The Challenging Life of Mutators: How Survives between Persistence and Evolution in Cystic Fibrosis Lung.

Cystic fibrosis (CF) is a life-threatening genetic disease characterised by chronic lung infections sustained by opportunistic pathogens such as During the chronic long-lasting lung infections, adapts to the host environment. Hypermutability, mainly due to defects in the DNA repair system, resulting in an increased spontaneous mutation rate, represents a way to boost the rapid adaptation frequently encountered in CF isolates. We selected 609 isolates from 51 patients with CF chronically colonised by to study, by full-length genome sequencing, the longitudinal evolution of the bacterium.

Altered brain and physiological stress responses in early psychosis.

Stress is proposed to be a crucial factor in the onset and presentation of psychosis. The early stage of psychosis provides a window into how stress interacts with the emergence of psychosis. Yet, how people with early psychosis respond to stress remains unclear.

First Evidence of Streptococcus pyogenes M1UK Clone in Pediatric Invasive Infections in Italy by Molecular Surveillance.

Invasive group A streptococci infections are increasing worldwide, mainly due to the emm1 lineage M1UK emergence. Although this variant has recently been described in adult Italian patients, its circulation in children has not yet been established. Characterizing by whole genome sequencing 6 invasive group A streptococci strains isolated between 2022 and 2023, we highlighted M1UK lineage circulation in pediatric patients in Italy.

Genomic characterization of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) strains circulating in three university hospitals in Northern Italy over three years.

Objectives: Genomic surveillance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is crucial for virulence, drug-resistance monitoring, and outbreak containment.

Methods: Genomic analysis on 87 KPC-Kp strains isolated from 3 Northern Italy hospitals in 2019-2021 was performed by whole genome sequencing (WGS), to characterize resistome, virulome, and mobilome, and to assess potential associations with phenotype resistance and clinical presentation. Maximum Likelihood and Minimum Spanning Trees were used to determine strain correlations and identify potential transmission clusters.

Biallelic EPCAM deletions induce tissue-specific DNA repair deficiency and cancer predisposition.

We report a case of Mismatch Repair Deficiency (MMRD) caused by germline homozygous EPCAM deletion leading to tissue-specific loss of MSH2. Through the use of patient-derived cells and organoid technologies, we performed stepwise in vitro differentiation of colonic and brain organoids from reprogrammed EPCAM iPSC derived from patient fibroblasts. Differentiation of iPSC to epithelial-colonic organoids exhibited continuous increased EPCAM expression and hypermethylation of the MSH2 promoter.

Molecular characterization of SARS-CoV-2 Omicron clade and clinical presentation in children.

Since its emergence, SARS-CoV-2 Omicron clade has shown a marked degree of variability and different clinical presentation compared with previous clades. Here we demonstrate that at least four Omicron lineages circulated in children since December 2021, and studied until November 2022: BA.1 (33.

Increase in invasive group A streptococcal infections in Milan, Italy: a genomic and clinical characterization.

Background: Group A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in 2022 a sharp increase of GAS was reported globally.

Methods: GAS strains collected in 09/2022-03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed.

Efficacy and safety of avatrombopag in combination with immunosuppressive therapy in treatment-naïve and relapsed/refractory severe aplastic anaemia: protocol for the DIAAMOND-Ava-FIRST and DIAAMOND-Ava-NEXT Bayesian Optimal Phase II trials.

Introduction: Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and ciclosporin is standard of care for patients with severe aplastic anaemia (sAA) not eligible or suitable for allogeneic stem cell transplant. While patients respond to IST, few achieve complete responses and a significant proportion are refractory or relapse. The addition of eltrombopag, a thrombopoietin-receptor agonist (TPO-A), to IST has been shown to improve haematological responses in sAA.

The Australian Aplastic Anaemia and other Bone Marrow Failure Syndromes Registry.

The bone marrow failure syndromes (BMFS) are a diverse group of acquired and inherited diseases which may manifest in cytopenias, haematological malignancy and/or syndromic multisystem disease. Patients with BMFS frequently experience poor outcomes, and improved treatment strategies are needed. Collation of clinical characteristics and patient outcomes in a national disease-specific registry represents a powerful tool to identify areas of need and support clinical and research collaboration.

Gastric Foveolar Hyperplastic Polyps in 2 Children With Short Bowel Syndrome on Long-Term Teduglutide.

The natural history of short bowel syndrome involves intestinal adaptation wherein the remnant small intestine undergoes histologic and anatomic changes aimed at increasing absorption. Teduglutide-a glucagon-like peptide 2 analog approved for pediatric use in 2019-stimulates this process by causing proliferation of intestinal epithelial cells resulting in increased villous height and crypt depth. Food and Drug Administration approval for pediatric patients followed safety and efficacy studies in children that were limited to 24-week duration.

A Whole-Genome Sequencing-Based Approach for the Characterization of Co-Producing KPC and OXA-48-like Carbapenemases Circulating in Sardinia, Italy.

Background: Whole-genome sequencing (WGS) provides important information for the characterization, surveillance, and monitoring of antimicrobial resistance (AMR) determinants, particularly in cases of multi- and extensively drug-resistant microorganisms. We reported the results of a WGS analysis carried out on carbapenemases-producing , which causes hospital-acquired infections (HAIs) and is characterized by a marked resistance profile.

