Reactive Oxygen Species-Responsive Polymeric Chloroquine Nanogel for Targeted Oral Therapy of Ulcerative Colitis.

Targeted drug delivery remains a critical challenge in the treatment of ulcerative colitis, as the side effects of current systemic therapies often outweigh their therapeutic benefits. In this study, we developed a reactive oxygen species (ROS)-responsive nanogel system that releases polymeric chloroquine (PCQ), a macromolecular derivative of hydroxychloroquine (HCQ), for localized treatment of ulcerative colitis. The initial nanogel formulation, measuring 183 nm in size with a surface charge of +13 mV, was synthesized via RAFT polymerization using a thioketal dimethacrylate cross-linker to demonstrate ROS-triggered degradation, physicochemical stability in simulated gastrointestinal fluids, favorable biocompatibility, and preferential accumulation in inflamed colonic tissue.

Assessment of the Psychological Burden Among Family Caregivers of People Living With Dementia, Parkinson's, and Alzheimer's Disease Using the Zarit Burden Interview From Bangladesh.

Objective: This study aimed to explore the burden experienced by family caregivers of individuals with dementia, Alzheimer's disease (AD), and Parkinson's disease (PD) in Bangladesh. It sought to identify the key contributing factors and determine the primary predictors influencing caregiver burden in this context.

Methods: Seventy-five caregivers were selected on the basis of specific criteria.

Programming megakaryocytes to produce engineered platelets for delivering non-native proteins.

Platelets are anucleate cells naturally filled with secretory granules that store large amounts of protein to be released in response to certain physiological conditions. Cell engineering can endow platelets with the ability to deliver non-native proteins by modifying them as they develop during the cell fate process. This study presents a strategy to efficiently generate mouse platelets from pluripotent stem cells and demonstrates their potential as bioengineered protein delivery platforms.

Effects of Palliative Esophageal External Beam Radiation Therapy in Patients with Stent for Esophageal Cancer: A Retrospective Cohort Study.

Purpose: Self-expandable metallic stents (SEMS) provide immediate but nondurable dysphagia relief in esophageal cancer, while external beam radiotherapy (EBRT) provides slower, more durable dysphagia relief. While the combination of SEMS with EBRT would seem to offer both rapid and durable dysphagia relief in the palliative setting, there remains controversy on its safety and efficacy. We investigated patient outcomes regarding EBRT after SEMS placement in patients with incurable esophageal cancer at a regional Canadian cancer program.

Polygenic Risk Score Analysis of Antidepressant Treatment Outcomes: A CAN-BIND-1 Study Report: Analyse des résultats du traitement antidépresseur à l'aide des scores de risque polygéniques : Rapport sur l'étude CAN-BIND-1.

ObjectiveThe genetic architecture of antidepressant response is poorly understood. This study investigated whether polygenic risk scores (PRSs) for major psychiatric disorders and a personality trait (neuroticism) are associated with antidepressant treatment outcomes.MethodsWe analysed 148 participants with major depressive disorder (MDD) from the Canadian Biomarker Integration Network for Depression-1 (CAN-BIND-1) cohort.

Evolution of long COVID over two years in hospitalised and non-hospitalised survivors in Bangladesh: a longitudinal cohort study.

Background: In developing settings, comparative data on COVID hospitalised survivors (HS) and non-hospitalised survivors (NHS) is scarce. We determined burdens, incidence, evolution, and associated factors of long COVID-19 over two years among these groups.

Methods: We conducted a longitudinal cohort study in Dhaka, Bangladesh, and recruited confirmed COVID-19 survivors from December 2020 to May 2021 (previously reported).

Comprehensive metabolite profiling and evaluation of anti-nociceptive and anti-inflammatory potencies of (Wurmb.) leaves: Experimental and in-silico approaches.

Globally, inflammation and pain are among the most prevalent health issues. The use of medicinal plants to alleviate these conditions is growing. This study comprehensively investigated the analgesic and anti-inflammatory properties of the ethyl-acetate extract of (EENF) leaves, traditionally used in folk Medicine.

Polygenic score analyses on antidepressant response in late-life depression, results from the IRL-GRey study.

