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Sample records for early estrogen prevention

  1. KEEPS: The Kronos Early Estrogen Prevention Study.

    Science.gov (United States)

    Harman, S M; Brinton, E A; Cedars, M; Lobo, R; Manson, J E; Merriam, G R; Miller, V M; Naftolin, F; Santoro, N

    2005-03-01

    Observational studies have indicated that hormone therapy given at or after menopause is linked to substantial reduction in cardiovascular disease and its risk factors. Recent findings from the Women's Health Initiative (WHI) clinical trial, however, indicate that combined estrogen plus progestin hormone therapy, as well as estrogen-alone hormone therapy (given to women without a uterus), is ineffective in preventing the new onset of cardiac events in previously healthy late menopausal women. Further, the secondary prevention trial, the Heart and Estrogen/progestin Replacement Study (HERS), also failed to demonstrate any benefit of initiation of hormone therapy in women with established coronary heart disease. In light of these results, a hypothesis has arisen that early initiation of hormone therapy, in women who are at the inception of their menopause, will delay the onset of subclinical cardiovascular disease in women. The rationale that earlier intervention than that performed in the WHI and HERS trials will provide cardiovascular benefit to women is the driving force behind the Kronos Early Estrogen Prevention Study, or KEEPS. KEEPS is a multicenter, 5-year clinical trial that will evaluate the effectiveness of 0.45 mg of conjugated equine estrogens, 50 microg weekly transdermal estradiol (both in combination with cyclic oral, micronized progesterone, 200 mg for 12 days each month), and placebo in preventing progression of carotid intimal medial thickness and the accrual of coronary calcium in women aged 42-58 years who are within 36 months of their final menstrual period. A total of 720 women are planned to be enrolled in 2005, with an anticipated close-out of the trial in 2010. This overview summarizes the recruitment and methodology of the KEEPS trial.

  2. Endothelial function in women of the Kronos Early Estrogen Prevention Study.

    Science.gov (United States)

    Kling, J M; Lahr, B A; Bailey, K R; Harman, S M; Miller, V M; Mulvagh, S L

    2015-04-01

    Endothelial dysfunction occurs early in the atherosclerotic disease process, often preceding clinical symptoms. Use of menopausal hormone treatment (MHT) to reduce cardiovascular risk is controversial. This study evaluated effects of 4 years of MHT on endothelial function in healthy, recently menopausal women. Endothelial function was determined by pulse volume digital tonometry providing a reactive hyperemia index (RHI) in a subset of women enrolled in the Kronos Early Estrogen Prevention Study. RHI was measured before and annually after randomization to daily oral conjugated equine estrogen (oCEE, 0.45 mg), weekly transdermal 17β-estradiol (tE2, 50 μg) each with intermittent progesterone (200 mg daily 12 days of the month) or placebo pills and patch. At baseline, RHI averaged 2.39 ± 0.69 (mean ± standard deviation; n = 83), and over follow-up did not differ significantly among groups: oCEE, 2.26 ± 0.48 (n = 26); tE2, 2.26 ± 0.45 (n = 24); and placebo, 2.37 ± 0.37 (n = 33). Changes in RHI did not correlate with changes in traditional cardiovascular risk factors, but may inversely correlate with carotid intima medial thickness (Spearman correlation coefficient ρ = -0.268, p = 0.012). In this 4-year prospective assessment of recently menopausal women, MHT did not significantly alter RHI when compared to placebo.

  3. Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS).

    Science.gov (United States)

    Taylor, Hugh S; Tal, Aya; Pal, Lubna; Li, Fangyong; Black, Dennis M; Brinton, Eliot A; Budoff, Matthew J; Cedars, Marcelle I; Du, Wei; Hodis, Howard N; Lobo, Rogerio A; Manson, JoAnn E; Merriam, George R; Miller, Virginia M; Naftolin, Frederick; Neal-Perry, Genevieve; Santoro, Nanette F; Harman, Sherman M

    2017-10-01

    Sexual dysfunction, an important determinant of women's health and quality of life, is commonly associated with declining estrogen levels around the menopausal transition. To determine the effects of oral or transdermal estrogen therapy vs placebo on sexual function in postmenopausal women. Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS), a 4-year prospective, randomized, double-blinded, placebo-controlled trial of menopausal hormone therapy in healthy, recently menopausal women. Of 727 KEEPS enrollees, 670 agreed to participate in this multicenter ancillary study. Women were 42 to 58 years old, within 36 months from last menstrual period. Data were collected from July 2005 through June 2008 and analyzed from July 2010 through June 2017. Women were randomized to either 0.45 mg/d oral conjugated equine estrogens (o-CEE), 50 µg/d transdermal 17β-estradiol (t-E2), or placebo. Participants also received 200 mg oral micronized progesterone (if randomized to o-CEE or t-E2) or placebo (if randomized to placebo estrogens) for 12 days each month. Aspects of sexual function and experience (desire, arousal, lubrication, orgasm, satisfaction, and pain) were assessed using the Female Sexual Function Inventory (FSFI; range, 0-36 points; higher scores indicate better sexual function). Low sexual function (LSF) was defined as an FSFI overall score of less than 26.55. Distress related to low FSFI score (required for the diagnosis of sexual dysfunction) was not evaluated. The 670 participants had a mean (SD) age of 52.7 (2.6) years. The t-E2 treatment was associated with a significant yet moderate improvement in the FSFI overall score across all time points compared with placebo (average efficacy, 2.6; 95% CI, 1.11-4.10; adjusted P = .002). With o-CEE treatment, there was no significant difference in FSFI overall score compared with placebo (mean efficacy, 1.4; 95% CI, -0.1 to 2.8; adjusted P = .13). There was no difference in FSFI overall score

  4. Pharmacogenomics of estrogens on changes in carotid artery intima-medial thickness and coronary arterial calcification: Kronos Early Estrogen Prevention Study.

    Science.gov (United States)

    Miller, Virginia M; Jenkins, Gregory D; Biernacka, Joanna M; Heit, John A; Huggins, Gordon S; Hodis, Howard N; Budoff, Matthew J; Lobo, Rogerio A; Taylor, Hugh S; Manson, JoAnn E; Black, Dennis M; Naftolin, Frederick; Harman, S Mitchell; de Andrade, Mariza

    2016-01-01

    Prior to the initiation of menopausal hormone treatment (MHT), genetic variations in the innate immunity pathway were found to be associated with carotid artery intima-medial thickness (CIMT) and coronary arterial calcification (CAC) in women (n = 606) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Whether MHT might affect these associations is unknown. The association of treatment outcomes with variation in the same 764 candidate genes was evaluated in the same KEEPS participants 4 yr after randomization to either oral conjugated equine estrogens (0.45 mg/day), transdermal 17β-estradiol (50 μg/day), each with progesterone (200 mg/day) for 12 days each month, or placebo pills and patch. Twenty SNPs within the innate immunity pathway most related with CIMT after 4 yr were not among those associated with CIMT prior to MHT. In 403 women who completed the study in their assigned treatment group, single nucleotide polymorphisms (SNPs) within the innate immunity pathway were found to alter the treatment effect on 4 yr change in CIMT (i.e., significant interaction between treatment and genetic variation in the innate immunity pathway; P 5 Agatston units after 4 yr. Results of this study suggest that hormonal status may interact with genetic variants to influence cardiovascular phenotypes, specifically, the pharmacogenomic effects within the innate immunity pathway for CIMT.

  5. Ectopic fat and adipokines in metabolically benign overweight/obese women: the Kronos Early Estrogen Prevention Study.

    Science.gov (United States)

    Ogorodnikova, Alexandra D; Khan, Unab I; McGinn, Aileen P; Zeb, Irfan; Budoff, Matthew J; Harman, S M; Miller, Virginia M; Brinton, Eliot A; Manson, JoAnn E; Hodis, Howard N; Merriam, George R; Cedars, Marcelle I; Taylor, Hugh S; Naftolin, Frederick; Lobo, Rogerio A; Santoro, Nanette; Wildman, Rachel P

    2013-08-01

    It is unclear why despite a comparable cardiometabolic risk profile, "metabolically benign" overweight/obese individuals show an elevated risk of cardiovascular disease compared to normal weight individuals. In cross-sectional analyses, we compared levels of ectopic fat (epicardial, pericardial, and hepatic fat) and adipokines (leptin, soluble leptin receptor, and high molecular weight [HMW] adiponectin) among metabolically benign (MBO) and at-risk overweight/obese (ARO), and metabolically benign normal weight (MBNW) women, screened for the Kronos Early Estrogen Prevention Study. We defined "metabolically benign" with ≤ 1, and "at-risk" with ≥2 components of the metabolic syndrome. Compared to MBO women, ARO women had significantly elevated odds of being in the top tertile of epicardial fat (OR: 1.76, 95% CI: 1.04-2.99), hepatic fat (OR: 1.90, 95% CI:1.12-3.24) and leptin (OR: 2.15, 95% CI: 1.23-3.76), and the bottom tertile of HMW-adiponectin (OR: 2.90, 95% CI: 1.62-5.19). Compared to MBNW women, MBO women had significantly higher odds of being in the top tertile of epicardial fat (OR: 5.17, 95% CI: 3.22-8.29), pericardial fat (OR: 9.27, 95% CI: 5.52-15.56) and hepatic fat (OR: 2.72, 95% CI: 1.77-4.19) and the bottom tertile of HMW adiponectin levels (OR: 2.51, 95% CI: 1.60-3.94). Levels of ectopic fat and the adverse adipokine profile increase on a continuum of BMI, suggesting that the metabolically benign phenotype may be a transient state. Copyright © 2013 The Obesity Society.

  6. Rationale and design of the Kronos Early Estrogen Prevention Study (KEEPS) and the KEEPS Cognitive and Affective sub study (KEEPS Cog).

    Science.gov (United States)

    Wharton, Whitney; Gleason, Carey E; Miller, Virginia M; Asthana, Sanjay

    2013-06-13

    This manuscript describes the study design and rationalle for the Kronos Early Estrogen Prevention Study (KEEPS) and the KEEPS Cognitive and Affective ancillary study (KEEPS Cog). KEEPS is a multicenter, randomized, double-blinded, placebo-controlled trial, designed to test the hypothesis that low-dose hormone therapy (HT) initiated in recently postmenopausal women will reduce the progression of subclinical atherosclerosis as measured by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC) over four years. The KEEPS Cog ancillary study was designed to assess potential estrogenic treatment effects on cognition and mood. We present the KEEPS trial in the context of issues raised by the Women's Health Initiative (WHI) and the Women's Health Initiative Memory Study (WHIMS). Here we also describe the most recent results and ongoing HT-related research studies designed to address similar issues. This article is part of a Special Issue entitled Hormone Therapy. Copyright © 2013. Published by Elsevier B.V.

  7. Self-reported menopausal symptoms, coronary artery calcification, and carotid intima-media thickness in recently menopausal women screened for the Kronos early estrogen prevention study (KEEPS).

    Science.gov (United States)

    Wolff, Erin Foran; He, Yunxiao; Black, Dennis M; Brinton, Eliot A; Budoff, Mathew J; Cedars, Marcelle I; Hodis, Howard N; Lobo, Rogerio A; Manson, Joann E; Merriam, George R; Miller, Virginia M; Naftolin, Fredrick; Pal, Lubna; Santoro, Nanette; Zhang, Heping; Harman, S Mitchell; Taylor, Hugh S

    2013-04-01

    To determine whether self-reported menopausal symptoms are associated with measures of subclinical atherosclerosis. Cross-sectional analysis. Multicenter, randomized controlled trial. Recently menopausal women (n = 868) screened for the Kronos Early Estrogen Prevention Study (KEEPS). None. Baseline menopausal symptoms (hot flashes, dyspareunia, vaginal dryness, night sweats, palpitations, mood swings, depression, insomnia, irritability), serum E2 levels, and measures of atherosclerosis were assessed. Atherosclerosis was quantified using coronary artery calcium (CAC) Agatston scores (n = 771) and carotid intima-media thickness (CIMT). Logistic regression model of menopausal symptoms and E2 was used to predict CAC. Linear regression model of menopausal symptoms and E2 was used to predict CIMT. Correlation between length of time in menopause with menopausal symptoms, E2, CAC, and CIMT were assessed. In early menopausal women screened for KEEPS, neither E2 nor climacteric symptoms predicted the extent of subclinical atherosclerosis. Palpitations and depression approached significance as predictors of CAC. Other symptoms of insomnia, irritability, dyspareunia, hot flashes, mood swings, night sweats, and vaginal dryness were not associated with CAC. Women with significantly elevated CAC scores were excluded from further participation in KEEPS; in women meeting inclusion criteria, neither baseline menopausal symptoms nor E2 predicted CIMT. Years since menopause onset correlated with CIMT, dyspareunia, vaginal dryness, and E2. Self-reported symptoms in recently menopausal women are not strong predictors of subclinical atherosclerosis. Continued follow-up of this population will be performed to determine whether baseline or persistent symptoms in the early menopause are associated with progression of cardiovascular disease. NCT00154180. Published by Elsevier Inc.

  8. Genetic polymorphisms associated with carotid artery intima-media thickness and coronary artery calcification in women of the Kronos Early Estrogen Prevention Study.

    Science.gov (United States)

    Miller, Virginia M; Petterson, Tanya M; Jeavons, Elysia N; Lnu, Abhinita S; Rider, David N; Heit, John A; Cunningham, Julie M; Huggins, Gordon S; Hodis, Howard N; Budoff, Matthew J; Santoro, Nanette; Hopkins, Paul N; Lobo, Rogerio A; Manson, JoAnn E; Naftolin, Frederick; Taylor, Hugh S; Harman, S Mitchell; de Andrade, Mariza

    2013-01-15

    Menopausal hormone treatment (MHT) may limit progression of cardiovascular disease (CVD) but poses a thrombosis risk. To test targeted candidate gene variation for association with subclinical CVD defined by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC), 610 women participating in the Kronos Early Estrogen Prevention Study (KEEPS), a clinical trial of MHT to prevent progression of CVD, were genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 764 genes from anticoagulant, procoagulant, fibrinolytic, or innate immunity pathways. According to linear regression, proportion of European ancestry correlated negatively, but age at enrollment and pulse pressure correlated positively with CIMT. Adjusting for these variables, two SNPs, one on chromosome 2 for MAP4K4 gene (rs2236935, β = 0.037, P value = 2.36 × 10(-06)) and one on chromosome 5 for IL5 gene (rs739318, β = 0.051, P value = 5.02 × 10(-05)), associated positively with CIMT; two SNPs on chromosome 17 for CCL5 (rs4796119, β = -0.043, P value = 3.59 × 10(-05); rs2291299, β = -0.032, P value = 5.59 × 10(-05)) correlated negatively with CIMT; only rs2236935 remained significant after correcting for multiple testing. Using logistic regression, when we adjusted for waist circumference, two SNPs (rs11465886, IRAK2, chromosome 3, OR = 3.91, P value = 1.10 × 10(-04); and rs17751769, SERPINA1, chromosome 14, OR = 1.96, P value = 2.42 × 10(-04)) associated positively with a CAC score of >0 Agatston unit; one SNP (rs630014, ABO, OR = 0.51, P value = 2.51 × 10(-04)) associated negatively; none remained significant after correcting for multiple testing. Whether these SNPs associate with CIMT and CAC in women randomized to MHT remains to be determined.

  9. Intra-thoracic fat, cardiometabolic risk factors, and subclinical cardiovascular disease in healthy, recently menopausal women screened for the Kronos Early Estrogen Prevention Study (KEEPS).

    Science.gov (United States)

    Huang, Gary; Wang, Dan; Zeb, Irfan; Budoff, Matthew J; Harman, S Mitchell; Miller, Virginia; Brinton, Eliot A; El Khoudary, Samar R; Manson, JoAnn E; Sowers, MaryFran R; Hodis, Howard N; Merriam, George R; Cedars, Marcelle I; Taylor, Hugh S; Naftolin, Frederick; Lobo, Rogerio A; Santoro, Nanette; Wildman, Rachel P

    2012-03-01

    To examine the correlations between intra-hepatic and intra-thoracic (total, epicardial, and pericardial) fat deposition with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis burden in healthy, recently postmenopausal women. Women screened for the Kronos Early Estrogen Prevention Study (mean age 52.9 years) who underwent electron beam or multidetector computed tomography (CT) imaging for the quantification of intra-hepatic fat and thoracic adipose tissue, and coronary artery calcification (CAC) were included (n=650). Higher levels of intra-hepatic and thoracic fat were each associated with CVD risk markers. After adjustment for BMI, the associations for intra-hepatic fat with hs-CRP and insulin persisted (r=0.21 and 0.19, respectively; P<0.001), while those between thoracic fat indices and lipids persisted (r for total thoracic fat with HDL, LDL, and triglycerides=-0.16, 0.11, and 0.11, respectively, P<0.05). Total thoracic fat was associated with CAC after initial multivariable adjustment (odds ratio [OR] of 2nd, 3rd, and 4th vs. 1st quartile and [95% confidence intervals]: 0.8 [0.4-1.6], 1.5 [0.8-2.9], and 1.8 [1.0-3.4]; p for linear trend=0.017) and was only slightly attenuated after additional adjustment for BMI. Associations between total thoracic fat and CVD risk markers and CAC appeared due slightly more to associations with epicardial than pericardial fat. While hepatic fat is related to hs-CRP and insulin, cardiac fat is associated with subclinical atherosclerosis as demonstrated by CAC. Cardiac fat may represent a useful marker for increased CVD risk beyond the standard adiposity measures of BMI and WC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Using basic science to design a clinical trial: baseline characteristics of women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS).

    Science.gov (United States)

    Miller, V M; Black, D M; Brinton, E A; Budoff, M J; Cedars, M I; Hodis, H N; Lobo, R A; Manson, J E; Merriam, G R; Naftolin, F; Santoro, N; Taylor, H S; Harman, S M

    2009-09-01

    Observational and epidemiological studies suggest that menopausal hormone therapy (MHT) reduces cardiovascular disease (CVD) risk. However, results from prospective trials showed neutral or adverse effects most likely due to differences in participant demographics, such as age, timing of initiation of treatment, and preexisting cardiovascular disease, which reflected in part the lack of basic science information on mechanisms of action of hormones on the vasculature at the time clinical trials were designed. The Kronos Early Estrogen Replacement Study (KEEPS) is a prospective, randomized, controlled trial designed, using findings from basic science studies, to test the hypothesis that MHT when initiated early in menopause reduces progression of atherosclerosis. KEEPS participants are younger, healthier, and within 3 years of menopause thus matching more closely demographics of women in prior observational and epidemiological studies than women in the Women's Health Initiative hormone trials. KEEPS will provide information relevant to the critical timing hypothesis for MHT use in reducing risk for CVD.

  11. Longitudinal changes in menopausal symptoms comparing women randomized to low-dose oral conjugated estrogens or transdermal estradiol plus micronized progesterone versus placebo: the Kronos Early Estrogen Prevention Study.

    Science.gov (United States)

    Santoro, Nanette; Allshouse, Amanda; Neal-Perry, Genevieve; Pal, Lubna; Lobo, Rogerio A; Naftolin, Frederick; Black, Dennis M; Brinton, Eliot A; Budoff, Matthew J; Cedars, Marcelle I; Dowling, N Maritza; Dunn, Mary; Gleason, Carey E; Hodis, Howard N; Isaac, Barbara; Magnani, Maureen; Manson, JoAnn E; Miller, Virginia M; Taylor, Hugh S; Wharton, Whitney; Wolff, Erin; Zepeda, Viola; Harman, S Mitchell

    2017-03-01

    The objective of the present study was to compare the efficacy of two forms of menopausal hormone therapy in alleviating vasomotor symptoms, insomnia, and irritability in early postmenopausal women during 4 years. A total of 727 women, aged 42 to 58, within 3 years of their final menstrual period, were randomized to receive oral conjugated estrogens (o-CEE) 0.45 mg (n = 230) or transdermal estradiol (t-E2) 50 μg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (PBOs; n = 275). Menopausal symptoms were recorded at screening and at 6, 12, 24, 36, and 48 months postrandomization. Differences in proportions of women with symptoms at baseline and at each follow-up time point were compared by treatment arm using exact χ tests in an intent-to-treat analysis. Differences in treatment effect by race/ethnicity and body mass index were tested using generalized linear mixed effects modeling. Moderate to severe hot flashes (from 44% at baseline to 28.3% for PBO, 7.4% for t-E2, and 4.2% for o-CEE) and night sweats (from 35% at baseline to 19% for PBO, 5.3% for t-E2, and 4.7% for o-CEE) were reduced significantly by 6 months in women randomized to either active hormone compared with PBO (P < 0.001 for both symptoms), with no significant differences between the active treatment arms. Insomnia and irritability decreased from baseline to 6 months postrandomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus PBO, with o-CEE being more effective than PBO at 36 and 48 months (P = 0.002 and 0.05) and t-E2 being more effective than PBO at 48 months (P = 0.004). Neither hormone treatment significantly affected irritability compared with PBO. Symptom relief for active treatment versus PBO was not significantly modified by body mass index or race/ethnicity. Recently postmenopausal women had similar and substantial reductions in hot flashes and night sweats with lower

  12. Effects of hormones on skin wrinkles and rigidity vary by race/ethnicity: four-year follow-up from the ancillary skin study of the Kronos Early Estrogen Prevention Study.

    Science.gov (United States)

    Owen, Carter M; Pal, Lubna; Mumford, Sunni L; Freeman, Ruth; Isaac, Barbara; McDonald, Linda; Santoro, Nanette; Taylor, Hugh S; Wolff, Erin F

    2016-10-01

    To measure skin wrinkles and rigidity in menopausal women of varying race/ethnicity with or without hormone therapy (HT) for up to four years. Randomized, double-blind, placebo-controlled trial. Academic medical centers. Women (42-58 years of age) within 36 months of last menstrual period and enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Treatment with 0.45 mg oral conjugated equine estrogens (CEE), transdermal E2 (50 μg/d) with micronized P (200 mg daily), or placebo for 4 years. Skin wrinkles were assessed at 11 locations on the face and neck, and skin rigidity was assessed at the forehead and cheek at baseline and yearly for 4 years. Neither total wrinkle score nor total rigidity score was significantly different at baseline or over the 4-year follow-up among patients randomized to CEE, E2, or placebo. Skin wrinkle and rigidity scores were primarily affected by race/ethnicity, with scores being significantly different between races for almost all of the wrinkle parameters and for all of the rigidity measures. There was no association between race and response to HT for total wrinkle or rigidity scores. Black women had the lowest wrinkle scores compared with white women across all 4 years. In general, skin rigidity decreased in all groups over time, but black women had significantly reduced total facial rigidity compared with white women after 4 years. Race is the strongest predictor of the advancement of skin aging in the 4 years following menopause. HT does not appear to affect skin wrinkles or rigidity at most facial locations. NCT00154180. Published by Elsevier Inc.

  13. Effects of oral versus transdermal menopausal hormone treatments on self-reported sleep domains and their association with vasomotor symptoms in recently menopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS).

    Science.gov (United States)

    Cintron, Dahima; Lahr, Brian D; Bailey, Kent R; Santoro, Nanette; Lloyd, Robin; Manson, JoAnn E; Neal-Perry, Genevieve; Pal, Lubna; Taylor, Hugh S; Wharton, Whitney; Naftolin, Fredrick; Harman, S Mitchell; Miller, Virginia M

    2017-08-21

    This study determined whether two different formulations of hormone therapy (HT): oral conjugated equine estrogens (o-CEE; 0.45 mg/d, n = 209), transdermal 17β-estradiol (t-E2; 50 μg/d, n = 201) plus cyclic progesterone (Prometrium, 200 mg) or placebo (PBO, n = 243) affected sleep domains in participants of the Kronos Early Estrogen Prevention Study. Participants completed the Pittsburgh Sleep Quality Index at baseline and during the intervention at 6, 18, 36, and 48 months. Global sleep quality and individual sleep domain scores were compared between treatments using analysis of covariance, and correlated with vasomotor symptom (VMS) scores using Spearman correlation coefficients. Global Pittsburgh Sleep Quality Index scores (mean 6.3; 24% with score >8) were similar across groups at baseline and were reduced (improved sleep quality) by both HT (average change -1.27 [o-CEE] and -1.32 [t-E2]) when compared with PBO (-0.60; P = 0.001 [o-CEE vs PBO] and P = 0.002 [t-E2 vs PBO]). Domain scores for sleep satisfaction and latency improved with both HT. The domain score for sleep disturbances improved more with t-E2 than o-CEE or PBO. Global sleep scores significantly correlated with VMS severity (rs = 0.170, P < 0.001 for hot flashes; rs = 0.177, P < 0.001 for night sweats). Change in scores for all domains except sleep latency and sleep efficiency correlated with change in severity of VMS. Poor sleep quality is common in recently menopausal women. Sleep quality improved with both HT formulations. The relationship of VMS with domains of sleep suggests that assessing severity of symptoms and domains of sleep may help direct therapy to improve sleep for postmenopausal women.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http

  14. Early prevention of obesity

    Directory of Open Access Journals (Sweden)

    Claudio Maffeis

    2014-06-01

    Full Text Available Childhood obesity is the metabolic disorder with the highest prevalence in both children and adults. Urgency to treat and prevent childhood obesity is based on the clear evidence that obesity tends to track from childhood to adulthood, is associated to morbidity also in childhood and to long-term mortality. Early life, i.e., intrauterine life and the first two years, is a sensitive window for prevention. Anatomical and functional maturation of the hypothalamic structures devoted to regulating energy intake and expenditure and body size mainly occurs in the first 1,000 days of life. Therefore, factors affecting the foetal exposition to maternal metabolic environment and early postnatal nutrition are crucial in modulating the definition of the metabolic programming processes in the brain. Maternal diseases, mainly malnutrition for defect or excess, obesity and diabetes, placental disorders and dysfunctions, maternal use of alcohol and drugs, smoking, affect long term metabolic programming of the foetus with lifelong consequences. Similarly, early nutrition contributes to complete the long-term metabolic regulating framework initiated in the uterus. Breastfeeding, adequate weaning, attention to portion size and diet composition are potential tools for reducing the obesity risk later in childhood. Longitudinal randomized controlled studies are needed for exploring the efficacy of obesity prevention strategies initiated after conception.Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  15. [Hormone replacement and selective estrogen receptor modulators (SERMS) in the prevention and treatment of postmenopausal osteoporosis].

    Science.gov (United States)

    Pfeilschifter, J

    2001-07-01

    For many years, hormone replacement therapy (HRT) has been regarded as one of the most reliable means of prophylaxis and treatment for postmenopausal osteoporosis. As HRT ameliorates menopausal symptoms, it is widely prescribed among early postmenopausal women. A variety of different modes of replacement that suit each individual requirement are available in terms of schedule (cyclic or combined application of gestagens) and route of application (oral or transdermal). HRT effectively prevents spinal bone loss and delays bone loss at the hip up to a very old age. With continued use after menopause, HRT might theoretically halve the incidence of vertebral and hip fractures. However, long-term use or use of HRT in old age is rarely practiced, and the actual benefit of a transient use for future fracture prevention remains unclear. Raloxifene is the first member of the novel class of selective estrogen receptor modulators (SERMs) that has been approved for the prophylaxis and treatment of postmenopausal osteoporosis. It combines the positive effects of estrogen on the skeleton with estrogen-antagonistic effects on sex tissues. Thus, raloxifene maintains bone mass and decreases the incidence of vertebral fractures in osteoporotic women, but avoids many of the side effects that are responsible for the poor long-term compliance to HRT such as resumption or continuation of regular menses, breast tenderness, or breast cancer. It even markedly reduces the risk of breast cancer. Both estrogen and raloxifene are characterized by a large number of extraskeletal effects that have to be taken into account when counseling postmenopausal women on the use of these agents for the prevention or treatment of osteoporosis.

  16. Estrogen prevents oxidative damage to the mitochondria in Friedreich's ataxia skin fibroblasts.

    Directory of Open Access Journals (Sweden)

    Timothy E Richardson

    Full Text Available Estrogen and estrogen-related compounds have been shown to have very potent cytoprotective properties in a wide range of disease models, including an in vitro model of Friedreich's ataxia (FRDA. This study describes a potential estrogen receptor (ER-independent mechanism by which estrogens act to protect human FRDA skin fibroblasts from a BSO-induced oxidative insult resulting from inhibition of de novo glutathione (GSH synthesis. We demonstrate that phenolic estrogens, independent of any known ER, are able to prevent lipid peroxidation and mitochondrial membrane potential (ΔΨm collapse, maintain ATP at near control levels, increase oxidative phosphorylation and maintain activity of aconitase. Estrogens did not, however, prevent BSO from depleting GSH or induce an increased expression level of GSH. The cytoprotective effects of estrogen appear to be due to a direct overall reduction in oxidative damage to the mitochondria, enabling the FRDA fibroblast mitochondria to generate sufficient ATP for energy requirements and better survive oxidative stress. These data support the hypothesis that phenol ring containing estrogens are possible candidate drugs for the delay and/or prevention of FRDA symptoms.

  17. Estrogenic endpoints in fish early life-stage tests: luciferase and vitellogenin induction in estrogen-responsive transgenic zebrafish

    NARCIS (Netherlands)

    Bogers, R.; Mutsaerds, E.; Druke, J.; Roode, de D.F.; Murk, A.J.; Burg, van der B.; Legler, J.

    2006-01-01

    This study incorporated specific endpoints for estrogenic activity in the early life-stage (ELS) test, as described in Guideline 210 of the Organization for Economic Cooperation and Development and traditionally used for toxicity screening of chemicals. A transgenic zebrafish model expressing an est

  18. [Selective Estrogen Receptor Modulators (SERMs) for prevention and treatment of postmenopausal osteoporosis].

    Science.gov (United States)

    Birkhäuser, Martin

    2012-03-01

    The three modern Selective Estrogen Receptor Modulators (SERMs) Raloxifene, Lasoxifene and Bazedoxifene registered in Europe reduce in postmenopausal women with a high risk for osteoporosis the incidence of vertebral fractures by 30 - 50 %, depending on the subgroup they belong to. Solid prospective fracture data for risk reduction in non-vertebral fractures, including the hip, are missing for Raloxifene and Bazedoxifene. However, a post hoc analysis suggests that the risk for non-vertebral fractures is significantly reduced by Raloxfene in women with severe osteoporosis. The simultaneous decrease of the incidence of ER-positive invasive breast cancer in Raloxifene users is highly relevant for clinicians. Unfortunately, Raloxifene and Bazedoxifene are, in the EU and in Switzerland, only labelled for the use in the prevention and treatment of postmenopausal osteoporosis. SERMs may induce or augment vasomotor symptoms. Therefore, SERMs are not a first line therapy in early postmenopause. Looking at other hormonal options, Hormone Replacement Therapy (HRT) remains the first line therapy for fracture reduction in the peri- and early postmenopause. SERMs are an appropriate choice for the continuation of fracture prevention after an initial HRT, particularly for the prevention of vertebral fractures. SERMs are safe if (as in oral HRT) the slightly increased risk for venous thrombo-embolism is respected. In conclusion, SERMs have today their well established place in the prevention and treatment of postmenopausal osteoporosis, particularly in women with a simultaneously increased breast cancer risk.

  19. Early effects of estrogen on the rat ventral prostate

    Directory of Open Access Journals (Sweden)

    García-Flórez M.

    2005-01-01

    Full Text Available Complex interactions between androgen and estrogen (E2 regulate prostatic development and physiology. We analyzed the early effects of a high single dose of E2 (25 mg/kg body weight and castration (separately or combined on the adult 90-day-old male Wistar rat ventral prostate. Androgen levels, prostate weight, and the variation in the relative and absolute volume of tissue compartments and apoptotic indices were determined for 7 days. Castration and exogenous E2 markedly reduced ventral prostate weight (about 50% of the control, with a significant reduction in the epithelial compartment and increased stroma. The final volume of the epithelium was identical at day 7 for all treatments (58.5% of the control. However, E2 had an immediate effect, causing a reduction in epithelial volume as early as day 1. An increase in smooth muscle cell volume resulted from the concentration of these cells around the regressing epithelium. The treatments resulted in differential kinetics in epithelial cell apoptosis. Castration led to a peak in apoptosis at day 3, with 5% of the epithelial cells presenting signs of apoptosis, whereas E2 caused an immediate increase (observed on day 1 and a sustained (up to day 7 effect. E2 administration to castrated rats significantly increased the level of apoptosis by day 3, reaching 9% of the epithelial cells. The divergent kinetics between treatments resulted in the same levels of epithelial regression after 7 days (~30% of control. These results show that E2 has an immediate and possibly direct effect on the prostate, and anticipates epithelial cell death before reducing testosterone to levels as low as those of castrated rats. In addition, E2 and androgen deprivation apparently cause epithelial cell death by distinct and independent pathways.

  20. Ezetimibe prevents the formation of estrogen-induced cholesterol gallstones in mice

    Science.gov (United States)

    de Bari, Ornella; Wang, Helen H.; Portincasa, Piero; Paik, Chang-Nyol; Liu, Min; Wang, David Q.-H.

    2014-01-01

    Background Estrogen is an important risk factor for cholesterol cholelithiasis not only in women of childbearing age taking oral contraceptives and postmenopausal women undergoing hormone replacement therapy, but also in male patients receiving estrogen therapy for prostatic cancer. In women, hormonal changes occurring during pregnancy markedly increase the risk of developing gallstones. We investigated whether the potent cholesterol absorption inhibitor ezetimibe could prevent the formation of estrogen-induced cholesterol gallstones in mice. Design Following ovariectomy, female AKR mice were implanted subcutaneously with pellets releasing 17β-estradiol at 6 μg/day and fed a lithogenic diet supplemented with ezetimibe in doses of 0 or 8 mg/kg/day for 8 weeks. Cholesterol crystallization and gallstone prevalence, lipid concentrations and composition in bile, and biliary lipid output were analyzed by physical-chemical methods. Intestinal cholesterol absorption efficiency was determined by fecal dual-isotope ratio methods. Results Ezetimibe inhibited intestinal cholesterol absorption, while significantly reducing hepatic secretion of biliary cholesterol. Consequently, bile was desaturated through the formation of numerous unsaturated micelles and gallstones were prevented by ezetimibe in mice exposed to high doses of estrogen and fed the lithogenic diet. Ezetimibe did not influence mRNA levels of the classical estrogen receptors α (ERα) and ERβ, as well as a novel estrogen receptor the G protein-coupled receptor 30 (GPR30) in the liver. Conclusions Ezetimibe protects against the estrogen-mediated lithogenic actions on gallstone formation in mice. Our finding may provide an efficacious novel strategy for the prevention of cholesterol gallstones in high-risk subjects, especially those exposed to high levels of estrogen. PMID:25303682

  1. EARLY MORNING URINE ESTROGEN-GLUCURONIDE DETERMINATION FOR OVULATION PREDICTION

    Institute of Scientific and Technical Information of China (English)

    ZHUMei-Guang; TULCHINSKYD

    1989-01-01

    Monitoring of ovulation is necessary for induction of ovulation in clinical trials. Bakerfound that the conoentration of estrogen glucuronides was high in female urine and devel-oped a RIA method for direct measurment. Adlevcrefutz and some other five groups

  2. Estrogen regulation of glucose metabolism and mitochondrial function: therapeutic implications for prevention of Alzheimer's disease.

    Science.gov (United States)

    Brinton, Roberta Diaz

    2008-01-01

    Estrogen-induced signaling pathways in hippocampal and cortical neurons converge upon the mitochondria to enhance mitochondrial function and to sustain aerobic glycolysis and citric acid cycle-driven oxidative phosphorylation and ATP generation. Data derived from experimental and clinical paradigms investigating estrogen intervention in healthy systems and prior to neurodegenerative insult indicate enhanced neural defense and survival through maintenance of calcium homeostasis, enhanced glycolysis coupled to the citric acid cycle (aerobic glycolysis), sustained and enhanced mitochondrial function, protection against free radical damage, efficient cholesterol trafficking and beta amyloid clearance. The convergence of E(2) mechanisms of action onto mitochondrial is also a potential point of vulnerability when activated in a degenerating neural system and could exacerbate the degenerative processes through increased load on dysregulated calcium homeostasis. The data indicate that as the continuum of neurological health progresses from healthy to unhealthy so too do the benefits of estrogen or hormone therapy. If neurons are healthy at the time of estrogen exposure, their response to estrogen is beneficial for both neuronal survival and neurological function. In contrast, if neurological health is compromised, estrogen exposure over time exacerbates neurological demise. The healthy cell bias of estrogen action hypothesis provides a lens through which to assess the disparities in outcomes across the basic to clinical domains of scientific inquiry and on which to predict future applications of estrogen and hormone therapeutic interventions sustain neurological health and to prevent age-associated neurodegenerative diseases such as Alzheimer's. Overall, E(2) promotes the energetic capacity of brain mitochondria by maximizing aerobic glycolysis (oxidative phosphorylation coupled to pyruvate metabolism). The enhanced aerobic glycolysis in the aging brain would be predicted

  3. Early expression of aromatase and the membrane estrogen receptor GPER in neuromasts reveals a role for estrogens in the development of the frog lateral line system.

    Science.gov (United States)

    Hamilton, Christine K; Navarro-Martin, Laia; Neufeld, Miriam; Basak, Ajoy; Trudeau, Vance L

    2014-09-01

    Estrogens and their receptors are present at very early stages of vertebrate embryogenesis before gonadal tissues are formed. However, the cellular source and the function of estrogens in embryogenesis remain major questions in developmental endocrinology. We demonstrate the presence of estrogen-synthesizing enzyme aromatase and G protein-coupled estrogen receptor (GPER) proteins throughout early embryogenesis in the model organism, Silurana tropicalis. We provide the first evidence of aromatase in the vertebrate lateral line. High levels of aromatase were detected in the mantle cells of neuromasts, the mechanosensory units of the lateral line, which persisted throughout the course of development (Nieuwkoop and Faber stages 34-47). We show that GPER is expressed in both the accessory and hair cells. Pharmacological activation of GPER with the agonist G-1 disrupted neuromast development and migration. Future study of this novel estrogen system in the amphibian lateral line may shed light on similar systems such as the mammalian inner ear.

  4. Estrogen, inflammation, and platelet phenotype.

    Science.gov (United States)

    Miller, Virginia M; Jayachandran, Muthuvel; Hashimoto, Kazumori; Heit, John A; Owen, Whyte G

    2008-01-01

    Although exogenous estrogenic therapies increase the risk of thrombosis, the effects of estrogen on formed elements of blood are uncertain. This article examines the genomic and nongenomic actions of estrogen on platelet phenotype that may contribute to increased thrombotic risk. To determine aggregation, secretion, protein expression, and thrombin generation, platelets were collected from experimental animals of varying hormonal status and from women enrolled in the Kronos Early Estrogen Prevention Study. Estrogen receptor beta predominates in circulating platelets. Estrogenic treatment in ovariectomized animals decreased platelet aggregation and adenosine triphosphate (ATP) secretion. However, acute exposure to 17beta-estradiol did not reverse decreases in platelet ATP secretion invoked by lipopolysaccharide. Thrombin generation was positively correlated to the number of circulating microvesicles expressing phosphatidylserine. Assessing the effect of estrogen treatments on blood platelets may lead to new ways of identifying women at risk for adverse thrombotic events with such therapies.

  5. Estrogen receptor-a in the medial amygdala prevents stress-induced elevations in blood pressure in females

    Science.gov (United States)

    Psychological stress contributes to the development of hypertension in humans. The ovarian hormone, estrogen, has been shown to prevent stress-induced pressor responses in females by unknown mechanisms. Here, we showed that the antihypertensive effects of estrogen during stress were blunted in femal...

  6. Select estrogens within the complex formulation of conjugated equine estrogens (Premarin® are protective against neurodegenerative insults: implications for a composition of estrogen therapy to promote neuronal function and prevent Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Brinton Roberta

    2006-03-01

    . Coadministration of two out of three neuroprotective estrogens, 17β-estradiol, equilin and Δ8,9-dehydroestrone, exerted greater neuroprotective efficacy than individual estrogens. Computer-aided analyses to determine structure/function relationships between the estrogenic structures and their neuroprotective activity revealed that the predicted intermolecular interactions of estrogen analogues with ER correlate to their overall neuroprotective efficacy. Conclusion The present study provides the first documentation of the neuroprotective profile of individual estrogens contained within the complex formulation of CEE at concentrations commensurate with their plasma levels achieved after an oral administration of 0.625 mg CEE in women. Our analyses demonstrate that select estrogens within the complex formulation of CEE contribute to its neuroprotective efficacy. Moreover, our data predict that the magnitude of neuroprotection induced by individual estrogens at relatively low concentrations may be clinically undetectable and ineffective, whereas, a combination of select neuroprotective estrogens could provide an increased and clinically meaningful efficacy. More importantly, these data suggest a strategy for determining neurological efficacy and rational design and development of a composition of estrogen therapy to alleviate climacteric symptoms, promote neurological health, and prevent age-related neurodegeneration, such as AD, in postmenopausal women.

  7. Estrogens, lactation and oral glucose tolerance test in the early puerperium.

    Science.gov (United States)

    Job, D; Eschwege, E

    1976-01-01

    An oral glucose tolerance test (OGTT) was performed on 98 women free from any known risk factor of diabetes on the fifth day of the puerperium. Results show that OGTT is greatly influenced by the conditions of lactation. A high proportion of abnormal curves (50%) is found among the group of women receiving estrogens as lactation suppressors at the time of the test. However, in breast feeding women or in non breast feeding women not given estrogen, the proportion of abnormal curves is less than 10%. It is concluded that the unexplained previously reported lack of specificity of the OGTT in the early puerperium could be related to hormonal treatment for lactation suppression.

  8. Triple-negative breast cancer risk in women is defined by the defect of estrogen signaling: preventive and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Suba Z

    2014-01-01

    Full Text Available Zsuzsanna Suba National Institute of Oncology, Surgical and Molecular Tumor Pathology Centre, Budapest, Hungary Abstract: Epidemiologic studies strongly support that triple-negative breast cancers (TNBCs may be distinct entities as compared with estrogen receptor (ER+ tumors, suggesting that the etiologic factors, clinical characteristics, and therapeutic possibilities may vary by molecular subtypes. Many investigations propose that reproductive factors and exogenous hormone use differently or even quite inversely affect the risk of TNBCs and ER+ cancers. Controversies concerning the exact role of even the same risk factor in TNBC development justify that the biological mechanisms behind the initiation of both TNBCs and non-TNBCs are completely obscure. To arrive at a comprehensive understanding of the etiology of different breast cancer subtypes, we should also reconsider our traditional concepts and beliefs regarding cancer risk factors. Malignancies are multicausal, but the disturbance of proper estrogen signaling seems to be a crucial risk factor for the development of mammary cancers. The grade of defect in metabolic and hormonal equilibrium is directly associated with TNBC risk for women during their whole life. Inverse impact of menopausal status or parity on the development of ER+ and ER- breast cancers may not be possible; these controversial results derive from the misinterpretation of percentage-based statistical evaluations. Exogenous or parity-associated excessive estrogen supply is suppressive against breast cancer, though the lower the ER expression of tumors, the weaker the anticancer capacity. In women, the most important preventive strategy against breast cancers – included TNBCs – is the strict control and maintenance of hormonal equilibrium from early adolescence through the whole lifetime, particularly during the periods of great hormonal changes. Keywords: cancer prevention, infertility, insulin resistance, menopause

  9. Targeting estrogen receptor β as preventive therapeutic strategy for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Pisano, Annalinda; Preziuso, Carmela; Iommarini, Luisa; Perli, Elena; Grazioli, Paola; Campese, Antonio F; Maresca, Alessandra; Montopoli, Monica; Masuelli, Laura; Sadun, Alfredo A; d'Amati, Giulia; Carelli, Valerio; Ghelli, Anna; Giordano, Carla

    2015-12-15

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease characterized by degeneration of retinal ganglion cells (RGCs) and consequent optic nerve atrophy. Peculiar features of LHON are incomplete penetrance and gender bias, with a marked male prevalence. Based on the different hormonal metabolism between genders, we proposed that estrogens play a protective role in females and showed that these hormones ameliorate mitochondrial dysfunction in LHON through the estrogen receptors (ERs). We also showed that ERβ localize to the mitochondria of RGCs. Thus, targeting ERβ may become a therapeutic strategy for LHON specifically aimed at avoiding or delaying the onset of disease in mutation carriers. Here, we tested the effects of ERβ targeting on LHON mitochondrial defective metabolism by treating LHON cybrid cells carrying the m.11778G>A mutation with a combination of natural estrogen-like compounds that bind ERβ with high selectivity. We demonstrated that these molecules improve cell viability by reducing apoptosis, inducing mitochondrial biogenesis and strongly reducing the levels of reactive oxygen species in LHON cells. These effects were abolished in cells with ERβ knockdown by silencing receptor expression or by using specific receptor antagonists. Our observations support the hypothesis that estrogen-like molecules may be useful in LHON prophylactic therapy. This is particularly important for lifelong disease prevention in unaffected LHON mutation carriers. Current strategies attempting to combat degeneration of RGCs during the acute phase of LHON have not been very effective. Implementing a different and preemptive approach with a low risk profile may be very helpful.

  10. Tamoxifen in the rat prevents estrogen-deficiency bone loss elicited with the LHRH agonist buserelin.

    Science.gov (United States)

    Goulding, A; Gold, E; Feng, W

    1992-08-01

    In young women chronic use of luteinizing hormone releasing hormone (LHRH) agonists such as buserelin to treat endometriosis leads to estrogen-deficiency bone loss. Tamoxifen citrate is an estrogen agonist/antagonist which protects the skeleton from osteopenia when ovarian hormones are depleted. The present study was undertaken to determine whether tamoxifen citrate (20 mg/kg body wt/week s.c.) could prevent the osteopenic effect of buserelin (25 micrograms/kg body wt/day s.c.). Four groups of rats with 45Ca-labelled bones were studied for 4 weeks: group A--placebo controls; group B--buserelin; Group C--tamoxifen; group D--buserelin+tamoxifen. Bone resorption was monitored by measuring the urinary excretion of 45Ca and hydroxyproline. Interestingly buserelin lowered both blood 17 beta-estradiol values and uterine weights in the presence and absence of tamoxifen. However, tamoxifen slowed bone breakdown and inhibited the bone-thinning effects of buserelin. Total body calcium values (mg; means +/- S.D.) were: 2227 +/- 137; 1926 +/- 124; 2233 +/- 94 and 2268 +/- 163, in groups A to D respectively. Osteopenia was thus present only in group B (P less than 0.001). Because tamoxifen inhibits estrogen-deficiency bone loss in buserelin-treated rats without depressing the hypoestrogenic actions of this LHRH-agonist, we suggest that use of tamoxifen to protect the skeleton during LHRH-agonist therapy in young women should be explored. Tamoxifen citrate might also help to prevent postmenopausal osteoporosis.

  11. Ritonavir binds to and downregulates estrogen receptors: Molecular mechanism of promoting early atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Jin [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Wang, Ying [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Su, Ke [Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Liu, Min [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Hu, Peng-Chao [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Ma, Tian; Li, Jia-Xi [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Wei, Lei [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zheng, Zhongliang, E-mail: biochem@whu.edu.cn [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China); Yang, Fang, E-mail: fang-yang@whu.edu.cn [Department of Physiology, School of Medicine, Wuhan University, Wuhan 430071 (China)

    2014-10-01

    Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist for E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and early events of atherosclerosis. - Graphical abstract: RTV directly binds to ERα and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: • RTV increases the thickness of rat coronary artery wall and foam cell formation. • RTV downregulates the expression of ERα and ERβ. • RTV inhibits ERα promoter activity. • RTV directly binds to ERα and the key amino acid is Leu536. • RTV inhibits the nuclear translocation of ERα and GPER.

  12. Estrogen activity as a preventive and therapeutic target in thyroid cancer.

    Science.gov (United States)

    Rajoria, Shilpi; Suriano, Robert; George, Andrea L; Shanmugam, Arulkumaran; Jussim, Casey; Shin, Edward J; Moscatello, Augustine L; Geliebter, Jan; Carpi, Angelo; Tiwari, Raj K

    2012-03-01

    Thyroid cancer is the most common endocrine-related cancer with increasing incidences during the last five years. Interestingly, according to the American Thyroid Association, the incidences of thyroid proliferative diseases occur four to five times more in women than in men with the risk of developing thyroid disorders being one in every eight females. Several epidemiological studies have suggested a possible correlation between incidences of thyroid malignancies and hormones but the precise contribution of estrogen in thyroid proliferative disease initiation, and progression is not well understood. This review is an attempt to define the phenotypic and genotypic modulatory effects of estrogen on thyroid proliferative diseases. The significance and relevance of expression of estrogen receptors, α and β, in normal and malignant thyroid tissues and their effects on different molecular pathways involved in growth and function of the thyroid gland are discussed. These novel findings open up areas of developing alternative therapeutic treatments and preventive approaches which employ the use of antiestrogen to treat thyroid malignancies. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  13. Preventing Child Sexual Abuse Early

    Directory of Open Access Journals (Sweden)

    Wenjing Zhang

    2015-02-01

    Full Text Available This study is aimed to examine preschool teachers’ knowledge of, attitudes about, and training related to child sexual abuse (CSA prevention in Beijing, China. Two hundred and forty-five preschool teachers were administered the 16-item questionnaire that contained questions on CSA prevention knowledge, attitudes, and teacher training. Results showed that Chinese preschool teachers had limited knowledge on CSA prevention (M = 4.86, SD = 2.12. Less than 5% of the teachers ever attended CSA prevention training programs. Preschool teachers’ training on CSA prevention was the significant factor for their knowledge and attitudes. To help protect children against sexual abuse, there is an urgent need to develop appropriate prevention training programs for preschool teachers in China.

  14. Tocopherols inhibit oxidative and nitrosative stress in estrogen-induced early mammary hyperplasia in ACI rats.

    Science.gov (United States)

    Das Gupta, Soumyasri; So, Jae Young; Wall, Brian; Wahler, Joseph; Smolarek, Amanda K; Sae-Tan, Sudathip; Soewono, Kelvin Y; Yu, Haixiang; Lee, Mao-Jung; Thomas, Paul E; Yang, Chung S; Suh, Nanjoo

    2015-09-01

    Oxidative stress is known to play a key role in estrogen-induced breast cancer. This study assessed the chemopreventive activity of the naturally occurring γ-tocopherol-rich mixture of tocopherols (γ-TmT) in early stages of estrogen-induced mammary hyperplasia in ACI rats. ACI rats provide an established model of rodent mammary carcinogenesis due to their high sensitivity to estrogen. Female rats were implanted with 9 mg of 17β-estradiol (E2) in silastic tubings and fed with control or 0.3% γ-TmT diet for 1, 3, 7, and 14 d. γ-TmT increased the levels of tocopherols and their metabolites in the serum and mammary glands of the rats. Histological analysis revealed mammary hyperplasia in the E2 treated rats fed with control or γ-TmT diet. γ-TmT decreased the levels of E2-induced nitrosative and oxidative stress markers, nitrotyrosine, and 8-oxo-dG, respectively, in the hyperplastic mammary tissues. 8-Isoprostane, a marker of oxidative stress in the serum, was also reduced by γ-TmT. Noticeably, γ-TmT stimulated Nrf2-dependent antioxidant response in the mammary glands of E2 treated rats, evident from the induced mRNA levels of Nrf2 and its downstream antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. Therefore, inhibition of nitrosative/oxidative stress through induction of antioxidant response is the primary effect of γ-TmT in early stages of E2-induced mammary hyperplasia. Due to its cytoprotective activity, γ-TmT could be a potential natural agent for the chemoprevention of estrogen-induced breast cancer.

  15. Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2-year randomized, double blind, placebo-controlled study

    DEFF Research Database (Denmark)

    Nielsen, Therese F; Ravn, Pernille; Bagger, Yu Z

    2004-01-01

    The aim of this study was to evaluate the efficacy of pulsed estrogen therapy (intranasal 17beta-estradiol) in the prevention of postmenopausal bone loss. A total of 386 women (40-65 years old), less than 5 years past menopause, were randomized to intranasal placebo, 17beta-estradiol 150 micro g...... tolerance were good. This study demonstrates that pulsed estrogen therapy at the dose of 150 microg and 300-microg per day prevents bone loss in a dose-dependant manner at each site studied, and normalizes bone turnover markers to premenopausal levels....

  16. Prevention Starts in Early Childhood

    Science.gov (United States)

    Maciel, B. A. P. C.; Neto, R. P.; Hartmann, R. P.; Melo, M. O.; Gonçalves, M.; Marques, G.; Rocha, F. L.; Silveira, G. M.

    2014-12-01

    Unlike other natural hazards, earthquakes strike suddenly and without warning. Consequently, prevention is the best we can do to ensure safety. In spite of the large and medium earthquakes, some of them tsunamigenic, that affected Portugal in the past, the Portuguese society is little aware of the seismic risk and has not developed an adequate culture of prevention. This is most probably due to the long time interval between destructive earthquakes. Earthquakes can be a real danger to societies, damaging human-made structures and endangering human lives. Earthquakes can trigger additional emergencies, and individuals should also be prepared to contend with it. By planning and practicing what to do if an earthquake strikes, children and their family can learn to react correctly and automatically when the shaking begins. Risks can then be dramatically lessened if the population is educated on how to react before, during and after an earthquake. Children's knowledge is ever growing. They have a fundamental role in changing societies. By educating the children of today we are forming better adults of tomorrow. We are simultaneously passing this knowledge to their caregivers and families. Through demonstrating how fundamental it is to be conscious of those issues, not only will the children will be informed, but also their relatives will be aware of such risks. We use this approach to explain children how to assess risk in a broader sense. We teach them other preventive measures, namely those related with electricity, gas and the danger on non-potable water, essential topics on "what to do before an earthquake" but also on the daily routines. This presentation will highlight the importance of encouraging a culture of prevention. This project funded by the Portuguese "Ciência Viva" program, and is conducted by science high-school students, teachers and the parents association. Scientific support is given by the seismology research group at Instituto Dom Luíz.

  17. Early detection of breast cancer: a molecular optical imaging approach using novel estrogen conjugate fluorescent dye

    Science.gov (United States)

    Bhattacharjee, Shubhadeep; Jose, Iven

    2011-02-01

    Estrogen induced proliferation of mutant cells is widely understood to be the one of major risk determining factor in the development of breast cancer. Hence determination of the Estrogen Receptor[ER] status is of paramount importance if cancer pathogenesis is to be detected and rectified at an early stage. Near Infrared Fluorescence [NIRf] Molecular Optical Imaging is emerging as a powerful tool to monitor bio-molecular changes in living subjects. We discuss pre-clinical results in our efforts to develop an optical imaging diagnostic modality for the early detection of breast cancer. We have successfully carried out the synthesis and characterization of a novel target-specific NIRf dye conjugate aimed at measuring Estrogen Receptor[ER] status. The conjugate was synthesized by ester formation between 17-β estradiol and a hydrophilic derivative of Indocyanine Green (ICG) cyanine dye, bis-1,1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. In-vitro studies regarding specific binding and endocytocis of the dye performed on ER+ve [MCF-7] and control [MDA-MB-231] adenocarcinoma breast cancer cell lines clearly indicated nuclear localization of the dye for MCF-7 as compared to plasma level staining for MDA-MB-231. Furthermore, MCF-7 cells showed ~4.5-fold increase in fluorescence signal intensity compared to MDA-MB-231. A 3-D mesh model mimicking the human breast placed in a parallel-plate DOT Scanner is created to examine the in-vivo efficacy of the dye before proceeding with clinical trials. Photon migration and florescence flux intensity is modeled using the finite-element method with the coefficients (quantum yield, molar extinction co-efficient etc.) pertaining to the dye as obtained from photo-physical and in-vitro studies. We conclude by stating that this lipophilic dye can be potentially used as a target specific exogenous contrast agent in molecular optical imaging for early detection of breast cancer.

  18. Effects of Mifepristone Compound on the Receptors of Estrogen and Progesterone in Early Pregnancy Deciduas

    Institute of Scientific and Technical Information of China (English)

    金力; 沈维雄; 孙志达; 范光升; 乌毓明; 王寒正

    2000-01-01

    Objectives To examine the effect of mifepristone compound (mifepristone + anordrin) on estrogen receptor (ER) and progesterone receptor (PR) in early pregnancy decidua.Materials & Methods A Controlled study was carried out among 60 normal early pregnant volunteers ( ≤ 49 d) in the department of obstetric and gynecology of Peking Union Medical Hospital. The concentrations of ER and PR were measured by radioligand and were compared with the control subjects after oral administration of mifepristone or mifepristone compound in different doses.Results The concentration of PR decreased while that of ER increased significantly in the decidua from all subjects administrated with mifepristone compound. We also found the concentration of EcR in Group 5 (mifepristone 30 mg + AF- 53 5 mg) was the highest among 6 groups. The compound may be in favor of estrogen's action on endometrium.Conclusion The results indicate that mi f epristone compound with AF-53 has a coordinated function and can change the proportion of PR and ER. Hence, it can facilitate abortion. The compound dose of mifepristone 30 mg q- AF- 53 5 mg is in favor of the endometrium recovering.

  19. Early Prevention Method for Power Systems Instability

    DEFF Research Database (Denmark)

    Dmitrova, Evgenia

    In the scope of this work, a method capable of fast identification of the proper countermeasure, that prevents emerging instability, has been developed. The focus is placed on the prevention of aperiodic small signal angular instability by means of manipulations applied to load nodes (nodes conta......’s evolution to self-curing systems, for which the human factor involved in control, will keep diminishing....... and defines which amount of countermeasure would be sufficient to bring a critical generator to the stable operation. The early prevention method is addressing the possibility of near real time analysis, utilizing computationally efficient algorithms. The method is providing efficient countermeasure matching...

  20. Estrogen and Osteoporosis.

    Science.gov (United States)

    Lindsay, Robert

    1987-01-01

    This article reviews the use of estrogen in the prevention and treatment of osteoporosis. Dosage levels, interactions with other factors, side effects, and the mechanism of estrogen action are discussed. (Author/MT)

  1. Estrogens, episodic memory, and Alzheimer's disease: a critical update.

    Science.gov (United States)

    Henderson, Victor W

    2009-05-01

    Estrogen-containing hormone therapy initiated during late postmenopause does not improve episodic memory (an important early symptom of Alzheimer's disease), and it increases dementia risk. Cognitive consequences of exogenous estrogen exposures during midlife are less certain. Observational evidence implies that use of hormone therapy at a younger age close to the time of menopause may reduce risk of Alzheimer's disease later in life. However, there are concerns that observational findings may be systematically biased. Partial insight on this critical issue may be gleaned from results of ongoing clinical trials involving midlife postmenopausal women (Early versus Late Intervention Trial with Estrogen; Kronos Early Estrogen Prevention Study). The effects of exogenous midlife estrogen exposures and Alzheimer risk can also be approached through better animal models, through carefully designed cohort studies, and through use of surrogate outcomes in randomized controlled trials in midlife women. Selective estrogen receptor modulators have the potential to affect cognitive outcomes and also merit additional study.

  2. Immunohistochemical Localization of Estrogen and Progesterone Receptorin Decidua and Villi of Human Early Pregnancy

    Institute of Scientific and Technical Information of China (English)

    王介东; 伏耀; 施文良; 朱逢第; 乔根梅; 王幼劬

    1992-01-01

    Imtnunohistochemical assessment of estrogen recceptor(ER) and progesterone receptors(PR) were performed using monoetonat antibodies to the receptors. A totalof 81 samples. from pregnant women at 5-13 weeks of gestation were immunostained by peroxidase anti-peroxidase method (PAP). hnmunostaining pattern of PR in early pregnant decidua was similar to that of the late luteal phase of normal endometrium characterized by little reaction in supecfieiat glandular epithelia and retatively intense in stroma. Positive stainig was atsa revealed in structure of blood vessels including pericyte and smooth muscle cells. An interesting finding is that endothelial cells Of the vessels expressed PR which has not been reported in normal cyclic endometrium. The endothelial nature of their PR partitive cell was further confirmed by immunostaining of specific endothelial marker, Factor VⅢ. The trophoblast population in villi anddecidua also showed positive reaction inctnding villous trophoblast, column andinterstitial trophobtast. In eontrast to PR, little ER were revealed in deteected tissue.

  3. Bazedoxifene acetate: a novel selective estrogen receptor modulator for the prevention and treatment of postmenopausal osteoporosis.

    Science.gov (United States)

    Chines, Arkadi A; Komm, Barry S

    2009-07-01

    Postmenopausal osteoporosis is an increasing worldwide health concern affecting an estimated 200 million individuals. Despite a wide range of available treatment options, many patients are not being treated or discontinue therapy. The ongoing need for new osteoporosis therapies has led to the development of new selective estrogen receptor modulators (SERMs) with an ideal tissue selectivity profile and beneficial effects on bone without undesirable effects on the endometrium and breast. Bazedoxifene acetate, a novel SERM in clinical development for the prevention and treatment of postmenopausal osteoporosis, resembles this ideal profile more closely than other currently available SERMs. Results from large prospective phase III trials showed that it increases bone mineral density, reduces bone turnover rate and decreases the risk for new vertebral fractures. Moreover, based on a post hoc analysis of a subgroup of women with a higher risk for fracture, bazedoxifene was demonstrated to significantly reduce the incidence of nonvertebral fractures compared with both raloxifene hydrochloride and placebo. Furthermore, it was reported to be well tolerated, with a favorable safety profile and no evidence of endometrial or breast tissue stimulation. Bazedoxifene represents an important new treatment option for women at risk for osteoporosis and fracture.

  4. EARLY CHILDHOOD CARIES: CAN YOU PREVENT IT?

    Directory of Open Access Journals (Sweden)

    K. B. Miloserdova

    2014-01-01

    Full Text Available The probability of the caries development largely depends on the oral microflora imbalance. This imbalance can be corrected with probiotics. The article analyzes the results of studies on the use of adapted milk formulas with probiotics to prevent caries in early childhood. It shows that the use of adapted formulas with probiotics is accompanied by a decrease in the frequency of releasing cariogenic streptococci and actinomycetes with a simultaneous increase in the frequency of detecting bacterial antagonists of the cariogenic flora, normalization of sIgA concentration in saliva, and decrease in the severity of the caries process. The survey results will contribute to the development of effective approaches to prevention of dental caries in children.

  5. Early Marriage: a Policy for Infertility Prevention

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Karimzadeh

    2008-06-01

    Full Text Available Female fertility begins to decline many years prior to the onset of menopause despite continued regular ovulatory cycles. Age related infertility is due to oocyte abnormalities and decreased ovarian reserve. Treatment of infertility when the cause is limited to decreased ovarian reserve is empirical at present except for oocyte donation. This mini review of the literature covers all available English biomedical journals that have been published from 1995 to 2008. The search based on combination of the words age, fertility, infertility, and oocyte abnormalities. The important findings from this search strategy are summarized and presented in the sub headings including female age and fertility, miscarriage and in vitro fertilization. Regarding infertility prevention, this mini review suggested that early marriage is a primordial, effective, inexpensive and easy way to prevent infertility.

  6. BMP-7 stimulates early diaphyseal fracture healing in estrogen deficient rats

    NARCIS (Netherlands)

    Blokhuis, T.J.; Buma, P.; Verdonschot, N.J.J.; Gotthardt, M.; Hendriks, T.

    2012-01-01

    Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti-resorptive agents or with anabolic agents such as bone morphog

  7. BMP-7 stimulates early diaphyseal fracture healing in estrogen deficient rats.

    NARCIS (Netherlands)

    Blokhuis, T.J.; Buma, P.; Verdonschot, N.J.; Gotthardt, M.; Hendriks, T.

    2012-01-01

    Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti-resorptive agents or with anabolic agents such as bone morphog

  8. Estrogen regulation of mitochondrial bioenergetics: implications for prevention of Alzheimer's disease.

    Science.gov (United States)

    Yao, Jia; Brinton, Roberta Diaz

    2012-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. Increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress in AD pathogenesis. Compromised aerobic glycolysis pathway coupled with oxidative stress is first accompanied by a shift toward a ketogenic pathway that eventually progresses into fatty acid oxidation (FAO) pathways and leads to white matter degeneration and overproduction and mitochondrial accumulation of β-amyloid. Estrogen-induced signaling pathways converge upon the mitochondria to enhance mitochondrial function and to sustain aerobic glycolysis coupled with citric acid cycle-driven oxidative phosphorylation to potentiate ATP (Adenosine triphosphate) generation. In addition to potentiated mitochondrial bioenergetics, estrogen also enhances neural survival and health through maintenance of calcium homeostasis, promotion of antioxidant defense against free radicals, efficient cholesterol trafficking, and beta amyloid clearance. Significantly, the convergence of E2 mechanisms of action onto mitochondria is also a potential point of vulnerability when activated in diseased neurons that exacerbates degeneration through increased load on dysregulated calcium homeostasis. The "healthy cell bias of estrogen action" hypothesis examines the role that regulating mitochondrial function and bioenergetics play in promoting neural health and the mechanistic crossroads that lead to divergent outcomes following estrogen exposure. As the continuum of neurological health progresses from healthy to unhealthy, so too do the benefits of estrogen or hormone therapy.

  9. Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis

    Institute of Scientific and Technical Information of China (English)

    Han Kyoung Choi; Hye Ri Kang; Eutteum Jung; Tae Eon Kim; Jing Jing Lin; Soo Young Lee

    2013-01-01

    The receptor activator of NF-kB (RANK) and immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptors are essential factors involved in regulating osteoclast formation and bone remodeling.Here,we identify early estrogen-induced gene 1 (EEIG1) as a novel RANK ligand (RANKL)-inducible protein that physically interacts with RANK and further associates with Gab2,PLCγ2 and Tec/Btk kinases upon RANKL stimulation.EEIG1 positively regulates RANKL-induced osteoclast formation,likely due to its ability to facilitate RANKL-stimulated PLCγ2 phosphorylation and NFATc1 induction.In addition,an inhibitory peptide designed to block RANK-EEIG1 interaction inhibited RANKL-induced bone destruction by reducing osteoclast formation.Together,our results identify EEIG1 as a novel RANK signaling component controlling RANK-mediated osteoclast formation,and suggest that targeting EEIG1 might represent a new therapeutic strategy for the treatment of pathological bone resorption.

  10. The bisphosphonate zoledronate prevents vertebral bone loss in mature estrogen-deficient rats as assessed by micro-computed tomography

    Directory of Open Access Journals (Sweden)

    Glatt M.

    2001-01-01

    Full Text Available The effect of long-term treatment with the bisphosphonate zoledronate on vertebral bone architecture was investigated in estrogen-deficient mature rats. 4-month-old rats were ovariectomized and development of cancellous osteopenia was assessed after 1 year. The change of bone architectural parameters was determined with a microtomographic instrument of high resolution. After 1 year of estrogen-deficiency, animals lost 55% of vertebral trabecular bone in comparison to sham operated control animals. Trabecular number (Tb.N and trabecular thickness (Tb.Th were significantly reduced in ovariectomized animals, whereas trabecular separation (Tb.Sp, bone surface to volume fraction (BS/BV and trabecular bone pattern factor (TBPf were significantly increased, indicating a loss of architectural integrity throughout the vertebral body. 3 groups of animals were treated subcutaneously with zoledronate for 1 year with 0.3, 1.5 and 7.5 microgram/kg/week to inhibit osteoclastic bone degradation. Administration started immediately after ovariectomy and treatment dose-dependently prevented the architectural bone deterioration and completely suppressed the effects of estrogen deficiency at the higher doses. The results show that microtomographic determination of static morphometric parameters can be used to quantitate the effects of drugs on vertebral bone architecture in small laboratory animals and that zoledronate is highly effective in this rat model.

