Multisystem involvement, defective lysosomes and impaired autophagy in a novel rat model of nephropathic cystinosis.

Recessive mutations in the CTNS gene encoding the lysosomal transporter cystinosin cause cystinosis, a lysosomal storage disease leading to kidney failure and multisystem manifestations. A Ctns knockout mouse model recapitulates features of cystinosis, but the delayed onset of kidney manifestations, phenotype variability and strain effects limit its use for mechanistic and drug development studies. To provide a better model for cystinosis, we generated a Ctns knockout rat model using CRISPR/Cas9 technology.

Hybrid Lipid/Polymer Nanoparticles to Tackle the Cystic Fibrosis Mucus Barrier in siRNA Delivery to the Lungs: Does PEGylation Make the Difference?

Inhaled siRNA therapy has a unique potential for treatment of severe lung diseases, such as cystic fibrosis (CF). Nevertheless, a drug delivery system tackling lung barriers is mandatory to enhance gene silencing efficacy in the airway epithelium. We recently demonstrated that lipid-polymer hybrid nanoparticles (hNPs), comprising a poly(lactic-co-glycolic) acid (PLGA) core and a lipid shell of dipalmitoyl phosphatidylcholine (DPPC), may assist the transport of the nucleic acid cargo through mucus-covered human airway epithelium.

Femoral neck fracture: the reliability of radiologic classifications.

Background: Femoral neck fractures (FNF) are one of the most common injury in the elderly. A valid radiographic classification system is mandatory to perform the correct treatment and to allow surgeons to facilitate communication. This study aims to evaluate reliability of 2018 AO/OTA Classification, AO/OTA simplified and Garden classification.

Genomic Surveillance Enables the Identification of Co-infections With Multiple SARS-CoV-2 Lineages in Equatorial Guinea.

COVID-19 disease caused by SARS-CoV-2 represents an ongoing global public health emergency. Rapid identification of emergence, evolution, and spread of SARS-CoV-2 variants of concern (VOC) would enable timely and tailored responses by public health decision-making bodies. Yet, global disparities in current SARS-CoV-2 genomic surveillance activities reveal serious geographical gaps.

Mechanical power in pediatric acute respiratory distress syndrome: a PARDIE study.

Background: Mechanical power is a composite variable for energy transmitted to the respiratory system over time that may better capture risk for ventilator-induced lung injury than individual ventilator management components. We sought to evaluate if mechanical ventilation management with a high mechanical power is associated with fewer ventilator-free days (VFD) in children with pediatric acute respiratory distress syndrome (PARDS).

Methods: Retrospective analysis of a prospective observational international cohort study.

Genetic Vaccination as a Flexible Tool to Overcome the Immunological Complexity of Invasive Fungal Infections.

The COVID-19 pandemic has highlighted genetic vaccination as a powerful and cost-effective tool to counteract infectious diseases. Invasive fungal infections (IFI) remain a major challenge among immune compromised patients, particularly those undergoing allogeneic hematopoietic bone marrow transplantation (HSCT) or solid organ transplant (SOT) both presenting high morbidity and mortality rates. Candidiasis and Aspergillosis are the major fungal infections among these patients and the failure of current antifungal therapies call for new therapeutic aids.

The LiberAction Project: Implementation of a Pediatric Liberation Bundle to Screen Delirium, Reduce Benzodiazepine Sedation, and Provide Early Mobilization in a Human Resource-Limited Pediatric Intensive Care Unit.

Delirium, bed immobilization, and heavy sedation are among the major contributors of pediatric post-intensive care syndrome. Recently, the Society of Critical Care Medicine has proposed the implementation of daily interventions to minimize the incidence of these morbidities and optimize children functional outcomes and quality of life. Unfortunately, these interventions require important clinical and economical efforts which prevent their use in many pediatric intensive care units (PICU).

Prenatal Diagnosis of Clubfoot: Where Are We Now? Systematic Review and Meta-Analysis.

The primary methods for prenatal diagnosis of Clubfoot are ultrasound (US) and magnetic resonance imaging (MRI). An ultrasound is performed between the 1st trimester and the 28th week of pregnancy and it is reported to be used as a diagnostic method alone or in combination with MRI. So far, an international consensus on the most effective screening method has not been reached.

Extracellular Vesicles Derived From Modulate Inflammatory Genes and Tight Junctions in a Human Model of Intestinal Epithelium.

It is widely acknowledged that mammalian exosomes (or extracellular vesicles), have a key role in intercellular communication, owing to the presence of various bioactive molecules such as lipids, proteins, and microRNAs within their inner compartment. Most recently, the discovery of extracellular vesicles isolated from edible plants (such as vegetables and fruits) and their similarity in terms of size and content with exosomes has opened new perspectives on possible intercellular communication and regulation of important biological processes in which these vesicles are involved. It is also well-known that a balanced diet rich of fruits and vegetables (i.

Extracellular vesicles and pasteurized cells derived from Akkermansia muciniphila protect against high-fat induced obesity in mice.

Background: Several studies have shown that probiotics have beneficial effects on weight control and metabolic health. In addition to probiotics, recent studies have investigated the effects of paraprobiotics and postbiotics. Therefore, we evaluated the preventive effects of live and pasteurized Akkermansia muciniphila MucT (A.

Pediatric autoimmune disorders with gastrointestinal expressions: from bench to bedside.

