Liposomal Formulation of Hydroxychloroquine Can Inhibit Autophagy In Vivo.

Preclinical studies have shown that the anti-malarial drug hydroxychloroquine (HCQ) improves the anti-cancer effects of various therapeutic agents by impairing autophagy. These findings are difficult to translate in vivo as reaching an effective HCQ concentration at the tumor site for extended times is challenging. Previously, we found that free HCQ in combination with gefitinib (Iressa, ZD1839) significantly reduced tumor volume in immunocompromised mice bearing gefitinib-resistant JIMT-1 breast cancer xenografts.

Periocular Aging Across Populations and Esthetic Considerations: A Narrative Review.

As the face ages, the skin, fat, muscle, and fascia descend, and the underlying bone, cartilage, and teeth may lose mass. Oculofacial aging is a multifactorial process that is influenced by genetic, environmental, and lifestyle factors. This review summarizes the patterns of oculofacial aging that are observed across populations, including variations in periorbital hollowing, eyelid ptosis, and skin elasticity.

Navigating the Semiochemical Landscape: Attraction of Subcortical Beetle Communities to Bark Beetle Pheromones, Fungal and Host Tree Volatiles.

Subcortical beetle communities interact with a wide range of semiochemicals released from different sources, including trees, fungi, and bark beetle pheromones. While the attraction of bark beetles, their insect predators, and competitors to bark beetle pheromones is commonly studied, the attraction of these beetle communities to other sources of semiochemicals remains poorly understood. We tested the attraction of bark and wood-boring beetles and their predators to host stress volatiles, fungal volatiles, and a mountain pine beetle lure in the field.

Structure-Function Relationship of the β-Hairpin of HB27 Laccase.

Thermus thermophilus HB27 laccase (Tth-Lac) is a thermostable enzyme that contains a β-hairpin (Ala292-Gln307) covering the substrate entrance. We analyzed the role of this β-hairpin in the enzymatic activity of Tth-Lac through three β-hairpin mutants: two variants without the β-hairpin (C1Tth-Lac and C2Tth-Lac) and one with a partially modified β-hairpin (P1Tth-Lac). Enzymatic activity was assayed with different substrates with and without copper.

I/D Genotype and Risk of Non-Contact Injury in Moroccan Elite Athletes: A Pilot Study.

The insertion/deletion (I/D) polymorphism in , the gene encoding the angiotensin-converting enzyme (ACE), has been suggested as a genetic variation that can influence exercise performance and risk of injury in elite athletes. The I allele has been associated with enhanced endurance performance and with reduced inflammation, while the D allele has been associated with improved performance in strength and power activities. However, the role of this genetic variant in the incidence of non-contact injury is underexplored.

A Precessing-Coin-like Rotary Actuator for Distal Endoscope Scanners: Proof-of-Concept Study.

This paper presents, for the first time, a rotary actuator functionalized by an inclined disc rotor that serves as a distal optical scanner for endoscopic probes, enabling side-viewing endoscopy in luminal organs using different imaging/analytic modalities such as optical coherence tomography and Raman spectroscopy. This scanner uses a magnetic rotor designed to have a mirror surface on its backside, being electromagnetically driven to roll around the cone-shaped hollow base to create a motion just like a precessing coin. An optical probing beam directed from the probe's optic fiber is passed through the hollow cone to be incident and bent on the back mirror of the rotating inclined rotor, circulating the probing beam around the scanner for full 360° sideway imaging.

Lipopolymers as the Basis of Non-Viral Delivery of Therapeutic siRNA Nanoparticles in a Leukemia (MOLM-13) Model.

Small interfering RNA (siRNA) therapy in acute myeloid leukemia (AML) is a promising strategy as the siRNA molecule can specifically target proteins involved in abnormal cell proliferation. The development of a clinically applicable method for delivering siRNA molecules is imperative due to the challenges involved in effectively delivering the siRNA into cells. We investigated the delivery of siRNA to AML MOLM-13 cells with the use of two lipid-substituted polyethyleneimines (PEIs), a commercially available reagent (Prime-Fect) and a recently reported reagent with improved lipid substitution (PEI1.

Enhanced Lung Cancer Survival Prediction Using Semi-Supervised Pseudo-Labeling and Learning from Diverse PET/CT Datasets.