  11. Lasofoxifene : Selective Estrogen Receptor Modulator for the Prevention and Treatment of Postmenopausal Osteoporosis

    NARCIS (Netherlands)

    Peterson, Gregory M.; Naunton, Mark; Tichelaar, Lisette K.; Gennari, Luigi

    2011-01-01

    OBJECTIVE: To review literature evaluating the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of lasofoxifene (CP-336156), a selective estrogen receptor modulator (SEAM) that is not approved for use in the US. DATA SOURCES: Literature was accessed through the MEDLINE and EMBA

  12. Anti-estrogen prevents xenoestrogen-induced testicular pathology of eelpout (Zoarces viviparus).

    Science.gov (United States)

    Rasmussen, Tina H; Teh, Swee J; Bjerregaard, Poul; Korsgaard, Bodil

    2005-04-30

    Estrogenic alkylphenols have been shown to affect the reproductive system of male fish causing induction of vitellogenin synthesis and altered testis structure. However, it is still unknown whether the histopathological effects on the testes is mediated by the estrogen receptor or if it represent general toxicopathological effects. In the present study, the effects of different concentrations of the estrogenic chemical 4-tert-octylphenol on vitellogenin (Vtg) synthesis and testicular structure were investigated in the eelpout Zoarces viviparus during spermatogenesis. Adult male eelpout were exposed to 4-tOP (nominal concentrations: 10, 50 or 100 microg l(-1)) or 17beta-estradiol (E2; 0.5 microg l(-1)) in a continuous flow-through system for 3 weeks. A group of fish were exposed to 4-tOP (50 microg l(-1)) concomitantly with the anti-estrogen ZM 189,154 (20 microg g(-1) week(-1), i.p.). The Vtg concentration in plasma was measured by enzyme-linked immunosorbent assay. The testicular structure was examined by light microscopy and gamma-glutamyl transpeptidase (gamma-GTP) activity was measured in the testes. The testicular localization of gamma-GTP was analysed by enzyme histochemistry. A marked increase in the plasma Vtg concentration was observed after exposure to the actual concentration of 35 microg l(-1) 4-tOP (nominal concentration, 50 microg l(-1)), 63 microg l(-1) 4-tOP (nominal concentration, 100 microg l(-1)) or E2. Co-treatment with ZM 189,154 totally abolished the 4-tOP-dependent induction of Vtg synthesis. Exposure to 4-tOP or E2 caused a marked reduction in the testis mass and severely affected the testicular development and structure including the Sertoli cells (based on histology and gamma-GTP activity), resulting in impairment of spermatogenesis and degeneration of lobular structures. Other cellular abnormalities such as accumulations of yellowish-brown pigmented cells and increased interstitial fibrosis in the testes was also observed in the exposed

  13. Early Prevention Toward Sexual Abuse on Children

    Directory of Open Access Journals (Sweden)

    Ira Paramastri

    2015-11-01

    Full Text Available Child sexual abuse is a worldwide problem. Although most studies on the longterm consequences of child sexual abuse have focused on women, sexual abuse of both boys and girls is common. Peer sexual abuse in schools was an often overlooked problem that contributes to a hostile school environment: one major study found that 85% of girls and 76% of boys reported experiencing some form of sexual abuse in school. 85% of child sexual abuse is committed by relatives, close family friend or an adult that the child knows and trusts. The childhood sexual abuse variables taken into account are commonly age of onset, duration, abuse forms and relationship between the child and the perpetrator. The objective of this study was to gather information or opinion about sexual abuse concept, methods and media of the elementary students, parents, teachers and experts. A qualitative study, involving one to one interviews, was conducted with 7 experts, focus group discussion with 40 elementary students, and with 40 parents in Yogyakarta district about child sexual abuse issues. Data were analysed according to Miles and Huberman’s data reduction, data display and conclusion verification process. These findings strongly indicate that boys and girls are vulnerable to this form of childhood sexual abuse ; the similarity in the likelihood for multiple behavioral, mental and social outcomes among men and women suggest the need to identify and treat all adults affected by child sexual abuse. Themes related to the child sexual abuse were: paperwork design, good facilitator, guidelines for students, parents and teachers. Students prefer media that can help them understand concept with komik paperwork as media for early prevention. Parents, teachers and experts prefer that this prevention program can run as soon. With careful paperwork design and evaluation of prevention program, the success of program implementation can be enhanced.

  14. Expression profile of E-cadherin, estrogen receptors, and P53 in early-onset gastric cancers.

    Science.gov (United States)

    Zhou, Fan; Xu, Yuanyuan; Shi, Jiong; Lan, Xing; Zou, Xiaoping; Wang, Lei; Huang, Qin

    2016-12-01

    Early-onset gastric cancer (EOGC) is predominant in females, diffuse histology, and hereditary pattern. Germline mutation of CDH1 and p53 has been reported previously and female dominance was speculated to be associated with estrogen and its receptors. Expression of E-cadherin, estrogen receptor α (ERα), estrogen receptor β (ERβ), and p53 in EOGC remains unclear, which was the focus of this study, to assess clinical significance of their expression in EOGC. The expression of E-cadherin, ERα, ERβ, and p53 in tumors and normal tissues from surgically resected EOGCs was assessed by immunohistochemistry (n = 139) and Western blot (n = 7) methods, respectively. The expression in tumor tissues was significantly higher for ERα, ERβ, and p53, but lower for E-cadherin, compared to uninvolved mucosa. Positive staining of ERβ and p53 was more frequently observed in younger patients with advanced TNM stages. For E-cadherin, significant correlation was observed between the immunopositivity and TNM stages IA+IB. P53-negative patients had significantly better outcomes than p53-positive patients. Significant association between expression of E-cadherin and histologic types was found in familial, but not in sporadic, EOGC. In conclusion, our results demonstrated E-cadherin may have a role in initiation of EOGC and positive ERβ and p53 expression may partially explained early-onset and tumor progression of EOGC.

  15. First Steps: Taking Action Early To Prevent Violence.

    Science.gov (United States)

    Davis, Rachel; Nageer, Sherlina; Cohen, Larry; Tepperman, Jean; Biderman, Fran; Henkle, Gretchen

    This report pulls together what is known about the intersection of early childhood development and violence prevention into a coherent strategy. It presents essential information about key risk and resiliency factors relevant to early development and violence prevention, research on a broad range of violence prevention issues, and recommendations…

  16. Dietary Genistein Prevents Denervation-Induced Muscle Atrophy in Male Rodents via Effects on Estrogen Receptor-α.

    Science.gov (United States)

    Aoyama, Shinya; Jia, Huijuan; Nakazawa, Kyoko; Yamamura, Junki; Saito, Kenji; Kato, Hisanori

    2016-06-01

    Genistein has high estrogenic activity. Previous studies have shown beneficial effects of estrogen or hormone replacement therapy on muscle mass and muscle atrophy. We investigated the preventive effects and underlying mechanisms of genistein on muscle atrophy. In Expt. 1, male Wistar rats were fed a diet containing no genistein [control (CON)] or 0.05% genistein (GEN; wt:wt diet) for 24 d. On day 14, the sciatic nerve in the left hind leg was severed, and the right hind leg was sham-treated. In Expt. 2, male C57BL6J mice were subcutaneously administered a vehicle (Veh group) or the estrogen receptor (ER) antagonist ICI 182,780 (ICI group) via an osmotic pump for 27 d, and each group was subsequently fed CON or GEN diets from day 3 to day 27. Muscle atrophy was induced on day 17 as in Expt. 1. In Expt. 3, male C57BL6J mice were subcutaneously administered vehicle or a selective ER agonist-ER-α [4,4',4'-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT)] or ER-β [2,3-bis(4-hydroxyphenyl)-propionitrile (DPN)]-or genistein (GEN-sc-i) via an osmotic pump for 13 d, and muscle atrophy was induced on day 3 as in Expt. 1. The ratio of denervated soleus muscle weight to sham-operated soleus muscle weight (d/s ratio) was used as the index of muscle atrophy. Expt. 1: The d/s ratio in the GEN group was 20% higher than that in the CON group (P muscle atrophy. ER-α was related to the preventive effect of genistein on muscle atrophy. © 2016 American Society for Nutrition.

  17. Estrogen, Estrogen Receptor and Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li-Han Hsu

    2017-08-01

    Full Text Available Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors (ER in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR, and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Estrogen and its receptor have the potential to become a prognosticator and a therapeutic target in lung cancer. On the other hand, tobacco smoking aggravates the effect of estrogen and endocrine disruptive chemicals from the environment targeting ER may well contribute to the lung carcinogenesis. They have gradually become important issues in the course of preventive medicine.

  18. Gastric cancer: prevention, screening and early diagnosis.

    Science.gov (United States)

    Pasechnikov, Victor; Chukov, Sergej; Fedorov, Evgeny; Kikuste, Ilze; Leja, Marcis

    2014-10-14

    Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the treatment is largely ineffective. Helicobacter pylori (H. pylori) infection is a well-established carcinogen for gastric cancer. While lifestyle factors are important, the efficacy of interventions in their modification, as in the use of antioxidant supplements, is unconvincing. No organized screening programs can be found outside Asia (Japan and South Korea). Although several screening approaches have been proposed, including indirect atrophy detection by measuring pepsinogen in the circulation, none of them have so far been implemented, and more study data is required to justify any implementation. Mass eradication of H. pylori in high-risk areas tends to be cost-effective, but its adverse effects and resistance remain a concern. Searches for new screening biomarkers, including microRNA and cancer-autoantibody panels, as well as detection of volatile organic compounds in the breath, are in progress. Endoscopy with a proper biopsy follow-up remains the standard for early detection of cancer and related premalignant lesions. At the same time, new advanced high-resolution endoscopic technologies are showing promising results with respect to diagnosing mucosal lesions visually and targeting each biopsy. New histological risk stratifications (classifications), including OLGA and OLGIM, have recently been developed. This review addresses the current means for gastric cancer primary and secondary prevention, the available and emerging methods for screening, and new developments in endoscopic detection of early lesions of the stomach.

  19. Estrogen-DNA Adducts as Novel Biomarkers for Ovarian Cancer Risk and for Use in Prevention

    Science.gov (United States)

    2013-03-01

    urine samples [4] and genetic polymorphisms in four selected estrogen- metabolizing enzymes in DNA saliva samples from 50 women diagnosed with ovarian...The views, opinions and/or findings contained in this report are those of the author( s ) and should not be construed...5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: 5f. WORK UNIT

  20. Glutamate-induced apoptosis in primary cortical neurons is inhibited by equine estrogens via down-regulation of caspase-3 and prevention of mitochondrial cytochrome c release

    Directory of Open Access Journals (Sweden)

    Zhang YueMei

    2005-02-01

    absence of 17β-estradiol or Δ8, 17β-estradiol (10 nM-10 μM resulted in the prevention of cell death and was associated with a significant dose-dependent decrease in caspase-3 protein levels, with Δ8, 17β-E2 being more potent than 17β-E2. Protein levels of Fas receptor remained unchanged in the presence of glutamate. In contrast, treatment with glutamate induced, in a time-dependent manner, the release of cytochrome c into the cytosol. Cytosolic cytochrome c increased as early as 1.5 h after glutamate treatment and these levels were 5 fold higher after 6 h, compared to levels in the untreated cells. Concomitant with these changes, the levels of cytochrome c in mitochondria decreased significantly. Both 17β-E2 and Δ8, 17β-E2 reduced the release of cytochrome c from mitochondria into the cytosol and this decrease in cytosolic cytochrome c was associated with inhibition of glutamate-induced cell death. Conclusion In the primary cortical cells, glutamate-induced apoptosis is accompanied by up-regulation of caspase-3 and its activity is blocked by caspase protease inhibitors. These effects of glutamate on caspase-3 appear to be independent of changes in Fas receptor, but are associated with the rapid release of mitochondrial cytochrome c, which precedes changes in caspase-3 protein levels leading to apoptotic cell death. This process was differentially inhibited by estrogens with the novel equine estrogen Δ8, 17β-E2 being more potent than 17β-E2. To our knowledge, this is the first study to demonstrate that equine estrogens can prevent glutamate-induced translocation of cytochrome c from mitochondria to cytosol in rat primary cortical cells.

  1. Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model

    OpenAIRE

    Zhang, Huaqiu; Xie, Minjie; Gary P. Schools; Feustel, Paul F.; Wang, Wei; Lei, Ting; Kimelberg, Harold K.; Zhou, Min

    2008-01-01

    Pretreatment of ovarectomized rats with estrogen shows long-term protection via activation of the estrogen receptor (ER). However, it remains unknown whether activation of the ER can provide protection against early neuronal damage when given acutely, we simulated ischemic conditions by applying oxygen and glucose deprived (OGD) solution to acute male rat hippocampal slices and examined the neuronal electrophysiological changes. Pyramidal neurons and interneurons showed a time-dependent membr...

  2. Circulating microparticles and endogenous estrogen in newly menopausal women.

    Science.gov (United States)

    Jayachandran, M; Litwiller, R D; Owen, W G; Miller, V M

    2009-04-01

    Estrogen modulates antithrombotic characteristics of the vascular endothelium and the interaction of blood elements with the vascular surface. A marker of these modulatory activities is formation of cell-specific microparticles. This study examined the relationship between blood-borne microparticles and endogenous estrogen at menopause. Platelet activation and plasma microparticles were characterized from women being screened (n = 146) for the Kronos Early Estrogen Prevention Study. Women were grouped according to serum estrogen ( 40 pg/ml; high estrogen, n = 11). Age, body mass index, blood pressure and blood chemistries were the same in both groups. No woman was hypertensive, diabetic or a current smoker. Platelet counts, basal and activated expression of P-selectin on platelet membranes were the same, but activated expression of glycoprotein IIb/IIIa was greater in the high-estrogen group. Numbers of endothelium-, platelet-, monocyte- and granulocyte-derived microparticles were greater in the low-estrogen group. Of the total numbers of microparticles, those positive for phosphatidylserine and tissue factor were also greater in the low-estrogen group. These results suggest that, with declines in endogenous estrogen at menopause, numbers of procoagulant microparticles increase and thus may provide a means to explore mechanisms for cardiovascular risk development in newly menopausal women.

  3. Estrogenic compounds, estrogen receptors and vascular cell signaling in the aging blood vessels.

    Science.gov (United States)

    Smiley, Dia A; Khalil, Raouf A

    2009-01-01

    The cardiovascular benefits of menopausal hormone therapy (MHT) remain controversial. The earlier clinical observations that cardiovascular disease (CVD) was less common in MHT users compared to non-users suggested cardiovascular benefits of MHT. Also, experimental studies have identified estrogen receptors ERalpha, ERbeta and GPR30, which mediate genomic or non-genomic effects in vascular endothelium, smooth muscle, and extracellular matrix (ECM). However, data from randomized clinical trials (RCTs), most notably the Women's Health Initiative (WHI) study, have challenged the cardiovascular benefits and highlighted adverse cardiovascular events with MHT. The discrepancies have been attributed to the design of RCTs, the subjects' advanced age and preexisting CVD, and the form of estrogen used. The discrepancies may also stem from age-related changes in vascular ER amount, distribution, integrity, and post-receptor signaling pathways as well as structural changes in the vasculature. Age-related changes in other sex hormones such as testosterone may also alter the hormonal environment and influence the cardiovascular effects of estrogen. Investigating the chemical properties, structure-activity relationship and pharmacology of natural and synthetic estrogens should improve the effectiveness of conventional MHT. Further characterization of phytoestrogens, selective estrogen-receptor modulators (SERMs), and specific ER agonists may provide substitutes to conventional MHT. Conditions with excess or low estrogen levels such as polycystic ovary syndrome (PCOS) and Turner syndrome may provide insight into the development and regulation of ER and the mechanisms of aberrant estrogen-ER interactions. The lessons learned from previous RCTs have led to more directed studies such as the Kronos Early Estrogen Prevention Study (KEEPS). Careful design of experimental models and RCTs, coupled with the development of specific ER modulators, hold the promise of improving the actions of

  4. Pulsed estrogen therapy prevents post-OVX porcine dura mater microvascular network weakening via a PDGF-BB-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Olga V Glinskii

    Full Text Available In postmenopausal women, estrogen (E2 deficiencies are frequently associated with higher risk of intracranial hemorrhage, increased incidence of stroke, cerebral aneurysm, and decline in cognitive abilities. In younger postpartum women and those using oral contraceptives, perturbations in E2 are associated with higher risk of cerebral venous thrombosis. A number of serious intracranial pathologic conditions linked to E2 deficiencies, such as dural sinus thrombosis, dural fistulae, non-parenchymal intracranial hemorrhages, migraines, and spontaneous cerebrospinal fluid leaks, involve the vessels not of the brain itself, but of the outer fibrous membrane of the brain, the dura mater (DM. The pathogenesis of these disorders remains mysterious and how estrogen regulates structural and functional integrity of DM vasculature is largely unknown. Here, we demonstrate that post ovariectomy (OVX DM vascular remodeling is manifested by microvessel destabilization, capillary rarefaction, increased vascular permeability, and aberrant angio-architecture, and is the result of disrupted E2-regulated PDGF-BB signaling within dura microvasculature. These changes, associated with the reduction in systemic PDGF-BB levels, are not corrected by a flat-dose E2 hormone replacement therapy (HRT, but are largely prevented using HRT schedules mimicking physiological E2 fluctuations. We demonstrate that 1 E2 regulates PDGF-BB production by endothelial cells in a dose-dependent manner and 2 optimization of PDGF-BB levels and induction of robust PDGF-mediated endothelial cell-vascular pericyte interactions require high (estrous E2 concentrations. We conclude that high (estrous levels of E2 are important in controlling PDGF-mediated crosstalk between endothelial cells and pericytes, a fundamental mechanism governing microvessel stability and essential for preserving intracranial homeostasis.

  5. Pulsed Estrogen Therapy Prevents Post-OVX Porcine Dura Mater Microvascular Network Weakening via a PDGF-BB-Dependent Mechanism

    Science.gov (United States)

    Glinskii, Olga V.; Huxley, Virginia H.; Glinskii, Vladimir V.; Rubin, Leona J.; Glinsky, Vladislav V.

    2013-01-01

    In postmenopausal women, estrogen (E2) deficiencies are frequently associated with higher risk of intracranial hemorrhage, increased incidence of stroke, cerebral aneurysm, and decline in cognitive abilities. In younger postpartum women and those using oral contraceptives, perturbations in E2 are associated with higher risk of cerebral venous thrombosis. A number of serious intracranial pathologic conditions linked to E2 deficiencies, such as dural sinus thrombosis, dural fistulae, non-parenchymal intracranial hemorrhages, migraines, and spontaneous cerebrospinal fluid leaks, involve the vessels not of the brain itself, but of the outer fibrous membrane of the brain, the dura mater (DM). The pathogenesis of these disorders remains mysterious and how estrogen regulates structural and functional integrity of DM vasculature is largely unknown. Here, we demonstrate that post ovariectomy (OVX) DM vascular remodeling is manifested by microvessel destabilization, capillary rarefaction, increased vascular permeability, and aberrant angio-architecture, and is the result of disrupted E2-regulated PDGF-BB signaling within dura microvasculature. These changes, associated with the reduction in systemic PDGF-BB levels, are not corrected by a flat-dose E2 hormone replacement therapy (HRT), but are largely prevented using HRT schedules mimicking physiological E2 fluctuations. We demonstrate that 1) E2 regulates PDGF-BB production by endothelial cells in a dose-dependent manner and 2) optimization of PDGF-BB levels and induction of robust PDGF-mediated endothelial cell-vascular pericyte interactions require high (estrous) E2 concentrations. We conclude that high (estrous) levels of E2 are important in controlling PDGF-mediated crosstalk between endothelial cells and pericytes, a fundamental mechanism governing microvessel stability and essential for preserving intracranial homeostasis. PMID:24349391

  6. A dominant negative ERβ splice variant determines the effectiveness of early or late estrogen therapy after ovariectomy in rats.

    Directory of Open Access Journals (Sweden)

    Jun Ming Wang

    Full Text Available The molecular mechanisms for the discrepancy in outcome of initiating estrogen therapy (ET around peri-menopause or several years after menopause in women are unknown. We hypothesize that the level of expression of a dominant negative estrogen receptor (ER β variant, ERβ2, may be a key factor determining the effectiveness of ET in post-menopausal women. We tested this hypothesis in ovariectomized nine month-old (an age when irregular estrous cycles occur female Sprague Dawley rats. Estradiol treatment was initiated either 6 days (Early ET, analogous to 4 months post-menopause in humans, or 180 days (Late ET, analogous to 11 years post-menopause in humans after ovariectomy. Although ERβ2 expression increased in all OVX rats, neurogenic and neuroprotective responses to estradiol differed in Early and Late ET. Early ET reduced ERβ2 expression in both hippocampus and white blood cells, increased the hippocampal cell proliferation as assessed by Ki-67 expression, and improved mobility in the forced swim test. Late ET resulted in either no or modest effects on these parameters. There was a close correlation between the degree of ERβ2 expression and the preservation of neural effects by ET after OVX in rats, supporting the hypothesis that persistent elevated levels of ERβ2 are a molecular basis for the diminished effectiveness of ET in late post-menopausal women. The correlation between the expression of ERβ2 in circulating white blood cells and brain cells suggests that ERβ2 expression in peripheral blood cells may be an easily accessible marker to predict the effective window for ET in the brain.

  7. Exercise, Eating, Estrogen, and Osteoporosis.

    Science.gov (United States)

    Brown, Jim

    1986-01-01

    Osteoporosis affects millions of people, especially women. Three methods for preventing or managing osteoporosis are recommended: (1) exercise; (2) increased calcium intake; and (3) estrogen replacement therapy. (CB)

  8. Estrogen and Bazedoxifene

    Science.gov (United States)

    ... frequent and stop and women may experience other symptoms and body changes). Estrogen and bazedoxifene tablets are also used to prevent osteoporosis (condition in which the bones become thin and ...

  9. Prevention and early detection of prostate cancer

    NARCIS (Netherlands)

    J. Cuzick (Jack); M.A. Thorat (Mangesh A); G. Andriole (Gerald); O.W. Brawley (Otis W); P.H. Brown (Powel H); Z. Culig (Zoran); R. Eeles (Rosalind); L.G. Ford (Leslie G); F. Hamdy (Freddie); L. Holmberg (Lars); D. Ilic (Dragan); T.J. Key (Timothy J); C.L. Vecchia (Carlo La); H. Lilja (Hans); M. Marberger (Michael); F.L. Meyskens (Frank L); L.M. Minasian (Lori M); C. Parker (C.); H.L. Parnes (Howard L); S. Perner (Sven); H. Rittenhouse (Harry); J.A. Schalken (J.); H.-P. Schmid (Hans-Peter); B.J. Schmitz-Dräger (Bernd J); F.H. Schröder (Fritz); A. Stenzl (Arnulf); B. Tombal (Bertrand); T.J. Wilt (Timothy J.); K. Wolk (Kerstin)

    2014-01-01

    textabstractProstate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by pr

  10. Prevention and early detection of prostate cancer

    NARCIS (Netherlands)

    J. Cuzick (Jack); M.A. Thorat (Mangesh A); G. Andriole (Gerald); O.W. Brawley (Otis W); P.H. Brown (Powel H); Z. Culig (Zoran); R. Eeles (Rosalind); L.G. Ford (Leslie G); F. Hamdy (Freddie); L. Holmberg (Lars); D. Ilic (Dragan); T.J. Key (Timothy J); C.L. Vecchia (Carlo La); H. Lilja (Hans); M. Marberger (Michael); F.L. Meyskens (Frank L); L.M. Minasian (Lori M); C. Parker (C.); H.L. Parnes (Howard L); S. Perner (Sven); H. Rittenhouse (Harry); J.A. Schalken (J.); H.-P. Schmid (Hans-Peter); B.J. Schmitz-Dräger (Bernd J); F.H. Schröder (Fritz); A. Stenzl (Arnulf); B. Tombal (Bertrand); T.J. Wilt (Timothy J.); K. Wolk (Kerstin)

    2014-01-01

    textabstractProstate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by pr

  11. Bullying Prevention Strategies in Early Childhood Education

    Science.gov (United States)

    Saracho, Olivia N.

    2017-01-01

    Bullying is a serious problem that affects the young children's well being. Early childhood educators find it difficult to manage bullying in the classroom. Preschool is the first environment outside of the home setting where children encounter difficulties when they socially interact with their peers. Based on the principles of protecting and…

  12. Severe malformations of eelpout (Zoarces viviparus) fry are induced by maternal estrogenic exposure during early embryogenesis.

    Science.gov (United States)

    Morthorst, Jane E; Korsgaard, Bodil; Bjerregaard, Poul

    2016-02-01

    Pregnant eelpout were exposed via the water to known endocrine disrupting compounds (EDCs) to clarify if EDCs could be causing the increased eelpout fry malformation frequencies observed in coastal areas receiving high anthropogenic input. The presence of a teratogenic window for estrogen-induced malformations was also investigated by starting the exposure at different times during eelpout pregnancy. Both 17α-ethinylestradiol (EE2) (17.8 ng/L) and pyrene (0.5 μg/L) significantly increased fry malformation frequency whereas 4-t-octylphenol (4-t-OP) up to 14.3 μg/L did not. Vitellogenin was significantly induced by EE2 (5.7 and 17.8 ng/L) but not by 4-t-OP and pyrene. A critical period for estrogen-induced fry malformations was identified and closed between 14 and 22 days post fertilization (dpf). Exposure to 17β-estradiol (E2) between 0 and 14 dpf caused severe malformations and severity increased the closer exposure start was to fertilization, whereas malformations were absent by exposure starting later than 14 dpf. Data on ovarian fluid volume and larval length supported the suggested teratogenic window. Larval mortality also increased when exposure started right after fertilization.

  13. Alendronate and estrogen-progestin in the long-term prevention of bone loss

    DEFF Research Database (Denmark)

    Ravn, Pernille; Bidstrup, M; Wasnich, R D

    1999-01-01

    BACKGROUND: Up to 3 years of treatment with alendronate, 5 mg/d, prevents postmenopausal bone loss. OBJECTIVE: To determine whether the effect of alendronate is sustained at 4 years of treatment and persists after treatment is discontinued. DESIGN: Randomized, controlled trial. SETTING: United St...... alendronate therapy was stopped; however, continuous alendronate treatment was more effective in preventing postmenopausal bone loss than 2 years of alendronate followed by 2 years of placebo....

  14. ROCK inhibition prevents early mouse embryo development.

    Science.gov (United States)

    Duan, Xing; Chen, Kun-Lin; Zhang, Yu; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2014-08-01

    ROCK is a Rho-GTPase effector that is important for actin assembly and is involved in various cellular functions, including cell contraction, migration, motility, and tumor cell invasion. In this study, we investigated ROCK expression and function during early mouse embryo development. Inhibiting ROCK by Y-27632 treatment at the zygote stage resulted in first cleavage failure, and most embryos failed to develop to the 8-cell stage. When adding Y-27632 at the 8-cell stage, embryos failed to undergo compaction and could not develop into blastocysts. In addition, fluorescence staining intensity analysis indicated that actin expression at blastomere membranes was significantly reduced. After ROCK inhibition, two or more nuclei were observed in a cell, which indicated possible cytokinesis failure. Moreover, after ROCK inhibition with Y-27632, the phosphorylation levels of LIMK1/2, a downstream molecule of ROCK, were decreased at blastomere membranes. Thus, our results showed conserved roles for ROCK in this mammalian embryo model and indicated that a ROCK-LIMK1/2-actin pathway might regulate cleavage and blastocyst formation during early mouse embryo development.

  15. The effect of grape seed extract on estrogen levels of postmenopausal women: a pilot study.

    Science.gov (United States)

    Wahner-Roedler, Dietlind L; Bauer, Brent A; Loehrer, Laura L; Cha, Stephen S; Hoskin, Tanya L; Olson, Janet E

    2014-06-01

    The role of estrogens in breast cancer (BC) development is widely accepted, leading to the development of selective estrogen receptor modulators and aromatase inhibitors for BC treatment and prevention. However, because of potential adverse effects, healthy women with high risk of BC are hesitant to take them. Preliminary evidence from animal studies shows that grapes may have an aromatase-inhibiting effect, decreasing estrogen synthesis and increasing androgen precursors. We conducted a randomized, double-blind, dose-finding early-phase trial on the effect of grape seed extract (GSE) on estrogen levels. Postmenopausal women who met study inclusion criteria (N = 46) were randomly assigned to daily GSE at a dose of 200, 400, 600, or 800 mg for 12 weeks. Primary outcome was change in plasma levels of estrogen conjugates from baseline to 12 weeks posttreatment. Thirty-nine participants (84.8%) completed the study. GSE in the 4 daily doses did not significantly decrease estrogen or increase androgen precursors.

  16. Preventing urinary tract infections in early childhood.

    Science.gov (United States)

    Williams, Gabrielle J; Craig, Jonathan C; Carapetis, Jonathan R

    2013-01-01

    Urinary tract infection (UTI) is common in children, causes them considerable discomfort, as well as distress to parents and has a tendency to recur. Approximately 20% of those children who experience one infection will have a repeat episode. Since 1975, 11 trials of long-term antibiotics compared with placebo or no treatment in 1,550 children have been published. Results have been heterogeneous, but the largest trial demonstrated a small reduction (6% absolute risk reduction, risk ratio 0.65) in the risk of repeat symptomatic UTI over 12 months of treatment. This effect was consistent across sub groups of children based upon age, gender, vesicoureteric reflux status and number of prior infections. Trials involving re-implantation surgery (and antibiotics compared with antibiotics alone) for the sub-group of children with vesicoureteric reflux have not shown a reduction in repeat UTI, with the possible exception of a very small benefit for febrile UTI. Systematic reviews have shown that circumcision reduces the risk of repeat infection but 111 circumcisions would need to be performed to prevent one UTI in unpredisposed boys. Given the need for anaesthesia and the risk of surgical complication, net clinical benefit is probably restricted to those who are predisposed (such as those with recurrent infection). Many small trials in complementary therapies have been published and many suggest some benefit, however inclusion of children is limited. Only three trials involving 394 children for cranberry products, two trials with a total of 252 children for probiotics and one trial with 24 children for vitamin A are published. Estimates of efficacy vary widely and imprecision is evident. Multiple interventions to prevent UTI in children exist. Of those, long-term low dose antibiotics has the strongest evidence base, but the benefit is small. Circumcision in boys reduces the risk substantially, but should be restricted to those at risk. There is little evidence of benefit of

  17. Strategies for the prevention and treatment of osteoporosis during early postmenopause.

    Science.gov (United States)

    Delaney, Miriam F

    2006-02-01

    During the perimenopause, both the quantity and quality of bone decline rapidly, resulting in a dramatic increase in the risk of fracture in postmenopausal women. Although many factors are known to be associated with osteoporotic fractures, measures to identify and treat women at risk are underused in clinical practice. Consequently, osteoporosis is frequently not detected until a fracture occurs. Identification of postmenopausal women at high risk of fracture therefore is a priority and is especially important for women in early postmenopause who can benefit from early intervention to maintain or to increase bone mass and, thus, reduce the risk of fracture. Most authorities recommend risk-factor assessment for all postmenopausal women, followed by bone mineral density measurements for women at highest risk (ie, all women aged > or =65 years, postmenopausal women aged or =1 additional risk factors for osteoporosis, and postmenopausal women with fragility fractures). All postmenopausal women can benefit from nonpharmacologic interventions to reduce the risk of fracture, including a balanced diet with adequate intake of calcium and vitamin D, regular exercise, measures to prevent falls or to minimize their impact, smoking cessation, and moderation of alcohol intake. Several pharmacologic agents, including the bisphosphonates (eg, alendronate, risedronate, and ibandronate) and the selective estrogen receptor modulator, raloxifene, have been shown to increase bone mass, to reduce fracture risk, and to have acceptable side-effect profiles. Women who have discontinued hormone therapy are in particular need of monitoring for fracture risk, in light of the accelerated bone loss and increased risk of fracture that occurs after withdrawal of estrogen treatment.

  18. Clinicopathological factors predicting early and late distant recurrence in estrogen receptor-positive, HER2-negative breast cancer.

    Science.gov (United States)

    Yamashita, Hiroko; Ogiya, Akiko; Shien, Tadahiko; Horimoto, Yoshiya; Masuda, Norikazu; Inao, Touko; Osako, Tomofumi; Takahashi, Masato; Endo, Yumi; Hosoda, Mitsuchika; Ishida, Naoko; Horii, Rie; Yamazaki, Kieko; Miyoshi, Yuichiro; Yasojima, Hiroyuki; Tomioka, Nobumoto

    2016-11-01

    Most studies analyzing prognostic factors for late relapse have been performed in postmenopausal women who received tamoxifen or aromatase inhibitors as adjuvant endocrine therapy for estrogen receptor (ER)-positive breast cancer. A total of 223 patients (108 premenopausal and 115 postmenopausal) with early distant recurrence and 149 patients (62 premenopausal and 87 postmenopausal) with late distant recurrence of ER-positive, HER2-negative breast cancer who were given their initial treatment between 2000 and 2004 were registered from nine institutions. For each late recurrence patient, approximately two matched control patients without relapse for more than 10 years were selected. Clinicopathological factors and adjuvant therapies were compared among the three groups by menopausal status and age. Factors predicting early recurrence in premenopausal women were large tumor size, high lymph node category and high tumor grade, whereas predictors for late recurrence were large tumor size and high lymph node category. In postmenopausal women under 60 years of age, factors predicting early recurrence were bilateral breast cancer, large tumor size, high lymph node category, low PgR expression and high Ki67 labeling index (LI), while predictors for late recurrence were large tumor size and high lymph node category. On the other hand, in postmenopausal women aged 60 years or older, factors predicting early recurrence were bilateral breast cancer, large tumor size, high lymph node category, high tumor grade, low ER expression and high Ki67 LI, whereas predictors for late recurrence were high lymph node category, low ER expression and short duration of adjuvant endocrine therapy. Predictors of early and late distant recurrence might differ according to menopausal status and age.

  19. Effects of alachlor on the early development and induction of estrogen-responsive genes in Medaka, Oryzias latipes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C.; Ryu, J.; Park, S.Y.; Choi, K.; Jeon, S.H.; Na, J.G.; Rhee, D.G. [National Inst. of Environmental Research, Incheon (Korea)

    2004-09-15

    Alachlor is an acetanilide herbicide used to control annual grasses and weeds in field corn, soybeans, and peanuts. It is a selective systemic herbicide, absorbed by germinating shoots and by roots. Although the specific pathways are not exactly understood, the acetanilide herbicides apparently interfere with several physiological processes including biosynthesis of lipids, proteins and flavonoids. These herbicides are widely used in agriculture and are commonly detected in surface water and groundwater. Alachlor has a relatively low acute toxicity, however, repeated exposure has been reported to cause hepatotoxicity, irreversible uveal degeneration and tumour formation in some animals. Besides alachlor is one of the herbicides reported to have endocrine disrupting effects. 2,4-D, 2,4,5-T, amitrole and atrazine also belong to these types of herbicides. Alachlor is a strongly suspected endocrine disruptor in that it is listed by EPA and the World Wildlife Fund [WWF] as a potential endocrine disrupting chemical. Many mammalian and aquatic toxicological studies with alachlor were performed under the conditions of acute, subacute and chronic experiment. However, not many studies using fish have been carried out with the purpose of screening and testing of endocrine disrupting effects of alachlor. The purpose of this study was to determine the effects of alachlor on the early morphological development of medaka (Oryzias latipes). Embryonic growth, deformation and hatching success were determined to see the effects of this chemical. Also, we tried to measure the estrogenic activity of alachlor using the ELISA and RT-PCR methods. By using these techniques, we evaluated the induction of the estrogen-responsive genes, vitellogenin (precursor of yolk protein) and choriogenin (precursor of egg envelope protein) in male medaka exposed to alachlor.

  20. Selective Activation of Estrogen Receptor α Activation Function-1 Is Sufficient to Prevent Obesity, Steatosis, and Insulin Resistance in Mouse.

    Science.gov (United States)

    Guillaume, Maeva; Handgraaf, Sandra; Fabre, Aurélie; Raymond-Letron, Isabelle; Riant, Elodie; Montagner, Alexandra; Vinel, Alexia; Buscato, Melissa; Smirnova, Natalia; Fontaine, Coralie; Guillou, Hervé; Arnal, Jean-François; Gourdy, Pierre

    2017-06-01

    Estrogen receptor α (ERα) regulates gene transcription through two activation functions (ERα-AF1 and ERα-AF2). We recently found that the protection conferred by 17β-estradiol against obesity and insulin resistance requires ERα-AF2 but not ERα-AF1. However, the interplay between the two ERα-AFs is poorly understood in vivo and the metabolic influence of a specific ERα-AF1 action remains to be explored. To this end, wild-type, ERα-deficient, or ERα-AF1-deficient ovariectomized female mice were fed a high-fat diet and concomitantly administered with vehicle or tamoxifen, a selective ER modulator that acts as a ERα-AF1 agonist/ERα-AF2 antagonist. In ovariectomized wild-type mice, tamoxifen significantly reduced food intake and totally prevented adiposity, insulin resistance, and steatosis. These effects were abolished in ERα-deficient and ERα-AF1-deficient mice, revealing the specific role of ERα-AF1 activation. Finally, hepatic gene expression changes elicited by tamoxifen in wild-type mice were abrogated in ERα-AF1-deficient mice. The combination of pharmacologic and transgenic approaches thus indicates that selective ERα-AF1 activation by tamoxifen is sufficient to elicit metabolic protection, contrasting with the specific requirement of ERα-AF2 in the metabolic actions of 17β-estradiol. This redundancy in the ability of the two ERα-AFs to separately mediate metabolic prevention strikingly contrasts with the contribution of both ERα-AFs in breast cancer proliferation, shedding new light on the therapeutic potential of selective ER modulation. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Early membrane initiated transcriptional effects of estrogens in breast cancer cells: First pharmacological evidence for a novel membrane estrogen receptor element (ERx).

    Science.gov (United States)

    Kampa, Marilena; Notas, George; Pelekanou, Vassiliki; Troullinaki, Maria; Andrianaki, Maria; Azariadis, Kalliopi; Kampouri, Errika; Lavrentaki, Katerina; Castanas, Elias

    2012-08-01

    The complexity of estrogen actions mainly relies to the presence of different identified receptors (ERα, ERβ, their isoforms, and GPR30/GPER) and their discrete cellular distribution. Depending on the localization of the receptor that mediates estrogen effects, nuclear and extra-nuclear actions have been described. The latter can trigger a number of signaling events leading also to transcriptional modifications. In an attempt to clarify the nature of the receptor(s) involved in the membrane initiated effect of estrogens on gene expression, we performed a whole transcriptome analysis of breast cancer cell lines with different receptor profiles (T47D, MCF7, MDA-MB-231, SK-BR-3). A pharmacological approach was conducted with the use of estradiol (E(2)) or membrane-impermeable E(2)-BSA in the absence or presence of a specific ERα-β or GPR30/GPER antagonist. Our results clearly show that in addition to the ERα isoforms and/or GPR30/GPER that mainly mediate the transcriptional effect of E(2)-BSA, there is a specific transcriptional signature (found in T47D and MCF-7 cells) suggesting the presence of an unidentified membrane ER element (ERx). Analysis of its signature and phenotypic verification revealed that important cell function such as apoptosis, transcriptional regulation, and growth factor signaling are associated with ERx. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Estrogen Injection

    Science.gov (United States)

    The estradiol cypionate and estradiol valerate forms of estrogen injection are used to treat hot flushes (hot ... should consider a different treatment. These forms of estrogen injection are also sometimes used to treat the ...

  3. Acute respiratory distress syndrome: prevention and early recognition.

    Science.gov (United States)

    de Haro, Candelaria; Martin-Loeches, Ignacio; Torrents, Eva; Artigas, Antonio

    2013-04-24

    Acute respiratory distress syndrome (ARDS) is common in critically ill patients admitted to intensive care units (ICU). ARDS results in increased use of critical care resources and healthcare costs, yet the overall mortality associated with these conditions remains high. Research focusing on preventing ARDS and identifying patients at risk of developing ARDS is necessary to develop strategies to alter the clinical course and progression of the disease. To date, few strategies have shown clear benefits. One of the most important obstacles to preventive interventions is the difficulty of identifying patients likely to develop ARDS. Identifying patients at risk and implementing prevention strategies in this group are key factors in preventing ARDS. This review will discuss early identification of at-risk patients and the current prevention strategies.

  4. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    Science.gov (United States)

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Preventing Poor Vocational Functioning in Psychosis Through Early Intervention.

    Science.gov (United States)

    Hegelstad, Wenche Ten Velden; Bronnick, Kolbjorn S; Barder, Helene Eidsmo; Evensen, Julie Horgen; Haahr, Ulrik; Joa, Inge; Johannessen, Jan Olav; Langeveld, Johannes; Larsen, Tor Ketil; Melle, Ingrid; Opjordsmoen, Stein; Rund, Bjørn Rishovd; Rossberg, Jan Ivar; Simonsen, Erik; Vaglum, Per Wiggen; McGlashan, Thomas H; Friis, Svein

    2017-01-01

    This study tested the hypothesis that early detection of psychosis improves long-term vocational functioning through the prevention of negative symptom development. Generalized estimating equations and mediation analysis were conducted to examine the association between employment and negative symptoms over ten years among patients in geographic areas characterized by usual detection (N=140) or early detection (N=141) of psychosis. Improved vocational outcome after ten years among patients in the early-detection area was mediated by lower levels of negative symptoms during the first five years. Regardless of symptoms, rates of full-time employment or study were lower among patients in the usual-detection versus the early-detection area. Patients from an early-detection area attained lower negative symptom levels earlier compared with patients from a usual-detection area, which seemed to have facilitated vocational careers.

  6. A Cognitive Behavioral Depression Prevention Program for Early Adolescents

    Science.gov (United States)

    Miloseva, Lence

    2013-01-01

    The aim of this study was to present results of our one year experience with Cognitive Behavioral Psychology Program, in order to contribute to the building of whole school approach and positive psychology preventive mental health problems model. Based on Penn Resilience program (PRP), we modify and create program for early adolescents: how to…

  7. Selective Prevention Approaches to Build Protective Factors in Early Intervention

    Science.gov (United States)

    Shapiro, Cheri J.

    2014-01-01

    Young children with disabilities may be at elevated risk for behavior problems as well as maltreatment. preventive approaches that can be infused into early intervention services are needed to support parents, build competencies among young children, and enhance protective factors that may temper risk. Two interventions--Stepping Stones Triple P,…

  8. Bazedoxifene and conjugated estrogen prevent diet-induced obesity, hepatic steatosis, and type 2 diabetes in mice without impacting the reproductive tract.

    Science.gov (United States)

    Barrera, Jose; Chambliss, Ken L; Ahmed, Mohamed; Tanigaki, Keiji; Thompson, Bonne; McDonald, Jeffrey G; Mineo, Chieko; Shaul, Philip W

    2014-08-01

    Despite the capacity of estrogens to favorably regulate body composition and glucose homeostasis, their use to combat obesity and type 2 diabetes is not feasible, because they promote sex steroid-responsive cancers. The novel selective estrogen receptor modulator (SERM) bazedoxifene acetate (BZA) uniquely antagonizes both breast cancer development and estrogen-related changes in the female reproductive tract. How BZA administered with conjugated estrogen (CE) or alone impacts metabolism is unknown. The effects of BZA or CE + BZA on body composition and glucose homeostasis were determined in ovariectomized female mice fed a Western diet for 10-12 wk. In contrast to vehicle, estradiol (E₂), CE, BZA, and CE + BZA equally prevented body weight gain by 50%. In parallel, all treatments caused equal attenuation of the increase in body fat mass invoked by the diet as well as the increases in subcutaneous and visceral white adipose tissue. Diet-induced hepatic steatosis was attenuated by E₂ or CE, and BZA alone or with CE provided even greater steatosis prevention; all interventions improved pyruvate tolerance tests. Glucose tolerance tests and HOMA-IR were improved by E₂, CE, and CE + BZA. Whereas E₂ or CE alone invoked a uterotrophic response, BZA alone or CE + BZA had negligible impact on the uterus. Thus, CE + BZA affords protection from diet-induced adiposity, hepatic steatosis, and insulin resistance with minimal impact on the female reproductive tract in mice. These combined agents may provide a valuable new means to favorably regulate body composition and glucose homeostasis and combat fatty liver.

  9. Environmental Estrogens and Obesity

    Science.gov (United States)

    Newbold, Retha R.; Padilla-Banks, Elizabeth; Jefferson, Wendy N.

    2009-01-01

    Many chemicals in the environment, in particular those with estrogenic activity, can disrupt the programming of endocrine signaling pathways that are established during development and result in adverse consequences that may not be apparent until much later in life. Most recently, obesity and diabetes join the growing list of adverse consequences that have been associated with developmental exposure to environmental estrogens during critical stages of differentiation. These diseases are quickly becoming significant public health issues and are fast reaching epidemic proportions worldwide. In this review, we summarize the literature from experimental animal studies documenting an association of environmental estrogens and the development of obesity, and further describe an animal model of exposure to diethylstilbestrol (DES) that has proven useful in studying mechanisms involved in abnormal programming of various differentiating estrogen- target tissues. Other examples of environmental estrogens including the phytoestrogen genistein and the environmental contaminant Bisphenol A are also discussed. Together, these data suggest new targets (i.e., adipocyte differentiation and molecular mechanisms involved in weight homeostasis) for abnormal programming by estrogenic chemicals, and provide evidence that support the scientific hypothesis termed “the developmental origins of adult disease”. The proposal of an association of environmental estrogens with obesity and diabetes expands the focus on the diseases from intervention/treatment to include prevention/avoidance of chemical modifiers especially during critical windows of development. PMID:19433252

  10. Increase in estrogen signaling in the early brain of orange-spotted grouper Epinephelus coioides: a mini-review.

    Science.gov (United States)

    Nagarajan, Ganesan; Aruna, Adimoolam; Chang, Ching-Fong

    2013-02-01

    Despite neurosteroidogenic enzymes are playing important roles in the regulation of brain development and function, the potential link between brain and gonad by the action of steroid hormones during gonadal sex differentiation is still not clear in teleosts. In this mini-review, we summarized our understanding on the early brain development related to the synthesis of neurosteroids and receptor signaling during gonadal sex differentiation in protogynous orange-spotted grouper, Epinephelus coioides (functional females for the first 6 years of life and start to sex change around the age of 7 years) and protandrous black porgy (functional males for the first 2 years of life but begin to change sex during the third year). We found a similar profile in the increased expression of brain aromatase gene (aromatatse B or cyp19a1b), aromatase activity, estradiol (E(2)), and estrogen signaling in the brain of both grouper and black porgy fish during gonadal sex differentiation. In contrast to mammals, teleost fish Cyp19a1b expressed in a unique cell type, a radial glial cell, which is acted as progenitors in the brain of developing and adult fish. In agreement with these pioneer studies, we demonstrated that the grouper cyp19a1b/Cyp19a1b was expressed in radial glial cells. Further, in vivo data in the grouper brain showed that exogenous E(2) upregulated Cyp19a1b immunoreactivity (ir) in radial glial cells. These data suggest the possible roles of Cyp19a1b and E(2) in early brain development which is presumably related to gonadal sex differentiation.

  11. A Suppressive Antagonism Evidences Progesterone and Estrogen Receptor Pathway Interaction with Concomitant Regulation of Hand2, Bmp2 and ERK during Early Decidualization.

    Directory of Open Access Journals (Sweden)

    Ana C Mestre-Citrinovitz

    Full Text Available Progesterone receptor and estrogen receptor participate in growth and differentiation of the different rat decidual regions. Steroid hormone receptor antagonists were used to study steroid regulation of decidualization. Here we describe a suppressive interaction between progesterone receptor (onapristone and estrogen receptor (ICI182780 antagonists and their relation to a rescue phenomenon with concomitant regulation of Hand2, Bmp2 and p-ERK1/2 during the early decidualization steps. Phenotypes of decidua development produced by antagonist treatments were characterized by morphology, proliferation, differentiation, angiogenesis and expression of signaling molecules. We found that suppression of progesterone receptor activity by onapristone treatment resulted in resorption of the implantation sites with concomitant decrease in progesterone and estrogen receptors, PCNA, KI67 antigen, DESMIN, CCND3, CX43, Prl8a2, and signaling players such as transcription factor Hand2, Bmp2 mRNAs and p-ERK1/2. Moreover, FGF-2 and Vegfa increased as a consequence of onapristone treatment. Implantation sites from antagonist of estrogen receptor treated rats developed all decidual regions, but showed an anomalous blood vessel formation at the mesometrial part of the decidua. The deleterious effect of onapristone was partially counteracted by the impairment of estrogen receptor activity with rescue of expression levels of hormone steroid receptors, proliferation and differentiation markers, and the induction of a probably compensatory increase in signaling molecules Hand2, Bmp2 and ERK1/2 activation compared to oil treated controls. This novel drug interaction during decidualization could be applied to pathological endometrial cell proliferation processes to improve therapies using steroid hormone receptor targets.

  12. Prevention and early intervention for depression in adolescence and early adult life.

    Science.gov (United States)

    Harrington, R; Clark, A

    1998-01-01

    Over the past decade there has been increasing interest in the possibility that early intervention might prevent mental disorders later in life. Indeed, in the United Kingdom the Department of Health recommends that health promotion should be one of the main functions of child mental health services, a suggestion that has been endorsed by professional bodies. It is easy to see why both purchasers and providers of mental health services would be interested in prevention, but will preventive interventions work in practice? This paper discusses the possibility of preventing depressive disorder in late adolescence and early adult life by intervening in childhood and early adolescence. The paper begins with a description of the phenomenology of depression and its risk factors. It then goes on to describe a framework of prevention and within this framework explores whether there is an adequate knowledge base. The general perspective that is presented is one of cautious scepticism. It is argued that difficulties in defining depression and identifying risk factors that can easily be remedied make it unlikely that within the foreseeable future primary prevention programmes will prove to be more effective than treatment and rehabilitation of affected individuals. The possibility that preventive programmes could do harm will also be discussed. The paper concludes with some proposals about appropriate targets for prevention. It is suggested that apart from a few policy areas where there are some relatively harmless measures that could protect from later depression, a balanced preventive programme will give higher priority to treatment services than to those concerned with early intervention.

  13. Kidney diseases in children - early diagnosis and prevention.

    Science.gov (United States)

    Polenakovic, Momir; Gucev, Zoran; Tasic, Velibor

    2016-01-01

    Pediatric kidney diseases were in the focus of the World Kidney Day 2016. Macedonian pediatric nephrologists gave their contribution with public appearance in kindergartens, primary and secondary schools, with interactive lectures and discussion with the youngest about the kidney function, healthy life style and simple measures to prevent kidney and urinary tract diseases. Besides promotive appearance in the media, series of lectures were presented in front of the health professionals. The aim was to attract the attention of the professionals for early diagnosis and prevention of kidney disease. The action starts in utero, followed by early postnatal imaging and assessment, conservative treatment and in selected cases surgical treatment. The emphasis is on the multidisciplinary and comprehensive approach to children and adolescents with kidney diseases.

  14. Early causes of child obesity and implications for prevention

    OpenAIRE

    Cole, T J

    2007-01-01

    Child obesity is becoming a serious public health concern, and major research effort is being devoted both to understand its aetiology and to improve the effectiveness of prevention strategies. Early growth patterns, both prenatally and postnatally, are emerging as important markers of later obesity risk, with rapid neonatal weight gain a clear risk factor for later obesity and metabolic syndrome. Thus, in two distinct senses child obesity is a growing problem. The paper summarises current ev...

  15. The Relationship between Periodontopathy and Estrogen

    Institute of Scientific and Technical Information of China (English)

    YAN Shiguang; LI Dexiang

    2002-01-01

    Objecitve To discuss the relationship between peridontopathy and estrogen. Method We discussed the relationship between periodontopathy and increasing of estrogen, the relationship between peridontopoathy and deficiency of estrogen and the relationship between osteoprotegerin in osteoblasts and estrogen. Results When estrogen increased or decreased abnormally, osteoporosis could occur, which induced alveolar ridge resorption and alveolar bone atrophy. Then the teeth exfoliated.Teeth uncleanness facilitated periodontopathy. Conclusion No matter how young or old, keeping the relative balance of estrogen can protect gingiva and alveolar bone. At the same time, keeping teeth clean is also essential to prevent periodontopathy.

  16. Breast cancer risk accumulation starts earlyPrevention must also

    Science.gov (United States)

    Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S.

    2014-01-01

    Purpose Nearly 1 in 4 breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. Methods Literature review Results Exposures during childhood and adolescence affect a woman’s long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors are related to breast cancer risk and risk of premalignant proliferative benign lesions. Conclusion Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention. PMID:24820413

  17. Effect of Mifepristone and Anordrin Compound on Lev-els of Estrogen and Progesterone Receptor mRNAs in Human Decidua of Early Pregnancy

    Institute of Scientific and Technical Information of China (English)

    张翔; 孙志达; 沈维雄; 江德琦; 朱月华; 王寒正; 金力

    2000-01-01

    Objective To provide the theoretical fundation for the further clinical application of mifepristone and anordrin compound.Materials & Methods Ribonuclease protection assay was used for the detection and quantitation of estrogen and progesterone receptor mRNAs in human decidua from the termination of early pregnancy. Three groups, each of which had 6~8 cases, were studied.Results Compared to the normal control group, estrogen and progesterone receptor mRNAs increased significantly (P <0. 05) in the mifepristone group, whereas the changes in the group administrated mifepristone compound which contains anordrin were not obvious.Conclusions The result suggests that with the similar clinical effect, mifepristone compound has less side effect on the patients, thus being more suitable for the anti-ear-ly pregnancy drug.

  18. Effect of Mifepristone and Anordrin Compound on Levels of Estrogen and Progesterone Receptor mRNAs in Human Decidua of Early Pregnancy

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To provide the theoretical fundation for the further clinical application of mi fepristone and anordrin compound. Materials & Methods Ribonuclease protection assay was used for the detection and quantitation of estrogen and progesterone receptor mRNAs in human decidua from the termination of early pregnancy. Three groups, each of which had 6~8 cases, were studied. Results Compared to the normal control group, estrogen and progesterone receptor mRNAs increased significantly (P<0.05) in the mifepristone group, whereas the changes in the group administrated mifepristone compound which contains anordrin were not obvious. Conclusions The result suggests that with the similar clinical effect, mifepristone compound has less side effect on the patients, thus being more suitable for the anti-ear ly pregnancy drug.

  19. [Integrated risk profiling allows prevention and early intervention].

    Science.gov (United States)

    Stegeman, Inge; Kraaijenhagen, Roderik A; Bossuyt, Patrick M M

    2010-01-01

    Prevention and early intervention can alter the course and incidence of several chronic diseases. Integrated risk profiling is based on the fact that a single risk factor affects more than one condition. Integrated risk profiling uses these overlapping risk factors to calculate the risks of a number of conditions. When used in screening, these risks can be communicated to participants, providing feedback and helping them understand the conditions they are at risk of, eventually leading to better compliance with preventive and therapeutic interventions. In this paper we discuss the underlying principles and background of the rise in integrated risk profiling in public health. We demonstrate why the attractive concept of risk profiling needs further assessment to estimate its effectiveness relative to other methods of prevention, population screening and case finding.

  20. Menopause and mitochondria: windows into estrogen effects on Alzheimer's disease risk and therapy.

    Science.gov (United States)

    Henderson, Victor W; Brinton, Roberta Diaz

    2010-01-01

    Metabolic derangements and oxidative stress are early events in Alzheimer's disease pathogenesis. Multi-faceted effects of estrogens include improved cerebral metabolic profile and reduced oxidative stress through actions on mitochondria, suggesting that a woman's endogenous and exogenous estrogen exposures during midlife and in the late post-menopause might favourably influence Alzheimer risk and symptoms. This prediction finds partial support in the clinical literature. As expected, early menopause induced by oophorectomy may increase cognitive vulnerability; however, there is no clear link between age at menopause and Alzheimer risk in other settings, or between natural menopause and memory loss. Further, among older post-menopausal women, initiating estrogen-containing hormone therapy increases dementia risk and probably does not improve Alzheimer's disease symptoms. As suggested by the 'critical window' or 'healthy cell' hypothesis, better outcomes might be expected from earlier estrogen exposures. Some observational results imply that effects of hormone therapy on Alzheimer risk are indeed modified by age at initiation, temporal proximity to menopause, or a woman's health. However, potential methodological biases warrant caution in interpreting observational findings. Anticipated results from large, ongoing clinical trials [Early Versus Late Intervention Trial with Estradiol (ELITE), Kronos Early Estrogen Prevention Study (KEEPS)] will help settle whether midlife estrogen therapy improves midlife cognitive skills but not whether midlife estrogen exposures modify late-life Alzheimer risk. Estrogen effects on mitochondria adumbrate the potential relevance of estrogens to Alzheimer's disease. However, laboratory models are inexact embodiments of Alzheimer pathogenesis and progression, making it difficult to surmise net effects of estrogen exposures. Research needs include better predictors of adverse cognitive outcomes, biomarkers for risks associated with

  1. Endometrial caspase 1 and interleukin-18 expression during the estrous cycle and peri-implantation period of porcine pregnancy and response to early exogenous estrogen administration

    Directory of Open Access Journals (Sweden)

    Stein Daniel R

    2010-04-01

    Full Text Available Abstract Background The role for endometrial secretion of cytokines during the establishment of pregnancy in a number of mammals is well established. The current study determined endometrial expression of caspase 1 (CASP1 and interleukin-18 (IL18 during the estrous cycle and early pregnancy, and following early estrogen administration, which induces conceptus loss during early development in pigs. Methods Gilts were hysterectomized on either D 0, 5, 10, 12, 15 and 18 of the estrous cycle, or D 10, 12, 15 or 18 of pregnancy. The abundance of endometrial CASP1 mRNA was unaffected by day of the estrous cycle, however there was a 6 and 10-fold increase in expression on D 15 and 18 of pregnancy. Endometrial expression of IL18 mRNA increased 5-fold between D 10 to 18 in cyclic and pregnant gilts. Total recoverable IL18 in uterine flushings was greater in pregnant compared to cyclic gilts on D 15 and 18. In the second experiment, mated gilts were treated with either corn oil (CO or estrogen (E on D 9 and 10 and hysterectomized on either D 10, 12, 13, 15 or 17 of pregnancy. The current study localizes the presence of CASP1 to the epithelial layer of the endometrium for the first time. Further, a day × treatment interaction was detected for endometrial CASP1 mRNA and protein abundance as E stimulated an earlier increase on D 13 compared to CO gilts. Although IL18 mRNA expression remained unaltered from the E treatment, protein abundance was significantly attenuated on D 15 and 18 in response to E treatment. Conclusions Endometrial expression of CASP1 and IL18 is associated with establishment of pregnancy in pigs. Alteration of CASP1 and IL18 following premature exposure of the uterus to estrogen during early pregnancy may contribute to conceptus loss between Days 15 to 18 of pregnancy.

  2. Fluoride Varnish Efficacy in Preventing Early Childhood Caries

    OpenAIRE

    Weintraub, J.A.; Ramos-Gomez, F; Jue, B.; Shain, S.; Hoover, C I; Featherstone, J.D.B.; Gansky, S.A.

    2006-01-01

    To determine the efficacy of fluoride varnish (5% NaF, Duraphat®, Colgate) added to caregiver counseling to prevent early childhood caries, we conducted a two-year randomized, dental-examiner-masked clinical trial. Initially, 376 caries-free children, from low-income Chinese or Hispanic San Francisco families, were enrolled (mean age ± standard deviation, 1.8 ± 0.6 yrs). All families received counseling, and children were randomized to the following groups: no fluoride varnish, fluoride varni...

  3. Early detection of occult atrial fibrillation and stroke prevention.

    Science.gov (United States)

    Keach, Joseph Walker; Bradley, Steven M; Turakhia, Mintu P; Maddox, Thomas M

    2015-07-01

    Atrial fibrillation (AF) is a very common arrhythmia and significantly increases stroke risk. This risk can be mitigated with oral anticoagulation, but AF is often asymptomatic, or occult, preventing timely detection and treatment. Accordingly, occult AF may cause stroke before it is clinically diagnosed. Currently, guidelines for the early detection and treatment of occult AF are limited. This review addresses recent advancements in occult AF detection methods, identification of populations at high risk for occult AF, the treatment of occult AF with oral anticoagulation, as well as ongoing trials that may answer critically important questions regarding occult AF screening.

  4. Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model.

    Science.gov (United States)

    Zhang, Huaqiu; Xie, Minjie; Schools, Gary P; Feustel, Paul F; Wang, Wei; Lei, Ting; Kimelberg, Harold K; Zhou, Min

    2009-01-09

    Pretreatment of ovarectomized rats with estrogen shows long-term protection via activation of the estrogen receptor (ER). However, it remains unknown whether activation of the ER can provide protection against early neuronal damage when given acutely. We simulated ischemic conditions by applying oxygen and glucose deprived (OGD) solution to acute male rat hippocampal slices and examined the neuronal electrophysiological changes. Pyramidal neurons and interneurons showed a time-dependent membrane potential depolarization and reduction in evoked action potential frequency and amplitude over a 10 to 15 min OGD exposure. These changes were largely suppressed by 10 microM TAM. The TAM effect was neuron-specific as the OGD-induced astrocytic membrane potential depolarization was not altered. The TAM effect was mediated through ER activation because it could be simulated by 17beta-estradiol and was completely inhibited by the ER inhibitor ICI 182, 780, and is therefore an example of TAM's selective estrogen receptor modulator (SERM) action. We further show that TAM's effects on OGD-induced impairment of neuronal excitability was largely due to activation of neuroprotective BK channels, as the TAM effect was markedly attenuated by the BK channel inhibitor paxilline at 10 microM. TAM also significantly reduced the frequency and amplitude of AMPA receptor mediated spontaneous excitatory postsynaptic currents (sEPSCs) in pyramidal neurons which is an early consequence of OGD. Altogether, this study demonstrates that both 17beta-estradiol and TAM attenuate neuronal excitability impairment early on in a simulated ischemia model via ER activation mediated potentiation of BK K(+) channels and reduction in enhanced neuronal AMPA/NMDA receptor-mediated excitotoxicity.

  5. Neonatal Respiratory Distress Syndrome: Early Diagnosis, Prevention, and Treatment

    Directory of Open Access Journals (Sweden)

    S. A. Perepelitsa

    2012-01-01

    Full Text Available to improve treatment results in premature infants with neonatal respiratory distress syndrome (NRDS, by establishing developmental mechanisms and elaborating methods for its early diagnosis, treatment, and prevention. Material and methods. The paper analyzes the results of a clinical observation and laboratory, instrumental, immunological, morphological, and radiological studies of 320 premature neonates at 26—35 weeks gestational age. The following groups of neonates were identified: 1 40 premature neonatal infants without NRDS and with the physiological course of an early neonatal period (a comparison group; 2 190 premature neonates with severe NRDS in whom the efficiency of therapy with exogenous surfactants, such as surfactant BL versus curosurf, was evaluated; 3 90 premature newborn infants who had died from NRDS at its different stages. Results. The poor maternal somatic, obstetric, and gynecological histories in the early periods of the current pregnancy create prerequisites for its termination, favor the development of severe acute gestosis, and cause abnormal placental changes. Each gestational age is marked by certain placental changes that promote impaired uterineplacentalfetal blood flow and premature birth. Alveolar and bronchial epithelial damages, including those ante and intranatally, microcircula tory disorders play a leading role in the tanatogenesis of NRDS. Intranatal hypoxia and amniotic fluid aspiration are one of the important factors contributing to alveolar epithelial damage and NRDS in premature neonates. Exogenous surfactants prevent the development of hyaline membranes and are useful in the normalization of ventilation-perfusion relationships and lung biomechanical properties. Conclusion. This study could improve the diagnosis and treatment of NRDS, which assisted in reducing the duration of mechanical ventilation from 130±7.6 to 65±11.6 hours, the number of complications (the incidence of intragastric

  6. Incidence and prevention of early parturition in sows.

    Science.gov (United States)

    Vanderhaeghe, C; Dewulf, J; Jourquin, J; De Kruif, A; Maes, D

    2011-06-01

    A retrospective study, based on 60,990 farrowing records from 35 commercial herds, was performed to determine the incidence of early parturition (gestation length was 115.4 ± 1.62 d, and early parturition occurred in 10% of all farrowing records. Sows with early parturition had significantly more stillborn piglets and a larger litter size compared to sows with a normal gestation length (114-117 d). Sows with a gestation length gestation length of sows of the altrenogest group (T112 + T113) (115.3 ± 1.23 d) was significantly longer compared to gestation length of the non-treated sows (114.7 ± 1.69d) (p<0.01). Altrenogest treatment had no negative effect on the reproductive performances of the sows. In conclusion, the administration of altrenogest in late gestation is an effective and safe method to prevent early parturition and can counteract the reproductive losses because of premature farrowing, which may occur in a substantial part of the farrowing events.

  7. Alterations in Circulating miRNA Levels following Early-Stage Estrogen Receptor-Positive Breast Cancer Resection in Post-Menopausal Women

    DEFF Research Database (Denmark)

    Kodahl, Annette R; Zeuthen, Pernille; Binder, Harald

    2014-01-01

    design and the same qPCR profiling platform, resulting in limited agreement. CONCLUSIONS: A panel of 4 circulating miRNAs exhibited significantly altered levels following radical resection of primary ER+ breast cancers in post-menopausal women. These specific miRNAs may be involved in tumorigenesis...... these alterations were also observed in an independent data set. METHODS: Global miRNA analysis was performed on prospectively collected serum samples from 24 post-menopausal women with estrogen receptor-positive early-stage breast cancer before surgery and 3 weeks after tumor resection using global LNA...

  8. Tanshinone IIA Prevents Leu27IGF-II-Induced Cardiomyocyte Hypertrophy Mediated by Estrogen Receptor and Subsequent Akt Activation.

    Science.gov (United States)

    Weng, Yueh-Shan; Wang, Hsueh-Fang; Pai, Pei-Ying; Jong, Gwo-Ping; Lai, Chao-Hung; Chung, Li-Chin; Hsieh, Dennis Jine-Yuan; HsuanDay, Cecilia; Kuo, Wei-Wen; Huang, Chih-Yang

    2015-01-01

    IGF-IIR plays important roles as a key regulator in myocardial pathological hypertrophy and apoptosis, which subsequently lead to heart failure. Salvia miltiorrhiza Bunge (Danshen) is a traditional Chinese medicinal herb used to treat cardiovascular diseases. Tanshinone IIA is an active compound in Danshen and is structurally similar to 17[Formula: see text]-estradiol (E[Formula: see text]. However, whether tanshinone IIA improves cardiomyocyte survival in pathological hypertrophy through estrogen receptor (ER) regulation remains unclear. This study investigates the role of ER signaling in mediating the protective effects of tanshinone IIA on IGF-IIR-induced myocardial hypertrophy. Leu27IGF-II (IGF-II analog) was shown in this study to specifically activate IGF-IIR expression and ICI 182,780 (ICI), an ER antagonist used to investigate tanshinone IIA estrogenic activity. We demonstrated that tanshinone IIA significantly enhanced Akt phosphorylation through ER activation to inhibit Leu27IGF-II-induced calcineurin expression and subsequent NFATc3 nuclear translocation to suppress myocardial hypertrophy. Tanshinone IIA reduced the cell size and suppressed ANP and BNP, inhibiting antihypertrophic effects induced by Leu27IGF-II. The cardioprotective properties of tanshinone IIA that inhibit Leu27IGF-II-induced cell hypertrophy and promote cell survival were reversed by ICI. Furthermore, ICI significantly reduced phospho-Akt, Ly294002 (PI3K inhibitor), and PI3K siRNA significantly reduced the tanshinone IIA-induced protective effect. The above results suggest that tanshinone IIA inhibited cardiomyocyte hypertrophy, which was mediated through ER, by activating the PI3K/Akt pathway and inhibiting Leu27IGF-II-induced calcineurin and NFATC3. Tanshinone IIA exerted strong estrogenic activity and therefore represented a novel selective ER modulator that inhibits IGF-IIR signaling to block cardiac hypertrophy.

  9. Cardiovascular prevention: components, levels, early origins, and metrics.

    Science.gov (United States)

    Kones, Richard; Rumana, Umme

    2014-08-01

    This article presents core epidemiological studies that establish the basis for cardiovascular prevention strategies. The results of the classic INTERHEART and INTERSTROKE studies that delineated population-attributed risk for myocardial infarction and stroke are described. Differences in the levels or types of prevention-primordial, primary, and secondary-lead to the concept that risk occurs on a continuum throughout life with great variability, beginning in infancy. Any meaningful and sustained reduction in cardiovascular risk must begin in childhood, as habits formed early in life have an impact for decades. Although it is never too late to improve unhealthy habits, interventions early in life are more likely to be effective in preventing disease from developing, in delaying manifestations, or in reversing pathology through evidence-based therapies that are applied later. There is compelling evidence that coronary atherosclerosis, heart disease related to diabetes, and hypertension begin with endothelial activation. Oxidative stress and reduced nitric oxide availability are also among the earliest of events, from which a self-amplifying web of events proceed. The American Heart Association, even prior to its now-validated and classic definition of risk metrics, developed a strategic plan to improve health habits in the population and at the community level for promoting and monitoring behavior change and patients' self-reported health status. Other initiatives for improving cardiovascular health are in place as well. Despite improvements in treatment of risk factors, there has been minimal, if any, success in reversing the dual epidemics of obesity and diabetes. These 2 factors continue to drive the high burden of cardiovascular risk, and now lead current public health issues. Because treatment alone cannot fully address this tsunami of risk, it has been suggested that all physicians assume an unprecedented and aggressive role as advocates for behavior change to

  10. Readiness for work injury management and prevention: important attributes for early graduate occupational therapists and physiotherapists.

