Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone.

Background: Klebsiella pneumoniae is one of the most prevalent pathogens responsible for multiple infections in healthcare settings and the community. K. pneumoniae CG147, primarily including ST147 (the founder ST), ST273, and ST392, is one of the most globally successful MDR clone linked to various carbapenemases.

The relationship between optical coherence tomography and magnetic resonance imaging measurements in people with multiple sclerosis: A systematic review and meta-analysis.

Background: Several studies show that optical coherence tomography (OCT) metrics e with cognition, disability, and brain structure in people with multiple sclerosis (PwMS). This review the correlation between OCT parameters and magnetic resonance imaging (MRI) measurements in PwMS.

Methods: A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Web of Science was performed, including studies published in English up to November 29, 2024 to identify studies reporting quantitative data on the correlation between baseline OCT parameters and MRI measurements in PwMS.

A-kinase anchor protein 12 promotes oligodendrogenesis and cognitive recovery in carbon monoxide therapy for traumatic brain injury.

Therapeutic drug development for central nervous system injuries, such as traumatic brain injury (TBI), presents significant challenges. TBI results in primary mechanical damage followed by secondary injury, leading to cognitive dysfunction and memory loss. Our recent study demonstrated the potential of carbon monoxide-releasing molecules (CORMs) to improve TBI recovery by enhancing neurogenesis.

Life satisfaction around the world: Measurement invariance of the Satisfaction With Life Scale (SWLS) across 65 nations, 40 languages, gender identities, and age groups.

The Satisfaction With Life Scale (SWLS) is a widely used self-report measure of subjective well-being, but studies of its measurement invariance across a large number of nations remain limited. Here, we utilised the Body Image in Nature (BINS) dataset-with data collected between 2020 and 2022 -to assess measurement invariance of the SWLS across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). All participants completed the SWLS under largely uniform conditions.

Magnetic chromatography improves colloidal and MRI attributes of magnetoliposomes enabling evaluation of the impact of size on bio-distribution in an model of pancreatic cancer.

Magnetic chromatography was exploited to fractionate suspensions of magnetoliposomes (SML: lumen-free lipid-encapsulated clusters of multiple magnetic iron-oxide nanoparticles) improving their colloidal properties and relaxivity (magnetic resonance image contrast capability). Fractionation (i) removed sub-populations that do not contribute to the MRI response, and thus (ii) enabled evaluation of the size-dependence of relaxivity for the MRI-active part, which was surprisingly weak in the 55-90 nm range. MC was therefore implemented for processing multiple PEGylated SML types having average sizes ranging from 85 to 105 nm, which were then shown to have strongly size-dependent uptake in an pancreatic cancer model.

Meta-Analysis of the Input and Disposition of Various Dosage Forms of Methylprednisolone in Healthy Subjects Utilizing a Physiologically Based Pharmacokinetic Model.

The study quantitatively analyzes and compares the pharmacokinetics (PK) of methylprednisolone (MPL) in humans upon administration of various dosage forms. The PK parameters and profiles of MPL in healthy subjects were collected from 22 literature sources. A minimal physiologically based pharmacokinetic (mPBPK) model consisting of blood and two tissue (lumped liver and kidney, remainder) compartments with nonlinear tissue partitioning was applied to describe MPL disposition.

Streptococcus mutans serotyping, collagen-binding genes and Candida albicans in dentin carious lesions: a molecular approach.

Objectives: This cross-sectional study aimed to evaluate the occurrence of Streptococcus spp., Streptococcus mutans, its serotypes (c, e, f, and k), collagen-binding genes (cnm/cbm), and Candida albicans in medium deep (D2) and deep (D3) dentin carious lesions of permanent teeth.

Materials And Methods: Carious dentin was collected from D2 (n = 23) and D3 (n = 24) lesions in posterior teeth from 31 individuals.

Systematic Review of Intrauterine Contraceptive Use and the Development of Toxic Shock Syndrome.

The objective of this systematic review was to characterize the literature regarding the risk factors associated with the development of toxic shock syndrome (TSS) secondary to the use of intrauterine contraceptives (IUCs), as well as patient outcomes. A literature search was conducted spanning origin through December 12, 2022, using Embase and MEDLINE ALL. Primary literature that discussed development of TSS along with the presence of an IUC were included.

Semisynthesis of Alkaloid Derivatives: Pyranoacridone-Hydroxamic Acid Cytotoxic Conjugates with HDAC and Topoisomerase II α Dual Inhibitory Activity.

Inspired by our previous efforts in the semisynthetic modification of naturally occurring pyranoacridones, we report the targeted design and semisynthesis of dual inhibitors of HDAC and topoisomerase II α (Topo II α) derived from des--methylacronycine () and noracronycine () pyranoacridone alkaloids. Designed from the clinically approved SAHA, the cytotoxic pyranoacridone nuclei from the alkaloids served as the capping group, while a hydroxamic acid moiety functioned as the zinc-binding group. Out of 16 compounds evaluated in an cytotoxicity assay, KT32 () with noracronycine () as the capping group and five-carbon linker hydroxamic acid side chains showed good cytotoxic activity with IC values of 1.

Evaluation of the Drug-Drug Interaction Potential of Cannabidiol Against UGT2B7-Mediated Morphine Metabolism Using Physiologically Based Pharmacokinetic Modeling.

