses indicated that children in the early and late-onset group, compared to the never overweight group, had 3 common types of risk factors: parental overweight, preschool overweight history, and large size for gestational age. Maternal overprotection (OR= 1.12, CI: 1.01-1.25), short nighttime sleep duration (OR=1.66, CI: 1.07-2.57), and immigrant status (OR=2.01, CI: 1.05-3.84) were factors specific to the early-onset group. Finally, family food insufficiency (OR=1.81, CI: 1.00-3.28) was weakly associated with membership in the late-onset trajectory group. Conclusions The development of overweight in childhood follows two different trajectories, which have common and distinct risk factors that could be the target of early preventive interventions. PMID:26121682
Increasing Running Step Rate Reduces Patellofemoral Joint Forces
Lenhart, Rachel L.; Thelen, Darryl G.; Wille, Christa M.; Chumanov, Elizabeth S.; Heiderscheit, Bryan C.
2013-01-01
Purpose Increasing step rate has been shown to elicit changes in joint kinematics and kinetics during running, and has been suggested as a possible rehabilitation strategy for runners with patellofemoral pain. The purpose of this study was to determine how altering step rate affects internal muscle forces and patellofemoral joint loads, and then to determine what kinematic and kinetic factors best predict changes in joint loading. Methods We recorded whole body kinematics of 30 healthy adults running on an instrumented treadmill at three step rate conditions (90%, 100%, and 110% of preferred step rate). We then used a 3D lower extremity musculoskeletal model to estimate muscle, patellar tendon, and patellofemoral joint forces throughout the running gait cycles. Additionally, linear regression analysis allowed us to ascertain the relative influence of limb posture and external loads on patellofemoral joint force. Results Increasing step rate to 110% of preferred reduced peak patellofemoral joint force by 14%. Peak muscle forces were also altered as a result of the increased step rate with hip, knee and ankle extensor forces, and hip abductor forces all reduced in mid-stance. Compared to the 90% step rate condition, there was a concomitant increase in peak rectus femoris and hamstring loads during early and late swing, respectively, at higher step rates. Peak stance phase knee flexion decreased with increasing step rate, and was found to be the most important predictor of the reduction in patellofemoral joint loading. Conclusion Increasing step rate is an effective strategy to reduce patellofemoral joint forces and could be effective in modulating biomechanical factors that can contribute to patellofemoral pain. PMID:23917470
Reusing, Jose O; Feitosa, Emanoela B; Agena, Fabiana; Pierroti, Lígia C; Azevedo, Luiz S F; Kotton, Camille N; David-Neto, Elias
2018-05-29
Anti-thymocyte globulin (ATG) therapy is a risk factor for CMV disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. We studied a retrospective cohort of 423 RTx (2010-2014) CMV-seropositive adults given ATG induction therapy. 54 (13%) patients developed cytomegalovirus (CMV) disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no-CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤ 40 ml/min/1.73 m 2 (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤ 45 and lymphocyte count ≤ 800 cells/mm 3 at the end of prophylaxis remained predictive of late CMV disease occurrence. These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Salas-Wright, Christopher P; Vaughn, Michael G; Cummings-Vaughn, Lenise A; Holzer, Katherine J; Nelson, Erik J; AbiNader, Millan; Oh, Sehun
2017-02-01
Recent trend studies suggest that marijuana use is on the rise among the general population of adults ages 18 and older in the United States. However, little is known about the trends in marijuana use and marijuana-specific risk/protective factors among American adults during the latter part of adulthood. Findings are based on repeated, cross-sectional data collected from late middle-aged (ages 50-64) and older adults (ages 65 and older) surveyed as part of the National Survey on Drug Use and Health between 2002 and 2014. The prevalence of past-year marijuana use among late middle-aged adults increased significantly from a low of 2.95% in 2003 to a high of 9.08% in 2014. Similarly, the prevalence of marijuana use increased significantly among older adults from a low of 0.15% in 2003 to a high of 2.04% in 2014. Notably, the upward trends in marijuana use remained significant even when accounting for sociodemographic, substance use, behavioral, and health-related factors. We also found that decreases in marijuana-specific protective factors were associated with the observed trend changes in marijuana use among late middle-aged and older adults, and observed a weakening of the association between late-middle aged marijuana use and risk propensity, other illicit drug use, and criminal justice system involvement over the course of the study. Findings from the present study provide robust evidence indicating that marijuana use among older Americans has increased markedly in recent years, with the most evident changes observed between 2008 and 2014. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Johannessen, Hege Hølmo; Wibe, Arne; Stordahl, Arvid; Sandvik, Leiv; Mørkved, Siv
2015-09-01
Pregnancy- and delivery-related factors affect postpartum anal incontinence. We aimed to explore changes in continence status among primiparas from late pregnancy through the first year postpartum. In this prospective cohort study set in two Norwegian hospitals, 862 healthy primiparas completed questionnaires about the main outcome measure anal incontinence, including flatus incontinence and urgency, at three time points; late pregnancy, 6 and 12 months postpartum. Socioeconomic and delivery-related data were obtained from hospital records. Logistic regression analyses were applied to determine the association between continence status at 12 months postpartum, and continence status in late pregnancy, 6 months postpartum, demographic and delivery-related characteristics. Among the 189 (22%) primiparas reporting anal incontinence in late pregnancy, 34 (18%) had persistent anal incontinence 1 year later. Forty-eight (43%) of the 113 women incontinent at 6 months postpartum experienced persistent anal incontinence at 12 months. Eight percent of previously continent women reported new onset anal incontinence at 6 and 12 months after delivery. Occipitoposterior presentation was the only delivery-related factor increasing the risk of postpartum anal incontinence [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.0-3.4]. Young age increased the risk of anal incontinence at 1 year after delivery, whereas incontinence in late pregnancy increased the risk of anal incontinence persisting through 6 and 12 months postpartum. In most first-time mothers with postpartum anal incontinence, the onset of anal incontinence was before delivery. Except for occipitoposterior presentation, no delivery-related factors increased the risk of postpartum anal incontinence. This may indicate that hormonal, mechanical or neuromuscular changes in pregnancy affect long-term anal incontinence more than vaginal delivery. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.
Salas-Wright, Christopher P.; Vaughn, Michael G.; Cummings-Vaughn, Lenise A.; Holzer, Katherine J.; Nelson, Erik J.; AbiNader, Millan; Oh, Sehun
2016-01-01
Background Recent trend studies suggest that marijuana use is on the rise among the general population of adults ages 18 and older in the United States. However, little is known about the trends in marijuana use and marijuana-specific risk/protective factors among American adults during the latter part of adulthood. Method Findings are based on repeated, cross-sectional data collected from late middle-aged (ages 50–64) and older adults (ages 65 and older) surveyed as part of the National Survey on Drug Use and Health between 2002 and 2014. Results The prevalence of past-year marijuana use among late middle-aged adults increased significantly from a low of 2.95% in 2003 to a high of 9.08% in 2014. Similarly, the prevalence of marijuana use increased significantly among older adults from a low of 0.15% in 2003 to a high of 2.04% in 2014. Notably, the upward trends in marijuana use remained significant even when accounting for sociodemographic, substance use, behavioral, and health-related factors. We also found that decreases in marijuana-specific protective factors were associated with the observed trend changes in marijuana use among late middle-aged and older adults, and observed a weakening of the association between late-middle aged marijuana use and risk propensity, other illicit drug use, and criminal justice system involvement over the course of the study. Conclusions Findings from the present study provide robust evidence indicating that marijuana use among older Americans has increased markedly in recent years, with the most evident changes observed between 2008 and 2014. PMID:28063338
Cherven, Brooke; Mertens, Ann; Meacham, Lillian R; Williamson, Rebecca; Boring, Cathy; Wasilewski-Masker, Karen
2014-01-01
Survivors of childhood cancer are at risk for a variety of treatment-related late effects and require lifelong individualized surveillance for early detection of late effects. This study assessed knowledge and perceptions of late effects risk before and after a survivor clinic visit. Young adult survivors (≥ 16 years) and parents of child survivors (< 16 years) were recruited prior to initial visit to a cancer survivor program. Sixty-five participants completed a baseline survey and 50 completed both a baseline and follow-up survey. Participants were found to have a low perceived likelihood of developing a late effect of cancer therapy and many incorrect perceptions of risk for individual late effects. Low knowledge before clinic (odds ratio = 9.6; 95% confidence interval, 1.7-92.8; P = .02) and low perceived likelihood of developing a late effect (odds ratio = 18.7; 95% confidence interval, 2.7-242.3; P = .01) were found to predict low knowledge of late effect risk at follow-up. This suggests that perceived likelihood of developing a late effect is an important factor in the individuals' ability to learn about their risk and should be addressed before initiation of education. © 2014 by Association of Pediatric Hematology/Oncology Nurses.
