Nuclear versus cytoplasmic IKKα signaling in keratinocytes leads to opposite skin phenotypes and inflammatory responses, and a different predisposition to cancer.

IKKα is known as an essential protein for skin homeostasis. However, the lack of suitable models to investigate its functions in the skin has led to IKKα being mistakenly considered as a suppressor of non-melanoma skin cancer (NMSC) development. In this study, using our previously generated transgenic mouse models expressing exogenous IKKα in the cytoplasm (C-IKKα mice) or in the nucleus (N-IKKα mice) of basal keratinocytes, we demonstrate that at each subcellular localization, IKKα differently regulates signaling pathways important for maintaining the balance between keratinocyte proliferation and differentiation, and for the cutaneous inflammatory response.

Could an evaluative conditioning intervention ameliorate paranoid beliefs? Self-reported and neurophysiological evidence from a brief intervention focused on improving self-esteem.

Introduction: Much research on the treatment of paranoia has involved cognitive-behavioural interventions that address explicit social cognition processes. However, much of human cognition is preverbal or implicit, raising the possibility that such social judgements are implicated in paranoia. One type of implicit social cognition that has been investigated concerning paranoia is implicit self-esteem with some evidence that it may be possible to change implicit self-esteem using techniques based on conditioning theory.

Feasibility and Improved Diagnostic Yield of Intracoronary Adenosine to Assess Microvascular Dysfunction With Bolus Thermodilution.

Background: Bolus thermodilution and intravenous adenosine are established methods for coronary microcirculatory assessment. Yet, its adoption remains low, partly due to procedural time and patient discomfort associated with intravenous adenosine. We investigated differences between intracoronary and intravenous adenosine using bolus thermodilution in terms of microcirculatory indices, procedural time, and side effects associated with adenosine in patients with myocardial ischemia and nonobstructive coronary arteries.

Dormancy-inducing 3D engineered matrix uncovers mechanosensitive and drug-protective FHL2-p21 signaling axis.

Solid cancers frequently relapse with distant metastasis, despite local and systemic treatment. Cellular dormancy has been identified as an important mechanism underlying drug resistance enabling late relapse. Therefore, relapse from invisible, minimal residual cancer of seemingly disease-free patients call for in vitro models of dormant cells suited for drug discovery.

Follow-up on patients with initial negative mpMRI target and systematic biopsy for PI-RADS ≥ 3 lesions - an EAU-YAU study enhancing prostate cancer detection.

Purpose: To investigate the detection and predictors of prostate cancer (PCA) and clinically significant prostate cancer (csPCA) in patients with positive multiparametric MRI (mpMRI) followed by a negative MRI - guided target biopsy (TB) and systematic biopsy (SB).

Materials And Methods: This retrospective multicenter study included 694 patients from 10 tertiary referral centers with an initial positive mpMRI (PI-RADS ≥ 3) and negative results on both MRI-TB and SB. Patients were classified into three groups based on follow-up: Group 1 (prostate re-biopsy without new mpMRI), Group 2 (standardized second prostate mpMRI and subsequent re-biopsy), and Group 3 (follow-up with mpMRIs and biopsy based on clinical and radiological triggers).

Decoding YouTube: An In-depth Analysis of Living Donor Kidney Transplantation Videos and Their Implications for Patient Education.

Background And Objective: YouTube is an open online video platform that both patients and health care professionals use to access information. Our aim was to evaluate the quality of videos related to living-donor kidney transplantation (LDKT) on YouTube.

Methods: Research was conducted using the keywords "living donor kidney transplant" and "kidney transplant".

Comparative accuracy of Mini-Linguistic State Examination, Addenbrooke's Cognitive Examination, and Depistage Cognitif de Quebec for the diagnosis of primary progressive aphasia.

Background: Clinical diagnosis in primary progressive aphasia (PPA) is challenging. Recently, emphasis has been placed on the importance of screening evaluation. Three different screening tests that use different strategies based on the assessment of language (Mini-Linguistic State Examination, MLSE) or different cognitive domains (Addenbrooke's Cognitive Examination, ACE-III and Dépistage Cognitif de Québec, DCQ) have been proposed and independently validated.

Use of Stiripentol in Patients with Dravet Syndrome: Common Practice Among Experts in Spain.

Background: Despite considerable evidence for the efficacy and safety of stiripentol in Dravet syndrome (DS), some aspects of stiripentol use remain challenging in clinical practice, such as dose titration and the adjustment of concomitant antiseizure medications (ASMs) to prevent potential adverse effects.

Aim: To (1) provide practical recommendations on the initiation of stiripentol treatment in patients with DS, (2) evaluate its effectiveness in the patient, and (3) guide the management of drug interactions and other aspects of treatment monitoring.

Methods: Six Spanish neurologists (the authors) with expertise in the management of pediatric and adult patients with DS held a meeting in early 2024 to develop expert recommendations regarding the use of stiripentol in DS, based on a review of the literature and their common clinical experience.

SIRT1 Mediates the Antagonism of Wnt/β-Catenin Pathway by Vitamin D in Colon Carcinoma Cells.

