External evaluation of intravenous vancomycin population pharmacokinetic models in adults receiving high-flux intermittent haemodialysis.

Aims: Patients undergoing haemodialysis (HD) are at greater risk of methicillin-resistant Staphylococcus aureus infections requiring intravenous vancomycin. Close vancomycin therapeutic drug monitoring is warranted in HD patients as renal clearance is the primary elimination pathway. Clinically, population pharmacokinetics (popPK) model-informed dosing is commonly used.

Physiotherapy experiences of injured immigrant workers in Quebec: an intersectional perspective.

Purpose: Immigrant workers are more likely to suffer work-related injuries compared to native-born Canadians. Their physical rehabilitation usually involves physiotherapy. This study sought to better understand the experiences of injured immigrant workers receiving compensation and physiotherapy treatments.

Age-related modifications of muscle synergies during daily-living tasks: A scoping review.

Background: Aging is associated with changes in neuromuscular control that can lead to difficulties in performing daily living tasks. Muscle synergy analysis allows the assessment of neuromuscular control strategies and functional deficits. However, the age-related changes of muscle synergies during functional tasks are scattered throughout the literature.

Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.

Effect of Robotic-Assisted Gait at Different Levels of Guidance and Body Weight Support on Lower Limb Joint Kinematics and Coordination.

The Lokomat provides task-oriented therapy for patients with gait disorders. This robotic technology drives the lower limbs in the sagittal plane. However, normative gait also involves motions in the coronal and transverse planes.

Longitudinal Study of Early Adversity and Disturbing Dream Frequency: Moderating Role of Early Negative Emotionality.

Although disturbing dreams are prevalent in youth and are associated with psychopathology, little is known about their developmental course and risk factors. We aimed to examine the association between early social environment and subsequent disturbing dream frequency across adolescence as moderated by early negative emotionality. Measures of children's early social environment and negative emotionality were collected from the mothers of 410 children (5-42 months old) and measures of disturbing dream frequency directly from the children (13-18 years old).

Genomic Sequence of Canadian : A North American Wild Relative of Quinoa.

(pitseed goosefoot) is a widespread native North American plant, which was cultivated and consumed by indigenous peoples prior to the arrival of European colonists. is closely related to, and freely hybridizes with the domesticated South American food crop . As such it is a potential source of wild germplasm for breeding with , for improved quinoa production in North America.

Molecular basis for antiviral activity of two pediatric neutralizing antibodies targeting SARS-CoV-2 Spike RBD.

Neutralizing antibodies (NAbs) hold great promise for clinical interventions against SARS-CoV-2 variants of concern (VOCs). Understanding NAb epitope-dependent antiviral mechanisms is crucial for developing vaccines and therapeutics against VOCs. Here we characterized two potent NAbs, EH3 and EH8, isolated from an unvaccinated pediatric patient with exceptional plasma neutralization activity.

Senescence and Aging: Does It Impact Cancer Immunotherapies?

Cancer incidence increases drastically with age. Of the many possible reasons for this, there is the accumulation of senescent cells in tissues and the loss of function and proliferation potential of immune cells, often referred to as immuno-senescence. Immune checkpoint inhibitors (ICI), by invigorating immune cells, have the potential to be a game-changers in the treatment of cancer.

The Intracerebroventricular Injection of Murine Mesenchymal Stromal Cells Engineered to Secrete Epidermal Growth Factor Does Not Prevent Loss of Neurogenesis in Irradiated Mice.

Decreased neurogenesis after brain exposure to ionizing radiation is linked to neurocognitive impairments. Using transgenic mouse models, we previously showed that abrogation of radiation-induced senescence, or apoptosis, can partially rescue neurogenesis in the subventricular and hippocampus regions. Here, we evaluate whether the injection of recombinant epidermal growth factor (rEGF) or mesenchymal stromal cells (MSC) engineered to secrete EGF (MSC-EGF) can preserve neurogenesis.

Breast Milk Virome and Bacterial Microbiome Resilience in Kenyan Women Living with HIV.

Breast milk is nutritionally and immunologically beneficial in early life but is also a potential source of infection. Little is known about breast milk microbiota of women living with HIV (WLHIV), the impact of severe immunosuppression, and the contribution to mortality of HIV-exposed infants. Here, we performed metagenomic sequencing to characterize the bacterial microbiome and DNA virome of breast milk samples at 1 month postpartum from Kenyan WLHIV who were not receiving combination antiretroviral therapy (cART), 23 women with CD4 counts of <250 and 30 women with CD4 of >500; and additionally, 19 WLHIV with infants that lived and 26 WLHIV with infants that died during the first 2 years of life were included.

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.

Ethanol-mediated upregulation of APOA1 gene expression in HepG2 cells is independent of de novo lipid biosynthesis.

Background: Moderate alcohol intake in human increases HDL-cholesterol, and has protective effects against cardiovascular disease (CVD). Although de novo lipid synthesis inhibitors are highly effective in lowering total and LDL-cholesterol they have only modest effects on raising HDL-C. A better understanding of the mechanism of ethanol-mediated HDL-C regulation could suggest new therapeutic approaches for CVD.