ERIC Educational Resources Information Center
Malin, Heather; Han, Hyemin; Liauw, Indrawati
2017-01-01
This study investigated the effects of internal and demographic variables on civic development in late adolescence using the construct "civic purpose." We conducted surveys on civic engagement with 480 high school seniors, and surveyed them again 2 years later. Using multivariate regression and linear mixed models, we tested the main…
Tactile Sensitivity and Braille Reading in People with Early Blindness and Late Blindness
ERIC Educational Resources Information Center
Oshima, Kensuke; Arai, Tetsuya; Ichihara, Shigeru; Nakano, Yasushi
2014-01-01
Introduction: The inability to read quickly can be a disadvantage throughout life. This study focused on the associations of braille reading fluency and individual factors, such as the age at onset of blindness and number of years reading braille, and the tactile sensitivity of people with early and late blindness. The relationship between reading…
Sundaresan, Periasamy; Vashist, Praveen; Ravindran, Ravilla D.; Shanker, Ashwini; Nitsch, Dorothea; Nonyane, Bareng A. S.; Smeeth, Liam; Chakravarthy, Usha; Fletcher, Astrid E.
2012-01-01
Purpose. Association between genetic variants in complement factor H (CFH), factor B (CFB), component 2 (C2), and in the ARMS2/HTRA1 region with age-related macular degeneration (AMD) comes mainly from studies of European ancestry and case-control studies of late-stage disease. We investigated associations of both early and late AMD with these variants in a population-based study of people aged 60 years and older in India. Methods. Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System and participants assigned to one of four mutually exclusive stages based on the worse affected eye (0 = no AMD, 1–3 = early AMD, 4 = late AMD). Multinomial logistic regression was used to derive risk ratios (RR) accounting for sampling method and adjusting for age, sex, and study center. Results. Of 3569 participants, 53.2% had no signs of AMD, 45.6% had features of early AMD, and 1.2% had late AMD. CFH (rs1061170), C2 (rs547154), or CFB (rs438999) was not associated with early or late AMD. In the ARMS2 locus, rs10490924 was associated with both early (adjusted RR 1.22, 95% confidence interval [CI]: 1.13–1.33, P < 0.0001) and late AMD (adjusted RR 1.81, 95% CI: 1.15–2.86; P = 0.01); rs2672598 was associated only with early AMD (adjusted RR 1.12, 95% CI: 1.02–1.23; P = 0.02); rs10490923 was not associated with early or late AMD. Conclusions. Two variants in ARMS2/HTRA1 were associated with increased risk of early AMD, and for one of these, the increased risk was also evident for late AMD. The study provides new insights into the role of these variants in early stages of AMD in India. PMID:23060141
Leal, Maria do Carmo; Esteves-Pereira, Ana Paula; Nakamura-Pereira, Marcos; Torres, Jacqueline Alves; Domingues, Rosa Maria Soares Madeira; Dias, Marcos Augusto Bastos; Moreira, Maria Elizabeth; Theme-Filha, Mariza; da Gama, Silvana Granado Nogueira
2016-01-01
Background A large proportion of the rise in prematurity worldwide is owing to late preterm births, which may be due to the expansion of obstetric interventions, especially pre-labour caesarean section. Late preterm births pose similar risks to overall prematurity, making this trend a concern. In this study, we describe factors associated with provider-initiated late preterm birth and verify differences in provider-initiated late preterm birth rates between public and private health services according to obstetric risk. Methods This is a sub-analysis of a national population-based survey of postpartum women entitled “Birth in Brazil”, performed between 2011 and 2012. We included 23,472 singleton live births. We performed non-conditional multiple logistic regressions assessing associated factors and analysing differences between public and private health services. Results Provider-initiated births accounted for 38% of late preterm births; 32% in public health services and 61% in private health services. They were associated with previous preterm birth(s) and maternal pathologies for women receiving both public and private services and with maternal age ≥35 years for women receiving public services. Women receiving private health services had higher rates of provider-initiated late preterm birth (rate of 4.8%) when compared to the ones receiving public services (rate of 2.4%), regardless of obstetric risk–adjusted OR of 2.3 (CI 1.5–3.6) for women of low obstetric risk and adjusted OR of 1.6 (CI 1.1–2.3) for women of high obstetric risk. Conclusion The high rates of provider-initiated late preterm birth suggests a considerable potential for reduction, as such prematurity can be avoided, especially in women of low obstetric risk. To promote healthy births, we advise introducing policies with incentives for the adoption of new models of birth care. PMID:27196102
Ebonwu, Joy; Mumbauer, Alexandra; Uys, Margot; Wainberg, Milton L.
2018-01-01
Objective To investigate and compare determinates for delayed first presentation to antenatal care (ANC) services. Methods A cross-sectional study was conducted amongst pregnant women attending their first ANC visit in rural Capricorn District and peri-urban Tlokwe sub-district communities in South Africa. Data collection included questionnaires and medical record abstraction. Bivariate and multivariate analyses assessed factors associated with late ANC presentation. Results We recruited 807 pregnant women. Of these, 51% of rural women and 28% of peri-urban women presented late for first ANC. Rural women were more likely to present late for first ANC (AOR = 2.65; 95% CI 1.98–3.55) and report barriers to accessing ANC services (P<0.0001). Late ANC presentation in rural communities was associated with being married (AOR = 2.36; 95% CI 1.33–4.19), employed (AOR = 1.90; 95% CI 1.03–3.50), <20 years of age (AOR = 2.19; 95% CI 1.10–4.37), and reporting an unplanned pregnancy (AOR = 2.21; 95% CI 1.40–3.50). Late presentation in peri-urban communities was associated with unplanned pregnancy (AOR = 1.67; 95% CI 1.01–2.74), being told to come back later to initiate ANC after presenting early (AOR 0.51; 95% CI 0.30–0.89) and being pregnant for the first time (AOR = 0.56; 95% CI 0.34–0.94) Conclusion Both rural and peri-urban women had high rates of late presentation for first ANC. However, women in the rural communities were more likely to present late. Unplanned pregnancy was an independent risk factor in both rural and peri-urban communities. Interventions around family planning, especially for adolescent girls and young women, are needed to improve early presentation for ANC. PMID:29518082
Cryo-EM structure of a late pre-40S ribosomal subunit from Saccharomyces cerevisiae
Schmidt, Christian; Berninghausen, Otto; Becker, Thomas
2017-01-01
Mechanistic understanding of eukaryotic ribosome formation requires a detailed structural knowledge of the numerous assembly intermediates, generated along a complex pathway. Here, we present the structure of a late pre-40S particle at 3.6 Å resolution, revealing in molecular detail how assembly factors regulate the timely folding of pre-18S rRNA. The structure shows that, rather than sterically blocking 40S translational active sites, the associated assembly factors Tsr1, Enp1, Rio2 and Pno1 collectively preclude their final maturation, thereby preventing untimely tRNA and mRNA binding and error prone translation. Moreover, the structure explains how Pno1 coordinates the 3’end cleavage of the 18S rRNA by Nob1 and how the late factor’s removal in the cytoplasm ensures the structural integrity of the maturing 40S subunit. PMID:29155690
Harnett, James; Wiederkehr, Daniel; Gerber, Robert; Gruben, David; Bourret, Jeffrey; Koenig, Andrew
2016-03-01
Adherence to biologic disease-modifying antirheumatic drugs (bDMARDs) among patients with rheumatoid arthritis (RA) is often suboptimal in routine clinical practice. Low or nonadherence can reduce the effectiveness of bDMARD therapies. To evaluate filling of newly prescribed initial bDMARDs for the treatment of RA and evaluate potential for characterizing treatment decisions and patient outcomes. In this retrospective cohort analysis, patients aged ≥ 18 years with an RA diagnosis (ICD-9-CM code 714.xx) were selected from a de-identified database of clinical information from the Electronic Health Record (EHR; Humedica) database linked to health care claims (Optum) from commercial and Medicare Advantage health plans (2007-2013). The first biologic prescription date in EHR was the index date. Patients were categorized as filling the prescription within 30 days (early fillers), 31-180 days (late fillers), or not at all within 180 days (nonfillers) of index date. Of 373 patients meeting inclusion criteria, 170 (45.6%), 59 (15.8%), and 144 (38.6%) were categorized as early fillers, late fillers, and nonfillers, respectively. Most prescriptions were written or ordered for tumor necrosis factor inhibitors (88.7%). Compared with late and nonfillers, early fillers were younger and more likely to be female, with higher pain scores (among those reporting pain scores) and RA severity scores pre-index, and filled more prescriptions for any reason pre-index. More nonfillers (66.0%) were Medicare patients than early (17.7%) and late (35.6%) fillers. During days 0-30 post-index, conventional synthetic DMARD use was greatest for early fillers (45.9%) and lowest among nonfillers (24.3%); however, during days 31-180 post-index, the proportion was highest for late fillers (61.0%) and lowest for nonfillers (35.4%). Of early fillers, 12.9% did not fill/receive a bDMARD after 30 days. Only 23 patients had pre/post-index pain scores, and 47 patients had a rationale for stopping or not filling a bDMARD. In patients with pharmacy and medical coverage for 180 days post-index, early fillers had greater RA-related pharmacy and medical resource use and costs than late and nonfillers combined. These findings confirm a high rate of primary nonadherence to bDMARDs among patients with RA.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.
