Sexual function in prostatic cancer patients treated with radiotherapy, orchiectomy or oestrogens

International Nuclear Information System (INIS)

Bergman, B.; Damber, J.-E.; Littbrand, B.; Sjoegren, K.; Tomic, R.

1984-01-01

Sexual function in prostatic carcinoma patients was studied in 12 patients from each of three treatment groups: radiotherapy, orchiectomy and oestrogen treatment. Significant deterioration occurred in all groups. Although erectile potency was preserved in 9 of 12 patients treated with radiotherapy, 7 of these had a marked reduction in the frequency of sexual activity. Men subjected to orchiectomy or oestrogen treatment were seldom capable of having intercourse or of experiencing orgasm. However, oestrogen-treated men continued sexual activity with their partner more often than orchiectomised subjects. Patients receiving oestrogen treatment scored significantly higher for mental depression than those in the other two treatment groups. (author)

Sexual function in prostatic cancer patients treated with radiotherapy, orchiectomy or oestrogens

Energy Technology Data Exchange (ETDEWEB)

Bergman, B.; Damber, J.E.; Littbrand, B.; Sjoegren, K.; Tomic, R. (Umeaa Univ. (Sweden))

1984-02-01

Sexual function in prostatic carcinoma patients was studied in 12 patients from each of three treatment groups: radiotherapy, orchiectomy and oestrogen treatment. Significant deterioration occurred in all groups. Although erectile potency was preserved in 9 of 12 patients treated with radiotherapy, 7 of these had a marked reduction in the frequency of sexual activity. Men subjected to orchiectomy or oestrogen treatment were seldom capable of having intercourse or of experiencing orgasm. However, oestrogen-treated men continued sexual activity with their partner more often than orchiectomised subjects. Patients receiving oestrogen treatment scored significantly higher for mental depression than those in the other two treatment groups.

Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway

International Nuclear Information System (INIS)

Dorssers, Lambert CJ; Agthoven, Ton van; Brinkman, Arend; Veldscholte, Jos; Smid, Marcel; Dechering, Koen J

2005-01-01

Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, but their direct effect on breast cancer cell proliferation is not known. The aim of this study was to investigate the growth control mediated by these BCAR genes by gene expression profiling. We have measured the expression changes induced by overexpression of the BCAR1 or BCAR3 gene in ZR-75-1 cells and have made direct comparisons with the expression changes after cell stimulation with oestrogen or epidermal growth factor (EGF). A comparison with published gene expression data of cell models and breast tumours is made. Relatively few changes in gene expression were detected in the BCAR-transfected cells, in comparison with the extensive and distinct differences in gene expression induced by oestrogen or EGF. Both BCAR1 and BCAR3 regulate discrete sets of genes in these ZR-75-1-derived cells, indicating that the proliferation signalling proceeds along distinct pathways. Oestrogen-regulated genes in our cell model showed general concordance with reported data of cell models and gene expression association with oestrogen receptor status of breast tumours. The direct comparison of the expression profiles of BCAR transfectants and oestrogen or EGF-stimulated cells strongly suggests that anti-oestrogen-resistant cell proliferation is not caused by alternative activation of the oestrogen receptor or by the epidermal growth factor receptor signalling pathway

Oestrogen receptor alpha in pulmonary hypertension.

Science.gov (United States)

Wright, Audrey F; Ewart, Marie-Ann; Mair, Kirsty; Nilsen, Margaret; Dempsie, Yvonne; Loughlin, Lynn; Maclean, Margaret R

2015-05-01

Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2(+/-) mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression. By immunohistochemistry, we showed that ERα, ERβ, and G-protein-coupled receptors are expressed in human pulmonary arteries localizing mainly to the smooth muscle layer which also expresses the serotonin transporter (SERT). Protein expression of ERα protein was higher in female PAH patient hPASMCs compared with male and serotonin also increased the expression of ERα. 17β-estradiol induced proliferation of hPASMCs via ERα activation and this engaged mitogen-activated protein kinase and Akt signalling. Female mice over-expressing SERT (SERT(+) mice) develop PH and the ERα antagonist MPP attenuated the development of PH in normoxic and hypoxic female SERT(+) mice. The therapeutic effects of MPP were accompanied by increased expression of BMPR2 in mouse lung. ERα is highly expressed in female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can increase ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent PH in the mouse and increases BMPR2 expression. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Immunolocalisation of oestrogen receptor beta in human tissues.

Science.gov (United States)

Taylor, A H; Al-Azzawi, F

2000-02-01

Oestrogens exert their actions via specific nuclear protein receptors that are members of the steroid/thyroid receptor superfamily of transcription factors. Recently, a second oestrogen receptor (ERbeta) has been cloned, and using reverse transcription-PCR and immunohistochemistry it has been shown to have a wide tissue distribution in the rat that is distinct from the classical oestrogen receptor, ERalpha. Using commercial polyclonal antisera against peptides specific to human ERbeta, we have determined the sites of ERbeta expression in archival and formalin-fixed human tissue and compared its expression with that of ERalpha. ERbeta was localised to the cell nuclei of a wide range of normal adult human tissues including ovary, Fallopian tube, uterus, lung, kidney, brain, heart, prostate and testis. In the ovary, ERbeta was present in multiple cell types including granulosa cells in small, medium and large follicles, theca and corpora lutea, whereas ERalpha was weakly expressed in the nuclei of granulosa cells, but not in the theca nor in the copora lutea. In the endometrium, both ERalpha and ERbeta were observed in luminal epithelial cells and in the nuclei of stromal cells but, significantly, ERbeta was weak or absent from endometrial glandular epithelia. Epithelial cells in most male tissues including the prostate, the urothelium and muscle layers of the bladder, and Sertoli cells in the testis, were also immunopositive for ERbeta. Significant ERbeta immunoreactivity was detected in most areas of the brain, with the exception of the hippocampus - a tissue that stained positively for ERalpha. In conclusion, the almost ubiquitous immunohistochemical localisation of ERbeta indicates that ERbeta may play a major role in the mediation of oestrogen action. The differential expression of ERalpha and ERbeta in some of these tissues suggests a more complex control mechanism in oestrogenic potential than originally envisioned.

A radioimmunoassay for equilin in post-menopausal plasma: plasma levels of equilin determined after oral administration of conjugated equine oestrogens (Premarin)

International Nuclear Information System (INIS)

Morgan, M.R.A.; Whittaker, P.G.; Fuller, B.P.; Dean, P.D.G.

1980-01-01

Preparations containing equilin are widely used in hormone therapy at the menopause. No suitable routine assay exists for this steroid. Antisera have been raised to equilin-3-hemisuccinyl-bovine serum albumin, and have been found to be highly specific for equilin. A direct sensitive assay for this steroid in post-menopausal plasma has been established. The implications of the cross-reaction data for the synthesis of oestrogen immunogens are discussed. Equilin has been assayed in samples obtained from oophorectomised women receiving conjugated equine oestrogens (Premarin). (author)

Deep vein thrombosis and the oestrogen content in oral contraceptives. An epidemiological analysis.

Science.gov (United States)

Kierkegaard, A

1985-01-01

Epidemiological studies have pointed to a correlation between the oestrogen content of oral contraceptives and the risk of deep vein thrombosis (DVT). The correlation has been strongest in studies which partially consisted of adverse drug reaction reports to the Swedish Adverse Drug Reaction Advisory Committee (SADRAC). The present study analyzes the epidemiological basis of the adverse drug reaction reports on DVT in women on oral contraceptives to SADRAC. It verifies the reported correlation between the oestrogen content of the pills and the risk of DVT but it also demonstrates that this correlation probably was secondary to differences in the diagnostic standard of DVT, to differences in reporting policies to SADRAC and to an age difference between women on low-oestrogen-pills and those on high-oestrogen pills and is thus due to bias. It is concluded that adverse drug reaction reporting on oral contraceptives has been very unreliable, for which reason it cannot support any epidemiological conclusion concerning the relative thrombogenicity of high-oestrogen pills compared with that of low-oestrogen pills.

Orchidectomy and oestrogen therapy revisited

DEFF Research Database (Denmark)

Iversen, P

1998-01-01

with gynaecomastia, loss of sexual function and unacceptable cardiovascular toxicity. Low dose oestrogens in combination with antiandrogens or antithrombotic agents may be better tolerated treatments. The route of administration is a crucial factor in the genesis of cardiovascular toxicity and parenterally...

Xeno-oestrogenic activity in serum as marker of occupational pesticide exposure

DEFF Research Database (Denmark)

Andersen, Helle Raun; Nielsen, Flemming; Nielsen, Jesper Bo

2007-01-01

-oestrogenic activity in serum was statistically significant for women who had been at work within the last week, while no association was observed for women who had not been at work during the most recent week. Conclusions: The study illustrates the usefulness of this biomarker for qualitative assessment...... with oestrogen-like properties in an occupational setting. Methods: Serum samples were obtained from two separate cohorts representing non-pregnant and pregnant female greenhouse workers in Denmark. Serum samples from 270 non-pregnant women and 173 pregnant women were analysed for xeno-oestrogenic activity......, medium or high based on information collected by detailed interviews of the women and the employers. Results: In both cohorts, an exposure-associated increase in the xeno-oestrogenic activity in serum was demonstrated. Among the pregnant women, the association between pesticide exposure and xeno...

Study of the effects of radiation on prevention of gynaecomastia due to oestrogen therapy

Energy Technology Data Exchange (ETDEWEB)

Waterfall, N B; Glaser, M G [Charing Cross Group of Hospitals, London (UK)

1979-09-01

A study of the effects of irradiation in prevention of gynaecomastia due to oestrogen therapy for carcinoma is reported. Twenty patients were treated with oestrogens without radiotherapy, of these 17 developed gynaecomastia. Twenty-seven patients were treated with radiotherapy prior to oestrogens, of these only 3 developed gynaecomastia. Previous studies have shown similar results but have used larger doses of irradiation and recommended a delay of 1 month between radiotherapy and treatment. In this study a low dose of radiation was used and oestrogens were started immediately after radiotherapy.

Partial characterization of a novel oestrogen-induced protein in the rat adenohypophysis.

Science.gov (United States)

Casabiell, X; Zugaza, J L; Pombo, C M; Bokser, L; Mulet, N; Casanueva, F F

1993-06-01

In order to detect putative markers of prolactin-secreting pituitary tumours, adult rats were subjected to long-term oestrogenization with oestradiol benzoate (OE2) on a monthly basis. At 6 months, anterior pituitaries were dissected and incubated either as tissue fragments or as dispersed cells with a [35S]methionine mix for labelling. Proteins released into the incubation medium and from tissue extracts were further analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and fluorography. Oestrogen induced the appearance in the incubation medium of a protein (OE2 band) with an M(r) of 38,000 under reducing conditions, and high specific activity. Surprisingly, such a protein was not detected in tissue extracts. The OE2 band was detectable by 7 days after the first dose of oestrogen, and remained throughout 1 year of treatment. The tumour cell line GH3 showed a similar OE2 band which was further enhanced by oestrogens. The protein was observed similarly in both female and male pituitary donors, either intact or gonadectomized, and also in rats of different strains, suggesting that its appearance was independent of the strain of rat and gonadal status. Furthermore, the OE2 band was specific for pituitary cells and not produced by other oestrogenized tissues. No alteration in the rate of generation or the electrophoretic pattern of the OE2 band was observed when pituitary cells from oestrogenized rats were metabolically labelled while being incubated with tunicamycin. Furthermore, a system for glycan detection, adsorption to Concanavalin A or incubation with endoglycosidase F also failed to show a clear amount of glycosylation of the oestrogen-induced protein. Both immunoprecipitation experiments and time-limited proteolysis with V8 protease ruled out the possibility that the OE2 band could be structurally related to either GH or prolactin. In conclusion, oestrogens induce the generation of a new monocatenary protein with an apparent M(r) of 38

Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.

LENUS (Irish Health Repository)

Hogan, A M

2012-02-01

BACKGROUND: Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women. METHODS: Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically. RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.

The relationship between oestrogen and muscle strength: a current perspective

Directory of Open Access Journals (Sweden)

Kirsty Jayne Elliott-Sale

2014-04-01

Full Text Available The relationship between muscle strength and oestrogen is ambiguous and is still largely unresolved. The evidence for and against an effect of oestradiol on determinants of muscle function is equivocal and often contradictory. The bulk of the research in this area was performed during the eighties and nineties, using models of reproductive functioning such as; the menstrual cycle, the menopause and hormone replacement therapy, oral contraceptives and in vitro fertilisation treatment, to alter the female hormonal milieu. In the last decade, approximately 15 papers have demonstrated a relationship, both positive and negative, between the concentration of oestrogen and skeletal muscle strength. Conversely, around 20 articles have not shown any influence of oestrogen on a number of strength measures. The majority of these studies were performed using post-menopausal and eumenorrheic females. Most current studies use hormonal assays to confirm oestrogen status, however no recent studies have reported the bioavailable concentration of oestradiol. Similarly, no research in the last 10 years has used in vitro fertilisation treatment or pregnancy as acute and chronic models of supra-physiological changes in sex hormone concentration. Future work should focus on performing meta-analyses on each of the key components of muscle strength in an attempt to elucidate a causal relationship. In addition, models of reproductive functioning that cause the greatest magnitude of change to oestrogen concentration should be used, while controlling as many confounding factors as possible.

Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer

DEFF Research Database (Denmark)

Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei

2017-01-01

BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas...... was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p expression in polyps (p ..., no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages...

Phyto-oestrogens and their metabolites in milk produced on two pastures with different botanical compositions

DEFF Research Database (Denmark)

Adler, S. A.; Purup, S.; Hansen-Møller, J.

2014-01-01

. The objective of this study was to assess the effects of grazing a recently established pasture containing red clover (Trifolium pratense L.) and an older pasture containing a variety of sown and unsown plant species on milk concentrations of phyto-oestrogens. Sixteen Norwegian Red dairy cows [mean (standard......Phyto-oestrogens are a group of secondary plant metabolites that may bind to oestrogen receptors and exert oestrogenic or anti-oestrogenic effects in humans and can protect against cancer diseases. When ingested by dairy cows, phyto-oestrogens can be metabolised and transferred to the milk...... deviation); body weight 599 (45.1). kg, stage of lactation 73 (15.0) d in milk, milk yield 29.9 (2.90) kg/d at the start of the experiment] were divided into two groups and grazed either a short-term pasture (SP) or a long-term pasture (LP). The SP was representative of organically managed leys in Norway...

Blockade of oestrogen biosynthesis in peripubertal boys: effects on lipid metabolism, insulin sensitivity, and body composition.

Science.gov (United States)

Hero, Matti; Ankarberg-Lindgren, Carina; Taskinen, Marja-Riitta; Dunkel, Leo

2006-09-01

In males, the pubertal increase in sex hormone production has been associated with proatherogenic changes in lipid and carbohydrate metabolism. Aromatase inhibitors, a novel treatment modality for some growth disorders, may significantly influence these risk factors for cardiovascular disease by suppressing oestrogen biosynthesis and stimulating gonadal androgen production. In the current study, we explored the effects of aromatase inhibition on lipid metabolism, insulin sensitivity, body composition and serum adiponectin in peripubertal boys. Prospective, double-blind, randomised, placebo-controlled clinical study. Thirty-one boys, aged 9.0-14.5 years, with idiopathic short stature were treated with the aromatase inhibitor letrozole (2.5 mg/day) or placebo for 2 years. During the treatment, the concentrations of sex hormones, IGF-I, lipids, lipoproteins and adiponectin were followed-up. The percentage of fat mass (FM) was assessed by skinfold measurements and insulin resistance by homeostasis model assessment (HOMA) index. In pubertal boys, who received letrozole, high-density lipoprotein cholesterol (HDL-C) decreased by 0.47 mmol/l (P<0.01) during the study. Simultaneously, their percentage of FM decreased from 17.0 to 10.5 (P<0.001), in an inverse relationship with serum testosterone. The concentrations of low-density lipoprotein cholesterol, triglycerides and HOMA index remained at pretreatment level in both groups. Serum adiponectin decreased similarly in letrozole- and placebo-treated pubertal boys (2.9 and 3.3 mg/l respectively). In males, aromatase inhibition reduces HDL-C and decreases relative FM after the start of puberty. The treatment does not adversely affect insulin sensitivity in lean subjects.

Oestrogen, an evolutionary conserved regulator of T cell differentiation and immune tolerance in jawed vertebrates?

Science.gov (United States)

Paiola, Matthieu; Knigge, Thomas; Duflot, Aurélie; Pinto, Patricia I S; Farcy, Emilie; Monsinjon, Tiphaine

2018-07-01

In teleosts, as in mammals, the immune system is tightly regulated by sexual steroid hormones, such as oestrogens. We investigated the effects of 17β-oestradiol on the expression of several genes related to T cell development and resulting T cell subpopulations in sea bass, Dicentrarchus labrax, for a primary lymphoid organ, the thymus, and two secondary lymphoid organs, the head-kidney and the spleen. In parallel, the oxidative burst capacity was assessed in leucocytes of the secondary lymphoid organs. Apoptosis- and proliferation-related genes, indicative of B and T cell clonal selection and lymphoid progenitor activity, were not affected by elevated oestrogen-levels. Sex-related oestrogen-responsiveness in T cell and antigen-presenting cell markers was observed, the expression of which was differentially induced by oestrogen-exposure in the three lymphoid organs. Remarkably, in the spleen, oestrogen increased regulatory T cell-related gene expression was associated with a decrease in oxidative burst capacity. To the best of our knowledge, this study indicates for the first time that physiological levels of oestrogen are likely to promote immune tolerance by modulating thymic function (i.e., T cell development and output) and peripheral T cells in teleosts, similar to previously reported oestrogenic effects in mammals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Oestrogen influences on mitochondrial gene expression and respiratory chain activity in cortical and mesencephalic astrocytes.

Science.gov (United States)

Araújo, G W; Beyer, C; Arnold, S

2008-07-01

The regulation of mitochondrial energy metabolism plays an essential role in the central nervous system (CNS). Abnormalities of the mitochondrial respiratory chain often accompany neurodegenerative diseases. This makes mitochondria a perfect target for strategies of cellular protection against toxic compounds and pathological conditions. Steroid hormones, such as oestrogen, are well-known to fulfil a protective role in the brain during ischaemic and degenerative processes. Because astrocytes function as the major energy supplier in the CNS, we have analysed oestrogen effects on the mitochondrial respiratory chain of this cell type. In our studies, we applied semi- and quantitative polymerase chain reaction analysis of gene expression and polarographic measurements of the respiratory chain activity of mitochondria. We observed that structural and functional properties were regulated dependent on the oestrogen exposure time and the brain region, but independent of the nuclear oestrogen receptors. We could demonstrate that long-term oestrogen exposure increases the subunit gene expression of respiratory chain complexes and the mitochondrial DNA content, thereby indicating an up-regulation of the amount of mitochondria per cell together with an increase of mitochondrial energy production. This could represent an important indirect mechanism by which long-term oestrogen exposure protects neurones from cell death under neurotoxic conditions. On the other hand, we observed short-term effects of oestrogen on the activity of mitochondrial, proton-pumping respiratory chain complexes. In astrocytes from the cortex, respiratory chain activity was decreased, whereas it was increased in astrocytes from the mesencephalon. An increased production of reactive oxygen species would be the consequence of an increased respiratory chain activity in mesencephalic astrocytes. This could explain the different efficiencies of oestrogen-mediated short-term protection in distinct brain

Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites.

Science.gov (United States)

Santillán, R; Pérez-Palacios, G; Reyes, M; Damián-Matsumura, P; García, G A; Grillasca, I; Lemus, A E

2001-09-14

Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestrogen-like effects induced by this synthetic progestin are exerted via its metabolic conversion products, we studied the binding affinity of three A-ring levonorgestrel derivatives to the ER and their capability to transactivate an oestrogen-dependent yeast system co-transfected with the human ER gene and oestrogen responsive elements fused to a beta-galactosidase reporter vector. The results demonstrated that the 3beta,5alpha reduced levonorgestrel derivative and to a lesser extent its 3alpha isomer interact with the oestrogen receptor, with a significantly lower relative binding affinity (2.4% and 0.4%, respectively) than that of oestradiol (100%), while levonorgestrel does not. Both levonorgestrel metabolites were able to activate, in a dose-dependent manner, the beta-galactosidase reporter gene in the yeast expression system, an effect that was precluded by a steroidal antioestrogen. The oestrogenic potency of levonorgestrel metabolites was significantly lower (750-fold) than that of oestradiol. Furthermore, high doses of 3beta,5alpha levonorgestrel (2.5 mg/day/6 days) induced an increase of oestrogen-dependent progestin receptor in the anterior pituitary of castrated rats. The overall data offer a plausible explanation for the weak oestrogenic effects induced by high, non-pharmacological doses of levonorgestrel.

Oestrogen receptor evaluation in Pomeranian dogs with hair cycle arrest (alopecia X) on melatonin supplementation.

Science.gov (United States)

Frank, Linda A; Donnell, Robert L; Kania, Stephen A

2006-08-01

The role of oestrogen receptors in dogs with hair cycle arrest (alopecia X) was investigated by immunohistochemistry. The purpose of this study was to determine if hair regrowth in dogs with hair cycle arrest treated with melatonin was associated with a decrease in follicular oestrogen receptors. Fifteen Pomeranians (excluding intact females) with hair cycle arrest were enrolled. Two biopsies were obtained from alopecic areas of the trunk before and after 3 months on melatonin. Haematoxylin and eosin-stained tissues were examined and oestrogen receptor-alpha was demonstrated immunohistochemically. Common histopathological findings included hyperkeratosis, follicular keratosis, excessive tricholemmal keratinization (flame follicles), thin epidermis, few small anagen bulbs, epidermal pigmentation and melanin aggregates within follicular keratin. Melanin aggregates within basal cells and hair were an occasional finding. After 3 months, 40% (six) dogs had mild to moderate hair regrowth. Biopsies from six dogs showed histological evidence of an increase in anagen hairs and eight dogs had a decrease in epidermal pigmentation. Moderate to marked staining intensity of oestrogen receptor-alpha was noted in all sebaceous gland basal cells, all small hair bulbs and follicular epithelium of telogen hairs. There was no oestrogen receptor-alpha staining of nuclei within the epidermis, apocrine glands or dermal fibroblasts. Large anagen hair bulbs had minimal to no oestrogen receptor staining. Hair regrowth was not associated with a change in oestrogen receptor-alpha staining.

Oestrogen, testosterone, cytotoxin and cholinesterase inhibitor ...

African Journals Online (AJOL)

Oestrogen, testosterone, cytotoxin and cholinesterase inhibitor removal during reclamation of sewage to drinking water. ... Risks associated with sewage effluent and reclaimed sewage should be closely monitored; therefore water at the Gammams Sewage Treatment Plant (GSTP) inlet and outlet, as well as reclaimed water ...

Effect of forage on the content of phyto-oestrogens in bovine milk

DEFF Research Database (Denmark)

Andersen, Charlotte; Weisbjerg, Martin Riis; Hansen-Møller, Jens

2009-01-01

Phyto-oestrogens are believed to have a range of beneficial effects on predominant Western diseases. A few studies on phyto-oestrogens in milk exist and show that the composition can be affected by feeding. Therefore, the aim was to study how feeding of lucerne and grass/clover silages (GCSs) aff...

Indomethacin inhibits the effects of oestrogen in the anterior pituitary gland of the rat.

Science.gov (United States)

Rosental, D G; Machiavelli, G A; Cherñavsky, A C; Speziale, N S; Burdman, J A

1989-06-01

Two inhibitors of prostaglandin synthesis, indomethacin and aspirin, blocked the increase of oestrogen-binding sites in the nuclear subcellular fraction, an increase which occurs after the administration of oestradiol. Consequently the biological effects of oestrogens in the anterior pituitary gland of the rat (prolactin synthesis, concentration of progesterone-binding sites and cell proliferation) are diminished. The anterior pituitary gland synthesized prostaglandin F2 alpha (PGF2 alpha), PGE2 and PGD2 from arachidonic acid. This synthesis was blocked when indomethacin was added to the culture media. Oestrogen increased the concentration of PGE2: an increase that was partially prevented by indomethacin. Prostaglandins may have an important role on the effects of oestrogen in the anterior pituitary gland of the rat.

On the evocability of a positive oestrogen feedback action on LH secretion in transsexual men and women.

Science.gov (United States)

Dörner, G; Rohde, W; Seidel, K; Haas, W; Schott, G S

1976-03-01

In transsexual men with homosexual behaviour and intact testicular function, as well as in homosexual men with normal gender identity, following a negative oestrogen feedback effect a delayed positive oestrogen feedback action on LH secretion was evoked. By contrast, in transsexual men with hypo- or asexuality and intact testes or hypergonadotrophic hypo- or agonadism, as well as in heterosexual men with normal gender identity, a negative oestrogen feedback effect was not followed by a positive feedback action on LH release. In transsexual women with homosexual behaviour and oligo- and/or hypomenorrhoea, only a weak or at best moderate positive oestrogen feedback action on LH release was evocable, similarly as in castrated and oestrogen-primed heterosexual men. By contrast, in a transsexual woman with bisexual behaviour and eumenorrhoea, a strong positive oestrogen feedback action on LH secretion was evocable, as well as in heterosexual women with normal gender identity.

Ketoprofen and antinociception in hypo-oestrogenic Wistar rats fed on a high sucrose diet.

Science.gov (United States)

Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; García-Martínez, Betzabeth Anali; López-Muñoz, Francisco Javier

2016-10-05

Non-steroidal anti-inflammatory drugs such as ketoprofen are the most commonly used analgesics for the treatment of pain. However, no studies have evaluated the analgesic response to ketoprofen in conditions of obesity. The aim of this study was to analyse the time course of nociceptive pain in Wistar rats with and without hypo-oestrogenism on a high sucrose diet and to compare the antinociceptive response using ketoprofen. Hypo-oestrogenic and naïve rats received a hyper caloric diet (30% sucrose) or water ad libitum for 17 weeks, the thermal nociception ("plantar test" method) and body weight were tested during this period. A biphasic response was observed: thermal latency decreased in the 4th week (hyperalgesia), while from 12th to 17th week, thermal latency increased (hypoalgesia) in hypo-oestrogenic rats fed with high sucrose diet compared with the hypo-oestrogenic control group. At 4th and 17th weeks, different doses of ketoprofen (1.8-100mg/kg p.o.), were evaluated in all groups. The administration of ketoprofen at 4th and 17th weeks showed dose-dependent effects in the all groups; however, a greater pharmacological efficacy was observed in the 4th week in the hypo-oestrogenic animals that received sucrose. Nevertheless, in all the groups significantly diminish the antinociceptive effects in the 17th week. Our data showed that nociception was altered in the hypo-oestrogenic animals that were fed sucrose (hyperalgesia and hypoalgesia). Ketoprofen showed a dose-dependent antinociceptive effect at both time points. However, hypo-oestrogenism plus high-sucrose diet modifies the antinociceptive effect of ketoprofen. Copyright © 2016 Elsevier B.V. All rights reserved.

Phyto-oestrogen levels in foods : The design and construction of the VENUS database

NARCIS (Netherlands)

Kiely, M.; Faughnan, M.; Wähälä, K.; Brants, H.; Mulligan, A.

2003-01-01

The objective of the Vegetal Estrogens in Nutrition and the Skeleton (VENUS) project was to evaluate existing data on dietary exposure to compounds with oestrogenic and anti-oestrogenic effects present in plant foods as constituents or contaminants, and to identify and disseminate in vitro and in

Lack of oestrogenic effects of food preservatives (parabens) in uterotrophic assays

DEFF Research Database (Denmark)

Hossaini, A.; Larsen, Jens-Jørgen; Larsen, John Christian

2000-01-01

The oestrogenic activity of the parabens, methyl-, ethyl- and propyl p-hydroxybenzoate, widely used as antimicrobials in food, and butyl p-hydroxybenzoate, which is used in cosmetic products, and their shared main metabolite p-hydroxybenzoic acid was investigated in a mouse uterotrophic assay......, Immature B6D2F1 mice were treated with oral or subcutaneous doses of the test compounds for three consecutive days, p-Hydroxgybenzoic acid and butyl p-hydroxybenzoate were also tested by the subcutaneous route in a rat uterotrophic assay. A significant increase in the uterus weight at day 4 was considered...... an oestrogenic effect. In the mouse assay, none of the compounds tested produced any oestrogenic response at dose levels up to 100 mg/kg body weight per day, for ethyl p-hydroxybenzoate even at a dose level of 1000 mg/kg body weight per day. In immature Wistar rats, subcutaneous administration of butyl p...

Immunocharacteristics of oestrogen and androgen target cells in the anterior pituitary gland of the chick as embryo demonstrated by a combined method of autoradiography and immunohistochemistry

International Nuclear Information System (INIS)

Gasc, J.-M.; Sar, M.; Stumpf, W.E.

1980-01-01

The distribution of oestrogen and androgen target cells in the anterior pituitary gland of the chick embryo on days 10, 12 and 15 of incubation was studied 1 h after the injection of tritium-labelled steroid hormone using the thaw-mount autoradiographic technique. Oestradiol target cells were localized in the caudal zone that corresponds to the so-called 'caudal lobe', while androgen target cells were found throughout the rostral and caudal lobes of the anterior gland. With a combined autoradiography and immunohistochemistry technique, most of the oestrogen target cells showed immunoreactivity to turkey LH antiserum but not to adrenocorticotrophin (1-24) and β-thyrotrophin antisera. In contrast, androgen target cells did not show positive immunoreactivity to the three antisera used. The results suggested a direct and early involvement of oestrogens but not of androgens in the feedback regulation of pituitary gonadotrophin secretion in the chick embryo. (U.K.)

The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study.

Science.gov (United States)

Golebiowski, Blanka; Badarudin, Noor; Eden, John; Gerrand, Leanne; Robinson, Jennifer; Liu, Jinzhu; Hampel, Ulrike; You, Jingjing; Stapleton, Fiona

2017-07-01

Sex hormones could provide a future treatment avenue for dry eye post menopause. However, there are few well-controlled studies. This study investigates the impact of testosterone and oestrogen on dry eye symptoms and signs in postmenopausal women. A randomised double-blind placebo-controlled pilot study was conducted involving 40 women with dry eye (age 63.9±5.1 years, 13.2±6.3 years post menopause). Ten women were assigned to each of four treatment groups: transdermal testosterone, oestradiol, testosterone/oestradiol combination and placebo. Assessment at baseline and after 8 weeks: ocular symptoms, tear osmolarity, tear stability, tear secretion, meibomian gland assessment, corneal and conjunctival sensitivity, serum concentrations of 17β-oestradiol, 3-α-androstanediol-glucuronide and dehydroepiandrosterone sulfate. Differences from placebo were examined using one-way analysis of variance and Dunnett's t-test. Within-group analyses included paired t-tests and Spearman correlation. Dryness intensity after 8 weeks was significantly worse in the oestrogen group compared with placebo (p=0.04). No significant changes in other symptoms, tear function, meibomian gland function, lid morphology, corneal or conjunctival sensitivity were observed in any of the groups when compared with the change in placebo after 8 weeks. Within-group analyses showed increased tear secretion in the testosterone/oestradiol combination group (p=0.03) and a strong association between increased serum androgen and improved tear stability in the testosterone group (ρ=0.83,p=0.01). Oestrogen supplementation may worsen ocular symptoms in postmenopausal women with dry eye, whereas no impact of testosterone therapy on symptoms was apparent. The positive effects of oestrogen and testosterone on tear function require confirmation in a larger study, with sample size calculated from the data generated herein. Placebo control is essential in studies of dry eye therapies. ACTRN

In vivo relative quantitative proteomics reveals HMGB1 as a downstream mediator of oestrogen-stimulated keratinocyte migration.

Science.gov (United States)

Shin, Jung U; Noh, Ji Yeon; Lee, Ju Hee; Lee, Won Jai; Yoo, Jong Shin; Kim, Jin Young; Kim, Hyeran; Jung, Inhee; Jin, Shan; Lee, Kwang Hoon

2015-06-01

It is known that oestrogen influences skin wound healing by modulating the inflammatory response, cytokine expression and extracellular matrix deposition; accelerating re-epithelialization; and stimulating angiogenesis. To identify novel proteins associated with effects of oestrogen on keratinocyte, stable isotope labelling by amino acids in cell culture (SILAC)-based mass spectrometry was performed. Using SILAC, quantification of 1085 proteins was achieved. Among these proteins, 60 proteins were upregulated and 32 proteins were downregulated. Among significantly upregulated proteins, high-mobility group protein B1 (HMGB1) has been further evaluated for its role in the effect of oestrogen on keratinocytes. HMGB1 expression was strongly induced in oestrogen-treated keratinocytes in dose- and time-dependent manner. Further, HMGB1 was able to significantly accelerate the rate of HaCaT cell migration. To determine whether HMGB1 is involved in E2-induced HaCaT cell migration, cells were transfected with HMGB1 siRNA. Knockdown of HMGB1 blocked oestrogen-induced keratinocyte migration. Collectively, these experiments demonstrate that HMGB1 is a novel downstream mediator of oestrogen-stimulated keratinocyte migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Iodine-125-labelled tamoxifen is differentially cytoxic to cells containing oestrogen receptors

International Nuclear Information System (INIS)

Bloomer, W.D.; McLaughlin, W.H.; Weichselbaum, R.R.

1980-01-01

Tamoxifen, a non-steroidal anti-oestrogen competes with 17 - oestradiol for oestrogen receptor protein and is translocated to the nucleus. Carrier-free 125 I-TAM was tested for cytotoxicity in oestrogen receptor rich (human breast cancer MCF-7) and poor (V-79 Chinese hamster) cells. 125 I-TAM was differentially cytotoxic to MCF-7 cells. The D 37 values for MCF-7 and V-79 cells were 0.5 and 1.5 pCi/cell respectively. No radiotoxicity was observed with Na 125 I at doses equal to 125 I-TAM; iodide was effectively excluded from both cell lines and remained in the extracellular space. Also, nonradioactive 127 I-TAM and TAM were both non-toxic when tested at levels comparable to 125 I-TAM. It is suggested that the marked cytotoxicity in MCF-7 cells results from close approximation of 125 I with the genetic apparatus as a result of direct charging of specific nuclear receptors and/or translocation of 125 I-TAM receptor complexes from the cytoplasm to the nucleus, and that the minimal toxicity in V-79 cells reflects transmitted cytoplasmic radiation effects, limited direct nuclear charging and/or limited nuclear translocation resulting from the relative paucity of oestrogen in the cells. (U.K.)

Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders

NARCIS (Netherlands)

Bao, Ai-Min; Hestiantoro, Andon; van Someren, Eus J. W.; Swaab, Dick F.; Zhou, Jiang-Ning

2005-01-01

Oestrogens may modulate the activity of the hypothalamic-pituitary-adrenal (HPA) axis. The present study was to investigate whether the activity of the HPA axis in mood disorders might be directly modulated by oestrogens via oestrogen receptors (ORs) in the corticotropin-releasing hormone (CRH)

The reduction in visceral fat mass in response to growth hormone is more marked in men than in oestrogen-deficient women

DEFF Research Database (Denmark)

Franco, Celina; Koranyi, Josef; Brandberg, John

2008-01-01

and postmenopausal women. METHODS: Fifteen men and 15 age- and BMI-matched women with abdominal obesity (mean age: 58; range 51-64 years) were treated for one year with similar doses (0.47 vs. 0.51 mg/day) of GH. All women were postmenopausal not receiving oestrogen treatment. Insulin sensitivity was assessed using...

Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer.

Science.gov (United States)

Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei; Kuasne, Hellen; Spencer, Ranyell Matheus; Nakagawa, Wilson Toshihiko; Bezerra, Tiago Santoro; Kupper, Bruna Catin; Takahashi, Renata Maymi; Barros Filho, Mateus; Rogatto, Silvia Regina; Lopes, Ademar

2017-11-13

Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. This study aimed to investigate the expression levels of the ERβ1, ERβ2, ERβ4 and ERβ5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. Decreased expression of ERβ isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERβ1 and ERβ5 expression levels were associated with better disease-free survival (p = 0.002). These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.

Oestrogen: an overlooked mediator in the neuropsychopharmacology of treatment response?

Science.gov (United States)

Keating, Charlotte; Tilbrook, Alan; Kulkarni, Jayashri

2011-05-01

Major depression (MD) and anorexia nervosa (AN) often present comorbidly and both share some affective symptoms, despite obvious phenotypic differences. In the illness phase, pathophysiological evidence indicates similar abnormalities in both clinical groups including dysfunction in the serotonin (5-HT) system (of which some abnormalities persist following recovery) and between 60% and 80% of patients in both groups present with significant hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis. First-line approach to treatment for MD involves modulation of the 5-HT system using selective serotonin reuptake inhibitors (SSRIs). For AN, treatment with SSRIs has been shown to be considerably less effective compared to MD. Both illnesses show marked dysregulation in the HPA axis. A consequence of SSRI treatment is a reduction and/or normalization of indices of the HPA axis [i.e. cortisol, adrenocorticotropic hormone (ACTH)], which is consistent with recovery levels in both clinical groups. Oestrogen (in high doses) has been shown to exert antidepressant effects and positively impact on MD symptoms as a treatment in its own right, or in combination with antidepressants, in women of menopausal age. It is proposed that a combination of SSRIs and oestrogen therapy may facilitate physiological normalization in MD in women of non-menopausal age and in AN. Preliminary evidence suggests oestrogen treatment alone is of some benefit to patients and it is proposed that a combination of SSRI and oestrogen will precipitate and potentially accelerate symptomatic remission. Should this approach be successful, it offers the capacity for improvement over traditional antidepressant use in women diagnosed with MD and a novel strategy for the treatment of AN, a serious clinical illness associated with the highest mortality of any psychiatric condition.

Oestrogens and Osteoporosis | Utian | South African Medical Journal

African Journals Online (AJOL)

The interrelationship between oestrogens, endogenous and exogenous, their effects on plasma calcium, phosphorus and alkaline phosphatase metabolism, and the pathogenesis of osteoporosis are reviewed. Aspects of research conducted by me at Groote Schuur Hospital, Cape Town are incorporated in the discussion.

Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM

NARCIS (Netherlands)

Brussaard, H.E.; Gevers Leuven, J.A.; Frölich, M.; Kluft, C.; Krans, H.M.J.

1997-01-01

Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin- dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for

DNA polymerases in the rat pituitary gland. Effect of oestrogens and sulpiride.

Science.gov (United States)

Jahn, G A; Kalbermann, L E; Machiavelli, G; Szijan, I; Burdman, J A

1980-06-01

Changes in the activity of DNA polymerase and [3H]thymidine incorporation into the DNA of the anterior pituitary gland were studied in oestrogenized male and pregnant rats. The activities of DNA polymerases alpha and beta, extracted in Tris--HCl or in sodium phosphate buffer were characterized according to their optimum pH and sensitivity to N-ethyl-maleimide. In the Tris-soluble fraction DNA polymerase activity is almost exclusively alpha, while in the phosphate soluble fraction it is a mixture of alpha and beta. The administration of oestrogens to male rats increases [3H]thymidine incorporation and enhances the activity of DNA polymerases in the Tris-soluble fraction, while the activity of the phosphate-soluble enzyme does not change. Sulpiride administration results in a further increment of [3H]thymidine incorporation and of DNA polymerase activity in the Tris-soluble fraction. In pregnant rats sulpiride also produces an increment of DNA polymerase activity only in the Tris-soluble fraction. Thus, the activity of the Tris-soluble fraction from APG behaves as DNA polymerase alpha. This activity changes in parallel with [3H]thymidine incorporation into DNA which is an indication of cell proliferation in the gland. This is discussed with respect to a negative feedback mechanism between intracellular prolactin concentration and DNA synthesis in the APG.

Oestrogen receptors in tumors of breast cancer patients

Energy Technology Data Exchange (ETDEWEB)

Levin, J; Kay, G; Da Fonseca, M [University of the Witwatersrand, Johannesburg (South Africa). Department of Nuclear Medicine; Lange, M [University of the Witwatersrand, Johannesburg (South Africa). Dept. of Surgery; De Moor, N G [University of the Witwatersrand, Johannesburg (South Africa). Department of Radiation Therapy; Savage, N [University of the Witwatersrand, Johannesburg (South Africa). Department of Physiological Chemistry

1978-04-15

Oestrogen receptors were measured in the cytoplasmic fraction of tumors from patients with breast cancer. Receptors were detected in 48% of patients, and 52% showed no receptors. A follow-up study of a small group of patients on hormone therapy is reported.

Cholesterol, coronary heart disease and oestrogens | Utian | South ...

African Journals Online (AJOL)

Present concepts of the interrelationship between oestrogens, endogenous and exogenous, and the development of atheromatosis and coronalY heart disease in the human female are reviewed. Aspects of research conducted by me at Groote Schuur Hospital, Cape Town, are incorporated in the discussion. The current ...

Sexual dimorphism and oestrogen regulation of KCNE3 expression modulates the functional properties of KCNQ1 K channels.

LENUS (Irish Health Repository)

Alzamora, Rodrigo

2012-02-01

The KCNQ1 potassium channel associates with various KCNE ancillary subunits that drastically affect channel gating and pharmacology. Co-assembly with KCNE3 produces a current with nearly instantaneous activation, some time-dependent activation at very positive potentials, a linear current-voltage relationship and a 10-fold higher sensitivity to chromanol 293B. KCNQ1:KCNE3 channels are expressed in colonic crypts and mediate basolateral K(+) recycling required for Cl(-) secretion. We have previously reported the female-specific anti-secretory effects of oestrogen via KCNQ1:KCNE3 channel inhibition in colonic crypts. This study was designed to determine whether sex and oestrogen regulate the expression and function of KCNQ1 and KCNE3 in rat distal colon. Colonic crypts were isolated from Sprague-Dawley rats and used for whole-cell patch-clamp and to extract total RNA and protein. Sheets of epithelium were used for short-circuit current recordings. KCNE1 and KCNE3 mRNA and protein abundance were significantly higher in male than female crypts. No expression of KCNE2 was found and no difference was observed in KCNQ1 expression between male and female (at oestrus) colonic crypts. Male crypts showed a 2.2-fold higher level of association of KCNQ1 and KCNE3 compared to female cells. In female colonic crypts, KCNQ1 and KCNE3 protein expression fluctuated throughout the oestrous cycle and 17beta-oestradiol (E2 10 nM) produced a rapid (<15 min) dissociation of KCNQ1 and KCNE3 in female crypts only. Whole-cell K(+) currents showed a linear current-voltage relationship in male crypts, while K(+) currents in colonic crypts isolated from females displayed voltage-dependent outward rectification. Currents in isolated male crypts and epithelial sheets were 10-fold more sensitive to specific KCNQ1 inhibitors, such as chromanol 293B and HMR-1556, than in female. The effect of E2 on K(+) currents mediated by KCNQ1 with or without different beta-subunits was assayed from current

Pattern of faecal 20-oxopregnane and oestrogen concentrations during pregnancy in wild plains zebra mares.

Science.gov (United States)

Ncube, Hlengisizwe; Duncan, Patrick; Grange, Sophie; Cameron, Elissa Z; Barnier, Florian; Ganswindt, Andre

2011-07-01

Regulative endocrine mechanisms influence the reproductive behaviour and success of mammals, but they have been studied predominantly in domestic and captive animals. The study aims at describing the pattern of faecal 20-oxopregnane and oestrogen concentrations during pregnancy in wild plains zebra Equus quagga chapmani. Data were collected during wet and dry seasons 2007-2009. Enzyme Immunoassays were used to determine 20-oxopregnane and oestrogen concentrations in faecal samples (n=74) collected from individual mares (n=32) whose dates of foaling were known through long-term monitoring. Hormonal profiles were described with a General Additive Model (GAM: Hormone ∼ Days to Foaling). Faecal 20-oxopregnanes have a complex cycle during pregnancy (GAM, n=70, R(2)=0.616, p200 ng/g DW) of faecal 20-oxopregnanes associated with high (>160 ng/g DW) faecal oestrogen levels indicate mid-pregnancy in c.90% of cases (16/17). High faecal 20-oxopregnanes (>200 ng/g DW) and low faecal oestrogen levels (<160 ng/g DW) indicate late pregnancy, again in c.90% of cases. Two faecal samples would allow the stage of pregnancy to be determined with confidence. Copyright © 2011 Elsevier Inc. All rights reserved.

Non-contraceptive oestrogen-containing preparations for controlling symptoms of premenstrual syndrome.

Science.gov (United States)

Naheed, Bushra; Kuiper, Jan Herman; Uthman, Olalekan A; O'Mahony, Fidelma; O'Brien, Patrick Michael Shaughn

2017-03-03

Premenstrual syndrome (PMS) is a psychological and somatic disorder of unknown aetiology, with symptoms typically including irritability, depression, mood swings, bloating, breast tenderness and sleep disturbances. About 3% to 10% of women who experience these symptoms may also meet criteria for premenstrual dysphoric disorder (PMDD). PMS symptoms recur during the luteal phase of the menstrual cycle and reduce by the end of menstruation. PMS results from ovulation and may be due to ovarian steroid interactions relating to neurotransmitter dysfunction. Premenstrual disorders have a devastating effect on women, their families and their work.Several treatment options have been suggested for PMS, including pharmacological and surgical interventions. The treatments thought to be most effective tend to fall into one of two categories: suppressing ovulation or correcting a speculated neuroendocrine anomaly.Transdermal oestradiol by patch, gel or implant effectively stops ovulation and the cyclical hormonal changes which produce the cyclical symptoms. These preparations are normally used for hormone therapy and contain lower doses of oestrogen than found in oral contraceptive pills. A shortened seven-day course of a progestogen is required each month for endometrial protection but can reproduce premenstrual syndrome-type symptoms in these women. To determine the effectiveness and safety of non-contraceptive oestrogen-containing preparations in the management of PMS. On 14 March 2016, we searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register; Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; PsycINFO; CINAHL; ClinicalTrials.gov; metaRegister of Controlled trials (mRCT); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal. In addition, we checked the reference lists of articles retrieved. We included published and unpublished randomized placebo or active

Monitoring ovarian cycle and pregnancy in the giant anteater (Myrmecophaga tridactyla) by faecal progestagen and oestrogen analysis.

Science.gov (United States)

Patzl, M; Schwarzenberger, F; Osmann, C; Bamberg, E; Bartmann, W

1998-10-01

Oestrogen and progestagen metabolites were measured in the faeces of five female giant anteaters (Myrmecophaga tridactyla), to characterise the oestrous cycle and pregnancy. Faecal samples were collected twice weekly for a minimum of 6 months, and immunoreactive progestagens and oestrogens were analysed using enzyme immunoassays (EIA). For progestagens, two antibodies that cross-reacted with 20alpha-hydroxy- or 20-oxo-progestagens were used. Both assays effectively monitored ovarian cyclicity; however, the concentrations obtained using the antibody for 20alpha-hydroxy-progestagens were higher, and the hormonal changes were more pronounced. Regular ovarian cycles were identified in three of the five females. Average (+/-SEM) length of the oestrous cycle (n=10) was 51.4+/-5.6 days. Peak concentrations of 20alpha-hydroxy-progestagens ranged from 80-660 ng/g of faeces and those of oestrogens from 20-100 ng/g. Hormone concentrations were measured during parts of two pregnancies and during four post-partum periods. The length of one gestation (from oestrous oestrogen peak until parturition) was 184 days. In the second half of gestation, progestagen concentration started to increase above luteal phase values; in the week before parturition it was approximately 20 times higher than those during the luteal phase. Concentrations of excreted oestrogens began to increase after two thirds of gestation and exceeded that of the follicular phase by approximately 2.5-fold in the week before parturition. Onset of ovarian cyclicity after parturition varied from 4-11 weeks. In conclusion, the measurement of faecal immunoreactive progestagens and oestrogens in the giant anteater indicated an ovarian cycle of approximately 7 weeks in length and provided potentially useful data for successful breeding management.

Radioimmunological oestrogen and progesterone measurement in the serum and ovaries of pseudogravid female rats after PMS and HCG treatment

International Nuclear Information System (INIS)

Hauck, P.

1978-01-01

Infantile female rats were made pseudogravid with PMS-HCG (according to Karg). Two bioassays were employed to investigate the effects of HCG on the ovaries; the HCG was injected subactaneously in the back of the animals in varying doses and at various intervals after the initial PMS administration. As specific parameters, oestrogen and progesterone levels in serum and ovary homogenate were determined radioimmunologically. The first animal experiment showed that the ovaries of pseudogravid animals had reached maximum sensitivity for corpus luteum production after HCG administration between 50 and 70 hours after PMS administration. In the second animal experiment with repeated HCG stimulus in the luteal phase, it was found that the corpus luteum of the rat ovary is apparently unable to synthesize oestrogens. In contrast, progesteron synthesis received maximum stimulation already with the lowest dose administered (3 IE HCG). The experiments clearly showed a dependence on HCG dose and the time which the test substance is allowed to take effect. (orig./AJ) 891 AJ/orig.- 892 KN [de

Detection and Quantification of Oestrogenic Endocrine Disruptors in ...

African Journals Online (AJOL)

The aim of this study was to detect the presence and quantify the total oestrogens (estriol (E1), estradiol (E2), and estrone (E3)) in Lake Victoria water with a view of assessing their contribution to the health status of fish. A total of 27 water samples; three from each of the nine sampling sites were collected in Mwanza gulf in ...

Effects of phyto-oestrogens on veal calf prostate histology

NARCIS (Netherlands)

Groot, M.J.

2006-01-01

In veal calf production plant-based proteins are frequently included in milk replacer fed to the animals. Since soy products, which are mostly used, are known for their high levels of phyto-oestrogens, the effects of these feeds on the veal calf prostate were examined. Goal was to determine whether

Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight.

Science.gov (United States)

Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

2015-03-01

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. © 2015 The authors.

Serum levels of oestrogen and some biochemical parameters in relation to reproductive activities and level of production in fowl

International Nuclear Information System (INIS)

El - Abiad, N.M.F.

1982-01-01

This work was carried out at the poultry experiment station department of animal production, faculty of agriculture zagazig university, benha branch. radioimmunological and biochemical assays were performed in the laboratories of radioimmunology and biochemistry unit of atomic energy establishment . It was intended to study: 1. The effect of oestrogen level along the time of egg formation on some parameters in blood serum related to metabolic efficiency. 2. The variations in oestrogen level and blood serum parameters due to clutch size of hens. 3.Changes in oestrogen levels and some blood constituents along the time of egg formation

Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse.

Science.gov (United States)

Meyer, Stephanie K; Probert, Philip M E; Lakey, Anne F; Axon, Andrew R; Leitch, Alistair C; Williams, Faith M; Jowsey, Paul A; Blain, Peter G; Kass, George E N; Wright, Matthew C

2017-05-05

Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oestrogenic effect may be a key event in this response, tartrazine, sulphonated metabolites and a food additive contaminant were screened for their ability to interact with murine oestrogen receptors. In all cases, there were no interactions as agonists or antagonists and further, no oestrogenicity was observed with tartrazine in an in vivo uterine growth assay. To examine the relevance of the hepatic effects of tartrazine to its use as a food additive, tartrazine was orally administered to transgenic NF-κB-Luc mice. Pre- and concurrent oral treatment with alcohol was incorporated given its potential to promote gut permeability and hepatic inflammation. Tartrazine alone induced NF- κB activities in the colon and liver but there was no periportal recruitment of inflammatory cells or fibrosis. Tartrazine, its sulphonated metabolites and the contaminant inhibited sulphotransferase activities in murine hepatic S9 extracts. Given the role of sulfotransferases in bile acid excretion, the initiating event giving rise to periportal inflammation and subsequent hepatic pathology through systemic tartrazine exposure is therefore potentially associated an inhibition of bile acid sulphation and excretion and not on oestrogen receptor-mediated transcriptional function. However, these effects were restricted to systemic exposures to tartrazine and did not occur to any significant effect after oral exposure. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9

DEFF Research Database (Denmark)

Lidegaard, Øjvind; Nielsen, Lars Hougaard; Skovlund, Charlotte Wessel

2011-01-01

To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose.......To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose....

Intrauterine and genetic factors in early childhood sensitization

DEFF Research Database (Denmark)

Bønnelykke, Klaus

2010-01-01

The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... with production of specific IgE-antibodies against allergens. Sensitization may cause allergic symptoms, and sensitization early in life is a strong risk factor for later disease. Fetal and early postnatal life seems to be a critical period for development of atopic disease and may be an important “window...... of opportunity” for prevention. The aim of this thesis was to increase the understanding of sensitization in early life. We studied indicators of sensitization in the newborn, and early development of sensitization and disease associated with a newly discovered genetic risk factor. Such insight may increase our...

Differences in the rate of oestrogen-induced apoptosis in breast cancer by oestradiol and the triphenylethylene bisphenol

Science.gov (United States)

Obiorah, I E; Jordan, V C

2014-01-01

Background and Purpose Triphenylethylene (TPE)-like compounds were the first agents to be used in the treatment of metastatic breast cancer in postmenopausal women. Although structurally related to the anti-oestrogen, 4-hydroxytamoxifen, TPEs possess oestrogenic properties in fully oestrogenized breast cancer cells but do not induce apoptosis with short-term treatment in long-term oestrogen-deprived breast cancer cells. This study determined the differential effects of bisphenol, a TPE, on growth and apoptosis based on the modulation of the shape of the ligand–oestrogen receptor complex. Experimental Approach Apoptotic flow cytometric studies were used to evaluate apoptosis over time. Proliferation of the breast cancer cells was assessed using DNA quantification and cell cycle analysis. Real-time PCR was performed to quantify mRNA levels of apoptotic genes. Regulation of cell cycle and apoptotic genes was determined using PCR-based arrays. Key Results Bisphenol induced an up-regulation of cell cycle genes similar to those induced by 17β oestradiol (E2). Unlike the changes induced by E2 that occur after 24 h, the apoptosis evoked by bisphenol occurred after 4 days, with quantifiable apoptotic changes noted at 6 days. A prolonged up-regulation of endoplasmic reticulum stress and inflammatory stress response genes was observed with subsequent activation of apoptosis-related genes in the second week of treatment with bisphenol. Conclusions and Implications The bisphenol: ERα complex induces delayed biological effects on the growth and apoptosis of breast cancer cells. Both the shape of the complex and the duration of treatment control the initiation of apoptosis. PMID:24819221

Compounds from Cynomorium songaricum with Estrogenic and Androgenic Activities Suppress the Oestrogen/Androgen-Induced BPH Process.

Science.gov (United States)

Wang, Xueni; Tao, Rui; Yang, Jing; Miao, Lin; Wang, Yu; Munyangaju, Jose Edouard; Wichai, Nuttapong; Wang, Hong; Zhu, Yan; Liu, Erwei; Chang, Yanxu; Gao, Xiumei

2017-01-01

To investigate the phytoestrogenic and phytoandrogenic activities of compounds isolated from CS and uncover the role of CS in prevention of oestrogen/androgen-induced BPH. Cells were treated with CS compounds, and immunofluorescence assay was performed to detect the nuclear translocation of ER α or AR in MCF-7 or LNCaP cells; luciferase reporter assay was performed to detect ERs or AR transcriptional activity in HeLa or AD293 cells; MTT assay was performed to detect the cell proliferation of MCF-7 or LNCaP cells. Oestrogen/androgen-induced BPH model was established in rat and the anti-BPH, anti-estrogenic, and anti-androgenic activities of CS in vivo were further investigated. The nuclear translocation of ER α was stimulated by nine CS compounds, three of which also stimulated AR translocation. The transcriptional activities of ER α and ER β were induced by five compounds, within which only ECG induced AR transcriptional activity as well. Besides, ECG stimulated the proliferation of both MCF-7 cells and LNCaP cells. CS extract suppressed oestrogen/androgen-induced BPH progress in vivo by downregulation of E2 and T level in serum and alteration of the expressions of ER α , ER β , and AR in the prostate. Our data demonstrates that compounds from CS exhibit phytoestrogenic and phytoandrogenic activities, which may contribute to inhibiting the oestrogen/androgen-induced BPH development.

Circumventing the natural, frequent oestrogen waves of the female cheetah (Acinonyx jubatus) using oral progestin (Altrenogest).

Science.gov (United States)

Crosier, Adrienne E; Comizzoli, Pierre; Koester, Diana C; Wildt, David E

2017-08-01

Cheetah are induced ovulators, experiencing short, variable oestrogen waves year-round. Exogenous gonadotrophin administration induces ovulation, but success is variable and often improves if ovaries are quiescent. After affirming the presence of short-term oestrogenic waves, we examined the effect of the timing of administration of exogenous equine and human chorionic gonadotrophins (eCG-hCG) within the oestrogen concentration pattern on subsequent follicle development and oocyte and corpus luteum quality. We also investigated ovarian suppression using an oral progestin (Altrenogest, 7 days) and assessed whether Altrenogest moderated adrenal activity by reducing glucocorticoid metabolites. All cheetahs exhibited short (every ~7-10 days), sporadic, year-round increases in faecal oestradiol punctuated by unpredictable periods (4-10 weeks) of baseline oestradiol (anoestrous). Gonadotrophin (eCG-hCG) efficacy was not affected by oestradiol 'wave' pattern if administered ≥3 days after an oestrogen peak. Such cheetahs produced normative faecal progestagen patterns and higher numbers (P<0.06) of mature oocytes than females given gonadotrophins ≤2 days after an oestradiol peak. Altrenogest supplementation expanded the interval between oestradiol peaks to 12.9 days compared with 7.3 days without progestin pretreatment. Altrenogest-fed females excreted less (P<0.05) glucocorticoid metabolites than non-supplemented counterparts. Results show that Altrenogest is effective for suppressing follicular activity, may contribute to reduced glucocorticoid production and may result in more effective ovulation induction via gonadotrophin therapy.

Phyto-oestrogen excretion and rate of bone loss in postmenopausal women

NARCIS (Netherlands)

Kardinaal, A.F.M.; Morton, M.S.; Brüggemann-Rotgans, I.E.M.; Beresteijn, E.C.H. van

1998-01-01

Objective: The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with long-term urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake. Design: Secondary analysis of a 10-year follow-up study (1979-1989) among postmenopausal women in the

Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse

OpenAIRE

Meyer, Stephanie K.; Probert, Philip M.E.; Lakey, Anne F.; Axon, Andrew R.; Leitch, Alistair C.; Williams, Faith M.; Jowsey, Paul A.; Blain, Peter G.; Kass, George E.N.; Wright, Matthew C.

2017-01-01

Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oes...

Reproductive effects from oestrogen activity in polluted water

Energy Technology Data Exchange (ETDEWEB)

Sumpter, J.P. [Brunel Univ., Uxbridge (United Kingdom). Dept. of Biology and Biochemistry

1998-12-31

A new area of ecotoxicology, now usually called endocrine disruption, has arisen in the last few years. However, despite the present topicality of this issue, some of the best documented examples of endocrine disruption were reported a decade or more ago (see, for example, Fry, 1995). The issue is concerned with the effects of chemicals that mimic endogenous hormones on the physiology of exposed wildlife and humans. As many of these xenohormones minic steroid hormones, especially oestrogens and androgens, most of the reported effects have involved effects on the reproductive system of exposed organisms. Many of these reported effects on wildlife have concerned aquatic, rather than terrestrial, organisms (even the well-documented effects on birds are primarily concerned with water birds, which feed predominantly on fish); the reproductive abnormalities seen in alligators living in some lakes in Florida and the oestrogenic effects on fish reported in British rivers (this example is discussed in detail below) provide good examples of the type of effects observed in aquatic organisms. This predominance of effects on aquatic organisms could reflect an unconscious bias of the interests of research scientists (are there more wildlife biologists interested in aquatic, rather than terrestrial, animals?), but is perhaps more likely a consequence of the fact that the aquatic environmemnt is the ultimate `sink` for the international or unintentional disposal of much waste. (orig.)

Isolated oestrogen deficiency in male 30-year-old: persistent growth plates with severe osteopenia

International Nuclear Information System (INIS)

Smith, T.; Roberts, J.; Howman-Giles, R.; Cowell, C.; Jeremy, R.

2000-01-01

Full text: A 31-year-old male presented with right rib pain and generalised skeletal symptoms. He has a past history of multiple fractures following trauma. No history of childhood fractures. Asthma (No steroids). A product of a consanguineous marriage, he has one child aged 7. Examination showed 178.6cm male with normal sexual characteristics. No abnormality detected apart from tenderness over right ribs. Bone scan showed active growth plates and right and left rib fractures. X-rays demonstrated a bone age of 15 1/2 - 16 yrs and a compression fracture of L2. His bone mineral density is severely reduced. Metabolic investigations revealed Testosterone 27.4 nmol (N 11-35), oestradiol < 70 pmol/L, ultrasensitive assay 14 and 17 pmol/L (consistent with 8-year-old male), LH N, FSH N, 46 XY Karyotype. Alkaline phosphatase. 148 (N<120), Normal glucose tolerance test. This patient illustrates a very rare condition of oestrogen deficiency in a male, probably due to aromatase deficiency. This enzyme converts testosterone to oestradiol. It illustrates the role of oestrogen in fusing growth plates and maintaining bone mass in males with otherwise normal androgen levels. A similar clinical picture can result from an oestrogen receptor abnormality. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

The effect of Ramadan fasting on LH, FSH, oestrogen, progesterone and leptin in pregnant women.

