GnRHR-II knockdown swine have constitutively lower serum testosterone concentrations, impaired senstitivity to GnRH analogues and reduced semen quality

USDA-ARS?s Scientific Manuscript database

The second mammalian GnRH isoform (GnRH-II) and its specific receptor (GnRHR-II) are abundantly produced within swine testes. GnRHR-II localizes to porcine Leydig cells and exogenous GnRH-II treatment robustly stimulates testosterone production in vivo, despite minimal secretion of luteinizing hormo...

[Correlation between resting heart rate and blood glucose level in elderly patients with coronary heart disease and diabetes mellitus].

PubMed

Liang, Dong-Liang; Li, Xiao-Ying; Wang, Lin; Xu, Hao; Tuo, Xi-Ping; Jian, Zai-Jin; Wang, Xiao-Na; Yun, Ji-Li; Zhang, Xu; Wang, Si-Yue

2016-05-01

To explore the correlation between resting heart rate (RHR) and blood glucose level in elderly patients with coronary heart disease (CHD) complicated by diabetes mellitus. Between April and July, 2011, a total of 1336 outpatients over 60 years of age recruited from 165 hospitals were asked to complete a questionnaire and received blood glucose and RHR examination. According to baseline RHR, the patients were divided into 3 groups with HRH <70 min-1 (group I, 372 cases), between 70 and 79 min(-1) (group II, 533 cases), and ≥80 min(-1) (group III, 431cases) for analysis of the relationships of RHR with blood glucose control rate. HbA1c levels in the total, male and female patients differed significantly among the 3 groups (F=15.436, 15.436, and 24.270, respectively, P<0.05), and increased in the order from group I to group III. Blood glucose control rate in the total, male and female patients also differed significantly among the 3 groups (χ(2)=13.471, 6.752, and 6.522, respectively, P<0.05), and was significantly lower in group III than in group I (P<0.05). RHR was found to positively correlate with FPG, 2 hPG and HbA1c by Pearson correlation analysis (r=0.058, 0.085, and 0.058, respectively; P<0.05) and multiple linear regression analysis (β=0.075, 0.075, and 0.018, respectively; P<0.05). Multivariable logistic regression equation showed that compared with patients with RHR <70 min-1, the total, male and female patients with RHR ≥80 min(-1) had OR values of blood glucose control failure of 1.99 (95% CI: 1.23-2.37, P<0.05), 1.81 (95% CI: 1.17-2.77, P<0.05), and 2.18 (95% CI: 1.12-3.74, P<0.05), respectively. RHR in elderly CHD patients with MD is positively correlated with their blood glucose level, and an increased RHR is associated with an increased risk of poor blood glucose control. Rigorous RHR control in such high-risk patients may prove beneficial for both blood glucose control and secondary prevention of CHD.

Association of resting heart rate and cardiovascular disease mortality in hypertensive and normotensive rural Chinese.

PubMed

Zhang, Ming; Han, Chengyi; Wang, Chongjian; Wang, Jinjin; Li, Linlin; Zhang, Lu; Wang, Bingyuan; Ren, Yongcheng; Zhang, Hongyan; Yang, Xiangyu; Zhao, Yang; Zhou, Junmei; Pang, Chao; Yin, Lei; Feng, Tianping; Zhao, Jingzhi; Luo, Xinping; Hu, Dongsheng

2017-05-01

Studies have demonstrated an increased risk of cardiovascular disease (CVD)-associated death (CVD death) with increased resting heart rate (RHR); however, whether the association is consistent in rural Chinese with hypertension and normotension is unknown. We examined the association of RHR and CVD death by hypertension and normotension status in rural Chinese people. Baseline data for 20,069 participants ≥18 years old were collected during July to August of 2007 and July to August of 2008; 17,151 (85.5%) participants were followed up in July to August of 2013 and July to October of 2014. The association of RHR and CVD death was determined by Cox proportional hazards regression. During a mean of 5.88 years (100,889 person-years) of follow-up, we recorded 479 CVD deaths (309 in hypertensive participants). CVD death increased significantly with increasing RHR, beginning from 80 beats per minute (bpm), for hypertensive and normotensive participants. After adjusting for pulse pressure and other covariates, for hypertensive participants, risk of CVD death was increased with RHR 80-89 and ≥90bpm. However, for normotensive participants, risk of CVD death was increased with only RHR≥90bpm. Risk of CVD death was associated with elevated RHR for both hypertensive and normotensive rural Chinese, and for hypertensive participants, even slightly elevated RHR was associated with CVD death. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Gonadotropin-releasing hormone II receptor (GnRHR-II) knockdown reduces testis size and decreases testosterone secretion during pubertal development in swine

USDA-ARS?s Scientific Manuscript database

The second mammalian isoform of gonadotropin-releasing hormone (GnRH-II) functions quite differently from the classical form (GnRH-I) as it is a poor stimulator of gonadotropin release. Unlike most species, a functional GnRHR-II has been identified in swine. Our laboratory detected GnRHR-IIs on Leyd...

Testicular gonadotropin-releasing hormone II receptor (GnRHR-II) knockdown constitutively impairs diurnal testosterone secretion in the boar

USDA-ARS?s Scientific Manuscript database

The second mammalian GnRH isoform (GnRH-II) and its specific receptor (GnRHR-II) are highly expressed in the testis, suggesting an important role in testis biology. Gene coding errors prevent the production of GnRH-II and GnRHR-II in many species, but both genes are functional in swine. We have demo...

Effects of corticotropin-releasing hormone and its antagonist on the gene expression of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in the hypothalamus and anterior pituitary gland of follicular phase ewes.

PubMed

Ciechanowska, Magdalena; Łapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek

2011-01-01

There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo-pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo-anterior pituitary unit. © CSIRO 2011 Open Access

Response of shortgrass plains vegetation to gamma radiation. I. Chronic irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraley, L. Jr.; Whicker, F.W.

1973-12-01

Native shortgrass plains vegetation was exposed to chronic gamma radiation with exposure rates varying from 0.01 to 650 R/hr starting in April 1969. The dominant species in the plant community was Bouteloua gracilis (blue grama). Density and frequency were recorded and these data were converted into community indices of coefficient of community (CC) and diversity (D). The results indicated that the shortgrass vegetation was very resistant to ionizing radiation. 50% effects of CC and D resulted from exposure of 15 and 12 R/hr, respectively and had not significantly decreased further by June 1972. Community changes took place within constant CCmore » and D values that resulted in the development of new communities and indicated a lack of sensitivity of these parameters for measuring community change and stability. One of the most resistant species was Lepidium densiflorum which became dominant at exposure rates of 12 to 28 R/hr. L. densiflorum was able to germinate, develop, and complete seed set at exposure rates greater than 28 R/hr. (auth)« less

Assessment and Application of the ROSE Code for Reactor Outage Thermal-Hydraulic and Safety Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, Thomas K.S.; Ko, F.-K.; Dai, L.-C

The currently available tools, such as RELAP5, RETRAN, and others, cannot easily and correctly perform the task of analyzing the system behavior during plant outages. Therefore, a medium-sized program aiming at reactor outage simulation and evaluation, such as midloop operation (MLO) with loss of residual heat removal (RHR), has been developed. Important thermal-hydraulic processes involved during MLO with loss of RHR can be properly simulated by the newly developed reactor outage simulation and evaluation (ROSE) code. The two-region approach with a modified two-fluid model has been adopted to be the theoretical basis of the ROSE code.To verify the analytical modelmore » in the first step, posttest calculations against the integral midloop experiments with loss of RHR have been performed. The excellent simulation capacity of the ROSE code against the Institute of Nuclear Energy Research Integral System Test Facility test data is demonstrated. To further mature the ROSE code in simulating a full-sized pressurized water reactor, assessment against the WGOTHIC code and the Maanshan momentary-loss-of-RHR event has been undertaken. The successfully assessed ROSE code is then applied to evaluate the abnormal operation procedure (AOP) with loss of RHR during MLO (AOP 537.4) for the Maanshan plant. The ROSE code also has been successfully transplanted into the Maanshan training simulator to support operator training. How the simulator was upgraded by the ROSE code for MLO will be presented in the future.« less

Autonomic Dysfunction Precedes Development of Rheumatoid Arthritis: A Prospective Cohort Study

PubMed Central

Koopman, F.A.; Tang, M.W.; Vermeij, J.; de Hair, M.J.; Choi, I.Y.; Vervoordeldonk, M.J.; Gerlag, D.M.; Karemaker, J.M.; Tak, P.P.

2016-01-01

Background Heart rate variability (HRV) is a validated method to establish autonomic nervous system (ANS) activity. Rheumatoid arthritis (RA) is accompanied by ANS imbalance. We hypothesized that ANS dysfunction may precede the development of RA, which would suggest that it plays a role in its etiopathogenesis. Methods First, we assessed HRV parameters in supine (resting) and upright (active) position in healthy subjects (HS, n = 20), individuals at risk of developing arthritis (AR subjects, n = 50) and RA patients (RA, n = 20). Next, we measured resting heart rate (RHR), a parasympathetic HRV parameter, in an independent prospective cohort of AR subjects (n = 45). We also evaluated expression levels of the parasympathetic nicotinic acetylcholine receptor type 7 (α7nAChR) on circulating monocytes. Findings Both AR subjects (68 beats per minute (bpm), interquartile range (IQR) 68–73) and RA patients (68 bpm, IQR 62–76) had a significantly higher RHR compared to HS (60 bpm, IQR 56–63). RHR was significantly higher at baseline in individuals who subsequently developed arthritis. Expression levels of α7nAChR were lower in AR subjects with RHR ≥ 70 bpm compared to those with RHR < 70 bpm, consistent with reduced activity of the parasympathetic cholinergic anti-inflammatory pathway. Interpretation These data support the notion that autonomic dysfunction precedes the development of RA. PMID:27211565

Hypoglycemic and antioxidant effect of Tai chi exercise training in older adults with metabolic syndrome

PubMed Central

Mendoza-Núñez, Víctor Manuel; Arista-Ugalde, Taide Laurita; Rosado-Pérez, Juana; Ruiz-Ramos, Mirna; Santiago-Osorio, Edelmiro

2018-01-01

Introduction The antioxidant and anti-inflammatory effects of Tai chi (TC) exercise training in healthy older adults has been demonstrated. However, there are no studies on this effect in older adults with metabolic syndrome (MetS). Purpose The aim of this study was to determine the effect of TC exercise on oxidative stress and inflammatory markers in older adults with MetS. Methods A quasi-experimental study was carried out with a sample of 110 older sedentary volunteers with clinical diagnoses of MetS: (i) a control group, n = 50, of individuals who do not participate in physical exercise, of which 37 fulfilled the entire study protocol, and (ii) an experimental group, n = 60, of subjects enrolled in a TC exercise training program (eight-form easy), 5 days a week for 6 months, in sessions of 50 min, under the supervision of a qualified instructor, of which 48 fulfilled the entire study protocol. We measured in both groups (pre- and post-intervention) the following cardiovascular parameters: resting heart rate (RHR), diastolic and systolic blood pressure (DBP and SBP), mean arterial pressure (MAP), RHR-SBP product, RHR-MAP product; glycosylated hemoglobin (HbA1c); oxidative stress markers (superoxide dismutase, total antioxidant status, thiobarbituric acid reacting substances, and oxidative stress score); and inflammation markers (TNF-α, IL-6, IL-8, and IL-10). Results A statistically significant decrease in HbA1c concentration was observed in the TC group compared with the control group (p < 0.05). This group also showed a statistically significant increase in TAS and a decrease in the oxidative stress score (p < 0.05). We did not observe changes in the cardiovascular parameters (RHR, DBP, SBP, MAP, RHR-SBP product, and RHR-MAP product) in the TC experimental group compared to the control group. Conclusion Our findings suggest that the practice of TC exercise has an antioxidative and hypoglycemic effect in the elderly with MetS. PMID:29662308

Heart rate recovery in elite Spanish male athletes.

PubMed

Peinado, A B; Benito, P J; Barriopedro, M; Lorenzo, I; Maffulli, N; Calderón, F J

2014-06-01

During postexercise recovery, heart rate (HR) initially falls rapidly, followed by a period of slower decrease, until resting values are reached. The aim of the present work was to examine the differences in the recovery heart rate (RHR) between athletes engaged in static and dynamic sports. The study subjects were 294 federated sportsmen competing at the national and international level in sports classified using the criteria of Mitchell et al. as either prevalently static (N.=89) or prevalently dynamic (N.=205). Within the dynamic group, the subjects who practised the most dynamic sports were assigned to further subgroups: triathlon (N.=20), long distance running (N.=58), cycling (N.=28) and swimming (N.=12). All athletes were subjected to a maximum exertion stress test and their HR recorded at 1, 2, 3 and 4 min (RHR1,2,3,4) into the HR recovery period. The following indices of recovery (IR) were then calculated: IR1=(HRpeak-RHR1,2,3,4)/(HRmax-HRrest)*100, IR2=(HRpeak-RHR1,2,3,4)/(HRmax/HRpeak), and IR3=HRpeak-RHR1,2,3,4. The differences in the RHR and IR for the static and dynamic groups were examined using two way ANOVA. The RHR at minutes 2 (138.7±15.2 vs. 134.8±14.4 beats·min⁻¹) and 3 (128.5±15.2 vs. 123.3±14.4 beats·min⁻¹) were significantly higher for the static group (Group S) than the dynamic group (Group D), respectively. Significant differences were seen between Group D and S with respect to IR1 at minutes 1 (26.4±8.7 vs. 24.8±8.4%), 2 (43.8±8.1 vs. 41.5±7.8%), 3 (52.1±8.3 vs. 49.1±8%) and 4 (56.8±8.6 vs. 55.4±7.4%) of recovery. For IR2, significant differences were seen between the same groups at minutes 2 (59.7±12.5 vs. 55.9±10.8 beats·min⁻¹) and 3 (71.0±13.5 vs. 66.1±11.4 beats·min⁻¹) of recovery. Finally, for IR3, the only significant difference between Group D and S was recorded at minute 3 of recovery (72.2±12.5 vs. 66.2±11.5 beats·min⁻¹). This work provides information on RHR of a large population of elite Spanish athletes, and shows marked differences in the way that HR recovers in dynamic and static sports.

Use of genetically engineered swine to elucidate testis function in the boar

USDA-ARS?s Scientific Manuscript database

The second mammalian GnRH isoform (GnRH-II) and its specific receptor (GnRHR-II) are abundant within the testis, suggesting a critical role. Gene coding errors prevent their production in many species, but both genes are functional in swine. We have demonstrated that GnRHR-II localizes to porcine Le...

RHrFPGA Radiation-Hardened Re-programmable Field-Programmable Gate Array

NASA Technical Reports Server (NTRS)

Sanders, A. B.; LaBel, K. A.; McCabe, J. F.; Gardner, G. A.; Lintz, J.; Ross, C.; Golke, K.; Burns, B.; Carts, M. A.; Kim, H. S.

2004-01-01

Viewgraphs on the development of the Radiation-Hardened Re-programmable Field-Programmable Gate Array (RHrFPGA) are presented. The topics include: 1) Radiation Test Suite; 2) Testing Interface; 3) Test Configuration; 4) Facilities; 5) Test Programs; 6) Test Procedure; and 7) Test Results. A summary of heavy ion and proton testing is also included.

Knockdown of the GnRH-II receptor in the porcine testis impairs the biosynthesis of 10 gonadal steroids

USDA-ARS?s Scientific Manuscript database

The second mammalian GnRH isoform (GnRH-II) and its cognate receptor (GnRHR-II) are poor modulators of gonadotropin secretion in swine. However, both are abundantly produced within the porcine testis suggesting an autocrine/paracrine role. Within the boar testis, GnRHR-II immunolocalizes to the plas...

Expression and role of gonadotropin-releasing hormone 2 and its receptor in mammals

USDA-ARS?s Scientific Manuscript database

Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2) and its receptor (GnRHR2) also exist in some mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, s...

77 FR 73926 - Approval and Promulgation of State Implementation Plans; State of Wyoming; Regional Haze Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-12

... Class I Areas Under 40 CFR 51.309 AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule... (RHR) for the mandatory Class I areas under 40 CFR 51.309. EPA proposed that the January 12, 2011 and... RHR requirements for the mandatory Class I areas under 40 CFR 51.309. EPA taking final action to find...

Effects of forest fires on visibility and air quality

Treesearch

Douglas G. Fox; Allen R. Riebau

2009-01-01

The U.S. Clean Air Act establishes the goal of preventing future and remedying existing visibility impairment in 156 Class I areas (national parks, wilderness areas, and wildlife refuges). A key element in implementing this goal is the Regional Haze Regulation (RHR). RHR is based on relating impaired visibility, using metrics of extinction (inverse megameters and/or ‘‘...

Cumulative dose of hydroxychloroquine is associated with a decrease of resting heart rate in patients with systemic lupus erythematosus: a pilot study.

PubMed

Cairoli, E; Danese, N; Teliz, M; Bruzzone, M J; Ferreira, J; Rebella, M; Cayota, A

2015-10-01

The use of hydroxychloroquine (HCQ) in patients with systemic lupus erythematosus (SLE) offers a wide range of benefits. However, there are evidence in favour of cardiotoxicity, including heart conduction disturbances and congestive heart failure. To determine the effects of HCQ in the resting heart rate (RHR) of SLE patients. Included were patients with non active SLE, with a sedentary lifestyle and treated with HCQ. Excluded were patients on beta blocker treatment, trained patients, pacemaker's users and patients with clinical or analytical evidence of anemia, renal disease, obstructive pulmonary disease, obesity, uncontrolled thyroid disease, fever or current infection. Standard 12-lead electrocardiogram was performed in the resting condition (supine decubitus and orthostatic position). Comparison between groups was performed using Mann-Whitney U test. A multiple linear regression was performed. A p value <0.05 was considered statistically significant. 42 patients were included. Patients were divided in two groups based on the cumulative dose of HCQ (CD-HCQ), considering 365 g as cut-off. There were 24 patients with low-HCQ (<365 g) and 18 patients with high-HCQ (>365 g). Non significant differences were found in age, sex, prednisone dose or SLEDAI. The mean RHR was 73 ± 6 beats/min in the low-HCQ and 65 ± 7 beats/min in the high-HCQ, with a significant decrease of 11% (p = 0.003). In multiple linear regressions, there were non significant association between the decrease of RHR and prednisone dose, age, SLEDAI or TSH, but there was significant association between RHR and CD-HCQ (p = 0.024) and RHR and time of exposure to HCQ (p = 0.029). CD-HCQ higher than 365 g was associated with a significant decrease (11%) in RHR in non-active SLE patients, although a larger prospective study is required to allow more definitive conclusions. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Fanconi anemia A is a nucleocytoplasmic shuttling molecule required for gonadotropin-releasing hormone (GnRH) transduction of the GnRH receptor.

PubMed

Larder, Rachel; Karali, Dimitra; Nelson, Nancy; Brown, Pamela

2006-12-01

GnRH binds its cognate G protein-coupled GnRH receptor (GnRHR) located on pituitary gonadotropes and drives expression of gonadotropin hormones. There are two gonadotropin hormones, comprised of a common alpha- and hormone-specific beta-subunit, which are required for gonadal function. Recently we identified that Fanconi anemia a (Fanca), a DNA damage repair gene, is differentially expressed within the LbetaT2 gonadotrope cell line in response to stimulation with GnRH. FANCA is mutated in more than 60% of cases of Fanconi anemia (FA), a rare genetically heterogeneous autosomal recessive disorder characterized by bone marrow failure, endocrine tissue cancer susceptibility, and infertility. Here we show that induction of FANCA protein is mediated by the GnRHR and that the protein constitutively adopts a nucleocytoplasmic intracellular distribution pattern. Using inhibitors to block nuclear import and export and a GnRHR antagonist, we demonstrated that GnRH induces nuclear accumulation of FANCA and green fluorescent protein (GFP)-FANCA before exporting back to the cytoplasm using the nuclear export receptor CRM1. Using FANCA point mutations that locate GFP-FANCA to the cytoplasm (H1110P) or functionally uncouple GFP-FANCA (Q1128E) from the wild-type nucleocytoplasmic distribution pattern, we demonstrated that wild-type FANCA was required for GnRH-induced activation of gonadotrope cell markers. Cotransfection of H1110P and Q1128E blocked GnRH activation of the alphaGsu and GnRHR but not the beta-subunit gene promoters. We conclude that nucleocytoplasmic shuttling of FANCA is required for GnRH transduction of the alphaGSU and GnRHR gene promoters and propose that FANCA functions as a GnRH-induced signal transducer.

Fanconi Anemia a Is a Nucleocytoplasmic Shuttling Molecule Required for Gonadotropin-Releasing Hormone (GnRH) Transduction of the GnRH Receptor

PubMed Central

Larder, Rachel; Karali, Dimitra; Nelson, Nancy; Brown, Pamela

2007-01-01

GnRH binds its cognate G protein-coupled GnRH receptor (GnRHR) located on pituitary gonadotropes and drives expression of gonadotropin hormones. There are two gonadotropin hormones, comprised of a common α- and hormone-specific β-subunit, which are required for gonadal function. Recently we identified that Fanconi anemia a (Fanca), a DNA damage repair gene, is differentially expressed within the LβT2 gonadotrope cell line in response to stimulation with GnRH. FANCA is mutated in more than 60% of cases of Fanconi anemia (FA), a rare genetically heterogeneous autosomal recessive disorder characterized by bone marrow failure, endocrine tissue cancer susceptibility, and infertility. Here we show that induction of FANCA protein is mediated by the GnRHR and that the protein constitutively adopts a nucleocytoplasmic intracellular distribution pattern. Using inhibitors to block nuclear import and export and a GnRHR antagonist, we demonstrated that GnRH induces nuclear accumulation of FANCA and green fluorescent protein (GFP)-FANCA before exporting back to the cytoplasm using the nuclear export receptor CRM1. Using FANCA point mutations that locate GFP-FANCA to the cytoplasm (H1110P) or functionally uncouple GFP-FANCA (Q1128E) from the wild-type nucleocytoplasmic distribution pattern, we demonstrated that wild-type FANCA was required for GnRH-induced activation of gonadotrope cell markers. Cotransfection of H1110P and Q1128E blocked GnRH activation of the αGsu and GnRHR but not the β-subunit gene promoters. We conclude that nucleocytoplasmic shuttling of FANCA is required for GnRH transduction of the αGSU and GnRHR gene promoters and propose that FANCA functions as a GnRH-induced signal transducer. PMID:16946016

The appeal of smokeless tobacco products among young Canadian smokers: the impact of pictorial health warnings and relative risk messages.

PubMed

Callery, William E; Hammond, David; O'Connor, Richard J; Fong, Geoffrey T

2011-05-01

Although the health risks from smokeless tobacco (ST) are lower than cigarettes, it remains unclear how smokers might use ST products, including as a substitute, a cessation aid, or concurrently with cigarette use, if at all. Additionally, there is little evidence examining the impact of health warning labels (HWL) on ST use and perceptions. The current study investigated perceptions of ST products with and without HWL and a relative health risk (RHR) message. The study consisted of a full-factorial "between-subjects" experiment in which 3 HWL and a RHR message were systematically varied. Canadian smokers aged 18-30 years (N = 611) completed an online survey where they viewed four brands of ST packages altered according to the experimental conditions. Approximately half of the smokers indicated that they were willing to try ST as a substitute and to help quit smoking. More than one quarter (28%) of smokers were unaware that using ST is less harmful than smoking. Pictorial HWL increased false beliefs about the RHR of ST and decreased smokers' willingness to try ST, whereas text warnings did not. Adding a RHR message communicating the lower risk of ST compared with cigarettes increased willingness to try ST when added to text HWL but decreased willingness to try ST even further when added to pictorial HWL. The findings indicate relatively high levels of appeal for ST among young adult Canadian cigarette smokers. Pictorial HWL reduced the appeal of ST products and increased perceived risks, including the false belief that ST is equally harmful as cigarettes. Further research could consider evaluating designs of HWL on ST products that better balance absolute and RHR.

Physical activity below the minimum international recommendations improves oxidative stress, ADMA levels, resting heart rate and small artery endothelial function.

PubMed

Merino, J; Ferré, R; Girona, J; Aguas, D; Cabré, A; Plana, N; Vinuesa, A; Ibarretxe, D; Basora, J; Buixadera, C; Masana, L

2015-01-01

A moderate level of physical activity (PA), such as a daily 30-min walk, reduces cardiovascular risk. There is a lack of evidence about the cardiovascular benefits of PA below this recommendation of minimum PA level. We aimed to study the impact of a lower level of PA on cardiovascular health. Sixty-four overweight/obese men and women were enrolled in a community programme consisting of 4 months of 1h, low-intensity PA two days per week. Before and after the intervention, PA level (METs/h/wk), endogenous antioxidant status (SOD and GPX concentration and activity and oxidised LDL), ADMA concentrations, endothelial function by small artery reactive hyperaemia index (saRHI), and resting heart rate (RHR) were assessed. After the intervention, significant increases in saRHI (P=0.031), SOD and GPX activities, and a decrease in ADMA plasma concentrations, and RHR (P<0.001 for all) were observed. Increases in PA were positively associated with increases in saRHI (r=0.341, P=0.022), GPx (r=0.303, P=0.047) and decreases in RHR (r=-0.302, P=0.047). Multivariate analyses showed that independent predictors of saRHI improvement were an increase in PA (2.65, 95%CI: 1.21-4.01), decrease in RHR (1.91, 95%CI: 1.01-4.98), and an increase in GPx (2.61, 95%CI: 1.16-5.01). In obese and overweight men and women, an increase in PA, even below the minimal international recommendations, improves antioxidant capacity, RHR and peripheral small artery reactivity. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Interactions between empathy and resting heart rate in early adolescence predict violent behavior in late adolescence and early adulthood.

PubMed

Galán, Chardée A; Choe, Daniel Ewon; Forbes, Erika E; Shaw, Daniel S

2017-12-01

Although resting heart rate (RHR) and empathy are independently and negatively associated with violent behavior, relatively little is known about the interplay between these psychophysiological and temperament-related risk factors. Using a sample of 160 low-income, racially diverse men followed prospectively from infancy through early adulthood, this study examined whether RHR and empathy during early adolescence independently and interactively predict violent behavior and related correlates in late adolescence and early adulthood. Controlling for child ethnicity, family income, and child antisocial behavior at age 12, empathy inversely predicted moral disengagement and juvenile petitions for violent crimes, while RHR was unrelated to all measures of violent behavior. Interactive effects were also evident such that among men with lower but not higher levels of RHR, lower empathy predicted increased violent behavior, as indexed by juvenile arrests for violent offenses, peer-reported violent behavior at age 17, self-reported moral disengagement at age 17, and self-reported violent behavior at age 20. Implications for prevention and intervention are considered. Specifically, targeting empathic skills among individuals at risk for violent behavior because of specific psychophysiological profiles may lead to more impactful interventions. © 2017 Association for Child and Adolescent Mental Health.

[Physical workload and maximum acceptable work time among supermarket workers in Cali, Colombia].

PubMed

Ariza, Luz Elena; Idrovo, Alvaro Javier

2005-01-01

In order to guarantee safety and health conditions in labor the maximum physical workload that can be supported by a worker during a labor day, without causing fatigue, must be determined. The objective of this study was to determine the relationship between the physical load, expressed as relative heart rate (RHR), and the maximum acceptable work time (MAWT) in a Colombian working population (n = 30) from a tropical environment. An observational study was carried out during a typical labor day in the warehouses of a supermarket. Physiological, demographic, health and labor conditions data were collected. The resting heart rate level and the average heart rate during work were measured, and the RHR was estimated according to with the model described by Wu & Wang. Significant correlations between MAWT and RHR and other physiological variables were observed. 43% of workers didn't fulfill the MAWT. The only single variable that was associated with fulfillment was a body mass index under 18.5 Kg/m2; the other associated variables were some specific conditions of the occupational environment. Results showed a negative correlation between physiological variables and MAWT. The RHR showed its potential usefulness in the enterprise's occupational health practice. It is important for companies to diminish extended schedules and implement physical conditioning programs.

High Physical Activity is Associated with an Improved Lipid Profile and Resting Heart Rate among Healthy Middle-aged Chinese People.