    Science.gov (United States)

    Adam, Kerry; Strong, Jenny; Chipchase, Lucy

    2014-01-01

    Early graduate occupational therapists (OTs) and physiotherapists (PTs) are routinely employed in work injury management and prevention in Australia. However, our understanding is limited about employer requirements for early graduates entering the field, and how commencing practitioners manage transition to practice. In addition, employers have expressed concerns anecdotally about the preparedness of early graduates for work injury management and prevention. However, evidence is limited about early gradutate preparedness for the field. The study aimed to develop a detailed qualitative account of the perceptions of employers and early graduates on the attributes required of early graduates in work injury management and prevention, and processes for effective transition to practice in this field. A purposive sample of 12 employers and 12 early graduates in work injury management and prevention participated in semi-structured interviews. Questions to employers focused on recruitment, supervision and readiness for practice. Questions to early graduates focused on challenges in transition and effective learning methods. Transcripts were analysed by Leximancer™ and supported by manual coding and synthesis. Four themes with findings were, 1) 'Job and workplace requirements'; skills required by employers and support needed for early graduates, 2) 'Learning for work injury management and prevention'; options for early graduate development and learning methods early graduates found effective, 3) 'Employer expectations of early graduates in transition to work injury management and prevention', responses to transition; and 4) 'Early graduate perceptions on transition to work injury management and prevention'; early graduates responses to transition. Findings for employers and early graduates were similar to those expected in other areas of practice for OTs and PTs. Work injury management and prevention skills were not expected of early graduates by employers. Employers and

  11. Severe malformations of eelpout (Zoarces viviparus) fry are induced by maternal estrogenic exposure during early embryogenesis

    DEFF Research Database (Denmark)

    Morthorst, Jane Ebsen; Korsgaard, Bodil; Bjerregaard, Poul

    2016-01-01

    Pregnant eelpout were exposed via the water to known endocrine disrupting compounds (EDCs) to clarify if EDCs could be causing the increased eelpout fry malformation frequencies observed in coastal areas receiving high anthropogenic input. The presence of a teratogenic window for estrogen...... the closer exposure start was to fertilization, whereas malformations were absent by exposure starting later than 14 dpf. Data on ovarian fluid volume and larval length supported the suggested teratogenic window. Larval mortality also increased when exposure started right after fertilization....

  12. Annual fasting; the early calories restriction for cancer prevention.

    Science.gov (United States)

    Eslami, Solat; Barzgari, Zahra; Saliani, Negar; Saeedi, Nazli; Barzegari, Abolfazl

    2012-01-01

    Essentially, people's diet and nutritional status has been changed substantially worldwide and several lines of evidence suggest that these changes are to the detriment of their health. Additionally, it has been well documented that unhealthy diet especially the fast foods, untraditional foods or bad-eating-habits influence the human gut microbiome. The gut microbiota shapes immune responses during human life and affects his/her metabolomic profiles. Furthermore, many studies highlight the molecular pathways that mediate host and symbiont interactions that regulate proper immune function and prevention of cancer in the body. Intriguingly, if cancer forms in a human body due to the weakness of immune system in detriment of microbiome, the removal of cancer stem cells can be carried out through early Calories Restriction with Annual Fasting (AF) before tumor development or progress. Besides, fasting can balance the gut microbiome for enhancement of immune system against cancer formation.

  13. Annual Fasting; the Early Calories Restriction for Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Solat Eslami

    2012-12-01

    Full Text Available Essentially, people’s diet and nutritional status has been changed substantially worldwide and several lines of evidence suggest that these changes are to the detriment of their health. Additionally, it has been well documented that unhealthy diet especially the fast foods, untraditional foods or bad-eating-habits influence the human gut microbiome. The gut microbiota shapes immune responses during human life and affects his/her metabolomic profiles. Furthermore, many studies highlight the molecular pathways that mediate host and symbiont interactions that regulate proper immune function and prevention of cancer in the body. Intriguingly, if cancer forms in a human body due to the weakness of immune system in detriment of microbiome, the removal of cancer stem cells can be carried out through early Calories Restriction with Annual Fasting (AF before tumor development or progress. Besides, fasting can b balance the gut microbiome for enhancement of immune system against cancer formation.

  14. Ebselen prevents early alcohol-induced liver injury in rats.

    Science.gov (United States)

    Kono, H; Arteel, G E; Rusyn, I; Sies, H; Thurman, R G

    2001-02-15

    Oxidants have been shown to be involved in alcohol-induced liver injury. Moreover, 2-phenyl-1,2-benzisoselenazole-3(2H)-one (ebselen), an organoselenium compound and glutathione peroxidase mimic, decreases oxidative stress and protects against stroke clinically. This study was designed to test the hypothesis that ebselen protects against early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-16 g/kg/d) continuously for up to 4 weeks using the intragastric enteral feeding protocol developed by Tsukamoto and French. Ebselen (50 mg/kg twice daily, intragastrically) or vehicle (1% tylose) was administered throughout the experiment. Mean urine ethanol concentrations were not significantly different between treatment groups, and ebselen did not affect body weight gains or cyclic patterns of ethanol concentrations in urine. After 4 weeks, serum ALT levels were increased significantly about 4-fold over control values (37 +/- 5 IU/l) by enteral ethanol (112 +/- 7 IU/l); ebselen blunted this increase significantly (61 +/- 8 IU/l). Enteral ethanol also caused severe fatty accumulation, mild inflammation, and necrosis in the liver (pathology score: 4.3 +/- 0.3). In contrast, these pathological changes were blunted significantly by ebselen (pathology score: 2.5 +/- 0.4). While there were no significant effects of either ethanol or ebselen on glutathione peroxidase activity in serum or liver tissue, ebselen blocked the increase in serum nitrate/nitrite caused by ethanol. Furthermore, ethanol increased the activity of NF-kappaB over 5-fold, the number of infiltrating neutrophils 4-fold, and the accumulation of 4-hydroxynonenal over 5-fold. Ebselen blunted all of these effects significantly. These results indicate that ebselen prevents early alcohol-induced liver injury, most likely by preventing oxidative stress, which decreases inflammation.

  15. Early Childhood Caries: Prevalence, Risk Factors, and Prevention

    Directory of Open Access Journals (Sweden)

    Sukumaran Anil

    2017-07-01

    Full Text Available Early childhood caries (ECC is major oral health problem, mainly in socially disadvantaged populations. ECC affects infants and preschool children worldwide. The prevalence of ECC differs according to the group examined, and a prevalence of up to 85% has been reported for disadvantaged groups. ECC is the presence of one or more decayed, missing, or filled primary teeth in children aged 71 months (5 years or younger. It begins with white-spot lesions in the upper primary incisors along the margin of the gingiva. If the disease continues, caries can progress, leading to complete destruction of the crown. The main risk factors in the development of ECC can be categorized as microbiological, dietary, and environmental risk factors. Even though it is largely a preventable condition, ECC remains one of the most common childhood diseases. The major contributing factors for the for the high prevalence of ECC are improper feeding practices, familial socioeconomic background, lack of parental education, and lack of access to dental care. Oral health plays an important role in children to maintain the oral functions and is required for eating, speech development, and a positive self-image. The review will focus on the prevalence, risk factors, and preventive strategies and the management of ECC.

  16. Impact of nutrition since early life on cardiovascular prevention.

    Science.gov (United States)

    Guardamagna, Ornella; Abello, Francesca; Cagliero, Paola; Lughetti, Lorenzo

    2012-12-21

    The cardiovascular disease represents the leading cause of morbidity and mortality in Western countries and it is related to the atherosclerotic process. Cardiovascular disease risk factors, such as dyslipidemia, hypertension, insulin resistance, obesity, accelerate the atherosclerotic process which begins in childhood and progresses throughout the life span. The cardiovascular disease risk factor detection and management through prevention delays the atherosclerotic progression towards clinical cardiovascular disease. Dietary habits, from prenatal nutrition, breastfeeding, complementary feeding to childhood and adolescence nutrition play a basic role for this topic.The metabolic and neuroendocrine environment of the fetus is fundamental in the body's "metabolic programming". Further several studies have demonstrated the beneficial effects of breastfeeding on cardiovascular risk factors reduction. Moreover the introduction of complementary foods represents another important step, with particular regard to protein intake. An adequate distribution between macronutrients (lipids, proteins and carbohydrates) is required for correct growth development from infancy throughout adolescence and for prevention of several cardiovascular disease risk determinants in adulthood.The purpose of this review is to examine the impact of nutrition since early life on disease.

  17. Early interventions to prevent retinal vasculopathy in diabetes: a review

    Directory of Open Access Journals (Sweden)

    Harrison WW

    2015-08-01

    Full Text Available Wendy W Harrison, Vladimir YevseyenkovArizona College of Optometry, Midwestern University, Glendale, AZ, USAAbstract: Diabetic eye disease is a public health concern in all areas of the world as a leading cause of blindness in the working aged to elderly populations. Diabetes damages the lining of the microvasculature throughout the body through prolonged exposure to hyperglycemic conditions. The ocular changes are progressive with very little recourse for improvement once damage begins. Current treatments for the eye focus mainly on the late stages of the disease when neovascularization or edema threatens sight. Early interventions for diabetic vasculopathy involve metabolic therapy to improve blood glucose and blood pressure control. Technology improvements have a large part to play in advancing diagnosis of diabetic eye disease. These new technologies offer both structural and functional means for assessment of retinal health. This review focuses on current treatments for diabetic eye disease at all stages with an emphasis on new and early interventions. It also details established and emerging technologies used for earlier detection of diabetic eye disease, which is vital to the development and approval of much needed treatments targeted at earlier stages of diabetic retinopathy. Possible future treatments should be aimed to prevent retinal vasculopathy from progressing. This review will explore current research on this topic and what is needed moving forward.Keywords: diabetes, diabetic retinopathy, vascular disease

  18. Distribution of aromatase and sex steroid receptors in the baculum during the rat life cycle: effects of estrogen during the early development of the baculum.

    Science.gov (United States)

    Yonezawa, Tomohiro; Higashi, Mayuko; Yoshioka, Kazuki; Mutoh, Ken-ichiro

    2011-07-01

    The baculum, also called os penis, plays an important role during copulation. However, the hormonal regulation of its development remains to be elucidated. To determine the direct involvement of sex steroids in the development of the baculum of rats, the distributions of androgen receptors (ARs), aromatase, and estrogen receptor alpha (ESR1) were observed immunohistochemically. On Postnatal Day 1, the rudiment of the baculum expressed ARs, aromatase, and ESR1. In the proximal segment of the baculum of neonatal rats, ARs were expressed in the parosteal layer but not in the periosteum or osteoblasts. Aromatase was expressed from the parosteal layer to the endosteum, particularly in the inner osteogenic layer. ESR1 was also abundantly expressed in almost all cells from the parosteal layer to the endosteum. ARs, aromatase, and ESR1 were all abundantly expressed during the neonatal period in the hyaline cartilage of the proximal segment and in fibrocartilage of the distal segment of the baculum. Expression in all the tissues was attenuated in an age-dependent manner and became quite weak at puberty. To determine the effect of estrogen on the growth of the baculum, the aromatase inhibitor 1,4,6-androstatrien-3,17-dione (ATD) was subcutaneously injected daily into pregnant rats from Days 19 to 23 of gestation and into pups on postnatal Days 1, 3, 5, 7, and 9. On Day 10, the length of the baculum in the ATD-treated rats was significantly shorter than that in the controls, although the body weight did not change. These findings suggest that not only androgen but also locally aromatized estrogen is involved in the early growth and development of the baculum.

  19. Estrogen-induced DNA synthesis in vascular endothelial cells is mediated by ROS signaling

    Directory of Open Access Journals (Sweden)

    Felty Quentin

    2006-04-01

    Full Text Available Abstract Background Since estrogen is known to increase vascular endothelial cell growth, elevated estrogen exposure from hormone replacement therapy or oral contraceptives has the potential to contribute in the development of abnormal proliferative vascular lesions and subsequent thickening of the vasculature. How estrogen may support or promote vascular lesions is not clear. We have examined in this study whether estrogen exposure to vascular endothelial cells increase the formation of reactive oxygen species (ROS, and estrogen-induced ROS is involved in the growth of endothelial cells. Methods The effect of estrogen on the production of intracellular oxidants and the role of estrogen-induced ROS on cell growth was studied in human umbilical vein endothelial cells. ROS were measured by monitoring the oxidation of 2'7'-dichlorofluorescin by spectrofluorometry. Endothelial cell growth was measured by a colorimetric immunoassay based on BrdU incorporation into DNA. Results Physiological concentrations of estrogen (367 fmol and 3.67 pmol triggered a rapid 2-fold increase in intracellular oxidants in endothelial cells. E2-induced ROS formation was inhibited to basal levels by cotreatment with the mitochondrial inhibitor rotenone (2 μM and xanthine oxidase inhibitor allopurinol (50 μM. Inhibitors of NAD(PH oxidase, apocynin and DPI, did not block E2-induced ROS formation. Furthermore, the NOS inhibitor, L-NAME, did not prevent the increase in E2-induced ROS. These findings indicate both mitochondria and xanthine oxidase are the source of ROS in estrogen treated vascular endothelial cells. E2 treated cells showed a 2-fold induction of BrdU incorporation at 18 h which was not observed in cells exposed to vehicle alone. Cotreatment with ebselen (20 μM and NAC (1 mM inhibited E2-induced BrdU incorporation without affecting the basal levels of DNA synthesis. The observed inhibitory effect of NAC and ebselen on E2-induced DNA synthesis was also shown

  20. The early postprandial dumping syndrome: prevention and treatment.

    Science.gov (United States)

    Woodward, E R; Bushkin, F L

    1976-01-01

    The early postprandial dumping syndrome can be prevented or minimized by the appropriate selection of the operative procedure to fit the patient and the peptic ulcer problem he presents, and by proper attention to diet in the early postoperative period. When it does occur, the syndrome usually responds favorably to dietary management and tends to spontaneously regress in severity with time. For these reasons further surgery is seldom required for the early postprandial dumping syndrome. In the patient who fails to improve with diet therapy and time and has disabling symptoms often accompanied by progressive malnutrition, revisional surgery should be undertaken. It is the objective of the surgeon to alter the reconstruction in such a way that emptying from the stomach or gastric remnant is delayed. Therefore, the upper small intestine dose not receive a large, rapidly introduced hyperosmolar bolus to initiate the release of humoral substances causing the syndrome. All revisions utilized are potentially ulcerogenic and if vagotomy has not been a part of the original procedure, it should routinely be performed at the time of revision. Patients who have primarily has a Billroth II gastrectomy will frequently improve markedly with simple conversion to a Billroth I reconstruction. This is particularly true when the residual stomach is moderately large (i.e., after antrectomy) and when the gastrojejunal stoma is larger in diameter than the normal jejunum. Under such circumstances approximately 80 per cent of patients will improve sufficiently so that a more complex procedure need not be utilized at once. Under all other conditions we prefer a 10 cm. segment of reversed jejunum anastomosed proximally to the gastric stump and distally to a 40 cm. isoperistaltic Roux-en-Y jejunal limb. This procedure is so successful that one can justify its use as first recourse even in the anatomically favorable Billroth II patient. It should be pointed out emphatically that an

  1. 17α-Ethinylestradiol (EE2) treatment of wild roach (Rutilus rutilus) during early life development disrupts expression of genes directly involved in the feedback cycle of estrogen.

    Science.gov (United States)

    Nikoleris, Lina; Hultin, Cecilia L; Hallgren, Per; Hansson, Maria C

    2016-02-01

    Fish are more sensitive to introduced disturbances from synthetic endocrine disrupting compounds during early life phases compared with mature stages. 17α-Ethinylestradiol (EE2), which is the active compound in human oral contraceptives and hormone replacement therapies, is today ever present in the effluents from sewage treatment plants. EE2 targets and interacts with the endogenous biological systems of exposed vertebrates resulting in to large extents unknown short- and long-term effects. We investigated how EE2 exposure affects expression profiles of a large number of target genes during early life of roach (Rutilus rutilus). We exposed fertilized roach eggs collected from a lake in Southern Sweden to EE2 for 12weeks together with 1+-year-old roach in aquaria. We measured the gene expression of the estrogen receptor (esr)1/2a/2b, androgen receptor (ar), vitellogenin, cytochrome P450 (cyp)19a1a/1b in fertilized eggs; newly hatched larvae; 12-week-old fry; and juvenile wild roach (1+-year-old). Results shows that an EE2 concentration as low as 0.5ng/L significantly affects gene expression during early development. Gene expression responses vary both among life stages and molecular receptors. We also show that the gene profile of the estrogen feedback cycle to a large extent depends on the relationship between the three esr genes and the two cyp19a1 genes, which are all up-regulated with age. Results indicate that a disruption of the natural activity of the dominant esr gene could lead to detrimental biological effects if EE2 exposure occurs during development, even if this exposure occurred for only a short period.

  2. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

    DEFF Research Database (Denmark)

    Bernsdorf, M.; Ingvar, C.; Jorgensen, L.

    2011-01-01

    a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups....... Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer a parts per thousand yen 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint...

  3. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

    DEFF Research Database (Denmark)

    Bernsdorf, Mogens; Ingvar, Christian; Jörgensen, Leif

    2011-01-01

    CR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher p....... Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer = 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response...

  4. Effects of butachlor on estrogen receptor, vitellogenin and P450 aromatase gene expression in the early life stage of zebrafish.

    Science.gov (United States)

    Chang, Juhua; Gui, Wenjun; Wang, Minghua; Zhu, Guonian

    2012-01-01

    Butachlor has adverse effects on fecundity and disrupts sex hormone homeostasis in adult zebrafish, but the underlying molecular mechanisms are still unclear. In the present study, zebrafish (Danio rerio) embryos were exposed to various concentrations of butachlor from 2 h post-fertilization (hpf) to 30 days post-fertilization (dpf). The transcription of genes involved estrogen receptors (ERα, ERβ1 and ERβ2), vitellogenins (VTG I and II), and cytochrome P450 aromatase (CYP19a) was analyzed by real-time quantitative PCR. The results showed that there was no significant alteration in the expression of VTGI, ERα, ERβ1, ERβ2 and CYP19a after 30 days of butachlor exposure, whereas the transcription of VTG II gene was significantly up-regulated in zebrafish exposed to 100 μg/L butachlor. It is suggested that butachlor may be a weak estrogen, and more endpoints need to be investigated to assess the effects of butachlor on the hypothalamus-pituitary-gonadal axis of zebrafish.

  5. Menopause, estrogens and frailty.

    Science.gov (United States)

    Nedergaard, Anders; Henriksen, Kim; Karsdal, Morten Asser; Christiansen, Claus

    2013-05-01

    The controversy surrounding the results from the Women's Health Initiative (WHI) trials published a decade ago caused a significant decline in the use of menopausal hormone replacement therapy. However, these results have been vehemently contested and several lines of evidence suggest that in perimenopausal and non-obese women, estrogen therapy may indeed be of benefit. There is ample proof that menopause causes a loss of musculoskeletal tissue mass and quality, thereby causing a loss of health and quality of life. There is also solid evidence that hormone replacement therapy in itself prevents most of these effects in connective tissue in itself. Besides the independent, direct effects on the musculoskeletal tissues, estrogen deficiency also reduces the ability to adequately respond and adapt to external mechanical and metabolic stressors, e.g. exercise, which are otherwise the main stimuli that should maintain musculoskeletal integrity and metabolic function. Thus, normophysiological estrogen levels appear to exert a permissive effect on musculoskeletal adaptations to loading, thereby likely improving the outcome of rehabilitation following critical illness, musculoskeletal trauma or orthopedic surgical therapy. These effects add to the evidence supporting the use of estrogen therapy, particularly accelerated gain of functional capacity and independence following musculoskeletal disuse.

  6. Impact of nutrition since early life on cardiovascular prevention

    Science.gov (United States)

    2012-01-01

    The cardiovascular disease represents the leading cause of morbidity and mortality in Western countries and it is related to the atherosclerotic process. Cardiovascular disease risk factors, such as dyslipidemia, hypertension, insulin resistance, obesity, accelerate the atherosclerotic process which begins in childhood and progresses throughout the life span. The cardiovascular disease risk factor detection and management through prevention delays the atherosclerotic progression towards clinical cardiovascular disease. Dietary habits, from prenatal nutrition, breastfeeding, complementary feeding to childhood and adolescence nutrition play a basic role for this topic. The metabolic and neuroendocrine environment of the fetus is fundamental in the body’s “metabolic programming”. Further several studies have demonstrated the beneficial effects of breastfeeding on cardiovascular risk factors reduction. Moreover the introduction of complementary foods represents another important step, with particular regard to protein intake. An adequate distribution between macronutrients (lipids, proteins and carbohydrates) is required for correct growth development from infancy throughout adolescence and for prevention of several cardiovascular disease risk determinants in adulthood. The purpose of this review is to examine the impact of nutrition since early life on disease. La malattia cardiovascolare rappresenta la principale causa di morbilità e mortalità dei paesi occidentali ed è correlata a degenerazione vascolare aterosclerotica. I fattori di rischio cardiovascolari quali dislipidemia, ipertensione, insulino resistenza e obesità accelerano tale processo il cui esordio è noto sin dell’età pediatrica ed evolve nel corso della vita. L’individuazione e la cura dei fattori di rischio cardiovascolari mediante la prevenzione dei fattori causali ritardano la progressione dell’aterosclerosi e l’insorgenza dei sintomi cardiovascolari. La nutrizione svolge un ruolo

  7. Impact of nutrition since early life on cardiovascular prevention

    Directory of Open Access Journals (Sweden)

    Guardamagna Ornella

    2012-12-01

    Full Text Available Abstract The cardiovascular disease represents the leading cause of morbidity and mortality in Western countries and it is related to the atherosclerotic process. Cardiovascular disease risk factors, such as dyslipidemia, hypertension, insulin resistance, obesity, accelerate the atherosclerotic process which begins in childhood and progresses throughout the life span. The cardiovascular disease risk factor detection and management through prevention delays the atherosclerotic progression towards clinical cardiovascular disease. Dietary habits, from prenatal nutrition, breastfeeding, complementary feeding to childhood and adolescence nutrition play a basic role for this topic. The metabolic and neuroendocrine environment of the fetus is fundamental in the body’s “metabolic programming”. Further several studies have demonstrated the beneficial effects of breastfeeding on cardiovascular risk factors reduction. Moreover the introduction of complementary foods represents another important step, with particular regard to protein intake. An adequate distribution between macronutrients (lipids, proteins and carbohydrates is required for correct growth development from infancy throughout adolescence and for prevention of several cardiovascular disease risk determinants in adulthood. The purpose of this review is to examine the impact of nutrition since early life on disease. La malattia cardiovascolare rappresenta la principale causa di morbilità e mortalità dei paesi occidentali ed è correlata a degenerazione vascolare aterosclerotica. I fattori di rischio cardiovascolari quali dislipidemia, ipertensione, insulino resistenza e obesità accelerano tale processo il cui esordio è noto sin dell’età pediatrica ed evolve nel corso della vita. L’individuazione e la cura dei fattori di rischio cardiovascolari mediante la prevenzione dei fattori causali ritardano la progressione dell’aterosclerosi e l’insorgenza dei sintomi cardiovascolari. La

  8. Human chorionic gonadotrophin in early gestation induces growth of estrogenic ovarian follicles and improves primiparous sow fertility during summer.

    Science.gov (United States)

    Seyfang, Jemma; Langendijk, P; Chen, T Y; Bouwman, E; Kirkwood, R N

    2016-09-01

    Reduced summer farrowing rates may be due to inadequate corpora luteal (CL) support. Porcine CL become dependent on LH from 12 d of pregnancy and the embryonic estrogen signal for maternal recognition of pregnancy (MRP) is initiated at about 11-12 d after insemination. We hypothesised that injection of the LH analogue human chorionic gonadotropin (hCG) would induce growth of estrogenic follicles and, by mimicking the signal for MRP and stimulating progesterone secretion, increase primiparous sow fertility. In Experiment 1, during a 28 d lactation 53 mixed parity sows were full-fed either throughout lactation (n=16) or until 18 d and then feed restricted during the last 10 d of lactation (n=36). At 12 d after mating restrict-fed sows were injected with 1000IU hCG (n=17) or were not injected (n=19); the full-fed sows acted as non-treated positive controls. Transrectal ovarian ultrasound exams were performed on days 12, 16, 20, 24, and 28; blood samples were obtained on days 12, 14, and 15 for estradiol and progesterone assay. For Experiment 2, during the summer months primiparous sows received 1000IU hCG 12 d after mating (n=28) or were non-injected controls (n=27). Pregnancy status was determined at 28 d and sows allowed to go to term to determine farrowing rates and litter sizes. In Experiment 1, injection of hCG increased (Pfeeding level on wean-estrus interval, farrowing rate or subsequent litter size. In Experiment 2, hCG injection was associated with a higher pregnancy rate (Psow fertility during the summer months.

  9. Addition of anti-estrogen therapy to anti-HER2 dendritic cell vaccination improves regional nodal immune response and pathologic complete response rate in patients with ER(pos)/HER2(pos) early breast cancer.

    Science.gov (United States)

    Lowenfeld, Lea; Zaheer, Salman; Oechsle, Crystal; Fracol, Megan; Datta, Jashodeep; Xu, Shuwen; Fitzpatrick, Elizabeth; Roses, Robert E; Fisher, Carla S; McDonald, Elizabeth S; Zhang, Paul J; DeMichele, Angela; Mick, Rosemarie; Koski, Gary K; Czerniecki, Brian J

    2017-01-01

    HER2-directed therapies are less effective in patients with ER(pos) compared to ER(neg) breast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2(pos)/ER(pos) early breast cancer patients. In pre-clinical studies of HER2(pos) breast cancer cell lines, ER(pos) cells were partially resistant to CD4(+) Th1 cytokine-induced metabolic suppression compared with ER(neg) cells. The addition of anti-estrogen treatment significantly enhanced cytokine sensitivity in ER(pos), but not ER(neg), cell lines. In two pooled phase-I clinical trials, patients with HER2(pos) early breast cancer were treated with neoadjuvant anti-HER2 dendritic cell vaccination; HER2(pos)/ER(pos) patients were treated with or without concurrent anti-estrogen therapy. The anti-HER2 Th1 immune response measured in the peripheral blood significantly increased following vaccination, but was similar across the three treatment groups (ER(neg) vaccination alone, ER(pos) vaccination alone, ER(pos) vaccination + anti-estrogen therapy). In the sentinel lymph nodes, however, the anti-HER2 Th1 immune response was significantly higher in ER(pos) patients treated with combination anti-HER2 vaccination plus anti-estrogen therapy compared to those treated with anti-HER2 vaccination alone. Similar rates of pathologic complete response (pCR) were observed in vaccinated ER(neg) patients and vaccinated ER(pos) patients treated with concurrent anti-estrogen therapy (31.4% vs. 28.6%); both were significantly higher than the pCR rate in vaccinated ER(pos) patients who did not receive anti-estrogen therapy (4.0%, p = 0.03). Since pCR portends long-term favorable outcomes, these results support additional clinical investigations using HER2-directed vaccines in combination with anti-estrogen treatments for ER(pos)/HER2(pos) DCIS and invasive breast cancer.

  10. [The new concept of osteoporosis. Early diagnosis, prevention and therapy are possible today].

    Science.gov (United States)

    Hesch, R D; Harms, H; Rittinghaus, E F; Brabant, G

    1990-04-15

    A paradigma of osteoporosis pathology is discussed, at the center of which is the hormone-related disturbance of the osteoblast/osteoclast functional unit. A liberal replacement of estrogen-gestagen in post-menopausal women is advocated. Early diagnosis with the aid of quantitative computed tomography makes it possible to establish the indication for timely hormonal treatment in the future, which can result in a measureable increase in bone mass. Late therapy, that is, treatment initiated after the occurrence of fractures, has proven largely ineffective.

  11. PRIMARY PREVENTION OF DIABETES MELLITUS: CORRECTION OF EARLY DISORDERS OF GLUCOSE METABOLISM IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2012-01-01

    Full Text Available Early glucose metabolism disorders (GMD are of interest in development of effective approaches to prevention of type 2 diabetes mellitus (DM. Data of international clinical trials shows that early GMD are an independent risk factor for cardiovascular disease. The possibilities of GMD prevention and early treatment are discussed. Antihyperglycemic medications classification, their mode of action and efficacy are presented from evidence-based medicine point of view. This data confirms that successful DM primary prevention at early stage of GMD reduces the risk of cardiovascular complications.

  12. PRIMARY PREVENTION OF DIABETES MELLITUS: CORRECTION OF EARLY DISORDERS OF GLUCOSE METABOLISM IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2015-12-01

    Full Text Available Early glucose metabolism disorders (GMD are of interest in development of effective approaches to prevention of type 2 diabetes mellitus (DM. Data of international clinical trials shows that early GMD are an independent risk factor for cardiovascular disease. The possibilities of GMD prevention and early treatment are discussed. Antihyperglycemic medications classification, their mode of action and efficacy are presented from evidence-based medicine point of view. This data confirms that successful DM primary prevention at early stage of GMD reduces the risk of cardiovascular complications.

  13. Progestogens and early pregnancy:prevention and treatment

    Institute of Scientific and Technical Information of China (English)

    Adolf E.Schindler

    2013-01-01

    During human and mammalian pregnancy,endogenous progesterone is the dominant hormone since it is not only essential for conception and implantation,but also needed throughout pregnancy.Progesterone provided the effects of prevention and treatment in human pregnancy by certain mechanisms.If one considers prevention or treatment with progestogens in human pregnancy,that all progestogens are progestogenic,if one condsiders the progestogens for prevention and therapeutic approaches,nowadays,only two progenstogens can be considered fully suitable for prevention and treatment in human pregnancy:progesterone and dydrogesteone.This review introduced the mechanism of progesterone and dydrogesterone in pregnancy and treatment in human.

  14. Preventive Intervention for Anxious Preschoolers and Their Parents: Strengthening Early Emotional Development

    Science.gov (United States)

    Fox, Jeremy K.; Warner, Carrie Masia; Lerner, Amy B.; Ludwig, Kristy; Ryan, Julie L.; Colognori, Daniela; Lucas, Christopher P.; Brotman, Laurie Miller

    2012-01-01

    The high prevalence and early onset of anxiety disorders have inspired innovative prevention efforts targeting young at-risk children. With parent-child prevention models showing success for older children and adolescents, the goal of this study was to evaluate a parent-child indicated preventive intervention for preschoolers with mild to moderate…

  15. Etiology and Early Marker Studies (EEMS) | Division of Cancer Prevention

    Science.gov (United States)

    The Etiology and Early Marker Studies (EEMS) is a component of the PLCO Trial. By collecting biologic materials and risk factor information from trial participants before the diagnosis of disease, PLCO EEMS adds substantial value to the trial, providing a resource for cancer research, focused, in particular, on cancer etiology and early markers. Etiologic studies investigate the environmental, biochemical and genetic risk factors for cancer. Early detection studies aim to develop reproducible, diagnostics-ready biomarkers of early disease. | Risk factor data and biospecimens collected before the diagnosis of disease from participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

  16. Obesity Prevention in Early Adolescence: Student, Parent, and Teacher Views

    Science.gov (United States)

    Power, Thomas G.; Bindler, Ruth C.; Goetz, Summer; Daratha, Kenneth B.

    2010-01-01

    Background: Obesity is a significant health problem among today's youth; however, most school-based prevention programs in this area have had limited success. Focus groups were conducted with seventh- to eighth-grade students, parents, and teachers to provide insight into the development of a comprehensive program for the prevention of adolescent…

  17. Prevention of Bullying in Early Educational Settings: Pedagogical and Organisational Factors Related to Bullying

    Science.gov (United States)

    Repo, Laura; Sajaniemi, Nina

    2015-01-01

    Research suggests that bullying behaviour begins at an early age (three to six years) and that preventive practices should target early educational settings. However, no previous studies focus on early educational settings (kindergartens) as an arena for bullying behaviour. The aim of this study was to find what kind of organisational and…

  18. Prevention of Bullying in Early Educational Settings: Pedagogical and Organisational Factors Related to Bullying

    Science.gov (United States)

    Repo, Laura; Sajaniemi, Nina

    2015-01-01

    Research suggests that bullying behaviour begins at an early age (three to six years) and that preventive practices should target early educational settings. However, no previous studies focus on early educational settings (kindergartens) as an arena for bullying behaviour. The aim of this study was to find what kind of organisational and…

  19. [Type 1 diabetes mellitus. Early detection and prevention].

    Science.gov (United States)

    Hummel, M; Achenbach, P

    2015-05-01

    Type 1 diabetes is the most common autoimmune disease in children and adolescents, with a rising incidence worldwide. Despite improvements in insulin therapy, in many cases complications cannot be avoided and mortality is increased. Therefore, the development of effective prevention strategies is an important medical but also economic goal. Exact prediction of the disease is necessary for prevention studies, and type 1 diabetes can be predicted very accurately with genetic and humoral markers. Primary prevention in genetically predisposed individuals is initiated before diabetes-associated autoantibodies occur. Secondary prevention aims to arrest the progression to type 1 diabetes in autoantibody-positive subjects. Some prevention studies show encouraging results.

  20. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial.

    Science.gov (United States)

    Bernsdorf, Mogens; Ingvar, Christian; Jörgensen, Leif; Tuxen, Malgorzata K; Jakobsen, Erik H; Saetersdal, Anna; Kimper-Karl, Marie Louise; Kroman, Niels; Balslev, Eva; Ejlertsen, Bent

    2011-04-01

    Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI -7.19 to 6.33; P = 0.44). CR was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI -9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI -9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE.

  1. [Microabrasive tooth preparation for early caries prevention and treatment].

    Science.gov (United States)

    Dmitrova, A G; Kulakov, A A; Vinnichenko, Iu A; Monastyreva, E G

    2011-01-01

    Based on the 4-year experience with the method of air-abrasion treatment on the stages of treatment and prevention of dental caries in the article provides data on the indications for its use, benefits and complications.

  2. Preventing disruptive behavior in early elementary schoolchildren: impact of a universal classroom-based preventive intervention

    NARCIS (Netherlands)

    P.A.C. van Lier (Pol)

    2002-01-01

    textabstractKnowledge about the development of children with disruptive behaviors, leading to disruptive disorders and related poor outcomes, guides prevention research in the development and evaluation of preventive interventions. The overview of effective interventions in this chapter showed that

  3. Exercise-like effects by Estrogen-related receptor-gamma in muscle do not prevent insulin resistance in db/db mice

    National Research Council Canada - National Science Library

    Badin, Pierre-Marie; Vila, Isabelle K; Sopariwala, Danesh H; Yadav, Vikas; Lorca, Sabina; Louche, Katie; Kim, Eun Ran; Tong, Qingchun; Song, Min Sup; Moro, Cedric; Narkar, Vihang A

    2016-01-01

    .... Muscle estrogen-related receptor gamma (ERRγ) is induced by exercise, and when over-expressed in the skeletal muscle mimics exercise by stimulating glycolytic-to-oxidative myofiber switch, mitochondrial biogenesis and angiogenesis in lean mice...

  4. [Estrogen therapy in menopause. Clinical study in evolution (KEEPS) to explain the risk-benefit dispute to administration].

    Science.gov (United States)

    Zárate, Arturo; Hernández-Valencia, Marcelino

    2010-03-01

    The Kronos Early Estrogen Prevention Study (KEEPS) is a randomized clinical and controlled study, with the objective of clarifying the controversy that arisen previous studies about the risk-benefit factor with use of estrogens in postmenopausal women. Healthy women aged 42-58 years who are within 36 months of their last menstrual period have been recruited to receive either oral estrogens or patches of estradiol; in addition both groups are given oral micronized progesterone for 11 days of each month. Outcomes will be carotid intimae medial thickness and the accrual of coronary calcium; collaterally subrogate outcomes will be lipoproteins concentrations, coagulation markers, bone densitometry, mammography, skin characteristics and cognitive evaluation. The hypothesis consists in the presence of a window of therapeutic opportunity for the use of estrogens in low dose in healthy women with recent menopause.

  5. Prevention of caries with probiotic bacteria during early childhood. Promising but inconsistent findings

    DEFF Research Database (Denmark)

    Jørgensen, Mette Rose; pqd956, pqd956; Twetman, Svante

    2016-01-01

    PURPOSE: This review summarized the available literature on the prevention of childhood caries through biofilm engineering with probiotic bacteria in early childhood. METHODS: Three databases (PubMed, Cochrane Library and Trip) were searched through January, 2016 for randomized controlled trials...... the caries prevalence and expressed as prevented fraction and number needed to treat. RESULTS: Probiotic supplements were better than placebo in preventing early childhood caries in all seven studies although the difference was statistically significant in only four of them. The prevented fraction ranged...

  6. Phosphorylated Peptides from Antarctic Krill (Euphausia superba) Prevent Estrogen Deficiency Induced Osteoporosis by Inhibiting Bone Resorption in Ovariectomized Rats.

    Science.gov (United States)

    Xia, Guanghua; Zhao, Yanlei; Yu, Zhe; Tian, Yingying; Wang, Yiming; Wang, Shanshan; Wang, Jingfeng; Xue, Changhu

    2015-11-04

    In the current study, we investigated the improvement of phosphorylated peptides from Antarctic krill Euphausia superba (PP-AKP) on osteoporosis in ovariectomized rats. PP-AKP was supplemented to ovariectomized Sprague-Dawley rats for 90 days. The results showed that PP-AKP treatment remarkably prevented the reduction of bone mass and improved cancellous bone structure and biochemical properties. PP-AKP also significantly decreased serum contents of tartrate-resistant acid phosphatase (TRACP), cathepsin K (Cath-k), matrix metalloproteinases-9 (MMP-9), deoxypyridinoline (DPD), C-terminal telopeptide of collagen I (CTX-1), Ca, and P. Mechanism investigation revealed that PP-AKP significantly increased the osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio in mRNA expression, protein expression, and serum content. Further research suggested that NF-κB signaling pathways were inhibited by suppressing the mRNA and protein expressions of nuclear factor of activated T-cells (NFATc1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), diminishing the mRNA expression and phosphorylation of nuclear factor κB p65 (NF-κB p65), three key transcription factors in NF-κB pathways. These results suggest that PP-AKP can improve osteoporosis by inhibiting bone resorption via suppressing the activation of osteoclastogenesis related NF-κB pathways.

  7. [Organisational aspects and existing problems in prevention and early diagnostics of lung cancer].

    Science.gov (United States)

    Dzhorbenadze, R A

    2005-10-01

    Thorough study of advanced stages of lung cancer has been held. Delayed detection of most of the malignant tumours (IV stages) points to a number of problems existing in Georgia in terms of primary prevention and early detection of oncologic diseases. Hence, elaboration of strategy for prevention and early detection of oncologic diseases is of great importance for our country. Activities aimed at early detection of lung cancer under the conditions of low-level resources primarily imply education of population and professionals, as well as implementation of screening procedures. Cheap and effective methods should be applied for early diagnosis of one or two most widespread malignant tumours.

  8. Estrogen May Influence Women's Depression Risk

    Science.gov (United States)

    ... news/fullstory_167353.html Estrogen May Influence Women's Depression Risk Early menstruation, more frequent periods seem to ... reproductive years may have a lower risk of depression, a new study finds. Previous research has suggested ...

  9. Solcoseryl prevents early postradiation changes in the lungs.

    Science.gov (United States)

    Starosławska, E; Chyczewski, L; Peszyński, J; Sobolewski, K; Bańkowski, E; Chyczewska, E; Nikliński, J; Donica, H; Kojtych, A

    1994-01-01

    The aim of the study was to test the influence of Solcoseryl on early postradiation changes in the lungs of rats. The chests of the rats were irradiated with Co-60, fractional dose 250 cGy/DT, total dose 2500 cGy/DT. Solcoseryl was given intraperitoneally in quantities of 0,1ml daily, during 60 days of the experiment. Morphological examinations of the lungs revealed that Solcoseryl decreased significantly the effects of early postradiation damage of the respiratory organ in rats.

  10. Impact of nutrition since early life on cardiovascular prevention.

    OpenAIRE

    2012-01-01

    Abstract The cardiovascular disease represents the leading cause of morbidity and mortality in Western countries and it is related to the atherosclerotic process. Cardiovascular disease risk factors, such as dyslipidemia, hypertension, insulin resistance, obesity, accelerate the atherosclerotic process which begins in childhood and progresses throughout the life span. The cardiovascular disease risk factor detection and management through prevention delays the atherosclerotic progression towa...

  11. Design and methods for evaluating an early childhood obesity prevention program in the childcare center setting

    National Research Council Canada - National Science Library

    Natale, Ruby; Scott, Stephanie Hapeman; Messiah, Sarah E; Schrack, Maria Mesa; Uhlhorn, Susan B; Delamater, Alan

    2013-01-01

    .... Presently, approximately 70 percent of children in the United States are currently enrolled in early childcare facilities, making this an ideal setting to implement and evaluate childhood obesity prevention efforts...

  12. DCP's Early Detection Research Guides Future Science | Division of Cancer Prevention

    Science.gov (United States)

    Early detection research funded by the NCI's Division of Cancer Prevention has positively steered both public health and clinical outcomes, and set the stage for findings in the next generation of research. |

  13. High-risk early breast cancer in patients under 40 years of age: Improved clinical outcome with total estrogen blockade and tailored chemotherapy.

    Science.gov (United States)

    Recchia, Francesco; Candeloro, Giampiero; Discepoli, Stefania; Grimaldi, Marisa; Desideri, Giovambattista; Necozione, Stefano; Rea, Silvio

    2010-09-01

    This multicenter prospective trial assessed the outcome in 63 patients, 40 years of age or younger, with high-risk early breast cancer (HREBC), included in an ovarian protection study. The patients were treated with a luteinizing hormone-releasing hormone (LH-RH) analogue administered for 5 years, tailored chemotherapy and an aromatase inhibitor, in estrogen receptor-positive (ER(+)) patients. T-regulatory cells (T-regs) and vascular endothelial growth factor (VEGF) were measured at baseline and yearly. The mean age of the patients was 36 years (range 26-40). Sixty-five percent had ER(+) tumors, 24% had negative axillary nodes with tumors >1 cm and high histological grade with lymphovascular invasion, while 76% had a mean of 3.6 positive axillary nodes (range 1-21). Serum estradiol was maintained at values <40 pg/ml in all of the patients. A statistically significant decrease in VEGF (P<0.0001) and T-regs (P<0.0001), with respect to baseline values, was observed after LH-RH administration. After a median follow-up of 110 months, the 10-year progression-free and overall survival rates were 86.1 and 89.7%, respectively. These data revealed that the administration of an LH-RH analogue to HREBC patients, followed by chemotherapy and hormonal therapy, decreased VEGF and T-regs and improved the expected clinical outcome.

  14. Early Detection of Heterotopic Ossification for Effective Prevention and Treatment

    Science.gov (United States)

    2014-04-01

    selectively induced in rat model of myocardial infarction . Inflammation. 2001;25(5):293-300. 20. Tögel F, Isaac J, Hu Z, Weiss K, Westenfelder C. Renal SDF...possibility of molecular imaging as a tool for early diagnosis of HO. BODY: To establish an animal model of HO and make molecular probe of SDF-1 were the

  15. Social and emotional competence : are preventive programmes necessary in early childhood education and care?

    OpenAIRE

    Valerie Sollars

    2010-01-01

    Just as young children begin to develop a wide range of skills, attitudes and behaviours during the early years, the development of social and emotional competence is also rooted in early childhood. Yet, whilst some argue that this competence is nurtured through preventive programmes (Schonert-Reichl, 2004), this paper argues against the need for preventive programmes as long as the adults caring for young children are themselves experiencing positive relationships and can be role models prov...

  16. Cancer: improving early detection and prevention. A community practice randomised trial.

    OpenAIRE

    Dietrich, A J; O'Connor, G. T.; Keller, A.; Carney, P A; Levy, D; Whaley, F. S.

    1992-01-01

    OBJECTIVE--To test the impact of physician education and facilitator assisted office system interventions on cancer early detection and preventive services. DESIGN--A randomised trial of two interventions alone and in combination. SETTING AND SUBJECTS--Physicians in 98 ambulatory care practices in the United States. INTERVENTIONS--The education intervention consisted of a day long physician meeting directed at improving knowledge, attitudes, and skills relevant to cancer prevention and early ...

  17. Comparison of quantitative ultrasound and dual X-ray absorptiometry in estrogen-treated early postmenopausal women

    DEFF Research Database (Denmark)

    Sørensen, H A; Jørgensen, N R; Jensen, J E

    2001-01-01

    Identifying individuals at risk of developing osteoporosis is important in order to initiate early treatment. Many new techniques have been proposed as alternatives for DXA-scanning. Some of these alternatives certainly have advantages, but none have so far been demonstrated to predict fractures ......, but it was unable to identify women with low BMD, although it might be able to identify persons not at risk of osteoporosis. Low QUS values should be followed by a regular DXA measurement to confirm the presence of osteoporosis.......Identifying individuals at risk of developing osteoporosis is important in order to initiate early treatment. Many new techniques have been proposed as alternatives for DXA-scanning. Some of these alternatives certainly have advantages, but none have so far been demonstrated to predict fractures...

  18. Effect of progesterone, mifepristone, and estrogen treatment during early pregnancy on conceptus development and uterine capacity in Swine.

    Science.gov (United States)

    Vallet, J L; Christenson, R K

    2004-01-01

    A series of experiments was performed to investigate the influence of progesterone at Days 2 and 3 of pregnancy on conceptus development and uterine capacity. In experiment 1, unilaterally hysterectomized-ovariectomized (UHO) white crossbred gilts were given no treatment, estradiol valerate (5 mg given on Days 11 and 12), or progesterone (200 mg/day on Days 2 and 3 after mating). On Day 105 of pregnancy, each fetus and its associated placenta were weighed, and the number of live and dead fetuses was recorded for each litter. Early progesterone treatment reduced (P gestation length was decreased (P swine influence the rate of conceptus development during early pregnancy and uterine capacity during later pregnancy.

  19. Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.

    Directory of Open Access Journals (Sweden)

    Kristian Ovaska

    Full Text Available Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for computational methods able to analyze dynamic and multi-level deep sequencing data. To answer this need we introduce here a data-driven algorithm, SPINLONG, which is designed to search for genes that match the user-defined hypotheses or models. SPINLONG is applicable to various experimental setups measuring several molecular markers in parallel. To demonstrate the SPINLONG approach, we analyzed ChIP-seq data reporting PolII, estrogen receptor α (ERα, H3K4me3 and H2A.Z occupancy at five time points in the MCF-7 breast cancer cell line after estradiol stimulus. We obtained 777 ERa early responsive genes and compared the biological functions of the genes having ERα binding within 20 kb of the transcription start site (TSS to genes without such binding site. Our results show that the non-genomic action of ERα via the MAPK pathway, instead of direct ERa binding, may be responsible for early cell responses to ERα activation. Our results also indicate that the ERα responsive genes triggered by the genomic pathway are transcribed faster than those without ERα binding sites. The survival analysis of the 777 ERα responsive genes with 150 primary breast cancer tumors and in two independent validation cohorts indicated the ATAD3B gene, which does not have ERα binding site within 20 kb of its TSS, to be significantly associated with poor patient survival.

  20. Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.

    Directory of Open Access Journals (Sweden)

    Kristian Ovaska

    Full Text Available Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for computational methods able to analyze dynamic and multi-level deep sequencing data. To answer this need we introduce here a data-driven algorithm, SPINLONG, which is designed to search for genes that match the user-defined hypotheses or models. SPINLONG is applicable to various experimental setups measuring several molecular markers in parallel. To demonstrate the SPINLONG approach, we analyzed ChIP-seq data reporting PolII, estrogen receptor α (ERα, H3K4me3 and H2A.Z occupancy at five time points in the MCF-7 breast cancer cell line after estradiol stimulus. We obtained 777 ERa early responsive genes and compared the biological functions of the genes having ERα binding within 20 kb of the transcription start site (TSS to genes without such binding site. Our results show that the non-genomic action of ERα via the MAPK pathway, instead of direct ERa binding, may be responsible for early cell responses to ERα activation. Our results also indicate that the ERα responsive genes triggered by the genomic pathway are transcribed faster than those without ERα binding sites. The survival analysis of the 777 ERα responsive genes with 150 primary breast cancer tumors and in two independent validation cohorts indicated the ATAD3B gene, which does not have ERα binding site within 20 kb of its TSS, to be significantly associated with poor patient survival.

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

    Science.gov (United States)

    Salim, Mubadda A.; Alpert, Bruce S.

    2001-01-01

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

  2. Early Childhood Intervention Programs: Opportunities and Challenges for Preventing Child Maltreatment

    Science.gov (United States)

    Asawa, Lindsay E.; Hansen, David J.; Flood, Mary Fran

    2008-01-01

    Due to the destructive impact of child maltreatment and limited available funding to address its consequences, the value of preventive measures is evident. Early Childhood Intervention Programs (ECIPs) provide excellent opportunities to prevent and identify cases of child maltreatment, among other varied objectives. These programs are typically…

  3. Early Childhood Malaria Prevention and Children's Patterns of School Leaving in the Gambia

    Science.gov (United States)

    Zuilkowski, Stephanie S.; Jukes, Matthew C. H.

    2014-01-01

    Background: Early childhood malaria is often fatal, but its impact on the development and education of survivors has not received much attention. Malaria impacts cognitive development in a number of ways that may impact later educational participation. Aims: In this study, we examine the long-term educational effects of preventing early childhood…

  4. Evidence that increased calcium intake does not prevent early postmenopausal bone loss

    DEFF Research Database (Denmark)

    Hosking, D J; Ross, P D; Thompson, D E

    1998-01-01

    Calcium's ability to prevent bone loss in early postmenopausal women is controversial. We used data on 394 women from the placebo group of the Early Postmenopausal Interventional Cohort study, a clinical trial of alendronate, to investigate the relation of calcium intake to bone loss. Calcium int...

  5. Early Childhood Malaria Prevention and Children's Patterns of School Leaving in the Gambia

    Science.gov (United States)

    Zuilkowski, Stephanie S.; Jukes, Matthew C. H.

    2014-01-01

    Background: Early childhood malaria is often fatal, but its impact on the development and education of survivors has not received much attention. Malaria impacts cognitive development in a number of ways that may impact later educational participation. Aims: In this study, we examine the long-term educational effects of preventing early childhood…

  6. Future Directions for Research on the Development and Prevention of Early Conduct Problems

    Science.gov (United States)

    Shaw, Daniel S.

    2013-01-01

    This article describes our state of knowledge regarding the development and prevention of conduct problems in early childhood, then identifies directions that would benefit future basic and applied research. Our understanding about the course and risk factors associated with early-developing conduct problems has been significantly enhanced during…

  7. Early Childhood Malaria Prevention and Children's Patterns of School Leaving in the Gambia

    Science.gov (United States)

    Zuilkowski, Stephanie S.; Jukes, Matthew C. H.

    2014-01-01

    Background: Early childhood malaria is often fatal, but its impact on the development and education of survivors has not received much attention. Malaria impacts cognitive development in a number of ways that may impact later educational participation. Aims: In this study, we examine the long-term educational effects of preventing early childhood…

  8. Prevention of alcohol use in early adolescents: A joint venture of school and parents

    NARCIS (Netherlands)

    Koning, H.M.

    2011-01-01

    More than half of the Dutch adolescents start drinking before age 12 (Monshouwer et al., 2009). Early drinking is related to several developmental risks and to later alcohol and drug abuse (Behrendt et al., 2009). A Dutch alcohol prevention program (PAS) targets early adolescents and their parents i

  9. Alzheimer's disease, menopause and the impact of the estrogenic environment.

    Science.gov (United States)

    Pines, A

    2016-10-01

    Decades ago, postmenopausal hormone replacement was considered the panacea for midlife women. Prevention of the age-related cognitive decline was among the top alleged benefits of this therapy. However, the data from the Women's Health Initiative Memory Study (WHI-WHIMS) study showed the opposite, indicating worsening of several cognitive domains in hormone users. Since WHIMS recruited women who were 65 years or older, it became crucial to investigate the effects of hormone therapy in the early menopause as well. Recent studies, such as WHIMS-Young, the Kronos Early Estrogen Prevention Study and the Early versus Late Intervention Trial with Estradiol targeted the younger women, and indeed showed that hormone therapy may have positive cognitive outcomes in this age group. Whether or not hormone therapy has an effect on already demented women remains to be further explored, as data are scarce.

  10. Early prediction of psychosocial risks and their prevention in preschools

    Directory of Open Access Journals (Sweden)

    M.S. Mirimanova

    2013-04-01

    Full Text Available We review approaches to creation of safe learning environment in preschools: protecting, training, personally developing, creative. We explore the possibilities of this environment examination. We reveal child development risks and threats to educational environment security of preschool institutions. A special emphasis is on personal developmental and constructive approaches. Tolerance development in children is seen as a means of prevention and creation conditions for psychological security of educational environment, and indirect control of children social development process. At the same time, the aim is development of interactional culture in preschool educational institution, built on important tolerance principles: non-violence, voluntary choice, personal responsibility, accepting the Other.

  11. Application of nanotechnology in cancers prevention, early detection and treatment

    Directory of Open Access Journals (Sweden)

    Shraddha P Patel

    2014-01-01

    Full Text Available Use of nanotechnology in medical science is a rapidly developing area. New opportunities of diagnosis, imaging and therapy have developed due to recent rapid advancement by nanotechnology. The most common areas to be affected are diagnostic, imaging and targeted drug delivery in gastroenterology, oncology, cardiovascular medicine, obstetrics and gynecology. Mass screening with inexpensive imaging might be possible in the near future with the help of nanotechnology. This review paper provides an overview of causes of cancer and the application of nanotechnology in cancer prevention, detection and treatment.

  12. Application of nanotechnology in cancers prevention, early detection and treatment.

    Science.gov (United States)

    Patel, Shraddha P; Patel, Parshottambhai B; Parekh, Bhavesh B

    2014-01-01

    Use of nanotechnology in medical science is a rapidly developing area. New opportunities of diagnosis, imaging and therapy have developed due to recent rapid advancement by nanotechnology. The most common areas to be affected are diagnostic, imaging and targeted drug delivery in gastroenterology, oncology, cardiovascular medicine, obstetrics and gynecology. Mass screening with inexpensive imaging might be possible in the near future with the help of nanotechnology. This review paper provides an overview of causes of cancer and the application of nanotechnology in cancer prevention, detection and treatment.

  13. Ultrasonographic Observation of the Breast in Early Postmenopausal Women during Therapy with Cimicifuga Foetida Extract and Sequential Therapy with Estrogen and Progestin

    Institute of Scientific and Technical Information of China (English)

    Sharen Gaowa; Ai-Jun Sun; Ying Jiang; Fa-Wei He; Ting-Ping Zheng; Ya-Ping Wang

    2015-01-01

    Background:It is now recognized that Cimicifugafoetida (C.foetida) extract is effective in alleviating menopausal symptoms.But the durations reported were usually short.The aim of this study was to investigate the effects of C.foetida extract therapy and different estrogen and progesterone sequential therapies,on the breasts of early postmenopausal women.Methods:This was a prospective randomized trial.Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years.Patients were given C.foetida extract in Group A,estradiol valerate and medroxyprogesterone acetate in Group B,and estradiol valerate and progesterone in Group C.Ultrasonography was used to monitor changes in breast during treatment.Results:In comparing breast glandular section thickness before and after 1 and 2 years of treatment,no significant difference was observed in Group A (11.97 ± 2.84 mm vs.12.09 ± 2.58 mm and 12.61 ± 3.73 mm,P > 0.05);in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs.11.84 ± 2.72 mm and 11.90 ± 3.33 mm,P < 0.05) after treatment,the same as Group C (11.56 ± 3.03 mm vs.12.5 ± 3.57 mm and 12.22 ± 4.39 mm P < 0.05).In comparing breast duct width before and after 1 and 2 years of treatment,no significant difference was seen in Group A (1.07 ± 0.19 mm vs.1.02 ± 0.18 mm and 0.98 ± 0.21 mm,P > 0.05);in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs.0.96 ± 0.22 mm and 0.90 ± 0.18 mm,P < 0.05),the same as Group C (1.07 ± 0.20mm vs.1.02 ± 0.17 mm and 0.91 ± 0.19 mm,P < 0.05).The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups.However,new breast nodules had appeared after 2 years of treatment:There was one case in Group A,two cases in Group B and four cases in Group C,with breast hyperplasia after the molybdenum target check.Conclusions:In early

  14. Lay Representations of Cancer Prevention and Early Detection: Associations With Prevention Behaviors

    Directory of Open Access Journals (Sweden)

    Helen W. Sullivan, PhD, MPH

    2010-01-01

    Full Text Available IntroductionThe Common Sense Model of illness representations posits that how people think about an illness affects how they try to prevent the illness. The purpose of this study was to determine whether prevention representations vary by cancer type (colon, lung, and skin cancer and whether representations are associated with relevant behaviors.MethodsWe analyzed data from the Health Information National Trends Survey (HINTS 2005, a nationally representative survey of American adults (N = 5,586 conducted by telephone interview.ResultsRespondents reported that all 3 types of cancer can be prevented through healthy behaviors; however, fewer did so for colon cancer. More respondents reported screening as a prevention strategy for colon cancer than did so for lung or skin cancer. Representations were associated with colon cancer screening, smoking status, and sunscreen use.ConclusionRepresentations of cancer were associated with relevant health behaviors, providing a target for health messages and interventions.

  15. Raloxifene: a selective estrogen receptor modulator.

    Science.gov (United States)

    Scott, J A; Da Camara, C C; Early, J E

    1999-09-15

    Raloxifene is a selective estrogen receptor modulator that produces both estrogen-agonistic effects on bone and lipid metabolism and estrogen-antagonistic effects on uterine endometrium and breast tissue. Because of its tissue selectivity, raloxifene may have fewer side effects than are typically observed with estrogen therapy. The most common adverse effects of raloxifene are hot flushes and leg cramps. The drug is also associated with an increased risk of thromboembolic events. The beneficial estrogenic activities of raloxifene include a lowering of total and low-density lipoprotein cholesterol levels and an augmentation of bone mineral density. Raloxifene has been labeled by the U.S. Food and Drug Administration for the prevention of osteoporosis. However, its effects on fracture risk and its ability to protect against cardiovascular disease have yet to be determined. Studies are also being conducted to determine its impact on breast and endometrial cancer reduction.

  16. Corruption Early Prevention: Decision Support System for President of the Republic of Indonesia

    Science.gov (United States)

    Sasmoko; Widhoyoko, S. A.; Ariyanto, S.; Indrianti, Y.; Noerlina; Muqsith, A. M.; Alamsyah, M.

    2017-01-01

    Corruption is an extraordinary crime, and then the prevention must also be extraordinary, simultaneously (national) in the form of early warning that involves all elements; government, industry, and society. To realize it the system needs to be built which in this study is called the Corruption Early Prevention (CEP) as a Decision Support System for President of the Republic of Indonesia. This study aims to examine 1) how is the construct of the Corruption Early Prevention as a Decision Support System for President of the Republic of Indonesia?, and 2) how is the design form of the system of Corruption Early Prevention as a Decision Support System for President of Republic of Indonesia? The research method is using Neuro-Research which is the collaboration of qualitative and quantitative research methods and the model development of Information Technology (IT). The research found that: 1) the construct of CEP is theoretically feasible, valid and reliable by content to be developed in the context of the prevention of corruption in Indonesia as an early prevention system that diagnoses Indonesia simultaneously and in real time, and 2) the concept of system design and business process of CEP is predicted to be realized in the IT-based program.

  17. A randomised controlled trial for overweight and obese parents to prevent childhood obesity - Early STOPP (STockholm Obesity Prevention Program

    Directory of Open Access Journals (Sweden)

    Cao Yingting

    2011-05-01

    Full Text Available Abstract Background Overweight and obesity have a dramatic negative impact on children's health not only during the childhood but also throughout the adult life. Preventing the development of obesity in children is therefore a world-wide health priority. There is an obvious urge for sustainable and evidenced-based interventions that are suitable for families with young children, especially for families with overweight or obese parents. We have developed a prevention program, Early STOPP, combating multiple obesity-promoting behaviors such unbalanced diet, physical inactivity and disturbed sleeping patterns. We also aim to evaluate the effectiveness of the early childhood obesity prevention in a well-characterized population of overweight or obese parents. This protocol outlines methods for the recruitment phase of the study. Design and methods This randomized controlled trial (RCT targets overweight and/or obese parents with infants, recruited from the Child Health Care Centers (CHCC within the Stockholm area. The intervention starts when infants are one year of age and continues until they are six and is regularly delivered by a trained coach (dietitian, physiotherapist or a nurse. The key aspects of Early STOPP family intervention are based on Swedish recommendations for CHCC, which include advices on healthy food choices and eating patterns, increasing physical activity/reducing sedentary behavior and regulating sleeping patterns. Discussion The Early STOPP trial design addresses weaknesses of previous research by recruiting from a well-characterized population, defining a feasible, theory-based intervention and assessing multiple measurements to validate and interpret the program effectiveness. The early years hold promise as a time in which obesity prevention may be most effective. To our knowledge, this longitudinal RCT is the first attempt to demonstrate whether an early, long-term, targeted health promotion program focusing on healthy

  18. Lipoxin A₄ prevents the progression of de novo and established endometriosis in a mouse model by attenuating prostaglandin E₂ production and estrogen signaling.

    Directory of Open Access Journals (Sweden)

    Rajesh Kumar

    Full Text Available Endometriosis, a leading cause of pelvic pain and infertility, is characterized by ectopic growth of endometrial-like tissue and affects approximately 176 million women worldwide. The pathophysiology involves inflammatory and angiogenic mediators as well as estrogen-mediated signaling and novel, improved therapeutics targeting these pathways are necessary. The aim of this study was to investigate mechanisms leading to the establishment and progression of endometriosis as well as the effect of local treatment with Lipoxin A4 (LXA₄, an anti-inflammatory and pro-resolving lipid mediator that we have recently characterized as an estrogen receptor agonist. LXA₄ treatment significantly reduced endometriotic lesion size and downregulated the pro-inflammatory cytokines IL-1β and IL-6, as well as the angiogenic factor VEGF. LXA₄ also inhibited COX-2 expression in both endometriotic lesions and peritoneal fluid cells, resulting in attenuated peritoneal fluid Prostaglandin E₂ (PGE₂ levels. Besides its anti-inflammatory effects, LXA₄ differentially regulated the expression and activity of the matrix remodeling enzyme matrix metalloproteinase (MMP-9 as well as modulating transforming growth factor (TGF-β isoform expression within endometriotic lesions and in peritoneal fluid cells. We also report for first time that LXA₄ attenuated aromatase expression, estrogen signaling and estrogen-regulated genes implicated in cellular proliferation in a mouse model of disease. These effects were observed both when LXA₄ was administered prior to disease induction and during established disease. Collectively, our findings highlight potential targets for the treatment of endometriosis and suggest a pleotropic effect of LXA₄ on disease progression, by attenuating pro-inflammatory and angiogenic mediators, matrix remodeling enzymes, estrogen metabolism and signaling, as well as downstream proliferative pathways.

  19. Does testosterone prevent early postoperative complications after gastrointestinal surgery?

    Institute of Scientific and Technical Information of China (English)

    Birendra Kumar Sah; Ming-Min Chen; Yi-Bing Peng; Xiao-Jing Feng; Min Yan; Bing-Ya Liu; Qi-Shi Fan; Zheng-Gang Zhu

    2009-01-01

    AIM: To investigate the role of sex hormones in the early postoperative complications of gastrointestinal diseases.METHODS: A total of 65 patients who underwent operations for gastric and colorectal diseases (mainly malignant diseases) were included in the study.Peripheral venous blood samples were collected at different times for analysis of estradiol, testosterone and progesterone. The only study endpoint was analysis of postoperative complications.RESULTS: Patients of both sexes were uniform but postoperative complication rate was significantly higher in female patients ( P = 0.027). There was no significant association of estradiol and progesterone with postoperative complications. Testosterone levels in complicated patients were significantly lower than in uncomplicated patients ( P < 0.05). Area under the receiver operating characteristic curve showed that a lower value of testosterone was a predictor for higher complication rate ( P < 0.05), and a lower value of testosterone at later times after surgery was a better predictor of complications.CONCLUSION: Patients with low testosterone level were prone to higher postoperative complications, which was evident in both sexes. However, further studies are necessary to support this result.

  20. Early prevention of the antisocial behaviour of youth: situation in Latvia

    Directory of Open Access Journals (Sweden)

    Ilona Kronberga

    2015-09-01

    Full Text Available Public opinion on prevention is often very narrow and stigmatised: the concept of prevention is more often related to a crime than to antisocial behaviour. Often such approach limits not only the understanding of the usability and content of prevention methods but also the age of children at which a successful use of these methods is acceptable. Due to the aforementioned, it is possible to put forward a hypothesis: successful prevention of antisocial behaviour in the work with children at a young age decreases the necessity of crime prevention in later years of children and youth development. Therefore, this publication will focus on the use and practice of prevention methods in the early period of child development – pre-school and primary school.

  1. Estrogen and estrogen receptors in cardiovascular oxidative stress.

    Science.gov (United States)

    Arias-Loza, Paula-Anahi; Muehlfelder, Melanie; Pelzer, Theo

    2013-05-01

    The cardiovascular system of a premenopausal woman is prepared to adapt to the challenges of increased cardiac output and work load that accompany pregnancy. Thus, it is tempting to speculate whether enhanced adaptability of the female cardiovascular system might be advantageous under conditions that promote cardiovascular disease. In support of this concept, 17β-estradiol as the major female sex hormone has been shown to confer protective cardiovascular effects in experimental studies. Mechanistically, these have been partially linked to the prevention and protection against oxidative stress. Current evidence indicates that estrogens attenuate oxidative stress at two levels: first, by preventing generation of reactive oxygen species (ROS) and, second, by scavenging ROS in the myocardium and in the vasculature. The purpose of this review is to give an overview on current concepts on conditions and mechanisms by which estrogens protect the cardiovascular system against ROS-mediated cellular injury.

  2. An update for the obstetrician-gynecologist on advances in the diagnosis, prevention, and treatment of postmenopausal osteoporosis.

    Science.gov (United States)

    Ettinger, B

    1993-06-01

    Improvements in bone densitometry and new biochemical tests allow early detection and prevention of postmenopausal bone loss. Interventions for osteoporosis-prone women include correction of adverse habits and lifestyles, optimization of calcium and vitamin D intake, and prescription of estrogen. Recent studies indicate that elderly women may still obtain significant benefit from estrogen. Calcitonin is an approved alternative to estrogen, and recent studies confirm its ability to prevent bone loss and fractures, even when administered intranasally. This review also summarizes clinical investigation of newer, yet unapproved, methods of treatment; the most promising of these treatments are the bisphosphonates, fluoride, and tamoxifen.

  3. Expression of the IGF and the aromatase/estrogen receptor systems in human adrenal tissues from early infancy to late puberty: implications for the development of adrenarche.

    Science.gov (United States)

    Belgorosky, Alicia; Baquedano, María Sonia; Guercio, Gabriela; Rivarola, Marco A

    2009-03-01

    Adrenarche is a process of postnatal sexual maturation occurring in higher primates, in which there is an increase in the secretion of adrenal androgens. It is the consequence of a process of postnatal organogenesis characterized by the development of a new zone in the adrenal cortex, the zona reticularis (ZR). The mechanism of this phenomenon remains poorly understood, suggesting that it might be a multifactorial event. A relationship between circulating IGF-I, insulin sensitivity, and adrenal androgens has been postulated. Boys and girls have different patterns of changes in insulin sensitivity at puberty, perhaps secondary to differences in the estrogen milieu. Estrogen effects may also play a role in premature adrenarche. Peripheral or local IGF-1 actions could regulate adrenal progenitor cell proliferation and migration. Since adrenal progenitor cells as well as IGF-I and the IGF-R1 are located in the outer zone of the adrenal cortex during childhood and adolescence, this peripheral cell layer, below the capsule, may contain undifferentiated progenitor cells. Therefore, the IGF-R1 signaling pathway might positively modulate the proliferation and migration of adrenal progenitor cell to stimulate the development of adrenal zones, including ZR. However, no evidence of a direct action of IGF-I on ZR was found. In addition, a role for estrogens in the ontogenesis of ZR is suggested by the presence of aromatase (CYP19) in the subcapsular zona glomerulosa and in the adrenal medulla. Estrogens produced locally could act on ZR by interacting with estrogen receptor beta (ERbeta), but not alpha, and membrane estrogen receptor GPR-30. An estradiol-induced increase in DHEA/cortisol ratio was indeed seen in cultures of adrenocortical cells from post-adrenarche adrenals. In summary, several lines of evidence point to the action of multiple factors, such as local adrenal maturational changes and peripheral metabolic signals, on postnatal human adrenal gland ZR formation.

  4. Estrogen Receptor β Activation Rapidly Modulates Male Sexual Motivation through the Transactivation of Metabotropic Glutamate Receptor 1a.