Objective: This study explores a semi-supervised learning (SSL), pseudo-labeled strategy using diverse datasets such as head and neck cancer (HNCa) to enhance lung cancer (LCa) survival outcome predictions, analyzing handcrafted and deep radiomic features (HRF/DRF) from PET/CT scans with hybrid machine learning systems (HMLSs).

Methods: We collected 199 LCa patients with both PET and CT images, obtained from TCIA and our local database, alongside 408 HNCa PET/CT images from TCIA. We extracted 215 HRFs and 1024 DRFs by PySERA and a 3D autoencoder, respectively, within the ViSERA 1.

MET Activation in Lung Cancer and Response to Targeted Therapies.

The hepatocyte growth factor receptor (MET) is a receptor tyrosine kinase (RTK) that mediates the activity of a variety of downstream pathways upon its activation. These pathways regulate various physiological processes within the cell, including growth, survival, proliferation, and motility. Under normal physiological conditions, this allows MET to regulate various development and regenerative processes; however, mutations resulting in aberrant MET activity and the consequent dysregulation of downstream signaling can contribute to cellular pathophysiology.

A Survey of Parents' Perspective of Receiving a Developmental Diagnosis for Their Child.

Receiving a diagnosis, such as cerebral palsy (CP), can have lasting impacts on caregivers and families. Previous literature has described that caregivers wish to receive a diagnosis together, without delay, in a private, direct, honest, and sympathetic way. This study aimed to understand the experience of caregivers of children with cerebral palsy (CP) or similar conditions when receiving a diagnosis for their child.

Empowerment in Adolescent Patients with a Disability/Chronic Condition: A Scoping Review.

Background/objectives: Empowerment has been associated with several positive outcomes in healthcare; however, there is limited insight on empowerment levels within the adolescent population of those with a chronic condition/disability. The aim of this scoping review was to identify gaps in the existing literature on empowerment levels within this population.

Methods: Five databases (MEDLINE [Ovid], EMBASE [Ovid], PsycINFO [Ebsco], CINHAL [Ebsco] and Web of Science [UBC]) and grey literature were searched.

Oncolytic Viruses and Immunotherapy for the Treatment of Uveal Melanoma and Retinoblastoma: The Current Landscape and Novel Advances.

Intraocular malignant tumors are rare; however, they can cause serious life-threatening complications. Uveal melanoma (UM) and retinoblastoma (RB) are the most common intraocular tumors in adults and children, respectively, and come with a great disease burden. For many years, several different treatment modalities for UM and RB have been proposed, with chemotherapy for RB cases and plaque radiation therapy for localized UM as first-line treatment options.

Challenges and Resiliency: Social Determinants of Health, COVID-19, and the Disproportionate Impact on Immigrants and Refugees Living with HIV.

The human immunodeficiency virus (HIV) pandemic is a global public health and social justice issue. HIV continues to disproportionately affect marginalized populations, including immigrants and refugees living with HIV (IRLHIV). This study investigated and captured the experiences of IRLHIV using the social determinants of health framework.

Comparative Analysis of One Health Policies in Asia for Exploring Opportunities for British Columbia in Canada.

In response to emerging challenges that intersect humans, animals, and environments, there is growing international exigent need to adopt 'One Health' approaches. While One Health efforts are emerging in British Columbia in Canada, there are still challenges to overcome in the adoption of a One Health approach in policymaking. We conducted a comparative analysis of One Health policies in Asia, specifically, Singapore, Hong Kong, Bangladesh, and Thailand, which have well-established and sophisticated One Health approaches, to determine good practices in the implementation of One Health that could be considered for adoption in British Columbia.

Oral Health, Anxiety, Depression, and Stress in Pregnancy: A Rapid Review of Associations and Implications for Perinatal Care.

Research demonstrates associations between oral health and specific mental health conditions in the general population, yet these relationships remain understudied during pregnancy, despite pregnancy's profound effects on both oral and psychological well-being. Our rapid review examines current evidence on associations between oral health conditions and psychological states (anxiety, depression, and stress) during pregnancy, aiming to inform and strengthen integrated prenatal care strategies. Following PRISMA-RR guidelines, we conducted a systematic search on OVID Medline, CINAHL, and PsycINFO (January 2000-November 2024) for studies examining relationships between oral health conditions (periodontal disease, dental caries) and psychological status during pregnancy and up to one year postpartum.

Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus.