PubMed

Hu, Bo; Liu, Xiao Yu; Zheng, Yao; Fan, Hong Min; Yin, Su Feng; Guo, Chun Yue; Li, Yun; Wu, Shou Ling; Feng, Fu Min; Yuan, Ju Xiang

2015-04-01

To investigate the effects of physical activity (PA) on dyslipidemia and elevated resting heart rate (RHR) in a large-scale cross-sectional study in China. We recruited community-based individuals who were 40-60 years old using a cluster sampling method. The PA levels of the participants were classified as low, moderate, or high, using the International Physical Activity Questionnaire. Dyslipidemia was defined as the detection of abnormalities in lipid indicators, and 4 lipid parameters were evaluated using fasting blood samples. Multivariate logistic regression analyses were used to evaluate the associations of PA with dyslipidemia and RHR. A total of 10,321 participants (38.88% men) were included in this study. The percentages of individuals with high, moderate, and low PA levels were 46.5%, 43.9%, and 9.6%, respectively. In both men and women, high PA provided odds ratios of 0.88 [95% confidence interval (CI): 0.83, 0.94] for dyslipidemia and 0.82 (95% CI: 0.73, 0.92) for elevated RHR, compared to participants with low PA. Our data suggested that substantial health benefits (related to dyslipidemia and elevated RHR) occurred at higher intensity PA, with greater energy consumption, in middle-aged Chinese people, and particularly in men. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Ammonia excretion in Caenorhabditis elegans: mechanism and evidence of ammonia transport of the Rhesus protein CeRhr-1

PubMed Central

Adlimoghaddam, Aida; Boeckstaens, Mélanie; Marini, Anna-Maria; Treberg, Jason R.; Brassinga, Ann-Karen C.; Weihrauch, Dirk

2015-01-01

ABSTRACT The soil-dwelling nematode Caenorhabditis elegans is a bacteriovorous animal, excreting the vast majority of its nitrogenous waste as ammonia (25.3±1.2 µmol gFW−1 day−1) and very little urea (0.21±0.004 µmol gFW−1 day−1). Although these roundworms have been used for decades as genetic model systems, very little is known about their strategy to eliminate the toxic waste product ammonia from their bodies into the environment. The current study provides evidence that ammonia is at least partially excreted via the hypodermis. Starvation reduced the ammonia excretion rates by more than half, whereas mRNA expression levels of the Rhesus protein CeRhr-2, V-type H+-ATPase (subunit A) and Na+/K+-ATPase (α-subunit) decreased correspondingly. Moreover, ammonia excretion rates were enhanced in media buffered to pH 5 and decreased at pH 9.5. Inhibitor experiments, combined with enzyme activity measurements and mRNA expression analyses, further suggested that the excretion mechanism involves the participation of the V-type H+-ATPase, carbonic anhydrase, Na+/K+-ATPase, and a functional microtubule network. These findings indicate that ammonia is excreted, not only by apical ammonia trapping, but also via vesicular transport and exocytosis. Exposure to 1 mmol l−1 NH4Cl caused a 10-fold increase in body ammonia and a tripling of ammonia excretion rates. Gene expression levels of CeRhr-1 and CeRhr-2, V-ATPase and Na+/K+-ATPase also increased significantly in response to 1 mmol l−1 NH4Cl. Importantly, a functional expression analysis showed, for the first time, ammonia transport capabilities for CeRhr-1 in a phylogenetically ancient invertebrate system, identifying these proteins as potential functional precursors to the vertebrate ammonia-transporting Rh-glycoproteins. PMID:25740900

Incorporating root hydraulic redistribution in CLM4.5: Effects on predicted site and global evapotranspiration, soil moisture, and water storage

NASA Astrophysics Data System (ADS)

Tang, Jinyun; Riley, William J.; Niu, Jie

2015-12-01

We implemented the Amenu-Kumar model in the Community Land Model (CLM4.5) to simulate plant Root Hydraulic Redistribution (RHR) and analyzed its influence on CLM hydrology from site to global scales. We evaluated two numerical implementations: the first solved the coupled equations of root and soil water transport concurrently, while the second solved the two equations sequentially. Through sensitivity analysis, we demonstrate that the sequentially coupled implementation (SCI) is numerically incorrect, whereas the tightly coupled implementation (TCI) is numerically robust with numerical time steps varying from 1 to 30 min. At the site-level, we found the SCI approach resulted in better agreement with measured evapotranspiration (ET) at the AmeriFlux Blodgett Forest site, California, whereas the two approaches resulted in equally poor agreement between predicted and measured ET at the LBA Tapajos KM67 Mature Forest site in Amazon, Brazil. Globally, the SCI approach overestimated annual land ET by as much as 3.5 mm d-1 in some grid cells when compared to the TCI estimates. These comparisons demonstrate that TCI is a more robust numerical implementation of RHR. However, we found, even with TCI, that incorporating RHR resulted in worse agreement with measured soil moisture at both the Blodgett Forest and Tapajos sites and degraded the agreement between simulated terrestrial water storage anomaly and Gravity Recovery and Climate Experiment (GRACE) observations. We find including RHR in CLM4.5 improved ET predictions compared with the FLUXNET-MTE estimates north of 20° N but led to poorer predictions in the tropics. The biases in ET were robust and significant regardless of the four different pedotransfer functions or of the two meteorological forcing data sets we applied. We also found that the simulated water table was unrealistically sensitive to RHR. Therefore, we contend that further structural and data improvements are warranted to improve the hydrological dynamics in CLM4.5.

Increased resting heart rate with pollutants in a population based study

PubMed Central

Ruidavets, J.; Cassadou, S.; Cournot, M.; Bataille, V.; Meybeck, M.; Ferrieres, J.

2005-01-01

Background: Air pollution is associated with cardiovascular mortality. Changes in the autonomic nervous system may contribute to cardiac arrhythmias and cardiovascular mortality. This study investigated the relations between air pollutant concentrations of sulphur dioxide (SO2), ozone (O3), nitric dioxide (NO2), and resting heart rate (RHR) in a population based study. Methods: A sample of 863 middle aged men and women, living in Toulouse (MONICA centre) area, was randomly recruited. A cross sectional survey on cardiovascular risk factors was carried. RHR was measured twice in a sitting position after a five minute rest. Multivariate analyses with quintiles of RHR were performed using polytomous logistic regression. Models were adjusted for temperature, season, relative humidity, sex, physical activity, blood pressure, C reactive protein, and cardiovascular drugs. Results: For NO2, the OR (odds ratio) (95% CI) associated with an increase of 5 µg/m3 in the current day of medical examination was 1.14 (1.03 to 1.25) in quintile Q5 of RHR compared with Q1, p for trend = 0.003. For SO2, OR was 1.16 (0.94 to 1.44) in Q5 compared with Q1, p for trend = 0.05, and for O3, OR was 0.96 (0.91 to 1.01) in Q5 compared with Q1, p for trend = 0.11. No significant association was seen when the daily mean concentration of NO2, SO2, and O3 was considered during the previous day as well as when day lag 2 or 3 was considered. The cumulative concentration (three consecutive days) of O3 is negatively associated with RHR (p for trend = 0.02). Conclusion: Changes in pulse rate could reflect cardiac rhythm changes and may be part of the pathophysiological link between pollution and cardiovascular mortality. PMID:16020647

Differences in Treatment Effect Size Between Overall Survival and Progression-Free Survival in Immunotherapy Trials: A Meta-Epidemiologic Study of Trials With Results Posted at ClinicalTrials.gov.

PubMed

Tan, Aidan; Porcher, Raphael; Crequit, Perrine; Ravaud, Philippe; Dechartres, Agnes

2017-05-20

Purpose We aimed to compare treatment effect sizes between overall survival (OS) and progression-free survival (PFS) in trials of US Food and Drug Administration-approved oncology immunotherapy drugs with results posted at ClinicalTrials.gov . Methods We searched ClinicalTrials.gov for phase II to IV cancer trials of Food and Drug Administration-approved immunotherapy drugs and selected those reporting results for both OS and PFS. For each trial, we extracted the hazard ratios (HRs) with 95% CIs for both outcomes and evaluated the differences by a ratio of HRs (rHRs): the HR for PFS to that for OS. We performed a random effects meta-analysis across trials to obtain a summary rHR. We also evaluated surrogacy of PFS for OS by the coefficient of determination and the surrogacy threshold effect, the minimal value of HR for PFS to predict a non-null effect on OS. Results We identified 51 trials assessing 14 drugs across 15 conditions. Treatment effect sizes were 17% greater, on average, with PFS than with OS (rHR, 0.83; 95% CI, 0.79 to 0.88; I 2 = 34.4%; P = .01; τ 2 = 0.0129). Nearly one half of the trials (n = 23, 45%) showed statistically significant benefits for PFS but not for OS. Differences were great for trials of obinutuzumab (rHR, 0.21; 95% CI, 0.08 to 0.54), bevacizumab (rHR, 0.75; 95% CI, 0.67 to 0.84), and rituximab (rHR, 0.79; 95% CI, 0.64 to 0.98). The coefficient of determination was 38% and the surrogacy threshold effect was 0.50. Conclusion Treatment effect sizes in trials of immunotherapy drugs were greater for PFS than for OS, with important differences for some drugs, which is consistent with surrogacy metrics. Caution must be taken when interpreting PFS in the absence of OS data.

Incorporating root hydraulic redistribution in CLM4.5: Effects on predicted site and global evapotranspiration, soil moisture, and water storage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Jinyun; Riley, William J.; Niu, Jie

We implemented the Amenu-Kumar model in the Community Land Model (CLM4.5) to simulate plant Root Hydraulic Redistribution (RHR) and analyzed its influence on CLM hydrology from site to global scales. We evaluated two numerical implementations: the first solved the coupled equations of root and soil water transport concurrently, while the second solved the two equations sequentially. Through sensitivity analysis, we demonstrate that the sequentially coupled implementation (SCI) is numerically incorrect, whereas the tightly coupled implementation (TCI) is numerically robust with numerical time steps varying from 1 to 30 min. At the site-level, we found the SCI approach resulted in bettermore » agreement with measured evapotranspiration (ET) at the AmeriFlux Blodgett Forest site, California, whereas the two approaches resulted in equally poor agreement between predicted and measured ET at the LBA Tapajos KM67 Mature Forest site in Amazon, Brazil. Globally, the SCI approach overestimated annual land ET by as much as 3.5 mm d -1 in some grid cells when compared to the TCI estimates. These comparisons demonstrate that TCI is a more robust numerical implementation of RHR. However, we found, even with TCI, that incorporating RHR resulted in worse agreement with measured soil moisture at both the Blodgett Forest and Tapajos sites and degraded the agreement between simulated terrestrial water storage anomaly and Gravity Recovery and Climate Experiment (GRACE) observations. We find including RHR in CLM4.5 improved ET predictions compared with the FLUXNET-MTE estimates north of 20° N but led to poorer predictions in the tropics. The biases in ET were robust and significant regardless of the four different pedotransfer functions or of the two meteorological forcing data sets we applied. We also found that the simulated water table was unrealistically sensitive to RHR. Therefore, we contend that further structural and data improvements are warranted to improve the hydrological dynamics in CLM4.5.« less

Incorporating root hydraulic redistribution in CLM4.5: Effects on predicted site and global evapotranspiration, soil moisture, and water storage

DOE PAGES

Tang, Jinyun; Riley, William J.; Niu, Jie

2015-11-12

We implemented the Amenu-Kumar model in the Community Land Model (CLM4.5) to simulate plant Root Hydraulic Redistribution (RHR) and analyzed its influence on CLM hydrology from site to global scales. We evaluated two numerical implementations: the first solved the coupled equations of root and soil water transport concurrently, while the second solved the two equations sequentially. Through sensitivity analysis, we demonstrate that the sequentially coupled implementation (SCI) is numerically incorrect, whereas the tightly coupled implementation (TCI) is numerically robust with numerical time steps varying from 1 to 30 min. At the site-level, we found the SCI approach resulted in bettermore » agreement with measured evapotranspiration (ET) at the AmeriFlux Blodgett Forest site, California, whereas the two approaches resulted in equally poor agreement between predicted and measured ET at the LBA Tapajos KM67 Mature Forest site in Amazon, Brazil. Globally, the SCI approach overestimated annual land ET by as much as 3.5 mm d -1 in some grid cells when compared to the TCI estimates. These comparisons demonstrate that TCI is a more robust numerical implementation of RHR. However, we found, even with TCI, that incorporating RHR resulted in worse agreement with measured soil moisture at both the Blodgett Forest and Tapajos sites and degraded the agreement between simulated terrestrial water storage anomaly and Gravity Recovery and Climate Experiment (GRACE) observations. We find including RHR in CLM4.5 improved ET predictions compared with the FLUXNET-MTE estimates north of 20° N but led to poorer predictions in the tropics. The biases in ET were robust and significant regardless of the four different pedotransfer functions or of the two meteorological forcing data sets we applied. We also found that the simulated water table was unrealistically sensitive to RHR. Therefore, we contend that further structural and data improvements are warranted to improve the hydrological dynamics in CLM4.5.« less

Identification of Ser153 in ICL2 of the gonadotropin-releasing hormone (GnRH) receptor as a phosphorylation-independent site for inhibition of Gq coupling.

PubMed

Shacham, Sharon; Cheifetz, Maya N; Fridkin, Mati; Pawson, Adam J; Millar, Robert P; Naor, Zvi

2005-08-12

Type I gonadotropin-releasing hormone (GnRH) receptor (GnRHR) is unique among mammalian G-protein-coupled receptors (GPCRs) in lacking a C-terminal tail, which is involved in desensitization in GPCRs. Therefore, we searched for inhibitory sites in the intracellular loops (ICLs) of the GnRHR. Synthetic peptides corresponding to the three ICLs were inserted into permeabilized alphaT3-1 gonadotrope cells, and GnRH-induced inositol phosphate (InsP) formation was determined. GnRH-induced InsP production was potentiated by ICL2 > ICL3 but not by the ICL1 peptides, suggesting they are acting as decoy peptides. We examined the effects of six peptides in which only one of the Ser or Thr residues was substituted with Ala or Glu. Only substitution of Ser153 with Ala or Glu ablated the potentiating effect upon GnRH-induced InsP elevation. ERK activation was enhanced, and the rate of GnRH-induced InsP formation was about 6.5-fold higher in the first 10 min in COS-1 cells that were transfected with mutants of the GnRHR in which the ICL2 Ser/Thr residues (Ser151, Ser153, and Thr142) or only Ser153 was mutated to Ala as compared with the wild type GnRHR. The data indicate that ICL2 harbors an inhibitory domain, such that exogenous ICL2 peptide serves as a decoy for the inhibitory site (Ser153) of the GnRHR, thus enabling further activation. GnRH does not induce receptor phosphorylation in alphaT3-1 cells. Because the phosphomimetic ICL2-S153E peptide did not mimic the stimulatory effect of the ICL2 peptide, the inhibitory effect of Ser153 operates through a phosphorylation-independent mechanism.

The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review).

PubMed

Aguilar-Rojas, Arturo; Pérez-Solis, Marco Allan; Maya-Núñez, Guadalupe

2016-03-01

Recently, an increasing amount of evidence indicates that human gonadotropin-releasing hormone (hGnRH) and its receptor (hGnRHR) are important regulatory components not only to the reproduction process but also in the regulation of some cancer cell functions such as cell proliferation, in both hormone-dependent and -independent types of tumors. The hGnRHR is a naturally misfolded protein that is retained mostly in the endoplasmic reticulum; however, this mechanism can be overcome by treatment with several pharmacoperones, therefore, increasing the amount of receptors in the cell membrane. In addition, several reports indicate that the expression level of hGnRHR in tumor cells is even lower than in pituitary or gonadotrope cells. The signal transduction pathways activated by hGnRH in both gonadotrope and different cancer cell types are described in the present review. We also discuss how the rescue of misfolded receptors in tumor cells could be a promising strategy for cancer therapy.

THE EFFECTS OF $gamma$-IRRADIATION AND ROLLING ON THE TEARING PROPERTIES OF POLYETHYLENE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsunekawa, Y.; Awatani, J.; Kojima, K.

1961-01-01

Polyethylene samples of 2 mm thickness were gamma irradiated in water. The total dosage for the samples irradiated after the rolling treatraent was 1.5 x lO/sup 5/ r/hr, while the dosage for the saraples irradiated before the rolling was 1.2 x lO/sup 5/ r/hr. The tensile strength of the irradiated and rolled saraple increased with increasing dosage. A comparison of tearing strengths between the rolled samples and the rolled and irradiated samples was raade. (OID)

Code Development and Assessment for Reactor Outage Thermal-Hydraulic and Safety Analysis - Midloop Operation with Loss of Residual Heat Removal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, Thomas K.S.; Ko, F.-K

Although only a few percent of residual power remains during plant outages, the associated risk of core uncovery and corresponding fuel overheating has been identified to be relatively high, particularly under midloop operation (MLO) in pressurized water reactors. However, to analyze the system behavior during outages, the tools currently available, such as RELAP5, RETRAN, etc., cannot easily perform the task. Therefore, a medium-sized program aiming at reactor outage simulation and evaluation, such as MLO with the loss of residual heat removal (RHR), was developed. All important thermal-hydraulic processes involved during MLO with the loss of RHR will be properly simulatedmore » by the newly developed reactor outage simulation and evaluation (ROSE) code. Important processes during MLO with loss of RHR involve a pressurizer insurge caused by the hot-leg flooding, reflux condensation, liquid holdup inside the steam generator, loop-seal clearance, core-level depression, etc. Since the accuracy of the pressure distribution from the classical nodal momentum approach will be degraded when the system is stratified and under atmospheric pressure, the two-region approach with a modified two-fluid model will be the theoretical basis of the new program to analyze the nuclear steam supply system during plant outages. To verify the analytical model in the first step, posttest calculations against the closed integral midloop experiments with loss of RHR were performed. The excellent simulation capacity of the ROSE code against the Institute of Nuclear Energy Research Integral System Test Facility (IIST) test data is demonstrated.« less

Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand-break repair

DOE PAGES

Andres, Sara N.; Appel, C. Denise; Westmoreland, James W.; ...

2015-01-12

Ctp1 (also known as CtIP or Sae2) collaborates with Mre11-Rad50-Nbs1 to initiate repair of DNA double-strand breaks (DSBs), but its functions remain enigmatic. In this paper, we report that tetrameric Schizosaccharomyces pombe Ctp1 contains multivalent DNA-binding and DNA-bridging activities. Through structural and biophysical analyses of the Ctp1 tetramer, we define the salient features of Ctp1 architecture: an N-terminal interlocking tetrameric helical dimer-of-dimers (THDD) domain and a central intrinsically disordered region (IDR) linked to C-terminal 'RHR' DNA-interaction motifs. The THDD, IDR and RHR are required for Ctp1 DNA-bridging activity in vitro, and both the THDD and RHR are required for efficientmore » DSB repair in S. pombe. Finally, our results establish non-nucleolytic roles of Ctp1 in binding and coordination of DSB-repair intermediates and suggest that ablation of human CtIP DNA binding by truncating mutations underlie the CtIP-linked Seckel and Jawad syndromes.« less

Amphioxus: beginning of vertebrate and end of invertebrate type GnRH receptor lineage.

PubMed

Tello, Javier A; Sherwood, Nancy M

2009-06-01

In vertebrates, activation of the GnRH receptor is necessary to initiate the reproductive cascade. However, little is known about the characteristics of GnRH receptors before the vertebrates evolved. Recently genome sequencing was completed for amphioxus, Branchiostoma floridae. To understand the GnRH receptors (GnRHR) from this most basal chordate, which is also classified as an invertebrate, we cloned and characterized four GnRHR cDNAs encoded in the amphioxus genome. We found that incubation of GnRH1 (mammalian GnRH) and GnRH2 (chicken GnRH II) with COS7 cells heterologously expressing the amphioxus GnRHRs caused potent intracellular inositol phosphate turnover in two of the receptors. One of the two receptors displayed a clear preference for GnRH1 over GnRH2, a characteristic not previously seen outside the type I mammalian GnRHRs. Phylogenetic analysis grouped the four receptors into two paralogous pairs, with one pair grouping basally with the vertebrate GnRH receptors and the other grouping with the octopus GnRHR-like sequence and the related receptor for insect adipokinetic hormone. Pharmacological studies showed that octopus GnRH-like peptide and adipokinetic hormone induced potent inositol phosphate turnover in one of these other two amphioxus receptors. These data demonstrate the functional conservation of two distinct types of GnRH receptors at the base of chordates. We propose that one receptor type led to vertebrate GnRHRs, whereas the other type, related to the mollusk GnRHR-like receptor, was lost in the vertebrate lineage. This is the first report to suggest that distinct invertebrate and vertebrate GnRHRs are present simultaneously in a basal chordate, amphioxus.

Anatomical, histological and immunohistochemical study of testicular development in Columba livia (Aves: Columbiformes).

PubMed

Olea, G B; Aguirre, M V; Lombardo, D M

2018-07-01

In this work, testicular ontogeny is analyzed at the anatomical, histological and immunohistochemical levels; the latter through the detection of GnRHR and PCNA in the testicles of embryos, neonates and juveniles of Columba livia. We analyzed 150 embryos, 25 neonates and 5 juveniles by means of observations under a stereoscopic magnifying glass and scanning electron microscope (SEM). The histological analysis was performed using hematoxylin-eosin staining techniques and the PAS reaction. For the immunohistochemical analysis, the expression of GnRHR and PCNA in embryos corresponding to stages 41, 43 and in neonates of 2, 5, 7 and 75 days post-hatch was revealed in testicular histological preparations. That gonadal outline is evident in stage 18. In stage 29, the testes are constituted of a medulla in which the PGCs are surrounded by the Sertoli cells, constituting the seminiferous tubules. From stage 37 a greater organization of the tubules is visualized and at the time of hatching the testicle is constituted of the closed seminiferous tubules, formed of the PGCs and Sertoli cells. The Leydig cells are evident outside the tubules. In the juvenile stages, the differentiation of germline cells and the organization of small vessels that irrigate the developing testicle begin to be visible. In the analyzed stages, the immunodetection of the GnRHR receptor and PCNA revealed specific marking in the plasma membrane and in the perinuclear zone for GnRHR and in the nucleus of the germline cells in juvenile testicles for PCNA. These results can be used as a basis for further study of endocrine regulation events during testicular ontogeny in avian species. Copyright © 2018 Elsevier GmbH. All rights reserved.

Molecular mechanism of action of pharmacoperone rescue of misrouted GPCR mutants: the GnRH receptor.

PubMed

Janovick, Jo Ann; Patny, Akshay; Mosley, Ralph; Goulet, Mark T; Altman, Michael D; Rush, Thomas S; Cornea, Anda; Conn, P Michael

2009-02-01

The human GnRH receptor (hGnRHR), a G protein-coupled receptor, is a useful model for studying pharmacological chaperones (pharmacoperones), drugs that rescue misfolded and misrouted protein mutants and restore them to function. This technique forms the basis of a therapeutic approach of rescuing mutants associated with human disease and restoring them to function. The present study relies on computational modeling, followed by site-directed mutagenesis, assessment of ligand binding, effector activation, and confocal microscopy. Our results show that two different chemical classes of pharmacoperones act to stabilize hGnRHR mutants by bridging residues D(98) and K(121). This ligand-mediated bridge serves as a surrogate for a naturally occurring and highly conserved salt bridge (E(90)-K(121)) that stabilizes the relation between transmembranes 2 and 3, which is required for passage of the receptor through the cellular quality control system and to the plasma membrane. Our model was used to reveal important pharmacophoric features, and then identify a novel chemical ligand, which was able to rescue a D(98) mutant of the hGnRHR that could not be rescued as effectively by previously known pharmacoperones.

Correlation between chronotropic incompetence and metabolic equivalents in patients with type 2 diabetes mellitus and concomitant metabolic syndrome.

PubMed

Gao, M; Chen, W; Gong, Z K; Han, L; Zhang, L

2015-09-01

The aim of the study was to examine the relationship between chronotropic incompetence and motor ability in patient with type 2 diabetes mellitus and concomitant metabolic syndrome (MS) in order to facilitate exercise prescriptions for these patients. A total of 120 patients with type 2 diabetes mellitus were randomly enrolled and divided into study groups with (N.=64) or without MS (N.=56). All patients completed the electrocardiographic exercise testing, after which ratio of heart rate (rHR) and heart rate reserve (HRR) were calculating to assess chronotropic incompetence. In addition, maximum metabolic equivalents (maxMETs) were calculated to assess the motor ability. The MS group had significantly higher indicators of chronotropic incompetence (rHR and HRR) as well as maxMETs than patients without MS (all P<0.05). Further, maxMETs significantly correlated with rHR (r=0.81, P=0.003) and HRR (r=0.78, P<0.001). Patients with type 2 diabetes mellitus and concomitant MS have higher chronotropic incompetence and maxMETs compared with those without MS. METs or perceived level of exertion can be used in patients in whom heart rate is not available during the exercise.

Effect of endotoxin on the expression of GnRH and GnRHR genes in the hypothalamus and anterior pituitary gland of anestrous ewes.

PubMed

Herman, Andrzej Przemysław; Tomaszewska-Zaremba, Dorota

2010-07-01

An immune/inflammatory challenge can affect reproduction at the level of the hypothalamus, pituitary gland, or gonads. Nonetheless, the major impact is thought to occur within the brain or the pituitary gland. The present study was designed to examine the effect of intravenous (i.v.) lipopolysaccharide (LPS) injection on the expression of gonadotropin-releasing hormone (GnRH) and the gonadotropin-releasing hormone receptor (GnRHR) genes in the hypothalamic structures where GnRH neurons are located as well as in the anterior pituitary gland (AP) of anestrous ewes. We also determined the effect of LPS on luteinizing hormone (LH) release. It was found that i.v. LPS injection significantly decreased GnRH and GnRHR mRNAs levels in the preoptic area (40%, p

Effect of hypothyroidism on the hypothalamic-pituitary-ovarian axis and reproductive function of pregnant rats.

PubMed

Sun, Jianran; Hui, Cancan; Xia, Tongjia; Xu, Min; Deng, Datong; Pan, Faming; Wang, Youmin

2018-05-24

This study aimed to detect changes in hormone levels in the hypothalamic-pituitary-ovarian axis in Sprague-Dawley (SD) rats with hypothyroidism, and identify differences in the pregnancy and abortion rates of female adult rats. The potential role of gonadotropin releasing hormone (GnRH) as the link between the hypothalamic-pituitary-ovarian axis and reproductive function regulated by thyroid hormones was also investigated. Female SD rats (n = 136) were causally classified into two groups: the normal-drinking-water group (n = 60) and the 0.05% propylthiouracil-drinking-water group (PTU 2 mg/kg/day, n = 76) to establish an adult rat model of hypothyroidism (6 weeks). Female and male rats at a ratio of 1:2 were used to establish a hypothyroidism pregnancy model. GnRH mRNA and GnRH receptor (GnRHR) expression in rats was detected using real time quantitative PCR(qRT-PCR) and immunohistochemistry, respectively. The abortion rate differed significantly between the hypothyroidism pregnancy group and the normal pregnancy group (P < 0.05). No significant differences were found in the distribution of the GnRHR among the five nuclei (hypothalamic arcuate nucleus, hypothalamic ventromedial nucleus, hypothalamic anterior nucleus, paraventricular nucleus of the hypothalamus, and ventral premammillary nucleus) of the hypothalamus and ovary (P > 0.05). Hypothyroidism had no significant effect on GnRH mRNA expression in the hypothalamic-pituitary-ovarian axis in the four groups (normal control group, normal pregnancy group, hypothyroidism pregnancy group, and hypothyroidism group) (P > 0.05). Hypothyroidism had an adverse impact on pregnancy in rats and may affect the distribution of pituitary GnRHR, whereas it did not obviously affect the distribution of GnRHR in the nuclei of the hypothalamus and ovary. Hypothyroidism had no effect on GnRH mRNA expression.

Optimal Hedging Rule for Reservoir Refill Operation

NASA Astrophysics Data System (ADS)

Wan, W.; Zhao, J.; Lund, J. R.; Zhao, T.; Lei, X.; Wang, H.

2015-12-01

This paper develops an optimal reservoir Refill Hedging Rule (RHR) for combined water supply and flood operation using mathematical analysis. A two-stage model is developed to formulate the trade-off between operations for conservation benefit and flood damage in the reservoir refill season. Based on the probability distribution of the maximum refill water availability at the end of the second stage, three zones are characterized according to the relationship among storage capacity, expected storage buffer (ESB), and maximum safety excess discharge (MSED). The Karush-Kuhn-Tucker conditions of the model show that the optimality of the refill operation involves making the expected marginal loss of conservation benefit from unfilling (i.e., ending storage of refill period less than storage capacity) as nearly equal to the expected marginal flood damage from levee overtopping downstream as possible while maintaining all constraints. This principle follows and combines the hedging rules for water supply and flood management. A RHR curve is drawn analogously to water supply hedging and flood hedging rules, showing the trade-off between the two objectives. The release decision result has a linear relationship with the current water availability, implying the linearity of RHR for a wide range of water conservation functions (linear, concave, or convex). A demonstration case shows the impacts of factors. Larger downstream flood conveyance capacity and empty reservoir capacity allow a smaller current release and more water can be conserved. Economic indicators of conservation benefit and flood damage compete with each other on release, the greater economic importance of flood damage is, the more water should be released in the current stage, and vice versa. Below a critical value, improving forecasts yields less water release, but an opposing effect occurs beyond this critical value. Finally, the Danjiangkou Reservoir case study shows that the RHR together with a rolling horizon decision approach can lead to a gradual dynamic refilling, indicating its potential for practical use.

Work Physiology Evaluation of Laundry Workers

NASA Astrophysics Data System (ADS)

Sari, A. D.; Suryoputro, M. R.; Pramaningtyas, M. D.; Putra, P. S.; Maulidyawati, S. B.

2016-01-01

This study aimed to assess cardiovascular strain during laundry operations in terms of physical workload, based on heart rate changes and level of pain complaints. Researchers measured resting and working heart rates and calculated cardiovascular load (%CVL), cardiovascular strain (%CVS), reserve heart rate (%RHR), energy expenditure, oxygen consumption, and measure level of pain complain in 6 laundry workers using Nordic Body Map questionnaire (NBM). Based on the result of %CVL and %CVS, the work in laundry was classified as acceptable level. Similarly, a high-level category was recorded for %RHR in moderate of energy expenditure. However, there are very pain level complain for hand using NBM questionnaire. Thus, there is a need to redesign the work content of equipment used and keep the physical workload in acceptable level, as this will increase their productivity and reduce their health risk.

Practical on-site measurement of heat strain with the use of a perceptual strain index.

PubMed

Chan, Albert P C; Yang, Y

2016-02-01

There have been increased interests in research on quantifying heat strain of construction workers and formulating corresponding guidelines for working in hot weather. The aim of this study was to validate a subjective measurement tool, the perceptual strain index (PeSI), for measuring heat strain in real-work settings. A total of sixteen construction workers were invited to participate in the field surveys. Empiric-based human monitoring was carried out with simultaneous micrometeorological (wet-bulb globe temperature, WBGT), physiological (heart rate, HR), and perceptual (perceived exertion, RPE; thermal sensation, TS) measurements throughout the test. The relative heart rate (RHR), the physiological strain index (PSIHR), and the PeSI were then calculated accordingly. The PeSI exhibited moderate correlations with WBGT and RHR (r = 0.42 and 0.40, respectively), which indicated the PeSI was sensitive to the variants of WBGT and RHR. The results of regression analysis indicated that the PeSI changed in the same general manner as the PSIHR, with a relatively large determination coefficient (R(2) = 0.67). The established perceptual strain zone illustrated that the PeSI ranging from 7 to 8 would be the exposure limit of construction workers in hot weather. The PeSI is a simple, robust, reliable, and user-friendly tool for heat strain assessment in occupational settings. The perceptual strain zone will provide practical guidelines for on-site heat strain monitoring for construction workers.