Cancer initiation and progression result from genetic and epigenetic alterations caused by interactions between environmental and endogenous factors leading to aberrant cell signalling. Colorectal cancers (CRC) are linked to abnormal activation of the Wnt/β-catenin pathway, whose key feature is the nuclear accumulation of acetylated β-catenin in colon epithelial cells. Nuclear β-catenin acts as a transcriptional co-activator, targeting genes involved in cell proliferation and invasion.

Editorial: Protein post-translational modifications in the nervous system: from development to disease and ageing.

PTMs are crucial for biological processes contributing to healthy organ function. Protein post-translational modifications (PTMs), such as phosphorylation (P), acetylation (Ac), SUMOylation (SUMO), S-nitrosylation (Nitro), ubiquitination (Ub) and glycosylation (Glyco), affect a wide range of cellular and biological functions as depicted in this cartoon. Perturbations lead to severe consequences for the normal function of the brain and other organs, such as muscle.

Benefits of a comprehensive care model in patients with heart failure and chronic obstructive pulmonary disease: UMIPIC Program.

Background: Patients with heart failure (HF) and chronic obstructive pulmonary disease (COPD) have a high risk of hospital admission and mortality. This study evaluated the benefit of a care model, characterized by comprehensive and continuous care (UMIPIC program) in patients with HF and a history of COPD.

Methods: A total of 5644 patients were prospectively recruited, of which 1320 had a history of COPD between March 2008 and March 2020.

Role of semaphorins, neuropilins and plexins in cancer progression.

Progress in understanding nervous system-cancer interconnections has emphasized the functional role of semaphorins (SEMAs) and their receptors, neuropilins (NRPs) and plexins (PLXNs), in cancer progression. SEMAs are a conserved and extensive family of broadly expressed soluble and membrane-associated proteins that were first described as regulators of axon guidance and neural and vascular development. However, recent advances have shown that they can have a dual role in cancer progression, acting either as tumor promoters or suppressors.

Metabolomic characterization of MC3T3-E1pre-osteoblast differentiation induced by ipriflavone-loaded mesoporous nanospheres.

This study reports on the metabolic changes accompanying the differentiation of MC3T3-E1 osteoprogenitor cells induced by mesoporous bioactive glass nanospheres (nMBG) loaded with ipriflavone (nMBG-IP). Ipriflavone (IP) is a synthetic isoflavone known for inhibiting bone resorption, maintaining bone density, and preventing osteoporosis. Delivering IP intracellularly is a promising strategy to modulate bone remodeling at significantly lower doses compared to free drug administration.

Beyond lines of treatment: embracing early high-efficacy disease-modifying treatments for multiple sclerosis management.

Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional "first-line" and "second-line" treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS.

Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial.

Background: Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires.

Intrastromal Corneal Ring Segments and Keratoconus Progression: A Case Series Study.

Objective: To assess keratoconus (KC) progression following the implant of intrastromal corneal ring segments (ICRSs) in young patients.

Materials And Methods: Retrospective, longitudinal, observational, controlled nonrandomized case series study. Keratoconus patients aged 25 years or younger who underwent uneventful ICRS surgery and completed at least 3 years of follow-up were enrolled.

Dosimetric study of bevel factors in IOERT with mobile linacs: Towards a unified code of practice.

Background: Dosimetry in intraoperative electron radiotherapy (IOERT) poses distinct challenges, especially with inclined applicators deviating from international protocols. Ion recombination in ionization chambers, electron beam degradation due to scattering in cylindrical applicators, coupled with a lack of a well-defined beam quality surrogate, complicate output factor determination with ionization chambers. Synthetic diamond-based detectors, offer potential solutions; however, their suitability requires further exploration.

Silicone kyphoplasty (elastoplasty) versus traditional cement kyphoplasty for osteoporotic vertebral fractures. Does this new technique reduce the complications?

Introduction: Stiffness is increased in vertebrae after kyphoplasty with bone cement is performed, which cause an increase in subsequent fractures in adjacent levels. This has led to increased interest in alternative filling materials such as bioactive calcium phosphate ceramics or silicon-based polymers. This study's objective is to compare the results between kyphoplasty with bone cement and with the VK100 silicone.

Validation of the Valve Academic Research Consortium High Bleeding Risk Definition in Patients Undergoing TAVR.

Background: The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) has recently introduced a consensus document that outlines risk factors to identify high bleeding risk in patients undergoing transcatheter aortic valve replacement. The objective of the present study was to evaluate the prevalence and predictive value of the VARC-HBR definition in a contemporary, large-scale transcatheter aortic valve replacement population.

Methods: Multicenter study including 10 449 patients undergoing transcatheter aortic valve replacement.

Prostate-specific Antigen at 3 Months as a Predictor of Radiologic Progression-free Survival in Metastatic Hormone-sensitive Prostate Cancer Treated with Apalutamide: Analysis of 633 Patients in a Real-world Database.

Background And Objective: The depth of the prostate-specific antigen (PSA) decline after androgen receptor pathway inhibitor (ARPI) treatment combined with androgen deprivation therapy for patients with metastatic hormone-sensitive prostate cancer (mHSPC) may affect prognosis. The primary objective in our study was the correlation between the PSA response at 3 mo and radiologic progression-free survival (rPFS) at 24 mo. Three groups were defined according to the PSA decline: complete response (PSA ≤0.

EAACI guidelines on the management of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist.