Balancing Group 1 Monoatomic Ion-Polar Compound Interactions in the Polarizable Drude Force Field: Application in Protein and Nucleic Acid Systems.

An accurate force field (FF) is the foundation of reliable results from molecular dynamics (MD) simulations. In our recently published work, we developed a protocol to generate atom pair-specific Lennard-Jones (known as NBFIX in CHARMM) and through-space Thole dipole screening (NBTHOLE) parameters in the context of the Drude polarizable FF based on readily accessible quantum mechanical (QM) data to fit condensed phase experimental thermodynamic benchmarks, including the osmotic pressure, diffusion coefficient, ionic conductivity, and solvation free energy, when available. In the present work, the developed protocol is applied to generate NBFIX and NBTHOLE parameters for interactions between monatomic ions (specifically Li, Na, K, Rb, Cs, and Cl) and common functional groups found in proteins and nucleic acids.

Food insecurity is associated with greater difficulty accessing care among people living with HIV with or without comorbid non-communicable diseases in western Kenya.

Introduction: The relationship between food insecurity and access to healthcare in low-resource settings remains unclear. Some studies find that food insecurity is a barrier to accessing care, while others report that food insecurity is associated with a greater need for care, leading to more care utilisation. We use data from the Harambee study in western Kenya to assess the association between food insecurity and difficulty accessing care among people living with HIV (PLWH) with or without comorbid non-communicable diseases (NCDs).

Antidepressant therapeutic strategies and health care utilization in patients with depression.

Background: Individuals with depression who do not respond to initial antidepressant may switch to a different antidepressant, add a second antidepressant, or add an atypical antipsychotic. Previous studies comparing these strategies' efficacy and safety reported conflicting results, and the impact of these strategies on subsequent health care utilization is unknown.

Objective: To compare health care utilization between individuals with depression who switched antidepressants, added a second antidepressant (ie, combination), or added an atypical antipsychotic (ie, augmentation) following their initial antidepressant.

KaMLs for Predicting Protein p Values and Ionization States: Are Trees All You Need?

Despite its relevance for understanding biology and computer-aided drug discovery, accurate prediction of protein ionization states remains a formidable challenge. Physics-based approaches struggle to capture the small, competing contributions in the complex protein environment, while machine learning (ML) is hampered by scarcity of experimental data. Here we developed the p ML (KaML) models based on decision trees and graph attention networks (GATs), exploiting physicochemical features and a new experiment p database (PKAD-3) enriched with highly shifted p 's.

International Consensus Statement on Platelet Function and Genetic Testing in Percutaneous Coronary Intervention: 2024 Update.

Current evidence indicates that dual antiplatelet therapy with aspirin plus a P2Y inhibitor is essential for the prevention of thrombotic events after percutaneous coronary interventions. However, dual antiplatelet therapy is associated with increased bleeding which may outweigh the benefits. This has set the foundations for customizing antiplatelet treatments to the individual patient.

Characterizing patient portal use of people with cognitive impairment and potentially inappropriate medications.

Background: People with cognitive impairment commonly use central nervous system-active potentially inappropriate medications (CNS-PIM), increasing risk of adverse outcomes. Patient portals may be a promising tool for facilitating medication-related conversations. Little is known about portal use by this population related to medications.

Exploration of the potential impact of batch-to-batch variability on the establishment of pharmacokinetic bioequivalence for inhalation powder drug products.

Batch-to-batch variability in inhalation powder has been identified as a potential challenge in the development of generic versions. This study explored the impact of batch-to-batch variability on the probability of establishing pharmacokinetic (PK) bioequivalence (BE) in a two-sequence, two-period (2 × 2) crossover study. A model-based parametric simulation approach was employed, incorporating batch-to-batch variability through the relative bioavailability (RBA) ratio.

Depression like-behavior and memory loss induced by methylglyoxal is associated with tryptophan depletion and oxidative stress: a new in vivo model of neurodegeneration.

Background: Depression and memory loss are prevalent neurodegenerative disorders, with diabetic patients facing an elevated risk of brain dysfunction. Methylglyoxal (MGO) formation, which is heightened in diabetes owing to hyperglycemia and gut dysbiosis, may serve as a critical link between diabetes and brain diseases. Despite the high prevalence of MGO, the precise mechanisms underlying MGO-induced depression and memory loss remain unclear.

A Nursing Home Clinician Survey to Explain Gabapentinoid Increases.

Objectives: Survey nursing home (NH) clinicians about the indications for NH gabapentinoid use, the factors driving increased prescribing, and their experiences with gabapentinoid deprescribing.