Polygenic risk scores of several subtypes of epilepsies in a founder population.

Objective: Polygenic risk scores (PRSs) are used to quantify the cumulative effects of a number of genetic variants, which may individually have a very small effect on susceptibility to a disease; we used PRSs to better understand the genetic contribution to common epilepsy and its subtypes.

Methods: We first replicated previous single associations using 373 unrelated patients. We then calculated PRSs in the same French Canadian patients with epilepsy divided into 7 epilepsy subtypes and population-based controls.

Examining the impact of a social skills training program on preschoolers' social behaviors: a cluster-randomized controlled trial in child care centers.

Background: Preschoolers regularly display disruptive behaviors in child care settings because they have not yet developed the social skills necessary to interact prosocially with others. Disruptive behaviors interfere with daily routines and can lead to conflict with peers and educators. We investigated the impact of a social skills training program led by childcare educators on children's social behaviors and tested whether the impact varied according to the child's sex and family socio-economic status.

Violent Behavior Is Associated With Emotion Salience Network Dysconnectivity in Schizophrenia.

Despite individuals with schizophrenia being at an elevated risk of violence compared to the general population, limited efforts have been invested in investigating the neurobiological etiology explaining the increase. Among the few studies examining functional disruptions pertaining to violent schizophrenia patients using fMRI, only one study has considered functional connectivity. The current state of knowledge does not allow to infer deficits in functional connectivity specific to distinct cognitive/emotional states that have been associated with the emergence of violence in schizophrenia, such as negative emotion processing.

The Canadian Rare Diseases Models and Mechanisms (RDMM) Network: Connecting Understudied Genes to Model Organisms.

Advances in genomics have transformed our ability to identify the genetic causes of rare diseases (RDs), yet we have a limited understanding of the mechanistic roles of most genes in health and disease. When a novel RD gene is first discovered, there is minimal insight into its biological function, the pathogenic mechanisms of disease-causing variants, and how therapy might be approached. To address this gap, the Canadian Rare Diseases Models and Mechanisms (RDMM) Network was established to connect clinicians discovering new disease genes with Canadian scientists able to study equivalent genes and pathways in model organisms (MOs).

Extracellular vesicles derived from injured vascular tissue promote the formation of tertiary lymphoid structures in vascular allografts.

Tertiary lymphoid structures (TLS) accumulate at sites of chronic injury where they function as an ectopic germinal center, fostering local autoimmune responses. Vascular injury leads to the release of endothelial-derived apoptotic exosome-like vesicles (ApoExo) that contribute to rejection in transplanted organs. The purpose of the study was to evaluate the impact of ApoExo on TLS formation in a model of vascular allograft rejection.

Restored immune cell functions upon clearance of senescence in the irradiated splenic environment.

Some studies show eliminating senescent cells rejuvenate aged mice and attenuate deleterious effects of chemotherapy. Nevertheless, it remains unclear whether senescence affects immune cell function. We provide evidence that exposure of mice to ionizing radiation (IR) promotes the senescent-associated secretory phenotype (SASP) and expression of p16 in splenic cell populations.

Genetics of the patella.

We review genetic diseases with identified molecular bases that include abnormal, reduced (hypoplasia), or absent (aplasia) patellae as a significant aspect of the phenotype. The known causal genes can be broadly organized according to three major developmental and cellular processes, although some genes may act in more than one of these: limb specification and pattern formation; DNA replication and chromatin structure; bone development and differentiation. There are also several genes whose phenotypes in mice indicate relevance to patellar development, for which human equivalent syndromes have not been reported.

Grey Matter Volume Differences Associated with Extremely Low Levels of Cannabis Use in Adolescence.

Rates of cannabis use among adolescents are high, and are increasing concurrent with changes in the legal status of marijuana and societal attitudes regarding its use. Recreational cannabis use is understudied, especially in the adolescent period when neural maturation may make users particularly vulnerable to the effects of Δ-9-tetrahydrocannabinol (THC) on brain structure. In the current study, we used voxel-based morphometry to compare gray matter volume (GMV) in forty-six 14-year-old human adolescents (males and females) with just one or two instances of cannabis use and carefully matched THC-naive controls.

N-Guanidyl and C-Tetrazole Leu-Enkephalin Derivatives: Efficient Mu and Delta Opioid Receptor Agonists with Improved Pharmacological Properties.

Leu-enkephalin and d-Ala-Leu-enkephalin were modified at their N- and C-termini with guanidyl and tetrazole groups. The resulting molecules were prepared in solution or by solid phase peptide synthesis. The affinity of the different analogues at mu (MOP) and delta opioid receptors (DOP) was then assessed by competitive binding in stably transfected DOP and MOP HEK293 cells.

Increased Connectivity Between the Nucleus Accumbens and the Default Mode Network in Patients With Schizophrenia During Cigarette Cravings.

Compared to the general population, tobacco smoking cessation rates are lower in populations with schizophrenia. Unfortunately, the potential neurophysiologic mechanisms underlying these low cessation rates in schizophrenia have been seldom studied using functional neuroimaging. Recently, it has been shown that tobacco cravings are increased in smokers with schizophrenia compared to smokers with no comorbid psychiatric disorder.