The brain presents various structural and functional sex differences, for which multiple factors are attributed: genetic, epigenetic, metabolic, and hormonal. While biological sex is determined by both sex chromosomes and sex hormones, little is known about how these two factors interact to establish this dimorphism. Sex differences in the brain also affect its resident immune cells, microglia, which actively survey the brain parenchyma and interact with sex hormones throughout life.

Prenatal depression and child developmental vulnerability.

Background: Prenatal depression is a potentially important fetal exposure as it may alter fetal development and have lasting effects.

Methods: We examined all live births from 2001 to 2012 in British Columbia with follow-up data on the Early Development Instrument (EDI) in Kindergarten. The odds of developmental vulnerability on EDI domains among those with and without depression during pregnancy were estimated.

Pediatric COVID-19 severity by SARS-CoV-2 lineage and vaccine status in Canada: an IMPACT study.

Background: Interpretations of pediatric COVID-19 severity are complicated by novel lineages and COVID-19 vaccine introduction. We estimated the risk of severe COVID-19 by SARS-CoV-2 lineage and vaccination status among hospitalized Canadian children.

Methods: Data were collected through the Canadian Paediatric Surveillance Program (April 2020-May 2021) and Canadian Immunization Monitoring Program, ACTive (June 2021-December 2022).

HDR brachytherapy combined with external beam radiotherapy for unfavorable localized prostate cancer: A single center experience from inception to standard of care.

Purpose: High dose rate (HDR) brachytherapy is increasingly adopted for dose escalation in prostate cancer treatment. We report the clinical efficacy and toxicity of HDR prostate brachytherapy combined with external beam radiotherapy (EBRT) and evaluate the predictability of the biochemical definition of cure of 4-year PSA ≤0.2 ng/mL for failure free survival (FFS).

Environmental sampling for Dermacentor species (Acari: Ixodidae) in southern British Columbia, Canada in May, 2022.

Traditionally, the most commonly encountered Dermacentor spp. (Acari: Ixodidae) in southern British Columbia, Canada has been Dermacentor andersoni Stiles. However, with the novel detection of Dermacentor similis Lado in southern British Columbia, environmental sampling for Dermacentor spp.

Fingolimod and risk of skin cancer among individuals with multiple sclerosis: a population-based cohort study protocol.

Introduction: Long-term population-based safety studies, applying advanced causal inference techniques, including an active comparator with new-user design, are needed to investigate skin cancer outcomes among individuals with multiple sclerosis (MS) treated with fingolimod. This study aims to describe a protocol for investigating the relationship between fingolimod use and the incidence of skin cancer among individuals with MS.

Methods And Analysis: We will use population-based administrative health data from two Canadian provinces (British Columbia and Alberta) to conduct an observational cohort 'trial emulation' study with an active comparator and new-user design.

Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-versus-Host Disease Survivorship after Hematopoietic Cell Transplantation: Part II. Organ Dysfunction and Immune Reconstitution Considerations for children with chronic GVHD after Hematopoietic Cell Transplantation.

While highly morbid forms of chronic graft versus host disease (cGVHD) and severe late effects of allogeneic hematopoietic cell transplant (HCT) can impact children and adults alike, unique considerations arise in pediatric cases regarding diagnosis, monitoring, treatment, and likelihood of resolution. As children can present with atypical features of cGVHD, and with more significant disease due to inability to communicate symptoms, they may be at increased risk for highly morbid forms of cGVHD and incur greater subsequent late effects, which may be more pronounced in those with underlying chromosomal breakage syndromes, with higher prevalence in pediatric HCT recipients. The long-term effects of cGVHD and its therapies include impaired immune reconstitution, leading to increased risks of infection and secondary malignant neoplasms.

Accessory uterine cavities: a review of cases and an appeal for standard terminology.

Objective: To study and address the diagnostic, management, and classification challenges of unilocular myometrial cystic lesions adjacent to a normal uterine cavity.

Design: Describe 23 further cases, and undertake a systematic review using Medline, PubMed and Ovid for similar lesions.

Subjects: 23 cases of accessory uterine cavities presenting to pediatric and adolescent gynecologists in Australia and New Zealand.

Clinical Care Pathways for Second and Third Trimester Termination of Pregnancy for Medical Reasons in Canada.

Objective: Termination of pregnancy in the 2/3 trimester for fetal or maternal complications (i.e., for medical reasons) is an essential health service.