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.

The Passage of Chaperonins to Extracellular Locations in Requires a Functional Dot/Icm System.

HtpB, the chaperonin of the bacterial pathogen , is found in extracellular locations, even the cytoplasm of host cells. Although chaperonins have an essential cytoplasmic function in protein folding, HtpB exits the cytoplasm to perform extracellular virulence-related functions that support 's lifestyle. The mechanism by which HtpB reaches extracellular locations is not currently understood.

The Role of Neuroglia in the Development and Progression of Schizophrenia.

Schizophrenia is a complex heterogenous disorder thought to be caused by interactions between genetic and environmental factors. The theories developed to explain the etiology of schizophrenia have focused largely on the dysfunction of neurotransmitters such as dopamine, serotonin and glutamate with their receptors, although research in the past several decades has indicated strongly that other factors are also involved and that the role of neuroglial cells in psychotic disorders including schizophrenia should be given more attention. Although glia were originally thought to be present in the brain only to support neurons in a physical, metabolic and nutritional capacity, it has become apparent that these cells have a variety of important physiological roles and that abnormalities in their function may make significant contributions to the symptoms of schizophrenia.

Sources and Transmission Routes of Carbapenem-Resistant : Study Design and Methodology of the SAMPAN Study.

: The global spread of carbapenem-resistant (CRPA) warrants collaborative action. Guidance should come from integrated One Health surveillance; however, a surveillance strategy is currently unavailable due to insufficient knowledge on the sources and transmission routes of CRPA. The aim of the SAMPAN study ("A Smart Surveillance Strategy for Carbapenem-resistant ") is to develop a globally applicable surveillance strategy.

Pharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age.

: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7-15) mg/kg. Currently, there are no INH suspensions available in Europe.

Monitoring the Spread of Multidrug-Resistant Throughout the Broiler Production Cycle.

The extensive use of antimicrobials in broiler production is changing the bird microbiota, fostering drug-resistant bacteria, and complicating therapeutic interventions, making the problem of multidrug resistance global. The monitoring of antimicrobial virulence and resistance genes are tools that have come to assist the breeding of these animals, directing possible treatments as already used in human medicine and collecting data to demonstrate possible dissemination of multidrug-resistant strains that may cause damage to industry and public health. This work aimed to monitor broiler farms in southern Brazil, isolating samples of and classifying them according to the profile of resistance to antimicrobials of interest to human and animal health.

Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage and bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) and biologics, some patients remain refractory to conventional treatments. Tetracyclines, such as minocycline and doxycycline, exhibit anti-inflammatory and immunomodulatory properties, making them potential supplementary treatments.

Application of Genomic Selection in Beef Cattle Disease Prevention.

Genomic applications in beef cattle disease prevention have gained traction in recent years, offering new strategies for improving herd health and reducing economic losses in the livestock industry. Advances in genomics, including identification of genetic markers linked to disease resistance, provide powerful tools for early detection, selection, and management of cattle resistant to infectious diseases. By incorporating genomic technologies such as whole-genome sequencing, genotyping, and transcriptomics, researchers can identify specific genetic variants associated with resistance to pathogens like bovine respiratory disease and Johne's disease.

The Wildcat That Lives in Me: A Review on Free-Roaming Cats () in Brazil, Focusing on Research Priorities, Management, and Their Impacts on Cat Welfare.

Domestic cats () currently occupy the 38th place in the Global Invasive Species Database. Free-roaming cats potentially have broad-ranging impacts on wildlife, occupying most terrestrial environments globally as house pets, strays, or feral animals. In Australia, for example, cats are responsible for the decline in many vertebrate populations and extinction of several native mammals.

A Framework for Comprehensive Dairy Calf Health Investigations.

The objective of this narrative review is to provide a systematic framework for veterinarians to investigate dairy calf health, focusing on critical control points and key performance indicators (KPIs) to address morbidity and mortality challenges in preweaned calves. Recommendations target prenatal maternal nutrition, heat stress abatement, and optimal calving management to minimize risks associated with perinatal mortality and preweaning morbidity. Further, comprehensive colostrum management is discussed to ensure excellent transfer of passive immunity, which includes prompt collection and feeding within two hours of birth at a volume of 8.

Validation of a Portable Ionized Calcium Detection Device and Changes in the Ionized-to-Total-Calcium Ratio in the Blood of Postpartum Holstein Cows.

The calcium requirements of dairy cows increase dramatically soon after calving, and many cows have subclinical hypocalcemia, adversely affecting health and performance. Traditional laboratory tests for calcium are complex and not easily adapted to rapid point-of-care applications. The objectives were to evaluate a portable iCa testing device, Horiba LAQUAtwin Ca-11C, for measuring ionized calcium (iCa) in the whole blood of dairy cows and to investigate the iCa-to-total-calcium (tCa) ratio in blood collected from dairy cows within 9 days after calving.

A Comparative Study of the Effect of Including Full-Fat for Replacing Conventional Ingredients in Practical Diets for Juveniles.

(TM) meal is a potential alternative ingredient to plant and fishmeal in aquafeeds due to its high protein content, digestibility, and low environmental impact. However, its low n-3 PUFA (EPA and DHA) content represents one of its main limitations. This study evaluated the effects of replacing fishmeal and plant-derived ingredients (plant proteins and soybean oil) with full-fat TM meal on the growth performance and lipid composition of tissues in juvenile European seabass ().

