Hippocampal reelin and GAD67 gene expression and methylation in the GFAP.HMOX1 mouse model of schizophrenia.

Schizophrenia is a complex neuropsychiatric disorder featuring enhanced brain oxidative stress and deficient reelin protein. GFAP.HMOX1 mice that overexpress heme oxygenase-1 (HO-1) in astrocytes manifest a schizophrenia-like neurochemical, neuropathological and behavioral phenotype including brain oxidative stress and reelin downregulation.

A Concussion Management Policy Change Promoted Earlier Initiation of Rehabilitation Services and Improved Clinical Recovery Outcomes in Concussion.

Context: In line with emerging research, an interprofessional specialty concussion clinic instituted a policy change permitting earlier physiotherapy-based treatment entry. Our objective was to determine the effect of this policy change on concussion recovery outcomes.

Design: Secondary analysis of prospectively collected clinical data.

Preparation, modification, characterization, and stability evaluation of 5-methyltetrahydrofolate liposomes.

As an essential B vitamin, folate participates in one‑carbon metabolism. The 5-methyltetrahydrofolate (5-MTHF) avoids the drawbacks associated with folic acid and native folylpolyglutamate folate in food, thereby emerging as a superior alternative to folate supplement. To enhance the stability and digestibility of 5-MTHF, nanoliposome (NL) was modified using a layer-by-layer self-assembly method with chitosan (CH) and pectin (P).

A Phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): Rationale, design, and baseline data.

Introduction: Prasinezumab was shown to potentially delay motor progression in individuals with early-stage Parkinson's disease (PD) who were either treatment-naïve or on monoamine oxidase type B inhibitor (MAO-Bi) therapy in the PASADENA study. We report the rationale, design, and baseline patient characteristics of the PADOVA study, designed to evaluate prasinezumab in an early-stage PD population receiving standard-of-care (SOC) symptomatic medications.

Methods: PADOVA (NCT04777331) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, in which individuals with early-stage PD on SOC stable symptomatic monotherapy (levodopa or MAO-Bi) receive intravenous prasinezumab 1500 mg every 4 weeks.

The effects of referential continuity on novel word learning in bilingual and monolingual preschoolers.

Previous research suggests that monolingual children learn words more readily in contexts with referential continuity (i.e., repeated labeling of the same referent) than in contexts with referential discontinuity (i.

Stored elastic bending tension as a mediator of embryonic body folding.

During development, amniote vertebrate embryos transform from a flat sheet into a three-dimensional cylindrical form through ventral folding of the lateral sides of the sheet (the lateral plate [LP]) and their fusion in the ventral midline. Using a chick embryo slice system, we find that the flat stage is actually a poised balance of opposing dorsal and ventral elastic bending tensions. An intact extracellular matrix (ECM) is required for generating tension, as localized digestion of ECM dissipates tension, while removal of endoderm or ectoderm layers has no significant effect.

CAR/CSACI Practice Guidance for Contrast Media Hypersensitivity.

Contrast media, including iodinated contrast media and gadolinium-based contrast agents, are commonly administered pharmaceuticals with excellent safety profiles. However, a minority of the population may experience a hypersensitivity reaction following intravenous administration. Hypersensitivity reactions can be immediate or delayed, and range from mild, such as urticaria, to severe, including anaphylaxis.

Comparative effectiveness and safety of single inhaler triple therapies for chronic obstructive pulmonary disease: new user cohort study.

Objective: To compare the effectiveness and safety of budesonide-glycopyrrolate-formoterol, a twice daily metered dose inhaler, and fluticasone-umeclidinium-vilanterol, a once daily dry powder inhaler, in patients with chronic obstructive pulmonary disease (COPD) treated in routine clinical practice.

Design: New user cohort study.

Setting: Longitudinal commercial US claims data.

Fracture Risk Assessment in the 2023 Osteoporosis Canada Guideline.

Radiologists and other diagnostic imaging specialists play a pivotal role in the management of osteoporosis, a highly prevalent condition of reduced bone strength and increased fracture risk. Bone mineral density (BMD) measurement with dual-energy X-ray absorptiometry (DXA) is a critical component of identifying individuals at high risk for fracture. Strategies to prevent fractures are consolidated in the Osteoporosis Canada clinical practice guideline which was updated in 2023.

Advancing Colorectal Cancer Prevention in Inflammatory Bowel Disease (IBD): Challenges and Innovations in Endoscopic Surveillance.

Patients with inflammatory bowel disease (IBD) face an elevated risk of developing colorectal cancer (CRC). Endoscopic surveillance is a cornerstone in CRC prevention, enabling early detection and intervention. However, despite recent advancements, challenges persist.

Cost-Effectiveness of PARP Inhibitors for Patients with BRCA1/2-Positive Metastatic Castration-Resistant Prostate Cancer-The Canadian Perspective.

Background/objectives: Through phase III clinical trials, PARP inhibitors have demonstrated outcome improvements in mCRPC patients with alterations in BRCA1/2 genes who have progressed on a second-generation androgen receptor pathway inhibitor (ARPI). While improving outcomes, PARP inhibitors contribute to the ever-growing economic burden of PCa. The objective of this project is to evaluate the cost-effectiveness of PARP inhibitors (olaparib, rucaparib, or talazoparib) versus the SOC (docetaxel or androgen receptor pathway inhibitors (ARPI)) for previously progressed mCRPC patients with BRCA1/2 mutations from the Canadian healthcare system perspective.

Folic Acid and Methyltetrahydrofolate Supplementation in the Mouse Model with Hepatic Steatosis.

Background/objectives: The gene variant results in a thermolabile MTHFR enzyme associated with elevated plasma homocysteine in TT individuals. Health risks associated with the TT genotype may be modified by dietary and supplemental folate intake. Supplementation with methyltetrahydrofolate (methylTHF) may be preferable to folic acid because it is the MTHFR product, and does not require reduction by DHFR to enter one-carbon folate metabolism.

Quantitative Physiologic MRI Combined with Feature Engineering for Developing Machine Learning-Based Prediction Models to Distinguish Glioblastomas from Single Brain Metastases.

: The accurate and early distinction of glioblastomas (GBMs) from single brain metastases (BMs) provides a window of opportunity for reframing treatment strategies enabling optimal and timely therapeutic interventions. We sought to leverage physiologically sensitive parameters derived from diffusion tensor imaging (DTI) and dynamic susceptibility contrast (DSC)-perfusion-weighted imaging (PWI) along with machine learning-based methods to distinguish GBMs from single BMs. : Patients with histopathology-confirmed GBMs ( = 62) and BMs ( = 26) and exhibiting contrast-enhancing regions (CERs) underwent 3T anatomical imaging, DTI and DSC-PWI prior to treatment.

FOGS: A SNPSTR Marker Database to Combat Wildlife Trafficking and a Cell Culture Bank for Ex-Situ Conservation.

Illegal wildlife trade is a growing problem internationally. Poaching of animals not only leads to the extinction of populations and species but also has serious consequences for ecosystems and economies. This study introduces a molecular marker system that authorities can use to detect and substantiate wildlife trafficking.

Integrating artificial intelligence with mechanistic epidemiological modeling: a scoping review of opportunities and challenges.

Integrating prior epidemiological knowledge embedded within mechanistic models with the data-mining capabilities of artificial intelligence (AI) offers transformative potential for epidemiological modeling. While the fusion of AI and traditional mechanistic approaches is rapidly advancing, efforts remain fragmented. This scoping review provides a comprehensive overview of emerging integrated models applied across the spectrum of infectious diseases.

Is Specific Consent for Educational Sensitive Exams on Anesthetized Patients Necessary? Arguments for and Against From Canadian Medical Students.

Objective: Discussions related to the importance of seeking specific consent for sensitive (e.g., pelvic, rectal) exams performed on anesthetized patients by medical students have been growing.

Oncogenic IDH1 drives robust loss of histone acetylation and increases chromatin heterogeneity.

Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.

Beyond Increasing Sample Sizes: Optimizing Effect Sizes in Neuroimaging Research on Individual Differences.

Linking neurobiology to relatively stable individual differences in cognition, emotion, motivation, and behavior can require large sample sizes to yield replicable results. Given the nature of between-person research, sample sizes at least in the hundreds are likely to be necessary in most neuroimaging studies of individual differences, regardless of whether they are investigating the whole brain or more focal hypotheses. However, the appropriate sample size depends on the expected effect size.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Mapping patterns of thought onto brain activity during movie-watching.

Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the 'here and now' depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching.

Patterns of Cerebellar-Cortical Structural Covariance Mirror Anatomical Connectivity of Sensorimotor and Cognitive Networks.

The cortex and cerebellum are densely connected through reciprocal input/output projections that form segregated circuits. These circuits are shown to differentially connect anterior lobules of the cerebellum to sensorimotor regions, and lobules Crus I and II to prefrontal regions. This differential connectivity pattern leads to the hypothesis that individual differences in structure should be related, especially for connected regions.

Photochemical Stabilization of Self-Assembled Spherical Nucleic Acids.

Oligonucleotide therapeutics, including antisense oligonucleotides and small interfering RNA, offer promising avenues for modulating the expression of disease-associated proteins. However, challenges such as nuclease degradation, poor cellular uptake, and unspecific targeting hinder their application. To overcome these obstacles, spherical nucleic acids have emerged as versatile tools for nucleic acid delivery in biomedical applications.

Household water security is a mediator of household food security in a nationally representative sample of Mexico.

Objective: Explore the relationship between water insecurity and food security and their covariates in Mexican households.

Design: A cross-sectional study with nationally representative data from the National Health and Nutrition Survey-Continuous 2021 (in Spanish, ENSANUT-Continua 2021), collected data from 12,619 households.

Setting: Water insecurity was measured using the Household Water Insecurity Experiences (HWISE) Scale in Spanish and adapted to the Mexican context.

Evolving trends in novel sleep tracking and sleep testing technology publications between 2020-2022.

Study Objectives: To update sleep medicine providers regarding (1) published research on the uses and performance of novel sleep tracking and testing technologies (2) the use of artificial intelligence to acquire and process sleep data and (3) research trends and gaps regarding the development and/or evaluation of these technologies.

Methods: Medline and Embase electronic databases were searched for studies utilizing screening and diagnostic sleep technologies, published between 2020 and 2022 in journals focusing on human sleep. Studies' quality was determined based on the Study Design criteria of The Oxford Centre for Evidence-Based Medicine Levels of Evidence.