Science.gov (United States)

Khoshdel, A; Kheiri, S; Hashemi-Dehkordi, E; Nasiri, J; Shabanian-Borujeni, S; Saedi, E

2014-10-01

Many pregnant Muslim women fast during Ramadan. Leptin has an important role in the reproductive system and hormones. In this study, FSH, LH, oestrogen, progesterone and leptin were measured in the first, second and fourth week of Ramadan and the second week post-Ramadan, in 30 fasting pregnant women. Data were analysed using repeated measures ANOVA by SPSS. The weight and BMI did not change during the study. A significant change in FSH, oestrogen, progesterone and leptin was observed (p Ramadan. Progesterone increased at the end of Ramadan and the second week after. Oestrogen increased significantly during Ramadan and decreased after Ramadan. A decreasing trend was seen in LH during the Ramadan and 2 weeks after (p Ramadan. We found poor weight gain and hypoleptinaemia in pregnant fasted women during the study. Food restriction in pregnant fasted women during Ramadan may induce poor weight gain during pregnancy. These data confirm that Ramadan fasting by pregnant women may have potential risks during pregnancy. We recommend further study to evaluate long-term effects of Ramadan fasting during pregnancy in different countries with different food habits and traditions, to obtain reliable and documented data.

The response to oestrogen deprivation of the cartilage collagen degradation marker, CTX-II, is unique compared with other markers of collagen turnover

DEFF Research Database (Denmark)

Bay-Jensen, Anne-Christine; Tabassi, Nadine C B; Sondergaard, Lene V

2009-01-01

The urinary level of the type II collagen degradation marker CTX-II is increased in postmenopausal women and in ovariectomised rats, suggesting that oestrogen deprivation induces cartilage breakdown. Here we investigate whether this response to oestrogen is also true for other type II collagen tu...

Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like symptomatology.

Science.gov (United States)

Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2004-07-01

We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or 'depressive-like' symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild-type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit 'depressive-like' symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the 'depressive-like' profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression.

Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution

DEFF Research Database (Denmark)

Andersen, Ove; Pedersen, Steen B; Svenstrup, Birgit

2007-01-01

of alpha2A-adrenergic-receptor correlated positively with expression of oestrogen-receptor-alpha. CONCLUSIONS: The results fit the hypothesis that sex hormones play a role in altered fat distribution and insulin sensitivity of male patients with HIV-lipodystrophy. The effect of oestradiol...... patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression...

The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.

LENUS (Irish Health Repository)

Kavanagh, Dara O

2012-02-01

Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

Science.gov (United States)

Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

2016-01-01

Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

Yes to early detection of cancer - no to routine mammography examinations. Parting from wishful thinking, turning to new strategies

International Nuclear Information System (INIS)

Dersee, T.; Dieckmann, H.; Koehnlein, W.; Kuni, H.; Lengfelder, E.; Pflugbeil, S.; Schmitz-Feuerhake, I.

2002-01-01

Many experts find it difficult to accept what experience has shown, namely that routine mammography examinations have lowered neither the breast cancer fatality rate nor the crude death rate. One aspect that has been neglected in propagating screenings is the high radiation sensitivity of genetically predisposed females (0.5% - 1.0%). These females should not be exposed to repeated X-rays for screening purposes. True preventive measures, which promise significant effects, include the avoidance of radiation exposure, especially during the early stages of life, and a restrictive use of oestrogen substitution therapies

Yes to early detection of cancer - no to routine mammography examinations. Parting from wishful thinking, turning to new strategies

CERN Document Server

Dersee, T; Koehnlein, W; Kuni, H; Lengfelder, E; Pflugbeil, S; Schmitz-Feuerhake, I

2002-01-01

Many experts find it difficult to accept what experience has shown, namely that routine mammography examinations have lowered neither the breast cancer fatality rate nor the crude death rate. One aspect that has been neglected in propagating screenings is the high radiation sensitivity of genetically predisposed females (0.5% - 1.0%). These females should not be exposed to repeated X-rays for screening purposes. True preventive measures, which promise significant effects, include the avoidance of radiation exposure, especially during the early stages of life, and a restrictive use of oestrogen substitution therapies.

Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity

International Nuclear Information System (INIS)

Axon, Andrew; May, Felicity E.B.; Gaughan, Luke E.; Williams, Faith M.; Blain, Peter G.; Wright, Matthew C.

2012-01-01

Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings – sunset yellow and tartrazine – were identified as novel human ERα activators, activating the human ER with an EC 50% concentration of 220 and 160 nM, respectively.

Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity.

Science.gov (United States)

Axon, Andrew; May, Felicity E B; Gaughan, Luke E; Williams, Faith M; Blain, Peter G; Wright, Matthew C

2012-08-16

Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings--sunset yellow and tartrazine--were identified as novel human ERα activators, activating the human ER with an EC(50%) concentration of 220 and 160 nM, respectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

NARCIS (Netherlands)

F.J. Couch (Fergus); K.B. Kuchenbaecker (Karoline); K. Michailidou (Kyriaki); G.A. Mendoza-Fandino (Gustavo A.); S. Nord (Silje); J. Lilyquist (Janna); C. Olswold (Curtis); B. Hallberg (Boubou); S. Agata (Simona); H. Ahsan (Habibul); K. Aittomäki (Kristiina); C.B. Ambrosone (Christine); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); V. Arndt (Volker); B.K. Arun (Banu); B. Arver (Brita Wasteson); M. Barile (Monica); R.B. Barkardottir (Rosa); D. Barrowdale (Daniel); L. Beckmann (Lars); M.W. Beckmann (Matthias); J. Benítez (Javier); S.V. Blank (Stephanie); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); S.E. Bojesen (Stig); M.K. Bolla (Manjeet); B. Bonnani (Bernardo); H. Brauch (Hiltrud); H. Brenner (Hermann); B. Burwinkel (Barbara); S.S. Buys (Saundra S.); T. Caldes (Trinidad); M.A. Caligo (Maria); F. Canzian (Federico); T.A. Carpenter (Adrian); J. Chang-Claude (Jenny); S.J. Chanock (Stephen J.); W.K. Chung (Wendy K.); K.B.M. Claes (Kathleen B.M.); A. Cox (Angela); S.S. Cross (Simon); J.M. Cunningham (Julie); K. Czene (Kamila); M.B. Daly (Mary B.); F. Damiola (Francesca); H. Darabi (Hatef); M. de La Hoya (Miguel); P. Devilee (Peter); O. Díez (Orland); Y.C. Ding (Yuan); R. Dolcetti (Riccardo); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); I. dos Santos Silva (Isabel); M. Dumont (Martine); A.M. Dunning (Alison); D. Eccles (Diana); H. Ehrencrona (Hans); A.B. Ekici (Arif); H. Eliassen (Heather); S.D. Ellis (Steve); P.A. Fasching (Peter); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); A. Försti (Asta); F. Fostira (Florentia); W.D. Foulkes (William); M.O.W. Friebel (Mark ); E. Friedman (Eitan); D. Frost (Debra); M. Gabrielson (Marike); M. Gammon (Marilie); P.A. Ganz (Patricia A.); S.M. Gapstur (Susan M.); J. Garber (Judy); M.M. Gaudet (Mia); S.A. Gayther (Simon); A-M. Gerdes (Anne-Marie); M. Ghoussaini (Maya); G.G. Giles (Graham); G. Glendon (Gord); A.K. Godwin (Andrew K.); M.S. Goldberg (Mark); D. Goldgar (David); A. González-Neira (Anna); M.H. Greene (Mark H.); J. Gronwald (Jacek); P. Guénel (Pascal); M.J. Gunter (Marc J.); L. Haeberle (Lothar); C.A. Haiman (Christopher A.); U. Hamann (Ute); T.V.O. Hansen (Thomas); S. Hart (Stewart); S. Healey (Sue); T. Heikkinen (Tuomas); B.E. Henderson (Brian); J. Herzog (Josef); F.B.L. Hogervorst (Frans); A. Hollestelle (Antoinette); M.J. Hooning (Maartje); R.N. Hoover (Robert); J.L. Hopper (John); K. Humphreys (Keith); D. Hunter (David); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny N.); C. Isaacs (Claudine); A. Jakubowska (Anna); M. James (Margaret); R. Janavicius (Ramunas); U.B. Jensen; E.M. John (Esther); M. Jones (Michael); M. Kabisch (Maria); S. Kar (Siddhartha); B.Y. Karlan (Beth Y.); S. Khan (Sofia); K.T. Khaw; M.G. Kibriya (Muhammad); J.A. Knight (Julia); Y.-D. Ko (Yon-Dschun); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); A. Kwong (Ava); Y. Laitman (Yael); D. Lambrechts (Diether); C. Lazaro (Conxi); E. Lee (Eunjung); L. Le Marchand (Loic); K.J. Lester (Kathryn); A. Lindblom (Annika); N.M. Lindor (Noralane); S. Lindstrom (Stephen); J. Liu (Jianjun); J. Long (Jirong); J. Lubinski (Jan); P.L. Mai (Phuong); E. Makalic (Enes); K.E. Malone (Kathleen E.); A. Mannermaa (Arto); S. Manoukian (Siranoush); S. Margolin (Sara); F. Marme (Federick); J.W.M. Martens (John); L. McGuffog (Lesley); A. Meindl (Alfons); A. Miller (Austin); R.L. Milne (Roger); P. Miron (Penelope); M. Montagna (Marco); S. Mazoyer (Sylvie); A.-M. Mulligan (Anna-Marie); T.A. Muranen (Taru); K.L. Nathanson (Katherine); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); B.G. Nordestgaard (Børge); R. Nussbaum (Robert); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); A. Osorio (Ana); S.K. Park (Sue K.); P.H.M. Peeters; B. Peissel (Bernard); P. Peterlongo (Paolo); J. Peto (Julian); C. Phelan (Catherine); R. Pilarski (Robert); B. Poppe (Bruce); K. Pykäs (Katri); P. Radice (Paolo); N. Rahman (Nazneen); J. Rantala (Johanna); C. Rappaport (Christine); G. Rennert (Gad); A.L. Richardson (Andrea); M. Robson (Mark); I. Romieu (Isabelle); A. Rudolph (Anja); E.J.T. Rutgers (Emiel); M.-J. Sanchez (Maria-Jose); R. Santella (Regina); E.J. Sawyer (Elinor); D.F. Schmidt (Daniel); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); F.R. Schumacher (Fredrick); R.J. Scott (Rodney); L. Senter (Leigha); P. Sharma (Priyanka); J. Simard (Jacques); C.F. Singer (Christian); O. Sinilnikova (Olga); P. Soucy (Penny); M.C. Southey (Melissa); D. Steinemann (Doris); M. Stenmark-Askmalm (Marie); D. Stoppa-Lyonnet (Dominique); A.J. Swerdlow (Anthony ); C. Szabo (Csilla); R. Tamimi (Rulla); W. Tapper (William); P.J. Teixeira; S.-H. Teo (Soo-Hwang); M.B. Terry (Mary Beth); M. Thomassen (Mads); D. Thompson (Deborah); L. Tihomirova (Laima); A.E. Toland (Amanda); R.A.E.M. Tollenaar (Rob); I.P. Tomlinson (Ian); T. Truong (Thérèse); H. Tsimiklis (Helen); A. Teulé (A.); R. Tumino (Rosario); N. Tung (Nadine); C. Turnbull (Clare); G. Ursin (Giski); C.H.M. van Deurzen (Carolien); E.J. van Rensburg (Elizabeth); R. Varon-Mateeva (Raymonda); Z. Wang (Zhaoming); S. Wang-Gohrke (Shan); E. Weiderpass (Elisabete); J.N. Weitzel (Jeffrey); A.S. Whittemore (Alice S.); H. Wildiers (Hans); R. Winqvist (Robert); X.R. Yang (Xiaohong R.); D. Yannoukakos (Drakoulis); S. Yao (Song); M.P. Zamora (Pilar); W. Zheng (Wei); P. Hall (Per); P. Kraft (Peter); C. Vachon (Celine); S. Slager (Susan); G. Chenevix-Trench (Georgia); P.D.P. Pharoah (Paul); A.A.N. Monteiro (Alvaro A. N.); M. García-Closas (Montserrat); D.F. Easton (Douglas F.); A.C. Antoniou (Antonis C.)

2016-01-01

textabstractCommon variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10-8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative

Cell life and death in the anterior pituitary gland: role of oestrogens.

Science.gov (United States)

Seilicovich, A

2010-07-01

Apoptotic processes play an important role in the maintenance of cell numbers in the anterior pituitary gland during physiological endocrine events. In this review, we summarise the regulation of apoptosis of anterior pituitary cells, particularly lactotrophs, somatotrophs and gonadotrophs, and analyse the possible mechanisms involved in oestrogen-induced apoptosis in anterior pituitary cells. Oestrogens exert apoptotic actions in several cell types and act as modulators of pituitary cell renewal, sensitising cells to both mitogenic and apoptotic signals. Local synthesis of growth factors and cytokines induced by oestradiol as well as changes in phenotypic features that enhance the responsiveness of anterior pituitary cells to pro-apoptotic factors may account for cyclical apoptotic activity in anterior pituitary cells during the oestrous cycle. Considering that tissue homeostasis results from a balance between cell proliferation and death and that mechanisms involved in apoptosis are tightly regulated, defects in cell death processes could have a considerable physiopathological impact.

Novel G Protein-Coupled Oestrogen Receptor GPR30 Shows Changes in mRNA Expression in the Rat Brain over the Oestrous Cycle

Directory of Open Access Journals (Sweden)

Emma J. Spary

2012-02-01

Full Text Available Oestrogen influences autonomic function via actions at classical nuclear oestrogen receptors α and β in the brain, and recent evidence suggests the orphan G protein-coupled receptor GPR30 may also function as a cytoplasmic oestrogen receptor. We investigated the expression of GPR30 in female rat brains throughout the oestrous cycle and after ovariectomy to determine whether GPR30 expression in central autonomic nuclei is correlated with circulating oestrogen levels. In the nucleus of the solitary tract (NTS, ventrolateral medulla (VLM and periaqueductal gray (PAG GPR30 mRNA, quantified by real-time PCR, was increased in proestrus and oestrus. In ovariectomised (OVX rats, expression in NTS and VLM appeared increased compared to metoestrus, but in the hypothalamic paraventricular nucleus and PAG lower mRNA levels were seen in OVX. GPR30-like immunoreactivity (GPR30-LI colocalised with Golgi in neurones in many brain areas associated with autonomic pathways, and analysis of numbers of immunoreactive neurones showed differences consistent with the PCR data. GPR30-LI was found in a variety of transmitter phenotypes, including cholinergic, serotonergic, catecholaminergic and nitrergic neurones in different neuronal groups. These observations support the view that GPR30 could act as a rapid transducer responding to oestrogen levels and thus modulate the activity of central autonomic pathways.

Oestrogen receptors in breast tumours: associations with age, menopausal status and epidemiological and clinical features in 735 patients.

Science.gov (United States)

Elwood, J M; Godolphin, W

1980-11-01

Comparisons between oestrogen-receptor (RE)-positive or negative patients were made on a continuous series of 735 patients with primary breast tumours seen at the major treatment centre in British Columbia between 1975 and 1978. RE positivity was commoner in older patients, and was not associated with menopausal status independently of age. The concentration of receptor protein also increased with increasing age, but was not affected by menopausal status. Neither RE status nor quantity was associated with any of the epidemiological risk factors studied, which included parity, age at first birth, weight, family history and exposure to oestrogenic drugs and oral contraceptives. Patients with RE- tumours were more likely to present with symptoms other than a breast lump, pain or nipple inversion, and had less-differentiated tumours; they did not differ from RE+ patients in terms of stage, size of tumour, or interval from first symptom. These findings are discussed in terms of the biological origin and determinants of oestrogen receptors.

Prediction of in vitro and in vivo oestrogen receptor activity using hierarchical clustering

Science.gov (United States)

In this study, hierarchical clustering classification models were developed to predict in vitro and in vivo oestrogen receptor (ER) activity. Classification models were developed for binding, agonist, and antagonist in vitro ER activity and for mouse in vivo uterotrophic ER bindi...

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

DEFF Research Database (Denmark)

Couch, Fergus J; Kuchenbaecker, Karoline B; Michailidou, Kyriaki

2016-01-01

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci...

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

NARCIS (Netherlands)

Couch, Fergus J; Kuchenbaecker, Karoline B; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomäki, Kristiina; Ambrosone, Christine; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W; Benitez, Javier; Blank, Stephanie V; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S; Caldes, Trinidad; Caligo, Maria A; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J; Chung, Wendy K; Claes, Kathleen B M; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Darabi, Hatef; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M; Eccles, Diana M; Ehrencrona, Hans; Ekici, Arif B; Eliassen, Heather; Ellis, Steve; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Försti, Asta; Fostira, Florentia; Foulkes, William D; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D; Ganz, Patricia A; Gapstur, Susan M; Garber, Judy; Gaudet, Mia M; Gayther, Simon A; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G; Glendon, Gord; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E; Herzog, Josef; Hogervorst, Frans B L; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Humphreys, Keith; Hunter, David J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G; Knight, Julia A; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L; Makalic, Enes; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W M; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M; Muranen, Taru A; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nordestgaard, Børge G; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Osorio, Ana; Park, Sue K; Peeters, Petra H; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M; Pilarski, Robert; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J; Sanchez, Maria-Jose; Santella, Regina M; Sawyer, Elinor J; Schmidt, Daniel F; Schmidt, Marjanka K; Schmutzler, Rita K; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F; Sinilnikova, Olga M; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary B; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Thérèse; Tsimiklis, Helen; Teulé, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; van Deurzen, Carolien H M; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R; Yannoukakos, Drakoulis; Yao, Song; Zamora, M Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D P; Monteiro, Alvaro A N; García-Closas, Montserrat; Easton, Douglas F; Antoniou, Antonis C

2016-01-01

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci,

Oestrogen receptor α gene haplotype and postmenopausal breast cancer risk: a case control study

International Nuclear Information System (INIS)

Wedrén, Sara; Stiger, Fredrik; Persson, Ingemar; Baron, John; Weiderpass, Elisabete; Lovmar, Lovisa; Humphreys, Keith; Magnusson, Cecilia; Melhus, Håkan; Syvänen, Ann-Christine; Kindmark, Andreas; Landegren, Ulf; Fermér, Maria Lagerström

2004-01-01

Oestrogen receptor α, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor α gene (ESR1) are associated with breast cancer risk. We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TA n , 1514 cases and 1514 controls; c.454-397C → T, 1557 cases and 1512 controls; c.454-351A → G, 1556 cases and 1512 controls; c.729C → T, 1562 cases and 1513 controls; c.975C → G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data. There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A → G or c.454-397C → T and c.975C → G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A → G and c.975C → G haplotype entailed an OR of 1.19 (95% CI 1.06–1.33) and two copies with an OR of 1.42 (95% CI 1.15–1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C → T and c.975C → G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant. We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women

Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence with Oestrogen Receptors α and β, and Androgen Receptors

Science.gov (United States)

Stanić, Davor; Dubois, Sydney; Chua, Hui Kheng; Tonge, Bruce; Rinehart, Nicole; Horne, Malcolm K.; Boon, Wah Chin

2014-01-01

Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα−, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females. PMID:24646567

Cytotoxic effects of the synthetic oestrogens and androgens on Balb/c 3T3 and HepG2 cells

Directory of Open Access Journals (Sweden)

Minta Maria

2014-12-01

Full Text Available The aim of the study was to test and compare the cytotoxic potential of two synthetic oestrogens: diethylstilboestrol (DES and ethinyloestradiol (EE2 and two androgens: testosterone propionate (TP and trenbolone (TREN on two cell lines. The fibroblast cell line Balb/c 3T3 and the hepatoma cell line HepG2 were selected. To get more insight into the mode of toxic action, four methods were used, which evaluated different biochemical endpoints: mitochondrial activity (3-(4,5-dimethylthiazol-2-yl- 2,5-diphenyltetrazolium bromide reduction assay, lysosomal activity (neutral red uptake assay, total protein content, and lactate dehydrogenase release. Cytotoxicity was assessed after 24, 48, and 72 h exposure to eight concentrations ranging from 0.78 to 100 μg/mL. Concentration- and time- dependent effects were observed. Depending on the line and assay used, half maximal effective concentration after 72 h (EC50-72h values ranged as follows: DES 1-13.7 μg/mL (Balb/c 3T3 and 3.7-5.2 μg/mL (HepG2; EE2 2.1-14.3 μg/mL (Balb/c 3T3 and 1.8-7.8 μg/mL (HepG2; TP-14.9-17.5 μg/mL (Balb/c 3T3, and 63.9- 100 μg/mL (HepG2; and TREN 11.3-31.4 μg/mL (Balb/c 3T3 and 12.5-59.4 μg/mL (HepG2. The results revealed that oestrogens were more toxic than androgens and the most affected endpoint was mitochondrial activity. In contrast to oestrogens, for which EC50-72h values were similar in both lines and by all assays used, Balb/c 3T3 cells were more sensitive than HepG2 cells to TP.

Partial and weak oestrogenicity of the red wine constituent resveratrol: consideration of its superagonist activity in MCF-7 cells and its suggested cardiovascular protective effects.

Science.gov (United States)

Ashby, J; Tinwell, H; Pennie, W; Brooks, A N; Lefevre, P A; Beresford, N; Sumpter, J P

1999-01-01

It was recently reported that the red wine phytoestrogen resveratrol (RES) acts as a superagonist to oestrogen-responsive MCF-7 cells. This activity of RES was speculated to be relevant to the 'French paradox' in which moderate red wine consumption is reported to yield cardiovascular health benefits to humans. We report here that RES binds to oestrogen receptors (ER) isolated from rat uterus with an affinity approximately 5 orders of magnitude lower than does either the reference synthetic oestrogen diethylstilboestrol (DES) or oestradiol (E2). In comparison with E2 or DES, RES is only a weak and partial agonist in a yeast hER-alpha transcription assay and in cos-1 cell assays employing transient transfections of ER-alpha or ER-beta associated with two different ER-response elements. Resveratrol was also concluded to be inactive in immature rat uterotrophic assays conducted using three daily administrations of 0.03-120 mgkg(-1)/day(-1) RES (administered by either oral gavage or subcutaneous injection). These data weaken the suggestion that the oestrogenicity of RES may account for the reported cardiovascular protective effects of red wine consumption, and they raise questions regarding the extent to which oestrogenicity data derived for a chemical using MCF-7 cells (or any other single in vitro assay) can be used to predict the hormonal effects likely to occur in animals or humans.

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-12-15

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

Sexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent.

Science.gov (United States)

Toogood, A A; Taylor, N F; Shalet, S M; Monson, J P

2000-01-01

The net interconversion of inactive cortisone to active cortisol by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) may determine hepatic and adipose tissue exposure to glucocorticoid action. Cortisol metabolism exhibits a sexual dimorphism with an apparently lower activity of 11betaHSD1 in females that, in an animal model, has been attributed to the effects of oestrogen. The aim of this study is to determine whether the sexual dimorphism of cortisol metabolism persists between post-menopausal, oestrogen-deficient women and elderly men. Fifteen healthy men, aged 60.8-82.0 years, and 7 healthy women, aged 62.4-87.5 years, were studied. None of the subjects was receiving steroid medication at the time of the study. All the women were post-menopausal and none was receiving sex steroid replacement therapy. 24-h urine collections were taken from each patient and assayed for steroid metabolites by gas chromatography. Body composition was determined by dual energy X-ray absorptiometry. Blood was drawn, after an overnight fast, for the determination of serum IGF-I and IGFBP1 levels. The ratio of 11-hydroxy cortisol metabolites to 11-oxo cortisol metabolites (Fm/Em) was significantly higher in men than in women, 0.80 (0.55-1.86) vs. 0.67 (0.46-0.98) (P cortisol and cortisone metabolite (Fm/Em) and total fat mass approached significance, r = - 0.39 (P = 0.07). These relationships were not apparent in the women when considered alone. Among the men there were negative relationships between Fm/Em and total fat mass, r = - 0.48, and Fm/Em and trunk fat mass, r = - 0.48 which approached significance (both P = 0.07). Serum IGFBP-1 levels were not significantly different between the two sexes. There was a significant correlation between IGFBP-1 and Fm/Em in the men, r = 0. 84 (P sexual dimorphism in cortisol metabolism is not dependent on oestrogen, although the possibility that oestrogen exerts a permanent modifying effect on 11beta-HSD1 gene expression during the pre

The integrative role of leptin, oestrogen and the insulin family in obesity-associated breast cancer: potential effects of exercise.

Science.gov (United States)

Schmidt, S; Monk, J M; Robinson, L E; Mourtzakis, M

2015-06-01

Obesity is an established risk factor for postmenopausal breast cancer. The mechanisms through which obesity influences the development and progression of breast cancer are not fully elucidated; however, several factors such as increased oestrogen, concentrations of various members of the insulin family and inflammation that are associated with adiposity are purported to be important factors in this relationship. Emerging research has also begun to focus on the role of adipokines, (i.e. adipocyte secreted factors), in breast cancer. Leptin secretion is directly related to adiposity and is believed to promote breast cancer directly and independently, as well as through involvement with the oestrogen and insulin signalling pathways. As leptin is secreted from white adipose tissue, any intervention that reduces adiposity may be favourable. However, it is also important to consider that energy expenditure through exercise, independent of fat loss, may improve leptin regulation. The purpose of this narrative review was to explore the role of leptin in breast cancer development and progression, identify key interactions with oestrogen and the insulin family, and distinguish the potential effects of exercise on these interactions. © 2015 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity.

Fathers' sensitive parenting and the development of early executive functioning.

Science.gov (United States)

Towe-Goodman, Nissa R; Willoughby, Michael; Blair, Clancy; Gustafsson, Hanna C; Mills-Koonce, W Roger; Cox, Martha J

2014-12-01

Using data from a diverse sample of 620 families residing in rural, predominately low-income communities, this study examined longitudinal links between fathers' sensitive parenting in infancy and toddlerhood and children's early executive functioning, as well as the contribution of maternal sensitive parenting. After accounting for the quality of concurrent and prior parental care, children's early cognitive ability, and other child and family factors, fathers' and mothers' sensitive and supportive parenting during play at 24 months predicted children's executive functioning at 3 years of age. In contrast, paternal parenting quality during play at 7 months did not make an independent contribution above that of maternal care, but the links between maternal sensitive and supportive parenting and executive functioning seemed to operate in similar ways during infancy and toddlerhood. These findings add to prior work on early experience and children's executive functioning, suggesting that both fathers and mothers play a distinct and complementary role in the development of these self-regulatory skills.

Fathers’ Sensitive Parenting and the Development of Early Executive Functioning

Science.gov (United States)

Towe-Goodman, Nissa R.; Willoughby, Michael; Blair, Clancy; Gustafsson, Hanna C.; Mills-Koonce, W. Roger; Cox, Martha J.

2014-01-01

Using data from a diverse sample of 620 families residing in rural, predominately low-income communities, this study examined longitudinal links between fathers’ sensitive parenting in infancy and toddlerhood and children’s early executive functioning, as well as the contribution of maternal sensitive parenting. After accounting for the quality of concurrent and prior parental care, children’s early cognitive ability, and other child and family factors, fathers’ and mothers’ sensitive and supportive parenting during play at 24-months predicted children’s executive functioning at 3-years of age. In contrast, paternal parenting quality during play at 7-months did not make an independent contribution above that of maternal care, but the links between maternal sensitive and supportive parenting and executive functioning seemed to operate in similar ways during infancy and toddlerhood. These findings add to prior work on early experience and children’s executive functioning, suggesting that both fathers and mothers play a distinct and complementary role in the development of these self-regulatory skills. PMID:25347539

The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

NARCIS (Netherlands)

Chakravarty, Dimple; Sboner, Andrea; Nair, Sujit S; Giannopoulou, Eugenia; Li, Ruohan; Hennig, Sven; Mosquera, Juan Miguel; Pauwels, Jonathan; Park, Kyung; Kossai, Myriam; MacDonald, Theresa Y; Fontugne, Jacqueline; Erho, Nicholas; Vergara, Ismael A; Ghadessi, Mercedeh; Davicioni, Elai; Jenkins, Robert B; Palanisamy, Nallasivam; Chen, Zhengming; Nakagawa, Shinichi; Hirose, Tetsuro; Bander, Neil H; Beltran, Himisha; Fox, Archa H; Elemento, Olivier; Rubin, Mark A

2014-01-01

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers,

Oestrogenic activity of a textile industrial wastewater treatment plant effluent evaluated by the E-screen test and MELN gene-reporter luciferase assay

Energy Technology Data Exchange (ETDEWEB)

Schiliro, Tiziana, E-mail: tiziana.schiliro@unito.it [Department of Public Health and Microbiology, University of Torino, Via Santena 5bis, 10126 Torino (Italy); Porfido, Arianna [Department of Public Health and Microbiology, University of Torino, Via Santena 5bis, 10126 Torino (Italy); Spina, Federica; Varese, Giovanna Cristina [Department of Life Sciences and Systems Biology, University of Torino, Viale Mattioli 25, 10125 Torino (Italy); Gilli, Giorgio [Department of Public Health and Microbiology, University of Torino, Via Santena 5bis, 10126 Torino (Italy)

2012-08-15

This study quantified the biological oestrogenic activity in the effluent of a textile industrial wastewater treatment plant (IWWTP) in northwestern Italy. Samples of the IWWTP effluent were collected monthly, both before and after tertiary treatment (ozonation). After solid phase extraction, all samples were subjected to two in vitro tests of total estrogenic activity, the human breast cancer cell line (MCF-7 BUS) proliferation assay, or E-screen test, and the luciferase-transfected human breast cancer cell line (MELN) gene-reporter assay, to measure the 17{beta}-oestradiol equivalent quantity (EEQ). In the E-screen test, the mean EEQ values were 2.35 {+-} 1.68 ng/L pre-ozonation and 0.72 {+-} 0.58 ng/L post-ozonation; in the MELN gene-reporter luciferase assay, the mean EEQ values were 4.18 {+-} 3.54 ng/L pre-ozonation and 2.53 {+-} 2.48 ng/L post-ozonation. These results suggest that the post-ozonation IWWTP effluent had a lower oestrogenic activity (simple paired t-tests, p < 0.05). The average reduction of estrogenic activity of IWWTP effluent after ozonation was 67 {+-} 26% and 52 {+-} 27% as measured by E-screen test and MELN gene-reporter luciferase assay, respectively. There was a positive and significant correlation between the two tests (Rho S = 0.650, p = 0.022). This study indicates that the environmental risk is low because oestrogenic substances are deposited into the river via IWWTP at concentrations lower than those at which chronic exposure has been reported to affect the endocrine system of living organisms. -- Highlights: Black-Right-Pointing-Pointer The two in vitro tests are suited for oestrogenic activity assessment in textile WWTP. Black-Right-Pointing-Pointer There is a significant correlation between the results of the two in vitro tests. Black-Right-Pointing-Pointer The oestrogenic activity of the effluent is reduced by ozonation. Black-Right-Pointing-Pointer The input of estrogenic substances into the river via textile WWTP is low.

Intrauterine and genetic factors in early childhood sensitization

DEFF Research Database (Denmark)

Bønnelykke, Klaus

2010-01-01

The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... and identifying the environmental risk factors interacting with this genetic susceptibility and the age at which intervention should be initiated. We found a FLG-associated pattern of atopic disease in early childhood characterized by early onset of eczema, early onset of asthma with severe exacerbations...... a subtype of disease where skin barrier dysfunction leads to early eczema, early asthma symptoms and later sensitization. Future FLG-targeted research has the potential of improving understanding prevention and treatment of atopic diseases in childhood....

Enzyme immunoassay of oestrogen receptors in needle biopsies from human liver

DEFF Research Database (Denmark)

Becker, U; Andersen, J; Poulsen, H S

1991-01-01

For quantitative assessments of sex hormone receptors in liver tissue, ligand binding assays are inconvenient, as they require large biopsies (0.5-1.0 g). The present study shows that it is possible to measure oestrogen receptors (ER) quantitatively in needle biopsy specimens as small as 10 mg...... by modifications of a commercial enzyme immunoassay employing monoclonal antibodies. Sucrose gradient centrifugation and the dextran charcoal method served as reference methods. A consecutive series of needle biopsies from patients suspected of liver disease were investigated. The biopsies (n = 37) had a median...

Oestrogen receptor beta over expression in males with non-small cell lung cancer is associated with better survival

DEFF Research Database (Denmark)

Skov, Birgit Guldhammer; Sode, Birgitte M Fischer; Pappot, H.

2008-01-01

BACKGROUND: Adenocarcinoma of the lung is more frequent in females than in males and the association with smoking is less pronounced than for the other histological subtypes of lung cancer. Oestrogen induction of cell proliferation has been found in breast adenocarcinomas, and since oestrogen...... the results to gender and survival. METHODS: Paraffin embedded, histological material was collected from 104 patients (71 men and 33 women), operated in the period 1989-1992 for NSCLC (56 squamous cell carcinomas, 40 adenocarcinomas and 8 large cell carcinomas). ERalpha, ERbeta and progesterone were...... and progesterone expression for the prognosis. RESULTS: ERbeta positivity was demonstrated in 69% (72 of 104) of the tumours. There was no statistically significant correlation between ERbeta positivity and age, gender, stage, or histology. After adjusting for gender, age, stage at diagnosis and histology...

Normal variation in early parental sensitivity predicts child structural brain development.

Science.gov (United States)

Kok, Rianne; Thijssen, Sandra; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Verhulst, Frank C; White, Tonya; van IJzendoorn, Marinus H; Tiemeier, Henning

2015-10-01

Early caregiving can have an impact on brain structure and function in children. The influence of extreme caregiving experiences has been demonstrated, but studies on the influence of normal variation in parenting quality are scarce. Moreover, no studies to date have included the role of both maternal and paternal sensitivity in child brain maturation. This study examined the prospective relation between mothers' and fathers' sensitive caregiving in early childhood and brain structure later in childhood. Participants were enrolled in a population-based prenatal cohort. For 191 families, maternal and paternal sensitivity was repeatedly observed when the child was between 1 year and 4 years of age. Head circumference was assessed at 6 weeks, and brain structure was assessed using magnetic resonance imaging (MRI) measurements at 8 years of age. Higher levels of parental sensitivity in early childhood were associated with larger total brain volume (adjusted β = 0.15, p = .01) and gray matter volume (adjusted β = 0.16, p = .01) at 8 years, controlling for infant head size. Higher levels of maternal sensitivity in early childhood were associated with a larger gray matter volume (adjusted β = 0.13, p = .04) at 8 years, independent of infant head circumference. Associations with maternal versus paternal sensitivity were not significantly different. Normal variation in caregiving quality is related to markers of more optimal brain development in children. The results illustrate the important role of both mothers and fathers in child brain development. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Sensitive endpoints in extended one-generation reproductive toxicity study versus two generation?

DEFF Research Database (Denmark)

Christiansen, Sofie

. The protocol includes assessment of novel endpoints of concern and developmental landmarks such as anogenital distance, nipple retention (both sensitive endpoints for anti-androgenic effects in male offspring) and mammary gland development (sensitive endpoint for oestrogen action) and may also include...... during critical period of development in contrast to the parental generation. Retrospective analysis of available two-generation studies, however, indicate that the assessment included in the study of other endpoints in the male offspring such as histopathology of reproductive organs and semen quality...

Synthesis of DNA in oestrogen-induced pituitary tumurs in rats: effect of bromocriptine.

Science.gov (United States)

Kalbermann, L E; Machiavelli, G A; De Nicola, A F; Weissenberg, L S; Burdman, J A

1980-11-01

Bromocriptine increased the concentration of prolactin in oestrogen-induced tumours of the rat pituitary gland. Prolactinaemia was significantly reduced and at the same time there was a considerable decrease in the weight of the tumour, in the incorporation of tritiated thymidine into DNA and in the activity of DNA polymerase alpha. The results suggested that the intracellular content of prolactin controls cell proliferation in this experimental tumour. A hypothalamic disorder is proposed as the primary cause of these tumours.

Effects of sewage effluent and ethynyl oestradiol upon molecular markers of oestrogenic exposure, maturation and reproductive success in the sand goby (Pomatoschistus minutus, Pallas)

International Nuclear Information System (INIS)

Robinson, Craig D.; Brown, Elaine; Craft, John A.; Davies, Ian M.; Moffat, Colin F.; Pirie, David; Robertson, Fiona; Stagg, Ronald M.; Struthers, Susan

2003-01-01

Male fish in several UK estuaries are known to be exposed to oestrogenic contamination, and whilst a limited number of studies have shown that exposure to oestrogens can reduce the reproductive success of fish, the impact of environmentally relevant exposures is less clear. The aim of this study was, therefore, to investigate the effects of exposure to environmentally realistic concentrations of a sewage effluent and the synthetic oestrogen 17α-ethynyl oestradiol (EE 2 ) upon the reproductive success of a marine fish. Sand goby (Pomatoschistus minutus) were exposed for 7 months to EE 2 or a sewage effluent containing known xeno-oestrogens (alkylphenol polyethoxylates) and bred using within treatment crosses. Nominal exposure concentrations were 6 ng l -1 EE 2 , 0.3 or 0.03% v/v sewage effluent. At the end of the breeding trials, expression of hepatic zona radiata protein (Zrp) and vitellogenin (Vtg) mRNA were determined using two recently developed cDNA probes. Exposure to 6 ng l -1 EE 2 induced Zrp and Vtg mRNA expression in male and female sand goby, impaired male maturation and reproductive behaviour, reduced female fecundity and reduced egg fertility. As a consequence, fertile egg production of the EE 2 -exposed population was reduced by 90%. Exposure to sewage effluent (0.3% v/v) increased adult mortality and female Zrp and Vtg mRNA expression, but did not induce male vitellogenesis. Exposure to EE 2 and 0.3% v/v sewage effluent impaired development of the male urogenital papilla. Fish exposed to 0.03% v/v sewage effluent produced more fertile eggs than those exposed to 0.3% effluent, or those receiving no effluent. It is concluded that male vitellogenesis in an oestrogenically exposed population may be accompanied by reduced reproductive success, but that it may not be indicative of altered reproductive output in a population exposed to an industrial sewage effluent

Phyto-oestrogens in herbage and milk from cows grazing whiteclover, red clover, lucerne or chicory-rich pastures

DEFF Research Database (Denmark)

Andersen, C; Nielsen, T S; Purup, S

2009-01-01

A grazing experiment was carried out to study the concentration of phyto-oestrogens in herbage for cattle and in milk during two periods (May and June). Forty-eight Danish Holstein cows were divided into four groups with four treatment diets; white clover, red clover, lucerne and chicory-rich pas...

Biodistribution and dosimetry of iodine-123-labelled Z-MIVE: an oestrogen receptor radioligand for breast cancer imaging

NARCIS (Netherlands)

Rijks, L. J.; Busemann Sokole, E.; Stabin, M. G.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.

1998-01-01

This study reports on the distribution and radiation dosimetry of iodine-123-labelled cis-11beta-methoxy-17alpha-iodovinyloestradiol (Z-[123I]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 24 h after intravenous

The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice.

Science.gov (United States)

Wehrle, Esther; Liedert, Astrid; Heilmann, Aline; Wehner, Tim; Bindl, Ronny; Fischer, Lena; Haffner-Luntzer, Melanie; Jakob, Franz; Schinke, Thorsten; Amling, Michael; Ignatius, Anita

2015-01-01

Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 G: peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (-81%) and bone formation (-80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in

The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice

Directory of Open Access Journals (Sweden)

Esther Wehrle

2015-01-01

Full Text Available Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV. We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96 were either ovariectomised (OVX or sham operated (non-OVX at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day with 0.3 g peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine were evaluated using bending-testing, micro-computed tomography (μCT, histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (−81% and bone formation (−80% in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2 and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398% and bone formation (+637%, which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet. On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and

Histomorphometric analysis and immunolocalization of RANKL and OPG during the alveolar healing process in female ovariectomized rats treated with oestrogen or raloxifene.

Science.gov (United States)

Luvizuto, Eloá Rodrigues; Queiroz, Thallita Pereira; Dias, Sheila Mônica Damásio; Okamoto, Tetuo; Dornelles, Rita Cássia Menegati; Garcia, Idelmo Rangel; Okamoto, Roberta

2010-01-01

To investigate the effects of bone-resorption inhibitors (oestrogen and raloxifene) on the RANKL/OPG balance during the chronology of the alveolar healing process in ovariectomized (OVX) rats by means of immunocolocalization and histomorphometric analysis. One hundred sixty female Wistar rats at 70 days of age were either OVX or sham-operated and divided into four groups: sham, OVX/Oil, OVX with E(2) replacement (17beta-estradiol, 400 microg/month), OVX with RLX treatment (1mg/kg bw/day). The 60-day treatment started 8 days after ovariectomy. The incisors were extracted to allow analysis of 7, 14, 21, 28 and 42 days of wound healing. After obtaining the histological samples, slides were stained with hematoxylin and eosin or subjected to immunocolocalization reaction for RANKL and OPG. Results were quantitatively evaluated. Histomorphometric analysis showed that the sham group presented the highest and OVX/Oil group the lowest mean bone formation value in the post-extraction period. The immunocolocalization analysis showed a larger increase in bone turnover at 7 postoperative days in OVX/Oil and sham groups and decreasing bone turnover in the other periods. The OVX/Oil group showed a large decrease in bone turnover at 14 postoperative days, a period demonstrated by mild cellular activity. OVX/E(2) and sham groups showed a decreased bone turnover at 28 postoperative days while OVX/RLX group showed a decreased bone turnover at 21 postoperative days. On the 42nd postoperative day, sham and OVX/RLX groups showed an established alveolar bone healing process. Ovariectomy delays the alveolar healing process and interferes with bone turnover through the balance between RANKL and OPG. Oestrogen replacement or raloxifene treatment did not totally recover the oestrogen-deficient state. However raloxifene treatment showed more satisfactory results than oestrogen replacement. Copyright 2009 Elsevier Ltd. All rights reserved.

Examining Appearance-Based Rejection Sensitivity during Early Adolescence

Science.gov (United States)

Bowker, Julie C.; Thomas, Katelyn K.; Spencer, Sarah V.; Park, Lora E.

2013-01-01

The present study of 150 adolescents ("M" age = 13.05 years) examined the associations between appearance-based rejection sensitivity (Appearance-RS) and psychological adjustment during early adolescence, and evaluated three types of other-gender peer experiences (other-gender friendship, peer acceptance, and romantic relationships) as…

Menstrual phase-related differences in the pulsatility index on the central retinal artery suggest an oestrogen vasodilatation effect that antagonizes with progesterone.

Science.gov (United States)

Viana, Luiz Carlos; Faria, Marcos; Pettersen, Heverton; Sampaio, Marcos; Geber, Selmo

2011-03-01

The actual effect of steroid hormones on cerebral microcirculation is still controversial. Therefore, the aim of our study was to investigate vascular flow variations in the central retinal artery that may exist during the ovulatory menstrual cycle. A total of 34 healthy women were included in this observational, longitudinal, and prospective study. All participants were submitted to dopplerfluxometric evaluation of the eyes in order to study the pulsatility index (PI) of the central retinal arteries, during four phases of the menstrual cycle: early follicular, mid follicular, periovulatory, and mid luteal phases. Subjects' ages ranged from 14 to 47 years old (mean: 29.7 ± 10.1) and PI did not differ among age groups. The PI of the central retinal artery was different among the four phases of the menstrual cycle. PI showed a significant decrease from early follicular phase (1.72) to mid follicular phase (1.57) (p = 0.037), and was similar during periovulatory phase (1.56) and significantly increased in mid luteal phase (1.70). After that it returned to the values observed in the early follicular phase. Our results suggest the existence of an oestrogen vasodilatation effect on the central retinal artery that is menstrual phase-related and antagonized by progesterone.

Increasing Early Childhood Preservice Teachers' Intercultural Sensitivity through the ABCs

Science.gov (United States)

Monroe, Lisa; Ruan, Jiening

2018-01-01

While the early childhood student population has become increasingly diverse in the U.S., its teaching force remains primarily European American. The diverse student population demands that early childhood educators possess intercultural sensitivity in order to teach their culturally diverse learners effectively. This study examined the…

Sensitivity of a Clinical Decision Rule and Early Computed Tomography in Aneurysmal Subarachnoid Hemorrhage

Directory of Open Access Journals (Sweden)

Dustin G. Mark

2015-10-01

Full Text Available Introduction: Application of a clinical decision rule for subarachnoid hemorrhage, in combination with cranial computed tomography (CT performed within six hours of ictus (early cranial CT, may be able to reasonably exclude a diagnosis of aneurysmal subarachnoid hemorrhage (aSAH. This study’s objective was to examine the sensitivity of both early cranial CT and a previously validated clinical decision rule among emergency department (ED patients with aSAH and a normal mental status. Methods: Patients were evaluated in the 21 EDs of an integrated health delivery system between January 2007 and June 2013. We identified by chart review a retrospective cohort of patients diagnosed with aSAH in the setting of a normal mental status and performance of early cranial CT. Variables comprising the SAH clinical decision rule (age >40, presence of neck pain or stiffness, headache onset with exertion, loss of consciousness at headache onset were abstracted from the chart and assessed for inter-rater reliability. Results: One hundred fifty-five patients with aSAH met study inclusion criteria. The sensitivity of early cranial CT was 95.5% (95% CI [90.9-98.2]. The sensitivity of the SAH clinical decision rule was also 95.5% (95% CI [90.9-98.2]. Since all false negative cases for each diagnostic modality were mutually independent, the combined use of both early cranial CT and the clinical decision rule improved sensitivity to 100% (95% CI [97.6-100.0]. Conclusion: Neither early cranial CT nor the SAH clinical decision rule demonstrated ideal sensitivity for aSAH in this retrospective cohort. However, the combination of both strategies might optimize sensitivity for this life-threatening disease.

Visual Contrast Sensitivity in Early-Stage Parkinson's Disease.

Science.gov (United States)

Ming, Wendy; Palidis, Dimitrios J; Spering, Miriam; McKeown, Martin J

2016-10-01

Visual impairments are frequent in Parkinson's disease (PD) and impact normal functioning in daily activities. Visual contrast sensitivity is a powerful nonmotor sign for discriminating PD patients from controls. However, it is usually assessed with static visual stimuli. Here we examined the interaction between perception and eye movements in static and dynamic contrast sensitivity tasks in a cohort of mildly impaired, early-stage PD patients. Patients (n = 13) and healthy age-matched controls (n = 12) viewed stimuli of various spatial frequencies (0-8 cyc/deg) and speeds (0°/s, 10°/s, 30°/s) on a computer monitor. Detection thresholds were determined by asking participants to adjust luminance contrast until they could just barely see the stimulus. Eye position was recorded with a video-based eye tracker. Patients' static contrast sensitivity was impaired in the intermediate spatial-frequency range and this impairment correlated with fixational instability. However, dynamic contrast sensitivity and patients' smooth pursuit were relatively normal. An independent component analysis revealed contrast sensitivity profiles differentiating patients and controls. Our study simultaneously assesses perceptual contrast sensitivity and eye movements in PD, revealing a possible link between fixational instability and perceptual deficits. Spatiotemporal contrast sensitivity profiles may represent an easily measurable metric as a component of a broader combined biometric for nonmotor features observed in PD.

Early-life sensitization to hen's egg predicts asthma and rhinoconjunctivitis at 14 years of age

DEFF Research Database (Denmark)

Christiansen, Elisabeth Soegaard; Kjaer, Henrik Fomsgaard; Eller, Esben

2017-01-01

to groups of and to individual allergens and asthma and RC at 6 and 14 years compared to a reference group with no sensitization. RESULTS: Both transient and persistent early-life sensitization to cow's milk or hen's egg proteins were associated with asthma (aOR 3.99(1.41-11.32) and 5.95(1.78-19.92)) and RC...... (aOR 2.94(1.19-7.28) and 6.18(1.86-20.53)) at 14 years, this association being driven mainly by sensitization to hen's egg. Transient early-life sensitization to HDM had increased risk of asthma (aOR 3.80(1.17-12.41)) at 14 years. CONCLUSIONS: Early transient and persistent IgE sensitization to hen......'s egg was associated with asthma and RC at 14 years. Furthermore, sensitization to HDM was associated with asthma at 14 years. This article is protected by copyright. All rights reserved....

Sensitivity to selected contaminants in a biological early warning ...

African Journals Online (AJOL)

Several early warning systems for the monitoring of water quality are based on the assessment of valve opening/closing in bivalves. Tests were conducted to assess the sensitivity of the mussel Anodonta woodiana, installed on the Mosselmonitor, to seven contaminants and evaluate the usefulness of these sensors for ...

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

Science.gov (United States)

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

2014-12-01

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

Changes in serum somatomedin and growth hormone concentrations after 3 weeks oestrogen substitution in post-menopausal women; a pilot study

NARCIS (Netherlands)

Duursma, S. A.; Bijlsma, J. W.; van Paassen, H. C.; van Buul-Offers, S. C.; Skottner-Lundin, A.

1984-01-01

Oestrogens have a preventive effect on bone loss in post-menopausal women; however, little is known about their mechanism of action. The aim of this study was to investigate the changes in somatomedins (SM) and growth hormone (GH) concentrations in serum in post-menopausal women after 3 weeks of

Sensitive Situations. The DLM Early Childhood Program Professional Library.

Science.gov (United States)

Schiller, Pam

Teachers know how to educate young children, but many feel ill-prepared when faced with students' emotional issues in the classroom. This book is intended as a resource for early childhood teachers who find themselves in the middle of such "sensitive situations." The information is presented by using a fictional, but typical, scenario…

Multiresidue analysis of oestrogenic compounds in cow, goat, sheep and human milk using core-shell polydopamine coated magnetic nanoparticles as extraction sorbent in micro-dispersive solid-phase extraction followed by ultra-high-performance liquid chromatography tandem mass spectrometry.

Science.gov (United States)

Socas-Rodríguez, Bárbara; Hernández-Borges, Javier; Herrera-Herrera, Antonio V; Rodríguez-Delgado, Miguel Ángel

2018-03-01

In this work, the suitability of Fe 3 O 4 nanoparticles coated with polydopamine was evaluated as sorbent for the extraction of a group of 21 compounds with oestrogenic activity including seven phytoestrogens, six mycotoxins as well as four synthetic and four natural oestrogens from different types of milk, including sheep milk, in which the evaluation of oestrogenic compounds have never been developed before. Extraction was carried out using magnetic micro-dispersive solid-phase extraction after a previous deproteinisation step. Separation, determination and quantification of the target analytes were achieved by ultra-high-performance liquid chromatography coupled to triple quadrupole-tandem mass spectrometry. The methodology was validated for five milk samples using 17β-estradiol-2,4,16,16,17-d 5 as internal standard for natural and synthetic oestrogens, β-zearalanol-10,10,11,12,12-d 5 for mycotoxins and prunetin for phytoestrogens. Recovery values ranged from 70 to 120% for the five types of matrices with relative standard deviation values lower than 18%. Limits of quantification of the method were in the range 0.55-11.8 μg L -1 for all samples. Graphical abstract General scheme of the multiresidue analysis of oestrogenic compounds in milk using core-shell polydopamine coated magnetic nanoparticles as extraction sorbent in μ-dSPE.

Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women

DEFF Research Database (Denmark)

Cassidy, A.; Albertazzi, P.; Nielsen, I. L.

2006-01-01

or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were...... to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus...... on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health....

Endocrine sensitivity of the receptor-positive T61 human breast carcinoma serially grown in nude mice

DEFF Research Database (Denmark)

Brünner, N; Spang-Thomsen, M; Skovgaard Poulsen, H

1985-01-01

A study was made on the effect of ovariectomy, 17 beta-oestradiol, and tamoxifen on the oestrogen and progesterone receptor-positive T61 human breast carcinoma grown in nude mice. The effect of the treatment was evaluated by the specific growth delay calculated on the basis of Gompertz growth cur...... but is not a sufficiently clear marker to allow prediction of the endocrine sensitivity of individual breast tumours....

Inverse antagonist activities of parabens on human oestrogen-related receptor γ (ERRγ): In vitro and in silico studies

International Nuclear Information System (INIS)

Zhang, Zhaobin; Sun, Libei; Hu, Ying; Jiao, Jian; Hu, Jianying

2013-01-01

Parabens are p-hydroxybenzoic acid esters that have been used extensively as preservatives in foods, cosmetics, drugs and toiletries. These intact esters are commonly detected in human breast cancer tissues and other human samples, thus arousing concern about the involvement of parabens in human breast cancer. In this study, an in vitro nuclear receptor coactivator recruiting assay was developed and used to evaluate the binding activities of parabens, salicylates and benzoates via antagonist competitive binding on the human oestrogen-related receptor γ (ERRγ), which is known as both a diagnostic biomarker and a treatment target of breast cancer. The results showed that all of the test parabens (methyl-, ethyl-, propyl-, butyl- and benzylparaben) possessed clear inverse antagonist activities on ERRγ, with a lowest observed effect level (LOEL) of 10 −7 M and the 50% relative effective concentrations (REC50) varying from 3.09 × 10 −7 to 5.88 × 10 −7 M, whereas the salicylates possessed much lower activities and the benzoates showed no obvious activity. In silico molecular docking analyses showed that parabens fitted well into the active site of ERRγ, with hydrogen bonds forming between the p-hydroxyl group of parabens and the Glu275/Arg316 of ERRγ. As the paraben levels reported in breast cancer tissues are commonly higher than the LOELs observed in this study, parabens may play some role via ERRγ in the carcinogenesis of human breast cancer. In addition, parabens may have significant effects on breast cancer patients who are taking tamoxifen, as ERRγ is regarded as a treatment target for tamoxifen. - Highlights: • An oestrogen-related receptor γ coactivator recruiting assay was developed. • Strong binding activities of parabens with oestrogen-related receptor γ were found. • The paraben levels reported in breast cancer tissues were higher than their LOELs. • Parabens may play some role via ERRγ in the carcinogenesis of human breast cancer. �

Effect of PREDICT on chemotherapy/trastuzumab recommendations in HER2-positive patients with early-stage breast cancer

OpenAIRE

DOWN, SUE K.; LUCAS, OLIVIA; BENSON, JOHN R.; WISHART, GORDON C.

2014-01-01

PREDICT is an online prognostication tool for early-stage breast cancer, which incorporates human epidermal growth factor 2 (HER2) status and stratifies absolute treatment benefits for hormone therapy, chemotherapy and trastuzumab. The present study compared historical multidisciplinary team (MDT) decisions regarding adjuvant treatment with PREDICT estimates, to determine whether certain patients are being over- or undertreated, particularly when stratified by age and oestrogen-receptor (ER) ...

Chalkley estimates of angiogenesis in early breast cancer--relevance to prognosis

DEFF Research Database (Denmark)

Offersen, Birgitte V; Sørensen, Flemming Brandt; Yilmaz, Mette

2002-01-01

The aim of this study was to investigate whether Chalkley estimates of angiogenesis add new knowledge regarding prediction of prognosis in 455 consecutive early breast carcinomas, both node-positive (52%) and node-negative (48%). Median follow-up was 101 months. Intense vascularization indicated......, high malignancy grade, negative oestrogen receptor, and increasing Chalkley counts (both tertiles and continuous) were independent markers of disease-specific death. Thus, in a univariate analysis it was found that high Chalkley estimates of angiogenesis indicated a poor prognosis, but high Chalkley...

Oestrogen receptors, nodes and stage as predictors of post-recurrence survival in 457 breast cancer patients.

Science.gov (United States)

Shek, L L; Godolphin, W; Spinelli, J J

1987-12-01

The relationship to survival after first recurrence of oestrogen receptor (ER), nodal status and TNM stage at diagnosis, and treatment for advanced disease was studied in 457 females whose primary breast cancer was diagnosed in 1975 to 1981. Receptor concentration was the most important predictor of post-recurrence survival, with some additional information conveyed by nodal status. ER predicted survival after recurrence independently of nodal status, clinical stage or mode of therapy. Response to endocrine therapy is only a facet of the generally favourable prognosis of ER positive patients, rather than the sole explanation.

Effects of ovarian steroids upon responses mediated by adrenoceptors in separated layers of the myometrium and in the costo-uterine muscle of the guinea-pig

Science.gov (United States)

Hartley, Margaret L.; Pennefather, Jocelyn N.; Story, Margot E.

1983-01-01

1 This study describes the effects of ovarian steroid hormones upon the responses to adrenoceptor agonists of isolated myometrium, separated into its longitudinal and circular layers, and of costo-uterine muscle from guinea-pigs. The preparations were field-stimulated at 100 s intervals, and the adrenoceptor agonists phenylephrine and isoprenaline produced enhancement or inhibition of the evoked contractions. 2 Isoprenaline produced propranolol-sensitive inhibitory effects in longitudinal and circular myometrium and costo-uterine muscle preparations from animals from all experimental groups: i.e. from nonsteroid-treated animals (ovariectomized and intact); intact animals treated with either oestrogen or progesterone alone; ovariectomized animals treated with oestrogen; ovariectomized and intact animals treated with progesterone following oestrogen priming; and from animals 1-4 days post-partum. Longitudinal myometrial preparations from progesterone-treated oestrogen-primed and from post-partum animals were most sensitive to this agonist. 3 Phenylephrine produced phentolamine-sensitive excitatory effects in circular myometrial and costo-uterine muscle preparations from animals from all the experimental groups. In contrast, propranolol-sensitive inhibitory responses to phenylephrine occurred in longitudinal myometrial preparations taken from animals treated with progesterone following oestrogen priming, and from post-partum animals. Longitudinal myometrium from animals from the remaining experimental groups exhibited phentolamine-sensitive excitatory responses to phenylephrine. 4 The basis for the selective effect upon the longitudinal myometrium of exposure to progesterone following a period of oestrogen priming, is discussed. The results described are consistent with the possibility that in the longitudinal layer of guinea-pig uterus exposed to progesterone following oestrogen priming there is an increase in the proportion of β-adrenoceptors in this layer. This

Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

Science.gov (United States)

Lagergren, Katarina; Ek, Weronica E; Levine, David; Chow, Wong-Ho; Bernstein, Leslie; Casson, Alan G; Risch, Harvey A; Shaheen, Nicholas J; Bird, Nigel C; Reid, Brian J; Corley, Douglas A; Hardie, Laura J; Wu, Anna H; Fitzgerald, Rebecca C; Pharoah, Paul; Caldas, Carlos; Romero, Yvonne; Vaughan, Thomas L; MacGregor, Stuart; Whiteman, David; Westberg, Lars; Nyren, Olof; Lagergren, Jesper

2015-01-01

The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

Directory of Open Access Journals (Sweden)

Katarina Lagergren

Full Text Available The strong male predominance in oesophageal adenocarcinoma (OAC and Barrett's oesophagus (BO continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute.This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1, receptor beta (ESR2, and aromatase (CYP19A1, and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR, oxytocin protein (OXT, and cyclic ADP ribose hydrolase glycoprotein (CD38, were analysed using a gene-based approach, versatile gene-based test association study (VEGAS.Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058 and an increased risk of OAC and BO combined in males (p = 0.0023. Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035 and in males (p = 0.0012. We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only.Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

Confidence interval estimation of the difference between two sensitivities to the early disease stage.

Science.gov (United States)

Dong, Tuochuan; Kang, Le; Hutson, Alan; Xiong, Chengjie; Tian, Lili

2014-03-01

Although most of the statistical methods for diagnostic studies focus on disease processes with binary disease status, many diseases can be naturally classified into three ordinal diagnostic categories, that is normal, early stage, and fully diseased. For such diseases, the volume under the ROC surface (VUS) is the most commonly used index of diagnostic accuracy. Because the early disease stage is most likely the optimal time window for therapeutic intervention, the sensitivity to the early diseased stage has been suggested as another diagnostic measure. For the purpose of comparing the diagnostic abilities on early disease detection between two markers, it is of interest to estimate the confidence interval of the difference between sensitivities to the early diseased stage. In this paper, we present both parametric and non-parametric methods for this purpose. An extensive simulation study is carried out for a variety of settings for the purpose of evaluating and comparing the performance of the proposed methods. A real example of Alzheimer's disease (AD) is analyzed using the proposed approaches. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Parenting Supports for Early Vocabulary Development: Specific Effects of Sensitivity and Stimulation through Infancy

Science.gov (United States)

Vallotton, Claire; Mastergeorge, Ann; Foster, Tricia; Decker, Kalli B.; Ayoub, Catherine

2016-01-01

Growing recognition of disparities in early childhood language environments prompt examination of parent-child interactions which support vocabulary. Research links parental sensitivity and cognitive stimulation to child language, but has not explicitly contrasted their effects, nor examined how effects may change over time. We examined maternal sensitivity and stimulation throughout infancy using two observational methods – ratings of parents’ interaction qualities, and coding of discrete parenting behaviors - to assess the relative importance of these qualities to child vocabulary over time, and determine whether mothers make related changes in response to children’s development. Participants were 146 infants and mothers, assessed when infants were 14, 24, and 36 months. At 14 months, sensitivity had a stronger effect on vocabulary than did stimulation, but the effect of stimulation grew throughout toddlerhood. Mothers’ cognitive stimulation grew over time, whereas sensitivity remained stable. While discrete parenting behaviors changed with child age, there was no evidence of trade-offs between sensitive and stimulating behaviors, and no evidence that sensitivity moderated the effect of stimulation on child vocabulary. Findings demonstrate specificity of timing in the link between parenting qualities and child vocabulary which could inform early parent interventions, and supports a reconceptualization of the nature and measurement of parental sensitivity. PMID:28111526

Exposure to 17β-Oestradiol Induces Oxidative Stress in the Non-Oestrogen Receptor Invertebrate Species Eisenia fetida.

