Mechanistic insight into the mode of inhibition of dietary flavonoids; targeting macrophage migration inhibitory factor.

The Macrophage Migration Inhibitory Factor (MIF), a key pro-inflammatory mediator, is responsible for modulating immune responses. An array of inflammatory and autoimmune diseases has been linked to the dysregulated activity of MIF. The significance in physiological as well as pathophysiological phenomena underscores the potential of MIF as an attractive target with pharmacological relevance.

Reducing economic burden through split-shared care model for people living with uncontrolled type 2 diabetes and polypharmacy: a multi-center randomized controlled trial.

Background: Interprofessional collaborative care such as a split-shared care model involving family physicians and community pharmacists can reduce the economic burden of diabetes management. This study aimed to evaluate the economic outcome of a split-shared care model between family physicians and community pharmacists within a pharmacy chain in managing people with uncontrolled type 2 diabetes and polypharmacy.

Method: This was a multi-center, parallel arm, open label, randomized controlled trial comparing the direct and indirect economic outcomes of people who received collaborative care involving community pharmacists (intervention) versus those who received usual care without community pharmacist involvement (control).

Eculizumab for Shiga-toxin-induced hemolytic uremic syndrome in adults with neurological involvement.

The role of eculizumab in treating Shiga-toxin-producing (STEC) hemolytic uremic syndrome (HUS) patients with neurological involvement remains unclear. We describe two distinctly different STEC-HUS patients with neurologic involvement successfully managed with eculizumab, and perform a literature review of all published cases. Both patients had complete resolution of neurological symptoms after initiation of eculizumab.

Hepatic LRP-1 plays an important role in amyloidosis in Alzheimer's disease mice: Potential role in chronic heavy alcohol feeding.

Background: Hepatic lipoprotein receptor-related protein 1 (LRP-1) plays a central role in peripheral amyloid beta (Aβ) clearance, but its importance in Alzheimer's disease (AD) pathology is understudied. Our previous work showed that intragastric alcohol feeding to C57BL/6 J mice reduced hepatic LRP-1 expression which correlated with significant AD-relevant brain changes. Herein, we examined the role of hepatic LRP-1 in AD pathogenesis in APP/PS1 AD mice using two approaches to modulate hepatic LRP-1, intragastric alcohol feeding to model chronic heavy drinking shown by us to reduce hepatic LRP-1, and hepato-specific LRP-1 silencing.

Pharmacokinetics, pharmacodynamics, safety, and tolerability of dopamine-receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting.

Introduction: Dopamine (D)-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV).

Areas Covered: Eight D-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects.

Expert Opinion: Since the introduction of D-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)-RAs and neurokinin (NK)-RAs have been developed.

The 6 degrees of curriculum integration in medical education in the United States.

Despite explicit expectations and accreditation requirements for integrated curriculum, there needs to be more clarity around an accepted common definition, best practices for implementation, and criteria for successful curriculum integration. To address the lack of consensus surrounding integration, we reviewed the literature and herein propose a definition for curriculum integration for the medical education audience. We further believe that medical education is ready to move beyond “horizontal” (1-dimensional) and “vertical” (2-dimensional) integration and propose a model of “6 degrees of curriculum integration” to expand the 2-dimensional concept for future designs of medical education programs and best prepare learners to meet the needs of patients.

Exploring conformational landscapes and binding mechanisms of convergent evolution for the SARS-CoV-2 spike Omicron variant complexes with the ACE2 receptor using AlphaFold2-based structural ensembles and molecular dynamics simulations.

In this study, we combined AlphaFold-based approaches for atomistic modeling of multiple protein states and microsecond molecular simulations to accurately characterize conformational ensembles evolution and binding mechanisms of convergent evolution for the SARS-CoV-2 spike Omicron variants BA.1, BA.2, BA.

Perceptions of metabolic syndrome management utilization in relation to patient experience and health-related quality of life.

Background: One factor for the poor health outcomes among adult people with metabolic syndrome (MetS) is poor utilization of disease management resources, which may be attributable to prior experience with pharmacists (PEwP) and perceptions of disease management resource utilization (PMU). Therefore, understanding patients' experience could be critical to improving their perceptions and promoting health outcomes.

Objectives: The study explored the influence of PEwP and PMU on the health-related quality of life (HRQoL) of people with MetS.