Steps through the revision process of reproductive health sections of ICD-11.

PubMed

Chou, Doris; Tunçalp, Özge; Hotamisligil, Selen; Norman, Jane; Say, Lale; Volkmer, Björn; Pattinson, Bob; Rooney, Cleo; Serour, Gamal; de Mouzon, Jacques; Gardosi, Jason; Thueroff, Joachim; Mark, Morgan; D'Hooghe, Thomas

2012-01-01

In 2007, the WHO initiated an organizational structure for the 11th revision of the International Classification of Diseases (ICD). Effective deployment of ICD-derived tools facilitates the use and collection of health information in a variety of resource settings, promoting quantitatively informed decisions. They also facilitate comparison of disease incidence and outcomes between different countries and different health care systems around the world. The Department of Reproductive Health and Research (RHR) coordinates the revision of chapters 14 (diseases of the genitourinary system), 15 (pregnancy, childbirth, and puerperium), and 16 (conditions originating in the perinatal period). RHR convened a technical advisory group (TAG), the Genito-Urinary Reproductive Medicine (GURM) TAG, for the ICD revision. The TAG's work reflects the collective understanding of sexual and reproductive health and is now available for review within the ICD-11 revision process. Copyright © 2012 S. Karger AG, Basel.

Hemodynamic responses of unfit healthy women at a training session with nintendo wii: a possible impact on the general well-being.

PubMed

Monteiro-Junior, Renato S; Figueiredo, Luiz F; Conceição, Isabel; Carvalho, Carolina; Lattari, Eduardo; Mura, Gioia; Machado, Sérgio; da Silva, Elirez B

2014-01-01

The purpose of this study was assess the effect of a training session with Nintendo Wii® on the hemodynamic responses of healthy women not involved in regular physical exercise. Twenty-five healthy unfit women aged 28 ± 6 years played for 10 minutes the game Free Run (Wii Fit Plus). The resting heart rate (RHR), systolic and diastolic blood pressures (SBP and DBP), and double (rate-pressure) product (DP) were measured before and after activity. The HR during the activity (exercise heart rate, EHR) was measured every minute. A statistically significant difference was observed between the RHR (75 ± 9 bpm) and the mean EHR (176 ± 15 bpm) (P < 0.001). The EHR remained in the target zone for aerobic exercise until the fifth minute of activity, which coincided with the upper limit of the aerobic zone (80% heart rate reserve (HRR) + RHR) from the sixth to tenth minute. The initial (110 ± 8 mmHg) and final (145 ± 17 mmHg) SBP (P < 0.01) were significantly different, as were the initial (71 ± 8 mmHg) and final (79 ± 9 mmHg) DBP (P < 0.01). A statistically significant difference was observed between the pre- (8.233 ± 1.141 bpm-mmHg) and post-activity (25.590 ± 4.117 bpm-mmHg) DP (P < 0.01). Physical exercise while playing Free Run sufficed to trigger acute hemodynamic changes in healthy women who were not engaged in regular physical exercise.

Hemodynamic Responses of Unfit Healthy Women at a Training Session with Nintendo Wii: A Possible Impact on the General Well-Being

PubMed Central

Monteiro-Junior, Renato S; Figueiredo, Luiz F; Conceição, Isabel; Carvalho, Carolina; Lattari, Eduardo; Mura, Gioia; Machado, Sérgio; da Silva, Elirez B

2014-01-01

Aims: The purpose of this study was assess the effect of a training session with Nintendo Wii® on the hemodynamic responses of healthy women not involved in regular physical exercise. Method: Twenty-five healthy unfit women aged 28 ± 6 years played for 10 minutes the game Free Run (Wii Fit Plus). The resting heart rate (RHR), systolic and diastolic blood pressures (SBP and DBP), and double (rate-pressure) product (DP) were measured before and after activity. The HR during the activity (exercise heart rate, EHR) was measured every minute. Results: A statistically significant difference was observed between the RHR (75 ± 9 bpm) and the mean EHR (176 ± 15 bpm) (P < 0.001). The EHR remained in the target zone for aerobic exercise until the fifth minute of activity, which coincided with the upper limit of the aerobic zone (80% heart rate reserve (HRR) + RHR) from the sixth to tenth minute. The initial (110 ± 8 mmHg) and final (145 ± 17 mmHg) SBP (P < 0.01) were significantly different, as were the initial (71 ± 8 mmHg) and final (79 ± 9 mmHg) DBP (P < 0.01). A statistically significant difference was observed between the pre- (8.233 ± 1.141 bpm-mmHg) and post-activity (25.590 ± 4.117 bpm-mmHg) DP (P < 0.01). Conclusion: Physical exercise while playing Free Run sufficed to trigger acute hemodynamic changes in healthy women who were not engaged in regular physical exercise. PMID:25614754

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandl, V.; Oliveira, L.

A portable alpha monitor with solid state detectors is described. The full scale range is 1000 p.p.s., and an auditive indication is also provided. The battery life is about 70 hr. The instrument operates correctly in a gamma field up to 8 r/hr. (auth)

Leptin Regulation of Gonadotrope Gonadotropin-Releasing Hormone Receptors As a Metabolic Checkpoint and Gateway to Reproductive Competence

PubMed Central

Odle, Angela K.; Akhter, Noor; Syed, Mohsin M.; Allensworth-James, Melody L.; Beneš, Helen; Melgar Castillo, Andrea I.; MacNicol, Melanie C.; MacNicol, Angus M.; Childs, Gwen V.

2018-01-01

The adipokine leptin signals the body’s nutritional status to the brain, and particularly, the hypothalamus. However, leptin receptors (LEPRs) can be found all throughout the body and brain, including the pituitary. It is known that leptin is permissive for reproduction, and mice that cannot produce leptin (Lep/Lep) are infertile. Many studies have pinpointed leptin’s regulation of reproduction to the hypothalamus. However, LEPRs exist at all levels of the hypothalamic–pituitary–gonadal axis. We have previously shown that deleting the signaling portion of the LEPR specifically in gonadotropes impairs fertility in female mice. Our recent studies have targeted this regulation to the control of gonadotropin releasing hormone receptor (GnRHR) expression. The hypotheses presented here are twofold: (1) cyclic regulation of pituitary GnRHR levels sets up a target metabolic checkpoint for control of the reproductive axis and (2) multiple checkpoints are required for the metabolic signaling that regulates the reproductive axis. Here, we emphasize and explore the relationship between the hypothalamus and the pituitary with regard to the regulation of GnRHR. The original data we present strengthen these hypotheses and build on our previous studies. We show that we can cause infertility in 70% of female mice by deleting all isoforms of LEPR specifically in gonadotropes. Our findings implicate activin subunit (InhBa) mRNA as a potential leptin target in gonadotropes. We further show gonadotrope-specific upregulation of GnRHR protein (but not mRNA levels) following leptin stimulation. In order to try and understand this post-transcriptional regulation, we tested candidate miRNAs (identified with in silico analysis) that may be binding the Gnrhr mRNA. We show significant upregulation of one of these miRNAs in our gonadotrope-Lepr-null females. The evidence provided here, combined with our previous work, lay the foundation for metabolically regulated post-transcriptional control of the gonadotrope. We discuss possible mechanisms, including miRNA regulation and the involvement of the RNA binding protein, Musashi. We also demonstrate how this regulation may be vital for the dynamic remodeling of gonadotropes in the cycling female. Finally, we propose that the leptin receptivity of both the hypothalamus and the pituitary are vital for the body’s ability to delay or slow reproduction during periods of low nutrition. PMID:29354094

Impaired motorcycle operation, final report. Volume 1, Riders helping riders evaluation

DOT National Transportation Integrated Search

2008-08-01

Riders Helping Riders (RHR) is an instructional program designed to encourage motorcyclists to intervene to prevent drinking and riding by their motorcyclist peers. The program is based on focus group research which found that riders consider themsel...

Impaired motorcycle operation, final report. Volume 3, Riders helping riders student manual

DOT National Transportation Integrated Search

2007-08-22

Riders Helping Riders (RHR) is an instructional program designed to encourage motorcyclists to intervene to prevent drinking and riding by their motorcyclist peers. The program is based on focus group research which found that riders consider themsel...

Impaired motorcycle operation, final report. Volume 2, Riders helping riders instructor manual

DOT National Transportation Integrated Search

2007-08-22

Riders Helping Riders (RHR) is an instructional program designed to encourage motorcyclists to intervene to prevent drinking and riding by their motorcyclist peers. The program is based on focus group research which found that riders consider themsel...

Primary hypogonadism in gonadotropin-releasing hormone II receptor knockdown boars

USDA-ARS?s Scientific Manuscript database

Paradoxically, the second mammalian GnRH isoform (GnRH-II) and its receptor (GnRHR-II) are not physiological regulators of gonadotropin secretion. Instead, our data suggests that both are abundantly produced in the porcine testis and mediate testosterone secretion, independent of luteinizing hormone...

Response of shortgrass Plains vegetation to chronic and seasonally administered gamma radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraley, Jr., Leslie

1971-08-01

In order to determine the effect of radiation on the structure of native shortgrass plains vegetation, an 8750 Ci 137Cs source was installed on the Central Plains Experimental Range near Nunn, Colorado; The experimental area was divided into 6 treatment sectors, a control, 2 sectors for chronic exposure (irradiation initiated April 1969 and continuing as of August 1971), and one each for spring, summer and late fall seasonal semi-acute (30 day), exposures which were administered during April, July and December, 1969, respectively. Community structure was measured by coefficient of community and diversity index. Yield was determined by clipping plots inmore » September 1970 and visual estimates in September 1969 and 1970 for the grass-sedge component of the vegetation. Individual species sensitivity was determined by density data recorded in April, June and September of 1969 and 1970 and by a phenological index recorded at weekly intervals during the 1969 and 1970 growing seasons. The response of the vegetation was similar whether determined by coefficient of community or diversity with diversity being a more sensitive measure of effects. In the chronically exposed sectors, the exposure rate which resulted in a 50 per cent reduction in these 2 parameters (CC50 or D50) was still decreasing the second growing season and was approximately 18 R/hr for the CC50 as of June 1970 and 10 R/hr for the D50 as of September 1970. For the seasonally exposed sectors, the late fall period (December, 1969) was the most sensitive, summer (July, 1969) the least sensitive and spring (April, 1969) intermediate with CC50 and D50 values of 195 and 90, 240 and 222, and 120 and 74 R/hr for the spring, summer and late fall exposed sectors, respectively. Yield and density data indicated a rapid revegetation of the spring and summer exposed sectors during 1970 as a result of an influx of invader species such as Salsola kali tenuifolia, Chenopodium leptophyllum and Lepidium densiflorum and the reappearance of perennials with underground perennating organs such as Lygodesmia juncea, Gaura coccinea and Oenothera coronopifolia. The most sensitive indicator of radiation damage was the phenological index with a chronic exposure rate of 1 R/hr delaying the development of Tradescantia occidentalis and Opuntia polyacantha. The shortgrass plains vegetation appears to be one of the most resistant community types studied to date with semi-acute exposures of 45 to 75 kR necessary to decrease diversity to 50 per cent of the control value.« less

Dairy and nondairy beverage consumption for childhood atopic eczema: what health advice to give?

PubMed

Hon, K L; Tsang, Y C; Poon, T C W; Pong, N H H; Luk, N M; Leung, T N H; Chow, C M; Leung, T F

2016-03-01

Many parents of children with atopic eczema (AE) practise empirical dietary avoidance and supplementation, and seek healthcare advice on whether consumption of dairy and nondairy beverages may be beneficial or detrimental for this condition. We investigated if frequency of consumption of beverages was associated with disease severity and quality of life (QoL). Parent-reported frequency of drinks and beverages were recorded in consecutive children with AE, and disease severity (Nottingham Eczema Severity Score; NESS), QoL (Children's Dermatology Life Quality Index; CDLQI), skin hydration (SH), transepidermal water loss (TEWL), blood pressure (BP), resting heart rate (RHR) and body mass index (BMI) were evaluated. AE was associated with worse QoL than miscellaneous non-AE skin diseases (P < 0.001). Compared with children without AE, there was a trend for children with AE to drink less milk (P = 0.06) and more miscellaneous beverages (such as Chinese herbal tea and soymilk; P = 0.03). In children with AE, NESS correlated with CDLQI (ρ = 0.66, P < 0.001) and reduced SH (ρ = -0.32, P < 0.001), whereas CDLQI correlated with a higher RHR (ρ = 0.25, P < 0.01). Multiple logistic regression showed that male sex (OR = 0.44, 95% CI 0.20-0.97; P = 0.04) and drinking fresh milk (OR = 0.42, 95% CI 0.20-0.93; P = 0.03) were independent factors associated with less severe disease. Moderate to severe impairment of CDLQI was associated with NESS (OR = 1.48, 95% CI 1.28-1.71; P < 0.001) and RHR (OR = 1.05, 95% CI 1.02-1.08; P < 0.01) but not with reported habits of beverage consumption. Concerning cardiovascular health in AE, frequency of formula milk consumption was associated with RHR (ρ = 0.17, P = 0.04), and soft drink consumption was associated with higher systolic blood pressure (SBP) (ρ = 0.18, P = 0.04). This study provides evidence for parental/patient guidance. Children with AE who reported more fresh milk consumption had less severe disease. There was no correlation between consumption of nondairy beverages with disease severity or QoL, but frequency of soft drink consumption correlated with SBP. With these results being supported by a literature review, it is reasonable to advise parents that fresh milk can be consumed by unsensitized children with AE. Soft drinks and other beverages should not be consumed in excess for optimal cardiovascular health and for other health reasons. © 2015 British Association of Dermatologists.

Aberrant secretion of 10 gonadal steroids in gonadotropin-releasing hormone II receptor knockdown boars

USDA-ARS?s Scientific Manuscript database

Paradoxically, the second mammalian GnRH isoform (GnRH-II) and its receptor (GnRHR-II) are not physiological regulators of gonadotropin secretion. Instead, data from our laboratory suggests that both are abundantly produced in the porcine testis and mediate testosterone secretion independent of lute...

Testis composition and steroidogenic protein abundance in GnRH-II receptor knockdown boars

USDA-ARS?s Scientific Manuscript database

Testosterone, secreted from Leydig cells, is classically stimulated by luteinizing hormone (LH) from the anterior pituitary gland, but an LH-independent mechanism of testosterone production has also been identified in the boar. Gonadotropin-releasing hormone II (GnRH-II) and its receptor (GnRHR-II) ...

Chitosan-based DNA delivery vector targeted to gonadotropin-releasing hormone (GnRH) receptor.

PubMed

Boonthum, Chatwalee; Namdee, Katawut; Boonrungsiman, Suwimon; Chatdarong, Kaywalee; Saengkrit, Nattika; Sajomsang, Warayuth; Ponglowhapan, Suppawiwat; Yata, Teerapong

2017-02-10

The main purpose of this study was to investigate the application of modified chitosan as a potential vector for gene delivery to gonadotropin-releasing hormone receptor (GnRHR)-expressing cells. Such design of gene carrier could be useful in particular for gene therapy for cancers related to the reproductive system, gene disorders of sexual development, and contraception and fertility control. In this study, a decapeptide GnRH was successfully conjugated to chitosan (CS) as confirmed by proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The synthesized GnRH-conjugated chitosan (GnRH-CS) was able to condense DNA to form positively charged nanoparticles and specifically deliver plasmid DNA to targeted cells in both two-dimensional (2D) and three-dimensional (3D) cell cultures systems. Importantly, GnRH-CS exhibited higher transfection activity compared to unmodified CS. In conclusion, GnRH-conjugated chitosan can be a promising carrier for targeted DNA delivery to GnRHR-expressing cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Background radiation dose of dumpsites in Ota and Environs

NASA Astrophysics Data System (ADS)

Usikalu, M. R.; Ola, O. O.; Achuka, J. A.; Babarimisa, I. O.; Ayara, W. A.

2017-05-01

In-situ measurement of background radiation dose from selected dumpsites in Ota and its environs was done using Radialert Nuclear Radiation Monitor (Digilert 200). Ten measurements were taken from each dumpsite. The measured background radiation range between 0.015 mRhr-1 for AOD and 0.028 mRhr-1 for SUS dumpsites. The calculated annual equivalent doses vary between 1.31 mSvyr-1 for AOD and 2.28 mSv/yr for SUS dumpsites. The air absorbed dose calculated ranged from 150 nGyhr-1 to 280 nGy/hr for AOD and SUS dumpsites respectively with an average value of 217 nGyhr-1 for all the locations. All the estimated parameters were higher than permissible limit set for background radiation for the general public. Conclusively, the associated challenge and radiation burden posed by the wastes on the studied locations and scavengers is high. Therefore, there is need by the regulatory authorities to look into the way and how waste can be properly managed so as to alleviate the effects on the populace leaving and working in the dumpsites vicinity.

Motion-dependent levels of order in a relativistic universe.

PubMed

Frieden, B Roy; Petri, Michael

2012-09-01

Consider a generally closed system of continuous three-space coordinates x with a differentiable amplitude function ψ(x). What is its level of order R? Define R by the property that it decreases (or stays constant) after the system is coarse grained. Then R turns out to obey R=8(-1)L(2)I,where quantity I=4∫dx[nabla]ψ(*)·[nabla]ψ is the classical Fisher information in the system and L is the longest chord that can connect two points on the system surface. In general, order R is (i) unitless, and (ii) invariant to uniform stretch or compression of the system. On this basis, the order R in the Universe was previously found to be invariant in time despite its Hubble expansion, and with value R=26.0×10(60) for flat space. By comparison, here we model the Universe as a string-based "holostar," with amplitude function ψ(x)[proportionality]1/r over radial interval r=(r(0),r(H)). Here r(0) is of order the Planck length and r(H) is the radial extension of the holostar, estimated as the known value of the Hubble radius. Curvature of space and relative motion of the observer must now be taken into account. It results that a stationary observer observes a level of order R=(8/9)(r(H)/r(0))(3/2)=0.42×10(90); while for a free-falling observer R=2(-1)(r(H)/r(0))(2)=0.85×10(120). Both order values greatly exceed the above flat-space value. Interestingly, they are purely geometric measures, depending solely upon ratio r(H)/r(0). Remarkably, the free-fall value ~10(120) of R approximates the negentropy of a universe modeled as discrete. This might mean that the Universe contains about equal amounts of continuous and discrete structure.

Association of pulmonary, cardiovascular, and hematologic metrics with carbon nanotube and nanofiber exposure among U.S. workers: a cross-sectional study.

PubMed

Schubauer-Berigan, Mary K; Dahm, Matthew M; Erdely, Aaron; Beard, John D; Eileen Birch, M; Evans, Douglas E; Fernback, Joseph E; Mercer, Robert R; Bertke, Stephen J; Eye, Tracy; de Perio, Marie A

2018-05-16

Commercial use of carbon nanotubes and nanofibers (CNT/F) in composites and electronics is increasing; however, little is known about health effects among workers. We conducted a cross-sectional study among 108 workers at 12 U.S. CNT/F facilities. We evaluated chest symptoms or respiratory allergies since starting work with CNT/F, lung function, resting blood pressure (BP), resting heart rate (RHR), and complete blood count (CBC) components. We conducted multi-day, full-shift sampling to measure background-corrected elemental carbon (EC) and CNT/F structure count concentrations, and collected induced sputum to measure CNT/F in the respiratory tract. We measured (nonspecific) fine and ultrafine particulate matter mass and count concentrations. Concurrently, we conducted physical examinations, BP measurement, and spirometry, and collected whole blood. We evaluated associations between exposures and health measures, adjusting for confounders related to lifestyle and other occupational exposures. CNT/F air concentrations were generally low, while 18% of participants had evidence of CNT/F in sputum. Respiratory allergy development was positively associated with inhalable EC (p=0.040) and number of years worked with CNT/F (p=0.008). No exposures were associated with spirometry-based metrics or pulmonary symptoms, nor were CNT/F-specific metrics related to BP or most CBC components. Systolic BP was positively associated with fine particulate matter (p-values: 0.015-0.054). RHR was positively associated with EC, at both the respirable (p=0.0074) and inhalable (p=0.0026) size fractions. Hematocrit was positively associated with the log of CNT/F structure counts (p=0.043). Most health measures were not associated with CNT/F. The positive associations between CNT/F exposure and respiratory allergies, RHR, and hematocrit counts may not be causal and require examination in other studies.

INFLUENCE OF $gamma$-IRRADIATION ON SOME KINDS OF FRUITS AND ON CANNED FRUIT (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khatiashvili, Sh.M.; Tsetskhladze, T.V.; Cherkezishvili, L.I.

1960-01-01

Some results of observations of changes in organoleptic properties of different fresh fruits, their juices, and canned fruit under the influence of gamma irradiation (Co/sup 60/) are given. Irradiation of green persimmons to 1.5 million roentgen at 8500 r/hr leads to the gradual artificial ripening of the fruits. They do not gain any strange taste and are sweeter than the controls. During the same period of time the control green persimmons wither. Figs irradiated with 1.5 million roentgen are well conserved in hermetically closed jars for several weeks without changing their taste. Control flgs go sour in 2 to 3more » days under the same conditions. A wild plum is well conserved under gamma irradiation during a month without any changes of its taste or appearance. The total dose reached 1 miilion rcentgen per month. Control plums wither and rot after two or three days. Peaches irradiated in hermetically closed jars conserve their freshness, consistence, color, and taste for weeks when irradiated with 1.5 million roentgen at 8500 r/hr. With further storage the smell and taste of peaches changes sharply, but the appearance and consistence are conserved without any changes for more than 7 months. The control peaches under the same conditions of storage rot after 4 to 5 days. Tangerines and lemons under irradiation acquire a strange taste beginning at 100 thousand roentgen. If they are irradiated with 750 thousand roentgen, the period of storage is doubled or tripled. The irradiated tangerines have the taste of boiled ones. Grapes under the influence of gamma irradiation begin to spoil at 10000 r. Pink and black cherries are conserved for several weeks without changing their organoleptic properties if the dose is 750,000 r and the dose rate is 8500 r/hr. (auth)« less

Foetal hypothalamic and pituitary expression of gonadotrophin-releasing hormone and galanin systems is disturbed by exposure to sewage sludge chemicals via maternal ingestion.

PubMed

Bellingham, M; Fowler, P A; Amezaga, M R; Whitelaw, C M; Rhind, S M; Cotinot, C; Mandon-Pepin, B; Sharpe, R M; Evans, N P

2010-06-01

Animals and humans are chronically exposed to endocrine disrupting chemicals (EDCs) that are ubiquitous in the environment. There are strong circumstantial links between environmental EDC exposure and both declining human/wildlife reproductive health and the increasing incidence of reproductive system abnormalities. The verification of such links, however, is difficult and requires animal models exposed to 'real life', environmentally relevant concentrations/mixtures of environmental contaminants (ECs), particularly in utero, when sensitivity to EC exposure is high. The present study aimed to determine whether the foetal sheep reproductive neuroendocrine axis, particularly gondotrophin-releasing hormone (GnRH) and galaninergic systems, were affected by maternal exposure to a complex mixture of chemicals, applied to pasture, in the form of sewage sludge. Sewage sludge contains high concentrations of a spectrum of EDCs and other pollutants, relative to environmental concentrations, but is frequently recycled to land as a fertiliser. We found that foetuses exposed to the EDC mixture in utero through their mothers had lower GnRH mRNA expression in the hypothalamus and lower GnRH receptor (GnRHR) and galanin receptor (GALR) mRNA expression in the hypothalamus and pituitary gland. Strikingly, this, treatment had no significant effect on maternal GnRH or GnRHR mRNA expression, although GALR mRNA expression within the maternal hypothalamus and pituitary gland was reduced. The present study clearly demonstrates that the developing foetal neuroendocrine axis is sensitive to real-world mixtures of environmental chemicals. Given the important role of GnRH and GnRHR in the regulation of reproductive function, its known role programming role in utero, and the role of galanin in the regulation of many physiological/neuroendocrine systems, in utero changes in the activity of these systems are likely to have long-term consequences in adulthood and represent a novel pathway through which EC mixtures could perturb normal reproductive function.

77 FR 25753 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-01

... provide post accident design basis cooling. Therefore, the proposed change does not involve a significant... operating margin inherent in the design orifices of the RHR suppression pool cooling test return line and... information in comment submissions that you do not want to be publicly disclosed. The NRC posts all comment...

77 FR 11452 - Approval and Promulgation of Air Quality Implementation Plans; State of Georgia; Regional Haze...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... Problem B. Requirements of the CAA and EPA's Regional Haze Rule (RHR) C. Roles of Agencies in Addressing.... The Regional Haze Problem Regional haze is visibility impairment that is produced by a multitude of... of kilometers. Therefore, to effectively address the problem of visibility impairment in Class I...

77 FR 42833 - Approval, Disapproval and Promulgation of Air Quality Implementation Plans; Arizona; Regional...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-20

... the problem of visibility impairment in Class I areas, states, or the EPA when implementing a FIP... explanation and rationale for its determinations. While we find these problems in all of ADEQ's BART analyses... problems resulted in control determinations that are inconsistent with the RHR and the BART Guidelines. We...

GnRH-II and its receptor are critical regulators of testicular steroidogenesis in swine

USDA-ARS?s Scientific Manuscript database

The second mammalian form of GnRH (GnRH-II) and its receptor (GnRHR-II) are produced in one livestock species, the pig. However, the interaction of GnRH-II with its receptor does not stimulate gonadotropin secretion. Instead, both are abundantly produced in the gonads and have been implicated in aut...

Effect of gonadotropin-releasing hormone II receptor (GnRHR-II) knockdown on testosterone secretion in the boar

USDA-ARS?s Scientific Manuscript database

Unlike the classical gonadotropin-releasing hormone (GnRH-I), the second mammalian GnRH isoform (GnRH-II; His5, Trp7, Tyr8) is a poor stimulator of gonadotropin secretion. In addition, GnRH-II is ubiquitously expressed, with transcript levels highest in tissues outside of the brain. A receptor speci...

Published methodological quality of randomized controlled trials does not reflect the actual quality assessed in protocols

PubMed Central

Mhaskar, Rahul; Djulbegovic, Benjamin; Magazin, Anja; Soares, Heloisa P.; Kumar, Ambuj

2011-01-01

Objectives To assess whether reported methodological quality of randomized controlled trials (RCTs) reflect the actual methodological quality, and to evaluate the association of effect size (ES) and sample size with methodological quality. Study design Systematic review Setting Retrospective analysis of all consecutive phase III RCTs published by 8 National Cancer Institute Cooperative Groups until year 2006. Data were extracted from protocols (actual quality) and publications (reported quality) for each study. Results 429 RCTs met the inclusion criteria. Overall reporting of methodological quality was poor and did not reflect the actual high methodological quality of RCTs. The results showed no association between sample size and actual methodological quality of a trial. Poor reporting of allocation concealment and blinding exaggerated the ES by 6% (ratio of hazard ratio [RHR]: 0.94, 95%CI: 0.88, 0.99) and 24% (RHR: 1.24, 95%CI: 1.05, 1.43), respectively. However, actual quality assessment showed no association between ES and methodological quality. Conclusion The largest study to-date shows poor quality of reporting does not reflect the actual high methodological quality. Assessment of the impact of quality on the ES based on reported quality can produce misleading results. PMID:22424985

Remote-handled/special case TRU waste characterization summary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Detamore, J.A.

1984-03-30

TRU wastes are those (other than high level waste) contaminated with specified quantities of certain alpha-emitting radionuclides of long half-life and high specific radiotoxicity. TRU waste is defined as /sup 226/Ra isotopic sources and those other materials that, without regard to source or form, are contaminated with transuranic elements with half-lives greater than 20 years, and have TRU alpha contamination greater than 100 nCi/g. RH TRU waste has high beta and gamma radiation levels, up to 30,000 R/hr, and thermal output may be a few hundred watts per container. The radiation levels in most of this remotely handled (RH) TRUmore » waste, however, are below 100 R/hr. Remote-handled wastes are stored at Los Alamos, Hanford, Oak Ridge, and the Idaho National Engineering Laboratory. This report presents a site by site discussion of RH waste handling, placement, and container data. This is followed by a series of data tables that were compiled in the TRU Waste Systems Office. These tables are a compendium of data that are the most up to date and accurate data available today. 10 tables.« less

LH independent testosterone production is mediated by the interaction between GnRH-II and its receptor in the boar testis

USDA-ARS?s Scientific Manuscript database

The second mammalian isoform of gonadotropin-releasing hormone (GnRH-II) functions quite differently from the classical form (GnRH-I), being an ineffective modulator of gonadotropin release. Not all species that produce GnRH-II maintain a full length GnRH-II receptor (GnRHR-II). Instead, GnRH-II can...

Analytical model of flame spread in full-scale room/corner tests (ISO9705)

Treesearch

Mark Dietenberger; Ondrej Grexa

1999-01-01

A physical, yet analytical, model of fire growth has predicted flame spread and rate of heat release (RHR) for an ISO9705 test scenario using bench-scale data from the cone calorimeter. The test scenario simulated was the propane ignition burner at the comer with a 100/300 kW program and the specimen lined on the walls only. Four phases of fire growth were simulated....

Published methodological quality of randomized controlled trials does not reflect the actual quality assessed in protocols.

PubMed

Mhaskar, Rahul; Djulbegovic, Benjamin; Magazin, Anja; Soares, Heloisa P; Kumar, Ambuj

2012-06-01

To assess whether the reported methodological quality of randomized controlled trials (RCTs) reflects the actual methodological quality and to evaluate the association of effect size (ES) and sample size with methodological quality. Systematic review. This is a retrospective analysis of all consecutive phase III RCTs published by eight National Cancer Institute Cooperative Groups up to 2006. Data were extracted from protocols (actual quality) and publications (reported quality) for each study. Four hundred twenty-nine RCTs met the inclusion criteria. Overall reporting of methodological quality was poor and did not reflect the actual high methodological quality of RCTs. The results showed no association between sample size and actual methodological quality of a trial. Poor reporting of allocation concealment and blinding exaggerated the ES by 6% (ratio of hazard ratio [RHR]: 0.94; 95% confidence interval [CI]: 0.88, 0.99) and 24% (RHR: 1.24; 95% CI: 1.05, 1.43), respectively. However, actual quality assessment showed no association between ES and methodological quality. The largest study to date shows that poor quality of reporting does not reflect the actual high methodological quality. Assessment of the impact of quality on the ES based on reported quality can produce misleading results. Copyright © 2012 Elsevier Inc. All rights reserved.

