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Showing papers by "Laval University published in 2005"


Journal ArticleDOI
15 Dec 2005-Nature
TL;DR: It is shown that ATP-stimulated microglia cause a depolarizing shift in the anion reversal potential (Eanion) in spinal lamina I neurons, and that BDNF is a crucial signalling molecule betweenmicroglia and neurons.
Abstract: Neuropathic pain that occurs after peripheral nerve injury depends on the hyperexcitability of neurons in the dorsal horn of the spinal cord. Spinal microglia stimulated by ATP contribute to tactile allodynia, a highly debilitating symptom of pain induced by nerve injury. Signalling between microglia and neurons is therefore an essential link in neuropathic pain transmission, but how this signalling occurs is unknown. Here we show that ATP-stimulated microglia cause a depolarizing shift in the anion reversal potential (E(anion)) in spinal lamina I neurons. This shift inverts the polarity of currents activated by GABA (gamma-amino butyric acid), as has been shown to occur after peripheral nerve injury. Applying brain-derived neurotrophic factor (BDNF) mimics the alteration in E(anion). Blocking signalling between BDNF and the receptor TrkB reverses the allodynia and the E(anion) shift that follows both nerve injury and administration of ATP-stimulated microglia. ATP stimulation evokes the release of BDNF from microglia. Preventing BDNF release from microglia by pretreating them with interfering RNA directed against BDNF before ATP stimulation also inhibits the effects of these cells on the withdrawal threshold and E(anion). Our results show that ATP-stimulated microglia signal to lamina I neurons, causing a collapse of their transmembrane anion gradient, and that BDNF is a crucial signalling molecule between microglia and neurons. Blocking this microglia-neuron signalling pathway may represent a therapeutic strategy for treating neuropathic pain.

1,768 citations


Journal ArticleDOI
TL;DR: A review of recent developments in preparation, characterization, properties, crystallization behaviors, melt rheology, processing, and future applications possibilities of biodegradable polymers and their layered silicate nanocomposites can be found in this paper.

1,482 citations


Journal ArticleDOI
TL;DR: Selective CB1-receptor blockade with rimonabant significantly reduces body weight and waist circumference and improves the profile of several metabolic risk factors in high-risk patients who are overweight or obese and have an atherogenic dyslipidemia.
Abstract: background Rimonabant, a selective cannabinoid-1 receptor (CB 1 ) blocker, has been shown to reduce body weight and improve cardiovascular risk factors in obese patients. The Rimonabant in Obesity–Lipids (RIO-Lipids) study examined the effects of rimonabant on metabolic risk factors, including adiponectin levels, in high-risk patients who are overweight or obese and have dyslipidemia. methods We randomly assigned 1036 overweight or obese patients (body-mass index [the weight in kilograms divided by the square of the height in meters], 27 to 40) with untreated dyslipidemia (triglyceride levels >1.69 to 7.90 mmol per liter, or a ratio of cholesterol to high-density lipoprotein [HDL] cholesterol of >4.5 among women and >5 among men) to double-blinded therapy with either placebo or rimonabant at a dose of 5 mg or 20 mg daily for 12 months in addition to a hypocaloric diet. results The rates of completion of the study were 62.6 percent, 60.3 percent, and 63.9 percent in the placebo group, the group receiving 5 mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively. The most frequent adverse events resulting in discontinuation of the drug were depression, anxiety, and nausea. As compared with placebo, rimonabant at a dose of 20 mg was associated with a significant (P<0.001) mean weight loss (repeated-measures method, i6.7±0.5 kg, and last-observation-carriedforward analyses, i5.4±0.4 kg), reduction in waist circumference (repeated-measures method, i5.8±0.5 cm, and last-observation-carried-forward analyses, i4.7±0.5 cm), increase in HDL cholesterol (repeated-measures method, +10.0±1.6 percent, and lastobservation-carried-forward analyses, +8.1±1.5 percent), and reduction in triglycerides (repeated-measures method, i13.0±3.5 percent, and last-observation-carriedforward analyses, i12.4±3.2 percent). Rimonabant at a dose of 20 mg also resulted in an increase in plasma adiponectin levels (repeated-measures method, 57.7 percent, and last-observation-carried-forward analyses, 46.2 percent; P<0.001), for a change that was partly independent of weight loss alone. conclusions Selective CB 1 -receptor blockade with rimonabant significantly reduces body weight and waist circumference and improves the profile of several metabolic risk factors in high-risk patients who are overweight or obese and have an atherogenic dyslipidemia.