Integration of a Randomized Sequence Scanning Approach in AlphaFold2 and Local Frustration Profiling of Conformational States Enable Interpretable Atomistic Characterization of Conformational Ensembles and Detection of Hidden Allosteric States in the ABL1 Protein Kinase.

Despite the success of AlphaFold methods in predicting single protein structures, these methods showed intrinsic limitations in the characterization of multiple functional conformations of allosteric proteins. The recent NMR-based structural determination of the unbound ABL kinase in the active state and discovery of the inactive low-populated functional conformations that are unique for ABL kinase present an ideal challenge for the AlphaFold2 approaches. In the current study, we employ several adaptations of the AlphaFold2 methodology to predict protein conformational ensembles and allosteric states of the ABL kinase including randomized alanine sequence scanning combined with the multiple sequence alignment subsampling proposed in this study.

Current evidence of integrative oncology modalities for managing adverse effects and survivorship issues among adolescents and young adult (AYA) cancer patients and survivors.

Purpose Of Review: Symptom burden of cancer diagnosis and treatment has led adolescents and young adult cancer patients (AYAC) and survivors to seek different self-management strategies including integrative oncology (IO) modalities. IO holds great promise to improve survivorship issues in adolescents and young adult (AYA) cancer survivors. This review aims to encompass the current evidence of IO modalities and to analyze the efficacy of IO for managing survivorship issues among AYA cancer patients and survivors.

Impact of a Multidisciplinary Supportive Care Model Using Distress Screening at an Asian Ambulatory Cancer Center: A Cluster Randomized Controlled Trial.

Purpose: The Accessible Cancer Care to Enable Support for Cancer Survivors (ACCESS) program adopts a multidisciplinary supportive care model with routine distress screening to triage newly diagnosed cancer survivors for additional support on the basis of distress levels. This study aimed to evaluate the clinical impact of ACCESS over 1 year.

Methods: We performed cluster random assignment at the oncologist level in a 1:1 ratio to receive ACCESS or usual care.

Data driven approach to characterize rapid decline in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disease with high phenotypic variability. Furthering insights into patients' ADPKD progression could lead to earlier detection, management, and alter the course to end stage kidney disease (ESKD). We sought to identify patients with rapid decline (RD) in kidney function and to determine clinical factors associated with RD using a data-driven approach.

Effectiveness of empiric carbapenem versus non-carbapenem therapy for extended-spectrum β-lactamase producing Enterobacterales infections in non-intensive care unit patients: a real-world investigation in a hospital with high-prevalence of extended-spectrum β-lactamase producing Enterobacterales.

Objective: To investigate whether empiric carbapenem therapy, compared to empiric non-carbapenem therapy, was associated with improved clinical outcomes among hospitalized, non-intensive care unit (ICU) patients with extended-spectrum β-lactamase (ESBL)-producing Enterobacterales infections.

Methods: We performed a retrospective cohort study of adult, non-ICU patients admitted with ESBL-producing Enterobacterales infections. Primary outcome was time to clinical stability from the first empiric antibiotic dose.

Evaluation of Financial Interventions in Breast Cancer Care Worldwide: A Systematic Review.

Background: Out-of-pocket costs are burdensome for breast cancer patients. Cost-reducing interventions, though implemented, have unclear comparative efficacy. This study aimed to critically evaluate characteristics of successful versus unsuccessful interventions designed to decrease out-of-pocket costs for breast cancer patients.

Proteomic characterization and cytotoxic potential of proteins from Cuscuta (Cuscuta epithymum (L.) crude herbal product against MCF-7 human breast cancer cell line.

Background: The burden of breast cancer, the second leading cause of death worldwide, is increasing at an alarming rate. Cuscuta, used in traditional medicine for different ailments, including cancer, is known for containing phytochemicals that exhibit anticancer activity; however, the bioactivities of proteins from this plant remain unexplored. This study aimed to screen the cytotoxic potential of proteins from the crude herbal product of Cuscuta epithymum(L.

Structural features of the glassy state and their impact on the solid-state properties of organic molecules in pharmaceutical systems.