Functional significance of GnRH and kisspeptin, and their cognate receptors in teleost reproduction.

PubMed

Gopurappilly, Renjitha; Ogawa, Satoshi; Parhar, Ishwar S

2013-01-01

Guanine nucleotide binding protein (G-protein)-coupled receptors (GPCRs) are eukaryotic transmembrane proteins found in all living organisms. Their versatility and roles in several physiological processes make them the single largest family of drug targets. Comparative genomic studies using various model organisms have provided useful information about target receptors. The similarity of the genetic makeup of teleosts to that of humans and other vertebrates aligns with the study of GPCRs. Gonadotropin-releasing hormone (GnRH) represents a critical step in the reproductive process through its cognate GnRH receptors (GnRHRs). Kisspeptin (Kiss1) and its cognate GPCR, GPR54 (=kisspeptin receptor, Kiss-R), have recently been identified as a critical signaling system in the control of reproduction. The Kiss1/Kiss-R system regulates GnRH release, which is vital to pubertal development and vertebrate reproduction. This review highlights the physiological role of kisspeptin-Kiss-R signaling in the reproductive neuroendocrine axis in teleosts through the modulation of GnRH release. Moreover, we also review the recent developments in GnRHR and Kiss-R with respect to their structural variants, signaling mechanisms, ligand interactions, and functional significance. Finally, we discuss the recent progress in identifying many teleost GnRH-GnRHR and kisspeptin-Kiss-R systems and consider their physiological significance in the control of reproduction.

Terrain Analysis Procedural Guide for Surface Configuration.

DTIC Science & Technology

1984-03-01

34’’~ ,w j 0 V~l s A., ; 54 . ’ sC 01.,)f ttt’t 1.f’ &~~ w tS*’tCSA 𔄃’a Ats4 tArot A"- t𔃾 Do’ .’ a’’ SQ t#"N4 psCn9’A’ rhr ta4sto"%t ac’c- 40 " jpV*’ Ae

Comparison of yoga and walking-exercise on cardiac time intervals as a measure of cardiac function in elderly with increased pulse pressure.

PubMed

Patil, Satish Gurunathrao; Patil, Shankargouda S; Aithala, Manjunatha R; Das, Kusal Kanti

Arterial aging along with increased blood pressure(BP) has become the major cardiovascular(CV) risk in elderly. The aim of the study was to compare the effects of yoga program and walking-exercise on cardiac function in elderly with increased pulse pressure (PP). An open label, parallel-group randomized controlled study design was adopted. Elderly individuals aged ≥60 years with PP≥60mmHg were recruited for the study. Yoga (study) group (n=30) was assigned for yoga training and walking (exercise) group (n=30) for walking with loosening practices for one hour in the morning for 6days in a week for 3 months. The outcome measures were cardiac time intervals derived from pulse wave analysis and ECG: resting heart rate (RHR), diastolic time(DT), ventricular ejection time(LVET), upstroke time(UT), ejection duration index (ED%), pre-ejection period (PEP), rate pressure product (RPP) and percentage of mean arterial pressure (%MAP). The mean within-yoga group change in RHR(bpm) was 4.41 (p=0.031), PD(ms): -50.29 (p=0.042), DT(ms): -49.04 (p=0.017), ED%: 2.107 (p=0.001), ES(mmHg/ms): 14.62 (p=0.118), ET(ms): -0.66 (p=0.903), UT(ms): -2.54 (p=0.676), PEP(ms): -1.25 (p=0.11) and %MAP: 2.08 (p=0.04). The mean within-control group change in HR (bpm) was 0.35 (p=0.887), PD (ms): 11.15(p=0.717), DT (ms): 11.3 (p=0.706), ED%: -0.101 (p=0.936), ES (mmHg/ms): 0.75 (p=0.926), ET(ms): 2.2 (p=0.721), UT(ms):4.7(p=455), PEP (ms): 2.1(p=0.11), %MAP: 0.65 (p=0.451). A significant difference between-group was found in RHR (p=0.036), PD (p=0.02), ED% (p=0.049), LVET (p=0.048), DT (p=0.02) and RPP (p=0.001). Yoga practice for 3 months showed a significant improvement in diastolic function with a minimal change in systolic function. Yoga is more effective than walking in improving cardiac function in elderly with high PP. Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

National Economic Development Procedures Manual. Coastal Storm Damage and Erosion

DTIC Science & Technology

1991-09-01

study area is temperate with warm summers and moderate winters. The annual temperature averages approximately 53 degrees Fahrenheit (*F). On average ...January is the coolest month with a mean temperature of 32°F and July is the warmest month. The average annual precipitation is about 45 inches with...0704.0188 Public rooing burden for rhr$ LoIlecton of ,nformaton .s estma eO to average I hour oer resiorse including the time for resrewing inttuctiOn

Functional Significance of GnRH and Kisspeptin, and Their Cognate Receptors in Teleost Reproduction

PubMed Central

Gopurappilly, Renjitha; Ogawa, Satoshi; Parhar, Ishwar S.

2012-01-01

Guanine nucleotide binding protein (G-protein)-coupled receptors (GPCRs) are eukaryotic transmembrane proteins found in all living organisms. Their versatility and roles in several physiological processes make them the single largest family of drug targets. Comparative genomic studies using various model organisms have provided useful information about target receptors. The similarity of the genetic makeup of teleosts to that of humans and other vertebrates aligns with the study of GPCRs. Gonadotropin-releasing hormone (GnRH) represents a critical step in the reproductive process through its cognate GnRH receptors (GnRHRs). Kisspeptin (Kiss1) and its cognate GPCR, GPR54 (=kisspeptin receptor, Kiss-R), have recently been identified as a critical signaling system in the control of reproduction. The Kiss1/Kiss-R system regulates GnRH release, which is vital to pubertal development and vertebrate reproduction. This review highlights the physiological role of kisspeptin-Kiss-R signaling in the reproductive neuroendocrine axis in teleosts through the modulation of GnRH release. Moreover, we also review the recent developments in GnRHR and Kiss-R with respect to their structural variants, signaling mechanisms, ligand interactions, and functional significance. Finally, we discuss the recent progress in identifying many teleost GnRH-GnRHR and kisspeptin-Kiss-R systems and consider their physiological significance in the control of reproduction. PMID:23482509

Orthostatic responses at 4860 m in low, moderate, and high altitude residents.

PubMed

Davis, John E; Wagner, Dale R; Thorington, Jessica; Schall, Cory

2013-09-01

This study evaluated the influence of altitude of residence on orthostatic responses when exposed to high altitude. Data collection took place at the Carrel hut (4860 m) on Chimborazo in Ecuador. After being transported to the hut by vehicle, 69 people volunteered for the study. A 3-min stand test (rapid change from supine to standing) provided an orthostatic challenge while resting heart rate (RHR), systolic (SBP) and diastolic (DBP) blood pressures, and arterial oxygen saturation (SpO2) were measured. Participants were separated into four groups based on altitude of residence and ethnicity: LOW (<1500 m; n=15), MOD (1500-3000 m, n=30), and HIGH (>3000 m, n=11) Ecuadorians, and non-Ecuadorian lowlanders (NE-LOW, n=13). Supine and standing RHRs were lower (p<0.05) for HIGH compared to other groups. Furthermore, standing increased RHR in LOW, MOD, and NE-LOW by 11.9 ± 5.3, 9.5 ± 4.1, and 11.6 ± 7.4 bpm, respectively, while HIGH stayed the same (0.6 bpm increase ± 3.3). Additionally, mean arterial pressure decreased slightly but not significantly upon standing in all groups except HIGH. The difference in Spo2 among groups was not significant (p>0.05). Altitude of residence influences the cardiovascular responses to orthostatic stress with HIGH having blunted responses and greater tolerance.

Measurement of Functional Capacity Requirements of Farmers: IMPLICATIONS FOR A CARDIAC REHABILITATION TRAINING PROGRAM.

PubMed

Jordan, Shannon; Karcher, Justin; Rogers, Rebecca; Kennedy, Kathleen; Lawrence, Anne; Adams, Jenny

2017-03-01

Updated cardiac rehabilitation (CR) and return-to-work guidelines from the American College of Sports Medicine (ACSM) now include specificity of training for industrial athletes (exercise training that involves the muscle groups, movements, and energy systems that these patients use during occupational tasks). However, many CR facilities do not apply this principle, relying instead on the traditional protocol that consists primarily of aerobic exercise. This study was conducted to measure the metabolic cost of typical farming tasks and to compare 2 methods of calculating training intensities. Metabolic data were collected from 28 participants (23 men and 5 women, aged 18 to 57 years) while they loaded 10 hay bales, dug a fence posthole, filled 8 seed hoppers, and shoveled grain. Mean metabolic equivalent levels during these activities were 5.9 to 7.6 and participants reached 60% to 70% of heart rate reserve (HRR). By comparison, their mean resting heart rate + 30 beats per minute (RHR+30, a traditional CR intensity level) represented only 28% of HRR. Participants in the current study performed farming tasks within the ACSM's recommended range of 40% to 80% of HRR, and the results suggest that training at RHR+30 would have been inadequate for helping a farmer return to work after a cardiac event. Using the study tasks as a basis, we described exercises that would be appropriate for the supervised resistance training of farmers in a CR setting.

Identification of an ionotropic glutamate receptor AMPA1/GRIA1 polymorphism in crossbred beef cows differing in fertility.

PubMed

Cushman, R A; Miles, J R; Rempel, L A; McDaneld, T G; Kuehn, L A; Chitko-McKown, C G; Nonneman, D; Echternkamp, S E

2013-06-01

A proposed functional polymorphism in the ionotropic glutamate receptor AMPA1 (GRIA1) has been reported to influence antral follicle numbers and fertility in cows. Repeat breeder cows that fail to produce a calf in multiple seasons have been reported to have reduced numbers of small (1 to 3 mm) antral follicles in their ovaries. Therefore, we tested the hypothesis that this GRIA1 polymorphism was affecting antral follicle numbers in repeat breeder cows. Repeat breeder cows (n = 64) and control cows (n = 72) that had always produced a calf were housed in a dry lot and observed twice daily for behavioral estrus. Blood samples were collected, and cows were genotyped for this GRIA1 polymorphism and for a polymorphism in the GnRH receptor (GnRHR) that was proposed to influence age at puberty. On d 3 to 8 after estrus cows were slaughtered, and reproductive organs were collected to determine antral follicle count, ovary size, and uterine horn diameter. Repeat breeder cows were older at first calving than control cows (P = 0.006). The length (P = 0.03) and height (P = 0.02) of the ovary contralateral to the corpus luteum (CL) were greater in control cows than repeat breeder cows. The endometrial diameter in the horn ipsilateral to the CL was greater in the control cows than the repeat breeder cows. Repeat breeder cows had fewer small (1 to 5 mm) antral follicles than control cows (P = 0.003); however, there was no association between GRIA1 genotype and antral follicle number. The GnRHR polymorphism was associated with age at first calving because cows that were homozygous for the C allele had a greater age at first calving than heterozygous cows or cows that were homozygous for the T allele (P = 0.01). In the granulosa cells from small (1 to 5 mm) antral follicles, mRNA abundances of 2 markers of oocyte quality, anti-Müllerian hormone and pentraxin 3, did not differ between fertility groups (P ≥ 0.12). We conclude that this GRIA1 polymorphism exists in beef cows but that it does not influence antral follicle numbers. The association between GnRHR genotype and age at first calving is likely not causal as this polymorphism is not functional. The utility of this polymorphism as a genetic marker for early conception in heifers will require further validation. Screening postpartum cows by ultrasonography to determine antral follicle numbers may aid in making culling decisions.

A study of the dynamic flammability of radiation cross-linked flame-retardant HDPE/EPDM/silicon-elastomer compound

NASA Astrophysics Data System (ADS)

Jia, Shaojin; Zhang, Zhicheng; Du, Zhiwen; Teng, Renrui; Wang, Zhengzhou

2003-04-01

A dynamic flammability study of flame-retardant compound consisting of HDPE, EPDM and silicon elastomer blended with additives, as wire and cable insulation was made before and after irradiation. The data of RHR, EHC, SEC and the concentration of CO and CO 2 from cone colorimeter shown in the burning process were accessed. By blending silicon elastomer, CO release rate was reduced and the thermal endurance was improved. Oxygen index, mechanical property, morphology of the char formed in dynamical flame and thermal stability were also investigated.

Evaluating a Nationwide Recreational Football Intervention: Recruitment, Attendance, Adherence, Exercise Intensity, and Health Effects.

PubMed

Fløtum, Liljan Av; Ottesen, Laila S; Krustrup, Peter; Mohr, Magni

2016-01-01

The present study evaluated a nationwide exercise intervention with Football Fitness in a small-scale society. In all, 741 adult participants (20-72 yrs) were successfully recruited for Football Fitness training in local football clubs, corresponding to 2.1% of the adult population. A preintervention test battery including resting heart rate (RHR), blood pressure, and body mass measurements along with performance tests (Yo-Yo Intermittent Endurance level 1 (Yo-Yo IE1), the Arrowhead Agility Test, and the Flamingo Balance Test) were performed (n = 502). Training attendance (n = 310) was 1.6 ± 0.2 sessions per week (range: 0.6-2.9), corresponding to 28.8 ± 1.0 sessions during the 18 wk intervention period. After 18 wks mean arterial pressure (MAP) was -2.7 ± 0.7 mmHg lower (P < 0.05; n = 151) with even greater (P < 0.05) reductions for those with baseline MAP values >99 mmHg (-5.6 ± 1.5 mmHg; n = 50). RHR was lowered (P < 0.05) by 6 bpm after intervention (77 ± 1 to 71 ± 1 bpm). Yo-Yo IE1 performance increased by 41% (540 ± 27 to 752 ± 45 m), while agility and postural balance were improved (P < 0.05) by ~6 and ~45%, respectively. In conclusion, Football Fitness was shown to be a successful health-promoting nationwide training intervention for adult participants with an extraordinary recruitment, a high attendance rate, moderate adherence, high exercise intensity, and marked benefits in cardiovascular health profile and fitness.

A Randomized, Double-Blind, Placebo-Controlled Trial to Determine the Effectiveness and Safety of a Thermogenic Supplement in Addition to an Energy-Restricted Diet in Apparently Healthy Females.

PubMed

Kendall, Kristina L; Hyde, Parker N; Fairman, Ciaran M; Hollaway, Kaitlyn M; Mumford, Petey W; Haun, Cody T; Mobley, Brooks; Kephart, Wesley C; Tribby, Aaron C; Kimber, Dylan; Moon, Jordan R; Beck, Darren T; Roberts, Michael D; Young, Kaelin C

2017-11-02

The increasing interest in weight loss has seen a concurrent rise in the supplemental use of thermogenics to aid weight loss efforts. To date, the effectiveness and safety of supplemental proprietary blend thermogenics, in conjunction with high-protein energy-restricted diets have not been thoroughly evaluated. The purpose of this study was to investigate the efficacy of a low-calorie, high-protein diet with and without the concomitant use of a thermogenic supplement on body weight and body composition in apparently healthy females. Subjects were divided into three groups, Bizzy Diet+FitMiss Burn (BURN, N = 12), Bizzy Diet+Placebo (PLA, N = 13), and Control (CON, N = 14), and underwent two testing sessions separated by approximately 3 weeks. Resting blood pressure (BP), resting heart rate (RHR), clinical safety markers, body weight (BW), and body composition were assessed during each testing session. Repeated measures analysis of variance (ANOVA) revealed a significant effect for time relative to BW, total body fat mass (FM), leg FM, and trunk FM. Post hoc analysis revealed that the BURN and PLA groups experienced significant decreases in both BW and total body FM compared to CON (p <.05). There were no significant interactions for BP, RHR, or clinical safety markers over the course of the study. The Bizzy Diet, both with and without the addition of FitMiss Burn thermogenic, appears to be safe for short-term use and may lead to greater improvement in body composition and BW in an apparently healthy female population.

[Oxygen peak consumption is a better predictor of cardiovascular risk than handgrip strength in older Chilean women].

PubMed

Farías-Valenzuela, Claudio; Pérez-Luco, Cristian; Ramírez-Campillo, Rodrigo; Álvarez, Cristian; Castro-Sepúlveda, Mauricio

Handgrip strength (HS) and peak oxygen consumption (Vo2peak) are powerful predictors of cardiovascular risk, although it is unknown which of the two variables is the better predictor. The objective of the following study was to relate HS and Vo2peak to cardiovascular risk markers in older Chilean women. Physically active adult women (n=51; age, 69±4.7years) participated in this study. The HS and Vo2peak were evaluated and related to the anthropometric variables of body mass, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist ratio (WR), and waist height ratio (WHR), as well as with the cardiovascular variables systolic (SBP) and diastolic (DBP) and cardiac recovery in one minute (RHR1). A multilinear regression model was used for the analysis of the associated variables (P<.05). The cardiovascular risk markers associated (P<.05) with the handgrip strength of the dominant limb (HS DL ) were body mass, BMI, WR, and WHR. The handgrip strength of the non-dominant limb (HS NDL ) was associated with body mass. Vo2peak was associated with body mass, BMI, HC and RHR1. The multilinear regression model showed a value of r=0.43 in HS DL , r=0.39 in HS NDL and r=0.69 in peak Vo2. Although HS and Vo2peak were related to cardiovascular risk markers, Vo2peak offers greater associative power with these cardiovascular risk factors. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Lotus LADM Based Self-Decontaminating Surfaces

DTIC Science & Technology

2007-05-01

nylon composite was examined with a scanning electron microscope (SEM), Hitachi S -3200N, operated at 10kV and magnifications from 50x to 2000x. For...cos1( HL H S p L p S d L d SeL γγγγγγθγ ⋅+⋅+⋅=+ (1) To make the nylon film surface hydrophobic, we need to attach a low surface tension material to...views of roughness pattern. For this rough surface, r and ФS are defined as: ( ) 1 2 2 2 ++ = dR Rhr π (4) ( )2 2 2 dR R S + =Φ π (5

Changes in cardiac function after pedicle subtraction osteotomy in patients with a kyphosis due to ankylosing spondylitis.

PubMed

Fu, J; Song, K; Zhang, Y G; Zheng, G Q; Zhang, G Y; Liu, C; Wang, Y

2015-10-01

Cardiac disease in patients with ankylosing spondylitis (AS) has previously been studied but not in patients with a kyphosis or in those who have undergone an operation to correct it. The aim of this study was to measure the post-operative changes in cardiac function of patients with an AS kyphosis after pedicle subtraction osteotomy (PSO). The original cohort consisted of 39 patients (33 men, six women). Of these, four patients (two men, two women) were lost to follow-up leaving 35 patients (31 men, four women) to study. The mean age of the remaining patients was 37.4 years (22.3 to 47.8) and their mean duration of AS was 17.0 years (4.6 to 26.4). Echocardiographic measurements, resting heart rate (RHR), physical function score (PFS), and full-length standing spinal radiographs were obtained before surgery and at the two-year follow-up. The mean pre-operative RHR was 80.2 bpm (60.6 to 112.3) which dropped to a mean of 73.7 bpm (60.7 to 90.6) at the two-year follow-up (p = 0.0000). Of 15 patients with normal ventricular function pre-operatively, two developed mild left ventricular diastolic dysfunction (LVDD) at the two-year follow-up. Of 20 patients with mild LVDD pre-operatively only five had this post-operatively. Overall, 15 patients had normal LV diastolic function before their operation and 28 patients had normal LV function at the two-year follow-up. The clinical improvement was 15 out of 20 (75.0%): cardiac function in patients with AS whose kyphosis was treated by PSO was significantly improved. ©2015 The British Editorial Society of Bone & Joint Surgery.

The Highly conserved gonadotropin-releasing hormone-2 form acts as a melatonin-releasing factor in the pineal of a teleost fish, the european sea bass Dicentrarchus labrax.

PubMed

Servili, Arianna; Lethimonier, Christèle; Lareyre, Jean-Jacques; López-Olmeda, José Fernando; Sánchez-Vázquez, Francisco Javier; Kah, Olivier; Muñoz-Cueto, José Antonio

2010-05-01

With the exception of modern mammals, most vertebrate species possess two GnRH genes, GnRH-1 and GnRH-2. In addition, in many teleost fish, there is a third gene called GnRH-3. If the main function of GnRH-1 is unambiguously to stimulate gonadotropin release, the other two GnRH forms still lack clear functions. This is particularly true for the highly conserved GnRH-2 that encodes chicken GnRH-II. This GnRH variant is consistently expressed in neurons of the dorsal synencephalon in most vertebrate groups but still has no clear functions supported by anatomical, pharmacological, and physiological data. In this study performed on a perciform fish, the European sea bass, we show for the first time that the pineal organ receives GnRH-2-immunoreactive fibers originating from the synencephalic GnRH-2 neurons. This was shown through a combination of retrograde tracing and immunohistochemistry, using highly specific antibodies. Supporting the presence of GnRH-2 functional targets, RT-PCR data together with the in situ hybridization studies showed that the sea bass pineal gland strongly expressed a GnRH receptor (dlGnRHR-II-2b) with clear selectivity for GnRH-2 and, to a lesser extent, the dlGnRHR-II-1a subtype. Finally, in vitro and in vivo experiments demonstrate stimulatory effects of GnRH-2 on nocturnal melatonin secretion by the sea bass pineal organ. Altogether, these data provide, for the first time in a vertebrate species, converging evidence supporting a role of GnRH-2 in the modulation of fish pineal functions.

Evaluating a Nationwide Recreational Football Intervention: Recruitment, Attendance, Adherence, Exercise Intensity, and Health Effects

PubMed Central

Fløtum, Liljan av; Ottesen, Laila S.; Krustrup, Peter

2016-01-01

The present study evaluated a nationwide exercise intervention with Football Fitness in a small-scale society. In all, 741 adult participants (20–72 yrs) were successfully recruited for Football Fitness training in local football clubs, corresponding to 2.1% of the adult population. A preintervention test battery including resting heart rate (RHR), blood pressure, and body mass measurements along with performance tests (Yo-Yo Intermittent Endurance level 1 (Yo-Yo IE1), the Arrowhead Agility Test, and the Flamingo Balance Test) were performed (n = 502). Training attendance (n = 310) was 1.6 ± 0.2 sessions per week (range: 0.6–2.9), corresponding to 28.8 ± 1.0 sessions during the 18 wk intervention period. After 18 wks mean arterial pressure (MAP) was −2.7 ± 0.7 mmHg lower (P < 0.05; n = 151) with even greater (P < 0.05) reductions for those with baseline MAP values >99 mmHg (−5.6 ± 1.5 mmHg; n = 50). RHR was lowered (P < 0.05) by 6 bpm after intervention (77 ± 1 to 71 ± 1 bpm). Yo-Yo IE1 performance increased by 41% (540 ± 27 to 752 ± 45 m), while agility and postural balance were improved (P < 0.05) by ~6 and ~45%, respectively. In conclusion, Football Fitness was shown to be a successful health-promoting nationwide training intervention for adult participants with an extraordinary recruitment, a high attendance rate, moderate adherence, high exercise intensity, and marked benefits in cardiovascular health profile and fitness. PMID:27437401

Staging quality is related to the survival of women with endometrial cancer: a Scottish population based study.Deficient surgical staging and omission of adjuvant radiotherapy is associated with poorer survival of women diagnosed with endometrial cancer in Scotland during 1996 and 1997

PubMed Central

Crawford, S C; De Caestecker, L; Gillis, C R; Hole, D; Davis, J A; Penney, G; Siddiqui, N A

2002-01-01

The association between treatment variation and survival of women with endometrial cancer was investigated. A retrospective cohort based upon the complete Scottish population registered on in-patient and day-case hospital discharge data (Scottish Morbidity Record-1) and cancer registration (Scottish Morbidity Record-6) coded C54 and C55 in ICD10, between 1st January 1996 to 31st December 1997 were analysed. Seven hundred and three patients who underwent surgical treatment out of 781 patients that were diagnosed with endometrial cancer in Scotland during 1996 and 1997. The overall quality of surgical staging was poor. The quality of staging was related to both the year that the surgeon passed the Member of the Royal College of Obstetricians and Gynaecologists examination and also to ‘specialist’ status but was not related to surgeon caseload. Two clinically important prognostic factors were found to be associated with survival; whether the International Federation of Obstetrics and Gynaecology stage was documented, RHR=2.0 (95% CI=1.3 to 3.1) and also to the use of adjuvant radiotherapy, RHR=2.2 (95% CI=1.5 to 3.5). The associations with survival were strongest in patients with advanced disease, International Federation of Obstetrics and Gynaecology stages 1C through to stage 3. Deficiencies in staging and variations in the use of adjuvant radiotherapy represent a possible source of avoidable mortality in patients with endometrial cancer. Consequently, there should be a greater emphasis on improving the overall quality of surgical staging in endometrial cancer. British Journal of Cancer (2002) 86, 1837–1842. doi:10.1038/sj.bjc.6600358 www.bjcancer.com © 2002 Cancer Research UK PMID:12085172

Acute effects of ingesting Java Fittrade mark energy extreme functional coffee on resting energy expenditure and hemodynamic responses in male and female coffee drinkers.

PubMed

Taylor, Lemuel W; Wilborn, Colin D; Harvey, Travis; Wismann, Jennifer; Willoughby, Darryn S

2007-10-05

The purpose of this study was to examine the effects of a functional coffee beverage containing additional caffeine, green tea extracts, niacin and garcinia cambogia to regular coffee to determine the effects on resting energy expenditure (REE) and hemodynamic variables. Subjects included five male (26 +/- 2.1 y, 97.16 +/- 10.05 kg, 183.89 +/- 6.60 cm) and five female (28.8 +/- 5.3 y, 142.2 +/- 12.6 lbs) regular coffee drinkers. Subjects fasted for 10 hours and were assessed for 1 hour prior (PRE) and 3 hours following 1.5 cups of coffee ingestion [JavaFittrade mark Energy Extreme (JF) ~400 mg total caffeine; Folgers (F) ~200 mg total caffeine] in a double-blind, crossover design. REE, resting heart rate (RHR), and systolic (SBP) and diastolic (DBP) blood pressure was assessed at PRE and 1, 2, and 3-hours post coffee ingestion. Data were analyzed by three-factor repeated measures ANOVA (p < 0.05). JF trial resulted in a significant main effect for REE (p < 0.01), SBP (p < 0.01), RER (p < 0.01), and VO2 (p < 0.01) compared to F, with no difference between trials on the RHR and DBP variables. A significant interaction for trial and time point (p < 0.05) was observed for the variable REE. The JF trial resulted in a significant overall mean increase in REE of 14.4% (males = 12.1%, females = 17.9%) over the observation period (p < 0.05), while the F trial produced an overall decrease in REE of 5.7%. SBP was significantly higher in the JF trial; however, there was no significant increase from PRE to 3-hours post. Results from this study suggest that JavaFittrade mark Energy Extreme coffee is more effective than Folgers regular caffeinated coffee at increasing REE in regular coffee drinkers for up to 3 hours following ingestion without any adverse hemodynamic effects.

Effect of folic acid supplementation on homocysteine concentration and association with training in handball players

PubMed Central

2013-01-01

Background Strenuous physical activity can alter the status of folic acid, a vitamin directly associated with homocysteine (Hcy); alterations in this nutrient are a risk factor for cardiovascular disease. Handball players are a population at risk for nutrient deficiency because of poor dietary habits. Objective The aims of this study were to evaluate nutritional status for macronutrients and folic acid in members of a high-performance handball team, and determine the effect of a nutritional intervention with folic acid supplementation and education. Design A total of 14 high-performance handball players were monitored by recording training time, training intensity (according to three levels of residual heart rate (RHR): <60%, 60%–80% and >80%), and subjective perceived exertion (RPE) during a 4-month training period. Nutritional, laboratory and physical activity variables were recorded at baseline (Week 0), after 2 months of dietary supplementation with 200 μg folic acid (50% of the recommended daily allowance) (Week 8) and after 2 months without supplementation (Week 16). We compared training load and analyzed changes in plasma concentrations of Hcy before and after the intervention. Results Bivariate analysis showed a significant negative correlation (P < 0.01) between Hcy and folic acid concentrations (r = −0.84) at Week 8, reflecting a significant change in Hcy concentration (P < 0.05) as a result of hyperhomocysteinemia following the accumulation of high training loads. At Week 16 we observed a significant negative correlation (P < 0.01) between Hcy concentration and training time with an RHR <60%, indicating that aerobic exercise avoided abrupt changes in Hcy and may thus reduce the risk of cardiovascular accidents in high-performance athletes. Conclusion Integral monitoring and education are needed for practitioners of handball sports to record their folic acid status, a factor that directly affects Hcy metabolism. Folic acid supplementation may protect athletes against alterations that can lead to cardiovascular events related to exertion during competition. PMID:23432819

Ground reaction forces and heart rate profile of aerobic dance instructors during a low and high impact exercise programme.