1,364 citations


Journal ArticleDOI
01 May 2005-Ecology
TL;DR: In this article, the authors investigated whether the observed trophic cascade might have a behavioral basis by exploring environmental factors influencing the movements of 13 female elk equipped with GPS radio collars and found that elk movements were influenced by multiple factors, such as the distance from roads, the presence of a steep slope along the step, and the cover type in which they ended.
Abstract: A trophic cascade recently has been reported among wolves, elk, and aspen on the northern winter range of Yellowstone National Park, Wyoming, USA, but the mechanisms of indirect interactions within this food chain have yet to be established. We investigated whether the observed trophic cascade might have a behavioral basis by exploring environmental factors influencing the movements of 13 female elk equipped with GPS radio collars. We developed a simple statistical approach that can unveil the concurrent influence of several environmental features on animal movements. Paths of elk traveling on their winter range were broken down into steps, which correspond to the straight-line segment between successive locations at 5-hour intervals. Each observed step was paired with 200 random steps having the same starting point, but differing in length and/or direction. Comparisons between the characteristics of observed and random steps using conditional logistic regression were used to model environmental features influencing movement patterns. We found that elk movements were influenced by multiple factors, such as the distance from roads, the presence of a steep slope along the step, and the cover type in which they ended. The influence of cover type on elk movements depended on the spatial distribution of wolves across the northern winter range of the park. In low wolf-use areas, the relative preference for end point locations of steps followed: aspen stands > open areas > conifer forests. As the risks of wolf encounter increased, the preference of elk for aspen stands gradually decreased, and selection became strongest for steps ending in conifer forests in high wolf-use areas. Our study clarifies the behavioral mechanisms involved in the trophic cascade of Yellowstone's wolf-elk-aspen system: elk respond to wolves on their winter range by a shift in habitat selection, which leads to local reductions in the use of aspen by elk.

1,132 citations


Journal ArticleDOI
TL;DR: This paper presents the 12th update of the human obesity gene map, which incorporates published results up to the end of October 2005, and shows putative loci on all chromosomes except Y.
Abstract: This paper presents the eleventh update of the human obesity gene map, which incorporates published results up to the end of October 2004. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, transgenic and knockout murine models relevant to obesity, quantitative trait loci (QTLs) from animal cross-breeding experiments, association studies with candidate genes, and linkages from genome scans is reviewed. As of October 2004, 173 human obesity cases due to single-gene mutations in 10 different genes have been reported, and 49 loci related to Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. There are 166 genes which, when mutated or expressed as transgenes in the mouse, result in phenotypes that affect body weight and adiposity. The number of QTLs reported from animal models currently reaches 221. The number of human obesity QTLs derived from genome scans continues to grow, and we have now 204 QTLs for obesity-related phenotypes from 50 genome-wide scans. A total of 38 genomic regions harbor QTLs replicated among two to four studies. The number of studies reporting associations between DNA sequence variation in specific genes and obesity phenotypes has also increased considerably with 358 findings of positive associations with 113 candidate genes. Among them, 18 genes are supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. Overall, >600 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. The electronic version of the map with links to useful publications and genomic and other relevant sites can be found at http://obesitygene.pbrc.edu.

