Genetics of bone diseases: Paget's disease, fibrous dysplasia, osteopetrosis, and osteogenesis imperfecta.

Over the last few years, research into the genetics of bone diseases has produced new insights into the pathophysiology of bone remodeling. The identification of SQSTM1 mutations in Paget's disease of bone established that osteoclast activation involved both binding to ubiquitin and the proteasome pathway. However, murine models fail to replicate the full phenotype, and somatic SQSTM1 mutations have been identified, suggesting a role for complex mechanisms.

Rapid testing versus karyotyping in Down's syndrome screening: cost-effectiveness and detection of clinically significant chromosome abnormalities.

In all, 80% of antenatal karyotypes are generated by Down's syndrome screening programmes (DSSP). After a positive screening, women are offered prenatal foetus karyotyping, the gold standard. Reliable molecular methods for rapid aneuploidy diagnosis (RAD: fluorescence in situ hybridization (FISH) and quantitative fluorescence PCR (QF-PCR)) can detect common aneuploidies, and are faster and less expensive than karyotyping.

Neonatal stress and attenuation of the hypercapnic ventilatory response in adult male rats: the role of carotid chemoreceptors and baroreceptors.

Neonatal maternal separation (NMS) is a form of stress that disrupts respiratory control development. Awake adult male rats previously subjected to NMS show a ventilatory response to hypercapnia (HCVR; Fi(CO(2)) = 0.05) 47% lower than controls; however, the underlying mechanisms are unknown.

Computational simulation of vasopressin secretion using a rat model of the water and electrolyte homeostasis.

Background: In mammals, vasopressin (AVP) is released from magnocellular neurons of the hypothalamus when osmotic pressure exceeds a fixed set-point. AVP participates to the hydromineral homeostasis (HH) by controlling water excretion at the level of the kidneys. Our current understanding of the HH and AVP secretion is the result of a vast amount of data collected over the five past decades.

Hypoxia-inducible factor-1 activation in nonhypoxic conditions: the essential role of mitochondrial-derived reactive oxygen species.

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor for responses to low oxygen. Different nonhypoxic stimuli, including hormones and growth factors, are also important HIF-1 activators in the vasculature. Angiotensin II (Ang II), the main effecter hormone in the renin-angiotensin system, is a potent HIF-1 activator in vascular smooth muscle cells (VSMCs).

Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration.

Type III RNase Dicer is responsible for the maturation and function of microRNA (miRNA) molecules in the cell. It is now well-documented that Dicer and the fine-tuning of the miRNA gene network are important for neuronal integrity. However, the underlying mechanisms involved in neuronal death, particularly in the adult brain, remain poorly defined.

HIF-1 inhibition decreases systemic vascular remodelling diseases by promoting apoptosis through a hexokinase 2-dependent mechanism.

Aims: Vascular remodelling diseases are characterized by the presence of proliferative and apoptosis-resistant vascular smooth muscle cells (VSMC). There is evidence that pro-proliferative and anti-apoptotic states are characterized by metabolic remodelling (a glycolytic phenotype with hyperpolarized mitochondria) involving Akt pathway activation by circulating growth factors. Hypoxia-inducible factor-1 (HIF-1) is involved in different vascular diseases.

Meganucleases can restore the reading frame of a mutated dystrophin.

Mutations in Duchenne muscular dystrophy (DMD) are either inducing a nonsense codon or a frameshift. Meganucleases (MGNs) can be engineered to induce double-strand breaks (DSBs) at specific DNA sequences. These breaks are repaired by homologous recombination or by non-homologous end joining (NHEJ), which results in insertions or deletions (indels) of a few base pairs.

Behavioural correlates of the P3b event-related potential in school-age children.

The latency and amplitude of the P3b component of event-related potentials (ERPs) have been related to behavioural performance on several attention and memory tasks in adult populations. However, the extent to which these results apply to children is unknown. This study examined the neurobehavioral correlates of the P3b component in a longitudinal sample of school-age children from Arctic Québec.

Neonatal maternal separation disrupts regulation of sleep and breathing in adult male rats.

Study Objectives: Neonatal maternal separation (NMS) disrupts development of cardiorespiratory regulation. Adult male rats previously subjected to NMS are hypertensive and show a hypoxic ventilatory response greater than that of controls. These results have been obtained in awake or anesthetised animals, and the consequences of NMS on respiratory control during normal sleep are unknown.

Putative Role of MicroRNA-Regulated Pathways in Comorbid Neurological and Cardiovascular Disorders.

Background. The conserved noncoding microRNAs (miRNAs) that function to regulate gene expression are essential for the development and function of the brain and heart. Changes in miRNA expression profiles are associated with an increased risk for developing neurodegenerative disorders as well as heart failure.

How much do family physicians involve pregnant women in decisions about prenatal screening for Down syndrome?

Objective: To assess the extent to which family physicians (FPs) involve women in decisions about prenatal screening for Down syndrome.

Methods: Based on transcripts of consultations between 41 FPs and 128 women, two raters independently assessed clinician's efforts to involve women in decisions about prenatal screening for Down syndrome using the French-language version of OPTION. Descriptive statistics of OPTION scores were calculated.

Oxysterols in biological systems: the gastrointestinal tract, liver, vascular wall and central nervous system.

Oxysterols are oxygenated derivatives of cholesterol generated from exogenous (food) or endogenous (auto-oxidation and enzymatic conversion) sources. Despite their hepatic capacity to transform into bile acids, oxysterols are present in the blood circulation and central nervous system. This review aims to provide a better understanding of the origins and roles of oxysterols under normal and pathophysiological conditions, such as atherosclerosis and Alzheimer's disease.