PubMed

Rousanoglou, E N; Boudolos, K D

2005-06-01

The magnitude of ground reaction forces (GRF) has been associated, although never verified, with the high incidence of lower extremities injuries in aerobic dance (AD) instructors. Moreover, during their working activities AD instructors have demonstrated HR levels, such as 70% HRmax, values, more in training rather in working status. This study was designed to investigate GRF and heart rate (HR) exhibited by AD instructors of both genders, during a simulated AD instruction, from the perspective of accepted occupational workloads. Fourteen females and 14 males instructors performed a 35 min AD exercise programme (warm up--low impact (LI) interval--in high impact (HI) interval--cool down). Four GRF measurements were taken during LI and HI time intervals, respectively. HR was recorded throughout the whole experimental procedure and was synchronised to GRF measurements. All GRF and HR values were significantly increased in HI exercise (p<0.05) with a non significant (p>0.05) time effect for GRF. In both LI and HI exercises, females demonstrated significantly higher vertical but lower lateral GRF (p<0.05) and significantly shorter cycles of movement (p<0.05) while in HI exercise they had significant longer flight times (p<0.05). For both genders, HR was kept at 70% and 80% of HR(max-calc) and RHR was 60% and 70%, during LI and HI intervals respectively, with females showing a trend, though non-significant, for higher HR values. The gender specificity of the significant vertical and lateral GRF pattern differences, may possibly be associated with the significant anthropometric differences of male and female AD instructors. HR(max-calc) and RHR exceeded the accepted occupational levels rising to training status levels. We suggest that AD instructors take up such instructing methods which allow them to minimize the magnitude or the rate of GRF, as well as HR levels, developed in the course of their working hour.

Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice

PubMed Central

Busby, Ellen R.; Sherwood, Nancy M.

2017-01-01

Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15–28 may account for the altered metabolism in the prepubertal female pups. PMID:28346489

GnRH and GnRH receptors in the pathophysiology of the human female reproductive system.

PubMed

Maggi, Roberto; Cariboni, Anna Maria; Marelli, Marina Montagnani; Moretti, Roberta Manuela; Andrè, Valentina; Marzagalli, Monica; Limonta, Patrizia

2016-04-01

Human reproduction depends on an intact hypothalamic-pituitary-gonadal (HPG) axis. Hypothalamic gonadotrophin-releasing hormone (GnRH) has been recognized, since its identification in 1971, as the central regulator of the production and release of the pituitary gonadotrophins that, in turn, regulate the gonadal functions and the production of sex steroids. The characteristic peculiar development, distribution and episodic activity of GnRH-producing neurons have solicited an interdisciplinary interest on the etiopathogenesis of several reproductive diseases. The more recent identification of a GnRH/GnRH receptor (GnRHR) system in both the human endometrium and ovary has widened the spectrum of action of the peptide and of its analogues beyond its hypothalamic function. An analysis of research and review articles published in international journals until June 2015 has been carried out to comprehensively summarize both the well established and the most recent knowledge on the physiopathology of the GnRH system in the central and peripheral control of female reproductive functions and diseases. This review focuses on the role of GnRH neurons in the control of the reproductive axis. New knowledge is accumulating on the genetic programme that drives GnRH neuron development to ameliorate the diagnosis and treatment of GnRH deficiency and consequent delayed or absent puberty. Moreover, a better understanding of the mechanisms controlling the episodic release of GnRH during the onset of puberty and the ovulatory cycle has enabled the pharmacological use of GnRH itself or its synthetic analogues (agonists and antagonists) to either stimulate or to block the gonadotrophin secretion and modulate the functions of the reproductive axis in several reproductive diseases and in assisted reproduction technology. Several inputs from other neuronal populations, as well as metabolic, somatic and age-related signals, may greatly affect the functions of the GnRH pulse generator during the female lifespan; their modulation may offer new possible strategies for diagnostic and therapeutic interventions. A GnRH/GnRHR system is also expressed in female reproductive tissues (e.g. endometrium and ovary), both in normal and pathological conditions. The expression of this system in the human endometrium and ovary supports its physiological regulatory role in the processes of trophoblast invasion of the maternal endometrium and embryo implantation as well as of follicular development and corpus luteum functions. The GnRH/GnRHR system that is expressed in diseased tissues of the female reproductive tract (both benign and malignant) is at present considered an effective molecular target for the development of novel therapeutic approaches for these pathologies. GnRH agonists are also considered as a promising therapeutic approach to counteract ovarian failure in young female patients undergoing chemotherapy. Increasing knowledge about the regulation of GnRH pulsatile release, as well as the therapeutic use of its analogues, offers interesting new perspectives in the diagnosis, treatment and outcome of female reproductive disorders, including tumoral and iatrogenic diseases. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Impact of an external radiation field on handheld XRF measurements for nuclear forensics applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steeb, Jennifer L.; Mertz, Carol J.; Finck, Martha R.

X-ray fluorescence (XRF) is an attractive technique for nuclear forensics applications. We evaluated a handheld, portable XRF device by applying an external radiation field (10 mR/h to 17 R/h) using two types of radiography sources: a 60Co radiography camera to observe effects from high-energy gamma emissions and an 192Ir radiography camera to observe effects from several low-energy gamma (0.604, 0.468, and 0.317 MeV) and decay daughter x-ray emissions. External radiation tests proved that radiation, in general, has a significant effect on the dead time or background at dose rates over 1 R/hr for both the 192Ir and 60Co sources.

Pulmonary-impedance power spectral analysis: A facile means of detecting radiation-induced gastrointestinal distress and performance decrement in man

NASA Technical Reports Server (NTRS)

Rick, R. C.; Lushbaugh, C. C.; Mcdow, E.; Frome, E.

1972-01-01

Changes in respiratory variance revealed by power spectral analysis of the pulmonary impedance pneumogram can be used to detect and measure stresses directly or indirectly affecting human respiratory function. When gastrointestinal distress occurred during a series of 5 total-body exposures of 30 R at a rate of 1.5 R/min, it was accompanied by typical shifts in pulmonary impedance power spectra. These changes did not occur after protracted exposure of 250 R (30 R daily) at 1.5 R/hr that failed to cause radiation sickness. This system for quantitating respiratory effort can also be used to detect alterations in one's ability to perform under controlled exercise conditions.

Application of reliability-centered-maintenance to BWR ECCS motor operator valve performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feltus, M.A.; Choi, Y.A.

1993-01-01

This paper describes the application of reliability-centered maintenance (RCM) methods to plant probabilistic risk assessment (PRA) and safety analyses for four boiling water reactor emergency core cooling systems (ECCSs): (1) high-pressure coolant injection (HPCI); (2) reactor core isolation cooling (RCIC); (3) residual heat removal (RHR); and (4) core spray systems. Reliability-centered maintenance is a system function-based technique for improving a preventive maintenance program that is applied on a component basis. Those components that truly affect plant function are identified, and maintenance tasks are focused on preventing their failures. The RCM evaluation establishes the relevant criteria that preserve system function somore » that an RCM-focused approach can be flexible and dynamic.« less

Ionizing radiation detector

DOEpatents

Thacker, Louis H.

1990-01-01

An ionizing radiation detector is provided which is based on the principle of analog electronic integration of radiation sensor currents in the sub-pico to nano ampere range between fixed voltage switching thresholds with automatic voltage reversal each time the appropriate threshold is reached. The thresholds are provided by a first NAND gate Schmitt trigger which is coupled with a second NAND gate Schmitt trigger operating in an alternate switching state from the first gate to turn either a visible or audible indicating device on and off in response to the gate switching rate which is indicative of the level of radiation being sensed. The detector can be configured as a small, personal radiation dosimeter which is simple to operate and responsive over a dynamic range of at least 0.01 to 1000 R/hr.

Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer.

PubMed

Rebbeck, Timothy R; Mitra, Nandita; Wan, Fei; Sinilnikova, Olga M; Healey, Sue; McGuffog, Lesley; Mazoyer, Sylvie; Chenevix-Trench, Georgia; Easton, Douglas F; Antoniou, Antonis C; Nathanson, Katherine L; Laitman, Yael; Kushnir, Anya; Paluch-Shimon, Shani; Berger, Raanan; Zidan, Jamal; Friedman, Eitan; Ehrencrona, Hans; Stenmark-Askmalm, Marie; Einbeigi, Zakaria; Loman, Niklas; Harbst, Katja; Rantala, Johanna; Melin, Beatrice; Huo, Dezheng; Olopade, Olufunmilayo I; Seldon, Joyce; Ganz, Patricia A; Nussbaum, Robert L; Chan, Salina B; Odunsi, Kunle; Gayther, Simon A; Domchek, Susan M; Arun, Banu K; Lu, Karen H; Mitchell, Gillian; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Godwin, Andrew K; Pathak, Harsh; Ross, Eric; Daly, Mary B; Whittemore, Alice S; John, Esther M; Miron, Alexander; Terry, Mary Beth; Chung, Wendy K; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Steele, Linda; Neuhausen, Susan L; Ding, Yuan Chun; Ejlertsen, Bent; Gerdes, Anne-Marie; Hansen, Thomas v O; Ramón y Cajal, Teresa; Osorio, Ana; Benitez, Javier; Godino, Javier; Tejada, Maria-Isabel; Duran, Mercedes; Weitzel, Jeffrey N; Bobolis, Kristie A; Sand, Sharon R; Fontaine, Annette; Savarese, Antonella; Pasini, Barbara; Peissel, Bernard; Bonanni, Bernardo; Zaffaroni, Daniela; Vignolo-Lutati, Francesca; Scuvera, Giulietta; Giannini, Giuseppe; Bernard, Loris; Genuardi, Maurizio; Radice, Paolo; Dolcetti, Riccardo; Manoukian, Siranoush; Pensotti, Valeria; Gismondi, Viviana; Yannoukakos, Drakoulis; Fostira, Florentia; Garber, Judy; Torres, Diana; Rashid, Muhammad Usman; Hamann, Ute; Peock, Susan; Frost, Debra; Platte, Radka; Evans, D Gareth; Eeles, Rosalind; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J; Walker, Lisa; Porteous, Mary E; Kennedy, M John; Izatt, Louise; Adlard, Julian; Donaldson, Alan; Ellis, Steve; Sharma, Priyanka; Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Becker, Alexandra; Rhiem, Kerstin; Hahnen, Eric; Engel, Christoph; Meindl, Alfons; Engert, Stefanie; Ditsch, Nina; Arnold, Norbert; Plendl, Hans Jörg; Mundhenke, Christoph; Niederacher, Dieter; Fleisch, Markus; Sutter, Christian; Bartram, C R; Dikow, Nicola; Wang-Gohrke, Shan; Gadzicki, Dorothea; Steinemann, Doris; Kast, Karin; Beer, Marit; Varon-Mateeva, Raymonda; Gehrig, Andrea; Weber, Bernhard H; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M; Mazoyer, Sylvie; Houdayer, Claude; Belotti, Muriel; Gauthier-Villars, Marion; Damiola, Francesca; Boutry-Kryza, Nadia; Lasset, Christine; Sobol, Hagay; Peyrat, Jean-Philippe; Muller, Danièle; Fricker, Jean-Pierre; Collonge-Rame, Marie-Agnès; Mortemousque, Isabelle; Nogues, Catherine; Rouleau, Etienne; Isaacs, Claudine; De Paepe, Anne; Poppe, Bruce; Claes, Kathleen; De Leeneer, Kim; Piedmonte, Marion; Rodriguez, Gustavo; Wakely, Katie; Boggess, John; Blank, Stephanie V; Basil, Jack; Azodi, Masoud; Phillips, Kelly-Anne; Caldes, Trinidad; de la Hoya, Miguel; Romero, Atocha; Nevanlinna, Heli; Aittomäki, Kristiina; van der Hout, Annemarie H; Hogervorst, Frans B L; Verhoef, Senno; Collée, J Margriet; Seynaeve, Caroline; Oosterwijk, Jan C; Gille, Johannes J P; Wijnen, Juul T; Gómez Garcia, Encarna B; Kets, Carolien M; Ausems, Margreet G E M; Aalfs, Cora M; Devilee, Peter; Mensenkamp, Arjen R; Kwong, Ava; Olah, Edith; Papp, Janos; Diez, Orland; Lazaro, Conxi; Darder, Esther; Blanco, Ignacio; Salinas, Mónica; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sukiennicki, Grzegorz; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Złowocka-Perłowska, Elżbieta; Menkiszak, Janusz; Arason, Adalgeir; Barkardottir, Rosa B; Simard, Jacques; Laframboise, Rachel; Montagna, Marco; Agata, Simona; Alducci, Elisa; Peixoto, Ana; Teixeira, Manuel R; Spurdle, Amanda B; Lee, Min Hyuk; Park, Sue K; Kim, Sung-Won; Friebel, Tara M; Couch, Fergus J; Lindor, Noralane M; Pankratz, Vernon S; Guidugli, Lucia; Wang, Xianshu; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Robson, Mark; Rau-Murthy, Rohini; Kauff, Noah; Fink-Retter, Anneliese; Singer, Christian F; Rappaport, Christine; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; Tea, Muy-Kheng; Berger, Andreas; Greene, Mark H; Mai, Phuong L; Imyanitov, Evgeny N; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Pedersen, Inge Sokilde; Skytte, Anne-Bine; Sunde, Lone; Thomassen, Mads; Moeller, Sanne Traasdahl; Kruse, Torben A; Jensen, Uffe Birk; Caligo, Maria Adelaide; Aretini, Paolo; Teo, Soo-Hwang; Selkirk, Christina G; Hulick, Peter J; Andrulis, Irene

2015-04-07

Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. To identify mutation-specific cancer risks for carriers of BRCA1/2. Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. Mutations of BRCA1 or BRCA2. Breast and ovarian cancer risks. Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.

Ultra-wide Range Gamma Detector System for Search and Locate Operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Odell, D. Mackenzie Odell; Harpring, Larry J.; Moore, Frank S. Jr.

2005-10-26

Collecting debris samples following a nuclear event requires that operations be conducted from a considerable stand-off distance. An ultra-wide range gamma detector system has been constructed to accomplish both long range radiation search and close range hot sample collection functions. Constructed and tested on a REMOTEC Andros platform, the system has demonstrated reliable operation over six orders of magnitude of gamma dose from 100's of uR/hr to over 100 R/hr. Functional elements include a remotely controlled variable collimator assembly, a NaI(Tl)/photomultiplier tube detector, a proprietary digital radiation instrument, a coaxially mounted video camera, a digital compass, and both local andmore » remote control computers with a user interface designed for long range operations. Long range sensitivity and target location, as well as close range sample selection performance are presented.« less

Physical Activity Self-Efficacy and Fitness: Family Environment Relationship Correlates and Self-Esteem as a Mediator among Adolescents Who Are Overweight or Obese.

PubMed

Nock, Nora L; Ievers-Landis, Carolyn E; Dajani, Rachel; Knight, Darryl; Rigda, Alexander; Narasimhan, Sumana; Uli, Naveen

2016-10-01

Little is known regarding how dimensions of the family social environment relate to fitness levels and physical activity self-efficacy (PASE) among adolescents who are overweight or obese and whether these relationships are mediated by self-esteem. Potential associations were evaluated between relationship subdomains (cohesion, conflict, expressivity) of the Family Environment Scale (FES), self-esteem (Rosenberg Self-Esteem Scale, RSES), and PASE and fitness, using recovery heart rate [RHR, beats per minute (bpm)] from a 3-minute submaximal step test at baseline. Participants were 108 adolescents who were overweight or obese and were seeking weight-loss treatment as part of the Healthy Kids, Healthy Weight 12-week multidisciplinary pediatric weight management program. Structural equation modeling (SEM) was used to simultaneously evaluate paths between these variables and test for mediation. In multivariable models, higher FES cohesion (β = -2.18, s.e. = 0.98; p = 0.02), expressivity (β = -1.97, s.e. = 0.99; p < 0.05), and PASE (β = -0.64, s.e. = 0.33; p < 0.05) scores were associated with lower RHR, which represents higher fitness. Furthermore, higher FES conflict scores were associated with lower RSES scores (β = -0.83, s.e. = 0.29; p < 0.01), and FES conflict (β = -0.63, s.e. = 0.22; p < 0.01) and RSES (β = 0.33, s.e. = 0.07; p < 0.01) were associated with PASE scores. In a good-fitting multivariate SEM [Comparative Fit Index (CFI) = 1.00; Standardized Root Mean Square Residual (SRMR) = 0.02; Tucker-Lewis index (TLI) = 1.22; Root Mean Squared Error of Approximation (RMSEA) <0.01], RSES mediated the relationship between FES conflict and PASE (sum of indirect paths: β = -0.30, s.e. = 0.11; p < 0.01) scores. Our results highlight the importance of the relationship domain of the family environment on self-esteem, PASE, and physical fitness in adolescents who are overweight or obese.

Pituitary estrogen receptor alpha is involved in luteinizing hormone pulsatility at mid-gestation in the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha).

PubMed

Proietto, Sofía; Yankelevich, Lorena; Villarreal, Federico Martín; Inserra, Pablo Ignacio Felipe; Charif, Santiago Elías; Schmidt, Alejandro Raúl; Cortasa, Santiago Andrés; Corso, María Clara; Di Giorgio, Noelia Paula; Lux-Lantos, Victoria; Vitullo, Alfredo Daniel; Halperin, Julia; Dorfman, Verónica Berta

2018-04-12

The South American plains vizcacha, Lagostomus maximus, is a caviomorph rodent native from Argentina, Bolivia and Paraguay. It shows peculiar reproductive features like pre-ovulatory follicle recruitment during pregnancy with an ovulatory process at around mid-gestation. We have described the activation of the hypothalamic - pituitary - ovarian (HPO) axis during pregnancy. A progressive decrease of progesterone (P4) at mid-pregnancy elicits the delivery of gonadotropin-releasing hormone (GnRH) with the consequent secretion of follicle stimulating hormone (FSH) and estradiol (E 2 ) followed by luteinizing hormone (LH) release resulting in follicular luteinization and the P4 concentration recover. Pituitary gland is the central regulator of the HPO axis being E 2 a key hormone involved in the regulation of its activity. In this work we analyzed the action of E 2 on the pituitary response to the GnRH wave as well as its involvement on LH secretion at mid-gestation in L. maximus. The expression of GnRHR at the pituitary pars distalis showed a significant decrease at mid-pregnancy compared to early- and term-gestating females. ERα showed a significant increment from mid-gestation whereas ERβ did not show variations throughout pregnancy; whereas the LH expression in the pituitary pars distalis showed a significant increase at mid-gestation, concordantly with serum LH, which was followed by a decrease at term-gestation with similar values than at early-pregnancy. The number of cells with co-localization of ERα and GnRHR showed a decline at mid-pregnancy related to early- and term-gestation, whereas the cells with co-localization of ERα and LH increased at mid- and term-pregnancy. On the other hand, ex vivo measuring of LH pulsatility showed a significant increment in the total mass of LH delivered at mid-pregnancy followed by a decrease at term-gestation. The stimulation of ERα with the PPT specific agonist induced a significant increment in the total mass of LH released, whereas no changes were determined when ERβ was stimulated with its specific agonist MPP. These results suggest that LH pulsatility rise at mid-pregnancy would be enabled by the increase of E 2 acting through ERα. Copyright © 2018 Elsevier Inc. All rights reserved.

Activity-Dependent Dysfunction in Visual and Olfactory Sensory Systems in Mouse Models of Down Syndrome

PubMed Central

Saqran, Lubna; Herrick, Scott P.; Frosch, Matthew P.; Hyman, Bradley T.

2017-01-01

Activity-dependent synaptic plasticity plays a critical role in the refinement of circuitry during postnatal development and may be disrupted in conditions that cause intellectual disability, such as Down syndrome (DS). To test this hypothesis, visual cortical plasticity was assessed in Ts65Dn mice that harbor a chromosomal duplication syntenic to human chromosome 21q. We find that Ts65Dn mice demonstrate a defect in ocular dominance plasticity (ODP) following monocular deprivation. This phenotype is similar to that of transgenic mice that express amyloid precursor protein (APP), which is duplicated in DS and in Ts65DN mice; however, normalizing APP gene copy number in Ts65Dn mice fails to rescue plasticity. Ts1Rhr mice harbor a duplication of the telomeric third of the Ts65Dn-duplicated sequence and demonstrate the same ODP defect, suggesting a gene or genes sufficient to drive the phenotype are located in that smaller duplication. In addition, we find that Ts65Dn mice demonstrate an abnormality in olfactory system connectivity, a defect in the refinement of connections to second-order neurons in the olfactory bulb. Ts1Rhr mice do not demonstrate a defect in glomerular refinement, suggesting that distinct genes or sets of genes underlie visual and olfactory system phenotypes. Importantly, these data suggest that developmental plasticity and connectivity are impaired in sensory systems in DS model mice, that such defects may contribute to functional impairment in DS, and that these phenotypes, present in male and female mice, provide novel means for examining the genetic and molecular bases for neurodevelopmental impairment in model mice in vivo. SIGNIFICANCE STATEMENT Our understanding of the basis for intellectual impairment in Down syndrome is hindered by the large number of genes duplicated in Trisomy 21 and a lack of understanding of the effect of disease pathology on the function of neural circuits in vivo. This work describes early postnatal developmental abnormalities in visual and olfactory sensory systems in Down syndrome model mice, which provide insight into defects in the function of neural circuits in vivo and provide an approach for exploring the genetic and molecular basis for impairment in the disease. In addition, these findings raise the possibility that basic dysfunction in primary sensory circuitry may illustrate mechanisms important for global learning and cognitive impairment in Down syndrome patients. PMID:28899917

Second-generation ethanol production from elephant grass at high total solids.

PubMed

Menegol, Daiane; Fontana, Roselei Claudete; Dillon, Aldo José Pinheiro; Camassola, Marli

2016-07-01

The enzymatic hydrolysis of Pennisetum purpureum (elephant grass) was evaluated at high total solid levels (from 4% to 20% (w/v)) in a concomitant ball milling treatment in a rotating hydrolysis reactor (RHR). The greatest glucose yield was 20.17% when 4% (w/v) untreated biomass was employed. When sugars obtained from enzymatic hydrolysis were submitted to fermentation with Saccharomyces cerevisiae, the greatest ethanol yield was 22.61% when 4% (w/v) untreated biomass was employed; however, the highest glucose concentration (12.47g/L) was obtaining using 20% (w/v) solids and highest ethanol concentration (6.1g/L) was obtained using 16% (w/v) solids. When elephant grass was hydrolyzed in the rotating hydrolysis reactor, ethanol production was about double that was produced when the biomass was hydrolyzed in a static reactor (SR). These data indicate that it is possible to produce ethanol from elephant grass when milling treatment and enzymatic hydrolysis are performed at the same time. Copyright © 2016. Published by Elsevier Ltd.

Loss of DHR sequences at Browns Ferry Unit One - accident-sequence analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, D.H.; Grene, S.R.; Harrington, R.M.

1983-05-01

This study describes the predicted response of Unit One at the Browns Ferry Nuclear Plant to a postulated loss of decay heat removal (DHR) capability following scram from full power with the power conversion system unavailable. In accident sequences without DHR capability, the residual heat removal (RHR) system functions of pressure suppression pool cooling and reactor vessel shutdown cooling are unavailable. Consequently, all decay heat energy is stored in the pressure suppression pool with a concomitant increase in pool temperature and primary containment pressure. With the assumption that DHR capability is not regained during the lengthy course of this accidentmore » sequence, the containment ultimately fails by overpressurization. Although unlikely, this catastrophic failure might lead to loss of the ability to inject cooling water into the reactor vessel, causing subsequent core uncovery and meltdown. The timing of these events and the effective mitigating actions that might be taken by the operator are discussed in this report.« less

RAMONA-3B application to Browns Ferry ATWS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slovik, G.C.; Neymotin, L.Y.; Saha, P.

1985-01-01

The Anticipated Transient Without Scram (ATWS) is known to be a dominant accident sequence for possible core melt in a Boiling Water Reactor (BWR). A recent Probabilistic Risk Assessment (PRA) analysis for the Browns Ferry nuclear power plant indicates that ATWS is the second most dominant transient for core melt in BWR/4 with Mark I containment. The most dominant sequence being the failure of long term decay heat removal function of the Residual Heat Removal (RHR) system. Of all the various ATWS scenarios, the Main Steam Isolation Valve (MSIV) closure ATWS sequence was chosen for present analysis because of itsmore » relatively high frequency of occurrence and its challenge to the residual heat removal system and containment integrity. The objective of this paper is to discuss four MSIV closure ATWS calculations using the RAMONA-3B code. The paper is a summary of a report being prepared for the USNRC Severe Accident Sequence Analysis (SASA) program which should be referred to for details. 10 refs., 20 figs., 3 tabs.« less

Effects of TDCPP or TPP on gene transcriptions and hormones of HPG axis, and their consequences on reproduction in adult zebrafish (Danio rerio).

PubMed

Liu, Xiaoshan; Ji, Kyunghee; Jo, Areum; Moon, Hyo-Bang; Choi, Kyungho

2013-06-15

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP) belong to the group of triester organophosphate flame retardants (OPFRs), which have been used in a wide range of consumer products. These chemicals have been frequently detected in effluents, surface water, and fish, and hence their potential adverse effects on aquatic ecosystem are of concern. The present study was conducted to investigate the reproduction-related effects and possible molecular mechanisms of TDCPP and TPP using a 21 day reproduction test employing adult zebrafish (Danio rerio). After 21 d of exposure to TDCPP or TPP, significant decrease in fecundity along with significant increases of plasma 17β-estradiol (E2) concentrations, vitellogenin (VTG) levels, and E2/testosterone (T) and E2/11-ketotestosterone (11-KT) ratios were observed. The transcriptional profiles of several genes of the hypothalamus-pituitary-gonad (HPG) axis changed as well after the exposure, but the trend was sex-dependent. In male fish, gonadotropin-releasing hormone2 (GnRH2), GnRHR3, cytochrome P450 (CYP) 19B, estrogen receptor α (ERα), ER2 β1, and follicle stimulating hormone β (FSHβ) were upregulated in the brain, while luteinizing hormone β (LHβ) and androgen receptor (AR) were downregulated. Corresponding to the upregulation of FSHβ and downregulation of LHβ in the brain, FSHR was upregulated and LHR was downregulated in the testis. Among the genes that regulate the steroidogenesis pathway, transcription of hydroxyl methyl glutaryl CoA reductase (HMGRA), steroidogenic acute regulatory protein (StAR), and 17β-hydroxysteroid dehydrogenase (17βHSD) decreased, while transcription of CYP11A, CYP17, and CYP19A increased. In female fish, transcription ofGnRH2 and GnRHR3 decreased, but FSHβ, LHβ, CYP19B, ERα, ER2β1, and AR transcription increased in the brain. In the ovary, FSHR and LHR were significantly upregulated, and most steroidogenic genes were significantly upregulated. The observed disruption of GnRH and GtHs could be further related to subsequent disruption in both sex steroid hormone balance and plasma VTG levels, as well as reproductive performance. Overall, our observation indicates that both TDCPP and TPP could disturb the sex hormone balance by altering regulatory mechanisms of the HPG axis, eventually leading to disruption of reproductive performance in fish. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of BPA and E2 on expression profiles of genes related to hypothalamic-pituitary-gonadal axis of half-smooth tongue sole Cynoglossus semilaevis

NASA Astrophysics Data System (ADS)

Li, Fengling; Li, Zhaoxin; Wang, Qingyin; Zhai, Yuxiu

2013-05-01

Endocrine disrupting chemicals (EDCs) are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes ( DMRT, VTG GnRHR FSHR CYP17A CYP19A, and CYP19B) involved in sex steroid synthesis and action as well as sexual development in adult male and female Cynoglossus semilaevis, after exposure to different concentrations of Bisphenol A (BPA) and 17β-estradiol (E2). Both BPA (1, 10, 50, 125, and 250 mg/kg) and E2 (0.5, 5, and 10 mg/kg) induced changes in target gene expression, although the estrogenic effects of E2 as a model estrogen were stronger. Among the 7 genes, VTG CYP17A and CYP19 responded strongly to BPA or E2 exposure and can thus serve as reference biomarkers for estrogenic EDCs exposure in marine teleosts. These data will provide a window to establish a hypothalamic-pituitary-gonadal model in C. semilaevis to better understand the effect pathways of EDCs.

Effects of dietary omega-3/omega-6 fatty acid ratios on reproduction in the young breeder rooster.

PubMed

Feng, Yun; Ding, Yu; Liu, Juan; Tian, Ye; Yang, Yanzhou; Guan, Shuluan; Zhang, Cheng

2015-03-21

Polyunsaturated fatty acids (PUFAs) are necessary for the body's metabolism, growth and development. Although PUFAs play an important role in the regulation of reproduction, their role in testis development in the rooster is unknown. The present study was conducted to investigate the effects of omega-3/omega-6 (n-3/n-6, PUFAs) ratios on reproductive performance in young breeder roosters. Plasma levels of reproductive hormones, testis development, and reproductive hormone receptor and StAR mRNA expression were also assessed. Although PUFAs (n-3/n-6: 1/4.15) had no significant effect on the testis index (P > 0.05), the spermatogonial development and germ cell layers were increased. Moreover, serum levels of hormones (GnRH, FSH, LH and T) on day 35 were also significantly increased by PUFAs (n-3/n-6: 1/4.15). To investigate whether PUFAs regulate the expression of hormone receptors and StAR, real time-PCR was used to measure GnRHR, FSHR, LHR and StAR mRNA levels. PUFAs significantly increased the mRNA levels of all of these genes. These results indicate that PUFAs enhance the reproductive performance of young roosters by increasing hormone secretion and function, the latter by up-regulating receptor expression. These findings provide a sound basis for a balanced n-3/n-6 PUFA ratio being beneficial to young rooster reproduction.

Gender Difference in Aerobic Capacity and the Contribution by Body Composition and Haemoglobin Concentration: A Study in Young Indian National Hockey Players

PubMed Central

Kailashiya, Jyotsna

2016-01-01

Introduction Although gender difference in aerobic capacity is known, the contributing factors have been researched seldom. Aim To investigate the gender gap and the contribution by percentage Body Fat (BF), Body Mass Index (BMI) and haemoglobin concentration Hb. Materials and Methods The study was conducted on 30 (17 males, 13 females) training status matched young hockey players. Healthy players who were playing upto national level competition were included. BW (Body Weight), BF, BMI, LBM (Lean Body Mass), rHR (restring Heart Rate), HRR (Heart Rate Recovery), Hb, a/rVO2max (absolute/relative), a/rPWC (Physical Work Capacity) and RMR (Resting Metabolic Rate) were measured and analysed. Results There was significant gender difference in the measured parameters. Difference in a/rVO2max remained significant even after controlling for BF, BMI and Hb. Multiple regression and correlation analysis revealed gender difference in VO2max/LBM was due to: BMI(31.91%)>BF(27.60%)>Hb(9.91%). BMI also significantly contributed 3.66% of VO2max/LBM variance, independent of that by gender. Difference in RMR was mainly related to LBM, BF and BMI. Conclusion The study provided an understanding for gender gap in aerobic capacity. Differences in BMI & BF were one of the main reasons. PMID:28050360

Effect of steam generator configuration in a loss of the RHR during mid-loop operation at PKL facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villanueva, J. F.; Carlos, S.; Martorell, S.