Late-life depression (LLD) is often accompanied by medical comorbidities such as psychiatric disorders and cardiovascular diseases, posing challenges to antidepressant treatment. Recent studies highlighted significant associations between treatment-resistant depression (TRD) and polygenic risk score (PRS) for attention deficit hyperactivity disorder (ADHD) in adults as well as a negative association between antidepressant symptom improvement with both schizophrenia and bipolar. Here, we sought to validate these findings with symptom remission in LLD.

Lean Six Sigma quality improvement approach to implement clinical practice guidelines for prescribing opiates for chronic pain in a primary care setting.

Background: Implementing guidelines for chronic opioid management during a clinic merger posed significant challenges. Our aim was to increase the percentage of chronic pain evaluations and urine toxicology tests in patients on chronic opioid therapy from the baseline rate of less than 20% to 50% within 1 year at an academic, primary care clinic.

Methods: We applied the Define, Measure, Analyze, Improve, Control (DMAIC) approach of Lean Six Sigma for this quality improvement (QI) project.

Development of an extended action fostemsavir lipid nanoparticle.

An extended action fostemsavir (FTR) lipid nanoparticle (LNP) formulation prevents human immunodeficiency virus type one (HIV-1) infection. This FTR formulation establishes a drug depot in monocyte-derived macrophages that extend the drug's plasma residence time. The LNP's physicochemical properties improve FTR's antiretroviral activities, which are linked to the drug's ability to withstand fluid flow forces and levels of drug cellular internalization.

Integrative Genetic Variation, DNA Methylation, and Gene Expression Analysis of Escitalopram and Aripiprazole Treatment Outcomes in Depression: A CAN-BIND-1 Study.

Introduction: Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, , , , and , and its effect on these outcomes.

Methods: The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole.

An Integrated Smart Pond Water Quality Monitoring and Fish Farming Recommendation Aquabot System.

The integration of cutting-edge technologies such as the Internet of Things (IoT), robotics, and machine learning (ML) has the potential to significantly enhance the productivity and profitability of traditional fish farming. Farmers using traditional fish farming methods incur enormous economic costs owing to labor-intensive schedule monitoring and care, illnesses, and sudden fish deaths. Another ongoing issue is automated fish species recommendation based on water quality.

Molecular Insight into the Structural Dynamics of Holliday Junctions Modulated by Integration Host Factor.

The integration host factor (IHF) in is a nucleoid-associated protein with multifaceted roles that encompass DNA packaging, viral DNA integration, and recombination. IHF binds to double-stranded DNA featuring a 13-base pair (bp) consensus sequence with high affinity, causing a substantial bend of approximately 160° upon binding. Although wild-type IHF (WtIHF) is principally involved in DNA bending to facilitate foreign DNA integration into the host genome, its engineered counterpart, single-chain IHF (ScIHF), was specifically designed for genetic engineering and biotechnological applications.

Advancing in vivo reprogramming with synthetic biology.

Reprogramming cells will play a fundamental role in shaping the future of cell therapies by developing new strategies to engineer cells for improved performance and higher-order physiological functions. Approaches in synthetic biology harness cells' natural ability to sense diverse signals, integrate environmental inputs to make decisions, and execute complex behaviors based on the health of the organism or tissue. In this review, we highlight strategies in synthetic biology to reprogram cells, and discuss how recent approaches in the delivery of modified mRNA have created new opportunities to alter cell function in vivo.

Trajectories of resting energy expenditure and performance of predictive equations in children hospitalized with an acute illness and malnutrition: a longitudinal study.

There is scarce data on energy expenditure in ill children with different degrees of malnutrition. This study aimed to determine resting energy expenditure (REE) trajectories in hospitalized malnourished children during and after hospitalization. We followed a cohort of children in Bangladesh and Malawi (2-23 months) with: no wasting (NW); moderate wasting (MW), severe wasting (SW), or edematous malnutrition (EM).

Programming megakaryocytes to produce engineered platelets for delivering non-native proteins.

Platelets are anucleate cells naturally filled with secretory granules that store large amounts of protein to be released in response to certain physiological conditions. Cell engineering can endow platelets with the ability to deliver non-native proteins by modifying them as they develop during the cell fate process. This study presents a strategy to efficiently generate mouse platelets from pluripotent stem cells and demonstrates their potential as bioengineered protein delivery platforms.

