Barriers and new opportunities in developing effective therapies for diabetic neuropathy: International expert consensus recommendations.

Background: Diabetic neuropathy (DN) affects up to half of individuals with type 1 and type 2 diabetes. Despite evidence that improving metabolic and cardiovascular health can slow its progression, DN remains a significant clinical challenge due to the lack of disease-modifying therapies and effective pain management strategies. This consensus aimed to identify gaps and recommend strategies to address these challenges.

Resting-state electroencephalographic rhythms depend on sex in patients with dementia due to Parkinson's and Lewy Body diseases: An exploratory study.

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are more prevalent in males than females. Furthermore, they typically showed abnormally high delta (< 4 Hz) and low alpha (8-10 Hz) rhythms from resting-state electroencephalographic (rsEEG) activity. Here, we hypothesized that those abnormalities may depend on the patient's sex.

Exploring the Benefits and Prescribing Informations of Combining East Asian Herbal Medicine with Conventional Medicine in the Treatment of Rheumatoid Arthritis: A Systematic Review and Multifaceted Analysis of 415 Randomized Controlled Trials.

Background: Notwithstanding progress in conventional medicine (CM), the management of rheumatoid arthritis (RA) continues to be problematic due to factors such as limited patient response to treatment and restricted medication access. This study aimed to evaluate the extent to which East Asian herbal medicine with CM combination therapy (EACM) provides additional benefits in effectiveness and safety.

Methods: We conducted a comprehensive search across 11 databases in English, Chinese, Korean, and Japanese for randomized controlled trials.

Molecular allergy diagnosis enabling personalized medicine.

Allergic patients are characterized by complex and patient-specific IgE sensitization profiles to various allergens, which are accompanied by different phenotypes of allergic disease. Molecular allergy (MA) diagnosis establishes the patient's IgE reactivity profile at a molecular allergen level and has moved allergology into the "Precision Medicine" era. Molecular allergology started in the late 1980s with the isolation of the first allergen-encoding DNA sequences.

Granisetron ameliorates doxorubicin-evoked nephrotoxicity via modulation of Nrf2 and TLR4/p38 MAPK/NLRP3 signals in rats.

Doxorubicin (DOX) is an anthracycline chemotherapy employed in treating malignancies. Unfortunately, the clinical application of DOX is limited due to its nephrotoxicity. Granisetron (GRAN) is a 5-HT3 receptor blocker used widely to manage post-chemotherapy nausea and vomiting with anti-inflammatory, anti-oxidant, and anti-apoptotic bioactivities.

Impact of attaining an aggressive PK/PD target with continuous infusion beta-lactams on the clinical efficacy of targeted therapy of early post-transplant Gram-negative infections in critically ill OLT recipients. An interim analysis of a 3-year prospective, observational, study.

Background: To assess the impact of attaining aggressive beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets on clinical efficacy in critical orthotopic liver transplant (OLT) recipients with documented early Gram-negative infections.

Methods: OLT recipients admitted to the post-transplant ICU between June 2021 and May 2024 having documented Gram-negative infections treated with targeted therapy continuous infusion (CI) beta-lactams, and undergoing therapeutic drug monitoring (TDM)-guided beta-lactam dosing adjustment in the first 72 hours were prospectively enrolled. Free steady-state concentrations (fCss) of beta-lactams (BL) and/or of beta-lactamase inhibitors (BLI) were calculated, and aggressive PK/PD target attainment was measured.

Comparative study of bovine and synthetic hydroxyapatite in micro- and nanosized on osteoblasts action and bone growth.

Hydroxyapatite (HA) is widely used as a bone graft. However, information on the head-to-head osteoinductivity and in vivo performance of micro- and nanosized natural and synthetic HA is still lacking. Here, we fabricated nanosized bovine HA (nanoBHA) by using a wet ball milling method and compared its in vitro and in vivo performance with microsized BHA, nanosized synthetic HA (nanoHA), and microsized synthetic HA (HA).

Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials.