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Zbynek Heger

Full Text Available The environmental impacts of various substances on all levels of organisms are under investigation. Among these substances, endocrine-disrupting compounds (EDCs present a threat, although the environmental significance of these compounds remains largely unknown. To shed some light on this field, we assessed the effects of 17β-oestradiol on the growth, reproduction and formation of free radicals in Eisenia fetida.Although the observed effects on growth and survival were relatively weak, a strong impact on reproduction was observed (50.70% inhibition in 100 μg/kg of E2. We further demonstrated that the exposure of the earthworm Eisenia fetida to a contaminant of emerging concern, 17β-oestradiol (E2, significantly affected the molecules involved in antioxidant defence. Exposure to E2 results in the production of reactive oxygen species (ROS and the stimulation of antioxidant systems (metallothionein and reduced oxidized glutathione ratio but not phytochelatins at both the mRNA and translated protein levels. Matrix-assisted laser desorption/ionization (MALDI-imaging revealed the subcuticular bioaccumulation of oestradiol-3,4-quinone, altering the levels of local antioxidants in a time-dependent manner.The present study illustrates that although most invertebrates do not possess oestrogen receptors, these organisms can be affected by oestrogen hormones, likely reflecting free diffusion into the cellular microenvironment with subsequent degradation to molecules that undergo redox cycling, producing ROS, thereby increasing environmental contamination that also perilously affects keystone animals, forming lower trophic levels.

Maternal sensitivity and mental health: does an early childhood intervention programme have an impact?

Science.gov (United States)

Brahm, Paulina; Cortázar, Alejandra; Fillol, María Paz; Mingo, María Verónica; Vielma, Constanza; Aránguiz, María Consuelo

2016-06-01

Maternal sensitivity (MS) and mental health influence mother-child attachment and the child's mental health. Early interventions may promote resilience and facilitate healthy development of the children through an impact on mothers' outcomes such as their sensitivity and mental health. Play with Our Children (POC) is an early intervention programme aiming to promote a positive mother-child interaction for children who attend three family health centres of deprived areas of Santiago de Chile. To estimate the effect of the programme POC on MS and mental health. A quasi-experimental design with propensity score matching estimations was employed. MS was measured with the Q-Sort of Maternal Sensitivity, and maternal mental health was assessed with the Patient Health Questionnaire and the Parenting Stress Index. Mean-difference comparison and difference-in-difference method were used as statistical strategies. The sample included 102 children from 2 to 23 months of age, 54 of them participated in the intervention and 48 children were the comparison group. Estimates showed that participation in POC was positively associated with less stress in mothers of children younger than 12 months (P early intervention POC may influence mother's mental health and indirectly impact children's well-being during critical stages of their development by strengthening their mother's sensitivity towards them. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.

Science.gov (United States)

Ribas, Ricardo; Pancholi, Sunil; Rani, Aradhana; Schuster, Eugene; Guest, Stephanie K; Nikitorowicz-Buniak, Joanna; Simigdala, Nikiana; Thornhill, Allan; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dowsett, Mitch; Johnston, Stephen R; Martin, Lesley-Ann

2018-06-08

Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER + ) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. A panel of ER + BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1 wt or ESR1 Y537S , modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER

The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats

International Nuclear Information System (INIS)

Wang, Chao; Luo, Fei; Zhou, Ying; Du, Xiaoling; Shi, Jiandang; Zhao, Xiaoling; Xu, Yong; Zhu, Yan; Hong, Wei; Zhang, Ju

2016-01-01

Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3 polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti-inflammatory and tumour-growth inhibitory effects. Here, the therapeutic potential of DHA in treating BPH was investigated. Seal oil effectively prevented the development of prostatic hyperplasia induced by oestradiol/testosterone in a rat model by suppressing the increase of the prostatic index (PI), reducing the thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation of both prostate epithelial and stromal cells, and downregulating the expression of androgen receptor (AR) and oestrogen receptor α (ERα). An in vitro study showed that DHA inhibited the growth of the human prostate stromal cell line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In addition, DHA also reduced the expression of ERα and AR in the WPMY-1 and RWPE-1 cells. These results indicate that DHA inhibits the multiplication of prostate stromal and epithelial cells through a mechanism that may involve cell cycle arrest and the downregulation of ERα and AR expression. - Highlights: • Seal oil prevents oestradiol/testosterone (E2/T)-induced BPH in castrated rats. • Seal oil downregulates the expression of oestrogen receptor α(ERα) and androgen receptor (AR) in rat BPH tissues. • DHA inhibits the growth of human prostate stromal and epithelial cells in vitro. • DHA arrests human prostate stromal and epithelial cells in the G2/M phase and downregulates the expression of cyclin B1. • DHA inhibits the expression of ERα and AR in human prostate stromal and epithelial cells.

The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats

Energy Technology Data Exchange (ETDEWEB)

Wang, Chao [Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071 (China); Luo, Fei [Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211 (China); Zhou, Ying; Du, Xiaoling; Shi, Jiandang; Zhao, Xiaoling [Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071 (China); Xu, Yong [Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211 (China); Zhu, Yan [Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193 (China); Hong, Wei, E-mail: hongwei@tijmu.edu.cn [Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070 (China); Zhang, Ju, E-mail: zhangju@nankai.edu.cn [Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071 (China)

2016-07-15

Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3 polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti-inflammatory and tumour-growth inhibitory effects. Here, the therapeutic potential of DHA in treating BPH was investigated. Seal oil effectively prevented the development of prostatic hyperplasia induced by oestradiol/testosterone in a rat model by suppressing the increase of the prostatic index (PI), reducing the thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation of both prostate epithelial and stromal cells, and downregulating the expression of androgen receptor (AR) and oestrogen receptor α (ERα). An in vitro study showed that DHA inhibited the growth of the human prostate stromal cell line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In addition, DHA also reduced the expression of ERα and AR in the WPMY-1 and RWPE-1 cells. These results indicate that DHA inhibits the multiplication of prostate stromal and epithelial cells through a mechanism that may involve cell cycle arrest and the downregulation of ERα and AR expression. - Highlights: • Seal oil prevents oestradiol/testosterone (E2/T)-induced BPH in castrated rats. • Seal oil downregulates the expression of oestrogen receptor α(ERα) and androgen receptor (AR) in rat BPH tissues. • DHA inhibits the growth of human prostate stromal and epithelial cells in vitro. • DHA arrests human prostate stromal and epithelial cells in the G2/M phase and downregulates the expression of cyclin B1. • DHA inhibits the expression of ERα and AR in human prostate stromal and epithelial cells.

Diet Quality throughout Early Life in Relation to Allergic Sensitization and Atopic Diseases in Childhood

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Anh N. Nguyen

2017-08-01

Full Text Available Early-life nutrition is an important modifiable determinant in the development of a child’s immune system, and may thereby influence the risk of allergic sensitization and atopic diseases. However, associations between overall dietary patterns and atopic diseases in childhood remain unclear. We examined associations of diet quality in early life with allergic sensitization, self-reported physician-diagnosed inhalant and food allergies, eczema, and asthma among 5225 children participating in a population-based cohort in the Netherlands. Diet was assessed during pregnancy, infancy, and childhood using validated food-frequency questionnaires. We calculated food-based diet quality scores (0–10 or 0–15, reflecting adherence to dietary guidelines. At age 10 years, allergic sensitization was assessed with skin prick tests. Information on physician-diagnosed inhalant and food allergies, eczema, and asthma was obtained with questionnaires. We observed no associations between diet quality during pregnancy and allergic sensitization (odds ratio (OR = 1.05 per point in the diet score, 95% confidence interval (CI: 0.99, 1.13, allergies (0.96, 95% CI: 0.88, 1.04, eczema (0.99, 95% CI: 0.93, 1.06, or asthma (0.93, 95% CI: 0.85, 1.03 in childhood. Also, diet quality in infancy or childhood were not associated with atopic outcomes in childhood. Our findings do not support our hypothesis that a healthy dietary pattern in early life is associated with a lower risk of allergic sensitization or atopic diseases in childhood.

Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

KAUST Repository

Liu, Peng

2015-02-27

Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response.

Sensitivity of CA 15-3, CEA and serum HER2 in the early detection of recurrence of breast cancer

DEFF Research Database (Denmark)

Eriksen, Ann Christina; Sørensen, Patricia Diana; Jacobsen, Erik Hugger

2013-01-01

The aim of this project was to investigate the sensitivity of CA 15-3, CEA and HER2 in the early diagnosis of metastatic breast cancer.......The aim of this project was to investigate the sensitivity of CA 15-3, CEA and HER2 in the early diagnosis of metastatic breast cancer....

Effects of phyto-oestrogen quercetin on productive performance, hormones, reproductive organs and apoptotic genes in laying hens.

Science.gov (United States)

Yang, J X; Chaudhry, M T; Yao, J Y; Wang, S N; Zhou, B; Wang, M; Han, C Y; You, Y; Li, Y

2018-04-01

Quercetin, a polyphenolic flavonoid with diverse biological activities including anti-inflammatory and antiviral, inhibits lipid peroxidation, prevents oxidative injury and cell death. The purpose of the research was to investigate the effect of quercetin on productive performance, reproductive organs, hormones and apoptotic genes in laying hens between 37 and 45 weeks of age, because of the structure and oestrogenic activities similar to 17β-oestradiol. The trial was conducted using 240 Hessian laying hens (37 weeks old), housed in wire cages with two hens in each cage. These hens were randomly allotted to four treatments with six replicates, 10 hens in each replicate and fed with diets containing quercetin as 0, 0.2, 0.4 and 0.6 g/kg feed for 8 weeks. The results showed that dietary quercetin significantly increased (p feed-egg ratio was decreased (p  .05) on average egg weight and average daily feed intake. Compared with control, secretion of hormones, oestradiol (E 2 ) , progesterone (P4), follicle-stimulating hormone (FSH), luteinizing hormone (LH), insulin-like growth factors-1 (IGF-1) and growth hormone (GH), was found to be significantly higher (p  .05) by quercetin, whereas magnum index, isthmus index, magnum length, isthmus length and follicle numbers were significantly increased (p < .05) with quercetin supplementation. Additionally, expression of apoptotic genes was significantly (p < .05) up-regulated or down-regulated by quercetin. These results indicated that quercetin improved productive performance, and its mechanism may be due to the oestrogen-like activities of quercetin. © 2017 Blackwell Verlag GmbH.

The effects of oestrogens and their receptors on cardiometabolic health.

Science.gov (United States)

Morselli, Eugenia; Santos, Roberta S; Criollo, Alfredo; Nelson, Michael D; Palmer, Biff F; Clegg, Deborah J

2017-06-01

Cardiovascular disease (CVD) is one of the leading causes of mortality in developed countries. The incidence of CVD is sexually dimorphic, and research has focused on the contribution of sex steroids to the development and progression of the cardiometabolic syndrome, which is defined as a clustering of interrelated risk factors that promote the development of atherosclerosis (which can lead to CVD) and type 2 diabetes mellitus. Data are inconclusive as to how sex steroids and their respective receptors increase or suppress the risk of developing the cardiometabolic syndrome and thus CVD. In this Review, we discuss the potential role, or roles, of sex hormones in cardiometabolic health by first focusing on the influence of oestrogens and their receptors on the risk of developing cardiometabolic syndrome and CVD. We also highlight what is known about testosterone and its potential role in protecting against the development of the cardiometabolic syndrome and CVD. Given the inconclusive nature of the data regarding the direct effects of each sex hormone, we advocate and highlight the importance of studying the relative levels and the ratio of sex hormones to each other, as well as the use of cross sex hormone therapy and its effect on cardiometabolic health.

Changes in corneal sensitivity following cross-linking for progressive early-stage keratoconus

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Anelise de Medeiros Lago

2014-04-01

Full Text Available Purpose: To evaluate changes in corneal sensitivity following corneal cross-linking (CXL in patients with progressive earlier stage keratoconus. Methods: Thirty-eight eyes of 19 patients (11 women, 8 men were included in a prospective, nonrandomized clinical study. The mean patient age was 22 years (range, 18-26 years. Inclusion criteria were early stage bilateral progressive keratoconus, a transparent cornea, and a thickness of ≥440 µm in the thinnest area of the cornea. Using the Cochet-Bonnet esthesiometer, central corneal sensitivity was measured before surgery, 7 days after surgery, and once a month thereafter until recovery of baseline preoperative levels. Central corneal sensitivity >40 mm was considered normal. Results: Corneal sensitivity gradually returned to preoperative levels in all treated eyes. The mean central corneal sensitivity was 52.2, 24.0, 38.2, 42.5, 50.0, and 52.5 mm before surgery, 7 days after surgery, and at 1, 2, 3, and 4 months after surgery, respectively. Normal levels of corneal sensation, but not baseline (preoperative levels, were observed 2 months after surgery. The preoperative levels were observed 3 months after surgery. Conclusions: Our results suggest that central corneal sensitivity can be decreased for as long as 3 months after CXL for progressive earlier stage keratoconus.

Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

KAUST Repository

Liu, Peng; Zhang, Huoming; Yu, Boying; Xiong, Liming; Xia, Yiji

2015-01-01

in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional

Is the Prediction of Adolescent Outcomes From Early Child Care Moderated by Later Maternal Sensitivity? Results From the NICHD Study of Early Child Care and Youth Development

Science.gov (United States)

Burchinal, Margaret R.; Vandell, Deborah Lowe; Belsky, Jay

2016-01-01

Longitudinal data are used to examine whether effects of early child care are amplified and/or attenuated by later parenting. Analyses tested these interactions using parenting as both a categorical and continuous variable to balance power and flexibility in testing moderation. The most consistent finding was that maternal sensitivity during adolescence accentuated the association between child care quality and adolescent academic-cognitive skills at age 15 years when maternal sensitivity during adolescence was high. This interaction was obtained in analyses with maternal sensitivity as both a categorical and continuous variable. Relations between early child care hours and adolescent behavioral outcomes also were moderated by maternal sensitivity, with longer child care hours predicting more impulsivity and externalizing at age 15 when maternal sensitivity during middle childhood, scored as a categorical variable, was low to moderate and when maternal sensitivity during adolescence, scored as a continuous variable, was lower. These findings suggest that some child care effects are moderated by subsequent parenting and that this moderation may take both linear and nonlinear forms. PMID:23937381

Immunolocalization of androgen and oestrogen receptors in the ventral lobe of rat (Rattus norvegicus) prostate after long-term treatment with ethanol and nicotine.

Science.gov (United States)

Fávaro, W J; Cagnon, V H A

2008-12-01

Nicotine and alcohol adversely affect prostate gland function. In this work, immunohistochemistry was used to investigate the immunoreactivity and distribution of androgen and alpha, beta-oestrogen receptors following chronic treatment with alcohol, nicotine or a combination of both substances, as well as to relate these results to the development of possible prostatic pathologies. Forty male rats were divided into four groups: the Control group received tap water; the Alcoholic group received diluted 10% Gay Lussac ethanol; the Nicotine group received a 0.125 mg/100 g body weight dose of nicotine injected subcutaneously on a daily basis (Sigma Chemical Company, St. Louis, MO, USA); the Nicotine-Alcohol group received simultaneous alcohol and nicotine treatment. After 90 days of treatment, samples of the ventral lobe of the prostate were collected and processed for immunohistochemistry, light microscopy and the quantification of serum hormonal concentrations. The results showed significantly decreased serum testosterone levels and increased serum oestrogen levels in the animals from the nicotine-alcohol, the alcoholic and the nicotine groups, as well as their hormonal receptor levels. Then, it was concluded that ethanol and nicotine compromised the prostatic hormonal balance, which is a crucial factor to maintain the morphological and physiological features of this organ.

Tactile Sensitivity and Braille Reading in People with Early Blindness and Late Blindness

Science.gov (United States)

Oshima, Kensuke; Arai, Tetsuya; Ichihara, Shigeru; Nakano, Yasushi

2014-01-01

Introduction: The inability to read quickly can be a disadvantage throughout life. This study focused on the associations of braille reading fluency and individual factors, such as the age at onset of blindness and number of years reading braille, and the tactile sensitivity of people with early and late blindness. The relationship between reading…

Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status

Energy Technology Data Exchange (ETDEWEB)

Farquharson, M J [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main St W Hamilton, Ontario, L8S 4L8 (Canada); Al-Ebraheem, A [Department of Radiography, City Community and Health Sciences, City University, London, EC1V 0HB (United Kingdom); Geraki, K [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxon, OX11 0DE (United Kingdom); Leek, R; Jubb, A; Harris, A L [Cancer Research UK, Oxford Cancer Centre, Molecular Oncology Laboratories, University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, 0X3 9DS (United Kingdom)], E-mail: farquhm@mcmaster.ca

2009-07-07

Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01)

Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status

International Nuclear Information System (INIS)

Farquharson, M J; Al-Ebraheem, A; Geraki, K; Leek, R; Jubb, A; Harris, A L

2009-01-01

Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01).

Role of Oestrogen α Receptors in Sociosexual Behaviour in Female Rats Housed in a Seminatural Environment.

Science.gov (United States)

Snoeren, E M S; Antonio-Cabrera, E; Spiteri, T; Musatov, S; Ogawa, S; Pfaff, D W; Ågmo, A

2015-11-01

The present study investigated the role of oestrogen receptor (ER)α in the ventromedial nucleus of the hypothalamus (VMN), the preoptic area (POA), the medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in sociosexual behaviour in female rats. This was conducted in two sets of experiments, with the VMN and POA investigated in the first set, and the MePD and BNST in the second set. The VMN and POA received intense projections from the MePD and BNST. We used a short hairpin RNA encoded within an adeno-associated viral vector directed against the gene for ERα to reduce the number of ERα in the VMN or POA (first set of experiments) or in the BNST or MePD (second set of experiments) in female rats. The rats were housed in groups of four ovariectomised females and three males in a seminatural environment for 8 days. Compared with traditional test set-ups, the seminatural environment provides an arena in which the rats can express their full behavioural repertoire, which allowed us to investigate multiple aspects of social and sexual behaviour in groups of rats. Behavioural observation was performed after oestrogen and progesterone injections. A reduction of ERα expression in the VMN or POA diminished the display of paracopulatory behaviours and lordosis responses compared to controls, whereas the lordosis quotient remained unaffected. This suggests that ERα in the VMN and POA play an important role in intrinsic sexual motivation. The reduction in ERα did not affect the social behaviour of the females, although the males sniffed and pursued the females with reduced ERα less than the controls. This suggests that the ERα in the VMN and POA is involved in the regulation of sexual attractiveness of females. The ERα in the MePD and BNST, on the other hand, plays no role in sociosexual behaviour. © 2015 British Society for Neuroendocrinology.

Understanding the effect of uniaxial tensile strain on the early stages of sensitization in AISI 304 austenitic stainless steel

Energy Technology Data Exchange (ETDEWEB)

Chowdhury, P.S., E-mail: psc0126@gmail.com [Techno India Agartala, Maheshkhola, Agartala, West Tripura PIN – 799004 (India); Guchhait, S.K.; Mitra, P.K. [Department of Metallurgical and Material Engineering, Jadavpur University, Kolkata 700032 (India); Mukherjee, P.; Gayathri, N. [Variable Energy Cyclotron Centre (VECC), 1/AF Bidhan Nagar, Kolkata 700064 (India); Mitra, M.K. [Department of Metallurgical and Material Engineering, Jadavpur University, Kolkata 700032 (India)

2015-04-01

In the present study, an attempt has been made to understand the effect of different competing mechanisms controlling the overall degree of sensitization (DOS) of deformed austenitic stainless steel at the early stage of sensitization. The Double Loop Electrochemical Potentiokinetic Reactivation (DL-EPR) studies were performed to characterize the Degree of Sensitization (DOS) as a function of both pre-defined strain and sensitization temperature. X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) were used to explain the phenomena qualitatively. A non monotonous behaviour in the variation of DOS has been observed with deformation and sensitization temperature. The presence of Deformation Induced Martensites (DIM) and their transformation into tempered martensites (α + M{sub 23}C{sub 6}) at higher temperatures was found to play major roles in controlling the overall sensitization and desensitization processes. - Highlights: • Interplay of various dynamic processes (four) in the early sensitization. • Deformation induced martensite (α′) playing major role at low temperature. • α (Tempered martensite) induced processes plays a vital role at higher temperatures. • Results in non monotonous variation in degree of sensitisation (DOS)

Influence of chronic alcoholism and oestrogen deficiency on the variation of stoichiometry of hydroxyapatite within alveolar bone crest of rats.

Science.gov (United States)

Marchini, Adriana M P S; Deco, Camila P; Lodi, Karina B; Marchini, Leonardo; Santo, Ana M E; Rocha, Rosilene F

2012-10-01

Previous findings suggest that chronic alcoholism and oestrogenic deficiency may affect bones in general (including alveolar bone) and increase individuals' susceptibility to the development of periodontal disease. The aim of this study was to assess possible alterations in the chemical composition of alveolar bone in rats subjected to chronic alcoholism, oestrogen deficiency or both. Fifty-four rats were initially divided into two groups: ovariectomized (Ovx), and Sham operated (Sham). A month after surgery, the groups were sub-divided and received the following dietary intervention for eight weeks: 20% alcohol, isocaloric diet and ad libitum diet. Samples of the mandible, in the alveolar bone crest region, were analyzed to verify possible changes in the stoichiometric composition of bone hydroxyapatite, by measuring the relationship between the concentration of calcium and phosphorus (Ca/P ratios), using micro X-ray fluorescence spectrometry. The ad libitum groups presented the highest average values of Ca/P ratios, while the groups with dietary restrictions presented the smallest average values. The Ovx ad libitum group presented the highest values of Ca/P ratios (2.03 ± 0.04). However, these values were not considered statistically different (p>0.05) from the Sham ad libitum group (2.01 ± 0.01). The Ovx alcohol group presented lower values for Ca/P ratios (1.92 ± 0.06), being the only group statistically different (palcohol consumption at 20% significantly changed the stoichiometry composition of hydroxyapatite in the alveolar bone crest, leading to a reduction in Ca/P ratios. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ozone oxidation of oestrogenic active substances in wastewater and drinking water.

Science.gov (United States)

Baig, S; Hansmann, G; Paolini, B

2008-01-01

Ozone oxidation is proven to be an effective solution for the degradation of selected oestrogenic active substances detected in secondary wastewaters such as beta-oestradiol, oestrone, oestriol, 17-alpha-ethinyloestradiol, mestranol, daidzeine, beta-sitosterol, bisphenol A, norethisterone, 4-tert-octylphenol and 4-iso-nonylphenol, up to their limit of detection. The matrix-effect of wastewater was investigated performing ozone experiments under batch mode and continuous mode using drinking water and a wastewater issued from a local plant both spiked with the non-detected substances. The results obtained indicate that the wastewater matrix greatly affects the kinetics of ozone reaction with these substances but does not really change the related reactivity scale. The ozone dose corresponding to the full conversion of target EDCs consequently increases as their oxidation takes place competing with reactions of background pollutants represented by the COD and DOC content. However, a usual dose close to 12 mg/L was found sufficient to provide high degradation yields for all substances studied while 35% of COD was removed. This is a contribution to the numerous current works focused on technologies able to improve the quality of water discharged from wastewater treatment plants, both considering conventional parameters and emerging contaminants. IWA Publishing 2008.

Effect of Oestrogen on Altering the Serum and Urinary Levels of Calcium, Phosphate and Magnesium in Hysterectomised Women Compared to Natural Menopausal South Indian Women: A Case Control Study.

Science.gov (United States)

Sonu, Yeldose; Avinash, S S; Sreekantha; Arun Kumar, K; Malathi, M; Shivashankara, A R

2016-07-01

Given the paucity of studies conducted to know the effect of suddenness and earlier onset of endocrinological changes associated with hysterectomy, on the serum and urinary levels of calcium, magnesium and phosphate the present study was conducted to compare the levels of calcium, magnesium and phosphate in serum and urine of hysterectomised and natural menopausal south Indian women. This is a cross-sectional observational study. The study included three groups of 30 healthy premenopausal, 30 early surgical menopausal and 30 natural post menopausal women. Women suffering from any endocrine disease were excluded. Analysis was performed in serum and urine sample. The levels of calcium, magnesium and phosphate in serum and calcium/creatinine, magnesium/creatinine and phosphate/creatinine ratio were estimated in urine by spectrophotometric method. Hysterectomised women (serum calcium: 8.7 ± 0.09 mg/dl; urine calcium/creatinine: 0.16 ± 0.02) have significantly low serum calcium (p women (serum magnesium: 2.1 ± 0.03; serum phosphate: 4.4 ± 0.16; urinary calcium/creatinine: 0.17 ± 0.02; urinary magnesium/creatinine: 0.09 ± 0.01) have significantly high serum magnesium (p = 0.016), serum phosphate (p = 0.043) and high urinary calcium/creatinine (p = 0.002), magnesium/creatinine ratio (p = 0.025) compared to healthy pre menopausal women. Post menopausal women (serum calcium: 9.1 ± 0.08) have significantly high serum calcium and phosphate compared to hysterectomised women (serum phosphate: 3.93 ± 0.11). Hysterectomised women have significantly low serum calcium, oestrogen and high urinary calcium/creatinine ratio compared to healthy premenopausal women and low serum calcium and low serum phosphate compared to natural postmenopausal women. Natural postmenopausal women had low serum oestrogen and high serum magnesium, serum phosphate, urinary calcium creatinine ratio and urinary magnesium creatinine ratio compared to healthy premenopausal

Maternal Sensitivity and Effortful Control in Early Childhood as Predictors of Adolescents' Adjustment: The Mediating Roles of Peer Group Affiliation and Social Behaviors

Science.gov (United States)

Laible, Deborah; Carlo, Gustavo; Davis, Alexandra N.; Karahuta, Erin

2016-01-01

Longitudinal links between early childhood temperament, maternal sensitivity, and adolescents' adjustment have been proposed and found in several longitudinal studies, but the mechanisms of influence have not been explored. The authors examined the paths from maternal sensitivity and temperament in early childhood to adolescents' prosocial,…

Switch of Sensitivity Dynamics Revealed with DyGloSA Toolbox for Dynamical Global Sensitivity Analysis as an Early Warning for System's Critical Transition

Science.gov (United States)

Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

2013-01-01

Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA – a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits. PMID:24367574

Switch of sensitivity dynamics revealed with DyGloSA toolbox for dynamical global sensitivity analysis as an early warning for system's critical transition.

Science.gov (United States)

Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

2013-01-01

Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA - a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits.

Does endogenous serum oestrogen play a role in meibomian gland dysfunction in postmenopausal women with dry eye?

Science.gov (United States)

Golebiowski, Blanka; Badarudin, Noor; Eden, John; You, Jingjing; Hampel, Ulrike; Stapleton, Fiona

2017-02-01

To explore the relationship between serum concentration of sex hormones and dry eye symptoms and signs in postmenopausal women. A cross-sectional analysis was undertaken. Subjects were 46 postmenopausal women with dry eye (mean age 64.4±5.2 years, 13.7±6.4 years since menopause; not undergoing hormone replacement therapy). Ocular symptoms (Ocular Surface Disease Index (OSDI) and Ocular Comfort Index (OCI)), tear function (tear osmolarity, non-invasive tear break-up time, tear secretion), corneal and conjunctival staining, and meibomian gland (MG) appearance, were recorded. Venous blood was collected and serum concentrations of 17β-oestradiol (E2), 3-α-androstanediol-glucuronide (3α-diol-G), and dehydroepiandrosterone sulfate (DHEA-S) were determined using ELISA. Multiple linear regression analysis was used to examine predictors of dry eye symptoms and signs. Mean serum concentration of E2, 3α-diol-G and DHEA-S was 9.02±13.40 pg/mL, 1.59±1.02 ng/mL and 0.74±0.53 μg/mL, respectively. Ocular symptoms were elevated (mean scores 27.0±18.1 (OSDI) and 40.3±8.4 (OCI)) but signs were within normal ranges. Higher serum E2 concentration along with capped glands, lid telangiectasia and older age was a significant predictor of worse MG secretion quality (p0.05). Serum oestrogen appears to be a key factor in MG signs. Although serum hormone levels did not contribute significantly to dry eye symptoms in this study, it is possible that oestrogen plays a role through its effect on meibum secretion. These findings suggest that MG dysfunction underpins dry eye symptoms in non-Sjögren's dry eye in postmenopausal women. ACTRN12612000281897. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

RIGIDITY, SENSITIVITY AND QUALITY OF ATTACHMENT - THE ROLE OF MATERNAL RIGIDITY IN THE EARLY SOCIOEMOTIONAL DEVELOPMENT OF PREMATURE-INFANTS

NARCIS (Netherlands)

BUTCHER, PR; KALVERBOER, A; MINDERAA, RB; VANDOORMAAL, EF; TENWOLDE, Y

1993-01-01

The associations between a mother's rigidity, her sensitivity in early (3 month) interaction and the quality of her premature infant's attachment at 13 months were investigated. Rigidity as a personality characteristic was not found to be significantly associated with sensitivity or quality of

Developmental Trajectories of Anxiety Symptoms in Early Adolescence: The Influence of Anxiety Sensitivity

OpenAIRE

Allan, Nicholas P.; Capron, Daniel W.; Lejuez, Carl W.; Reynolds, Elizabeth K.; MacPherson, Laura; Schmidt, Norman B.

2014-01-01

Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity...

Maternal Sensitivity and Child Secure Base Use in Early Childhood: Studies in Different Cultural Contexts

Science.gov (United States)

Posada, German; Trumbell, Jill; Noblega, Magaly; Plata, Sandra; Peña, Paola; Carbonell, Olga A.; Lu, Ting

2016-01-01

This study tested whether maternal sensitivity and child security are related during early childhood and whether such an association is found in different cultural and social contexts. Mother-child dyads (N = 237) from four different countries (Colombia, Mexico, Peru, and the United States) were observed in naturalistic settings when children were…

Environmental chemical exposures and breast cancer

Directory of Open Access Journals (Sweden)

E. Stanley

2016-02-01

Full Text Available As a hormone-sensitive condition with no single identifiable cause, breast cancer is a major health problem. It is characterized by a wide range of contributing factors and exposures occurring in different combinations and strengths across a lifetime that may be amplified during periods of enhanced developmental susceptibility and impacted by reproductive patterns and behaviours. The vast majority of cases are oestrogen-receptor positive and occur in women with no family history of the disease suggesting that modifiable risk factors are involved. A substantial body of evidence now links oestrogen-positive breast cancer with environmental exposures. Synthetic chemicals capable of oestrogen mimicry are characteristic of industrial development and have been individually and extensively assessed as risk factors for oestrogen-sensitive cancers. Existing breast cancer risk assessment tools do not take such factors into account. In the absence of consensus on causation and in order to better understand the problem of escalating incidence globally, an expanded, integrated approach broadening the inquiry into individual susceptibility breast cancer is proposed. Applying systems thinking to existing data on oestrogen-modulating environmental exposures and other oestrogenic factors characteristic of Westernisation and their interactions in the exposure, encompassing social, behavioural, environmental, hormonal and genetic factors, can assist in understanding cancer risks and the pursuit of prevention strategies. A new conceptual framework based on a broader understanding of the “system” that underlies the development of breast cancer over a period of many years, incorporating the factors known to contribute to breast cancer risk, could provide a new platform from which government and regulators can promulgate enhanced and more effective prevention strategies.

The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

Science.gov (United States)

Chakravarty, Dimple; Sboner, Andrea; Nair, Sujit S.; Giannopoulou, Eugenia; Li, Ruohan; Hennig, Sven; Mosquera, Juan Miguel; Pauwels, Jonathan; Park, Kyung; Kossai, Myriam; MacDonald, Theresa Y.; Fontugne, Jacqueline; Erho, Nicholas; Vergara, Ismael A.; Ghadessi, Mercedeh; Davicioni, Elai; Jenkins, Robert B.; Palanisamy, Nallasivam; Chen, Zhengming; Nakagawa, Shinichi; Hirose, Tetsuro; Bander, Neil H.; Beltran, Himisha; Fox, Archa H.; Elemento, Olivier; Rubin, Mark A.

2014-01-01

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription. PMID:25415230

Developmental trajectories of anxiety symptoms in early adolescence: the influence of anxiety sensitivity.

Science.gov (United States)

Allan, Nicholas P; Capron, Daniel W; Lejuez, Carl W; Reynolds, Elizabeth K; MacPherson, Laura; Schmidt, Norman B

2014-05-01

Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity has been identified as an important risk factor in the development of anxiety psychopathology. This study prospectively examined the development of anxiety symptoms in a sample of 277 adolescents (M age = 11.52; 44 % female, 56 % male) over a 3 year period including the influence of anxiety sensitivity on this development. Further, this study investigated whether there were distinct classes of adolescents based on their anxiety symptom trajectories and including anxiety sensitivity as a predictor. Consistent with other reports, findings indicated an overall decline in anxiety symptoms over time in the sample. However, three classes of adolescents were found with distinct anxiety symptom trajectories and anxiety sensitivity was an important predictor of class membership. Adolescents with elevated anxiety sensitivity scores were more likely to be classified as having high and increasing anxiety symptoms over time versus having moderate to low and decreasing anxiety symptoms over time. There are important implications for identification of adolescents and children who are at risk for the development of an anxiety disorder.

Uncertainty and sensitivity analysis of early exposure results with the MACCS Reactor Accident Consequence Model

International Nuclear Information System (INIS)

Helton, J.C.; Johnson, J.D.; McKay, M.D.; Shiver, A.W.; Sprung, J.L.

1995-01-01

Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the early health effects associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 34 imprecisely known input variables on the following reactor accident consequences are studied: number of early fatalities, number of cases of prodromal vomiting, population dose within 10 mi of the reactor, population dose within 1000 mi of the reactor, individual early fatality probability within 1 mi of the reactor, and maximum early fatality distance. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: scaling factor for horizontal dispersion, dry deposition velocity, inhalation protection factor for nonevacuees, groundshine shielding factor for nonevacuees, early fatality hazard function alpha value for bone marrow exposure, and scaling factor for vertical dispersion

Sensitivity of early-life-stage golden trout to low pH and elevated aluminum

International Nuclear Information System (INIS)

DeLonay, A.J.; Little, E.E.; Woodward, F.; Brumbaugh, W.G.; Farag, A.M.; Rabeni, C.F.

1993-01-01

Early-life-stage golden trout (Oncorhynchus aguabonita) were exposed to acid and Al to examine the response and determine the sensitivity of a western, alpine salmonid to conditions simulating an episodic pH depression. Freshly fertilized eggs, alevins, and swim-up larvae were exposed for 7 d to one of 12 combinations of pH and Al, and surviving fish were held to 40 d post-hatch to determine the effect of exposure on subsequent survival and recovery. Golden trout are sensitive to conditions simulating episodic acidification events typically observed in the field. Significant mortality occurred when the pH of test waters was below 5.0 in the absence of Al or when pH was 5.5 in the presence of 100 μg/L total Al. Behavioral impairments were sensitive indicators of low pH and Al stress. Impaired locomotory and feeding behavior occurred at pH 5.5 without Al and at Al concentrations ≥ μg/L. In contrast, growth, RNA-to-DNA ratio, and whole-body ion concentration were relatively less sensitive indicators of sublethal acid and Al stress

The contribution of SHBG to the variation in HOMA-IR is not dependent on endogenous oestrogen or androgen levels in postmenopausal women.

Science.gov (United States)

Davis, Susan R; Robinson, Penelope J; Moufarege, Alain; Bell, Robin J

2012-10-01

Sex hormone-binding globulin (SHBG) is a robust predictor of insulin resistance. Whether this is independent of circulating sex steroid levels remains uncertain. The aim of this study was to investigate the determinants of SHBG in postmenopausal women and whether the relationship between SHBG and insulin resistance is independent of oestrogen and androgen levels. A cross-sectional study of naturally and surgically menopausal women. Seven hundred and sixty three postmenopausal women not using any systemic hormone therapy, mean age 54·4 ± 5·8 years, recruited in the US, Canada, Australia, UK and Sweden between July 2004 and February 2005. Relationships between log-transformed (ln) SHBG and ln homoeostasis model assessment for insulin resistance (HOMA-IR) were explored, taking into account age, body mass index (BMI), blood pressure (BP) and circulating oestradiol, oestrone, testosterone and dihydrotestosterone. Taking into account age, race, years since menopause, menopause type, BMI, BP, prior postmenopausal hormone use and the sex steroids measured, 34·4% of the variation in SHBG could be explained by the model that included negative contributions by HOMA-IR, BMI and diastolic BP, and a positive contribution by total testosterone (P HOMA-IR, which was best explained by the model that included BMI, SHBG, systolic BP and surgical menopause, with each variable being positively related to HOMA-IR (r(2) = 0·3152, P = 0·03). The relationship between SHBG and HOMA-IR, as an estimate of insulin resistance, is not explained by endogenous oestrogen and androgen levels and is, at least in part, independent of BMI in postmenopausal women. © 2011 Blackwell Publishing Ltd.

Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Science.gov (United States)

Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

2018-03-15

Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Oxytocin receptor gene polymorphisms (rs53576) and early paternal care sensitize males to distressing female vocalizations.

Science.gov (United States)

Truzzi, Anna; Poquérusse, Jessie; Setoh, Peipei; Shinohara, Kazuyuki; Bornstein, Marc H; Esposito, Gianluca

2018-04-01

The oxytocinergic system is highly involved in social bonding and early caregiver-infant interactions. Here, we hypothesize that oxytocin receptor (OXTR) gene genotype and parental bonding history interact in influencing social development. To address this question, we assessed adult males' arousal (heart rate changes) in response to different distress vocalizations (human female, human infant and bonobo). Region rs53576 of the OXTR gene was genotyped from buccal mucosa cell samples, and a self-report Parental Bonding Instrument was used (which provide information about parental care or parental overprotection). A significant gene-environment interaction between OXTR genotype and parenting style was found to influence participants' social responsivity to female cry vocalizations. Specifically, a history of appropriate paternal care in participants accentuated the heightened social sensitivity determined by G/G homozygosity, while higher versus lower paternal overprotection lead to distinct levels of physiological arousal particularly in A carriers individuals. These results add to our understanding of the dynamic interplay between genetic susceptibility and early environmental experience in shaping the development of appropriate social sensitivity in males. © 2018 Wiley Periodicals, Inc.

Early sensitivity of left perisylvian cortex to relationality in nouns and verbs.

Science.gov (United States)

Williams, Adina; Reddigari, Samir; Pylkkänen, Liina

2017-06-01

The ability to track the relationality of concepts, i.e., their capacity to encode a relationship between entities, is one of the core semantic abilities humans possess. In language processing, we systematically leverage this ability when computing verbal argument structure, in order to link participants to the events they participate in. Previous work has converged on a large region of left posterior perisylvian cortex as a locus for such processing, but the wide range of experimental stimuli and manipulations has yielded an unclear picture of the region's exact role(s). Importantly, there is a tendency for effects of relationality in single-word studies to localize to posterior temporo-parietal cortex, while argument structure effects in sentences appear in left superior temporal cortex. To characterize these sensitivities, we designed two MEG experiments that cross the factors relationality and eventivity. The first used minimal noun phrases and tested for an effect of semantic composition, while the second employed full sentences and a manipulation of grammatical category. The former identified a region of the left inferior parietal lobe sensitive to relationality, but not eventivity or combination, beginning at 170ms. The latter revealed a similarly-timed effect of relationality in left mid-superior temporal cortex, independent of eventivity and category. The results suggest that i) multiple sub-regions of perisylvian cortex are sensitive to the relationality carried by concepts even in the absence of arguments, ii) linguistic context modulates the locus of this sensitivity, consistent with prior studies, and iii) relationality information is accessed early - before 200ms - regardless of the concept's event status or syntactic category. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of steroids in follicular growth

Directory of Open Access Journals (Sweden)

Drummond Ann E

2006-04-01

Full Text Available Abstract The steroidogenic pathway within the ovary gives rise to progestins, androgens and oestrogens, all of which act via specific nuclear receptors to regulate reproductive function and maintain fertility. The role of progestins in follicular growth and development is limited, its action confined largely to ovulation, although direct effects on granulosa cell function have been reported. Consistent with these findings, progesterone receptor knockout mice are infertile because they cannot ovulate. Androgens have been shown to promote early follicular growth, but also to impede follicular development by stimulating atresia and apoptosis. The inability of androgens to transduce a signal in mice lacking androgen receptors culminates in reduced fertility. Oestrogens are known to exert effects on granulosa cell growth and differentiation in association with gonadotrophins. Studies with oestrogen receptor knockouts and oestrogen depleted mice have shown us that oestrogen is essential for folliculogenesis beyond the antral stage and is necessary to maintain the female phenotype of ovarian somatic cells. In summary, the action of steroids within the ovary is based on the developmental status of the follicle. In the absence of any single sex steroid, ovarian function and subsequently fertility, are compromised.

Early life trauma exposure and stress sensitivity in young children.

Science.gov (United States)

Grasso, Damion J; Ford, Julian D; Briggs-Gowan, Margaret J

2013-01-01

The current study replicates and extends work with adults that highlights the relationship between trauma exposure and distress in response to subsequent, nontraumatic life stressors. The sample included 213 2-4-year-old children in which 64.3% had a history of potential trauma exposure. Children were categorized into 4 groups based on trauma history and current life stress. In a multivariate analysis of variance, trauma-exposed children with current life stressors had elevated internalizing and externalizing problems compared with trauma-exposed children without current stress and nontrauma-exposed children with and without current stressors. The trauma-exposed groups with or without current stressors did not differ on posttraumatic stress disorder symptom severity. Accounting for number of traumatic events did not change these results. These findings suggest that early life trauma exposure may sensitize young children and place them at risk for internalizing or externalizing problems when exposed to subsequent, nontraumatic life stressors.

Specificity and sensitivity of the Beck Hopelessness Scale for suicidal ideation among adolescents entering early intervention service.

Science.gov (United States)

Granö, Niklas; Oksanen, Jorma; Kallionpää, Santeri; Roine, Mikko

2017-01-01

Previous studies have shown an association between hopelessness and suicidal behaviour in clinical populations. The aim of the study was to investigate sensitivity, specificity, and predictive validity of the Beck Hopelessness Scale (BHS) for suicidal ideation in adolescents who show early risk signs on the psychiatric disorder continuum. Three-hundred and two help-seeking adolescents (mean age = 15.5 years) who were entering an early intervention team at Helsinki University Central Hospital, Finland, completed questionnaires of BHS and suicidal ideation, derived from Beck Depression Inventory (BDI-II). Results suggest that a BHS cut-off score ≥8 (sensitivity = 0.70, specificity = 0.76) or cut-off score ≥9 (sensitivity = 0.63, specificity = 0.80) may be useful to detect suicidal ideation with BHS in help-seeking adolescents population. Results remain mainly the same in a separate analysis with adolescents at risk for psychosis. The results support previous cut-off points for BHS in identification of suicidal ideation. The results suggest also that lower cut-off scores may be useful in sense of sensitivity, especially in clinical settings.

The radiological consequences of notional accidental releases of radioactivity from fast breeder reactors: sensitivity to the dose-effect relationships adopted for early biological effects

International Nuclear Information System (INIS)

Kelly, G.N.; Simmonds, J.R.; Smith, H.; Stather, J.W.

1979-07-01

This study considered the sensitivity to the dose-response relationships adopted for the estimation of early biological effects from notional accidental releases of radioactivity from fast breeder reactors. Two distinct aspects were considered: the sensitivity of the predicted consequences to variation in the dose-mortality relationships for irradiation of the bone marrow and the lung; and the influence of simple supportive medical treatment in reducing the incidence of early deaths in the exposed population. The numbers of early effects estimated in the initial study were relatively insensitive to variation in the dose-mortality relationships within the bounds proposed. The few exceptions concerned releases of particular nuclide composition, and the variation in the predicted consequences could be around an order of magnitude; the absolute numbers of effects however were in general small when the sensitivity was most pronounced. The reduction in the incidence of early deaths when using simple supportive treatment varied markedly with the nuclide composition of the release. Areas of uncertainty were identified where further research and investigation might most profitably be directed with a view to improving the reliability of the dose-effect relationships adopted and hence of the predicted consequences of the release considered. (author)

Is the Prediction of Adolescent Outcomes from Early Child Care Moderated by Later Maternal Sensitivity? Results from the NICHD Study of Early Child Care and Youth Development

Science.gov (United States)

Burchinal, Margaret R.; Lowe Vandell, Deborah; Belsky, Jay

2014-01-01

Longitudinal data are used to examine whether effects of early child care are amplified and/or attenuated by later parenting. Analyses tested these interactions using parenting as both a categorical and continuous variable to balance power and flexibility in testing moderation. The most consistent finding was that maternal sensitivity during…

The influence of selenium, vitamin E, and oestrogen on the development of tumours in mice exposed to 90Sr

International Nuclear Information System (INIS)

Bierke, P.

1994-01-01

The primary object of this experiment was to evaluate the potential role of the antioxidants, selenium and vitamin E, in the anti-tumour defence of mice internally irradiated with 90 Sr. Comparison in terms of neoplastic response was made between mice kept on a selenium and vitamin E deficient diet and mice given the same deficient diet but administered selenium and/or vitamin E in a controlled manner. The influence of simultaneous oestrogen treatment, known to promote radiogenic osteosarcoma induction, was also investigated. Non-irradiated mice were used as controls. Results are presented as crude and actuarial tumour incidence. No significant difference in tumour yield or actuarial tumour incidence was found when the differently treated mouse groups were compared, and accordingly no support was gained for the theory that the antioxidants selenium and vitamin E constitute a critical part of the complex defence system against neoplasms. (orig.)

Stress Sensitivity, Aberrant Salience, and Threat Anticipation in Early Psychosis: An Experience Sampling Study

Science.gov (United States)

Reininghaus, Ulrich; Kempton, Matthew J.; Valmaggia, Lucia; Craig, Tom K. J.; Garety, Philippa; Onyejiaka, Adanna; Gayer-Anderson, Charlotte; So, Suzanne H.; Hubbard, Kathryn; Beards, Stephanie; Dazzan, Paola; Pariante, Carmine; Mondelli, Valeria; Fisher, Helen L.; Mills, John G.; Viechtbauer, Wolfgang; McGuire, Philip; van Os, Jim; Murray, Robin M.; Wykes, Til; Myin-Germeys, Inez; Morgan, Craig

2016-01-01

While contemporary models of psychosis have proposed a number of putative psychological mechanisms, how these impact on individuals to increase intensity of psychotic experiences in real life, outside the research laboratory, remains unclear. We aimed to investigate whether elevated stress sensitivity, experiences of aberrant novelty and salience, and enhanced anticipation of threat contribute to the development of psychotic experiences in daily life. We used the experience sampling method (ESM) to assess stress, negative affect, aberrant salience, threat anticipation, and psychotic experiences in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls with no personal or family history of psychosis. Linear mixed models were used to account for the multilevel structure of ESM data. In all 3 groups, elevated stress sensitivity, aberrant salience, and enhanced threat anticipation were associated with an increased intensity of psychotic experiences. However, elevated sensitivity to minor stressful events (χ2 = 6.3, P = 0.044), activities (χ2 = 6.7, P = 0.036), and areas (χ2 = 9.4, P = 0.009) and enhanced threat anticipation (χ2 = 9.3, P = 0.009) were associated with more intense psychotic experiences in FEP individuals than controls. Sensitivity to outsider status (χ2 = 5.7, P = 0.058) and aberrantly salient experiences (χ2 = 12.3, P = 0.002) were more strongly associated with psychotic experiences in ARMS individuals than controls. Our findings suggest that stress sensitivity, aberrant salience, and threat anticipation are important psychological processes in the development of psychotic experiences in daily life in the early stages of the disorder. PMID:26834027

Coincidence of pollen season with the first fetal trimester together with early pet exposure is associated with sensitization to cat and dog allergens in early childhood: A Finnish population-based study.

Science.gov (United States)

Pyrhönen, K; Kulmala, P; Näyhä, S

2018-03-01

Children whose 11th fetal week falls in pollen season (spring) reportedly have an increased risk of sensitization to food allergens. No such finding has been reported for pet allergens. The aim of the study was to (i) evaluate the incidence of pet (dog and cat) sensitization according to the season of the 11th fetal week and (ii) whether the association between pet exposure and respective sensitization is modified by the coincidence of the 11th fetal week with pollen season. The study population comprised all children (born between 2001 and 2006) in the province of South Karelia, Finland (N = 5920). Their data of immunoglobulin E antibodies and skin prick tests to pet allergens (N = 538) were collected from patient records and linked with questionnaire data on pet exposure. The seasonal incidence peak of cat sensitization was observed in children whose 11th fetal week occurred in June (7.4%) and that of dog sensitization in April (3.8%) and June (4.7%). The relative rate (RR) for cat sensitization was 2.92 (95% CI 1.40-6.08) in children with cat exposure alone, 8.53 (4.07-17.86) in children with cat and fetal pollen exposures and 0.61 (0.20-1.83) in children exposed to pollen alone, compared with children without these exposures. The respective RRs for dog sensitization were 2.17 (1.13-4.19), 4.40 (2.19-8.83) and 1.65 (0.77-3.53). Coincidence of the first fetal trimester with pollen season strengthens the association between pet exposure and respective sensitization. Pollen exposure at early pregnancy may deviate immune system towards Th2-type reactivity promoting development of specific allergy in case allergen exposure occurred. Therefore, primary prevention of allergic diseases may need to begin during early pregnancy. © 2017 John Wiley & Sons Ltd.

Sensitivity to cocaine in adult mice is due to interplay between genetic makeup, early environment and later experience.

Science.gov (United States)

Di Segni, Matteo; Andolina, Diego; Coassin, Alessandra; Accoto, Alessandra; Luchetti, Alessandra; Pascucci, Tiziana; Luzi, Carla; Lizzi, Anna Rita; D'Amato, Francesca R; Ventura, Rossella

2017-10-01

Although early aversive postnatal events are known to increase the risk to develop psychiatric disorders later in life, rarely they determine alone the nature and outcome of the psychopathology, indicating that interaction with genetic factors is crucial for expression of psychopathologies in adulthood. Moreover, it has been suggested that early life experiences could have negative consequences or confer adaptive value in different individuals. Here we suggest that resilience or vulnerability to adult cocaine sensitivity depends on a "triple interaction" between genetic makeup x early environment x later experience. We have recently showed that Repeated Cross Fostering (RCF; RCF pups were fostered by four adoptive mothers from postnatal day 1 to postnatal day 4. Pups were left with the last adoptive mother until weaning) experienced by pups affected the response to a negative experience in adulthood in opposite direction in two genotypes leading DBA2/J, but not C57BL/6J mice, toward an "anhedonia-like" phenotype. Here we investigate whether exposure to a rewarding stimulus, instead of a negative one, in adulthood induces an opposite behavioral outcome. To test this hypothesis, we investigated the long-lasting effects of RCF on cocaine sensitivity in C57 and DBA female mice by evaluating conditioned place preference induced by different cocaine doses and catecholamine prefrontal-accumbal response to cocaine using a "dual probe" in vivo microdialysis procedure. Moreover, cocaine-induced c-Fos activity was assessed in different brain regions involved in processing of rewarding stimuli. Finally, cocaine-induced spine changes were evaluated in the prefrontal-accumbal system. RCF experience strongly affected the behavioral, neurochemical and morphological responses to cocaine in adulthood in opposite direction in the two genotypes increasing and reducing, respectively, the sensitivity to cocaine in C57 and DBA mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stress Sensitivity, Aberrant Salience, and Threat Anticipation in Early Psychosis: An Experience Sampling Study.

Science.gov (United States)

Reininghaus, Ulrich; Kempton, Matthew J; Valmaggia, Lucia; Craig, Tom K J; Garety, Philippa; Onyejiaka, Adanna; Gayer-Anderson, Charlotte; So, Suzanne H; Hubbard, Kathryn; Beards, Stephanie; Dazzan, Paola; Pariante, Carmine; Mondelli, Valeria; Fisher, Helen L; Mills, John G; Viechtbauer, Wolfgang; McGuire, Philip; van Os, Jim; Murray, Robin M; Wykes, Til; Myin-Germeys, Inez; Morgan, Craig

2016-05-01

While contemporary models of psychosis have proposed a number of putative psychological mechanisms, how these impact on individuals to increase intensity of psychotic experiences in real life, outside the research laboratory, remains unclear. We aimed to investigate whether elevated stress sensitivity, experiences of aberrant novelty and salience, and enhanced anticipation of threat contribute to the development of psychotic experiences in daily life. We used the experience sampling method (ESM) to assess stress, negative affect, aberrant salience, threat anticipation, and psychotic experiences in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls with no personal or family history of psychosis. Linear mixed models were used to account for the multilevel structure of ESM data. In all 3 groups, elevated stress sensitivity, aberrant salience, and enhanced threat anticipation were associated with an increased intensity of psychotic experiences. However, elevated sensitivity to minor stressful events (χ(2)= 6.3,P= 0.044), activities (χ(2)= 6.7,P= 0.036), and areas (χ(2)= 9.4,P= 0.009) and enhanced threat anticipation (χ(2)= 9.3,P= 0.009) were associated with more intense psychotic experiences in FEP individuals than controls. Sensitivity to outsider status (χ(2)= 5.7,P= 0.058) and aberrantly salient experiences (χ(2)= 12.3,P= 0.002) were more strongly associated with psychotic experiences in ARMS individuals than controls. Our findings suggest that stress sensitivity, aberrant salience, and threat anticipation are important psychological processes in the development of psychotic experiences in daily life in the early stages of the disorder. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

SPATIOTEMPORAL CONTRAST SENSITIVITY OF EARLY VISION

NARCIS (Netherlands)

Hateren, J.H. van

Based on the spatial and temporal statistics of natural images, a theory is developed that specifies spatiotemporal filters that maximize the flow of information through noisy channels of limited dynamic range. Sensitivities resulting from these spatiotemporal filters are very similar to the human

Prolactin release, oestrogens and proliferation of prolactin-secreting cells in the anterior pituitary gland of adult male rats.

Science.gov (United States)

Pérez, R L; Machiavelli, G A; Romano, M I; Burdman, J A

1986-03-01

Relationships among the release of prolactin, the effect of oestrogens and the proliferation of prolactin-secreting cells were studied under several experimental conditions. Administration of sulpiride or oestradiol released prolactin and stimulated cell proliferation in the anterior pituitary gland of adult male rats. Clomiphene completely abolished the rise in cell proliferation, but did not interfere with the sulpiride-induced release of prolactin. Treatment with oestradiol plus sulpiride significantly increased serum prolactin concentrations and the mitotic index compared with the sum of the stimulation produced by both drugs separately. Bromocriptine abolished the stimulatory effect of oestradiol on the serum prolactin concentration and on cell proliferation. In oestradiol- and/or sulpiride-treated rats, 80% of the cells in mitoses were lactotrophs. The remaining 20% did not stain with antisera against any of the pituitary hormones. The number of prolactin-secreting cells in the anterior pituitary gland significantly increased after the administration of oestradiol or sulpiride. The results demonstrate that treatment with sulpiride and/or oestradiol increases the proliferation and the number of lactotrophs in the anterior pituitary gland of the rat.

2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy.

Science.gov (United States)

Li, Jingmei; Lindström, Linda S; Foo, Jia N; Rafiq, Sajjad; Schmidt, Marjanka K; Pharoah, Paul D P; Michailidou, Kyriaki; Dennis, Joe; Bolla, Manjeet K; Wang, Qin; Van 't Veer, Laura J; Cornelissen, Sten; Rutgers, Emiel; Southey, Melissa C; Apicella, Carmel; Dite, Gillian S; Hopper, John L; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Blomqvist, Carl; Muranen, Taru A; Aittomäki, Kristiina; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M; Kataja, Vesa; Chenevix-Trench, Georgia; Phillips, Kelly-Anne; McLachlan, Sue-Anne; Lambrechts, Diether; Thienpont, Bernard; Smeets, Ann; Wildiers, Hans; Chang-Claude, Jenny; Flesch-Janys, Dieter; Seibold, Petra; Rudolph, Anja; Giles, Graham G; Baglietto, Laura; Severi, Gianluca; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Kristensen, Vessela; Alnæs, Grethe I Grenaker; Borresen-Dale, Anne-Lise; Nord, Silje; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert; Seynaeve, Caroline; Hooning, Maartje; Kriege, Mieke; Hollestelle, Antoinette; van den Ouweland, Ans; Li, Yi; Hamann, Ute; Torres, Diana; Ulmer, Hans U; Rüdiger, Thomas; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Chen, Shou-Tung; Teo, Soo Hwang; Taib, Nur Aishah Mohd; Har Yip, Cheng; Fuang Ho, Gwo; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Yoo, Keun-Young; Maishman, Tom; Tapper, William J; Dunning, Alison; Shah, Mitul; Luben, Robert; Brown, Judith; Khor, Chiea Chuen; Eccles, Diana M; Nevanlinna, Heli; Easton, Douglas; Humphreys, Keith; Liu, Jianjun; Hall, Per; Czene, Kamila

2014-06-17

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.

Detection of oral early cancerous lesion by using polarization-sensitive optical coherence tomography: mice model

Science.gov (United States)

Lee, Hong-Yi; Chen, Ping-Hsien; Lee, Tzu-Han; Chang, Kuo-Wei; Kuo, Wen-Chuan

2018-02-01

Oral cancer is the 11th most common cancer worldwide, especially in a male adult. The median age of death in oral cancer was 55 years, 10-20 years earlier than other cancers. Presently, oral cancer is often found in late stage, because the lesion is often flat in early stage and is difficult to diagnose under traditional white light imaging. The only definitive method for determining cancer is an invasive biopsy and then using histology examination. How to detect precancerous lesions or early malignant lesions is an important issue for improving prognosis of oral cancer. Optical coherence tomography (OCT) is a new optical tool for diagnosing early malignant lesions in the skin or gastrointestinal tract recently. Here we report a new method for detecting precancerous or early malignant oral lesions by using swept source polarization-sensitive optical coherence tomography (PS-OCT) with center-wavelength 1310 nm, bandwidth 110 nm and 100 kHz swept rate. We used all single-mode fiber design to detect the change of birefringence information in the epithelium structure. This system has an advantage that enables measurement of backscattered intensity and birefringence simultaneously with only one A-scan per transverse location. In preliminary result, we computed the slope of the every A-scan signal in tissue part using a linear-curve fitting in backscattered intensity and birefringence on the enface. In this research, we used an oral cancer mice model for observing the change of structure and birefringence properties in different stages of oral cancer mice. We presented the parametric enface imaging that can detect the early oral malignant lesions.

Leg vascular and skeletal muscle mitochondrial adaptations to aerobic high-intensity exercise training are enhanced in the early postmenopausal phase

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Egelund, Jon; Mandrup Jensen, Camilla Maria

2017-01-01

the haemodynamic response to acute exercise in matched pre- and postmenopausal women before and after 12 weeks of aerobic high intensity exercise training. Twenty premenopausal and 16 early postmenopausal (3.1 ± 0.5 [mean ± SEM] years after final menstrual period) women only separated by 4 (50 ± 0 versus 54 ± 1...... receptor α (ERRα) were increased (P training in the postmenopausal women whereas only the levels of mitochondrial complex V, eNOS, and COX-2 were increased (P aerobic......Exercise training leads to favourable adaptations within skeletal muscle; however, this effect of exercise training may be blunted in postmenopausal women due to the loss of oestrogens. Furthermore, postmenopausal women may have an impaired vascular response to acute exercise. We examined...

Robustness of an uncertainty and sensitivity analysis of early exposure results with the MACCS reactor accident consequence model

International Nuclear Information System (INIS)

Helton, J.C.; Johnson, J.D.; McKay, M.D.; Shiver, A.W.; Sprung, J.L.

1995-01-01

Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis were used in an investigation with the MACCS model of the early health effects associated with a severe accident at a nuclear power station. The following results were obtained in tests to check the robustness of the analysis techniques: two independent Latin hypercube samples produced similar uncertainty and sensitivity analysis results; setting important variables to best-estimate values produced substantial reductions in uncertainty, while setting the less important variables to best-estimate values had little effect on uncertainty; similar sensitivity analysis results were obtained when the original uniform and loguniform distributions assigned to the 34 imprecisely known input variables were changed to left-triangular distributions and then to right-triangular distributions; and analyses with rank-transformed and logarithmically-transformed data produced similar results and substantially outperformed analyses with raw (i.e., untransformed) data

Schizophrenia: do men and women suffer from the same disease?

Directory of Open Access Journals (Sweden)

Heinz Häfner

2002-01-01

Full Text Available This article reviews the literature on normal brain development and behavioural development in men and women as well as on aetiological risk factors for schizophrenia, such as pre-, peri- and postnatal complications. The male-female comparisons of age and type of onset, symptomatology, course and outcome were based on a population-based sample of 232 first illness episodes - the ABC Schizophrenia Study sample. The probands were assessed using the IRAOS interview and other instruments retrospectively at first admission and prospectively at six cross sections over five years after first contact. A representative subsample of 130 first admissions or 115 first illness episodes were compared with 130 controls, matched by age, sex and area of residence. Women, 3 to 4 years older than men at illness onset, showed a second peak of onsets in age group 45 to 50 years. After animal experiments and a controlled clinical study this finding was explained by a protective effect of oestrogen persisting until menopause. The underlying neurobiological mechanism consisted in a sensitivity reducing effect of oestrogen on D2 receptors in the brain. The effect of oestrogen, meanwhile confirmed in randomised control trials, also includes genomic effects as well as interactions with free-radical detoxifying systems, thus demonstrating the neuroprotective capabilities of oestrogen. Postmenopausal schizophrenia was more frequent and more severe in women. Men fell ill more frequently and more severely at young age and less frequently and more mildly later in life. Illness course, too, was more unfavourable in postmenopausal women than in their male peers. The protective effect of oestrogen in women depended on the degree of their predisposition to the illness: the higher the familial load for schizophrenia, the weaker the protection by oestrogen. The more favourable illness course in premenopausal women resulted from their higher level of social development at illness

Early continuous white noise exposure alters auditory spatial sensitivity and expression of GAD65 and GABAA receptor subunits in rat auditory cortex.