Morphine is a commonly prescribed opioid analgesic used to treat chronic pain. Morphine undergoes glucuronidation by UDP-glucuronosyltransferase (UGT) 2B7 to form morphine-3-glucuronide and morphine-6-glucuronide. Morphine is the gold standard for chronic pain management and has a narrow therapeutic index.

Medication non-adherence: reflecting on two decades since WHO adherence report and setting goals for the next twenty years.

Background: Non-adherence to medication remains a persistent and significant challenge, with profound implications for patient outcomes and the long-term sustainability of healthcare systems. Two decades ago, the World Health Organization (WHO) dedicated its seminal report to adherence to long-term therapies, catalysing notable changes that advanced both research and practice in medication adherence. The aim of this paper was to identify the most important progress made over the last 2 decades in medication adherence management and to initiate a discussion on future objectives, suggesting priority targets for the next 20 years.

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.

Phage-Encoded Virulence Factor, Gp05, Alters Membrane Phospholipids and Reduces Antimicrobial Susceptibility in Methicillin-Resistant Staphylococcus aureus.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen causing severe endovascular infections. The prophage-encoded protein Gp05 has been identified as a critical virulence factor that contributes to MRSA persistence during vancomycin (VAN) treatment in an experimental endocarditis model. However, the underlining mechanisms driving this persistence phenotype remain poorly understood.

Proton Pump Inhibitor Use and Incident Cardiovascular Disease in Older Postmenopausal Women.

Background: Epidemiological studies have been inconsistent regarding an association between proton pump inhibitor (PPI) use and risk of primary cardiovascular disease (CVD) events.

Methods: We studied 85,189 postmenopausal women (mean age 63 years at baseline) without known CVD at enrollment into the Women's Health Initiative Observational Study (1993-1998). PPI use was determined from medication inventories at baseline and Year-3.

Teratological abnormalities in hard ticks (Acari: Ixodidae) from Pakistan.

Studying teratological abnormalities in ticks are taxonomically important because this poorly understood biological phenomenon causes difficulties in tick's identification. Globally, reports regarding these abnormalities in ticks, reasons of their causes and their impacts are scarce. According to the available published data, there are no studies regarding teratological abnormalities in ticks from Pakistan.

Effectiveness and Safety of Sodium-Glucose Cotransporter-2 Inhibitor Continuation in Patients With Type 2 Diabetes and Late-Stage Chronic Kidney Disease.

Expansion of sodium-glucose cotransporter-2 inhibitor (SGLT2i) use in chronic kidney disease (CKD) prompted a pragmatic study of their safety and effectiveness in patients with type 2 diabetes mellitus (T2DM) and late-stage CKD. The primary clinical endpoint was change in HbA. Secondary clinical endpoints included change in body weight and blood pressure.

PK/PD Evaluation of Antibody-Drug Conjugates with Enhanced Immune Effector Functions.

Optimizing the interaction between antibody (mAb)-based therapeutics and immune effector functions (EFs) offers opportunities to improve the therapeutic window of these molecules. However, the role of EFs in antibody-drug conjugate (ADC) efficacy and toxicity remains unknown, with limited studies that have investigated how modulation of EF affects the pharmacology of ADCs. This study aimed to evaluate the effect of EF modulation on ADC efficacy using trastuzumab-vc-MMAE as a model ADC.

Collaborative design of a care pathway for pharmacy-based PrEP delivery in Nigeria: insights from stakeholder consultation.

Background: HIV remains a significant public health problem, particularly in Africa, where two-thirds of global cases occur. Nigeria is among the three countries with the highest burden. Despite free access to pre- and post-exposure prophylaxis (PrEP and PEP) in Nigerian hospitals, stigma, distance, and restrictive clinic hours hinder uptake, especially among vulnerable populations.

Magnetic resonance imaging-based biomarkers of multiple sclerosis and neuromyelitis optica spectrum disorder: a systematic review and meta-analysis.

Background/objective: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are neuroinflammatory conditions with overlapping clinical and imaging features. Distinguishing between these diseases is crucial for appropriate diagnosis and management. Magnetic resonance imaging (MRI) may have the potential to differentiate these disorders.

Optimal Dosing Recommendations of Clonidine in Pediatrics Using Physiologically Based Pharmacokinetic Modeling.

Objective: Clonidine has been widely used in the pediatric population to treat neonatal abstinence syndrome (NAS), attention deficit hyperactivity disorder (ADHD), sedation, and Tourette's syndrome; however, there is no consensus on dosing. This research aims to recommend optimal dosing of clonidine in the pediatric population using physiologically based pharmacokinetic (PBPK) modeling.

Methods: The pediatric PBPK model was developed from an adult model by scaling the clearance processes from adults to pediatrics using ontogeny equations.

Characteristics of Academic Pharmacy Fellowship Programs: Results of a Cross-Sectional Online Search.

Objective: The pharmacy Academy faces an urgent need for diverse, experienced faculty members. However, although many faculty candidates may come from advanced training backgrounds, many do not have all the skills required to transition seamlessly into an academic role. Academic pharmacy fellowships are a promising strategy to address these gaps.

Neuroimaging markers and disability scales in multiple sclerosis: A systematic review and meta-analysis.

Background: Multiple sclerosis (MS) is a central nervous system disorder marked by progressive neurological impairments. Magnetic resonance imaging (MRI) parameters are key paraclinical measures that play a crucial role in the diagnosis, prognosis, and monitoring of MS-related disability. This study aims to analyze and summarize the existing literature on the correlation between MRI parameters and disability in people with MS (pwMS).