This paper reviews the structure and properties of amorphous active pharmaceutical ingredients (APIs), including small molecules and proteins, in the glassy state (below the glass transition temperature, T). Amorphous materials in the neat state and formulated with excipients as miscible amorphous mixtures are included, and the role of absorbed water in affecting glass structure and stability has also been considered. We defined the term "structure" to indicate the way the various molecules in a glass interact with each other and form distinctive molecular arrangements as regions or domains of varying number of molecules, molecular packing, and density.

Double-duty isomerases: a case study of isomerization-coupled enzymatic catalysis.

Enzymes can usually be unambiguously assigned to one of seven classes specifying the basic chemistry of their catalyzed reactions. Less frequently, two or more reaction classes are catalyzed by a single enzyme within one active site. Two examples are an isomerohydrolase and an isomero-oxygenase that catalyze isomerization-coupled reactions crucial for production of vision-supporting 11-cis-retinoids.

Anti-inflammatory activities of novel heat shock protein 90 isoform selective inhibitors in BV-2 microglial cells.

Heat shock protein 90 (Hsp90) is a family of chaperone proteins that consists of four isoforms: Hsp90α, Hsp90β, glucose-regulated protein 94 (Grp94), and tumor necrosis factor type 1 receptor-associated protein (TRAP1). They are involved in modulating the folding, maturation, and activation of their client proteins to regulate numerous intracellular signaling pathways. Previous studies demonstrated that pan-Hsp90 inhibitors reduce inflammatory signaling pathways resulting in a reduction of inflammation and pain but show toxicities in cancer-related clinical trials.

The Characteristics of White Dot Syndromes Following SARS-COV-2 Infection: A Systematic Review.

Purpose: To review all studies reporting the occurrence of white dot syndromes (WDSs) following SARS-COV-2 infection.

Methods: On May 12, 2023, we registered our protocol on PROSPERO [registration number: CRD42023426012]. Five different databases including PubMed, Scopus, Web of Science, Google Scholar, and Science Direct were searched up to May 2023.

Impact of bariatric surgery on circulating irisin levels: a systematic review and meta‑analysis.

This systematic review and meta-analysis evaluated changes in circulating irisin levels after bariatric surgery. A systematic search was performed across Embase, Scopus, PubMed, and Web of Science for this study. The meta-analysis was conducted using Comprehensive Meta-Analysis (CMA) V4 software.

Revealing the oncogenic role of elevated GNL3L expression in esophageal squamous cell carcinoma: insights into the STAT3 pathway.

Background: Esophageal squamous cell carcinoma (ESCC) patients carries a poor prognosis, with limited effective therapeutic targets. This study aimed to clarify the clinical significance of guanine nucleotide-binding protein like 3-like (GNL3L) protein expression in ESCC and its role in malignant progression.

Methods: GNL3L expression and associated cancer-promoting pathways in ESCC were interrogated via bioinformatics analysis through use of The Cancer Genome Atlas (TCGA) database.

Exploring Binding Pockets in the Conformational States of the SARS-CoV-2 Spike Trimers for the Screening of Allosteric Inhibitors Using Molecular Simulations and Ensemble-Based Ligand Docking.

Understanding mechanisms of allosteric regulation remains elusive for the SARS-CoV-2 spike protein, despite the increasing interest and effort in discovering allosteric inhibitors of the viral activity and interactions with the host receptor ACE2. The challenges of discovering allosteric modulators of the SARS-CoV-2 spike proteins are associated with the diversity of cryptic allosteric sites and complex molecular mechanisms that can be employed by allosteric ligands, including the alteration of the conformational equilibrium of spike protein and preferential stabilization of specific functional states. In the current study, we combine conformational dynamics analysis of distinct forms of the full-length spike protein trimers and machine-learning-based binding pocket detection with the ensemble-based ligand docking and binding free energy analysis to characterize the potential allosteric binding sites and determine structural and energetic determinants of allosteric inhibition for a series of experimentally validated allosteric molecules.

Association of Opioid and Concurrent Benzodiazepine, Skeletal Muscle Relaxant, and Gabapentinoid Usage on Healthcare Expenditure and Resource Utilization: A Serial Cross-Sectional Study, 2009 to 2019.

Background: Healthcare providers may be utilizing central nervous system (CNS) depressants to reduce opioid use due to recent changes in public policy. Combination use of these agents with opioids increases the risk of respiratory depression and death. Healthcare expenditures by individuals using these drug combinations have not been previously quantified.