    Science.gov (United States)

    Seredynski, Aurore L; Balthazart, Jacques; Ball, Gregory F; Cornil, Charlotte A

    2015-09-23

    In addition to the transcriptional activity of their liganded nuclear receptors, estrogens, such as estradiol (E2), modulate cell functions, and consequently physiology and behavior, within minutes through membrane-initiated events. The membrane-associated receptors (mERs) underlying the acute effects of estrogens on behavior have mostly been documented in females where active estrogens are thought to be of ovarian origin. We determined here, by acute intracerebroventricular injections of specific agonists and antagonists, the type(s) of mERs that modulate rapid effects of brain-derived estrogens on sexual motivation in male Japanese quail. Brain aromatase blockade acutely inhibited sexual motivation. Diarylpropionitrile (DPN), an estrogen receptor β (ERβ)-specific agonist, and to a lesser extent 17α-estradiol, possibly acting through ER-X, prevented this effect. In contrast, drugs targeting ERα (PPT and MPP), GPR30 (G1 and G15), and the Gq-mER (STX) did not affect sexual motivation. The mGluR1a antagonist LY367385 significantly inhibited sexual motivation but mGluR2/3 and mGluR5 antagonists were ineffective. LY367385 also blocked the behavioral restoration induced by E2 or DPN, providing functional evidence that ERβ interacts with metabotropic glutamate receptor 1a (mGluR1a) signaling to acutely regulate male sexual motivation. Together these results show that ERβ plays a key role in sexual behavior regulation and the recently uncovered cooperation between mERs and mGluRs is functional in males where it mediates the acute effects of estrogens produced centrally in response to social stimuli. The presence of an ER-mGluR interaction in birds suggests that this mechanism emerged relatively early in vertebrate history and is well conserved. Significance statement: The membrane-associated receptors underlying the acute effects of estrogens on behavior have mostly been documented in females, where active estrogens are thought to be of ovarian origin. Using acute

  5. Changes in uterine secretion of prostaglandin F2 alpha in response to oxytocin during the estrous cycle, early pregnancy, and estrogen-induced pseudopregnancy in swine.

    Science.gov (United States)

    Edgerton, L A; Kaminski, M A; Silvia, W J

    1996-09-01

    .02). Similar relationships were apparent for the AUC. These results demonstrate that uterine secretory responsiveness to oxytocin is suppressed during early pregnancy and that this effect may be mediated through estrogen secreted by conceptuses.

  6. HIV treatment as prevention: debate and commentary--will early infection compromise treatment-as-prevention strategies?

    Directory of Open Access Journals (Sweden)

    Myron S Cohen

    Full Text Available Universal HIV testing and immediate antiretroviral therapy for infected individuals has been proposed as a way of reducing the transmission of HIV and thereby bringing the HIV epidemic under control. It is unclear whether transmission during early HIV infection--before individuals are likely to have been diagnosed with HIV and started on antiretroviral therapy--will compromise the effectiveness of treatment as prevention. This article presents two opposing viewpoints by Powers, Miller, and Cohen, and Williams and Dye, followed by a commentary by Fraser.

  7. Identifying target groups for the prevention of depression in early adolescence : The TRAILS study

    NARCIS (Netherlands)

    Monshouwer, K.; Smit, F.; Ruiter, M.; Ormel, Johan; Verhulst, F.; Vollebergh, W.; Oldehinkel, T.

    Background: Depression in adolescence is associated with long-term adverse consequences. The aim of the present study is to identify target groups at increased risk of developing depression in early adolescence, such that prevention is associated with the largest health benefit at population-level

  8. Cross-National Perspectives on Early Adolescence: Implications and Strategies for Public Health Prevention and Interventions

    Science.gov (United States)

    Swahn, Monica H.

    2012-01-01

    The current special issue brings together intriguing and important cross-country comparisons of issues pertinent to early adolescence that can inform the design and implementation of broader and relevant public health prevention strategies. The findings illustrate the importance of cross-country analyses for better understanding a range of…

  9. Evidence of Effectiveness of Current Therapies to Prevent and Treat Early Childhood Caries

    DEFF Research Database (Denmark)

    Twetman, Svante; Dhar, Vineet

    2015-01-01

    PURPOSE: The purpose of this paper was to systematically review the quality of evidence related to self-applied and professionally applied fluorides, antimicrobial agents, fissure sealants, temporary restorations, and restorative care for the prevention and management of early childhood caries (E...

  10. Obesity Prevention Interventions in Early Childhood Education and Care Settings with Parental Involvement: A Systematic Review

    Science.gov (United States)

    Morris, Heather; Skouteris, Helen; Edwards, Susan; Rutherford, Leonie

    2015-01-01

    Partnering early childhood education and care (ECEC) and the home together may be more effective in combating obesogenic risk factors in preschool children. Thus, an evaluation of ECEC obesity prevention interventions with a parental component was conducted, exploring parental engagement and its effect on obesity and healthy lifestyle outcomes. A…

  11. Obesity Prevention Interventions in Early Childhood Education and Care Settings with Parental Involvement: A Systematic Review

    Science.gov (United States)

    Morris, Heather; Skouteris, Helen; Edwards, Susan; Rutherford, Leonie

    2015-01-01

    Partnering early childhood education and care (ECEC) and the home together may be more effective in combating obesogenic risk factors in preschool children. Thus, an evaluation of ECEC obesity prevention interventions with a parental component was conducted, exploring parental engagement and its effect on obesity and healthy lifestyle outcomes. A…

  12. Early preventive treatment for severe acute pancreatitis combined with lung injury

    Institute of Scientific and Technical Information of China (English)

    刘学民; 刘青光; 潘承恩

    2002-01-01

    @@ Severe acute pancreatitis (SAP) can cause systematic inflammatory response syndrome (SIRS),which leads to injury or failure of the internal organs and systems.1 Among them,acute respiratory distress syndrome(ARDS)is a severe or fatal complication.In this article,the early preventive treatment for SAP combined with lung injure is studied.

  13. Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis.

    Science.gov (United States)

    Lewiecki, E Michael

    2007-10-01

    Bazedoxifene acetate (WAY-140424; TSE-424) is an investigational non-steroidal indole-based selective estrogen receptor modulator (SERM) - also classified as an estrogen agonist/antagonist - that is being developed as a daily oral drug for the prevention and treatment of postmenopausal osteoporosis (PMO). Clinical studies have shown favorable effects on the skeleton, with prevention of bone loss in postmenopausal women without osteoporosis and reduction in vertebral fracture risk in women with PMO, without stimulation of endometrium or breast. Bazedoxifene combined with conjugated estrogens is an investigational tissue-selective estrogen complex, the first in a new class of therapeutic agents that pairs a selective estrogen receptor modulator with estrogens. Clinical trials with bazedoxifene/conjugated estrogens in postmenopausal women have shown skeletal benefit with improvement in menopausal vasomotor symptoms and little or no stimulation of endometrial or breast tissue. Bazedoxifene/conjugated estrogens is a potential agent for the prevention of PMO and control of menopausal symptoms.

  14. Estrogens, inflammation and cognition.

    Science.gov (United States)

    Au, April; Feher, Anita; McPhee, Lucy; Jessa, Ailya; Oh, Soojin; Einstein, Gillian

    2016-01-01

    The effects of estrogens are pleiotropic, affecting multiple bodily systems. Changes from the body's natural fluctuating levels of estrogens, through surgical removal of the ovaries, natural menopause, or the administration of exogenous estrogens to menopausal women have been independently linked to an altered immune profile, and changes to cognitive processes. Here, we propose that inflammation may mediate the relationship between low levels of estrogens and cognitive decline. In order to determine what is known about this connection, we review the literature on the cognitive effects of decreased estrogens due to oophorectomy or natural menopause, decreased estrogens' role on inflammation--both peripherally and in the brain--and the relationship between inflammation and cognition. While this review demonstrates that much is unknown about the intersection between estrogens, cognition, inflammation, we propose that there is an important interaction between these literatures.

  15. Estrogenic effects of nonylphenol and octylphenol isomers in vitro by recombinant yeast assay (RYA) and in vivo with early life stages of zebrafish.

    Science.gov (United States)

    Puy-Azurmendi, E; Olivares, A; Vallejo, A; Ortiz-Zarragoitia, M; Piña, B; Zuloaga, O; Cajaraville, M P

    2014-01-01

    Commercial OP and NP are complex isomer mixtures that can be individually present in the environment, showing different estrogenic potencies. The aims of this study were to establish the estrogenic potency of some AP isomers in comparison to the commercial NP (cNP) mixture in vitro and to investigate in vivo their possible effects during the embryo and larval development of zebrafish. An in vitro estrogen receptor-based recombinant yeast assay was used to test the estrogenicity of specific AP isomers (22-OP, 33-OP, 22-NP, 33-NP and 363-NP) and cNP. The EC₅₀ was in the range of 0.6-7.7 mg/L. Both OP isomers and 363-NP exhibited higher estrogenic activity than cNP. For in vivo experiments, one-day postfertilisation (dpf) embryos were exposed to cNP (50, 250 and 500 μg/L), 363-NP and 33-OP (50 μg/L), 17β-estradiol (100 ng/L) and DMSO (0.01% v/v) for 4weeks. After exposure fish were maintained for 2 weeks in clean water in order to evaluate a possible recovery. Fish of groups exposed to cNP and 363-NP were the last to hatch. Histological alterations were not observed after 7, 28 or 42 dpf. Exposure to 33-OP increased transcriptional levels of erα, vtg and cyp19a1b genes. However, transcriptional response in E2 exposure was observed at later stages and with higher fold induction levels. Exposure to cNP decreased levels of erα whereas increased levels of rxrγ and cyp19a1b. Exposure to 363-NP did not cause changes in transcriptional levels of studied genes. The differences in response of the OP isomer compared to the NP isomer in zebrafish could be related to the rapid decay in concentration of the latter.

  16. N1-Guanyl-1,7-Diaminoheptane Sensitizes Estrogen Receptor Negative Breast Cancer Cells to Doxorubicin by Preventing Epithelial-Mesenchymal Transition through Inhibition of Eukaryotic Translation Initiation Factor 5A2 Activation

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2015-08-01

    Full Text Available Background: Approximately 30% of breast cancer does not express the estrogen receptor (ER, which is necessary for endocrine-based therapy approaches. Many studies demonstrated that eukaryotic translation initiation factor 5A2 (eIF5A2 serves as a proliferation-related oncogene in tumorigenic processes. Methods: The present study used cell viability assays, EdU incorporation assays, western blot, and immunofluorescence to explore whether N1-guanyl-1,7-diaminoheptane (GC7, which inhibits eIF5A2 activation, exerts synergistic cytotoxicity with doxorubicin in breast cancer. Results: We found that GC7 enhanced doxorubicin cytotoxicity in ER-negative HCC1937 cells but had little effect in ER-positive MCF-7 and Bcap-37 cells. Administration of GC7 reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT in ER-negative breast cancer cells. Knockdown of eIF5A2 by siRNA inhibited the doxorubicin-induced EMT in ER-negative HCC1937 cells. Conclusion: These data demonstrated that GC7 combination therapy may enhance the therapeutic efficacy of doxorubicin in estrogen negative breast cancer cells by preventing EMT through inhibition of eIF5A2 activation.

  17. [Estrogen replacement].

    Science.gov (United States)

    Søgaard, A J; Berntsen, G K; Magnus, J H; Tollan, A

    1998-02-10

    Recent research on long-term postmenopausal hormone replacement therapy (HRT) indicates a positive effect on both total mortality and morbidity. This has raised the question of widespread preventive long-term use of HRT. Possible side-effects and ideological issues related to preventive HRT have led to debate and uncertainty among health professionals, in the media, and in the population at large. In order to evaluate the level of knowledge about and attitudes towards HRT, a randomly selected group of 737 Norwegian women aged 16-79 was interviewed by the Central Bureau of Statistics. One in three women had received information about HRT in the last two years, mainly through weekly magazines and physicians. The proportion who answered the questions on knowledge correctly varied from 36% to 47%. Those who had been given information by a physician possessed accurate knowledge, had more positive attitudes towards HRT and were more willing to use HRT than women who had reviewed information through other channels. Women with a higher level of education were better informed and more knowledgeable than others, but were nevertheless more reluctant to use HRT than those who were less educated. The limited number of women who actually receive information on HRT, the low level of knowledge and the ambivalent attitudes toward HRT are a major challenge to the public health service.

  18. Economic Evaluation of Obesity Prevention in Early Childhood: Methods, Limitations and Recommendations

    Science.gov (United States)

    Döring, Nora; Mayer, Susanne; Rasmussen, Finn; Sonntag, Diana

    2016-01-01

    Despite methodological advances in the field of economic evaluations of interventions, economic evaluations of obesity prevention programmes in early childhood are seldom conducted. The aim of the present study was to explore existing methods and applications of economic evaluations, examining their limitations and making recommendations for future cost-effectiveness assessments. A systematic literature search was conducted using PubMed, Cochrane Library, the British National Health Service Economic Evaluation Databases and EconLit. Eligible studies included trial-based or simulation-based cost-effectiveness analyses of obesity prevention programmes targeting preschool children and/or their parents. The quality of included studies was assessed. Of the six studies included, five were intervention studies and one was based on a simulation approach conducted on secondary data. We identified three main conceptual and methodological limitations of their economic evaluations: Insufficient conceptual approach considering the complexity of childhood obesity, inadequate measurement of effects of interventions, and lack of valid instruments to measure child-related quality of life and costs. Despite the need for economic evaluations of obesity prevention programmes in early childhood, only a few studies of varying quality have been conducted. Moreover, due to methodological and conceptual weaknesses, they offer only limited information for policy makers and intervention providers. We elaborate reasons for the limitations of these studies and offer guidance for designing better economic evaluations of early obesity prevention. PMID:27649218

  19. In vitro prevention of Pseudomonas aeruginosa early biofilm formation with antibiotics used in cystic fibrosis patients.

    Science.gov (United States)

    Fernández-Olmos, Ana; García-Castillo, María; Maiz, Luis; Lamas, Adelaida; Baquero, Fernando; Cantón, Rafael

    2012-08-01

    The ability of antibiotics used in bronchopulmonary infections in cystic fibrosis (CF) patients to prevent Pseudomonas aeruginosa early biofilm formation was studied using a biofilm microtitre assay with 57 non-mucoid P. aeruginosa isolates (44 first colonisers and 13 recovered during the initial intermittent colonisation stage) obtained from 35 CF patients. Minimum biofilm inhibitory concentrations (BICs) of levofloxacin, ciprofloxacin, imipenem, ceftazidime, tobramycin, colistin and azithromycin were determined by placing a peg lid with a formed biofilm onto microplates containing antibiotics. A modification of this protocol consisting of antibiotic challenge during biofilm formation was implemented in order to determine the biofilm prevention concentration (BPC), i.e. the minimum concentration able to prevent biofilm formation. The lowest BPCs were for fluoroquinolones, tobramycin and colistin and the highest for ceftazidime and imipenem. The former antibiotics had BPCs identical to or only slightly higher than their minimum inhibitory concentrations (MICs) determined by standard Clinical and Laboratory Standards Institute (CLSI) microdilution and were also active on formed biofilms as reflected by their low BIC values. In contrast, ceftazidime and imipenem were less effective for prevention of biofilm formation and on formed biofilms. In conclusion, the new BPC parameter determined in non-mucoid P. aeruginosa isolates recovered during early colonisation stages in CF patients supports early aggressive antimicrobial treatment guidelines in first P. aeruginosa-colonised CF patients. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  20. Effects of early prevention programs on adult criminal offending: a meta-analysis.

    Science.gov (United States)

    Deković, Maja; Slagt, Meike I; Asscher, Jessica J; Boendermaker, Leonieke; Eichelsheim, Veroni I; Prinzie, Peter

    2011-06-01

    This meta-analysis investigated the long term effects of prevention programs conducted during early and middle childhood on criminal offending during adulthood. The analyses included 3611 participants in 9 programs. The effect size for adult criminal offending was significant, but small in magnitude (OR=1.26; 95% CI=1.06-1.50, p=.011). The effects of the programs on positive outcomes (academic attainment and involvement in productive activity, such as being engaged in school or work) were somewhat larger and more consistent than effects on crime (OR=1.36, 95% CI=1.20-1.55, p<.001). Several participant and program characteristics moderated the effectiveness of (early) prevention. Children who were more at-risk and those from a lower SES benefited more. Shorter, but more intensive programs, and programs that focus on social and behavioral skills, rather than on academic skills or family support, tend to produce larger effects. Taken together, these results indicate that early prevention programs can help put children on a more positive developmental trajectory that is maintained into adulthood, but there is still no convincing evidence that they can prevent adult crime. Implications of the findings for research, policy and clinical practice are discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Economic Evaluation of Obesity Prevention in Early Childhood: Methods, Limitations and Recommendations

    Directory of Open Access Journals (Sweden)

    Nora Döring

    2016-09-01

    Full Text Available Despite methodological advances in the field of economic evaluations of interventions, economic evaluations of obesity prevention programmes in early childhood are seldom conducted. The aim of the present study was to explore existing methods and applications of economic evaluations, examining their limitations and making recommendations for future cost-effectiveness assessments. A systematic literature search was conducted using PubMed, Cochrane Library, the British National Health Service Economic Evaluation Databases and EconLit. Eligible studies included trial-based or simulation-based cost-effectiveness analyses of obesity prevention programmes targeting preschool children and/or their parents. The quality of included studies was assessed. Of the six studies included, five were intervention studies and one was based on a simulation approach conducted on secondary data. We identified three main conceptual and methodological limitations of their economic evaluations: Insufficient conceptual approach considering the complexity of childhood obesity, inadequate measurement of effects of interventions, and lack of valid instruments to measure child-related quality of life and costs. Despite the need for economic evaluations of obesity prevention programmes in early childhood, only a few studies of varying quality have been conducted. Moreover, due to methodological and conceptual weaknesses, they offer only limited information for policy makers and intervention providers. We elaborate reasons for the limitations of these studies and offer guidance for designing better economic evaluations of early obesity prevention.

  2. First Consensus on Primary Prevention and Early Intervention in Aesthetic Medicine.

    Science.gov (United States)

    Landau, Marina; Anand, Chytra V; Besins, Thierry; Chao, Yates Yen Yu; Fabi, Sabrina Guillen; Gout, Uliana; Kerscher, Martina; Pavicic, Tatjana; Peng, Peter Hsien Li; Rzany, Berthold; Sattler, Gerhard; Tiryaki, Tunk; Waldorf, Heidi A; Braz, Andre

    2017-09-01

    Facial aging is a complex interplay of extrinsic and intrinsic factors leading to progressive changes in the skin, subcutaneous tissue, and bone. Clinical experience suggests that early aesthetic intervention may slow the signs of aging, but treatment in the absence of symptoms or with minimal signs of aging has not yet been properly addressed. To provide treatment recommendations for primary prevention and early intervention in individuals with no or minimal signs of aging. Fourteen specialists in aesthetic medicine convened over a full-day meeting under the guidance of a certified moderator. Tailored treatment recommendations have been provided for prevention and early intervention of fine wrinkles, static lines and folds, irregular pigmentation, laxity, and subcutaneous volume loss by protecting the epidermis, stimulating neocollagenesis, reducing hyperkinetic musculature, and reinforcing supporting structures. Preventive measures and early therapeutic interventions that may alter the course of facial aging were defined. Further studies are needed to support these recommendations with the best possible evidence. J Drugs Dermatol. 2017;16(9):846-854..

  3. Prevention of postmenopausal bone loss: six-year results from the Early Postmenopausal Intervention Cohort Study

    DEFF Research Database (Denmark)

    McClung, Michael R; Wasnich, Richard D; Hosking, David J;

    2004-01-01

    We report the effect of continuous treatment with alendronate for 6 yr vs. placebo in the Early Postmenopausal Intervention Cohort study. A total of 1609 healthy, early postmenopausal women were recruited; we describe results for the 585 women who received continuous placebo or alendronate (2.5 o.......5 mg alendronate, or 5 mg alendronate daily, respectively. Therapy with alendronate is an effective and promising strategy for the prevention of postmenopausal osteoporosis.......We report the effect of continuous treatment with alendronate for 6 yr vs. placebo in the Early Postmenopausal Intervention Cohort study. A total of 1609 healthy, early postmenopausal women were recruited; we describe results for the 585 women who received continuous placebo or alendronate (2...

  4. Role of fluoride varnish in preventing early childhood caries: A systematic review.

    Science.gov (United States)

    Mishra, Poulami; Fareed, Nusrath; Battur, Hemant; Khanagar, Sanjeev; Bhat, Manohar A; Palaniswamy, Jagan

    2017-01-01

    Early childhood caries is a public health problem that continues to affect babies and preschool children worldwide. This untreated caries process results in progressive destruction of the crowns of the teeth, often accompanied by severe pain and suffering, affecting the quality of life. Fluoride varnish which is one of the most important materials to prevent ECC is easy to apply and well tolerated by children. This study aimed to evaluate the scientific evidence regardingthe role of fluoride varnish in preventing early childhood caries. Records were searched from various databases such as PubMed/Medline, Cochrane, and EMBASE. Articles published over the past 36 years (1979-2015) were identified using the key search terms. A total of 190 records were identified by title/abstracts/full text articles and were retrieved. Potentially relevant reports identified from the reference lists of relevant studies, review articles and chapters were hand-searched, which yielded an additional 10 articles. The main outcome of our investigation was prevention of early childhood caries following application of fluoride varnish and unavoidable fluoride exposure. Out of 190 articles originally identified, 30 records were considered potentially eligible and sought for further assessment. 17 articles met the inclusion criteria and these studies were assessed independently for methodology and performance. Analysis of literature revealed that basically two concentrations of fluoride varnishes have been used: 1% and 5%, with a caries preventive fraction ranges of 6.4-30% and 5-63%, respectively. The results showed that fluoride varnishes have been used at concentrations of 1% and 5% in the prevention of ECC. The preventive fraction was influenced by the frequency of application, the duration of study and sample size. The evidence level of the studies was of moderate to limited value.

  5. Preventing Posttraumatic Stress Related to Sexual Assault Through Early Intervention: A Systematic Review.

    Science.gov (United States)

    Dworkin, Emily R; Schumacher, Julie A

    2016-09-28

    Sexual assault survivors come into contact with a variety of community responders after assault, and these interactions may play an important role in mitigating distress. Given theoretical understandings of the importance of early experiences in the development of posttraumatic stress (PTS), early contact with formal systems (e.g., health care, criminal justice, social services) and informal responders (e.g., friends, family) might be particularly important in preventing PTS. However, the effectiveness of these early interventions is unclear. Understanding the key elements of early interventions, both formal and informal, that successfully prevent the development of PTS could help to improve community responses to sexual assault and ultimately promote survivor well-being. In this systematic review, we investigate the types of experiences with responders in the early aftermath of assault that are associated with PTS, the duration of effects on PTS, and the role of the timing of these responses in the development of PTS. Findings indicate that responder contact alone is not typically associated with significant differences in PTS, and there is insufficient evidence to indicate that the timing of seeking help is associated with PTS, but the quality of services provided and perceptions of interactions with certain responders appear to be associated with PTS. Although many effects were short-lived, interventions that were perceived positively may be associated with lower PTS up to a year postassault. These findings support the importance of offering best practice interventions that are perceived positively, rather than simply encouraging survivors to seek help.

  6. Extra-gonadal sites of estrogen biosynthesis and function.

    Science.gov (United States)

    Barakat, Radwa; Oakley, Oliver; Kim, Heehyen; Jin, Jooyoung; Ko, CheMyong Jay

    2016-09-01

    Estrogens are the key hormones regulating the development and function of reproductive organs in all vertebrates. Recent evidence indicates that estrogens play important roles in the immune system, cancer development, and other critical biological processes related to human well-being. Obviously, the gonads (ovary and testis) are the primary sites of estrogen synthesis, but estrogens synthesized in extra- gonadal sites play an equally important role in controlling biological activities. Understanding non-gonadal sites of estrogen synthesis and function is crucial and will lead to therapeutic interventions targeting estrogen signaling in disease prevention and treatment. Developing a rationale targeting strategy remains challenging because knowledge of extra-gonadal biosynthesis of estrogens, and the mechanism by which estrogen activity is exerted, is very limited. In this review, we will summarize recent discoveries of extra-gonadal sites of estrogen biosynthesis and their local functions and discuss the significance of the most recent novel discovery of intestinal estrogen biosynthesis. [BMB Reports 2016; 49(9): 488-496].

  7. Estrogen replacement therapy and cardioprotection: mechanisms and controversies

    Directory of Open Access Journals (Sweden)

    M.T.R. Subbiah

    2002-03-01

    Full Text Available Epidemiological and case-controlled studies suggest that estrogen replacement therapy might be beneficial in terms of primary prevention of coronary heart disease (CHD. This beneficial effect of estrogens was initially considered to be due to the reduction of low density lipoproteins (LDL and to increases in high density lipoproteins (HDL. Recent studies have shown that estrogens protect against oxidative stress and decrease LDL oxidation. Estrogens have direct effects on the arterial tissue and modulate vascular reactivity through nitric oxide and prostaglandin synthesis. While many of the effects of estrogen on vascular tissue are believed to be mediated by estrogen receptors alpha and ß, there is evidence for `immediate non-genomic' effects. The role of HDL in interacting with 17ß-estradiol including its esterification and transfer of esterified estrogens to LDL is beginning to be elucidated. Despite the suggested positive effects of estrogens, two recent placebo-controlled clinical trials in women with CHD did not detect any beneficial effects on overall coronary events with estrogen therapy. In fact, there was an increase in CHD events in some women. Mutations in thrombogenic genes (factor V Leiden, prothrombin mutation, etc. in a subset of women may play a role in this unexpected finding. Thus, the cardioprotective effect of estrogens appears to be more complicated than originally thought and requires more research.

  8. [The diagnosis, treatment and prevention of early stages of cerebral blood flow insufficiency].

    Science.gov (United States)

    Martynov, Iu S; Girich, T I; Kuntsevich, G I; Sokov, E L; Malkova, E V; Borisova, N F; Nozdriukhina, N V; Shuvakhina, N A

    1998-01-01

    Biomicroscopy of bulbar conjuctiva as well as oencephalography were quite informative for discovery of subclinical manifestations of disorders of cerebral circulation (DCC). That conclusion resulted from the observation of 133 patients with early forms of vascular pathology of brain. Besides, to find the early signs, it was also worth while to perform some biochemical studies (coagulogram, studies of both rheologic properties and lipids of blood). In order to establish discirculatory encephalopathy it was also expedient to use ultrasonic dopplerography and electroencephalography. Efficiency of some medical-prophylactic measures (normalization of the diet, weight, muscular activity, administration of antiatherosclerotic drugs) that prevented the progression of aorta's stenosis was also demonstrated.

  9. Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton

    Science.gov (United States)

    Estrogen withdrawal in women due to natural or artificial menopause is followed by rapid bone loss, osteoporosis, and a high fracture risk. Replacement with estrogen prevents this bone loss and reduces the risk of fracture. Estrogen uses two mechanisms to exert this effect: it inhibits bone resorpti...

  10. Prevention of early childhood caries through training in parental toothbrushing and fluoride varnish application

    OpenAIRE

    Jiang, Ming; 姜鸣

    2013-01-01

    Introduction: Early childhood caries (ECC) is common among Hong Kong preschool children. It is a disease caused by dental plaque bacteria and may be controlled by good toothbrushing habits. However, preschool children are often too young to perform effective tothbrushing, and therefore parental toothbrushing is recommended for them. The oral hygiene status of Hong Kong preschool children is usually not good and parental toothbrushing is not common. Fluoride varnish is effective in preventing ...

  11. Home visitation programs: An untapped opportunity for the delivery of early childhood obesity prevention

    Science.gov (United States)

    Salvy, Sarah-Jeanne; de la Haye, Kayla; Galama, Titus; Goran, Michael I.

    2016-01-01

    Background Extant obesity efforts have had limited impact among low-income underserved children, in part because of limitations inherent to existing programs: 1) short duration and low intensity; 2) late timing of implementation, when children are already overweight or obese; 3) intervention delivery limiting their accessibility and sustainability; and 4) failure to address barriers such as a lack of culturally competent services, poverty and housing instability, which interfere with healthy lifestyle changes. Objective This concept paper proposes an innovative model of obesity prevention implemented in infancy and sustained throughout early childhood to address the limitations of current obesity prevention efforts. Specifically, we propose to integrate sustained, weekly, in-home obesity prevention as part of the services already delivered by ongoing Home Visitation Programs, which currently do not target obesity prevention. Conclusion The home visiting structure represents an ideal model for impactful obesity prevention as home visitation programs: (1) already provide comprehensive services to diverse low-income infants and families who are most at risk for obesity and poor health due to socio-economic and structural conditions; (2) services are initiated in infancy and sustained throughout critical developmental periods for the formation of healthy/unhealthy behaviors; and (3) have been in place for more than 40 years, with a widespread presence across the United States and nationwide, which is critical for the scalability and sustainability of obesity prevention. PMID:27911984

  12. Nonsteroidal Anti-Inflammatory Treatment Prevents Delayed Effects of Early Life Stress in Rats

    Science.gov (United States)

    Brenhouse, Heather C.; Andersen, Susan L.

    2017-01-01

    Background Early developmental insults can cause dysfunction within parvalbumin (PVB)-containing interneurons in the prefrontal cortex. The neuropsychiatric disorders associated with such dysfunction might involve neuroinflammatory processes. Cyclooxygenase-2 (COX-2) is a key mediator of inflammation and is therefore a potential target for preventive treatment. Here, we investigated whether the developmental trajectories of PVB expression and COX-2 induction in the prelimbic region of the prefrontal cortex are altered after maternal separation stress in male rats. Methods Male rat pups were separated from their mother and littermates for 4 hours/day between postnatal Days 2 and 20. Western blotting and immunohistochemistry were used to analyze PVB and COX-2 expression in the prefrontal cortex and hippocampus. A separate cohort of animals was treated with a COX-2 inhibitor during preadolescence and analyzed for PVB, COX-2, and working memory performance. Results We demonstrate that maternal separation causes a reduction of PVB and an increase in COX-2 expression in the prefrontal cortex in adolescence, with concurrent working memory deficits. Parvalbumin was not affected earlier in development. Prophylactic COX-2 inhibition preadolescence prevents PVB loss and improves working memory deficits induced by maternal separation. Conclusions These data are the first to show a preventive pharmacological intervention for the delayed effects of early life stress on prefrontal cortex interneurons and working memory. Our results suggest a possible mechanism for the relationship between early life stress and interneuron dysfunction in adolescence. PMID:21679927

  13. [Early detection, prevention and management of renal failure in liver transplantation].

    Science.gov (United States)

    Castells, Lluís; Baliellas, Carme; Bilbao, Itxarone; Cantarell, Carme; Cruzado, Josep Maria; Esforzado, Núria; García-Valdecasas, Juan Carlos; Lladó, Laura; Rimola, Antoni; Serón, Daniel; Oppenheimer, Federico

    2014-10-01

    Renal failure is a frequent complication in liver transplant recipients and is associated with increased morbidity and mortality. A variety of risk factors for the development of renal failure in the pre- and post-transplantation periods have been described, as well as at the time of surgery. To reduce the negative impact of renal failure in this population, an active approach is required for the identification of those patients with risk factors, the implementation of preventive strategies, and the early detection of progressive deterioration of renal function. Based on published evidence and on clinical experience, this document presents a series of recommendations on monitoring RF in LT recipients, as well as on the prevention and management of acute and chronic renal failure after LT and referral of these patients to the nephrologist. In addition, this document also provides an update of the various immunosuppressive regimens tested in this population for the prevention and control of post-transplantation deterioration of renal function.

  14. The educative prevention of the early stage of educationist’s formation.

    Directory of Open Access Journals (Sweden)

    Marta Alfonso Nazco

    2010-04-01

    Full Text Available The article introduces a characterization of the educative prevention stage at the early professional formation process of educacionist in Sancti Spìritus province. The study is done by the indication analysis of assistant, learning, permanence and behavior at youths who course pedagogical carrers, and haven’t expressed a desire stage yet. The main shown results dealt with the assumption of the searching variables and its indicators, the construction of instruments and the definition of aspects concerning the educative prevention at the early stage of educationist’s formation in the selected choosing. Theoretical, empirical and statistical- math, methods were used which were helped by the constructed instruments and the triangulations among them thus arriving to generalizations for the caracterization. The results have better the work at the area project of the educative prevention in adolescents and youths in the territory, witch mainly concern the desing and implementation of actions withing the pedagogical process, foccuse in the integration of institutions, socializer and educative agents functioning to eductive prevention.

  15. Estrogen biosynthesis and action in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Theresia eThalhammer

    2014-11-01

    Full Text Available Ovarian cancer is still the deadliest of all gynecologic malignancies in women worldwide. This is attributed to two main features of these tumors, namely, i a diagnosis at an advanced tumor stage, and, ii the rapid onset of resistance to standard chemotherapy after an initial successful therapy with platin- and taxol-derivatives. Therefore, novel targets for an early diagnosis and better treatment options for these tumors are urgently needed. Epidemiological data show that induction and biology of ovarian cancer is related to life-time estrogen exposure. Also experimental data reveal that ovarian cancer cells share a number of estrogen regulated pathways with other hormone-dependent cancers, e.g. breast and endometrial cancer. However, ovarian cancer is a heterogeneous disease and the subtypes are quite different with respect to mutations, origins, behaviours, markers and prognosis and respond differently to standard chemotherapy. Therefore, a characterization of ovarian cancer subtypes may lead to better treatment options for the various subtypes and in particular for the most frequently observed high-grade serous ovarian carcinoma. For this intention, further studies on estrogen-related pathways and estrogen formation in ovarian cancer cells are warranted. The review gives an overview on ovarian cancer subtypes and explains the role of estrogen in ovarian cancer. Furthermore, enzymes active to synthesize and metabolize estrogens are described and strategies to target these pathways are discussed.

  16. Docosahexaenoic Acid Supplementation Early in Pregnancy May Prevent Deep Placentation Disorders

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    Jorge A. Carvajal

    2014-01-01

    Full Text Available Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction. Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called “deep placentation disorders”; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction.

  17. Opportunities During Early Life for Cancer Prevention: Highlights From a Series of Virtual Meetings With Experts.

    Science.gov (United States)

    Holman, Dawn M; Buchanan, Natasha D

    2016-11-01

    Compelling evidence suggests that early life exposures can affect lifetime cancer risk. In 2014, the Centers for Disease Control and Prevention's (CDC's) Cancer Prevention Across the Lifespan Workgroup hosted a series of virtual meetings with select experts to discuss the state of the evidence linking factors during the prenatal period and early childhood to subsequent risk of both pediatric and adult cancers. In this article, we present the results from a qualitative analysis of the meeting transcripts and summarize themes that emerged from our discussions with meeting participants. Themes included the state of the evidence linking early life factors to cancer risk, research gaps and challenges, the level of evidence needed to support taking public health action, and the challenges of communicating complex, and sometimes conflicting, scientific findings to the public. Opportunities for collaboration among public health agencies and other stakeholders were identified during these discussions. Potential next steps for the CDC and its partners included advancing and building upon epidemiology and surveillance work, developing and using evidence from multiple sources to inform decision-making, disseminating and communicating research findings in a clear and effective way, and expanding collaborations with grantees and other partners. As the science on early life factors and cancer risk continues to evolve, there are opportunities for collaboration to translate science into actionable public health practice.

  18. Primary Prevention of Celiac Disease: Environmental Factors with a Focus on Early Nutrition.

    Science.gov (United States)

    Chmielewska, Anna; Pieścik-Lech, Małgorzata; Szajewska, Hania; Shamir, Raanan

    2015-01-01

    Celiac disease (CD) is a common autoimmune disorder caused by ingestion of gluten. When diagnosed, it should be treated with a lifelong, strict gluten-free diet. Early infant feeding practices have been suggested as a means of preventing CD. In the last few decades, observational data have suggested that breastfeeding, especially at the time of introducing gluten into the infant's diet, as well as the time and mode of gluten first being given to a child could prevent or delay the occurrence of CD. As a result, recommendations advised that it is prudent to avoid both early (months) and late (>7 months) introduction of gluten, and to introduce gluten gradually while the infant is still being breastfed, as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Recently, the results of two large randomized trials have shown that breastfeeding in general, breastfeeding during gluten introduction, and early or delayed gluten introduction do not influence the total risk of CD in genetically predisposed individuals. Introducing gluten at 4 versus 6 months in very small amounts, or at 6 versus 12 months, resulted in similar rates of CD in these children. Thus, early feeding practices seem to have no impact on the risk of developing CD during childhood. In children without the genetic predisposition, the age and mode of gluten introduction do not influence the risk anyway.

  19. Diaphragmatic suture with tubular stomach to prevent early delayed gastric emptying after esophagectomy

    Institute of Scientific and Technical Information of China (English)

    Chao Sun; Weiping Shi; Yusheng Shu; Hongcan Shi; Shichun Lu; Kang Wang

    2015-01-01

    Objective The objective of this study was to evaluate the clinical ef icacy of a diaphragmatic suture with tubular stomach to prevent delayed gastric emptying (DGE) after esophagectomy through the cervico-tho-racoabdominal approach. Methods A total of 980 patients with esophageal cancer undergoing esophagectomy through the cer-vico-thoracoabdominal approach were retrospectively included in this study and divided into two groups. Al patients underwent tubular stomach creation (group A; n = 530) or a diaphragmatic suture and tubular stomach creation (group B; n = 450). The incidence of early DGE was observed. Results The incidence of early DGE in group A was significantly higher than that in group B (P Conclusion This observation study suggests that the use of a diaphragmatic suture with tubular stomach through the cervico-thoracoabdominal approach can decrease the incidence of early DGE after esopha-gectomy.

  20. Long-term use of estrogens: benefit or risk

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    Bogusława Pietrzak

    2015-03-01

    Full Text Available Estrogens are widely used in hormone replacement therapy, gynecology, urogynecology and rarely in dermatology. Non-therapeutic use of estrogens is very widespread. Estrogens are used as contraceptives, which cause a lot of serious side effects. A common clinical problem is skin hyperpigmentation (melasma, occurring mainly in women who take contraceptives with high doses of estrogens. But low doses of estrogens may also cause skin side effects. The mechanism of melasma development is very complicated and not fully understood. It is very likely that UV radiation and genetic background can affect melasma development. Effective therapy should lead to prevention or alleviation of relapses. Treatment should also reduce the area of lesions and improve the appearance of skin. There is no effective and universal pattern of treatment, in which only one substance or method is used. A combination of different methods is used to optimize the therapy. An important role is attributed to prevention, especially protection from UV radiation.

  1. Functional associations between two estrogen receptors, environmental estrogens, and sexual disruption in the roach (Rutilus rutilus).

    Science.gov (United States)

    Katsu, Yoshinao; Lange, Anke; Urushitani, Hiroshi; Ichikawa, Rie; Paull, Gregory C; Cahill, Laura L; Jobling, Susan; Tyler, Charles R; Iguchi, Taisen

    2007-05-01

    Wild male roach (Rutilus rutilus) living in U.K. rivers contaminated with estrogenic effluents from wastewater treatment works show feminized responses and have a reduced reproductive capability, but the chemical causation of sexual disruption in the roach has not been established. Feminized responses were induced in male roach exposed to environmentally relevant concentrations of the pharmaceutical estrogen 17alpha-ethinylestradiol, EE2 (up to 4 ng/ L), during early life (from fertilization to 84 days posthatch, dph), and these effects were signaled by altered patterns of expression of two cloned roach estrogen receptor (ER) subtypes, ERalpha. and ERbeta, in the brain and gonad/ liver. Transactivation assays were developed for both roach ER subtypes and the estrogenic potencies of steroidal estrogens differed markedly at the different ER subtypes. EE2 was by far the most potent chemical, and estrone (E1, the most prevalent environmental steroid in wastewater discharges) was equipotent with estradiol (E2) in activating the ERs. Comparison of the EC50 values for the compounds tested showed that ERbeta was 3-21-fold more sensitive to natural steroidal estrogens and 54-fold more sensitive to EE2 as compared to ERalpha. These findings add substantial support to the hypothesis that steroidal estrogens play a significant role in the induction of intersex in roach populations in U.K. rivers and that the molecular approach described could be usefully applied to understand interspecies sensitivity to xenoestrogens.

  2. Enzymatic treatment of estrogens and estrogen glucuronide

    Institute of Scientific and Technical Information of China (English)

    Takaaki Tanaka; Toshiyuki Tamura; Yuuichi Ishizaki; Akito Kawasaki; Tomokazu Kawase; Masahiro Teraguchi; Masayuki Taniguchi

    2009-01-01

    Natural and synthetic estrogens from sewage treatment systems are suspected to influence the reproductive health of the animals in the rivers.In this article we investigated the enzymatic treatment of three estrogens (estrone,17β-estradiol,and 17α-ethynyletstradiol) by a fungal laccase which oxidize phenolic compounds with dissolved oxygen.The elimination of the estrogenic activities by enzymatic oxidation was demonstrated by medaka vitellogenin assay.In addition,we developed an enzymatic treatment system comprised of β-D-glucuronidase and the laccase for 17β-estradiol 3-(β-D-glucuronide) degradation.The two enzymes eliminated 17β-estradiol 3-(β-D-glucuronide) and the intermediate,17β-estradiol,efficiently.

  3. “Greenlight Study”: A Controlled Trial of Low-Literacy, Early Childhood Obesity Prevention

    Science.gov (United States)

    Perrin, Eliana M.; Yin, H. Shonna; Bronaugh, Andrea; Rothman, Russell L.

    2014-01-01

    Children who become overweight by age 2 years have significantly greater risks of long-term health problems, and children in low-income communities, where rates of low adult literacy are highest, are at increased risk of developing obesity. The objective of the Greenlight Intervention Study is to assess the effectiveness of a low-literacy, primary-care intervention on the reduction of early childhood obesity. At 4 primary-care pediatric residency training sites across the US, 865 infant-parent dyads were enrolled at the 2-month well-child checkup and are being followed through the 24-month well-child checkup. Two sites were randomly assigned to the intervention, and the other sites were assigned to an attention-control arm, implementing the American Academy of Pediatrics' The Injury Prevention Program. The intervention consists of an interactive educational toolkit, including low-literacy materials designed for use during well-child visits, and a clinician-centered curriculum for providing low-literacy guidance on obesity prevention. The study is powered to detect a 10% difference in the number of children overweight (BMI > 85%) at 24 months. Other outcome measures include observed physician–parent communication, as well as parent-reported information on child dietary intake, physical activity, and injury-prevention behaviors. The study is designed to inform evidence-based standards for early childhood obesity prevention, and more generally to inform optimal approaches for low-literacy messages and health literacy training in primary preventive care. This article describes the conceptual model, study design, intervention content, and baseline characteristics of the study population. PMID:24819570

  4. "Greenlight study": a controlled trial of low-literacy, early childhood obesity prevention.

    Science.gov (United States)

    Sanders, Lee M; Perrin, Eliana M; Yin, H Shonna; Bronaugh, Andrea; Rothman, Russell L

    2014-06-01

    Children who become overweight by age 2 years have significantly greater risks of long-term health problems, and children in low-income communities, where rates of low adult literacy are highest, are at increased risk of developing obesity. The objective of the Greenlight Intervention Study is to assess the effectiveness of a low-literacy, primary-care intervention on the reduction of early childhood obesity. At 4 primary-care pediatric residency training sites across the US, 865 infant-parent dyads were enrolled at the 2-month well-child checkup and are being followed through the 24-month well-child checkup. Two sites were randomly assigned to the intervention, and the other sites were assigned to an attention-control arm, implementing the American Academy of Pediatrics' The Injury Prevention Program. The intervention consists of an interactive educational toolkit, including low-literacy materials designed for use during well-child visits, and a clinician-centered curriculum for providing low-literacy guidance on obesity prevention. The study is powered to detect a 10% difference in the number of children overweight (BMI > 85%) at 24 months. Other outcome measures include observed physician-parent communication, as well as parent-reported information on child dietary intake, physical activity, and injury-prevention behaviors. The study is designed to inform evidence-based standards for early childhood obesity prevention, and more generally to inform optimal approaches for low-literacy messages and health literacy training in primary preventive care. This article describes the conceptual model, study design, intervention content, and baseline characteristics of the study population. Copyright © 2014 by the American Academy of Pediatrics.

  5. At the heart of an early psychosis centre: the core components of the 2014 Early Psychosis Prevention and Intervention Centre model for Australian communities.

    Science.gov (United States)

    Hughes, Frank; Stavely, Heather; Simpson, Raelene; Goldstone, Sherilyn; Pennell, Kerryn; McGorry, Patrick

    2014-06-01

    To describe the core components of the Early Psychosis Prevention and Intervention Centre service model as the template agreed with the Australian Federal Government for national upscaling. The Early Psychosis Prevention and Intervention Centre model of early intervention has two main goals: to reduce the period of time between the onset of psychosis and the commencement of treatment and to bring about symptomatic recovery and restore the normal developmental trajectory as early as possible. The Early Psychosis Prevention and Intervention Centre comprises three elements of service provision for young people experiencing a first episode of psychosis: (i) early detection; (ii) acute care during and immediately following a crisis; (iii) recovery-focused continuing care, featuring multimodal interventions to enable the young person to maintain or regain their social, academic and/or career trajectory during the critical first 2-5 years following the onset of a psychotic illness. It does this via a combination of 16 core components, which provide a flexible, comprehensive, integrated service that is able to respond quickly, appropriately and consistently to the individual needs of the young person and their family. Innovative service reforms, such as Early Psychosis Prevention and Intervention Centre, that recognise the value of early intervention are crucial to reducing the impact of serious mental illness on young people and their families and, ultimately, on our society. © The Royal Australian and New Zealand College of Psychiatrists 2014.

  6. Tamoxifen in early-stage estrogen receptor-positive breast cancer: overview of clinical use and molecular biomarkers for patient selection

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    Carmen Criscitiello

    2010-12-01

    Full Text Available Carmen Criscitiello1, Debora Fumagalli1, Kamal S Saini2, Sherene Loi11Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels; 2Breast Data Centre, Institut Jules Bordet, Brussels, BelgiumAbstract: Tamoxifen was the first targeted anticancer agent for breast cancer patients and its effects on reduction of breast cancer events and improvement in overall survival are undisputed. Hence, it has long been considered an essential part of patient care. Recent results of several large adjuvant hormonal trials evaluating the use of aromatase inhibitors in comparison with the previous standard of five years of tamoxifen has led to a paradigm shift, ensuring the inclusion of an aromatase inhibitor as part of standard endocrine therapy for most postmenopausal women diagnosed today with estrogen receptor-positive breast cancer. However, one could argue that despite statistically significant improvements in breast cancer events, an overall survival advantage has not been clear. In this review, we discuss recent genomic and molecular data pertaining to estrogen receptor-positive breast cancer and how this knowledge may aid clinicians to prescribe adjuvant hormonal treatment in the future. A combination of gene expression and genetic aberration markers may be most useful in discerning a population that is still appropriate for adjuvant tamoxifen treatment.Keywords: tamoxifen, aromatase inhibitors, resistance, prediction, mutation, endocrine therapy, PI3K

  7. Early-onset neonatal group B streptococcus sepsis following national risk-based prevention guidelines.

    Science.gov (United States)

    Darlow, Brian A; Voss, Lesley; Lennon, Diana R; Grimwood, Keith

    2016-02-01

    Neonatal infection with group B streptococcus (GBS) is an important cause of infant mortality. Intrapartum antibiotics reduce early-onset GBS sepsis, but recommendations vary as to whether they should be offered following antenatal screening or based on risk factors alone. We aimed to determine the incidence of early-onset GBS sepsis in New Zealand five years after the publication of national risk-based GBS prevention guidelines. Prospective surveillance of early-onset GBS sepsis (defined as infection in the first 48 h of life) was undertaken between April 2009 and March 2011 through the auspices of the New Zealand Paediatric Surveillance Unit as part of a survey of infection presenting in the first week of life. There were 29 cases of confirmed early-onset GBS sepsis, including one case of meningitis, giving an incidence rate of 0.23 per 1000 (95% CI 0.16-0.33) live births. Three infants (10.3%) died. In 16 cases (55%), a maternal risk factor qualifying the mother for intrapartum antibiotics was present, but only five (31%) received this intervention. A retrospective review of the major hospital laboratory databases for this period identified two additional cases. A secondary sensitivity analysis taking account of these cases provided an estimated national incidence of 0.26 (95% CI 0.18-0.37) per 1000 live births. Ten years after a similar survey and five years after promoting a single, risk-based prevention protocol nationally, the incidence of early-onset GBS disease in New Zealand has more than halved, but opportunities remain to further reduce the rate. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  8. Long-term consequences of nutrition and growth in early childhood and possible preventive interventions.

    Science.gov (United States)

    Adair, Linda S

    2014-01-01

    Maternal nutritional deficiencies and excesses during pregnancy, and faster infant weight gain in the first 2 years of life are associated with increased risk of noncommunicable diseases (NCDs) in adulthood. The first 1,000 days of life (from conception until the child reaches age 2 years) represent a vulnerable period for programming of NCD risk, and are an important target for prevention of adult disease. This paper takes a developmental perspective to identify periconception, pregnancy, and infancy nutritional stressors, and to discuss mechanisms through which they influence later disease risk with the goal of informing age-specific interventions. Low- and middle-income countries need to address the dual burden of under- and overnutrition by implementing interventions to promote growth and enhance survival and intellectual development without increasing chronic disease risk. In the absence of good evidence from long-term follow-up of early life interventions, current recommendations for early life prevention of adult disease presume that interventions designed to optimize pregnancy outcomes and promote healthy infant growth and development will also reduce chronic disease risk. These include an emphasis on optimizing maternal nutrition prior to pregnancy, micronutrient adequacy in the preconception period and during pregnancy, promotion of breastfeeding and high-quality complementary foods, and prevention of obesity in childhood and adolescence. © 2014 Nestec Ltd., Vevey/S. Karger AG, Basel.

  9. Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice.

    Science.gov (United States)

    Massaro, Donald; Massaro, Gloria Decarlo

    2004-12-01

    Lung tissue elastic recoil and the dimension and number of pulmonary gas-exchange units (alveoli) are major determinants of gas-exchange function. Loss of gas-exchange function accelerates after menopause in the healthy aged and is progressively lost in individuals with chronic obstructive pulmonary disease (COPD). The latter, a disease of midlife and later, though more common in men than in women, is a disease to which women smokers and never smokers may be more susceptible than men; it is characterized by diminished lung tissue elastic recoil and presently irremediable alveolar loss. Ovariectomy in sexually immature rats diminishes the formation of alveoli, and estrogen prevents the diminution. In the present work, we found that estrogen receptor-alpha and estrogen receptor-beta, the only recognized mammalian estrogen receptors, are required for the formation of a full complement of alveoli in female mice. However, only the absence of estrogen receptor-beta diminishes lung elastic tissue recoil. Furthermore, ovariectomy in adult mice results, within 3 wk, in loss of alveoli and of alveolar surface area without a change of lung volume. Estrogen replacement, after alveolar loss, induces alveolar regeneration, reversing the architectural effects of ovariectomy. These studies 1) reveal estrogen receptors regulate alveolar size and number in a nonredundant manner, 2) show estrogen is required for maintenance of already formed alveoli and induces alveolar regeneration after their loss in adult ovariectomized mice, and 3) offer the possibility estrogen can slow alveolar loss and induce alveolar regeneration in women with COPD.

  10. Usage of Probabilistic and General Regression Neural Network for Early Detection and Prevention of Oral Cancer

    Directory of Open Access Journals (Sweden)

    Neha Sharma

    2015-01-01

    Full Text Available In India, the oral cancers are usually presented in advanced stage of malignancy. It is critical to ascertain the diagnosis in order to initiate most advantageous treatment of the suspicious lesions. The main hurdle in appropriate treatment and control of oral cancer is identification and risk assessment of early disease in the community in a cost-effective fashion. The objective of this research is to design a data mining model using probabilistic neural network and general regression neural network (PNN/GRNN for early detection and prevention of oral malignancy. The model is built using the oral cancer database which has 35 attributes and 1025 records. All the attributes pertaining to clinical symptoms and history are considered to classify malignant and non-malignant cases. Subsequently, the model attempts to predict particular type of cancer, its stage and extent with the help of attributes pertaining to symptoms, gross examination and investigations. Also, the model envisages anticipating the survivability of a patient on the basis of treatment and follow-up details. Finally, the performance of the PNN/GRNN model is compared with that of other classification models. The classification accuracy of PNN/GRNN model is 80% and hence is better for early detection and prevention of the oral cancer.

  11. Usage of Probabilistic and General Regression Neural Network for Early Detection and Prevention of Oral Cancer.

    Science.gov (United States)

    Sharma, Neha; Om, Hari

    2015-01-01

    In India, the oral cancers are usually presented in advanced stage of malignancy. It is critical to ascertain the diagnosis in order to initiate most advantageous treatment of the suspicious lesions. The main hurdle in appropriate treatment and control of oral cancer is identification and risk assessment of early disease in the community in a cost-effective fashion. The objective of this research is to design a data mining model using probabilistic neural network and general regression neural network (PNN/GRNN) for early detection and prevention of oral malignancy. The model is built using the oral cancer database which has 35 attributes and 1025 records. All the attributes pertaining to clinical symptoms and history are considered to classify malignant and non-malignant cases. Subsequently, the model attempts to predict particular type of cancer, its stage and extent with the help of attributes pertaining to symptoms, gross examination and investigations. Also, the model envisages anticipating the survivability of a patient on the basis of treatment and follow-up details. Finally, the performance of the PNN/GRNN model is compared with that of other classification models. The classification accuracy of PNN/GRNN model is 80% and hence is better for early detection and prevention of the oral cancer.

  12. Design and methods for evaluating an early childhood obesity prevention program in the childcare center setting

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    Natale Ruby

    2013-01-01

    Full Text Available Abstract Background Many unhealthy dietary and physical activity habits that foster the development of obesity are established by the age of five. Presently, approximately 70 percent of children in the United States are currently enrolled in early childcare facilities, making this an ideal setting to implement and evaluate childhood obesity prevention efforts. We describe here the methods for conducting an obesity prevention randomized trial in the child care setting. Methods/design A randomized, controlled obesity prevention trial is currently being conducted over a three year period (2010-present. The sample consists of 28 low-income, ethnically diverse child care centers with 1105 children (sample is 60% Hispanic, 15% Haitian, 12% Black, 2% non-Hispanic White and 71% of caregivers were born outside of the US. The purpose is to test the efficacy of a parent and teacher role-modeling intervention on children’s nutrition and physical activity behaviors. . The Healthy Caregivers-Healthy Children (HC2 intervention arm schools received a combination of (1 implementing a daily curricula for teachers/parents (the nutritional gatekeepers; (2 implementing a daily curricula for children; (3 technical assistance with meal and snack menu modifications such as including more fresh and less canned produce; and (4 creation of a center policy for dietary requirements for meals and snacks, physical activity and screen time. Control arm schools received an attention control safety curriculum. Major outcome measures include pre-post changes in child body mass index percentile and z score, fruit and vegetable and other nutritious food intake, amount of physical activity, and parental nutrition and physical activity knowledge, attitudes, and beliefs, defined by intentions and behaviors. All measures were administered at the beginning and end of the school year for year one and year two of the study for a total of 4 longitudinal time points for assessment

  13. Early screening and prevention of preterm preeclampsia with aspirin: time for clinical implementation.

    Science.gov (United States)

    Rolnik, Daniel L; O'Gorman, Neil; Roberge, Stephanie; Bujold, Emmanuel; Hyett, Jonathan; Uzan, Serge; Beaufils, Michel; da Silva Costa, Fabricio

    2017-09-09

    Despite all the research published in the last three decades on screening and prevention of preeclampsia (PE), this condition remains one of the main causes of maternal and perinatal morbidity and mortality, both in low and high-income countries. It affects 2-8% of all pregnancies, being responsible for one out of five maternal deaths and 15% of all premature deliveries(1) . An ideal screening test requires identification of women at high-risk of developing severe and early-onset forms of the disease, a high detection rate (DR) with an acceptable false-positive rate (FPR), and the availability of an effective preventive measure(2) . This article is protected by copyright. All rights reserved.

  14. Early ambulation and prevention of post-operative thrombo-embolic risk.

    Science.gov (United States)

    Talec, P; Gaujoux, S; Samama, C M

    2016-12-01

    The prevention of post-operative risk of venous thrombo-embolism (VTE) is of fundamental importance, but preventive methods have progressed with the introduction of direct oral anticoagulants (DOAC), the development of ambulatory surgery and enhanced recovery programs (ERP) after surgery. Surgery is, inherently a trigger for venous thrombo-embolic disease, as is prolonged immobilization. However, the risk of VTE is very low following ambulatory surgery, especially in this selected population. ERP, consists of a set of measures to optimize the patient's peri-operative management while reducing length of stay, costs and morbidity and mortality; one measure is the encouragement of early ambulation. This will undoubtedly have an impact on the incidence of VTE and lessen the need for prolonged thrombo-prophylaxis.

  15. Conditions of the Implementation of Selected Early Prevention Behaviours by High School Students from Radom

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    Mogiła-Lisowska Jolanta

    2016-10-01

    Full Text Available The specific type of human activities that aim to maintain full health by maintaining biological, psychological and social comfort indicate the need to adopt a holistic perspective in any analysis of determinants of pro-health behaviour. When analysing the aetiology of somatic diseases, it is important to take into account biological and mental well-being as well as the connections between needs, interests and lifestyle decisions and their consequences. One of the measures used to reduce the risk of a progressive lack of immunity to non-infectious diseases is prevention, understood as actions aimed at preventing diseases or other adverse health phenomena by controlling their causes and risk factors. An important component of prevention programmes is preventing the occurrence of negative social behaviour patterns that contribute to the increased risk of diseases. Three basic components of a healthy lifestyle – regular physical activity, proper nutrition and sufficient rest and relaxation (stress management – justify the importance of practising healthy habits from an early age. The role of promoting pro-health behaviours among children and adolescents is of particular importance in the context of increasingly sedentary lifestyles, obesity and weight problems.

  16. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice.

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    David P Funda

    Full Text Available Induction of long-term tolerance to β-cell autoantigens has been investigated both in animal models and in human type 1 diabetes (T1D in order to prevent the disease. As regards external compounds, the dietary plant protein fraction has been associated with high penetrance of the disease, whereas gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n. administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4(+Foxp3(+ T cells and even more significant induction of γδ T cells in mucosal, but not in non-mucosal lymphoid compartments. This prevention strategy was characterized by an increased proportion of IL-10 and a decreased proportion of IL-2, IL-4 and IFN-γ-positive CD4(+Foxp3(+ T cells, and IFN-γ-positive γδ T cells, preferentially in mucosal lymphoid organs. In conclusion, i.n. vaccination with gliadin, an environmental antigen with possible etiological influence in T1D, may represent a novel, safer strategy for prevention or even early cure of T1D.

  17. Maltreatment in early childhood: a scoping review of prevention, detection and treatment

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    Luis Lefio Celedón

    2013-08-01

    Full Text Available Purpose. To identify and synthesize the best available evidence on the effectiveness of interventions for universal prevention, detection and treatment of early childhood maltreatment (0-4 years. Design. Scoping Review. Data sources. MEDLINE, LILACS, PsycINFO, Psyclist, SciELO, ISI Web of Knowledge, Science Direct, EBSCO, EMBASE, Cochrane Library, DARE, Google Scholar and UNICEF Base. Methods. A variety of keywords were used to identify quantitative experimental and observational studies on detection, prevention and treatment strategies in different situations of child maltreatment. Sexual abuse was excluded. The search spanned from 2002 to 2012, in English and Spanish. Results. Of 105 articles, 36 met the selection criteria. In prevention, the best evaluated strategies were parenting programs based on cognitive or cognitive-behavioral approach and interactive learning strategies. In detection, only two instruments were identified with optimum specificity and positive predictive value. In treatment, a variety of treatment strategies were identified with favorable effects on behavioral, functional and psycho affective indicators. The population relevance of these interventions is unclear, as the differential effectiveness of these therapeutic approaches. Conclusions. There are many child maltreatment prevention strategies at the individual and family level. The instruments used for detection are not reliable for use at the collective level. Insofar as therapy, not enough evidence was found both in quality and quantity to favor one intervention over another. It is recommended to understand the problem from the public health perspective and to generate multisectoral and interdisciplinary approaches.

  18. Mexican adolescents’ goals as determinants in the prevention of early pregnancies

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    Erika E Atienzo

    2014-05-01

    Full Text Available Objective. This study aims to explore adolescents’ intentions related to the early formation of a family. Materials and methods. We administered a survey to students in eight schools in Morelos and Mexico City, in 2010. We analyzed intentions of marrying or having a child and fitted an exploratory path model to assess predictors of the intentions of having a child before the age of 20 (n=2974. Results. Around 77% of adolescents expect to have their first child at 20 years or later; 21% show ambivalence or incongruence regarding this, whereas 2% expect to have a child before the age of 20. Parents’ expectations for their child’s education influence the importance that adolescents give to education. The latter promotes the idea of postponing childbearing until 20 years or later (β=0.13. Conclusions. In order to prevent early pregnancies, interventions and programs should encourage the construction of personal and professional goals.

  19. Intravenous calcitriol therapy in an early stage prevents parathyroid gland growth

    Science.gov (United States)

    Taniguchi, Masatomo; Tokumoto, Masanori; Tsuruya, Kazuhiko; Hirakata, Hideki; Iida, Mitsuo

    2008-01-01

    Background. Both the phenotypic alterations of parathyroid (PT) cells, e.g. down-regulation of the calcium-sensing receptor, and the increase of the PT cell number in nodular hyperplasia are the main causes of refractory secondary hyperparathyroidism. It is of great importance to prevent PT growth in an early stage. Methods. To examine a more effective method of calcitriol therapy for the prevention of PT hyperplasia, we randomized haemodialysis patients with mild hyperparathyroidism to receive either daily orally administered calcitriol (n = 33) or intravenous calcitriol (n = 27) over a 12-month study period. Calcitriol was modulated so as to keep the serum intact PTH level between 100 and 150 pg/ml. Results. Both groups showed similar reductions of the serum PTH level and similar increases in serum calcium. In both groups, there were no significant changes in the serum phosphate level. Long-term daily oral calcitriol therapy failed to prevent the increase of both maximum PT volume and total volume, as assessed by ultrasonography; however, intravenous calcitriol therapy successfully suppressed this progression. In the daily, oral group, both the bone-specific alkaline phosphatase (BAP) and the N-telopeptide cross-linked of type I collagen (NTX) significantly decreased, which was probably due to the PTH suppression. However, these bone metabolism markers remained stable in the intravenous group. The total dosage of calcitriol during the study was comparable in both groups. Conclusions. These data indicate that intravenous calcitriol therapy in an early stage of secondary hyperparathyroidism is necessary to prevent PT growth and to keep a good condition of bone metabolism. PMID:18515308

  20. [Early detection and prevention of cancers in various therapeutic areas. Discussion].

    Science.gov (United States)

    Akaza, H; Tsuruo, T; Tsukamoto, T; Noguchi, S; Moriwaki, H; Isonishi, S; Masuda, N; Hinotsu, S; Nash, A F; von Euler, M; Wildin, J; Stribling, D

    1999-10-01

    As illustrated by prostate cancer screening provides an opportunity for early intervention and treatment. However the screening test needs to detect patients with cancer with a low rate of false positives and at a stage which can be treated. Recently the concept of treating patients at high risk of developing breast cancer or suffering a recurrence has been highlighted by the western studies with Nolvadex (tamoxifen). Thus roundtable discussion (held in Tokyo) discussed the different strategies in Japan compared to US & Europe for screening & early intervention/prevention of cancer for breast, prostate, bladder, liver, lung, gynaecological & GI cancers. The range of strategies for cancer screening, how it is funded, whether it is appropriately targeted and whether there is any evidence for a beneficial effect on morbidity or mortality & future prospects for improved sensitivity through new methodology or markers were discussed. Although the relative rates of cancer vary between Japan & the West, the same factors seem to influence cancer development & the data on intervention were seen to be valid. The changing patterns of cancer in Japan suggest a clear opportunity for reducing, the incidence of cancer through lifestyle modification. For some cancers, e.g. cervical & bladder where there is a clear link between abnormal cytology & development cancer true prevention is already practiced. In other cases, preventive treatment is limited by the efficacy of available therapies. As far as drug treatment is concerned, funding of healthcare in Japan does not recognise the concept of prevention although there is, in practice, no barrier to the use of interventions where there is a clear link between biochemical/histological markers & development of cancer.

  1. Core competencies and the prevention of school failure and early school leaving.

    Science.gov (United States)

    Bradshaw, Catherine P; O'Brennan, Lindsey M; McNeely, Clea A

    2008-01-01

    There is an increasing awareness that school failure and early school leaving are processes, rather than discrete events, that often co-occur and can have lasting negative effects on children's development. Most of the literature has focused on risk factors for failure and dropout rather than on the promotion of competencies that can increase youths' likelihood of successfully completing high school. This chapter applies the core competencies framework to the promotion of youths' success within the school environment. We conclude with a brief review of evidence-based prevention strategies that address the five competencies and identify avenues for future research.

  2. Early intervention for preventing posttraumatic stress disorder: an Internet-based virtual reality treatment

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    Sara A. Freedman

    2015-04-01

    Full Text Available Background: Posttraumatic stress disorder (PTSD develops in approximately 20% of people exposed to a traumatic event, and studies have shown that cognitive-behavioral therapy (CBT is effective as a treatment for chronic PTSD. It has also been shown to prevent PTSD when delivered early after a traumatic event. However, studies have shown that uptake of early treatment is generally low, and therefore, the need to provide interventions through other mediums has been identified. The use of technology may overcome barriers to treatment. Objective: This paper describes a randomized controlled trial that will examine an early CBT intervention for PTSD. The treatment incorporates virtual reality (VR as a method for delivering exposure-based elements of the treatment. The intervention is Internet based, such that the therapist and patient will “meet” in a secure online site. This site will also include multi-media components of the treatment (such as videos, audios, VR that can be accessed by the patient between sessions. Method: Two hundred patients arriving to a Level 1 emergency department following a motor vehicle accident will be randomly assigned to either treatment or control groups. Inclusion criteria are age 18–65, PTSD symptoms 2 weeks posttrauma related to current trauma, no suicidality, no psychosis. Patients will be assessed by telephone by a team blind to the study group, on four occasions: before and after treatment, and 6 and 12 months posttreatment. The primary outcome is PTSD symptoms at follow up. Secondary outcomes include depression and cost effectiveness. Analyses will be on an intention-to-treat basis. Discussion: The results will provide more insight into the effects of preventive interventions, in general, and Internet-based early interventions, in particular, on PTSD, in an injured population, during the acute phase after trauma. We will discuss possible strengths and limitations.

  3. Stabilizing ER Ca2+ channel function as an early preventative strategy for Alzheimer's disease.

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    Shreaya Chakroborty

    Full Text Available Alzheimer's disease (AD is a devastating neurodegenerative condition with no known cure. While current therapies target late-stage amyloid formation and cholinergic tone, to date, these strategies have proven ineffective at preventing disease progression. The reasons for this may be varied, and could reflect late intervention, or, that earlier pathogenic mechanisms have been overlooked and permitted to accelerate the disease process. One such example would include synaptic pathology, the disease component strongly associated with cognitive impairment. Dysregulated Ca(2+ homeostasis may be one of the critical factors driving synaptic dysfunction. One of the earliest pathophysiological indicators in mutant presenilin (PS AD mice is increased intracellular Ca(2+ signaling, predominantly through the ER-localized inositol triphosphate (IP(3 and ryanodine receptors (RyR. In particular, the RyR-mediated Ca(2+ upregulation within synaptic compartments is associated with altered synaptic homeostasis and network depression at early (presymptomatic AD stages. Here, we offer an alternative approach to AD therapeutics by stabilizing early pathogenic mechanisms associated with synaptic abnormalities. We targeted the RyR as a means to prevent disease progression, and sub-chronically treated AD mouse models (4-weeks with a novel formulation of the RyR inhibitor, dantrolene. Using 2-photon Ca(2+ imaging and patch clamp recordings, we demonstrate that dantrolene treatment fully normalizes ER Ca(2+ signaling within somatic and dendritic compartments in early and later-stage AD mice in hippocampal slices. Additionally, the elevated RyR2 levels in AD mice are restored to control levels with dantrolene treatment, as are synaptic transmission and synaptic plasticity. Aβ deposition within the cortex and hippocampus is also reduced in dantrolene-treated AD mice. In this study, we highlight the pivotal role of Ca(2+ aberrations in AD, and propose a novel strategy to

  4. The neglected shadow: European perspectives on emotional supports for early school leaving prevention

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    Paul Downes

    2011-11-01

    Full Text Available OECD reports emphasise ten key steps to equity in education, with concrete targets related to low attainment and early school leaving. Such steps, however, neglect the importance of emotional dimensions to early school leaving and the consequent need for system level emotional supports. The current study involves qualitative research interviews with senior government officials and secondary school management representatives across eight European countries, with a particular focus on school climate and emotional support issues. Issues raised by interviewees for students at risk of early school leaving include supports for withdrawn children, for those at risk of suicide and those being bullied at school affecting their nonattendance. Other emerging themes include alternatives to suspension and teacher education for improving their conflict resolution skills. Some interviewees explicitly observe the dearth of emotional support services available in practice in their countries. The pervasive policy gaps across national levels for a mental health and emotional support strategy, as part of an early school leaving prevention strategy, requires serious and immediate attention.