Risk Factors for Treatment Toxicity and High Side Effect Burden Among Breast Cancer Survivors: A Retrospective Chart Review.

Background/objectives: This study describes the sequelae, side effects, and toxicities experienced by Canadian breast cancer survivors at a breast cancer survivorship clinic at a tertiary academic cancer centre and identifies potential risk factors which may be associated with increased side effect burden.

Methods: A retrospective chart review was performed of adult patients treated at the Sunnybrook Breast Cancer Survivorship Clinic from 6 July 2022, to 30 September 2023 ( = 435).

Results: Most patients (72.

The Impact of Radiotherapy on the Primary Tumor in Patients with Metastatic High-Volume Castration-Sensitive Prostate Cancer: A Propensity Score Matching Analysis.

Retrospective studies suggest that local radiotherapy on the prostate improves overall survival in the metastatic setting, but its benefit in patients with high-burden metastatic disease is still uncertain. We conducted a retrospective study of 100 high-metastatic-burden prostate cancer patients at Hadassah Ein Karem Medical Center from 2004 to 2021. Patients receiving local RT alongside standard treatment were compared to those receiving standard treatment alone.

Calreticulin-From the Endoplasmic Reticulum to the Plasma Membrane-Adventures of a Wandering Protein.

Calreticulin (CRT) is a 46 kDa highly conserved protein initially identified as calregulin, a prominent Ca-binding protein of the endoplasmic reticulum (ER). Subsequent studies have established that CRT functions in the ER's protein folding response and Ca homeostatic mechanisms. An ER retention signal on the carboxyl terminus of CRT suggested that CRT was restricted to the ER.

Systemic Mechanisms of Ionic Regulation in Carcinogenesis.

Cancer is a complex disease characterized by uncontrolled cell proliferation at various levels, leading to tumor growth and spread. This review focuses on the role of ion homeostasis in cancer progression. It describes a model of ion-mediated regulation in both normal and cancerous cell proliferation.

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.

Neuroendocrine Transformation as a Mechanism of Resistance to Targeted Lung Cancer Therapies: Emerging Mechanisms and Their Therapeutic Implications.

Lung cancer is the leading cause of cancer-related deaths worldwide, highlighting a major clinical challenge. Lung cancer is broadly classified into two histologically distinct subtypes, termed small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Identification of various oncogenic drivers of NSCLC has facilitated the development of targeted therapies that have dramatically improved patient outcomes.

Diagnosis and Management of Skin Toxicities in Systemic Treatment of Genitourinary Cancers.

The landscape of available therapeutic options for treatment of genitourinary (GU) cancers is expanding dramatically. Many of these treatments have distinct, sometimes severe, skin toxicities including morbilliform, bullous, pustular, lichenoid, eczematous, psoriasiform, and palmoplantar eruptions. Pruritus and skin pigmentation changes have also been noted.

Characteristics, Treatment and Outcomes of Stage I to III Colorectal Cancer in Patients Aged over 80 Years Old.

Background: Colorectal cancer primarily affects older adults and poses treatment challenges due to age-related comorbidities and frailty, which hinder surgical and chemotherapy options for many elderly patients. This study aims to analyze treatment and disease patterns in elderly colorectal cancer patients, aged over 80 years old, to inform personalized therapies that accommodate their unique clinical needs and improve their outcomes.

Patients And Methods: The medical records of all patients aged 80 years old and above, and those aged 65 to 75 years old, who were diagnosed with colorectal cancer at a cancer center in Canada over a seven year period, were retrospectively reviewed.

Female Oncofertility and Immune Checkpoint Blockade in Melanoma: Where Are We Today?

The incidence of melanoma among young adults has risen, yet mortality has declined annually since the introduction of immune checkpoint inhibitors (ICI). The utilization of peri-operative ICI has significantly altered the treatment landscape in melanoma, with PD-1 inhibitors showing promising efficacy in improving relapse-free survival rates in high-risk stage II-III disease. With the increasing use of ICI, secondary concerns have emerged regarding the impact of cancer drugs on fertility and reproductive health among women of childbearing potential, especially in early-stage cancer settings.

Early Versus Delayed Androgen Deprivation Therapy for Biochemical Recurrence After Local Curative Treatment in Non-Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review of the Literature.

Background: The ideal timing of androgen deprivation therapy (ADT) for patients with biochemical recurrence (BCR) of prostate cancer (PCa) remains controversial due to its side effects and uncertain impact on survival outcomes.

Methods: We performed a review of the current literature by comprehensively searching the PubMed, Embase, and Cochrane databases to determine the optimal timing of ADT initiation after biochemical recurrence. We selected 26 studies including systematic reviews, randomized controlled trials (RCTs), and retrospective studies, while also reviewing practice guidelines.

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.

Unpacking the Mood States of Children and Youth in Saskatchewan, Canada, in the Context of the COVID-19 Pandemic: Insights from the "See Us, Hear Us 2.0" Study.

Background/objectives: The COVID-19 pandemic created a growing need for insights into the mental health of children and youth and their use of coping mechanisms during this period. We assessed mood symptoms and related factors among children and youth in Saskatchewan. We examined if coping abilities mediated the relationship between risk factors and mood states.