Multi-target gene therapy AUP1602-C to improve healing and quality of life for diabetic foot ulcer patients: a phase I, open-label, dose-finding study.

Background: Diabetic foot ulcer (DFU) is a common and highly morbid complication of diabetes with high unmet medical needs. AUP1602-C, a topical four-in-one gene therapy medicinal product (GTMP), consisting of a strain that produces fibroblast growth factor-2, interleukin-4, and colony-stimulating factor-1, is a promising novel treatment for DFU.

Objectives: The aim of this first-in-human study was to investigate whether AUP1602-C is safe and effective in improving wound healing and quality of life (QoL) in patients with non-healing DFU (nhDFU), and to determine the recommended phase II dose.

Efficacy and Safety of a Mixture of Microencapsulated Sodium Butyrate, Probiotics, and Short Chain Fructooligosaccharides in Patients with Irritable Bowel Syndrome-A Randomized, Double-Blind, Placebo-Controlled Study.

Biotics are increasingly being used in the treatment of irritable bowel syndrome (IBS). This study aimed to assess the efficacy and safety of a mixture of microencapsulated sodium butyrate, probiotics ( DSM 26357, DSM 32418, DSM 32946, DSM 32403, and DSM 32269), and short-chain fructooligosaccharides (scFOSs) in IBS patients. This was a randomized, double-blind, placebo-controlled trial involving 120 adult participants with IBS.

New Polymer-Carbon Lustrous Carbon Precursor in Synthetic Molding Sands-Part I: Studies on the Properties of Sands.

In the first part of this publication, selected technological and strength properties of synthetic molding sand bound with sodium bentonite with the addition of a new lustrous carbon carrier (R, R, R, W, P, Z, P, P, S, ρ) were determined. The introduction of polyethylene as a substitute for hydrocarbon resin, and shungite as a replacement for coal dust, demonstrated the achievement of an optimal molding sand composition for practical use in casting technology. The sand containing a new lustrous carbon carrier (SH/PE) demonstrates the highest permeability and flowability.

Real-world safety and efficacy of rADAMTS13 in the treatment of congenital thrombotic thrombocytopenic purpura in pediatric patients in Poland.

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultrarare microvascular disease caused by the deficiency of the metalloprotease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motifs 13). Approximately half of all cases remain undiagnosed until a triggering event in adulthood; therefore, the prevalence rates may be underestimated. The current standard of care is based on regular transfusions of fresh frozen plasma, which often lead to allergic reactions in patients.

Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis.

Context: Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens.

Objective: To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials.

Adjuvant Use of Pembrolizumab for Stage III Melanoma in a Real-World Setting in Europe.

Background: Although data on patients treated with pembrolizumab are available from clinical trials and single-country real-world reports, to our knowledge no multi-country real-world studies have investigated the use of pembrolizumab as an adjuvant treatment for stage III melanoma.

Methods: We used the European Melanoma Registry (EUMelaReg), a disease entity-based registry specific for melanoma, to examine treatment and outcomes for adult patients with stage III melanoma with lymph node involvement who had complete resection and received adjuvant treatment with pembrolizumab. The primary objectives were to describe the demographic and clinical characteristics of the included patients as well as time on adjuvant pembrolizumab treatment (TOT), real-world recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) from adjuvant pembrolizumab initiation.

Does Online Social Support Affect the Eating Behaviors of Polish Women with Insulin Resistance?

Background: Insulin resistance, a key factor in developing type 2 diabetes mellitus, is linked to various health conditions. The basis of its treatment is lifestyle modification. However, adherence to nutritional and other medical recommendations can be challenging for chronic disease patients due to many factors, including demographics, social context, gender, age, and the patient's baseline health condition.

Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE.

The ALPINE trial established the superiority of zanubrutinib over ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma; here, we present data from the final comparative analysis with extended follow-up. Overall, 652 patients received zanubrutinib (n = 327) or ibrutinib (n = 325). At an overall median follow-up of 42.

An insight in to microwave induced defects and its impact on nonlinear process in NiO nanostructures under femtosecond and continuous wave laser excitation.

This work demonstrates the impact of microwave (MW) irradiation on third-order nonlinear optical (NLO) processes in chemically deposited NiO nanostructure films. The optical nonlinearity of the NiO nanostructure films was studied using third-harmonic generation (THG) measurements in the pulsed femtosecond laser regime and the Z-scan technique in the continuous wave laser regime. In the ultrafast pulsed regime, THG measurements revealed a significant increase in the THG signal of MW-irradiated NiO nanostructures due to photoexcitation and relaxation processes, resulting from an enhancement in defect concentration.

Stabilization of Anterior Aspect of Distal Tibiofibular Syndesmosis: A Fully Arthroscopic Technique.

The anteroinferior tibiofibular ligament (AITFL) is 1 of the 4 ligaments forming the distal tibiofibular syndesmosis. When damaged, it is crucial to assess and address the lesion properly because a neglected or underdiagnosed lesion may invoke ankle osteoarthritis with underlying tibiofibular joint instability. In this technical note, we present a fully arthroscopic stabilization of the AITFL without the need for soft-tissue grafting.