The gastrointestinal (GI) tract may be involved in systemic autoimmune diseases or may be the target of organ-specific autoimmunity. Autoimmune enteropathy (AIE) is a rare disorder characterized by severe and protracted diarrhea, weight loss from malabsorption and immune-mediated damage to the intestinal mucosa, generally occurring in infants and young children, only rarely in adult. The salient histopathologic features of AIE are most prominent in the small intestine: villous blunting, crypt hyperplasia, mononuclear cell inflammatory expansion of the lamina propria with intraepithelial lymphocytosis, crypt apoptosis and absence of Paneth cells, goblet cells or both.

Risk and protective factors of quality of life for children with autism spectrum disorder and their families during the COVID-19 lockdown. An Italian study.

Background: The lockdown due to the COVID-19 pandemic has been a difficult period for children with Autism Spectrum Disorder (ASD), and their families.

Aims: The aim of this study was to investigate the predictors of the quality of life (QoL) of children with ASD and their parents throughout the first lockdown, providing a snapshot of the impact of the pandemic on these families life.

Method And Procedures: A cohort of 243 parents of children with ASD (2-15 years old) completed an original online survey regarding the modification of ASD cores symptoms during lockdown, the type of interventions they had done before and during lockdown and the activities performed by the child.

A UHPLC-MS/MS Method for Therapeutic Drug Monitoring of Aciclovir and Ganciclovir in Plasma and Dried Plasma Spots.

The role of therapeutic drug monitoring (TDM) of valaciclovir (VA)/aciclovir (A) and valganciclovir/ganciclovir (VG/G) in critically ill patients is still a matter of debate. More data on the dose-concentration relationship might therefore be useful, especially in pediatrics where clinical practice is not adequately supported by robust PK studies. We developed and validated a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) micro-method to simultaneously quantify A and G from plasma and dried plasma spots (DPS).

Pattern-based Histologic Approach in Very Early Onset IBD: Main Features and Differential Diagnosis.

Very early onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella classification composed of IBD-like diseases encompassing both classic IBD (Crohn's disease and ulcerative colitis) and monogenic disorder, both arising before 6 years of age. VEO-IBD patients present significant clinical differences from IBD occurring in older children and in adults, including more severe disease, often unresponsive to conventional IBD therapy and a greater proportion of cases featuring an underlying genetic alteration. Histologic findings of gastrointestinal biopsies can show an IBD-like pattern (both Crohn's disease-like and ulcerative colitis-like pattern), an apoptotic-like and enterocolitis-like pattern.

p53 Activation Effect in the Balance of T Regulatory and Effector Cell Subsets in Patients With Thyroid Cancer and Autoimmunity.

Carcinomas evade the host immune system by negatively modulating CD4+ and CD8+ T effector lymphocytes through forkhead box protein 3 (FOXP3) positive T regulatory cells' increased activity. Furthermore, interaction of the programmed cell death 1 (PD1) molecule and its ligand programmed cell death ligand 1 (PDL1) inhibits the antitumor activity of PD1+ T lymphocytes. Immunotherapy has become a powerful strategy for tailored cancer patients' treatment both in adult and pediatric patients aiming to generate potent antitumor responses.

Comparative effects of alive and pasteurized Akkermansia muciniphila on normal diet-fed mice.

Recently, Akkermansia muciniphila an anaerobic member of the gut microbiota, has been proposed as a next-generation probiotic. The aim of this study was evaluation of the effect of alive and pasteurized A. muciniphila on health status, intestinal integrity, immune response, lipid metabolism, and gut microbial composition in normal-diet fed mice as well as direct effects of the bacterium on Caco-2 cell line.

Italian consensus on the therapeutic management of uncomplicated acute hematogenous osteomyelitis in children.

Background: Acute hematogenous osteomyelitis (AHOM) is an insidious infection of the bone that more frequently affects young males. The etiology, mainly bacterial, is often related to the patient's age, but it is frequently missed, owing to the low sensitivity of microbiological cultures. Thus, the evaluation of inflammatory biomarkers and imaging usually guide the diagnosis and follow-up of the infection.

Personalized profiles of antioxidant signaling pathway in patients with tuberculosis.

Background/purpose: The non-protein thiol glutathione is protective against infection by Mycobacterium tuberculosis (MTB) and, together with the transcription factor NRF2 (the nuclear factor erythroid 2-related factor 2), plays a crucial role in counteracting MTB-induced redox imbalance. Many genes implicated in the antioxidant response belong to the NRF2-signalling pathway, whose central role in the pathogenesis of tuberculosis (TB) has been recently proposed.

Methods: In this study, we measured GSH levels in blood of patients with active TB and analysed the individual NRF2-mediated redox profile, in order to provide additional tools for discriminating the pathologic TB state and addressing therapeutic interventions.

Relaxation Response in Stressed Volunteers: Psychometric Tests and Neurotrophin Changes in Biological Fluids.

To evaluate the beneficial effects of relaxation response (RR) training in adult stressed subjects by evaluating the psychometric response recorded at relaxation session. Cortisol as well as nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) mediators were quantified in both saliva and tears, and their levels were related to each other and to the psychometric response. Stressed subjects ( = 23; 10M/13F; age range 21-53 years old) were voluntarily enrolled in the study.

COVID-19 Changed the Incidence and the Pattern of Pediatric Traumas: A Single-Centre Study in a Pediatric Emergency Department.

The first wave of COVID-19 spread worldwide from March to May 2020. Italy was one of the countries in the world where the lockdown period was most prolonged and restrictive. To date, the impact of prolonged lockdown on pediatric traumas has not fully investigated.