Delivery of gene editing therapeutics.

For the past decades, gene editing demonstrated the potential to attenuate each of the root causes of genetic, infectious, immune, cancerous, and degenerative disorders. More recently, Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated protein 9 (CRISPR-Cas9) editing proved effective for editing genomic, cancerous, or microbial DNA to limit disease onset or spread. However, the strategies to deliver CRISPR-Cas9 cargos and elicit protective immune responses requires safe delivery to disease targeted cells and tissues.

Influence of , , and Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study.

Objectives: Treatment-emergent sexual dysfunction is frequently reported by individuals with major depressive disorder (MDD) on antidepressants, which negatively impacts treatment adherence and efficacy. We investigated the association of polymorphisms in pharmacokinetic genes encoding cytochrome-P450 drug-metabolizing enzymes, and , and the transmembrane efflux pump, P-glycoprotein (i.e.

Insights into the Dynamics and Helicase Activity of RecD2 of during DNA Repair: A Single-Molecule Perspective.

While the double helix is the most stable conformation of DNA inside cells, its transient unwinding and subsequent partial separation of the two complementary strands yields an intermediate single-stranded DNA (ssDNA). The ssDNA is involved in all major DNA transactions such as replication, transcription, recombination, and repair. The process of DNA unwinding and translocation is shouldered by helicases that transduce the chemical energy derived from nucleotide triphosphate (NTP) hydrolysis to mechanical energy and utilize it to destabilize hydrogen bonds between complementary base pairs.

ABCB1 Gene Variants and Antidepressant Treatment Outcomes: A Systematic Review and Meta-Analysis Including Results from the CAN-BIND-1 Study.

The P-glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a systematic review and meta-analysis to investigate the association between six ABCB1 single-nucleotide polymorphisms (SNPs; rs1045642, rs2032582, rs1128503, rs2032583, rs2235015, and rs2235040) and antidepressant treatment outcomes in individuals with major depressive disorder (MDD), including new data from the Canadian Biomarker and Integration Network for Depression (CAN-BIND-1) cohort. For the CAN-BIND-1 sample, we applied regression models to investigate the association between ABCB1 SNPs and antidepressant treatment response, remission, tolerability, and antidepressant serum levels.

Features and risk factors of post-COVID-19 syndrome: findings from a longitudinal study in Bangladesh.

Background: A comprehensive study of the post-COVID syndrome (PCS) remains scarce in low-and middle-income countries. We assessed the prevalence, incidence rate, evolution over time, and risk factors of PCS among hospitalized (HS) and non-hospitalized (NHS) COVID-19 survivors.

Methods: We undertook a prospective longitudinal study of COVID-19 survivors at months 1, 3, and 5 post-discharge or post-isolation period.

Next-Generation 3D Scaffolds for Nano-Based Chemotherapeutics Delivery and Cancer Treatment.

Cancer is the leading cause of death after cardiovascular disease. Despite significant advances in cancer research over the past few decades, it is almost impossible to cure end-stage cancer patients and bring them to remission. Adverse effects of chemotherapy are mainly caused by the accumulation of chemotherapeutic agents in normal tissues, and drug resistance hinders the potential therapeutic effects and curing of this disease.

Development of a porous layer-by-layer microsphere with branched aliphatic hydrocarbon porogens.

Porous polymer microspheres are employed in biotherapeutics, tissue engineering, and regenerative medicine. Porosity dictates cargo carriage and release that are aligned with the polymer physicochemical properties. These include material tuning, biodegradation, and cargo encapsulation.

A single-molecule approach to unravel the molecular mechanism of the action of Deinococcus radiodurans RecD2 and its interaction with SSB and RecA in DNA repair.

Helicases are ATP-driven molecular machines that directionally remodel nucleic acid polymers in all three domains of life. They are responsible for resolving double-stranded DNA (dsDNA) into single-strands, which is essential for DNA replication, nucleotide excision repair, and homologous recombination. RecD2 from Deinococcus radiodurans (DrRecD2) has important contributions to the organism's unusually high tolerance to gamma radiation and hydrogen peroxide.