955 citations


Journal ArticleDOI
TL;DR: In this paper, a comparison of eight iron experiments shows that maximum Chl a, the maximum DIC removal, and the overall DIC/Fe efficiency all scale inversely with depth of the wind mixed layer (WML) defining the light environment.
Abstract: Comparison of eight iron experiments shows that maximum Chl a, the maximum DIC removal, and the overall DIC/Fe efficiency all scale inversely with depth of the wind mixed layer (WML) defining the light environment. Moreover, lateral patch dilution, sea surface irradiance, temperature, and grazing play additional roles. The Southern Ocean experiments were most influenced by very deep WMLs. In contrast, light conditions were most favorable during SEEDS and SERIES as well as during IronEx-2. The two extreme experiments, EisenEx and SEEDS, can be linked via EisenEx bottle incubations with shallower simulated WML depth. Large diatoms always benefit the most from Fe addition, where a remarkably small group of thriving diatom species is dominated by universal response of Pseudo-nitzschia spp. Significant response of these moderate (10–30 μm), medium (30–60 μm), and large (>60 μm) diatoms is consistent with growth physiology determined for single species in natural seawater. The minimum level of “dissolved” Fe (filtrate < 0.2 μm) maintained during an experiment determines the dominant diatom size class. However, this is further complicated by continuous transfer of original truly dissolved reduced Fe(II) into the colloidal pool, which may constitute some 75% of the “dissolved” pool. Depth integration of carbon inventory changes partly compensates the adverse effects of a deep WML due to its greater integration depths, decreasing the differences in responses between the eight experiments. About half of depth-integrated overall primary productivity is reflected in a decrease of DIC. The overall C/Fe efficiency of DIC uptake is DIC/Fe ∼ 5600 for all eight experiments. The increase of particulate organic carbon is about a quarter of the primary production, suggesting food web losses for the other three quarters. Replenishment of DIC by air/sea exchange tends to be a minor few percent of primary CO2 fixation but will continue well after observations have stopped. Export of carbon into deeper waters is difficult to assess and is until now firmly proven and quite modest in only two experiments.

921 citations


Journal ArticleDOI
TL;DR: Adjuvant chemotherapy with TAC, as compared with FAC, significantly improves the rates of disease-free and overall survival among women with operable node-positive breast cancer.
Abstract: results At a median follow-up of 55 months, the estimated rates of disease-free survival at five years were 75 percent among the 745 patients randomly assigned to receive TAC and 68 percent among the 746 randomly assigned to receive FAC, representing a 28 percent reduction in the risk of relapse (P=0.001) in the TAC group. The estimated rates of overall survival at five years were 87 percent and 81 percent, respectively. Treatment with TAC resulted in a 30 percent reduction in the risk of death (P=0.008). The incidence of grade 3 or 4 neutropenia was 65.5 percent in the TAC group and 49.3 percent in the FAC group (P<0.001); rates of febrile neutropenia were 24.7 percent and 2.5 percent, respectively (P<0.001). Grade 3 or 4 infections occurred in 3.9 percent of the patients who received TAC and 2.2 percent of those who received FAC (P=0.05); no deaths occurred as a result of infection. Two patients in each group died during treatment. Congestive heart failure and acute myeloid leukemia occurred in less than 2 percent of the patients in each group. Quality-of-life scores decreased during chemotherapy but returned to baseline levels after treatment. conclusions Adjuvant chemotherapy with TAC, as compared with FAC, significantly improves the rates of disease-free and overall survival among women with operable node-positive breast cancer.

884 citations


Journal ArticleDOI
TL;DR: In this paper, the most relevant approach to calculate potential evapotranspiration (PE) for use in a daily rainfall-runoff model, while answering the following question: How can we use available atmospheric variables to represent the evaporative demand at the basin scale?