The loss of the residual heat removal system in mid-loop conditions may occur with a non-negligible contribution to the plant risk, so the analysis of the accidental sequences and the actions to mitigate the accident are of great interest in shutdown conditions. In order to plan the appropriate measures to mitigate the accident is necessary to understand the thermal-hydraulic processes following the loss of the residual heat removal system during shutdown. Thus, transients of this kind have been simulated using best-estimate codes in different integral test facilities and compared with experimental data obtained in different facilities. In PKL (Primaerkreislauf-Versuchsanlage, primarymore » coolant loop test facility) test facility different series of experiments have been undertaken to analyze the plant response in shutdown. In this context, the E3 and F2 series consist of analyzing the loss of the residual heat removal system with a reduced inventory in the primary system. In particular, the experiments were developed to investigate the influence of the steam generators secondary side configuration on the plant response, what involves the consideration of different number of steam generators filled with water and ready for activation, on the heat transfer mechanisms inside the steam generators U-tubes. This work presents the results of such experiments calculated using, RELAP5/Mod 3.3. (authors)« less

Changes in muscle spindle firing in response to length changes of neighboring muscles

PubMed Central

Smilde, Hiltsje A.; Vincent, Jake A.; Baan, Guus C.; Nardelli, Paul; Lodder, Johannes C.; Mansvelder, Huibert D.; Cope, Tim C.

2016-01-01

Skeletal muscle force can be transmitted to the skeleton, not only via its tendons of origin and insertion but also through connective tissues linking the muscle belly to surrounding structures. Through such epimuscular myofascial connections, length changes of a muscle may cause length changes within an adjacent muscle and hence, affect muscle spindles. The aim of the present study was to investigate the effects of epimuscular myofascial forces on feedback from muscle spindles in triceps surae muscles of the rat. We hypothesized that within an intact muscle compartment, muscle spindles not only signal length changes of the muscle in which they are located but can also sense length changes that occur as a result of changing the length of synergistic muscles. Action potentials from single afferents were measured intra-axonally in response to ramp-hold release (RHR) stretches of an agonistic muscle at different lengths of its synergist, as well as in response to synergist RHRs. A decrease in force threshold was found for both soleus (SO) and lateral gastrocnemius afferents, along with an increase in length threshold for SO afferents. In addition, muscle spindle firing could be evoked by RHRs of the synergistic muscle. We conclude that muscle spindles not only signal length changes of the muscle in which they are located but also local length changes that occur as a result of changing the length and relative position of synergistic muscles. PMID:27075540

A Preliminary Exploration of the Effects of a 6-week Interactive Video Dance Exercise Program in an Adult Population

PubMed Central

Fruth, Stacie J; Clifford, Anne; Hine, Stephanie; Huckstep, Jeremy; Merkel, Heidi; Wilkinson, Hilary; Yoder, Jason

2011-01-01

Purpose: The purpose of this study was to determine the effects of a 6-week interactive video dance game (IVDG) program on adult participants’ cardiorespiratory status and body mass index (BMI). Methods: Twenty-seven healthy adult participants attended IVDG sessions over a 6-week period. Participants completed pre- and post-testing consisting of a submaximal VO2 treadmill test, assessment of resting heart rate (RHR) and blood pressure (BP), BMI, and general health questionnaires. Data were analyzed using descriptives, paired t-tests to assess pre-to post-testing differences, and one-way ANOVAs to analyze variables among select groups of participants. Questionnaire data was manually coded and assessed. Results: Twenty participants attended at least 75% of available sessions and were used in data analysis. Mean BMI decreased significantly (from 26.96 kg/m2 to 26.21 kg/m2; 2.87%) and cardiorespiratory fitness measured by peak VO2 increased significantly (from 20.63 ml/kg/min to 21.69 ml/kg/min; 5.14%). Most participants reported that the IVDG program was a good workout, and that they were encouraged to continue or start an exercise routine. Forty percent reported improvements in sleep, and nearly half stated they had or were considering purchasing a home version of a video dance game. Conclusions: Interactive video dance game is an effective and enjoyable exercise program for adults who wish to decrease their BMI and improve components of cardiorespiratory fitness. PMID:22163175

Nuclear factor of activated T cells (NFAT) in pearl oyster Pinctada fucata: molecular cloning and functional characterization.

PubMed

Huang, Xian-De; Wei, Guo-jian; Zhang, Hua; He, Mao-Xian

2015-01-01

Nuclear factor of activated T cells (NFAT) plays an important role in nonimmune cells and also in T cells and many other cells of the immune system, by regulating the expression of a variety of genes involved in the immune response, organ development, developmental apoptosis and angiogenesis. In the present study, the NFAT homology gene, PfNFAT, from the pearl oyster Pinctada fucata was cloned and its genomic structure and promoter were analyzed. PfNFAT encodes a putative protein of 1226 amino acids, and contains a highly conserved Rel homology region (RHR) with DNA-binding specificity, and a regulatory domain (NFAT homology region, NHR) containing a potent transactivation domain (TAD). The PfNFAT gene consists of 12 exons and 11 introns, and its promoter contains potential binding sites for transcription factors such as NF-κB (Nuclear factor κB), STATx (signal transducer and activator of transcription), AP-1 (activator protein-1) and Sox-5/9 (SRY type HMG box-5/9), MyoD (Myogenic Differentiation Antigen) and IRF (Interferon regulatory factor). Comparison and phylogenetic analysis revealed that PfNFAT shows high identity with other invertebrate NFAT, and clusters with the NFAT5 subgroup. Furthermore, gene expression analysis revealed that PfNFAT is involved in the immune response to lipopolysaccharide (LPS) and Polyinosinic-polycytidylic acid (poly I:C) stimulation and in the nucleus inserting operation. The study of PfNFAT may increase understanding of molluscan innate immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Water contamination in fallout areas. Project No. 7806

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robeck, G.G.; Woodward, R.L.; Muschler, W.K.

1958-05-01

An evaluation of the potential radiological hazard to Air Force personnel from drinking water contaminated with fission products is presented. Ground water supplies should be safe from fallout contamination and only surface supplies may need special treatment. Even in untreated water, the radioactivity in surface supplies is not likely to reduce significantly the military effectiveness of personnel using it except where the general level of contamination is greater than 1000 r/hr at H + 1. Dust samples were collected at the Priscilla shot of Operation Plumbbob 24 June 1957. In each of the samples, material containing approximately 10% of themore » activity was soluble; however, strontium was preferentially dissolved by a factor of 5. For the first 10 days after fallout, a supply of one gallon of water per person per day will suffice for drinking and culinary purposes. Ion-exchange, which is over 99% efficient, is the most practical and economical method of supplying decontaminated water. For immediate demand, small mixed-bed demineralizers, which are easily installed and maintained, are recommended; for long term demand, pressure cation-exchange beds operated on the sodium cycle are recommended. A shelter accommodating 100 people would require a small mixed-bed demineralizer with an initial cost of $81 and an operating cost of $9 per day. A pressure cation-exchange bed could be installed for $7,500 which would have an operating cost of 15 cents per 1,000 gallons. This could supply an average daily water requirement of 50,000 gallons.« less

WATER CONTAMINATION IN FALLOUT AREAS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robeck, G.G.; Woodward, R.L.; Muschler, W.K.

1958-05-01

An evaluation of the potential radiological hazard to Air Force personnel from drinking water contaminated with fission products is presented. Ground water supplies should be safe from fall-out contamination and only surface supplies may need special treatment. Even in untreated water, the radioactivity in surface supplies is not likely to reduce significantly the military effectiveness of personnel using it except where the general level of contamination is greater than 1000 r/hr at H + 1. Dust samples were collected at the Priscilla shot of Operation Plumbbob 24 June 1957. In each of the samples, material containing approximately 10% of themore » activity was soluble; however, strontium was preferentially dissolved by a factor of 5. For the first 10 days after fall-out, a supply of one gallon of water per person per day will suffice for drinking and culinary purposes, Ion-exchange, which is over 99% efficient, is the most practical and economical method of supplying decontaminated water, For immediate demand, small mixed-bed demineralizers, which are easily installed and maintained, are recommended; for long term demand, pressure cation-exchange beds operated on the sodium cycle are recommended. A shelter accommodating 100 people would require a small mixed-bed demineralizer with an initial cost of and an operating cost of per day. A pressure cation-exchange bed could be installed for 500 which would have an operating cost of 15 cents per 1,000 gallons. This could supply an average daily water requirement of 50,000 gallons. (auth)« less

Effectiveness of Long and Short Bout Walking on Increasing Physical Activity in Women

PubMed Central

Serwe, Katrina M.; Swartz, Ann M.; Hart, Teresa L.; Strath, Scott J.

2011-01-01

Abstract Background The accumulation of physical activity (PA) throughout the day has been suggested as a means to increase PA behavior. It is not known, however, if accumulated PA results in equivalent increases in PA behavior compared with one continuous session. The purpose of this investigation was to compare changes in PA between participants assigned to walk daily in accumulated shorter bouts vs. one continuous session. Methods In this 8-week randomized controlled trial, 60 inactive women were randomly assigned to one of the following: (1) control group, (2) 30 minutes a day of walking 5 days a week in one continuous long bout (LB), or (3) three short 10-minute bouts (SB) of walking a day, all at a prescribed heart rate intensity. Walking was assessed by pedometer and self-reported walking log. Before and after measures were taken of average steps/day, resting systolic and diastolic blood pressure (SBP, DBP), resting heart rate (RHR), six-minute walk test (6MWT) distance, height, weight, body mass index (BMI), and hip and waist circumference. Results Both walking groups significantly increased PA measured as steps/day compared to controls (p < 0.001), and no significant differences were found between LB and SB groups. The LB group demonstrated significant decreases in hip circumference and significant increases in 6MWT distance compared to the control group. Conclusions Both walking groups significantly increased PA participation. LB group participants completed more walking at a higher intensity than the SB and control groups, which resulted in significant increases in health benefits. PMID:21314449

Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial

PubMed Central

Matloub, Yousif; Broxson, Emmett; La, Mei; Yanofsky, Rochelle; Sather, Harland; Hutchinson, Ray; Heerema, Nyla A.; Sorrell, April D.; Masterson, Margaret; Bleyer, Archie; Gaynon, Paul S.

2010-01-01

The Children's Cancer Group 1952 (CCG-1952) clinical trial studied the substitution of oral 6-thioguanine (TG) for 6-mercaptopurine (MP) and triple intrathecal therapy (ITT) for intrathecal methotrexate (IT-MTX) in the treatment of standard-risk acute lymphoblastic leukemia. After remission induction, 2027 patients were randomized to receive MP (n = 1010) or TG (n = 1017) and IT-MTX (n = 1018) or ITT (n = 1009). The results of the thiopurine comparison are as follows. The estimated 7-year event-free survival (EFS) for subjects randomized to TG was 84.1% (± 1.8%) and to MP was 79.0% (± 2.1%; P = .004 log rank), although overall survival was 91.9% (± 1.4%) and 91.2% (± 1.5%), respectively (P = .6 log rank). The TG starting dose was reduced from 60 to 50 mg/m2 per day after recognition of hepatic veno-occlusive disease (VOD). A total of 257 patients on TG (25%) developed VOD or disproportionate thrombocytopenia and switched to MP. Once portal hypertension occurred, all subjects on TG were changed to MP. The benefit of randomization to TG over MP, as measured by EFS, was evident primarily in boys who began TG at 60 mg/m2 (relative hazard rate [RHR] 0.65, P = .002). The toxicities of TG preclude its protracted use as given in this study. This study is registered at http://clinicaltrials.gov as NCT00002744. PMID:20124218

Proteins involved in wine aroma compounds metabolism by a Saccharomyces cerevisiae flor-velum yeast strain grown in two conditions.

PubMed

Moreno-García, Jaime; García-Martínez, Teresa; Millán, M Carmen; Mauricio, Juan Carlos; Moreno, Juan

2015-10-01

A proteomic and exometabolomic study was conducted on Saccharomyces cerevisiae flor yeast strain growing under biofilm formation condition (BFC) with ethanol and glycerol as carbon sources and results were compared with those obtained under no biofilm formation condition (NBFC) containing glucose as carbon source. By using modern techniques, OFFGEL fractionator and LTQ-Orbitrap for proteome and SBSE-TD-GC-MS for metabolite analysis, we quantified 84 proteins including 33 directly involved in the metabolism of glycerol, ethanol and 17 aroma compounds. Contents in acetaldehyde, acetic acid, decanoic acid, 1,1-diethoxyethane, benzaldehyde and 2-phenethyl acetate, changed above their odor thresholds under BFC, and those of decanoic acid, ethyl octanoate, ethyl decanoate and isoamyl acetate under NBFC. Of the twenty proteins involved in the metabolism of ethanol, acetaldehyde, acetoin, 2,3-butanediol, 1,1-diethoxyethane, benzaldehyde, organic acids and ethyl esters, only Adh2p, Ald4p, Cys4p, Fas3p, Met2p and Plb1p were detected under BFC and as many Acs2p, Ald3p, Cem1p, Ilv2p, Ilv6p and Pox1p, only under NBFC. Of the eight proteins involved in glycerol metabolism, Gut2p was detected only under BFC while Pgs1p and Rhr2p were under NBFC. Finally, of the five proteins involved in the metabolism of higher alcohols, Thi3p was present under BFC, and Aro8p and Bat2p were under NBFC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Limonene inhibits Candida albicans growth by inducing apoptosis.

PubMed

Thakre, Archana; Zore, Gajanan; Kodgire, Santosh; Kazi, Rubina; Mulange, Shradha; Patil, Rajendra; Shelar, Amruta; Santhakumari, Bayitigeri; Kulkarni, Mahesh; Kharat, Kiran; Karuppayil, Sankunny Mohan

2018-07-01

Anti-Candida potential of limonene was evaluated against planktonic growth, biofilm (adhesion, development and maturation) and morphogenesis of Candida albicans in this study. Limonene is a major constituent of citrus oil and most frequently used terpene in food and beverage industry due to its pleasant fragrance, nontoxic, and is generally recognized as safe (GRAS) flavoring agent as well as treatment option in many gastrointestinal diseases.Limonene exhibited excellent anti-Candida activity and was equally effective against planktonic growth of C. albicans isolates differentially susceptible to FLC (N = 35). Limonene inhibited morphogenesis significantly at low concentration. However, it showed stage dependent activity against biofilm formation, that is, it was more effective against adhesion followed by development and maturation. Limonene also exhibited excellent synergy with FLC against planktonic and biofilm growth. SWATH-MS analysis led to identification of limonene responsive proteins that provided molecular insight of its anti-Candida activity. Proteomic analysis revealed upregulation of proteins involved in cell wall glucan synthesis (Kre6); oxidative stress (Rhr2, Adh7 and Ebp1); DNA damage stress (Mbf1 and Npl3); nucleolar stress (Rpl11, Rpl7, Rpl29, Rpl15) and down regulation of cytoskeleton organization (Crn1, Pin3, Cct8, Rbl2), and so forth, in response to limonene. Limonene mediated down regulation of Tps3 indicates activation of caspase (CaMca1) and induction of apoptosis in C. albicans. These results suggest that limonene inhibits C. albicans growth by cell wall/membrane damage induced oxidative stress that leads to DNA damage resulting into modulation of cell cycle and induction of apoptosis through nucleolar stress and metacaspase dependent pathway.

Differences in Physical Fitness and Cardiovascular Function Depend on BMI in Korean Men.

PubMed

So, Wi-Young; Choi, Dai-Hyuk

2010-01-01

We investigated the associations between cardiovascular function and both body mass index and physical fitness in Korean men. The subjects were 2,013 men, aged 20 to 83 years, who visited a health promotion center for a comprehensive medical and fitness test during 2006-2009. The WHO's Asia-Pacific Standard Report definition of BMI was used in this study. Fitness assessment of cardiorespiratory endurance, muscular strength, muscular endurance, flexibility, power, agility, and balance were evaluated by VO2max (ml/kg/min), grip strength (kg), sit-ups (reps/min), sit and reach (cm), vertical jump (cm), side steps (reps/30s), and standing on one leg with eyes closed (sec), respectively. For cardiovascular function, we evaluated systolic blood pressure (SBP), diastolic blood pressure (DBP), resting heart rate (RHR), double product (DP), and vital capacity. There were significant decreases in cardiorespiratory endurance (p < 0.001), power (p < 0.001), and balance (p < 0.001), and increases in muscular strength (p < 0.001). Further, cardiovascular function, including SBP (p < 0.001), DBP (p < 0.001), double product (p < 0.001), and vital capacity (p=0.006) appeared to be lower for the obesity group. We conclude that an obese person exhibits lower fitness level and weaker cardiovascular function than a normal person. Key pointsThe obese group had a lower fitness level, including cardiorespiratory endurance, power, and balance.Obese group demonstrated an increase in muscular strength.Obese group had higher blood pressure and weaker cardiovascular function, including DP and vital capacity, than the normal group.

Differences in Physical Fitness and Cardiovascular Function Depend on BMI in Korean Men

PubMed Central

So, Wi-Young; Choi, Dai-Hyuk

2010-01-01

We investigated the associations between cardiovascular function and both body mass index and physical fitness in Korean men. The subjects were 2,013 men, aged 20 to 83 years, who visited a health promotion center for a comprehensive medical and fitness test during 2006-2009. The WHO's Asia-Pacific Standard Report definition of BMI was used in this study. Fitness assessment of cardiorespiratory endurance, muscular strength, muscular endurance, flexibility, power, agility, and balance were evaluated by VO2max (ml/kg/min), grip strength (kg), sit-ups (reps/min), sit and reach (cm), vertical jump (cm), side steps (reps/30s), and standing on one leg with eyes closed (sec), respectively. For cardiovascular function, we evaluated systolic blood pressure (SBP), diastolic blood pressure (DBP), resting heart rate (RHR), double product (DP), and vital capacity. There were significant decreases in cardiorespiratory endurance (p < 0.001), power (p < 0.001), and balance (p < 0.001), and increases in muscular strength (p < 0.001). Further, cardiovascular function, including SBP (p < 0.001), DBP (p < 0.001), double product (p < 0.001), and vital capacity (p=0.006) appeared to be lower for the obesity group. We conclude that an obese person exhibits lower fitness level and weaker cardiovascular function than a normal person. Key points The obese group had a lower fitness level, including cardiorespiratory endurance, power, and balance. Obese group demonstrated an increase in muscular strength. Obese group had higher blood pressure and weaker cardiovascular function, including DP and vital capacity, than the normal group. PMID:24149691

Application of reliability-centered maintenance to boiling water reactor emergency core cooling systems fault-tree analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Y.A.; Feltus, M.A.

1995-07-01

Reliability-centered maintenance (RCM) methods are applied to boiling water reactor plant-specific emergency core cooling system probabilistic risk assessment (PRA) fault trees. The RCM is a technique that is system function-based, for improving a preventive maintenance (PM) program, which is applied on a component basis. Many PM programs are based on time-directed maintenance tasks, while RCM methods focus on component condition-directed maintenance tasks. Stroke time test data for motor-operated valves (MOVs) are used to address three aspects concerning RCM: (a) to determine if MOV stroke time testing was useful as a condition-directed PM task; (b) to determine and compare the plant-specificmore » MOV failure data from a broad RCM philosophy time period compared with a PM period and, also, compared with generic industry MOV failure data; and (c) to determine the effects and impact of the plant-specific MOV failure data on core damage frequency (CDF) and system unavailabilities for these emergency systems. The MOV stroke time test data from four emergency core cooling systems [i.e., high-pressure coolant injection (HPCI), reactor core isolation cooling (RCIC), low-pressure core spray (LPCS), and residual heat removal/low-pressure coolant injection (RHR/LPCI)] were gathered from Philadelphia Electric Company`s Peach Bottom Atomic Power Station Units 2 and 3 between 1980 and 1992. The analyses showed that MOV stroke time testing was not a predictor for eminent failure and should be considered as a go/no-go test. The failure data from the broad RCM philosophy showed an improvement compared with the PM-period failure rates in the emergency core cooling system MOVs. Also, the plant-specific MOV failure rates for both maintenance philosophies were shown to be lower than the generic industry estimates.« less

A novel loss-of-function mutation in GPR54/KISS1R leads to hypogonadotropic hypogonadism in a highly consanguineous family.

PubMed

Nimri, Revital; Lebenthal, Yael; Lazar, Liora; Chevrier, Lucie; Phillip, Moshe; Bar, Meytal; Hernandez-Mora, Eva; de Roux, Nicolas; Gat-Yablonski, Galia

2011-03-01

The G protein-coupled receptor 54 (GPR54), the kisspeptin receptor, is essential for stimulation of GnRH secretion and induction of puberty. Recently loss-of-function mutations of the GPR54 have been implicated as a cause of isolated idiopathic hypogonadotropic hypogonadism (IHH). The objective of the study was to identify the genetic cause of IHH in a consanguineous pedigree and to characterize the phenotypic features from infancy through early adulthood. In six patients with normosmic IHH belonging to two families of Israeli Muslim-Arab origin highly related to one another, DNA was analyzed for mutations in the GnRHR and GPR54 genes, with functional analysis of the mutation found. The five males underwent comprehensive endocrine evaluation and were under longitudinal follow-up; the one female presented in early adulthood. A new homozygous mutation (c.T815C) in GPR54 leading to a phenylalanine substitution by serine (p.F272S) was detected in all patients. Functional analysis showed an almost complete inhibition of kisspeptin-induced GPR54 signaling and a dramatic decrease of the mutated receptor expression at the cell surface. The males exhibited the same clinical features from infancy to adulthood, characterized by cryptorchidism, a relatively short penis, and no spontaneous pubertal development. The female patient presented at 18 yr with impuberism and primary amenorrhea. Repeated stimulation tests demonstrated complete gonadotropin deficiency throughout follow-up. A novel loss-of-function mutation (p.F272S) in the GPR54 gene is associated with familial normosmic IHH. Underdeveloped external genitalia and impuberism point to the major role of GPR54 in the activation of the gonadotropic axis from intrauterine life to adulthood.

Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH.

PubMed

Acampora, D; Mazan, S; Tuorto, F; Avantaggiato, V; Tremblay, J J; Lazzaro, D; di Carlo, A; Mariano, A; Macchia, P E; Corte, G; Macchia, V; Drouin, J; Brûlet, P; Simeone, A

1998-04-01

Genetic and molecular approaches have enabled the identification of regulatory genes critically involved in determining cell types in the pituitary gland and/or in the hypothalamus. Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland. Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (betaFSH), luteinizing hormone (betaLH) and alpha-glycoprotein subunit (alphaGSU) genes. Analysis of Otx1 null mice indicates that, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism due to low levels of pituitary GH, FSH and LH hormones which, in turn, dramatically affect downstream molecular and organ targets. Nevertheless, Otx1-/- mice gradually recover from most of these abnormalities, showing normal levels of pituitary hormones with restored growth and gonadal function at 4 months of age. Expression patterns of related hypothalamic and pituitary cell type restricted genes, growth hormone releasing hormone (GRH), gonadotropin releasing hormone (GnRH) and their pituitary receptors (GRHR and GnRHR) suggest that, in Otx1-/- mice, hypothalamic and pituitary cells of the somatotropic and gonadotropic lineages appear unaltered and that the ability to synthesize GH, FSH and LH, rather than the number of cells producing these hormones, is affected. Our data indicate that Otx1 is a new pituitary transcription factor involved at the prepubescent stage in the control of GH, FSH and LH hormone levels and suggest that a complex regulatory mechanism might exist to control the physiological need for pituitary hormones at specific postnatal stages.

Remote Handled WIPP Canisters at Los Alamos National Laboratory Characterized for Retrieval

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griffin, J.; Gonzales, W.

2007-07-01

The Los Alamos National Laboratory (LANL) is pursuing retrieval, transportation, and disposal of 16 remote handled transuranic waste canisters stored below ground in shafts since 1994. These canisters were retrievably stored in the shafts to await Nuclear Regulatory Commission certification of the Model Number RH-TRU 72B transportation cask and authorization of the Waste Isolation Pilot Plant (WIPP) to accept the canisters for disposal. Retrieval planning included radiological characterization and visual inspection of the canisters to confirm historical records, verify container integrity, determine proper personnel protection for the retrieval operations, provide radiological dose and exposure rate data for retrieval operations, andmore » to provide exterior radiological contamination data. The radiological characterization and visual inspection of the canisters was performed in May 2006. The effort required the development of remote techniques and equipment due to the potential for personnel exposure to radiological doses approaching 300 R/hr. Innovations included the use of two nested 1.5 meter (m) (5-feet [ft]) long concrete culvert pipes (1.1-m [42 inch (in.)] and 1.5-m [60-in] diameter, respectively) as radiological shielding and collapsible electrostatic dusting wands to collect radiological swipe samples from the annular space between the canister and shaft wall. Visual inspection indicated that the canisters are in good condition with little or no rust, the welded seams are intact, and ten of the canisters include hydrogen gas sampling equipment on the pintle that will have to be removed prior to retrieval. The visual inspection also provided six canister identification numbers that matched historical storage records. The exterior radiological data indicated alpha and beta contamination below LANL release criteria and radiological dose and exposure rates lower than expected based upon historical data and modeling of the canister contents. (authors)« less

Assessing Metabolic Syndrome Through Increased Heart Rate During Exercise.

PubMed

Sadeghi, Masoumeh; Gharipour, Mojgan; Nezafati, Pouya; Shafie, Davood; Aghababaei, Esmaeil; Sarrafzadegan, Nizal

2016-11-01

The present study aimed to assess changes in resting and maximum heart rates as primary indicators of cardiac autonomic function in metabolic syndrome (MetS) patients and to determine their value for discriminating MetS from non-MetS. 468 participants were enrolled in this cross-sectional study and assessed according to the updated adult treatment panel III (ATP-III) definition of MetS. Resting and maximum heart rates were recorded following the Bruce protocol during an exercise. A receiver operating characteristic (ROC) curve was used to identify the best cutoff point for discriminating MetS from the non-MetS state. 194 participants (41.5%) were diagnosed as MetS. The mean resting heart rate (RHR) was not statistically different between the two groups (P=0.078). However, the mean maximum heart (MHR) rate was considerably higher in participants with MetS (142.37±14.84 beats per min) compared to the non-MetS group (134.62±21.63 beats per min) (P<0.001). In the MetS group, the MHR was positively correlated with the serum triglyceride level (β=0.185, P=0.033) and was inversely associated with age (β=-0.469, P<0.001). The MHR had a moderate value for discriminating MetS from the non-MetS state (c=0.580, P=0.004) with the optimal cutoff point of 140 beats per min. In MetS patients, the MHR was significantly greater compared to non-MetS subjects and was directly correlated with serum triglyceride levels and inversely with advanced age. Moreover, MHR can be used as a suspicious indicator for identifying MetS.

The benefits of endurance training in cardiomyocyte function in hypertensive rats are reversed within four weeks of detraining.

PubMed

Carneiro-Júnior, Miguel Araujo; Quintão-Júnior, Judson Fonseca; Drummond, Lucas Rios; Lavorato, Victor Neiva; Drummond, Filipe Rios; da Cunha, Daise Nunes Queiroz; Amadeu, Marco Aurélio; Felix, Leonardo Bonato; de Oliveira, Edilamar Menezes; Cruz, Jader Santos; Prímola-Gomes, Thales Nicolau; Mill, José Geraldo; Natali, Antonio José

2013-04-01

The aim of the present study was to verify the effects of low-intensity endurance training and detraining on the mechanical and molecular properties of cardiomyocytes from spontaneously hypertensive rats (SHRs). Male SHRs and normotensive control Wistar rats at 16-weeks of age were randomly divided into eight groups of eight animals: NC8 and HC8 (normotensive and hypertensive control for 8weeks); NT8 and HT8 (normotensive and hypertensive trained at 50-60% of maximal exercise capacity for 8weeks); NC12 and HC12 (normotensive and hypertensive control for 12weeks); NDT and HDT (normotensive and hypertensive trained for 8weeks and detrained for 4weeks). The total exercise time until fatigue (TTF) was determined by a maximal exercise capacity test. Resting heart rate (RHR) and systolic arterial pressure (SAP) were measured. After the treatments, animals were killed by cervical dislocation and left ventricular myocytes were isolated by enzymatic dispersion. Isolated cells were used to determine intracellular global Ca(2+) ([Ca(2+)]i) transient and cardiomyocyte contractility (1Hz; ~25°C). [Ca(2+)]i regulatory proteins were measured by Western blot, and the markers of pathologic cardiac hypertrophy by quantitative real-time polymerase chain reaction (q-RT-PCR). Exercise training augmented the TTF (NC8, 11.4±1.5min vs. NT8, 22.5±1.4min; HC8, 11.7±1.4min vs. HT8, 24.5±1.3min; P<0.05), reduced RHR (NT8initial, 340±8bpm vs. NT8final, 322±10bpm; HT8initial, 369±8bpm vs. HT8final, 344±10bpm; P<0.05), and SBP in SHR animals (HC8, 178±3mmHg vs. HT8, 161±4mmHg; P<0.05). HC8 rats showed a slower [Ca(2+)]i transient (Tpeak, 83.7±1.8ms vs. 71.7±2.4ms; T50%decay, 284.0±4.3ms vs. 264.0±4.1ms; P<0.05) and cell contractility (Vshortening, 86.1±6.7μm/s vs. 118.6±6.7μm/s; Vrelengthening, 57.5±7.4μm/s vs. 101.3±7.4μm/s; P<0.05), and higher expression of ANF (300%; P<0.05), skeletal α-actin (250%; P<0.05) and a decreased α/β-MHC ratio (70%; P<0.05) compared to NC8. Exercise training increased [Ca(2+)]i transient (NC8, 2.39±0.06F/F0 vs. NT8, 2.72±0.06F/F0; HC8, 2.28±0.05F/F0 vs. HT8, 2.82±0.05F/F0; P<0.05), and cell contractility (NC8, 7.4±0.3% vs. NT8, 8.4±0.3%; HC8, 6.8±0.3% vs. HT8, 7.8±0.3%; P<0.05). Furthermore, exercise normalized the expression of ANF, skeletal α-actin, and the α/β-MHC ratio in HT8 rats, augmented the expression of SERCA2a (NC8, 0.93±0.15 vs. NT8, 1.49±0.14; HC8, 0.83±0.13 vs. HT8, 1.32±0.14; P<0.05) and PLBser16 (NC8, 0.89±0.18 vs. NT8, 1.23±0.17; HC8, 0.77±0.17 vs. HT8, 1.32±0.16; P<0.05), and reduced PLBt/SERCA2a (NC8, 1.21±0.19 vs. NT8, 0.50±0.21; HC8, 1.38±0.17 vs. HT8, 0.66±0.21; P<0.05). However, all these adaptations returned to control values within 4weeks of detraining in both SHR and normotensive control animals. In conclusion, low-intensity endurance training induces positive benefits to left ventricular myocyte mechanical and molecular properties, which are reversed within 4weeks of detraining. Copyright © 2013 Elsevier Ltd. All rights reserved.