Methods: Clinical, phenotypic, and genotypic data were collected for the AMR surveillance screening program of the University Hospital of Sassari (Italy) during 2020-2021.

The (A)/(D)-carrying streptococcal prophage Φ1207.3 encodes an SOS-like system, induced by UV-C light, responsible for increased survival and increased mutation rate.

Bacterial SOS response is an inducible system of DNA repair and mutagenesis. Streptococci lack a canonical SOS response, but an SOS-like response was reported in some species. The (A)-(D)-carrying prophage Ф1207.

Pediatric Colonic Xanthomas, a Previously Unreported Colonoscopic Finding.

Gastrointestinal xanthomas are benign, usually sessile, polypoid lesions occasionally incidentally seen in adults, usually in the stomach, but have not been reported in the large intestine in children. We identified xanthomas in the sigmoid colon of the 15-year-old girl confirmed histologically. Our findings suggest that colonic xanthomas may occur as an incidental finding in pediatric patients.

Pancreatitis-Associated Medication Use in Hospitalized Pediatric and Young Adult Patients With Acute Pancreatitis.

Objective: The objective of this study is (1) to describe the prevalence of pancreatitis-associated medication (PAM) use at admission and discharge in pediatric and young adult patients hospitalized with acute pancreatitis (AP) and (2) to describe the prevalence of PAM use at admission in patients classified as having idiopathic AP.

Study Design: A single-center retrospective study of patients <21 years who were hospitalized with AP or acute recurrent pancreatitis from March 2015 to July 2017 was performed. Charts were reviewed for demographic data, etiology of pancreatitis, comorbidities, and use of PAMs at admission and discharge.

Nutrition delivery across hospitalisation in critically ill patients with COVID-19: An observational study of the Australian experience.

Background: Data on nutrition delivery over the whole hospital admission in critically ill patients with COVID-19 are scarce, particularly in the Australian setting.

Objectives: The objective of this study was to describe nutrition delivery in critically ill patients admitted to Australian intensive care units (ICUs) with coronavirus disease 2019 (COVID-19), with a focus on post-ICU nutrition practices.

Methods: A multicentre observational study conducted at nine sites included adult patients with a positive COVID-19 diagnosis admitted to the ICU for >24 h and discharged to an acute ward over a 12-month recruitment period from 1 March 2020.

The Curiosity Rover's Exploration of Glen Torridon, Gale Crater, Mars: An Overview of the Campaign and Scientific Results.

The Mars Science Laboratory rover, , explored the clay mineral-bearing Glen Torridon region for 1 Martian year between January 2019 and January 2021, including a short campaign onto the Greenheugh pediment. The Glen Torridon campaign sought to characterize the geology of the area, seek evidence of habitable environments, and document the onset of a potentially global climatic transition during the Hesperian era. roved 5 km in total throughout Glen Torridon, from the Vera Rubin ridge to the northern margin of the Greenheugh pediment.

Impact of Trainee Involvement on Pediatric ERCP Procedures: Results From the Pediatric ERCP Initiative.

This study examines the role of trainee involvement with pediatric endoscopic retrograde cholangiopancreatography (ERCP) and whether it affects the procedure's success, post-procedural adverse outcomes, and duration. A secondary analysis of the Pediatric ERCP Database Initiative, an international database, was performed. Consecutive ERCPs on children <19 years of age from 18 centers were entered prospectively into the database.

Pediatric ERCP in the Setting of Acute Pancreatitis: A Secondary Analysis of an International Multicenter Cohort Study.

Previous studies have demonstrated the safety of performing endoscopic retrograde cholangiopancreatography (ERCP) in the pediatric population; however, few have addressed the outcomes of children undergoing ERCP during acute pancreatitis (AP). We hypothesize that ERCP performed in the setting of AP can be executed with similar technical success and adverse event profiles to those in pediatric patients without pancreatitis. Using the Pediatric ERCP Database Initiative, a multi-national and multi-institutional prospectively collected dataset, we analyzed 1124 ERCPs.

Genomic Characterization of KPC-31 and OXA-181 Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations.

Background: Carbapenem resistant (cr-Kp) causes serious infections associated with a high mortality rate. The clinical efficacy of ceftazidime/avibactam (CZA), meropenem/vaborbactam (M/V), and imipenem/relebactam (I/R) against cr-Kp is challenged by the emergence of resistant strains, making the investigation and monitoring of the main resistance mechanisms crucial. In this study, we reported the genome characterization of a strain isolated from a critically ill patient and characterized by a multidrug resistant (MDR) profile, including resistance to CZA, M/V, and I/R.

Streptococcus pyogenes Φ1207.3 Is a Temperate Bacteriophage Carrying the Macrolide Resistance Gene Pair (A)-(D) and Capable of Lysogenizing Different Streptococci.

Streptococcus pyogenes prophage Φ1207.3 (formerly Tn) carries the (A)-(D) resistance genes, responsible for type M macrolide resistance. To investigate if Φ1207.