Polycyclic aromatic hydrocarbons from environmental tobacco smoke and wood stoves dominate in settled house dust from Northwestern Ontario First Nations communities.

Rates of respiratory tract infections for children living in remote First Nations communities in the Sioux Lookout Zone in Northwestern Ontario are elevated and associated with poor indoor environmental quality including high exposures to endotoxin and serious dampness and mould damage. The studies also revealed a high prevalence of cigarette smoking and most houses have wood stoves, of variable quality. Depending on structure, polycyclic aromatic hydrocarbons (PAH) are carcinogens, immunotoxins and/or inflammatory mediators that are byproducts of the incomplete combustion of organic materials.

Disco-Interacting Protein 2 Homolog B CGG Repeat Expansion in Siblings with Neurodevelopmental Disability and Progressive Movement Disorder.

Background: Trinucleotide repeat expansions are an emerging class of genetic variants associated with various movement disorders. Unbiased genome-wide analyses can reveal novel genotype-phenotype associations and provide a diagnosis for patients and families.

Objective: The aim was to identify the genetic cause of a severe progressive movement disorder phenotype in 2 affected brothers.

Fixed dosing of alpelisib for children with vascular anomalies: Can we do better?

Severe forms of vascular malformations (VM) can highly impact patients' quality of life and lead to life-threatening organ dysfunction. Numerous VM are caused by somatic activating mutations in the PI3K/AKT/mTOR signalling pathway. Alpelisib, a PIK3CA inhibitor was recently FDA-approved for paediatric PIK3CA-related overgrowth syndrome (PROS).

Neonatal Nutrition and Brain Structure at 7 Years in Children Born Very Preterm.

Importance: Neonatal protein intake following very preterm birth has long lasting effects on brain development. However, it is uncertain whether these effects are associated with improved or impaired brain maturation.

Objective: To assess the association of neonatal protein intake following very preterm birth with brain structure at 7 years of age.

Performance-Based Outcome Measures After Hip or Knee Arthroplasty: A Systematic Review and Content Analysis Using the International Classification of Functioning, Disability and Health (ICF).

Rational: One of the important considerations to select the appropriate outcome measures is determining if the tool is relevant to patients. Despite the availability of various performance-based tests to objectively assess function, it is unknown which performance-based tests best capture important aspects of function after hip or knee arthroplasty.

Aims And Objectives: Our systematic review aimed to identify the existing performance-based tests used in hip or knee arthroplasty and link the activity component of each test to the modified International Classification of Functioning, Disability and Health (ICF) core set for osteoarthritis (OA).

Brain-derived neurotrophic factor drives muscle adaptation similar to aerobic training in mice.

This study, in vivo and in vitro, investigated the role of brain-derived neurotrophic factor (BDNF) in skeletal muscle adaptations to aerobic exercise. BDNF is a contraction-induced protein that may play a role in muscle adaptations to aerobic exercise. BDNF is involved in muscle repair, increased fat oxidation, and mitochondrial biogenesis, all of which are adaptations observed with aerobic training.

Bioequivalence Design With Sampling Distribution Segments.

In bioequivalence design, power analyses dictate how much data must be collected to detect the absence of clinically important effects. Power is computed as a tail probability in the sampling distribution of the pertinent test statistics. When these test statistics cannot be constructed from pivotal quantities, their sampling distributions are approximated via repetitive, time-intensive computer simulation.

International Validation of a Novel PEACE Scale to Improve the Quality of Upper Gastrointestinal Mucosal Inspection During Endoscopy.

Introduction: The performance of a high quality esophagogastroduodenoscopy (EGD) is dependent on the mucosal cleanliness. Recently, the Polprep: Effective Assessment of Cleanliness in EGD (PEACE) scale was created to assess the degree of mucosal cleanliness during EGD. The aim of this study was to validate this scoring system in a cohort of international endoscopists.

Postoperative Rehabilitation Interventions in Patients at Risk of Poorer Outcomes Following Total Knee Arthroplasty: A Systematic Review.

Purpose: This systematic review evaluated the efficacy of postoperative rehabilitation for patients at risk of poorer outcomes after total knee arthroplasty.

Methods: Six databases were searched, and only randomised controlled trials were included. Two reviewers independently screened, extracted data, and appraised the quality of the studies.

Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution.

Prostate cancer is a common malignancy that in 5%-30% leads to treatment-resistant and highly aggressive disease. Metastasis-potential and treatment-resistance is thought to rely on increased plasticity of the cancer cells-a mechanism whereby cancer cells alter their identity to adapt to changing environments or therapeutic pressures to create cellular heterogeneity. To understand the molecular basis of this plasticity, genomic studies have uncovered genetic variants to capture clonal heterogeneity of primary tumors and metastases.

Development and Pilot Implementation of a Theory-Based Cognitive Rehabilitation Protocol for Adults With Chronic Cognitive Complaints After Mild Traumatic Brain Injury.

Purpose: The aim of this study was to describe the development of and pilot feasibility outcomes for a strategy-based, brief, intensive cognitive rehabilitation intervention delivered to U.S. service members and veterans with mild traumatic brain injury in a recently completed 3-year pragmatic clinical trial: Symptom-Targeted Approach to Rehabilitation for Concussion (STAR-C).