Functional cooperation between Stat-1 and ets-1 to optimize icam-1 gene transcription.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the immune system, enabling the interactions between effector cells and target cells. It is also known to be involved in tumor growth and metastasis. Its expression is transcriptionally regulated by several proinflammatory cytokines including IFN-gamma, which induces ICAM-1 transcription via the JAK-STAT signaling pathway in a Stat1-dependent fashion.

Neuroanatomical characterization of endogenous opioids in the bed nucleus of the stria terminalis.

Numerous neuroanatomical data indicate that the bed nucleus of the stria terminalis (BST) provides an interface between cortical and amygdaloid neurons, and effector neurons modulating motor, autonomic and neuroendocrine responses. Distinct divisions of the BST may be involved in stress response, homeostatic regulation, nociception, and motivated behaviors. Endogenous opioid peptides and receptors are expressed in the BST, but their exact distribution is poorly characterized.

Human angiomotin-like 1 associates with an angiomotin protein complex through its coiled-coil domain and induces the remodeling of the actin cytoskeleton.

Angiostatin is a potent inhibitor of angiogenesis. One mechanism through which angiostatin inhibits angiogenesis is by binding to the cell surface protein p80-angiomotin. The p80-angiomotin protein promotes angiogenesis, in part, by conferring a hypermigratory phenotype to endothelial cells.

Phylogenetic trends in respiratory rhythmogenesis: insights from ectothermic vertebrates.

Understanding the neural substrate driving breathing has puzzled physiologists for more than a century. The discovery of the pre-Bötzinger complex (preBötC) in newborn rodents as a structure with a unique physiological function in respiratory rhythm generation was an important progress in respiratory neurobiology that stimulated much research. Owing to the extensive literature describing the location, organisation, and function of the preBötC mainly in newborn rodents, this structure has become the point of reference in studies addressing respiratory rhythm generation in other mammals and various classes of vertebrates.

Down regulation of KMP-11 in Leishmania infantum axenic antimony resistant amastigotes as revealed by a proteomic screen.

The therapeutic mainstay against the protozoan parasite Leishmania is still based on the antiquated pentavalent antimonials, but resistance is increasing in several parts of the world. Resistance is now partly understood in laboratory promastigote isolates, but the mechanism leading to drug resistance in amastigote isolates is lagging behind. Here we describe a comparative proteomic analysis of a genetically related pair of antimonial-sensitive and -resistant Leishmania infantum axenic amastigote strains.

Neutrophils exhibit distinct phenotypes toward chitosans with different degrees of deacetylation: implications for cartilage repair.

Introduction: Osteoarthritis is characterized by the progressive destruction of cartilage in the articular joints. Novel therapies that promote resurfacing of exposed bone in focal areas are of interest in osteoarthritis because they may delay the progression of this disabling disease in patients who develop focal lesions. Recently, the addition of 80% deacetylated chitosan to cartilage microfractures was shown to promote the regeneration of hyaline cartilage.

Use of a remote car starter in relation to smog and climate change perceptions: a population survey in Québec (Canada).

Remote car starters encourage motorists to warm up their vehicles by idling the motor--thus increasing atmospheric pollutants, including several greenhouse gas (GHG) with impacts on public health. This study about climate change (CC) adaptation and mitigation actions examined perceptions on air pollution and climate change and individual characteristics associated with the use of a remote car starter. A telephone survey (n = 2,570; response rate: 70%) of adults living in Québec (Canada) measured the respondents' beliefs and current behaviours regarding CC.

Sphingosine-1-phosphate: a novel nonhypoxic activator of hypoxia-inducible factor-1 in vascular cells.

Objective: Sphingosine-1-phosphate (S1P) is a potent bioactive phospholipid responsible for a variety of vascular cell responses. Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator of genes essential for adaptation to low oxygen. S1P and HIF-1 are both important mediators of vascular cell responses such as migation, proliferation, and survival.

[Individual determinants of the Quebec electronic health record adoption].

Aim: The potential of electronic health records to improve effectiveness, safety and quality of health care has been shown in several previous studies. However healthcare professionals remain reticent as for its use, which limits its potential effect on the health care system. The present study aimed to evaluate physicians' perceptions towards the electronic health record of Quebec.

Thrombocytopenia alters early but not late repair in a mouse model of Achilles tendon injury.

Besides their hemostatic function, platelets can express key factors involved in tissue healing. However, the role of platelets in tendon healing following acute injury is poorly understood. We investigated this role by injecting male C57BL/6 mice with an antiplatelet antibody to induce thrombocytopenia.

Comparison of different strategies in prenatal screening for Down's syndrome: cost effectiveness analysis of computer simulation.

Objectives: To assess and compare the cost effectiveness of three different strategies for prenatal screening for Down's syndrome (integrated test, sequential screening, and contingent screenings) and to determine the most useful cut-off values for risk.

Design: Computer simulations to study integrated, sequential, and contingent screening strategies with various cut-offs leading to 19 potential screening algorithms.

Data Sources: The computer simulation was populated with data from the Serum Urine and Ultrasound Screening Study (SURUSS), real unit costs for healthcare interventions, and a population of 110 948 pregnancies from the province of Québec for the year 2001.

Diabetes and related metabolic conditions in an aboriginal cree community of quebec, Canada.

Objective: We evaluated the prevalence of type 2 diabetes, obesity and metabolic syndrome according to International Diabetes Federation criteria in the First Nations Cree community of Mistissini, Quebec.

Methods: A cross-sectional study of 172 adults was performed as part of a broader regional environmental study.

Results: Type 2 diabetes, hyperinsulinemia and abdominal obesity were documented in 20%, 70% and 91% of participants, respectively.