Purpose: Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. Methods and Materials: Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78 Gy in 39 fractionsmore » were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. Results: The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age. Conclusions: Treatment with IG-IMRT reduced the risk of late grade ≥2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Keyes, Mira, E-mail: mkeyes@bccancer.bc.ca; Miller, Stacy; Pickles, Tom
2014-11-01
Purpose: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. Methods and Materials: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network–defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 ({sup 125}I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier andmore » log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. Results: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower in patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. Conclusion: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer follow-up (27% RTOG 2 and 10% RTOG 3 at 13 years), symptoms resolve relatively quickly; between 5 and 13 years' follow-up, >90% of patients have minimal urinary toxicity. Refining patient selection criteria, planning, and treatment delivery may further reduce toxicity.« less
Carling, Anna; Forsberg, Anette; Gunnarsson, Martin; Nilsagård, Ylva
2017-09-01
Imbalance leading to falls is common in people with multiple sclerosis (PwMS). To evaluate the effects of a balance group exercise programme (CoDuSe) on balance and walking in PwMS (Expanded Disability Status Scale, 4.0-7.5). A multi-centre, randomized, controlled single-blinded pilot study with random allocation to early or late start of exercise, with the latter group serving as control group for the physical function measures. In total, 14 supervised 60-minute exercise sessions were delivered over 7 weeks. Pretest-posttest analyses were conducted for self-reported near falls and falls in the group starting late. Primary outcome was Berg Balance Scale (BBS). A total of 51 participants were initially enrolled; three were lost to follow-up. Post-intervention, the exercise group showed statistically significant improvement ( p = 0.015) in BBS and borderline significant improvement in MS Walking Scale ( p = 0.051), both with large effect sizes (3.66; -2.89). No other significant differences were found between groups. In the group starting late, numbers of falls and near falls were statistically significantly reduced after exercise compared to before ( p < 0.001; p < 0.004). This pilot study suggests that the CoDuSe exercise improved balance and reduced perceived walking limitations, compared to no exercise. The intervention reduced falls and near falls frequency.
NASA Astrophysics Data System (ADS)
Aberhan, Martin; Weidemeyer, Sven; Kiessling, Wolfgang; Scasso, Roberto A.; Medina, Francisco A.
2007-03-01
The mass extinction at the Cretaceous-Paleogene boundary is generally explained by a severe crisis in primary productivity, following a catastrophic bolide impact. Consistent with this scenario, Danian mollusk-dominated benthic shelf ecosystems of southern middle paleolatitudes (Neuquén Basin, Argentina) are characterized by (1) a stratigraphically limited low in macrofossil abundances; (2) an increase in starvation-resistant, nonplanktotrophic deposit feeders and chemosymbionts; (3) a reduction in the average body size of individuals; and (4) individuals with inactive lifestyles being more common than in the late Maastrichtian. Return to pre-extinction conditions of the various synecological attributes occurred over unequal time spans, indicating that recovery was uncoordinated with respect to ecological traits. Global comparison of ecological patterns suggests that reduced food supply (1) was a controlling factor in both hemispheres; (2) affected macrobenthic marine faunas at various distances from the Chicxulub impact site; and (3) was more effective in siliciclastic environments as compared to oligotrophic carbonate settings.
Canopy carbon budget of Siebold's beech (Fagus crenata) sapling under free air ozone exposure.
Watanabe, Makoto; Hoshika, Yasutomo; Inada, Naoki; Koike, Takayoshi
2014-01-01
To determine the effects of ozone (O3) on the canopy carbon budget, we investigated photosynthesis and respiration of leaves of Siebold's beech saplings under free air O3 exposure (60 nmol mol(-1), during daytime) in relation to the within-canopy light gradient; we then calculated the canopy-level photosynthetic carbon gain (PCG) and respiratory carbon loss (RCL) using a canopy photosynthesis model. Susceptibilities of photosynthesis and respiration to O3 were greater in leaves of upper canopy than in the lower canopy. The canopy net carbon gain (NCG) was reduced by O3 by 12.4% during one growing season. The increased RCL was the main factor for the O3-induced reduction in NCG in late summer, while contributions of the reduced PCG and the increased RCL to the NCG were almost the same in autumn. These results indicate contributions of changes in PCG and RCL under O3 to NCG were different between seasons. Copyright © 2013 Elsevier Ltd. All rights reserved.
Shimoji, Sonoko; Hashimoto, Daigo; Teshima, Takanori
2017-01-01
Ovarian failure-associated infertility is a serious late complication for female patients who have undergone allogeneic hematopoietic stem cell transplantation (SCT). Although the role of a pretransplant conditioning regimen has been well appreciated, the increasing application of reduced-intensity conditioning has led us to reconsider other factors possibly affecting ovarian function after allogeneic SCT. We recently reported that graft-versus-host disease (GVHD) targets granulosa cells of the ovarian follicles, thereby significantly reducing ovarian reserves and fertility after SCT. We also found that ovarian GVHD impairs fertility independently of the toxicities of the conditioning regimens, and pharmacological GVHD prophylaxis preserves fertility after SCT. For the first time, these results demonstrated that GVHD targets the ovary and impairs ovarian functions and fertility, thereby having important clinical implications in young female transplant recipients with nonmalignant diseases, for whom minimally toxic regimens are used. Here we review recently published articles regarding clinical and basic researches on female infertility after SCT.
Olmstead, Keedrian I.; La Frano, Michael R.; Fahrmann, Johannes; Grapov, Dmitry; Viscarra, Jose A.; Newman, John W.; Fiehn, Oliver; Crocker, Daniel E.; Filipp, Fabian V.; Ortiz, Rudy M.
2017-01-01
Introduction Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical elevation in FFA despite comparable increases in insulin during both periods suggestive of a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion. Objective To better assess the contribution of insulin to this fasting-associated shift in substrate metabolism. Methods We compared the responses of plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late-fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS technologies. Results In early fasting, the majority (72%) of metabolite trajectories return to baseline levels within 2 h, but not in late fasting indicative of an increase in tissue sensitivity to insulin. In late-fasting, increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased protein catabolism. Conversely, insulin increased PCM AUC in late fasting suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA AUC between early and late fasting suggesting that insulin suppresses triglyceride hydrolysis. Conclusion Naturally adapted tolerance to prolonged fasting in these mammals is likely accomplished by suppressing insulin levels and activity, providing novel insight on the evolution of insulin during a condition of temporary, reversible insulin resistance. PMID:28757815
Olmstead, Keedrian I; La Frano, Michael R; Fahrmann, Johannes; Grapov, Dmitry; Viscarra, Jose A; Newman, John W; Fiehn, Oliver; Crocker, Daniel E; Filipp, Fabian V; Ortiz, Rudy M
2017-05-01
Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical elevation in FFA despite comparable increases in insulin during both periods suggestive of a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion. To better assess the contribution of insulin to this fasting-associated shift in substrate metabolism. We compared the responses of plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late-fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS technologies. In early fasting, the majority (72%) of metabolite trajectories return to baseline levels within 2 h, but not in late fasting indicative of an increase in tissue sensitivity to insulin. In late-fasting, increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased protein catabolism. Conversely, insulin increased PCM AUC in late fasting suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA AUC between early and late fasting suggesting that insulin suppresses triglyceride hydrolysis. Naturally adapted tolerance to prolonged fasting in these mammals is likely accomplished by suppressing insulin levels and activity, providing novel insight on the evolution of insulin during a condition of temporary, reversible insulin resistance.