  5. Tissue Specific Effects of Loss of Estrogen During Menopause and Aging

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    Korinna eWend

    2012-02-01

    Full Text Available The roles of estrogens have been best studied in the breast, breast cancers and in the female reproductive tract. However, estrogens have important functions in almost every tissue in the body. Recent clinical trials such as the Women’s Health Initiative have highlighted both the importance of estrogens and how little we know about the molecular mechanism of estrogens in these other tissues. In this review, we illustrate the diverse functions of estrogens in the bone, adipose tissue, skin, hair, brain, skeletal muscle and cardiovascular system, and how the loss of estrogens during aging affects these tissues. Early transcriptional targets of estrogen are reviewed in each tissue. We also describe the tissue-specific effects of selective estrogen receptor modulators (SERMs used for the treatment of breast cancers and post-menopausal symptoms.

  6. Estrogen, schizophrenia and neurodevelopment.

    Science.gov (United States)

    Seeman, Mary V

    2006-07-01

    Women are relatively protected against schizophrenia. The illness has a similar rate in women and men, but it starts later in women and is less severe. It is tempting to attribute this to the neuroprotective effect of estrogen, but the story is not straightforward and contains many unknowns. Women begin their schizophrenia trajectory later in development compared with men and this probably accounts for their relatively superior prognosis. Estrogen agonists are potential therapeutic agents but need to be proven safe, and the timing of administration may be crucial. This article examines what is known about estrogen and the development of schizophrenia.

  7. Estrogenic activity of glyceollins isolated from soybean elicited with Aspergillus sojae.

    Science.gov (United States)

    Kim, Hyo Jung; Suh, Hwa-Jin; Kim, Jeong Hwan; Kang, Sun Chul; Park, Sunmin; Lee, Choong Hwan; Kim, Jong-Sang

    2010-04-01

    Glyceollins, which are synthesized from daidzein in soybeans cultured with fungi, have been shown to have antifungal effects and cancer preventive properties. Several studies have proposed that isoflavones and their metabolites act as a mixed agonist/antagonist for estrogen. Although glyceollins were reported to suppress some cancer cells via anti-estrogenic activity, it is not clear whether the compounds possess estrogenic potential. In contrast to the anti-estrogenic action reported thus far, we observed estrogenic effects of glyceollins using E-screen assay and pS2 expression, whereas glyceollins showed higher affinity for estrogen receptor (ER) beta than ERalpha. We also found that glyceollins were more efficiently produced de novo in minced than in half-sliced soybean, following infection with Aspergillus sojae. In conclusion, glyceollins may be useful in the prevention or amelioration of postmenopausal complications because they had strong estrogenic activity, and their production could be variable depending upon processing prior to fungal inoculation.

  8. [Effect of 21-gene recurrence score on chemotherapy decisions for patients with estrogen receptor-positive, epidermal growth factor receptor 2-negative and lymph node-negative early stage-breast cancer].

    Science.gov (United States)

    Mao, Y; Chen, X S; Liang, Y; Wu, J Y; Huang, O; Zong, Y; Fang, Q; He, J R; Zhu, L; Chen, W G; Li, Y F; Lin, L; Fei, X C; Shen, K W

    2017-07-23

    Objective: To investigate the effect of 21-gene recurrence score on adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive, epidermal growth factor receptor 2 (HER-2)-negative and lymph node (LN)-negative early stage-breast cancer. Methods: One hundred and forty-eight patients with ER+ , HER-2- and LN- early stage breast cancer were recruited in the Ruijin hospital, Shanghai Jiao Tong University School of Medicine. The 21-gene recurrence score (RS)assay was performed and systemic therapeutic decisions were made before and after knowing the RS results under multidisciplinary discussion. The effects of RS assay and the other influential factors on adjuvant chemotherapy decision were further analyzed. Results: After knowing the RS results, treatment decisions were changed in 26 out of 148 patients(17.6%). Among them, 9 out of 26 patients were not recommended for chemotherapy; 16 of 26 had treatment recommendation changed to chemotherapy, and chemotherapy regimen was changed in the last one patient. Multivariate analysis showed that RS, age and histological grade were independent factors of decision-making for adjuvant chemotherapy. Conclusion: Our results suggest that 21-gene recurrence score significantly influences decision making for adjuvant chemotherapy in patients with ER+ , HER-2- and LN- early stage breast cancer.

  9. Tactile stimulation partially prevents neurodevelopmental changes in visual tract caused by early iron deficiency.

    Science.gov (United States)

    Horiquini-Barbosa, Everton; Gibb, Robbin; Kolb, Bryan; Bray, Douglas; Lachat, Joao-Jose

    2017-02-15

    Iron deficiency has a critical impact on maturational mechanisms of the brain and the damage related to neuroanatomical parameters is not satisfactorily reversed after iron replacement. However, emerging evidence suggest that enriched early experience may offer great therapeutic efficacy in cases of nutritional disorders postnatally, since the brain is remarkably responsive to its interaction with the environment. Given the fact that tactile stimulation (TS) treatment has been previously shown to be an effective therapeutic approach and with potential application to humans, here we ask whether exposure to TS treatment, from postnatal day (P) 1 to P32 for 3min/day, could also be employed to prevent neuroanatomical changes in the optic nerve of rats maintained on an iron-deficient diet during brain development. We found that iron deficiency changed astrocyte, oligodendrocyte, damaged fiber, and myelinated fiber density, however, TS reversed the iron-deficiency-induced alteration in oligodendrocyte, damaged fiber and myelinated fiber density, but failed to reverse astrocyte density. Our results suggest that early iron deficiency may act by disrupting the timing of key steps in visual system development thereby modifying the normal progression of optic nerve maturation. However, optic nerve development is sensitive to enriching experiences, and in the current study we show that this sensitivity can be used to prevent damage from postnatal iron deficiency during the critical period. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Awareness of Skin Cancer, Prevention, and Early Detection among Turkish University Students

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    Ziyafet Ugurlu

    2016-01-01

    Full Text Available Objective: The aim of this study was to determine the awareness about skin cancer, prevention, and early detection among university students. Methods: This descriptive cross-sectional study was carried out with 404 students in a university located in Ankara, the capital city of Turkey. A 35-item questionnaire was used for data collection. Results: Less than half of the students (37.9% had knowledge about skin cancer mostly through the internet (24.5% and media (24.1%. Half of them aware of the risk factors; mostly as avoiding direct exposure to the Sun between 10 am and 4 pm (45.3%; smoking and alcohol (38.4%; having fair skin color (34.9%; and ultraviolet light exposure (25.7%. Only one-third of them (32.9% are knowledgeable about skin cancer signs and symptoms, such as a change in color and appearance of the nevus/moles (24%. The majority of the responders (77.3% did not know about screening tests for skin cancer and only 18 (4.5% students were practicing skin self-examination. Conclusions: This study showed a lack of knowledge about skin cancer, prevention, and early detection among university students and reported the need for educational interventions to raise awareness in this target group.

  11. Early insulin treatment to prevent cardiovascular disease in prediabetes and overt diabetes.

    Science.gov (United States)

    Roman, G; Hancu, N

    2009-02-01

    Type 2 diabetes mellitus (DM) is a major risk factor for cardiovascular disease (CVD), and CVD represents the leading cause of death in people with type 2 DM. The cardiovascular risk is increased long before diabetes is diagnosed, in the prediabetes stage, when impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) develop. These stages are characterized by dysglycemia, defined as any elevated fasting or postprandial glycemia, extending from the normal range into diabetic range, associated with an increased risk of CVD. Due to metabolic memory demonstrated for type 2 DM as well, early interventions addressed to achieve and maintain glycemic control are required for long-term benefits in terms of both microvascular and macrovascular complications. The recommendation of early insulin therapy in type 2 DM is sustained by its pleiotropic effects, which may be cardioprotective and potentially anti-atherosclerotic. Insulin therapy in prediabetes and earlier in type 2 DM, could be a strategy in preventing cardiovascular disease and type 2 DM progression. To test this hypothesis, a large trial has been designed. Outcome Reduction with an Initial Glargine Intervention trial (ORIGIN) is an international, multicenter, randomized controlled, 2 x 2 factorial trial, investigating the possibility to prevent cardiovascular morbidity and mortality in people with type 2 DM, IGT, and/or IFG, and high cardiovascular risk by treating the normoglycemia with either insulin glargine or omega-3 fatty acid, compared to the standard intervention.

  12. Neurogenesis requires TopBP1 to prevent catastrophic replicative DNA damage in early progenitors

    Science.gov (United States)

    Lee, Youngsoo; Katyal, Sachin; Downing, Susanna M.; Zhao, Jingfeng; Russell, Helen R.; McKinnon, Peter J.

    2012-01-01

    The rapid proliferation of progenitors during neurogenesis requires a stringent genomic maintenance program to ensure transmission of genetic fidelity. However the essential factors that govern neural progenitor genome integrity are unknown. Here we report that conditional inactivation of mouse TopBP1, a protein linked to DNA replication, and a key activator of the DNA damage response kinase ATR (ataxia telangiectasia and rad3 related) is critical for maintenance of early-born neural progenitors. During cortical development TopBP1 prevented replication-associated DNA damage in Emx1-progenitors which otherwise resulted in profound tissue ablation. Importantly, disrupted neurogenesis in TopBP1-depleted tissues was substantially rescued by p53- but not ATM-inactivation. Our data establish that TopBP1 is essential for preventing replication-associated DNA strand breaks, but is not essential per se for DNA replication. Thus, TopBP1 is crucial for maintaining genome integrity in the early progenitors that drive neurogenesis. PMID:22522401

  13. Environmental and Economic Strategies for Primary Prevention of Cancer in Early Life.

    Science.gov (United States)

    Kriebel, David; Hoppin, Polly J; Jacobs, Molly M; Clapp, Richard W

    2016-11-01

    This article summarizes the evidence for environmental toxic exposures contributing to cancers in early life, focusing on the most common cancer sites in this age group. It provides examples of widespread avoidable exposures to human carcinogens through air, water, and food and then describes recent examples of successful initiatives to reduce exposure to chemicals linked to these cancer sites, through government policy, industry initiatives, and consumer activism. State government initiatives to reduce toxic chemical exposures have made important gains; the Toxics Use Reduction Act of Massachusetts is now 25 years old and has been a major success story. There are a growing number of corporate initiatives to eliminate toxics, especially carcinogens, from the products they manufacture and sell. Another important opportunity for cancer prevention is provided by online databases that list chemicals, their toxicity, and lower-toxicity alternatives; these can be used by businesses, health care institutions, consumers, and workers to reduce exposures to chemicals of concern. The article concludes by inviting pediatricians and public health professionals to include elimination of carcinogen exposures in their work to promote primary prevention of cancer in early life.

  14. Early Intervention and Maltreated Children: A Current Look at the Child Abuse Prevention and Treatment Act and Part C

    Science.gov (United States)

    Moxley, Kathleen M.; Squires, Jane; Lindstrom, Lauren

    2012-01-01

    Current literature regarding the prevalence of child abuse and neglect, resulting developmental impacts on children, and early intervention services for children and families involved in the child welfare system is summarized. While early intervention eligibility referrals are mandated for this population under the Child Abuse Prevention and…

  15. Early Intervention and Maltreated Children: A Current Look at the Child Abuse Prevention and Treatment Act and Part C

    Science.gov (United States)

    Moxley, Kathleen M.; Squires, Jane; Lindstrom, Lauren

    2012-01-01

    Current literature regarding the prevalence of child abuse and neglect, resulting developmental impacts on children, and early intervention services for children and families involved in the child welfare system is summarized. While early intervention eligibility referrals are mandated for this population under the Child Abuse Prevention and…

  16. Early Fesoterodine Fumarate Administration Prevents Neurogenic Detrusor Overactivity in a Spinal Cord Transected Rat Model.

    Science.gov (United States)

    Biardeau, Xavier; Przydacz, Mikolaj; Aharony, Shachar; Loutochin, George; Campeau, Lysanne; Kyheng, Maeva; Corcos, Jacques

    2017-01-01

    In spinal cord injury, onset of detrusor overactivity (DO) is detrimental for quality of life (incontinence) and renal risk. Prevention has only been achieved with complex sophisticated electrical neuromodulation techniques. To assess the efficacy of early fesoterodine fumarate (FF) administration in preventing bladder overactivity in a spinal cord transected (SCT) rat model. 33 Sprague-Dawley rats were allocated to 6 groups-Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10. FF was continuously administered. Cystometry was undertaken 6 weeks after SCT in awake rats recording intermicturition pressure (IMP), baseline pressure, threshold pressure (Pthres) and maximum pressure (Pmax). Normal controls and SCT controls were initially compared using the Mann-Whitney U tests in order to confirm the SCT effect on cystometric parameters. The comparisons in cystometric and metabolic cage parameters between SCT controls and treated rats were done using post-hoc Dunn's tests for Kruskal-Wallis analysis. Statistical testing was conducted at the two-tailed α-level of 0.05. Pressure parameters were significantly higher in SCT control group compared to normal controls. Six weeks after SCT, IMP was significantly lower in low dose treated group than in SCT controls. Pmax was significantly lower in 3 treated groups compared to SCT controls. Pthres was significantly lower in full time treated groups than in SCT controls. Early administration of FF modulates bladder overactivity in a SCT rat model. Whereas short-term prevention has been demonstrated, the long-term should be further analyzed. Clinical application of these results should confirm this finding through randomized research protocols.

  17. Evaluation of a feasible educational intervention in preventing early childhood caries.

    Science.gov (United States)

    Azevedo, Marina Sousa; Romano, Ana Regina; Correa, Marcos Britto; Santos, Iná da Silva dos; Cenci, Maximiliano Sérgio

    2015-01-01

    Early childhood caries (ECC) in the primary dentition of preschoolers remains high. Young children have limited access to oral healthcare, and oral health education (OHE) measures can be a valuable tool to prevent caries in this population. The aim of this study was to evaluate the impact of an early educational intervention on ECC prevention. The study group (SG) comprised 271 children aged 0-12 months and their mothers, who attended 12 selected public health centers (PHC). The SG received oral health instructions from a pamphlet and by verbal explanation of some topics. One year later, a similar sample of children from another 12 PHCs were selected to serve as the control (CG; n = 251). The children were examined to determine their caries status: decayed = cavitated and/or white spot lesion (maxillary anterior surface); missing; and filled surface index > 0. There was a one-year follow-up. Socioeconomic and demographic information was collected. Logistic regression was used to estimate the effects of the educational intervention on the ECC odds. A sample of 445 (SG = 194 and CG = 251) children remained to the end of the study and were examined. The prevalence of caries was 12.9% in the SG and 17.9% in the CG. The odds of caries were 80% higher in the CG than in the SG (p = 0.037). The strategy of providing OHE from a pamphlet and with a brief verbal instruction to mothers during their child's first year of life can constitute a valuable tool for ECC prevention.

  18. Fifty years of tobacco carcinogenesis research: from mechanisms to early detection and prevention of lung cancer.

    Science.gov (United States)

    Hecht, Stephen S; Szabo, Eva

    2014-01-01

    The recognition of the link between cigarette smoking and lung cancer in the 1964 Surgeon General's Report initiated definitive and comprehensive research on the identification of carcinogens in tobacco products and the relevant mechanisms of carcinogenesis. The resultant comprehensive data clearly illustrate established pathways of cancer induction involving carcinogen exposure, metabolic activation, DNA adduct formation, and consequent mutation of critical genes along with the exacerbating influences of inflammation, cocarcinogenesis, and tumor promotion. This mechanistic understanding has provided a framework for the regulation of tobacco products and for the development of relevant tobacco carcinogen and toxicant biomarkers that can be applied in cancer prevention. Simultaneously, the recognition of the link between smoking and lung cancer paved the way for two additional critical approaches to cancer prevention that are discussed here: detection of lung cancer at an early, curable stage, and chemoprevention of lung cancer. Recent successes in more precisely identifying at-risk populations and in decreasing lung cancer mortality with helical computed tomography screening are notable, and progress in chemoprevention continues, although challenges with respect to bringing these approaches to the general population exist. Collectively, research performed since the 1964 Report demonstrates unequivocally that the majority of deaths from lung cancer are preventable.

  19. Early childhood family intervention and long-term obesity prevention among high-risk minority youth.

    Science.gov (United States)

    Brotman, Laurie Miller; Dawson-McClure, Spring; Huang, Keng-Yen; Theise, Rachelle; Kamboukos, Dimitra; Wang, Jing; Petkova, Eva; Ogedegbe, Gbenga

    2012-03-01

    To test the hypothesis that family intervention to promote effective parenting in early childhood affects obesity in preadolescence. Participants were 186 minority youth at risk for behavior problems who enrolled in long-term follow-up studies after random assignment to family intervention or control condition at age 4. Follow-up Study 1 included 40 girls at familial risk for behavior problems; Follow-up Study 2 included 146 boys and girls at risk for behavior problems based on teacher ratings. Family intervention aimed to promote effective parenting and prevent behavior problems during early childhood; it did not focus on physical health. BMI and health behaviors were measured an average of 5 years after intervention in Study 1 and 3 years after intervention in Study 2. Youth randomized to intervention had significantly lower BMI at follow-up relative to controls (Study 1 P = .05; Study 2 P = .006). Clinical impact is evidenced by lower rates of obesity (BMI ≥95th percentile) among intervention girls and boys relative to controls (Study 2: 24% vs 54%, P = .002). There were significant intervention-control group differences on physical and sedentary activity, blood pressure, and diet. Two long-term follow-up studies of randomized trials show that relative to controls, youth at risk for behavior problems who received family intervention at age 4 had lower BMI and improved health behaviors as they approached adolescence. Efforts to promote effective parenting and prevent behavior problems early in life may contribute to the reduction of obesity and health disparities.

  20. The Cool Little Kids randomised controlled trial: Population-level early prevention for anxiety disorders

    Directory of Open Access Journals (Sweden)

    Hiscock Harriet

    2011-01-01

    Full Text Available Abstract Background The World Health Organization predicts that by 2030 internalising problems (e.g. depression and anxiety will be second only to HIV/AIDS in international burden of disease. Internalising problems affect 1 in 7 school aged children, impacting on peer relations, school engagement, and later mental health, relationships and employment. The development of early childhood prevention for internalising problems is in its infancy. The current study follows two successful 'efficacy' trials of a parenting group intervention to reduce internalising disorders in temperamentally inhibited preschool children. Cool Little Kids is a population-level randomised trial to determine the impacts of systematically screening preschoolers for inhibition then offering a parenting group intervention, on child internalising problems and economic costs at school entry. Methods/Design This randomised trial will be conducted within the preschool service system, attended by more than 95% of Australian children in the year before starting school. In early 2011, preschool services in four local government areas in Melbourne, Australia, will distribute the screening tool. The ≈16% (n≈500 with temperamental inhibition will enter the trial. Intervention parents will be offered Cool Little Kids, a 6-session group program in the local community, focusing on ways to develop their child's bravery skills by reducing overprotective parenting interactions. Outcomes one and two years post-baseline will comprise child internalising diagnoses and symptoms, parenting interactions, and parent wellbeing. An economic evaluation (cost-consequences framework will compare incremental differences in costs of the intervention versus control children to incremental differences in outcomes, from a societal perspective. Analyses will use the intention-to-treat principle, using logistic and linear regression models (binary and continuous outcomes respectively to compare outcomes

  1. Advances in menopausal therapy: the tissue-selective estrogen complex.

    Science.gov (United States)

    Moore, Anne

    2013-03-01

    Most menopausal women experience vasomotor symptoms, vulvar-vaginal atrophy, and/or bone loss. Although available estrogen and progestin therapies are effective in treating menopausal symptoms and preventing bone loss, some women may seek a therapy that provides symptom relief and has an improved tolerability profile. One option is a tissue-selective estrogen complex (TSEC), or the pairing of estrogen(s) with a selective estrogen receptor modulator (SERM) to achieve the benefits of each component with fewer side effects. The first TSEC in clinical development combines the SERM bazedoxifene (BZA) with conjugated estrogens (CEs). The purpose of this article is to review published data for BZA/CE. Data were obtained from phase 3 BZA/CE clinical trial study articles. Daily BZA 20 mg/CE 0.625 mg or 0.45 mg effectively relieved hot flushes, maintained or increased bone mineral density, treated vulvar-vaginal atrophy, and improved quality of life. Further, BZA prevented stimulation of the endometrium by CE, and resulted in rates of amenorrhea and breast pain similar to placebo. These results support the use of a TSEC consisting of BZA/CE as a promising therapy for managing the signs and symptoms from reduced estrogen levels associated with menopause. ©2012 The Author(s) Journal compilation ©2012 American Association of Nurse Practitioners.

  2. Evaluation of Pacific Islands Early Childhood Caries Prevention Project: Republic of the Marshall Islands

    Science.gov (United States)

    Milgrom, Peter; Tut, Ohnmar

    2009-01-01

    Objectives This communication reports an outcomes evaluation of the Pacific Islands Early Childhood Caries Prevention Project. Methods The evaluation includes children in three conditions: (1) three times per school year topical fluoride varnish; (2) varnish plus twice per day toothbrushing; and (3) intervention 2 plus three times per day xylitol containing gummy bear snacks at school and home visits to encourage parental involvement. For this evaluation, groups 2 and 3 have been combined. Results One year after project implementation, mean deft was 10.3 (SD=4.3) teeth for group 1 and 8.2 (SD=4.0) teeth for the combination of groups 2 and 3 (p.05). Conclusions Evaluation confirms the outcome of a program including both in-school twice-daily toothbrushing with fluoridated toothpaste and frequent applications of fluoride varnish. PMID:19486466

  3. Toxic scarlet fever complicating cellulitis: early clinical diagnosis is crucial to prevent a fatal outcome.

    Science.gov (United States)

    Lau, S K; Woo, P C; Yuen, K Y

    2004-04-01

    We describe a case of toxic scarlet fever in a healthy adult with streptococcal cellulitis of the right elbow as a result of skin abrasion. The clinical picture mimicked that of drug eruption after treatment of cellulitis with antibiotics. Among the five cases of scarlet fever complicating cellulitis, including the present one, reported in the English literature, four had severe systemic complications and two died. As a result of re-emergence of invasive streptococcal infections, clinicians should be aware of the differential diagnosis of scarlet fever in patients presenting with cellulitis and skin rash. Early clinical diagnosis is crucial to exclude drug eruptions, prompt initiation of antibiotic treatment, and prevention of the potentially fatal outcome.

  4. Prevention

    Science.gov (United States)

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  5. Effects of estrogen with micronized progesterone on cortical and trabecular bone mass and microstructure in recently postmenopausal women.

    Science.gov (United States)

    Farr, Joshua N; Khosla, Sundeep; Miyabara, Yuko; Miller, Virginia M; Kearns, Ann E

    2013-02-01

    In women, cortical bone mass decreases significantly at menopause. By contrast, loss of trabecular bone begins in the third decade and accelerates after menopause. The aim of the study was to investigate the effects of estrogen on cortical and trabecular bone. The Kronos Early Estrogen Prevention Study is a double-blind, randomized, placebo-controlled trial of menopausal hormone treatment (MHT) in women, enrolled within 6-36 months of their final menstrual period. The study was conducted at the Mayo Clinic, Rochester, Minnesota. Subjects were treated with placebo (n = 31), or .45 mg/d conjugated equine estrogens (n = 20), or transdermal 50 μg/d 17β-estradiol (n = 25) with pulsed micronized progesterone. Cortical and trabecular microarchitecture at the distal radius was assessed by high-resolution peripheral quantitative computed tomography. At the distal radius, cortical volumetric bone mineral density (vBMD) decreased, and cortical porosity increased in the placebo group; MHT prevented these changes. By contrast, MHT did not prevent decreases in trabecular microarchitecture at the radius. However, MHT prevented decreases in trabecular vBMD at the thoracic spine (assessed in a subset of subjects; n = 51). These results indicate that MHT prevents deterioration in radial cortical vBMD and porosity in recently menopausal women. The maintenance of cortical bone in response to estrogen likely has important clinical implications because cortical bone morphology plays an important role in bone strength. However, effects of MHT on trabecular bone at the radius differ from those at the thoracic spine. Underlying mechanisms for these site-specific effects of MHT on cortical vs trabecular bone require further investigation.

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

    Science.gov (United States)

    Nakai, Yukie; Mori, Yukako; Tamaoka, Izumi

    2016-01-01

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

  7. Early or late antibiotic intervention prevents Helicobacter pylori-induced gastric cancer in a mouse model.

    Science.gov (United States)

    Zhang, Songhua; Lee, Dong Soo; Morrissey, Rhiannon; Aponte-Pieras, Jose R; Rogers, Arlin B; Moss, Steven F

    2014-12-01

    H. pylori infection causes gastritis, peptic ulcers and gastric cancer. Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer remains unknown, especially if given after intestinal metaplasia has developed. H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking the tumor suppressor p27 do so, thus providing an experimental model of H. pylori-induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8 weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls. Mice in the eradication arms received antimicrobial therapy (omeprazole, metronidazole and clarithromycin) either "early" (at 15 weeks post infection, WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori determination, histopathology and cytokine/chemokine expression. Persistently infected mice developed premalignant lesions including high-grade dysplasia, whereas those given antibiotics did not. Histologic activity scores in the eradication groups were similar to each other, and were significantly decreased compared with controls for inflammation, epithelial defects, hyperplasia, metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received antibiotics were significantly lower than controls. There were no significant differences in expression of IFN-γ, TNF-α, IL-1β, RANTES, MCP-1, MIP-1α or MIP-1β among the three groups. Thus, H. pylori eradication given either early or late after infection significantly attenuated gastric inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient mice model of H. pylori-induced gastric cancer, irrespective of the timing of antibiotic administration. This was associated with reduced expression of IP-10 and MIG.

  8. Early life respiratory infections and asthma development: role in disease pathogenesis and potential targets for disease prevention

    Science.gov (United States)

    Beigelman, Avraham; Bacharier, Leonard B.

    2016-01-01

    Purpose of review To present recent findings and perspectives on the relationship between early life respiratory infections and asthma inception and to discuss emerging concepts on strategies that target these infectious agents for asthma prevention. Recent findings Cumulative evidence supports the role of early life viral infections, especially respiratory syncytial virus and human rhinovirus, as major antecedents of childhood asthma. These viruses may have different mechanistic roles in the pathogenesis of asthma. The airway microbiome and virus-bacteria interactions in early life have emerged as additional determinants of childhood asthma. Innovative strategies for the prevention of these early life infections, or for attenuation of acute infection severity, are being investigated and may identify effective strategies for the primary and secondary prevention of childhood asthma. Summary Early life infections are major determinants of asthma development. The pathway from early life infections to asthma is the result of complex interactions between the specific type of the virus, genetic and environmental factors. Novel intervention strategies that target these infectious agents have been investigated in proof-of-concepts trials, and further study is necessary to determine their capacity for asthma prevention. PMID:26854761

  9. Dendrobium officinale Prevents Early Complications in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Shao-zhen Hou

    2016-01-01

    Full Text Available Background. Dendrobium officinale (DO Kimura et Migo is a precious Chinese herb that is considered beneficial for health due to its antioxidant and antidiabetes properties, and so on. In this research, we try to determine the preventive effect of DO on the early complications of STZ-induced diabetic rats. Methods. Type 1 diabetic rats were produced with a single intraperitoneal injection of STZ (50 mg/kg. DO (1 g/kg/day was then orally administered for 5 weeks. Blood glucose, TC, TG, BUN, CREA, and GSH-PX levels were determined, and electroretinographic activity and hypoalgesia were investigated. Pathological sections of the eyes, hearts, aortas, kidneys, and livers were analyzed. Results. Treatment with DO significantly attenuated the serum levels of TC, TG, BUN, and CREA, markedly increased the amplitudes of ERG a- and b-waves and Ops, and reduced the hypoalgesia and histopathological changes of vital organs induced by hyperglycemia. The protective effect of DO in diabetic rats may be associated with its antioxidant activity, as evidenced by the marked increase in the serum level of glutathione peroxidase. However, DO had no significant effect on blood glucose levels and bodyweight of diabetic rats. Conclusions. DO supplementation is an effective treatment to prevent STZ-induced diabetic complications.

  10. Dendrobium officinale Prevents Early Complications in Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Hou, Shao-Zhen; Liang, Chu-Yan; Liu, Hua-Zhen; Zhu, Dong-Mei; Wu, Ya-Yun; Liang, Jian; Zhao, Ya; Guo, Jian-Ru; Huang, Song; Lai, Xiao-Ping

    2016-01-01

    Background. Dendrobium officinale (DO) Kimura et Migo is a precious Chinese herb that is considered beneficial for health due to its antioxidant and antidiabetes properties, and so on. In this research, we try to determine the preventive effect of DO on the early complications of STZ-induced diabetic rats. Methods. Type 1 diabetic rats were produced with a single intraperitoneal injection of STZ (50 mg/kg). DO (1 g/kg/day) was then orally administered for 5 weeks. Blood glucose, TC, TG, BUN, CREA, and GSH-PX levels were determined, and electroretinographic activity and hypoalgesia were investigated. Pathological sections of the eyes, hearts, aortas, kidneys, and livers were analyzed. Results. Treatment with DO significantly attenuated the serum levels of TC, TG, BUN, and CREA, markedly increased the amplitudes of ERG a- and b-waves and Ops, and reduced the hypoalgesia and histopathological changes of vital organs induced by hyperglycemia. The protective effect of DO in diabetic rats may be associated with its antioxidant activity, as evidenced by the marked increase in the serum level of glutathione peroxidase. However, DO had no significant effect on blood glucose levels and bodyweight of diabetic rats. Conclusions. DO supplementation is an effective treatment to prevent STZ-induced diabetic complications.

  11. Developmental epidemiologically based preventive trials: baseline modeling of early target behaviors and depressive symptoms.

    Science.gov (United States)

    Kellam, S G; Werthamer-Larsson, L; Dolan, L J; Brown, C H; Mayer, L S; Rebok, G W; Anthony, J C; Laudolff, J; Edelsohn, G

    1991-08-01

    Describes a conceptual framework for identifying and targeting developmental antecedents in early childhood that have been shown in previous work to predict delinquency and violent behavior, heavy drug use, depression, and other psychiatric symptoms and possibly disorders in late adolescence and into adulthood. Criteria are described that guided choices of targets for two epidemiologically based, randomized preventive trials carried out in 19 elementary schools in the eastern half of Baltimore, involving more than 2,400 first-grade children over the course of first and second grades. Baseline models derived from the first of two cohorts show the evolving patterns of concurrence among the target antecedents. The central role of concentration problems emerged. From Fall to Spring in first grade, concentration problems led to shy and aggressive behavior and poor achievement in both genders and to depressive symptoms among girls. There was evidence for reciprocal relationships in girls. For example, depressive symptoms led to poor achievement in both girls and boys, whereas poor achievement led to depressive symptoms in girls but not boys, at least over the first-grade year. These results provide important epidemiological data relevant to the developmental paths leading to the problem outcomes and suggest preventive trials.

  12. Acceptability of early infant male circumcision among chinese parents: strategy implications of HIV prevention for china

    Directory of Open Access Journals (Sweden)

    Pan Lianjun

    2012-09-01

    Full Text Available Abstract Background Recent evidence has confirmed that circumcision can be performed as a preventive strategy for HIV and early infant male circumcision (EIMC is regarded to be safer than circumcision in adulthood; however, limited data are available in the literature about EIMC in China. Therefore, the present study was designed to determine the willingness and attitudes of Chinese parents on newborn male circumcision so as to provide data for exploring the feasibility of implementing EIMC as an HIV prevention strategy in China. Methods Simple random sampling was used to draw participants from parents who had a newborn son delivered at Nanjing Maternity and Child Health Care Hospital, which is affiliated to Nanjing Medical University, between March and December 2010. A questionnaire was used to determine general medical knowledge or information about circumcision, attitudes about EIMC, and level of decision-making on circumcision for the newborn son. Results Data derived from 558 responses were analyzed and the ratio of respondents was 56.3% for fathers and 43.6% for mothers. Of the respondents, 34.4% agreed to circumcise their newborn son, and the level of agreement was 3.25 ± 1.17 (range, 1–5 with “1” being “reluctantly agree” and “5” being “very strongly agree”. The major reason for EIMC was for health (44.8%, followed by doctor’s advice (31.2%. The major reason not to agree to EIMC was concern about pain (50.5%, followed by the risk of the procedure (23.5%. Conclusion The willingness and acceptability of EIMC in China is low and the parents of newborn sons are usually not very affirmative when making a decision on such a procedure, suggesting that significant effort will be needed if EIMC is to be implemented as an HIV prevention strategy for China.

  13. Observation on the Effects of Estrogen on the Prevention of Adhesion of Hysteroscopic Operation%雌激素在宫腔镜手术粘连预防中的应用效果探讨

    Institute of Scientific and Technical Information of China (English)

    高永星; 庄育红

    2014-01-01

    目的:探讨雌激素在宫腔镜分离后宫腔粘连的疗效与安全性。方法选择该院2010年1月—2014年1月收治入院的宫腔镜电切术后患者200例,随机分为观察组和对照组,每组100例。对照组术后宫腔内放置金属圆形IUD,而观察组口服戊酸雌二醇预防宫腔粘连。定期随诊,治疗结束后复查肝功,并在宫腔镜下行取环术。结果两组患者治疗后肝功能均无异常,粘连治疗前镜下宫腔狭窄呈条状,宫腔两侧壁与双侧宫角及输卵管口均消失,部分宫腔闭锁严重的广泛粘连使宫腔形态完全消失。治疗后基本恢复正常;观察组子宫内膜厚度0.8~1.2、月经恢复正常88例、月经量少8例、恢复妊娠12例,对照组宫内膜厚度0.4~1.1 cm、月经恢复正常69例、月经量少23例、恢复妊娠8例,两组比较差异有统计学意义(P<0.05)。结论雌激素预防宫腔镜分离后宫腔粘连的疗效好,预防范围广,安全性强,值得推广应用。%Objective To evaluate the safety and efficacy of estrogen in hysteroscopic intrauterine adhesion separation. Methods 200 cases after hysteroscopic surgery admitted in our hospital from January 2010 to January 2014 were randomly divided into the observation group and the control group with 100 cases in each. For the prevention of intrauterine adhesions, the control group was given metal circular IUD placing in the uterine cavity, and the observation group was given estradiol valerate orally. The patients were followed up regularly. And liver function of the patients was detected after the treatment; IUD was removed in hysteroscopy. Results After treatment, the liver function of the two groups of patients showed no abnormality. Before the treatment of intrauterine adhesions, the uterine cavity was in the shape of narrow strip, both sides of the uterine cavity wall and bilateral uterine horn and the fallopian tube were all disappeared, uterine cavity shape

  14. The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications.

    Science.gov (United States)

    Brinton, Roberta Diaz

    2008-10-01

    The 'healthy cell bias of estrogen action' hypothesis examines the role that regulating mitochondrial function and bioenergetics play in promoting neural health and the mechanistic crossroads that lead to divergent outcomes following estrogen exposure. Estrogen-induced signaling pathways in hippocampal and cortical neurons converge upon the mitochondria to enhance aerobic glycolysis coupled to the citric acid cycle, mitochondrial respiration and ATP generation. Convergence of estrogen-induced signaling onto mitochondria is also a point of vulnerability when activated in diseased neurons which exacerbates degeneration through increased load on dysregulated calcium homeostasis. As the continuum of neurological health progresses from healthy to unhealthy so too do the benefits of estrogen or hormone therapy. The healthy cell bias of estrogen action hypothesis provides a lens through which to assess disparities in outcomes across basic and clinical science and on which to predict outcomes of estrogen interventions for sustaining neurological health and preventing age-associated neurodegenerative diseases such as Alzheimer's.

  15. Messenger RNA levels of estrogen receptors alpha and beta and progesterone receptors in the cyclic and inseminated/early pregnant sow uterus.

    Science.gov (United States)

    Sukjumlong, S; Persson, E; Dalin, A-M; Janson, V; Sahlin, L

    2009-06-01

    The aim of the present study was to investigate differences in the expression of mRNAs for ERalpha, ERbeta and PR in the sow uterus at different stages of the estrous cycle as well as in inseminated sows at estrus and during early pregnancy by use of solution hybridization and in relation to plasma levels of estradiol and progesterone. Uterine samples were collected at different stages of the estrous cycle and after insemination/early pregnancy. In the endometrium, the expression of ERalpha mRNA and PR mRNA was similar for cyclic and early pregnant groups. Both were highest at early diestrus/70 h after ovulation and ERalpha mRNA was lowest at late diestrus/d 19 while PR mRNA was lowest at diestrus and late diestrus/d 11 and d 19. The expression of endometrial ERbeta was constantly low during the estrous cycle but higher expression was found in inseminated/early pregnant sows at estrus and 70 h after ovulation. In the myometrium, high expression of ERalpha mRNA and PR mRNA was observed at proestrus and estrus in cyclic sows and at estrus in newly inseminated sows. Higher expression of myometrial ERbeta mRNA was found in inseminated/early pregnant sows compared with cyclic sows, although significant only at estrus. In conclusion, the expression of mRNAs for ERalpha, ERbeta and PR in the sow uterus differed between endometrium and myometrium as well as with stages of the estrous cycle and early pregnancy. In addition to plasma steroid levels, the differences between cyclic and inseminated/early pregnant sows suggest that other factors, e.g. insemination and/or the presence of embryos, influence the expression of these steroid receptor mRNAs in the sow uterus.

  16. ACTH Prevents Deficits in Fear Extinction Associated with Early Life Seizures

    Directory of Open Access Journals (Sweden)

    Andrew T Massey

    2016-05-01

    Full Text Available Early life seizures are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of early life seizures (ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action. We found that while rats with a history of ELS were able to acquire a conditioned fear learning paradigm as well as controls, these rats had significant deficits in their ability to extinguish fearful memories. ACTH treatment did not alter any seizure parameters but nevertheless was able to significantly improve this fear extinction, while dexamethasone treatment during the same period did not. This ACTH effect was specific for fear extinction deficits and not for spatial learning deficits in a water maze. Additionally, ACTH did not alter seizure latency or duration suggesting that cognitive and seizure outcomes may be dissociable. Expression levels of melanocortin receptors, which bind ACTH, were found to be significantly lower in animals that had experienced ELS than in control animals, potentially implicating central melanocortin receptor dysregulation in the effects of ELS and suggesting a mechanism of action for ACTH. Taken together, these data suggest that early treatment with ACTH can have significant long-term consequences for cognition in animals with a history of ELS independently of seizure cessation, and may act in part through a CNS melanocortin receptor pathway.

  17. Early Fesoterodine Fumarate Administration Prevents Neurogenic Detrusor Overactivity in a Spinal Cord Transected Rat Model

    Science.gov (United States)

    Biardeau, Xavier; Przydacz, Mikolaj; Aharony, Shachar; Loutochin, George; Campeau, Lysanne; Kyheng, Maeva; Corcos, Jacques

    2017-01-01

    Background In spinal cord injury, onset of detrusor overactivity (DO) is detrimental for quality of life (incontinence) and renal risk. Prevention has only been achieved with complex sophisticated electrical neuromodulation techniques. Purpose To assess the efficacy of early fesoterodine fumarate (FF) administration in preventing bladder overactivity in a spinal cord transected (SCT) rat model. Methods 33 Sprague-Dawley rats were allocated to 6 groups–Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10. FF was continuously administered. Cystometry was undertaken 6 weeks after SCT in awake rats recording intermicturition pressure (IMP), baseline pressure, threshold pressure (Pthres) and maximum pressure (Pmax). Normal controls and SCT controls were initially compared using the Mann-Whitney U tests in order to confirm the SCT effect on cystometric parameters. The comparisons in cystometric and metabolic cage parameters between SCT controls and treated rats were done using post-hoc Dunn’s tests for Kruskal-Wallis analysis. Statistical testing was conducted at the two-tailed α-level of 0.05. Results Pressure parameters were significantly higher in SCT control group compared to normal controls. Six weeks after SCT, IMP was significantly lower in low dose treated group than in SCT controls. Pmax was significantly lower in 3 treated groups compared to SCT controls. Pthres was significantly lower in full time treated groups than in SCT controls. Conclusion Early administration of FF modulates bladder overactivity in a SCT rat model. Whereas short-term prevention has been demonstrated, the long-term should be further analyzed. Clinical application of these results should confirm this finding through randomized research protocols. PMID:28060912

  18. Profile of bazedoxifene/conjugated estrogens for the treatment of estrogen deficiency symptoms and osteoporosis in women at risk of fracture.

    Science.gov (United States)

    Rossini, Maurizio; Lello, Stefano; Sblendorio, Ignazio; Viapiana, Ombretta; Fracassi, Elena; Adami, Silvano; Gatti, Davide

    2013-01-01

    Decreasing levels of estrogens during menopause are associated with reduced bone density and an increased risk of osteoporosis. Many women also experience bothersome vasomotor and vaginal symptoms during the menopausal transition. Results of systematic reviews and meta-analyses of randomized controlled trials have shown that both systemic estrogen therapy or hormone therapy (estrogen combined with a progestin) are useful to prevent bone loss, and they are the most effective treatment for such climacteric symptoms as hot flushes, sweating, vaginal dryness, and dyspareunia. Unfortunately, estrogen therapy and hormone therapy increase the risk of endometrial and breast cancer, respectively. The selective estrogen receptor modulators (SERMs) result in positive estrogenic effects on bone, with no negative effects on the endometrium and breast but do not provide relief from postmenopausal symptoms. The combination of a SERM with estrogen as a tissue selective estrogen complex (TSEC) is a new strategy for the prevention of bone loss and the treatment of climacteric symptoms. This combination is particularly interesting from a clinical point of view, taking into account that estrogen alone did not increase breast cancer risk by the Women's Health Initiative. TSEC is hypothesized to provide the benefits of estrogen-alone therapy, with an improved tolerability profile because the SERM component can make possible the elimination of progestin. The objective of this review was to critically evaluate the evidence from the reports published to date on the use of bazedoxifene (a third-generation SERM) in combination with conjugated estrogens in postmenopausal women. The conclusion is that effectively, the combination of bazedoxifene and conjugated estrogens may be a promising alternative to hormone therapy for the prevention of osteoporosis and the treatment of postmenopausal symptoms in non-hysterectomized postmenopausal women.

  19. Yeast Estrogen Screen Assay as a Tool for Detecting Estrogenic Activity in Water Bodies

    Directory of Open Access Journals (Sweden)

    Mirjana Bistan

    2012-01-01

    Full Text Available The presence of endocrine-disrupting compounds in wastewater, surface water, groundwater and even drinking water has become a major concern worldwide, since they negatively affect wildlife and humans. Therefore, these substances should be effectively removed from effluents before they are discharged into surface water to prevent pollution of groundwater, which can be a source of drinking water. Furthermore, an efficient control of endocrine-disrupting compounds in wastewater based on biological and analytical techniques is required. In this study, a yeast estrogen screen (YES bioassay has been introduced and optimized with the aim to assess potential estrogenic activity of waters. First, assay duration, concentration of added substrate to the assay medium and wavelength used to measure the absorbance of the substrate were estimated. Several compounds, such as 17-β-estradiol, 17-α-ethinylestradiol, bisphenol A, nonylphenol, genisteine, hydrocortisone, dieldrin, atrazine, methoxychlor, testosterone and progesterone were used to verify its specificity and sensitivity. The optimized YES assay was sensitive and responded specifically to the selected estrogenic and nonestrogenic compounds in aqueous samples. Potential estrogenicity of influent and effluent samples of two wastewater treatment plants was assessed after the samples had been concentrated by solid-phase extraction (SPE procedure using Oasis® HLB cartridges and methanol as eluting solvent. Up to 90 % of relative estrogenic activity was detected in concentrated samples of influents to wastewater treatment plants and estrogenic activity was still present in the concentrated effluent samples. We found that the introduced YES assay is a suitable screening tool for monitoring the potential estrogenicity of effluents that are discharged into surface water.

  20. Associations among circulating CSF-1, estrogen, and bone mineral density in postmenopausal women: results from a randomized placebo-controlled trial.

    Science.gov (United States)

    Haas, Andrea V; Cong, Elaine; Simpson, Christine A; Sukumar, Nitin; Deng, Yanhong; Insogna, Karl L

    2017-08-14

    This study addresses the relationship between circulating levels of colony-stimulating factor 1 (CSF-1) and rates of postmenopausal bone loss. The purpose was to test the hypothesis that CSF-1 levels would correlate with the rate of bone loss in estrogen-deficient woman. We further hypothesized that estrogen replacement would eliminate this association. This was an ancillary study to the parent Kronos Early Estrogen Prevention Study (KEEPS)-a 4-year randomized placebo-controlled study that evaluated the effects of estrogen therapy on cardiovascular endpoints. Women between of the ages of 42 and 58, who had been amenorrheic for ≥6 months and ≤36 months, were enrolled in KEEPS. Participants were randomized to conjugated equine estrogen 0.45 mg daily, transdermal estradiol 50 micrograms weekly, or placebo. There was no correlation between serum levels of CSF-1 and bone mineral density at the spine, hip, or femoral neck in estrogen-deficient women (correlation 0.0017, P = 0.99 for spine; correlation 0.0010, P = 0.0079 for hip, and correlation 0.0019, P = 0.99 for femoral neck). There was also no significant correlation in the treatment group (correlation 0.0015, P = 0.99; correlation -0.00024, P = 0.99; correlation 0.0011, P = 0.99 at spine, hip, and femoral neck respectively). This study did not demonstrate a meaningful relationship between circulating levels of CSF-1 and bone mineral density in either the placebo group or estrogen-treated group. Although CSF-1 is required for osteoclastic bone resorption, our data suggest that circulating levels of the cytokine may not reflect this process.

  1. Estrogen supplements in menopause.

    Science.gov (United States)

    Booher, D L

    1990-01-01

    The number of women aged 65 and older is expected to double by the year 2000, increasing the need for effective management of symptoms related to menopause. Contemporary management of menopause addresses the continuum of events associated with the effects of estrogen deprivation on quality and duration of life, including neuroendocrine changes, urogenital atrophy, sexual dysfunction, skin and hair changes, osteoporosis, and cardiovascular disease. The risks and benefits of management strategies, including hormone replacement therapy, must be weighted carefully by both physician and patient. The use of estrogens and progestins, alterative compounds, dosages, routes of administration, and their advantages and disadvantages must be analyzed.

  2. The SAFE project: community-driven partnerships in health, mental health, and education to prevent early school failure.

    Science.gov (United States)

    Poole, D L

    1997-11-01

    This article presents a case study of an innovative school-based health and mental health project that prevents early school failure in one county in Oklahoma. Success is attributed to social work development of broad-based partnerships involving families, schools, communities, and public policy officials. Citizen-driven, these partnerships have meshed previously fixed institutional boundaries in health, mental health, and education to prevent early school failure. The article describes school-family partnerships that form the core of the project's service intervention model. Statistics on service activities and outcomes are presented, along with a discussion of lessons learned for implementation of the project.

  3. Prevention of hip fractures.

    Science.gov (United States)

    Meunier, P J

    1993-11-30

    For a 50-year old Caucasian woman today, the risk of a hip fracture over her remaining life-time is about 17%. Tomorrow the situation will clearly be worse because the continuous increase in life expectancy will cause a three-fold increase in worldwide fracture incidence over the next 60 years. Through diagnostic bone mass measurements at the hip and assessment of biochemical parameters, a great deal has been learned in recent years about reduction of hip fracture risk. Preventive strategies are based on prevention of falls, use of hip protectors, and prevention of bone fragility. The latter includes the optimization of peak bone mass during childhood, postmenopausal estrogen replacement therapy, and also late prevention consisting in reversing senile secondary hyperparathyroidism, which plays an important role in the decrease of skeletal strength. This secondary hyperparathyroidism, which results from both vitamin D insufficiency and low calcium intake, is preventable with vitamin D3 and calcium supplements. They have recently been shown capable of providing effective prevention of hip fractures in elderly women living in nursing homes, with a reduction of about 25% in the number of hip fractures noted in a 3-year controlled study in 3,270 women (intention-to-treat analysis). In conclusion, it is never too early to reduce the risk of osteoporosis and never too late to prevent hip fractures.

  4. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  5. Estrogens Mediate Cardiac Hypertrophy in a Stimulus-Dependent Manner

    Science.gov (United States)

    Haines, Christopher D.; Harvey, Pamela A.

    2012-01-01

    The incidence of cardiac hypertrophy, an established risk factor for heart failure, is generally lower in women compared with men, but this advantage is lost after menopause. Although it is widely believed that estrogens are cardioprotective, there are contradictory reports, including increased cardiac events in postmenopausal women receiving estrogens and enhanced cardiac protection from ischemic injury in female mice without estrogens. We exposed aromatase knockout (ArKO) mice, which produce no estrogens, to both pathologic and physiologic stimuli. This model allows an investigation into the effects of a complete, chronic lack of estrogens in male and female hearts. At baseline, female ArKO mice had normal-sized hearts but decreased cardiac function and paradoxically increased phosphorylation of many progrowth kinases. When challenged with the pathological stimulus, isoproterenol, ArKO females developed 2-fold more hypertrophy than wild-type females. In contrast, exercise-induced physiological hypertrophy was unaffected by the absence of estrogens in either sex, although running performance was blunted in ArKO females. Thus, loss of estrogen signaling in females, but not males, impairs cardiac function and sensitizes the heart to pathological insults through up-regulation of multiple hypertrophic pathways. These findings provide insight into the apparent loss of cardioprotection after menopause and suggest that caution is warranted in the long-term use of aromatase inhibitors in the setting of breast cancer prevention. PMID:22759381

  6. HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions

    Science.gov (United States)

    TESTI, D.; NARDONE, M.; MELONE, P.; CARDELLI, P.; OTTRIA, L.; ARCURI, C.

    2015-01-01

    SUMMARY The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%–90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before “sexual puberty”. The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer. PMID:27555904

  7. Early diagnosis of the urofacial syndrome is essential to prevent irreversible renal failure

    Directory of Open Access Journals (Sweden)

    Francisco A. Nicanor

    2005-10-01

    Full Text Available INTRODUCTION: The urofacial or Ochoa syndrome is a rare disease characterized by the presence of functional obstructive uropathy associated with peculiar facial features when patients attempt to smile or laugh. Unfortunately, many of these patients remain without proper diagnosis or adequate treatment due to lack of recognition of the disease. This can ultimately result in upper tract deterioration and eventual renal failure. We present our experience with this rare syndrome. MATERIALS AND METHODS: We identified 3 patients who presented initially with acute renal failure, urinary tract infection (UTI and severe dysfunctional elimination. All patients were thoroughly evaluated, including screening for spinal cord anomalies, and were subsequently diagnosed with urofacial syndrome. RESULTS: At the outset, the two older patients (aged 4 and 9 years presented with the typical facial features when attempting to smile or laugh. One patient in the newborn period presented with urinary and fecal retention and septicemia and, to our knowledge, represents the youngest case of urofacial syndrome reported so far. All patients were evaluated with ultrasonography, renal scan, voiding cystourethrogram (VCUG and urodynamics. Findings included hydronephrosis and a thick-walled, trabeculated bladder with poor compliance and detrusor hypereflexia respectively in each patient. All were subsequently treated with clean intermittent catheterization (CIC, antibiotic prophylaxis and anticholinergic therapy. One patient required appendicovesicostomy for CIC due to discomfort secondary to a sensate urethra. CONCLUSIONS: Our series demonstrates that early recognition of this rare syndrome is necessary to adequately treat and prevent upper tract deterioration in these unique individuals. Although the urofacial is difficult to diagnose in infants, cognizance must be maintained in order to prevent severe subsequent sequalae.

  8. Domestic Violence and Abuse Prevention Programmes in the Early Years Classroom: A Pastoral, Academic and Financial Priority?

    Science.gov (United States)

    McKee, Bronagh E.; Mason, Sarah

    2015-01-01

    Prevention programmes underpin every child's right to "feel" safe and to "be" safe from all forms of harm. Delivered in schools across the globe, they aim to equip children with knowledge about safety and the skills to seek help early. By drawing upon international prevalence and impact research, as well as the legal, policy…

  9. [The NETWASS prevention model for early identification and assessment of adolescents in psychosocial crisis].

    Science.gov (United States)

    Sommer, Friederike; Fiedler, Nora; Leuschner, Vincenz; Scheithauer, Herbert

    2016-01-01

    The research-based NETWASS prevention model aims to enable school staff to identify students experiencing a psychosocial crisis that could lead to severe targeted school violence and to initiate appropriate support measures. A detailed analysis of the adolescent psychosocial crisis is conducted at an early stage by evaluating possible warning behaviors, crisis symptoms, a student’s individual and social background, and resources. The model was implemented in 98 schools. During the project duration of seven months staff from 59 schools reported 99 cases of a student’s psychosocial crisis. Three experts conducted a content analysis of the reported qualitative data focusing on crisis symptoms of the students as well as the initiated measures. Results show a broad spectrum of risk factors, whereas aggressive behavior of students was reported most frequently. On the basis of theoretical assumptions, the reported cases were divided into three distinct risk groups. A total of eight high-risk cases were observed and reported by the school staff. The school staff mostly reacted to the student crisis by initiating resource-orientated measures, the expertise of child and youth therapists was mostly requested for the high risk cases. By describing the impact of cases and choice of measures undertaken, the study aims to give an overview of incidents schools as well as clinical psychologists and therapists are confronted with.

  10. Carcinogenesis, prevention and early detection of gastric cancer: where we are and where we should go.

    Science.gov (United States)

    González, Carlos A; Agudo, Antonio

    2012-02-15

    Helicobacter pylori is the most common cause of gastric cancer (GC), though smoking, alcohol, diet, genetics and epigenetic factors may also have a role in the occurrence of the disease. Why H. pylori cause GC in only a minority of those infected remains unknown. Although mechanisms of H. pylori-induced carcinogenesis are not yet well understood, several genotypes of H. pylori have been associated with strain virulence and disease risk. Primary prevention of GC should be addressed by avoiding exposure to factors that increase the risk and to promote factors associated with decrease risk. Vaccines against H. pylori are an ongoing promise and not yet available. Chemoprevention through vitamin supplementation has shown no benefit. Screening and eradication of H. pylori in the general population is not advised. Given that GC is a multiple-steps process, the identification of patients with preneoplastic lesions with high risk of progression, and periodic endoscopic surveillance of them represents the most effective way for early diagnosis of GC. However, clinical guidelines for surveillance are lacking and there are no clear criteria to classify patients into high or low risk of progressing to GC. No study has shown the potential usefulness of combining the information on the type of preneoplastic lesions, genetic and epigenetic, lifestyle and virulence bacterial factors in order to identify high risk patients who need more intensive surveillance. The integration of all this information, in a prediction model requires further research and could be the most important contribution for reducing the burden of GC.

  11. Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer.

    Science.gov (United States)

    Bang, Chang Seok; Baik, Gwang Ho; Shin, In Soo; Kim, Jin Bong; Suk, Ki Tae; Yoon, Jai Hoon; Kim, Yeon Soo; Kim, Dong Joon

    2015-06-01

    Controversies persist regarding the effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer (EGC). The aim of this study was to assess the efficacy of Helicobacter pylori eradication after endoscopic resection of EGC for the prevention of metachronous gastric cancer. A systematic literature review and meta-analysis were conducted using the core databases PubMed, EMBASE, and the Cochrane Library. The rates of development of metachronous gastric cancer between the Helicobacter pylori eradication group vs. the non-eradication group were extracted and analyzed using risk ratios (RRs). A random effect model was applied. The methodological quality of the enrolled studies was assessed by the Risk of Bias table and by the Newcastle-Ottawa Scale. Publication bias was evaluated through the funnel plot with trim and fill method, Egger's test, and by the rank correlation test. Ten studies (2 randomized and 8 non-randomized/5,914 patients with EGC or dysplasia) were identified and analyzed. Overall, the Helicobacter pylori eradication group showed a RR of 0.467 (95% CI: 0.362-0.602, P < 0.001) for the development of metachronous gastric cancer after endoscopic resection of EGC. Subgroup analyses showed consistent results. Publication bias was not detected. Helicobacter pylori eradication after endoscopic resection of EGC reduces the occurrence of metachronous gastric cancer.

  12. An 'Early Warning System' for the prevention of dredging potential impacts on sensitive areas

    Science.gov (United States)

    Piermattei, Viviana; Martellucci, Riccardo; Pierattini, Alberto; Bonamano, Simone; Paladini de Mendoza, Francesco; Albani, Marta; Stefanì, Chiara; Madonia, Alice; Fersini, Giorgio; Marcelli, Marco

    2016-04-01

    Coastal marine ecosystems are increasingly subject to multiple pressures and stressors produced by the effects of human activities. Intense and frequent disturbances which affect marine environment can derive from dredging activity, which is a fundamental management for most ports and harbours. The potential environmental effects of dredging procedures are generally due to the excavation of material from the sea bottom and the relocation elsewhere for disposal, overflow from the dredger and loss of material from pipelines during transport. Depending on the location and the intensity of these activities the marine environment, particularly sensitive areas, may be affected by dredging. The main environmental effects can be associated with suspended sediments and increases in turbidity into the water column, which can have adverse effects on marine animals and plants by reducing light penetration and by physical disturbance. For this reason it is fundamental to implement a real time monitoring system to control and prevent negative effects, enabling a rapid response to adverse water quality conditions and a fast activation of mitigation procedures, in agreement with all the reference authorities. In this work we present the development of an innovative 'Early Warning System' based on fixed stations, ad hoc in situ surveys and forecasting models, which was applied to a dredging activity carried out in the Gulf of Gaeta (Latium, Italy). It represents an extension of the C-CEMS (Civitavecchia Coastal Environmental Monitoring System) network, which is operative in the Tyrrhenian sea since 2005.

  13. Counseling role of primary care physicians in preventing early childhood caries in children with congenital heart disease.

    Science.gov (United States)

    Liu, Zifeng; Yu, Dongsheng; Zhou, Lijie; Yang, Jing; Lu, Jiaxuan; Lu, Hui; Zhao, Wei

    2014-12-01

    The dental health of preschool children with congenital heart disease (CHD) is usually poor, which may contribute to the development of infective endocarditis (IE). Primary care physicians play an important role in providing access to preventive dental services, particularly for preschool children. The object of this study was to provide epidemiologic evidence for the impact of primary care physicians' (PCP's) counseling role on early childhood caries in children with CHD in Guangzhou, China, which might guide future caries prevention to decrease the risk of IE in children with CHD. A hospital-based, case-control study was performed, which contained 100 children with newly diagnosed early childhood caries and 100 matched (sex and age) children without dental caries. All of the subjects were diagnosed with CHD at birth and recruited from Guangdong Cardiovascular Institute from 2012 through 2013. A conditional multivariate logistic-regression model was used to assess the associations between PCPs' role and early childhood caries with a significance level of 5%. Our findings revealed that mother's education level (OR = 0.36, CL = 0.14-0.92) and knowledge, being educated on the relationship between CHD and infective endocarditis (OR = 0.48, CL = 0.25-0.94) and the impact of oral health on infective endocarditis (OR = 0.37, CL = 0.18-0.79) by the PCP were associated with early childhood caries. PCPs played an important role in preventing early childhood caries among preschool children with CHD in Guangzhou, China.

  14. Prevention, early detection and team management of skin cancer in primary care: contribution to The health of the nation objectives.

    Science.gov (United States)

    Jackson, A

    1995-02-01

    The incidence of all skin cancers is increasing. If The health of the nation targets are to be addressed, incidence figures need to be more accurate. Solar damage is the major causal factor in all skin cancers. Certain individual risk factors also play an important part, especially in the development of malignant melanoma. Prevention and early detection are crucial in reducing morbidity and mortality from skin cancer. This paper considers the role of primary care skin screening clinics and cutaneous surgery facilities in the early detection and management of skin cancer. It also illustrates the value of a team approach in primary care in the prevention and early detection of skin cancer and in the more accurate recording of incidence rates.

  15. Breast cancer prevention: lessons to be learned from mechanisms of early pregnancy-mediated breast cancer protection.

    Science.gov (United States)

    Meier-Abt, Fabienne; Bentires-Alj, Mohamed; Rochlitz, Christoph

    2015-03-01

    Pregnancy at early, but not late age, has a strong and life-long protective effect against breast cancer. The expected overall increase in breast cancer incidence demands the development of a pharmaceutical mimicry of early-age pregnancy-mediated protection. Recently, converging results from rodent models and women on molecular and cellular mechanisms underlying the protective effect of early-age pregnancy have opened the door for translational studies on pharmacologic prevention against breast cancer. In particular, alterations in Wnt and TGFβ signaling in mammary stem/progenitor cells reveal new potential targets for preventive interventions, and thus might help to significantly reduce the incidence of breast cancer in the future. ©2015 American Association for Cancer Research.

  16. Circulatory Estrogen Level Protects Against Breast Cancer in Obese Women

    Science.gov (United States)

    Suba, Zsuzsanna

    2013-01-01

    Literary data suggest apparently ambiguous interaction between menopausal status and obesity-associated breast cancer risk based on the principle of the carcinogenic capacity of estrogen. Before menopause, breast cancer incidence is relatively low and adiposity is erroneously regarded as a protective factor against this tumor conferred by the obesity associated defective estrogen-synthesis. By contrast, in postmenopausal cases, obesity presents a strong risk factor for breast cancer being mistakenly attributed to the presumed excessive estrogen-production of their adipose-tissue mass. Obesity is associated with dysmetabolism and endangers the healthy equilibrium of sexual hormone-production and regular menstrual cycles in women, which are the prerequisites not only for reproductive capacity but also for somatic health. At the same time, literary data support that anovulatory infertility is a very strong risk for breast cancer in young women either with or without obesity. In the majority of premenopausal women, obesity associated insulin resistance is moderate and may be counteracted by their preserved circulatory estrogen level. Consequently, it is not obesity but rather the still sufficient estrogen-level, which may be protective against breast cancer in young adult females. In obese older women, never using hormone replacement therapy (HRT) the breast cancer risk is high, which is associated with their continuous estrogen loss and increasing insulin-resistance. By contrast, obese postmenopausal women using HRT, have a decreased risk for breast cancer as the protective effect of estrogen-substitution may counteract to their obesity associated systemic alterations. The revealed inverse correlation between circulatory estrogen-level and breast cancer risk in obese women should advance our understanding of breast cancer etiology and promotes primary prevention measures. New patents recommend various methods for the prevention and treatment of obesity

  17. Identifying economic hurdles to early adoption of preventative practices: The case of trunk diseases in California winegrape vineyards

    Directory of Open Access Journals (Sweden)

    Jonathan Kaplan

    2016-12-01

    Full Text Available Despite the high likelihood of infection and substantial yield losses from trunk diseases, many California practitioners wait to adopt field-tested, preventative practices (delayed pruning, double pruning, and application of pruning-wound protectants until after disease symptoms appear in the vineyard at around 10 years old. We evaluate net benefits from adoption of these practices before symptoms appear in young Cabernet Sauvignon vineyards and after they become apparent in mature vineyards to identify economic hurdles to early adoption. We simulate winegrape production in select counties of California and find widespread benefits from early adoption, increasing vineyard profitable lifespans, in some cases, by close to 50%. However, hurdles may result from uncertainty about the cost and returns from adoption, labor constraints, long time lags in benefits from early adoption, growers’ perceived probabilities of infection, and their discount rate. Development of extension resources communicating benefits and potential hurdles to growers likely reduces uncertainty, increasing early adoption. Improvements in efficacy of preventative practices, perhaps by detecting when pathogen spores are released into the vineyard, will increase early adoption. Lastly, practice cost reductions will increase early adoption too, especially when the time it takes for adoption to payoff and infection uncertainty are influential in adoption decisions.

  18. Implementation of program of prevention and early detection of osteoporosis among women of Primorsko-goranska County.

    Science.gov (United States)

    Janković, Suzana; Kresina, Helena Glibotić; Zezelj, Sandra Pavicić; Kresina, Sandro

    2011-09-01

    The aim of this paper is to present preliminary data of Program of prevention and early detection of osteoporosis among women in Primorsko-goranska County. Osteoporosis is recognized as a public health problem for which clearly preventive measures are defined. Measurement of bone density was done by ultrasound densitometry of the calcaneus among women aged from 45 to 69 years old. 688 women were examined and they were classified in five five-year age groups. The women with the osteoporosis (T-score educative booklet with advices for healthy nutrition and physical activity. Implementation of this program indicated the importance of proper lifestyle in the prevention of osteoporosis. Average T-scores of all five groups of women show that osteopenia occurs also in the youngest ones. This indicates the need for a systematic approach to preventing osteoporosis through education of women including younger ones and creating conditions for organized physical activities at the community level.

  19. Estrogen therapy in older patients with recurrent urinary tract infections: a review.

    Science.gov (United States)

    Rozenberg, S; Pastijn, A; Gevers, R; Murillo, D

    2004-01-01

    Although urogenital complaints, such as recurrent lower urinary tract infections (UTI), and dysuria, are commonly encountered in elderly women, few women have participated in randomized studies of estrogen therapy for this condition. This is a paradox in view of the often cited beneficial effect of estrogen in reducing the incidence of UTI. Present evidence documents that in postmenopausal women, hormone replacement therapy using topical estrogen normalizes the vaginal flora and greatly reduces the risk of vaginal atrophy. Similarly, vaginal estrogen administration seems to be effective for preventing recurrent urinary tract infections (UTI).

  20. Early prevention and intervention of Class II division 1 in growing patients

    Science.gov (United States)

    Keerthi, V. Naga; Kanya, S. Dhivya; Babu, K. Pradeep; Mathew, Anoop; Kumar, A. Nanda

    2016-01-01

    Early screening and diagnosis help in preventing and intercepting the severity of the malocclusion which helps in addressing the esthetic and functional concerns. Growth modulation such as mandibular advancement has been an effective procedure in orthodontics. Mandibular growth advancer (MGA) and PowerScope are gaining popularity recently as these are effective in achieving the mandibular advancement and ease of fabrication, placement, and wear. MGA was fabricated by making the upper and lower splints separately and are placed in the oral cavity by joining the two splints in the new construction bite using cold cure, MGA when worn during growth phase helps in condylar remodeling in the temporomandibular joint thus helps in advancement of the mandible. The proclination of the upper anteriors in Class II division 1 can be moved lingually by activating the labial bow in the splint. Dr. Andy Hayes worked in conjunction with American orthodontics developed PowerScope. PowerScope delivers Class II correction with a combination of patient comfort and ease of use that was unmatched among other appliances. This ready to use chairside solution required no laboratory setup, making for a much quicker, and easier installation process and appointment. PowerScopes high quality, fixed one-piece design requires no patient compliance. These superior qualities of PowerScope help in correction of Class II skeletal growing patient in conjunction with fixed orthodontic therapy. MGA and PowerScope were chosen as a functional appliance for this study, which shows decreased ANB angle and effective mandible length was increased. PMID:27195234

  1. Cluster-randomized xylitol toothpaste trial for early childhood caries prevention.

    Science.gov (United States)

    Chi, Donald L; Tut, Ohnmar; Milgrom, Peter

    2014-01-01

    The purpose of this study was to assess the efficacy of supervised tooth-brushing with xylitol toothpaste to prevent early childhood caries (ECC) and reduce mutans streptococci. In this cluster-randomized efficacy trial, 196 four- to five-year-old children in four Head Start classrooms in the Marshall Islands were randomly assigned to supervised toothbrushing with 1,400 ppm/31 percent fluoride xylitol or 1,450 ppm fluoride sorbitol toothpaste. We hypothesized that there would be no difference in efficacy between the two types of toothpaste. The primary outcome was the surface-level primary molar caries increment (d(2-3)mfs) after six months. A single examiner was blinded to classroom assignments. Two classrooms were assigned to the fluoride-xylitol group (85 children), and two classrooms were assigned to the fluoride-sorbitol group (83 children). The child-level analyses accounted for clustering. There was no difference between the two groups in baseline or end-of-trial mean d(2-3)mfs. The mean d(2-3)mfs increment was greater in the fluoride-xylitol group compared to the fluoride-sorbitol group (2.5 and 1.4 d(2-3)mfs, respectively), but the difference was not significant (95% confidence interval: -0.17, 2.37; P=.07). No adverse effects were reported. After six months, brushing with a low-strength xylitol/fluoride tooth-paste is no more efficacious in reducing ECC than a fluoride-only toothpaste in a high caries-risk child population.

  2. Acceptability of early infant male circumcision as an HIV prevention intervention in Zimbabwe: a qualitative perspective.