Science.gov (United States)

Xu, Jinghong; Yu, Liping; Cai, Rui; Zhang, Jiping; Sun, Xinde

2010-04-01

Sensory experiences have important roles in the functional development of the mammalian auditory cortex. Here, we show how early continuous noise rearing influences spatial sensitivity in the rat primary auditory cortex (A1) and its underlying mechanisms. By rearing infant rat pups under conditions of continuous, moderate level white noise, we found that noise rearing markedly attenuated the spatial sensitivity of A1 neurons. Compared with rats reared under normal conditions, spike counts of A1 neurons were more poorly modulated by changes in stimulus location, and their preferred locations were distributed over a larger area. We further show that early continuous noise rearing induced significant decreases in glutamic acid decarboxylase 65 and gamma-aminobutyric acid (GABA)(A) receptor alpha1 subunit expression, and an increase in GABA(A) receptor alpha3 expression, which indicates a returned to the juvenile form of GABA(A) receptor, with no effect on the expression of N-methyl-D-aspartate receptors. These observations indicate that noise rearing has powerful adverse effects on the maturation of cortical GABAergic inhibition, which might be responsible for the reduced spatial sensitivity.

The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

Science.gov (United States)

Finn, Richard S; Crown, John P; Lang, Istvan; Boer, Katalin; Bondarenko, Igor M; Kulyk, Sergey O; Ettl, Johannes; Patel, Ravindranath; Pinter, Tamas; Schmidt, Marcus; Shparyk, Yaroslav; Thummala, Anu R; Voytko, Nataliya L; Fowst, Camilla; Huang, Xin; Kim, Sindy T; Randolph, Sophia; Slamon, Dennis J

2015-01-01

Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer. In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409. Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib

Oestrogen and progesterone receptor assays in breast tumours. The Prince Henry's Hospital experience, 1983-1990.

Science.gov (United States)

Pearce, P T; Myles, K M; Funder, J W

1993-08-16

To present and analyse the results of eight years of experience (1983-1990) in breast tumour receptor analysis. All female primary breast tumour samples received (4683) were analysed for seasonal variation, patient age, relative risk index, oestrogen receptor (ER) and progesterone receptor (PR) status, ER and PR status as a function of age, ER and PR levels as a function of age, and ER and PR levels as a function of month of analysis. The assays were done at the Medical Research Centre, Prince Henry's Hospital, Melbourne, as a non-profit service to surgeons, oncologists and pathologists. The numbers of samples referred for assay increased progressively each year, from 473 in 1983 to 1097 in 1990, but the receptor status (ER +/-, PR +/-) appeared not to vary from year to year. ER+PR+ tumours were the most common in all age groups, steadily increasing from between 50% and 60% in premenopausal women to 70% or more in those aged over 80. In postmenopausal women, levels of ER in ER+ tumours were three times those in premenopausal women; PR levels in PR+ tumours, however, were bimodal, with higher levels in the age groups 35-49 and 70-89 years than in women aged 50-69 years. No significant seasonal variation was seen, and the overall patterns of receptor status are similar to those seen in Northern hemisphere studies.

A combined sensitivity analysis and kriging surrogate modeling for early validation of health indicators

International Nuclear Information System (INIS)

Lamoureux, Benjamin; Mechbal, Nazih; Massé, Jean-Rémi

2014-01-01

To increase the dependability of complex systems, one solution is to assess their state of health continuously through the monitoring of variables sensitive to potential degradation modes. When computed in an operating environment, these variables, known as health indicators, are subject to many uncertainties. Hence, the stochastic nature of health assessment combined with the lack of data in design stages makes it difficult to evaluate the efficiency of a health indicator before the system enters into service. This paper introduces a method for early validation of health indicators during the design stages of a system development process. This method uses physics-based modeling and uncertainties propagation to create simulated stochastic data. However, because of the large number of parameters defining the model and its computation duration, the necessary runtime for uncertainties propagation is prohibitive. Thus, kriging is used to obtain low computation time estimations of the model outputs. Moreover, sensitivity analysis techniques are performed upstream to determine the hierarchization of the model parameters and to reduce the dimension of the input space. The validation is based on three types of numerical key performance indicators corresponding to the detection, identification and prognostic processes. After having introduced and formalized the framework of uncertain systems modeling and the different performance metrics, the issues of sensitivity analysis and surrogate modeling are addressed. The method is subsequently applied to the validation of a set of health indicators for the monitoring of an aircraft engine’s pumping unit

Comparison of the Sensitivity of Three Methods for the Early Diagnosis of Sporotrichosis in Cats.

Science.gov (United States)

Silva, J N; Miranda, L H M; Menezes, R C; Gremião, I D F; Oliveira, R V C; Vieira, S M M; Conceição-Silva, F; Ferreiro, L; Pereira, S A

2018-04-01

Sporotrichosis is caused by species of fungi within the Sporothrix schenckii complex that infect man and animals. In Rio de Janeiro, Brazil, an epidemic has been observed since 1998, with most of the cases being related to transmission from infected cats. Although the definitive diagnosis of feline sporotrichosis is made by fungal culture, cytopathological and histopathological examinations are used routinely, because the long culture period may delay treatment onset. However, alternative methods are desirable in cases of low fungal burden. Immunohistochemistry (IHC) has been described as a sensitive method for diagnosing human and canine sporotrichosis, but there are no reports of its application to cats. The aim of this study was to analyse the sensitivity of cytopathological examination (Quick Panoptic method), histopathology (Grocott silver stain) and anti-Sporothrix IHC by blinded comparisons, using fungal culture as the reference standard. Samples were collected from 184 cats with sporotrichosis that exhibited skin ulcers. The sensitivities of Grocott silver stain, cytopathological examination and IHC were 91.3%, 87.0% and 88.6%, respectively. Grocott silver stain showed the best performance. IHC showed high sensitivity, as did cytopathological examination and these may be considered as alternative methodologies. When the three methods were combined, the diagnosis was established in 180 (97.8%) out of 184 cases. Taken together, these findings indicate the need to implement these methods as routine tools for the early diagnosis of sporotrichosis in cats, notably when fungal culture is not available. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments

Science.gov (United States)

Loo, Lit-Hsin; Bougen-Zhukov, Nicola Michelle; Tan, Wei-Ling Cecilia

2017-03-01

Signaling pathways can generate different cellular responses to the same cytotoxic agents. Current quantitative models for predicting these differential responses are usually based on large numbers of intracellular gene products or signals at different levels of signaling cascades. Here, we report a study to predict cellular sensitivity to tumor necrosis factor alpha (TNFα) using high-throughput cellular imaging and machine-learning methods. We measured and compared 1170 protein phosphorylation events in a panel of human lung cancer cell lines based on different signals, subcellular regions, and time points within one hour of TNFα treatment. We found that two spatiotemporal-specific changes in an intermediate signaling protein, p90 ribosomal S6 kinase (RSK), are sufficient to predict the TNFα sensitivity of these cell lines. Our models could also predict the combined effects of TNFα and other kinase inhibitors, many of which are not known to target RSK directly. Therefore, early spatiotemporal-specific changes in intermediate signals are sufficient to represent the complex cellular responses to these perturbations. Our study provides a general framework for the development of rapid, signaling-based cytotoxicity screens that may be used to predict cellular sensitivity to a cytotoxic agent, or identify co-treatments that may sensitize or desensitize cells to the agent.

Exploring Intercultural Sensitivity in Early Adolescence: A Mixed Methods Study

Science.gov (United States)

Mellizo, Jennifer M.

2017-01-01

The purpose of this mixed methods study was to explore levels of intercultural sensitivity in a sample of fourth to eighth grade students in the United States (n = 162). "Intercultural sensitivity" was conceptualised through Bennett's Developmental Model of Sensitivity, and assessed through the Adapted Intercultural Sensitivity Index.…

Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer.

Science.gov (United States)

Clarke, Charlotte H; Yip, Christine; Badgwell, Donna; Fung, Eric T; Coombes, Kevin R; Zhang, Zhen; Lu, Karen H; Bast, Robert C

2011-09-01

The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P=0.015, McNemar's test). Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer. Copyright © 2011. Published by Elsevier Inc.

Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

International Nuclear Information System (INIS)

Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin

2006-01-01

Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor β immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent

Sensitivity of different MRI sequences in the early detection of melanoma brain metastases

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Breckwoldt, Michael O.; Schwarz, Daniel; Radbruch, Alexander; Enk, Alexander; Bendszus, Martin; Hassel, Jessica; Schlemmer, Heinz-Peter

2018-01-01

Background After the emergence of new MRI techniques such as susceptibility- and diffusion-weighted imaging (SWI and DWI) and because of specific imaging characteristics of melanoma brain metastases (MBM), it is unclear which MRI sequences are most beneficial for detection of MBM. This study was performed to investigate the sensitivity of six clinical MRI sequences in the early detection of MBM. Methods Medical records of all melanoma patients referred to our center between November 2005 and December 2016 were reviewed for presence of MBM. Analysis encompassed six MRI sequences at the time of initial diagnosis of first or new MBM, including non-enhanced T1-weighted (T1w), contrast-enhanced T1w (ceT1w), T2-weighted (T2w), T2w-FLAIR, susceptibility-weighted (SWI) and diffusion-weighted (DWI) MRI. Each lesion was rated with respect to its conspicuity (score from 0—not detectable to 3—clearly visible). Results Of 1210 patients, 217 with MBM were included in the analysis and up to 5 lesions per patient were evaluated. A total of 720 metastases were assessed and all six sequences were available for 425 MBM. Sensitivity (conspicuity ≥2) was 99.7% for ceT1w, 77.0% for FLAIR, 64.7% for SWI, 61.0% for T2w, 56.7% for T1w, and 48.4% for DWI. Thirty-one (7.3%) of 425 lesions were only detectable by ceT1w but no other sequence. Conclusions Contrast-enhanced T1-weighting is more sensitive than all other sequences for detection of MBM. Disruption of the blood-brain-barrier is consistently an earlier sign in MBM than perifocal edema, signal loss on SWI or diffusion restriction. PMID:29596475

Radiation induced variations in photoperiod-sensitivity, thermo-sensitivity and the number of days to heading in rice

International Nuclear Information System (INIS)

Hsieh, S.C.

1975-01-01

Radiation induced semi-dwarf mutants derived from five japonica type varieties of rice were studied with regard to their photoperiod-sensitivity, thermo-sensitivity and the number of days to heading. The experiment was carried out under the natural conditions at Taipei. The coefficient of photoperiod-sensitivity and thermo-sensitivity as developed by Oka (1954) were estimated for the mutants in comparison with their original varieties. It was observed that these various physiological characters could be altered easily by mutations. Mutants showed wider ranges in both positive and negative directions than their original varieties in all physiological characters studied. Even though heading date depends on both photoperiod-sensitivity and thermo-sensitivity, it was estimated which of the two contributed more to the induced earliness in each mutant. This offers a basis for selecting early maturing lines of rice

Pilot evaluation of short-term changes in macular pigment and retinal sensitivity in different phenotypes of early age-related macular degeneration after carotenoid supplementation.

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Corvi, Federico; Souied, Eric H; Falfoul, Yousra; Georges, Anouk; Jung, Camille; Querques, Lea; Querques, Giuseppe

2017-06-01

To investigate the response of carotenoid supplementation in different phenotypes of early age-related macular degeneration (AMD) by measuring macular pigment optical density (MPOD) and retinal sensitivity. Consecutive patients with only medium/large drusen and only reticular pseudodrusen (RPD) and age-matched and sex-matched controls were enrolled. At baseline, participants underwent a complete ophthalmological examination including measurement of best-corrected visual acuity (BCVA), MPOD and retinal sensitivity. Patients were put on vitamin supplementation (lutein 10 mg/day, zeaxanthin 2 mg/day) and 3 months later underwent a repeated ophthalmological examination. Twenty patients with medium/large drusen, 19 with RPD and 15 control subjects were included. At baseline, in controls, mean MPOD and BCVA were significantly higher compared with RPD (p=0.001 and p=0.01) but similar to medium/large drusen (p=0.9 and p=0.4). Mean retinal sensitivity was significantly higher in controls compared with RPD and medium/large drusen (for all p<0.0001). After 3 months of carotenoid supplementation the mean MPOD significantly increased in RPD (p=0.002), thus showing no more difference compared with controls (p=0.3); no significant changes were found in mean retinal sensitivity and BCVA (p=0.3 and p=0.7). Medium/large drusen did not show significant changes on MPOD, retinal sensitivity and BCVA (p=0.5, p=0.7 and p=0.7, respectively). Patients with early AMD, especially RPD phenotype, show lower macular sensitivity and MPOD than controls. After supplementation, MPOD significantly increased in RPD. These results suggest different pathophysiology for RPD as compared with medium/large drusen and may open new ways to identifying further therapeutic targets in this phenotype of early AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Mammographic density changes following discontinuation of tamoxifen in premenopausal women with oestrogen receptor-positive breast cancer.

Science.gov (United States)

Kim, Won Hwa; Cho, Nariya; Kim, Young-Seon; Yi, Ann

2018-04-06

To evaluate the changes in mammographic density after tamoxifen discontinuation in premenopausal women with oestrogen receptor-positive breast cancers and the underlying factors METHODS: A total of 213 consecutive premenopausal women with breast cancer who received tamoxifen treatment after curative surgery and underwent three mammograms (baseline, after tamoxifen treatment, after tamoxifen discontinuation) were included. Changes in mammographic density after tamoxifen discontinuation were assessed qualitatively (decrease, no change, or increase) by two readers and measured quantitatively by semi-automated software. The association between % density change and clinicopathological factors was evaluated using univariate and multivariate regression analyses. After tamoxifen discontinuation, a mammographic density increase was observed in 31.9% (68/213, reader 1) to 22.1% (47/213, reader 2) by qualitative assessment, with a mean density increase of 1.8% by quantitative assessment compared to density before tamoxifen discontinuation. In multivariate analysis, younger age (≤ 39 years) and greater % density decline after tamoxifen treatment (≥ 17.0%) were independent factors associated with density change after tamoxifen discontinuation (p density change with a mean density increase of 1.8%, which was associated with younger age and greater density change after tamoxifen treatment. • Increased mammographic density after tamoxifen discontinuation can occur in premenopausal women. • Mean density increase after tamoxifen discontinuation was 1.8%. • Density increase is associated with age and density decrease after tamoxifen.

Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer.

Science.gov (United States)

Huo, Dezheng; Feng, Ye; Haddad, Stephen; Zheng, Yonglan; Yao, Song; Han, Yoo-Jeong; Ogundiran, Temidayo O; Adebamowo, Clement; Ojengbede, Oladosu; Falusi, Adeyinka G; Zheng, Wei; Blot, William; Cai, Qiuyin; Signorello, Lisa; John, Esther M; Bernstein, Leslie; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Deming, Sandra L; Rodriguez-Gil, Jorge L; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Ruiz-Narváez, Edward A; Sucheston-Campbell, Lara E; Bensen, Jeannette T; Simon, Michael S; Hennis, Anselm; Nemesure, Barbara; Leske, M Cristina; Ambs, Stefan; Chen, Lin S; Qian, Frank; Gamazon, Eric R; Lunetta, Kathryn L; Cox, Nancy J; Chanock, Stephen J; Kolonel, Laurence N; Olshan, Andrew F; Ambrosone, Christine B; Olopade, Olufunmilayo I; Palmer, Julie R; Haiman, Christopher A

2016-11-01

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina’s HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 − 8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 − 10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 − 8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

Patterns of Sensitivity to Parenting and Peer Environments: Early Temperament and Adolescent Externalizing Behavior.

Science.gov (United States)

Tung, Irene; Noroña, Amanda N; Morgan, Julia E; Caplan, Barbara; Lee, Steve S; Baker, Bruce L

2018-03-14

Although parenting behavior and friendship quality predict adolescent externalizing behaviors (EBs), individual differences in temperament may differentially affect susceptibility to these factors over time. In a multi-method and multi-informant study of 141 children followed prospectively from toddlerhood to adolescence, we tested the independent and interactive associations of age 3 reactive temperament (e.g., negative emotionality) and age 13 observed parenting (i.e., positive and negative behavior) and friendship (i.e., conflict and warmth), with multi-informant ratings of age 15 aggression and rule-breaking behavior. Negative parenting predicted growth in parent-rated EB, but only for adolescents with early reactive temperament. Temperament did not affect sensitivity to positive parenting or friendship. Results are discussed in the context of differential susceptibility theory and intervention implications for adolescents. © 2018 Society for Research on Adolescence.

Combined determination of highly sensitive troponin T and copeptin for early exclusion of acute myocardial infarction: first experience in an emergency department of a general hospital

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Lotze U

2011-08-01

Full Text Available Ulrich Lotze1, Holger Lemm2, Anke Heyer2, Karin Müller31Department of Internal Medicine, German Red Cross Hospital Sondershausen, Sondershausen, 2Department of Internal Medicine, 3Department of Laboratory Medicine, Saale-Unstrut Hospital Naumburg, Naumburg, GermanyBackground: The purpose of this observational study was to test the diagnostic performance of the Elecsys® troponin T high-sensitive system combined with copeptin measurement for early exclusion of acute myocardial infarction (MI in clinical practice.Methods: Troponin T high-sensitive (diagnostic cutoff: <14 pg/mL and copeptin (diagnostic cutoff: <14 pmol/L levels were determined at admission in addition to other routine laboratory parameters in patients with suspected acute MI presenting to the emergency department of a general hospital over a period of five months.Results: Data from 142 consecutive patients (mean age 71.2 ± 13.5 years, 76 men were analyzed. Final diagnoses were acute MI in 13 patients (nine ST elevation MI, four non-ST elevation MI, 9.2% unstable angina pectoris in three (2.1%, cardiac symptoms not primarily associated with myocardial ischemia in 79 (55.6%, and noncardiac disease in 47 patients (33.1%. The patients with acute MI were younger and had higher troponin T high-sensitive and copeptin values than patients without acute MI. Seventeen patients had very high copeptin values (>150 pmol/L, one of whom had a level of >700 pmol/L and died of pulmonary embolism. A troponin T high-sensitive level of <14 pg/mL in combination with copeptin <14 pmol/L at initial presentation ruled out acute MI in 45 of the 142 patients (31.7%, each with a sensitivity and negative predictive value of 100%.Conclusion: According to this early experience, a single determination of troponin T high-sensitive and copeptin may enable early and accurate exclusion of acute MI in one third of patients, even in an emergency department of a general hospital.Keywords: highly sensitive troponin T

Removal of natural hormones in dairy farm wastewater using reactive and sorptive materials.

Science.gov (United States)

Cai, Kai; Phillips, Debra H; Elliott, Christopher T; Muller, Marc; Scippo, Marie-Louise; Connolly, Lisa

2013-09-01

The objective of this study was to examine the oestrogen and androgen hormone removal efficiency of reactive (Connelly zero-valent iron (ZVI), Gotthart Maier ZVI) and sorptive (AquaSorb 101 granular activated carbon (GAC) and OrganoLoc PM-100 organoclay (OC)) materials from HPLC grade water and constructed wetland system (CWS) treated dairy farm wastewater. Batch test studies were performed and hormone concentration analysis carried out using highly sensitive reporter gene assays (RGAs). The results showed that hormonal interaction with these materials is selective for individual classes of hormones. Connelly ZVI and AquaSorb 101 GAC were more efficient in removing testosterone (Te) than 17β-estradiol (E2) and showed faster removal rates of oestrogen and androgen than the other materials. Gotthart Maier ZVI was more efficient in removing E2 than Te. OrganoLoc PM-100 OC achieved the lowest final concentration of E2 equivalent (EEQ) and provided maximum removal of both oestrogens and androgens. Copyright © 2013 Elsevier B.V. All rights reserved.

Sensitivity and uncertainty studies of the CRAC2 computer code

International Nuclear Information System (INIS)

Kocher, D.C.; Ward, R.C.; Killough, G.G.; Dunning, D.E. Jr.; Hicks, B.B.; Hosker, R.P. Jr.; Ku, J.Y.; Rao, K.S.

1985-05-01

This report presents a study of the sensitivity of early fatalities, early injuries, latent cancer fatalities, and economic costs for hypothetical nuclear reactor accidents as predicted by the CRAC2 computer code (CRAC = Calculation of Reactor Accident Consequences) to uncertainties in selected models and parameters used in the code. The sources of uncertainty that were investigated in the CRAC2 sensitivity studies include (1) the model for plume rise, (2) the model for wet deposition, (3) the procedure for meteorological bin-sampling involving the selection of weather sequences that contain rain, (4) the dose conversion factors for inhalation as they are affected by uncertainties in the physical and chemical form of the released radionuclides, (5) the weathering half-time for external ground-surface exposure, and (6) the transfer coefficients for estimating exposures via terrestrial foodchain pathways. The sensitivity studies were performed for selected radionuclide releases, hourly meteorological data, land-use data, a fixed non-uniform population distribution, a single evacuation model, and various release heights and sensible heat rates. Two important general conclusions from the sensitivity and uncertainty studies are as follows: (1) The large effects on predicted early fatalities and early injuries that were observed in some of the sensitivity studies apparently are due in part to the presence of thresholds in the dose-response models. Thus, the observed sensitivities depend in part on the magnitude of the radionuclide releases. (2) Some of the effects on predicted early fatalities and early injuries that were observed in the sensitivity studies were comparable to effects that were due only to the selection of different sets of weather sequences in bin-sampling runs. 47 figs., 50 tabs

Increased sensitivity to climate change in disturbed ecosystems

DEFF Research Database (Denmark)

Kroël-Dulay, György; Ransijn, Johannes; Schmidt, Inger Kappel

2015-01-01

Human domination of the biosphere includes changes to disturbance regimes, which push many ecosystems towards early-successional states. Ecological theory predicts that early-successional ecosystems are more sensitive to perturbations than mature systems, but little evidence supports this relatio......Human domination of the biosphere includes changes to disturbance regimes, which push many ecosystems towards early-successional states. Ecological theory predicts that early-successional ecosystems are more sensitive to perturbations than mature systems, but little evidence supports...... this relationship for the perturbation of climate change. Here we show that vegetation (abundance, species richness and species composition) across seven European shrublands is quite resistant to moderate experimental warming and drought, and responsiveness is associated with the dynamic state of the ecosystem...

The influence of certain environmental factors on the sexual development and reproductive ability of Karakul sheep

International Nuclear Information System (INIS)

Faure, A.S.

1986-01-01

An investigation conducted on the influence of season of birth on sexual development, reproduction and luteinizing hormone of karakul sheep is described. The influence of season of birth on testosterone and semen properties of rams as well as nutrition and exogenous oestrogen of ewes are discussed. A radioimmunology technique was used for the determination of testosterone concentration of karakul rams. A Radioimmunology technique was also used for the determination of the plasma concentration of oestrogen and progesterone of ewe lambs. Results obtained, provided sufficient evidence that the Karakul sheep can reproduce successfully early in life which is desirable to enhance reproduction. It also emphasised the importance of optimal nutrition to promote sexual development and reproduction

Influence of certain environmental factors on the sexual development and reproductive ability of Karakul sheep. Die invloed van sekere omgewingsfakfore op die geslagsontwikkeling en reproduksievermoe van Karakoelskape

Energy Technology Data Exchange (ETDEWEB)

Faure, A S

1986-01-01

An investigation conducted on the influence of season of birth on sexual development, reproduction and luteinizing hormone of Karakul sheep is described. The influence of season of birth on testosterone and semen properties of rams as well as nutrition and exogenous oestrogen of ewes are discussed. A radioimmunology technique was used for the determination of testosterone concentration of Karakul rams. A radioimmunology technique was also used for the determination of the plasma concentration of oestrogen and progesterone of ewe lambs. Results obtained, provided sufficient evidence that the Karakul sheep can reproduce successfully early in life which is desirable to enhance reproduction. It also emphasised the importance of optimal nutrition to promote sexual development and reproduction.

Internal noise sources limiting contrast sensitivity.

Science.gov (United States)

Silvestre, Daphné; Arleo, Angelo; Allard, Rémy

2018-02-07

Contrast sensitivity varies substantially as a function of spatial frequency and luminance intensity. The variation as a function of luminance intensity is well known and characterized by three laws that can be attributed to the impact of three internal noise sources: early spontaneous neural activity limiting contrast sensitivity at low luminance intensities (i.e. early noise responsible for the linear law), probabilistic photon absorption at intermediate luminance intensities (i.e. photon noise responsible for de Vries-Rose law) and late spontaneous neural activity at high luminance intensities (i.e. late noise responsible for Weber's law). The aim of this study was to characterize how the impact of these three internal noise sources vary with spatial frequency and determine which one is limiting contrast sensitivity as a function of luminance intensity and spatial frequency. To estimate the impact of the different internal noise sources, the current study used an external noise paradigm to factorize contrast sensitivity into equivalent input noise and calculation efficiency over a wide range of luminance intensities and spatial frequencies. The impact of early and late noise was found to drop linearly with spatial frequency, whereas the impact of photon noise rose with spatial frequency due to ocular factors.

Comparative study of the sensitivity of ADC value and T2 relaxation time for early detection of Wallerian degeneration

International Nuclear Information System (INIS)

Zhang Fan; Lu Guangming; Zee Chishing

2011-01-01

Background and purpose: Wallerian degeneration (WD), the secondary degeneration of axons from cortical and subcortical injuries, is associated with poor neurological outcome. There is some quantitative MR imaging techniques used to estimate the biologic changes secondary to delayed neuronal and axonal losses. Our purpose is to assess the sensitivity of ADC value and T 2 relaxation time for early detection of WD. Methods: Ten male Sprague-Dawley rats were used to establish in vivo Wallerian degeneration model of CNS by ipsilateral motor-sensory cortex ablation. 5 days after cortex ablation, multiecho-T 2 relaxometry and multi-b value DWI were acquired by using a 7 T MR imaging scanner. ADC-map and T 2 -map were reconstructed by post-processing. ROIs are selected according to pathway of corticospinal tract from cortex, internal capsule, cerebral peduncle, pons, medulla oblongata to upper cervical spinal cord to measure ADC value and T 2 relaxation time of healthy side and affected side. The results were compared between the side with cortical ablation and the side without ablation. Results: Excluding ablated cortex, ADC values of the corticospinal tract were significantly increased (P 2 relaxation time was observed between the affected and healthy sides. Imaging findings were correlated with histological examinations. Conclusion: As shown in this animal experiment, ADC values could non-invasively demonstrate the secondary degeneration involving descending white matter tracts. ADC values are more sensitive indicators for detection of early WD than T 2 relaxation time.

A Longitudinal Study of Rejecting and Autonomy-Restrictive Parenting, Rejection Sensitivity, and Socioemotional Symptoms in Early Adolescents.

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Rowe, Susan L; Gembeck, Melanie J Zimmer; Rudolph, Julia; Nesdale, Drew

2015-08-01

Rejection sensitivity (RS) has been defined as the tendency to readily perceive and overreact to interpersonal rejection. The primary aim of this study was to test key propositions of RS theory, namely that rejecting experiences in relationships with parents are antecedents of early adolescents' future RS and symptomatology. We also expanded this to consider autonomy-restrictive parenting, given the importance of autonomy in early adolescence. Participants were 601 early adolescents (age 9 to 13 years old, 51% boys) from three schools in Australia. Students completed questionnaires at school about parent and peer relationships, RS, loneliness, social anxiety, and depression at two times with a 14-month lag between assessments. Parents also reported on adolescents' difficulties at Time 1 (T1). It was anticipated that more experience of parental rejection, coercion, and psychological control would be associated with adolescents' escalating RS and symptoms over time, even after accounting for peer victimisation, and that RS would mediate associations between parenting and symptoms. Structural equation modelling supported these hypotheses. Parent coercion was associated with adolescents' increasing symptoms of social anxiety and RS over time, and parent psychological control was associated with increasing depressive symptoms over time. Indirect effects via RS were also found, with parent rejection and psychological control linked to higher T1 RS, which was then associated with increasing loneliness and RS. Lastly, in a separate model, peer victimisation and RS, but not parenting practices, were positively associated with concurrent parent reports of adolescents' difficulties.

Food allergy and food sensitization in early childhood:

DEFF Research Database (Denmark)

Eller, E; Kjaer, H F; Høst, A

2009-01-01

of AD using Hanifin-Rajka criteria and for FHS using interviews, skin prick test (SPT), specific immunoglobulin E (IgE), and food challenge according to EAACI guidelines. Results: Twenty children were confirmed with FHS to milk, egg, and peanut. FHS peaked at 18 months (3.6%) and then decreased to 1......Background: The prevalence of food hypersensitivity (FHS) and the relationship with atopic dermatitis (AD) is controversial. The aim of this study was to determine the development of FHS and to correlate this with AD in relation to sensitization and symptoms. Methods: This study combines new data.......2% at 72 months of age. No new cases were found after 3 years. Self-reporting could only be confirmed in 31% of cases. Among the 122 children with AD, 18 had FHS (14.8%). FHS was IgE-mediated in 95% of the cases but 16 of 20 children were additionally sensitized to other foods which they tolerated...

Climate sensitivity to Arctic seaway restriction during the early Paleogene

Science.gov (United States)

Roberts, Christopher D.; LeGrande, Allegra N.; Tripati, Aradhna K.

2009-09-01

The opening and closing of ocean gateways affects the global distribution of heat, salt, and moisture, potentially driving climatic change on regional to global scales. Between 65 and 45 million years ago (Ma), during the early Paleogene, exchange between the Arctic and global oceans occurred through two narrow and shallow seaways, the Greenland-Norway seaway and the Turgai Strait. Sediments from the Arctic Ocean suggest that, during this interval, the surface ocean was warm, brackish, and episodically enabled the freshwater fern Azolla to bloom. The precise mechanisms responsible for the development of these conditions in the Paleogene Arctic remain uncertain. Here we show results from an isotope-enabled, atmosphere-ocean general circulation model, which indicate that Northern Hemisphere climate would have been very sensitive to the degree of oceanic exchange through the Arctic seaways. We also present modelled estimates of seawater and calcite δ18O for the Paleogene. By restricting these seaways, we simulate freshening of the surface Arctic Ocean to ~ 6 psu and warming of sea-surface temperatures by 2 °C in the North Atlantic and 5-10 °C in the Labrador Sea. Our results may help explain the occurrence of low-salinity tolerant taxa in the Arctic Ocean during the Eocene and provide a mechanism for enhanced warmth in the north western Atlantic. We propose that the formation of a volcanic land-bridge between Greenland and Europe could have caused increased ocean convection and warming of intermediate waters in the Atlantic. If true, this result is consistent with the theory that bathymetry changes may have caused thermal destabilisation of methane clathrates and supports a tectonic trigger hypothesis for the Paleocene Eocene Thermal Maximum (PETM).

Early (N170/M170 face-sensitivity despite right lateral occipital brain damage in acquired prosopagnosia

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Esther eAlonso Prieto

2011-12-01

Full Text Available Compared to objects, pictures of faces elicit a larger early electromagnetic response at occipito-temporal sites on the human scalp, with an onset of 130 ms and a peak at about 170 ms. This N170 face effect is larger in the right than the left hemisphere and has been associated with the early categorization of the stimulus as a face. Here we tested whether this effect can be observed in the absence of some of the visual areas showing a preferential response to faces as typically identified in neuroimaging. Event related potentials were recorded in response to faces, cars and their phase-scrambled versions in a well-known brain-damaged case of prosopagnosia (PS. Despite the patient’s right inferior occipital gyrus lesion encompassing the most posterior cortical area showing preferential response to faces (occipital face area, OFA, we identified an early face-sensitive component over the right occipito-temporal hemisphere of the patient that was identified as the N170. A second experiment supported this conclusion, showing the typical N170 increase of latency and amplitude in response to inverted faces. In contrast, there was no N170 in the left hemisphere, where PS has a lesion to the middle fusiform gyrus and shows no evidence of face-preferential response in neuroimaging (no left fusiform face area, or lFFA. These results were replicated by a magneto-encephalographic (MEG investigation of the patient, disclosing a M170 component only in the right hemisphere. These observations indicate that face preferential activation in the inferior occipital cortex is not necessary to elicit early visual responses associated with face perception (N170/M170 on the human scalp. These results further suggest that when the right inferior occipital cortex is damaged, the integrity of the middle fusiform gyrus and/or the superior temporal sulcus – two areas showing face preferential responses in the patient’s right hemisphere - might be necessary to generate

Characterization of early events involved in human dendritic cell maturation induced by sensitizers: Cross talk between MAPK signalling pathways

International Nuclear Information System (INIS)

Trompezinski, Sandra; Migdal, Camille; Tailhardat, Magalie; Le Varlet, Beatrice; Courtellemont, Pascal; Haftek, Marek; Serres, Mireille

2008-01-01

Dendritic cells (DCs), efficient-antigen presenting cells play an important role in initiating and regulating immune responses. DC maturation following exposure to nickel or DNCB induced an up-regulation of phenotypic markers and inflammatory cytokine secretion. Early intracellular mechanisms involved in DC maturation required to be precise. To address this purpose, DCs derived from human monocytes were treated with sensitizers (nickel, DNCB or thimerosal) in comparison with an irritant (SDS). Our data confirming the up-regulation of CD86, CD54 and cytokine secretion (IL-8 and TNFα) induced by sensitizers but not by SDS, signalling transduction involved in DC maturation was investigated using these chemicals. Kinase activity measurement was assessed using two new sensitive procedures (Face TM and CBA) requiring few cells. SDS did not induce changes in signalling pathways whereas NiSO 4 , DNCB and thimerosal markedly activated p38 MAPK and JNK, in contrast Erk1/2 phosphorylation was completely inhibited by DNCB or thimerosal and only activated by nickel. A pre-treatment with p38 MAPK inhibitor (SB203580) suppressed Erk1/2 inhibition induced by DNCB or thimerosal demonstrating a direct interaction between p38 MAPK and Erk1/2. A pre-treatment with an antioxidant, N-acetyl-L-cysteine (NAC) markedly reduced Erk1/2 inhibition and p38 MAPK phosphorylation induced by DNCB and thimerosal, suggesting a direct activation of p38 MAPK via an oxidative stress and a regulation of MAPK signalling pathways depending on chemicals. Because of a high sensitivity of kinase activity measurements, these procedures will be suitable for weak or moderate sensitizer screening

Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

LENUS (Irish Health Repository)

Hogan, A M

2012-02-01

Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38\\/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta

Comparison of surrogate indices for insulin sensitivity with parameters of the intravenous glucose tolerance test in early lactation dairy cattle.

Science.gov (United States)

Alves-Nores, V; Castillo, C; Hernandez, J; Abuelo, A

2017-10-01

The aim of this study was to investigate the correlation between different surrogate indices and parameters of the intravenous glucose tolerance test (IVGTT) in dairy cows at the start of their lactation. Ten dairy cows underwent IVGTT on Days 3 to 7 after calving. Areas under the curve during the 90 min after infusion, peak and nadir concentrations, elimination rates, and times to reach half-maximal and basal concentrations for glucose, insulin, nonesterified fatty acids, and β-hydroxybutyrate were calculated. Surrogate indices were computed using the average of the IVGTT basal samples, and their correlation with the IVGTT parameters studied through the Spearman's rank test. No statistically significant or strong correlation coefficients (P > 0.05; |ρ| insulin sensitivity measures derived from the IVGTT and any of the surrogate indices. Therefore, these results support that the assessment of insulin sensitivity in early lactation cattle cannot rely on the calculation of surrogate indices in just a blood sample, and the more laborious tests (ie, hyperinsulinemic euglycemic clamp test or IVGTT) should be employed to predict the sensitivity of the peripheral tissues to insulin accurately. Copyright © 2017 Elsevier Inc. All rights reserved.

Validation of the Early Functional Abilities scale

DEFF Research Database (Denmark)

Poulsen, Ingrid; Kreiner, Svend; Engberg, Aase W

2018-01-01

model item analysis. A secondary objective was to examine the relationship between the Early Functional Abilities scale and the Functional Independence Measurement™, in order to establish the criterion validity of the Early Functional Abilities scale and to compare the sensitivity of measurements using......), facio-oral, sensorimotor and communicative/cognitive functions. Removal of one item from the sensorimotor scale confirmed unidimensionality for each of the 4 subscales, but not for the entire scale. The Early Functional Abilities subscales are sensitive to differences between patients in ranges in which......OBJECTIVE: The Early Functional Abilities scale assesses the restoration of brain function after brain injury, based on 4 dimensions. The primary objective of this study was to evaluate the validity, objectivity, reliability and measurement precision of the Early Functional Abilities scale by Rasch...

Early Oral Ovalbumin Exposure during Maternal Milk Feeding Prevents Spontaneous Allergic Sensitization in Allergy-Prone Rat Pups

Directory of Open Access Journals (Sweden)

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.

The Paradox of Oestradiol-Induced Breast Cancer Cell Growth and Apoptosis.

Science.gov (United States)

Maximov, Philipp Y; Lewis-Wambi, Joan S; Jordan, V Craig

2009-05-01

High dose oestrogen therapy was used as a treatment for postmenopausal patients with breast cancer from the 1950s until the introduction of the safer antioestrogen, tamoxifen in the 1970s. The anti-tumour mechanism of high dose oestrogen therapy remained unknown. There was no enthusiasm to study these signal transduction pathways as oestrogen therapy has almost completely been eliminated from the treatment paradigm. Current use of tamoxifen and the aromatase inhibitors seek to create oestrogen deprivation that prevents the growth of oestrogen stimulated oestrogen receptor (ER) positive breast cancer cells. However, acquired resistance to antihormonal therapy does occur, but it is through investigation of laboratory models that a vulnerability of the cancer cell has been discovered and is being investigated to provide new opportunities in therapy with the potential for discovering new cancer-specific apoptotic drugs. Laboratory models of resistance to raloxifene and tamoxifen, the selective oestrogen receptor modulators (SERMs) and aromatase inhibitors demonstrate an evolution of drug resistance so that after many years of oestrogen deprivation, the ER positive cancer cell reconfigures the survival signal transduction pathways so oestrogen now becomes an apoptotic trigger rather than a survival signal. Current efforts are evaluating the mechanisms of oestrogen-induced apoptosis and how this new biology of oestrogen action can be amplified and enhanced, thereby increasing the value of this therapeutic opportunity for the treatment of breast cancer. Several synergistic approaches to therapeutic enhancement are being advanced which involve drug combinations to impair survival signaling with the use of specific agents and to impair bcl-2 that protects the cancer cell from apoptosis. We highlight the historical understanding of oestrogen's role in cell survival and death and specifically illustrate the progress that has been made in the last five years to understand the

Association of aromatase (TTTA)n repeat polymorphisms with central precocious puberty in girls.

Science.gov (United States)

Lee, Hae Sang; Kim, Kyung Hee; Hwang, Jin Soon

2014-09-01

Precocious puberty is characterized by early activation of the pituitary-gonadal axis. Oestrogen is the final key factor to start the onset of puberty. The cytochrome P450 19A1 (CYP19A1) gene encodes an aromatase that is responsible for the conversion of androgens to oestrogen, which is a key step in oestrogen biosynthesis. The aim of this study was to identify CYP19A1 gene mutations or polymorphisms in girls with central precocious puberty (CPP). We evaluated the frequency of allelic variants of the CYP19A1 exons and the tetranucleotide tandem repeat (TTTA)n in intron 4 in 203 idiopathic central precocious puberty (CPP) girls and 101 normal healthy women. The genotype analysis of the CYP19A1 (TTTA)n polymorphism revealed six different alleles ranging from seven to 13 repeats. Among the six different repeat alleles detected in this study, the (TTTA)₁₃ repeat allele was only detected in the patient group and carriers of the (TTTA)₁₃ allele were significantly associated with an increased risk of CPP (OR = 1·509, 95% CI = 1·425-1·598, P = 0·033). Carriers of the (TTTA)₁₃ repeat allele were significantly younger at pubertal onset and had higher levels of oestrogen than noncarriers of the (TTTA)₁₃ repeat allele. Although nine polymorphisms were detected in exons of the CYP19A1 gene, no clinical significance was observed. In this study, carriers of a higher repeat (TTTA)₁₃ polymorphism in intron 4 of the CYP19A1 gene had higher levels of oestrogen. Those carrying the (TTTA)₁₃ repeat allele may have a higher risk of developing CPP. © 2014 John Wiley & Sons Ltd.

Early life stress sensitizes the renal and systemic sympathetic system in rats.

Science.gov (United States)

Loria, Analia S; Brands, Michael W; Pollock, David M; Pollock, Jennifer S

2013-08-01

We hypothesized that maternal separation (MS), an early life stress model, induces a sensitization of the sympathetic system. To test this hypothesis, we evaluated the renal and systemic sympathetic system in 12- to 14-wk-old male control or MS rats with the following parameters: 1) effect of renal denervation on conscious renal filtration capacity, 2) norepinephrine (NE) content in key organs involved in blood pressure control, and 3) acute systemic pressor responses to adrenergic stimulation or ganglion blockade. MS was performed by separating pups from their mothers for 3 h/day from day 2 to 14; controls were nonhandled littermates. Glomerular filtration rate (GFR) was examined in renal denervated (DnX; within 2 wk) or sham rats using I¹²⁵-iothalamate plasma clearance. MS-DnX rats showed significantly increased GFR compared with MS-SHAM rats (3.8 ± 0.4 vs. 2.4 ± 0.2 ml/min, respectively, P renal nerves regulate GFR in MS rats. NE content was significantly increased in organ tissues from MS rats (P renal and systemic sympathetic system. Conscious MS rats displayed a significantly greater increase in mean arterial pressure (MAP) in response to NE (2 μg/kg ip) and a greater reduction in MAP in response to mecamylamine (2 mg/kg ip, P renal and systemic sympathetic system ultimately impairing blood pressure regulation.

Sensitivity to UV radiation in early life stages of the Mediterranean sea urchin Sphaerechinus granularis (Lamarck)

International Nuclear Information System (INIS)

Nahon, Sarah; Castro Porras, Viviana A.; Pruski, Audrey M.; Charles, Francois

2009-01-01

The sea urchin Sphaerechinus granularis was used to investigate the impact of relevant levels of UV-B radiation on the early life stages of a common Mediterranean free spawning benthic species. Sperm, eggs and embryos were exposed to a range of UV radiation doses. The resulting endpoints were evaluated in terms of fertilisation success, development and survival rates. Above a weighted UV radiation dose of 0.0029 kJ m -2 , fertilisation capability of irradiated sperm decreased rapidly. The exposure of the eggs to 0.0175 kJ m -2 and more led to delayed and inhibited development with ensuing embryonic morphological abnormalities. One-day old larvae remained strongly sensitive to UV radiation as shown by the 50% decrease of the larval survival rate for a dose of 0.025 kJ m -2 UVR. The elevated sensitivity of embryos to experimental UVR went along with a lack of significant amount of sunscreen compounds (e.g., mycosporine-like amino acids) in the eggs. The present results demonstrated that gamete viability and embryonic development may be significantly impaired by solar UV radiation in S. granularis, compromising in this way the reproduction of the species. Unless adaptive behavioural reproductive strategies exist, the influence of ambient UV radiation appears as a selective force for population dynamics of broadcast spawners in the shallow benthic Mediterranean environment

Sensitivity to UV radiation in early life stages of the Mediterranean sea urchin Sphaerechinus granularis (Lamarck)

Energy Technology Data Exchange (ETDEWEB)

Nahon, Sarah [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); CNRS, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); Castro Porras, Viviana A. [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); Pruski, Audrey M. [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); CNRS, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); Charles, Francois [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); CNRS, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France)], E-mail: charles@obs-banyuls.fr

2009-03-01

The sea urchin Sphaerechinus granularis was used to investigate the impact of relevant levels of UV-B radiation on the early life stages of a common Mediterranean free spawning benthic species. Sperm, eggs and embryos were exposed to a range of UV radiation doses. The resulting endpoints were evaluated in terms of fertilisation success, development and survival rates. Above a weighted UV radiation dose of 0.0029 kJ m{sup -2}, fertilisation capability of irradiated sperm decreased rapidly. The exposure of the eggs to 0.0175 kJ m{sup -2} and more led to delayed and inhibited development with ensuing embryonic morphological abnormalities. One-day old larvae remained strongly sensitive to UV radiation as shown by the 50% decrease of the larval survival rate for a dose of 0.025 kJ m{sup -2} UVR. The elevated sensitivity of embryos to experimental UVR went along with a lack of significant amount of sunscreen compounds (e.g., mycosporine-like amino acids) in the eggs. The present results demonstrated that gamete viability and embryonic development may be significantly impaired by solar UV radiation in S. granularis, compromising in this way the reproduction of the species. Unless adaptive behavioural reproductive strategies exist, the influence of ambient UV radiation appears as a selective force for population dynamics of broadcast spawners in the shallow benthic Mediterranean environment.

Reward sensitivity, attentional bias, and executive control in early adolescent alcohol use.

Science.gov (United States)

van Hemel-Ruiter, Madelon E; de Jong, Peter J; Ostafin, Brian D; Wiers, Reinout W

2015-01-01

This study examined whether attentional bias for alcohol stimuli was associated with alcohol use in young adolescents, and whether the frequently demonstrated relationship between reward sensitivity and adolescent alcohol use would be partly mediated by attentional bias for alcohol cues. In addition, this study investigated the potential moderating role of executive control (EC), and tested whether the relationship between alcohol-related attentional bias and alcohol use was especially present in young adolescents with weak EC. Participants were 86 adolescents (mean age=14.86), who completed a Visual Probe Task (VPT) as an index of attentional bias, a flanker-task based Attention Network Task (ANT) as an index of EC, the sensitivity of punishment and sensitivity of reward questionnaire (SPSRQ) as an index of reward sensitivity, and an alcohol use questionnaire. High reward sensitivity, high alcohol-related attentional bias, and weak EC were all related to alcohol use. The relationship between reward sensitivity and alcohol use was not mediated by alcohol-related attentional bias. As hypothesized, attentional bias was only associated with alcohol use in participants with weak EC. Together, the present findings are consistent with the view that high reward sensitivity and low EC may be considered as risk factors for adolescent alcohol use. The independent contribution of reward sensitivity and attentional bias might suggest that adolescents who are highly reward sensitive and display an attentional bias for alcohol cues are at even higher risk for excessive alcohol use and developing alcohol abuse problems. Future research using a longitudinal approach would allow an examination of these risk factors on subsequent alcohol use. Treatment implications are discussed, including the importance of strengthening EC and reducing the rewarding value of alcohol use. Copyright © 2014 Elsevier Ltd. All rights reserved.

The impact of menstrual phase on brachial artery flow-mediated dilatation during handgrip exercise in healthy premenopausal women.

Science.gov (United States)

D'Urzo, Katrina A; King, Trevor J; Williams, Jennifer S; Silvester, Morgan D; Pyke, Kyra E

2018-02-01

What is the central question of this study? The aim of this study was to determine the influence of menstrual phase on flow-mediated dilatation in response to sustained, exercise-induced increases in shear stress. What is the main finding and its importance? We showed, for the first time, that in healthy, premenopausal women the flow-mediated dilatation stimulated by exercise-induced increases in shear stress did not fluctuate across two phases of the menstrual cycle, despite significant fluctuations in oestrogen. This suggests that endothelial function is not consistently augmented in the high-oestrogen phase. Flow-mediated dilatation (FMD) in response to a sustained shear-stress stimulus (e.g. via handgrip exercise; HGEX) is emerging as a useful tool for assessing endothelial function; however, the impact of menstrual phase on HGEX-FMD is unknown. The purpose of this study was to determine whether HGEX-FMD fluctuates with cyclical changes in oestrogen concentrations over two discrete phases (low and high oestrogen) of the menstrual cycle. Brachial artery (BA) diameter and blood velocity were assessed with two-dimesional and Doppler ultrasound, respectively. Shear stress was estimated using shear rate (SR = BA blood velocity/BA diameter). Participants (12 healthy, regularly cycling women, 21 ± 2 years of age) completed two experimental visits: (i) low oestrogen (early follicular, EF); and (ii) high oestrogen (late follicular, LF). Reactive hyperaemia-stimulated FMD (RH-FMD) and HGEX-FMD (6 min of handgrip exercise) were assessed during each visit. Results are mean values ± SD. Oestrogen increased from the EF to LF phase (EF, 33 ± 9 pg ml -1 ; LF, 161 ± 113 pg ml -1 , P = 0.003). However, neither the SR stimuli (HGEX, P = 0.501; RH, P = 0.173) nor the FMD responses differed between phases (EF versus LF: HGEX-FMD, 4.8 ± 2.8 versus 4.6 ± 2.2%, P = 0.601; RH-FMD, 7.9 ± 4.3 versus 6.4 ± 3.1%, P = 0.071). These results extend

Early life adversity: Lasting consequences for emotional learning

Directory of Open Access Journals (Sweden)

Harm J. Krugers

2017-02-01

Full Text Available The early postnatal period is a highly sensitive time period for the developing brain, both in humans and rodents. During this time window, exposure to adverse experiences can lastingly impact cognitive and emotional development. In this review, we briefly discuss human and rodent studies investigating how exposure to adverse early life conditions – mainly related to quality of parental care - affects brain activity, brain structure, cognition and emotional responses later in life. We discuss the evidence that early life adversity hampers later hippocampal and prefrontal cortex functions, while increasing amygdala activity, and the sensitivity to stressors and emotional behavior later in life. Exposure to early life stress may thus on the one hand promote behavioral adaptation to potentially threatening conditions later in life –at the cost of contextual memory formation in less threatening situations- but may on the other hand also increase the sensitivity to develop stress-related and anxiety disorders in vulnerable individuals.

Absence of systemic hormonal effects in an oestradiol diether topically active on the vaginal mucosa.

Science.gov (United States)

Wolff, J P; Cachelou, R; Guéritée, N

1982-12-01

The women in this study were either post-menopausal or ovariectomised for at least 1 yr prior to the study. They had also been treated for cancer of the cervix (27 women), endometrium (5), ovaries (5) or breast (1). All women presented with sexual troubles, mainly genital discomfort (dyspareunia or vaginism). In a double-blind fashion, gynaecological capsules containing either an oestradiol diether (ICD: promestriene) or only the excipient were administered for 40 consecutive days. At the end of the treatment, the FSH, LH, oestrone (E1) and oestradiol (E2) plasma levels were not found to be significantly different from the pre-therapeutic values. These results suggest that promestriene acts on the vaginal mucosa, therefore not being converted back into the hormone from which it was derived. Also, in its dietheroxide form, promestriene is incapable of crossing the malpighian (vaginal or epidermal) epithelium and of reaching the general blood circulation. This discrepancy between the local anti-atrophic effects and the inability to exert systemic oestrogen activities singles out promestriene and justifies its therapeutic use when hormonally active oestrogens are contra-indicated, as in patients who have an oestrogen-sensitive cancer in their medical history.

East-West cultural differences in context-sensitivity are evident in early childhood.

Science.gov (United States)

Imada, Toshie; Carlson, Stephanie M; Itakura, Shoji

2013-03-01

Accumulating evidence suggests that North Americans tend to focus on central objects whereas East Asians tend to pay more attention to contextual information in a visual scene. Although it is generally believed that such culturally divergent attention tendencies develop through socialization, existing evidence largely depends on adult samples. Moreover, no past research has investigated the relation between context-sensitivity and other domains of cognitive development. The present study examined children in the United States and Japan (N = 175, age 4-9 years) to investigate the developmental pattern in context-sensitivity and its relation to executive function. The study found that context-sensitivity increased with age across cultures. Nevertheless, Japanese children showed significantly greater context-sensitivity than American children. Also, context-sensitivity fully mediated the cultural difference in a set-shifting executive function task, which might help explain past findings that East Asian children outperformed their American counterparts on executive function. © 2012 Blackwell Publishing Ltd.

Petunia cultivar sensitivity to ozone and sulfur dioxide

Energy Technology Data Exchange (ETDEWEB)

Elkiey, T.; Ormrod, D.P.

1979-01-01

Ozone and sulfur dioxide are widespread pollutants in many of the areas in which petunias are grown as bedding-plants. Controlled environment experiments were conducted to evaluate the sensitivity of Capri, White Magic and White Cascade to separate or combined O3 and SO2 at 2 growth stages. Relative cultivar sensitivity was the same for O3, SO2 or O3 + SO2, with Capri leaves least injured and White Cascade leaves most injured. Visible injury symptoms were similar in all cultivars. Leaves of intermediate age were most sensitive, but early vegetative plants were more sensitive to O3 than plants in immediate prefloral stage. Severity of leaf injury was generally greater from the combined gases than from the single gases, and the combination treatment at the early vegetative stage significantly reduced plant growth and flower weight 4 weeks later. 29 references, 4 figures, 7 tables.

Comparative study of the sensitivity of ADC value and T{sub 2} relaxation time for early detection of Wallerian degeneration

Energy Technology Data Exchange (ETDEWEB)

Zhang Fan [Department of Radiology, Nanjing Jinling Hospital, Clinical School of Medical College of Nanjing University, Nanjing 210002 (China); Lu Guangming, E-mail: cjr.luguangming@vip.163.com [Department of Radiology, Nanjing Jinling Hospital, Clinical School of Medical College of Nanjing University, Nanjing 210002 (China); Zee Chishing, E-mail: chishing@usc.edu [Department of Radiology, USC Keck School of Medicine (United States)

2011-07-15

Background and purpose: Wallerian degeneration (WD), the secondary degeneration of axons from cortical and subcortical injuries, is associated with poor neurological outcome. There is some quantitative MR imaging techniques used to estimate the biologic changes secondary to delayed neuronal and axonal losses. Our purpose is to assess the sensitivity of ADC value and T{sub 2} relaxation time for early detection of WD. Methods: Ten male Sprague-Dawley rats were used to establish in vivo Wallerian degeneration model of CNS by ipsilateral motor-sensory cortex ablation. 5 days after cortex ablation, multiecho-T{sub 2} relaxometry and multi-b value DWI were acquired by using a 7 T MR imaging scanner. ADC-map and T{sub 2}-map were reconstructed by post-processing. ROIs are selected according to pathway of corticospinal tract from cortex, internal capsule, cerebral peduncle, pons, medulla oblongata to upper cervical spinal cord to measure ADC value and T{sub 2} relaxation time of healthy side and affected side. The results were compared between the side with cortical ablation and the side without ablation. Results: Excluding ablated cortex, ADC values of the corticospinal tract were significantly increased (P < 0.05) in affected side compared to the unaffected, healthy side; no difference in T{sub 2} relaxation time was observed between the affected and healthy sides. Imaging findings were correlated with histological examinations. Conclusion: As shown in this animal experiment, ADC values could non-invasively demonstrate the secondary degeneration involving descending white matter tracts. ADC values are more sensitive indicators for detection of early WD than T{sub 2} relaxation time.

Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate.

Science.gov (United States)

Soldovieri, Maria Virginia; Ambrosino, Paolo; Mosca, Ilaria; De Maria, Michela; Moretto, Edoardo; Miceli, Francesco; Alaimo, Alessandro; Iraci, Nunzio; Manocchio, Laura; Medoro, Alessandro; Passafaro, Maria; Taglialatela, Maurizio

2016-12-01

Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K + current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP 2 ). Kv7.2 gene mutations cause early-onset neonatal seizures with heterogeneous clinical outcomes, ranging from self-limiting benign familial neonatal seizures to severe early-onset epileptic encephalopathy (Kv7.2-EE). In this study, the biochemical and functional consequences prompted by a recurrent variant (R325G) found independently in four individuals with severe forms of neonatal-onset EE have been investigated. Upon heterologous expression, homomeric Kv7.2 R325G channels were non-functional, despite biotin-capture in Western blots revealed normal plasma membrane subunit expression. Mutant subunits exerted dominant-negative effects when incorporated into heteromeric channels with Kv7.2 and/or Kv7.3 subunits. Increasing cellular PIP 2 levels by co-expression of type 1γ PI(4)P5-kinase (PIP5K) partially recovered homomeric Kv7.2 R325G channel function. Currents carried by heteromeric channels incorporating Kv7.2 R325G subunits were more readily inhibited than wild-type channels upon activation of a voltage-sensitive phosphatase (VSP), and recovered more slowly upon VSP switch-off. These results reveal for the first time that a mutation-induced decrease in current sensitivity to PIP 2 is the primary molecular defect responsible for Kv7.2-EE in individuals carrying the R325G variant, further expanding the range of pathogenetic mechanisms exploitable for personalized treatment of Kv7.2-related epilepsies.

The radiological consequences of notional accidental releases of radioactivity from fast breeder reactors: sensitivity of the incidence of early effects to the duration

International Nuclear Information System (INIS)

Hemming, C.R.; Hallam, J.; Kelly, G.N.

1979-12-01

The radiological consequences of a wide range of notional accidental releases from a 1300 MW(e) LMFBR were assessed in a study published in 1977 (NRPB-R53). In that study representative values were in general adopted for each of the important parameters while recognising that in reality they could vary considerably. In this study the sensitivity of the predicted incidence of early effects to the release duration, in so far as it affects the crosswind spread of the activity, is investigated. Two situations are considered; a short release in which the crosswind distribution of the activity is assumed to be Gaussian and a more prolonged release (as modelled in the initial study) in which the crosswind distribution of activity is assumed uniform over a 30 0 sector. For the particular conditions and population distributions considered, the incidence of early effects is greater for the short compared with the more prolonged release. The size of the increase depends upon the radionuclide composition, the magnitude of the release, the distribution of the exposed population, and the prevailing meteorological conditions, but in general the increase is not large. This relatively limited sensitivity indicates that the results obtained in the initial study can be assumed, to a good approximation, to be applicable irrespective of the release duration. (author)

Performance of classification criteria for gout in early and established disease

DEFF Research Database (Denmark)

Taylor, William J; Fransen, Jaap; Dalbeth, Nicola

2016-01-01

OBJECTIVES: To compare the sensitivity and specificity of different classification criteria for gout in early and established disease. METHODS: This was a cross-sectional study of consecutive rheumatology clinic patients with joint swelling in which gout was defined by presence or absence...... of monosodium urate crystals as observed by a certified examiner at presentation. Early disease was defined as patient-reported onset of symptoms of 2 years or less. RESULTS: Data from 983 patients were collected and gout was present in 509 (52%). Early disease was present in 144 gout cases and 228 non.......3%/84.4% and 86.4%/63.6%. Criteria not requiring synovial fluid analysis had sensitivity and specificity of less than 80% in early and established disease. CONCLUSIONS: Existing classification criteria for gout have sensitivity of over 80% in early and established disease but currently available criteria that do...

Sex, stress and sleep apnoea: Decreased susceptibility to upper airway muscle dysfunction following intermittent hypoxia in females.

Science.gov (United States)

O'Halloran, Ken D; Lewis, Philip; McDonald, Fiona

2017-11-01

Obstructive sleep apnoea syndrome (OSAS) is a devastating respiratory control disorder more common in men than women. The reasons for the sex difference in prevalence are multifactorial, but are partly attributable to protective effects of oestrogen. Indeed, OSAS prevalence increases in post-menopausal women. OSAS is characterized by repeated occlusions of the pharyngeal airway during sleep. Dysfunction of the upper airway muscles controlling airway calibre and collapsibility is implicated in the pathophysiology of OSAS, and sex differences in the neuro-mechanical control of upper airway patency are described. It is widely recognized that chronic intermittent hypoxia (CIH), a cardinal feature of OSAS due to recurrent apnoea, drives many of the morbid consequences characteristic of the disorder. In rodents, exposure to CIH-related redox stress causes upper airway muscle weakness and fatigue, associated with mitochondrial dysfunction. Of interest, in adults, there is female resilience to CIH-induced muscle dysfunction. Conversely, exposure to CIH in early life, results in upper airway muscle weakness equivalent between the two sexes at 3 and 6 weeks of age. Ovariectomy exacerbates the deleterious effects of exposure to CIH in adult female upper airway muscle, an effect partially restored by oestrogen replacement therapy. Intriguingly, female advantage intrinsic to upper airway muscle exists with evidence of substantially greater loss of performance in male muscle during acute exposure to severe hypoxic stress. Sex differences in upper airway muscle physiology may have relevance to human OSAS. The oestrogen-oestrogen receptor α axis represents a potential therapeutic target in OSAS, particularly in post-menopausal women. Copyright © 2016 Elsevier B.V. All rights reserved.

Do sensitive parents foster kind children, or vice versa? Bidirectional influences between children's prosocial behavior and parental sensitivity.

Science.gov (United States)

Newton, Emily K; Laible, Deborah; Carlo, Gustavo; Steele, Joel S; McGinley, Meredith

2014-06-01

Bidirectional theories of social development have been around for over 40 years (Bell, 1968), yet they have been applied primarily to the study of antisocial development. In the present study, the reciprocal relationship between parenting behavior and children's socially competent behaviors were examined. Using the National Institute of Child Health and Development Study of Early Child Care data set (NICHD Early Child Care Research Network, 2005), bidirectional relationships between parental sensitivity and children's prosocial behavior were modeled using latent variables in structural equation modeling for mothers and fathers, separately. Children and their parents engaged in structured interactions when children were 54-month-olds, 3rd graders, and 5th graders, and these interactions were coded for parental sensitivity. At 3rd, 5th, and 6th grades, teachers and parents reported on children's prosocial behavior. Parental education and child gender were entered as covariates in the models. The results provide support for a bidirectional relationship between children's prosocial behavior and maternal sensitivity (but not paternal sensitivity) in middle childhood. The importance of using a bidirectional approach to examine the development of social competence is emphasized. PsycINFO Database Record (c) 2014 APA, all rights reserved.