Working multiple jobs over a day or a week: Short-term effects on sleep duration
Marucci-Wellman, Helen R.; Lombardi, David A.; Willetts, Joanna L.
2016-01-01
ABSTRACT Approximately 10% of the employed population in the United States works in multiple jobs. They are more likely to work long hours and in nonstandard work schedules, factors known to impact sleep duration and quality, and increase the risk of injury. In this study we used multivariate regression models to compare the duration of sleep in a 24-hour period between workers working in multiple jobs (MJHs) with single job holders (SJHs) controlling for other work schedule and demographic factors. We used data from the Bureau of Labor Statistics US American Time Use Survey (ATUS) pooled over a 9-year period (2003–2011). We found that MJHs had significantly reduced sleep duration compared with SJHs due to a number of independent factors, such as working longer hours and more often late at night. Male MJHs, working in their primary job or more than one job on the diary day, also had significantly shorter sleep durations (up to 40 minutes less on a weekend day) than male SJHs, even after controlling for all other factors. Therefore, duration of work hours, time of day working and duration of travel for work may not be the only factors to consider when understanding if male MJHs are able to fit in enough recuperative rest from their busy schedule. Work at night had the greatest impact on sleep duration for females, reducing sleep time by almost an hour compared with females who did not work at night. We also hypothesize that the high frequency or fragmentation of non-leisure activities (e.g. work and travel for work) throughout the day and between jobs may have an additional impact on the duration and quality of sleep for MJHs. PMID:27092404
Working multiple jobs over a day or a week: Short-term effects on sleep duration.
Marucci-Wellman, Helen R; Lombardi, David A; Willetts, Joanna L
Approximately 10% of the employed population in the United States works in multiple jobs. They are more likely to work long hours and in nonstandard work schedules, factors known to impact sleep duration and quality, and increase the risk of injury. In this study we used multivariate regression models to compare the duration of sleep in a 24-hour period between workers working in multiple jobs (MJHs) with single job holders (SJHs) controlling for other work schedule and demographic factors. We used data from the Bureau of Labor Statistics US American Time Use Survey (ATUS) pooled over a 9-year period (2003-2011). We found that MJHs had significantly reduced sleep duration compared with SJHs due to a number of independent factors, such as working longer hours and more often late at night. Male MJHs, working in their primary job or more than one job on the diary day, also had significantly shorter sleep durations (up to 40 minutes less on a weekend day) than male SJHs, even after controlling for all other factors. Therefore, duration of work hours, time of day working and duration of travel for work may not be the only factors to consider when understanding if male MJHs are able to fit in enough recuperative rest from their busy schedule. Work at night had the greatest impact on sleep duration for females, reducing sleep time by almost an hour compared with females who did not work at night. We also hypothesize that the high frequency or fragmentation of non-leisure activities (e.g. work and travel for work) throughout the day and between jobs may have an additional impact on the duration and quality of sleep for MJHs.
Reuben, David B; Gazarian, Priscilla; Alexander, Neil; Araujo, Katy; Baker, Dorothy; Bean, Jonathan F; Boult, Chad; Charpentier, Peter; Duncan, Pamela; Latham, Nancy; Leipzig, Rosanne M; Quintiliani, Lisa M; Storer, Thomas; McMahon, Siobhan
2017-12-01
In response to the epidemic of falls and serious falls-related injuries in older persons, in 2014, the Patient Centered Outcomes Research Institute (PCORI) and the National Institute on Aging funded a pragmatic trial, Strategies to Reduce Injuries and Develop confidence in Elders (STRIDE) to compare the effects of a multifactorial intervention with those of an enhanced usual care intervention. The STRIDE multifactorial intervention consists of five major components that registered nurses deliver in the role of falls care managers, co-managing fall risk in partnership with patients and their primary care providers (PCPs). The components include a standardized assessment of eight modifiable risk factors (medications; postural hypotension; feet and footwear; vision; vitamin D; osteoporosis; home safety; strength, gait, and balance impairment) and the use of protocols and algorithms to generate recommended management of risk factors; explanation of assessment results to the patient (and caregiver when appropriate) using basic motivational interviewing techniques to elicit patient priorities, preferences, and readiness to participate in treatments; co-creation of individualized falls care plans that patients' PCPs review, modify, and approve; implementation of the falls care plan; and ongoing monitoring of response, regularly scheduled re-assessments of fall risk, and revisions of the falls care plan. Custom-designed falls care management software facilitates risk factor assessment, the identification of recommended interventions, clinic note generation, and longitudinal care management. The trial testing the effectiveness of the STRIDE intervention is in progress, with results expected in late 2019. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.
Abdala, A P L; Rybak, I A; Smith, J C; Paton, J F R
2009-01-01
We studied respiratory neural activity generated during expiration. Motoneuronal activity was recorded simultaneously from abdominal (AbN), phrenic (PN), hypoglossal (HN) and central vagus nerves from neonatal and juvenile rats in situ. During eupnoeic activity, low-amplitude post-inspiratory (post-I) discharge was only present in AbN motor outflow. Expression of AbN late-expiratory (late-E) activity, preceding PN bursts, occurred during hypercapnia. Biphasic expiratory (biphasic-E) activity with pre-inspiratory (pre-I) and post-I discharges occurred only during eucapnic anoxia or hypercapnic anoxia. Late-E activity generated during hypercapnia (7–10% CO2) was abolished with pontine transections or chemical suppression of retrotrapezoid nucleus/ventrolateral parafacial (RTN/vlPF). AbN late-E activity during hypercapnia is coupled with augmented pre-I discharge in HN, truncated PN burst, and was quiescent during inspiration. Our data suggest that the pons provides a necessary excitatory drive to an additional neural oscillatory mechanism that is only activated under conditions of high respiratory drive to generate late-E activity destined for AbN motoneurones. This mechanism may arise from neurons located in the RTN/vlPF or the latter may relay late-E activity generated elsewhere. We hypothesize that this oscillatory mechanism is not a necessary component of the respiratory central pattern generator but constitutes a defensive mechanism activated under critical metabolic conditions to provide forced expiration and reduced upper airway resistance simultaneously. Possible interactions of this oscillator with components of the brainstem respiratory network are discussed. PMID:19491247
Optimal timing of autologous cranioplasty after decompressive craniectomy in children.
Piedra, Mark P; Thompson, Eric M; Selden, Nathan R; Ragel, Brian T; Guillaume, Daniel J
2012-10-01
The object of this study was to determine if early cranioplasty after decompressive craniectomy for elevated intracranial pressure in children reduces complications. Sixty-one consecutive cases involving pediatric patients who underwent autologous cranioplasty after decompressive craniectomy for raised intracranial pressure at a single academic children's hospital over 15 years were studied retrospectively. Sixty-one patients were divided into early (< 6 weeks; 28 patients) and late (≥ 6 weeks; 33 patients) cranioplasty cohorts. The cohorts were similar except for slightly lower age in the early (8.03 years) than the late (10.8 years) cranioplasty cohort (p < 0.05). Bone resorption after cranioplasty was significantly more common in the late (42%) than the early (14%) cranioplasty cohort (p < 0.05; OR 5.4). No other complication differed in incidence between the cohorts. After decompressive craniectomy for raised intracranial pressure in children, early (< 6 weeks) cranioplasty reduces the occurrence of reoperation for bone resorption, without altering the incidence of other complications.
Simulation of lake ice and its effect on the late-Pleistocene evaporation rate of Lake Lahontan
Hostetler, S.W.
