The experience of Tunisian public healthcare system toward decentralization to the reduction of health inequalities in low-, middle- income countries.

From 2014 to 2021, Tunisian government had a firm will to implement a progressive decentralization of welfare state governance, as outlined in its democratic Constitution. The Tunisian public healthcare system was selected as a pilot sector for experimenting with decentralization to reduce disparities in access to and quality of health services across different regions. This paper aimed to formulate an effective strategy for healthcare system decentralization in low- and middle-income countries, drawing on past experiences of its implementation.

Benralizumab: from tissue distribution to eosinophilic cytotoxicity up to potential immunoregulation.

Introduction: Benralizumab, a monoclonal IgG antibody, has emerged as a key therapeutic agent in severe asthma by specifically targeting eosinophils, pivotal cells that drive inflammation and tissue damage. Over the past two decades, the availability of such targeted therapies has allowed patients to achieve better disease control. Real-world evidence has consistently demonstrated the effectiveness of benralizumab in managing severe asthma.

Endpoint Selection in Randomized Clinical Trials for Hypertrophic Cardiomyopathy.

Randomized clinical trials (RCTs) for hypertrophic cardiomyopathy (HCM) have long been challenging caused by the condition's rarity, low event rates, and diverse clinical presentations. However, recent advances in targeted therapies have sparked increased interest in HCM research. Despite this, designing effective RCTs remains complex, particularly in identifying clinically meaningful endpoints.

Rare dysfunctional SCN2A variants are associated with malformation of cortical development.

Objective: SCN2A encodes the voltage-gated sodium (Na+) channel α subunit Na1.2, which is important for the generation and forward and back propagation of action potentials in neurons. Genetic variants in SCN2A are associated with a spectrum of neurodevelopmental disorders.

De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

Achieving Medication-Free Remission in Patients With Juvenile Dermatomyositis.

Objective: Prognostic factors associated with medication discontinuation in children with juvenile dermatomyositis (JDM) remain largely elusive. We aim to identify the predictors of medication-free remission (MFR) in children with JDM.

Methods: In this retrospective study, patients diagnosed with JDM according to Peter & Bohan criteria and followed for ≥18 months at a tertiary care center from 2006 through 2022 were included.

Hymenoptera venom allergy in children.

From a taxonomic point of view, Hymenoptera are subclassified into families: Apidae, including honeybees (Apis mellifera) and bumblebees (Bombus), and Vespidae, which, in turn, are divided into the subfamilies of Vespinae (wasps, including hornets, vespules, dolichovespules) and Polistinae (paper wasp). Hypersensitivity to Hymenoptera venom can be linked to immunological (IgE-mediated or non-IgE-mediated) and non-immunological mechanisms. Reactions are classified into local reactions, large local reactions, systemic reactions, toxic reactions, and unusual reactions.

L-Arginine supplementation as mitochondrial therapy in diabetic cardiomyopathy.

In patients with type II diabetes, the development of diabetic cardiomyopathy (DC) is associated with a high risk of mortality. Left ventricular hypertrophy, diastolic dysfunction, and exercise intolerance are the first signs of DC. The underlying mechanisms are not fully elucidated, and there is an urgent need for specific biomarkers and molecular targets for early diagnosis and treatment.

Limiting serine availability during tumor progression promotes muscle wasting in cancer cachexia.

Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of body weight occurring in about 80% of cancer patients, frequently representing the leading cause of death. Dietary intervention is emerging as a promising therapeutic strategy to counteract cancer-induced wasting. Serine is the second most-consumed amino acid (AA) by cancer cells and has emerged to be strictly necessary to preserve skeletal muscle structure and functionality.

Large, protracted, multispecies and multiclonal spread of VIM-type Metallo-ß-Lactamase-Producing Enterobacterales in an Italian Hospital.

Background: Carbapenem-resistant Enterobacterales, particularly those producing carbapenemases (CPE), pose a major threat to human health, being listed among critical-priority resistant pathogens by the World Health Organization.

Aim: In this study we report on a large nosocomial spread of CPE of different species producing VIM-type carbapenemases, and on the infection prevention and control measures thata were adopted to contrast the spread.

Methods: Conventional culture and molecular methods were used for detection and identification of VIM-positive CPE (VIM-CPE) causing infections or colonizing patients or present in environmental specimens.

How does the tidal cycle influence the estuarine dynamics of microplastics?

Estuaries are the main pathway for the microplastics (MPs) to enter into the oceans. However, factors that drive river-sea transport of MPs are not yet fully understood. Therefore, our research investigated the influence of the tidal cycle on the abundance and characteristics of MPs in an urban estuary, through high-frequency sampling (every 2-3 h) using a plankton net (120 μm mesh size) in two seasons (rainy and dry seasons).

Supramolecular dextran/polyamine phosphate nanocapsules with smart responsiveness for encapsulation of therapeutics.

The polyallylamine hydrochloride (PAH) polymer is here functionalized with branched and biocompatible polysaccharide dextran (DEX) molecules. Covalent conjugation of DEX to PAH has been achieved through a straightforward reductive amination approach, allowing for a controlled number of DEX chains per PAH polymer (PAH:DEX, n = 0.1, 0.

Differences in microorganism profile in periprosthetic joint infections of the hip in patients affected by chronic kidney disease.

Background: Patients affected by chronic kidney disease (CKD) are at increased risk of periprosthetic joint infection (PJI) after total hip arthroplasty (THA). This patient population has a higher risk of recurrent infections and hospitalization. The aim of this study is to compare the profile of microorganisms in patients with CKD and PJI of the hip versus controls and to individuate potentially unusual and drug-resistant microorganisms among the causative bacteria.