Genomic analyses reveal high diversity and rapid evolution of within a neonatal intensive care unit in Delhi, India.

causes life-threatening infections in immunocompromised hosts, including hospitalized neonates. This pathogen is intrinsically resistant to fluconazole, while uncommon strains resistant to multiple antifungal drugs, including voriconazole, amphotericin B, and echinocandins, have also been reported from healthcare environments. Thus, understanding how spread, persist, and adapt to healthcare settings could help us develop better infection management strategies.

Acute Febrile Illness Accompanied by 7th and 12th Cranial Nerve Palsy Due to Lyme Disease Following Travel to Rural Ecuador: A Case Report and Mini-Review.

The causative agent of Lyme disease, , is endemic to Canada, the northeastern United States, northern California, and temperate European regions. It is rarely associated with a travel-related exposure. In this report, we describe a resident of southern Ontario, Canada who developed rash, fever, and cranial nerve VII and XII palsies following a 12 day trip to Ecuador and the Galapagos islands approximately four weeks prior to referral to our center.

: Co-Design of a Novel Approach for Engaging People with Dementia in Physical Activity.

Background: Promoting physical activity among people living with dementia is critical to maximise physical, cognitive and social benefits; yet the lack of knowledge, skills and confidence among health professionals, informal care partners and people with dementia deters participation. As the initial phase of a larger feasibility study, co-design was employed to develop a new model of community care, to facilitate the physical activity participation of older people living with mild dementia.

Methods: Co-design methodology was utilised with nine stakeholders (with experience in referring to or providing physical activity programs and/or contributing to policy and program planning) over three workshops plus individual interviews with four care partners of people with dementia.

Deep learning analyses of splicing variants identify the link of PCP4 with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease, with most sporadic cases lacking clear genetic causes. Abnormal pre-mRNA splicing is a fundamental mechanism in neurodegenerative diseases. For example, TAR DNA-binding protein 43 (TDP-43) loss-of-function (LOF) causes widespread RNA mis-splicing events in ALS.

Assessing the TNM Classification for Periprosthetic Joint Infections of the Knee: Predictive Validity for Functional and Subjective Outcomes.

Periprosthetic joint infection (PJI) following knee arthroplasty can significantly compromise patient mobility and quality of life. The newly proposed TNM classification system, adapted from oncology, categorizes PJI severity but has not yet been correlated with both subjective and objective outcomes post PJI treatment. This study evaluates the applicability of the TNM classification system for predicting outcomes in knee PJI revision surgeries.

A Mediation Appraisal of Neuropathic-like Symptoms, Pain Catastrophizing, and Central Sensitization-Related Signs in Adults with Knee Osteoarthritis-A Cross-Sectional Study.

To investigate the relationships among neuropathic pain (NP), pain catastrophizing (PC), and central sensitization (CS) in relation to functional status and radiological damage in patients with knee osteoarthritis (OA). This cross-sectional study included knee OA patients derived from an observational cohort. The Spearman correlation test was used to analyze the relationship between the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the PainDetect Questionnaire (PDQ), Central Sensitization Inventory (CSI), and Pain Catastrophizing Scale (PCS).

Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 Inhibitors.

Introduction: The optimal treatment of estrogen receptor-positive (ER +) metastatic breast cancer (MBC) after progression on cyclin-dependent 4/6 kinase inhibitors (CDK4/6i) is unknown.

Methods: We conducted a systematic review and network meta-analysis (NMA) of phase-II/-III randomized trials of ER + MBC post CDK4/6i + ET progression. We calculated the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) using generic inverse variance and odds ratios (ORs) using the Mantel-Haenszel method for adverse events (AEs) with Review-Manager version-5.

Trends in Real-World Clinical Outcomes of Patients with Anaplastic Lymphoma Kinase (ALK) Rearranged Non-Small Cell Lung Cancer (NSCLC) Receiving One or More ALK Tyrosine Kinase Inhibitors (TKIs): A Cohort Study in Ontario, Canada.

The treatment landscape for patients with advanced ALK-positive NSCLC has rapidly evolved following the approval of several ALK TKIs in Canada. However, public funding of ALK TKIs is mostly limited to the first line treatment setting. Using linked provincial health administrative databases, we examined real-world outcomes of patients with advanced ALK-positive NSCLC receiving ALK TKIs in Ontario between 1 January 2012 and 31 December 2021.

A Real-World Comparison Between Adjuvant Docetaxel with Cyclophosphamide (TC) and Anthracycline-Taxane Chemotherapy in Early HER-2 Negative Breast Cancer.

Background: Anthracycline-taxane chemotherapy is the gold standard in high-risk breast cancer (BC), despite the potential risk of congestive heart failure (CHF). A suitable alternative for anthracycline-sparing chemotherapy is through the combination of docetaxel and cyclophosphamide (TC).

Methods: Through a retrospective study of stage I-III HER2-negative BC, using administrative databases, we analyzed a total of 10,634 women treated with adjuvant chemotherapy in Ontario, Canada, between 2009 and 2017.