1991-01-01
A model of lake ice was coupled with a model of lake temperature and evaporation to assess the possible effect of ice cover on the late-Pleistocene evaporation rate of Lake Lahontan. The simulations were done using a data set based on proxy temperature indicators and features of the simulated late-Pleistocene atmospheric circulation over western North America. When a data set based on a mean-annual air temperature of 3?? C (7?? C colder than present) and reduced solar radiation from jet-stream induced cloud cover was used as input to the model, ice cover lasting ??? 4 months was simulated. Simulated evaporation rates (490-527 mm a-1) were ??? 60% lower than the present-day evaporation rate (1300 mm a-1) of Pyramid Lake. With this reduced rate of evaporation, water inputs similar to the 1983 historical maxima that occurred in the Lahontan basin would have been sufficient to maintain the 13.5 ka BP high stand of Lake Lahontan. ?? 1991 Springer-Verlag.
Late dislocation of rotating platform in New Jersey Low-Contact Stress knee prosthesis.
Huang, Chun-Hsiung; Ma, Hon-Ming; Liau, Jiann-Jong; Ho, Fang-Yuan; Cheng, Cheng-Kung
2002-12-01
Five patients with late rotational dislocation of the rotating platform bearing in the New Jersey Low-Contact Stress total knee arthroplasty are reported. The prostheses had functioned well for 8 to 12 years before failure. Preoperative radiographs showed asymmetric femorotibial joint spaces. Entrapment of the dislocated bearing in three patients and spontaneous reduction of the dislocated bearing in another two patients were seen at revision. Femorotibial ligamentous instability was found after reduction. The retrieved polyethylene bearings showed advanced wear and cold flow deformities and the thickness was reduced. The revision arthroplasty was accomplished by replacement with a thicker bearing element. Progressive femorotibial ligament laxity and reduction of the thickness of polyethylene with wearing break down the originally well-balanced soft tissue tension of the knee. The rotational degree of the rotating platform bearing is unrestricted, which may result in late dislocation. Polyethylene wear is unavoidable in knee prostheses using metal contact with polyethylene even with a mobile-bearing design. Efforts to reduce polyethylene wear are mandatory.
Placenta accreta is an independent risk factor for late pre-term birth and perinatal mortality.
Vinograd, Adi; Wainstock, Tamar; Mazor, Moshe; Beer-Weisel, Ruthy; Klaitman, Vered; Dukler, Doron; Hamou, Batel; Novack, Lena; Ben-Shalom Tirosh, Neta; Vinograd, Ofir; Erez, Offer
2015-08-01
This study is aimed to identify the risk factors for the development of placenta accreta (PA) and characterize its effect on maternal and perinatal outcomes. This population-based retrospective cohort study included all deliveries at our medical center during the study period. Those with placenta accreta (n = 551) comprised the study group, while the rest of the deliveries (n = 239 089) served as a comparison group. The prevalence of placenta accerta is 0.2%. Women with this complication had higher rates of ≥2 previous CS (p < 0.001), recurrent abortions (p = 0.03), and previous placenta accreta [p < 0.001]. The rates of placenta previa and peripartum hemorrhage necessitating blood transfusion were higher in women with placenta accreta than in the comparison group. PTB before 34 and 37 weeks of gestation was more common among women with placenta accreta (p < 0.01), as was the rate of perinatal mortality (p < 0.001). Placenta accreta was an independent risk factor for perinatal mortality (adj. OR 8.2; 95% CI 6.4-10.4, p < 0.001) and late PTB (adj. OR 1.4; 95% CI 1.1-1.7, p = 0.002). Placenta accreta is an independent risk factor for late PTB and perinatal mortality.
Wan, Xinru
2017-01-01
Climate change and humans are proposed as the two key drivers of total extinction of many large mammals in the Late Pleistocene and Early Holocene, but disentangling their relative roles remains challenging owing to a lack of quantitative evaluation of human impact and climate-driven distribution changes on the extinctions of these large mammals in a continuous temporal–spatial dimension. Here, our analyses showed that temperature change had significant effects on mammoth (genus Mammuthus), rhinoceros (Rhinocerotidae), horse (Equidae) and deer (Cervidae). Rapid global warming was the predominant factor driving the total extinction of mammoths and rhinos in frigid zones from the Late Pleistocene and Early Holocene. Humans showed significant, negative effects on extirpations of the four mammalian taxa, and were the predominant factor causing the extinction or major extirpations of rhinos and horses. Deer survived both rapid climate warming and extensive human impacts. Our study indicates that both the current rates of warming and range shifts of species are much faster than those from the Late Pleistocene to Holocene. Our results provide new insight into the extinction of Late Quaternary megafauna by demonstrating taxon-, period- and region-specific differences in extinction drivers of climate change and human disturbances, and some implications about the extinction risk of animals by recent and ongoing climate warming. PMID:28330916
Wan, Xinru; Zhang, Zhibin
2017-03-29
Climate change and humans are proposed as the two key drivers of total extinction of many large mammals in the Late Pleistocene and Early Holocene, but disentangling their relative roles remains challenging owing to a lack of quantitative evaluation of human impact and climate-driven distribution changes on the extinctions of these large mammals in a continuous temporal-spatial dimension. Here, our analyses showed that temperature change had significant effects on mammoth (genus Mammuthus ), rhinoceros (Rhinocerotidae), horse (Equidae) and deer (Cervidae). Rapid global warming was the predominant factor driving the total extinction of mammoths and rhinos in frigid zones from the Late Pleistocene and Early Holocene. Humans showed significant, negative effects on extirpations of the four mammalian taxa, and were the predominant factor causing the extinction or major extirpations of rhinos and horses. Deer survived both rapid climate warming and extensive human impacts. Our study indicates that both the current rates of warming and range shifts of species are much faster than those from the Late Pleistocene to Holocene. Our results provide new insight into the extinction of Late Quaternary megafauna by demonstrating taxon-, period- and region-specific differences in extinction drivers of climate change and human disturbances, and some implications about the extinction risk of animals by recent and ongoing climate warming. © 2017 The Author(s).
Ethnicity and the risk of late-pregnancy stillbirth.
Drysdale, Henry; Ranasinha, Sanjeeva; Kendall, Amanda; Knight, Michelle; Wallace, Euan M
2012-09-03
To determine if maternal country of birth is associated with the risk of antepartum stillbirth in late pregnancy. Retrospective cross-sectional study of all singleton births at 37-42 weeks' gestation, excluding those with congenital abnormalities and intrapartum stillbirths, between 1 June 2001 and 31 May 2011 at Southern Health, a large metropolitan maternity service in Melbourne, Australia. Rate of late-pregnancy antepartum stillbirth, analysed by maternal country of birth. Among 44 326 births, there was a significant difference in the stillbirth rate by maternal country of birth (P < 0.001). The rate of stillbirth per 1000 births was 1.48 among Australian-born women, 3.55 among South Asian-born women and 1.06 among South-East-East Asian-born women. Women born in South Asia were 2.4 (95% CI, 1.4-4.0) times more likely to have a late-pregnancy stillbirth than women born in Australia (P < 0.001). There was no significant difference between women born in Australia and women born in South-East-East Asia (P = 0.34). Adjusting for potential confounding factors, South Asian maternal birth remained an independent risk factor for stillbirth (adjusted odds ratio, 2.5; 95% CI, 1.3-5.1; P = 0.009). Women born in South Asia have an increased risk of antepartum stillbirth in late pregnancy, compared with other women. This observation may have implications for the delivery of pregnancy care in Australia.