This study identifies the secondary metabolites from Alternaria alternate and evaluates their ACE-2: Spike RBD (SARS-CoV-2) inhibitory activity confirmed via immunoblotting in human lung microvascular endothelial cells. In addition, their in vitro anti-inflammatory potential was assessed using a cell-based assay in LPS-treated RAW 264.7 macrophage cells.

Low regulatory T-cells frequency is associated with graft rejection after small bowel transplantation: Clinical and experimental evidence.

Background: Intestinal transplantation (ITx) represents the only curative option for patients with irreversible intestinal failure. Nevertheless, its rejection rate surpasses that of other solid organ transplants due to the heightened immunological load of the gut. Regulatory T-cells (Tregs) are key players in the induction and maintenance of peripheral tolerance, suggesting their potential involvement in modulating host vs.

Nebulization of 2% lidocaine has no detectable impact on the healthy equine respiratory microbiota.

Glucocorticosteroids remain the most common pharmaceutical approach for the treatment of equine asthma but can be associated with significant side effects, including respiratory microbiome alterations. The goal of the study was to assess the impact of 2% lidocaine nebulization, a projected alternative treatment of equine asthma, on the healthy equine respiratory microbiota. A prospective, randomized, controlled, blinded, 2-way crossover study was performed, to assess the effect of 1 mg/kg 2% lidocaine (7 treatments over 4 days) on the equine respiratory microbiota compared to control horses (saline and no treatment).

Respiratory extracellular vesicle isolation optimization through proteomic profiling of equine samples and identification of candidates for cell-of-origin studies.

Growing evidence supports the importance of extracellular vesicle (EV) as mediators of communication in pathological processes, including those underlying respiratory disease. However, establishing methods for isolating and characterizing EVs remains challenging, particularly for respiratory samples. This study set out to address this challenge by comparing different EV isolation methods and evaluating their impacts on EV yield, markers of purity, and proteomic signatures, utilizing equine/horse bronchoalveolar lavage samples.

Structure-guided identification of mitogen-activated protein kinase-1 inhibitors towards anticancer therapeutics.

Mitogen-activated protein kinase 1 (MAPK1) is a serine/threonine kinase that plays a crucial role in the MAP kinase signaling transduction pathway. This pathway plays a crucial role in various cellular processes, including cell proliferation, differentiation, adhesion, migration, and survival. Besides, many chemotherapeutic drugs targeting the MAPK pathway are used in clinical practice, and novel inhibitors of MAPK1 with improved specificity and efficacy are required.

Iodinated Contrast Adsorption in Cartridges With Styrene-Divinylbenzene Sorbent.

Background: Contrast-associated acute kidney injury (CA-AKI) is frequent in patients with chronic kidney disease who are submitted to cardiac endovascular procedures using iodinated contrast. In hemoadsorption, cartridges containing styrene-divinylbenzene sorbent resin are applied to remove substances from the blood through an extracorporeal circuit. Importantly, iodinated contrast is also removed via adsorption.

Indole-3-Lactic Acid Inhibits Doxorubicin-Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway.

The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which is primarily attributed to its interaction with iron in mitochondria, leading to lipid peroxidation and myocardial ferroptosis. This study aimed to investigate the role of the gut microbiota-derived metabolite, indole-3-lactic acid (ILA), in mitigating DOX-induced cardiotoxicity (DIC). Cardiac function, pathological changes, and myocardial ferroptosis were assessed in vivo.

Fixed dosing of alpelisib for children with vascular anomalies: Can we do better?

Severe forms of vascular malformations (VM) can highly impact patients' quality of life and lead to life-threatening organ dysfunction. Numerous VM are caused by somatic activating mutations in the PI3K/AKT/mTOR signalling pathway. Alpelisib, a PIK3CA inhibitor was recently FDA-approved for paediatric PIK3CA-related overgrowth syndrome (PROS).

Simvastatin-Induced Ferroptosis in Orbital Fibroblasts in Graves' Ophthalmopathy.