Design: Online clinician survey.

Setting And Participants: NH clinicians prescribing gabapentinoids in US NHs.

Comprehensive Evidence-Based Guidelines for Implantable Peripheral Nerve Stimulation (PNS) in the Management of Chronic Pain: From the American Society Of Interventional Pain Physicians (ASIPP).

Background: Peripheral nerve stimulation (PNS) has been used for over 50 years to treat chronic pain by delivering electrical pulses through small electrodes placed near targeted peripheral nerves those outside the brain and spinal cord. Early PNS systems often required invasive neurosurgical procedures. However, since 2015, the Food and Drug Administration (FDA) approved percutaneously implanted PNS leads and neurostimulators  offering a much less invasive, non-opioid option for managing recalcitrant chronic pain.

A systematic review and meta-analysis of patient-relevant outcomes in comprehensive cancer centers versus noncomprehensive cancer centers.

This systematic review describes difference in patient-relevant outcomes between comprehensive cancers (CCCs) versus non-CCCs. Studies were identified in PubMed, Cochrane CENTRAL, Epistemonikos, and gray literature from January 2002 to May 2024. Data were extracted and appraised by two authors.

Pharmacological inhibition of macrophage triglyceride biosynthesis pathways does not improve Mycobacterium tuberculosis control in infected mice.

Tuberculosis (TB) necrotic granulomas contain triglyceride-rich macrophages (foam cells) with reduced antimicrobial functions. We assessed the ability of two compounds to reduce triglyceride content and Mycobacterium tuberculosis (Mtb) burden in infected human monocyte-derived macrophages and in the lungs of Mtb-infected C3HeB/FeJ mice: A-922500 (DGATi), an inhibitor of diacylglycerol acyltransferase 1; and LY2584702 (p70S6Ki), an inhibitor of p70 S6 kinase. DGATi and p70S6Ki significantly reduced the lipid content and bacillary burden in Mtb-infected macrophages.

Combination of polymeric micelle formulation of TGFβ receptor inhibitors and paclitaxel produces consistent response across different mouse models of Triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is notoriously difficult to treat due to the lack of targetable receptors and sometimes poor response to chemotherapy. The transforming growth factor beta (TGFβ) family of proteins and their receptors (TGFRs) are highly expressed in TNBC and implicated in chemotherapy-induced cancer stemness. Here, we evaluated combination treatments using experimental TGFR inhibitors (TGFβi), SB525334 (SB), and LY2109761 (LY) with paclitaxel (PTX) chemotherapy.

Implementation of pharmacogenomics: Experience at Ochsner Health.

Purpose: Pharmacogenomics is the study of how individual responses to medication are influenced by genetics. As medication experts, pharmacists are uniquely suited to practicing this application of precision medicine. Fundamental operational aspects of developing a pharmacy clinical pharmacogenomics practice are described, and the specific experience of a multisite health system in developing a pharmacogenomics service is discussed.

Trajectories of antidepressant use after tamoxifen initiation among young and middle-aged women with breast cancer.

Purpose: Antidepressant treatment patterns may change after women with breast cancer (BC) initiate tamoxifen, potentially impacting health outcomes. We characterized trajectories of antidepressant use after initiating tamoxifen among young and middle-aged women with BC, identifying risk factors for trajectory group membership.

Methods: A retrospective cohort included women 18-64 years-old with BC and antidepressant treatment history who received a new tamoxifen dispensing (index date).

Biowaiver monographs for immediate-release solid oral dosage forms: Voriconazole.

According to the ICH M9 Guideline, the triazole antifungal voriconazole is a Biopharmaceutics Classification System (BCS) class II drug, being highly soluble at the highest dose strength but not at the highest single dose. Although the ICH M9 allows for consideration of BCS-based biowaivers in such cases, voriconazole does not meet the additional requirement of dose proportional pharmacokinetics (PK) over the therapeutic dose range. By contrast, if the classification were based on the FDA solubility criteria that were in place prior to ICH M9 (based on the highest dose strength), voriconazole would belong to BCS class I and thus qualify for the BCS-based biowaiver.

Protein phosphatase 2A inhibitors: a possible pharmacotherapy for benzodiazepine dependence.

Objectives: Benzodiazepines (BZDs) activate the γ-aminobutyric acid (GABA) subtype A (GABAA) receptors, and thus are widely used medicines for the treatment of anxiety and insomnia. For chronic use, tolerance to BZDs is a major problem. Patients with chronic insomnia that develop tolerance to BZDs lose therapeutic effects but also potentially suffer from BZD dependence resulting in BZD withdrawal.