827 citations


Journal ArticleDOI
TL;DR: The Atmospheric Chemistry Experiment (ACE) is a Canadian satellite mission for remote sensing of the Earth's atmosphere that was launched into low Earth circular orbit (altitude 650 km, inclination 74°) on 12 Aug. 2003.
Abstract: SCISAT-1, also known as the Atmospheric Chemistry Experiment (ACE), is a Canadian satellite mission for remote sensing of the Earth's atmosphere. It was launched into low Earth circular orbit (altitude 650 km, inclination 74°) on 12 Aug. 2003. The primary ACE instrument is a high spectral resolution (0.02 cm-1) Fourier Transform Spectrometer (FTS) operating from 2.2 to 13.3 μm (750-4400 cm-1). The satellite also features a dual spectrophotometer known as MAESTRO with wavelength coverage of 285-1030 nm and spectral resolution of 1-2 nm. A pair of filtered CMOS detector arrays records images of the Sun at 0.525 and 1.02 μm. Working primarily in solar occultation, the satellite provides altitude profile information (typically 10-100 km) for temperature, pressure, and the volume mixing ratios for several dozen molecules of atmospheric interest, as well as atmospheric extinction profiles over the latitudes 85°N to 85°S. This paper presents a mission overview and some of the first scientific results. Copyright 2005 by the American Geophysical Union.

807 citations


01 Feb 2005
TL;DR: Children who are at highest risk of not learning to regulate physical aggression in early childhood have mothers with a history of antisocial behaviour during their school years, mothers who start childbearing early and who smoke during pregnancy, and parents who have low income and have serious problems living together.
Abstract: Introduction: This study aimed to identify the trajectories of physical aggression during early childhood and antecedents of high levels of physical aggression early in life Methods: 572 families with a 5-month-old newborn were recruited Assessments of physical aggression frequency were obtained from mothers at 17, 30, and 42 months after birth Using a semiparametric mixture model and multivariate logit regression analyses, distinct clusters of physical aggression trajectories were identified, as well as family and child characteristics that predict high level aggression trajectories Results: Three trajectories of physical aggression were identified: 1 children (28% of sample) who displayed little or no physical aggression, 2 approximately 58% followed a rising trajectory of modest aggression, and 3 a rising trajectory of high physical aggression (14%) Conclusions: Children who are at highest risk of not learning to regulate physical aggression in early childhood have mothers with a history of antisocial behaviour during their school years, mothers who start childbearing early and who smoke during pregnancy, and parents who have low income and have serious problems living together Preventive interventions should target families with high-risk profiles on these variables Language: en

746 citations


Journal ArticleDOI
TL;DR: The current review will briefly survey the literature, which initially identified the problem of PU degradation in vivo and the subsequent studies that have led to the field's further understanding of the biological processes mediating the breakdown.

Journal ArticleDOI
TL;DR: Silicon possesses unique biochemical properties that may explain its bioactivity as a regulator of plant defense mechanisms, and may interact with several key components of plant stress signaling systems leading to induced resistance.
Abstract: Silicon (Si) is a bioactive element associated with beneficial effects on mechanical and physiological properties of plants. Silicon alleviates abiotic and biotic stresses, and increases the resistance of plants to pathogenic fungi. Several studies have suggested that Si activates plant defense mechanisms, yet the exact nature of the interaction between the element and biochemical pathways leading to resistance remains unclear. Silicon possesses unique biochemical properties that may explain its bioactivity as a regulator of plant defense mechanisms. It can act as a modulator influencing the timing and extent of plant defense responses in a manner reminiscent of the role of secondary messengers in induced systemic resistance; it can also bind to hydroxyl groups of proteins strategically involved in signal transduction; or it can interfere with cationic co-factors of enzymes influencing pathogenesis-related events. Silicon may therefore interact with several key components of plant stress signaling systems leading to induced resistance.