A Study to investigate the role of p27 and Cyclin E immunoexpression as a prognostic factor in early breast carcinoma

Directory of Open Access Journals (Sweden)

Chetty Runjan

2011-03-01

Full Text Available Abstract Background Cyclin E and p27 expression is easy to assess in human tissues by standard immunohistochemical techniques. Immunohistochemistry is cost effective, relatively easy to perform and will play more of a role in the future management of cancer. The aim of this study was to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma. Methods Cyclin E and p27 immunohistochemistry was performed on sixty six cases of breast carcinoma submitted over a five year period to the Division of Anatomical Pathology, Groote Schuur hospital; Whittaker and Associates; and PathCare. All tumours included in this study were less than 5 cm in diameter (pT1 and pT2 stage and all the patients had wide local excisions performed. Follow up information was obtained from patient folders in the Department of Radiation Oncology. Results There was no significant association of cyclin E and p27 expression with distant metastasis free survival (MFS for all invasive carcinomas in contrast to grade, lymph node spread and vascular invasion. However, there was a statistically significant direct association of cyclin E with distant metastases in all invasive carcinomas, in the subgroup of infiltrating duct carcinomas (IDC and in the node negative group when cyclin E was stratified as negative and positive (low/high. In this study of early breast carcinoma, only 9/66 cases showed cyclin E expression. Of these, four patients had distant metastases, one patient had a local recurrence and four patients were alive at last follow-up. Furthermore, cyclin E expression was significantly associated with grade, lymph node spread, oestrogen receptor status and histological type. None of the lobular carcinomas showed cyclin E positivity and only one case of lobular carcinoma presented with distant metastases. 59/66 cases were positive (low/high for p27 while seven cases were negative, 22 cases showed low expression and 37 cases

A direct comparison of decision rules for early discharge of suspected acute coronary syndromes in the era of high sensitivity troponin.

Science.gov (United States)

Chew, Pei Gee; Frost, Fredrick; Mullen, Liam; Fisher, Michael; Zadeh, Heidar; Grainger, Ruth; Albouaini, Khaled; Dodd, James; Patel, Bilal; Velavan, Periaswamy; Kunadian, Babu; Rawat, Anju; Obafemi, Toba; Tong, Sarah; Jones, Julia; Khand, Aleem

2018-02-01

We tested the hypothesis that a single high sensitivity troponin at limits of detection (LOD HSTnT) (Acute Coronary Events (GRACE) (acute coronary syndrome. In a prospective cohort study, risk scores were computed in consecutive patients with suspected acute coronary syndrome presenting to the Emergency Room of a large English hospital. Adjudication of myocardial infarction, as per third universal definition, involved a two-physician, blinded, independent review of all biomarker positive chest pain re-presentations to any national hospital. The primary and secondary outcome was a composite of type 1 myocardial infarction, unplanned coronary revascularisation and all cause death (MACE) at six weeks and one year. Of 3054 consecutive presentations with chest pain 1642 had suspected acute coronary syndrome (52% male, median age 59 years, 14% diabetic, 20% previous myocardial infarction). Median time from chest pain to presentation was 9.7 h. Re-presentations occurred in eight hospitals with 100% follow-up achieved. Two hundred and eleven (12.9%) and 279 (17%) were adjudicated to suffer MACE at six weeks and one year respectively. Only HEART ≤3 (negative predictive value MACE 99.4%, sensitivity 97.6%, %discharge 53.4) and LOD HSTnT strategy (negative predictive value MACE 99.8%, sensitivity 99.5%, %discharge 36.9) achieved pre-specified negative predictive value of >99% for MACE at six weeks. For type 1 myocardial infarction alone the negative predictive values at six weeks and one year were identical, for both HEART ≤3 and LOD HSTnT at 99.8% and 99.5% respectively. HEART ≤3 or LOD HSTnT strategy rules out short and medium term myocardial infarction with ≥99.5% certainty, and short-term MACE with >99% certainty, allowing for early discharge of 53.4% and 36.9% respectively of suspected acute coronary syndrome. Adoption of either strategy has the potential to greatly reduce Emergency Room pressures and minimise follow-up investigations. Very early presenters (<3 h

High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people eith acute chest pain: a systematic review and cost-effectiveness analysis

NARCIS (Netherlands)

M. Westwood (Marie); T. van Asselt (Thea); B. Ramaekers (Bram); P. Whiting (Penny); P. Tokala (Praveen); M.A. Joore (Manuela); N. Armstrong (Nigel); J. Ross (Janine); J.L. Severens (Hans); J. Kleijnen (Jos)

2015-01-01

textabstractBackground: Early diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions for chest pain have an AMI. High-sensitivity cardiac troponin (hs-cTn) assays may allow rapid rule-out of AMI and avoidance of

High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people with acute chest pain : a systematic review and cost-effectiveness analysis

NARCIS (Netherlands)

Westwood, Marie; van Asselt, Thea; Ramaekers, Bram; Whiting, Penny; Thokala, Praveen; Joore, Manuela; Armstrong, Nigel; Ross, Janine; Severens, Johan; Kleijnen, Jos

BACKGROUND: Early diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions for chest pain have an AMI. High-sensitivity cardiac troponin (hs-cTn) assays may allow rapid rule-out of AMI and avoidance of unnecessary

Early Building Design

DEFF Research Database (Denmark)

Østergård, Torben; Jensen, Rasmus Lund; Maagaard, Steffen

2017-01-01

Highlights •Development of a design methodology that can handle the vast design space in early building design. •A global design space is modelled from extensive Monte Carlo simulations. •Sensitivity analysis methods applied to guide decision-makers. •Interactive visualizations help the multi-act...

Divergent oestrogen receptor-specific breast cancer trends in Ireland (2004-2013): Amassing data from independent Western populations provide etiologic clues.

Science.gov (United States)

Mullooly, Maeve; Murphy, Jeanne; Gierach, Gretchen L; Walsh, Paul M; Deady, Sandra; Barron, Thomas I; Sherman, Mark E; Rosenberg, Philip S; Anderson, William F

2017-11-01

The aetiology and clinical behaviour of breast cancers vary by oestrogen receptor (ER) expression, HER2 expression and over time. Data from the United States and Denmark show rising incidence rates for ER+ and falling incidence rates for ER- breast cancers. Given that Ireland is a somewhat similar Western population but with distinctive risk exposures (especially for lactation), we analysed breast cancer trends by ER status; and for the first time, by the joint expression of ER±/HER2±. We assessed invasive breast cancers (n = 24,845; 2004-2013) within the population-based National Cancer Registry of Ireland. The population at risk was obtained from the Irish Central Statistics Office (n = 10,401,986). After accounting for missing ER and HER2 data, we assessed receptor-specific secular trends in age-standardised incidence rates (ASRs) with the estimated annual percentage change (EAPC) and corresponding 95% confidence intervals (95% CI). Age-period-cohort models were also fitted to further characterise trends accounting for age, calendar-period and birth-cohort interactions. ASRs increased for ER+ (EAPC: 2.2% per year [95% CI: 0.97, 3.45%/year]) and decreased for ER- cancers (EAPC: -3.43% per year [95% CI: -5.05, -1.78%/year]), as well as for specific age groups at diagnosis (rates among independent Western populations likely reflects calendar-period and/or risk factor changes with differential effects for ER+ and ER- breast cancers. Published by Elsevier Ltd.

Balance between early life tolerance and sensitization in allergy: dependence on the timing and intensity of prenatal and postnatal allergen exposure of the mother.

Science.gov (United States)

Fusaro, Ana Elisa; de Brito, Cyro Alves; Taniguchi, Eliana Futata; Muniz, Bruno Pacola; Victor, Jefferson Russo; Orii, Noemia Mie; Duarte, Alberto José da Silva; Sato, Maria Notomi

2009-09-01

Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.

Sensitivity and Specificity of Cystatin C in Detecting Early Renal ...

African Journals Online (AJOL)

trimester since it maximizes the value of sensitivity and specificity. Keywords: Cystatin C ... Recruitment was done on patients that meet the inclusion and exclusion ... mm Hg. CKD stage was defined based on creatinine clearance value.

Long-term impact of preeclampsia on maternal endometrial cancer risk

DEFF Research Database (Denmark)

Hallum, Sara; Pinborg, Anja; Kamper-Jørgensen, Mads

2016-01-01

BACKGROUND: Endometrial cancer is mainly dependent on oestrogen exposure. Preeclampsia has shown to reduce oestrogen levels hence preeclampsia may affect later endometrial cancer risk. METHODS: We conducted a case-control study of 523 Danish women with endometrial cancer and 52 299controls during...... 1978-2010. The association between preeclampsia and later endometrial cancer was evaluated overall and according to preeclampsia onset and type of endometrial cancer in conditional logistic regression models. RESULTS: We observed no overall association between preeclampsia and endometrial cancer risk...... (OR=1.11 (95% CI 0.68-1.81)). This was true for all endometrial cancer subtypes. In an analysis of preeclampsia onset, however, we report a markedly increased risk of endometrial cancer following early-onset preeclampsia (OR=2.64 (95% CI 1.29-5.38)). CONCLUSIONS: Although we report no obvious...

A longitudinal study on the maternal–fetal relationship and postnatal maternal sensitivity

NARCIS (Netherlands)

Maas, A.J.B.M.; de Cock, E.S.A.; Vreeswijk, C.M.J.M.; Vingerhoets, A.J.J.M.; van Bakel, H.J.A.

2016-01-01

Objective: The present study examined whether early signs of maternal sensitivity can be detected during pregnancy by focusing on the maternal–fetal relationship and postnatal maternal sensitivity. Background: Earlier research has identified maternal sensitive behaviour as an important factor for

Exemestane in early breast cancer: a review

Directory of Open Access Journals (Sweden)

Michael Untch

2008-12-01

Full Text Available Michael Untch1, Christian Jackisch21Interdisciplinary Breast Centre, Helios Klinikum Berlin-Buch, University Charité, Berlin, Germany; 2Department of Gynecology/Obstetrics, Klinikum Offenbach GmbH, Offenbach, GermanyAbstract: The adjuvant treatment of women with endocrine-sensitive early breast cancer has been dominated for the last 40 years by tamoxifen. However, the side-effects associated with this therapy have prompted a search for safer and biochemically more selective endocrine agents and led to the development of the third-generation aromatase inhibitors (AIs anastrozole, letrozole and exemestane. Promising results in advanced disease have paved the way for treating early breast cancer, and AIs are increasingly replacing tamoxifen in the adjuvant setting. Several large, randomized trials with AIs have been completed or are ongoing in women with early-stage breast cancer, documenting the significant impact that these drugs are making on the risk for recurrence of breast cancer. As a result, there is increasing and widespread use of AI therapy for the treatment of early-stage endocrine-responsive breast cancer. This review summarizes the data for exemestane in the adjuvant setting, showing that a switch to exemestane after 2 to 3 years of tamoxifen therapy is associated with a statistically significant survival benefit and is regarded as being sensitive by international and national experts.Keywords: early breast cancer, adjuvant setting, endocrine-sensitive, tamoxifen, aromatase inhibitor, exemestane, switch, IES 31, NSABP B-33, TEAM

Growth of a progesterone receptor-positive meningioma in a female patient with congenital adrenal hyperplasia.

Science.gov (United States)

O'Shea, T; Crowley, R K; Farrell, M; MacNally, S; Govender, P; Feeney, J; Gibney, J; Sherlock, M

2016-01-01

Meningioma growth has been previously described in patients receiving oestrogen/progestogen therapy. We describe the clinical, radiological, biochemical and pathologic findings in a 45-year-old woman with congenital adrenal hyperplasia secondary to a defect in the 21-hydroxylase enzyme who had chronic poor adherence to glucocorticoid therapy with consequent virilisation. The patient presented with a frontal headache and marked right-sided proptosis. Laboratory findings demonstrated androgen excess with a testosterone of 18.1 nmol/L (0-1.5 nmol) and 17-Hydroxyprogesterone >180 nmol/L (transsexual patients undergoing therapy with high-dose oestrogen and progestogens. Progesterone receptor positivity has been described previously in meningiomas. 17-Hydroxyprogesterone is elevated in CAH and has affinity and biological activity at the progesterone receptor. Therefore, we hypothesise that patients who have long-standing increased adrenal androgen precursor concentrations may be at risk of meningioma growth. Patients with long-standing CAH (particularly if not optimally controlled) may present with other complications, which may be related to long-standing elevated androgen or decreased glucocorticoid levels.Chronic poor control of CAH is associated with adrenal myelolipoma and adrenal rest tissue tumours.Meningiomas are sensitive to endocrine stimuli including progesterone, oestrogen and androgens as they express the relevant receptors.

Radioimmunoassay study of neurophysins in human plasma

International Nuclear Information System (INIS)

Reinharz, A.C.; Tissot-Berthet, M.-C.; Vallotton, M.B.

1978-01-01

Using a homologous system we have developed a specific and sensitive radioimmunoassay for the measurement of one of the human neurophysins in unextracted human plasma. This neurophysin is specifically secreted in response to oestrogen and has therefore been referred to as human oestrogen-stimulated neurophysin (h-OeSN). The plasma concentration was 0.57 plus minus 0.17 ng/ml (SD) in females and 0.88 plus minus 0.76 ng/ml (SD) in males. This difference is not significant. In women on oral contraceptives, plasma h-OeSN was 2.0 plus minus 1.1 ng/ml. During pregnancy h-OeSN increased progressively to 3.7 plus minus 2.9 ng/ml at the end of the first trimester, and 5.2 plus minus 2.8 ng/ml at term. Plasma h-OeSN concentrations increased rapidly and markedly in men treated with ethinyl-oestradiol. We have also demonstrated the presence of h-OeSN in amniotic and cerebrospinal fluids. A second human neurophysin, which is stimulated by nicotine but not by oestrogen, was also measured. This neurophysin was monitored by a heterologous system using antiserum raised against bovine neurophysin II (b-NII), and b-NII as the standard and tracer. (author)

Effects of visual attention on chromatic and achromatic detection sensitivities.

Science.gov (United States)

Uchikawa, Keiji; Sato, Masayuki; Kuwamura, Keiko

2014-05-01

Visual attention has a significant effect on various visual functions, such as response time, detection and discrimination sensitivity, and color appearance. It has been suggested that visual attention may affect visual functions in the early visual pathways. In this study we examined selective effects of visual attention on sensitivities of the chromatic and achromatic pathways to clarify whether visual attention modifies responses in the early visual system. We used a dual task paradigm in which the observer detected a peripheral test stimulus presented at 4 deg eccentricities while the observer concurrently carried out an attention task in the central visual field. In experiment 1, it was confirmed that peripheral spectral sensitivities were reduced more for short and long wavelengths than for middle wavelengths with the central attention task so that the spectral sensitivity function changed its shape by visual attention. This indicated that visual attention affected the chromatic response more strongly than the achromatic response. In experiment 2 it was obtained that the detection thresholds increased in greater degrees in the red-green and yellow-blue chromatic directions than in the white-black achromatic direction in the dual task condition. In experiment 3 we showed that the peripheral threshold elevations depended on the combination of color-directions of the central and peripheral stimuli. Since the chromatic and achromatic responses were separately processed in the early visual pathways, the present results provided additional evidence that visual attention affects responses in the early visual pathways.

Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.

Science.gov (United States)

Albain, Kathy S; Barlow, William E; Shak, Steven; Hortobagyi, Gabriel N; Livingston, Robert B; Yeh, I-Tien; Ravdin, Peter; Bugarini, Roberto; Baehner, Frederick L; Davidson, Nancy E; Sledge, George W; Winer, Eric P; Hudis, Clifford; Ingle, James N; Perez, Edith A; Pritchard, Kathleen I; Shepherd, Lois; Gralow, Julie R; Yoshizawa, Carl; Allred, D Craig; Osborne, C Kent; Hayes, Daniel F

2010-01-01

The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogen-receptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence. The phase 3 trial SWOG-8814 for postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer showed that chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) before tamoxifen (CAF-T) added survival benefit to treatment with tamoxifen alone. Optional tumour banking yielded specimens for determination of recurrence score by RT-PCR. In this retrospective analysis, we assessed the effect of recurrence score on disease-free survival by treatment group (tamoxifen vs CAF-T) using Cox regression, adjusting for number of positive nodes. There were 367 specimens (40% of the 927 patients in the tamoxifen and CAF-T groups) with sufficient RNA for analysis (tamoxifen, n=148; CAF-T, n=219). The recurrence score was prognostic in the tamoxifen-alone group (p=0.006; hazard ratio [HR] 2.64, 95% CI 1.33-5.27, for a 50-point difference in recurrence score). There was no benefit of CAF in patients with a low recurrence score (score or =31; log-rank p=0.033; HR 0.59, 0.35-1.01), after adjustment for number of positive nodes. The recurrence score by treatment interaction was significant in the first 5 years (p=0.029), with no additional prediction beyond 5 years (p=0.58), although the cumulative benefit remained at 10 years. Results were similar for overall survival and breast-cancer-specific survival. The recurrence score is prognostic for tamoxifen-treated patients with positive nodes and predicts significant benefit of CAF in tumours with a high recurrence score. A low recurrence

Contamination Sensitivity in Young Children.

Science.gov (United States)

Siegal, Michael; Share, David L.

1990-01-01

Revealed that children were able to indicate that an apparently safe substance such as juice may be contaminated by contact with a foreign body such as a cockroach. Supported the hypothesis that early sensitivity to substances that contain invisible contaminates may be guided by knowledge of a distinction between appearance and reality. (RH)

Effect of haloperidol on the synthesis of DNA in the pituitary gland of the rat.

Science.gov (United States)

Machiavelli, G A; Jahn, G A; Kalbermann, L E; Szijan, I; Alonso, G E; Burdman, J A

1982-03-01

The administration of haloperidol increased serum prolactin and decreased the pituitary concentration of prolactin 15 min after its administration. Concomitantly there was a stimulation in the synthesis of DNA and the activity of DNA polymerase alpha in the anterior pituitary gland that was greater in oestrogenized than in non-oestrogenized male rats. Both these effects were greatly reduced by clomiphene in the oestrogenized male rats, although it did not affect the release of prolactin produced by haloperidol. In non-oestrogenized animals clomiphene abolished the stimulatory effect of haloperidol on the synthesis of DNA. These results suggest that the reduction in the intracellular levels of prolactin are a primary event in the oestrogen mediated stimulation of cell proliferation by prolactin releasing agents.

Validation of Candidate Serum Ovarian Cancer Biomarkers for Early Detection

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Feng Su

2007-01-01

Full Text Available Objective: We have previously analyzed protein profi les using Surface Enhanced Laser Desorption and Ionization Time-Of-Flight Mass Spectroscopy (SELDI-TOF-MS [Kozak et al. 2003, Proc. Natl. Acad. Sci. U.S.A. 100:12343–8] and identified 3 differentially expressed serum proteins for the diagnosis of ovarian cancer (OC [Kozak et al. 2005, Proteomics, 5:4589–96], namely, apolipoprotein A-I (apoA-I, transthyretin (TTR and transferin (TF. The objective of the present study is to determine the efficacy of the three OC biomarkers for the detection of early stage (ES OC, in direct comparison to CA125.Methods: The levels of CA125, apoA-I, TTR and TF were measured in 392 serum samples [82 women with normal ovaries (N, 24 women with benign ovarian tumors (B, 85 women with ovarian tumors of low malignant potential (LMP, 126 women with early stage ovarian cancer (ESOC, and 75 women with late stage ovarian cancer (LSOC], obtained through the GOG and Cooperative Human Tissue Network. Following statistical analysis, multivariate regression models were built to evaluate the utility of the three OC markers in early detection.Results: Multiple logistic regression models (MLRM utilizing all biomarker values (CA125, TTR, TF and apoA-I from all histological subtypes (serous, mucinous, and endometrioid adenocarcinoma distinguished normal samples from LMP with 91% sensitivity (specifi city 92%, and normal samples from ESOC with a sensitivity of 89% (specifi city 92%. MLRM, utilizing values of all four markers from only the mucinous histological subtype showed that collectively, CA125, TTR, TF and apoA-I, were able to distinguish normal samples from mucinous LMP with 90% sensitivity, and further distinguished normal samples from early stage mucinous ovarian cancer with a sensitivity of 95%. In contrast, in serum samples from patients with mucinous tumors, CA125 alone was able to distinguish normal samples from LMP and early stage ovarian cancer with a sensitivity of

[Diagnosis and monitoring of endangered early pregnancies with determination of oestrone, oestradiol 17beta, oestriol, progesterone and HPL in plasma and the pregnancy test in graduated dilutions of urine (author's transl)].

Science.gov (United States)

Strecker, J R; Negulescu, R; Dahlén, H; Musch, K

1977-06-01

Unconjugated oestrone (Oe1), oestradiol-17beta (Oe2), oestriol (Oe3), progesterone (P) and HPL in plasma were determined by radioimmunoassay and the immunological pregnancy-test in urine was carried out in 70 patients with normal pregnancy or imminent abortion from 4th-20th week of gestation. Oe2 and HPL showed the most pronounced rises, Oe3 increased especially after the first trimester. In cases with abortion symptoms and poor prognosis Oe2 and HPL gave the most reliable results concerning the endocrin function of early normal pregnancy. Oe1- and P-values in normal pregnancy did not differ so clearly from concentrations observed during normal menstrual cycles and were thus of less value. The pregnancy-test was positive (greater than 1000 IU/1) even in most cases of dead pregnancy and therefore not reliable. With increasing production of oestrogen precursors in the fetal adrenal cortex after the first trimester determination of Oe3 becomes more important. In cases with abortion symptoms in early pregnancy and subsequent normal development, plasma Oe2- and Oe3- values represented best criteria for a prognosis. -- For the diagnosis and control of the endangered early pregnancy we recommend, as a consequence of this study, determination of Oe2 up to the 13th week of pregnancy and thereafter Oe3 in maternal plasma.

125I-Fibrin deposition in contact sensitivity reactions in the mouse. Sensitivity of the assay for quantitating reactions after active or passive sensitization

International Nuclear Information System (INIS)

Mekori, Y.A.; Dvorak, H.F.; Galli, S.J.

1986-01-01

The clotting associated with delayed hypersensitivity (DH) responses in the mouse by sensitizing the animals to the contactant oxazolone (Ox), and then administering 125 I-guinea pig fibrinogen i.v. 10 to 30 min before antigen challenge 5 days later. Early (4 to 8 hr) contact sensitivity (CS) responses in immunized mice were barely detectable by three conventional measures of CS, but the total 125 I-cpm in ears challenged with hapten was 3.6 to 4.5 x that in control ears challenged with vehicle alone; moreover, the amount of urea-insoluble cpm (cross-linked 125 I-fibrin-associated cpm) in the reactions to Ox was 6.5-fold to 8.2-fold that present in the control reactions. In 24 hr reactions that were near peak intensity by measurements of ear swelling, ear weight ratios, and ratios of 125 I-5-iodo-2-deoxyuridine-labeled leukocyte infiltration, the cpm in antigen-challenged ears exceeded that in control ears by 13-fold to 53-fold. In addition, antigen-challenged ears contained 27 to 300 x the urea-insoluble cpm present in control ears. 125 I-Fibrin deposition was not a specific characteristic of CS reactions, because a small amount of urea-insoluble reactivity was also detected in some reactions to Ox in native mice. Nevertheless, the assay was exquisitely sensitive and readily detected quantitative differences between the immunologically specific and nonspecific reactions at very early intervals after challenge or with suboptimal doses of antigen

Østrogen til forebyggelse af recidiverende urinvejsinfektioner hos postmenopausale kvinder--gennemgang af et Cochrane-review

DEFF Research Database (Denmark)

Brostrøm, Søren; Lose, Gunnar

2009-01-01

Recurrent urinary tract infections (UTIs) are common in postmenopausal women. While the pathophysiology is often complex, it is evident that the urogenital atrophy due to the decrease of endogenous oestrogen production is a key factor. Two small randomized controlled studies have proven the effic......Recurrent urinary tract infections (UTIs) are common in postmenopausal women. While the pathophysiology is often complex, it is evident that the urogenital atrophy due to the decrease of endogenous oestrogen production is a key factor. Two small randomized controlled studies have proven...... the efficacy of local (vaginal) oestrogen therapy in the prevention of recurrent UTIs. Conversely, four randomized trials, reviewed in a weighted meta-analysis with pooled data from 2,798 women, have shown the lack of efficacy of systemic oestrogen-progesterone therapy. Local oestrogen therapy is recommended...

Father Involvement, Paternal Sensitivity, and Father-Child Attachment Security in the First Three Years

Science.gov (United States)

Brown, Geoffrey L.; Mangelsdorf, Sarah C.; Neff, Cynthia

2014-01-01

To reach a greater understanding of the early father-child attachment relationship, this study examined concurrent and longitudinal associations among father involvement, paternal sensitivity, and father-child attachment security at 13 months and 3 years of age. Analyses revealed few associations among these variables at 13 months of age, but involvement and sensitivity independently predicted father-child attachment security at age 3. Moreover, sensitivity moderated the association between involvement and attachment security at 3 years. Specifically, involvement was unrelated to attachment security when fathers were highly sensitive, but positively related to attachment security when fathers were relatively less sensitive. Father involvement was also moderately stable across the two timepoints, but paternal sensitivity was not. Furthermore, there was significant stability in father-child attachment security from 13 months to 3 years. Secure attachment at 13 months also predicted greater levels of paternal sensitivity at 3 years, with sensitivity at age 3 mediating the association between 13 month and 3 year attachment security. In sum, a secure father-child attachment relationship a) was related to both quantity and quality of fathering behavior, b) remained relatively stable across early childhood, and c) predicted increased paternal sensitivity over time. These findings further our understanding of the correlates of early father-child attachment, and underscore the need to consider multiple domains of fathers’ parenting and reciprocal relations between fathering behavior and father-child attachment security. PMID:22468691

Bidirectional Associations among Sensitive Parenting, Language Development, and Social Competence

Science.gov (United States)

Barnett, Melissa A.; Gustafsson, Hanna; Deng, Min; Mills-Koonce, W. Roger; Cox, Martha

2012-01-01

Rapid changes in language skills and social competence, both of which are linked to sensitive parenting, characterize early childhood. The present study examines bidirectional associations among mothers' sensitive parenting and children's language skills and social competence from 24 to 36?months in a community sample of 174 families. In addition,…

Tough Adults, Frail Babies: An Analysis of Stress Sensitivity across Early Life-History Stages of Widely Introduced Marine Invertebrates

Science.gov (United States)

Pineda, M. Carmen; McQuaid, Christopher D.; Turon, Xavier; López-Legentil, Susanna; Ordóñez, Víctor; Rius, Marc

2012-01-01

All ontogenetic stages of a life cycle are exposed to environmental conditions so that population persistence depends on the performance of both adults and offspring. Most studies analysing the influence of abiotic conditions on species performance have focussed on adults, while studies covering early life-history stages remain rare. We investigated the responses of early stages of two widely introduced ascidians, Styela plicata and Microcosmus squamiger, to different abiotic conditions. Stressors mimicked conditions in the habitats where both species can be found in their distributional ranges and responses were related to the selection potential of their populations by analysing their genetic diversity. Four developmental stages (egg fertilisation, larval development, settlement, metamorphosis) were studied after exposure to high temperature (30°C), low salinities (26 and 22‰) and high copper concentrations (25, 50 and 100 µg/L). Although most stressors effectively led to failure of complete development (fertilisation through metamorphosis), fertilisation and larval development were the most sensitive stages. All the studied stressors affected the development of both species, though responses differed with stage and stressor. S. plicata was overall more resistant to copper, and some stages of M. squamiger to low salinities. No relationship was found between parental genetic composition and responses to stressors. We conclude that successful development can be prevented at several life-history stages, and therefore, it is essential to consider multiple stages when assessing species' abilities to tolerate stress. Moreover, we found that early development of these species cannot be completed under conditions prevailing where adults live. These populations must therefore recruit from elsewhere or reproduce during temporal windows of more benign conditions. Alternatively, novel strategies or behaviours that increase overall reproductive success might be

Tough adults, frail babies: an analysis of stress sensitivity across early life-history stages of widely introduced marine invertebrates.

Directory of Open Access Journals (Sweden)

M Carmen Pineda

Full Text Available All ontogenetic stages of a life cycle are exposed to environmental conditions so that population persistence depends on the performance of both adults and offspring. Most studies analysing the influence of abiotic conditions on species performance have focussed on adults, while studies covering early life-history stages remain rare. We investigated the responses of early stages of two widely introduced ascidians, Styela plicata and Microcosmus squamiger, to different abiotic conditions. Stressors mimicked conditions in the habitats where both species can be found in their distributional ranges and responses were related to the selection potential of their populations by analysing their genetic diversity. Four developmental stages (egg fertilisation, larval development, settlement, metamorphosis were studied after exposure to high temperature (30°C, low salinities (26 and 22‰ and high copper concentrations (25, 50 and 100 µg/L. Although most stressors effectively led to failure of complete development (fertilisation through metamorphosis, fertilisation and larval development were the most sensitive stages. All the studied stressors affected the development of both species, though responses differed with stage and stressor. S. plicata was overall more resistant to copper, and some stages of M. squamiger to low salinities. No relationship was found between parental genetic composition and responses to stressors. We conclude that successful development can be prevented at several life-history stages, and therefore, it is essential to consider multiple stages when assessing species' abilities to tolerate stress. Moreover, we found that early development of these species cannot be completed under conditions prevailing where adults live. These populations must therefore recruit from elsewhere or reproduce during temporal windows of more benign conditions. Alternatively, novel strategies or behaviours that increase overall reproductive success

Early life adversity during the infant sensitive period for attachment: Programming of behavioral neurobiology of threat processing and social behavior

Directory of Open Access Journals (Sweden)

Maya Opendak

2017-06-01

Full Text Available Animals, including humans, require a highly coordinated and flexible system of social behavior and threat evaluation. However, trauma can disrupt this system, with the amygdala implicated as a mediator of these impairments in behavior. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its immediate and enduring consequences, with trauma experienced from an attachment figure, such as occurs in cases of caregiver-child maltreatment, as particularly detrimental. This review focuses on the unique role of caregiver presence during early-life trauma in programming deficits in social behavior and threat processing. Using data primarily from rodent models, we describe the interaction between trauma and attachment during a sensitive period in early life, which highlights the role of the caregiver’s presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. These data suggest that trauma experienced directly from an abusive caregiver and trauma experienced in the presence of caregiver cues produce similar neurobehavioral deficits, which are unique from those resulting from trauma alone. We go on to integrate this information into social experience throughout the lifespan, including consequences for complex scenarios, such as dominance hierarchy formation and maintenance.

Addressing Early Life Sensitivity Using Physiologically Based Pharmacokinetic Modeling and In Vitro to In Vivo Extrapolation.

Science.gov (United States)

Yoon, Miyoung; Clewell, Harvey J

2016-01-01

Physiologically based pharmacokinetic (PBPK) modeling can provide an effective way to utilize in vitro and in silico based information in modern risk assessment for children and other potentially sensitive populations. In this review, we describe the process of in vitro to in vivo extrapolation (IVIVE) to develop PBPK models for a chemical in different ages in order to predict the target tissue exposure at the age of concern in humans. We present our on-going studies on pyrethroids as a proof of concept to guide the readers through the IVIVE steps using the metabolism data collected either from age-specific liver donors or expressed enzymes in conjunction with enzyme ontogeny information to provide age-appropriate metabolism parameters in the PBPK model in the rat and human, respectively. The approach we present here is readily applicable to not just to other pyrethroids, but also to other environmental chemicals and drugs. Establishment of an in vitro and in silico-based evaluation strategy in conjunction with relevant exposure information in humans is of great importance in risk assessment for potentially vulnerable populations like early ages where the necessary information for decision making is limited.

Radiation induction of developmental effects during the very early stages of pregnancy

International Nuclear Information System (INIS)

Jacquet, P.

2009-01-01

Various studies have shown that early embryos of several mouse strains are sensitive to radiation-induction of congenital anomalies. The presence of mutations in particular genes seems to increase the sensitivity of embryos to such effects, but studies in that field are extremely limited. The aim of these studies is to determine (1) whether the sensitivity to radiation-induction of congenital anomalies during very early stages of gestation is transmitted to the following generation; (2) how mutations in genes involved in important cellular processes, like DNA repair, cell cycle regulation and apoptosis (cell suicide of a damaged cell), can influence the radiation sensitivity of the mammalian embryo during sensitive stages of early pregnancy. Emphasis is put on heterozygous mutations (in which only one of the two copies of the gene is mutated), which are relatively numerous in the human population and do not affect the viability and the fertility of individuals carrying them. The studies under way in that field are supported by contracts with the European Union and the Federal Agency for Nuclear Control (FANC-AFCN)

Malnutrition and mental development: Is there a sensitive period? A ...

African Journals Online (AJOL)

To examine the possibility that there is an early sensitive period for the effects of malnutrition on cognitive development, three groups of children (N = 197) were recruited from a birth cohort with known growth characteristics in south-west Ethiopia (N = 1563). All had initial weights;: 2500 g. Early growth falterers dropped in ...

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.

Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

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Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

2014-10-13

Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

Mammography combined with breast dynamic contrast-enhanced-magnetic resonance imaging for the diagnosis of early breast cancer

Institute of Scientific and Technical Information of China (English)

Yakun He; Guohui Xu; Jin Ren; Bin Feng; Xiaolei Dong; Hao Lu; Changjiu He

2016-01-01

Objective The aim of this study was to investigate the application of mammography combined with breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the diagnosis of early breast cancer. Methods Mammography and DCE-MRI were performed for 120 patients with breast cancer (malignant, 102; benign; 18). Results The sensitivity of mammography for early diagnosis of breast cancer was 66.67%, specificity was 77.78%, and accuracy was 68.33%. The sensitivity of MRI for early diagnosis of breast cancer was 94.12%, specificity was 88.89%, and accuracy was 93.33%. However, the sensitivity of mammography combined with DCE-MRI volume imaging with enhanced water signal (VIEWS) scanning for early diagnosis of breast cancer was 97.06%, specificity was 94.44%, and accuracy was 96.67%. Conclusion Mammography combined with DCE-MRI increased the sensitivity, specificity, and accuracy of diagnosing early breast cancer.

Climate change sensitivity of multi-species afforestation in semi-arid Benin

NARCIS (Netherlands)

Noulèkoun, Florent; Khamzina, Asia; Naab, Jesse B.; Khasanah, N.; Noordwijk, van Meine; Lamers, John P.A.

2018-01-01

The early growth stage is critical in the response of trees to climate change and variability. It is not clear, however, what climate metrics are best to define the early-growth sensitivity in assessing adaptation strategies of young forests to climate change. Using a combination of field

Early X-ray diagnosis of coxarthrosis

International Nuclear Information System (INIS)

Lingg, G.; Nebel, G.

1982-01-01

Radiological and pathological comparisons on specimen of femurhead and neck at autopsy have shown a statistical relationship between osteophytosis of the femoral head and ulcerations of the joint cartilage. Especially there are highly significant relationships between the length of osteophytes and the diameter of the ulcera. The 'plaque'-sign shows to be a very sensitive indicator of early arthrosis. So there exist semiquantitative parameters for the X-ray diagnosis of early coxarthrosis. (orig.) [de

Inhibitory effects of inhaled complex traditional Chinese medicine on early and late asthmatic responses induced by ovalbumin in sensitized guinea pigs

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Gong Cheng-Chung

2011-09-01

Full Text Available Abstract Background Many formulae of traditional Chinese medicines (TCMs have been used for antiasthma treatment dating back many centuries. There is evidence to suggest that TCMs are effective as a cure for this allergenic disease administered via gastric tubes in animal studies; however, their efficacy, safety and side effects as an asthmatic therapy are still unclear. Methods In this study, guinea pigs sensitized with ovalbumin (OVA were used as an animal model for asthma challenge, and the sensitization of animals by bronchial reactivity to methacholine (Mch and the IgE concentration in the serum after OVA challenge were estimated. Complex traditional Chinese herbs (CTCM were administered to the animals by nebulization, and the leukocytes were evaluated from bronchoalveolar lavage fluid (BALF. Results The results showed that inhalation of CTCM could abolish the increased lung resistance (13-fold increase induced by challenge with OVA in the early asthmatic response (EAR, reducing to as low as baseline (1-fold. Moreover, our results indicated higher IgE levels (range, 78-83 ng/ml in the serum of sensitized guinea pigs than in the unsensitized controls (0.9 ± 0.256 ng/ml. In addition, increased total leukocytes and higher levels of eosinophils and neutrophils were seen 6 hours after challenge, and the increased inflammatory cells were reduced by treatment with CTCM inhalation. The interleukin-5 (IL-5 level in BALF was also reduced by CTCM. Conclusion Our findings indicate a novel method of administering traditional Chinese medicines for asthma treatment in an animal model that may be more effective than traditional methods.

Interpersonal sensitivity and persistent attenuated psychotic symptoms in adolescence.

Science.gov (United States)

Masillo, Alice; Brandizzi, M; Valmaggia, L R; Saba, R; Lo Cascio, N; Lindau, J F; Telesforo, L; Venturini, P; Montanaro, D; Di Pietro, D; D'Alema, M; Girardi, P; Fiori Nastro, P

2018-03-01

Interpersonal sensitivity defines feelings of inner-fragility in the presence of others due to the expectation of criticism or rejection. Interpersonal sensitivity was found to be related to attenuated positive psychotic symptom during the prodromal phase of psychosis. The aims of this study were to examine if high level of interpersonal sensitivity at baseline are associated with the persistence of attenuated positive psychotic symptoms and general psychopathology at 18-month follow-up. A sample of 85 help-seeking individuals (mean age = 16.6, SD = 5.05) referred an Italian early detection project, completed the interpersonal sensitivity measure and the structured interview for prodromal symptoms (SIPS) at baseline and were assessed at 18-month follow-up using the SIPS. Results showed that individuals with high level of interpersonal sensitivity at baseline reported high level of attenuated positive psychotic symptoms (i.e., unusual thought content) and general symptoms (i.e., depression, irritability and low tolerance to daily stress) at follow-up. This study suggests that being "hypersensitive" to interpersonal interactions is a psychological feature associated with attenuated positive psychotic symptoms and general symptoms, such as depression and irritability, at 18-month follow-up. Assessing and treating inner-self fragilities may be an important step of early detection program to avoid the persistence of subtle but very distressing long-terms symptoms.

Early x-ray diagnosis of coxarthrosis

Energy Technology Data Exchange (ETDEWEB)

Lingg, G.; Nebel, G.

Radiological and pathological comparisons on specimen of femur head and neck at autopsy have shown a statistical relationship between osteophytosis of the femoral head and ulcerations of the joint cartilage. Especially, there are highly significant relationships between the length of osteophytes and the diameter of the ulcera. The 'plaque'-sign is shown to be a very sensitive indicator of early arthrosis. So there exist semiquantitative parameters for the X-ray diagnosis of early coxarthrosis.

Improved Detection of Microsatellite Instability in Early Colorectal Lesions.

Directory of Open Access Journals (Sweden)

Jeffery W Bacher

Full Text Available Microsatellite instability (MSI occurs in over 90% of Lynch syndrome cancers and is considered a hallmark of the disease. MSI is an early event in colon tumor development, but screening polyps for MSI remains controversial because of reduced sensitivity compared to more advanced neoplasms. To increase sensitivity, we investigated the use of a novel type of marker consisting of long mononucleotide repeat (LMR tracts. Adenomas from 160 patients, ranging in age from 29-55 years old, were screened for MSI using the new markers and compared with current marker panels and immunohistochemistry standards. Overall, 15 tumors were scored as MSI-High using the LMRs compared to 9 for the NCI panel and 8 for the MSI Analysis System (Promega. This difference represents at least a 1.7-fold increase in detection of MSI-High lesions over currently available markers. Moreover, the number of MSI-positive markers per sample and the size of allelic changes were significantly greater with the LMRs (p = 0.001, which increased confidence in MSI classification. The overall sensitivity and specificity of the LMR panel for detection of mismatch repair deficient lesions were 100% and 96%, respectively. In comparison, the sensitivity and specificity of the MSI Analysis System were 67% and 100%; and for the NCI panel, 75% and 97%. The difference in sensitivity between the LMR panel and the other panels was statistically significant (p<0.001. The increased sensitivity for detection of MSI-High phenotype in early colorectal lesions with the new LMR markers indicates that MSI screening for the early detection of Lynch syndrome might be feasible.

Sensitization does not develop in utero

DEFF Research Database (Denmark)

Bønnelykke, Klaus; Pipper, Christian Bressen; Bisgaard, Hans

2008-01-01

to sensitization in early infancy and the origin of such IgE. METHODS: Inhalant and food allergen-specific IgE in cord blood was analyzed and compared with specific IgE in infant blood at 6 months of age and in parental blood. Cord blood IgA was measured to detect maternal blood contamination of cord blood...

Induction stage-dependent expression of vascular endothelial growth factor and aquaporin-1 in diethylstilbestrol-treated rat pituitary

Directory of Open Access Journals (Sweden)

W Zhao

2009-03-01

Full Text Available The anterior pituitary gland undergoes tumourigenic changes in response to oestrogen treatment in several breeds of rats. We administered diethylstilbestrol (DES to female Wistar rats and assessed whether the expression of vascular endothelial growth factor (VEGF and aquaporin-1 (AQP-1 was altered at different time points following DES administration. In vivo magnetic resonance imaging (MRI scans showed that the mass index corresponding to the mid-sagittal area of DES-treated pituitary was significantly higher than the vehicle-controlled pituitary (p less than 0.01 at three specific time points, accompanied by a significant reduction in body weight. Haematoxylin and eosin (HE staining and immunohistochemical analysis demonstrated that during early stages of induction, DES increased cell proliferation and sprouting of endothelial cells, and VEGF expression transitioned from a vessel-surrounding pattern to a diffuse pattern. During later stages, angiogenesis was predominant, and VEGF expression decreased. In contrast to the early abundant expression of VEGF, endothelial expression of AQP- 1 increased during later stages. Our data indicated a dynamic scenario of biological alterations in DES-treated pituitary tissue, in which VEGF and AQP-1 exert their functions at different stages of induction, and we provide novel insights into understanding oestrogen-related tumourigenesis in the anterior pituitary gland.

Induction stage-dependent expression of vascular endothelial growth factor and aquaporin-1 in diethylstilbestrol-treated rat pituitary

Directory of Open Access Journals (Sweden)

Z Wang

2009-03-01

Full Text Available The anterior pituitary gland undergoes tumourigenic changes in response to oestrogen treatment in several breeds of rats. We administered diethylstilbestrol (DES to female Wistar rats and assessed whether the expression of vascular endothelial growth factor (VEGF and aquaporin-1 (AQP-1 was altered at different time points following DES administration. In vivo magnetic resonance imaging (MRI scans showed that the mass index corresponding to the mid-sagittal area of DES-treated pituitary was significantly higher than the vehicle-controlled pituitary (p<0.01 at three specific time points, accompanied by a significant reduction in body weight. Haematoxylin and eosin (HE staining and immunohistochemical analysis demonstrated that during early stages of induction, DES increased cell proliferation and sprouting of endothelial cells, and VEGF expression transitioned from a vessel-surrounding pattern to a diffuse pattern. During later stages, angiogenesis was predominant, and VEGF expression decreased. In contrast to the early abundant expression of VEGF, endothelial expression of AQP- 1 increased during later stages. Our data indicated a dynamic scenario of biological alterations in DES-treated pituitary tissue, in which VEGF and AQP-1 exert their functions at different stages of induction, and we provide novel insights into understanding oestrogen-related tumourigenesis in the anterior pituitary gland.

Ultrasonographic findings of early abortion: suggested predictors

International Nuclear Information System (INIS)

Jun, Soon Ae; Ahn, Myoung Ock; Cha, Kwang Yul; Lee, Young Doo

1992-01-01

To investigate predictable ultrasonographic findings of early abortion. To investigate objective rules for the screening of abortion. Ultrasonographic examination of 111 early pregnancies between the sixth and ninth week in women who had regular 28 day menstrual cycles was performed. Ultrasonographic measurements of the gestational sac, crown rump length and fetal heart rate were performed using a linear array real time transducer with doppler ultrasonogram. All measurements of 17 early abortions were compared to those of 94 normal pregnancies. Most of early aborted pregnancies were classified correctly by discriminant analysis with G-SAC and CRL (G-SAC=0.5 CRL + 15, sensitivity 76.5%, specificity 96.8%). With the addition of FHR, 94.1% of early abortions could be predicted. In conclusion, ultrasonographic findings of early intrauterine growth retardation, small gestational sac and bradycardia can be predictable signs suggestive of poor prognosis of early pregnancies

Differential expression of oestrogen receptor isoforms and androgen receptor in the normal vulva and vagina compared with vulval lichen sclerosus and chronic vaginitis.

Science.gov (United States)

Taylor, A H; Guzail, M; Al-Azzawi, F

2008-02-01

Although the expression of the oestrogen receptor (ER) alpha isoform and androgen receptor (AR) has been examined in vulval lichen sclerosus (VLS), the distribution pattern of ERalpha, ERbeta and AR has not been described in chronic atrophic vaginitis nor correlated with markers of proliferation (Ki-67) in either of these diseased tissues. To measure the levels and distribution of ERalpha, ERbeta and AR immunoreactivity in relation to Ki-67 in normal and diseased vulva and vagina. The expression of ERalpha, ERbeta and AR in relation to the proliferation marker Ki-67 in VLS, squamous hyperplasia of the vulva and chronic atrophic vaginitis was determined by immunohistomorphometric analysis and compared with that in normal vulva and vagina. VLS showed similar ERalpha and ERbeta expression in the 'epidermal' and 'dermal' tissue layers to that of normal vulvae, whereas AR expression appeared to be absent in most cases. ERbeta and Ki-67 expression was correlated with ERalpha expression but only in the 'fibrovascular' layer of the vulva. ERalpha expression was absent from the 'fibromuscular' layer of diseased vulvae, while ERbeta expression was absent in normal tissues but was highly expressed in diseased vulvae. ERalpha expression was significantly correlated with AR expression in the fibrovascular layer of the vagina and inversely correlated with Ki-67 staining in the parabasal cells of the epidermis in patients with chronic atrophic vaginitis. These data suggest that ER expression and levels may be implicated in the aetiopathology of VLS and chronic atrophic vaginitis.

Epicutaneous aeroallergen sensitization in atopic dermatitis infants - determining the role of epidermal barrier impairment.

Science.gov (United States)

Boralevi, F; Hubiche, T; Léauté-Labrèze, C; Saubusse, E; Fayon, M; Roul, S; Maurice-Tison, S; Taïeb, A

2008-02-01

Sensitization to atopens is an early phenomenon that overlaps with the onset of atopic dermatitis (AD) in infancy. Early epidermal barrier impairment may facilitate the epicutaneous penetration of atopens. To correlate transepidermal water loss (TEWL) and aeroallergen sensitization in infants with AD. In this cross-sectional study we enrolled 59 AD children and 30 controls aged 3-12 months. Transepidermal water loss in uninvolved skin, specific immunoglobulin E, atopy patch test (APT) and skin prick tests were performed with respect to seven aeroallergens, i.e., Dermatophagoides pteronyssinus, D. farinae, cat, dog, birch pollen, ambrosia, and cockroach. Environmental conditions were assessed by a questionnaire, and the house dust mite (HDM) concentration was determined in dust samples. Eighty-nine percent of AD infants had a positive APT vs one out of eleven controls. AD infants had a significantly higher mean TEWL than controls (27.4 vs 11.1 g/m(2)/h, P cats, and dogs at home. This study confirms the high prevalence of delayed sensitization to indoor and outdoor aeroallergens in AD infants, and shows that the higher the TEWL, the higher the prevalence of sensitization to aeroallergens. These data are in favor of a major role of a constitutive epidermal barrier impairment in determining early atopen sensitization in infants with AD.

Early feeding: setting the stage for healthy eating habits.

Science.gov (United States)

Mennella, Julie A; Ventura, Alison K

2011-01-01

Food habits, an integral part of all cultures, have their beginnings during early life. This chapter reviews the development of the senses of taste and smell, which provide information on the flavor of foods, and discusses how children's innate predispositions interact with early-life feeding experiences to form dietary preferences and habits. Young children show heightened preferences for foods that taste sweet and salty and rejection of that which tastes bitter. These innate responses are salient during development since they likely evolved to encourage children to ingest that which is beneficial, containing needed calories or minerals, and to reject that which is harmful. Early childhood is also characterized by plasticity, partially evidenced by a sensitive period during early life when infants exhibit heightened acceptance of the flavors experienced in amniotic fluid and breast milk. While learning also occurs with flavors found in formulae, it is likely that this sensitive period formed to facilitate acceptance of and attraction to the flavors of foods eaten by the mother. A basic understanding of the development and functioning of the chemical senses during early childhood may assist in forming evidence-based strategies to improve children's diets. Copyright © 2011 S. Karger AG, Basel.

Intakes and sources of isoflavones, lignans, enterolignans, coumestrol and soya-containing foods in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk), from 7 d food diaries, using a newly updated database.

Science.gov (United States)

Mulligan, Angela A; Kuhnle, Gunter G C; Lentjes, Marleen A H; van Scheltinga, Veronica; Powell, Natasha A; McTaggart, Alison; Bhaniani, Amit; Khaw, Kay-Tee

2013-08-01

A diet rich in phyto-oestrogens has been suggested to protect against a variety of common diseases but UK intake data on phyto-oestrogens or their food sources are sparse. The present study estimates the average intakes of isoflavones, lignans, enterolignans and coumestrol from 7 d food diaries and provides data on total isoflavone, lignan and phyto-oestrogen consumption by food group. Development of a food composition database for twelve phyto-oestrogens and analysis of soya food and phyto-oestrogen consumption in a populationbased study. Men and women, aged 40–79 years, from the general population participating in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) between 1993 and 1997, with nutrient and food data from 7 d food diaries. A subset of 20 437 participants. The median daily phyto-oestrogen intake for all men was 1199 mg (interquartile range 934–1537mg; mean 1504mg, SD 1502mg) and 888mg for all women (interquartile range 710–1135 mg; mean 1205 mg, SD 1701mg). In soya consumers, median daily intakes were higher: 2861 mg in men (interquartile range 1304–7269mg; mean 5051mg, SD 5031mg) and 3142 mg in women (interquartile range 1089–7327mg; mean 5396 mg, SD 6092 mg). In both men and women, bread made the greatest contribution to phyto-oestrogen intake – 40?8% and 35?6%, respectively. In soya consumers, vegetable dishes and soya/goat’s/sheep’s milks were the main contributors – 45?7% and 21?3% in men and 38?4% and 33?7% in women, respectively. The ability to estimate phyto-oestrogen intake in Western populations more accurately will aid investigations into their suggested effects on health.

Sensitivity and uncertainty studies of the CRAC2 computer code

International Nuclear Information System (INIS)

Kocher, D.C.; Ward, R.C.; Killough, G.G.; Dunning, D.E. Jr.; Hicks, B.B.; Hosker, R.P. Jr.; Ku, J.Y.; Rao, K.S.

1987-01-01

The authors have studied the sensitivity of health impacts from nuclear reactor accidents, as predicted by the CRAC2 computer code, to the following sources of uncertainty: (1) the model for plume rise, (2) the model for wet deposition, (3) the meteorological bin-sampling procedure for selecting weather sequences with rain, (4) the dose conversion factors for inhalation as affected by uncertainties in the particle size of the carrier aerosol and the clearance rates of radionuclides from the respiratory tract, (5) the weathering half-time for external ground-surface exposure, and (6) the transfer coefficients for terrestrial foodchain pathways. Predicted health impacts usually showed little sensitivity to use of an alternative plume-rise model or a modified rain-bin structure in bin-sampling. Health impacts often were quite sensitive to use of an alternative wet-deposition model in single-trial runs with rain during plume passage, but were less sensitive to the model in bin-sampling runs. Uncertainties in the inhalation dose conversion factors had important effects on early injuries in single-trial runs. Latent cancer fatalities were moderately sensitive to uncertainties in the weathering half-time for ground-surface exposures, but showed little sensitivity to the transfer coefficients for terrestrial foodchain pathways. Sensitivities of CRAC2 predictions to uncertainties in the models and parameters also depended on the magnitude of the source term, and some of the effects on early health effects were comparable to those that were due only to selection of different sets of weather sequences in bin-sampling

Maternal BIS Sensitivity, Overprotective Parenting, and Children’s Internalizing Behaviors

Science.gov (United States)

Kiel, Elizabeth J.; Maack, Danielle J.

2012-01-01

Although sensitivity to the Behavioral Inhibition System within Gray’s (1970) reinforcement sensitivity theory relates to individuals’ own depressive and anxious symptomatology, less is known about how parental BIS sensitivity relates to early indicators of internalizing problems in young children. Moreover, the extent to which this parental characteristic relates to parenting behavior, and children’s internalizing problems above and beyond parenting, remains unknown. The current study assessed maternal BIS sensitivity, overprotective parenting, and toddlers’ internalizing behaviors in a sample of 91 mothers while controlling for mothers’ own internalizing symptomatology. Heightened BIS sensitivity related to both overprotective parenting and internalizing behaviors. Overprotective parenting partially mediated the relation between BIS sensitivity and children’s internalizing behaviors, although BIS sensitivity maintained a marginal relation to internalizing behaviors. Maternal BIS sensitivity and toddler internalizing behaviors may represent a shared disposition towards inhibition that is somewhat accounted for by overprotective parenting. PMID:22904590

Influence of pollen feeding and physiological condition on pesticide sensitivity of the honey bee Apis mellifera carnica.

Science.gov (United States)

Wahl, O; Ulm, K

1983-08-01

In two consecutive years heavy bee mortality at end April/early May followed the use of pesticides classed as harmless for bees along road verges. It was thought that old weak winter bees had succumbed to a preparation otherwise innocuous. Extensive tests to reveal any links between the bees' physiological condition and pesticide sensitivity involved 6 hormone herbicides, 11 fungicides and 2 insecticides, all approved harmless for bees and functioning on them wholly or mainly as stomach poisons. As a rule bee sensitivity was measured as LD 50 per os, in smaller tests as percentage mortality. Amount and quality of pollen ingested in the first days of life affected the pesticide sensitivity of young and older bees. Bees fed adequate high quality pollen are less sensitive than counterparts fed inadequate or inferior pollen or pollen substitute; such differences persisted if the LD 50 was calculated for the same body weight. Pesticides containing manganese are an exception. To these, bees fed inadequate pollen are no more or even less sensitive than comparable well-fed bees. Pesticide sensitivity decreases generally from early to late summer. Quality of pollen available for larvae has no effect on poison sensitivity of imagines. Food supply conditions however exert a clear influence: tested with the same pesticides, hive bees from colonies having had a rich early food supply, and young bees bred then, are less sensitive than their counterparts having had moderate or no early food supply. Poison sensitivity of summer bees increases with age; most sensitive are old winter bees which had practiced broodcare in early spring.Inadequate pollen intake can be regarded as causing protein deficiency. Investigation of this in mammals and man indicate that the higher poison sensitivity in bees results from inhibition of the enzymatic decomposition of pesticides. For practical bee protection it is important that all organic fungicides tested are effectively harmless. Hormone

Intestinal absorption of /sup 47/Ca in elderly patients with osteoporosis, Paget's disease, and osteomalacia. Effects of calcitonin, oestrogen, and vitamin D2

Energy Technology Data Exchange (ETDEWEB)

Lender, M.; Verner, E.; Stankiewicz, H.; Menczel, J.

1977-01-01

The intestinal absorption of /sup 47/Ca was studied in elderly patients. A standard dose of 10 ..mu..Ci of /sup 47/Ca was given orally. The radioactivity was measured in the plasma, and expressed as percentage of the administered dose per litre plasma. As a control group served 12 patients aged 60--80 years, hospitalized for observation for various reasons, receiving no medical treatment and not suffering from any known metabolic bone diseases or other metabolic pathological conditions. Results of kinetic curves demonstrate in elderly patients a decreased absorption with maximum specific activity in plasma reached at 120 min, when compared to data from the literature referring to a group of young people with a mean age of 35 years. Oestrogen treatment, given as ethinyl oestradiol 10 ..mu..g once daily per os for 10 days proved to increase /sup 47/Ca absorption as was demonstrated in 2 patients with osteoporosis. The effect of calcitonin (160 MRC units given 45 min before the test) on calcium absorption, in 5 patients with Paget's disease or osteoporosis appears as biphasic: in the first hour depressing calcium absorption and then in the second and third hours increasing the absorption, suggesting a hyperparathyroid state secondary to the calcitonin effect. The vitamin D2 treatment proved to increase calcium absorption.

Bidirectional effects between parenting sensitivity and child behavior: A cross-lagged analysis across middle childhood and adolescence.

Science.gov (United States)

Zvara, Bharathi J; Sheppard, Kelly W; Cox, Martha

2018-04-26

Using a longitudinal, cross-lagged design, this study examined the bidirectional relations between mothers' and fathers' sensitivity and children's externalizing (EXT) and internalizing (INT) behavior from middle childhood into adolescence. The subsample comprised families (N = 578) in which the mother and father cohabitated from the study's first time point (child age = 54 months) through Age 15 in the longitudinal NICHD Study of Early Child Care and Youth Development. Study results revealed differential patterns for mother-child and father-child relations in the full sample and separately for males and females. The full cross-lagged models revealed that child EXT behavior predicted maternal sensitivity, but not vice versa, and fathers' sensitivity and child behavior were reciprocally interrelated. There was a significant indirect pathway from early paternal sensitivity to later EXT in males, and from early maternal sensitivity to INT in females. The results point to the important roles that fathers play in child INT and EXT behaviors and important differences between males and females. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Is There a Sensitive Period in Human Incest Avoidance?

Directory of Open Access Journals (Sweden)

Liqun Luo

2011-04-01

Full Text Available Many studies support the proposition that early cosocialization with opposite-sex children has the effect of inhibiting later mutual sexual attraction, but the existence of a period in the life cycle in which individuals are sensitive to the effect of early cosocialization has been a matter of controversy. Drawing on earlier traditional psychological research, and on more recent work guided by parental investment theory, we hypothesized that only for maternal perinatal association (MPA-absent males a less-than-around-three-years age difference with the sister can predict stronger aversion to sibling incest. The results corroborated the hypothesis. The results can be interpreted as support for the existence of a sensitive period as well as for the potent role of MPA. Cross-cultural comparative studies were called on to further test the hypothesis.

Balancing data sharing requirements for analyses with data sensitivity

Science.gov (United States)

Jarnevich, C.S.; Graham, J.J.; Newman, G.J.; Crall, A.W.; Stohlgren, T.J.

2007-01-01

Data sensitivity can pose a formidable barrier to data sharing. Knowledge of species current distributions from data sharing is critical for the creation of watch lists and an early warning/rapid response system and for model generation for the spread of invasive species. We have created an on-line system to synthesize disparate datasets of non-native species locations that includes a mechanism to account for data sensitivity. Data contributors are able to mark their data as sensitive. This data is then 'fuzzed' in mapping applications and downloaded files to quarter-quadrangle grid cells, but the actual locations are available for analyses. We propose that this system overcomes the hurdles to data sharing posed by sensitive data. ?? 2006 Springer Science+Business Media B.V.

Early Diagnosis of Breast Cancer.

Science.gov (United States)

Wang, Lulu

2017-07-05

Early-stage cancer detection could reduce breast cancer death rates significantly in the long-term. The most critical point for best prognosis is to identify early-stage cancer cells. Investigators have studied many breast diagnostic approaches, including mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. However, these techniques have some limitations such as being expensive, time consuming and not suitable for young women. Developing a high-sensitive and rapid early-stage breast cancer diagnostic method is urgent. In recent years, investigators have paid their attention in the development of biosensors to detect breast cancer using different biomarkers. Apart from biosensors and biomarkers, microwave imaging techniques have also been intensely studied as a promising diagnostic tool for rapid and cost-effective early-stage breast cancer detection. This paper aims to provide an overview on recent important achievements in breast screening methods (particularly on microwave imaging) and breast biomarkers along with biosensors for rapidly diagnosing breast cancer.

Allergic Sensitization at School Age is a Systemic Low-grade Inflammatory Disorder

DEFF Research Database (Denmark)

Chawes, B. L.; Stokholm, J.; Schoos, A.-M. M.

2017-01-01

allergic sensitization. Methods High-sensitivity C-reactive protein (hs-CRP), interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and chemokine (C-X-C motif) ligand 8 (CXCL8) were measured in plasma at age 6 months (N = 214) and 7 years (N = 277) in children from the Copenhagen Prospective...... sensitization in school-aged children suggesting systemic low-grade inflammation as a phenotypic characteristic of this early-onset NCD....

Sensitive periods in human development: evidence from musical training.

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Penhune, Virginia B

2011-10-01

One of the primary goals of cognitive neuroscience is to understand the interaction between genes, development and specific experience. A particularly fascinating example of this interaction is a sensitive period - a time during development when experience has a differential effect on behavior and the brain. Behavioral and brain imaging studies in musicians have provided suggestive evidence for a possible sensitive period for musical training; showing that musicians who began training early show better task performance and greater changes in auditory and motor regions of the brain. However, these studies have not controlled for likely differences between early- (ET) and late-trained (LT) musicians in the number of years of musical experience. This review presents behavioral work from our laboratory comparing the performance of ET (before age seven) and LT musicians who were matched for years of experience on the ability to tap in synchrony with auditory and visual rhythms. The results demonstrate the existence of a possible sensitive period for musical training that has its greatest impact on measures of sensorimotor integration. Work on motor learning in children and how this might relate to the observed sensitive period effect is also reviewed. These studies are described in the context of what is currently known about sensitive periods in animals and humans; drawing on evidence from anatomy and physiology, studies of deafness, as well as structural and functional neuroimaging studies in trained musicians. The possible mechanisms underlying sensitive periods for musical training are discussed based on current theories describing the influence of both low-level features of sensory experience and higher-level cognitive processing. Copyright © 2011 Elsevier Srl. All rights reserved.