High Hospitalization Rates in Survivors of Childhood Cancer: A Longitudinal Follow-Up Study Using Medical Record Linkage

PubMed Central

Sieswerda, Elske; Font-Gonzalez, Anna; Reitsma, Johannes B.; Dijkgraaf, Marcel G. W.; Heinen, Richard C.; Jaspers, Monique W.; van der Pal, Helena J.; van Leeuwen, Flora E.; Caron, Huib N.

2016-01-01

Hospitalization rates over time of childhood cancer survivors (CCS) provide insight into the burden of unfavorable health conditions on CCS and health care resources. The objective of our study was to examine trends in hospitalizations of CCS and risk factors in comparison with the general population. We performed a medical record linkage study of a cohort of 1564 ≥five-year CCS with national registers. We obtained a random sample of the general population matched on year of birth, gender and calendar year per CCS retrieved. We quantified and compared hospitalization rates of CCS and reference persons from 1995 until 2005, and we analyzed risk factors for hospitalization within the CCS cohort with multivariable Poisson models. We retrieved hospitalization information from 1382 CCS and 25583 reference persons. The overall relative hospitalization rate (RHR) was 2.2 (95%CI:1.9–2.5) for CCS compared to reference persons. CCS with central nervous system and solid tumors had highest RHRs. Hospitalization rates in CCS were increased compared to reference persons up to at least 30 years after primary diagnosis, with highest rates 5–10 and 20–30 years after primary cancer. RHRs were highest for hospitalizations due to neoplasms (10.7; 95%CI:7.1–16.3) and endocrine/nutritional/metabolic disorders (7.3; 95%CI:4.6–11.7). Female gender (P<0.001), radiotherapy to head and/or neck (P<0.001) or thorax and/or abdomen (P = 0.03) and surgery (P = 0.01) were associated with higher hospitalization rates in CCS. In conclusion, CCS have increased hospitalization rates compared to the general population, up to at least 30 years after primary cancer treatment. These findings imply a high and long-term burden of unfavorable health conditions after childhood cancer on survivors and health care resources. PMID:27433937

Characterization of the FoxL2 proximal promoter and coding sequence from the common snapping turtle (Chelydra serpentina).

PubMed

Guo, Lei; Rhen, Turk

2017-10-01

Sex is determined by temperature during embryogenesis in snapping turtles, Chelydra serpentina. Previous studies in this species show that dihydrotestosterone (DHT) induces ovarian development at temperatures that normally produce males or mixed sex ratios. The feminizing effect of DHT is associated with increased expression of FoxL2, suggesting that androgens regulate transcription of FoxL2. To test this hypothesis, we cloned the proximal promoter (1.6kb) and coding sequence for snapping turtle FoxL2 (tFoxL2) in frame with mCherry to produce a fluorescent reporter. The tFoxL2-mCherry fusion plasmid or mCherry control plasmid were stably transfected into mouse KK1 granulosa cells. These cells were then treated with 0, 1, 10, or 100nM DHT to assess androgen effects on tFoxL2-mCherry expression. In contrast to the main hypothesis, DHT did not alter expression of the tFoxL2-mCherry reporter. However, normal serum increased expression of tFoxL2-mCherry when compared to charcoal-stripped serum, indicating that the cloned region of tFoxL2 contains cis regulatory elements. We also used the tFoxL2-mCherry plasmid as an expression vector to test the hypothesis that DHT and tFoxL2 interact to regulate expression of endogenous genes in granulosa cells. While tFoxL2-mCherry and DHT had independent effects on mouse FoxL2, FshR, GnRHR, and StAR expression, tFoxL2-mCherry potentiated low concentration DHT effects on mouse aromatase expression. Further studies will be required to determine whether synergistic regulation of aromatase by DHT and FoxL2 also occurs in turtle gonads during the sex-determining period, which would explain the feminizing effect of DHT in this species. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of dance movement therapy on selected cardiovascular parameters and estimated maximum oxygen consumption in hypertensive patients.

PubMed

Aweto, H A; Owoeye, O B A; Akinbo, S R A; Onabajo, A A

2012-01-01

Objective:Arterial hypertension is a medical condition associated with increased risks of of death, cardiovascular mortality and cardiovascular morbidity including stroke, coronary heart disease, atrial fibrillation and renal insufficiency. Regular physical exercise is considered to be an important part of the non-pharmacologictreatment of hypertension. The purpose of this study was to investigate the effects of dance movement therapy (DMT) on selected cardiovascular parameters and estimated maximum oxygen consumption in hypertensive patients. Fifty (50) subjects with hypertension participated in the study. They were randomly assigned to 2 equal groups; A (DMT group) and B (Control group). Group A carried out dance movement therapy 2 times a week for 4 weeks while group B underwent some educational sessions 2 times a week for the same duration. All the subjects were on anti-hypertensive drugs. 38 subjects completed the study with the DMTgroup having a total of 23 subjects (10 males and 13 females) and the control group 15 subjects (6 males and 9 females). Descriptive statistics of mean, standard deviation and inferential statistics of paired and independentt-testwere used for data analysis. Following four weeks of dance movement therapy, paired t-test analysis showed that there was a statistically significant difference in the Resting systolic blood pressure (RSBP) (p < 0.001*), Resting diastolic blood pressure (RDBP) (p < 0.001*), Resting heart rate (RHR) (p = 0.024*), Maximum heart rate (MHR) (p=0.002*) and Estimated oxygen consumption (VO2max) (p = 0.023*) in subjects in group A (p < 0.05) while there was no significant difference observed in outcome variables of subjects in group B (p > 0.05). Independent t-test analysis between the differences in the pre and post intervention scores of groups A and B also showed statistically significant differences in all the outcome variables (p <0.05). DMT was effective in improving cardiovascular parameters and estimated maximum oxygen consumption in hypertensive patients.

High Hospitalization Rates in Survivors of Childhood Cancer: A Longitudinal Follow-Up Study Using Medical Record Linkage.

PubMed

Sieswerda, Elske; Font-Gonzalez, Anna; Reitsma, Johannes B; Dijkgraaf, Marcel G W; Heinen, Richard C; Jaspers, Monique W; van der Pal, Helena J; van Leeuwen, Flora E; Caron, Huib N; Geskus, Ronald B; Kremer, Leontien C

2016-01-01

Hospitalization rates over time of childhood cancer survivors (CCS) provide insight into the burden of unfavorable health conditions on CCS and health care resources. The objective of our study was to examine trends in hospitalizations of CCS and risk factors in comparison with the general population. We performed a medical record linkage study of a cohort of 1564 ≥five-year CCS with national registers. We obtained a random sample of the general population matched on year of birth, gender and calendar year per CCS retrieved. We quantified and compared hospitalization rates of CCS and reference persons from 1995 until 2005, and we analyzed risk factors for hospitalization within the CCS cohort with multivariable Poisson models. We retrieved hospitalization information from 1382 CCS and 25583 reference persons. The overall relative hospitalization rate (RHR) was 2.2 (95%CI:1.9-2.5) for CCS compared to reference persons. CCS with central nervous system and solid tumors had highest RHRs. Hospitalization rates in CCS were increased compared to reference persons up to at least 30 years after primary diagnosis, with highest rates 5-10 and 20-30 years after primary cancer. RHRs were highest for hospitalizations due to neoplasms (10.7; 95%CI:7.1-16.3) and endocrine/nutritional/metabolic disorders (7.3; 95%CI:4.6-11.7). Female gender (P<0.001), radiotherapy to head and/or neck (P<0.001) or thorax and/or abdomen (P = 0.03) and surgery (P = 0.01) were associated with higher hospitalization rates in CCS. In conclusion, CCS have increased hospitalization rates compared to the general population, up to at least 30 years after primary cancer treatment. These findings imply a high and long-term burden of unfavorable health conditions after childhood cancer on survivors and health care resources.

Effects of methomyl on steroidogenic gene transcription of the hypothalamic-pituitary-gonad-liver axis in male tilapia.

PubMed

Meng, ShunLong; Qiu, LiPing; Hu, GengDong; Fan, LiMin; Song, Chao; Zheng, Yao; Wu, Wei; Qu, JianHong; Li, DanDan; Chen, JiaZhang; Xu, Pao

2016-12-01

Male tilapia were exposed to sub-lethal methomyl concentrations of 0, 0.2, 2, 20 or 200 μg/L for 30 d, and were subsequently cultured in methomyl-free water for 18 d. Relative transcript abundance of steroidogenic genes involved in the HPGL axis of male tilapia was examined at 30 d in the exposure test and at 18 d in the recovery test. The results revealed that low concentrations of methomyl (0.2 and 2 μg/L) did not cause significant changes in gene mRNA levels in the HPGL axis of male tilapia; thus, we considered 2 μg/L concentrations as the level that showed no apparent adverse endocrine disruption effects. However, higher concentrations of methomyl (20 and 200 μg/L) disrupted the endocrine system and caused significant increase in the levels of GnRH2, GnRH3, ERα, and ERβ genes in the hypothalamus, GnRHR and FSHβ genes in the pituitary, CYP19a, FSHR, and ERα genes in the testis, and VTG and ERα genes in the liver, and significantly decreased the levels of LHR, StAR, 3β-HSD, and ARα genes in the testis and LHβ gene in the pituitary, leading to changes in sex steroid hormone and vitellogenin levels in the serum and ultimately resulting in reproductive dysfunction in male tilapia. The recovery tests showed that the toxicity effect caused by 20 μg/L methomyl was reversible; however, the toxicity effect at 200 μg/L of methomyl was irreversible after 18 d. Therefore, we concluded that 200 μg/L was the threshold concentration for methomyl-induced irreversible endocrine disruption in male tilapia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Workload assessment in building construction related activities in India.

PubMed

Maiti, Rina

2008-11-01

A field study was conducted to highlight the occupational risk factors related to building construction activities in India among female workers. These workers were engaged in eight different types of activities and related work parameters were studied in detail. From field environmental parameters, the calculated WBGT was obtained as 30.26+/-1.52 degrees C, indicated that these workers worked under a positive heat load condition. Whole day work study was conducted on 11 adult female workers performing concreting operation. They were having age of 28-32 years with 5-7 years of work experience. These workers were mainly performing two types of operations in the field: (A) asymmetric lifting during concreting a boundary wall formwork of a lift unit and (B) carrying the concrete mixture. During asymmetric lifting, the average field working heart rate (HR) was calculated as 124.1+/-12.5 beats min(-1), equivalent to 45.03+/-6.93% of VO(2) max level. These working heart rates (HRs) were significantly (p

Effects Ala54Thr polymorphism of FABP2 on obesity index and biochemical variable in response to a aerobic exercise training

PubMed Central

Han, Tae Kyung

2013-01-01

The purpose of the current study was to investigate whether or not the FABP2 gene polymorphism modulated obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers through 12-week aerobic exercise training in abdominal obesity group of Korean mid-life women. A total of 243 abdominally obese subjects of Korean mid-life women voluntarily participated in aerobic exercise training program for 12 weeks. Polymerase Chain Reaction with Restriction Fragment Length Polymorphism (PCR-RFLP) assay was used to assess the FABP2 genotype of the participants (117 of AA homozygotes, 100 of AT heterozygotes, 26 of TT homozygotes). Prior to the participation of the exercise training program, baseline obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers were measured. All the measurements were replicated following the 12-week aerobic exercise training program, and then the following results were found. After 12-week aerobic exercise training program, wild type (Ala54Ala) and mutant type (Ala54Thr+Thr54Thr) significantly decreased weight (P > .001), BMI (P > .001), %bf (P > .001), waist circumference (P > .001), WHR (P > .001), muscle mass (wild type p < .022; mutant type P > .001), RHR (P > .001), viseceral adipose area (wild type p < .005; mutant type P > .001), subcutaneous area (P > .001), insulin (wild type p < .005; mutant type P > .001) and significantly increased VO2max (P > .001). And wild type significantly decresed NEFA (P > .05), glucose (P > .05), OGTT 120min glucose (P > .05) and significantly increased HDLC (p > .005). Mutant type significantly decreased SBP (P > .001), DBP (P > .01), TC (P > .01), LPL (P > .05), LDL (P > .001), HOMA index (P > .01). The result of the present study represents that regular aerobic exercise training may beneficially prevent obesity index, blood pressure, blood lipids and insulin resistance markers independent of FABP Ala54Thr wild type and mutant type. PMID:25566432

Effect of light intensity on ovarian gene expression, reproductive performance and body weight of rabbit does.

PubMed

Sun, Liangzhan; Wu, Zhenyu; Li, Fuchang; Liu, Lei; Li, Jinglin; Zhang, Di; Sun, Chaoran

2017-08-01

The objective of the experiment was to find the minimum light intensity which could improve reproduction by examining its effect on ovarian gene expression, reproductive performance and body weight of rabbit does with three different light intensities: 60 (L), 80 (M), and 100 (H)lx. A total of 144 Rex-rabbits submitted to a 49-day reproductive regimen were used in this study. Ovaries were collected and relative abundance of mRNA for ovarian proteins of interest was examined with real-time PCR. Amount of protein for proteins of interest was examined by immunohistochemistry. Reproductive performance and doe bodyweight of the first three consecutive reproductive periods after initiation of the light intensity treatments were evaluated. The results provided evidence that light intensity had no effect on relative abundance of estradiol receptor-α (ER-α), follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), gonadotropin releasing hormone receptor 1 (GnRHR1) and progesterone receptor (PGR) mRNA. The relative abundance of growth hormone receptor (GHR) mRNA was, however, greater in Group L than M and H (P<0.05). No difference was observed for all reproductive indices as a result of submission to the three light intensities (P>0.05). The bodyweight of the does in Group L was greater than the other two groups at first insemination, second insemination and the second postpartum period (P<0.05). There was no difference in bodyweight after the second postpartum period (P>0.05). These observations suggest that light intensity between 60 and 100lx has no effect on the reproductive performance of rabbit does, however, the amounts of GHR mRNA and growth hormone (GH) protein were affected and the greater light intensity had a negative effect on bodyweight between the time of the first insemination and the second partum period. Copyright © 2017 Elsevier B.V. All rights reserved.

Congenital Hypogonadotropic Hypogonadism during Childhood: Presentation and Genetic Analyses in 46 Boys

PubMed Central

Vizeneux, Audrey; Hilfiger, Aude; Bouligand, Jérôme; Pouillot, Monique; Brailly-Tabard, Sylvie; Bashamboo, Anu; McElreavey, Ken; Brauner, Raja

2013-01-01

Background The majority of the patients reported with mutations in isolated hypogonadotropic hypogonadism (HH) are adults. We analysed the presentation and the plasma inhibin B and anti-müllerian hormone (AMH) concentrations during childhood and adolescence, and compared them to the genetic results. Methods This was a retrospective, single-center study of 46 boys with HH. Results Fourteen (30.4%) had Kallmann syndrome (KS), 4 (8.7%) had CHARGE syndrome and 28 (60.9%) had HH without olfaction deficit nor olfactive bulb hypoplasia. Eighteen (39%) had an associated malformation or syndromes. At diagnosis, 22 (47.8%) boys were aged

Conditioning of the 4 Curies Radium-226 Sealed Radiation Source in Thailand

DOE Office of Scientific and Technical Information (OSTI.GOV)

Punnachaiya, M.; Sawangsri, T.; Wanabongse, P.

This paper describes the conditioning of the 4 curies Radium-226 (Ra-226) sealed radiation source using as a teletherapy unit for cancer treatment in Thailand. The conditioning was under the International Atomic Energy Agency (IAEA) supervision and budgetary supports, comprised of 6 operational steps: the surface dose rate and actual dimension of radium unit measurements, the appropriate lead shielding design with IAEA approval, confirmation of radioactive contamination before conditioning (smear test and radon gas leakage test), transfer of radium source unit into the designed shielding, confirmation of radioactive contamination and dose rate measurement after conditioning, and transportation of Ra-226 conditioning wastemore » package to OAP interim waste storage. The Ra-226 unit was taken out of OAP temporary waste storage for the surface dose rate and the actual dimension measurements behind the 12 inches thick heavy concrete shielding. The maximum measured surface dose rate was 70 R/hr. The special lead container was designed according to its surface dose rate along the source unit which the maximum permissible dose limit for surface dose rate of waste package after conditioning at 2 mSv/hr was applied. The IAEA approved container had total weight of 2.4 ton. After the confirmation of radioactive contamination, Ra-226 source unit was transferred and loaded in the designed lead shielding within 2 minutes. The results of smear test before and after conditioning including radon gas leakage test revealed that there was no radioactive contamination. After conditioning, the surface dose rate measured on the top, bottom were 15,10 mR/hr and varied from 6 - 50 mR/hr around lead container. The Ra-226 conditioning waste package was safely transported to store in OAP interim waste storage. Total working time including the time consumed for radon gas leakage test was 3.5 hours. The total radiation dose received by 16 operators, were ranged from 1 - 69.84 {mu}Sv and the operational team completed the conditioning safely within the effective dose limit for occupational exposure of 50 mSv/year (200 {mu}Sv/day). (authors)« less

A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes

PubMed Central

Peiris, Heshan; Duffield, Michael D.; Fadista, Joao; Kashmir, Vinder; Genders, Amanda J.; McGee, Sean L.; Martin, Alyce M.; Saiedi, Madiha; Morton, Nicholas; Carter, Roderick; Cousin, Michael A.; Oskolkov, Nikolay; Volkov, Petr; Hough, Tertius A.; Fisher, Elizabeth M. C.; Tybulewicz, Victor L. J.; Busciglio, Jorge; Coskun, Pinar E.; Becker, Ann; Belichenko, Pavel V.; Mobley, William C.; Ryan, Michael T.; Chan, Jeng Yie; Laybutt, D. Ross; Coates, P. Toby; Yang, Sijun; Ling, Charlotte; Groop, Leif; Pritchard, Melanie A.; Keating, Damien J.

2016-01-01

Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D. PMID:27195491

In vivo oestrogenic modulation of Egr1 and Pitx1 gene expression in female rat pituitary gland.

PubMed

Gajewska, Alina; Herman, Andrzej P; Wolińska-Witort, Ewa; Kochman, Kazimierz; Zwierzchowski, Lech

2014-12-01

EGR1 and PITX1 are transcription factors required for gonadotroph cell Lhb promoter activation. To determine changes in Egr1 and Pitx1 mRNA levels in central and peripheral pituitary stimulations, an in vivo model based on i.c.v. pulsatile (1 pulse/0.5 h over 2 h) GnRH agonist (1.5 nM buserelin) or antagonist (2 nM antide) microinjections was used. The microinjections were given to ovariectomised and 17β-oestradiol (E2) (3×20 μg), ERA (ESR1) agonist propyl pyrazole triol (PPT) (3×0.5 mg), ERB (ESR2) agonist diarylpropionitrile (DPN) (3×0.5 mg) s.c. pre-treated rats 30 min after last pulse anterior pituitaries were excised. Relative mRNA expression was determined by quantitative RT-PCR (qRT-PCR). Results revealed a gene-specific response for GnRH and/or oestrogenic stimulations in vivo. Buserelin pulses enhanced Egr1 expression by 66% in ovariectomised rats, whereas the oestradiol-supplemented+i.c.v. NaCl-microinjected group showed a 50% increase in Egr1 mRNA expression. The oestrogenic signal was transmitted via ERA (ESR1) and ERB (ESR2) activation as administration of PPT and DPN resulted in 97 and 62%, respectively, elevation in Egr1 mRNA expression. A synergistic action of GnRH agonist and 17β-oestradiol (E2) stimulation of the Egr1 gene transcription in vivo were found. GnRHR activity did not affect Pitx1 mRNA expression; regardless of NaCl, buserelin or antide i.c.v. pulses, s.c. oestrogenic supplementation (with E2, PPT or DPN) consistently decreased (by -46, -48 and -41% respectively) the Pitx1 mRNA in the anterior pituitary gland. Orchestrated Egr1 and Pitx1 activities depending on specific central and peripheral regulatory inputs could be responsible for physiologically variable Lhb gene promoter activation in vivo. © 2014 Society for Endocrinology.

Fatty Acid β-Oxidation Is Essential in Leptin-Mediated Oocytes Maturation of Yellow Catfish Pelteobagrus fulvidraco.

PubMed

Song, Yu-Feng; Tan, Xiao-Ying; Pan, Ya-Xiong; Zhang, Li-Han; Chen, Qi-Liang

2018-05-14

Although several studies have been conducted to study leptin function, information is very scarce on the molecular mechanism of leptin in fatty acid β-oxidation and oocytes maturation in fish. In this study, we investigated the potential role of fatty acid β-oxidation in leptin-mediated oocytes maturation in Pelteobagrus fulvidraco . Exp. 1 investigated the transcriptomic profiles of ovary and the differential expression of genes involved in β-oxidation and oocytes maturation following rt-hLEP injection; rt-hLEP injection was associated with significant changes in the expression of genes, including twenty-five up-regulated genes ( CPT1 , Acsl , Acadl , Acadm , Hadhb , Echsl , Hsd17b4 , Acca , PPARα , CYP8B1 , ACOX1 , ACBP , MAPK , RINGO , Cdc2 , MEK1 , IGF-1R , APC/C, Cdk2 , GnRHR, STAG3 , SMC1 , FSHβ and C-Myc ) and ten down-regulated gene ( PPARγ , FATCD36 , UBC , PDK1 , Acads , Raf , Fizzy , C3H-4 , Raf and PKC ), involved in fatty acid β-oxidation and oocytes maturation. In Exp. 2, rt-hLEP and specific inhibitors AG490 (JAK-STAT inhibitor) were used to explore whether leptin induced oocytes maturation, and found that leptin incubation increased the diameters of oocytes and percentage of germinal vesicle breakdown (GVBD)-MII oocytes, up-regulated mRNA levels of genes involved in oocytes maturation and that leptin-induced oocyte maturation was related to activation of JAK-STAT pathway. In Exp. 3, primary oocytes of P. fulvidraco were treated with (R)-(+)-etomoxir (an inhibitor of β-oxidation) or l-carnitine (an enhancer of β-oxidation) for 48 h under rt-hLEP incubation. Exp. 3 indicated that the inhibition of fatty acid β-oxidation resulted in the down-regulation of gene expression involved in oocytes maturation, and repressed the leptin-induced up-regulation of these gene expression. Activation of fatty acid β-oxidation improved the maturation rate and mean diameter of oocytes, and up-regulated gene expression involved in oocytes maturation. Leptin is one of the main factors that links fatty acid β-oxidation with oocyte maturation; β-oxidation is essential for leptin-mediated oocyte maturation in fish.

Effects of Age, Exercise Duration, and Test Conditions on Heart Rate Variability in Young Endurance Horses

PubMed Central

Younes, Mohamed; Robert, Céline; Barrey, Eric; Cottin, François

2016-01-01

Although cardiac recovery is an important criterion for ranking horses in endurance competitions, heart rate variability (HRV) has hardly ever been studied in the context of this equestrian discipline. In the present study, we sought to determine whether HRV is affected by parameters such as age, exercise duration and test site. Accordingly, HRV might be used to select endurance horses with the fastest cardiac recovery. The main objective of the present study was to determine the effects of age, exercise duration, and test site on HRV variables at rest and during exercise and recovery in young Arabian endurance horses. Over a 3-year period, 77 young Arabian horses aged 4–6 years performed one or more exercise tests (consisting of a warm-up, cantering at 22 km.h−1and a final 500 m gallop at full speed) at four different sites. Beat-to-beat RR intervals were continuously recorded and then analyzed (using a time-frequency approach) to determine the instantaneous HRV components before, during and after the test. At rest, the root-mean-square of successive differences in RR intervals (RMSSD) was higher in the 4-year-olds (54.4 ± 14.5 ms) than in the 5-or 6-year-olds (44.9 ± 15.5 and 49.1 ± 11.7 ms, respectively). During the first 15 min of exercise (period T), the heart rate (HR) and RMSSD decreased with age. In 6-year-olds, RMSSD decreased as the exercise duration increased (T: 3.0 ± 1.4 vs. 2T: 3.6 ± 2.2 vs. 3T: 2.8 ± 1.0). During recovery, RMSSD was negatively correlated with the cardiac recovery time (CRT) and the recovery heart rate (RHR; R = −0.56 and −0.53, respectively; p < 0.05). At rest and during exercise and recovery, RMSSD and several HRV variables differed significantly as a function of the test conditions. HRV in endurance horses appears to be strongly influenced by age and environmental factors (such as ambient temperature, ambient humidity, and track quality). Nevertheless, RMSSD can be used to select endurance horses with the fastest cardiac recovery. PMID:27199770

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spriggs, G D

In a previous paper, the composite exposure rate conversion factor (ECF) for nuclear fallout was calculated using a simple theoretical photon-transport model. The theoretical model was used to fill in the gaps in the FGR-12 table generated by ORNL. The FGR-12 table contains the individual conversion factors for approximate 1000 radionuclides. However, in order to calculate the exposure rate during the first 30 minutes following a nuclear detonation, the conversion factors for approximately 2000 radionuclides are needed. From a human-effects standpoint, it is also necessary to have the dose rate conversion factors (DCFs) for all 2000 radionuclides. The DCFs aremore » used to predict the whole-body dose rates that would occur if a human were standing in a radiation field of known exposure rate. As calculated by ORNL, the whole-body dose rate (rem/hr) is approximately 70% of the exposure rate (R/hr) at one meter above the surface. Hence, the individual DCFs could be estimated by multiplying the individual ECFs by 0.7. Although this is a handy rule-of-thumb, a more consistent (and perhaps, more accurate) method of estimating the individual DCFs for the missing radionuclides in the FGR-12 table is to use the linear relationship between DCF and total gamma energy released per decay. This relationship is shown in Figure 1. The DCFs for individual organs in the body can also be estimated from the estimated whole-body DCF. Using the DCFs given FGR-12, the ratio of the organ-specific DCFs to the whole-body DCF were plotted as a function of the whole-body DCF. From these plots, the asymptotic ratios were obtained (see Table 1). Using these asymptotic ratios, the organ-specific DCFs can be estimated using the estimated whole-body DCF for each of the missing radionuclides in the FGR-12 table. Although this procedure for estimating the organ-specific DCFs may over-estimate the value for some low gamma-energy emitters, having a finite value for the organ-specific DCFs in the table is probably better than having no value at all. A summary of the complete ECF and DCF values are given in Table 2.« less

Research trends with food irradiation in Japan (in Japanese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, T.

Potatoes and onions are irradiated to prevent their germination for 8 months after harvest. Twenty-seven tons of potatoes were exposed to /sup 60/Co gamma irradiation at a dose rate of 7 x 10/sup 4/ R/hr. Potatoes irradiated with a dose of 7 to 15 Krads were stored for 8 months at room temperature, and were suitable market produce. Sapporo yellow onions, produced in Hokkaido and which passed the year-end for storage, were mainly studied. It was possible to prevent germination of the onions if irradiated at a dose of 3 to 10 Krads within the dormant period. Concerning rice, itmore » was suggested that prevention of the main harmful insects of rice, such as rice weevil, Sordidus zeamais and Sordidus oryzal, was possible by sterilization and inactivation through irradiation at a dose of 15 Krads. The sterilization dose for harmful insects of wheat was 5 to 7 Krads. Theoff flavor in the wheat was recognized immediately after irradiation at a dose of 20 Krads, but after three months wheat did not show off flavor even with 50 Krads irradiation. As a result, the volume of bread was larger in irradiated bread rather than in nonirradiated bread. Vienna sausage without preservatives was irradiated in 500 Krads under the condition of being kept in cold storage at 10 deg C. Its decomposition was delayed one week. The proper dose for boiled fishpaste was determined to be 300 Krads, and its preservation period was prolonged from 7 to 10 days to 21 days by irradiation. In mandarin oranges, off flavor was caused by a dose level of 50 Krads of /sup 60/Co gamma radiation. Therefore, irradiation of mandarin oranges has to depend on electron irnadiation, but problems remain regarding the irradiation technique. In a study of the safety of irradiated food, potato irradiation was permitted by the Ministry of Health and Welfare at a dose of 15 Knads in August of 1972. Lastly, the condition of potato irradiation in the producing and consuming districts and economic problems are discussed. (JA)« less

The status of ABWR-II development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiroyuki, Okada; Hideya Kitamura; Kumiaki, Moriya

This paper reports on the current development status of the ABWR-II project, a next generation reactor design based on the ABWR. In the early 90's, a program to develop the next generation reactor for the 21. century was launched, at a time when the first ABWR was still under construction. At the initial stage of this project, development of a 'user friendly' plant design was the primary objective. Thus, the main focus was placed on selecting a design with features promoting ease of operation and maintenance. Meanwhile, the circumstances surrounding the Japanese nuclear power industry changed. The delay of FBRmore » development and the deregulation of the power generation market have significantly boosted the role of light water reactors, and accelerated the need to improve LWR economics. For these reasons, economic competitiveness became an overriding objective in the development of the ABWR-II, with no less importance placed on achieving the highest standards of safety. Several new features were adopted to enhance economic performance: 1700 MW electric output, large fuel bundles, simplified MSIV, large capacity SRV. An output of 1700 MWe was selected for compatibility with the Japanese power grid, and with consideration of current reactor pressure vessel manufacturing capability. Large fuel bundles will contribute to a shortened refueling outage period and a reduction of CRDs. For enhanced safety, the reference design implements a modified ECCS with four subdivision RHR, a diversified power source incorporating gas turbine generators (GTG), an advanced RCIC (ARCIC) and passive heat removal systems consisting of a passive containment cooling system (PCCS) and a passive reactor cooling system (PRCS). The modified ECCS configuration also enables on-line maintenance. While current reactors rely on complex accident management (AM) procedures, implemented by operators in the event of a serious accident, the ABWR-II incorporated severe accident countermeasures at the design stage, to eliminate the need of operator induced AM procedures. The ABWR-II represents one of the most promising and reliable options for the future replacement of older units, without incurring excessive R and D costs. (authors)« less

The KFM, A Homemade Yet Accurate and Dependable Fallout Meter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kearny, C.H.