Journal ArticleDOI
TL;DR: In this paper, the effective conjugation length of poly(2,7-carbazole) and poly(p-phenylene)-like structure is compared to poly(3,6-carbazole).
Abstract: Summary: Carbazole-based oligomeric and polymeric materials have been studied for almost 25 years for their unique electrical, electrochemical and optical properties. Interestingly, carbazole units can be linked in two different ways leading to either poly(3,6-carbazole) or poly(2,7-carbazole) derivatives. While the former class seems to be very interesting for electrochemical and phosphorescence applications, the latter shows very promising optical properties in the visible range for light emitting diodes (LED). The major intrinsic difference between these two classes is the effective conjugation length: poly(2,7-carbazole) materials having the longer one, due to their poly(p-phenylene)-like structure. Using different synthetic strategies and substitution patterns, the physico-chemical properties of both classes can be fine-tuned, leading to high performance materials for a large number electronic applications. Chemical structures for poly(3,6-carbazole) and poly(2,7-carbazole) and the materials used as the starting points for their respective syntheses.

Journal ArticleDOI
TL;DR: Activation of the mTOR pathway is increased in liver and muscle of high fat-fed obese rats and in vitro studies with rapamycin suggest that mTOR/S6K1 overactivation contributes to elevated serine phosphorylation of IRS-1, leading to impaired insulin signaling to Akt in liver or muscle of this dietary model of obesity.
Abstract: The mammalian target of rapamycin (mTOR) pathway integrates insulin and nutrient signaling in numerous cell types. Recent studies also suggest that this pathway negatively modulates insulin signaling to phosphatidylinositol 3-kinase/Akt in adipose and muscle cells. However, it is still unclear whether activation of the mTOR pathway is increased in obesity and if it could be involved in the promotion of insulin resistance. In this paper we show that basal (fasting state) activation of mTOR and its downstream target S6K1 is markedly elevated in liver and skeletal muscle of obese rats fed a high fat diet compared with chow-fed, lean controls. Time-course studies also revealed that mTOR and S6K1 activation by insulin was accelerated in tissues of obese rats, in association with increased inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1) on Ser636/Ser639 and impaired Akt activation. The relationship between mTOR/S6K1 overactivation and impaired insulin signaling to Akt was also examined in hepatic cells in vitro. Insulin caused a time-dependent activation of mTOR and S6K1 in HepG2 cells. This was associated with increased IRS-1 phosphorylation on Ser636/Ser639. Inhibition of mTOR/S6K1 by rapamycin blunted insulin-induced Ser636/Ser639 phosphorylation of IRS-1, leading to a rapid (approximately 5 min) and persistent increase in IRS-1-associated phosphatidylinositol 3-kinase activity and Akt phosphorylation. These results show that activation of the mTOR pathway is increased in liver and muscle of high fat-fed obese rats. In vitro studies with rapamycin suggest that mTOR/S6K1 overactivation contributes to elevated serine phosphorylation of IRS-1, leading to impaired insulin signaling to Akt in liver and muscle of this dietary model of obesity.

Journal ArticleDOI
TL;DR: Differences between hypoxic and non-hypoxic induction and activation of Hif-1 are focused on and the biological functions of HIF-1 associated with these two induction pathways are discussed.

Journal ArticleDOI
TL;DR: Some of the signaling pathways and intermediates that are repressed in infected cells are described, including JAK/STAT, Ca2+-dependent protein kinase C (PKC) isoforms, and mitogen-activated protein kinases (especially ERK1/2), and proteasome-mediated transcription factor degradation.
Abstract: The obligate intracellular parasite Leishmania must survive the antimicrobial activities of its host cell, the macrophage, and prevent activation of an effective immune response. In order to do this, it has developed numerous highly successful strategies for manipulating activities, including antigen presentation, nitric oxide and oxygen radical generation, and cytokine production. This is generally the result of interactions between Leishmania cell surface molecules, particularly gp63 and LPG, and less well identified macrophage surface receptors, causing the distortion of specific intracellular signaling cascades. We describe some of the signaling pathways and intermediates that are repressed in infected cells, including JAK/STAT, Ca2+-dependent protein kinase C (PKC) isoforms, and mitogen-activated protein kinases (especially ERK1/2), and proteasome-mediated transcription factor degradation. We also discuss protein tyrosine phosphatases (particularly SHP-1), intracellular Ca2+, Ca2+-independent PKC, ceramide, and the suppressors of cytokine signaling family of repressors, which are all reported to be activated following infection, and the role of parasite-secreted cysteine proteases.

