Impact of chronic exposure to legacy environmental contaminants on the corpus callosum microstructure: A diffusion MRI study of Inuit adolescents.

Exposure to environmental contaminants is an important public health concern for the Inuit population of northern Québec, who have been exposed to mercury (Hg), polychlorinated biphenyls (PCBs) and lead (Pb). During the last 25 years, the Nunavik Child Development Study (NCDS) birth cohort has reported adverse associations between these exposures and brain function outcomes. In the current study, we aimed to determine whether contaminant exposure is associated with alterations of the corpus callosum (CC), which plays an important role in various cognitive, motor and sensory function processes.

Prime Editing Permits the Introduction of Specific Mutations in the Gene Responsible for Duchenne Muscular Dystrophy.

The Prime editing technique derived from the CRISPR/Cas9 discovery permits the modification of selected nucleotides in a specific gene. We used it to insert specific point mutations in exons 9, 20, 35, 43, 55 and 61 of the Duchenne Muscular Dystrophy (DMD) gene coding for the dystrophin protein, which is absent in DMD patients. Up to 11% and 21% desired mutations of the DMD gene in HEK293T cells were obtained with the PRIME Editor 2 (PE2) and PE3, respectively.

Altered functional activations of prefrontal brain areas during emotional processing of fear in Inuit adolescents exposed to environmental contaminants.

Exposure to mercury, lead and polychlorinated biphenyls (PCBs) have been associated with emotional dysregulation, but their neuronal correlates have yet to be examined. Inuit from Nunavik (Northern Quebec, Canada) face internalizing problems and are among the most exposed individuals to these environmental contaminants in the world. The aim of this study was to examine the link between pre- and postnatal exposure to these contaminants and brain fear-circuitry in Inuit adolescents.

Current Clinical Applications of In Vivo Gene Therapy with AAVs.

Hereditary diseases are caused by mutations in genes, and more than 7,000 rare diseases affect over 30 million Americans. For more than 30 years, hundreds of researchers have maintained that genetic modifications would provide effective treatments for many inherited human diseases, offering durable and possibly curative clinical benefit with a single treatment. This review is limited to gene therapy using adeno-associated virus (AAV) because the gene delivered by this vector does not integrate into the patient genome and has a low immunogenicity.

Myogenic progenitor cells derived from human induced pluripotent stem cell are immune-tolerated in humanized mice.

It is still unclear if immune responses will compromise the large-scale utilization of human induced pluripotent stem cells (hiPSCs)-derived cell therapies. To answer this question, we used humanized mouse models generated by the adoptive transfer of peripheral blood mononuclear cells or the cotransplantation of hematopoietic stem cells and human thymic tissue. Using these mice, we evaluated the engraftment in skeletal muscle of myoblasts derived either directly from a muscle biopsy or differentiated from hiPSCs or fibroblasts.

Inhaled Epoprostenol for Pulmonary Hypertension Treatment in Neonates: A 12-Year Experience.

Background: Persistent pulmonary hypertension of the newborn (PPHN) occurs in 10% of neonatal respiratory insufficiency. To selectively reduce pulmonary vascular resistance, several treatments have been tried. Inhaled epoprostenol (iPGI) has been used for 12 years in our institution for the management of refractory PPHN despite the gaps in the literature to support this use.

Prenatal exposure to an environmentally relevant mixture of Canadian Arctic contaminants decreases male reproductive function in an aging rat model.

Elevated levels of organochlorines (OC) have been reported in Inuit populations in the Arctic. We hypothesized that prenatal exposure to a Canadian Arctic OC mixture adversely affects male reproductive function and health with age. Sprague-Dawley female rats (F0) were gavaged with an environmentally relevant concentration of an Arctic OC mixture or corn oil (Control) during mating with untreated males until parturition (F1 litters).

A cluster-randomized trial to reduce major perinatal morbidity among women with one prior cesarean delivery in Québec (PRISMA trial): study protocol for a randomized controlled trial.

Background: Rates of cesarean delivery are continuously increasing in industrialized countries, with repeated cesarean accounting for about a third of all cesareans. Women who have undergone a first cesarean are facing a difficult choice for their next pregnancy, i.e.

Novel technical strategies to optimize cryopreservation of goat semen using cholesterol-loaded cyclodextrin.

Artificial insemination is well-established in dairy cattle, with sires housed in commercial studs for processing. In some species, however, sires located on-farm are used for artificial insemination by shipping their semen to an off-site laboratory for processing within 24 h of collection. To expedite semen transport from the farm to laboratory, protocols must be uncomplicated.

Failure to Return for Posttest Counseling and HIV Test Results at the Prevention and Voluntary Testing and Counseling Centers of Douala, Cameroon: An Evaluation of a Routine Five-Year Program.

This study examined the magnitude and time trends in failure to return (FTR) rates and the relation between FTR and individual characteristics, tests procedures, waiting period for the results, and HIV test results among people who were screened for HIV in the prevention and voluntary testing and counseling centers (PVTCCs) of six district hospitals of the city of Douala in Cameroon, between January 2009 and December 2013. It was a retrospective analysis of medical records. Among the 32,020 analyzed records, the failure to return (FTR) rate was 14.