    Directory of Open Access Journals (Sweden)

    Webster Mavhu

    Full Text Available BACKGROUND: Early infant male circumcision (EIMC is simpler, safer and more cost-effective than adult circumcision. In sub-Saharan Africa, there are concerns about acceptability of EIMC which could affect uptake. In 2009 a quantitative survey of 2,746 rural Zimbabweans (aged 18-44 indicated that 60% of women and 58% of men would be willing to have their newborn son circumcised. Willingness was associated with knowledge of HIV and male circumcision. This qualitative study was conducted to better understand this issue. METHODS: In 2010, 24 group discussions were held across Zimbabwe with participants from seven ethnic groups. Additionally, key informant interviews were held with private paediatricians who offer EIMC (n = 2 plus one traditional leader. Discussions were audio-recorded, transcribed, translated into English (where necessary, coded using NVivo 8 and analysed using grounded theory principles. RESULTS: Knowledge of the procedure was poor. Despite this, acceptability of EIMC was high among parents from most ethnic groups. Discussions suggested that fathers would make the ultimate decision regarding EIMC although mothers and extended family can have (often covert influence. Participants' concerns centred on: safety, motive behind free service provision plus handling and disposal of the discarded foreskin. Older men from the dominant traditionally circumcising population strongly opposed EIMC, arguing that it separates circumcision from adolescent initiation, as well as allowing women (mothers to nurse the wound, considered taboo. CONCLUSIONS: EIMC is likely to be an acceptable HIV prevention intervention for most populations in Zimbabwe, if barriers to uptake are appropriately addressed and fathers are specifically targeted by the programme.

  3. Early HIV treatment in the United States prevented nearly 13,500 infections per year during 1996-2009.

    Science.gov (United States)

    Goldman, Dana P; Juday, Timothy; Seekins, Daniel; Linthicum, Mark T; Romley, John A

    2014-03-01

    In recent years, guidelines for HIV treatment have recommended initiation of combination antiretroviral therapy (cART) earlier in the course of the disease than was previously the case. These recommendations stem in part from growing evidence that treatment reduces the risk of sexual transmission. We used an epidemiological model of disease transmission and progression to assess HIV prevention through early treatment-that is, initiation of cART when CD4 white blood cell counts are in excess of 350 cells per cubic millimeter. (CD4 cells are involved in the immune system's defense against tumors and infection; the number of CD4 cells in a cubic millimeter of blood is a standard measure of immune response to antiretroviral therapy.) We estimated that the actual timing of treatment initiation in the United States prevented 188,000 HIV cases in the period 1996-2009. "Very early" treatment (at CD4 counts greater than 500) accounted for four-fifths of the prevented cases. For all of the prevented cases, the losses in life expectancy that were avoided were worth $128 billion, assuming that a life-year has a value of $150,000. These findings underscore the cost-effectiveness of early HIV treatment.

  4. [Influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma].

    Science.gov (United States)

    Xiong, Tao; Wanggou, Siyi; Li, Xuejun; Liu, Qing; Jiang, Xingjun; Peng, Zefeng; Yuan, Xianrui

    2016-10-28

    To explore the influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma.
 Methods: The data of 83 patients, who underwent unilateral sub-frontal approach resection of craniopharyngioma between 2010 and 2014 by the same senior neurosurgeon, were retrospectively analyzed. The patients were divided into a vasopressin tannate group (used group) and a control group. The diabetes insipidus and serum sodium changes were compared between the two groups.
 Results: Compared with the control group, the incidence of diabetes insipidus decreased at the early postoperation in the vasopressin tannate group (Pdiabetes insipidus in patients with pituitary stalk excision and tumor close adhesion to the third ventricle floor at the early postoperation (Pdiabetes insipidus in the vasopressin tannate group was decreased compared with the control group (Pdiabetes insipidus and hypernatremia incidence at the early postoperative stage after microsurgery for craniopharyngioma.

  5. Rapid estrogen receptor alpha signaling mediated by ERK activation regulates vascular tone in male and ovary-intact female mice.

    Science.gov (United States)

    Kim, Seong Chul; Boese, Austin C; Moore, Matthew H; Cleland, Rea M; Chang, Lin; Delafontaine, Patrice; Yin, Ke-Jie; Lee, Jean-Pyo; Hamblin, Milton H

    2017-09-08

    Estrogen has been shown to affect vascular reactivity. Here, we assessed estrogen receptor-alpha (ERα) dependency of estrogenic effects on vasorelaxation via a rapid nongenomic pathway in both male and ovary-intact female mice. We compared the effect of a primary estrogen, 17 beta-estradiol (E2) or 4,4',4"-(4-propyl-[1H]pyrazole-1,3,5-triyl)tris-phenol (PPT) (selective ERα agonist). We found that E2 and PPT induced greater aortic relaxation in females than males, indicating ERα mediation, which is further validated by employing ERα antagonism. Treatment with 1,3-Bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP dihydrochloride) (ERα antagonist) attenuated PPT-mediated vessel relaxation in both sexes. ERα-mediated vessel relaxation is further validated by the absence of significant PPT-mediated relaxation in aortas isolated from ERα knockout mice. Treatment with a specific extracellular signal-regulated kinase (ERK) inhibitor, PD98059 reduced E2-induced vessel relaxation in both sexes, but to a lesser extent in females. Further, PD98059 prevented PPT-induced vessel relaxation in both sexes. Both E2 and PPT treatment activated ERK as early as 5-10 min, which was attenuated by PD98059 in aortic tissue, cultured primary vascular smooth muscle cells (VSMCs), and endothelial cells (ECs). Aortic rings denuded of endothelium showed no differences in vessel relaxation following E2 or PPT treatment, implicating a role of ECs in the observed sex differences. Here, our results are unique to show estrogen-stimulated rapid ERα signaling mediated by ERK activation in aortic tissue, as well as VSMCs and ECs in vitro, in regulating vascular function by employing side-by-side comparisons in male and ovary-intact female mice in response to E2 or PPT. Copyright © 2017, American Journal of Physiology-Heart and Circulatory Physiology.

  6. Effects of Chronic Estrogen Administration in the Ventromedial Nucleus of the Hypothalamus (VMH) on Fat and Bone Metabolism in Ovariectomized Rats

    NARCIS (Netherlands)

    Zhang, Z; Liu, J; Veldhuis-Vlug, A G; Su, Y; Foppen, E; van der Eerden, B C J; Koedam, M; Bravenboer, N; Kalsbeek, A.; Boelen, A; Fliers, E; Bisschop, P H

    2016-01-01

    Estrogen deficiency after ovariectomy (OVX) results in increased adiposity and bone loss, which can be prevented by systemic 17-β estradiol (E2) replacement. Studies in transgenic mice suggested that in addition to direct actions of estrogen in peripheral tissues, also estrogen signaling in the

  7. Effects of Chronic Estrogen Administration in the Ventromedial Nucleus of the Hypothalamus (VMH) on Fat and Bone Metabolism in Ovariectomized Rats

    NARCIS (Netherlands)

    Zhang, Z; Liu, J; Veldhuis-Vlug, A G; Su, Y; Foppen, E; van der Eerden, B C J; Koedam, M; Bravenboer, N; Kalsbeek, A.; Boelen, A; Fliers, E; Bisschop, P H

    2016-01-01

    Estrogen deficiency after ovariectomy (OVX) results in increased adiposity and bone loss, which can be prevented by systemic 17-β estradiol (E2) replacement. Studies in transgenic mice suggested that in addition to direct actions of estrogen in peripheral tissues, also estrogen signaling in the hypo

  8. Estrogen receptor agonists/antagonists in breast cancer therapy: A critical review.

    Science.gov (United States)

    Jameera Begam, A; Jubie, S; Nanjan, M J

    2017-04-01

    Estrogens display intriguing tissue selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer. There are also strong evidences to show that both endogenous and exogenous estrogens are involved in the pathogenesis of breast cancer. Tamoxifen has been the only drug of choice for more than 30years to treat patients with estrogen related (ER) positive breast tumors. There is a need therefore, for identifying newer, potential and novel candidates for breast cancer. Keeping this in view, the present review focuses on selective estrogen receptor modulators and estrogen antagonists such as sulfatase and aromatase inhibitors involved in breast cancer therapy. A succinct and critical overview of the structure of estrogen receptors, their signaling and involvement in breast carcinogenesis are herein described. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Estrogen and progesterone receptor status determined by the Ventana ES 320 automated immunohistochemical stainer and the CAS 200 image analyzer in 236 early-stage breast carcinomas: prognostic significance.

    Science.gov (United States)

    Layfield, L J; Saria, E A; Conlon, D H; Kerns, B J

    1996-03-01

    The quantitation of estrogen and progesterone receptors (ER and PgR) has become the standard of care in the evaluation of patients with primary breast carcinoma. It has been demonstrated that ER and PgR detected by immunohistochemical methods in formalin-fixed paraffin-embedded tissue can be quantified by computerized image analysis. In this study, ER and PgR levels were determined by using an automated immunochemistry stainer (Ventana ES 320) and an image analyzer (CAS 200) in a series of 236 patients with stage I/II carcinoma of the breast. The degree of correlation of the ER and PgR levels determined by the dextran-coated charcoal method (DCC) with image analysis quantitation was high (r=0.75). The agreement between both methods was 77% for ER and 73% for PgR. Hormone receptor levels were correlated with prognosis as determined by overall survival. An ER level of 30 fmol/mg as determined by image analysis was established to stratify the patient population most effectively into favorable and unfavorable prognostic groups (P=0.003). An ER level of 20 fmol/mg for prognostic stratification reached statistical significance (P=0.03). The DCC method was not able to stratify the patients into prognostic groups at the traditionally accepted cutpoint of 10 fmol/mg (P=0.52). We conclude that when used in combination, automated immunohistochemistry and quantitative image analysis offer a favorable alternative to the DCC method in assessment of ER and PgR status in human mammary carcinoma. In addition, quantitative immunocytochemistry techniques may prove superior to the DCC method in specimens in which there is limited tumor volume (including fine-needle aspirates), stroma-rich tumors, and early-stage lesions including intraductal carcinoma.

  10. Engaging pregnant and parenting teens: early challenges and lessons learned from the Evaluation of Adolescent Pregnancy Prevention Approaches.

    Science.gov (United States)

    Asheer, Subuhi; Berger, Amanda; Meckstroth, Alicia; Kisker, Ellen; Keating, Betsy

    2014-03-01

    This article draws on data from the ongoing federal Evaluation of Adolescent Pregnancy Prevention Approaches to discuss the early implementation experiences of two new and innovative programs intended to delay rapid repeat pregnancy among teen mothers: (1) AIM 4 Teen Moms, in Los Angeles County, California; and (2) Teen Options to Prevent Pregnancy (T.O.P.P.), in Columbus, Ohio. Program staff report common challenges in working with teen mothers, particularly concerning recruitment and retention, staff capacity and training, barriers to participation, and participants' overarching service needs. Lessons learned in addressing these challenges provide useful guidance to program developers, providers, policy makers, and stakeholders working with similar populations.

  11. Estrogenic effects from household stoves.

    Science.gov (United States)

    Wu, W Z; Chen, J; Rehmann, K; Schramm, K W; Kettrup

    2002-09-01

    With the application of a genetically modified yeast, estrogen receptor-activating compounds were detected in the soot and emission gas of a wood-burning household stove. The EC50 value of 17beta-estradiol was divided by the EC50 value of soot, and the obtained relative estrogenic value for raw soot was 2.37E-5, indicating that soot was about 100,000 times less estrogenic than 17beta-estradiol. Chemical analysis revealed that alkyl phenol, benzonic acid, and PAHs represented the major constituents in the most potent fractions of the soot. Along with PAHs, other constituents might also contribute to the estrogenicity of soot.

  12. Evolution of estrogen receptors in ray-finned fish and their comparative responses to estrogenic substances.

    Science.gov (United States)

    Tohyama, Saki; Miyagawa, Shinichi; Lange, Anke; Ogino, Yukiko; Mizutani, Takeshi; Ihara, Masaru; Tanaka, Hiroaki; Tatarazako, Norihisa; Kobayashi, Tohru; Tyler, Charles R; Iguchi, Taisen

    2016-04-01

    In vertebrates, estrogens play fundamental roles in regulating reproductive activities through estrogen receptors (ESRs), and disruption of estrogen signaling is now of global concern for both wildlife and human health. To date, ESRs of only a limited number of species have been characterized. We investigated the functional diversity and molecular basis or ligand sensitivity of ESRs among ray-finned fish species (Actinopterygii), the most variable group within vertebrates. We cloned and characterized ESRs from several key species in the evolution of ray-finned fish including bichir (Polypteriformes, ESR1 and ESR2) at the basal lineage of ray-finned fish, and arowana (Osteoglossiformes, ESR1 and ESR2b) and eel (Anguilliformes, ESR1, ESR2a and ESR2b) both belonging to ancient early-branching lineages of teleosts, and suggest that ESR2a and ESR2b emerged through teleost-specific whole genome duplication, but an ESR1 paralogue has been lost in the early lineage of euteleost fish species. All cloned ESR isoforms showed similar responses to endogenous and synthetic steroidal estrogens, but they responded differently to non-steroidal estrogenic endocrine disrupting chemicals (EDCs) (e.g., ESR2a exhibits a weaker reporter activity compared with ESR2b). We show that variation in ligand sensitivity of ESRs can be attributed to phylogeny among species of different taxonomic groups in ray-finned fish. The molecular information provided contributes both to understanding of the comparative role of ESRs in the reproductive biology of fish and their comparative responses to EDCs.

  13. Signaling from the membrane via membrane estrogen receptor-alpha: estrogens, xenoestrogens, and phytoestrogens.

    Science.gov (United States)

    Watson, Cheryl S; Bulayeva, Nataliya N; Wozniak, Ann L; Finnerty, Celeste C

    2005-01-01

    Estrogen mimetics in the environment and in foods can have important consequences for endocrine functions. When previously examined for action via genomic steroid signaling mechanisms, most of these compounds were found to be very weak agonists. We have instead tested their actions via several membrane-initiated signaling mechanisms in GH3/B6 pituitary tumor cells extensively selected for high (responsive) or low (nonresponsive) expression of the membrane version of estrogen receptor-alpha (mERalpha). We found many estrogen mimetic compounds to be potently active in our quantitative extracellular-regulated kinase (ERK) activation assays, to increase cellular Ca++ levels, and to cause rapid prolactin release. However, these compounds may activate one or both mechanisms with different potencies. For instance, some compounds activate ERKs in both pM and nM concentration ranges, while others are only active at nM and higher concentrations. Compounds also show great differences in their temporal activation patterns. While estradiol causes a bimodal time-dependent ERK activation (peaking at both 3 and 30 min), most estrogen mimetics cause either an early phase activation, a late phase activation, or an early sustained activation. One xenoestrogen known to be a relatively potent activator of estrogen response element-mediated actions (bisphenol A) is inactive as an ERK activator, and only a modest inducer of Ca++ levels and prolactin release. Many different signaling machineries culminate in ERK activation, and xenoestrogens differentially affect various pathways. Clearly individual xenoestrogens must be individually investigated for their differing abilities to activate distinct membrane-initiated signal cascades that lead to a variety of cellular functions.

  14. The balance of estrogen metabolites in breast cancer and the ways of its correction

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    L. A. Ashrafyan

    2015-01-01

    Full Text Available Background. A clear relationship is now found between the activity of estrogen metabolites and the development of tumors in estrogen-dependent tissues. Many international and Russian studies could identify a number of compounds involved in the regulation of estrogen metabolites. Indole-3-carbinol is one of these compounds that correct a ratio of 2-hydroxyestrone (2-OHE1 to 16-OHE1. It is a phytonutrient that is contained in Cruciferous vegetables and has antitumor activity. Our investigations used highly purified indole-3-carbinol (Indinol. The ability to identify the role of metabolic syndrome, by applying the current methodological approaches, allowed us to study the effect of highly purified indole-3-carbinol on the level of expression of estrogen metabolites and to attempt to expand views on procedures to prevent and treat breast tumors. Materials and methods. A total of 136 women were comprehensively examined; of them 44 patients formed a group of those with morphologically verified hormone-independent breast cancer (BC and 42 patients were a group of those with hormone-dependent BC. A control group included 50 women without signs of breast disease. In all the patients, body mass index was calculated; the ratio of urinary estrogen metabolites (2-ОНЕ1/16α-ОНЕ1 was quantified; and biopsy specimens and operative material were histologically and immunohistologically studied. Results. The BC patients were noted to have the high expression of 16α-OHE1 and the low values of 2-OHE1 (ratio, 0.42 as compared to the control group (2.09, which was an important component of metabolic syndrome. The BC patients had the high level of concomitant endocrine metabolic disturbances with the high body mass index, which reflected the clinical manifestation of metabolic syndrome. Indinol used to treat both hormone-dependent and hormone-independent BC showed an antimetabolic effect that was most pronounced 6 months later. Conclusion. Thus, early correction

  15. Prevention and Treatment of Esophageal Stenosis after Endoscopic Submucosal Dissection for Early Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Jing Wen

    2014-01-01

    Full Text Available Endoscopic submucosal dissection (ESD for the treatment of esophageal mucosal lesions is associated with a risk of esophageal stenosis, especially for near-circumferential or circumferential esophageal mucosal defects. Here, we review historic and modern studies on the prevention and treatment of esophageal stenosis after ESD. These methods include prevention via pharmacological treatment, endoscopic autologous cell transplantation, endoscopic esophageal dilatation, and stent placement. This short review will focus on direct prevention and treatment, which may help guide the way forward.

  16. Do estrogen or selective estrogen receptor modulators improve quality of life for women with postmenopausal osteoporosis?

    Science.gov (United States)

    Gold, Deborah T; Silverman, Stuart L

    2007-03-01

    Osteoporotic fractures result in significant deficits in health-related quality of life (HRQOL). The accumulation of deficits resulting from osteoporosis and fractures is now recognized as a major cause of reduced HRQOL in women after the menopause and in later life. Some of these same postmenopausal women may also have deficits in HRQOL related to vasomotor symptoms during the menopausal transition. Although estrogen therapy has not been shown to improve overall HRQOL in late postmenopausal women in randomized, controlled trials, it may improve menopausal symptoms. In contrast, selective estrogen receptor modulators (SERMs) such as raloxifene may increase vasomotor symptoms. Although estrogen is not indicated for the primary prevention of osteoporosis, estrogen therapy may be considered for the postmenopausal woman at risk of osteoporotic fracture who is symptomatic and who is not at high risk of breast cancer or cardiovascular events. Raloxifene decreases risk of invasive breast cancer and may be considered in women at high risk of breast cancer. Decision making about osteoporosis treatment should also consider the impact of the treatment on HRQOL.

  17. Early life opportunities for prevention of diabetes in low and middle income countries

    Directory of Open Access Journals (Sweden)

    Hanson Mark A

    2012-11-01

    Full Text Available Abstract Background The global burden of diabetes and other non-communicable diseases is rising dramatically worldwide and is causing a double poor health burden in low- and middle-income countries. Early life influences play an important part in this scenario because maternal lifestyle and conditions such as gestational diabetes and obesity affect the risk of diabetes in the next generation. This indicates important periods during the lifecourse when interventions could have powerful affects in reducing incidence of non-communicable diseases. However, interventions to promote diet and lifestyle in prospective parents before conception have not received sufficient attention, especially in low- and middle-income countries undergoing socio-economic transition. Discussion Interventions to produce weight loss in adults or to reduce weight gain in pregnancy have had limited success and might be too late to produce the largest effects on the health of the child and his/her later risk of non-communicable diseases. A very important factor in the prevention of the developmental component of diabetes risk is the physiological state in which the parents enter pregnancy. We argue that the most promising strategy to improve prospective parents’ body composition and lifestyle is the promotion of health literacy in adolescents. Multiple but integrated forms of community-based interventions that focus on nutrition, physical activity, family planning, breastfeeding and infant feeding practices are needed. They need to address the wider social economic context in which adolescents live and to be linked with existing public health programmes in sexual and reproductive health and maternal and child health initiatives. Summary Interventions aimed at ensuring a healthy body composition, diet and lifestyle before pregnancy offer a most effective solution in many settings, especially in low- and middle-income countries undergoing socio-economic transition. Preparing

  18. Lithium prevents early cytosolic calcium increase and secondary injurious calcium overload in glycolytically inhibited endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Bosche, Bert, E-mail: bert.bosche@uk-essen.de [Department of Neurology, University of Duisburg-Essen (Germany); Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne (Germany); Schäfer, Matthias, E-mail: matthias.schaefer@sanofi.com [Institute of Physiology, Justus-Liebig-University Giessen (Germany); Graf, Rudolf, E-mail: rudolf.graf@nf.mpg.de [Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne (Germany); Härtel, Frauke V., E-mail: frauke.haertel@tu-dresden.de [Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden (Germany); Schäfer, Ute, E-mail: ute.schaefer@medunigraz.at [Research Unit for Experimental Neurotraumatology, Medical University of Graz (Austria); Noll, Thomas, E-mail: thomas.noll@tu-dresden.de [Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden (Germany)

    2013-05-03

    Highlights: •We investigate free calcium as a central signalling element in endothelial cells. •Inhibition of glycolysis with 2-deoxy-D-glucose reduces cellular ATP. •This manoeuvre leads to a biphasic increase and overload of free calcium. •Pre-treatment with lithium for 24 h abolishes both phases of the calcium increase. •This provides a new strategy to protect endothelial calcium homeostasis and barrier function. -- Abstract: Cytosolic free calcium concentration ([Ca{sup 2+}]{sub i}) is a central signalling element for the maintenance of endothelial barrier function. Under physiological conditions, it is controlled within narrow limits. Metabolic inhibition during ischemia/reperfusion, however, induces [Ca{sup 2+}]{sub i} overload, which results in barrier failure. In a model of cultured porcine aortic endothelial monolayers (EC), we addressed the question of whether [Ca{sup 2+}]{sub i} overload can be prevented by lithium treatment. [Ca{sup 2+}]{sub i} and ATP were analysed using Fura-2 and HPLC, respectively. The combined inhibition of glycolytic and mitochondrial ATP synthesis by 2-desoxy-D-glucose (5 mM; 2-DG) plus sodium cyanide (5 mM; NaCN) caused a significant decrease in cellular ATP content (14 ± 1 nmol/mg protein vs. 18 ± 1 nmol/mg protein in the control, n = 6 culture dishes, P < 0.05), an increase in [Ca{sup 2+}]{sub i} (278 ± 24 nM vs. 71 ± 2 nM in the control, n = 60 cells, P < 0.05), and the formation of gaps between adjacent EC. These observations indicate that there is impaired barrier function at an early state of metabolic inhibition. Glycolytic inhibition alone by 10 mM 2-DG led to a similar decrease in ATP content (14 ± 2 nmol/mg vs. 18 ± 1 nmol/mg in the control, P < 0.05) with a delay of 5 min. The [Ca{sup 2+}]{sub i} response of EC was biphasic with a peak after 1 min (183 ± 6 nM vs. 71 ± 1 nM, n = 60 cells, P < 0.05) followed by a sustained increase in [Ca{sup 2+}]{sub i}. A 24-h pre-treatment with 10 mM of lithium

  19. The efficacy of lower uterine segment compression for prevention of early postpartum hemorrhage after vaginal delivery.

    Science.gov (United States)

    Chantrapitak, Wanchai; Srijuntuek, Kamol; Wattanaluangarun, Renu

    2011-06-01

    To determine the efficacy and amount of blood loss of the maneuver utilizing lower uterine segment compression (LUSC) for the prevention of early postpartum hemorrhage. The present study enrolled 686 mothers with singleton pregnancy, gestational ages between 28 and 42 weeks, at the Department of Obstetrics and Gynecology, Charoenkrung Pracharak Hospital, Bangkok between July 2009 and March 2010. All subjects had no past medical history and delivered by vaginal route. They were divided into two groups, the experimental group and the control group. Mothers in both experimental and control groups were treated with the same methods, oxytocin administration before and after delivery, clamping and cutting umbilical cords within three minutes after birth of the newborns, and placental delivery done by controlled cord traction together with uterine massage at the fundus through the abdominal wall immediately. In addition, in the experimental group, the subjects were assisted by LUSC for 10 minutes. The amount of blood loss was measured and recorded two hours after delivery of the placentas in both experimental and control groups. Among 686 cases, nine cases were excluded from the present study. They were composed of five cases in the control group, with retained placenta, and four cases in the experimental group because of retained placenta, retained placental fragments, severe perineum tear, and vaginal hematoma. Subjects in the experimental group who were additionally assisted by LUSC were found to have lesser incidence of PPH with statistical significance in comparison to those in the control group (2.9% vs. 6.8%; relative risk 0.43, 95% confidence interval 0.21-0.90, p = 0.02). The amount of blood loss reduced by 29.26 ml (289.70 +/- 179.53 mlvs. 260.44 +/- 116.30 ml), p = 0.012). Lower uterine segment compression (LUSC) significantly reduced the rate of PPH and amount of blood loss after vaginal delivery The efficacy of this technique was over the conventional method

  20. A cluster randomised school-based lifestyle intervention programme for the prevention of childhood obesity and related early cardiovascular disease (JuvenTUM 3

    Directory of Open Access Journals (Sweden)

    Haller Bernhard

    2011-04-01

    Full Text Available Abstract Background Childhood obesity is not only associated with adult obesity but also with increased risk of adult onset of type 2 diabetes and subsequent coronary heart disease. The potential effects of school-based health intervention programmes on cardiovascular risk and surrogate markers are unclear, as only few studies have attempted to investigate a complete risk profile including a detailed laboratory analysis or micro- and macrovascular function. In this study a comprehensive school-based randomized intervention programme will be investigated in 10-14-year old children addressing the influence of lifestyle intervention on inactivity, cardiometabolic risk factors and early signs of vascular disease. Methods/Design 15 secondary schools in Southern Germany are randomly assigned to intervention or control schools. Children in the fifth grade (10-11 years will be observed over four years. The study combines a school-based with a home-based approach, aiming at children, teachers and parents. The main components are weekly lifestyle-lessons for children, taught by regular classroom teachers to increase physical activity in- and outside of school, to improve eating patterns at school and at home, to reduce media consumption and to amplify well-being. In 4-6 annual meetings, teachers receive information about health-related topics with worksheets for children and supporting equipment, accounting for school-specific needs and strategies. Parents' trainings are provided on a regular basis. All examinations are performed at the beginning and at the end of every school year. Anthropometry includes measurements of BMI, waist and upper arm circumferences, skinfold thickness as well as peripheral blood pressure. Blood sampling includes lipid parameters, insulin, glucose, hsCRP, adiponectin, and IL-6 as well as testosteron and estrogen to determine maturation status. Vascular function is non-invasively assessed by measuring arterial stiffness in large

  1. Feeding blueberry diets in early life prevent senescence of osteoblasts and bone loss in ovariectomized adult female rats.

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    Jian Zhang

    Full Text Available BACKGROUND: Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied. METHODOLOGY AND PRINCIPAL FINDINGS: In this report, we show that feeding a high quality diet supplemented with blueberries (BB to pre-pubertal rats throughout development or only between postnatal day 20 (PND20 and PND34 prevented ovariectomy (OVX-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation. CONCLUSIONS/SIGNIFICANCE: These results indicate: 1 a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2 the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence.

  2. Counseling role of primary care physicians in preventing early childhood caries in children with congenital heart disease.

    Science.gov (United States)

    Liu, Zifeng; Yu, Dongsheng; Zhou, Lijie; Yang, Jing; Lu, Jiaxuan; Lu, Hui; Zhao, Wei

    2014-12-01

    The dental health of preschool children with congenital heart disease (CHD) is usually poor, which may contribute to the development of infective endocarditis (IE).Primary care physicians play an important role in providing access to preventive dental services, particularly for preschool children. The object of this study was to provide epidemiologic evidence for the impact of primary care physicians’ (PCP’s) counseling role on early childhood caries in children with CHD in Guangzhou, China, which might guide future caries prevention to decrease the risk of IE in children with CHD. A hospital-based,case-control study was performed, which contained 100 children with newly diagnosed early childhood caries and 100 matched (sex and age) children without dental caries. All of the subjects were diagnosed with CHD at birth and recruited from Guangdong Cardiovascular Institute from 2012 through 2013. A conditional multivariate logistic-regression model was used to assess the associations between PCPs’ role and early childhood caries with a significance level of 5%. Our findings revealed that mother's education level (OR = 0.36,CL = 0.14–0.92) and knowledge, being educated on the relationship between CHD and infective endocarditis (OR = 0.48, CL = 0.25–0.94) and the impact of oral health on infective endocarditis (OR = 0.37, CL = 0.18–0.79) by the PCP were associated with early childhood caries. PCPs played an important role in preventing early childhood caries among preschool children with CHD in Guangzhou, China.

  3. The rationale for preventive treatments for early post-tympanostomy tube otorrhea in persistent otitis media with effusion.

    Science.gov (United States)

    Faramarzi, Mohammad; Roosta, Sareh; Shishegar, Mahmood; Abbasi, Rohollah; Atighechi, Saeid

    2016-06-01

    Some studies have shown that post-tympanostomy tube otorrhea (PTTO) is a common complication after tympanostomy tube insertion. There are wide range of controversies about the incidence of PTTO and different methods of preventive treatment. The aim of this study was to determine the incidence of early PTTO in persistent otitis media with effusion in our centers. We also investigated the effect of preventive treatments on the incidence of early PTTO in children with persistent otitis media with effusion. This multi-central study comprised 536 ears belonging to children with otitis media and effusion for at least 3 months, referred for complications arising from post-tympanostomy tube insertion. The patients were randomly divided into three treatment and control groups. In the first group of patients, the middle ear cavity was irrigated with isotonic saline after myringotomy. The second group received oral amoxicillin three times a day for 7 days postoperatively. The third group had similar treatment as the second group, in addition to topical ciprofloxacin drop, 4 drops three times a day for 3 days after operation. The control group did not undergo any treatment. Early post-tympanostomy tube otorrhea was detected in 6 ears (1.1 %), including 3 (2.2 %) from the control group and 3 (2.3 %) from the first group. There was no statistically significant difference in early PTTO between integrated treatment groups and control group (P = 0.111). As the total rate of early post-tympanostomy tube otorrhea was very low, there was no significant difference between the 3 treatment groups and control group. Our study did not support the routine use of preventive therapy. A period of at least 3 months watchful waiting before tympanostomy tube insertion may help reduce the incidence of PTTO.

  4. Counseling Role of Primary Care Physicians in Preventing Early Childhood Caries in Children with Congenital Heart Disease

    Directory of Open Access Journals (Sweden)

    Zifeng Liu

    2014-12-01

    Full Text Available The dental health of preschool children with congenital heart disease (CHD is usually poor, which may contribute to the development of infective endocarditis (IE. Primary care physicians play an important role in providing access to preventive dental services, particularly for preschool children. The object of this study was to provide epidemiologic evidence for the impact of primary care physicians’ (PCP’s counseling role on early childhood caries in children with CHD in Guangzhou, China, which might guide future caries prevention to decrease the risk of IE in children with CHD. A hospital-based, case-control study was performed, which contained 100 children with newly diagnosed early childhood caries and 100 matched (sex and age children without dental caries. All of the subjects were diagnosed with CHD at birth and recruited from Guangdong Cardiovascular Institute from 2012 through 2013. A conditional multivariate logistic-regression model was used to assess the associations between PCPs’ role and early childhood caries with a significance level of 5%. Our findings revealed that mother’s education level (OR = 0.36, CL = 0.14–0.92 and knowledge, being educated on the relationship between CHD and infective endocarditis (OR = 0.48, CL = 0.25–0.94 and the impact of oral health on infective endocarditis (OR = 0.37, CL = 0.18–0.79 by the PCP were associated with early childhood caries. PCPs played an important role in preventing early childhood caries among preschool children with CHD in Guangzhou, China.

  5. The effect of a depression prevention program on negative cognitive style trajectories in early adolescents

    NARCIS (Netherlands)

    Kindt, K.C.M.; Kleinjan, M.; Janssens, J.M.A.M.; Scholte, R.H.J.

    2016-01-01

    As restructuring a negative cognitive style is a central skill taught in many depression prevention programs, we tested whether a universal prevention program evoked a change in negative cognitive style in adolescents. In addition, we examined distinct developmental trajectories of negative cognitiv

  6. Early Childhood Education. National Dropout Prevention Center/Network Newsletter. Volume 22, Number 2

    Science.gov (United States)

    Duckenfield, Marty, Ed.

    2011-01-01

    The "National Dropout Prevention Newsletter" is published quarterly by the National Dropout Prevention Center/Network. This issue contains the following articles: (1) Laying the Foundation for Success (Mary Caputo); (2) Ready or Not? (Laura Koenig); (3) Every Child A School-Ready Child (Leah Newkirk Meunier); (4) Parents As Teachers (Erin Garner);…

  7. Cervical cancer in Mexico and importance of sex education for early prevention in young people and rural population

    Directory of Open Access Journals (Sweden)

    Raúl S. Moran García

    2012-08-01

    Full Text Available Cervical cancer is a serious health problem due to high mortality rates that are associated with it. The high incidence rates can be explained by women and their families’ ignorance about this disease. In fact, cervical cancer can be diagnosed early and, if detected on time, the likelihood of cure is high. Latin America is considered at high risk for cervical cancer. More specifically, cervical cancer in Mexico ranks second in incidence after breast cancer, in spite of having a screening program for over 20 years, which has only been able to prevent 13% of potentially preventable cases. The purpose of this analysis is to once again address the importance cervical cancer, to offer a general overview of the nature of this disease, but most of all, to underscore the relevance of education as a means of detection and prevention.

  8. Prevention of microalbuminuria using early intervention with renin-angiotensin system inhibitors in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Lindhardt, Morten; Rossing, Peter

    2016-01-01

    HYPOTHESIS/OBJECTIVES: Early prevention of diabetic nephropathy by way of blocking the renin-angiotensin system (RAS) in patients with normoalbuminuria seems rational, but trials have so far shown conflicting results. The present meta-analysis was undertaken to investigate if such treatment can...... prevent development of microalbuminuria. MATERIALS AND METHODS: We searched MEDLINE, EMBASE and the Cochrane Library (2 June 2014) for randomised controlled trials, with a population of patients with type 2 diabetes and normoalbuminuria, comparing angiotensin-converting enzyme inhibitors (ACEis...... was variable. In a fixed model analysis ACE or ARB treatment was superior to placebo in relation to prevention of development of microalbuminuria, risk ratio 0.84 (95% confidence interval (CI) 0.79-0.88) pTreatment also showed a trend towards a reduction...

  9. Prevention of microalbuminuria using early intervention with renin-angiotensin system inhibitors in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Lindhardt, Morten; Rossing, Peter

    2016-01-01

    Hypothesis/objectives: Early prevention of diabetic nephropathy by way of blocking the renin-angiotensin system (RAS) in patients with normoalbuminuria seems rational, but trials have so far shown conflicting results. The present meta-analysis was undertaken to investigate if such treatment can...... prevent development of microalbuminuria. Materials and methods: We searched MEDLINE, EMBASE and the Cochrane Library (2 June 2014) for randomised controlled trials, with a population of patients with type 2 diabetes and normoalbuminuria, comparing angiotensin-converting enzyme inhibitors (ACEis...... was variable. In a fixed model analysis ACE or ARB treatment was superior to placebo in relation to prevention of development of microalbuminuria, risk ratio 0.84 (95% confidence interval (CI) 0.79–0.88) p

  10. Estrogen, Progesterone and Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Ho Shuk-Mei

    2003-10-01

    Full Text Available Abstract Ovarian carcinoma (OCa continues to be the leading cause of death due to gynecologic malignancies and the vast majority of OCa is derived from the ovarian surface epithelium (OSE and its cystic derivatives. Epidemiological evidence strongly suggests that steroid hormones, primarily estrogens and progesterone, are implicated in ovarian carcinogenesis. However, it has proved difficult to fully understand their mechanisms of action on the tumorigenic process. New convincing data have indicated that estrogens favor neoplastic transformation of the OSE while progesterone offers protection against OCa development. Specifically, estrogens, particularly those present in ovulatory follicles, are both genotoxic and mitogenic to OSE cells. In contrast, pregnancy-equivalent levels progesterone are highly effective as apoptosis inducers for OSE and OCa cells. In this regard, high-dose progestin may exert an exfoliation effect and rid an aged OSE of pre-malignant cells. A limited number of clinical studies has demonstrated efficacies of antiestrogens, aromatase inhibitors, and progestins alone or in combination with chemotherapeutic drugs in the treatment of OCa. As a result of increased life expectancy in most countries, the number of women taking hormone replacement therapies (HRT continues to grow. Thus, knowledge of the mechanism of action of steroid hormones on the OSE and OCa is of paramount significance to HRT risk assessment and to the development of novel therapies for the prevention and treatment of OCa.

  11. Estrogenic activity of isoflavonoids from Onobrychis ebenoides.

    Science.gov (United States)

    Halabalaki, Maria; Alexi, Xanthippi; Aligiannis, Nektarios; Lambrinidis, George; Pratsinis, Harris; Florentin, Ida; Mitakou, Sofia; Mikros, Emmanuel; Skaltsounis, Alexios-Leandros; Alexis, Michael N

    2006-05-01

    Fractionation of the neutral extract of Onobrychis ebenoides (Leguminosae) yielded a new isoflavone, named ebenosin (1), in addition to the known ones, afrormosin (2), formononetin (3) and daidzein (4). Although the relative binding affinities of 1 - 4 for estrogen receptor alpha (ERalpha) were nearly comparable and matched those of 1-3 for ERbeta, that of 4 for the latter receptor was significantly higher than any of the other. Compounds 1 - 4 induced cell proliferation and gene expression in breast and endometrial cancer cells in an ER-dependent manner. Nonetheless, the rank order of induction potencies ( 4 > 3 >or= 2 >or= 1) matched better that of affinities for ERbeta ( 4 > 3 >or= 2 >or= 1) rather than ERalpha ( 4 >or= 3 >or= 2 >or= 1). While the antiestrogen ICI 182,780 could inhibit the induction of proliferation of ER-positive breast cancer cells by 1-4, it could not prevent 1 from exhibiting significant ER-independent cytotoxicity at 10 microM. By contrast, 1 was much less cytotoxic and only weakly estrogenic for ER-positive endometrial adenocarcinoma cells. In conclusion, our data suggest that the C-8 isoprenyl substituent of 1 renders it cytotoxic and/or estrogenic in a cell-dependent manner.

  12. The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone.

    Science.gov (United States)

    Martin-Millan, Marta; Almeida, Maria; Ambrogini, Elena; Han, Li; Zhao, Haibo; Weinstein, Robert S; Jilka, Robert L; O'Brien, Charles A; Manolagas, Stavros C

    2010-02-01

    Estrogens attenuate osteoclastogenesis and stimulate osteoclast apoptosis, but the molecular mechanism and contribution of these effects to the overall antiosteoporotic efficacy of estrogens remain controversial. We selectively deleted the estrogen receptor (ER)alpha from the monocyte/macrophage cell lineage in mice (ERalpha(LysM)(-/-)) and found a 2-fold increase in osteoclast progenitors in the marrow and the number of osteoclasts in cancellous bone, along with a decrease in cancellous bone mass. After loss of estrogens these mice failed to exhibit the expected increase in osteoclast progenitors, the number of osteoclasts in bone, and further loss of cancellous bone. However, they lost cortical bone indistinguishably from their littermate controls. Mature osteoclasts from ERalpha(LysM)(-/-) were resistant to the proapoptotic effect of 17beta-estradiol. Nonetheless, the effects of estrogens on osteoclasts were unhindered in mice bearing an ERalpha knock-in mutation that prevented binding to DNA. Moreover, a polymeric form of estrogen that is not capable of stimulating the nuclear-initiated actions of ERalpha was as effective as 17beta-estradiol in inducing osteoclast apoptosis in cells with the wild-type ERalpha. We conclude that estrogens attenuate osteoclast generation and life span via cell autonomous effects mediated by DNA-binding-independent actions of ERalpha. Elimination of these effects is sufficient for loss of bone in the cancellous compartment in which complete perforation of trabeculae by osteoclastic resorption precludes subsequent refilling of the cavities by the bone-forming osteoblasts. However, additional effects of estrogens on osteoblasts, osteocytes, and perhaps other cell types are required for their protective effects on the cortical compartment, which constitutes 80% of the skeleton.

  13. Development of a theory-based sexual and reproductive health promotion and HIV prevention program for Chinese early adolescents.

    Science.gov (United States)

    Hong, Jingfang; Fongkaew, Warunee; Senaratana, Wilawan; Tonmukayakul, Ouyporn

    2010-09-01

    The purpose of this study was to develop a theory-based program for Chinese early adolescents in order to promote their sexual and reproductive health and to prevent HIV infection. The program was designed based on the Information-Motivation-Behavioral skills model and a needs assessment among the stakeholders. A technical collaborative action research approach was applied. The study's participants were 102 early adolescents in a public middle school in mainland China, with the involvement of other key stakeholders, including 15 teachers and 12 parents. The results revealed a statistically significant improvement in the scores of sexual and reproductive health promotion and HIV prevention information, motivation, and behavioral skills after the program's implementation. Meanwhile, qualitative data from the early adolescents' reflection indicated that the content was useful and comprehensive, the trainers were friendly and knowledgeable, and participatory learning with an "edutainment" style was especially impressive. Additionally, the early adolescents expressed that they could apply the knowledge and skills in their daily life, which would benefit themselves and their family and peers. The Information-Motivation-Behavioral skills model could be explored in a non-Western context and the program was shown to be acceptable for use in a Chinese middle school setting.

  14. Preliminary report of spraying foliar fertilizer for preventing early senescence of early rice%早稻叶面肥防早衰试验初报

    Institute of Scientific and Technical Information of China (English)

    杨振华; 裴润根; 邓春云; 邓正根; 黄小龙

    2012-01-01

    用4种叶面肥品种在早稻上进行防早衰试验,结果表明:这4种叶面肥均可延长早稻功能叶寿命,增加实粒数,提高结实率和千粒重,达到增产增收的效果,且以喷施富万钾和磷酸二氢钾效果较好。%Experiments of using 4 kinds of foliar fertilizers to prevent early senescence of early rice were carried out. The results showed that all these 4 fertilizers could prolong the life period of function leaves, increase filled grain number and improve setting percentage and 1000-grain-weight, and obtain the effect of increasing yield and income. Comparatively, spraying application of both "Fu Wan Jia" organic potassium and KH2 PO4 had better effect.

  15. Estrogenic compounds -endocrine disruptors

    Directory of Open Access Journals (Sweden)

    Munteanu Constantin

    2011-11-01

    Full Text Available Endocrine disruptors (polychlorinated biphenyls, dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions.

  16. Estrogen receptors in breast carcinoma.

    Science.gov (United States)

    Huaman, A

    1979-11-01

    On the basis of estrogen receptor assays, breast carcinomas are presently classified as estrogen-dependent tumors, which respond to endocrine therapy, and autonomous tumors, for which endocrine therapy is useless. This paper presents a short review of the biochemical principles of estrogen dependence, the procedures used to determine estrogen receptors, and the clinical applications of the findings of these assay procedures. Biobhemically, the estroogen dependence of normal breast cells is explained as a biochemical reaction occurring between the circulating estradiol and the breast cell, which occurs in 3 steps: 1) circulating estradiol penetrates the cellular membrane by passive diffusion, followed by 2) combining of estradiol with the estrogen-binding protein (estrophilin) and formation of an estrogen receptor complex which undergoes activation and translocation into the nucleus, to result in 3) the activated steroid receptor which combines with the nuclear charomatin and stimulates ribonucleic acid synthesis for the formation of estradiol binding proteins or estradiol receptors. The cytosol method of Wittliff et al. is described in brief and entails radioactive competitive analysis; the other available laboratory procedure is immunofluorescence of tumor sections. Quantification of estrogen receptor content can be used clinically to decide on ablative endocrine therapy, to determine the effectiveness of anti-estrogen administration, to determine the primary site of metastatic carcinoma, and as a screenng device.

  17. ESTROGEN IN THE LIMBIC SYSTEM

    NARCIS (Netherlands)

    ter Horst, Gert J.; Litwack, G

    2010-01-01

    Estrogens are a group of steroid hormones that function as the primary female sex hormone. Estrogens not only have an important role in the regulation of the estrous or menstrual cycle but also control, for example, bone formation, the cardiovascular system, and cognitive functions. Estradiol (E2),

  18. Early Mathematical Knowledge: Deficits among Low-Income Children and Insights into Prevention

    Science.gov (United States)

    University of Pittsburgh Office of Child Development, 2009

    2009-01-01

    Just as mathematical ability begins to form in early childhood, so, too, does the knowledge gap separating low-income children from their more affluent peers, who generally enter school with much greater math knowledge. This gap is troubling given that early deficits in mathematical knowledge can have profound implications for future learning. One…

  19. Preventing Early Mathematics Difficulties: The Feasibility of a Rigorous Kindergarten Mathematics Curriculum

    Science.gov (United States)

    Chard, David J.; Baker, Scott K.; Clarke, Ben; Jungjohann, Kathleen; Davis, Karen; Smolkowski, Keith

    2008-01-01

    Concern about poor mathematics achievement in U.S. schools has increased in recent years. In part, poor achievement may be attributed to a lack of attention to early instruction and missed opportunities to build on young children's early understanding of mathematics. This study examined the development and feasibility testing of a kindergarten…

  20. Early detection versus primary prevention in the PLCO flexible sigmoidoscopy screening trial: Which has the greatest impact on mortality?

    Science.gov (United States)

    Doroudi, Maryam; Schoen, Robert E; Pinsky, Paul F

    2017-10-04

    Screening for colorectal cancer (CRC) with flexible sigmoidoscopy (FS) has been shown to reduce CRC mortality. The current study examined whether the observed mortality reduction was due primarily to the prevention of incident CRC via removal of adenomatous polyps or to the early detection of cancer and improved survival. The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial randomized 154,900 men and women aged 55 to 74 years. Individuals underwent FS screening at baseline and at 3 or 5 years versus usual care. CRC-specific survival was analyzed using Kaplan-Meier curves and proportional hazards modeling. The authors estimated the percentage of CRC deaths averted by early detection versus primary prevention using a model that applied intervention arm survival rates to CRC cases in the usual-care arm and vice versa. A total of 1008 cases of CRC in the intervention arm and 1291 cases of CRC in the usual-care arm were observed. Through 13 years of follow-up, there was no significant difference noted between the trial arms with regard to CRC-specific survival for all CRC (68% in the intervention arm vs 65% in the usual-care arm; P =.16) or proximal CRC (68% vs 62%, respectively; P = .11) cases; however, survival in distal CRC cases was found to be higher in the intervention arm compared with the usual-care arm (77% vs 66%; Pscreen-detected cases. Overall, approximately 29% to 35% of averted CRC deaths were estimated to be due to early detection and 65% to 71% were estimated to be due to primary prevention. CRC-specific survival was similar across arms in the PLCO trial, suggesting a limited role for early detection in preventing CRC deaths. Modeling suggested that approximately two-thirds of avoided deaths were due to primary prevention. Future CRC screening guidelines should emphasize primary prevention via the identification and removal of precursor lesions. Cancer 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  1. 婴幼儿龋的早期防治%Early prevention and cure of early childhood caries

    Institute of Scientific and Technical Information of China (English)

    文玲英

    2008-01-01

    婴幼儿龋(early childhood caries,ECC)是发生在婴幼儿时期的一类龋病,最早是由儿科医师Jacobi于1862年描述与报道,他认为牙齿大面积破坏的龋病与婴幼儿喂食的牛奶和含糖饮料有关,但当时未能引起人们的注意。20世纪60年代后期,病例报道增多,于是将这种与奶瓶喂养有关的具有典型特征的乳牙龋病称为奶瓶龋(baby bottle tooth decay,BBTD)。后来,在母乳喂养的婴儿中也发现了这种类型的龋病,

  2. Effect of source-separated urine storage on estrogenic activity detected using bioluminescent yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Jaatinen, Sanna; Kivistö, Anniina; Palmroth, Marja R T; Karp, Matti

    2016-09-01

    The objective was to demonstrate that a microbial whole cell biosensor, bioluminescent yeast, Saccharomyces cerevisiae (BMAEREluc/ERα) can be applied to detect overall estrogenic activity from fresh and stored human urine. The use of source-separated urine in agriculture removes a human originated estrogen source from wastewater influents, subsequently enabling nutrient recycling. Estrogenic activity in urine should be diminished prior to urine usage in agriculture in order to prevent its migration to soil. A storage period of 6 months is required for hygienic reasons; therefore, estrogenic activity monitoring is of interest. The method measured cumulative female hormone-like activity. Calibration curves were prepared for estrone, 17β-estradiol, 17α- ethinylestradiol and estriol. Estrogen concentrations of 0.29-29,640 μg L(-1) were detectable while limit of detection corresponded to 0.28-35 μg L(-1) of estrogens. The yeast sensor responded well to fresh and stored urine and gave high signals corresponding to 0.38-3,804 μg L(-1) of estrogens in different urine samples. Estrogenic activity decreased during storage, but was still higher than in fresh urine implying insufficient storage length. The biosensor was suitable for monitoring hormonal activity in urine and can be used in screening anthropogenic estrogen-like compounds interacting with the receptor.

  3. The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

    Science.gov (United States)

    Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto

    2017-09-02

    Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

  4. "Greenlight study": a controlled trial of low-literacy, early childhood obesity prevention

    National Research Council Canada - National Science Library

    Sanders, Lee M; Perrin, Eliana M; Yin, H Shonna; Bronaugh, Andrea; Rothman, Russell L

    2014-01-01

    ..., are at increased risk of developing obesity. The objective of the Greenlight Intervention Study is to assess the effectiveness of a low-literacy, primary-care intervention on the reduction of early childhood obesity...

  5. Influence of Parenting Practices on Eating Behaviors of Early Adolescents during Independent Eating Occasions: Implications for Obesity Prevention

    Science.gov (United States)

    Reicks, Marla; Banna, Jinan; Cluskey, Mary; Gunther, Carolyn; Hongu, Nobuko; Richards, Rickelle; Topham, Glade; Wong, Siew Sun

    2015-01-01

    Among early adolescents (10–14 years), poor diet quality along with physical inactivity can contribute to an increased risk of obesity and associated biomarkers for chronic disease. Approximately one-third of United States (USA) children in this age group are overweight or obese. Therefore, attention to factors affecting dietary intake as one of the primary contributors to obesity is important. Early adolescents consume foods and beverages during eating occasions that occur with and without parental supervision. Parents may influence eating behaviors of early adolescents during eating occasions when they are present or during independent eating occasions by engaging in practices that affect availability of foods and beverages, and through perceived normative beliefs and expectations for intake. Therefore, the purpose of this article was to describe the influence of parenting practices on eating behaviors in general and when specifically applied to independent eating occasions of early adolescents. This information may be helpful to inform parenting interventions targeting obesity prevention among early adolescents focusing on independent eating occasions. PMID:26506384

  6. Influence of Parenting Practices on Eating Behaviors of Early Adolescents during Independent Eating Occasions: Implications for Obesity Prevention

    Directory of Open Access Journals (Sweden)

    Marla Reicks

    2015-10-01

    Full Text Available Among early adolescents (10–14 years, poor diet quality along with physical inactivity can contribute to an increased risk of obesity and associated biomarkers for chronic disease. Approximately one-third of United States (USA children in this age group are overweight or obese. Therefore, attention to factors affecting dietary intake as one of the primary contributors to obesity is important. Early adolescents consume foods and beverages during eating occasions that occur with and without parental supervision. Parents may influence eating behaviors of early adolescents during eating occasions when they are present or during independent eating occasions by engaging in practices that affect availability of foods and beverages, and through perceived normative beliefs and expectations for intake. Therefore, the purpose of this article was to describe the influence of parenting practices on eating behaviors in general and when specifically applied to independent eating occasions of early adolescents. This information may be helpful to inform parenting interventions targeting obesity prevention among early adolescents focusing on independent eating occasions.

  7. The estrogen antagonist ICI 182,780 reduces cancellous bone volume in female rats.

    Science.gov (United States)

    Gallagher, A; Chambers, T J; Tobias, J H

    1993-12-01

    Although estrogen is thought to protect the skeleton by inhibiting bone resorption, we have also found that in the rat, estrogen stimulates cancellous bone formation. However, the extent to which the various skeletal actions of estrogen are mediated by classical estrogen receptors remains unclear. Although estrogen receptor antagonists such as tamoxifen have been used to study this question, interpretation of the results is complicated by the fact that this agent also acts as a partial estrogen agonist. However, the recent development of estrogen antagonists devoid of agonist activity provides an opportunity to explore this question further. We, therefore, investigated the effect of administration of the pure estrogen antagonist ICI 182,780 on the skeleton of adult female rats. We found that ICI 182,780 reduced bone volume at the proximal tibial metaphysis by approximately 30%, associated with an increase in osteoclast surface. We then investigated the effect of ICI 182,780 on the anabolic action of estrogen. We used ovariectomized rats treated with 3-amino-1-hydroxypropylidene-1-bisphosphonate to inhibit bone resorption, thereby preventing any increase in bone formation as a result of the stimulation of bone resorption due to estrogen deficiency. 17 beta-Estradiol (1 micrograms/kg) stimulated cancellous bone formation in such animals by approximately 8-fold; this increase was abolished when ICI 182,780 was also given. In contrast, ICI 182,780 affected neither longitudinal nor periosteal tibial growth in either intact animals or ovariectomized rats given estradiol or vehicle. We conclude that ICI 182,780 reduces cancellous bone volume in the rat by antagonizing estrogen's actions on bone formation and resorption, suggesting that these processes are both mediated by classical estrogen receptors.

  8. Estrogen Receptor Gene Polymorphisms Associated with Incident Aging Macula Disorder

    NARCIS (Netherlands)

    Boekhoorn, S.S.; Vingerling, J.R.; Uitterlinden, A.G.; Meurs, J.B.J. van; Duijn, C.M. van; Pols, H.A.P.; Hofman, A.; de Jong, P.T.V.M.

    2007-01-01

    PURPOSE. It has been suggested that early menopause increases the risk of aging-macula disorder (AMD), the major cause of incurable blindness with a dry and wet late subtype, and that exposure to endogenous or postmenopausal exogenous estrogens reduces this risk. This study was undertaken to investi

  9. Estrogen Receptor Agonists and Antagonists in the Yeast Estrogen Bioassay.

    Science.gov (United States)

    Wang, Si; Bovee, Toine F H

    2016-01-01

    Cell-based bioassays can be used to predict the eventual biological activity of a substance on a living organism. In vitro reporter gene bioassays are based on recombinant vertebrate cell lines or yeast strains and especially the latter are easy-to-handle, cheap, and fast. Moreover, yeast cells do not express estrogen, androgen, progesterone or glucocorticoid receptors, and are thus powerful tools in the development of specific reporter gene systems that are devoid of crosstalk from other hormone pathways. This chapter describes our experience with an in-house developed RIKILT yeast estrogen bioassay for testing estrogen receptor agonists and antagonists, focusing on the applicability of the latter.

  10. The Early Prevention of Obesity in CHildren (EPOCH Collaboration - an Individual Patient Data Prospective Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Simes John

    2010-11-01

    Full Text Available Abstract Background Efforts to prevent the development of overweight and obesity have increasingly focused early in the life course as we recognise that both metabolic and behavioural patterns are often established within the first few years of life. Randomised controlled trials (RCTs of interventions are even more powerful when, with forethought, they are synthesised into an individual patient data (IPD prospective meta-analysis (PMA. An IPD PMA is a unique research design where several trials are identified for inclusion in an analysis before any of the individual trial results become known and the data are provided for each randomised patient. This methodology minimises the publication and selection bias often associated with a retrospective meta-analysis by allowing hypotheses, analysis methods and selection criteria to be specified a priori. Methods/Design The Early Prevention of Obesity in CHildren (EPOCH Collaboration was formed in 2009. The main objective of the EPOCH Collaboration is to determine if early intervention for childhood obesity impacts on body mass index (BMI z scores at age 18-24 months. Additional research questions will focus on whether early intervention has an impact on children's dietary quality, TV viewing time, duration of breastfeeding and parenting styles. This protocol includes the hypotheses, inclusion criteria and outcome measures to be used in the IPD PMA. The sample size of the combined dataset at final outcome assessment (approximately 1800 infants will allow greater precision when exploring differences in the effect of early intervention with respect to pre-specified participant- and intervention-level characteristics. Discussion Finalisation of the data collection procedures and analysis plans will be complete by the end of 2010. Data collection and analysis will occur during 2011-2012 and results should be available by 2013. Trial registration number ACTRN12610000789066

  11. Profile of bazedoxifene/conjugated estrogens for the treatment of estrogen deficiency symptoms and osteoporosis in women at risk of fracture

    Directory of Open Access Journals (Sweden)

    Rossini M

    2013-07-01

    Full Text Available Maurizio Rossini,1 Stefano Lello,2 Ignazio Sblendorio,3 Ombretta Viapiana,1 Elena Fracassi,1 Silvano Adami,1 Davide Gatti11Department of Medicine, Rheumatology Unit, University of Verona, Italy; 2Endocrinological Gynecology, Pathophysiology of Menopause and Osteoporosis, Dermopathic Institute of Immacolata, Roma, Italy; 3Medical Coach Italia Center, Bari, ItalyAbstract: Decreasing levels of estrogens during menopause are associated with reduced bone density and an increased risk of osteoporosis. Many women also experience bothersome vasomotor and vaginal symptoms during the menopausal transition. Results of systematic reviews and meta-analyses of randomized controlled trials have shown that both systemic estrogen therapy or hormone therapy (estrogen combined with a progestin are useful to prevent bone loss, and they are the most effective treatment for such climacteric symptoms as hot flushes, sweating, vaginal dryness, and dyspareunia. Unfortunately, estrogen therapy and hormone therapy increase the risk of endometrial and breast cancer, respectively. The selective estrogen receptor modulators (SERMs result in positive estrogenic effects on bone, with no negative effects on the endometrium and breast but do not provide relief from postmenopausal symptoms. The combination of a SERM with estrogen as a tissue selective estrogen complex (TSEC is a new strategy for the prevention of bone loss and the treatment of climacteric symptoms. This combination is particularly interesting from a clinical point of view, taking into account that estrogen alone did not increase breast cancer risk by the Women's Health Initiative. TSEC is hypothesized to provide the benefits of estrogen-alone therapy, with an improved tolerability profile because the SERM component can make possible the elimination of progestin. The objective of this review was to critically evaluate the evidence from the reports published to date on the use of bazedoxifene (a third

  12. Community and team member factors that influence the early phase functioning of community prevention teams: the PROSPER project.

    Science.gov (United States)

    Greenberg, Mark T; Feinberg, Mark E; Meyer-Chilenski, Sarah; Spoth, Richard L; Redmond, Cleve

    2007-11-01

    This research examines the early development of community teams in a specific university-community partnership project called PROSPER (Spoth et al., Prev Sci 5:31-39, 2004). PROSPER supports local community teams in rural areas and small towns to implement evidence-based programs intended to support positive youth development and reduce early substance use. The study evaluated 14 community teams and included longitudinal data from 108 team members. Specifically, it examined how community demographics and team member characteristics, perceptions, and attitudes at initial team formation were related to local team functioning 6 months later, when teams were planning for prevention program implementation. Findings indicate that community demographics (poverty), perceived community readiness, characteristics of local team members (previous collaborative experience) and attitudes toward prevention played a substantial role in predicting the quality of community team functioning 6 months later. EDITORS' STRATEGIC IMPLICATIONS: The authors identify barriers to successful long-term implementation of prevention programs and add to a small, but important, longitudinal research knowledge base related to community coalitions.

  13. An innovative community-oriented approach to prevention and early intervention with refugees in the United States.

    Science.gov (United States)

    Nazzal, Kristel Heidi; Forghany, Marzieh; Geevarughese, M Charis; Mahmoodi, Venus; Wong, Jorge

    2014-11-01

    Thousands of refugees from around the world resettle in the United States every year. Many refugees suffer from mental health disorders as a result of experiences living in or escaping from their turbulent homelands, and many also experience mental health issues as they settle in their new host countries. As such, it is important to intervene during the early stages of refugee resettlement to help prevent or mitigate mental illness symptoms. However, because of several access and utilization barriers, such as stigma, refugees are not apt to receive needed mental health services. Moreover, the traditional Western model of treatment can be culturally incongruent with refugee practices. Alternative, culturally sensitive, community-based approaches must be considered. This article presents a community-oriented prevention and early intervention model that can be used with newly arrived refugees with limited English proficiency. Goals of the model are to increase knowledge of mental health and mental health service options to refugees, as well as support the process of adjusting to life in the United States. The New Refugee Services Project, developed by the Center for Survivors of Torture department of Asian Americans for Community Involvement (AACI) in San Santa Clara County, California is presented as an example case study. The structure outlined in this article aims to support the development, implementation, and assessment of future preventative interventions for refugee populations.

  14. Identification of estrogen target genes during zebrafish embryonic development through transcriptomic analysis.

    Directory of Open Access Journals (Sweden)

    Ruixin Hao

    Full Text Available Estrogen signaling is important for vertebrate embryonic development. Here we have used zebrafish (Danio rerio as a vertebrate model to analyze estrogen signaling during development. Zebrafish embryos were exposed to 1 µM 17β-estradiol (E2 or vehicle from 3 hours to 4 days post fertilization (dpf, harvested at 1, 2, 3 and 4 dpf, and subjected to RNA extraction for transcriptome analysis using microarrays. Differentially expressed genes by E2-treatment were analyzed with hierarchical clustering followed by biological process and tissue enrichment analysis. Markedly distinct sets of genes were up and down-regulated by E2 at the four different time points. Among these genes, only the well-known estrogenic marker vtg1 was co-regulated at all time points. Despite this, the biological functional categories targeted by E2 were relatively similar throughout zebrafish development. According to knowledge-based tissue enrichment, estrogen responsive genes were clustered mainly in the liver, pancreas and brain. This was in line with the developmental dynamics of estrogen-target tissues that were visualized using transgenic zebrafish containing estrogen responsive elements driving the expression of GFP (Tg(5xERE:GFP. Finally, the identified embryonic estrogen-responsive genes were compared to already published estrogen-responsive genes identified in male adult zebrafish (Gene Expression Omnibus database. The expressions of a few genes were co-regulated by E2 in both embryonic and adult zebrafish. These could potentially be used as estrogenic biomarkers for exposure to estrogens or estrogenic endocrine disruptors in zebrafish. In conclusion, our data suggests that estrogen effects on early embryonic zebrafish development are stage- and tissue- specific.

  15. Bringing skin assessments to life using human patient simulation: an emphasis on cancer prevention and early detection.

    Science.gov (United States)

    Kuhrik, Marilee; Seckman, Christy; Kuhrik, Nancy; Ahearn, Tina; Ercole, Patrick

    2011-12-01

    Skin cancer is the most common cancer in the United States, with about 1,000,000 people developing the disease each year. The incidence of melanoma has rapidly increased in young white women between the ages of 15-34 over the last three decades. While melanoma accounts for approximately 3% of skin cancers, it causes more than 75% of skin cancer deaths. Thorough skin assessments and awareness of new or changing appearance of skin lesions are critical to early detection and treatment of skin cancer, as well as teaching sun-protective behaviors. Educators created a novel approach to "bring to life" skin cancer assessment skills to promote awareness of prevention and early detection of skin cancer using moulage in a human patient simulation lab. Through the use of moulage-like lesions, simulated patients were evaluated and taught skin cancer prevention and early detection principles by baccalaureate nursing students. The average age of study participants (n = 104) was 26.50 years. The majority of responders were female. At the end of the lab, students' average responses to an evaluation based on program goals were very positive. Anecdotal comments affirmed positive student perceptions of their simulation experience. Data analyses indicated item means were consistently higher for upper-division students. The age and gender of students who participated in this study align with the NCI statistics on age and gender of the population with increased incidence of melanoma.

  16. Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    J. Thomas

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is the leading cause of dementia and the most common neurodegenerative disease in the elderly. Furthermore, AD has provided the most positive indication to support the fact that inflammation contributes to neurodegenerative disease. The exact etiology of AD is unknown, but environmental and genetic factors are thought to contribute, such as advancing age, family history, presence of chronic diseases such as cardiovascular disease (CVD and diabetes, and poor diet and lifestyle. It is hypothesised that early prevention or management of inflammation could delay the onset or reduce the symptoms of AD. Normal physiological changes to the brain with ageing include depletion of long chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic acid (DHA levels. DHA supplementation can reduce markers of inflammation. This review specifically focusses on the evidence in humans from epidemiological, dietary intervention, and supplementation studies, which supports the role of long chain omega-3 fatty acids in the prevention or delay of cognitive decline in AD in its early stages. Longer term trials with long chain omega-3 supplementation in early stage AD are warranted. We also highlight the importance of overall quality and composition of the diet to protect against AD and dementia.

  17. Social Aspects of Suicidal Behavior and Prevention in Early Life: A Review

    Directory of Open Access Journals (Sweden)

    Alan Apter

    2012-03-01

    Full Text Available Purpose: The present review summarizes the updated literature on the social aspects of suicidal behavior and prevention in adolescents. Recent findings: The predictive role of psychiatric disorders and past history are well recognized in adolescent suicide, but the role of social and cultural factors is less clear. Studies have focused on the importance of ethnicity, gender, family characteristics, and socioeconomic status. More recently, attention has been addressed to broader social risk factors, such as bullying in adolescents, suicide contagion, sexual orientation, and the popular media. Further empirical evidence is needed to advance our understanding of suicidal youth, develop better assessment tools, and formulate effective prevention and treatment programs. Summary: Suicidal behavior remains an important clinical problem and major cause of death in youth. Social factors may be at least as important as genetics. Advancing our understanding of underlying cultural and sociological issues in youth suicide will help clinicians achieve more efficient prediction, prevention and treatment.

  18. Social Aspects of Suicidal Behavior and Prevention in Early Life: A Review

    Science.gov (United States)

    Amitai, Maya; Apter, Alan

    2012-01-01

    Purpose: The present review summarizes the updated literature on the social aspects of suicidal behavior and prevention in adolescents. Recent findings: The predictive role of psychiatric disorders and past history are well recognized in adolescent suicide, but the role of social and cultural factors is less clear. Studies have focused on the importance of ethnicity, gender, family characteristics, and socioeconomic status. More recently, attention has been addressed to broader social risk factors, such as bullying in adolescents, suicide contagion, sexual orientation, and the popular media. Further empirical evidence is needed to advance our understanding of suicidal youth, develop better assessment tools, and formulate effective prevention and treatment programs. Summary: Suicidal behavior remains an important clinical problem and major cause of death in youth. Social factors may be at least as important as genetics. Advancing our understanding of underlying cultural and sociological issues in youth suicide will help clinicians achieve more efficient prediction, prevention and treatment. PMID:22690178

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  20. Prevention and early intervention of anxiety problems in young children: A pilot evaluation of Cool Little Kids Online

    Directory of Open Access Journals (Sweden)

    Amy J. Morgan

    2016-05-01

    Full Text Available Anxiety disorders are common, debilitating, and begin early in life. Early intervention to prevent anxiety disorders in children who are at risk could have long-term impact. The ‘Cool Little Kids’ parenting group program has previously been shown to be efficacious in preventing anxiety disorders in temperamentally inhibited young children. Wider dissemination of the program could be achieved with an internet-based delivery platform, affording greater accessibility and convenience for parents. The aim of this study was to evaluate ‘Cool Little Kids Online’, a newly developed online version of the existing parenting group program. Fifty-one parents of children aged 3–6 years were recruited to evaluate the online program's acceptability and preliminary efficacy in reducing inhibited young children's anxiety problems. Parents were randomized to receive either a clinician-supported version or an unsupported version of the program. Parents had 10 weeks to access the program and completed questionnaires at baseline and post-intervention. Both groups showed medium-to-large reductions in children's anxiety symptoms, emotional symptoms, number of child anxiety diagnoses, and improvements in life interference from anxiety. The effect of clinician support was inconsistent and difficult to interpret. Parents reported high levels of satisfaction with the program. These encouraging results indicate that the online version is acceptable and useful for parents with temperamentally inhibited young children. Cool Little Kids Online may be a promising direction for improving access to an evidence-based prevention and early intervention program for child anxiety problems. A large randomized trial is warranted to further evaluate efficacy.

  1. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  2. Estrogen and gastrointestinal malignancy.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    The concept that E2 exerts an effect on the gastrointestinal tract is not new and its actions on intestinal mucosa have been investigated for at least three decades. An attempt to consolidate results of these investigations generates more questions than answers, thus suggesting that many unexplored avenues remain and that the full capabilities of this steroid hormone are far from understood. Evidence of its role in esophageal, gastric and gallbladder cancers is confusing and often equivocal. The most compelling evidence regards the protective role conferred by estrogen (or perhaps ERbeta) against the development and proliferation of colon cancer. Not only has the effect been described but also many mechanisms of action have been explored. It is likely that, along with surgery, chemotherapy and radiotherapy, hormonal manipulation will play an integral role in colon cancer management in the very near future.

  3. Early prevention of instability - search for optimal grid nodes for applying countermeasures

    DEFF Research Database (Denmark)

    Dmitrova, Evgeniya; Jóhannsson, Hjörtur; Nielsen, Arne Hejde

    2012-01-01

    has on the stability of the given generator is based on sensitivity analysis. The sensitivity of the stability criteria for aperiodic small signal angular stability to the corresponding change in the nodal admittances used to generate a prioritized candidate list over possible nodes for preventive...

  4. Prediction and prevention of failure: an early intervention to assist at-risk medical students

    NARCIS (Netherlands)

    Winston, K.A.; Vleuten, C.P.M. van der; Scherpbier, A.J.J.A.

