High-throughput non-homogenous 3D polycaprolactone scaffold for cancer cell and cancer-associated fibroblast mini-tumors to evaluate drug treatment response.

High-throughput screening (HTS) three-dimensional (3D) tumor models are a promising approach for cancer drug discovery, as they more accurately replicate cell behavior than two-dimensional (2D) models. However, assessing and comparing current 3D models for drug efficacy remains essential, given the significant influence of cellular conditions on treatment response. To develop mimicking 3D models, we evaluated two HTS 3D models established in 96-well plates with 3D polycaprolactone (PCL) scaffolds fabricated using two distinct methods, resulting in scaffolds with either homogenous or non-homogenous fiber networks.

Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

Novel antimalarial 3-substituted quinolones isosteres with improved pharmacokinetic properties.

Aryl quinolone derivatives can target the cytochrome bc complex of Plasmodium falciparum, exhibiting excellent in vitro and in vivo antimalarial activity. However, their clinical development has been hindered due to their poor aqueous solubility profiles. In this study, a series of bioisosteres containing saturated heterocycles fused to a 4-pyridone ring were designed to replace the inherently poorly soluble quinolone core in antimalarial quinolones with the aim to reduce π-π stacking interactions in the crystal packing solid state, and a synthetic route was developed to prepare these alternative core derivatives.

Advantage of bedside versus conventional operating room surgery in the management of term and preterm newborn infants: a single center retrospective observational study.

Purpose: To compare postoperative outcomes of bedside surgery (BS) with those of surgery performed in the operating room (ORS) in preterm and full-term neonates.

Methods: Data from neonates undergoing major surgical interventions were retrospectively evaluated. Primary outcome was the incidence of postoperative hypothermia.

Therapeutic Potential of Feline Adipose-Derived Stem Cell Exosomes in the Treatment of Feline Idiopathic Cystitis: A Characterization and Functional Analysis of miRNA Content.

Feline Idiopathic Cystitis (FIC), is a chronic lower urinary tract condition in cats analogous to PBS/IC in women, which presents significant treatment challenges due to its idiopathic nature. Recent advancements in regenerative medicine highlight the potential of Adipose Tissue-Derived Stem Cells (ADSCs), particularly through their secretome, which includes mediators, bioactive molecules, and extracellular vesicles (EVs). Notably, exosomes, a subset of EVs, facilitate cell-to-cell communication and, when derived from ADSCs, exhibit anti-inflammatory properties and contribute to tissue regeneration.

Effectiveness of the BNT162b2 XBB.1.5-adapted vaccine against COVID-19 hospitalization related to the JN.1 variant in Europe: a test-negative case-control study using the id.DRIVE platform.

Background: Prior studies have reported lower effectiveness of XBB.1.5-adapted vaccines against hospitalization related to the Omicron JN.

Education Programs for Informal Caregivers of Noncancer Patients in Home-Based Palliative Care: A Scoping Review.

The literature available on the topic of education programs for noncancer patients' informal caregivers (ICs) is heterogeneous and fragmented in the setting of palliative care (PC). We conducted a scoping review (ScR) to map the literature on educational programs for ICs in home-based PC, considering the available reviews, qualitative studies, observational studies, studies of validation of measurement tools, uncontrolled trials, nonrandomized controlled trials, and feasibility studies. This ScR included 21 eligible records by searching PubMed, Web of Science, Embase, Scopus, and CINAHL databases.

Actionable mutations in early-stage ovarian cancer according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT): a descriptive analysis on a large prospective cohort.

Background: According to the European Society for Clinical Oncology (ESMO) guidelines, the therapeutic algorithm for early-stage epithelial ovarian carcinoma (EOC) is primarily based on grading and histotype. Adjuvant chemotherapy is usually recommended for high-grade tumors and for the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IC; however, overtreatment remains a concern. Conversely, patients truly at higher risk of recurrence currently lack access to additional therapeutic strategies.

Amitriptyline-perphenazine therapy for persistent idiopathic facial pain: translational perspectives from a retrospective study.

Background: Persistent idiopathic facial pain (PIFP) can be challenging, both in its diagnosis, which appears to be purely exclusionary, and in its treatment, which currently lacks a gold standard. Amitriptyline is considered a first-line therapy, although not always effective. Recent insights into the role of dopamine in facial pain suggest that a novel therapeutic approach could target the dopamine system.

5-methyl-2-carboxamidepyrrole-based novel dual mPGES-1/sEH inhibitors as promising anticancer candidates.

Inhibiting microsomal prostaglandin E synthase-1 (mPGES-1), an inducible enzyme involved in prostaglandin E (PGE) biosynthesis and tumor microenvironment (TME) homeostasis, is a valuable strategy for treating inflammation and cancer. In this work, 5-methylcarboxamidepyrrole-based molecules were designed and synthesized as new compounds targeting mPGES-1. Remarkably, compounds 1f, 2b, 2c, and 2d were able to significantly reduce the activity of the isolated enzyme, showing IC values in the low micromolar range.

Risk factors for benign uretero-enteric anastomotic strictures after open radical cystectomy and ileal conduit.

Introduction And Objective: Radical Cystectomy (RC) is one of the most common and complex surgical procedures in urologic surgery, and benign ureteroenteric anastomosis strictures (UAS) are complications described in about 15% of patients undergoing RC with different urinary diversion (UD). The aim of this study is to evaluate and analyze risk factors related to the development of ureteral stenosis after RC.

Materials And Methods: All consecutive patients who underwent RC with ileal conduit from December 2019 to December 2022 were included.

Assessment of clot-lysing and membrane-stabilizing capacity of ascorbic acid: approach with molecular docking.