Multivalent GCase Enhancers: Synthesis and Evaluation of Glyco-Gold Nanoparticles Decorated with Trihydroxypiperidine Iminosugars.

The present study reports the preparation of the first multivalent iminosugars built onto a glyco-gold nanoparticle core (glyco-AuNPs) capable of stabilizing or enhancing the activity of the lysosomal enzyme GCase, which is defective in Gaucher disease. An -nonyltrihydroxypiperidine was selected as the bioactive iminosugar unit and further functionalized, via copper-catalyzed alkyne-azide cycloaddition, with a thiol-ending linker that allowed the conjugation to the gold core. These bioactive ligands were obtained with either a linear monomeric or dendritic trimeric arrangement of the iminosugar.

European S2k guidelines for hidradenitis suppurativa/acne inversa part 2: Treatment.

Introduction: This second part of the S2k guidelines is an update of the 2015 S1 European guidelines.

Objective: These guidelines aim to provide an accepted decision aid for the selection, implementation and assessment of appropriate and sufficient therapy for patients with hidradenitis suppurativa/acne inversa (HS).

Methods: The chapters have been selected after a Delphi procedure among the experts/authors.

Placental and Fetal Metabolic Reprogramming in Pregnancies with Intrauterine Growth Restriction.

The high-altitude hypoxia model demonstrates that insufficiently oxygenated placentas activate compensatory mechanisms to ensure fetal survival, hinging on the transcription factor hypoxia-inducible factor-1. The aim of the present study is to investigate whether and when similar mechanisms are also activated during intrauterine growth restriction (IUGR). A retrospective observational study evaluated a series of umbilical cord blood samples, which provide a realistic representation of the fetal intrauterine status, collected from a cohort of preterm and term neonates, both affected and not affected by IUGR.

Tactile sensitivity to softness in virtual reality can increase when visual expectation and tactile feedback contradict each other.

Objective: The perception of softness plays a key role in interactions with various objects, both in the real world and in virtual/augmented reality (VR/AR) systems. The latter can be enriched with haptic feedback on the softness of virtual objects, to improve immersivity and realism. In such systems, visual expectation can influence tactile sensitivity to softness, as multisensory integration attempts to create a coherent perceptual experience.

Structural Commonalities Determined by Physicochemical Principles in the Complex Polymorphism of the Amyloid State of Proteins.

Advances in solid-state nuclear magnetic resonance (ssNMR) spectroscopy and cryogenic electron microscopy (cryoEM) have revealed the polymorphic nature of the amyloid state of proteins. Given the association of amyloid with protein misfolding disorders, it is important to understand the principles underlying this polymorphism. To address this problem, we combined computational tools to predict the specific regions of the sequence forming the β-spine of amyloid fibrils with the availability of 30, 83 and 24 amyloid structures deposited in the Protein Data Bank (PDB) and Amyloid Atlas (AA) for the amyloid β (Aβ) peptide, α-synuclein (αS), and the 4R isoforms of tau, associated with Alzheimer's disease, Parkinson's disease, and various tauopathies, respectively.

The metabolic hypothesis for restrictive eating behaviors: A computational and evolutionary approach.

Background: Restrictive eating behaviors, widespread in humans and animals, are often conceptualized as maladaptive, but may serve adaptive purposes under specific circumstances.

Aim: To investigate the adaptive potential of restrictive eating behaviors.

Methods: Computational models explored the relationship between food availability, basal metabolic rate, and restrictive eating behaviors.

Robotic Versus Open Distal Pancreatectomy: A Propensity Score Matching Analysis.

Background: Minimally invasive distal pancreatectomy offers recognised benefits over open surgery. Robotic surgery, with its shorter learning curve and technical advancements, presents a promising alternative to laparoscopy in managing pancreatic diseases.

Methods: This study enrolled consecutive patients undergoing distal pancreatectomy between January 2013 and May 2022.

The Antiepileptic Drug Levetiracetam Inhibits Carbonic Anhydrase: and Studies on Catalytically Active Human Isoforms.

Several antiepileptic drugs (AEDs) have been found to inhibit human carbonic anhydrases (hCAs), paving the way for repurposing AEDs for the treatment of various diseases, including cancer. Here, the hCAs inhibitory effects of levetiracetam, a highly prescribed AED that does not bear a common zinc-binding group, were investigated and . Levetiracetam inhibited all tested hCAs, although with a specific profile compared to the reference acetazolamide, with remarkable efficacy against tumor-associated hCA IX and XII.

Monoclonal gammopathy is present in one fourth of patients undergoing renal biopsy but is pathogenic only in half of them.

Background: About 4-7% of renal biopsies show a monoclonal gammopathy-related nephropathy, such as AL amyloidosis, cast nephropathy, or light chain deposition disease. Both a high prevalence and a causal role of monoclonal gammopathy have been observed in patients with C3 glomerulopathy or thrombotic microangiopathy, although a definitive causative role cannot be established in most cases (potentially monoclonal gammopathy-related nephropathies). A coexisting monoclonal gammopathy has been identified in many cases of nephropathy without a defined causative role (monoclonal gammopathy-unrelated nephropathies).

How Italian radiation oncologists use ChatGPT: a survey by the young group of the Italian association of radiotherapy and clinical oncology (yAIRO).

Purpose: To investigate the awareness and the spread of ChatGPT and its possible role in both scientific research and clinical practice among the young radiation oncologists (RO).

Material And Methods: An anonymous, online survey via Google Forms (including 24 questions) was distributed among young (< 40 years old) ROs in Italy through the yAIRO network, from March 15, 2024, to 31, 2024. These ROs were officially registered with yAIRO in 2023.