Cholesterol-Loaded Cyclodextrin Increases the Cholesterol Content of Goat Sperm to Improve Cold and Osmotic Resistance and Maintain Sperm Function after Cryopreservation.

The success of semen cryopreservation depends on sperm membrane integrity and function after thawing. Cholesterol-loaded cyclodextrin (CLC) is used for in vitro incorporation of cholesterol to protect cells against cold temperatures. We hypothesized that CLC treatment also enhances sperm cholesterol content to increase tolerance to osmotic shock and cryoresistance, thereby improving fertility.

Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease.

Background: Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS.

Menopausal status and physical performance in middle aged women: a cross-sectional community-based study in Northeast Brazil.

Objective: To examine associations between menopausal status and physical performance in middle-aged women from the Northeast region of Brazil.

Methods: Cross-sectional study of women between 40 to 65 years old living in Parnamirim. Women were recruited by advertisements in primary care neighborhood centers across the city.

Impairment of neutrophil migration to remote inflammatory site during lung histoplasmosis.

Histoplasma capsulatum (Hc) induces a pulmonary disease in which leukotrienes promote activation and recruitment of effectors cells. It is also well-recognized that leukotriene B4 (LTB4) and platelet-activating factor (PAF) induce leukocyte recruitment to inflammatory sites. We investigated the impact of pulmonary Hc infection on PMN migration to a remote inflammatory site.

Detection and quantification of microparticles from different cellular lineages using flow cytometry. Evaluation of the impact of secreted phospholipase A2 on microparticle assessment.

Microparticles, also called microvesicles, are submicron extracellular vesicles produced by plasma membrane budding and shedding recognized as key actors in numerous physio(patho)logical processes. Since they can be released by virtually any cell lineages and are retrieved in biological fluids, microparticles appear as potent biomarkers. However, the small dimensions of microparticles and soluble factors present in body fluids can considerably impede their quantification.

Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice.

miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia.

Effect of oral bisphosphonates for osteoporosis on development of skeletal metastases in women with breast cancer: results from a pharmaco-epidemiological study.

Background: Treatment with bisphosphonates in women with breast cancer and established bone metastasis delays further skeletal-related events. Evidence is emerging that bisphosphonates are beneficial for secondary prevention of bone metastasis. The study aimed to estimate the effect of oral bisphosphonates for treatment or prevention of osteoporosis on development of bone metastasis in a population of women with breast cancer.

Relationship between the esterase paraoxonase-1 (PON1) and metal concentrations in the whole blood of Inuit in Canada.

The esterase paraoxonase (PON1), a major component of high-density lipoprotein (HDL), protects against the development of atherosclerosis in humans. Although variation in PON1 activity is primarily governed by PON1 genotype, there is growing evidence that environmental chemicals may also modulate its activity. This cross-sectional study aimed to determine whether environmental exposure to various metals is associated with PON1 activity in Inuit people routinely exposed to mercury (Hg), cadmium (Cd), lead (Pb), and (Se) selenium.

Exposure of young children to household water lead in the Montreal area (Canada): the potential influence of winter-to-summer changes in water lead levels on children's blood lead concentration.

Drinking water represents a potential source of lead exposure. The purpose of the present study was to estimate the magnitude of winter-to-summer changes in household water lead levels (WLLs), and to predict the impact of these variations on BLLs in young children. A study was conducted from September, 2009 to March, 2010 in 305 homes, with a follow-up survey carried out from June to September 2011 in a subsample of 100 homes randomly selected.

The dynamic protein Knl1 - a kinetochore rendezvous.

Knl1 (also known as CASC5, UniProt Q8NG31) is an evolutionarily conserved scaffolding protein that is required for proper kinetochore assembly, spindle assembly checkpoint (SAC) function and chromosome congression. A number of recent reports have confirmed the prominence of Knl1 in these processes and provided molecular details and structural features that dictate Knl1 functions in higher organisms. Knl1 recruits SAC components to the kinetochore and is the substrate of certain protein kinases and phosphatases, the interplay of which ensures the exquisite regulation of the aforementioned processes.

Influence of polyunsaturated fatty acids on blood pressure, resting heart rate and heart rate variability among French Polynesians.

Objective: To analyze the associations between marine n-3 polyunsaturated fatty acids (PUFAs) and blood pressure (BP), resting heart rate (HR), and heart rate variability (HRV) in a population highly exposed to methylmercury through the diet.

Methods: Concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in erythrocytes membranes were measured in 180 French Polynesian adults (≥18 years) residing in Tubuai, which is a community with a traditional lifestyle, or Papeete, which has a modern lifestyle. HRV was measured using a 2-hour ambulatory electrocardiogram (Holter).

Training and nutritional components of PMTCT programmes associated with improved intrapartum quality of care in Mali and Senegal.

Objective: Scale-up of prevention of mother-to-child transmission (PMTCT) of HIV programmes in sub-Saharan Africa has stimulated interest to assess whether these programmes can indirectly affect other health priorities. This study assesses whether PMTCT programmes, or components of these programmes, are associated with better obstetrical quality of care and how PMTCT may reinforce existing maternal health programmes.

Design: Cross-sectional analysis of data from a cluster-randomized trial called QUARITE.