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.

Impact of Repeated Glucocorticoid Oral Administration on the Urinary Steroid Profile.

The detection of endogenous anabolic androgenic steroids (EAAS) is performed with the Steroidal Module of the Athlete Biological Passport (ABP). Glucocorticoids (GC) could be a confounding factor to the ABP Steroidal Module because they inhibit the hypothalamic-pituitary-adrenal axis, and ABP metabolites have partial adrenal origin. In previous studies, single-dose systemic GC administrations have been shown to reduce the urinary ratios A/T and 5αdiol/E.

Two case reports of biliary stent infections by extensively drug-resistant Escherichia coli carrying bla at a tertiary-care hospital in West Bengal, India.

Background: Rising antimicrobial resistance (AMR) is an acute public health emergency impeding the clinical efficacy of surgical interventions. Biliary stent placement is one of the routine surgical procedures that rarely lead to infections that are empirically managed by broad-spectrum β-lactams and fluoroquinolones. Critical priority pathogens, such as carbapenem-resistant Escherichia coli challenge treatment outcomes and infection prevention.

Unraveling the immunomodulatory and metabolic effects of bioactive glass S53P4 on macrophages in vitro.

Macrophage metabolism is closely linked to their phenotype and function, which is why there is growing interest in studying the metabolic reprogramming of macrophages. Bioactive glass (BG) S53P4 is a bioactive material used especially in bone applications. Additionally, BG S53P4 has been shown to affect macrophages, but the mechanisms through which the possible immunomodulatory effects are conveyed remain unclear.

Phenotypic variability in progressive encephalopathy with brain atrophy and thin corpus callosum: insights from two families.

The cytoskeleton, composed of microtubules, intermediate filaments and actin filaments is vital for various cellular functions, particularly within the nervous system, where microtubules play a key role in intracellular transport, cell morphology, and synaptic plasticity. Tubulin-specific chaperones, including tubulin folding cofactors (TBCA, TBCB, TBCC, TBCD, TBCE), assist in the proper formation of α/β-tubulin heterodimers, essential for microtubule stability. Pathogenic variants in these chaperone-encoding genes, especially TBCD, have been linked to Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum (PEBAT, OMIM #604,649), a severe neurodevelopmental disorder.

Cutting-edge insights into liver fibrosis: advanced therapeutic strategies and future perspectives using engineered mesenchymal stem cell-derived exosomes.

Liver fibrosis is still a serious health concern worldwide, and there is increasing interest in mesenchymal stem cells (MSCs) with tremendous potential for treating this disease because of their regenerative and paracrine effects. Recently, many researches have focused on using the released exosomes (EXOs) from stem cells to treat liver fibrosis rather than using parent stem cells themselves. MSC-derived EXOs (MSC-EXOs) have demonstrated favourable outcomes similar to cell treatment in terms of regenerative, immunomodulatory, anti-apoptotic, anti-oxidant, anti-necroptotic, anti-inflammatory and anti-fibrotic actions in several models of liver fibrosis.

Targeting Kv7 Potassium Channels for Epilepsy.

Voltage-gated Kv7 potassium channels, particularly Kv7.2 and Kv.7.

Aloin remodels the cell wall of Candida albicans to reduce its hyphal virulence against oral candidiasis.

Aloe vera (L.) Burm.f.

Anodized Ti6Al4V-ELI, electroplated with copper is bactericidal against Staphylococcus aureus and enhances macrophage phagocytosis.

Implants aim to restore skeletal dysfunction associated with ageing and trauma, yet infection and ineffective immune responses can lead to failure. This project characterized the microbiological and host cell responses to titanium alloy with or without electroplated metallic copper. Bacterial viability counting and scanning electron microscopy quantified and visualized the direct and indirect bactericidal effects of the Cu-electroplated titanium (Cu-Ep-Ti) against two different Staphylococcus aureus strains.

A review of the current status of biological effects of plant-derived therapeutics in breast cancer.

Phytochemicals are bioactive secondary plant metabolites found in high concentrations in fruits, grains, and vegetables. Recent studies provide evidence of usage of plant-based diets rich in phytochemicals and their corelation to reduction in cancer incidence. Several phytochemicals have demonstrated effectiveness as chemotherapeutic agents against various cancers, including breast cancer.

EpiAge: a next-generation sequencing-based epigenetic clock for biological age assessment in saliva and blood across health and disease.

This study introduces EpiAgePublic, a new method to estimate biological age using only three specific sites on the gene known for its connection to aging. Unlike traditional methods that require complex and extensive data, our model uses a simpler approach that is well-suited for next-generation sequencing technology, which is a more advanced method of analyzing DNA methylation. This new model overcomes some of the common challenges found in older methods, such as errors due to sample quality and processing variations.

The role of Iowa gambling task performance in response to citalopram treatment for cocaine use disorder.

Cocaine use disorder (CUD) is associated with executive functioning impairments linked to serotonergic function. Previous studies reported efficacy with the selective serotonin reuptake inhibitor citalopram in reducing cocaine use. The current study explored moderation and mediation of citalopram effects on cocaine use by performance across executive function domains.

Improvement in XIa Selectivity of Snake Venom Peptide Analogue BF9-N17K Using P2' Amino Acid Replacements.

Coagulation factor XIa is a new serine-protease family drug target for next-generation anticoagulants. With the snake venom Kunitz-type peptide BF9 as the scaffold, we obtained a highly active XIa inhibitor BF9-N17K in our previous work, but it also inhibited the hemostatic target plasmin. Here, in order to enhance the selectivity of BF9-N17K toward XIa, four mutants, BF9-N17K-L19A, BF9-N17K-L19S, BF9-N17K-L19D, and BF9-N17K-L19K, were further designed using the P2' amino acid classification scanning strategy.

Snake Venom Pharmacokinetics and Acute Toxic Outcomes Following Envenoming: Experimental and Clinical Correlations.

An understanding of snake venom pharmacokinetics is essential for determining clinical outcomes of envenoming and developing therapeutic approaches to the treatment of envenoming, especially regarding the timing and optimal dosage of antivenom administration. (Eastern Russell's viper) envenoming causes systemic coagulopathy and severe hemorrhage including acute kidney injury. These toxic outcomes can be diminished by the administration of high quantities of Russell's viper antivenom.

Machine learning and confirmatory factor analysis show that buprenorphine alters motor and anxiety-like behaviors in male, female, and obese C57BL/6J mice.

Buprenorphine is an opioid approved for medication-assisted treatment of opioid use disorder. Used off-label, buprenorphine has been reported to contribute to the clinical management of anxiety. Although human anxiety is a highly prevalent disorder, anxiety is a latent construct that cannot be directly measured.

Efficacy of Chlorogenic Acid in Treating Tripterygium Glycoside-Induced Asthenozoospermia in Rats and Its Possible Mechanisms.

Tripterygium glycosides (TGs) are the most common form of traditional Chinese medicine, known as Tripterygium wilfordii Hook F (TWHF) [...