    2014-01-01

    BACKGROUND: Consistent identification and prevention of failure for at-risk medical students is challenging, failing courses is costly to all stakeholders, and there is need for further research into duration, timing and structure of interventions to help students in difficulty. AIMS: To verify the

  5. Modelling the economics and efficacy of early adoption of preventative practices for managing trunk diseases

    Science.gov (United States)

    Trunk diseases pose one of the most significant threats to vineyard longevity, since the introduction of Phylloxera. Research on resistant germplasm and detection tools will help in the long term. In the short term, we aim to promote preventative practices. Experimental trials show three practices t...

  6. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    DEFF Research Database (Denmark)

    Funda, David; Fundova, Petra; Hansen, Axel Kornerup

    2014-01-01

    gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis...

  7. Early detection of children at risk for antisocial behaviour using data from routine preventive child healthcare

    NARCIS (Netherlands)

    Reijneveld, Sijmen A.; Crone, Matty R.; de Meer, Gea

    2012-01-01

    Background: Youth antisocial behaviour is highly prevalent. Young people are usually not willing to disclose such behaviour to professionals and parents. Our aim was to assess whether child health professionals (CHP) working in preventive child healthcare could identify pre-adolescents at risk for a

  8. An Evaluation of the Early Implementation of School-Based Bullying Prevention Programs in Massachusetts

    Science.gov (United States)

    Sautter Errichetti, Karen

    2014-01-01

    Background: A quarter of U.S. children are bullied annually. State legislatures have responded to high profile media exposure of bullying and increased public concern by passing legislation aimed at preventing bullying among school children. Methods: The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework was used to…

  9. Evidence of Effectiveness of Current Therapies to Prevent and Treat Early Childhood Caries

    DEFF Research Database (Denmark)

    Twetman, Svante; Dhar, Vineet

    2015-01-01

    and Evaluation) system. RESULTS: There was moderate and limited quality of evidence in support of fluoride toothpaste and fluoride varnish for ECC prevention, while the evidence for fluoride tablets/drops was insufficient. The support for the use of silver diamine fluoride, xylitol, chlorhexidine varnish...

  10. Early lingual frenectomy assisted by CO2 laser helps prevention and treatment of functional alterations caused by ankyloglossia.

    Science.gov (United States)

    Fiorotti, Renata C; Bertolini, Milene M; Nicola, Jorge H; Nicola, Ester M D

    2004-11-01

    Incorrectly produced speech sounds, the presence of dentofacial alterations and acquired functional adaptations may be due to a short and inadequate lingual frenum. When frenectomy is indicated, it should be performed as early as possible to prevent functional alterations. This study presents a literature review on correct lingual positioning in relation to orthodontic and phonetic function as well as an assessment of 15 patients who underwent frenectomy utilizing the carbon dioxide laser. The results demonstrated that this technique is safe, effective and perfect for use in young children and can be performed in an outpatient unit.

  11. Fluorides for the prevention of early tooth decay (demineralised white lesions) during fixed brace treatment.

    Science.gov (United States)

    Benson, Philip E; Parkin, Nicola; Dyer, Fiona; Millett, Declan T; Furness, Susan; Germain, Peter

    2013-12-12

    Demineralised white lesions (DWLs) can appear on teeth during fixed brace treatment because of early decay around the brackets that attach the braces to the teeth. Fluoride is effective in reducing decay in susceptible individuals in the general population. Individuals receiving orthodontic treatment may be prescribed various forms of fluoride treatment. This review compares the effects of various forms of fluoride used during orthodontic treatment on the development of DWLs. This is an update of a Cochrane review first published in 2004. The primary objective of this review was to evaluate the effects of fluoride in reducing the incidence of DWLs on the teeth during orthodontic treatment.The secondary objectives were to examine the effectiveness of different modes of fluoride delivery in reducing the incidence of DWLs, as well as the size of lesions. Participant-assessed outcomes, such as perception of DWLs, and oral health-related quality of life data were to be included, as would reports of adverse effects. We searched the Cochrane Oral Health Group's Trials Register (to 31 January 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12); MEDLINE via OVID (1946 to 31 January 2013); and EMBASE via OVID (1980 to 31 January 2013). We included trials if they met the following criteria: (1) parallel-group randomised clinical trials comparing the use of a fluoride-containing product versus placebo, no treatment or a different type of fluoride treatment, in which (2) the outcome of enamel demineralisation was assessed at the start and at the end of orthodontic treatment. At least two review authors independently, in duplicate, conducted risk of bias assessments and extracted data. Authors of trials were contacted to obtain missing data or to ask for clarification of aspects of trial methodology. The Cochrane Collaboration's statistical guidelines were followed. For the 2013 update of this review, three changes were made

  12. Core Competencies and the Prevention of School Failure and Early School Leaving

    Science.gov (United States)

    Bradshaw, Catherine P.; O'Brennan, Lindsey M.; McNeely, Clea A.

    2008-01-01

    There is an increasing awareness that school failure and early school leaving are processes, rather than discrete events, that often co-occur and can have lasting negative effects on children's development. Most of the literature has focused on risk factors for failure and dropout rather than on the promotion of competencies that can increase…

  13. Can Intervention Early Prevent Crime Later? The Abecedarian Project Compared with Other Programs.

    Science.gov (United States)

    Clarke, Stevens H.; Campbell, Frances A.

    1998-01-01

    Examined whether the Abecedarian Project affected young adult crime. Found no effects of program on crime. Comparison with other early-intervention programs suggests that reducing boys' delinquency is possible without improving school performance, improving school performance does not guarantee youth crime reductions, and working with parents on…

  14. A Dynamic Learning Concept in Early Years' Education: A Possible Way to Prevent Schoolification

    Science.gov (United States)

    Broström, Stig

    2017-01-01

    In early childhood education and care, Nordic social pedagogy approach is challenged by a learning orientation that often results in unproductive "either/or" thinking. Therefore, based on the two approaches and by analysing several dimensions of Froebel's ideas and prevailing social-historical activity (play) theory, the author deduces…

  15. Core Competencies and the Prevention of School Failure and Early School Leaving

    Science.gov (United States)

    Bradshaw, Catherine P.; O'Brennan, Lindsey M.; McNeely, Clea A.

    2008-01-01

    There is an increasing awareness that school failure and early school leaving are processes, rather than discrete events, that often co-occur and can have lasting negative effects on children's development. Most of the literature has focused on risk factors for failure and dropout rather than on the promotion of competencies that can increase…

  16. Autocrine role of estrogens in the augmentation of luteinizing hormone receptor formation in cultured rat granulosa cells.

    Science.gov (United States)

    Kessel, B; Liu, Y X; Jia, X C; Hsueh, A J

    1985-06-01

    The effects of estrogens on gonadotropin-stimulated luteinizing hormone (LH) receptor formation were examined in primary cultures of rat granulosa cells. Granulosa cells were cultured for 3 days with increasing concentrations of follicle-stimulating hormone (FSH) in the presence or absence of native and synthetic estrogens. Follicle-stimulating hormone stimulated LH receptor formation in a dose-dependent fashion, and estrogens enhanced the FSH-stimulated LH receptor content by decreasing the apparent ED50 of FSH. At 6.25 ng/ml FSH, the enhancement in LH receptor was estrogen dose dependent, with an ED50 value of about 3 X 10(-9) M for 17 beta-estradiol. The increased LH receptor content seen in cells treated with FSH and estrogen was correlated with increased cAMP production by these cells in response to LH stimulation. Time course studies revealed enhancement of FSH-stimulated LH receptor induction at 48 and 72 h of culture. Granulosa cells were also cultured with FSH for 2 days to induce functional LH receptors, then further cultured for 3 days with LH in the presence or absence of estrogens. At 30 ng/ml LH, increasing concentrations of estrogens maintained LH receptor content in a dose-dependent fashion, with their relative estrogenic potencies in keeping with reported binding affinities to estrogen receptors. An autocrine role of estrogens on LH receptor formation was further tested in granulosa cells treated with FSH and an aromatase substrate (androstenedione) to increase estrogen biosynthesis. Cotreatment with semipurified estrogen antibodies partially blocked the FSH stimulation of LH receptors, whereas nonimmune serum was ineffective. Also, inclusion of diethylstilbestrol prevented the inhibitory effect of the estrogen antibodies. Thus, local estrogens in ovarian follicles may play an autocrine role in granulosa cells to enhance LH receptor formation and to increase granulosa cell responsiveness to the LH surge, with subsequent ovulation and adequate

  17. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    DEFF Research Database (Denmark)

    Funda, David; Fundova, Petra; Hansen, Axel Kornerup;

    2014-01-01

    gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis......Induction of long-term tolerance to β-cell autoantigens has been investigated both in animal models and in human type 1 diabetes (T1D) in order to prevent the disease. As regards external compounds, the dietary plant protein fraction has been associated with high penetrance of the disease, whereas...... was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4+Foxp3+ T cells and even more significant induction of γδ T cells in mucosal...

  18. EARLY POSTOPERATIVE HOMEOSTATIC CHANGES AFTER TRANSURETHRAL RESECTION OF THE PROSTATE AND WAYS OF PREVENTING ITS COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    D. Yu. Volkov

    2014-07-01

    Full Text Available During the study, the authors assessed changes in the blood coagulation system and made a spectral analysis of serum and prostate tissue. They revealed immunological changes suggesting occult disseminated intravascular coagulation, an evolving systemic inflammatory response and the latter caused by endothelial damage, microcirculatory disorders, lipid peroxidation, and release of inflammatory factors. The findings permit a tactic for medical prevention of complications to be elaborated.

  19. A Look at Uganda's Early HIV Prevention Strategies Through a Moderate 'African' Communitarian Lens.

    Science.gov (United States)

    Wathuta, Jane

    2016-12-28

    This paper seeks to highlight the benefits of prioritizing moderate African communitarian principles as partly demonstrated in the HIV prevention strategies implemented in Uganda in the late 1980s. Pertinent lessons could be drawn so as to achieve the HIV prevention targets envisioned in the post-2015 development era. Communitarianism emphasizes the importance of communities as part of healthy human existence. Its core ethical values include the virtues of generosity, compassion, and solidarity. Persuasion through communication, consensus through dialogue, and the awareness and commitment to responsibilities towards other members of the community, are chief practices relied upon to achieve appropriate social behaviour. All these elements signify individual rootedness in communities and contribute to the healthy existence of its members. Communitarianism is usually classified as either authoritarian/radical or responsive/moderate, depending on the primacy given to either community interests or the individual will and rights. Moderate communitarianism recognizes the individual's capacity for moral reasoning, virtue and free choice. The ensuing form of society is deemed more ethical as it relies on education in the virtues, moral persuasion and informal social controls, without stifling individual identity, agency, and capacity for self-determination. If moderate African communitarianism, in particular, can to a certain extent be associated with the significant aspects of Uganda's HIV prevention strategies in the stated period, then its present-day relevance for HIV prevention and other public health interventions may be emphasized accordingly. This applies especially in view of the ongoing efforts to achieve a balance between individual and collective interests in bioethics. © 2016 John Wiley & Sons Ltd.

  20. Prevention of Ovarian High Grade Serous Carcinoma by Elucidating Its Early Changes

    Science.gov (United States)

    2015-10-01

    associated precursor lesions are modifiable by oral contraceptives (OCPs) or anti- inflammatory agents as OCPs in particular are known to prevent ovarian...all patients in study was 26.9 months (range, 0.3-52.7). Of those with STIC lesions , 70 (75.3%) were reported in the original pathology report; 23...representative tubal sections, 8 (6%) were tubal carcinomas without STIC lesions , and 79 (59%) are pending review. After pathologic re-review of cases

  1. Social Aspects of Suicidal Behavior and Prevention in Early Life: A Review

    OpenAIRE

    Alan Apter; Maya Amitai

    2012-01-01

    Purpose: The present review summarizes the updated literature on the social aspects of suicidal behavior and prevention in adolescents. Recent findings: The predictive role of psychiatric disorders and past history are well recognized in adolescent suicide, but the role of social and cultural factors is less clear. Studies have focused on the importance of ethnicity, gender, family characteristics, and socioeconomic status. More recently, attention has been addressed to broader social risk fa...

  2. EARLY POSTOPERATIVE HOMEOSTATIC CHANGES AFTER TRANSURETHRAL RESECTION OF THE PROSTATE AND WAYS OF PREVENTING ITS COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    D. Yu. Volkov

    2011-01-01

    Full Text Available During the study, the authors assessed changes in the blood coagulation system and made a spectral analysis of serum and prostate tissue. They revealed immunological changes suggesting occult disseminated intravascular coagulation, an evolving systemic inflammatory response and the latter caused by endothelial damage, microcirculatory disorders, lipid peroxidation, and release of inflammatory factors. The findings permit a tactic for medical prevention of complications to be elaborated.

  3. Child health insurance and early preventive care in three South American countries.

    Science.gov (United States)

    Wehby, George L

    2013-05-01

    Not much is known about how health insurance affects preventive care for children who have access to general routine paediatric care, especially in less developed settings. This study evaluates the effects of child health insurance on preventive care (measured by whether the child had received all the age-appropriate immunizations) for children with access to routine paediatric care. It uses a unique sample of 1958 children aged 3-24 months attending paediatric practices for routine well-child care in Argentina, Brazil and Ecuador. It compares insured and uninsured children attending the same paediatric clinics for routine care at the time of enrolment into the study and only uses within-clinic variation in insurance status when evaluating its effect on immunization status. Regression models for adequate immunization status adjust for several demographic, socio-economic and health characteristics and are estimated both separately for each country and combining the three countries. The majority of children in the study sample have received all age-appropriate immunizations. However, publicly insured children in Argentina and Ecuador are more likely to have received all age-appropriate immunizations compared with uninsured children by 3.5 and 2.3 percentage points, respectively. In the model that combines the three country samples, insured children (regardless of insurance type) are significantly more likely to have adequate immunization status by 2.5 percentage points compared with uninsured children. The study provides evidence that health insurance may enhance preventive care for young children.

  4. Design of a Digital-Based, Multicomponent Nutrition Guidance System for Prevention of Early Childhood Obesity

    Science.gov (United States)

    Black, Maureen M.; Saavedra, Jose M.

    2016-01-01

    Interventions targeting parenting focused modifiable factors to prevent obesity and promote healthy growth in the first 1000 days of life are needed. Scale-up of interventions to global populations is necessary to reverse trends in weight status among infants and toddlers, and large scale dissemination will require understanding of effective strategies. Utilizing nutrition education theories, this paper describes the design of a digital-based nutrition guidance system targeted to first-time mothers to prevent obesity during the first two years. The multicomponent system consists of scientifically substantiated content, tools, and telephone-based professional support delivered in an anticipatory and sequential manner via the internet, email, and text messages, focusing on educational modules addressing the modifiable factors associated with childhood obesity. Digital delivery formats leverage consumer media trends and provide the opportunity for scale-up, unavailable to previous interventions reliant on resource heavy clinic and home-based counseling. Designed initially for use in the United States, this system's core features are applicable to all contexts and constitute an approach fostering healthy growth, not just obesity prevention. The multicomponent features, combined with a global concern for optimal growth and positive trends in mobile internet use, represent this system's future potential to affect change in nutrition practice in developing countries. PMID:27635257

  5. Design of a Digital-Based, Multicomponent Nutrition Guidance System for Prevention of Early Childhood Obesity

    Directory of Open Access Journals (Sweden)

    Keriann H. Uesugi

    2016-01-01

    Full Text Available Interventions targeting parenting focused modifiable factors to prevent obesity and promote healthy growth in the first 1000 days of life are needed. Scale-up of interventions to global populations is necessary to reverse trends in weight status among infants and toddlers, and large scale dissemination will require understanding of effective strategies. Utilizing nutrition education theories, this paper describes the design of a digital-based nutrition guidance system targeted to first-time mothers to prevent obesity during the first two years. The multicomponent system consists of scientifically substantiated content, tools, and telephone-based professional support delivered in an anticipatory and sequential manner via the internet, email, and text messages, focusing on educational modules addressing the modifiable factors associated with childhood obesity. Digital delivery formats leverage consumer media trends and provide the opportunity for scale-up, unavailable to previous interventions reliant on resource heavy clinic and home-based counseling. Designed initially for use in the United States, this system’s core features are applicable to all contexts and constitute an approach fostering healthy growth, not just obesity prevention. The multicomponent features, combined with a global concern for optimal growth and positive trends in mobile internet use, represent this system’s future potential to affect change in nutrition practice in developing countries.

  6. Fish populations surviving estrogen pollution.

    Science.gov (United States)

    Wedekind, Claus

    2014-02-10

    Among the most common pollutants that enter the environment after passing municipal wastewater treatment are estrogens, especially the synthetic 17α-ethinylestradiol that is used in oral contraceptives. Estrogens are potent endocrine disruptors at concentrations frequently observed in surface waters. However, new genetic analyses suggest that some fish populations can be self-sustaining even in heavily polluted waters. We now need to understand the basis of this tolerance.

  7. Immunomodulation of Mytilus hemocytes by individual estrogenic chemicals and environmentally relevant mixtures of estrogens: in vitro and in vivo studies.

    Science.gov (United States)

    Canesi, Laura; Lorusso, Lucia Cecilia; Ciacci, Caterina; Betti, Michele; Rocchi, Marco; Pojana, Giulio; Marcomini, Antonio

    2007-02-15

    Endocrine disrupting compounds (EDCs) are almost ubiquitous in the aquatic environment. In the marine bivalve Mytilus the natural estrogen 17beta-estradiol (E2) and different EDCs have been recently demonstrated to affect the function of the immune cells, the hemocytes. The effects were Tamoxifen-sensitive and were mediated by rapid modulation of kinase-mediated transduction pathways. In this work we compared the in vitro effects of individual estrogenic chemicals (E2, EE: 17alpha-ethynyl estradiol; MES: mestranol; NP: nonylphenol; NP1EC: nonylphenol monoethoxylate carboxylate; BPA: bisphenol A; BP: benzophenone) on hemocyte parameters: lysosomal membrane stability (LMS), phagocytosis, lysozyme release. LMS was the most sensitive effect parameter, showing a decreasing trend at increasing concentrations of estrogens. EC50 values obtained from LMS data were utilized to calculate the estradiol equivalency factor (EEF) for each compound; these EEFs allowed for an estimation of the estrogenic potential of a synthetic mixture with a composition very similar to that previously found in waters of the Venice lagoon. Concentrated mixtures significantly affected hemocyte parameters in vitro and the effects were prevented by Tamoxifen. Significant effects of the mixture were also observed in vivo, at longer exposure times and at concentrations comparable with environmental exposure levels. The results indicate that Mytilus immune parameters can be suitably utilized to evaluate the estrogenic potential of environmental samples.

  8. Endometrial effects of a tissue selective estrogen complex containing bazedoxifene/conjugated estrogens as a menopausal therapy.

    Science.gov (United States)

    Pickar, James H; Yeh, I-Tien; Bachmann, Gloria; Speroff, Leon

    2009-09-01

    To evaluate the endometrial safety of a tissue selective estrogen complex (TSEC; pairing of a selective estrogen receptor modulator [SERM] with estrogens) composed of bazedoxifene/conjugated estrogens (BZA/CE) in postmenopausal women. Randomized, double-blind, multicenter, placebo- and active-controlled, phase 3 study (Selective estrogen Menopause And Response to Therapy [SMART]-1). Outpatient clinical. Healthy, postmenopausal women (n = 3,397) age 40-75 with an intact uterus. Single tablets of BZA (10, 20, or 40 mg) combined with CE (0.625 or 0.45 mg); raloxifene (60 mg); or placebo daily for 2 years. Incidence of endometrial hyperplasia at 12 months in the efficacy evaluable population. Treatment with BZA (20 or 40 mg)/CE (0.625 or 0.45 mg) was associated with low rates (<1%) of endometrial hyperplasia that were not significantly different from those reported with placebo over 24 months. Endometrial thickness with BZA (20 or 40 mg)/CE (0.625 or 0.45 mg) was not significantly different from that with placebo. When combined with CE (0.625 mg or 0.45 mg), BZA (20 mg) was the lowest effective dose that prevented endometrial hyperplasia over 2 years of study, creating the possibility for a new, progestin-free menopausal therapy.

  9. Implementation of a cost-effective strategy to prevent neonatal early-onset group B haemolytic streptococcus disease in the Netherlands

    NARCIS (Netherlands)

    Kolkman, D.G.E.; Rijnders, M.E.B.; Wouters, M.G.A.J.; Akker-van Marle, M.E. van den; Ploeg, K. van der; Groot, C.J.M. de; Fleuren, M.A.H.

    2013-01-01

    Early-onset Group B haemolytic streptococcus infection (EOGBS) is an important cause of neonatal morbidity and mortality in the first week of life. Primary prevention of EOGBS is possible with intra-partum antibiotic prophylaxis (IAP.) Different prevention strategies are used internationally based o

  10. Implementation of a cost-effective strategy to prevent neonatal early-onset group B haemolytic streptococcus disease in the Netherlands

    NARCIS (Netherlands)

    Kolkman, D.G.E.; Rijnders, M.E.B.; Wouters, M.G.A.J.; Akker-van Marle, M.E. van den; Ploeg, K. van der; Groot, C.J.M. de; Fleuren, M.A.H.

    2013-01-01

    Early-onset Group B haemolytic streptococcus infection (EOGBS) is an important cause of neonatal morbidity and mortality in the first week of life. Primary prevention of EOGBS is possible with intra-partum antibiotic prophylaxis (IAP.) Different prevention strategies are used internationally based

  11. The effects of early prevention programs for families with young children at risk for physical child abuse and neglect : A meta-analysis

    NARCIS (Netherlands)

    Geeraert, L; Van den Noortgate, W; Grietens, H; Onghena, P

    2004-01-01

    In this article, a meta-analysis is presented on 40 evaluation studies of early prevention programs for families with young children at risk for physical child abuse and neglect with mostly nonrandomized designs. The main aim of all programs was to prevent physical child abuse and neglect by providi

  12. Oral precancerous lesions: Problems of early detection and oral cancer prevention

    Science.gov (United States)

    Gileva, Olga S.; Libik, Tatiana V.; Danilov, Konstantin V.

    2016-08-01

    The study presents the results of the research in the structure, local and systemic risk factors, peculiarities of the clinical manifestation, and quality of primary diagnosis of precancerous oral mucosa lesions (OMLs). In the study a wide range of OMLs and high (25.4%) proportion of oral precancerous lesions (OPLs) in their structure was indicated. The high percentage of different diagnostic errors and the lack of oncological awareness of dental practitioners, as well as the sharp necessity of inclusion of precancer/cancer early detection techniques into their daily practice were noted. The effectiveness of chemilumenescence system of early OPLs and oral cancer detection was demonstrated, the prospects of infrared thermography as a diagnostic tool were also discussed.

  13. Linolenic acid prevents early and advanced glycation end-products (AGEs) modification of albumin.

    Science.gov (United States)

    Prasanna, Govindarajan; Saraswathi, N T

    2017-02-01

    In this study, we report the protective effects of linolenic acid towards the formation of early (HbA1c) and advanced glycation end-products (AGEs) based on fluorescence, circular dichroism, confocal microscopy and molecular interaction studies. Linolenic acid was found to be a potent inhibitor of AGEs formed by both glucose and fructose. The HbA1c (early glycation product) level was found to be reduced to 7.4% when compared to glycated control (8.4%). Similarly, linolenic acid also inhibited the methylglyoxal mediated AGEs formation. Circular dichroism spectroscopy studies suggested that the protective effect of linolenic acid for the helical structure of albumin. The molecular interaction studies showed that linolenic acid interacts with arginine residues of albumin with high affinity. Results suggested linolenic acid to be a potent antiglycation compound and also it could be a better lead compound for AGE inhibition.

  14. Paracrine and intracrine contributions of androgens and estrogens to adipose tissue biology: physiopathological aspects.

    Science.gov (United States)

    Waraich, Rizwana S; Mauvais-Jarvis, Franck

    2013-08-01

    In mammals, the male and female hormones androgen and estrogen act as endocrine regulators of energy metabolism. However, adipose tissue is also a site of androgen and estrogen synthesis; androgens convert to estrogens in these tissues, and adipose tissue is also a reservoir of steroids that act locally in a paracrine and intracrine manner. Thus, in adipose tissue, the local output of sex hormones is more complex than would be suggested by routine measurement of serum hormone concentrations. This review integrates studies on the effects of androgens and estrogens in the developmental programming of adipose tissue function in early life and addresses the contributions of local androgen and estrogen metabolism on adipose tissue function in adults.

  15. Early Rehabilitation in the Intensive Care Unit: Preventing Physical and Mental Health Impairments

    OpenAIRE

    Parker, Ann; Sricharoenchai, Thiti; Needham, Dale M.

    2013-01-01

    Survivors of critical illness often experience new or worsening impairments in physical, cognitive and/or mental health, referred to as post-intensive care syndrome (PICS). Such impairments can be long-lasting and negatively impact survivors’ quality of life. Early rehabilitation in the intensive care unit (ICU), while patients remain on life-support therapies, may reduce the complications associated with PICS. This article addresses evidence-based rehabilitation interventions to reduce the p...

  16. Early Rehabilitation in the Intensive Care Unit: Preventing Physical and Mental Health Impairments

    OpenAIRE

    Parker, Ann; Sricharoenchai, Thiti; Needham, Dale M.

    2013-01-01

    Survivors of critical illness often experience new or worsening impairments in physical, cognitive and/or mental health, referred to as post-intensive care syndrome (PICS). Such impairments can be long-lasting and negatively impact survivors’ quality of life. Early rehabilitation in the intensive care unit (ICU), while patients remain on life-support therapies, may reduce the complications associated with PICS. This article addresses evidence-based rehabilitation interventions to reduce the p...

  17. Students' Reports of Severe Violence in School as a Tool for Early Detection and Prevention

    Science.gov (United States)

    Yablon, Yaacov B.

    2017-01-01

    Early detection of severe violence is a significant challenge for many schools. Three studies were conducted on samples of 6th, 8th, and 10th graders (12-16 years old). The first study, based on paired reports of teachers and students (n = 130), showed that a high percentage of both victims and perpetrators of severe violence are not identified by…

  18. Breast Cancer Awareness and Prevention Behavior Among Women of Delhi, India: Identifying Barriers to Early Detection

    Science.gov (United States)

    Dey, Subhojit; Sharma, Surabhi; Mishra, Arti; Krishnan, Suneeta; Govil, Jyotsna; Dhillon, Preet K.

    2016-01-01

    BACKGROUND Globally, breast cancer (BC) has become the leading cause of mortality in women. Awareness and early detection can curb the growing burden of BC and are the first step in the battle against BC. The aim of this qualitative study was to explore the awareness and perceived barriers concerning the early detection of BC. METHODS A total of 20 focus group discussions (FGDs) were conducted during May 2013–March 2014. Pre-existing themes were used to conduct FGDs; each FGD group consisted of an average of ~10 women (aged ≥18–70 years) who came to participate in a BC awareness workshop. All FGDs were audio taped and transcribed verbatim. The transcripts were inductively analyzed using ATLAS.ti. Based on emerged codes and categories, thematic analysis was done, and theory was developed using the grounded theory approach. RESULTS Data were analyzed in three major themes: i) knowledge and perception about BC; ii) barriers faced by women in the early presentation of BC; and iii) healthcare-seeking behavior. The findings revealed that shyness, fear, and posteriority were the major behavioral barriers in the early presentation of BC. Erroneously, pain was considered as an initial symptom of BC by most women. Financial constraint was also mentioned as a cause for delay in accessing treatment. Social stigma that breast problems reflect bad character of women also contributed in hiding BC symptoms. CONCLUSIONS Lack of BC awareness was prevalent, especially in low socioeconomic class. Women’s ambivalence in prioritizing their own health and social and behavioral hurdles should be addressed by BC awareness campaigns appropriately suited for various levels of social class.

  19. Estrogen Signaling in Metabolic Inflammation

    Directory of Open Access Journals (Sweden)

    Rosário Monteiro

    2014-01-01

    Full Text Available There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

  20. Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity.

    Science.gov (United States)

    Kaliannan, K; Wang, B; Li, X-Y; Bhan, A K; Kang, J X

    2016-06-01

    Early-life antibiotic exposure can disrupt the founding intestinal microbial community and lead to obesity later in life. Recent studies show that omega-3 fatty acids can reduce body weight gain and chronic inflammation through modulation of the gut microbiota. We hypothesize that increased tissue levels of omega-3 fatty acids may prevent antibiotic-induced alteration of gut microbiota and obesity later in life. Here, we utilize the fat-1 transgenic mouse model, which can endogenously produce omega-3 fatty acids and thereby eliminates confounding factors of diet, to show that elevated tissue levels of omega-3 fatty acids significantly reduce body weight gain and the severity of insulin resistance, fatty liver and dyslipidemia resulting from early-life exposure to azithromycin. These effects were associated with a reversal of antibiotic-induced dysbiosis of gut microbiota in fat-1 mice. These results demonstrate the beneficial effects of omega-3 fatty acids on antibiotic-induced gut dysbiosis and obesity, and suggest the potential utility of omega-3 supplementation as a safe and effective means for the prevention of obesity in children who are exposed to antibiotics.

  1. Feasibility and Acceptability of an Early Childhood Obesity Prevention Intervention: Results from the Healthy Homes, Healthy Families Pilot Study

    Directory of Open Access Journals (Sweden)

    Akilah Dulin Keita

    2014-01-01

    Full Text Available Background. This study examined the feasibility and acceptability of a home-based early childhood obesity prevention intervention designed to empower low-income racially/ethnically diverse parents to modify their children’s health behaviors. Methods. We used a prospective design with pre-/posttest evaluation of 50 parent-child pairs (children aged 2 to 5 years to examine potential changes in dietary, physical activity, and sedentary behaviors among children at baseline and four-month follow-up. Results. 39 (78% parent-child pairs completed evaluation data at 4-month follow-up. Vegetable intake among children significantly increased at follow-up (0.54 cups at 4 months compared to 0.28 cups at baseline, P=0.001 and ounces of fruit juice decreased at follow-up (11.9 ounces at 4 months compared to 16.0 ounces at baseline, P=0.036. Sedentary behaviors also improved. Children significantly decreased time spent watching TV on weekdays (P<0.01 and also reduced weekend TV time. In addition, the number of homes with TV sets in the child’s bedroom also decreased (P<0.0013. Conclusions. The findings indicate that a home-based early childhood obesity prevention intervention is feasible, acceptable and demonstrates short-term effects on dietary and sedentary behaviors of low-income racially/ethnically diverse children.

  2. The Effect of Topical Iodine and Fluoride Varnish Combination in Preventing Early Childhood Caries: A Pilot Study

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    Zahra Hashemi

    2015-12-01

    Full Text Available Background: Early Childhood Caries (ECC in the earliest stage is preventable. The studies indicate oral bacteria play an important role in pathogenesis of dental caries. According to high prevalence of ECC, alternative therapies should be explored in order to reduce the occurrence of it. Aim: This study aims to assess the effectiveness of a product containing Povidone Iodine 10% and Sodium Fluoride 0.2% as a supplementary intervention for preventing ECC.Materials and Methods: Thirty-seven children aged 4 to 6 year-old were recruited. Maxillary incisors on each side of the mouth were selected either as a test or control group. Early caries detection examinations were conducted using International Caries Detection and Assessment System (ICDAS clinically and photographically. In a double-blind, placebo-controlled clinical study, a product containing a mixture of  Povidone Iodine 10%  and Sodium Fluoride 0.2%  was applied to the designated incisors of the test group participants. This application was performed every week for a 3-month. The control group participants received a placebo mixture during the same time interval. The caries detection examinations were conducted again after 6 months and the results were compared. The data was analyzed with SPSS V.18, using McNemar test.Results: The incidence of carious lesions increased for the control group while it decreased in the test group (P

  3. The Sense of School Belonging and Implementation of a Prevention Program: Toward Healthier Interpersonal Relationships Among Early Adolescents.

    Science.gov (United States)

    Drolet, Marie; Arcand, Isabelle; Ducharme, Daphne; Leblanc, Raymond

    2013-01-01

    The purpose of this qualitative study is to pave the way for the establishment of healthy interpersonal relations by facilitating an understanding of the impacts of Lions Quest Skills for Adolescence as perceived by adolescents and teachers who took part in it. Lions Quest has become recognized as an evidence-based program for preventing alcohol and drug use through the development of social skills and the promotion of meaningful engagement in the school community (Lions Clubs International, Overview of Skills for Adolescence 2013). Semi-structured interviews were conducted with 7th and 8th grade Francophone and Anglophone adolescents from three schools in Eastern Ontario who had participated in Lions Quest. Deductive and inductive analysis of interview transcripts clearly underscored that the positive perceptions of those early adolescents on the quality of their relationships with friends outweigh the negative impression that can be created by peer pressures at this age. It is through such a filter that these adolescents came to appreciate the impact of Lions Quest. Their need to be part of a circle of friends also comes to the fore as a crucial component of a sense of school belonging (Faircloth and Hamm (2005) J Youth Adolesc 34:293-309), highlighting the need to incorporate more of this form of positive social norm into interventions and prevention geared toward early adolescents. The data also underline the complementary importance attributed to having positive relationships with supportive adults.

  4. Preventing breast cancer in LMICs via screening and/or early detection: The real and the surreal.

    Science.gov (United States)

    Dey, Subhojit

    2014-08-10

    To review the present status of breast cancer (BC) screening/early detection in low- and middle-income countries (LMICs) and identify the way forward, an open focused search for articles was undertaken in PubMed, Google Scholar and Google, and using a snowball technique, further articles were obtained from the reference list of initial search results. In addition, a query was put up on ResearchGate to obtain more references and find out the general opinion of experts on the topic. Experts were also personally contacted for their opinion. Breast cancer (BC) is the most common cancer in women in the world. The rise in incidence is highest in LMICs where the incidence has often been much lower than high-income countries. In spite of more women dying of cancer than pregnancy or childbirth related causes in LMICs, most of the focus and resources are devoted to maternal health. Also, the majority of women in LMICs present at late stages to a hospital to initiate treatment. A number of trials have been conducted in various LMICs regarding the use of clinical breast examination and mammography in various combinations to understand the best ways of implementing a population level screening/early detection of BC; nevertheless, more research in this area is badly needed for different LMIC specific contexts. Notably, very few LMICs have national level programs for BC prevention via screening/early detection and even stage reduction is not on the public health agenda. This is in addition to other barriers such as lack of awareness among women regarding BC and the presence of stigma, inappropriate attitudes and lack of following proper screening behavior, such as conducting breast self-examinations. The above is mixed with the apathy and lack of awareness of policy makers regarding the fact that BC prevention is much more cost-effective and humane than BC treatment. Implementation of population level programs for screening/early detection of BC, along with use of ways to improve

  5. Prevention of problem behavior through annual family check-ups in early childhood: intervention effects from home to early elementary school.

    Science.gov (United States)

    Dishion, Thomas J; Brennan, Lauretta M; Shaw, Daniel S; McEachern, Amber D; Wilson, Melvin N; Jo, Booil

    2014-01-01

    This randomized intervention trial examined the effects of yearly Family Check-Ups (FCUs) and tailored parent management training on parent report of problem behavior from age 2 to 5 years and teacher report of oppositional behavior at age 7.5. A multiethnic risk sample of 731 families in 3 distinct geographical settings who were receiving assistance from the Women, Infants, and Children Nutritional Supplement (WIC) program were randomly assigned to a yearly FCU. Intention to treat (ITT) analyses were used to examine overall intervention effects, and complier average causal effect (CACE) modeling was used to examine the effects of annual intervention engagement in the FCU on parent reports of child problem behavior from age 2 to 5 and teacher reports of problem behavior at age 7.5. ITT intervention effects were found regarding parent report at ages 2 to 5 and teacher report at age 7.5, indicating less growth in problem behavior for children in the intervention group than for those in the control group. CACE modeling of intervention engagement revealed that the effect sizes on parent- and teacher-reported problem behavior increased as a function of the number of yearly FCUs caregivers participated in. Findings suggest that embedding yearly FCU services within the context of social, health, and educational services in early childhood can potentially prevent early-onset trajectories of antisocial behavior. The increases in effect size with successive FCU engagement underscores the importance of a motivational approach to parenting support among high-risk families.

  6. Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.

    Science.gov (United States)

    Hadar, Ravit; Dong, Le; Del-Valle-Anton, Lucia; Guneykaya, Dilansu; Voget, Mareike; Edemann-Callesen, Henriette; Schweibold, Regina; Djodari-Irani, Anais; Goetz, Thomas; Ewing, Samuel; Kettenmann, Helmut; Wolf, Susanne A; Winter, Christine

    2017-07-01

    In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Application of nanophotosensitizers (aluminum phthalocyanine nanoparticles) for early diagnosis and prevention of inflammatory diseases

    Science.gov (United States)

    Kuznetsova, J. O.; Makarov, V. I.

    2016-08-01

    This paper deals with a possibility of new types of photosensitizers application - Aluminum Phthalocyanine nanoparticles (nAlPc) in clinical practice for diagnosis, prevention and therapy of inflammatory diseases in dentistry and traumatology. It was detected that the aluminum phthalocyanine (AlPc) fluoresces in the nanoparticle form in the presence of pathologic microflora or inflammation process. It will make possible to detect the local accumulation of pathological microflora on the enamel surface and also for diagnostics and treatment of inflammatory diseases. Experimental studies of interaction of NP-AlPc with tooth enamel and with biological joint tissue at arthrosis are presented.

  8. Early Treatment With Olmesartan Prevents Juxtamedullary Glomerular Podocyte Injury and the Onset of Microalbuminuria in Type 2 Diabetic Rats

    Science.gov (United States)

    Sofue, Tadashi; Kiyomoto, Hideyasu; Kobori, Hiroyuki; Urushihara, Maki; Nishijima, Yoko; Kaifu, Kumiko; Hara, Taiga; Matsumoto, Sachiko; Ichimura, Atsuhiko; Ohsaki, Hiroyuki; Hitomi, Hirofumi; Kawachi, Hiroshi; Hayden, Melvin R.; Whaley-Connell, Adam; Sowers, James R.; Ito, Sadayoshi; Kohno, Masakazu; Nishiyama, Akira

    2012-01-01

    Background Studies were performed to determine if early treatment with an angiotensin II (Ang II) receptor blocker (ARB), olmesartan, prevents the onset of microalbuminuria by attenuating glomerular podocyte injury in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes mellitus. Methods OLETF rats were treated with either a vehicle, olmesartan (10 mg/kg/day) or a combination of nonspecific vasodilators (hydralazine 15 mg/kg/day, hydrochlorothiazide 6 mg/kg/day, and reserpine 0.3 mg/kg/day; HHR) from the age of 7–25 weeks. Results OLETF rats were hypertensive and had microalbuminuria from 9 weeks of age. At 15 weeks, OLETF rats had higher Ang II levels in the kidney, larger glomerular desmin-staining areas (an index of podocyte injury), and lower gene expression of nephrin in juxtamedullary glomeruli, than nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. At 25 weeks, OLETF rats showed overt albuminuria, and higher levels of Ang II in the kidney and larger glomerular desmin-staining areas in superficial and juxtamedullary glomeruli compared to LETO rats. Reductions in mRNA levels of nephrin were also observed in superficial and juxtamedullary glomeruli. Although olmesartan did not affect glucose metabolism, it decreased blood pressure and prevented the renal changes in OLETF rats. HHR treatment also reduced blood pressure, but did not affect the renal parameters. Conclusions This study demonstrated that podocyte injury occurs in juxtamedullary glomeruli prior to superficial glomeruli in type 2 diabetic rats with microalbuminuria. Early treatment with an ARB may prevent the onset of albuminuria through its protective effects on juxtamedullary glomerular podocytes. PMID:22318512

  9. Influence of SULT1A1 genetic variation on age at menopause, estrogen levels, and response to hormone therapy in recently postmenopausal white women.

    Science.gov (United States)

    Moyer, Ann M; de Andrade, Mariza; Weinshilboum, Richard M; Miller, Virginia M

    2016-08-01

    Onset and symptoms of menopause, and response to hormone therapy (HT) show large interindividual variability. SULT1A1 encodes for a highly expressed enzyme that metabolizes estrogens. We evaluated the relationship between genetic variation in SULT1A1, menopause age, symptoms, and response to HT. Women enrolled in the Kronos Early Estrogen Prevention Study at Mayo Clinic were randomized to 48 months of treatment with oral conjugated equine estrogen (n = 34), transdermal 17β-estradiol (E2) (n = 33), or placebo (n = 35). Linear regression models and ANOVA were used to test for association of SULT1A1 copy number, rs3760091, rs750155, and rs9282861 (SULT1A12), with age at menopause and symptoms, levels of estrogens (estrone [E1], estrone sulfate [E1S], E2, and estradiol sulfate [E2S]), before and after HT. SULT1A1 gene copy number affected the minor allele frequency for each single nucleotide polymorphisms tested. Before administration of exogenous hormones, increasing number of G alleles at rs9282861 was associated with earlier age at menopause (P = 0.014), lower frequency of night sweats (P = 0.009), and less severe insomnia (P = 0.046). After 48 months of treatment, SULT1A1 genotype was not associated with the presence of menopausal symptoms. In women randomized to oral conjugated equine estrogen, increasing number of the A allele at rs750155 was associated with lower E1S and E2S (P = 0.004 and 0.017), whereas increasing number of the C allele at rs3760091 was associated with lower E2S/E2 (P = 0.044). Interindividual variability in onset of menopause and symptoms before initiation of HT is explained in part by genetic variation in SULT1A1 and may represent a step toward individualizing HT treatment decisions.

  10. Randomized prevention trial for early conduct problems: effects on proactive parenting and links to toddler disruptive behavior.

    Science.gov (United States)

    Gardner, Frances; Shaw, Daniel S; Dishion, Thomas J; Burton, Jennifer; Supplee, Lauren

    2007-09-01

    Despite knowledge of early pathways to conduct problems, few preventive interventions are specifically designed to modify disruptive behavior in toddlerhood. One potential prevention target is proactive and positive parenting, which is associated with reduced risk of conduct problems in preschoolers. This randomized trial with 120 low-income 2-year-old boys examined whether a brief family-centered intervention that reduces disruptive behavior (D. Shaw, T. Dishion, L. Supplee, F. Gardner, & K. Arnds, 2006) also leads to increases in proactive and positive parenting. It also explored whether change in parenting predicts change in disruptive behavior. In the intervention group, proactive and positive parenting skills increased among parents of 3-year-olds. Change in proactive and positive parenting of 2- to 3-year-old toddlers correlated with change in child disruptive behavior, although the mediation effect of positive parenting was of only borderline significance. Findings suggest that even within a brief and multifaceted preventive intervention, change in proactive parenting skills contributes modestly but significantly to change in child problem behavior.

  11. Integrating Antiretroviral Strategies for Human Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis and Early Treatment

    Science.gov (United States)

    Grant, Robert M.; Smith, Dawn K.

    2015-01-01

    Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers. PMID:26512356

  12. Effects of estrogen on diverse stem cells and relevant intracellular mechanisms

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Sexual dimorphism definitely exists in the pathogenesis of a variety of cardiovascular,neurodegenerative and bone metabolism disorders.Estrogen affects the healing of ischemic myocardium partially through paracrine growth hormone production by bone marrow mesenchymal stem cells(MSCs) and facilitation on mobilization of endothelial progenitors cells(EPCs) to the ischemic myocardium.Estrogen can also inhibit the proliferation of the cardiac fibroblasts.Therefore,estrogen effectively enhances the neovascularization at the ischemic border zone and limits pathological myocardial remodeling.Moreover,estrogen increases proliferation of embryonic neural stem cells and accelerates differentiation of neurons during neurogenesis,suggesting a possible role of estrogen in transplantation of neural stem cells as a therapeutic approach for neurodegenerative diseases.Finally,estrogen can modulate osteogenic progenitors and osteoclasts,preventing the osteoporosis.In general,estrogen offers significant benefits on diverse stem/progenitor cell populations.A great understanding of estrogens on these cells and relevant intracellular mechanisms will allow modulation of the potent stem cells directly for the ultimate clinical applications.

  13. Drug targeting of estrogen receptor signaling in the cardiovascular system: preclinical and clinical studies.

    Science.gov (United States)

    Sanz-González, Silvia M; Cano, Antonio; Valverde, M A; Hermenegildo, Carlos; Andrés, Vicente

    2004-04-01

    Atherosclerosis and associated coronary heart disease events have lower prevalence in women than in men, especially during young adult years. Although multiple lines of evidence suggest that estrogens contribute to this difference, the efficacy of hormone replacement therapy for the prevention of cardiovascular disease in postmenopausal women is controversial. The protective action of estrogen in the cardiovascular system appears to be mediated indirectly by an effect on serum lipoprotein and triglyceride profiles and on the expression of coagulant and fibrinolytic proteins, and by a direct effect on the vessel wall itself. Estrogen has both rapid effects involving alteration of membrane ionic permeability and activation of membrane-bound enzymes and increases in endothelial cell nitric oxide synthase activity, as well as longer-term effects on gene expression that are mediated, at least in part, by the ligand-activated transcription factors, estrogen receptor alpha and beta. Compounds with pure antiestrogenic activity and selective estrogen receptor modulators that regulate estrogen receptor function in a tissue-specific manner have been developed in an attempt to achieve the cardioprotective effects of estrogens while minimizing the undesirable risks associated with hormone replacement therapy (e.g., endometrial and breast cancer). In this review, we will discuss recent developments on the mechanisms of estrogen action in the cardiovascular system. The results of clinical trials testing the long-term efficacy of hormone replacement therapy for the treatment of cardiovascular disease will also be discussed.

  14. Early Oral Ovalbumin Exposure during Maternal Milk Feeding Prevents Spontaneous Allergic Sensitization in Allergy-Prone Rat Pups

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    Adaweyah El-Merhibi

    2012-01-01

    Full Text Available There are conflicting data to support the practice of delaying the introduction of allergenic foods into the infant diet to prevent allergy development. This study investigated immune response development after early oral egg antigen (Ovalbumin; OVA exposure in a rat pup model. Brown Norway (BN rat pups were randomly allocated into groups: dam reared (DR, DR pups challenged daily (days 4–13 with oral OVA (DR + OVAc, DR pups challenged intermittently (on day 4, 10, 12, and 13 with oral OVA (DR + OVAi, formula-fed pups (FF, and FF pups challenged daily with oral OVA (FF + OVA. Immune parameters assessed included OVA-specific serum IgE, IgG1, and IgA. Ileal and splenic messenger ribonucleic acid (mRNA expression of transforming growth factor-beta (TGF-β1, mothers against decapentaplegic (Smad 2/4/7, and forkhead box P3 (Foxp3 were determined. Ileum was stained for TGF-β1 and Smad4. Results. Feeding OVA daily to DR pups maintained systemic and local gut antibody and immunoregulatory marker mRNA responses. Systemic TGF-β1 was lower in DR + OVAi pups compared to DR and DR + OVAc pups. Feeding OVA to FF pups resulted in significantly greater OVA-specific IgE and IgG1, and lower IgA and TGF-β1 and Smad expression compared to DR pups. Conclusions. Early daily OVA exposure in the presence of maternal milk maintains immune markers associated with a regulated immune response, preventing early allergic sensitization.

  15. Reprint of: From the 90's to now: A brief historical perspective on more than two decades of estrogen neuroprotection

    Science.gov (United States)

    Engler-Chiurazzi, E.B.; Singh, M.; Simpkins, J.W.

    2016-01-01

    Historical perspective abstract: From the 90's to now: a historical perspective on more than two decades of estrogen neuroprotection: In the early 90's, estrogens were known to exert organizational and activational effects on reproductive tissues and sexual behavior. As well, the role of sex and gonadal hormones in altering the risk for developing Alzheimer's Disease (AD) was only beginning to be elucidated. Preliminary investigations suggested that estrogen-containing therapies typically given for the management of disruptive menopausal symptoms could reduce AD risk, attenuate disease-associated cognitive deficits, and modulate brain substrates known to be dysregulated by the condition, such as the cholingeric system. The findings from our seminal paper demonstrating cognitive benefits and cholinergic impacts with exogenous estrogen treatment in a rodent model of surgical hormone depletion provided initial support for use of estrogen-containing therapies as a treatment for age-related brain disorders. We then went on to demonstrate neuroprotective actions of estrogen in several other in vivo and in vitro models of neurological challenge, including stroke and AD. Further, our findings of the chemical structure requirements for estrogen's neuroprotective effects identified a novel approach for optimizing future estrogen-containing hormone therapy options. These early efforts laid the groundwork for later, large-scale clinical investigations into the potential of estrogen-based menopausal hormone therapies for the prevention of a variety of age-related disorders. Although findings of these studies were equivocal, the neuroprotective actions of estrogen, and specifically 17β-estradiol, identified by early investigations, remain well-documented. Future development of interventions that optimize cognitive aging are crucial and, with proper understanding of the factors that influence the realization of beneficial impacts, estrogen-containing treatments may still be

  16. “Greenlight Study”: A Controlled Trial of Low-Literacy, Early Childhood Obesity Prevention

    OpenAIRE

    Sanders, Lee M.; Perrin, Eliana M.; Yin, H. Shonna; Bronaugh, Andrea; Rothman, Russell L.

    2014-01-01

    Children who become overweight by age 2 years have significantly greater risks of long-term health problems, and children in low-income communities, where rates of low adult literacy are highest, are at increased risk of developing obesity. The objective of the Greenlight Intervention Study is to assess the effectiveness of a low-literacy, primary-care intervention on the reduction of early childhood obesity. At 4 primary-care pediatric residency training sites across the US, 865 infant-paren...

  17. Loneliness Literacy Scale: Development and Evaluation of an Early Indicator for Loneliness Prevention.

    Science.gov (United States)

    Honigh-de Vlaming, Rianne; Haveman-Nies, Annemien; Bos-Oude Groeniger, Inge; Hooft van Huysduynen, Eveline J C; de Groot, Lisette C P G M; Van't Veer, Pieter

    2014-01-01

    To develop and evaluate the Loneliness Literacy Scale for the assessment of short-term outcomes of a loneliness prevention programme among Dutch elderly persons. Scale development was based on evidence from literature and experiences from local stakeholders and representatives of the target group. The scale was pre-tested among 303 elderly persons aged 65 years and over. Principal component analysis and internal consistency analysis were used to affirm the scale structure, reduce the number of items and assess the reliability of the constructs. Linear regression analysis was conducted to evaluate the association between the literacy constructs and loneliness. The four constructs "motivation", "self-efficacy", "perceived social support" and "subjective norm" derived from principal component analysis captured 56 % of the original variance. Cronbach's coefficient α was above 0.7 for each construct. The constructs "self-efficacy" and "perceived social support" were positively and "subjective norm" was negatively associated with loneliness. To our knowledge this is the first study developing a short-term indicator for loneliness prevention. The indicator contributes to the need of evaluating public health interventions more close to the intervention activities.

  18. Challenges Faced in Engaging American Indian Mothers in an Early Childhood Caries Preventive Trial.

    Science.gov (United States)

    Tiwari, Tamanna; Albino, Judith; Batliner, Terrence S

    2015-01-01

    Objective. This study explores the challenges faced by the research implementation team in engaging new mothers in a community oral health prevention intervention in an American Indian (AI) reservation community. Methods. Qualitative methods in the form of in-depth interviews were used in the study. Qualitative data were collected from research staff workers at a field site, who were involved in the implementation of a culturally tailored, randomized controlled trial of a behavioral intervention utilizing Motivational Interviewing (MI). Results. Several challenges were described by the field staff in engaging new mothers, including low priority placed on oral health, lack of knowledge, and distractions that reduced their ability to engage in learning about oral health of their child. Other difficulties faced in engaging the mothers and the AI community at large were distrust related to racial differences and physical and environmental barriers including poor road conditions, lack of transportation and communication, and remoteness of data collection sites. The field staff developed and applied many strategies, including conducting home visits, applying new communication strategies, and interacting with the community at various venues. Conclusion. Prevention interventions for ECC need to target AI mothers. Strategies developed by the field staff were successful for engaging mothers in the study.

  19. Do slums matter? Location and early childhood preventive care choices among urban residents of Bangladesh.

    Science.gov (United States)

    Heller, Lauren R

    2013-10-01

    Upward trends in the relative proportions of slum residents in developing countries have led to widespread concern regarding the impact of slum residency on health behaviors. Measurement of these impacts requires recognizing that unobservable household characteristics that affect the location decision may also affect health care choices and outcomes. To address the potential for bias, this paper models the location decision and the household's demand for maternal and child health services simultaneously using a flexible, semi-parametric approach. It uses a unique urban data set from Bangladesh that incorporates sophisticated geographical mapping techniques to carefully delineate between slum and non-slum areas at a particular point in time. The results suggest that accounting for the endogenous location decision of a family substantially reduces bias in estimated marginal effects of slum residence on preventive care demand. While community infrastructure variables appear correlated with preventive care demand, the causal effect of the availability of primary health care facilities is indistinguishable from zero when unobserved heterogeneity is taken into account. The findings suggest that improvements in community infrastructure in urban areas of developing countries are a more favorable health policy solution at the margin than the construction of additional health care facilities.

  20. Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein Graft In Vivo

    Directory of Open Access Journals (Sweden)

    Chengwei Liu

    2013-01-01

    Full Text Available The aim of this study was to detect the inhibitory action of the early growth response gene-1 DNA enzyme (EDRz as a carrying agent by liposomes on vascular smooth muscle cell proliferation and intimal hyperplasia. An autogenous vein graft model was established. EDRz was transfected to the graft vein. The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1 mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses. EDRz was located at the media of the vein graft from 2 to 24 h, 7 h after grafting. The Egr-1 protein was mainly located in the medial VSMCs, monocytes, and endothelium cells during the early phase of the vein graft. The degree of VSMC proliferation and thickness of intima were obviously relieved compared with the no-gene therapy group. EDRz can reduce Egr-1 expression in autogenous vein grafts, effectively restrain VSMC proliferation and intimal hyperplasia, and prevent vascular stenosis and occlusion after vein graft.

  1. Non-nuclear-initiated actions of the estrogen receptor protect cortical bone mass.

    Science.gov (United States)

    Bartell, Shoshana M; Han, Li; Kim, Ha-neui; Kim, Sung Hoon; Katzenellenbogen, John A; Katzenellenbogen, Benita S; Chambliss, Ken L; Shaul, Philip W; Roberson, Paula K; Weinstein, Robert S; Jilka, Robert L; Almeida, Maria; Manolagas, Stavros C

    2013-04-01

    Extensive evidence has suggested that at least some of the effects of estrogens on bone are mediated via extranuclear estrogen receptor α signaling. However, definitive proof for this contention and the extent to which such effects may contribute to the overall protective effects of estrogens on bone maintenance have remained elusive. Here, we investigated the ability of a 17β-estradiol (E2) dendrimer conjugate (EDC), incapable of stimulating nuclear-initiated actions of estrogen receptor α, to prevent the effects of ovariectomy (OVX) on the murine skeleton. We report that EDC was as potent as an equimolar dose of E2 in preventing bone loss in the cortical compartment that represents 80% of the entire skeleton, but was ineffective on cancellous bone. In contrast, E2 was effective in both compartments. Consistent with its effect on cortical bone mass, EDC partially prevented the loss of both vertebral and femoral strength. In addition, EDC, as did E2, prevented the OVX-induced increase in osteoclastogenesis, osteoblastogenesis, and oxidative stress. Nonetheless, the OVX-induced decrease in uterine weight was unaltered by EDC but was restored by E2. These results demonstrate that the protection of cortical bone mass by estrogens is mediated, at least in part, via a mechanism that is distinct from the classic mechanism of estrogen action on reproductive organs.

  2. Estrogenic environmental chemicals and drugs: mechanisms for effects on the developing male urogenital system.

    Science.gov (United States)

    Taylor, Julia A; Richter, Catherine A; Ruhlen, Rachel L; vom Saal, Frederick S

    2011-10-01

    Development and differentiation of the prostate from the fetal urogenital sinus (UGS) is dependent on androgen action via androgen receptors (AR) in the UGS mesenchyme. Estrogens are not required for prostate differentiation but do act to modulate androgen action. In mice exposure to exogenous estrogen during development results in permanent effects on adult prostate size and function, which is mediated through mesenchymal estrogen receptor (ER) alpha. For many years estrogens were thought to inhibit prostate growth because estrogenic drugs studied were administered at very high concentrations that interfered with normal prostate development. There is now extensive evidence that exposure to estrogen at very low concentrations during the early stages of prostate differentiation can stimulate fetal/neonatal prostate growth and lead to prostate disease in adulthood. Bisphenol A (BPA) is an environmental endocrine disrupting chemical that binds to both ER receptor subtypes as well as to AR. Interest in BPA has increased because of its prevalence in the environment and its detection in over 90% of people in the USA. In tissue culture of fetal mouse UGS mesenchymal cells, BPA and estradiol stimulated changes in the expression of several genes. We discuss here the potential involvement of estrogen in regulating signaling pathways affecting cellular functions relevant to steroid hormone signaling and metabolism and to inter- and intra-cellular communications that promote cell growth. The findings presented here provide additional evidence that BPA and the estrogenic drug ethinylestradiol disrupt prostate development in male mice at administered doses relevant to human exposures.

  3. Estrogenic flavonoids: structural requirements for biological activity.

    Science.gov (United States)

    Miksicek, R J

    1995-01-01

    A systematic survey of polycyclic phenols has been performed to identify members of this chemical group with estrogenic activity. Twelve compounds were found to be able to stimulate the transcriptional activity of the human estrogen receptor expressed in cultured cells by transient transfection. These natural estrogens belong to several distinct, but chemically related classes including chalcones, flavanones, flavones, flavonols, and isoflavones. Selected examples of estrogenic flavonoids were further analyzed to determine their biological potencies and their relative affinities for binding to the estrogen receptor. These data are interpreted with respect to the molecular structure of polycyclic phenols required for hormonal activity as nonsteroidal estrogens.

  4. Physical activity, sedentary behaviour and energy balance in the preschool child: opportunities for early obesity prevention.

    Science.gov (United States)

    Reilly, John J

    2008-08-01

    Prevalence of obesity in preschool children has increased dramatically in recent years. The preschool years (age 3-6 years) have been regarded as critical for the programming of energy balance, via the concept of early 'adiposity rebound'. Children who undergo early adiposity rebound are at increased risk of later obesity. Recent evidence suggests that associations between timing of adiposity rebound and later obesity may not reflect programming, but might denote that 'obesogenic' growth trajectories are often established by the preschool period. Studies of objectively-measured physical activity and sedentary behaviour in preschool children show that levels of physical activity are typically low and sedentary behaviour high. The review of evidence presented here is supportive of the hypothesis that physical activity is protective against obesity in the preschool period, and that sedentary behaviour, particularly television viewing, is obesogenic. Definitive evidence on dose-response relationships between physical activity, sedentary behaviour and obesity remain unclear. Dose-response evidence could be obtained fairly readily by intervention and longitudinal observational studies that use accelerometry in preschool children. The generalisability of much of the evidence base is limited and there is a need for research on the influence of physical activity and sedentary behaviour in the preschool years in the aetiology of obesity in the developing world.

  5. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

    Directory of Open Access Journals (Sweden)

    Inoue Takehiro

    2010-04-01

    Full Text Available Abstract Background Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6 is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA could ameliorate radiation-induced lung injury in mice. Methods BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1 or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA. Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. Results The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Conclusions Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

  6. Protocol for the SEED-trial: Supported Employment and preventing Early Disability.

    Science.gov (United States)

    Sveinsdottir, Vigdis; Tveito, Torill Helene; Bond, Gary R; Grasdal, Astrid Louise; Lie, Stein Atle; Reme, Silje Endresen

    2016-07-15

    Early withdrawal or exclusion from the labor market leads to significant personal and societal costs. In Norway, the increasing numbers of young adults receiving disability pension is a growing problem. While a large body of research demonstrates positive effects of Supported Employment (SE) in patients with severe mental illness, no studies have yet investigated the effectiveness of SE in young adults with a range of social and health conditions who are receiving benefits. The SEED-trial is a randomized controlled trial (RCT) comparing traditional vocational rehabilitation (TVR) to SE in 124 unemployed individuals between the ages of 18-29 who are receiving benefits due to various social- or health-related problems. The primary outcome is labor market participation during the first year after enrollment. Secondary outcomes include physical and mental health, health behaviors, and well-being, collected at baseline, 6, and 12 months. A cost-benefit analysis will also be conducted. The SEED-trial is the first RCT to compare SE to TVR in this important and vulnerable group, at risk of being excluded from working life at an early age. Clinicaltrials.gov, registration number NCT02375074 . Registered on December 3rd 2014.

  7. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice.

    Science.gov (United States)

    Ogata, Toshiyuki; Yamazaki, Hideya; Teshima, Teruki; Kihara, Ayaka; Suzumoto, Yuko; Inoue, Takehiro; Nishimoto, Norihiro; Matsuura, Nariaki

    2010-04-07

    Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6) is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA) could ameliorate radiation-induced lung injury in mice. BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1) or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA). Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

  8. The infrared-based early warning system for bird strike prevention at Frankfurt airport

    Science.gov (United States)

    Münzberg, M.; Schilling, A.; Schlemmer, H.; Vogel, H.; Cramer, H.; Schlosshauer, J.

    2011-06-01

    Flocks of migratory birds are very often using geographic structures like rivers, valleys or coast lines for orientation. Wherever the preferred migration routes are crossing the approach corridor of an airport there is an increased risk of bird strike. Flocks of birds crossing the runway corridor of the new runway Northwest of the Frankfurt airport are kept under surveillance now with in total three watch towers located at the river Main which in this case is the preferred used line of orientation. Each of the watch towers carries an early warning system which consists of two pairs of stereoscopic thermal imaging cameras sensitive in the mid wavelength infrared range (3 - 5 μm). A stereoscopic pair measures the swarm size, direction of flight and velocity in real time and with high accuracy. From these results an early warning is derived under all relevant weather conditions. The fixed focus thermal imaging cameras are thermally compensated and designed for ultra low image distortion. Each stereoscopic pair is aligned in the sub-pixel range and is controlled by a reference beam to ensure that the alignment is preserved under all environmental conditions and over a very long time. The technical concept is discussed and the design of the realized warning system at the Frankfurt airport is presented.

  9. Isoflavones: estrogenic activity, biological effect and bioavailability.

    Science.gov (United States)

    Vitale, Daniela Cristina; Piazza, Cateno; Melilli, Barbara; Drago, Filippo; Salomone, Salvatore

    2013-03-01

    Isoflavones are phytoestrogens with potent estrogenic activity; genistein, daidzein and glycitein are the most active isoflavones found in soy beans. Phytoestrogens have similarity in structure with the human female hormone 17-β-estradiol, which can bind to both alpha and beta estrogen receptors, and mimic the action of estrogens on target organs, thereby exerting many health benefits when used in some hormone-dependent diseases. Numerous clinical studies claim benefits of genistein and daidzein in chemoprevention of breast and prostate cancer, cardiovascular disease and osteoporosis as well as in relieving postmenopausal symptoms. The ability of isoflavones to prevent cancer and other chronic diseases largely depends on pharmacokinetic properties of these compounds, in particular absorption and distribution to the target tissue. The chemical form in which isoflavones occur is important because it influences their bioavailability and, therefore, their biological activity. Glucose-conjugated isoflavones are highly polar, water-soluble compounds. They are hardly absorbed by the intestinal epithelium and have weaker biological activities than the corresponding aglycone. Different microbial families of colon can transform glycosylated isoflavones into aglycones. Clinical studies show important differences between the aglycone and conjugated forms of genistein and daidzein. The evaluation of isoflavone metabolism and bioavailability is crucial to understanding their biological effects. Lipid-based formulations such as drug incorporation into oils, emulsions and self-microemulsifying formulations have been introduced to increase bioavailability. Complexation with cyclodextrin also represent a valid method to improve the physicochemical characteristics of these substances in order to be absorbed and distributed to target tissues. We review and discuss pharmacokinetic issues that critically influence the biological activity of isoflavones.

  10. Estrogens and selective estrogen receptor modulators in acromegaly.

    Science.gov (United States)

    Duarte, Felipe H; Jallad, Raquel S; Bronstein, Marcello D

    2016-11-01

    Despite recent advances in acromegaly treatment by surgery, drugs, and radiotherapy, hormonal control is still not achieved by some patients. The impairment of IGF-1 generation by estrogens in growth hormone deficient patients is well known. Patients on oral estrogens need higher growth hormone doses in order to achieve normal IGF-1 values. In the past, estrogens were one of the first drugs used to treat acromegaly. Nevertheless, due to the high doses used and the obvious side effects in male patients, this strategy was sidelined with the development of more specific drugs, as somatostatin receptor ligands and dopamine agonists. In the last 15 years, the antagonist of growth hormone receptor became available, making possible IGF-1 control of the majority of patients on this particular drug. However, due to its high cost, pegvisomant is still not available in many centers around the world. In this setting, the effect of estrogens and also of selective estrogen receptor modulators on IGF-1 control was reviewed, and proved to be an ancillary tool in the management of acromegaly. This review describes data concerning their efficacy and place in the treatment algorithm of acromegaly.

  11. Early intervention with intranasal NPY prevents single prolonged stress-triggered impairments in hypothalamus and ventral hippocampus in male rats.

    Science.gov (United States)

    Laukova, Marcela; Alaluf, Lishay G; Serova, Lidia I; Arango, Victoria; Sabban, Esther L

    2014-10-01

    Intranasal administration of neuropeptide Y (NPY) is a promising treatment strategy to reduce traumatic stress-induced neuropsychiatric symptoms of posttraumatic stress disorder (PTSD). We evaluated the potential of intranasal NPY to prevent dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, a core neuroendocrine feature of PTSD. Rats were exposed to single prolonged stress (SPS), a PTSD animal model, and infused intranasally with vehicle or NPY immediately after SPS stressors. After 7 days undisturbed, hypothalamus and hippocampus, 2 structures regulating the HPA axis activity, were examined for changes in glucocorticoid receptor (GR) and CRH expression. Plasma ACTH and corticosterone, and hypothalamic CRH mRNA, were significantly higher in the vehicle but not NPY-treated group, compared with unstressed controls. Although total GR levels were not altered in hypothalamus, a significant decrease of GR phosphorylated on Ser232 and increased FK506-binding protein 5 mRNA were observed with the vehicle but not in animals infused with intranasal NPY. In contrast, in the ventral hippocampus, only vehicle-treated animals demonstrated elevated GR protein expression and increased GR phosphorylation on Ser232, specifically in the nuclear fraction. Additionally, SPS-induced increase of CRH mRNA in the ventral hippocampus was accompanied by apparent decrease of CRH peptide particularly in the CA3 subfield, both prevented by NPY. The results show that early intervention with intranasal NPY can prevent traumatic stress-triggered dysregulation of the HPA axis likely by restoring HPA axis proper negative feedback inhibition via GR. Thus, intranasal NPY has a potential as a noninvasive therapy to prevent negative effects of traumatic stress.

  12. Evaluating early preventive antipsychotic and antidepressant drug treatment in an infection-based neurodevelopmental mouse model of schizophrenia.

    Science.gov (United States)

    Meyer, Urs; Spoerri, Erica; Yee, Benjamin K; Schwarz, Markus J; Feldon, Joram

    2010-05-01

    Current pharmacotherapy of schizophrenia remains unsatisfactory with little hope for complete functional restoration in patients once the disease has developed. A preventive approach based on intervention in the prodromal stage of the disease aiming to preserve functional integrity by halting the progress of the disease is therefore extremely attractive. Here, we investigated the effects of preventive antipsychotic or antidepressant drug treatment in a well-established neurodevelopmental mouse model of multiple schizophrenia-related abnormalities. Pregnant mice on gestation day 9 were exposed to the viral mimic polyriboinosinic-polyribocytidylic acid (2 mg/kg, intravenously) or corresponding vehicle treatment, and the resulting offspring from both prenatal treatment conditions were subjected to chronic antipsychotic (haloperidol or clozapine), antidepressant (fluoxetine), or placebo treatment during the periadolescent stage of development. The effects of the preventive pharmacotherapy on behavioral and pharmacological functions were then investigated in adulthood using paradigms relevant to schizophrenia, namely prepulse inhibition, latent inhibition, and sensitivity to psychostimulant drugs. We show that periadolescent treatment with the reference antipsychotic and antidepressant drugs can successfully block the emergence of multiple psychosis-related behavioral and pharmacological abnormalities in subjects predisposed to adult brain pathology by exposure to prenatal immune challenge. At the same time, however, our study reveals numerous negative influences of the early pharmacological intervention on normal behavioral development in control subjects. Hence, even though preventive pharmacotherapy may be beneficial in individuals with predisposition to psychosis-related brain dysfunctions, chronic antipsychotic or antidepressant drug treatment in false-positive subjects is associated with substantial risk for long-term behavioral disturbances in adulthood.