Effects of copper on early developmental stages of Lessonia nigrescens Bory (Phaeophyceae)

Energy Technology Data Exchange (ETDEWEB)

Contreras, Loretto [Departamento de Ecologia, Center for Advanced Studies in Ecology and Biodiversity, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Post-code 6513677, Alameda 340, Santiago (Chile); Medina, Matias H. [Departamento de Ecologia, Center for Advanced Studies in Ecology and Biodiversity, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Post-code 6513677, Alameda 340, Santiago (Chile); CIIMAR - Centro Interdisciplinar de Investigacao Marinha e Ambiental, Laboratory of Ecotoxicology, Universidade do Porto (Portugal); Andrade, Santiago [Departamento de Ecologia, Center for Advanced Studies in Ecology and Biodiversity, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Post-code 6513677, Alameda 340, Santiago (Chile); Oppliger, Valeria [Departamento de Ecologia, Center for Advanced Studies in Ecology and Biodiversity, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Post-code 6513677, Alameda 340, Santiago (Chile); Correa, Juan A. [Departamento de Ecologia, Center for Advanced Studies in Ecology and Biodiversity, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Post-code 6513677, Alameda 340, Santiago (Chile)]. E-mail: jcorrea@bio.puc.cl

2007-01-15

Copper effects on the early developmental gametophytic and sporophytic stages of the kelp Lessonia nigrescens were tested in gradients of increasing concentrations of ASV-labile copper. The results demonstrated a high sensitivity to copper of all life-history stages of the alga, where even the lowest tested concentration affected spore release as well as their subsequent settlement. More significant, concentrations higher than 7.87 {mu}g L{sup -1} totally interrupted the development of the spores after they settle. This effect led to a failure in the formation of male and female gametophytes and, as a consequence, to a complete disruption of the normal life cycle of the kelp. Thus, we suggest that the absence of L. nigrescens from copper-enriched environments results from the high sensitivity of its early life cycle stages, which limits growth and maturation of the gametophytic microscopic phase and, as a consequence, prevents development of the macroscopic sporophytic phase. - Early developmental stages of Lessonia nigrescens are highly sensitive to copper.

Effects of copper on early developmental stages of Lessonia nigrescens Bory (Phaeophyceae)

International Nuclear Information System (INIS)

Contreras, Loretto; Medina, Matias H.; Andrade, Santiago; Oppliger, Valeria; Correa, Juan A.

2007-01-01

Copper effects on the early developmental gametophytic and sporophytic stages of the kelp Lessonia nigrescens were tested in gradients of increasing concentrations of ASV-labile copper. The results demonstrated a high sensitivity to copper of all life-history stages of the alga, where even the lowest tested concentration affected spore release as well as their subsequent settlement. More significant, concentrations higher than 7.87 μg L -1 totally interrupted the development of the spores after they settle. This effect led to a failure in the formation of male and female gametophytes and, as a consequence, to a complete disruption of the normal life cycle of the kelp. Thus, we suggest that the absence of L. nigrescens from copper-enriched environments results from the high sensitivity of its early life cycle stages, which limits growth and maturation of the gametophytic microscopic phase and, as a consequence, prevents development of the macroscopic sporophytic phase. - Early developmental stages of Lessonia nigrescens are highly sensitive to copper

Sensitivity of the Early Development of Ramshorn Snail, Marisa cornuarietis (Ampullariidae) to Environmental Chemicals

OpenAIRE

Sawasdee, Banthita

2011-01-01

In this study, the suitability of the M. cornuarietis embryo toxicity test (MariETT) for environmental chemicals was investigated. The purpose of this study was to determine the sensitivity of the recently introduced M. cornuarietis embryo toxicity test (MariETT) using selected metals (inorganic pollutants) and pesticides (organic pollutants), and to compare its sensitivity and practicability to other established bioassay. The following endpoints were observed: mortality, formation of tentacl...

Mothers' and Fathers' Sensitivity with Their Two Children: A Longitudinal Study from Infancy to Early Childhood

Science.gov (United States)

Hallers-Haalboom, Elizabeth T.; Groeneveld, Marleen G.; van Berkel, Sheila R.; Endendijk, Joyce J.; van der Pol, Lotte D.; Linting, Mariëlle; Bakermans-Kranenburg, Marian J.; Mesman, Judi

2017-01-01

To examine the effects of child age and birth order on sensitive parenting, 364 families with 2 children were visited when the second-born children were 12, 24, and 36 months old, and their older siblings were on average 2 years older. Mothers showed higher levels of sensitivity than fathers at all assessments. Parental sensitivity increased from…

Early-life gut microbiome and egg allergy.

Science.gov (United States)

Fazlollahi, M; Chun, Y; Grishin, A; Wood, R A; Burks, A W; Dawson, P; Jones, S M; Leung, D Y M; Sampson, H A; Sicherer, S H; Bunyavanich, S

2018-07-01

Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10 -4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis P adj  = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10 -4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

[Impact of Socioeconomic Risk Exposure on Maternal Sensitivity, Stress and Family Functionality].

Science.gov (United States)

Sidor, Anna; Köhler, Hubert; Cierpka, Manfred

2018-03-01

Impact of Socioeconomic Risk Exposure on Maternal Sensitivity, Stress and Family Functionality Parental stress exposure can influence the parent-child relationship, child development and child wellbeing in negative ways. The aim of this study was to investigate the impact of socio-economic risk exposure on the quality of the mother-child-interaction and family functionality. A sample of 294 mother-infant dyads at psychosocial risk was compared with a lower-risk, middle-class sample of 125 mother-infant-dyads in regard to maternal sensitivity/child's cooperation (CARE-Index), maternal stress (PSI-SF) and family functionality (FB-K). Lower levels of maternal sensitivity/child's cooperation and by trend also of the family functionality were found among the mothers from the at-risk sample in comparison to the low-risk sample. The level of maternal stress was similar in both samples. The results underpin the negative effects of a socio-economic risk exposure on the mother-child relationship. An early, sensitivity-focused family support could be encouraged to counteract the negative effects of early socioeconomic stress.

Dose-Reduced Trastuzumab Emtansine: Active and Safe in Acute Hepatic Dysfunction

OpenAIRE

Sharp, Adam; Johnston, Stephen R.D.

2015-01-01

Breast cancer is the most common cancer in women worldwide. The majority of deaths attributed to breast cancer are a result of metastatic disease, and 30% of early breast cancers (EBC) will develop distant disease. The 5-year survival of patients with metastatic disease is estimated at 23%. Breast cancer subtypes continue to be stratified histologically on oestrogen, progesterone and human epidermal growth factor-2 (HER2) receptor expression. HER2-positive breast cancers represent 25% of all ...

Antenatal interpersonal sensitivity is more strongly associated than perinatal depressive symptoms with postnatal mother-infant interaction quality.

Science.gov (United States)

Raine, Karen; Cockshaw, Wendell; Boyce, Philip; Thorpe, Karen

2016-10-01

Maternal mental health has enduring effects on children's life chances and is a substantial cost driver for child health, education and social services. A key linking mechanism is the quality of mother-infant interaction. A body of work associates maternal depressive symptoms across the antenatal and postnatal (perinatal) period with less-than-optimal mother-infant interaction. Our study aims to build on previous research in the field through exploring the association of a maternal personality trait, interpersonal sensitivity, measured in early pregnancy, with subsequent mother-infant interaction quality. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine the association between antenatal interpersonal sensitivity and postnatal mother-infant interaction quality in the context of perinatal depressive symptoms. Interpersonal sensitivity was measured during early pregnancy and depressive symptoms in the antenatal year and across the first 21 months of the postnatal period. In a subsample of the ALSPAC, mother-infant interaction was measured at 12 months postnatal through a standard observation. For the subsample that had complete data at all time points (n = 706), hierarchical regression examined the contribution of interpersonal sensitivity to variance in mother-infant interaction quality. Perinatal depressive symptoms predicted little variance in mother-infant interaction. Antenatal interpersonal sensitivity explained a greater proportion of variance in mother-infant interaction quality. The personality trait, interpersonal sensitivity, measured in early pregnancy, is a more robust indicator of subsequent mother-infant-interaction quality than perinatal depressive symptoms, thus affording enhanced opportunity to identify vulnerable mother-infant relationships for targeted early intervention.

Combining High Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction.

Science.gov (United States)

van der Linden, Noreen; Wildi, Karin; Twerenbold, Raphael; Pickering, John W; Than, Martin; Cullen, Louise; Greenslade, Jaimi; Parsonage, William; Nestelberger, Thomas; Boeddinghaus, Jasper; Badertscher, Patrick; Rubini Giménez, Maria; Klinkenberg, Lieke J J; Bekers, Otto; Schöni, Aline; Keller, Dagmar I; Sabti, Zaid; Puelacher, Christian; Cupa, Janosch; Schumacher, Lukas; Kozhuharov, Nikola; Grimm, Karin; Shrestha, Samyut; Flores, Dayana; Freese, Michael; Stelzig, Claudia; Strebel, Ivo; Miró, Òscar; Rentsch, Katharina; Morawiec, Beata; Kawecki, Damian; Kloos, Wanda; Lohrmann, Jens; Richards, A Mark; Troughton, Richard; Pemberton, Christopher; Osswald, Stefan; van Dieijen-Visser, Marja P; Mingels, Alma M; Reichlin, Tobias; Meex, Steven J R; Mueller, Christian

2018-04-24

Background -Combining two signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction (AMI) with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of AMI. Methods -The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected AMI. The optimal rule out and rule in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule out was compared with the ESC 0/1 and 0/3 hour algorithms. Results -Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the ESC 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule out criteria after the baseline blood sampling was limited (6-24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34-41% in the original (sum: negative predictive value (NPV) 100% (95%CI: 99.5-100%); product: NPV 100% (95%CI: 99.5-100%) and in the validation cohort (sum: NPV 99.6% (95%CI: 99.0-99.9%); product: NPV 99.4% (95%CI: 98.8-99.8%). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule out (40-43% ruled out; NPV original cohort 99.9% (95%CI: 99.2-100%); NPV

Ectopic expression of soybean gmsbh1 confers aba sensitivity during seed germination and early seedling establishment in transgenic arabidopsis

International Nuclear Information System (INIS)

Shu, Y.; Zhou, Y.; Huang, S.; Chen, M.; Huang, L.; Ma, H.

2017-01-01

The class I KNOX homeobox transcription factors are known to play an important role in maintenance of plant phenotype, especially leaves and flowers. In this study, a soybean KNOX I homeobox transcription factor, GmSBH1, was analyzed and confirmed to play important roles in the process of seed germination and developing. Real time quantitative PCR assay showed that the transcript level of GmSBH1 in soybean seedlings was modulated by plant hormones, such as IAA, GA, MeJA and ABA.Yeast one-hybrid assay showed that GmSBH1 could bind to the ABRE cis-element. Overexpression of GmSBH1 in Arabidopsis resulted in the abnormal phenotype of flowers and siliques. In GmSBH1 transgenic lines, both seed germination and seedlings growth showed hypersensitive to ABA. Moreover, the expression of ABA-responsive genes, such as ABI3 and ABI5, were increased in the transgenic line seedlings. Taken together, ectopic expression of GmSBH1 could alter the morphology and confer ABA sensitivity during seed germination and early seedling growth in transgenic Arabidopsis. (author)

Sensitive Periods of Emotion Regulation: Influences of Parental Care on Frontoamygdala Circuitry and Plasticity

Science.gov (United States)

Gee, Dylan G.

2016-01-01

Early caregiving experiences play a central role in shaping emotional development, stress physiology, and refinement of limbic circuitry. Converging evidence across species delineates a sensitive period of heightened neuroplasticity when frontoamygdala circuitry is especially amenable to caregiver inputs early in life. During this period, parental…

The early clinical features of dengue in adults: challenges for early clinical diagnosis.

Directory of Open Access Journals (Sweden)

Jenny G H Low

Full Text Available BACKGROUND: The emergence of dengue throughout the tropical world is affecting an increasing proportion of adult cases. The clinical features of dengue in different age groups have not been well examined, especially in the context of early clinical diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: We structured a prospective study of adults (≥ 18 years of age presenting with acute febrile illness within 72 hours from illness onset upon informed consent. Patients were followed up over a 3-4 week period to determine the clinical outcome. A total of 2,129 adults were enrolled in the study, of which 250 (11.7% had dengue. Differences in the rates of dengue-associated symptoms resulted in high sensitivities when the WHO 1997 or 2009 classification schemes for probable dengue fever were applied to the cohort. However, when the cases were stratified into age groups, fewer older adults reported symptoms such as myalgia, arthralgia, retro-orbital pain and mucosal bleeding, resulting in reduced sensitivity of the WHO classification schemes. On the other hand, the risks of severe dengue and hospitalization were not diminished in older adults, indicating that this group of patients can benefit from early diagnosis, especially when an antiviral drug becomes available. Our data also suggests that older adults who present with fever and leukopenia should be tested for dengue, even in the absence of other symptoms. CONCLUSION: Early clinical diagnosis based on previously defined symptoms that are associated with dengue, even when used in the schematics of both the WHO 1997 and 2009 classifications, is difficult in older adults.

Hormone replacement therapy and risk of non-fatal stroke

DEFF Research Database (Denmark)

Pedersen, A T; Lidegaard, O; Kreiner, S

1997-01-01

haemorrhage, 846 thromboembolic infarction, 321 transient ischaemic attack) and 3171 controls. FINDINGS: After adjustment for confounding variables and correction for the trend in sales of HRT preparations, no significant associations were detected between current use of unopposed oestrogen replacement...... influence on the risk of subarachnoid haemorrhage (1.22 [0.79-1.89]), intracerebral haemorrhage (1.17 [0.64-2.13]), or thromboembolic infarction (1.17 [0.92-1.47]). A significantly increased incidence of transient ischaemic attacks among former users of HRT and among current users of unopposed oestrogen may...... to some extent be explained by selection--HRT users being more aware of symptoms than non-users. INTERPRETATION: Unopposed oestrogen and combined oestrogen-progestagen replacement therapy have no influence on the risk of non-fatal thromboembolic or haemorrhagic stroke in women aged 45-64 years....

[Early Intervention and Cognitive Development: A Longitudinal Study with Psychologically Stressed Mother-Child-Dyad during Early Childhood].

Science.gov (United States)

Zwönitzer, Annabel; Ziegenhain, Ute; Bovenschen, Ina; Pillhofer, Melanie; Spangler, Gottfried; Gerlach, Jennifer; Gabler, Sandra; Kindler, Heinz; Fegert, Jörg M; Künster, Anne Katrin

2016-01-01

Early intervention programs aiming at developing parents’ relationship and parenting skills and supporting young families have become increasingly established in Germany throughout the last decade. The present longitudinal study analyzed 53 children and their mothers receiving early intervention due to their psychosocially highly challenging life situations and personal circumstances. The children were examined at birth and at an age of twelve months as well as between ages two and four. The results revealed that the child’s cognitive development could be predicted by both maternal sensitivity and mother’s psychosocial stress. However, the amount, type, and intensity of early intervention did not have any effect on the child’s development. In terms of the effectiveness of early interventions the results implicate that interventions seems to be offered in an unspecific manner and does not contribute to an improvement of the child’s developmental status.

Sensitivity and specificity of scanning laser polarimetry using the GDx.

Science.gov (United States)

Munkwitz, S; Funk, J; Loeffler, K U; Harbarth, U; Kremmer, S

2004-09-01

To determine the sensitivity and the specificity of the GDx in the detection of (1) advanced glaucoma, (2) early glaucoma, and (3) nerve fibre bundle defects (NFBD). Group A comprised 20 eyes with reproducible glaucomatous visual field defects confirmed by octopus perimetry, group B consisted of 10 eyes with normal visual fields but either glaucomatous NFBD or deterioration of the disc over time clearly visible upon flicker comparison, and group C included 16 eyes with glaucomatous or non-glaucomatous NFBD clearly visible on red free photographs. Forty four eyes of 22 healthy volunteers served as controls. The GDx printouts of all subjects were evaluated by three independent observers in a masked fashion and without the clinical picture of the optic disc. Two of the three observers (SK, UH) were GDx experts, one (KUL) was an untrained GDx user. Among the GDx experts, sensitivity/specificity was 100%/100% (SK) and 90%/100% (UH) in detecting advanced glaucoma, and 100%/100% (SK) and 90%/100% (UH) in detecting early glaucoma. The sensitivity in detecting NFBD was only 37.5% (SK and UH). For the untrained GDx user the corresponding values were 50%/100% (group A), 20%/100% (group B), and 12.5%/91% (group C). Detection of (early) glaucoma damage by the GDx, evaluated by trained experts, can be extremely high. To optimise its benefit in clinical routine training in interpreting GDx printouts is highly recommended. Detection of localised NFBD is crucial, even for experts.

[The early pregnancy factor (EPF) as an early marker of disorders in pregnancy].

Science.gov (United States)

Straube, W; Römer, T; Zeenni, L; Loh, M

1995-01-01

The early pregnancy factor (EPF) seems to be very helpful in clinical applications such as early detection of pregnancy, differential diagnosis of failure of fertilization or implementation and prognosis of a fertilized ovum. Our purpose was to investigate the diagnostic value of single and serial measurement of EPF, especially in the differential diagnosis of abortion and extrauterine pregnancy. Women with a history of 6-16 weeks amenorrhoea with/without vaginal bleeding were included in the prospective study. The EPF-test system was carried out by means of the rosette inhibition method. EPF proved to be always positive in normal pregnant women and always negative in nonpregnant controls. In case of threatened abortion the prognosis was good, when the EPF values were positive, and poor when they became negative. Patients suffering from spontaneous and missed abortion mostly showed negative EPF-values. This was also true in ectopic pregnancies. The sensitivity and specificity of EPF-test system were 83%. The positive predictive value was observed to be 54% and the negative predictive value 95%. The EPF as an early embryonic signal may be a suitable parameter for the clinical use detecting pregnancy disturbances very early.

Plasticity during Early Brain Development Is Determined by Ontogenetic Potential.

Science.gov (United States)

Krägeloh-Mann, Ingeborg; Lidzba, Karen; Pavlova, Marina A; Wilke, Marko; Staudt, Martin

2017-04-01

Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building. Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of undrilled prospects. Sensitivity to economic and geological factors

International Nuclear Information System (INIS)

Hermanrud, C.; Abrahamsen, K.; Vollset, J.; Nordahl, S.; Jourdan, C.

1996-01-01

predictable to a greater accuracy than 40 % at early stages of exploration. This, and the fluctuations in oil price, adds to the uncertainty of early economic start-up. The operational and investment costs are not generally predictable to a greater accuracy than 40 % at early stages of exploration. This, and the fluctuations in oil price, adds to the uncertainty of early economic calculations. Sensitivity analysis of calculated net present values for exploration prospects shows that the investigated prospects are sensitive to many different factors, and that a separate sensitivity analysis for each prospect is needed. 15 refs

A prospective microbiome-wide association study of food sensitization and food allergy in early childhood.

Science.gov (United States)

Savage, Jessica H; Lee-Sarwar, Kathleen A; Sordillo, Joanne; Bunyavanich, Supinda; Zhou, Yanjiao; O'Connor, George; Sandel, Megan; Bacharier, Leonard B; Zeiger, Robert; Sodergren, Erica; Weinstock, George M; Gold, Diane R; Weiss, Scott T; Litonjua, Augusto A

2018-01-01

Alterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development. Intestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high-dose vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed. Food allergy was defined as caretaker report of healthcare provider-diagnosed allergy to the above foods prior to age 3 with evidence of IgE sensitization. Analysis was performed using Phyloseq and DESeq2; P-values were adjusted for multiple comparisons. Complete data were available for 225 children; there were 87 cases of food sensitization and 14 cases of food allergy. Microbial diversity measures did not differ between food sensitization and food allergy cases and controls. The genera Haemophilus (log 2 fold change -2.15, P=.003), Dialister (log 2 fold change -2.22, P=.009), Dorea (log 2 fold change -1.65, P=.02), and Clostridium (log 2 fold change -1.47, P=.002) were underrepresented among subjects with food sensitization. The genera Citrobacter (log 2 fold change -3.41, P=.03), Oscillospira (log 2 fold change -2.80, P=.03), Lactococcus (log 2 fold change -3.19, P=.05), and Dorea (log 2 fold change -3.00, P=.05) were underrepresented among subjects with food allergy. The temporal association between bacterial colonization and food sensitization and allergy suggests that the microbiome may have a causal role in the development of food allergy. Our findings have therapeutic implications for the prevention and treatment of food allergy. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Oxidative stress specifically downregulates survivin to promote breast tumour formation.

Science.gov (United States)

Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R

2013-03-05

Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.

The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

Science.gov (United States)

Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

2011-10-01

The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience

Anti-early pregnancy by PDT

Science.gov (United States)

Ding, Ai-Hua; Chen, Hui-Ling

1993-03-01

The effect of laser on anti-early pregnancy in rabbits showed that laser in combination with HPD could induce necrosis of blastocysts and complete absorption. The anti-fertility efficiency of the combined treatment was more effective than that of the He-Ne laser or the HPD treatment alone. The fluorescence spectrum of HPD determined by PNQ3 showed that its affinity to embryonic tissue was about 4 times greater than that to uterine tissue. This may underlie the mechanisms of anti-early pregnancy of the laser. The operation of artificial abortion is a routine method to terminate early pregnancy. Though it is simple and easy, its syndrome and complications can not be absolutely avoided. Many antifertility drugs have been reported, however, they often bring in general reaction. Our present work is to explore a new way of anti-early pregnancy in rabbits by means of the light inhibitory and light sensitive effects of laser. It is a quite safe and painless treatment without expanding and scraping of the uterus.

A sensitive detection assay based on signal amplification technology for Alzheimer's disease's early biomarker in exosome.

Science.gov (United States)

Zhou, Jie; Meng, Lingchang; Ye, Weiran; Wang, Qiaolei; Geng, Shizhen; Sun, Chong

2018-08-31

Alzheimer's disease (AD) considered as the third health "killer" has seriously threatened the health of the elderly. However, the modern diagnostic strategies of AD present several disadvantages: the low accuracy and specificity resulting in some false-negative diagnoses, and the poor sensitivity leading to a delayed treatment. In view of this situation, a enzyme-free and target-triggered signal amplification strategy, based on graphene oxide (GO) and entropy-driven strand displacement reaction (ESDR) principle, was proposed. In this strategy, when the hairpin structure probes (H)specially binds with beta-amyloid-(1-42) oligomers (Aβ42 oligomers), it's structure will be opened, causing the bases complementary to FAM-labeled replacement probes R (R1 and R2) exposed. At this time, R1 and R2 will hybridize with H, resulting in the bound Aβ42 oligomers released. The released Aβ42 oligomers would participate in the next cycle reaction, making the signal amplified. As a quencher, GO could absorb the free single-stranded DNA R1 and R2 and quench their fluorescence; however, the DNA duplex still exists free and keeps its signal-on. Through the detection of Aβ42 oligomers in exosomes, this ultrasensitive detection method with the advantages of low limit of detection (LOD, 20 pM), great accuracy, excellent precision and convenience provides an excellent prospect for AD's early diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Xenon ventilation-perfusion lung scans. The early diagnosis of inhalation injury

International Nuclear Information System (INIS)

Schall, G.L.; McDonald, H.D.; Carr, L.B.; Capozzi, A.

1978-01-01

The use of xenon Xe-133 ventilation-perfusion lung scans for the early diagnosis of inhalation injury was evaluated in 67 patients with acute thermal burns. Study results were interpreted as normal if there was complete pulmonary clearance of the radioactive gas by 150 seconds. Thirty-two scans were normal, 32 abnormal, and three technically inadequate. There were three true false-positive study results and one false-negative study result. Good correlation was found between the scan results and various historical, physical, and laboratory values currently used to evaluate inhalation injury. The scans appeared to be the most sensitive method for the detection of early involvement, often being abnormal several days before the chest roentgenogram. Xenon lung scanning is a safe, easy, accurate, and sensitive method for the early diagnosis of inhalation injury and has important therapeutic and prognostic implications as well

Effect of Ferrite Morphology on Sensitization of 316L Austenitic Stainless Steels

Energy Technology Data Exchange (ETDEWEB)

Jang, Hun; Lee, Jun Ho; Jang, Changheui [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2013-05-15

The sensitization behaviors of L-grade SSs having predominant austenitic structure with small amount of ferrite have not been well understood. In this regard, the effect of ferrite morphology on sensitization was investigated in this study. The sensitization behaviors of three heats of 316L and 316LN SSs were investigated, Stringer type of ferrite (316L - heat A and B) showed the early sensitization by chromium depletion at ferrite. austenite interface. And, later sensitization is due to GB sensitization. On the other hand, blocky type of ferrite (316L - heat C) showed lower DOS and higher resistance to GB sensitization. It could be due to sufficient supply of chromium from relatively large ferrite phase. As a consequence, the sensitization of 316L SSs could be affected by their ferrite morphology rather than ferrite content. The sensitized region was distinguishable from results of DL-EPR tests. It can be used as an effective method for evaluation of type of sensitization.

Developmental change in children's sensitivity to sound symbolism.

Science.gov (United States)

Tzeng, Christina Y; Nygaard, Lynne C; Namy, Laura L

2017-08-01

The current study examined developmental change in children's sensitivity to sound symbolism. Three-, five-, and seven-year-old children heard sound symbolic novel words and foreign words meaning round and pointy and chose which of two pictures (one round and one pointy) best corresponded to each word they heard. Task performance varied as a function of both word type and age group such that accuracy was greater for novel words than for foreign words, and task performance increased with age for both word types. For novel words, children in all age groups reliably chose the correct corresponding picture. For foreign words, 3-year-olds showed chance performance, whereas 5- and 7-year-olds showed reliably above-chance performance. Results suggest increased sensitivity to sound symbolic cues with development and imply that although sensitivity to sound symbolism may be available early and facilitate children's word-referent mappings, sensitivity to subtler sound symbolic cues requires greater language experience. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice.

Science.gov (United States)

Oliveira-Lima, A J; Santos, R; Hollais, A W; Gerardi-Junior, C A; Baldaia, M A; Wuo-Silva, R; Yokoyama, T S; Costa, J L; Malpezzi-Marinho, E L A; Ribeiro-Barbosa, P C; Berro, L F; Frussa-Filho, R; Marinho, E A V

2015-04-01

Hallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. In this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca (Aya) may have therapeutic effects on substance abuse problems. We investigated the effects of Aya on spontaneous locomotor activity and ethanol(Eth)-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of Aya on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with Eth (1.8g/kg) for 8 alternate days. Aya showed high sensitivity in preventing the development of Eth-induced behavioral sensitization, attenuating it at all doses (30, 100, 200, 300 or 500 mg/kg) without modifying spontaneous locomotor activity. At the highest doses (300 and 500 mg/kg), Aya also showed selectivity to both acute and sensitized Eth responses. Finally, a counter-sensitization strategy with 100 or 300 mg/kg of Aya for 8 consecutive days after the establishment of Eth-induced behavioral sensitization was effective in blocking its subsequent expression on an Eth challenge. We demonstrated that Aya not only inhibits early behaviors associated with the initiation and development of Eth addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of Eth-induced behavioral sensitization when administered in the Eth-associated environment. Copyright © 2015 Elsevier Inc. All rights reserved.

[Sensitivity and specificity of flicker perimetry with Pulsar. Comparison with achromatic (white-on-white) perimetry in glaucoma patients].

Science.gov (United States)

Göbel, K; Erb, C

2013-02-01

The early detection of functional glaucoma damage plays an increasingly more central role in the diagnosis and treatment of glaucoma disease. Using selective perimetry detection of early glaucomatous defects is more likely and one of these methods is flicker perimetry with Pulsar. Flicker perimetry is used to analyze the temporal visual function in combination with spatial resolution and contrast sensitivity as opposed to standard automated perimetry which measures the differential light sensitivity with a non-specific stimulus. This study showed a higher sensitivity and specificity of Pulsar perimetry in comparison to achromatic perimetry in glaucoma patients.

Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer.

Science.gov (United States)

Lu, Ya-Ching; Chang, Joseph Tung-Chieh; Huang, Yu-Chen; Huang, Chi-Che; Chen, Wen-Ho; Lee, Li-Yu; Huang, Bing-Shen; Chen, Yin-Ju; Li, Hsiao-Fang; Cheng, Ann-Joy

2015-02-01

The aim of this study was to determine whether the oncogenic microRNA family members miR-196a and miR-196b can be circulating biomarkers for the early detection of oral cancer. To determine the stability of circulating miRNA, the blood sample was aliquot and stored at different temperature conditions for analysis. To assess the diagnostic efficacy, we determined the levels of miR-196s in plasma samples, including 53 from healthy individuals, 16 from pre-cancer patients, and 90 from oral cancer patients. In general, circulating miRNA was very stable when storing plasma samples at -20°C or below. In clinical study, both circulating miR-196a and miR-196b were substantially up-regulated in patients with oral pre-cancer lesions (5.9- and 14.8-fold, respectively; P oral cancer patients (9.3- and 17.0-fold, respectively; P cancer patients (AUC = 0.764 or 0.840, miR-196a or miR-196b, respectively), and between normal and cancer patients (AUC = 0.864 or 0.960, miR-196a or miR-196b, respectively). The combined determination of miR-196a and miR-196b levels produces excellent sensitivity and specificity in the diagnosis of patients with oral pre-cancer (AUC = 0.845) or oral cancer (AUC = 0.963), as well as in the prediction of potential malignancy (AUC = 0.950, sensitivity = 91%, specificity = 85%). Combined determination of circulating miR-196a and miR-196b levels may serve as panel plasma biomarkers for the early detection of oral cancer. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Tailoring endocrine treatment for early breast cancer

NARCIS (Netherlands)

Fontein, Duveken Berthe Yvonne

2014-01-01

This thesis describes several important aspects of adjuvant endocrine therapy for postmenopausal women with endocrine-sensitive, early-stage breast cancer. In our ongoing efforts to tailor treatment so as to provide the best possible care to each of our patients, we studied the influence of various

Demonstration uncertainty/sensitivity analysis using the health and economic consequence model CRAC2

International Nuclear Information System (INIS)

Alpert, D.J.; Iman, R.L.; Johnson, J.D.; Helton, J.C.

1984-12-01

The techniques for performing uncertainty/sensitivity analyses compiled as part of the MELCOR program appear to be well suited for use with a health and economic consequence model. Two replicate samples of size 50 gave essentially identical results, indicating that for this case, a Latin hypercube sample of size 50 seems adequate to represent the distribution of results. Though the intent of this study was a demonstration of uncertainty/sensitivity analysis techniques, a number of insights relevant to health and economic consequence modeling can be gleaned: uncertainties in early deaths are significantly greater than uncertainties in latent cancer deaths; though the magnitude of the source term is the largest source of variation in estimated distributions of early deaths, a number of additional parameters are also important; even with the release fractions for a full SST1, one quarter of the CRAC2 runs gave no early deaths; and comparison of the estimates of mean early deaths for a full SST1 release in this study with those of recent point estimates for similar conditions indicates that the recent estimates may be significant overestimations of early deaths. Estimates of latent cancer deaths, however, are roughly comparable. An analysis of the type described here can provide insights in a number of areas. First, the variability in the results gives an indication of the potential uncertainty associated with the calculations. Second, the sensitivity of the results to assumptions about the input variables can be determined. Research efforts can then be concentrated on reducing the uncertainty in the variables which are the largest contributors to uncertainty in results

Mothers' and Fathers' Support for Child Autonomy and Early School Achievement

Science.gov (United States)

Developmental Psychology, 2008

2008-01-01

Data were analyzed from 641 children and their families in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development to test the hypotheses that in the early school years, mothers' and fathers' sensitive support for autonomy in observed parent-child interactions would each make unique predictions…

Prevalence of sensitization to cow’s milk and egg among patients with suspicion of IgE mediated diseases

Directory of Open Access Journals (Sweden)

José Mopan

2015-03-01

Conclusions: In Colombia, sensitization to milk and egg is relatively low compared to that reported in other studies with population with high risk of sensitization. Because of the association between sensitization of egg and the risk of having respiratory symptoms and gastrointestinal eosinophilia, an egg sensitization could be and early marker of poor prognosis in atopic patients.

exposure of growing and adult captive cheetahs (Acinony Jubatus) to dietary isoflavones: twenty years later

NARCIS (Netherlands)

Bell, K.M.; Rutherfurd, S.M.; Hendriks, W.H.

2010-01-01

Dietary isoflavones are associated with oestrogenic and anti-oestrogenic effects, and have been linked to infertility in cheetahs. This study aimed to determine the isoflavone content of commercially prepared diets consumed by captive cheetahs. Sixteen international zoological facilities provided

The early development of hypothyroidism after 131I treatment for hyperthyroid Graves' disease

International Nuclear Information System (INIS)

Kang Zengshou; Zhou Qian; Liu Shizhen

1995-01-01

827 patients with Graves' hyperthyroidism following 131 I treatment were followed up at 3 monthly intervals for 12∼36 months from 1985 to 1991. Physical examination and serum total T 3 , T 4 , TSH measurements were made at each visit. According to the authors data, 90% early hypothyroidism occurred within 2∼3 months after 131 I treatment, thereby, careful follow-up study is very important during this period. T 4 was much more sensitive than T 3 in diagnosing early hypothyroidism, while the TSH level shows thyroid reservation function, and is less sensitive than T 4 in diagnosing 131 I induced hypothyroidism. The study confirmed the view that the early incidence of post 131 I therapy hypothyroidism was strongly dose dependent

COMPARATIVE STUDY ON SPECIFIC AND EARLY DETECTION ...

African Journals Online (AJOL)

The objective of this study was to compare the sensitivity and specificity of smear and culture methods with rapid serological EIA myco kits manufactured by Omega diagnostics, for the early detection of Mycobacterium tuberculosis (MTB) complex. Sera from various categories of smear and culture results were compared ...

Early prevention of obesity

OpenAIRE

Claudio Maffeis

2014-01-01

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...

Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson's Disease.

Science.gov (United States)

San Luciano, Marta; Wang, Cuiling; Ortega, Roberto A; Yu, Qiping; Boschung, Sarah; Soto-Valencia, Jeannie; Bressman, Susan B; Lipton, Richard B; Pullman, Seth; Saunders-Pullman, Rachel

2016-01-01

Pre-clinical markers of Parkinson's Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown. 138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices. All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD. Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD.

A five-year model to assess the early cost-effectiveness of new diagnostic tests in the early diagnosis of rheumatoid arthritis.

Science.gov (United States)

Buisman, Leander R; Luime, Jolanda J; Oppe, Mark; Hazes, Johanna M W; Rutten-van Mölken, Maureen P M H

2016-06-10

There is a lack of information about the sensitivity, specificity and costs new diagnostic tests should have to improve early diagnosis of rheumatoid arthritis (RA). Our objective was to explore the early cost-effectiveness of various new diagnostic test strategies in the workup of patients with inflammatory arthritis (IA) at risk of having RA. A decision tree followed by a patient-level state transition model, using data from published literature, cohorts and trials, was used to evaluate diagnostic test strategies. Alternative tests were assessed as add-on to or replacement of the ACR/EULAR 2010 RA classification criteria for all patients and for intermediate-risk patients. Tests included B-cell gene expression (sensitivity 0.60, specificity 0.90, costs €150), MRI (sensitivity 0.90, specificity 0.60, costs €756), IL-6 serum level (sensitivity 0.70, specificity 0.53, costs €50) and genetic assay (sensitivity 0.40, specificity 0.85, costs €750). Patients with IA at risk of RA were followed for 5 years using a societal perspective. Guideline treatment was assumed using tight controlled treatment based on DAS28; if patients had a DAS28 >3.2 at 12 months or later patients could be eligible for starting biological drugs. The outcome was expressed in incremental cost-effectiveness ratios (€2014 per quality-adjusted life year (QALY) gained) and headroom. The B-cell test was the least expensive strategy when used as an add-on and as replacement in intermediate-risk patients, making it the dominant strategy, as it has better health outcomes and lower costs. As add-on for all patients, the B-cell test was also the most cost-effective test strategy. When using a willingness-to-pay threshold of €20,000 per QALY gained, the IL-6 and MRI strategies were not cost-effective, except as replacement. A genetic assay was not cost-effective in any strategy. Probabilistic sensitivity analysis revealed that the B-cell test was consistently superior in all strategies. When

Relationship between nickel and cobalt sensitization in hard metal workers

Energy Technology Data Exchange (ETDEWEB)

Rystedt, I; Fischer, T

1983-05-01

Eight hundred fifty-three hard metal workers were examined and patch tested with 20 substances from their environment, including nickel and cobalt. Nickel sensitivity was found in 2 men and 38 women. 88% of the nickel-sensitive individuals had developed a jewelry dermatitis prior to employment in the hard metal industry or before the appearance of hand eczema. 29% of the hard metal workers gave a history of slight irritant dermatitis. In the nickel sensitized group, 40% had had severe hand eczema which generally appeared 6-12 months after starting employment. In 25% of the cases, nickel sensitive individuals developed cobalt allergy, compared with 5% in the total population investigated. Most facts indicate that nickel sensitivity and irritant hand eczema precede cobalt sensitization. Hard metal workers with simultaneous nickel and cobalt sensitivity had a more severe hand eczema than those with isolated cobalt or nickel sensitivity or only irritant dermatitis. 64% of the female population had pierced ear lobes. Among the nickel allergic women, 95% had pierced ear lobes. The use of earrings containing nickel after piercing is strongly suspected of being the major cause of nickel sensitivity. Piercing at an early age seems to increase the risk of incurring nickel sensitivity.

Hormone patterns in early human gestation

International Nuclear Information System (INIS)

Mishell, D.R. Jr.; Thorneycroft, I.H.; Nagata, Y.; Murata, T.; Nakamura, R.M.

1974-01-01

Accurate measurement of the low concentration of gonadotropins and steroid hormones present in human serum has been made possible by the development of sensitive radioimmunoassay (RIA) techniques. With the use of RIA FSH and LH, progesterone and 17OH-progesterone have been previously measured in early normal pregnancy. In order to determine the daily pattern of hormone levels in early normal pregnancy, gonadotropins as well as steroid hormone levels were measured in serum samples obtained daily from three women from the time of the last menstrual period prior to conception throughout the first few months of gestation. To further identify the steroid hormone pattern in early normal pregnancy, concentrations of estradiol, progesterone, and 17OH-progesterone were measured in individual serum samples obtained from a group of 158 women with apparently normal gestations who subsequently had therapeutic abortions. (auth)

The Interplay of Maternal Sensitivity and Toddler Engagement of Mother in Predicting Self-Regulation

Science.gov (United States)

Ispa, Jean M.; Su-Russell, Chang; Palermo, Francisco; Carlo, Gustavo

2017-01-01

Using data from the Early Head Start Research and Evaluation Project, a cross-lag mediation model was tested to examine longitudinal relations among low-income mothers' sensitivity; toddlers' engagement of their mothers; and toddler's self-regulation at ages 1, 2, and 3 years (N = 2,958). Age 1 maternal sensitivity predicted self-regulation at…

Differential housing and novelty response: Protection and risk from locomotor sensitization.

Science.gov (United States)

Garcia, Erik J; Haddon, Tara N; Saucier, Donald A; Cain, Mary E

2017-03-01

High novelty seeking increases the risk for drug experimentation and locomotor sensitization. Locomotor sensitization to psychostimulants is thought to reflect neurological adaptations that promote the transition to compulsive drug taking. Rats reared in enrichment (EC) show less locomotor sensitization when compared to rats reared in isolation (IC) or standard conditions (SC). The current research study was designed to test if novelty response contributed locomotor sensitization and more importantly, if the different housing environments could change the novelty response to protect against the development of locomotor sensitization in both adolescence and adulthood. Experiment 1: rats were tested for their response to novelty using the inescapable novelty test (IEN) and pseudorandomly assigned to enriched (EC), isolated (IC), or standard (SC) housing conditions for 30days. After housing, they were tested with IEN. Rats were then administered amphetamine (0.5mg/kg) or saline and locomotor activity was measured followed by a sensitization test 14days later. Experiment 2: rats were tested in the IEN test early adulthood and given five administrations of amphetamine (0.3mg/kg) or saline and then either stayed in or switched housing environments for 30days. Rats were then re-tested in the IEN test in late adulthood and administered five more injections of their respective treatments and tested for locomotor sensitization. Results indicate that IC and SC increased the response to novelty. EC housing decreased locomotor response to amphetamine and saline, and SC housing increased the locomotor response to amphetamine. Mediation results indicated that the late adult novelty response fully mediates the locomotor response to amphetamine and saline, while the early adulthood novelty response did not. Differential housing changes novelty and amphetamine locomotor response. Novelty response is altered into adulthood and provides evidence that enrichment can be used to reduce

Development of a metabolic biosignature for detection of early Lyme disease.

Science.gov (United States)

Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Hess, Ann M; Delorey, Mark J; Mahapatra, Sebabrata; Schriefer, Martin E; Belisle, John T

2015-06-15

Early Lyme disease patients often present to the clinic prior to developing a detectable antibody response to Borrelia burgdorferi, the etiologic agent. Thus, existing 2-tier serology-based assays yield low sensitivities (29%-40%) for early infection. The lack of an accurate laboratory test for early Lyme disease contributes to misconceptions about diagnosis and treatment, and underscores the need for new diagnostic approaches. Retrospective serum samples from patients with early Lyme disease, other diseases, and healthy controls were analyzed for small molecule metabolites by liquid chromatography-mass spectrometry (LC-MS). A metabolomics data workflow was applied to select a biosignature for classifying early Lyme disease and non-Lyme disease patients. A statistical model of the biosignature was trained using the patients' LC-MS data, and subsequently applied as an experimental diagnostic tool with LC-MS data from additional patient sera. The accuracy of this method was compared with standard 2-tier serology. Metabolic biosignature development selected 95 molecular features that distinguished early Lyme disease patients from healthy controls. Statistical modeling reduced the biosignature to 44 molecular features, and correctly classified early Lyme disease patients and healthy controls with a sensitivity of 88% (84%-95%), and a specificity of 95% (90%-100%). Importantly, the metabolic biosignature correctly classified 77%-95% of the of serology negative Lyme disease patients. The data provide proof-of-concept that metabolic profiling for early Lyme disease can achieve significantly greater (P Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Parametric uncertainty and global sensitivity analysis in a model of the carotid bifurcation: Identification and ranking of most sensitive model parameters.

Science.gov (United States)

Gul, R; Bernhard, S

2015-11-01

In computational cardiovascular models, parameters are one of major sources of uncertainty, which make the models unreliable and less predictive. In order to achieve predictive models that allow the investigation of the cardiovascular diseases, sensitivity analysis (SA) can be used to quantify and reduce the uncertainty in outputs (pressure and flow) caused by input (electrical and structural) model parameters. In the current study, three variance based global sensitivity analysis (GSA) methods; Sobol, FAST and a sparse grid stochastic collocation technique based on the Smolyak algorithm were applied on a lumped parameter model of carotid bifurcation. Sensitivity analysis was carried out to identify and rank most sensitive parameters as well as to fix less sensitive parameters at their nominal values (factor fixing). In this context, network location and temporal dependent sensitivities were also discussed to identify optimal measurement locations in carotid bifurcation and optimal temporal regions for each parameter in the pressure and flow waves, respectively. Results show that, for both pressure and flow, flow resistance (R), diameter (d) and length of the vessel (l) are sensitive within right common carotid (RCC), right internal carotid (RIC) and right external carotid (REC) arteries, while compliance of the vessels (C) and blood inertia (L) are sensitive only at RCC. Moreover, Young's modulus (E) and wall thickness (h) exhibit less sensitivities on pressure and flow at all locations of carotid bifurcation. Results of network location and temporal variabilities revealed that most of sensitivity was found in common time regions i.e. early systole, peak systole and end systole. Copyright © 2015 Elsevier Inc. All rights reserved.

An optimal ultrasonographic diagnostic test for early gout: A prospective controlled study.

Science.gov (United States)

Norkuviene, Eleonora; Petraitis, Mykolas; Apanaviciene, Indre; Virviciute, Dalia; Baranauskaite, Asta

2017-08-01

Objective To identify the optimal sites for classification of early gout by ultrasonography. Methods Sixty patients with monosodium urate crystal-proven gout (25 with early gout [≤2-year symptom duration], 35 with late gout [>2-year symptom duration], and 36 normouricemic healthy controls) from one centre were prospectively evaluated. Standardized blinded ultrasound examination of 36 joints and the triceps and patellar tendons was performed to identify tophi and the double contour (DC) sign. Results Ultrasonographic sensitivity was lower in early than late gout. Binary logistic regression analysis showed that two ultrasonographic signs (tophi in the first metatarsophalangeal joint [odds ratio, 16.46] and the DC sign in the ankle [odds ratio, 25.18]) significantly contributed to the final model for early gout diagnosis (sensitivity and specificity of 84% and 81%, respectively). The inter-reader reliability kappa value for the DC sign and tophi was 0.712. Conclusions Four-joint investigation (both first metatarsophalangeal joints for tophi and both ankles for the DC sign) is feasible and reliable and could be proposed as a screening test for early ultrasonographic gout classification in daily practice.

The role of imaging in early hip OA.

Science.gov (United States)

Siebelt, M; Agricola, R; Weinans, H; Kim, Y J

2014-10-01

Hip osteoarthritis (OA) is characterized by cartilage degradation, subchondral bone sclerosis and osteophyte formation. Nowadays, OA is thought to develop via different etiologies that all lead to a similar form of end stage joint degradation. One of these subtypes is related to an abnormal shaped hip joint, like acetabular dysplasia and a cam deformity. These bony abnormalities are highly predictive for development of hip OA, but they are likely to already be present from childhood. This suggests that these deformations induce OA changes in the hip, well before extensive hip degradation becomes present three to four decades later. Accurate detection and successful characterization of these early OA events might lead to better treatment options for hip OA besides nowadays available invasive joint replacement surgery. However, current diagnostic imaging techniques like radiographs or plain magnetic resonance imaging (MRI), are not sensitive enough to detect these subtle early OA changes. Nor are they able to disentangle intertwined and overlapping cascades from different OA subtypes, and neither can they predict OA progression. New and more sensitive imaging techniques might enable us to detect first OA changes on a cellular level, providing us with new opportunities for early intervention. In this respect, shape analysis using radiography, MRI, computed tomography (CT), single photon emission computed tomography (SPECT)/CT, and positron emission tomography (PET) might prove promising techniques and be more suited to detect early pathological changes in the hip joint. A broad application of these techniques might give us more understanding what can be considered physiological adaptation of the hip, or when early OA really starts. With a more clear definition of early OA, more homogenous patient populations can be selected and help with the development of new disease modifying OA interventions. Copyright © 2014 Osteoarthritis Research Society International

High-Frame-Rate Power Doppler Ultrasound Is More Sensitive than Conventional Power Doppler in Detecting Rheumatic Vascularisation

NARCIS (Netherlands)

M. van der Ven (Myrthe); J.J. Luime (Jolanda); van der Velden, L.L. (Levinia L.); J.G. Bosch (Hans); J.M.W. Hazes (Mieke); H.J. Vos (Rik)

2016-01-01

textabstractEarly recognition of joint inflammation will increase treatment efficacy in rheumatoid arthritis (RA). Yet, conventional power Doppler (PD) ultrasound might not be sufficiently sensitive to detect minor inflammation. We investigated the sensitivity of high-frame rate Doppler, combined

Mothers' and fathers' sensitivity with their two children : A longitudinal study from infancy to early childhood

NARCIS (Netherlands)

Hallers-Haalboom, E.T.; Groeneveld, M.G.; van Berkel, S. R.; Endendijk, J. J.; van der Pol, L. D.; Linting, M.; Bakermans-Kranenburg, M. J.; Mesman, J.

2017-01-01

To examine the effects of child age and birth order on sensitive parenting, 364 families with two children were visited when the second-born children were 12, 24, and 36 months old, and their older siblings were on average two years older. Mothers showed higher levels of sensitivity than fathers at

EH AND S ANALYSIS OF DYE-SENSITIZED PHOTOVOLTAIC SOLAR CELL PRODUCTION

International Nuclear Information System (INIS)

BOWERMAN, B.; FTHENAKIS, V.

2001-01-01

Photovoltaic solar cells based on a dye-sensitized nanocrystalline titanium dioxide photoelectrode have been researched and reported since the early 1990's. Commercial production of dye-sensitized photovoltaic solar cells has recently been reported in Australia. In this report, current manufacturing methods are described, and estimates are made of annual chemical use and emissions during production. Environmental, health and safety considerations for handling these materials are discussed. This preliminary EH and S evaluation of dye-sensitized titanium dioxide solar cells indicates that some precautions will be necessary to mitigate hazards that could result in worker exposure. Additional information required for a more complete assessment is identified

Fluorescence photodiagnosis of early stage lung cancer

International Nuclear Information System (INIS)

Kato, H.; Sakai, H.; Konaka, C.; Okunaka, T.; Furukawa, K.; Saito, Y.; Aizawa, K.; Hayata, Y.

1992-01-01

Sputum cytology examination is the most effective method to detect early stage central type squamous cell carcinoma. As sputum-positive early stage lung cancer usually does not show any abnormal findings on chest X-ray film, fiberoptic bronchoscopy is subsequently performed for localization. However, sometimes cases do not show any abnormal findings of cancer endoscopically because they are very early stage cases. For the purpose of localization of invisible lesions the photodynamic reaction was employed in this study. Photodynamic reaction is achieved by transfer of energy of an excited photo-sensitizer induced by photoradiation of light. This phenomenon was already recognized in the beginning of this century. Study of tumor localization of the bronchial tree using hematoporphyrin derivative (HpD) and a mercury arc lamp was first performed in the Mayo Clinic in 1960s. In 1978, krypton laser was used first as a light source by Profio and Doiron. Authors have been doing research on early localization of such endoscopically occult early lung cancer since 1978. They recently developed an image processing system using an excimer dye laser for early localization of lung cancer. (author). 5 refs., 4 figs., 1 tab

Study on homologous series of induced early mutants in Indica rice Ⅱ. the relationship between the homologous series of early mutants induced and the ecotype in Indica rice

International Nuclear Information System (INIS)

Chen Xiulan; Yang Hefeng; He Zhentian; Han Yuepeng; Liu Xueyu

2001-01-01

The induced mutation in light sensitivity of the Indica rice leads to induction of the homologous series of early mutants along with the variation of ecological character and the ecoclimate. The induction of mutants was closely related to the ecotype of Indica rice, the homologous series of early mutants in different level were derived from the different ecotype of the Indica rice, otherwise, the similar homologous series of early mutants were derived from the same ecotypic variety. The induction of the early ecotypic variety derived from the homologous series of early mutants provides the basis and possibility for accelerating the development of the new cultivars. (authors)

Mapping Drought Sensitivity of Ecosystem Functioning in Mountainous Watersheds: Spatial Heterogeneity and Geological-Geomorphological Control

Science.gov (United States)

Wainwright, H. M.; Steefel, C. F.; Williams, K. H.; Hubbard, S. S.; Enquist, B. J.; Steltzer, H.; Sarah, T.

2016-12-01

Mountainous watersheds in the Upper Colorado River Basin play a critical role in supplying water and nutrients to western North America. Ecosystem functioning in those regions - including plant dynamics and biogeochemical cycling - is known to be limited by water availability. Under the climate change, early snowmelt and increasing temperature are expected to intensify the drought conditions in early growing seasons. Although the impact of early-season drought has been documented in plot-scale experiments, ascertaining its significance in mountainous watersheds is challenging given the highly heterogeneous nature of the systems with complex terrain and diverse plant functional types (PFTs). The objectives of this study are (1) to map the regions where the plant dynamics are relatively more sensitive to drought conditions based on historical satellite and climate data, and (2) to identify the environmental controls (e.g., geomorphology, elevation, geology, snow and PFT) on drought sensitivity. We characterize the spatial heterogeneity of drought sensitivity in four watersheds (a 15 x 15 km domain) near the Rocky Mountain Biological Laboratory in Colorado, USA. Following previous plot-scale studies, we first define the drought sensitivity based on annual peak NDVI (Landsat 5) and climatic datasets. Non-parametric tree-based machine learning methods are used to identify the significant environmental controls, using high-resolution LiDAR digital elevation map and peak snow-water-equivalent distribution from NASA airborne snow observatory. Results show that the drought sensitivity is negatively correlated with elevation, suggesting increased water limitations in lower elevation (less snow, higher temperature). The drought sensitivity is more spatially variable in shallow-rooted plant types, affected by local hydrological conditions. We also found geomorphological and geological controls, such as high sensitivity in the steep well-drained glacial moraine regions. Our

The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

DEFF Research Database (Denmark)

Cox, Thomas R; Rumney, Robin M H; Schoof, Erwin M

2015-01-01

Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present...... morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic...

Early intervention studies in infants and preschool children with cystic fibrosis: Are we ready?

NARCIS (Netherlands)

S. Stick; H.A.W.M. Tiddens (Harm); P. Aurora (Paul); P. Gustafsson (Per); S. Ranganathan (Surabhi); P. Robinson; M. Rosenfeld (Margaret); P.D. Sly; F. Ratjen (Felix)

2013-01-01

textabstractCystic fibrosis (CF) lung disease starts early in life and progresses even in the absence of clinical symptoms. Therefore, sensitive outcome measures to quantify and track these early abnormalities in infants and young children are needed; both for clinical care and interventional

In Vitro Contractile Response of Rabbit Myometrium to BKCa and KATP Potassium Channel Openers

Directory of Open Access Journals (Sweden)

Soňa Fraňová

2009-01-01

Full Text Available The aim of the study was to evaluate the participation of ligand-sensitive potassium large conductance calcium-activated channels (BKCa and ATP-sensitive potassium channels in uterine smooth muscle reactivity during different stages of the experimentally induced proliferatory and secretory phase in the sexual cycle in ovariectomised rabbits in vitro. The myometrial reactivity to oxytocin (10-6 mol l-1 was investigated by an in vitro method in female rabbits 14 days after ovariectomy treated with 17β-estradiol - 1 mg/kg/day i.m. for 7 days, or with a combination of progesterone 2 mg/kg/day s.c. for 7 days and 17β-estradiol - 0.2 mg/ kg/day (day 3–7. The strips of myometrial smooth muscle were incubated with a specific opener (NS 1619 and an antagonist (TEA of potassium large conductance calcium-activated channel, or with a specific opener (pinacidil and an antagonist (glybenclamide of ATP-sensitive potassium channels before the administration of oxytocin. NS1619 produced more potent inhibition of the oxytocin-induced contraction during the gestagen dominance (experimental secretory phase than the one observed during the oestrogen dominance (experimental proliferatory phase. TEA antagonized the NS1619 induced inhibition of the myometrial contraction. In the matter of KATP potassium channels, after the administration of pinacidil we observed a similar situation in the changes of myometrial contractility. Pinacidil produced more pronounced inhibition of oxytocin-induced contraction during the secretory phase, and its effect was abolished by the selective inhibitor glybenclamide. Our experimental results indicate that both potassium large conductance calcium-activated channels and ATP-sensitive potassium channels significantly participate in the regulation of myometrial oxytocin-induced contractions and the activity of these channels is probably influenced by the levels of oestrogens and gestagens.

HERBAL SUPPLEMENTS: CAUSE FOR CONCERN?

Directory of Open Access Journals (Sweden)

Paolo Borrione

2008-12-01

mouse liver, heart and muscles, and act on lipids methabolism, reduce glucagon-induced hyperglycaemia, and enhance glucose utilization by tissues. The mechanism involved seems to be an increase of tissue sensitivity to insulin (Bathori and Pongracz, 2005. PhytooestrogensPhytooestrogens are biologically active plant substances with a chemical structure similar to oestradiol. This structural similarity accounts for their ability to bind to oestrogen receptors, and exert various oestrogenic or anti-oestrogenic effects. There are three main classes of phytooestrogens: isoflavones, coumestans, and lignans. Most of the phytooestrogens have a higher affinity to oestrogen receptor beta than alpha. The former is strongly expressed in the ovary, uterus, brain, bladder, testis, prostate, bone, cardiovascular system, and lungs. Expression of oestrogen receptor beta appears to occur at different sites in the brain than oestrogen receptor alpha. (Setchell and Cassidy, 1999 The oestrogenic effect of phytooestrogens produces reproductive disturbances in sheep, and a phytooestrogen-rich diet is associated with a lower risk of breast and prostate cancer, and of cardiovascular disease (Adlercreutz, 1990. In vitro, phytooestrogens exert both proliferative (oestrogenic and antiproliferative (antioestrogenic effects in human cell lines (Wang et al., 1996. In humans, isoflavones increase the length of the follicular phase, with suppression of the midcycle surges of FSH and LH. Some dietary phytooestrogens can produce mild oestrogenic effects in postmenopausal women, including oestrogen- like effects on vaginal cytology and reductions in hot flushes, and oestrogen-like activity on bone and lipid metabolism (Cassidy et al., 1994. Isoflavones demonstrate anticarcinogenetic activity, inhibiting angiogenesis and cell progression, inhibiting aromatase enzyme, and stimulating sex hormone binding globulin synthesis (Messina et al. , 2006. Most of the phytooestrogens-based preparations freely

Early parental loss and depression history: associations with recent life stress in major depressive disorder.

Science.gov (United States)

Slavich, George M; Monroe, Scott M; Gotlib, Ian H

2011-09-01

Although exposure to early adversity and prior experiences with depression have both been associated with lower levels of precipitating life stress in depression, it is unclear whether these stress sensitization effects are similar for all types of stress or whether they are specific to stressors that may be particularly depressogenic, such as those involving interpersonal loss. To investigate this issue, we administered structured, interview-based measures of early adversity, depression history, and recent life stress to one hundred adults who were diagnosed with major depressive disorder. As predicted, individuals who experienced early parental loss or prolonged separation (i.e., lasting one year or longer) and persons with more lifetime episodes of depression became depressed following lower levels of life stress occurring in the etiologically-central time period of three months prior to onset of depression. Importantly, however, additional analyses revealed that these effects were unique to stressors involving interpersonal loss. These data highlight potential stressor-specific effects in stress sensitization and demonstrate for the first time that individuals exposed to early parental loss or separation, and persons with greater histories of MDD, may be selectively sensitized to stressors involving interpersonal loss. Copyright © 2011 Elsevier Ltd. All rights reserved.

RAS1, a quantitative trait locus for salt tolerance and ABA sensitivity in Arabidopsis

KAUST Repository

Ren, Zhonghai

2010-03-08

Soil salinity limits agricultural production and is a major obstacle for feeding the growing world population. We used natural genetic variation in salt tolerance among different Arabidopsis accessions to map a major quantitative trait locus (QTL) for salt tolerance and abscisic acid (ABA) sensitivity during seed germination and early seedling growth. A recombinant inbred population derived from Landsberg erecta (Ler; salt and ABA sensitive) x Shakdara (Sha; salt and ABA resistant) was used for QTL mapping. High-resolution mapping and cloning of this QTL, Response to ABA and Salt 1 (RAS1), revealed that it is an ABA- and salt stress-inducible gene and encodes a previously undescribed plant-specific protein. A premature stop codon results in a truncated RAS1 protein in Sha. Reducing the expression of RAS1 by transfer-DNA insertion in Col or RNA interference in Ler leads to decreased salt and ABA sensitivity, whereas overexpression of the Ler allele but not the Sha allele causes increased salt and ABA sensitivity. Our results suggest that RAS1 functions as a negative regulator of salt tolerance during seed germination and early seedling growth by enhancing ABA sensitivity and that its loss of function contributes to the increased salt tolerance of Sha.

Maternal-child adrenocortical attunement in early childhood: continuity and change.

Science.gov (United States)

Hibel, Leah C; Granger, Douglas A; Blair, Clancy; Finegood, Eric D

2015-01-01

This study evaluated continuity and change in maternal-child hypothalamic-pituitary-adrenal axis attunement in early childhood. Participants were drawn from a prospective study of 1,292 mother-child dyads, which were racially diverse, predominantly low-income, and non-urban. Child focused stress tasks designed to elicit anger, fear, and frustration were administered during early infancy, later infancy, and toddlerhood. Mothers' and children's saliva samples (later assayed for cortisol) were collected before and after the tasks. The strength of mother-child adrenocortical attunement was conserved across infancy and toddlerhood. The magnitude of maternal-child adrenocortical attunement decreased in response to the child-focused stress tasks. Maternal sensitivity and the child's task-related emotional reactivity moderated adrenocortical attunement across the task, with greater maternal sensitivity during a free-play, and lower levels of child emotional reactivity during the stress tasks, stabilizing attunement from pre- to post-task levels. The findings advance our understanding of individual differences in the social regulation of adrenocortical activity in early childhood. © 2014 Wiley Periodicals, Inc.

Disproportional geometry of the proximal femur in patients with Turner syndrome - a cross-sectional study

DEFF Research Database (Denmark)

Nissen, N.; Gravholt, Claus Højbjerg; Abrahamsen, Bo

2007-01-01

OBJECTIVE: Patients with Turner syndrome (TS) have altered growth and increased risk of osteoporosis due to oestrogen deficiency and possibly a host of other factors. Thus, TS patients have a 4.9-fold increased risk of femoral neck fractures. Most patients are treated with oestrogen during puberty...

The potential health effects of dietary phytoestrogens

NARCIS (Netherlands)

Rietjens, Ivonne M.C.M.; Louisse, Jochem; Beekmann, Karsten

2017-01-01

Phytoestrogens are plant-derived dietary compounds with structural similarity to 17-β-oestradiol (E2), the primary female sex hormone. This structural similarity to E2 enables phytoestrogens to cause (anti)oestrogenic effects by binding to the oestrogen receptors. The aim of the present review is to

Developing a yeast-based assay protocol to monitor total ...