More Than a Gut Feeling─A Combination of Physiologically Driven Dissolution and Pharmacokinetic Modeling as a Tool for Understanding Human Gastric Motility.

studies of formulation performance with and/or simulations are often limited by significant gaps in our knowledge of the interaction between administered dosage forms and the human gastrointestinal tract. This work presents a novel approach for the investigation of gastric motility influence on dosage form performance, by combining biopredictive dissolution tests in an innovative apparatus with mechanistic physiology-based pharmacokinetic modeling. The methodology was based on the pharmacokinetic data from a large ( = 118) cohort of healthy volunteers who ingested a capsule containing a highly soluble and rapidly absorbed drug under fasted conditions.

Prominent misinformation interventions reduce misperceptions but increase scepticism.

Current interventions to combat misinformation, including fact-checking, media literacy tips and media coverage of misinformation, may have unintended consequences for democracy. We propose that these interventions may increase scepticism towards all information, including accurate information. Across three online survey experiments in three diverse countries (the United States, Poland and Hong Kong; total n = 6,127), we tested the negative spillover effects of existing strategies and compared them with three alternative interventions against misinformation.

Inflammatory Bowel Diseases in the Elderly: A Focus on Disease Characteristics and Biological Therapy Patterns.

: The incidence of inflammatory bowel diseases (IBDs) in elderly patients is constantly increasing. It results from the combination of an aging population with compounding prevalence of IBD, as well as the growing burden of elderly-onset IBD. The clinical characteristics of elderly patients differ from young subjects with IBD due to the multimorbidity or polypharmacy, affecting the choice of adequate therapeutic options.

Acalabrutinib plus venetoclax and rituximab in treatment-naive mantle cell lymphoma: 2-year safety and efficacy analysis.

This phase 1b study evaluated safety and efficacy of acalabrutinib, venetoclax, and rituximab (AVR) in treatment-naive mantle cell lymphoma (TN MCL). Patients received acalabrutinib from cycle 1 until progressive disease (PD) or undue toxicity, rituximab for 6 cycles with maintenance every other cycle through cycle 24 or until PD, and venetoclax, beginning at cycle 2, for 24 cycles. Twenty-one patients were enrolled; 95.

The Defects Genome of Janus Transition Metal Dichalcogenides.

2D Janus Transition Metal Dichalcogenides (TMDs) have attracted much interest due to their exciting quantum properties arising from their unique two-faced structure, broken-mirror symmetry, and consequent colossal polarization field within the monolayer. While efforts are made to achieve high-quality Janus monolayers, the existing methods rely on highly energetic processes that introduce unwanted grain-boundary and point defects with still unexplored effects on the material's structural and excitonic properties Through high-resolution scanning transmission electron microscopy (HRSTEM), density functional theory (DFT), and optical spectroscopy measurements; this work introduces the most encountered and energetically stable point defects. It establishes their impact on the material's optical properties.

Effect of food on selumetinib pharmacokinetics and gastrointestinal tolerability in adolescents with neurofibromatosis type 1-related plexiform neurofibromas.

Background: Selumetinib is approved for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) in multiple countries, including the USA (≥ 2 years). Until recently, individuals had to take selumetinib twice daily (BID) in a fasted state. This study evaluated the effect of a low-fat meal on selumetinib PK parameters and gastrointestinal (GI) tolerability in adolescent participants with NF1-PN.

Hydromethylthionine rescues synaptic SNARE proteins in a mouse model of tauopathies: Interference by cholinesterase inhibitors.

In clinical trials for Alzheimer's disease (AD), hydromethylthionine mesylate (HMTM) showed reduced efficacy when administered as an add-on to symptomatic treatments, while it produced a significant improvement of cognitive function when taken as monotherapy. Interference of cholinesterase inhibition with HMTM was observed also in a tau transgenic mouse model, where rivastigmine reduced the pharmacological activity of HMTM at multiple brain levels including hippocampal acetylcholine release, synaptosomal glutamate release and mitochondrial activity. Here, we examined the effect of HMTM, given alone or in combination with the acetylcholinesterase inhibitor, rivastigmine, at the level of expression of selected pre-synaptic proteins (syntaxin-1; SNAP-25, VAMP-2, synaptophysin-1, synapsin-1, α-synuclein) in brain tissue harvested from tau-transgenic Line 1 (L1) and wild-type mice using immunohistochemistry.

Neuroprotection of Cholinergic Neurons with a Tau Aggregation Inhibitor and Rivastigmine in an Alzheimer's-like Tauopathy Mouse Model.

Basal forebrain cholinergic dysfunction, most likely linked with tau protein aggregation, is a characteristic feature of Alzheimer's disease (AD). Recent evidence suggests that tau protein is a putative target for the treatment of dementia, and the tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), has emerged as a potential disease-modifying treatment. However, its efficacy was diminished in patients already receiving approved acetylcholinesterase inhibitors.