  13. Early successes and late failures in the prevention of post endoscopic retrograde cholangiopancreatography

    Institute of Scientific and Technical Information of China (English)

    John G Lieb II; Peter V Draganov

    2007-01-01

    Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP).The only way to prevent this complication is to avoid an ERCP all together. Because of the risks involved, a careful consideration should be given to the indication for ERCP and the potential risk/benefit ratio of the test. Once a decision to perform an ERCP is made, the procedure should be carried out with meticulous care by an experienced endoscopist, and with a minimum of pancreatic duct opacification. Several pharmacologic agents have been tested, but to date the most important method of reducing post ERCP pancreatitis is the placement of pancreatic stent. Pancreatic stents should be placed in all patients at high risk of this complication such as those undergoing pancreatic sphincterotomy,pancreatic duct manipulation and intervention, and patients with suspected sphincter of Oddi dysfunction.Pancreatic stents should be also considered in patients requiring precut sphincterotomy to gain biliary access.

  14. Thiamine-responsive megaloblastic anemia: early diagnosis may be effective in preventing deafness.

    Science.gov (United States)

    Onal, Hasan; Bariş, Safa; Ozdil, Mine; Yeşil, Gözde; Altun, Gürkan; Ozyilmaz, Isa; Aydin, Ahmet; Celkan, Tiraje

    2009-01-01

    Thiamine-responsive megaloblastic anemia syndrome is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural hearing loss. Mutations in the SLC19A2 gene, encoding a high-affinity thiamine transporter protein, THTR-1, are responsible for the clinical features associated with thiamine-responsive megaloblastic anemia syndrome in which treatment with pharmacological doses of thiamine correct the megaloblastic anemia and diabetes mellitus. The anemia can recur when thiamine is withdrawn. Thiamine may be effective in preventing deafness if started before two months. Our patient was found homozygous for a mutation, 242insA, in the nucleic acid sequence of exon B, with insertion of an adenine introducing a stop codon at codon 52 in the high-affinity thiamine transporter gene, SLC19A2, on chromosome 1q23.3.

  15. Probiotics for Prevention of Atopy and Food Hypersensitivity in Early Childhood

    Science.gov (United States)

    Zhang, Guo-Qiang; Hu, Hua-Jian; Liu, Chuan-Yang; Zhang, Qiao; Shakya, Shristi; Li, Zhong-Yue

    2016-01-01

    Abstract Most studies investigated probiotics on food hypersensitivity, not on oral food challenge confirmed food allergy in children. The authors systematically reviewed the literature to investigate whether probiotic supplementation prenatally and/or postnatally could reduce the risk of atopy and food hypersensitivity in young children. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and 4 main Chinese literature databases (Wan Fang, VIP, China National Knowledge Infrastructure, and SinoMed) were searched for randomized controlled trials regarding the effect of probiotics on the prevention of allergy in children. The last search was conducted on July 11, 2015. Seventeen trials involving 2947 infants were included. The first follow-up studies were analyzed. Pooled analysis indicated that probiotics administered prenatally and postnatally could reduce the risk of atopy (relative risk [RR] 0.78; 95% confidence interval [CI] 0.66–0.92; I2 = 0%), especially when administered prenatally to pregnant mother and postnatally to child (RR 0.71; 95% CI 0.57–0.89; I2 = 0%), and the risk of food hypersensitivity (RR 0.77; 95% CI 0.61–0.98; I2 = 0%). When probiotics were administered either only prenatally or only postnatally, no effects of probiotics on atopy and food hypersensitivity were observed. Probiotics administered prenatally and postnatally appears to be a feasible way to prevent atopy and food hypersensitivity in young children. The long-term effects of probiotics, however, remain to be defined in the follow-up of existing trials. Still, studies on probiotics and confirmed food allergy, rather than surrogate measure of food hypersensitivity, are warranted. PMID:26937896

  16. Early Identification and Prevention of the Spread of Ebola - United States.

    Science.gov (United States)

    Van Beneden, Chris A; Pietz, Harald; Kirkcaldy, Robert D; Koonin, Lisa M; Uyeki, Timothy M; Oster, Alexandra M; Levy, Deborah A; Glover, Maleeka; Arduino, Matthew J; Merlin, Toby L; Kuhar, David T; Kosmos, Christine; Bell, Beth P

    2016-07-08

    In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC prepared for the potential introduction of Ebola into the United States. The immediate goals were to rapidly identify and isolate any cases of Ebola, prevent transmission, and promote timely treatment of affected patients. CDC's technical expertise and the collaboration of multiple partners in state, local, and municipal public health departments; health care facilities; emergency medical services; and U.S. government agencies were essential to the domestic preparedness and response to the Ebola epidemic and relied on longstanding partnerships. CDC established a comprehensive response that included two new strategies: 1) active monitoring of travelers arriving from countries affected by Ebola and other persons at risk for Ebola and 2) a tiered system of hospital facility preparedness that enabled prioritization of training. CDC rapidly deployed a diagnostic assay for Ebola virus (EBOV) to public health laboratories. Guidance was developed to assist in evaluation of patients possibly infected with EBOV, for appropriate infection control, to support emergency responders, and for handling of infectious waste. CDC rapid response teams were formed to provide assistance within 24 hours to a health care facility managing a patient with Ebola. As a result of the collaborations to rapidly identify, isolate, and manage Ebola patients and the extensive preparations to prevent spread of EBOV, the United States is now better prepared to address the next global infectious disease threat.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

  17. Estrogen protection against EAE modulates the microbiota and mucosal-associated regulatory cells.

    Science.gov (United States)

    Benedek, Gil; Zhang, Jun; Nguyen, Ha; Kent, Gail; Seifert, Hilary A; Davin, Sean; Stauffer, Patrick; Vandenbark, Arthur A; Karstens, Lisa; Asquith, Mark; Offner, Halina

    2017-09-15

    Sex hormones promote immunoregulatory effects on multiple sclerosis. In the current study we evaluated the composition of the gut microbiota and the mucosal-associated regulatory cells in estrogen or sham treated female mice before and after autoimmune encephalomyelitis (EAE) induction. Treatment with pregnancy levels of estrogen induces changes in the composition and diversity of gut microbiota. Additionally, estrogen prevents EAE-associated changes in the gut microbiota and might promote the enrichment of bacteria that are associated with immune regulation. Our results point to a possible cross-talk between the sex hormones and the gut microbiota, which could promote neuroprotection. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The EARLY ALLIANCE prevention trial: a dual design to test reduction of risk for conduct problems, substance abuse, and school failure in childhood.

    Science.gov (United States)

    Prinz, R J; Dumas, J E; Smith, E P; Laughlin, J E

    2000-06-01

    This paper describes a preventive intervention trial called EARLY ALLIANCE which is aimed at reducing risk for three adverse outcomes in childhood and adolescence: conduct problems, substance abuse, and school failure. The structure of the prevention trial is unique because two linked designs are being implemented concurrently. The primary design focuses on children at elevated risk for adverse outcomes, and compares a targeted, multicontextual preventive intervention with family, classroom, peer relational, and academic components to a universal, schoolwide preventive intervention that emphasizes peaceful conflict management and serves as a "usual care" control condition. The secondary design focuses on children at lower risk for adverse outcomes and compares a universally administered classroom program to the control condition. The paper describes the theoretical foundation for EARLY ALLIANCE, the goals of the prevention trial, the rationale for design choices, and the methods employed.

  19. Perfil oxidativo de la mujer menopáusica: Papel de los estrógenos en la prevención y tratamiento de las enfermedades Oxidative Profile of the Menopausal Woman: Estrogens´ Rol in the Prevention and Treatment of Diseases

    Directory of Open Access Journals (Sweden)

    Carlos Escalante-Gómez

    2009-12-01

    Full Text Available El balance entre la producción de radicales libres de oxigeno y el nivel de enzimas antioxidantes es permanentemente regulado por la célula. Las enzimas antioxidantes son esenciales para las células aeróbicas, puesto que mantienen en niveles aceptables las concentraciones de especies químicas conocidas como radicales libres. Durante el climaterio o etapa perimenopáusica, el cuerpo y metabolismo de una mujer cambia de forma importante, y los mecanismos que regulan el estrés oxidativo no son la excepción. Los estrógenos, per se, son antioxidantes, y esto ha impulsado recientemente estudios sobre los efectos antioxidativos de los estrógenos, como un posible mecanismo preventivo para algunas enfermedades. En los últimos años se le ha brindado gran importancia al papel del estrés oxidativo en la génesis de algunas enfermedades como la ateroesclerosis y la enfermedad cardiovascular, algunos tipos de cánceres y la enfermedad de Alzheimer. Pareciera que los estrógenos sí modifican el equilibro oxidativo / antioxidativo in vivo, sin embargo aun se requieren más estudios para puntualizar el rol de estos como posibles tratamientos preventivos para la menopáusica.The cell carefully regulates the balance between the production of radical oxygen species and antioxidant enzymes levels. Antioxidant enzymes are critical for aerobic cells to maintain within balance free radical production. During the climacteric transition, the body and its metabolism suffer many changes and the mechanisms that regulate oxidative balance are not the exception. Estrogens, per se, are antioxidants, and this has promoted several studies to investigate the potential role of estrogens in disease prevention. Within the last few years, a great deal of studies have shown the relationship between oxidative stress and diseases such as therosclerosis and cardiovascular disease, cancer and Alzheimer’s disease. It appears that estrogens do modify the oxidative / anti

  20. Early signs of mobility decline and physical activity counseling as a preventive intervention in older people

    DEFF Research Database (Denmark)

    Mänty, Minna Regina

    : Screening and Counseling for Physical activity and Mobility among Older People, SCAMOB, a 2-year single-blinded randomized controlled trial (n=632) with a 1.5-year post-intervention follow-up, focused on 75 to 81-year-old community-dwelling people and the FITSA study, a 3-year prospective observational...... to promote mobility, which is a crucial prerequisite for maintaining independence in the community in old age. Keywords: Aging, mobility limitation, falls, risk assessment, physical activity, promotion, older people......The purpose of this study was to examine the early signs of mobility decline and falls in older people. In addition, the effects of physical activity counseling on the development of mobility limitation in an older community-dwelling population were studied. Data from two larger studies were used...

  1. IMPORTANCE OF SEX EDUCATION SINCE EARLY AGE FOR PREVENTING SEXUAL HARASSMENT

    Directory of Open Access Journals (Sweden)

    Ch. Megawati Tirtawinata

    2016-09-01

    Full Text Available Lack of sex education in children could cause the violence or sexual abuse done by adults. Parents should give the lesson about early sex education to the children so that they had the right knowledge about it and knew how to treat and look after it. The method in this research was a discourse analysis of the literature in which the readings were taken in context with the research topic. Besides that, it included the observations and everyday practical experience in social life. This article described the notion of sex education, the impact of sexual harassment, the importance of sex education for children, and who would be responsible for sex education for the children. The research finds that through the moral education and faith to God, the children are expected to get protection from sexual abuse, so the nation's children as successor generation get mentally active.

  2. Early signs of mobility decline and physical activity counseling as a preventive intervention in older people

    DEFF Research Database (Denmark)

    Mänty, Minna Regina

    The purpose of this study was to examine the early signs of mobility decline and falls in older people. In addition, the effects of physical activity counseling on the development of mobility limitation in an older community-dwelling population were studied. Data from two larger studies were used......: Screening and Counseling for Physical activity and Mobility among Older People, SCAMOB, a 2-year single-blinded randomized controlled trial (n=632) with a 1.5-year post-intervention follow-up, focused on 75 to 81-year-old community-dwelling people and the FITSA study, a 3-year prospective observational......-up for 1 year with daily fall calendars. Self-reported preclinical mobility limitation and fall history increased the risk of manifest mobility limitation and future falls. A single individualized physical activity counseling session with a supportive phone contact every 4 months for 2 years had a positive...

  3. Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model

    Directory of Open Access Journals (Sweden)

    Siemers Eric R

    2010-04-01

    Full Text Available Abstract Background Alzheimer's Disease (AD affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. Methods A time-to-event (TTE simulation provided estimates of screening asymptomatic patients in the general population age ≥55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. Results The base case results indicated increased AD free years (AD-FYs through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90. Conclusions This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

  4. 雌激素对氧糖剥夺诱导神经元损伤的保护作用%Estrogen prevents OGD/R-induced injury in cortical neuron of rats

    Institute of Scientific and Technical Information of China (English)

    周艳丽; 滕军放

    2010-01-01

    Objective To explore the protective effects of estrogen on injury induced by OGD/R(oxygen-glucose deprivation/rehabilitation of oxygen-glucose) in neonatal rats.Methods Cortical neurons cultured for 7 days were randomly divided into group A (normal control group),group B (OGD/R, alone) and group C (pretreatment with estrogen-17βE2,and OGD/R). Then detect cell survival rate by MTT colorimetry, count the apoptotic neurons by TUNEL, observe the expression of growth associated protein(GAP-43), brain-derived neurotrophic factor (BDNF) using immunocytochemical on each time point after OGD/R 0,1, 6, 12, 24 h of each group. Results ①Compared with group A, the cell survival rate in group B decreased, the survival rate was increased in group C due to pretreatment of estrogen. ②The apoptotic neurons in group B were more than those in group A, and it was less in the group C than in group B after OGD/R 6,12,24 h. ③The expression of GAP-43, BDNF was increased in group B,and it was higher in group C than group B after OGD/R 6,12,24 h. Conclusions The study indicated that estrogen could improve the survival rate of neurons after OGD/R, increase expressions of GAP-43, BDNF,inhabit neurocyte apoptosis,and these mechanisms play neuroprotective effects.%目的 探讨雌激素对氧糖剥夺诱导新生大鼠皮质神经元损伤的保护作用.方法 将培养7 d的大鼠皮质神经元随机分为3组,A组为正常对照组,B组采用氧糖剥夺/复糖复氧(OGD/R)处理,C组采用雌激素预处理加OGD/R处理,各组在OGD/R后0、1、6、12、24 h各时间点,以MTT法检测细胞活性,采用TUNEL法检测神经元凋亡情况,采用细胞免疫组化方法检测生长相关蛋白(GAP-43)、脑源性神经营养因子(BDNF)的表达.结果 ①B组的神经元细胞活性较A组明显下降,C组细胞活性明显高于B组,三组比较差异有统计学意义(P<0.05).②B组凋亡神经元细胞明显多于正常对照组,OGD/R后6、12、24 h,C组凋亡细胞数目显

  5. Pilot evaluation of a media literacy program for tobacco prevention targeting early adolescents shows mixed results.

    Science.gov (United States)

    Kaestle, Christine E; Chen, Yvonnes; Estabrooks, Paul A; Zoellner, Jamie; Bigby, Brandon

    2013-01-01

    The purpose of this pilot study was to assess the impact of media literacy for tobacco prevention for youth delivered through a community site. A randomized pretest-posttest evaluation design with matched-contact treatment and control conditions. The pilot study was delivered through the YMCA in a lower-income suburban and rural area of Southwest Virginia, a region long tied, both economically and culturally, to the tobacco industry. Children ages 8 to 14 (76% white, 58% female) participated in the study (n = 38). The intervention was an antismoking media literacy program (five 1-hour lessons) compared with a matched-contact creative writing control program. General media literacy, three domains of tobacco-specific media literacy ("authors and audiences," "messages and meanings," and "representation and reality"), tobacco attitudes, and future expectations were assessed. Multiple regression modeling assessed the impact of the intervention, controlling for pretest measures, age, and sex. General media literacy and tobacco-specific "authors and audiences" media literacy improved significantly for treatment compared with control (p media literacy measures and for tobacco attitudes were not significant. Future expectations of smoking increased significantly for treatment participants ages 10 and younger (p media literacy are accompanied by an increase in future expectations to smoke for younger children.

  6. Verbal Fluency and Early Memory Decline: Results from the Wisconsin Registry for Alzheimer's Prevention

    Science.gov (United States)

    Mueller, Kimberly Diggle; Koscik, Rebecca L.; LaRue, Asenath; Clark, Lindsay R.; Hermann, Bruce; Johnson, Sterling C.; Sager, Mark A.

    2015-01-01

    This study examined the relationship between phonemic and semantic (category) verbal fluency and cognitive status in the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal cohort enriched for family history of Alzheimer’s disease. Participants were 283 WRAP subjects (age 53.1[6.5] years at baseline); who had completed three waves of assessment, over ∼6 years and met psychometric criteria either for “cognitively healthy” (CH) or for psychometric amnestic mild cognitive impairment (aMCI) using an approach that did not consider fluency scores. CH and aMCI groups differed significantly on phonemic total scores, category total scores, phonemic switching, and category mean cluster size. These results suggest that measures of both phonemic and semantic fluency yield lower scores in persons with evidence of psychometric aMCI compared with those who are CH. Differences have not previously been reported in a group this young, and provide evidence for the importance of including multiple verbal fluency tests targeting preclinical Alzheimer’s disease. PMID:26025231

  7. E-mentoring for violence and injury prevention: early lessons from a global programme.

    Science.gov (United States)

    Wadhwaniya, Shirin; Meddings, David; Gururaj, Gopalkrishna; Ozanne-Smith, Joan; Ameratunga, Shanthi; Hyder, Adnan A

    2015-01-01

    To address the growing burden of violence and injuries, especially in low- and middle-income countries, in 2007 the World Health Organization launched MENTOR-VIP, a global violence and injury prevention (VIP)-mentoring programme. The programme aims to develop human resource capacity through 12-month mentoring arrangements between individual VIP experts (mentors) and less-experienced injury practitioners (mentees). In this paper, we review the first five years of the programme (2007-2011) using a systems analysis and SWOT (Strengths, Weaknesses, Opportunities and Threats) frameworks, discuss programme findings and make recommendations. A well-defined programme with clear instructions, successful matching of mentorship pairs with similar interests and language, a formal accord agreement, institutional support and effective communication were identified as programme strengths. Overambitious projects, lack of funds and difficulties with communications were identified as programme weaknesses. Mentorship projects that require institutional permissions or resources could be potential threats to the success of mentorship. The study resulted in the four following recommendations to strengthen the programme: (1) institute additional steps in selection and matching mentor-mentee pair; (2) train mentors on e-mentoring; (3) conduct special orientation for mentees to the programme; and (4) maintain effective and open communication throughout the programme.

  8. Early Identification of Traumatic Durotomy Associated with Atlantooccipital Dislocation May Prevent Retropharyngeal Pseudomeningocele Development

    Directory of Open Access Journals (Sweden)

    Robert S. Qiu

    2015-01-01

    Full Text Available Atlantooccipital dislocation can be complicated by a traumatic durotomy that may lead to the rare development of a retropharyngeal pseudomeningocele. To our knowledge this has been reported only five times previously. We present the case of a 60-year-old man involved in a motor vehicle accident who suffered an atlantooccipital dislocation and C5-C6 three-column injury. A unique MRI image of a defect in the ventral dura posterior to C2 was appreciated. He underwent occiput to T2 internal fixation and arthrodesis. During surgery, CSF egress was seen caudal to the right C2 nerve root. A DuraMatrix onlay patch reinforced with DuraSeal was placed to stop the CSF leak. A lumbar subarachnoid drain was also placed. The patient made a satisfactory recovery with residual mild weakness of his right upper extremity. In this report, we demonstrate that careful MRI review can reveal a ventral durotomy in a traumatic atlantooccipital dislocation and, if discovered, effective treatment including a lumbar subarachnoid drain for CSF diversion may prevent progression to a retropharyngeal pseudomeningocele. The literature on this rare presentation and associated durotomy is provided.

  9. Pomegranate extract demonstrate a selective estrogen receptor modulator profile in human tumor cell lines and in vivo models of estrogen deprivation.

    Science.gov (United States)

    Sreeja, Sreekumar; Santhosh Kumar, Thankayyan R; Lakshmi, Baddireddi S; Sreeja, Sreeharshan

    2012-07-01

    Selective estrogen receptor modulators (SERMs) are estrogen receptor (ER) ligands exhibiting tissue-specific agonistic or antagonistic biocharacter and are used in the hormonal therapy for estrogen-dependent breast cancers. Pomegranate fruit has been shown to exert antiproliferative effects on human breast cancer cells in vitro. In this study, we investigated the tissue-specific estrogenic/antiestrogenic activity of methanol extract of pericarp of pomegranate (PME). PME was evaluated for antiproliferative activity at 20-320 μg/ml on human breast (MCF-7, MDA MB-231) endometrial (HEC-1A), cervical (SiHa, HeLa), ovarian (SKOV3) carcinoma and normal breast fibroblast (MCF-10A) cells. Competitive radioactive binding studies were carried out to ascertain whether PME interacts with ER. The reporter gene assay measured the estrogenic/antiestrogenic activity of PME in MCF-7 and MDA MB-231 cells transiently transfected with plasmids coding estrogen response elements with a reporter gene (pG5-ERE-luc) and wild-type ERα (hEG0-ER). PME inhibited the binding of [³H] estradiol to ER and suppressed the growth and proliferation of ER-positive breast cancer cells. PME binds ER and down-regulated the transcription of estrogen-responsive reporter gene transfected into breast cancer cells. The expressions of selected estrogen-responsive genes were down-regulated by PME. Unlike 17β-estradiol [1 mg/kg body weight (BW)] and tamoxifen (10 mg/kg BW), PME (50 and 100 mg/kg BW) did not increase the uterine weight and proliferation in ovariectomized mice and its cardioprotective effects were comparable to that of 17β-estradiol. In conclusion, our findings suggest that PME displays a SERM profile and may have the potential for prevention of estrogen-dependent breast cancers with beneficial effects in other hormone-dependent tissues.

  10. Induction of Hsp22 (HspB8) by estrogen and the metalloestrogen cadmium in estrogen receptor-positive breast cancer cells.

    Science.gov (United States)

    Sun, Xiankui; Fontaine, Jean-Marc; Bartl, Ingrid; Behnam, Babak; Welsh, Michael J; Benndorf, Rainer

    2007-01-01

    Estrogen (E2) plays a critical role in the etiology and progression of human breast cancer. The estrogenic response is complex and not completely understood, including in terms of the involved responsive genes. Here we show that Hsp22 (synonyms: HspB8, E2lG1, H11), a member of the small heat shock protein (sHSP) superfamily, was induced by E2 in estrogen receptor-positive MCF-7 breast cancer cells, resulting in an elevated Hsp22 protein level, whereas it was not induced in estrogen receptor-negative MDA-MB-231 cells. This induction was prevented by the pure anti-estrogen ICI182780 (faslodex, fulvestrant), whereas tamoxifen, a substance with mixed estrogenic and antiestrogenic properties, had no major inhibitory effect on this induction, nor did it induce Hsp22 on its own. Cadmium (Cd) is an environmental pollutant with estrogenic properties (metalloestrogen) that has been implicated in breast cancer. Treatment of MCF-7 cells with Cd also resulted in induction of Hsp22, and this induction was also inhibited by ICI182780. In live MCF-7 cells, Hsp22 interacted at the level of dimers with Hsp27, a related sHSP, as was shown by quantitative fluorescence resonance energy transfer measurements. In cytosolic extracts of MCF-7 cells, most of the E2- and Cd-induced Hsp22 was incorporated into high-molecular mass complexes. In part, Hsp22 and Hsp27 were components of distinct populations of these complexes. Finally, candidate elements in the Hsp22 promoter were identified by sequence analysis that could account for the induction of Hsp22 by E2 and Cd. Taken together, Hsp22 induction represents a new aspect of the estrogenic response with potential significance for the biology of estrogen receptor-positive breast cancer cells.

  11. [Early detection and prevention of elder abuse and neglect in family care giving: development of the PURFAM assessment].

    Science.gov (United States)

    Heidenblut, S; Schacke, C; Zank, S

    2013-07-01

    The purpose of the PURFAM ("potentials and risk factors of family caregiving for older people") project is to support staff members of home care services in preventing elder abuse by facilitating an assessment instrument for early recognition and a standard for action. During a pilot phase of the project nursing staff of home services were presented with training sessions in which the use of the PURFAM assessment was introduced using concrete examples from routine daily work. The article describes the development of the PURFAM assessment and its first evaluation by staff members of nursing home services. The preliminary results indicate a high practicability und acceptance of the instrument by staff members. The sustainability of PURFAM is yet to be tested using the data of the still ongoing main part of the evaluation.

  12. Early warning and prevention of pneumonia in acute leukemia by patient education, spirometry, and positive expiratory pressure

    DEFF Research Database (Denmark)

    Møller, Tom; Moser, Claus; Adamsen, Lis

    2016-01-01

    of positive expiratory pressure (PEP) in preventing pneumonia among 80 AML patients. Twenty-five incidences of pneumonia were detected among 23 patients (6 interventions, 17 controls), giving a prevalence of 28.75% during 5420 days of observation. We found a significant difference in incidence between...... fever, emphasizing the need to approach infection protection with complementary efforts. In a randomized controlled design, we examined the applicability of patient-performed daily spirometry [forced expiratory volume in one second (FEV1)] as an early warning tool and explored the effectiveness...... intervention versus control group (2.17 per 1000 days vs. 6.52 per 1000 days, P = 0.021, respectively). A cross point at 80-76% of the personal FEV1 reference value showed high sensitivity and specificity on pneumonia development. Our data demonstrate the feasibility of educating AML patients...

  13. HIV drug resistance in adults failing early antiretroviral treatment: results from the HIV Prevention Trials Network 052 trial

    Science.gov (United States)

    Fogel, Jessica M.; Hudelson, Sarah E.; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G.; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi Cindy; Eron, Joseph J.; Gallant, Joel E.; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C.; Santos, Breno Riegel; Godbole, Sheela V.; Pilotto, Jose Henrique; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H.; Chen, Ying Q.; Cohen, Myron S.; Eshleman, Susan H.

    2016-01-01

    Early initiation of antiretroviral therapy (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HPTN 052 trial who started ART at CD4 counts of 350–550 cells/mm3 and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7/8 (87.5%) participants who started ART at lower CD4 cell counts. PMID:26859828

  14. Nimodipine prevents early loss of hippocampal CA1 parvalbumin immunoreactivity after focal cerebral ischemia in the rat.

    Science.gov (United States)

    Benyó, Z; De Jong, G I; Luiten, P G

    1995-01-01

    The effect of focal cerebral ischemia induced by middle cerebral artery occlusion on hippocampal interneurons containing the calcium-binding protein parvalbumin (PV) was studied in rats. Four hours after the onset of ischemia, a reduced number of PV-immunoreactive (-ir) neurons was observed in the lateral part of the CA1 region, while PV-ir was not altered in the CA2 and CA3 areas. Pretreatment with the L-type Ca2+ channel blocker nimodipine prevented the ischemia-induced loss of PV-ir in the CA1, suggesting a role for L-type voltage sensitive calcium channels in the mechanism of early neuronal alterations in the hippocampus CA1 region after focal cerebral ischemia.

  15. Unbalanced estrogen metabolism in thyroid cancer

    National Research Council Canada - National Science Library

    Zahid, Muhammad; Goldner, Whitney; Beseler, Cheryl L; Rogan, Eleanor G; Cavalieri, Ercole L

    2013-01-01

    .... Greater exposure to estrogens may be a risk factor for thyroid cancer. To investigate the role of estrogens in thyroid cancer, a spot urine sample was obtained from 40 women with thyroid cancer and 40 age‐matched controls. Thirty...

  16. Estrogenic endocrine disruptors: Molecular mechanisms of action.

    Science.gov (United States)

    Kiyama, Ryoiti; Wada-Kiyama, Yuko

    2015-10-01

    A comprehensive summary of more than 450 estrogenic chemicals including estrogenic endocrine disruptors is provided here to understand the complex and profound impact of estrogen action. First, estrogenic chemicals are categorized by structure as well as their applications, usage and effects. Second, estrogenic signaling is examined by the molecular mechanism based on the receptors, signaling pathways, crosstalk/bypassing and autocrine/paracrine/homeostatic networks involved in the signaling. Third, evaluation of estrogen action is discussed by focusing on the technologies and protocols of the assays for assessing estrogenicity. Understanding the molecular mechanisms of estrogen action is important to assess the action of endocrine disruptors and will be used for risk management based on pathway-based toxicity testing.

  17. Breast Cancer and Estrogen-Alone Update

    Science.gov (United States)

    ... Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 Table of ... version of this page please turn Javascript on. Estrogen-alone hormone therapy does not increase the risk ...

  18. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

    Directory of Open Access Journals (Sweden)

    B.H. Bakkal

    2013-09-01

    Full Text Available Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg. Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  19. Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction.

    Directory of Open Access Journals (Sweden)

    Wilco P Pulskens

    Full Text Available Progressive renal disease is characterized by tubulo-interstitial injury with ongoing inflammation and fibrosis. The Nlrp3 inflammasome contributes to these pathophysiological processes through its canonical effects in cytokine maturation. Nlrp3 may additionally exert inflammasome-independent effects following tissue injury. Hence, in this study we investigated potential non-canonical effects of Nlrp3 following progressive renal injury by subjecting WT and Nlrp3-deficient (-/- mice to unilateral ureter obstruction (UUO. Our results revealed a progressive increase of renal Nlrp3 mRNA in WT mice following UUO. The absence of Nlrp3 resulted in enhanced tubular injury and dilatation and an elevated expression of injury biomarker NGAL after UUO. Moreover, interstitial edema was significantly elevated in Nlrp3-/- mice. This could be explained by increased intratubular pressure and an enhanced tubular and vascular permeability. In accordance, renal vascular leakage was elevated in Nlrp3-/- mice that associated with reduced mRNA expression of intercellular junction components. The decreased epithelial barrier function in Nlrp3-/- mice was not associated with increased apoptosis and/or proliferation of renal epithelial cells. Nlrp3 deficiency did not affect renal fibrosis or inflammation. Together, our data reveal a novel non-canonical effect of Nlrp3 in preserving renal integrity and protection against early tubular injury and interstitial edema following progressive renal injury.

  20. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bakkal, B.H. [Department of Radiation Oncology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Gultekin, F.A. [Department of General Surgery, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Guven, B. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Turkcu, U.O. [Mugla School of Health Sciences, Mugla Sitki Kocman University, Mugla (Turkey); Bektas, S. [Department of Pathology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Can, M. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey)

    2013-09-27

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  1. Setting the stage for child health and development: prevention of iron deficiency in early infancy.

    Science.gov (United States)

    Chaparro, Camila M

    2008-12-01

    Iron deficiency is estimated to be the most common nutritional deficiency worldwide and is particularly persistent among infants and children. The high prevalence of anemia in 6- to 9-mo-old children raises the concern that birth iron stores in some infants are inadequate to sustain growth and development through the first 6 mo of life, and postnatal factors are contributing to early depletion of iron stores and development of anemia. At the same time, there are concerns about negative effects of excess iron in infants. Maternal iron status, infant birth weight and gestational age, as well as the timing of umbilical cord clamping at birth all contribute to the establishment of adequate total body iron at birth. Postnatally, feeding practices and growth rate are factors that will affect how quickly birth iron is depleted during the first 6 mo of life. Under conditions in which maternal iron status, birth weight, gestational age, and umbilical cord clamping time are optimal, and exclusive breast-feeding is practiced, infants should have adequate iron stores for the first 6-8 mo of life. Under suboptimal conditions, infants may not reach this goal and may need to be targeted for iron supplementation before 6 mo of age.

  2. Prevention of ER-Negative Breast Cancer

    OpenAIRE

    Li, Yuxin; Brown, Powel H.

    2009-01-01

    The successful demonstration that the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene reduce the risk of breast cancer has stimulated great interest in using drugs to prevent breast cancer in high-risk women. In addition, recent results from breast cancer treatment trials suggest that aromatase inhibitors may be even more effective at preventing breast cancer than are SERMs. However, while SERMs and aromatase inhibitors do prevent the development of many estrogen-recep...

  3. DNA stabilization by the upregulation of estrogen signaling in BRCA gene mutation carriers.

    Science.gov (United States)

    Suba, Zsuzsanna

    2015-01-01

    Currently available scientific evidence erroneously suggests that mutagenic weakness or loss of the BRCA1/2 genes may liberate the proliferative effects of estrogen signaling, which provokes DNA damage and genomic instability. Conversely, BRCA mutation seems to be an imbalanced defect, crudely inhibiting the upregulation of estrogen receptor expression and liganded transcriptional activity, whereas estrogen receptor-repressor functions become predominant. In BRCA-proficient cases, estrogen signaling orchestrates the activity of cell proliferation and differentiation with high safety, while upregulating the expression and DNA-stabilizing impact of BRCA genes. In turn, BRCA proteins promote estrogen signaling by proper estrogen synthesis via CYP19 gene regulation and by induction of the appropriate expression and transcriptional activity of estrogen receptors. In this exquisitely organized regulatory system, the dysfunction of each player may jeopardize genome stability and lead to severe chronic diseases, such as cancer development. Female organs, such as breast, endometrium, and ovary, exhibiting regular cyclic proliferative activity are particularly vulnerable in case of disturbances in either estrogen signaling or BRCA-mediated DNA repair. BRCA mutation carrier women may apparently be healthy or exhibit clinical signs of deficient estrogen signaling in spite of hyperestrogenism. Even women who enjoy sufficient compensatory DNA-defending activities are at risk of tumor development because many endogenous and environmental factors may jeopardize the mechanisms of extreme compensatory processes. Natural estrogens have numerous benefits in tumor prevention and therapy even in BRCA mutation carriers. There are no toxic effects even in sky-high doses and all physiologic cellular functions are strongly upregulated, while malignant tumor cells are recognized and killed in a Janus-faced manner.

  4. Efficacy of early treatment with toltrazuril in prevention of coccidiosis and necrotic enteritis in chickens.

    Science.gov (United States)

    Alnassan, Alaa Aldin; Shehata, Awad Ali; Kotsch, Marianne; Schrödl, Wieland; Krüger, Monika; Daugschies, Arwid; Bangoura, Berit

    2013-01-01

    In the present study, efficacy of the toltrazuril treatment for prevention of coccidiosis and necrotic enteritis was tested. Ninety-six 14-day-old commercial broiler chickens were caged and divided into eight groups (n=12), designated groups 1 to 8. Chickens of groups 1 to 6 were inoculated orally at 18 days of age with 25,000 oocysts of Eimeria tenella and 75,000 oocysts of Eimeria brunetti. At 22 days of age, chickens of groups 1 to 6 were infected with 10(9) colony-forming unit Clostridium perfringens. Chickens of group 1 were treated with 75 parts/10(6) toltrazuril in drinking water for 8 h on two consecutive days up to 12 h before Eimeria infection, while chickens of groups 2 to 5 were treated with the same dose of toltrazuril at 12 h, 36 h, 60 h and 84 h after Eimeria infection, respectively. The non-treated group 6 served as a positive control. Chickens in group 7 were treated with toltrazuril at 17 and 18 days of age, and those of group 8 remained uninfected and non-treated as a negative control. The feed conversion ratio was higher in the positive control compared with other groups. The mortality rates were 16.8% and 41.7% in the late toltrazuril-treated (at 84 h) and infected non-treated chickens, respectively. Lesions scores of necrotic enteritis or coccidiosis in infected, non-treated chickens were significantly more severe compared with negative controls (Penteritis caused by C. perfringens infection.

  5. Early detection of children at risk for antisocial behaviour using data from routine preventive child healthcare

    Directory of Open Access Journals (Sweden)

    Reijneveld Sijmen A

    2012-03-01

    Full Text Available Abstract Background Youth antisocial behaviour is highly prevalent. Young people are usually not willing to disclose such behaviour to professionals and parents. Our aim was to assess whether child health professionals (CHP working in preventive child healthcare could identify pre-adolescents at risk for antisocial behaviour through using data that they obtain in routine practice. Methods CHPs examined a national sample of 974 pre-adolescents aged 8-12 years (response 79.1%, and interviewed parents and children during routine well-child assessments. We obtained data on family background and current health of the child from the CHP; on developmental concerns from parents, and on social and emotional well-being, injuries, and substance use from the children. Antisocial behaviour concerned the adolescent-reported 15 item International Self-Reported Delinquency study questionnaire, among which are 5 items on violence against people. Results The prevalence of 2+acts of any antisocial behaviour was 21.8%, and 33.9% for 1+acts of violence (10.5% for 2+. Children who were male, had a young mother, no parent employed, recent injuries, poor performance at school or who were bored by school, and who had parental concerns more often reported 2+antisocial acts and 1+violence against people. Detection algorithms on the basis of these variables were moderately able to classify outcomes, with Areas-Under-the-Curves ranging from 0.66 to 0.71. Conclusions Data from routine well-child assessment can help CHPs to detect pre-adolescents at risk for antisocial behaviour, but detection algorithms need to be further improved. This could be done by obtaining additional information on factors that are associated with antisocial behaviour.

  6. Preventing cervical cancer : overviews of the National Breast and Cervical Cancer Early Detection Program and 2 US immunization programs.

    Science.gov (United States)

    Khan, Kris; Curtis, C Robinette; Ekwueme, Donatus U; Stokley, Shannon; Walker, Chastity; Roland, Katherine; Benard, Vicki; Saraiya, Mona

    2008-11-15

    Three federal programs with the potential to reduce cervical cancer incidence, morbidity, and mortality, especially among underserved populations, are administered by the Centers for Disease Control and Prevention (CDC): the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), the Vaccines for Children (VFC) Program, and the Section 317 immunization grant program. The NBCCEDP provides breast and cervical cancer screening and diagnostic services to uninsured and underinsured women. The VFC program and the Section 317 immunization grant program provide vaccines, including human papillomavirus (HPV) vaccine, to targeted populations at no cost for these vaccines. This article describes the programs, their histories, populations served, services offered, and roles in preventing cervical cancer through HPV vaccination and cervical cancer screening. Potential long-term reduction in healthcare costs resulting from HPV vaccination is also discussed. As an example of an initiative to vaccinate uninsured women aged 19-26 years through a cancer services program, a state-based effort that was recently launched in New York, is highlighted.

  7. Preventing Early Child Maltreatment: Implications from a Longitudinal Study of Maternal Abuse History, Substance Use Problems, and Offspring Victimization

    Science.gov (United States)

    Appleyard, Karen; Berlin, Lisa J.; Rosanbalm, Katherine D.; Dodge, Kenneth A.

    2013-01-01

    In the interest of improving child maltreatment prevention science, this longitudinal, community based study of 499 mothers and their infants tested the hypothesis that mothers’ childhood history of maltreatment would predict maternal substance use problems, which in turn would predict offspring victimization. Mothers (35% White/non-Latina, 34% Black/non-Latina, 23% Latina, 7% other) were recruited and interviewed during pregnancy, and child protective services records were reviewed for the presence of the participants’ target infants between birth and age 26 months. Mediating pathways were examined through structural equation modeling and tested using the products of the coefficients approach. The mediated pathway from maternal history of sexual abuse to substance use problems to offspring victimization was significant (standardized mediated path [ab]=.07, 95% CI [.02, .14]; effect size=.26), as was the mediated pathway from maternal history of physical abuse to substance use problems to offspring victimization (standardized mediated path [ab]=.05, 95% CI [.01, .11]; effect size =.19). There was no significant mediated pathway from maternal history of neglect. Findings are discussed in terms of specific implications for child maltreatment prevention, including the importance of assessment and early intervention for maternal history of maltreatment and substance use problems, targeting women with maltreatment histories for substance use services, and integrating child welfare and parenting programs with substance use treatment. PMID:21240556

  8. Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis.

    Science.gov (United States)

    Kung, Annie W C; Chu, Eva Y W; Xu, Ling

    2009-06-01

    Bazedoxifene acetate (WAY-140424; TSE-424) is an oral, nonsteroidal, indole-based selective estrogen receptor modulator (SERM) being developed for the prevention and treatment of osteoporosis. Preclinical studies on bazedoxifene have demonstrated estrogen agonist effects on the skeleton and lipid metabolism but not on breast and uterine endometrium. In combination with estrogen, bazedoxifene antagonizes the stimulatory action of estrogens on proliferation of breast cancer cells and endometrium. Phase III clinical studies have shown favorable effects on the skeleton without stimulation of endometrium and breast. Bazedoxifene prevents bone loss in postmenopausal women without osteoporosis and reduces vertebral fractures in women with postmenopausal osteoporosis. In women at high risk of fracture with multiple risk factors, bazedoxifene reduces nonvertebral fracture risk in post-hoc analysis. Bazedoxifene in combination with conjugated estrogens represents a new form of therapeutic agents for the treatment of postmenopausal symptoms and prevention of postmenopausal osteoporosis. Clinical trials with bazedoxifene/conjugated estrogens have shown beneficial effects on bone mineral density and bone turnover markers with improvement in vasomotor symptoms and little or no stimulation of breast and endometrium.

  9. Vaginal atrophy in breast cancer survivors: role of vaginal estrogen therapy.

    Science.gov (United States)

    Mariani, Luciano; Gadducci, Angiolo; Vizza, Enrico; Tomao, Silverio; Vici, Patrizia

    2013-01-01

    Early menopause and related vaginal atrophy is a well known side-effect of hormone adjuvant treatment in breast cancer patients, particularly during aromatase-inhibitors therapy. Due to estrogens contra-indication, proper therapy for such symptom remains often an inadequately addressed clinical problem. After an accurate assessment of the risk/benefit ratio, vaginal low-dose estrogen treatment (better with estriol) [corrected] may have a role in controlling vaginal atrophy in selected and informed breast cancer women.

  10. New photoacoustic platform for early detection of circulating clots to prevent stroke and other fatal thromboembolic complications (Conference Presentation)

    Science.gov (United States)

    Carey, Kai A.

    2017-03-01

    Nearly 800,000 people in the U.S. experience an incident of stroke each year; 80% of these are first time occurrences and 87% are ischemic in nature. Someone dies of a stroke every few minutes in the U.S. but despite its prevalence there have been minimal advances in the early detection and screening of thromboembolic events, especially during patient post-operative periods or in genetically predisposed individuals. Environmental or genetic factors may disrupt the balance between coagulation and lysis of micro-thrombi in circulation and increase the risk of stroke. We introduced here a novel in vivo multicolor negative-contrast photoacoustic (PA) flow cytometry (PAFC ) platform with many innovations including customized high pulse repetition rate 1064 laser from IPG Photonics Corporation, powerful laser diode array, multichannel optical schematic, and time-resolved recording system. Using animal models, we verified the potential of this technology to detect small clots in relatively large vessels in vivo. If future clinical trials using a cost-effective, easy-to-use, safe, watch-like, wearable PA probe are successful, PAFC could provide breakthroughs in early monitoring of the growth in size and number of small clots that may predict and potentially prevent fatal thromboembolic complications. We also believe that this technology could be utilized to assess therapeutic benefits of anticoagulants and develop more efficient dosage in treatments by analyzing changes in the composition and frequency of micro-thrombi

  11. Prevention of chronic PTSD with early cognitive behavioral therapy. A meta-analysis using mixed-effects modeling.

    Science.gov (United States)

    Kliem, Sören; Kröger, Christoph

    2013-11-01

    Post-traumatic stress disorder (PTSD) is of great interest to public health, due to the high burden it places on both the individual and society. We meta-analyzed randomized-controlled trials to examine the effectiveness of early trauma-focused cognitive-behavioral treatment (TFCBT) for preventing chronic PTSD. Systematic bibliographic research was undertaken to find relevant literature from on-line databases (Pubmed, PsycINFO, Psyndex, Medline). Using a mixed-effect approach, we calculated effect sizes (ES) for the PTSD diagnoses (main outcome) as well as PTSD and depressive symptoms (secondary outcomes), respectively. Calculations of ES from pre-intervention to first follow-up assessment were based on 10 studies. A moderate effect (ES = 0.54) was found for the main outcome, whereas ES for secondary outcomes were predominantly small (ES = 0.27-0.45). The ES for the main outcome decreased to small (ES = 0.34) from first follow-up to long-term follow-up assessment. The mean dropout rate was 16.7% pre- to post-treatment. There was evidence for the impact of moderators on different outcomes (e.g., the number of sessions on PTSD symptoms). Future studies should include survivors of other trauma types (e.g., burn injuries) rather than predominantly survivors of accidents and physical assault, and should compare early TFCBT with other interventions that previously demonstrated effectiveness.

  12. Clinical practice guideline for the prevention, early detection, diagnosis, management and follow up of type 2 diabetes mellitus in adults.

    Science.gov (United States)

    Aschner, Pablo M; Muñoz, Oscar Mauricio; Girón, Diana; García, Olga Milena; Fernández-Ávila, Daniel Gerardo; Casas, Luz Ángela; Bohórquez, Luisa Fernanda; Arango T, Clara María; Carvajal, Liliana; Ramírez, Doris Amanda; Sarmiento, Juan Guillermo; Colon, Cristian Alejandro; Correa G, Néstor Fabián; Alarcón R, Pilar; Bustamante S, Álvaro Andrés

    2016-06-30

    In Colombia, diabetes mellitus is a public health program for those responsible for creating and implementing strategies for prevention, diagnosis, treatment, and follow-up that are applicable at all care levels, with the objective of establishing early and sustained control of diabetes. A clinical practice guide has been developed following the broad outline of the methodological guide from the Ministry of Health and Social Welfare, with the aim of systematically gathering scientific evidence and formulating recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The current document presents in summary form the results of this process, including the recommendations and the considerations taken into account in formulating them. In general terms, what is proposed here is a screening process using the Finnish Diabetes Risk Score questionnaire adapted to the Colombian population, which enables early diagnosis of the illness, and an algorithm for determining initial treatment that can be generalized to most patients with diabetes mellitus type 2 and that is simple to apply in a primary care context. In addition, several recommendations have been made to scale up pharmacological treatment in those patients that do not achieve the objectives or fail to maintain them during initial treatment. These recommendations also take into account the evolution of weight and the individualization of glycemic control goals for special populations. Finally, recommendations have been made for opportune detection of micro- and macrovascular complications of diabetes.

  13. Clinical practice guideline for the prevention, early detection, diagnosis, management and follow up of type 2 diabetes mellitus in adults

    Science.gov (United States)

    Muñoz, Oscar Mauricio; Girón, Diana; García, Olga Milena; Fernández-Ávila, Daniel Gerardo; Casas, Luz Ángela; Bohórquez, Luisa Fernanda; Arango T, Clara María; Carvajal, Liliana; Ramírez, Doris Amanda; Sarmiento, Juan Guillermo; Colon, Cristian Alejandro; Correa G, Néstor Fabián; Alarcón R, Pilar; Bustamante S, Álvaro Andrés

    2016-01-01

    In Colombia, diabetes mellitus is a public health program for those responsible for creating and implementing strategies for prevention, diagnosis, treatment, and follow-up that are applicable at all care levels, with the objective of establishing early and sustained control of diabetes. A clinical practice guide has been developed following the broad outline of the methodological guide from the Ministry of Health and Social Welfare, with the aim of systematically gathering scientific evidence and formulating recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The current document presents in summary form the results of this process, including the recommendations and the considerations taken into account in formulating them. In general terms, what is proposed here is a screening process using the Finnish Diabetes Risk Score questionnaire adapted to the Colombian population, which enables early diagnosis of the illness, and an algorithm for determining initial treatment that can be generalized to most patients with diabetes mellitus type 2 and that is simple to apply in a primary care context. In addition, several recommendations have been made to scale up pharmacological treatment in those patients that do not achieve the objectives or fail to maintain them during initial treatment. These recommendations also take into account the evolution of weight and the individualization of glycemic control goals for special populations. Finally, recommendations have been made for opportune detection of micro- and macrovascular complications of diabetes. PMID:27546934

  14. Identification of key performance indicators for on-farm animal welfare incidents: possible tools for early warning and prevention

    Directory of Open Access Journals (Sweden)

    Kelly Patricia C

    2011-10-01

    Full Text Available Abstract Background The objective of this study was to describe aspects of case study herds investigated by the Department of Agriculture, Fisheries and Food (DAFF in which animal welfare incidents occurred and to identify key performance indicators (KPIs that can be monitored to enhance the Early Warning System (EWS. Despite an EWS being in place for a number of years, animal welfare incidents continue to occur. Questionnaires regarding welfare incidents were sent to Superintending Veterinary Inspectors (SVIs, resulting in 18 herds being chosen as case study herds, 12 of which had a clearly defined welfare incident date. For each study herd, data on six potential KPIs were extracted from DAFF databases. The KPIs for those herds with a clearly defined welfare incident date were studied for a consecutive four year window, with the fourth year being the 'incident year', when the welfare incident was disclosed. For study herds without a clearly defined welfare incident date, the KPIs were determined on a yearly basis between 2001 and 2009. Results We found that the late registration of calves, the use of on-farm burial as a method of carcase disposal, an increasing number of moves to knackeries over time and records of animals moved to 'herd unknown' were notable on the case farms. Conclusion Four KPIs were prominent on the case study farms and warrant further investigation in control herds to determine their potential to provide a framework for refining current systems of early warning and prevention.

  15. Early environmental enrichment affects neurobehavioral development and prevents brain damage in rats submitted to neonatal hypoxia-ischemia.

    Science.gov (United States)

    Schuch, Clarissa Pedrini; Diaz, Ramiro; Deckmann, Iohanna; Rojas, Joseane Jiménez; Deniz, Bruna Ferrary; Pereira, Lenir Orlandi

    2016-03-23

    Our previous results demonstrated improved cognition in adolescent rats housed in environmental enrichment (EE) that underwent neonatal hypoxia-ischemia (HI). The aim of this study was to investigate the effects of early EE on neurobehavioral development and brain damage in rats submitted to neonatal HI. Wistar rats were submitted to the HI procedure on the 7th postnatal day (PND) and housed in an enriched environment (8th-20th PND). The maturation of physical characteristics and the neurological reflexes were evaluated and the volume of striatum, corpus callosum and neocortex was measured. Data analysis demonstrated a clear effect of EE on neurobehavioral development; also, daily performance was improved in enriched rats on righting, negative geotaxis and cliff aversion reflex. HI caused a transient motor deficit on gait latency. Brain atrophy was found in HI animals and this damage was partially prevented by the EE. In conclusion, early EE stimulated neurobehavioral development in neonate rats and also protects the neocortex and the corpus callosum from atrophy following HI. These findings reinforce the potential of EE as a strategy for rehabilitation following neonatal HI and provide scientific support to the use of this therapeutic strategy in the treatment of neonatal brain injuries in humans.

  16. Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure.

    Science.gov (United States)

    Jorgensen, Elisa M; Alderman, Myles H; Taylor, Hugh S

    2016-09-01

    Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure to BPA in utero has been linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-α (ERα)-binding genes. The majority of genes that demonstrated both altered expression and ERα binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERα. Gene-environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen-related disease in adults.-Jorgensen, E. M., Alderman, M. H., III, Taylor, H. S. Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure.

  17. Selectively targeting estrogen receptors for cancer treatment

    NARCIS (Netherlands)

    Shanle, Erin K.; Xu, Wei

    2010-01-01

    Estrogens regulate growth and development through the action of two distinct estrogen receptors (ERs), ER alpha and ER beta, which mediate proliferation and differentiation of cells. For decades, ER alpha mediated estrogen signaling has been therapeutically targeted to treat breast cancer, most nota

  18. Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture.

    OpenAIRE

    Zava, D T; Blen, M; Duwe, G

    1997-01-01

    We investigated the estrogenic activity of various environmental pollutants (xenobiotics), in particular the xenoestrogen o,p-DDT, and compared their effects with those of endogenous estrogens, phytoestrogens, and mycoestrogens on estrogen receptor binding capacity, induction of estrogen end products, and activation of cell proliferation in estrogen-sensitive human breast cancer cells in monolayer culture. We also quantified the levels of phytoestrogens in extracts of some common foods, herbs...

  19. In Vivo Imaging of Activated Estrogen Receptors in Utero by Estrogens and Bisphenol A

    OpenAIRE

    Lemmen, Josephine G.; Arends, Roel J.; van der Saag, Paul T.; van der Burg, Bart

    2004-01-01

    Environmental estrogens are of particular concern when exposure occurs during embryonic development. Although there are good models to study estrogenic activity of chemicals in adult animals, developmental exposure is much more difficult to test. The weak estrogenic activity of the environmental estrogen bisphenol A (BPA) in embryos is controversial. We have recently generated transgenic mice that carry a reporter construct with estrogen-responsive elements coupled to luciferase. We show that...

  20. The Infant Feeding Activity and Nutrition Trial (INFANT an early intervention to prevent childhood obesity: Cluster-randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Campbell Karen

    2008-03-01

    Full Text Available Abstract Background Multiple factors combine to support a compelling case for interventions that target the development of obesity-promoting behaviours (poor diet, low physical activity and high sedentary behaviour from their inception. These factors include the rapidly increasing prevalence of fatness throughout childhood, the instigation of obesity-promoting behaviours in infancy, and the tracking of these behaviours from childhood through to adolescence and adulthood. The Infant Feeding Activity and Nutrition Trial (INFANT aims to determine the effectiveness of an early childhood obesity prevention intervention delivered to first-time parents. The intervention, conducted with parents over the infant's first 18 months of life, will use existing social networks (first-time parent's groups and an anticipatory guidance framework focusing on parenting skills which support the development of positive diet and physical activity behaviours, and reduced sedentary behaviours in infancy. Methods/Design This cluster-randomised controlled trial, with first-time parent groups as the unit of randomisation, will be conducted with a sample of 600 first-time parents and their newborn children who attend the first-time parents' group at Maternal and Child Health Centres. Using a two-stage sampling process, local government areas in Victoria, Australia will be randomly selected at the first stage. At the second stage, a proportional sample of first-time parent groups within selected local government areas will be randomly selected and invited to participate. Informed consent will be obtained and groups will then be randomly allocated to the intervention or control group. Discussion The early years hold promise as a time in which obesity prevention may be most effective. To our knowledge this will be the first randomised trial internationally to demonstrate whether an early health promotion program delivered to first-time parents in their existing social groups

  1. Bazedoxifene: a novel selective estrogen receptor modulator for postmenopausal osteoporosis.

    Science.gov (United States)

    de Villiers, T J

    2010-06-01

    Several new selective estrogen receptor modulators (SERMs) are currently under clinical development for the prevention and/or treatment of postmenopausal osteoporosis, with the goal of optimizing the estrogen receptor agonist/antagonist activity in target tissues. Bazedoxifene is a novel SERM under clinical investigation for the prevention and treatment of postmenopausal osteoporosis. Emerging clinical data have shown that bazedoxifene is effective in preventing bone loss and osteoporotic fractures in postmenopausal women, with no evidence of breast or endometrial stimulation. Two large, prospective, international phase 3 studies have been completed. In postmenopausal women at risk for osteoporosis, bazedoxifene has been shown to preserve bone mineral density and to reduce bone turnover. In postmenopausal women with osteoporosis, bazedoxifene has demonstrated significant protection against new vertebral fractures and against non-vertebral fractures in women at higher fracture risk. The treatment effects of bazedoxifene were supported by findings from independent re-analyses using the Fracture Risk Assessment Tool (FRAX), which showed that bazedoxifene significantly reduced the risk of all clinical and morphometric vertebral fracture and of non-vertebral fracture in women at or above a FRAX-based threshold. Bazedoxifene was generally safe and well tolerated in the phase 3 studies and showed neutral effects on the breast and an excellent endometrial safety profile; such attributes allow for the partnering of bazedoxifene with conjugated estrogens for menopausal symptom relief. Collectively, these results suggest that bazedoxifene may be a promising new therapy for the prevention and treatment of postmenopausal osteoporosis as a monotherapy or in combination with conjugated estrogens in menopausal hormone therapy.

  2. Group B streptococcal immunisation of pregnant women for the prevention of early and late onset Group B streptococcal infection of the neonate as well as adult disease

    DEFF Research Database (Denmark)

    Kenchington, Anna L.; Lamont, Ronald F.

    2017-01-01

    or in the future, vaccination. Areas covered: The introduction of a vaccine to women in the third trimester is likely to further reduce the burden of disease and provide benefits beyond the prevention of early neonatal disease, including meningitis and disability following late onset disease. Development......Introduction: Early onset neonatal Group B streptococcal disease is preventable. Intrapartum antibiotic prophylaxis has resulted in a significant reduction in neonatal mortality and morbidity. National guidelines for the selection of women eligible for intrapartum antibiotic prophylaxis, whether...

  3. An estrogen receptor model to describe the regulation of prolactin synthesis by antiestrogens in vitro.

    Science.gov (United States)

    Lieberman, M E; Gorski, J; Jordan, V C

    1983-04-25

    A hypothetical model of the ligand interaction with the estrogen receptor binding site has been developed to describe the structural features necessary to initiate or to inhibit prolactin synthesis in vitro. The biological potency of the binding ligands is directly related to their relative binding affinity (RBA) for the estrogen receptor. The relative potencies of antiestrogens to inhibit estradiol-stimulated prolactin synthesis was trans-monohydroxytamoxifen identical to cis-monohydroxytamoxifen identical to tamoxifen, consistent with their RBAs for uterine estrogen receptor. Similarly the relative potency of estrogens to stimulate prolactin synthesis was diethylstilbestrol identical to estradiol greater than ICI 77,949 greater than ICI 47,699 identical to zuclomiphene, consistent with their RBAs. The compound LY126412 (trioxifene without the aminoethoxy side chain) did not interact with the estrogen receptor at the concentrations tested (10(-8)--10(-6) M) or exhibit estrogenic or antiestrogenic properties using the prolactin synthesis assay. Overall, the ligand-receptor model stresses the structural requirement for high affinity binding and the critical positioning of the alkylamino-ethoxy side chain in space (in relation to the ligand-binding site on the estrogen receptor) to prevent prolactin synthesis.

  4. Estrogen Receptor (ER-α36 Is Involved in Estrogen- and Tamoxifen-Induced Neuroprotective Effects in Ischemic Stroke Models.

    Directory of Open Access Journals (Sweden)

    Wei Zou

    Full Text Available The neuroprotection by estrogen (E2 and tamoxifen is well documented in experimental stroke models; however, the exact mechanism is unclear. A membrane-based estrogen receptor, ER-α36, has been identified. Postmenopausal-levels of E2 act through ER-α36 to induce osteoclast apoptosis due to a prolonged activation of the mitogen-activated protein kinase (MAPK/extracellular signal-related kinase (ERK signaling. We hypothesized that ER-α36 may play a role in the neuroprotective activities of estrogen and tamoxifen. Here, we studied ER-α36 expression in the brain, as well as its neuroprotective effects against oxygen and glucose deprivation (OGD in PC12 cells. We found that ER-α36 was expressed in both rat and human brain. In addition, OGD-induced cell death was prevented by l nmol/L 17β-estradiol (E2β. E2β activates the MAPK/ERK signaling pathway in PC12 cells under basal and OGD conditions by interacting with ER-α36 and also induces ER-α36 expression. Low-dose of tamoxifen up-regulated ER-α36 expression and enhanced neuronal survival in an ovariectomized ischemic stroke model. Furthermore, low-dose of tamoxifen enhanced neuroprotective effects by modulating activates or suppress ER-α36. Our results thus demonstrated that ER-α36 is involved in neuroprotective activities mediated by both estrogen and tamoxifen.

  5. The prevention of early-onset neonatal group B streptococcal disease.

    Science.gov (United States)

    Money, Deborah; Allen, Victoria M

    2013-10-01

    Objectif : Analyser les données issues de la littérature et formuler des recommandations sur la prise en charge des parturientes en vue de prévenir l’infection néonatale à streptocoques du groupe B d’apparition précoce. Parmi les révisions clés que renferme la présente directive clinique mise à jour, on trouve des modifications quant aux recommandations en ce qui concerne les schémas posologiques d’antibioprophylaxie, les épreuves de sensibilité et la prise en charge des femmes présentant une rupture prématurée des membranes. Issues : Parmi les issues maternelles évaluées, on trouvait l’exposition aux antibiotiques au cours de la grossesse et du travail, ainsi que les complications associées à l’administration d’antibiotiques. Les issues néonatales associées aux taux d’infection néonatale à streptocoques du groupe B d’apparition précoce ont été évaluées. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans PubMed, CINAHL et The Cochrane Library entre janvier 1980 et juillet 2012, au moyen d’un vocabulaire contrôlé et de mots clés appropriés (« Group B streptococcus », « antibiotic therapy », « infection », « prevention »). Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles. Aucune restriction n’a été appliquée en matière de date ou de langue. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu’en mai 2013. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d’organismes s’intéressant à l’évaluation des technologies dans le domaine de la santé et d’organismes connexes, dans des collections de directives cliniques, dans des registres d’essais cliniques et auprès de sociétés de sp

  6. Selective Estrogen Receptor Modulators and Prevention of Invasive Breast Cancer%选择性雌激素受体调节剂以及浸润性乳腺癌的预防

    Institute of Scientific and Technical Information of China (English)

    William J. Gradishar; David Cella; 武峰

    2007-01-01

    本年度美国有20万以上的妇女被诊断患有浸润性乳腺癌。过去20年的研究已将对基础生物学的了解转化为治疗实践,导致乳腺癌患者生存率和生活质量的很大改善。对预防乳腺癌的其他策略也进行了研究。这些策略包括改变生活方式(如饮食、酒精摄入、理想体重、外源性雌激素治疗)、手术切除(预防性乳房切除术、卵巢切除术或二者同时进行)以及最近采用的选择性雌激素受体调节剂(selective estrogen receptor modulators,SERMs)如他莫西芬进行化学预防。

  7. Estrogen mediation of hormone responses to exercise.

    Science.gov (United States)

    Kraemer, Robert R; Francois, Michelle; Castracane, V Daniel

    2012-10-01

    The roles of estrogens extend from the regulation of reproduction to other functions involved in control of metabolism, fluid balance, as well as gastrointestinal, lung, and brain function, with a strong effect on other hormones that subsequently alter the physiology of multiple tissues. As such, alteration of endogenous estrogens across the menstrual cycle, or from oral contraception and estrogen replacement therapy, can affect these tissues. Due to the important effects that estrogens have on different tissues, there are many investigations concerning the effects of a human estrogenic environment on endocrine responses to exercise. The following review will describe the consequences of varying estrogen levels on pituitary, adrenal, gonadal, and endocrine function, followed by discussion of the outcomes of different estrogen levels on endocrine tissues in response to exercise, problems encountered for interpretation of findings, and recommended direction for future research. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Unbalanced estrogen metabolism in thyroid cancer.

    Science.gov (United States)

    Zahid, Muhammad; Goldner, Whitney; Beseler, Cheryl L; Rogan, Eleanor G; Cavalieri, Ercole L

    2013-12-01

    Well-differentiated thyroid cancer most frequently occurs in premenopausal women. Greater exposure to estrogens may be a risk factor for thyroid cancer. To investigate the role of estrogens in thyroid cancer, a spot urine sample was obtained from 40 women with thyroid cancer and 40 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates significantly differed between cases and controls (p estrogen metabolism is unbalanced in thyroid cancer and suggest that formation of estrogen-DNA adducts might play a role in the initiation of thyroid cancer. Copyright © 2013 UICC.

  9. Incorporating bazedoxifene/conjugated estrogens into the current paradigm of menopausal therapy

    Directory of Open Access Journals (Sweden)

    Komm BS

    2012-03-01

    Full Text Available Barry S Komm, Sebastian MirkinPfizer Inc, Collegeville, PA, USAAbstract: Many women experience bothersome vasomotor and vaginal symptoms during the menopausal transition. Decreasing levels of estrogens during menopause are also associated with reduced bone density and an increased risk of osteoporosis. Combined estrogen/progestin therapy (hormone therapy effectively treats menopausal symptoms and prevents bone loss, but has been associated with some safety and tolerability concerns. A novel menopausal therapy is the tissue selective estrogen complex, which pairs a selective estrogen receptor modulator with one or more estrogens. In preclinical studies, the tissue selective estrogen complex partnering bazedoxifene (BZA with conjugated estrogens (CE antagonized stimulation of breast and endometrial tissue, reduced vasomotor instability, and preserved bone mass in rat and mouse models. The specific attributes seen with BZA/CE were different from those observed with other selective estrogen receptor modulator/estrogen pairings. BZA/CE has undergone clinical evaluation in the Phase III Selective estrogens, Menopause, And Response to Therapy (SMART trials in postmenopausal women with an intact uterus. Of the various doses of BZA/CE evaluated, BZA 20 mg/CE 0.45 mg and 0.625 mg were associated with a low incidence of endometrial hyperplasia (<1% similar to placebo, and showed significant improvements in hot flushes and vulvar/vaginal symptoms and increases in bone mineral density. BZA 20 mg/CE 0.45 mg and 0.625 mg were associated with a low incidence of breast-related adverse events and demonstrated no difference from placebo in age-related changes in mammographic breast density. Both BZA/CE doses showed a favorable tolerability profile, with no increases in uterine bleeding or breast tenderness, and had positive effects on metabolic parameters and quality of life. BZA/CE may be a promising alternative to hormone therapy for the treatment of menopausal

  10. Early treatment with fumagillin, an inhibitor of methionine aminopeptidase-2, prevents Pulmonary Hypertension in monocrotaline-injured rats.

    Directory of Open Access Journals (Sweden)

    Daniel J Kass

    Full Text Available Pulmonary Hypertension (PH is a pathophysiologic condition characterized by hypoxemia and right ventricular strain. Proliferation of fibroblasts, smooth muscle cells, and endothelial cells is central to the pathology of PH in animal models and in humans. Methionine aminopeptidase-2 (MetAP2 regulates proliferation in a variety of cell types including endothelial cells, smooth muscle cells, and fibroblasts. MetAP2 is inhibited irreversibly by the angiogenesis inhibitor fumagillin. We have previously found that inhibition of MetAP2 with fumagillin in bleomycin-injured mice decreased pulmonary fibrosis by selectively decreasing the proliferation of lung myofibroblasts. In this study, we investigated the role of fumagillin as a potential therapy in experimental PH. In vivo, treatment of rats with fumagillin early after monocrotaline injury prevented PH and right ventricular remodeling by decreasing the thickness of the medial layer of the pulmonary arteries. Treatment with fumagillin beginning two weeks after monocrotaline injury did not prevent PH but was associated with decreased right ventricular mass and decreased cardiomyocyte hypertrophy, suggesting a direct effect of fumagillin on right ventricular remodeling. Incubation of rat pulmonary artery smooth muscle cells (RPASMC with fumagillin and MetAP2-targeting siRNA inhibited proliferation of RPASMC in vitro. Platelet-derived growth factor, a growth factor that is important in the pathogenesis of PH and stimulates proliferation of fibroblasts and smooth muscle cells, strongly increased expression of MetP2. By immunohistochemistry, we found that MetAP2 was expressed in the lesions of human pulmonary arterial hypertension. We propose that fumagillin may be an effective adjunctive therapy for treating PH in patients.

  11. Invasive species information networks: Collaboration at multiple scales for prevention, early detection, and rapid response to invasive alien species

    Science.gov (United States)

    Simpson, Annie; Jarnevich, Catherine S.; Madsen, John; Westbrooks, Randy G.; Fournier, Christine; Mehrhoff, Les; Browne, Michael; Graham, Jim; Sellers, Elizabeth A.

    2009-01-01

    Accurate analysis of present distributions and effective modeling of future distributions of invasive alien species (IAS) are both highly dependent on the availability and accessibility of occurrence data and natural history information about the species. Invasive alien species monitoring and detection networks (such as the Invasive Plant Atlas of New England and the Invasive Plant Atlas of the MidSouth) generate occurrence data at local and regional levels within the United States, which are shared through the US National Institute of Invasive Species Science. The Inter-American Biodiversity Information Network's Invasives Information Network (I3N), facilitates cooperation on sharing invasive species occurrence data throughout the Western Hemisphere. The I3N and other national and regional networks expose their data globally via the Global Invasive Species Information Network (GISIN). International and interdisciplinary cooperation on data sharing strengthens cooperation on strategies and responses to invasions. However, limitations to effective collaboration among invasive species networks leading to successful early detection and rapid response to invasive species include: lack of interoperability; data accessibility; funding; and technical expertise. This paper proposes various solutions to these obstacles at different geographic levels and briefly describes success stories from the invasive species information networks mentioned above. Using biological informatics to facilitate global information sharing is especially critical in invasive species science, as research has shown that one of the best indicators of the invasiveness of a species is whether it has been invasive elsewhere. Data must also be shared across disciplines because natural history information (e.g. diet, predators, habitat requirements, etc.) about a species in its native range is vital for effective prevention, detection, and rapid response to an invasion. Finally, it has been our

  12. A familial risk enriched cohort as a platform for testing early interventions to prevent severe mental illness.

    Science.gov (United States)

    Uher, Rudolf; Cumby, Jill; MacKenzie, Lynn E; Morash-Conway, Jessica; Glover, Jacqueline M; Aylott, Alice; Propper, Lukas; Abidi, Sabina; Bagnell, Alexa; Pavlova, Barbara; Hajek, Tomas; Lovas, David; Pajer, Kathleen; Gardner, William; Levy, Adrian; Alda, Martin

    2014-12-02

    Severe mental illness (SMI), including schizophrenia, bipolar disorder and severe depression, is responsible for a substantial proportion of disability in the population. This article describes the aims and design of a research study that takes a novel approach to targeted prevention of SMI. It is based on the rationale that early developmental antecedents to SMI are likely to be more malleable than fully developed mood or psychotic disorders and that low-risk interventions targeting anteced