This study aimed to evaluate the clot-lysing and membrane stabilizing capacities of ascorbic acid (AA) using and methods. For this, we used clot lysis and hemolyzing tests to check the anti-atherothrombosis and membrane-stabilizing properties of AA, respectively. Additionally, molecular docking studies were performed to investigate AA's interactions with cyclooxygenase-1 (COX-1) and plasminogen enzymes.

The Evil Twins of Chronic Pelvic Pain Syndrome: A Systematic Review and Meta-Analysis on Interstitial Cystitis/Painful Bladder Syndrome and Endometriosis.

Background: Chronic pelvic pain is a debilitating condition affecting quality of life. Endometriosis is one of the leading causes of CPP, but recent studies highlighted the role of interstitial cystitis/bladder pain syndrome (IC/PBS) in causing CPP. Only some studies addressed the coexistence of these two conditions, which seems more frequent than what is supposed, leading to diagnostic delays and unnecessary surgeries.

Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.

This review explores some of the complex mechanisms underlying antitumor T-cell response, with a specific focus on the balance and cross-talk between selected co-stimulatory and inhibitory pathways. The tumor microenvironment (TME) fosters both T-cell activation and exhaustion, a dual role influenced by the local presence of inhibitory immune checkpoints (ICs), which are exploited by cancer cells to evade immune surveillance. Recent advancements in IC blockade (ICB) therapies have transformed cancer treatment.

Coumarin Derivative Hybrids: Novel Dual Inhibitors Targeting Acetylcholinesterase and Monoamine Oxidases for Alzheimer's Therapy.

Multi-target-directed ligands (MTDLs) represent a promising frontier in tackling the complexity of multifactorial pathologies like Alzheimer's disease (AD). The synergistic inhibition of MAO-B, MAO-A, and AChE is believed to enhance treatment efficacy. A novel coumarin-based molecule substituted with -phenylpiperazine via three- and four-carbon linkers at the 5- and 7-positions, has been identified as an effective MTDL against AD.

Using In Vitro and In Silico Analysis to Investigate the Chemical Profile and Biological Properties of Extracts.

The present study investigates the chemical profile and biological activities of M. Keskin, a species endemic to Turkey, aiming to explore its potential applications in pharmacology. We assessed its phenolic and flavonoid content by employing ethyl acetate, methanol, and water as extraction solvents.

Reuse of Almond Skin to Formulate a New Gluten- and Lactose-Free Bakery Product.

This work aimed to propose the reuse of processing waste from the Sicilian almond ( Batsch.) cultivar Tuono for the formulation of a new functional baked product (muffin) that is gluten- and lactose-free. Muffins were prepared using orange juice, rice flour, extra virgin olive oil, and enriched almond skin (3% and 6% /).

Adaptation of antibiotics and antifungal strategy to preoperative biliary drainage to improve postoperative outcomes after pancreatic head resection.

Background: Biliary contamination significantly correlates with major comorbidities during pancreatic head resection. Recently, a piperacillin-tazobactam prophylaxis demonstrated a lower rate of infectious complications (IC) and postoperative pancreatic fistula (POPF) in this population. However, bacterial contamination is rare in patients without a preoperative biliary drainage (PBD) and probably could not benefit from this antibiotic.

A sulfonimide derivative of bezafibrate as a dual inhibitor of cyclooxygenase-2 and PPARα.

Background: PPARα and cyclooxygenase (COX)-2 are overexpressed in certain types of cancer. Thus, developing a dual inhibitor that targets both could be more effective as an anticancer agent than single inhibitors. We have previously shown that an analog of the bezafibrate named AA520 is a PPARα antagonist.

Incorporating the concept of overtransfusion into hemovigilance monitoring: An expert-based definition and criteria from the International HIT-OVER Forum.

Background: Liberal or overtransfusion (OT) may be regarded as "inappropriate," but it is not reported as a transfusion-related adverse event. A definition of OT is lacking. OT may include overdosing of components, giving the incorrect component, or unnecessary administration without evidence of need for transfusion.

Azathioprine for people with multiple sclerosis.

Background: Multiple sclerosis (MS) is an immune-mediated, chronic, inflammatory demyelinating disease of the central nervous system, impacting around 2.8 million people worldwide. Characterised by recurrent relapses or progression, or both, it represents a substantial global health burden, affecting people, predominantly women, at a young age (the mean age of diagnosis is 32 years).

Analysis of Dental Arch Symmetry of Children With Unilateral Cleft Lip and Palate: Seven-Year Follow-Up.

Background: Orofacial cleft is the most common craniofacial deformity, resulting in facial anatomical disorders.

Aim: To evaluate maxillary dental arch symmetry of children with unilateral complete cleft lip, alveolus, and palate before and after primary surgeries.

Design: A total of 27 dental casts were analyzed: (T1) Presurgical; (T2) Postsurgical 1; and (T3) Postsurgical 2.

4-Aza Cyclopentenone Prostaglandin Analogues: Synthesis and NF-κB Inhibitory Activities.

Inspired by the cyclopentenone family of prostaglandins, a series of 4-aza, cross-conjugated cyclopentenones is described. Synthesised from N-protected (4R)-aza-cyclopentenone 5, the exocyclic alkene was installed using a modified Baylis-Hillman type aldol reaction, whereby carbon-carbon bond formation is accompanied by dehydration. In this manner octanal and octenal, for example, can be introduced to mimic the ω-group present in the natural prostaglandins.

Melleatin, an antibiofilm multitasking protein with rRNA N-glycosylase and nuclease activity from Armillaria mellea fruiting bodies.

Several studies highlight the identification of some enzymes with additional abilities, especially those involved in metabolic pathways and/or host defence processes, classified as multitasking proteins. In this context, we report the characterization of melleatin (17.5-kDa), a multitasking enzyme isolated from Armillaria mellea fruiting bodies.