Sweeney, Emma L; Kallapur, Suhas G; Gisslen, Tate; Lambers, Donna S; Chougnet, Claire A; Stephenson, Sally-Anne; Jobe, Alan H; Knox, Christine L
2016-04-15
The human Ureaplasma species are the microbes most frequently isolated from placentae of women who deliver preterm. The role of Ureaplasma species has been investigated in pregnancies at <32 weeks of gestation, but currently no studies have determined the prevalence of ureaplasmas in moderately preterm and late-preterm (hereafter, "moderate/late preterm") infants, the largest cohort of preterm infants. Women delivering moderate/late preterm infants (n = 477) and their infants/placentae (n = 535) were recruited, and swab specimens of chorioamnion tissue, chorioamnion tissue specimens, and cord blood specimens were obtained at delivery. Swab and tissue specimens were cultured and analyzed by 16S ribosomal RNA polymerase chain reaction (PCR) for the presence of microorganisms, while cord blood specimens were analyzed for the presence of cytokines, chemokines, and growth factors. We detected microorganisms in 10.6% of 535 placentae (443 were delivered late preterm and 92 were delivered at term). Significantly, Ureaplasma species were the most prevalent microorganisms, and their presence alone was associated with histologically confirmed chorioamnionitis in moderate/late preterm and term placentae (P < .001). The presence of ureaplasmas in the chorioamnion was also associated with elevated levels of granulocyte colony-stimulating factor (P = .02). These findings have important implications for infection and adverse pregnancy outcomes throughout gestation and should be of major consideration for obstetricians and neonatologists. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
Fuentes, Stina; Frödin, Jan-Erik
2015-07-01
Chemotherapy and targeted drugs are important tools in the treatment of malignant diseases. A number of the planned treatments are cancelled late which is a great challenge for the clinic to minimize in order to prevent the risk for misused resources. The aim of this study was to analyze the frequency and reasons for late (<48 hours) cancellations and also to get an overview of all intravenous medical anti-cancer treatment at the clinic. During four weeks in October 2010 all patients with intravenously administered chemotherapy and/or targeted drugs were registered at the Department of Oncology, Karolinska University Hospital. The survey comprehends the vast majority of all such treatment for solid tumors in adult patients in the Stockholm region with two million inhabitants. All bookings and late cancellations including their reasons were recorded. Diagnoses, treatment indication, line of treatment and survival, in particular short term survival, were analyzed. Almost 3000 bookings for 1460 patients were included and 13% were cancelled late. Patient detoriation was the dominating cause for late cancellation in patients with palliative treatment (59%), while hematological toxicity was most common in the adjuvant group (42%). The most common treatment indication was palliative (62%). Of the palliative treatments, 95% where given in the first to third treatment line. Breast cancer (31.9%) and colorectal cancer (29.9%) were the two most common diagnoses. Seventy-one patients (4.9%) died within two months after the treatment. A more careful selection and monitoring of the patients might reduce the number of late cancellations due to patient detoriation. To record performance status (PS) as a routine for all patients might be helpful in that process. If the number of late cancellations could be reduced, resources at the clinic could be used more efficiently.
Occludin as a functional marker of vascular endothelial cells on tube-forming activity.
Kanayasu-Toyoda, Toshie; Ishii-Watabe, Akiko; Kikuchi, Yutaka; Kitagawa, Hiroko; Suzuki, Hiroko; Tamura, Hiroomi; Tada, Minoru; Suzuki, Takuo; Mizuguchi, Hiroyuki; Yamaguchi, Teruhide
2018-02-01
Cell therapy using endothelial progenitor cells (EPCs) is a promising strategy for the treatment of ischemic diseases. Two types of EPCs have been identified: early EPCs and late EPCs. Late EPCs are able to form tube structure by themselves, and have a high proliferative ability. The functional marker(s) of late EPCs, which relate to their therapeutic potential, have not been fully elucidated. Here we compared the gene expression profiles of several human cord blood derived late EPC lines which exhibit different tube formation activity, and we observed that the expression of occludin (OCLN) in these lines correlated with the tube formation ability, suggesting that OCLN is a candidate functional marker of late EPCs. When OCLN was knocked down by transfecting siRNA, the tube formation on Matrigel, the S phase + G 2 /M phase in the cell cycle, and the spheroid-based sprouting of late EPCs were markedly reduced, suggesting the critical role of OCLN in tube formation, sprouting, and proliferation. These results indicated that OCLN plays a novel role in neovascularization and angiogenesis. © 2017 Wiley Periodicals, Inc.
Depression subtypes and 5-year risk of dementia and Alzheimer disease in patients aged 70 years.
Vilalta-Franch, Joan; López-Pousa, Secundino; Llinàs-Reglà, Jordi; Calvó-Perxas, Laia; Merino-Aguado, Javier; Garre-Olmo, Josep
2013-04-01
The objective of this study was to estimate several subtypes of depressive disorders as risk factors for dementia and Alzheimer disease (AD) specifically. This is a population-based cohort study using a sample of 451 non-demented older people. Adjusted Cox proportional hazard models were calculated to determine the association of depression with dementia or AD development after 5 years. Baseline evaluation included the Cambridge Mental Disorders of the Elderly Examination (CAMDEX). Depressive disorders (major episode [MD] and minor depressive disorders [MDDIS]) were assessed following DSM-IV criteria and further classified according to the age at onset (early versus late onset). In turn, all late-onset depressions were grouped as with or without depression-executive dysfunction syndrome (DEDS). Dementia (and dementia subtypes) diagnoses were made using the CAMDEX. When the patients were deceased, the Retrospective Collateral Dementia Interview was used. Late-onset depressions (both MD and MDDIS) were associated with increased dementia (hazard ratio [HR] = 2.635; 95% CI = 1.153-6.023; and HR = 2.517; 95% CI = 1.200-5.280, respectively), and AD (HR = 6.262; 95% CI = 2.017-19.446; and HR = 4.208; 95% CI = 1.828-9.685, respectively) after adjustment by age, gender, marital status, education, cognitive impairment, executive function and stroke history. A second model revealed that only late-onset depressions with DEDS increased the risk for both dementia (late-onset MD with DEDS: HR = 6.262; 95% CI = 2.017-19.446; late-onset MDDIS with DEDS: HR = 4.208; 95% CI = 1.828-9.685) and AD (late-onset MD with DEDS: HR = 7.807; 95% CI = 1.567-38.894; late-onset MDDIS with DEDS: HR = 6.099; 95% CI = 2.123-17.524). Late-onset depressive episodes with DEDS are risk factors for dementia and AD development, regardless of the severity of the depression. Copyright © 2012 John Wiley & Sons, Ltd.
Charlton, Mary E; Matthews, Kevin A; Gaglioti, Anne; Bay, Camden; McDowell, Bradley D; Ward, Marcia M; Levy, Barcey T
2016-09-01
Colorectal cancer (CRC) screening has been shown to decrease the incidence of late-stage colorectal cancer, yet a substantial proportion of Americans do not receive screening. Those in rural areas may face barriers to colonoscopy services based on travel time, and previous studies have demonstrated lower screening among rural residents. Our purpose was to assess factors associated with late-stage CRC, and specifically to determine if longer travel time to colonoscopy was associated with late-stage CRC among an insured population in Iowa. SEER-Medicare data were used to identify individuals ages 65 to 84 years old diagnosed with CRC in Iowa from 2002 to 2009. The distance between the centroid of the ZIP code of residence and the ZIP code of colonoscopy was computed for each individual who had continuous Medicare fee-for-service coverage for a 3- to 4-month period prior to diagnosis, and a professional claim for colonoscopy within that time frame. Demographic characteristics and travel times were compared between those diagnosed with early- versus late-stage CRC. Also, demographic differences between those who had colonoscopy claims identified within 3-4 months prior to diagnosis (81%) were compared to patients with no colonoscopy claims identified (19%). A total of 5,792 subjects met inclusion criteria; 31% were diagnosed with early-stage versus 69% with late-stage CRC. Those divorced or widowed (vs married) were more likely to be diagnosed with late-stage CRC (OR: 1.20, 95% CI: 1.06-1.37). Travel time was not associated with diagnosis of late-stage CRC. Among a Medicare-insured population, there was no relationship between travel time to colonoscopy and disease stage at diagnosis. It is likely that factors other than distance to colonoscopy present more pertinent barriers to screening in this insured population. Additional research should be done to determine reasons for nonadherence to screening among those with access to CRC screening services, given that over two-thirds of these insured individuals were diagnosed with late-stage CRC. © 2015 National Rural Health Association.
Greenzang, Katie A; Dauti, Angela; Mack, Jennifer W
2018-06-01
Though most childhood cancer survivors experience late effects of treatment, we know little about parent preferences for late effects information during therapy, or how parents weigh late effects when making treatment decisions. Our objective was to explore how parents of children with cancer consider late effects in initial treatment decision making and during active cancer treatment. Semistructured interviews were conducted with 12 parents of children with cancer who were actively receiving treatment at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Interviews were audio-recorded, transcribed verbatim, and qualitatively analyzed using thematic analysis. Ten of 12 parents reported that they had to decide between two or more treatment options for their child's cancer. Of those, 50% (5/10) considered late effects to be an important factor in their decision making. Most parents wanted early and detailed information about their child's risk of late effects to make treatment decisions and to feel prepared for the future. However, a few parents felt too overwhelmed to focus on late effects at diagnosis. While many recalled extensive late effects information in informed consent discussions, some parents felt these issues were minimally addressed. Parents desire detailed information about late effects to make informed treatment decisions and prepare for the future. Despite the role of late effects in treatment decision making, some parents feel that late effects are either inadequately addressed or too overwhelming to process at diagnosis. Parents may benefit from early assessment of their information needs and a return to these issues over time. © 2018 Wiley Periodicals, Inc.
Chronic kidney disease as a cardiovascular risk factor: lessons from kidney donors.
Price, Anna M; Edwards, Nicola C; Hayer, Manvir K; Moody, William E; Steeds, Richard P; Ferro, Charles J; Townend, Jonathan N
2018-07-01
Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease but is often associated with other risks such as diabetes and hypertension and can be both a cause and an effect of cardiovascular disease. Although epidemiologic data of an independent association of reduced glomerular filtration rate with cardiovascular risk are strong, causative mechanisms are unclear. Living kidney donors provide a useful model for assessing the "pure" effects of reduced kidney function on the cardiovascular system. After nephrectomy, the glomerular filtration rate ultimately falls by about one-third so many can be classified as having chronic kidney disease stages 2 or 3. This prompts concern based on the data showing an elevated cardiovascular risk with these stages of chronic kidney disease. However, initial data suggested no increase in adverse cardiovascular effects compared with control populations. Recent reports have shown a possible late increase in cardiovascular event rates and an early increase in left ventricular mass and markers of risk such as urate and albuminuria. The long-term significance of these small changes is unknown. More detailed and long-term research is needed to determine the natural history of these changes and their clinical significance. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.
Zhang, Chunhui; Willis, Charles G; Burghardt, Liana T; Qi, Wei; Liu, Kun; Souza-Filho, Paulo Roberto de Moura; Ma, Zhen; Du, Guozhen
2014-11-01
Within a community, species may germinate at different times so as to mitigate competition and to take advantage of different aspects of the seasonal environment (temporal niche differentiation). We illustrated a hypothesis of the combined effects of abiotic and biotic competitive factors on germination timing and the subsequent upscale effects on community assembly. We estimated the germination timing (GT) for 476 angiosperm species of the eastern Tibetan Plateau grasslands under two light treatments in the field: high (i.e. natural) light and low light. We also measured the shift in germination timing (SGT) across treatments for all species. Furthermore, we used phylogenetic comparative methods to test if GT and SGT were associated with seed mass, an important factor in competitive interactions. We found a significant positive correlation between GT and seed mass in both light treatments. Additionally, small seeds (early germinating seeds) tended to germinate later and large seeds (late germinating seeds) tended to germinate earlier under low light vs high light conditions. Low light availability can reduce temporal niche differentiation by increasing the overlap in germination time between small and large seeds. In turn, reduced temporal niche differentiation may increase competition in the process of community assembly. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.
Incidence of oral cavity and pharynx cancer in New Hampshire, 1990-2007.
Cherala, Sai S; Kelley, Kristina
2012-01-01
The purpose of this study is to describe trends of the statewide cancer and treatment-related characteristics of oral cavity and pharynx (OCP) cancer and prevalence of risk factors in New Hampshire residents from 1990-2007. This is a descriptive study on oral cavity and pharynx cancer using a state cancer registry dataset for 1990- 2007. The age-adjusted rates with 95% confidence intervals for cancer incidence rates and standard proportions for stage, treatment, and risk factors were calculated. The Joinpoint regression model was used for assessing linear trends for cancer rates. The overall differences for the period under study between age, female and male rate, and stage were analyzed using the test. During 1990-2007, oral cavity and pharynx cancer incidence rates for New Hampshire residents have remained stable. The cancer incidence rates have decreased for older age groups (greater than 59) and the 50-59 age group has shown increase in incidence rate of OCP cancer since 1990. There is significant increase in the late-stage diagnoses from 1990-2007. Early detection through periodic medical and dental examinations can reduce the risk of these cancers. Public health strategies that address the gaps identified by this study can reduce OCP cancer and protect the health of the New Hampshire population.
Cerebrovascular diseases and depression: epidemiology, mechanisms and treatment.
Göthe, F; Enache, D; Wahlund, L O; Winblad, B; Crisby, M; Lökk, J; Aarsland, D
2012-09-01
Both cerebrovascular disease (CVD) and depression are common conditions in the elderly, and there is emerging evidence of a bi-directional relationship: 1) depression can cause CVD and stroke, transient ischemic attack; and 2) subcortical CVD are associated with increased risk for depression. The frequency of poststroke depression is highest during the first month after the stroke, but remains high even after several years. Depression is associated with poorer functional prognosis and higher mortality after stroke. There is good evidence that severity of functional impairment, high neuroticism, low social support as well as genetic factors are associated with an increased risk for post-stroke depression. Deep white matter lesions are the most consistent imaging correlate of depression. Potential mechanisms mediating the association between depression and CVD are neuroinflammation and HPA-axis activation, fronto-subcortical circuit lesions, and serotonergic dysfunction. Antidepressants have demonstrated effect on poststroke depression in meta-analyses, and such drugs as well as vitamin B can reduce the incidence of depression in stroke survivors. In addition, serotonergic drugs may strengthen poststroke motor and cognitive recovery, potentially through restorative mechanisms. Psychotherapeutic strategies such as problem-solving therapy seem to be effective. There is emerging evidence that treatment of cardiovascular disease and risk-factors can reduce the risk for late-life depression, but more studies are needed to test this hypothesis.
Sociodemographic factors associated with anaemia in pregnancy at booking for antenatal care.
Adanikin, A I; Awoleke, J O
2016-01-01
Late patronage of antenatal care by women in low-resource areas makes timely intervention at correcting anaemia difficult. This study aimed to identify modifiable sociodemographic factors that predict anaemia before commencing antenatal care and make appropriate recommendation. A survey of sociodemographic features and haemoglobin concentrations of 232 women booking for antenatal care was conducted. Anaemia was diagnosed in 119 (51.3%), of which 87 (37.5%) had mild anaemia and 32 (13.8%) were moderately anaemic. There was no severe anaemia. Anaemia was highest among respondents who were 35 years of age, Muslims, of Igbo ethnicity (64.3%), single (55.0%), student/unemployed (58.8%), nulliparous (57.3%) and those who registered at 21 weeks' gestation (54.2%). Only occupation of the woman showed association with anaemia before antenatal care (p 0.007). A personal source of income may reduce anaemia in pregnancy; and it is advisable to have a social welfare package for unemployed pregnant women.
Optimizing Weight for Maternal and Infant Health – Tenable, or Too Late?
Barbour, Linda A.