African Journals Online (AJOL)

A yeast-based assay protocol developed for detecting oestrogenic activity in activated sludge (AS) supernatant is described. The protocol used Saccharomyces cerevisiae construct RMY/ER-ERE with human oestrogen receptor (ERα) and lacZ reporter genes, and was developed by modifying existing assays for use with AS ...

The menstrual cycle and the skin.

Science.gov (United States)

Raghunath, R S; Venables, Z C; Millington, G W M

2015-03-01

Perimenstrual exacerbations of dermatoses are commonly recognized, yet our knowledge of the underlying pathophysiological mechanisms remains imperfect. Research into the effects of oestrogen on the skin has provided evidence to suggest that oestrogen is associated with increases in skin thickness and dermal water content, improved barrier function, and enhanced wound healing. Research into the effects of progesterone suggests that the presence of various dermatoses correlates with peak levels of progesterone. Dermatoses that are exacerbated perimenstrually include acne, psoriasis, atopic eczema and irritant dermatitis, and possibly also erythema multiforme. Exacerbations occur at the peak levels of progesterone in the menstrual cycle. Underlying mechanisms include reduced immune and barrier functions as a result of cyclical fluctuations in oestrogen and/or progesterone. Autoimmune progesterone and oestrogen dermatitis are the best-characterized examples of perimenstrual cutaneous reactions to hormones produced during the menstrual cycle. In this review, we describe the current understanding of the menstrual cycle, and its effect on the skin and cutaneous disorders. © 2015 British Association of Dermatologists.

Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

Directory of Open Access Journals (Sweden)

Temesgen Fiseha

2016-01-01

Full Text Available Diabetic nephropathy (DN is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL, kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, N-acetyl-beta-glucosaminidase (NAG, alpha-1 microglobulin (A1M, beta 2-microglobulin (B2-M, and retinol binding protein (RBP associated with early DN.

Are infants differentially sensitive to parenting? Early maternal care, DRD4 genotype and externalizing behavior during adolescence.

Science.gov (United States)

Nikitopoulos, Jörg; Zohsel, Katrin; Blomeyer, Dorothea; Buchmann, Arlette F; Schmid, Brigitte; Jennen-Steinmetz, Christine; Becker, Katja; Schmidt, Martin H; Esser, Günter; Brandeis, Daniel; Banaschewski, Tobias; Laucht, Manfred

2014-12-01

Insensitive and unresponsive caregiving during infancy has been linked to externalizing behavior problems during childhood and adolescence. The 7-repeat (7r) allele of the dopamine D4 receptor (DRD4) gene has meta-analytically been associated with a heightened susceptibility to adverse as well as supportive environments. In the present study, we examined long-term effects of early maternal care, DRD4 genotype and the interaction thereof on externalizing and internalizing psychopathology during adolescence. As part of an ongoing epidemiological cohort study, early maternal care was assessed at child's age 3 months during a nursing and playing situation. In a sample of 296 offspring, externalizing and internalizing symptoms were assessed using a psychiatric interview conducted at age 15 years. Parents additionally filled out a questionnaire on their children's psychopathic behaviors. Results indicated that adolescents with the DRD4 7r allele who experienced less responsive and stimulating early maternal care exhibited more symptoms of ADHD and CD/ODD as well as higher levels of psychopathic behavior. In accordance with the hypothesis of differential susceptibility, 7r allele carriers showed fewer ADHD symptoms and lower levels of psychopathic behavior when exposed to especially beneficial early caregiving. In contrast, individuals without the DRD4 7r allele proved to be insensitive to the effects of early maternal care. This study replicates earlier findings with regard to an interaction between DRD4 genotype and early caregiving on externalizing behavior problems in preschoolers. It is the first one to imply continuity of this effect until adolescence. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nitric oxide-heat shock protein axis in menopausal hot flushes: neglected metabolic issues of chronic inflammatory diseases associated with deranged heat shock response.

Science.gov (United States)

Miragem, Antônio Azambuja; Homem de Bittencourt, Paulo Ivo

2017-09-01

Although some unequivocal underlying mechanisms of menopausal hot flushes have been demonstrated in animal models, the paucity of similar approaches in humans impedes further mechanistic outcomes. Human studies might show some as yet unexpected physiological mechanisms of metabolic adaptation that permeate the phase of decreased oestrogen levels in both symptomatic and asymptomatic women. This is particularly relevant because both the severity and time span of hot flushes are associated with increased risk of chronic inflammatory disease. On the other hand, oestrogen induces the expression of heat shock proteins of the 70 kDa family (HSP70), which are anti-inflammatory and cytoprotective protein chaperones, whose expression is modulated by different types of physiologically stressful situations, including heat stress and exercise. Therefore, lower HSP70 expression secondary to oestrogen deficiency increases cardiovascular risk and predisposes the patient to senescence-associated secretory phenotype (SASP) that culminates in chronic inflammatory diseases, such as obesities, type 2 diabetes, neuromuscular and neurodegenerative diseases. This review focuses on HSP70 and its accompanying heat shock response (HSR), which is an anti-inflammatory and antisenescent pathway whose intracellular triggering is also oestrogen-dependent via nitric oxide (NO) production. The main goal of the manuscript was to show that the vasomotor symptoms that accompany hot flushes may be a disguised clue for important neuroendocrine alterations linking oestrogen deficiency to the anti-inflammatory HSR. Results from our own group and recent evidence on hypothalamic control of central temperature guided a search on PubMed and Google Scholar websites. Oestrogen elicits rapid production of the vasodilatory gas NO, a powerful activator of HSP70 expression. Whence, part of the protective effects of oestrogen over cardiovascular and neuroendocrine systems is tied to its capacity of inducing the NO

Sprites and Early ionospheric VLF perturbations

Science.gov (United States)

Haldoupis, Christos; Amvrosiadi, Nino; Cotts, Ben; van der Velde, Oscar; Chanrion, Olivier; Neubert, Torsten

2010-05-01

Past studies have shown a correlation between sprites and early VLF perturbations, but the reported correlation varies widely from ~ 50% to 100%. The present study resolves these large discrepancies by analyzing several case studies of sprite and narrowband VLF observations, in which multiple transmitter-receiver VLF links with great circle paths (GCPs) passing near a sprite-producing thunderstorm were available. In this setup, the multiple links act in a complementary way that makes the detection of early VLF perturbations much more probable compared to a single VLF link that can miss several of them, a fact that was overlooked in past studies. The evidence shows that sprites are accompanied by early VLF perturbations in a one-to-one correspondence. This implies that the sprite generation mechanism may cause also sub-ionospheric conductivity disturbances that produce early VLF events. However, the one-to-one "sprite to early" event relationship, if viewed conversely as "early to sprite", appears not to be always reciprocal. This is because the number of early events detected in some cases was considerably larger than the number of sprites. Since the great majority of the early events not accompanied by sprites was caused by positive cloud to ground (+CG) lightning discharges, it is possible that sprites or sprite halos were concurrently present in these events as well but were missed by the sprite-watch detection system. In order for this option to be resolved we need more studies using highly sensitive optical systems capable of detecting weaker sprites, sprite halos and elves.

Fluorescent immunochromatography for rapid and sensitive typing of seasonal influenza viruses.

Directory of Open Access Journals (Sweden)

Akira Sakurai

Full Text Available Lateral flow tests also known as Immunochromatography (IC is an antigen-detection method conducted on a nitrocellulose membrane that can be completed in less than 20 min. IC has been used as an important rapid test for clinical diagnosis and surveillance of influenza viruses, but the IC sensitivity is relatively low (approximately 60% and the limit of detection (LOD is as low as 10³ pfu per reaction. Recently, we reported an improved IC assay using antibodies conjugated with fluorescent beads (fluorescent immunochromatography; FLIC for subtyping H5 influenza viruses (FLIC-H5. Although the FLIC strip must be scanned using a fluorescent reader, the sensitivity (LOD is significantly improved over that of conventional IC methods. In addition, the antibodies which are specific against the subtypes of influenza viruses cannot be available for the detection of other subtypes when the major antigenicity will be changed. In this study, we established the use of FLIC to type seasonal influenza A and B viruses (FLIC-AB. This method has improved sensitivity to 100-fold higher than that of conventional IC methods when we used several strains of influenza viruses. In addition, FLIC-AB demonstrated the ability to detect influenza type A and influenza type B viruses from clinical samples with high sensitivity and specificity (Type A: sensitivity 98.7% (74/75, specificity 100% (54/54, Type B: sensitivity 100% (90/90, specificity 98.2% (54/55 in nasal swab samples in comparison to the results of qRT-PCR. And furthermore, FLIC-AB performs better in the detection of early stage infection (under 13 h than other conventional IC methods. Our results provide new strategies to prevent the early-stage transmission of influenza viruses in humans during both seasonal outbreaks and pandemics.

Assessment and management of bone health in women with oestrogen receptor-positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australasian Menopause Society and the Clinical Oncology Society of Australia.

Science.gov (United States)

Grossmann, Mathis; Ramchand, Sabashini; Milat, Frances; Vincent, Amanda; Lim, Elgene; Kotowicz, Mark A; Hicks, Jill; Teede, Helena

2018-05-09

To formulate clinical consensus recommendations on bone health assessment and management of women with oestrogen receptor-positive early breast cancer receiving endocrine therapy. Representatives appointed by relevant Australian Medical Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing five key questions. Women receiving adjuvant aromatase inhibitors and the subset of premenopausal woman on tamoxifen have accelerated bone loss and increased fracture risk. Both bisphosphonates and denosumab prevent bone loss, additionally denosumab has proven anti-fracture benefit. Women considering endocrine therapy need fracture risk assessment, including clinical risk factors, biochemistry and bone mineral density (BMD) measurement, with monitoring based on risk factors. Weight-bearing exercise, vitamin D and calcium sufficiency is recommended routinely. Antiresorptive treatment should be considered in women with prevalent or incident clinical or morphometric fractures, a T-score (or Z-scores in women <50 years) of <-2.0 at any site, or if annual bone loss is ≥5%, considering baseline BMD and other fracture risk factors. Duration of antiresorptive treatment can be individualised based on absolute fracture risk. Relative to their skeletal benefits, risks of adverse events with antiresorptive treatments are low. Skeletal health should be considered in the decision-making process regarding choice and duration of endocrine therapy. Before and during endocrine therapy, skeletal health should be assessed regularly, optimised by nonpharmacological intervention and where indicated antiresorptive treatment, in an individualised, multidisciplinary approach. Clinical trials are needed to better delineate long-term fracture risks of adjuvant endocrine therapy, and to determine the efficacy of interventions designed to minimise these risks. This article is protected by copyright. All rights reserved. This

Maternal separation increases later immobility during forced swim in guinea pig pups: evidence for sensitization of a depressive-like state.

Science.gov (United States)

Hennessy, Michael B; Schreibeis, Amanda D; Schiml, Patricia A; Deak, Terrence

2017-01-01

Early-life stress is thought to increase later vulnerability for developing depressive illness by sensitizing underlying stress-responsive systems. Guinea pig pups separated from their mother and isolated in a novel cage for 3 hr exhibit a sensitized depressive-like behavioral response when separated again the following day as well as weeks later. The behavioral response and its sensitization appear to be mediated by inflammatory factors. To determine if this sensitization is specific to the separation response or if it reflects a broader underlying depressive-like state, guinea pig pups that had either been separated for 3 hr or remained with their mothers were observed in the forced swim test the following 3 days. Earlier separation was found to increase the duration of immobility, a measure sensitive to antidepressant treatment. These results support the use of the guinea pig as a model for examining mechanisms of inflammatory-mediated sensitization of depression following stress in early life. © 2016 Wiley Periodicals, Inc.

Can Biomarkers Help the Early Diagnosis of Parkinson's Disease?

Institute of Scientific and Technical Information of China (English)

Weidong Le; Jie Dong; Song Li; Amos D.Korczyn

2017-01-01

Parkinson's disease (PD) is a complex neurodegenerative disease with progressive loss of dopamine neurons.PD patients usually manifest a series of motor and non-motor symptoms.In order to provide better early diagnosis and subsequent disease-modifying therapies for PD patients,there is an urgent need to identify sensitive and specific biomarkers.Biomarkers can be divided into four categories:clinical,imaging,biochemical,and genetic.Ideal biomarkers not only improve our understanding of PD pathogenesis and progression,but also provide benefits for early risk evaluation and clinical diagnosis of PD.Although many efforts have been made and several biomarkers have been extensively investigated,few if any have been found useful for early diagnosis.Here,we summarize recent developments in the discovered biomarkers of PD and discuss their merits and limitations for the early diagnosis of PD.

Recent Advances in Optical Biosensors for Environmental Monitoring and Early Warning

Directory of Open Access Journals (Sweden)

Anna Zhu

2013-10-01

Full Text Available The growing number of pollutants requires the development of innovative analytical devices that are precise, sensitive, specific, rapid, and easy-to-use to meet the increasing demand for legislative actions on environmental pollution control and early warning. Optical biosensors, as a powerful alternative to conventional analytical techniques, enable the highly sensitive, real-time, and high-frequency monitoring of pollutants without extensive sample preparation. This article reviews important advances in functional biorecognition materials (e.g., enzymes, aptamers, DNAzymes, antibodies and whole cells that facilitate the increasing application of optical biosensors. This work further examines the significant improvements in optical biosensor instrumentation and their environmental applications. Innovative developments of optical biosensors for environmental pollution control and early warning are also discussed.

Application of Sensitivity Analysis in Design of Integrated Building Concepts

DEFF Research Database (Denmark)

Heiselberg, Per; Brohus, Henrik; Hesselholt, Allan Tind

2007-01-01

analysis makes it possible to identify the most important parameters in relation to building performance and to focus design and optimization of integrated building concepts on these fewer, but most important parameters. The sensitivity analyses will typically be performed at a reasonably early stage...... the design requirements and objectives. In the design of integrated building concepts it is beneficial to identify the most important design parameters in order to more efficiently develop alternative design solutions or more efficiently perform an optimization of the building performance. The sensitivity...

Reproduction and adaptation characteristics in D’man sheep

Directory of Open Access Journals (Sweden)

A. Lahlou-Kassi

1988-10-01

Full Text Available D’man breed (D is found in the oasis of the subsaharian regions of Morocco and reared usually in sedentary type of management with small flocks (< 10 ewes. Preliminary field surveys showed that D is early maturing, prolific and aseasonal. Hence, a multidisciplinary research programme on D was started in 1974. This paper reports the findings of these studies and describes the approach used to (1 characterize and evaluate the performances of D in field and station, (2 study the physiological mechanism involved in its peculiar reproduction and production, (3 study the genetic basis of reproduction parameters, and (4 evaluate use of D in crossbreeding schemes to improve the productivity of other Moroccoan breeds. Results show that D is one of the rare breeds that is simultaneously early maturing, highly prolific and completely aseasonal. However, studies on water turnover and nitrogen recycling show that D is not well adapted to hot climate and poor nutrition. Its reproduction parameters are relatively independent of photoperiod and related to a low sensitivity to negative oestrogen feedback. D male is characterized by high libido and can be used for synchronizing oestruses through the »ram effect». Crossbreeding experiments with non-prolific sheep confirm the heritability of reproductive parameters. However, the genetic basis for these is not yet well known.

Hormone replacement therapy is associated with gastro-oesophageal reflux disease: a retrospective cohort study

Directory of Open Access Journals (Sweden)

Close Helen

2012-05-01

Full Text Available Abstract Background Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT. Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. Methods 51,182 menopausal women were identified using the UK General Practice Research Database between 1995–2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs were calculated for GORD and proton-pump inhibitor (PPI use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. Results In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18–1.89. Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03–1.74. Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01–2.22. Conclusions This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance.

Reduced early growing season freezing resistance in alpine treeline plants under elevated atmospheric CO2.

NARCIS (Netherlands)

Martin, M.; Gavazov, K.S.; Körner, S.; Rixen, C.

2010-01-01

The frequency of freezing events during the early growing season and the vulnerability to freezing of plants in European high-altitude environments could increase under future atmospheric and climate change. We tested early growing season freezing sensitivity in 10 species, from four plant

Early reported rectal sensation predicts continence in anorectal anomalies.

Science.gov (United States)

Skerritt, Clare; Tyraskis, Athanasios; Rees, Clare; Cockar, Iram; Kiely, Edward

2016-03-01

Straining at stool is an automatic reflex in babies and implies the presence of rectal sensation. We hypothesised that early reported rectal sensation would predict future continence in children with anorectal anomalies. The aim of this study is to determine if early straining at stool was a useful predictor of future continence in infants born with high anorectal malformations. A retrospective case note review of prospectively collected clinical information was performed with institutional review board approval. All patients with intermediate/high anorectal malformation operated on by a single surgeon from 1984 to 2010 were included. After stoma closure, parents were asked: The responses were noted within the first year of stoma closure and then all patients were followed up until they were at least 3 ½years old and continence could be assessed using the Krickenbeck outcome classification. Data were compared using Fisher's exact test and sensitivity, specificity and positive predictive value (PPV) were calculated. Forty-eight patients were included in the study. Sixteen (33%) were female (12 cloacal malformation, 3 rectovaginal fistula, 1 rectal atresia) and 32 (66%) were male (6 rectovesical fistulae, 22 rectourethral fistulae, 4 no fistula). Median follow-up was 9.7years (range 3.5-17.9). Twenty-one children were noted by their parents to exhibit early straining at stool after stoma closure. Twenty of them achieved long term continence. The sensitivity of early straining as a predictor for long term continence was 77%, specificity 95% and positive predictive value 95%. The presence of early rectal sensation reported by parents is a good predictor of long term continence. This allows more informed discussion with families in the early years of life. Copyright © 2016 Elsevier Inc. All rights reserved.

Extended, regular HI structures around early-type galaxies

NARCIS (Netherlands)

Oosterloo, T.; Morganti, R.; Sadler, E. M. Van der; Hulst, J. M. van der; Serra, P.

Abstract: We discuss the morphology and kinematics of the HI of a sample of 30 southern gas-rich early-type galaxies selected from the HI Parkes All-Sky Survey (HIPASS). This is the largest collection of high-resolution HI data of a homogeneously selected sample. Given the sensitivity of HIPASS,

Prolonged early G1 arrest by selective CDK4/CDK6 inhibition sensitizes myeloma cells to cytotoxic killing through cell cycle–coupled loss of IRF4

Science.gov (United States)

Huang, Xiangao; Di Liberto, Maurizio; Jayabalan, David; Liang, Jun; Ely, Scott; Bretz, Jamieson; Shaffer, Arthur L.; Louie, Tracey; Chen, Isan; Randolph, Sophia; Hahn, William C.; Staudt, Louis M.; Niesvizky, Ruben; Moore, Malcolm A. S.

2012-01-01

Dysregulation of cyclin-dependent kinase 4 (CDK4) and CDK6 by gain of function or loss of inhibition is common in human cancer, including multiple myeloma, but success in targeting CDK with broad-spectrum inhibitors has been modest. By selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proliferation and enhance cytotoxic killing of cancer cells. We show that induction of prolonged early-G1 arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G1 and prevents expression of genes programmed for other cell-cycle phases. Removal of the early-G1 block leads to S-phase synchronization (pG1-S) but fails to completely restore scheduled gene expression. Consequently, the IRF4 protein required to protect myeloma cells from apoptosis is markedly reduced in pG1 and further in pG1-S in response to cytotoxic agents, such as the proteasome inhibitor bortezomib. The coordinated loss of IRF4 and gain of Bim sensitize myeloma tumor cells to bortezomib-induced apoptosis in pG1 in the absence of Noxa and more profoundly in pG1-S in cooperation with Noxa in vitro. Induction of pG1 and pG1-S by reversible CDK4/CDK6 inhibition further augments tumor-specific bortezomib killing in myeloma xenografts. Reversible inhibition of CDK4/CDK6 in sequential combination therapy thus represents a novel mechanism-based cancer therapy. PMID:22718837

Prolonged early G(1) arrest by selective CDK4/CDK6 inhibition sensitizes myeloma cells to cytotoxic killing through cell cycle-coupled loss of IRF4.

Science.gov (United States)

Huang, Xiangao; Di Liberto, Maurizio; Jayabalan, David; Liang, Jun; Ely, Scott; Bretz, Jamieson; Shaffer, Arthur L; Louie, Tracey; Chen, Isan; Randolph, Sophia; Hahn, William C; Staudt, Louis M; Niesvizky, Ruben; Moore, Malcolm A S; Chen-Kiang, Selina

2012-08-02

Dysregulation of cyclin-dependent kinase 4 (CDK4) and CDK6 by gain of function or loss of inhibition is common in human cancer, including multiple myeloma, but success in targeting CDK with broad-spectrum inhibitors has been modest. By selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proliferation and enhance cytotoxic killing of cancer cells. We show that induction of prolonged early-G(1) arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G(1) and prevents expression of genes programmed for other cell-cycle phases. Removal of the early-G(1) block leads to S-phase synchronization (pG1-S) but fails to completely restore scheduled gene expression. Consequently, the IRF4 protein required to protect myeloma cells from apoptosis is markedly reduced in pG1 and further in pG1-S in response to cytotoxic agents, such as the proteasome inhibitor bortezomib. The coordinated loss of IRF4 and gain of Bim sensitize myeloma tumor cells to bortezomib-induced apoptosis in pG1 in the absence of Noxa and more profoundly in pG1-S in cooperation with Noxa in vitro. Induction of pG1 and pG1-S by reversible CDK4/CDK6 inhibition further augments tumor-specific bortezomib killing in myeloma xenografts. Reversible inhibition of CDK4/CDK6 in sequential combination therapy thus represents a novel mechanism-based cancer therapy.

Perinatal risk factors for sensitization, atopic dermatitis and wheezing during the first year of life (PIPO study).

Science.gov (United States)

Hagendorens, M M; Bridts, C H; Lauwers, K; van Nuijs, S; Ebo, D G; Vellinga, A; De Clerck, L S; Van Bever, H P; Weyler, J J; Stevens, W J

2005-06-01

To evaluate the influence of perinatal environmental factors on early sensitization, atopic dermatitis and wheezing during the first year. Information on pregnancy-related factors, parental atopic history, environmental factors and the clinical course of the infant until age one was gathered by questionnaires, as part of a prospective birth cohort study (Prospective study on the Influence of Perinatal factors on the Occurrence of asthma and allergies [PIPO-study]). Quantification of total and specific IgE was performed in 810 children and their parents. Early sensitization was found in 107/810 (13%) of the infants. Multiple regression analysis showed that specific IgE in fathers was a risk factor for early sensitization in their daughters (adjusted odds ratios (OR(adj)) 2.21 (95% confidence interval (CI) 1.10-4.49); P=0.03), whereas in boys, day care attendance was shown to be protective for early sensitization (OR(adj) 0.38 (95% CI 0.20-0.71); P=0.001). Atopic dermatitis occurred in 195/792 infants (25%). Specific IgE in the mother (OR(adj) 1.52 (95% CI 1.06-2.19); P=0.02) and in the infant (OR(adj) 4.20 (95% CI 2.63-6.68); Patopic dermatitis, whereas postnatal exposure to cats was negatively associated with atopic dermatitis (OR(adj) 0.68 (0.47-0.97); P=0.03). Postnatal exposure to cigarette smoke (OR(adj) 3.31 (95% CI 1.79-6.09); Patopic dermatitis, whereas postnatal exposure to cats had a protective effect.

MP.EXE Microphone pressure sensitivity calibration calculation program

DEFF Research Database (Denmark)

Rasmussen, Knud

1999-01-01

MP.EXE is a program which calculates the pressure sensitivity of LS1 microphones as defined in IEC 61094-1, based on measurement results performed as laid down in IEC 61094-2.A very early program was developed and written by K. Rasmussen. The code of the present heavily extended version is writte...... by E.S. Olsen.The present manual is written by K.Rasmussen and E.S. Olsen....

Early Life Adversity as a Risk Factor for Fibromyalgia in Later Life

Directory of Open Access Journals (Sweden)

Lucie A. Low

2012-01-01

Full Text Available The impact of early life events is increasingly becoming apparent, as studies investigate how early childhood can shape long-term physiology and behaviour. Fibromyalgia (FM, which is characterised by increased pain sensitivity and a number of affective co-morbidities, has an unclear etiology. This paper discusses risk factors from early life that may increase the occurrence or severity of FM in later life: pain experience during neonatal life causes long-lasting changes in nociceptive circuitry and increases pain sensitivity in the older organism; premature birth and related stressor exposure cause lasting changes in stress responsivity; maternal deprivation affects anxiety-like behaviours that may be partially mediated by epigenetic modulation of the genome—all these adult phenotypes are strikingly similar to symptoms displayed by FM sufferers. In addition, childhood trauma and exposure to substances of abuse may cause lasting changes in developing neurotransmitter and endocrine circuits that are linked to anxiety and stress responses.

The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach.

Directory of Open Access Journals (Sweden)

Scott R Fry

2011-06-01

Full Text Available BACKGROUND: Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1 has been identified as an early marker for acute dengue, and is typically present between days 1-9 post-onset of illness but following seroconversion it can be difficult to detect in serum. AIMS: To evaluate the performance of a newly developed Panbio® Dengue Early Rapid test for NS1 and determine if it can improve diagnostic sensitivity when used in combination with a commercial IgM/IgG rapid test. METHODOLOGY: The clinical performance of the Dengue Early Rapid was evaluated in a retrospective study in Vietnam with 198 acute laboratory-confirmed positive and 100 negative samples. The performance of the Dengue Early Rapid in combination with the IgM/IgG Rapid test was also evaluated in Malaysia with 263 laboratory-confirmed positive and 30 negative samples. KEY RESULTS: In Vietnam the sensitivity and specificity of the test was 69.2% (95% CI: 62.8% to 75.6% and 96% (95% CI: 92.2% to 99.8 respectively. In Malaysia the performance was similar with 68.9% sensitivity (95% CI: 61.8% to 76.1% and 96.7% specificity (95% CI: 82.8% to 99.9% compared to RT-PCR. Importantly, when the Dengue Early Rapid test was used in combination with the IgM/IgG test the sensitivity increased to 93.0%. When the two tests were compared at each day post-onset of illness there was clear differentiation between the antigen and antibody markers. CONCLUSIONS: This study highlights that using dengue NS1 antigen detection in combination with anti-glycoprotein E IgM and IgG serology can significantly increase the sensitivity of acute dengue diagnosis and extends the possible window of detection to include very early acute samples and enhances the clinical utility of rapid immunochromatographic testing for dengue.

Relations among child negative emotionality, parenting stress, and maternal sensitive responsiveness in early childhood

NARCIS (Netherlands)

Paulussen-Hoogeboom, M.C.; Stams, G.J.J.M.; Hermanns, J.M.A.; Peetsma, T.T.D.

2008-01-01

This short-term longitudinal study focuses on relations between preschool-aged childrens' perceived "difficult" temperament (defined as high negative emotionality) and observed maternal sensitive responsiveness in the context of maternal parenting stress. Design. Participants were fifty-nine

Mutual best friendship involvement, best friends' rejection sensitivity, and psychological maladaptation.

Science.gov (United States)

Bowker, Julie C; Thomas, Katelyn K; Norman, Kelly E; Spencer, Sarah V

2011-05-01

Rejection sensitivity (RS) refers to the tendency to anxiously expect, readily perceive, and overreact to experiences of possible rejection. RS is a clear risk factor for psychological maladaptation during early adolescence. However, there is growing evidence of significant heterogeneity in the psychological correlates of RS. To investigate when RS poses the greatest psychological risk during early adolescence, this study examines mutual best friendship involvement (or lack thereof) and the best friends' RS as potential moderators of the associations between RS and psychological difficulties. Participants were 150 7th grade students (58 boys; M age = 13.05 years) who nominated their best friends, and reported on their RS, social anxiety, and self-esteem. Results from a series of hierarchical multiple regression analyses indicated that mutual best friendship involvement and best friends' RS were both significant moderators when fear of negative evaluation (a type of social anxiety) served as the dependent variable. The association between RS and fear of negative evaluation was stronger for adolescents without mutual best friends than adolescents with mutual best friends. In addition, the association between RS and fear of negative evaluation was the strongest for adolescents whose best friends were highly rejection sensitive (relative to adolescents whose best friends were moderately or low in RS). Findings highlight the importance of considering best friendships in studies of RS and strongly suggest that, although having mutual best friendships may be protective for rejection sensitive adolescents, having a rejection sensitive best friend may exacerbate difficulties. The significance of friends in the lives of rejection sensitive adolescents is discussed as well as possible applied implications of the findings and study limitations.

A comparative study of the sensitivity of diffusion-related parameters obtained from diffusion tensor imaging, diffusional kurtosis imaging, q-space analysis and bi-exponential modelling in the early disease course (24 h) of hyperacute (6 h) ischemic stroke patients.

Science.gov (United States)

Duchêne, Gaëtan; Peeters, Frank; Peeters, André; Duprez, Thierry

2017-08-01

To compare the sensitivity and early temporal changes of diffusion parameters obtained from diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), q-space analysis (QSA) and bi-exponential modelling in hyperacute stroke patients. A single investigational acquisition allowing the four diffusion analyses was performed on seven hyperacute stroke patients with a 3T system. The percentage change between ipsi- and contralateral regions were compared at admission and 24 h later. Two out of the seven patients were imaged every 6 h during this period. Kurtoses from both DKI and QSA were the most sensitive of the tested diffusion parameters in the few hours following ischemia. An early increase-maximum-decrease pattern of evolution was highlighted during the 24-h period for all parameters proportional to diffusion coefficients. A similar pattern was observed for both kurtoses in only one of two patients. Our comparison was performed using identical diffusion encoding timings and on patients in the same stage of their condition. Although preliminary, our findings confirm those of previous studies that showed enhanced sensitivity of kurtosis. A fine time mapping of diffusion metrics in hyperacute stroke patients was presented which advocates for further investigations on larger animal or human cohorts.

Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson’s Disease

Science.gov (United States)

San Luciano, Marta; Wang, Cuiling; Ortega, Roberto A.; Yu, Qiping; Boschung, Sarah; Soto-Valencia, Jeannie; Bressman, Susan B.; Lipton, Richard B.; Pullman, Seth; Saunders-Pullman, Rachel

2016-01-01

Introduction Pre-clinical markers of Parkinson’s Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown. Methods 138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices. Results All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD. Conclusion Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD. PMID:27732597

The effects of female sex steroids on the development of autoimmune thyroiditis in thymectomized and irradiated rats

International Nuclear Information System (INIS)

Ahmed, S.A.; Young, P.R.; Penhale, W.J.

1983-01-01

Female PVG/c strain rats are more susceptible to induction of autoimmune thyroiditis initiated by thymectomy and irradiation (Tx-X) than similarly treated males. Pre-pubertal ovariectomy further augmented susceptibility. Administration of oestrogen or progesterone to groups of 4 weeks old ovariectomized Tx-X animals over a period of 15 weeks significantly altered induction of this condition. Oestrogen administered repeatedly at dose levels of 1 μg and 10 μg/100 g body weight resulted in partial suppression of thyroiditis with a corresponding change in the incidence of antibodies to thyroglobulin. Oestrogen administered by a single implantation had a suppressive effect on the development of autoimmunity in ovariectomized Tx-X females. Oestrogen given by either of these procedures also reduced the incidence of thyroiditis and autoantibody induction in orchidectomized male Tx-X rats. In contrast, repeated administration of progesterone at a dose of 250 mg and 1,500 μg/100 g body weight appeared to augment levels of autoimmunity. It is concluded that the differential susceptibility to the induction of autoimmunity by thymectomy and irradiation is the direct consequence of sex hormonal influences. The higher incidence of the disease in the female would appear to be determined by the balance between the activity of oestrogen and progesterone which would further appear to have antagonistic influences in this particular situation. (UK)

EPHB6 augments both development and drug sensitivity of triple-negative breast cancer tumours.

Science.gov (United States)

Toosi, Behzad M; El Zawily, Amr; Truitt, Luke; Shannon, Matthew; Allonby, Odette; Babu, Mohan; DeCoteau, John; Mousseau, Darrell; Ali, Mohsin; Freywald, Tanya; Gall, Amanda; Vizeacoumar, Frederick S; Kirzinger, Morgan W; Geyer, C Ronald; Anderson, Deborah H; Kim, TaeHyung; Welm, Alana L; Siegel, Peter; Vizeacoumar, Franco J; Kusalik, Anthony; Freywald, Andrew

2018-04-27

Triple-negative breast cancer (TNBC) tumours that lack expression of oestrogen, and progesterone receptors, and do not overexpress the HER2 receptor represent the most aggressive breast cancer subtype, which is characterised by the resistance to therapy in frequently relapsing tumours and a high rate of patient mortality. This is likely due to the resistance of slowly proliferating tumour-initiating cells (TICs), and understanding molecular mechanisms that control TICs behaviour is crucial for the development of effective therapeutic approaches. Here, we present our novel findings, indicating that an intrinsically catalytically inactive member of the Eph group of receptor tyrosine kinases, EPHB6, partially suppresses the epithelial-mesenchymal transition in TNBC cells, while also promoting expansion of TICs. Our work reveals that EPHB6 interacts with the GRB2 adapter protein and that its effect on enhancing cell proliferation is mediated by the activation of the RAS-ERK pathway, which allows it to elevate the expression of the TIC-related transcription factor, OCT4. Consistent with this, suppression of either ERK or OCT4 activities blocks EPHB6-induced pro-proliferative responses. In line with its ability to trigger propagation of TICs, EPHB6 accelerates tumour growth, potentiates tumour initiation and increases TIC populations in xenograft models of TNBC. Remarkably, EPHB6 also suppresses tumour drug resistance to DNA-damaging therapy, probably by forcing TICs into a more proliferative, drug-sensitive state. In agreement, patients with higher EPHB6 expression in their tumours have a better chance for recurrence-free survival. These observations describe an entirely new mechanism that governs TNBC and suggest that it may be beneficial to enhance EPHB6 action concurrent with applying a conventional DNA-damaging treatment, as it would decrease drug resistance and improve tumour elimination.

Early childhood environment related to microbial exposure and the occurrence of atopic disease at school age.

Science.gov (United States)

de Meer, G; Janssen, N A H; Brunekreef, B

2005-05-01

There is a growing body of evidence that the early childhood environment with respect to day care attendance, older siblings, pet ownership, and early life airway infections may protect from developing atopic disease. Few studies have distinguished between atopic sensitization and symptoms, and none have evaluated independent contributions for all of these different environmental conditions. Examine independent effects on atopic sensitization and symptoms of day care attendance, older siblings, pet ownership, and early infancy's airway disease. A cross-sectional survey among 8-13-year-old school children with complete data for 1555 children. After adjustment for confounders, atopic sensitization occurred less frequently in children that had attended a day care centre (OR: 0.73, 95% CI: 0.55-0.98) or had a cat or dog before 2 years of age (OR: 0.78, 95% CI: 0.61-0.99). Having older siblings yielded a nonsignificant trend towards protection (OR: 0.88, 95% CI: 0.70-1.11). For symptoms, there was no relation with having older sibs, day care attendance and pet ownership, although there was a trend towards protection for the combination of atopy and symptoms. In contrast, children with doctors' treated airway disease before age 2, more frequently reported recent symptoms of wheeze, asthma, rhinitis, or dermatitis (all P atopic sensitization. Protection against symptoms only occurred if atopic sensitization was present as well.

Remaining or becoming secure: parental sensitive support predicts attachment continuity from infancy to adolescence in a longitudinal adoption study

NARCIS (Netherlands)

Beijersbergen, M.D.; Juffer, F.; Bakermans-Kranenburg, M.J.; IJzendoorn, M.H. van

2012-01-01

In a longitudinal study with 125 early adopted adolescents, we examined continuity of attachment from infancy to adolescence and the role of parental sensitive support in explaining continuity or discontinuity of attachment. Assessments of maternal sensitive support and infant attachment (Strange

In vivo and in vitro effects of Bidens pilosa l. (asteraceae) leaf ...

African Journals Online (AJOL)

In vivo and in vitro effects of Bidens pilosa l. (asteraceae) leaf aqueous and ethanol extracts on primed-oestrogenized rat uterine muscle. ... In vitro isometric contraction measurement of oestrogen-primed rat uterine strips showed a significant high aqueous extract-induced contractile effect from 0.03-1.97mg/ml: on the ...

Early diagnosis of sub-clinical stage of diabetic retinopathy

Directory of Open Access Journals (Sweden)

Xing-Hui Xu

2014-12-01

Full Text Available AIM: To evaluate the early diagnosis of sub-clinic stage of diabetic retinopathy.METHODS: This was cross sectional study,multifocal retina electroretinogram(mf-ERG, contrast sensitivity(CSand central retinal artery color Doppler examination were recorded from 30 cases(30 eyesmatched control subjects, 35 cases(35 eyeswith type 2 diabetes mellitus(DMwithout diabetic retinopathy(NDRand 38 cases(38 eyeswith non-prolifera tive diabetic retinopathy(NPDR. One-way ANOVA and SNK-q test were used for data analysis.RESULTS: P1 response density of NDR patients were found decrease, N1 implicit time were delayed. Which were related with the degree of retinopathy(PPPP>0.05, The differences between normal group, NDR group and NPDR group were found statistically significant(PCONCLUSION: mf-ERG and CS are sensitive indexes for early evaluation of visual function in patients with diabetes mellitus, with development of the disease, CRA blood flow also appears to decline.

Detection of early caries by laser-induced breakdown spectroscopy

Science.gov (United States)

Sasazawa, Shuhei; Kakino, Satoko; Matsuura, Yuji

2015-07-01

To improve sensitivity of dental caries detection by laser-induced breakdown spectroscopy (LIBS) analysis, it is proposed to utilize emission peaks in the ultraviolet. We newly focused on zinc whose emission peaks exist in ultraviolet because zinc exists at high concentration in the outer layer of enamel. It was shown that by using ratios between heights of an emission peak of Zn and that of Ca, the detection sensitivity and stability are largely improved. It was also shown that early caries are differentiated from healthy part by properly setting a threshold in the detected ratios. The proposed caries detection system can be applied to dental laser systems such as ones based on Er:YAG-lasers. When ablating early caries part by laser light, the system notices the dentist that the ablation of caries part is finished. We also show the intensity of emission peaks of zinc decreased with ablation with Er:YAG laser light.

Gender and teacher training in Early Childhood Education studies

Directory of Open Access Journals (Sweden)

Alfonso Romero Díaz

2008-12-01

Full Text Available This paper presents the findings of a research study funded by the European Union that aims to improve early childhood teacher training in gender-related topics. Spain has made considerable headway with the inclusion of gender mainstreaming in the political agenda. However, as we point out in this paper, this issue is still not a priority in vocational training for early childhood education. A series of qualitative interviews and a quantitative questionnaire revealed a lack of training, materials and sensitivity, all needed for the introduction of gender and sexual diversity issues.

Assay of oestrogen

International Nuclear Information System (INIS)

Edwards, J.C.

1981-01-01

A particular problem with the direct radioimmunoassay of unconjugated oestriol in pregnancy is caused by the increased amount of steroid-binding proteins present in pregnancy serum and plasma. The steroid-binding proteins react with oestriol and 125 I-labelled oestriol during the assay procedure and the steroid-protein bound 125 I-labelled oestriol is precipitated along with the antibody-bound 125 I-labelled oestriol by the ammonium sulphate solution separation system. A novel method is described whereby progesterone (1-20 μg/ml) is used to block the action of steroid-binding proteins in pregnancy serum and plasma samples, thus minimizing interference in a direct radioimmunoassay for unconjugated oestriol using a specific anti-oestriol serum. (U.K.)

Effects of menopause and high-intensity training on insulin sensitivity and muscle metabolism

DEFF Research Database (Denmark)

Mandrup, Camilla M; Egelund, Jon; Nyberg, Michael

2018-01-01

To investigate peripheral insulin sensitivity and skeletal muscle glucose metabolism in premenopausal and postmenopausal women, and evaluate whether exercise training benefits are maintained after menopause. Sedentary, healthy, normal-weight, late premenopausal (n = 21), and early postmenopausal (n...

Theta oscillations are sensitive to both early and late conflict processing stages: effects of alcohol intoxication.

Science.gov (United States)

Kovacevic, Sanja; Azma, Sheeva; Irimia, Andrei; Sherfey, Jason; Halgren, Eric; Marinkovic, Ksenija

2012-01-01

Prior neuroimaging evidence indicates that decision conflict activates medial and lateral prefrontal and parietal cortices. Theoretical accounts of cognitive control highlight anterior cingulate cortex (ACC) as a central node in this network. However, a better understanding of the relative primacy and functional contributions of these areas to decision conflict requires insight into the neural dynamics of successive processing stages including conflict detection, response selection and execution. Moderate alcohol intoxication impairs cognitive control as it interferes with the ability to inhibit dominant, prepotent responses when they are no longer correct. To examine the effects of moderate intoxication on successive processing stages during cognitive control, spatio-temporal changes in total event-related theta power were measured during Stroop-induced conflict. Healthy social drinkers served as their own controls by participating in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg women) and placebo conditions in a counterbalanced design. Anatomically-constrained magnetoencephalography (aMEG) approach was applied to complex power spectra for theta (4-7 Hz) frequencies. The principal generator of event-related theta power to conflict was estimated to ACC, with contributions from fronto-parietal areas. The ACC was uniquely sensitive to conflict during both early conflict detection, and later response selection and execution stages. Alcohol attenuated theta power to conflict across successive processing stages, suggesting that alcohol-induced deficits in cognitive control may result from theta suppression in the executive network. Slower RTs were associated with attenuated theta power estimated to ACC, indicating that alcohol impairs motor preparation and execution subserved by the ACC. In addition to their relevance for the currently prevailing accounts of cognitive control, our results suggest that alcohol-induced impairment of top-down strategic processing

Clinical study of electrophysiological changes of optic nerves in early period of type 1 diabetes mellitus

Directory of Open Access Journals (Sweden)

Quan-Liang Zhao

2016-07-01

Full Text Available AIM:To investigate the value of pattern visual evoked potential(PVEPand flash electroretinogram(FERGin early diagnosis and prevention of diabetic retinopathy(DR, analyzing the correlation of early stage DR with PVEP and FERG.METHODS:Sixty patients, 30 males and 30 females, participated in observation group. Their average age was 19.42±7.78years. The duration of DM was RESULTS:In observation group, P100 amplitude decreased and P100 latency increased, compared to those of control group(PPCONCLUSION: PVEP are sensitive to optic neuron damage; FERG is desirable to detect the lesion of Müller cells and bipolar cells. P100 amplitude by PVEP, b-wave amplitude by FERG may be the most sensitive parameter for DR at early stage.

Outcome for Children Receiving the Early Start Denver Model before and after 48 Months

Science.gov (United States)

Vivanti, Giacomo; Dissanayake, Cheryl

2016-01-01

The Early Start Denver Model (ESDM) is an intervention program recommended for pre-schoolers with autism ages 12-48 months. The rationale for this recommendation is the potential for intervention to affect developmental trajectories during early sensitive periods. We investigated outcomes of 32 children aged 18-48 months and 28 children aged…

Sensitivity analysis of the reactor safety study. Final report

International Nuclear Information System (INIS)

Parkinson, W.J.; Rasmussen, N.C.; Hinkle, W.D.

1979-01-01

The Reactor Safety Study (RSS) or Wash 1400 developed a methodology estimating the public risk from light water nuclear reactors. In order to give further insights into this study, a sensitivity analysis has been performed to determine the significant contributors to risk for both the PWR and BWR. The sensitivity to variation of the point values of the failure probabilities reported in the RSS was determined for the safety systems identified therein, as well as for many of the generic classes from which individual failures contributed to system failures. Increasing as well as decreasing point values were considered. An analysis of the sensitivity to increasing uncertainty in system failure probabilities was also performed. The sensitivity parameters chosen were release category probabilities, core melt probability, and the risk parameters of early fatalities, latent cancers and total property damage. The latter three are adequate for describing all public risks identified in the RSS. The results indicate reductions of public risk by less than a factor of two for factor reductions in system or generic failure probabilities as high as one hundred. There also appears to be more benefit in monitoring the most sensitive systems to verify adherence to RSS failure rates than to backfitting present reactors. The sensitivity analysis results do indicate, however, possible benefits in reducing human error rates

[Application of Big Data Mining Technology in Monitoring and Early-warning of Schistosomiasis].

Science.gov (United States)

Yang, Kun; Li, Shi-zhu

2015-12-01

The prevalence of schistosomiasis will soon be controlled to a low level in China. It is therefore imperative to establish a more sensitive and effective early warning system for schistosomiasis, so as to consolidate the achievements of the disease control. By covering four topics including the importance of early warning system for schistosomiasis and its research direction, as well as recent development in big data mining and its application in monitoring and early-warning of schistosomiasis, this review discusses the feasibility of data mining technology for monitoring and early warning of the disease. It is hoped that this technology would increase the efficacy of studies on monitoring and early warning, and promote the elimination of schistosomiasis in China.

Early extubation after congenital heart surgery

Directory of Open Access Journals (Sweden)

Mirza Halimić

2014-12-01

Full Text Available Introduction: Despite recent advances in anesthesia, cardiopulmonary bypass and surgical techniques, children undergoing congenital heart surgery require postoperativemechanical ventilation. Early extubation was definedas ventilation shorter than 12 hours. Aim of this study is to identify factors associated with successful early extubation after pediatric cardiac surgery.Methods: The study was performed during period from January 2006 to January 2011 at Pediatric Clinic and Heart Center University Clinical center Sarajevo. One hundred children up to 5 years of age, who have had congenital heart disease, with left–right shunt and obstructive heart disease were included in the study. Patients were divided into two groups: Group I - patients extubated within 12 hours after surgery and Group II - patients extubated 12 or more hours after surgery. Results: The most frequently encountered preoperative variables were age with odds ratio 4% 95%CI (1-7%, Down's syndrome 8.5 95%CI (1.6-43.15, failure to thrive 4.3 95%CI( 1-18. Statistically significant postoperative data included lung disease (reactive airways, pneumonia, atelectasis, pneumothorax and with odds ratio 35.1 95 %CI (4-286 and blood transfusion with odds ratio 4.6 95%CI (2-12. Blood transfusion (p=0.002 (Wald=9.2 95%CI (2-12, during as well as after operation procedure has statistically significant influence on prediction time of extubation. Proven markers were age with cut of 21.5 months (sensitivity 74% and specificity 70% and extracorporeal circulation (ECC with cut-of 45.5 minutes (sensitivity 71% and specificity 65%.Conclusion: Early extubation is possible in many children undergoing congenital heart surgery. Younger age and prolonged ECC time are markers associated with prolonged mechanical ventilation.

Anxiety sensitivity predicts increased perceived exertion during a 1-mile walk test among treatment-seeking smokers.

Science.gov (United States)

Farris, Samantha G; Uebelacker, Lisa A; Brown, Richard A; Price, Lawrence H; Desaulniers, Julie; Abrantes, Ana M

2017-12-01

Smoking increases risk of early morbidity and mortality, and risk is compounded by physical inactivity. Anxiety sensitivity (fear of anxiety-relevant somatic sensations) is a cognitive factor that may amplify the subjective experience of exertion (effort) during exercise, subsequently resulting in lower engagement in physical activity. We examined the effect of anxiety sensitivity on ratings of perceived exertion (RPE) and physiological arousal (heart rate) during a bout of exercise among low-active treatment-seeking smokers. Adult daily smokers (n = 157; M age  = 44.9, SD = 11.13; 69.4% female) completed the Rockport 1.0 mile submaximal treadmill walk test. RPE and heart rate were assessed during the walk test. Multi-level modeling was used to examine the interactive effect of anxiety sensitivity × time on RPE and on heart rate at five time points during the walk test. There were significant linear and cubic time × anxiety sensitivity effects for RPE. High anxiety sensitivity was associated with greater initial increases in RPE during the walk test, with stabilized ratings towards the last 5 min, whereas low anxiety sensitivity was associated with lower initial increase in RPE which stabilized more quickly. The linear time × anxiety sensitivity effect for heart rate was not significant. Anxiety sensitivity is associated with increasing RPE during moderate-intensity exercise. Persistently rising RPE observed for smokers with high anxiety sensitivity may contribute to the negative experience of exercise, resulting in early termination of bouts of prolonged activity and/or decreased likelihood of future engagement in physical activity.

ICU early physical rehabilitation programs: financial modeling of cost savings.

Science.gov (United States)

Lord, Robert K; Mayhew, Christopher R; Korupolu, Radha; Mantheiy, Earl C; Friedman, Michael A; Palmer, Jeffrey B; Needham, Dale M

2013-03-01

To evaluate the potential annual net cost savings of implementing an ICU early rehabilitation program. Using data from existing publications and actual experience with an early rehabilitation program in the Johns Hopkins Hospital Medical ICU, we developed a model of net financial savings/costs and presented results for ICUs with 200, 600, 900, and 2,000 annual admissions, accounting for both conservative- and best-case scenarios. Our example scenario provided a projected financial analysis of the Johns Hopkins Medical ICU early rehabilitation program, with 900 admissions per year, using actual reductions in length of stay achieved by this program. U.S.-based adult ICUs. Financial modeling of the introduction of an ICU early rehabilitation program. Net cost savings generated in our example scenario, with 900 annual admissions and actual length of stay reductions of 22% and 19% for the ICU and floor, respectively, were $817,836. Sensitivity analyses, which used conservative- and best-case scenarios for length of stay reductions and varied the per-day ICU and floor costs, across ICUs with 200-2,000 annual admissions, yielded financial projections ranging from -$87,611 (net cost) to $3,763,149 (net savings). Of the 24 scenarios included in these sensitivity analyses, 20 (83%) demonstrated net savings, with a relatively small net cost occurring in the remaining four scenarios, mostly when simultaneously combining the most conservative assumptions. A financial model, based on actual experience and published data, projects that investment in an ICU early rehabilitation program can generate net financial savings for U.S. hospitals. Even under the most conservative assumptions, the projected net cost of implementing such a program is modest relative to the substantial improvements in patient outcomes demonstrated by ICU early rehabilitation programs.

Comparison of early myocardial technetium-99m pyrophosphate uptake to early peaking of creatine kinase and creatine kinase-MB as indicators of early reperfusion in acute myocardial infarction

International Nuclear Information System (INIS)

Kondo, M.; Yuzuki, Y.; Arai, H.; Shimizu, K.; Morikawa, M.; Shimono, Y.

1987-01-01

The value of technetium-99m pyrophosphate (Tc-99m-PYP) scintigraphy as an indicator of reperfusion 2.8 to 8 hours after the onset of symptoms of acute myocardial infarction was compared with the value of early peak creatine kinase (CK) and CK-MB release within 16 hours after the onset of symptoms. In 29 patients who received thrombolytic therapy, recanalization was seen (group 1) and in 7 it was not (group 2). In 23 patients (79%) in group 1 scintigraphic findings were positive and in all 7 in group 2 they were negative. In 15 patients (52%) in group 1 and 1 patient (14%) in group 2, CK reached its peak level within 16 hours. In 20 patients (69%) in group 1 and 3 (43%) in group 2 the CK-MB level reached a peak within 16 hours. The sensitivity, specificity and predictive accuracy of positive results of early Tc-99m-PYP scintigraphy in predicting the reperfusion were 79%, 100% and 83%. These values are significantly higher than or similar to those of early peaking of CK and CK-MB release. In contrast to measurements of enzyme release, reperfusion data for Tc-99m-PYP scintigraphy are available immediately after thrombolytic therapy. Therefore, early Tc-99m-PYP scintigraphy (3 to 8 hours after onset of symptoms) is valuable as a noninvasive technique for early diagnosis of reperfusion

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

DEFF Research Database (Denmark)

McGranahan, Nicholas; Furness, Andrew J S; Rosenthal, Rachel

2016-01-01

demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+)tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non-small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4...

N-Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite Effects on Androgen and Oestrogens Receptors (Alpha and Beta in Rats with Testosterone-Induced Benign Prostatic Hyperplasia

Directory of Open Access Journals (Sweden)

Diego Fano

2017-01-01

Full Text Available Benign Prostatic Hyperplasia (BPH affects, worldwide, 50% of 60-year-old men. The Peruvian plant red maca (Lepidium meyenii inhibits BPH in rodents. This study aimed to determine the effects of methanolic red maca extract and its n-butanol and aqueous fractions on expression of androgen and oestrogen receptors in rats with testosterone enanthate-induced BPH. Thirty-six rats in six groups were studied. Control group received 2 mL of vehicle orally and 0.1 mL of propylene glycol intramuscularly. The second group received vehicle orally and testosterone enanthate (TE (25 mg/0.1 mL intramuscularly in days 1 and 7. The other four groups were BPH-induced with TE and received, during 21 days, 3.78 mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n-butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments with red maca extract and its n-butanol but not aqueous fraction reduced prostate weight similar to finasteride. All maca treated groups restored the expression of ERβ, but only the aqueous fraction increased androgen receptors and ERα. In conclusion, butanol fraction of red maca reduced prostate size in BPH by restoring expression of ERβ without affecting androgen receptors and ERα. This effect was not observed with aqueous fraction of methanolic extract of red maca.

N-Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite Effects on Androgen and Oestrogens Receptors (Alpha and Beta) in Rats with Testosterone-Induced Benign Prostatic Hyperplasia.

Science.gov (United States)

Fano, Diego; Vásquez-Velásquez, Cinthya; Gonzales-Castañeda, Cynthia; Guajardo-Correa, Emanuel; Orihuela, Pedro A; Gonzales, Gustavo F

2017-01-01

Benign Prostatic Hyperplasia (BPH) affects, worldwide, 50% of 60-year-old men. The Peruvian plant red maca (Lepidium meyenii) inhibits BPH in rodents. This study aimed to determine the effects of methanolic red maca extract and its n-butanol and aqueous fractions on expression of androgen and oestrogen receptors in rats with testosterone enanthate-induced BPH. Thirty-six rats in six groups were studied. Control group received 2 mL of vehicle orally and 0.1 mL of propylene glycol intramuscularly. The second group received vehicle orally and testosterone enanthate (TE) (25 mg/0.1 mL) intramuscularly in days 1 and 7. The other four groups were BPH-induced with TE and received, during 21 days, 3.78 mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n-butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments with red maca extract and its n-butanol but not aqueous fraction reduced prostate weight similar to finasteride. All maca treated groups restored the expression of ER β , but only the aqueous fraction increased androgen receptors and ER α . In conclusion, butanol fraction of red maca reduced prostate size in BPH by restoring expression of ER β without affecting androgen receptors and ER α . This effect was not observed with aqueous fraction of methanolic extract of red maca.

N-Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite Effects on Androgen and Oestrogens Receptors (Alpha and Beta) in Rats with Testosterone-Induced Benign Prostatic Hyperplasia

Science.gov (United States)

Vásquez-Velásquez, Cinthya

2017-01-01

Benign Prostatic Hyperplasia (BPH) affects, worldwide, 50% of 60-year-old men. The Peruvian plant red maca (Lepidium meyenii) inhibits BPH in rodents. This study aimed to determine the effects of methanolic red maca extract and its n-butanol and aqueous fractions on expression of androgen and oestrogen receptors in rats with testosterone enanthate-induced BPH. Thirty-six rats in six groups were studied. Control group received 2 mL of vehicle orally and 0.1 mL of propylene glycol intramuscularly. The second group received vehicle orally and testosterone enanthate (TE) (25 mg/0.1 mL) intramuscularly in days 1 and 7. The other four groups were BPH-induced with TE and received, during 21 days, 3.78 mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n-butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments with red maca extract and its n-butanol but not aqueous fraction reduced prostate weight similar to finasteride. All maca treated groups restored the expression of ERβ, but only the aqueous fraction increased androgen receptors and ERα. In conclusion, butanol fraction of red maca reduced prostate size in BPH by restoring expression of ERβ without affecting androgen receptors and ERα. This effect was not observed with aqueous fraction of methanolic extract of red maca. PMID:29375645

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African Journals Online (AJOL)

Pl“()(lll.lCli0U of testosterone uml oestrogen is controlled by the jiiitttitory release ol' the leiiteitnsing hormones (Lil). 'l'l'ie administration of testosterone and oestrogen or their. analogues, suppresses the release of Lt! by a negative feedback mechanism. The ii'iechanism of the hot flushes is wtiiclezit'2 although it is known to ...

Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations

OpenAIRE

Irfan Affan Bin; Reichlin Tobias R.; Twerenbold Raphael; Meister Marc; Moehring Berit; Wildi Karin; Bassetti Stefano; Zellweger Christa; Gimenez Maria Rubini; Hoeller Rebeca; Murray Karsten; Sou SeoungMann; Mueller Mira; Mosimann Tamina; Reiter Miriam

2013-01-01

Background: Absolute changes in high sensitivity cardiac troponin T (hs cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high sensitivity cardiac troponin I (hs cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. Methods: In a prospective international multicenter study high sensitivity cardiac troponin (hs cTn) was ...

Orientation of llama antibodies strongly increases sensitivity of biosensors.

Science.gov (United States)

Trilling, Anke K; Hesselink, Thamara; van Houwelingen, Adèle; Cordewener, Jan H G; Jongsma, Maarten A; Schoffelen, Sanne; van Hest, Jan C M; Zuilhof, Han; Beekwilder, Jules

2014-10-15

Sensitivity of biosensors depends on the orientation of bio-receptors on the sensor surface. The objective of this study was to organize bio-receptors on surfaces in a way that their analyte binding site is exposed to the analyte solution. VHH proteins recognizing foot-and-mouth disease virus (FMDV) were used for making biosensors, and azides were introduced in the VHH to function as bioorthogonal reactive groups. The importance of the orientation of bio-receptors was addressed by comparing sensors with randomly oriented VHH (with multiple exposed azide groups) to sensors with uniformly oriented VHH (with only a single azide group). A surface plasmon resonance (SPR) chip exposing cyclooctyne was reacted to azide functionalized VHH domains, using click chemistry. Comparison between randomly and uniformly oriented bio-receptors showed up to 800-fold increase in biosensor sensitivity. This technique may increase the containment of infectious diseases such as FMDV as its strongly enhanced sensitivity may facilitate early diagnostics. Copyright © 2014 Elsevier B.V. All rights reserved.

Tetrodotoxin Sensitivity of the Vertebrate Cardiac Na+ Current

Directory of Open Access Journals (Sweden)

Jaakko Haverinen

2011-11-01

Full Text Available Evolutionary origin and physiological significance of the tetrodotoxin (TTX resistance of the vertebrate cardiac Na+ current (INa is still unresolved. To this end, TTX sensitivity of the cardiac INa was examined in cardiac myocytes of a cyclostome (lamprey, three teleost fishes (crucian carp, burbot and rainbow trout, a clawed frog, a snake (viper and a bird (quail. In lamprey, teleost fishes, frog and bird the cardiac INa was highly TTX-sensitive with EC50-values between 1.4 and 6.6 nmol·L−1. In the snake heart, about 80% of the INa was TTX-resistant with EC50 value of 0.65 μmol·L−1, the rest being TTX-sensitive (EC50 = 0.5 nmol·L−1. Although TTX-resistance of the cardiac INa appears to be limited to mammals and reptiles, the presence of TTX-resistant isoform of Na+ channel in the lamprey heart suggest an early evolutionary origin of the TTX-resistance, perhaps in the common ancestor of all vertebrates.

Bone scintigraphy compared to MRI and ultrasound in the early diagnosis of arthritis

International Nuclear Information System (INIS)

Sandrock, D.

2006-01-01

Chronic inflammatory arthritis is recognized specifically by bone erosions, caused by characteristic pannus tissue. In the finger joints dynamic low-Tesla MRI is nearly double but not completely sensitive in the detection of erosions than conventional radiography, sonography takes an intermediate position. Less specific signs of synovitis and tenosynovitis are shown with high sensitivity by both 3(2)-phase bone scintigraphy and ultrasound, MRI is less sensitive in this respect. However, standard situation of inflammation in bone scintigraphy - positive finding in early as well as late phase - is of surprisingly low sensitivity, any singular finding in the early or late phase has to be regarded as positive. Specificity of these singular findings is nevertheless sufficiently high, acute inflammatory joint changes and even erosions are also seen with MRI in obviously healthy persons. Only 2-phase bone scintigraphy is easily able to present a simultaneous survey of all joints of the body. For this reason 2-phase bone scintigraphy is most suitable for exclusion but also for primary diagnosis of disease, specification must be done afterwards by other imaging modalities or by laboratory findings. (orig.)

Specificity and sensitivity assessment of selected nasal provocation testing techniques

Directory of Open Access Journals (Sweden)

Edyta Krzych-Fałta

2016-12-01

Full Text Available Introduction: Nasal provocation testing involves an allergen-specific local reaction of the nasal mucosa to the administered allergen. Aim: To determine the most objective nasal occlusion assessment technique that could be used in nasal provocation testing. Material and methods : A total of 60 subjects, including 30 patients diagnosed with allergy to common environmental allergens and 30 healthy subjects were enrolled into the study. The method used in the study was a nasal provocation test with an allergen, with a standard dose of a control solution and an allergen (5,000 SBU/ml administered using a calibrated atomizer into both nostrils at room temperature. Early-phase nasal mucosa response in the early phase of the allergic reaction was assessed via acoustic rhinometry, optical rhinometry, nitric oxide in nasal air, and tryptase levels in the nasal lavage fluid. Results : In estimating the homogeneity of the average values, the Levene’s test was used and receiver operating characteristic curves were plotted for all the methods used for assessing the nasal provocation test with an allergen. Statistically significant results were defined for p < 0.05. Of all the objective assessment techniques, the most sensitive and characteristic ones were the optical rhinometry techniques (specificity = 1, sensitivity = 1, AUC = 1, PPV = 1, NPV = 1. Conclusions : The techniques used showed significant differences between the group of patients with allergic rhinitis and the control group. Of all the objective assessment techniques, those most sensitive and characteristic were the optical rhinometry.