Journal ArticleDOI
TL;DR: To a large extent, the 3β-HSD gene family should have evolved to facilitate differential patterns of tissue- and cell-specific expression and regulation involving multiple signal transduction pathways, which are activated by multiple signalTransduction pathways.
Abstract: The 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta-HSD) isoenzymes are responsible for the oxidation and isomerization of Delta(5)-3beta-hydroxysteroid precursors into Delta(4)-ketosteroids, thus catalyzing an essential step in the formation of all classes of active steroid hormones. In humans, expression of the type I isoenzyme accounts for the 3beta-HSD activity found in placenta and peripheral tissues, whereas the type II 3beta-HSD isoenzyme is predominantly expressed in the adrenal gland, ovary, and testis, and its deficiency is responsible for a rare form of congenital adrenal hyperplasia. Phylogeny analyses of the 3beta-HSD gene family strongly suggest that the need for different 3beta-HSD genes occurred very late in mammals, with subsequent evolution in a similar manner in other lineages. Therefore, to a large extent, the 3beta-HSD gene family should have evolved to facilitate differential patterns of tissue- and cell-specific expression and regulation involving multiple signal transduction pathways, which are activated by several growth factors, steroids, and cytokines. Recent studies indicate that HSD3B2 gene regulation involves the orphan nuclear receptors steroidogenic factor-1 and dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1 (DAX-1). Other findings suggest a potential regulatory role for STAT5 and STAT6 in transcriptional activation of HSD3B2 promoter. It was shown that epidermal growth factor (EGF) requires intact STAT5; on the other hand IL-4 induces HSD3B1 gene expression, along with IL-13, through STAT 6 activation. However, evidence suggests that multiple signal transduction pathways are involved in IL-4 mediated HSD3B1 gene expression. Indeed, a better understanding of the transcriptional factors responsible for the fine control of 3beta-HSD gene expression may provide insight into mechanisms involved in the functional cooperation between STATs and nuclear receptors as well as their potential interaction with other signaling transduction pathways such as GATA proteins. Finally, the elucidation of the molecular basis of 3beta-HSD deficiency has highlighted the fact that mutations in the HSD3B2 gene can result in a wide spectrum of molecular repercussions, which are associated with the different phenotypic manifestations of classical 3beta-HSD deficiency and also provide valuable information concerning the structure-function relationships of the 3beta-HSD superfamily. Furthermore, several recent studies using type I and type II purified enzymes have elegantly further characterized structure-function relationships responsible for kinetic differences and coenzyme specificity.

Journal ArticleDOI
TL;DR: Reduced SAC is a frequent occurrence in elderly patients with AS, where it independently contributes to increased afterload and decreased LV function, and should be taken into consideration when evaluating these patients with regard to diagnosis and treatment.

Journal ArticleDOI
TL;DR: Seven issues that should be addressed when developing functional foods are examined: type or form of probiotic that should been used; addition level required to have a beneficial effect; toxicity; effect of the processing steps on viability; 5) determination, in the product, of the cell populations added; 6) stability during storage; 7) changes in sensory properties of the foods.
Abstract: Probiotic cultures are increasingly being added to foods in order to develop products with health-promoting properties. Although the literature is abundant on the beneficial effects of bifidobacteria and Lactobacillus acidophilus on health, little information is available on the challenges industry faces in adding these probiotic cultures to food products. The aim of this article is to examine seven issues that should be addressed when developing functional foods: 1) type or form of probiotic that should be used; 2) addition level required to have a beneficial effect; 3) toxicity; 4) effect of the processing steps on viability; 5) determination, in the product, of the cell populations added; 6) stability during storage; 7) changes in sensory properties of the foods.

Journal ArticleDOI
TL;DR: This study supports the efficacy of CBT for insomnia secondary to breast cancer among breast cancer survivors with significantly better subjective sleep indices and greater global quality of life at post-treatment compared with participants of the control group after their waiting period.
Abstract: Purpose Chronic insomnia is highly prevalent in cancer patients. Cognitive-behavioral therapy (CBT) is considered the treatment of choice for chronic primary insomnia. However, no randomized controlled study has been conducted on its efficacy for insomnia secondary to cancer. Using a randomized controlled design, this study conducted among breast cancer survivors evaluated the effect of CBT on sleep, assessed both subjectively and objectively, and on hypnotic medication use, psychological distress, and quality of life. Patients and Methods Fifty-seven women with insomnia caused or aggravated by breast cancer were randomly assigned to CBT (n = 27) or a waiting-list control condition (n = 30). The treatment consisted of eight weekly sessions administered in a group and combined the use of stimulus control, sleep restriction, cognitive therapy, sleep hygiene, and fatigue management. Follow-up evaluations were carried out 3, 6, and 12 months after the treatment. Results Participants who received the insomnia ...

Journal ArticleDOI
TL;DR: The new field of intracrinology or local formation of sex steroids from DHEA in target tissues has permitted major advances in the treatment of the two most frequent cancers, namely breast and prostate cancer, while its potential use as a physiological HRT could well provide a physiological balance of androgens and estrogens, thus offering exciting possibilities for women's health at menopause.
Abstract: Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important prohormone secreted in large amounts by the adrenals in humans and other primates, but not in lower species. It is secreted in larger quantities than cortisol and is present in the blood at concentrations only second to cholesterol. All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cell-specific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogen-sensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs. This new field of endocrinology has been called intracrinology. In women, after menopause, all estrogens and almost all androgens are made locally in peripheral tissues from DHEA which indirectly exerts effects, among others, on bone formation, adiposity, muscle, insulin and glucose metabolism, skin, libido and well-being. In men, where the secretion of androgens by the testicles continues for life, the contribution of DHEA to androgens has been best evaluated in the prostate where about 50% of androgens are made locally from DHEA. Such knowledge has led to the development of combined androgen blockade (CAB), a treatment which adds a pure anti-androgen to medical (GnRH agonist) or surgical castration in order to block the access of the androgens made locally to the androgen receptor. In fact, CAB has been the first treatment demonstrated to prolong life in advanced prostate cancer while recent data indicate that it can permit long-term control and probably cure in at least 90% of cases of localized prostate cancer. The new field of intracrinology or local formation of sex steroids from DHEA in target tissues has permitted major advances in the treatment of the two most frequent cancers, namely breast and prostate cancer, while its potential use as a physiological HRT could well provide a physiological balance of androgens and estrogens, thus offering exciting possibilities for women's health at menopause.

Journal ArticleDOI
Mircea Steriade1
TL;DR: The role of thalamic reticular neurons in the initiation of spindles, a hallmark oscillation during early sleep stages, and the reticular-induced inhibition of thalamocortical neurons during cortically generated spike-wave seizures are focused on.

Journal ArticleDOI
TL;DR: This article used the data of the 1999 Statistics Canada Innovation Survey to address a crucial question for the understanding of novelty of innovation in the manufacturing sector: what are the effects of sources of information on novelty in manufacturing firms?

Journal ArticleDOI
TL;DR: The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder.
Abstract: Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.