The KFM is a homemade fallout meter that can be made using only materials, tools, and skills found in millions of American homes. It is an accurate and dependable electroscope-capacitor. The KFM, in conjunction with its attached table and a watch, is designed for use as a rate meter. Its attached table relates observed differences in the separations of its two leaves (before and after exposures at the listed time intervals) to the dose rates during exposures of these time intervals. In this manner dose rates from 30 mR/hr up to 43 R/hr can be determined with an accuracy ofmore » {+-}25%. A KFM can be charged with any one of the three expedient electrostatic charging devices described. Due to the use of anhydrite (made by heating gypsum from wallboard) inside a KFM and the expedient ''dry-bucket'' in which it can be charged when the air is very humid, this instrument always can be charged and used to obtain accurate measurements of gamma radiation no matter how high the relative humidity. The heart of this report is the step-by-step illustrated instructions for making and using a KFM. These instructions have been improved after each successive field test. The majority of the untrained test families, adequately motivated by cash bonuses offered for success and guided only by these written instructions, have succeeded in making and using a KFM. NOTE: ''The KFM, A Homemade Yet Accurate and Dependable Fallout Meter'', was published by Oak Ridge National Laboratory report in1979. Some of the materials originally suggested for suspending the leaves of the Kearny Fallout Meter (KFM) are no longer available. Because of changes in the manufacturing process, other materials (e.g., sewing thread, unwaxed dental floss) may not have the insulating capability to work properly. Oak Ridge National Laboratory has not tested any of the suggestions provided in the preface of the report, but they have been used by other groups. When using these instructions, the builder can verify the insulating ability of his materials by checking the leakage rate and comparing it to the author's leakage tests.« less

Invertebrate Gonadotropin-Releasing Hormone-Related Peptides and Their Receptors: An Update

PubMed Central

Sakai, Tsubasa; Shiraishi, Akira; Kawada, Tsuyoshi; Matsubara, Shin; Aoyama, Masato; Satake, Honoo

2017-01-01

Gonadotropin-releasing hormones (GnRHs) play pivotal roles in reproductive functions via the hypothalamus, pituitary, and gonad axis, namely, HPG axis in vertebrates. GnRHs and their receptors (GnRHRs) are likely to be conserved in invertebrate deuterostomes and lophotrochozoans. All vertebrate and urochordate GnRHs are composed of 10 amino acids, whereas protostome, echinoderm, and amphioxus GnRH-like peptides are 11- or 12-residue peptide containing two amino acids after an N-terminal pyro-Glu. In urochordates, Halocynthia roretzi GnRH gene encodes two GnRH peptide sequences, whereas two GnRH genes encode three different GnRH peptides in Ciona intestinalis. These findings indicate the species-specific diversification of GnRHs. Intriguingly, the major signaling pathway for GnRHRs is intracellular Ca2+ mobilization in chordates, echinoderms, and protostomes, whereas Ciona GnRHRs (Ci-GnRHRs) are endowed with multiple GnRHergic cAMP production pathways in a ligand-selective manner. Moreover, the ligand-specific modulation of signal transduction via heterodimerization among Ci-GnRHR paralogs suggests the species-specific development of fine-tuning of gonadal functions in ascidians. Echinoderm GnRH-like peptides show high sequence differences compared to those of protostome counterparts, leading to the difficulty in classification of peptides and receptors. These findings also show both the diversity and conservation of GnRH signaling systems in invertebrates. The lack of the HPG axis in invertebrates indicates that biological functions of GnRHs are not release of gonadotropins in current invertebrates and common ancestors of vertebrates and invertebrates. To date, authentic or putative GnRHRs have been characterized from various echinoderms and protostomes as well as chordates and the mRNAs have been found to be distributed not only reproductive organs but also other tissues. Collectively, these findings further support the notion that invertebrate GnRHs have biological roles other than the regulation of reproductive functions. Moreover, recent molecular phylogenetic analysis suggests that adipokinetic hormone (AKH), corazonin (CRZ), and AKH/CRZ-related peptide (ACP) belong to the GnRH superfamily but has led to the different classifications of these peptides and receptors using different datasets including the number of sequences and structural domains. In this review, we provide current knowledge of, and perspectives in, molecular basis and evolutionary aspects of the GnRH, AKH, CRZ, and ACP. PMID:28932208

The Luminosity Function of OB Associations in the Galaxy

NASA Astrophysics Data System (ADS)

McKee, Christopher F.; Williams, Jonathan P.

1997-02-01

OB associations ionize the interstellar medium, producing both localized H II regions and diffuse ionized gas. The supernovae resulting from these associations pressurize and stir the interstellar medium. Using Smith, Biermann, & Mezger's compilation of radio H II regions in the Galaxy, and Kennicutt, Edgar, & Hodge's optical study of H II regions in nearby galaxies, we show that the luminosity distribution of giant OB associations in the Galaxy can be fit by a truncated power law of the form \\Nscra(>S)=\\Nscrau[(Su/S)-1], where S is the ionizing photon luminosity, \\Nscra(>S) is the number of associations with a luminosity of at least S, and Su is the upper limit to the distribution. The coefficient \\Nscrau is the number of the most luminous associations, with a luminosity between 0.5Su and Su. For the Galaxy, \\Nscrau=6.1 the fact that the number of the most luminous associations is significantly larger than unity indicates that there is a physical limit to the maximum size of H II regions in the Galaxy. To extend the luminosity distribution to small H II regions, we assume that the birthrate of associations, \\Nscr\\dota(>\\Nscr*), is also a truncated power law, \\Nscr\\dota(>\\Nscr*)~[(\\Nscr*u/\\Nscr*)-1], where \\Nscr* is the number of stars in the association. For large associations, the ionizing luminosity is proportional to the number of stars, S~\\Nscr* for smaller associations, we use both an analytic and a Monte Carlo approach to find the resulting luminosity distribution \\Nscra(>S). H II regions are generally centrally concentrated, with only the dense central regions being bright enough to appear in radio catalogs. Anantharamaiah postulated that radio H II regions have extended envelopes in order to account for diffuse radio recombination line emission in the Galaxy. Some of these envelopes are visible as the ionized ``worms'' discussed by Heiles and coworkers. We estimate that on the average the envelopes of radio H II regions absorb about twice as many ionizing photons as the radio H II regions themselves. Allowing for the ionizing radiation that is absorbed by dust (about 25% of the total), we find that the maximum ionizing photon luminosity of a Galactic OB association is Su ~= 4.9 × 1051 photons s-1, corresponding to an Hα luminosity of about 5 × 1039 ergs s-1. The total ionizing luminosity of this distribution of OB associations can account for the thermal radio emission and the N II far-infrared emission of the Galaxy. The number of massive stars in the associations is consistent with estimates of the rate of massive star supernovae in the Galaxy. Associations produce several generations of stars over their lifetimes, and the largest associations are predicted to produce about 7000 supernova progenitors. Fitting the surface density of associations to an exponential of the form d\\Nscra(\\Nscr*)/dA~ exp (-R/HR) with a scale length HR = 3.5 kpc gives a number of OB associations in the solar neighborhood that is consistent with observation. The H II envelopes contribute to pulsar dispersion measures and can account for the increased dispersion measure observed in the inner Galaxy.

The impact of professional status on the effects of and adherence to the outpatient followed by home-based telemonitored cardiac rehabilitation in patients referred by a social insurance institution.

PubMed

Szalewska, Dominika; Niedoszytko, Piotr; Gierat-Haponiuk, Katarzyna

2015-01-01

Legislators and policymakers have expressed strong interest in intervention programs to reduce dependence on social disability benefits. Hybrid: ambulatory followed by home-based cardiac telerehabilitation--hybrid cardiac rehabilitation (HCR) seems to be a novel alternative for standard cardiac rehabilitation for patients with cardiovascular diseases (CVD) as a form of pension prevention paid by the Social Insurance Institution (SII). The kind of professional status may bias the motivation to return to work after HCR. The aim of our study was to evaluate whether the professional status can affect the effects of HCR. One hundred fifty-two patients with CVD referred by the SII for a 5-week HCR were qualified for the study. Patients (87.7% males), aged 57.31 ± 5.61 years, were divided into 2 subgroups: W) white-collar employees (N = 22) and B) blue-collar employees (N = 130). To evaluate functional capacity, an exercise test on a treadmill was used. The number of days of absence in the cardiac rehabilitation program did not differ between the groups (mean ± standard deviation--B: 1.09 ± 3.10 days, W: 1.95 ± 3.64 days). There were significant improvements (p < 0.05) in measured variables after HCR in both (W and B) groups (max workload: 8.21 ± 2.88 METs (measured in metabolic equivalents) vs. 9.6 ± 2.49 METs, 7.76 ± 2.51 METs vs. 8.73 ± 2.7 METs, resting heart rate (RHR): 77 ± 16.22 bpm vs. 69.94 ± 12.93 bpm, 79.59 ± 14 bpm vs. 75.24 ± 11.87 bpm; double product, i.e., product of heart rate and systolic BP (DP rest) 10 815.22 ± 2968.24 vs. 9242.94 ± 1923.08, 10 927.62 ± 2508.47 vs. 9929.7 ± 2304.94). In group B, a decrease in systolic blood pressure (BP syst. - 137.03 ± 17.14 mm Hg vs. 131.82 ± 21.13 mm Hg), heart rate recovery in the 1st minute after the end of peak exercise (HRR1) (99.38 ± 19.25 vs. 93.9 ± 19.48) and New York Heart Association (NYHA) class (1.22 ± 0.53 vs. 1.11 ± 0.36) was observed. In group W, a decrease in diastolic blood pressure (BP diast.) at rest was observed (88.28 ± 9.79 mm Hg vs. 83.39 ± 8.95 mm Hg). The decrease in resting HR was significantly greater in group W (69.94 ± 12.93 vs. 75.24 ± 11.87, p = 0.034). Hybrid cardiac rehabilitation is feasible and safe with high adherence to the program regardless of the patient's professional status. Professional status did not influence the beneficial effect of HCR on exercise tolerance. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant.

PubMed

Ali, Moazzam; Akin, Ayse; Bahamondes, Luis; Brache, Vivian; Habib, Ndema; Landoulsi, Sihem; Hubacher, David

2016-11-01

Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years? The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5. The initial regulated trials on the ENG-releasing subdermal contraceptive implant conducted in the 1990 s were designed to measure cumulative 3-year efficacy. The ENG-implant has both well established safety and efficacy for up to 3 years. Pharmacokinetic data on ENG show high levels at 3 years and some previous clinical research confirms efficacy beyond the current approved duration of 3 years. Today, many women, because the labeled duration has been reached, have the ENG implant removed at 3 years, increasing costs, inconvenience and risks. For the first 3 years, this study was an open-label, multi-centre randomized trial comparing the 3-year ENG implant to the 5-year levonorgestrel (LNG)-releasing implant. After 3 years, a subset of 390 ENG participants, consented to extended use. We compared efficacy, side effects and removal procedures of both implants. We used Kaplan-Meier (K-M) analysis. We included an observational cohort of copper intrauterine device (IUD) users as non-users of hormonal contraceptive method for comparative purposes. The study took place in family planning clinics in seven countries worldwide. Women were enlisted after an eligibility check and informed consent, and 1328 women were enrolled: 390, 522 and 416 in the ENG-implant, LNG-implant and IUD groups, respectively. Over 200 women used the ENG implant for at least 5 years. No pregnancies occurred during the additional 2 years of follow up in the ENG or LNG implant group. The overall 5-year K-M cumulative pregnancy rates for ENG- and LNG- implants were 0.6 per 100 women-years (W-Y) [95% confidence interval (CI): 0.2-1.8] and 0.8 per 100 W-Y [95% CI: 0.2-2.3], respectively. Complaints of bleeding changes were similar; however, ENG-users were more likely than LNG-users to experience heavy bleeding (p < 0.05). The median duration of the implant removal procedure was 64 seconds shorter for the one-rod ENG-implant (inter-quartile range (IQR) = 30.5, 117.5) compared to the two-rod LNG product (IQR = 77.0, 180.0). The 2-year rate for pregnancy in the IUD group compared with the two implant groups combined was 4.1 per 100 W-Y [95% CI: 2.5-6.5]. Few women were ≤19 years old or nulligravida. Although there was no weight limit for enrolment in the study, the number of women ≥70 kg were few. The results from this study corroborate previous evidence showing high contraceptive efficacy through 4 years for the ENG-implant. Data through 5 years are a novel contribution and further proof of the product's capability to provide safe and effective contraception that rivals the current 5-year LNG-subdermal implant. The findings provide valuable information for policy makers, family planning programmers and clinicians that the ENG-releasing subdermal implant is still highly effective up to 5 years after insertion. Compared to previous efforts, our study population was geographically diverse and our study had the highest number of participants completing at least 5 years of use. The trial was registered as ISRCTN33378571. The contraceptive devices and funds for conduct of the study were provided by the United Nations Development Programme/United Nations Population Fund/World Health Organization (WHO)/UNICEF/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR), WHO. This report contains the collective views of an international group of experts, and does not necessarily represent the decisions or the stated policy of the WHO. All stated authors have no conflict of interest, except Dr Hubacher who reported grants from United States Agency for International Development, during the conduct of the study; other from Advisory Boards (Teva, Bayer, OCON), outside the submitted work. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant

PubMed Central

Ali, Moazzam; Akin, Ayse; Bahamondes, Luis; Brache, Vivian; Habib, Ndema; Landoulsi, Sihem; Hubacher, David

2016-01-01

STUDY QUESTION Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years? SUMMARY ANSWER The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5. WHAT IS KNOWN ALREADY The initial regulated trials on the ENG-releasing subdermal contraceptive implant conducted in the 1990 s were designed to measure cumulative 3-year efficacy. The ENG-implant has both well established safety and efficacy for up to 3 years. Pharmacokinetic data on ENG show high levels at 3 years and some previous clinical research confirms efficacy beyond the current approved duration of 3 years. Today, many women, because the labeled duration has been reached, have the ENG implant removed at 3 years, increasing costs, inconvenience and risks. STUDY DESIGN SIZE, DURATION For the first 3 years, this study was an open-label, multi-centre randomized trial comparing the 3-year ENG implant to the 5-year levonorgestrel (LNG)-releasing implant. After 3 years, a subset of 390 ENG participants, consented to extended use. We compared efficacy, side effects and removal procedures of both implants. We used Kaplan–Meier (K–M) analysis. We included an observational cohort of copper intrauterine device (IUD) users as non-users of hormonal contraceptive method for comparative purposes. PARTICIPANTS/MATERIALS, SETTING, METHODS The study took place in family planning clinics in seven countries worldwide. Women were enlisted after an eligibility check and informed consent, and 1328 women were enrolled: 390, 522 and 416 in the ENG-implant, LNG-implant and IUD groups, respectively. MAIN RESULTS AND THE ROLE OF CHANCE Over 200 women used the ENG implant for at least 5 years. No pregnancies occurred during the additional 2 years of follow up in the ENG or LNG implant group. The overall 5-year K–M cumulative pregnancy rates for ENG- and LNG- implants were 0.6 per 100 women-years (W-Y) [95% confidence interval (CI): 0.2–1.8] and 0.8 per 100 W-Y [95% CI: 0.2–2.3], respectively. Complaints of bleeding changes were similar; however, ENG-users were more likely than LNG-users to experience heavy bleeding (p < 0.05). The median duration of the implant removal procedure was 64 seconds shorter for the one-rod ENG-implant (inter-quartile range (IQR) = 30.5, 117.5) compared to the two-rod LNG product (IQR = 77.0, 180.0). The 2-year rate for pregnancy in the IUD group compared with the two implant groups combined was 4.1 per 100 W-Y [95% CI: 2.5–6.5]. LIMITATIONS, REASONS FOR CAUTION Few women were ≤19 years old or nulligravida. Although there was no weight limit for enrolment in the study, the number of women ≥70 kg were few. WIDER IMPLICATIONS OF THE FINDINGS The results from this study corroborate previous evidence showing high contraceptive efficacy through 4 years for the ENG-implant. Data through 5 years are a novel contribution and further proof of the product's capability to provide safe and effective contraception that rivals the current 5-year LNG-subdermal implant. The findings provide valuable information for policy makers, family planning programmers and clinicians that the ENG-releasing subdermal implant is still highly effective up to 5 years after insertion. Compared to previous efforts, our study population was geographically diverse and our study had the highest number of participants completing at least 5 years of use. TRIAL REGISTRATION The trial was registered as ISRCTN33378571. STUDY FUNDING/COMPETING INTEREST(S) The contraceptive devices and funds for conduct of the study were provided by the United Nations Development Programme/United Nations Population Fund/World Health Organization (WHO)/UNICEF/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR), WHO. This report contains the collective views of an international group of experts, and does not necessarily represent the decisions or the stated policy of the WHO. All stated authors have no conflict of interest, except Dr Hubacher who reported grants from United States Agency for International Development, during the conduct of the study; other from Advisory Boards (Teva, Bayer, OCON), outside the submitted work. PMID:27671673

A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg

PubMed Central

Festin, Mario P.R.; Bahamondes, Luis; Nguyen, Thi My Huong; Habib, Ndema; Thamkhantho, Manopchai; Singh, Kuldip; Gosavi, Arundhati; Bartfai, Gyorgy; Bito, Tamas; Bahamondes, M. Valeria; Kapp, Nathalie

2016-01-01

STUDY QUESTION Will the use of levonorgestrel (LNG) 1.5 mg taken at each day of coitus by women who have relatively infrequent sex be an efficacious, safe and acceptable contraceptive method? SUMMARY ANSWER Typical use of LNG 1.5 mg taken pericoitally, before or within 24 h of sexual intercourse, provides contraceptive efficacy of up to 11.0 pregnancies per 100 women-years (W-Y) in the primary evaluable population and 7.1 pregnancies per 100 W-Y in the evaluable population. WHAT IS KNOWN ALREADY LNG 1.5 mg is an effective emergency contraception following unprotected intercourse. Some users take it repeatedly, as their means of regular contraception. STUDY DESIGN, SIZE, DURATION This was a prospective, open-label, single-arm, multicentre Phase III trial study with women who have infrequent coitus (on up to 6 days a month). Each woman had a follow-up visit at 2.5, 4.5 and 6.5 months after admission or until pregnancy occurs if sooner, or she decided to interrupt participation. The study was conducted between 10 January 2012 and 15 November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 330 healthy fertile women aged 18–45 years at risk of pregnancy who reported sexual intercourse on up to 6 days a month, were recruited from four university centres located in Bangkok, Thailand; Campinas, Brazil; Singapore and Szeged, Hungary to use LNG 1.5 mg pericoitally (24 h before or after coitus) as their primary method of contraception. The participants were instructed to take one tablet every day she had sex, without taking more than one tablet in any 24-h period, and to maintain a paper diary for recording date and time for every coital act and ingestion of the study tablet, use of other contraceptive methods and vaginal bleeding patterns. Anaemia was assessed by haemoglobin evaluation. Pregnancy tests were performed monthly and pregnancies occurring during product use were assessed by ultrasound. At the 2.5-month and final visit at 6.5 months, acceptability questions were administered. MAIN RESULTS AND THE ROLE OF CHANCE There were 321 women included in the evaluable population (which includes all eligible women enrolled), with 141.9 woman-years (W-Y) of observation and with a rate (95% confidence interval [CI]) of 7.1 (3.8; 13.1) pregnancies per 100 W-Y of typical use (which reflects use of the study drug as main contraceptive method, but also includes possible use of other contraceptives from admission to end of study) and 7.5 (4.0; 13.9) pregnancies per 100 W-Y of sole use. In the primary evaluable population (which includes only eligible enrolled women <35 years old), the rate was 10.3 (5.4; 19.9) pregnancies per 100 W-Y of typical use, and 11.0 (5.7; 13.1) pregnancies per 100 W-Y of sole use. There were three reported severe adverse events and 102 other mild adverse events (most common were headache, nausea, abdominal and pelvic pain), with high recovery rate. The vaginal bleeding patterns showed a slight decrease in volume of bleeding and the number of bleeding-free days increased over time. There was only one case of severe anaemia, found at the final visit (0.4%). The method was considered acceptable, as over 90% of participants would choose to use it in the future or would recommend it to others. LIMITATIONS, REASONS FOR CAUTION This was a single-arm study with small sample size, without a control group, designed as a proof of concept study to explore the feasibility of this type of contraception. WIDER IMPLICATIONS OF THE FINDINGS A larger clinical study evaluating pericoital contraception with LNG is feasible and our data show that this method would be acceptable to many women. STUDY FUNDING/COMPETING INTEREST(S) This study received partial financial support from the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR) and the World Health Organization. Gynuity and the Bill and Melinda Gates Foundation (BMGF) provided financial support for project monitoring. HRA Pharma donated the LNG product. N.K. was the initial project manager when she was with WHO/HRP and was employed by HRA Pharma, which distributes LNG for emergency contraception. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER This study was registered on ANZCTR, Trial ID ACTRN12611001037998. TRIAL REGISTRATION DATE 4 October 2011. DATE OF FIRST PATIENT'S ENROLMENT 10 January 2012. PMID:26830816

A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg.

PubMed

Festin, Mario P R; Bahamondes, Luis; Nguyen, Thi My Huong; Habib, Ndema; Thamkhantho, Manopchai; Singh, Kuldip; Gosavi, Arundhati; Bartfai, Gyorgy; Bito, Tamas; Bahamondes, M Valeria; Kapp, Nathalie

2016-03-01

Will the use of levonorgestrel (LNG) 1.5 mg taken at each day of coitus by women who have relatively infrequent sex be an efficacious, safe and acceptable contraceptive method? Typical use of LNG 1.5 mg taken pericoitally, before or within 24 h of sexual intercourse, provides contraceptive efficacy of up to 11.0 pregnancies per 100 women-years (W-Y) in the primary evaluable population and 7.1 pregnancies per 100 W-Y in the evaluable population. LNG 1.5 mg is an effective emergency contraception following unprotected intercourse. Some users take it repeatedly, as their means of regular contraception. This was a prospective, open-label, single-arm, multicentre Phase III trial study with women who have infrequent coitus (on up to 6 days a month). Each woman had a follow-up visit at 2.5, 4.5 and 6.5 months after admission or until pregnancy occurs if sooner, or she decided to interrupt participation. The study was conducted between 10 January 2012 and 15 November 2014. A total of 330 healthy fertile women aged 18-45 years at risk of pregnancy who reported sexual intercourse on up to 6 days a month, were recruited from four university centres located in Bangkok, Thailand; Campinas, Brazil; Singapore and Szeged, Hungary to use LNG 1.5 mg pericoitally (24 h before or after coitus) as their primary method of contraception. The participants were instructed to take one tablet every day she had sex, without taking more than one tablet in any 24-h period, and to maintain a paper diary for recording date and time for every coital act and ingestion of the study tablet, use of other contraceptive methods and vaginal bleeding patterns. Anaemia was assessed by haemoglobin evaluation. Pregnancy tests were performed monthly and pregnancies occurring during product use were assessed by ultrasound. At the 2.5-month and final visit at 6.5 months, acceptability questions were administered. There were 321 women included in the evaluable population (which includes all eligible women enrolled), with 141.9 woman-years (W-Y) of observation and with a rate (95% confidence interval [CI]) of 7.1 (3.8; 13.1) pregnancies per 100 W-Y of typical use (which reflects use of the study drug as main contraceptive method, but also includes possible use of other contraceptives from admission to end of study) and 7.5 (4.0; 13.9) pregnancies per 100 W-Y of sole use. In the primary evaluable population (which includes only eligible enrolled women <35 years old), the rate was 10.3 (5.4; 19.9) pregnancies per 100 W-Y of typical use, and 11.0 (5.7; 13.1) pregnancies per 100 W-Y of sole use. There were three reported severe adverse events and 102 other mild adverse events (most common were headache, nausea, abdominal and pelvic pain), with high recovery rate. The vaginal bleeding patterns showed a slight decrease in volume of bleeding and the number of bleeding-free days increased over time. There was only one case of severe anaemia, found at the final visit (0.4%). The method was considered acceptable, as over 90% of participants would choose to use it in the future or would recommend it to others. This was a single-arm study with small sample size, without a control group, designed as a proof of concept study to explore the feasibility of this type of contraception. A larger clinical study evaluating pericoital contraception with LNG is feasible and our data show that this method would be acceptable to many women. This study received partial financial support from the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR) and the World Health Organization. Gynuity and the Bill and Melinda Gates Foundation (BMGF) provided financial support for project monitoring. HRA Pharma donated the LNG product. N.K. was the initial project manager when she was with WHO/HRP and was employed by HRA Pharma, which distributes LNG for emergency contraception. The other authors declare no conflicts of interest. This study was registered on ANZCTR, Trial ID ACTRN12611001037998. 4 October 2011. 10 January 2012. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

A 3-year multicentre randomized controlled trial of etonogestrel- and levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls.

PubMed

Bahamondes, Luis; Brache, Vivian; Meirik, Olav; Ali, Moazzam; Habib, Ndema; Landoulsi, Sihem

2015-11-01

Is there any difference in the clinical performance of the 3-year one-rod etonogestrel (ENG)- and the 5-year two-rod levonorgestrel (LNG)-releasing contraceptive implants during 3 years of insertion, and between implant and intrauterine device (IUD) contraception, in particular complaints possibly related to hormonal contraceptives? The cumulative contraceptive effectiveness after 3 years and method continuation through 2.5 years were not significantly different between ENG and LNG implants, but both outcomes were significantly worse in the non-randomized age-matched group of IUD users than in the combined implant group. ENG- and LNG-releasing implants are safe and highly efficacious contraceptives with pregnancy rates reported to be 0.0-0.5 per 100 women-years (W-Y). No head-to-head comparative study of the two implants has been undertaken, and little information is available on comparisons of complaints of side effects of implant and copper IUD users. This was an open parallel group RCT with 1:1 allocation ratio of the ENG and the LNG implants with non-randomized control group of women choosing TCu380A IUD to address lack of reliable data on common side effects typically attributed to the use of progestogen-only contraceptives. After device(s) placement, follow-ups were at 2 weeks, 3 and 6 months, and semi-annually thereafter for 3 years or until pregnancy, removal or expulsion of the implant/IUD occurred. The study took place in family planning clinics in Brazil, Chile, Dominican Republic, Hungary, Thailand, Turkey and Zimbabwe. Women seeking long-term contraception were enlisted after an eligibility check and informed consent, and 2982 women were enrolled: 1003, 1005 and 974 in the ENG-implant, LNG-implant and IUD groups, respectively; 995, 997 and 971, respectively, were included in the per protocol analysis reported here. ENG and LNG implants each had the same 3-year cumulative pregnancy rate of 0.4 per 100 W-Y [95% confidence interval (CI) 0.1-1.4]. A weight of ≥70 kg at admission was unrelated to pregnancy. Method continuation rates for ENG and LNG implants at 2.5 years were 69.8 (95% CI 66.8-72.6) and 71.8 per 100 W-Y (68.8-74.5), and at 3 years 12.1 (95% CI 5.2-22.0) and 52.0 per 100 W-Y (95% CI 41.8-61.2), respectively. Bleeding disturbances, the most frequent reason for method discontinuation, were significantly more common in the ENG group [16.7 (95% CI 14.4-19.3)] than in the LNG group [12.5 (95% CI 10.5-14.9)] (P 0.019). The 3-year cumulative loss to follow-up was lower in the ENG- than in the LNG-implant group, 8.1 (95% CI 6.4-10.2) and 14.4 per 100 W-Y (95% CI 12.1-17.1), respectively. The median duration of implant removal was 50 s shorter among women with ENG than among women with LNG implant (P < 0.0001). In the observational comparison between IUD and implant users, the 3-year relative risk for pregnancy in IUD group compared with the combined implant group was 5.7 per 100 W-Y (95% CI 4.4-7.3) (P = 0.0003). The 3-year expulsion rate of the IUD was 17.8 per 100 W-Y (95% CI 14.5-21.9), while the discontinuation rate for bleeding disturbances was 8.5 (95% CI 6.7-10.9). Frequency of complaints of headache and dizziness was not significantly different between implant and IUD users (P = 0.16 and 0.77, respectively), acne and bleeding irregularities were more frequent among implant users (P < 0.0001), while heavy bleeding and lower abdominal pain occurred more often among IUD than implant users (P < 0.0001). Few women were ≤19 years old or nulligravida, the proportion of implant users ≥70 kg was <20% and <8% were obese. Findings of the study can inform policy makers and clinicians about choice of implant, but also about TCu380A IUD in relation to implants. UNDP/UNFPA/WHO/UNICEF/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR), World Health Organization (WHO). This report contains the views of an international expert group and does not necessarily represent the decisions or the stated policy of the WHO. ISRCTN33378571 registered on 22 March 2004. The first participant was enrolled on 12 May 2003. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.