2015-01-01
Obesity in pregnancy is the leading cause of maternal and fetal morbidity, and gestational weight gain (GWG) is one modifiable risk factor that improves pregnancy outcomes. Most pregnant women gain more than the 2009 Institute of Medicine recommendations, particularly overweight and obese women. GWG even less than the 2009 IOM guidelines in obese women may improve pregnancy outcomes and reduce large-for-gestational-age (LGA) infants, an independent risk factor for childhood obesity, without increasing small-for-gestational-age (SGA) infants. Unfortunately, despite the fact that over 50 interventional trials designed to decrease excess GWG have been conducted, these interventions have been only modestly effective, and interventions designed to facilitate weight postpartum weight loss have also been disappointing. Successful interventions are of paramount importance not only to improve pregnancy outcomes but also for the future metabolic health of the mother and her infant, and may be key in attenuating the trans-generational risk on childhood obesity. PMID:26442123
Goetzenich, Andreas; Hatam, Nima; Preuss, Stephanie; Moza, Ajay; Bleilevens, Christian; Roehl, Anna B.; Autschbach, Rüdiger; Bernhagen, Jürgen; Stoppe, Christian
2014-01-01
OBJECTIVES The protective effects of late-phase preconditioning can be triggered by several stimuli. Unfortunately, the transfer from bench to bedside still represents a challenge, as concomitant medication or diseases influence the complex signalling pathways involved. In an established model of primary neonatal rat cardiomyocytes, we analysed the cardioprotective effects of three different stimulating pharmaceuticals of clinical relevance. The effect of additional β-blocker treatment was studied as these were previously shown to negatively influence preconditioning. METHODS Twenty-four hours prior to hypoxia, cells pre-treated with or without metoprolol (0.55 µg/ml) were preconditioned with isoflurane, levosimendan or xenon. The influences of these stimuli on hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) as well as inducible and endothelial nitric synthase (iNOS/eNOS) and cyclooxygenase-2 (COX-2) were analysed by polymerase chain reaction and western blotting. The preconditioning was proved by trypan blue cell counts following 5 h of hypoxia and confirmed by fluorescence staining. RESULTS Five hours of hypoxia reduced cell survival in unpreconditioned control cells to 44 ± 4%. Surviving cell count was significantly higher in cells preconditioned either by 2 × 15 min isoflurane (70 ± 16%; P = 0.005) or by xenon (59 ± 8%; P = 0.049). Xenon-preconditioned cells showed a significantly elevated content of VEGF (0.025 ± 0.010 IDV [integrated density values when compared with GAPDH] vs 0.003 ± 0.006 IDV in controls; P = 0.0003). The protein expression of HIF-1α was increased both by levosimendan (0.563 ± 0.175 IDV vs 0.142 ± 0.042 IDV in controls; P = 0.0289) and by xenon (0.868 ± 0.222 IDV; P < 0.0001) pretreatment. A significant elevation of mRNA expression of iNOS was measureable following preconditioning by xenon but not by the other chosen stimuli. eNOS mRNA expression was found to be suppressed by β-blocker treatment for all stimuli. In our model, independently of the chosen stimulus, β-blocker treatment had no significant effect on cell survival. CONCLUSIONS We found that the stimulation of late-phase preconditioning involves several distinct pathways that are variably addressed by the different stimuli. In contrast to isoflurane treatment, xenon-induced preconditioning does not lead to an increase in COX-2 gene transcription but to a significant increase in HIF-1α and subsequently VEGF. PMID:24351506
Goetzenich, Andreas; Hatam, Nima; Preuss, Stephanie; Moza, Ajay; Bleilevens, Christian; Roehl, Anna B; Autschbach, Rüdiger; Bernhagen, Jürgen; Stoppe, Christian
2014-03-01
The protective effects of late-phase preconditioning can be triggered by several stimuli. Unfortunately, the transfer from bench to bedside still represents a challenge, as concomitant medication or diseases influence the complex signalling pathways involved. In an established model of primary neonatal rat cardiomyocytes, we analysed the cardioprotective effects of three different stimulating pharmaceuticals of clinical relevance. The effect of additional β-blocker treatment was studied as these were previously shown to negatively influence preconditioning. Twenty-four hours prior to hypoxia, cells pre-treated with or without metoprolol (0.55 µg/ml) were preconditioned with isoflurane, levosimendan or xenon. The influences of these stimuli on hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) as well as inducible and endothelial nitric synthase (iNOS/eNOS) and cyclooxygenase-2 (COX-2) were analysed by polymerase chain reaction and western blotting. The preconditioning was proved by trypan blue cell counts following 5 h of hypoxia and confirmed by fluorescence staining. Five hours of hypoxia reduced cell survival in unpreconditioned control cells to 44 ± 4%. Surviving cell count was significantly higher in cells preconditioned either by 2 × 15 min isoflurane (70 ± 16%; P = 0.005) or by xenon (59 ± 8%; P = 0.049). Xenon-preconditioned cells showed a significantly elevated content of VEGF (0.025 ± 0.010 IDV [integrated density values when compared with GAPDH] vs 0.003 ± 0.006 IDV in controls; P = 0.0003). The protein expression of HIF-1α was increased both by levosimendan (0.563 ± 0.175 IDV vs 0.142 ± 0.042 IDV in controls; P = 0.0289) and by xenon (0.868 ± 0.222 IDV; P < 0.0001) pretreatment. A significant elevation of mRNA expression of iNOS was measureable following preconditioning by xenon but not by the other chosen stimuli. eNOS mRNA expression was found to be suppressed by β-blocker treatment for all stimuli. In our model, independently of the chosen stimulus, β-blocker treatment had no significant effect on cell survival. We found that the stimulation of late-phase preconditioning involves several distinct pathways that are variably addressed by the different stimuli. In contrast to isoflurane treatment, xenon-induced preconditioning does not lead to an increase in COX-2 gene transcription but to a significant increase in HIF-1α and subsequently VEGF.
Reducing the Complexity Gap: Expanding the Period of Human Nurturance
ERIC Educational Resources Information Center
Kiel, L. Douglas
2014-01-01
Socio-techno-cultural reality, in the current historical era, evolves at a faster rate than do human brain or human institutions. This reality creates a "complexity gap" that reduces human and institutional capacities to adapt to the challenges of late modernity. New insights from the neurosciences may help to reduce the complexity gap.…
Shtienberg, D; Elad, Y; Bornstein, M; Ziv, G; Grava, A; Cohen, S
2010-01-01
The individual and joint effects of covering the soil with polyethylene mulch before planting and fungicides commonly used by organic growers on tomato late blight (caused by Phytophthora infestans) were studied in three experiments conducted from 2002 to 2005. Application of fungicides resulted in inconsistent and insufficient late blight suppression (control efficacy +/- standard error of 34.5 +/- 14.3%) but the polyethylene mulch resulted in consistent, effective, and highly significant suppression (control efficacy of 83.6 +/- 5.5%) of the disease. The combined effect of the two measures was additive. In a second set of three experiments carried out between 2004 and 2006, it was found that the type of polyethylene mulch used (bicolor aluminized, clear, or black) did not affect the efficacy of late blight suppression (control efficacy of 60.1 to 95.8%) and the differences in the effects among the different polyethylene mulches used were insignificant. Next, the ability of the mulch to suppress cucumber downy mildew (caused by Pseudoperonospora cubensis) was studied in four experiments carried out between 2006 and 2008. The mulch effectively suppressed cucumber downy mildew but the effect was less substantial (control efficacy of 34.9 +/- 4.8%) than that achieved for tomato late blight. The disease-suppressing effect of mulch appeared to come from a reduction in leaf wetness duration, because mulching led to reductions in both the frequency of nights when dew formed and the number of dew hours per night when it formed. Mulching also reduced relative humidity in the canopy, which may have reduced sporulation.
Ugwumadu, Austin; Manyonda, Isaac; Reid, Fiona; Hay, Phillip
2003-03-22
Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery. We aimed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population. We screened 6120 pregnant women attending hospital for their first antenatal visit--who were at 12-22 weeks' gestation (mean 15.6 weeks)--for bacterial vaginosis or abnormal vaginal flora. We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis, in accordance with Nugent's criteria. We randomly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days. Primary endpoints were spontaneous preterm delivery (birth > or =24 but <37 weeks) and late miscarriage (pregnancy loss > or =13 but <24 weeks). Analysis was intention to treat. Nine women were lost to follow-up or had elective termination. Thus, we analysed 485 women with complete outcome data. Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries (13/244) than did those in the placebo group (38/241; percentage difference 10.4%, 95% CI 5.0-15.8, p=0.0003). Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores, with maximum effect in women with the highest Nugent score of 10. Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population.
Hummel, Sandra; Pflüger, Maren; Hummel, Michael; Bonifacio, Ezio; Ziegler, Anette-G.
2011-01-01
OBJECTIVE To determine whether delaying the introduction of gluten in infants with a genetic risk of islet autoimmunity is feasible, safe, and may reduce the risk of type 1 diabetes–associated islet autoimmunity. RESEARCH DESIGN AND METHODS A total of 150 infants with a first-degree family history of type 1 diabetes and a risk HLA genotype were randomly assigned to a first gluten exposure at age 6 months (control group) or 12 months (late-exposure group) and were followed 3 monthly until the age of 3 years and yearly thereafter for safety (for growth and autoantibodies to transglutaminase C [TGCAs]), islet autoantibodies to insulin, GAD, insulinoma-associated protein 2, and type 1 diabetes. RESULTS Adherence to the dietary-intervention protocol was reported from 70% of families. During the first 3 years, weight and height were similar in children in the control and late-exposure groups, as was the probability of developing TGCAs (14 vs. 4%; P = 0.1). Eleven children in the control group and 13 children in the late-exposure group developed islet autoantibodies (3-year risk: 12 vs. 13%; P = 0.6). Seven children developed diabetes, including four in the late-exposure group. No significant differences were observed when children were analyzed as per protocol on the basis of the reported first gluten exposure of the children. CONCLUSIONS Delaying gluten exposure until the age of 12 months is safe but does not substantially reduce the risk for islet autoimmunity in genetically at-risk children. PMID:21515839