Journal ArticleDOI
TL;DR: The results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.
Abstract: Objective— The objective of the present study was to investigate the association between large and small low-density lipoprotein (LDL) and long-term ischemic heart disease (IHD) risk in men of the Quebec Cardiovascular Study. Methods and Results— Cholesterol levels in the large and small LDL subfractions (termed LDL-C≥260A and LDL-C<255A, respectively) were estimated from polyacrylamide gradient gel electrophoresis of whole plasma in the cohort of 2072 men of the population-based Quebec Cardiovascular Study. All men were free of IHD at the baseline examination and followed-up for a period of 13 years, during which 262 first IHD events (coronary death, nonfatal myocardial infarction, and unstable angina pectoris) were recorded. Our study confirmed the strong and independent association between LDL-C<255A levels as a proxy of the small dense LDL phenotype and the risk of IHD in men, particularly over the first 7 years of follow-up. However, elevated LDL-C≥260A levels (third versus first tertile) were not associated with an increased risk of IHD over the 13-year follow-up (RR=0.76; P =0.07). Conclusions— These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.

Journal ArticleDOI
TL;DR: The main purpose of the current research was to develop an abbreviated form of the Dyadic Adjustment Scale (DAS) with nonparametric item response theory that was as effective in predicting couple dissolution and was significantly less contaminated by socially desirable responding.
Abstract: The main purpose of the current research was to develop an abbreviated form of the Dyadic Adjustment Scale (DAS) with nonparametric item response theory. The authors conducted 5 studies, with a total participation of 8,256 married or cohabiting individuals. Results showed that the item characteristic curves behaved in a monotonically increasing function for all items of the brief 4-item version of the DAS (DAS-4). The DAS-4 proved to be informative at all levels of couple satisfaction. Compared with the 32-item version of the DAS (DAS-32), it was as effective in predicting couple dissolution and was significantly less contaminated by socially desirable responding. In addition, structural equation modeling demonstrated that the underlying latent construct measured by the DAS-4 was very stable over a 2-year period. This brief version has the advantage of being less time consuming and constitutes a promising alternative to the original DAS-32 for clinicians and researchers.

Journal ArticleDOI
TL;DR: In this article, the authors provide a foundation for the safe and effective use of magnesium (Mg) alloys, including practical guidelines for the service use of Mg alloys in the atmosphere and/or in contact with aqueous solutions.
Abstract: This review aims to provide a foundation for the safe and effective use of magnesium (Mg) alloys, including practical guidelines for the service use of Mg alloys in the atmosphere and/or in contact with aqueous solutions. This is to provide support for the rapidly increasing use of Mg in industrial applications, particularly in the automobile industry. These guidelines should be firmly based on a critical analysis of our knowledge of SCC based on (1) service experience, (2) laboratory testing and (3) understanding of the mechanism of SCC, as well as based on an understanding of the Mg corrosion mechanism.

Journal ArticleDOI
TL;DR: It is concluded that the early vascularization observed in the ERS was most probably the result of inosculation of the CLS network with the host's capillaries, rather than neovascularization, which is a slower process.

Journal ArticleDOI
TL;DR: Although the effects of structured regular exercise were highly variable, there were improvements in virtually all i.v.GTT-derived variables, suggesting that regular exercise is required for sustained improvements in glucose homeostasis.
Abstract: OBJECTIVE —To determine the effect of a 20-week endurance training program in healthy, previously sedentary participants on measures derived from an intravenous glucose tolerance test (IVGTT). RESEARCH DESIGN AND METHODS —An IVGTT was performed before and after a standardized training program in 316 women and 280 men (173 blacks and 423 whites). Participants exercised on cycle ergometers 3 days per week for 60 sessions. The exercise intensity was progressively increased from 55% V o 2max for 30 min per session to 75% V o 2max for 50 min per session. RESULTS —Mean insulin sensitivity increased by 10% ( P P = 0.02). Improvements in fasting insulin were transitory, disappearing 72 h after the last bout of exercise. There were also significant mean increases in the glucose disappearance index (3%, P = 0.02) and in glucose effectiveness (11%, P P P = 0.02). CONCLUSIONS —Although the effects of structured regular exercise were highly variable, there were improvements in virtually all IVGTT-derived variables. In the absence of substantial weight loss, regular exercise is required for sustained improvements in glucose homeostasis.