Purpose: Graves' ophthalmopathy (GO), the most common extrathyroidal manifestation of Graves' disease, is disabling and disfiguring. Recent studies have shown that statins have a protective effect on individuals with GO. Statins were reported to trigger ferroptosis in some disorders, but little is known about whether statins protect against GO via ferroptosis.

Design and Discovery of Preclinical Candidate LYG-409 as a Highly Potent and Selective GSPT1 Molecular Glue Degraders.

Molecular glue degraders induce "undruggable" protein degradation by a proximity-induced effect. Inspired by the clinical success of immunomodulatory drugs, we aimed to design novel molecular glue degraders targeting GSPT1. Here, we report the design of a series of GSPT1 molecular glue degraders.

The Biological Properties of Co-Doped Monetite Are Influenced by Thermal Treatment.

Calcium phosphates, notably monetite, are valued biomaterials for bone applications owing to their osteogenic properties and rapid uptake by bone cells. This study investigates the enhancement of these properties through Cobalt doping, which is known to induce hypoxia and promote bone cell differentiation. Heat treatments at 700°C, 900°C, and 1050°C are applied to both monetite and Cobalt-doped monetite, facilitating the development of purer, more crystalline phases with varied particle sizes and optimized cellular responses.

A Clinical Practice-Based Comparison of Conventional and Individualized Dosing Strategies for Therapeutic Enoxaparin.

To understand differences in anti-factor-Xa levels produced by two different dosing strategies (conventional and individualized) for therapeutic enoxaparin in a cohort of hospital inpatients. A multicenter, retrospective cohort study over a two- and a half-year period for inpatients with stable renal function and on therapeutic enoxaparin. Anti-factor-Xa levels were taken 3-5 h after enoxaparin administration and a minimum of 48 h of dosing.

Drug-Induced Liver Injury Associated With Emerging Cancer Therapies.

Targeted therapies and immunotherapies have shown great promise as best-in-class treatments for several cancers with respect to efficacy and safety. While liver test abnormalities are rather common in patients treated with kinase inhibitors or immunotherapy, events of severe hepatotoxicity in these patients are rare in comparison with those associated with chemotherapeutics. The underlying mechanisms and risk factors for severe hepatotoxicity with novel oncology therapies are not well understood, complicating the drug-induced liver injury (DILI) risk assessment in the preclinical and clinical phases of drug development.

Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.

Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.

Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.

Biogenic Synthesis and Characterization of Silver Nanoparticles With Cyanobacterium Oscillatoria salina Using Against MDR Pathogenic Bacteria and Their Antiproliferative and Toxicity Study.

The biosynthesis of silver nanoparticles (AgNPs) using cyanobacteria has gained significant attention due to its cost-effective and eco-friendly advantages in green synthesis. Additionally, biogenic AgNPs show great potential for biological applications, particularly in combating infections caused by drug-resistant bacteria and fungi. This study synthesized using the cyanobacterium Oscillatoria salina (Os-AgNPs).

Neuroprotective Effects, Mechanisms of Action and Therapeutic Potential of the Kv7/KCNQ Channel Opener QO-83 in Ischemic Stroke.

Ischemic stroke is a worldwide disease with high mortality and morbidity. Kv7/KCNQ channels are key modulators of neuronal excitability and microglia function, and activation of Kv7/KCNQ channels has emerged as a potential therapeutic avenue for ischemic stroke. In the present study, we focused on a new Kv7/KCNQ channel opener QO-83 on the stroke outcomes and its therapeutic potential.

Cost-effectiveness of data driven personalised antibiotic dosing in critically ill patients with sepsis or septic shock.

Purpose: This study provides an economic evaluation of bedside, data-driven, and model-informed precision dosing of antibiotics in comparison with usual care among critically ill patients with sepsis or septic shock.

Methods: This economic evaluation was conducted alongside an AutoKinetics randomized controlled trial. Effect measures included quality-adjusted life years (QALYs), mortality and pharmacokinetic target attainment.