Associations of cigarette smoking, betel quid chewing and alcohol consumption with high-sensitivity C-reactive protein in early radiographic knee osteoarthritis: a cross-sectional study.

Science.gov (United States)

Zhang, Yi; Zeng, Chao; Wei, Jie; Li, Hui; Yang, Tuo; Yang, Ye; Deng, Zhen-han; Ding, Xiang; Lei, Guanghua

2016-03-11

High-sensitivity C-reactive protein (hsCRP) is possibly related to osteoarthritis (OA) progression and a variety of OA-related symptoms. This study aimed to examine associations between cigarette smoking, betel quid chewing and alcohol consumption and hsCRP in early radiographic knee OA. Cross-sectional health examination survey. This primary study was conducted in a health examination centre in China. 936 (656 men and 280 women) patients with early radiographic knee OA were included in this cross-sectional study. Smoking status was classified into four levels based on daily smoking habit: 0/day, 1-10/day, 11-20/day and >20/day. Betel quid chewing and alcohol consumption status was divided into 'Yes' or 'No'. Early radiographic knee OA was defined as Kellgren Lawrence (K-L) grade 1 or 2 in at least one leg, and elevated hsCRP was assessed as ≥ 3.0 mg/L. After adjustment for a number of potential confounding factors, a significant positive association between cigarette smoking and hsCRP was observed in the multivariable model. The multivariable-adjusted ORs (95% CI) of elevated hsCRP (≥ 3.0 mg/L) in the second (1-10/day, n=133), third (11-20/day, n=59) and highest (>20/day, n=104) cigarette smoking categories were 1.54 (95% CI 0.91 to 2.61), 1.27 (95% CI 0.57 to 2.79) and 2.09 (95% CI 1.20 to 3.64), respectively, compared with the non-smoker category (n=640). In addition, there was a positive dose-response relationship between cigarette smoking and elevated hsCRP (p for trend=0.01). No significant associations between betel quid chewing and alcohol consumption and hsCRP were observed in the multivariable model. This study indicated that cigarette smoking was positively associated with serum hsCRP level in patients with early radiographic knee OA. However, in view of the nature of cross-sectional designs, the results need to be confirmed by further prospective studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted

Application of radioimmunoassays to determine steroids at the time of parturition in the cow

International Nuclear Information System (INIS)

Agthe, O.; Kolm, H.P.

1976-01-01

The influence of single or repeated intramuscular injections of 100 or 200 IU ACTH on peripheral plasma levels of oestrogens, progesterone and corticosteroids was studied in cows during late pregnancy. Radioimmunoassays were applied for measuring unconjugated oestrogens (oestrone and oestradiol-17β) and progesterone. For determining corticoids competitive protein binding was used. Five German black pied cows pregnant for 260-67 days were injected with ACTH either once (two cows with one single injection) or repeatedly (one cow with five and two cows with 12 injections) at 4-h intervals. Blood samples were drawn at 4- to 12-h intervals from one day before to four days after the beginning of ACTH application. Four cows served as control animals. Corticosteroid levels increased drastically from about 3 up to 30 ng/ml after ACTH injection. This effect lasted for 4-6h after a single injection and for 4-6h after the last of the repeated applications. Oestrogen and progesterone levels were not affected by single ACTH applications. If repeated injections were given, oestrogen levels increased from about 0.6 to levels above 1.2 ng/ml. In contrast to oestrogen, progesterone levels fell from 7 ng/ml to about 2 ng/ml during the first 24 h but returned to initial values within the following 24 h. In one cow, however, progesterone concentration remained below 2 ng/ml. In this animal premature parturition occurred on day 270, i.e. 2 days after the last injection. (author)

Accuracy of a pediatric early warning score in the recognition of clinical deterioration

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Juliana de Oliveira Freitas Miranda

Full Text Available ABSTRACT Objective: to evaluate the accuracy of the version of the Brighton Pediatric Early Warning Score translated and adapted for the Brazilian context, in the recognition of clinical deterioration. Method: a diagnostic test study to measure the accuracy of the Brighton Pediatric Early Warning Score for the Brazilian context, in relation to a reference standard. The sample consisted of 271 children, aged 0 to 10 years, blindly evaluated by a nurse and a physician, specialists in pediatrics, with interval of 5 to 10 minutes between the evaluations, for the application of the Brighton Pediatric Early Warning Score for the Brazilian context and of the reference standard. The data were processed and analyzed using the Statistical Package for the Social Sciences and VassarStats.net programs. The performance of the Brighton Pediatric Early Warning Score for the Brazilian context was evaluated through the indicators of sensitivity, specificity, predictive values, area under the ROC curve, likelihood ratios and post-test probability. Results: the Brighton Pediatric Early Warning Score for the Brazilian context showed sensitivity of 73.9%, specificity of 95.5%, positive predictive value of 73.3%, negative predictive value of 94.7%, area under Receiver Operating Characteristic Curve of 91.9% and the positive post-test probability was 80%. Conclusion: the Brighton Pediatric Early Warning Score for the Brazilian context, presented good performance, considered valid for the recognition of clinical deterioration warning signs of the children studied.

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.

Science.gov (United States)

Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U; Gruber, Leonhard; Zebeli, Qendrim

2016-01-01

A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum

Science.gov (United States)

Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U.; Gruber, Leonhard; Zebeli, Qendrim

2016-01-01

A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows. PMID:27383746

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.

Directory of Open Access Journals (Sweden)

Elke Humer

Full Text Available A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10, medium (n = 8, and high (n = 12 lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.

Heightened emotional sensitivity intensifies associations between relational aggression and victimization among girls but not boys: a longitudinal study.

Science.gov (United States)

Zimmer-Gembeck, Melanie J; Duffy, Amanda L

2014-08-01

Founded in the social process model, the aim of this study was to identify whether the associations of relational aggression with concurrent and subsequent relational victimization differed depending on early adolescents' personal vulnerabilities and gender. The vulnerabilities of interest were social-information processing variables that convey greater emotional sensitivity, including rejection sensitivity, fear of negative evaluation, and avoidance of intimacy. Participants were 358 early adolescents (176 boys, 178 girls) aged 9 to 13 years. Relational aggression and victimization were assessed via peer nominations, whereas the three indicators of emotional sensitivity were assessed via self-report. Overall, results revealed greater relational aggression at Time 1 to be associated with greater relational victimization at both Time 1 and Time 2. However, this finding was qualified by both emotional sensitivity and gender. When considered separately, girls who were relationally aggressive and emotionally sensitive were at increased risk of victimization at both assessment points. In contrast, no link was found between relational aggression and victimization for boys, although relational vulnerabilities did have unique associations with boys' relational victimization. These findings have implications for our understanding of relational aggression and victimization, as well as for the development of interventions aimed at reducing these problems.

Insulin sensitivity and carotid intima-media thickness

DEFF Research Database (Denmark)

Kozakova, Michaela; Natali, Andrea; Dekker, Jacqueline

2013-01-01

Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. APPROACH AND RESULTS: We studied a European cohort of 525 men and 655 women (mean age, 44±8 years) free of conditions known...... to affect carotid wall (diabetes mellitus, hypertension, and dyslipidemia). All subjects received an oral glucose tolerance test, a euglycemic hyperinsulinemic clamp (M/I as a measure of insulin sensitivity), and B-mode carotid ultrasound. In 833 participants (380 men), the carotid ultrasound was repeated...

Review of early assessment models of innovative medical technologies.

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Fasterholdt, Iben; Krahn, Murray; Kidholm, Kristian; Yderstræde, Knud Bonnet; Pedersen, Kjeld Møller

2017-08-01

Hospitals increasingly make decisions regarding the early development of and investment in technologies, but a formal evaluation model for assisting hospitals early on in assessing the potential of innovative medical technologies is lacking. This article provides an overview of models for early assessment in different health organisations and discusses which models hold most promise for hospital decision makers. A scoping review of published studies between 1996 and 2015 was performed using nine databases. The following information was collected: decision context, decision problem, and a description of the early assessment model. 2362 articles were identified and 12 studies fulfilled the inclusion criteria. An additional 12 studies were identified and included in the review by searching reference lists. The majority of the 24 early assessment studies were variants of traditional cost-effectiveness analysis. Around one fourth of the studies presented an evaluation model with a broader focus than cost-effectiveness. Uncertainty was mostly handled by simple sensitivity or scenario analysis. This review shows that evaluation models using known methods assessing cost-effectiveness are most prevalent in early assessment, but seems ill-suited for early assessment in hospitals. Four models provided some usable elements for the development of a hospital-based model. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Environmental oxygen conditions during the origin and early evolution of life

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Towe, Kenneth M.

The well-known sensitivity of proteins and nucleic acids to UV-radiation requires that some internally consistent protection scenario be envisioned for the origin and early evolution of life on Earth. Although a variety of ozone-surrogates has been proposed, the available biochemical, geochemical and geological evidence best supports the conclusion that free oxygen was available at levels capable of providing at least a moderate ozone screen. Levels of oxygen near 1-2% of the present atmospheric level are consistent with such a screen, and with: (1) the biochemical needs of early procaryotes considered phylogenetically more primitive than the oxygen-producing Cyanobacteria; (2) the rare-earth element data from the oxide facies of the 3.8 Byr-old Isua banded-iron formations; (3) the nature and phylogenetic distribution of superoxide dismutases; (4) the need for aerobic recycling of early photosynthetic productivity dictated by the distribution of ancient sedimentary iron and organic carbon; (5) the incompatibility of dissolved reduced sulfur (to support anoxygenic photosynthesis) and ferrous iron (to support banded iron-formations) in the surface waters of the world oceans; and (6) the comparative oxygen and UV-sensitivities of modern procaryotes.

They Are What You Eat: Can Nutritional Factors during Gestation and Early Infancy Modulate the Neonatal Immune Response?

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Sarah Prentice

2017-11-01

Full Text Available The ontogeny of the human immune system is sensitive to nutrition even in the very early embryo, with both deficiency and excess of macro- and micronutrients being potentially detrimental. Neonates are particularly vulnerable to infectious disease due to the immaturity of the immune system and modulation of nutritional immunity may play a role in this sensitivity. This review examines whether nutrition around the time of conception, throughout pregnancy, and in early neonatal life may impact on the developing infant immune system.

Modification of visual function by early visual experience.

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Blakemore, C

1976-07-01

Physiological experiments, involving recording from the visual cortex in young kittens and monkeys, have given new insight into human developmental disorders. In the visual cortex of normal cats and monkeys most neurones are selectively sensitive to the orientation of moving edges and they receive very similar signals from both eyes. Even in very young kittens without visual experience, most neurones are binocularly driven and a small proportion of them are genuinely orientation selective. There is no passive maturation of the system in the absence of visual experience, but even very brief exposure to patterned images produces rapid emergence of the adult organization. These results are compared to observations on humans who have "recovered" from early blindness. Covering one eye in a kitten or a monkey, during a sensitive period early in life, produces a virtually complete loss of input from that eye in the cortex. These results can be correlated with the production of "stimulus deprivation amblyopia" in infants who have had one eye patched. Induction of a strabismus causes a loss of binocularity in the visual cortex, and in humans it leads to a loss of stereoscopic vision and binocular fusion. Exposing kittens to lines of one orientation modifies the preferred orientations of cortical cells and there is an analogous "meridional amblyopia" in astigmatic humans. The existence of a sensitive period in human vision is discussed, as well as the possibility of designing remedial and preventive treatments for human developmental disorders.

Cat sensitization according to cat window of exposure in adult asthmatics

NARCIS (Netherlands)

Oryszczyn, M.-P.; van Ree, R.; Maccario, J.; Nadif, R.; Kauffmann, F.

2009-01-01

P>Background In adults, there is limited information on tolerance to cat, which may be reflected by high IgG(4) without IgE sensitization. Early exposure to cat may play a critical role. Objective The aim was to assess among adults the association of Fel d 1 IgG(4), Fel d 1 IgE, skin prick test

Autism Spectrum Disorder in the DSM-5: Diagnostic Sensitivity and Specificity in Early Childhood

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Christiansz, Jessica A.; Gray, Kylie M.; Taffe, John; Tonge, Bruce J.

2016-01-01

Changes to the DSM-5 Autism Spectrum Disorder (ASD) criteria raised concerns among parents and practitioners that the criteria may exclude some children with Pervasive Developmental Disorder (PDD). Few studies have examined DSM-5 sensitivity and specificity in children less than 5 years of age. This study evaluated 185 children aged 20-55 months…

Accuracy of different diagnostic tests for early, delayed and late prosthetic joint infection.

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Fernández-Sampedro, M; Fariñas-Alvarez, C; Garces-Zarzalejo, C; Alonso-Aguirre, M A; Salas-Venero, C; Martínez-Martínez, L; Fariñas, M C

2017-08-25

A combination of laboratory, histopathological and microbiological tests for diagnosis of prosthetic joint infection (PJI) have been strongly recommended. This study aims to characterize the accuracy of individual or group tests, such as culture of sonicate fluid, synovial fluid and peri-implant tissue, C-reactive protein (CRP) and histopathology for detection of early, delayed and late PJI. A prospective study of patients undergoing hip or knee arthroplasty from February 2009 to February 2014 was performed in a Spanish tertiary health care hospital. The diagnostic accuracy of the different methods was evaluated constructing receiver-operating-characteristic (ROC) curve areas. One hundred thirty consecutive patients were included: 18 (13.8%) early PJI, 35 (27%) delayed PJI and 77 (59.2%) late PJI. For individual parameters, the area under the ROC curve for peri-implant tissue culture was larger for early (0.917) than for delayed (0.829) and late PJI (0.778), p = 0.033. There was a significantly larger difference for ROC area in the synovial fluid culture for delayed (0.803) than for early (0.781) and late infections (0.679), p = 0.039. The comparison of the areas under the ROC curves for the two microbiological tests showed that sonicate fluid was significantly different from peri-implant tissue in delayed (0.951 vs 0.829, p = 0.005) and late PJI (0.901 vs 0.778, p = 0.000). The conjunction of preoperative parameters, synovial fluid culture and CRP, improved the accuracy for late PJI (p = 0.01). The conjunction of histopathology and sonicate fluid culture increased the area under ROC curve of sonication in early (0.917 vs 1.000); p = 0.06 and late cases (0.901 vs 0.999); p < 0.001. For early PJI, sonicate fluid and peri-implant tissue cultures achieve the same best sensitivity. For delayed and late PJI, sonicate fluid culture is the most sensitive individual diagnostic method. By combining histopathology and peri-implant tissue, all early, 97% of

Generalized tolerance sensitivity and DEA metric sensitivity

OpenAIRE

Neralić, Luka; E. Wendell, Richard

2015-01-01

This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA). Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

Generalized tolerance sensitivity and DEA metric sensitivity

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Luka Neralić

2015-03-01

Full Text Available This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA. Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

A model to estimate insulin sensitivity in dairy cows

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Holtenius Kjell

2007-10-01

Full Text Available Abstract Impairment of the insulin regulation of energy metabolism is considered to be an etiologic key component for metabolic disturbances. Methods for studies of insulin sensitivity thus are highly topical. There are clear indications that reduced insulin sensitivity contributes to the metabolic disturbances that occurs especially among obese lactating cows. Direct measurements of insulin sensitivity are laborious and not suitable for epidemiological studies. We have therefore adopted an indirect method originally developed for humans to estimate insulin sensitivity in dairy cows. The method, "Revised Quantitative Insulin Sensitivity Check Index" (RQUICKI is based on plasma concentrations of glucose, insulin and free fatty acids (FFA and it generates good and linear correlations with different estimates of insulin sensitivity in human populations. We hypothesized that the RQUICKI method could be used as an index of insulin function in lactating dairy cows. We calculated RQUICKI in 237 apparently healthy dairy cows from 20 commercial herds. All cows included were in their first 15 weeks of lactation. RQUICKI was not affected by the homeorhetic adaptations in energy metabolism that occurred during the first 15 weeks of lactation. In a cohort of 24 experimental cows fed in order to obtain different body condition at parturition RQUICKI was lower in early lactation in cows with a high body condition score suggesting disturbed insulin function in obese cows. The results indicate that RQUICKI might be used to identify lactating cows with disturbed insulin function.

Maternal sensitivity and latency to positive emotion following challenge: pathways through effortful control.

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Conway, Anne; McDonough, Susan C; Mackenzie, Michael; Miller, Alison; Dayton, Carolyn; Rosenblum, Katherine; Muzik, Maria; Sameroff, Arnold

2014-01-01

The ability to self-generate positive emotions is an important component of emotion regulation. In this study, we focus on children's latency to express positive emotions following challenging situations and assess whether this ability operates through early maternal sensitivity and children's effortful control. Longitudinal relations between maternal sensitivity, infant negative affect, effortful control, and latency to positive emotion following challenge were examined in 156 children who were 33 months of age. Structural equation models supported the hypothesis that maternal sensitivity during infancy predicted better effortful control and, in turn, shorter latencies to positive emotions following challenge at 33 months. Directions for future research are discussed. © 2014 Michigan Association for Infant Mental Health.

The consequences of early life adversity: neurobiological, behavioural and epigenetic adaptations

NARCIS (Netherlands)

Maccari, S.; Krugers, H.J.; Morley-Fletcher, S.; Szyf, M.; Brunton, P.J.

2014-01-01

During the perinatal period, the brain is particularly sensitive to remodelling by environmental factors. Adverse early life experiences, such as stress exposure or sub-optimal maternal care can have long-lasting detrimental consequences for an individual. This phenomenon is often referred to as

Radiations - induced disorders in ovarian function

International Nuclear Information System (INIS)

Saleh, S.; Roushdy, H.M.; Abdel-Aziz, M.T.; Eldenshary, A.E.; Abdel-Khalek, A.; Ramadan, L.A.

1988-01-01

The effect of whole body gamma radiation exposure (7.5 and 6.5 Gy) on the secretory activity and the structure of the ovaries was investigated. The parameters studied were serum levels of oestrogen, progesterone, Lh and FSH, beside histopathological studies of the ovaries of femaler rats. These were measured on the next day after radiation exposure and then after one two oestrus cycles. Whole body gamma - irradiation of females rats at two levels of exposure progressively decreased the level of oestrogen and progesterone while increased the level of LH and FSH as compared with the control. moreover, the changes in the ovaries were demonstrated in the histopathological investigation. Keywords: Radiation exposure - ovarian function - hormone radioimmunoassay - oestrogen - progesterone - LH - FSH

Climate Change Sensitivity of Multi-Species Afforestation in Semi-Arid Benin

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Florent Noulèkoun

2018-06-01

Full Text Available The early growth stage is critical in the response of trees to climate change and variability. It is not clear, however, what climate metrics are best to define the early-growth sensitivity in assessing adaptation strategies of young forests to climate change. Using a combination of field experiments and modelling, we assessed the climate sensitivity of two promising afforestation species, Jatropha curcas L. and Moringa oleifera Lam., by analyzing their predicted climate–growth relationships in the initial two years after planting on degraded cropland in the semi-arid zone of Benin. The process-based WaNuLCAS model (version 4.3, World Agroforestry Centre, Bogor, Indonesia was used to simulate aboveground biomass growth for each year in the climate record (1981–2016, either as the first or as the second year of tree growth. Linear mixed models related the annual biomass growth to climate indicators, and climate sensitivity indices quantified climate–growth relationships. In the first year, the length of dry spells had the strongest effect on tree growth. In the following year, the annual water deficit and length of dry season became the strongest predictors. Simulated rooting depths greater than those observed in the experiments enhanced biomass growth under extreme dry conditions and reduced sapling sensitivity to drought. Projected increases in aridity implied significant growth reduction, but a multi-species approach to afforestation using species that are able to develop deep-penetrating roots should increase the resilience of young forests to climate change. The results illustrate that process-based modelling, combined with field experiments, can be effective in assessing the climate–growth relationships of tree species.

Uncertainty and sensitivity analyses of the complete program system UFOMOD and of selected submodels

International Nuclear Information System (INIS)

Fischer, F.; Ehrhardt, J.; Hasemann, I.

1990-09-01

Uncertainty and sensitivity studies with the program system UFOMOD have been performed since several years on a submodel basis to get a deeper insight into the propagation of parameter uncertainties through the different modules and to quantify their contribution to the confidence bands of the intermediate and final results of an accident consequence assessment. In a series of investigations with the atmospheric dispersion module, the models describing early protective actions, the models calculating short-term organ doses and the health effects model of the near range subsystem NE of UFOMOD, a great deal of experience has been gained with methods and evaluation techniques for uncertainty and sensitivity analyses. Especially the influence on results of different sampling techniques and sample sizes, parameter distributions and correlations could be quantified and the usefulness of sensitivity measures for the interpretation of results could be demonstrated. In each submodel investigation, the (5%, 95%)-confidende bounds of the complementary cumulative frequency distributions (CCFDs) of various consequence types (activity concentrations of I-131 and Cs-137, individual acute organ doses, individual risks of nonstochastic health effects, and the number of early deaths) were calculated. The corresponding sensitivity analyses for each of these endpoints led to a list of parameters contributing significantly to the variation of mean values and 99% - fractiles. The most important parameters were extracted and combined for the final overall analysis. (orig.) [de

Early diagnosis of Parkinson's disease: neurospect by trodat-1Tc99m, dopamine transporter marker

International Nuclear Information System (INIS)

Mena, Ismael; Diaz, Fernando; Gomez, Ariel

2001-01-01

Information: We have recently preliminarily reported that NeuroSPECT (NSP) of the Dopamine Transporter (DAT) is a highly sensitive method for early diagnosis of Parkinson disease (27). Objectives: To evaluate the sensitivity of NSP of DAT in patients with de novo hemiparkinsonism and compare the contralateral Vs ipsilateral to the symptomatic side results and also Vs. normal controls, in order to assess the sensitivity to detect pre symptomatic and symptomatic impairment of concentration of DAT (Au)

Early community context, genes, and youth body mass index trajectories: an investigation of gene-community interplay over early life course.

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Wickrama, Kandauda K A S; O'Neal, Catherine Walker; Lee, Tae Kyoung

2013-09-01

To investigate additive and interactive influences of community adversity and cumulative genetic sensitivity on youth body mass index (BMI) trajectories over adolescence and young adulthood. We used latent growth curve modeling to examine BMI trajectories over three waves (1995, 2001, and 2008) of the National Longitudinal Study of Adolescent Health (n = 14,563). We measured genetic sensitivity by a cumulative index of genes associated with serotonin and dopamine functions. Community adversity was positively associated with the initial level and rate of change in BMI trajectories over time. Adolescents experiencing community adversity had a higher BMI at Wave 1 and gained weight more quickly than those who did not live in adverse communities. Community adversity interacted with cumulative genetic sensitivity to explain variation in the rate of change in BMI trajectories. The influence of community adversity was greater for those with more sensitivity alleles than those with fewer sensitivity alleles. Gender, race/ethnicity, and family contexts were also associated with youth BMI trajectories. Community adversity in early adolescence, and its interaction with genes, has far-reaching consequences, including the rate of change in BMI trajectories extending into adulthood. This work has practical implications for future intervention/prevention programs. Published by Elsevier Inc.

An Early Years Toolbox for Assessing Early Executive Function, Language, Self-Regulation, and Social Development: Validity, Reliability, and Preliminary Norms.

Science.gov (United States)

Howard, Steven J; Melhuish, Edward

2017-06-01

Several methods of assessing executive function (EF), self-regulation, language development, and social development in young children have been developed over previous decades. Yet new technologies make available methods of assessment not previously considered. In resolving conceptual and pragmatic limitations of existing tools, the Early Years Toolbox (EYT) offers substantial advantages for early assessment of language, EF, self-regulation, and social development. In the current study, results of our large-scale administration of this toolbox to 1,764 preschool and early primary school students indicated very good reliability, convergent validity with existing measures, and developmental sensitivity. Results were also suggestive of better capture of children's emerging abilities relative to comparison measures. Preliminary norms are presented, showing a clear developmental trajectory across half-year age groups. The accessibility of the EYT, as well as its advantages over existing measures, offers considerably enhanced opportunities for objective measurement of young children's abilities to enable research and educational applications.

Symptoms to pollen and fruits early in life and allergic disease at 4 years of age.

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Mai, X-M; Neuman, A; Ostblom, E; Pershagen, G; Nordvall, L; Almqvist, C; van Hage, M; Wickman, M

2008-11-01

The predictive value of reported early symptoms to pollen or fruits on later allergic disease is unclear. Our aim is to evaluate if symptoms to pollen and/or to fruits early in life are associated with allergic disease and sensitization to pollen at 4 years. The study included 3619 children from the Barn (Children), Allergy, Milieu, Stockholm, Epidemiology project (BAMSE) birth cohort. Reported symptoms of wheeze, sneeze or rash to birch, grass or weed, symptoms (vomiting, diarrhea, rash, facial edema, sneeze, or wheeze) to fruits including tree-nuts at 1 or 2 years of age, and definitions of asthma, rhinitis and eczema at 4 years were derived from questionnaire data. Sensitization to pollen allergens was defined as allergen-specific IgE-antibodies to any pollen (birch/timothy/mugwort) > or =0.35 kU(A)/l. At 1 or 2 years of age, 6% of the children were reported to have pollen-related symptoms, 6% had symptoms to fruits, and 1.4% to both pollen and fruits. Children with symptoms to both pollen and fruits at 1 or 2 years of age had an increased risk for sensitization to any pollen allergen at age 4 (OR(adj) = 4.4, 95% CI = 2.1-9.2). This group of children also had a substantially elevated risk for developing any allergic disease (asthma, rhinitis, or eczema) at 4 years irrespective of sensitization to pollen (OR(adj) = 8.6, 95% CI = 4.5-16.4). The prevalence of reported symptoms to pollen and fruits is very low in early childhood. However, children with early symptoms to both pollen and fruits appear to have a markedly elevated risk for allergic disease.

Isolation of cell cycle-dependent gamma ray-sensitive Chinese hamster ovary cell

International Nuclear Information System (INIS)

Stamato, T.D.; Weinstein, R.; Giaccia, A.; Mackenzie, L.

1983-01-01

A technique for the isolation of gamma ray-sensitive Chinese hamster ovary (CHO) cell mutants is described, which uses nylon cloth replica plating and photography with dark-field illumination to directly monitor colonies for growth after gamma irradiation. Two gamma ray-sensitive mutants were isolated using this method. One of these cells (XR-1) had a two-slope survival curve: an initial steep slope and then a flattening of the curve at about 10% survival. Subsequently, it was found that this cell is sensitive to gamma irradiation in G1, early S, and late G2 phases of the cell cycle, whereas in the resistant phase (late S phase) its survival approaches that of the parental cells. The D37 in the sensitive G1 period is approximately 30 rads, compared with 300 rads of the parental cell. This mutant cell is also sensitive to killing by the DNA breaking agent, bleomycin, but is relatively insensitive to UV light and ethyl methane sulfonate, suggesting that the defect is specific for agents that produce DNA strand breakage

The impact of stress at different life stages on physical health and the buffering effects of maternal sensitivity.

Science.gov (United States)

Farrell, Allison K; Simpson, Jeffry A; Carlson, Elizabeth A; Englund, Michelle M; Sung, Sooyeon

2017-01-01

Many studies indicate that early life stress leads to negative health outcomes in adulthood, and some suggest that high-quality parenting might buffer these effects. Most prior research, however, has relied on cross-sectional retrospective reports of stress and parenting. Our study tests how coder-rated stress and parenting quality assessed at different life stages predict adult health outcomes in a prospective, longitudinal study. Participants were 163 individuals in the Minnesota Longitudinal Study of Risk and Adaptation studied since birth. Physical health was assessed at age 32 with body mass index, self-reports of symptoms and illnesses experienced, and self-ratings of overall physical health. Stress was assessed by coder-rated interviews involving participants or their mothers at 16 time points partitioned into 5 life stages: early childhood, middle childhood, adolescence, young adulthood, and at age 32 (when health was assessed). Parenting quality was measured by coder ratings of each mother's provision of sensitive, responsive support at 7 time points between birth and age 13. Early childhood, adolescent, and concurrent stress predicted adult health outcomes at age 32. Early childhood and adolescent stress, and adolescent and concurrent stress, both showed a "dual-risk" pattern, such that experiencing higher stress at both of these life stages predicted the worst health outcomes. Higher maternal sensitivity, however, buffered these deleterious effects. Our prospective data reveal that early childhood and adolescence are important developmental periods during which stress is influential for adult physical health. However, parenting interventions that promote greater sensitivity may help children in high-stress environments avoid negative adult health outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The impact of stress at different life stages on physical health and the buffering effects of maternal sensitivity

Science.gov (United States)

Farrell, Allison K.; Simpson, Jeffry A.; Carlson, Elizabeth A.; Englund, Michelle M.; Sung, Sooyeon

2016-01-01

Objective Many studies indicate that early life stress leads to negative health outcomes in adulthood, and some suggest that high-quality parenting might buffer these effects. Most prior research, however, has relied on cross-sectional retrospective reports of stress and parenting. Our study tests how coder-rated stress and parenting quality assessed at different life stages predict adult health outcomes in a prospective, longitudinal study. Methods Participants were 163 individuals in the Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) studied since birth. Physical health was assessed at age 32 with BMI, self-reports of symptoms and illnesses experienced, and self-ratings overall physical health. Stress was assessed by coder-rated interviews involving participants or their mothers at 16 time-points partitioned into five life stages: early childhood, middle childhood, adolescence, young adulthood, and at age 32 (when health was assessed). Parenting quality was measured by coder-ratings of each mother's provision of sensitive, responsive support at 7 time-points between birth and age 13. Results Early childhood, adolescent, and concurrent stress predicted adult health outcomes at age 32. Early childhood and adolescent stress, and adolescent and concurrent stress, both showed a “dual-risk” pattern, such that experiencing higher stress at both of these life stages predicted the worst health outcomes. Higher maternal sensitivity, however, buffered these deleterious effects. Conclusions Our prospective data reveals that early childhood and adolescence are important developmental periods during which stress is influential for adult physical health. However, parenting interventions that promote greater sensitivity may help children in high-stress environments avoid negative adult health outcomes. PMID:27669179

Stage sensitivity and dose response of meiotic chromosomes of pollen mother cells of Tradescantia to X-rays

Energy Technology Data Exchange (ETDEWEB)

Ma, T H; Kontos, Jr, G J; Anderson, V A [Western Illinois Univ., Macomb (USA). Dept. of Biological Sciences

1980-05-01

Chromosome damage induced by physical and chemical mutagens can be quantitated by the frequencies of micronuclei (MCN) produced in tetrads of the meiotic pollen mother cells of Tradescantia, i.e. the 'MCN-in-Tetrad' test. The stage sensitivity and dose response of these meiocytes to low exposures of X-rays was studied to improve the efficiency and reliability of this test. Stage sensitivity was determined by observing, at 3 hr intervals, the frequencies of X-ray (35 rads)-induced MCN in tetrads from a series of 16 fixations of tetrad-containing inflorescences. Late stages of meiosis (3-9 hr post-irradiation fixation groups) were insensitive (5-14 MCN/100 tetrads). Relatively high sensitivity was exhibited in the early stages of meiosis. The first and second sensitive peaks (62 and 61 MCN/100 tetrads) centered around the 21 and 39 hr post-irradiation fixation groups respectively. Control groups yielded around 3-4 MCN/100 tetrads. A dose-response relation for MCN was determined by treating early stages of meiotic pollen mother cells with X-ray exposures ranging from 9.5 to 57.5 rads. A linear regression line was established with about 20 MCN/100 tetrads per 10 rad increment.

Validation of Addenbrooke's cognitive examination for detecting early dementia in a Japanese population.

Science.gov (United States)

Yoshida, Hidenori; Terada, Seishi; Honda, Hajime; Ata, Toshie; Takeda, Naoya; Kishimoto, Yuki; Oshima, Etsuko; Ishihara, Takeshi; Kuroda, Shigetoshi

2011-01-30

There is a clear need for brief, but sensitive and specific, cognitive screening instruments for dementia. We assessed the diagnostic accuracy of the Japanese version of Addenbrooke's Cognitive Examination (ACE) in identifying early dementia in comparison with the conventional Mini-Mental State Examination (MMSE). Standard tests for evaluating dementia screening tests were applied. A total of 201 subjects (Alzheimer's disease (AD)=65, frontotemporal dementia (FTD)=24, vascular dementia=26, dementia with Lewy bodies=11, mild cognitive impairment (MCI)=13, and controls=62) participated in this study. The reliability of the ACE was very good (alpha coefficient=0.82). In our patient series, the sensitivity for diagnosing dementia with an ACE score of ≤74 was 0.889 with a specificity of 0.987, and the sensitivity of an ACE score of ≤80 was 0.984 with a specificity of 0.867. The Japanese version of the ACE is a very accurate instrument for the detection of early dementia, and should be widely used in clinical practice. Copyright © 2009 Elsevier Ltd. All rights reserved.

Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

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Dogus Murat Altintas

Full Text Available BACKGROUND: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa among androgen-regulated genes (ARG and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely give rise to cancer. METHODS: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1. RESULTS AND DISCUSSION: By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91 and DLX1 (0.94. CONCLUSIONS: We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could

Application of Nanotrap technology for high sensitivity measurement of urinary outer surface protein A carboxyl-terminus domain in early stage Lyme borreliosis.

Science.gov (United States)

Magni, Ruben; Espina, Benjamin H; Shah, Ketul; Lepene, Benjamin; Mayuga, Christine; Douglas, Temple A; Espina, Virginia; Rucker, Sally; Dunlap, Ross; Petricoin, Emanuel F Iii; Kilavos, Mary Frekko; Poretz, Donald M; Irwin, Gilbert R; Shor, Samuel M; Liotta, Lance A; Luchini, Alessandra

2015-11-04

Prompt antibiotic treatment of early stage Lyme borreliosis (LB) prevents progression to severe multisystem disease. There is a clinical need to improve the diagnostic specificity of early stage Lyme assays in the period prior to the mounting of a robust serology response. Using a novel analyte harvesting nanotechnology, Nanotrap particles, we evaluated urinary Borrelia Outer surface protein A (OspA) C-terminus peptide in early stage LB before and after treatment, and in patients suspected of late stage disseminated LB. We employed Nanotrap particles to concentrate urinary OspA and used a highly specific anti-OspA monoclonal antibody (mAb) as a detector of the C-terminus peptides. We mapped the mAb epitope to a narrow specific OspA C-terminal domain OspA236-239 conserved across infectious Borrelia species but with no homology to human proteins and no cross-reactivity with relevant viral and non-Borrelia bacterial proteins. 268 urine samples from patients being evaluated for all categories of LB were collected in a LB endemic area. The urinary OspA assay, blinded to outcome, utilized Nanotrap particle pre-processing, western blotting to evaluate the OspA molecular size, and OspA peptide competition for confirmation. OspA test characteristics: sensitivity 1.7 pg/mL (lowest limit of detection), % coefficient of variation (CV) = 8 %, dynamic range 1.7-30 pg/mL. Pre-treatment, 24/24 newly diagnosed patients with an erythema migrans (EM) rash were positive for urinary OspA while false positives for asymptomatic patients were 0/117 (Chi squared p antibiotic therapy, 10/10 were positive for urinary OspA. Urinary OspA of 8/8 patients switched from detectable to undetectable following symptom resolution post-treatment. Specificity of the urinary OspA test for the clinical symptoms was 40/40. Specificity of the urinary OspA antigen test for later serology outcome was 87.5 % (21 urinary OspA positive/24 serology positive, Chi squared p = 4.072e(-15)). 41 of 100 patients under

Enduring neurobehavioral effects of early life trauma mediated through learning and corticosterone suppression

Directory of Open Access Journals (Sweden)

Stephanie Moriceau

2009-09-01

Full Text Available Early life trauma alters later life emotions, including fear. To better understand mediating mechanisms, we subjected pups to either predictable or unpredictable trauma, in the form of paired or unpaired odor-0.5mA shock conditioning which, during a sensitive period, produces an odor preference and no learning respectively. Fear conditioning and its neural correlates were then assessed after the sensitive period at postnatal day (PN13 or in adulthood, ages when amygdala-dependent fear occurs. Our results revealed that paired odor-shock conditioning starting during the sensitive period (PN8-12 blocked fear conditioning in older infants (PN13 and pups continued to express olfactory bulb-dependent odor preference learning. This PN13 fear learning inhibition was also associated with suppression of shock-induced corticosterone, although the age appropriate amygdala-dependent fear learning was reinstated with systemic corticosterone (3mg/kg during conditioning. On the other hand, sensitive period odor-shock conditioning did not prevent adult fear conditioning, although freezing, amygdala and hippocampal 2-DG uptake and corticosterone levels were attenuated compared to adult conditioning without infant conditioning. Normal levels of freezing, amygdala and hippocampal 2-DG uptake were induced with systemic corticosterone (5mg/kg during adult conditioning. These results suggest that the contingency of early life trauma mediates at least some effects of early life stress through learning and suppression of corticosterone levels. However, developmental differences between infants and adults are expressed with PN13 infants’ learning consistent with the original learned preference, while adult conditioning overrides the original learned preference with attenuated amygdala-dependent fear learning.

M dwarfs from the Einstein extended medium sensitivity survey

International Nuclear Information System (INIS)

Fleming, T.A.; Liebert, J.; Gioia, I.M.; Maccacaro, T.

1988-01-01

A complete sample of X-ray selected M dwarfs are presented which were serendipitously detected in the extended Einstein Observatory Medium Sensitivity Survey (MSS). The MSS detected only early M dwarfs (type MO through M5), 84 percent of which were emission stars (i.e., type Me V). It was calculated that the X-ray luminosity function for early M dwarfs with a log Lx greater than 27.6 and, by comparison to optical luminosity functions, find that about 25 percent of all early M dwarfs emit X-rays at a level greater than log Lx = 27.6. This result is compared to luminosity function estimates from optically selected samples and discussed in light of the sample's kinematic and mean age. Also presented is H alpha and Ca II K line fluxes for each member of the sample and it is shown that the surface H alpha and Ca II K luminosities do indeed correlate with Lx. The significance of this effect to theories of chromospheric and coronal heating is explained. 76 references

Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells.

Science.gov (United States)

Ma, Jiao; Lu, Pin; Guo, Ailin; Cheng, Shuhua; Zong, Hongliang; Martin, Peter; Coleman, Morton; Wang, Y Lynn

2014-09-01

Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. A multicentre phase 2 trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) demonstrated a remarkable response rate. However, approximately one-third of patients have primary resistance to the drug while other patients appear to lose response and develop secondary resistance. Understanding the molecular mechanisms underlying ibrutinib sensitivity is of paramount importance. In this study, we investigated cell lines and primary MCL cells that display differential sensitivity to ibrutinib. We found that the primary cells display a higher BTK activity than normal B cells and MCL cells show differential sensitivity to BTK inhibition. Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities. Interestingly, inhibition of ERK1/2 and AKT, but not BTK phosphorylation per se, correlates well with cellular response to BTK inhibition in cell lines as well as in primary tumours. Our study suggests that, to prevent primary resistance or to overcome secondary resistance to BTK inhibition, a combinatory strategy that targets multiple components or multiple pathways may represent the most effective approach. © 2014 John Wiley & Sons Ltd.

Comparison of Swirl Sign and Black Hole Sign in Predicting Early Hematoma Growth in Patients with Spontaneous Intracerebral Hemorrhage.

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Xiong, Xin; Li, Qi; Yang, Wen-Song; Wei, Xiao; Hu, Xi; Wang, Xing-Chen; Zhu, Dan; Li, Rui; Cao, Du; Xie, Peng

2018-01-29

BACKGROUND Early hematoma growth is associated with poor outcome in patients with spontaneous intracerebral hemorrhage (ICH). The swirl sign (SS) and the black hole sign (BHS) are imaging markers in ICH patients. The aim of this study was to compare the predictive value of these 2 signs for early hematoma growth. MATERIAL AND METHODS ICH patients were screened for the appearance of the 2 signs within 6 h after onset of symptoms. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 2 signs in predicting early hematoma growth were assessed. The accuracy of the 2 signs in predicting early hematoma growth was analyzed by receiver-operator analysis. RESULTS A total of 200 patients were enrolled in this study. BHS was found in 30 (15%) patients, and SS was found in 70 (35%) patients. Of the 71 patients with early hematoma growth, BHS was found on initial computed tomography scans in 24 (33.8%) and SS in 33 (46.5%). The sensitivity, specificity, PPV, and NPV of BHS for predicting early hematoma growth were 33.8%, 95.3%, 80.0%, and 72.0%, respectively. The sensitivity, specificity, PPV, and NPV of SS were 46.5%, 71.3%, 47.0%, and 71.0%, respectively. The area under the curve was 0.646 for BHS and 0.589 for SS (P=0.08). Multivariate logistic regression showed that presence of BHS is an independent predictor of early hematoma growth. CONCLUSIONS The Black hole sign seems to be good predictor for hematoma growth. The presence of swirl sign on admission CT does not independently predict hematoma growth in patients with ICH.

Circulating cell-free nucleosomes as biomarkers for early detection of colorectal cancer

DEFF Research Database (Denmark)

Rasmussen, Louise; Christensen, Ib Jarle; Herzog, Marielle

2018-01-01

-malignant findings. Predictor models including ccfn containing 5-methylcytosine DNA, CEA, age and gender improved results (AUCROC = 0.736, sensitivity = 0.37 at specificity = 0.90). Further improvement was achieved in discrimination of individuals with CRC from individuals with clean colorectum (AUCROC = 0.......840, sensitivity = 0.57 at specificity = 0.90). The levels of ccfn among patients with CRC appeared to be stage-independent. In conclusion, the performance of the developed predictor models is potentially promising in early detection of CRC....

Use and discontinuation of hormone replacement therapy in women with myocardial infarction: a nationwide study

DEFF Research Database (Denmark)

Bretler, Ditte-Marie; Hansen, P. R.; Abildstrom, S. Z.

2011-01-01

of HRT were vaginal oestrogen and oral oestrogen alone (46.6% and 28.7%, respectively). The percentage of women who continued HRT during the first year after discharge was 85.0% in the period 2000-2002 and had decreased to 79.6% in the period 2003-2005. Vaginal oestrogen use was associated with overall...... pharmacies. Characteristics associated with HRT use at time of MI and subsequent HRT discontinuation were analysed by multivariable logistic regression. RESULTS In the study period, 34 778 women were discharged after MI. Of these, 3979 (11.4%) received HRT at the time of MI and their most used categories...... The majority of women experiencing an MI during ongoing HRT continued HRT after discharge and this pattern of HRT use did not change markedly after 2002....

Sensitivity and Specificity of Suspected Case Definition Used during West Africa Ebola Epidemic.

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Hsu, Christopher H; Champaloux, Steven W; Keïta, Sakoba; Martel, Lise; Bilivogui, Pepe; Knust, Barbara; McCollum, Andrea M

2018-01-01

Rapid early detection and control of Ebola virus disease (EVD) is contingent on accurate case definitions. Using an epidemic surveillance dataset from Guinea, we analyzed an EVD case definition developed by the World Health Organization (WHO) and used in Guinea. We used the surveillance dataset (March-October 2014; n = 2,847 persons) to identify patients who satisfied or did not satisfy case definition criteria. Laboratory confirmation determined cases from noncases, and we calculated sensitivity, specificity and predictive values. The sensitivity of the defintion was 68.9%, and the specificity of the definition was 49.6%. The presence of epidemiologic risk factors (i.e., recent contact with a known or suspected EVD case-patient) had the highest sensitivity (74.7%), and unexplained deaths had the highest specificity (92.8%). Results for case definition analyses were statistically significant (pdefinition used in Guinea contributed to improved overall sensitivity and specificity.

Early Life Experiences and Exercise Associate with Canine Anxieties.

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Katriina Tiira

Full Text Available Personality and anxiety disorders across species are affected by genetic and environmental factors. Shyness-boldness personality continuum exists across species, including the domestic dog, with a large within- and across-breed variation. Domestic dogs are also diagnosed for several anxiety-related behavioral conditions, such as generalized anxiety disorders, phobias, and separation anxiety. Genetic and environmental factors contributing to personality and anxiety are largely unknown. We collected questionnaire data from a Finnish family dog population (N = 3264 in order to study the associating environmental factors for canine fearfulness, noise sensitivity, and separation anxiety. Early life experiences and exercise were found to associate with anxiety prevalence. We found that fearful dogs had less socialization experiences (p = 0.002 and lower quality of maternal care (p < 0.0001 during puppyhood. Surprisingly, the largest environmental factor associating with noise sensitivity (p < 0.0001 and separation anxiety (p = 0.007 was the amount of daily exercise; dogs with noise sensitivity and separation anxiety had less daily exercise. Our findings suggest that dogs share many of the same environmental factors that contribute to anxiety in other species as well, such as humans and rodents. Our study highlights the importance of early life experiences, especially the quality of maternal care and daily exercise for the welfare and management of the dogs, and reveals important confounding factors to be considered in the genetic characterization of canine anxiety.

Effectiveness of near-infrared transillumination in early caries diagnosis

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Mirela Marinova-Takorova

2016-11-01

Full Text Available Early caries detection is essential for minimal intervention dentistry, since it could give the opportunity to reverse the process and eliminate or at least postpone the surgical treatment. The aim of the present study was to evaluate the effectiveness of near-infrared transillumination in early caries diagnosis for both occlusal and proximal lesions. Thirty-eight adult patients were included in the study. The results from the visual, radiological and near-infrared transillumination examination for proximal caries lesions were compared. The diagnostic abilities of these methods for occlusal lesions were assayed on 60 teeth. The three methods showed a very high level of correlation when there were caries lesions involving the enamel and dentin. Concerning proximal caries involving only the enamel, the visual--tactile diagnosis proved to be insufficiently sensitive even with the use of magnification. Radiographic examination and near-infrared transillumination correlated significantly, but the latter was more sensitive. Radiographic examination proved to be insufficiently sensitive for occlusal lesions. The results obtained with the near-infrared fluorescence correlated most with the visual–tactile examination. These results suggest that near-infrared transillumination is an effective method for diagnosis of lesions both involving only the enamel and involving the enamel and dentin. It could be used for both occlusal and proximal caries lesions and it could eventually substitute radiographic bitewings, especially in children and pregnant women, due to its efficiency as a diagnostic tool and the absence of radiation.

Interpreting the gamma statistic in phylogenetic diversification rate studies: a rate decrease does not necessarily indicate an early burst.

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Fordyce, James A

2010-07-23

Phylogenetic hypotheses are increasingly being used to elucidate historical patterns of diversification rate-variation. Hypothesis testing is often conducted by comparing the observed vector of branching times to a null, pure-birth expectation. A popular method for inferring a decrease in speciation rate, which might suggest an early burst of diversification followed by a decrease in diversification rate is the gamma statistic. Using simulations under varying conditions, I examine the sensitivity of gamma to the distribution of the most recent branching times. Using an exploratory data analysis tool for lineages through time plots, tree deviation, I identified trees with a significant gamma statistic that do not appear to have the characteristic early accumulation of lineages consistent with an early, rapid rate of cladogenesis. I further investigated the sensitivity of the gamma statistic to recent diversification by examining the consequences of failing to simulate the full time interval following the most recent cladogenic event. The power of gamma to detect rate decrease at varying times was assessed for simulated trees with an initial high rate of diversification followed by a relatively low rate. The gamma statistic is extraordinarily sensitive to recent diversification rates, and does not necessarily detect early bursts of diversification. This was true for trees of various sizes and completeness of taxon sampling. The gamma statistic had greater power to detect recent diversification rate decreases compared to early bursts of diversification. Caution should be exercised when interpreting the gamma statistic as an indication of early, rapid diversification.

Interpreting the gamma statistic in phylogenetic diversification rate studies: a rate decrease does not necessarily indicate an early burst.

Directory of Open Access Journals (Sweden)

James A Fordyce

Full Text Available BACKGROUND: Phylogenetic hypotheses are increasingly being used to elucidate historical patterns of diversification rate-variation. Hypothesis testing is often conducted by comparing the observed vector of branching times to a null, pure-birth expectation. A popular method for inferring a decrease in speciation rate, which might suggest an early burst of diversification followed by a decrease in diversification rate is the gamma statistic. METHODOLOGY: Using simulations under varying conditions, I examine the sensitivity of gamma to the distribution of the most recent branching times. Using an exploratory data analysis tool for lineages through time plots, tree deviation, I identified trees with a significant gamma statistic that do not appear to have the characteristic early accumulation of lineages consistent with an early, rapid rate of cladogenesis. I further investigated the sensitivity of the gamma statistic to recent diversification by examining the consequences of failing to simulate the full time interval following the most recent cladogenic event. The power of gamma to detect rate decrease at varying times was assessed for simulated trees with an initial high rate of diversification followed by a relatively low rate. CONCLUSIONS: The gamma statistic is extraordinarily sensitive to recent diversification rates, and does not necessarily detect early bursts of diversification. This was true for trees of various sizes and completeness of taxon sampling. The gamma statistic had greater power to detect recent diversification rate decreases compared to early bursts of diversification. Caution should be exercised when interpreting the gamma statistic as an indication of early, rapid diversification.

Profile of sensitization to allergens in children with atopic dermatitis assisting to Allergology Service of University Hospital, Nuevo Leon, Mexico

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Adrián Yong-Rodríguez

2015-04-01

Conclusion: Children with atopic dermatitis are often sensitized to high protease activity aeroallergens, polysensitization is very common and the association with airway allergy is seen early in life. Sensitization to food is also common in these patients, but only a small percentage showed a response large enough to be associated with disease severity.

Orthographic Context Sensitivity in Vowel Decoding by Portuguese Monolingual and Portuguese-English Bilingual Children

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Vale, Ana Paula

2011-01-01

This study examines the pronunciation of the first vowel in decoding disyllabic pseudowords derived from Portuguese words. Participants were 96 Portuguese monolinguals and 52 Portuguese-English bilinguals of equivalent Portuguese reading levels. The results indicate that sensitivity to vowel context emerges early, both in monolinguals and in…

The Transient High Energy Sky and Early Universe Surveyor (THESEUS)

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Amati, Lorenzo; O'Brien, Paul T.; Götz, Diego

2016-07-01

The Transient High Energy Sky and Early Universe Surveyor (THESEUS) is a mission concept under development by a large international collaboration aimed at exploiting gamma-ray bursts for investigating the early Universe. The main scientific objectives of THESEUS include: investigating the star formation rate and metallicity evolution of the ISM and IGM up to redshift 9-10, detecting the first generation (pop III) of stars, studying the sources and physics of re-ionization, detecting the faint end of galaxies luminosity function. These goals will be achieved through a unique combination of instruments allowing GRB detection and arcmin localization over a broad FOV (more than 1sr) and an energy band extending from several MeVs down to 0.3 keV with unprecedented sensitivity, as well as on-board prompt (few minutes) follow-up with a 0.6m class IR telescope with both imaging and spectroscopic capabilities. Such instrumentation will also allow THESEUS to unveil and study the population of soft and sub-energetic GRBs, and, more in general, to perform monitoring and survey of the X-ray sky with unprecedented sensitivity.

The diagnostic value of sacroiliac CT for detecting early changes of ankylosing spondylitis

Energy Technology Data Exchange (ETDEWEB)

Park, Ju Hyun; Park, Ji Seon; Ryu, Kyung Nam [Kyunghee University Medical Center, Seoul (Korea, Republic of); Jin, Wook [East-West Neo Medical Center, Seoul (Korea, Republic of)

2007-02-15

We wanted to evaluate the diagnostic value of the various findings on sacroiliac CT for detecting the early changes of ankylosing spondylitis (AS). Between April 2005 and March 2006, 51 sacroiliac CT images with the clinical suspicion of AS, but no definite evidence of AS on the plain radiograph only, were retrospectively reviewed. Finally, 36 patients (mean age: 28.6 years; 34 males and 2 females), who were clinically diagnosed as AS (AS group, n = 26) or they had no evidence of AS (non-AS group, n = 10), were evaluated. Two musculoskeletal radiologists analyzed the presence of marginal irregularity, bony erosion and subchondral sclerosis. A statistical analysis was performed to evaluate the incidence, sensitivity and specificity of each finding. Marginal irregularity was seen in 21 of 26 AS subjects, and in 8 of 10 non-AS subjects. Bony erosion was only seen in 13 of 26 AS subjects. Subchondral sclerosis was observed in 19 of 26 AS subjects and in 8 of 10 non-AS subjects. The sensitivity/specificity for each findings were 72.4%/28.6%, 100%/43.5% and 70.4%/22.2%, respectively. Except for bony erosions, these results showed no statistical significance ({rho} = .006). Bony erosion on CT is a very sensitive finding for the early changes of AS, whereas marginal irregularity or subchondral sclerosis is not so helpful in differentiating AS from non-AS. Attention to these results may further enhance the accurate diagnosis of the early changes in AS.

A longitudinal evaluation of Treponema pallidum PCR testing in early syphilis

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Shields Matt

2012-12-01

Full Text Available Abstract Background Syphilis is a growing public health problem among men who have sex with men (MSM globally. Rapid and accurate detection of syphilis is vital to ensure patients and their contacts receive timely treatment and reduce ongoing transmission. Methods We evaluated a PCR assay for the diagnosis of Treponema pallidum using swabs of suspected early syphilis lesions in longitudinally assessed MSM. Results We tested 260 MSM for T pallidum by PCR on 288 occasions: 77 (26.7% had early syphilis that was serologically confirmed at baseline or within six weeks, and 211 (73.3% remained seronegative for syphilis. Of 55 men with primary syphilis, 49 were PCR positive, giving a sensitivity of 89.1% (95% CI: 77.8%-95.9% and a specificity of 99.1% (95% CI: 96.5%-99.9%. Of 22 men with secondary syphilis, 11 were PCR positive, giving a sensitivity of 50% (95% CI: 28.2%-71.8% and a specificity of 100% (95% CI: 66.4%-71.8%. Of the 77 syphilis cases, 43 (56% were HIV positive and the sensitivity and specificity of the PCR test did not vary by HIV status. The PCR test was able to detect up to five (10% primary infections that were initially seronegative, including one HIV positive man with delayed seroconversion to syphilis (72 to 140 days and one HIV positive man who did not seroconvert to syphilis over 14 months follow-up. Both men had been treated for syphilis within a week of the PCR test. Conclusions T pallidum PCR is a potentially powerful tool for the early diagnosis of primary syphilis, particularly where a serological response has yet to develop.

Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System.

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Douw, Gooske; Huisman-de Waal, Getty; van Zanten, Arthur R H; van der Hoeven, Johannes G; Schoonhoven, Lisette

2017-09-01

To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. In 3522 patients, 102 (2·9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number

Partial-Breast Irradiation Versus Whole-Breast Irradiation for Early-Stage Breast Cancer: A Cost-Effectiveness Analysis

International Nuclear Information System (INIS)

Sher, David J.; Wittenberg, Eve; Suh, W. Warren; Taghian, Alphonse G.; Punglia, Rinaa S.

2009-01-01

Purpose: Accelerated partial-breast irradiation (PBI) is a new treatment paradigm for patients with early-stage breast cancer. Although PBI may lead to greater local recurrence rates, it may be cost-effective because of better tolerability and lower cost. We aim to determine the incremental cost-effectiveness of PBI compared with whole-breast radiation therapy (WBRT) for estrogen receptor-positive postmenopausal women treated for early-stage breast cancer. Methods and Materials: We developed a Markov model to describe health states in the 15 years after radiotherapy for early-stage breast cancer. External beam (EB) and MammoSite (MS) PBI were considered and assumed to be equally effective, but carried different costs. Patients received tamoxifen, but not chemotherapy. Utilities, recurrence risks, and costs were adapted from the literature; the baseline utility for no disease after radiotherapy was set at 0.92. Probabilistic sensitivity analyses were performed to model uncertainty in the PBI hazard ratio, recurrence pattern, and patient utilities. Costs (in 2004 US dollars) and quality-adjusted life-years were discounted at 3%/y. Results: The incremental cost-effectiveness ratio for WBRT compared with EB-PBI was $630,000/quality-adjusted life-year; WBRT strongly dominated MS-PBI. One-way sensitivity analysis found that results were sensitive to PBI hazard ratio, recurrence pattern, baseline recurrence risk, and no evidence of disease PBI utility values. Probabilistic sensitivity showed that EB-PBI was the most cost-effective technique over a wide range of assumptions and societal willingness-to-pay values. Conclusions: EB-PBI was the most cost-effective strategy for postmenopausal women with early-stage breast cancer. Unless the quality of life after MS-PBI proves to be superior, it is unlikely to be cost-effective.

Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.

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Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L

2017-09-01

Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.

Sensitive measurement of fluctuations in the cosmic microwave background

Energy Technology Data Exchange (ETDEWEB)

Davies, R D; Watson, R A; Daintree, E J; Hopkins, J; Lasenby, A N; Beckman, J; Sanchez-Almeida, J; Rebolo, R

1987-04-02

Extensive high sensitivity observations of the cosmic microwave background have been made on an angular scale of 8/sup 0/ covering a substantial fraction of the northern sky. An observed anisotropy in the sky emission at a level of ..delta..T/T = 3.7 x 10/sup -5/ has been detected (T is temperature). This level should strictly be interpreted as an upper limit to the cosmic microwave background fluctuations. It is possibly the direct imprint of density perturbations in the early Universe.

Sensitive measurement of fluctuations in the cosmic microwave background

International Nuclear Information System (INIS)

Davies, R.D.; Watson, R.A.; Daintree, E.J.; Hopkins, J.; Lasenby, A.N.

1987-01-01

Extensive high sensitivity observations of the cosmic microwave background have been made on an angular scale of 8 0 covering a substantial fraction of the northern sky. An observed anisotropy in the sky emission at a level of ΔT/T = 3.7 x 10 -5 has been detected (T is temperature). This level should strictly be interpreted as an upper limit to the cosmic microwave background fluctuations. It is possibly the direct imprint of density perturbations in the early Universe. (author)

Drought timing and local climate determine the sensitivity of eastern temperate forests to drought.

Science.gov (United States)

D'Orangeville, Loïc; Maxwell, Justin; Kneeshaw, Daniel; Pederson, Neil; Duchesne, Louis; Logan, Travis; Houle, Daniel; Arseneault, Dominique; Beier, Colin M; Bishop, Daniel A; Druckenbrod, Daniel; Fraver, Shawn; Girard, François; Halman, Joshua; Hansen, Chris; Hart, Justin L; Hartmann, Henrik; Kaye, Margot; Leblanc, David; Manzoni, Stefano; Ouimet, Rock; Rayback, Shelly; Rollinson, Christine R; Phillips, Richard P

2018-02-20

Projected changes in temperature and drought regime are likely to reduce carbon (C) storage in forests, thereby amplifying rates of climate change. While such reductions are often presumed to be greatest in semi-arid forests that experience widespread tree mortality, the consequences of drought may also be important in temperate mesic forests of Eastern North America (ENA) if tree growth is significantly curtailed by drought. Investigations of the environmental conditions that determine drought sensitivity are critically needed to accurately predict ecosystem feedbacks to climate change. We matched site factors with the growth responses to drought of 10,753 trees across mesic forests of ENA, representing 24 species and 346 stands, to determine the broad-scale drivers of drought sensitivity for the dominant trees in ENA. Here we show that two factors-the timing of drought, and the atmospheric demand for water (i.e., local potential evapotranspiration; PET)-are stronger drivers of drought sensitivity than soil and stand characteristics. Drought-induced reductions in tree growth were greatest when the droughts occurred during early-season peaks in radial growth, especially for trees growing in the warmest, driest regions (i.e., highest PET). Further, mean species trait values (rooting depth and ψ 50 ) were poor predictors of drought sensitivity, as intraspecific variation in sensitivity was equal to or greater than interspecific variation in 17 of 24 species. From a general circulation model ensemble, we find that future increases in early-season PET may exacerbate these effects, and potentially offset gains in C uptake and storage in ENA owing to other global change factors. © 2018 John Wiley & Sons Ltd.

Parenting begets parenting: A neurobiological perspective on early adversity and the transmission of parenting styles across generations.

Science.gov (United States)

Lomanowska, A M; Boivin, M; Hertzman, C; Fleming, A S

2017-02-07

The developing brains of young children are highly sensitive to input from their social environment. Nurturing social experience during this time promotes the acquisition of social and cognitive skills and emotional competencies. However, many young children are confronted with obstacles to healthy development, including poverty, inappropriate care, and violence, and their enhanced sensitivity to the social environment means that they are highly susceptible to these adverse childhood experiences. One source of social adversity in early life can stem from parenting that is harsh, inconsistent, non-sensitive or hostile. Parenting is considered to be the cornerstone of early socio-emotional development and an adverse parenting style is associated with adjustment problems and a higher risk of developing mood and behavioral disorders. Importantly, there is a growing literature showing that an important predictor of parenting behavior is how parents, especially mothers, were parented themselves. In this review, we examine how adversity in early-life affects mothering behavior in later-life and how these effects may be perpetuated inter-generationally. Relying on studies in humans and animal models, we consider evidence for the intergenerational transmission of mothering styles. We then describe the psychological underpinnings of mothering, including responsiveness to young, executive function and affect, as well as the physiological mediators of mothering behavior, including hormones, brain regions and neurotransmitters, and we consider how development in these relevant domains may be affected by adversity experienced in early life. Finally, we explore how genes and early experience interact to predict mothering behavior, including the involvement of epigenetic mechanisms. Understanding how adverse parenting begets adverse parenting in the next generation is critical for designing interventions aimed at preventing this intergenerational cycle of early adversity