Search

Objectives: A new variant of echovirus 11 (E11) infection is a major health concern in neonates. Here, we describe the clinical and virological characteristics of enterovirus (EV) infections in children hospitalized with acute respiratory infection in Southern Italy. Methods: Between July 2022 and August 2023, 173 EV infections were identified. Demographic and clinical characteristics, comorbidities, and coinfections were analyzed. Genotypes were identified by sequencing of VP1. Whole-genome sequencing of five E11 strains was performed. Results: Case numbers peaked in July 2022, November-December 2022, and June-July 2023. Coxsackievirus A2 was identified in 36.7%, coxsackievirus B5 in 13.8%, echovirus E11 in 9.2%, and EV-D68 in 6.4% of cases. No child had critical symptoms or a severe infection. The only neonate infected by E11 recovered fully after 5 days in hospital. Phylogenetic analysis revealed that four E11 strains were closely related to divergent lineage I E11 strains identified in France and Italy. Conclusions: The new variant of E11 was identified in children in Southern Italy. Although the cases were mild, the data suggest that transmission routes and host factors are likely to be main drivers for the development of potentially severe diseases. Systematic epidemiological/molecular surveillance will help us better understand the clinical impact of EV infections and develop preventive strategies.

ABSTRACT: Objectives: The recent worldwide spread of New Delhi metallo–beta-lactamase-producing Klebsiella pneumoniae (NDM-KP) in health-care settings remains a concern. The aim of the study was to describe an outbreak of extensively drug-resistant ST147 NDM-1-KP in the Apulia region of Southern Italy that occurred between 2020 and 2022 through genomic surveillance of carbapenem-resistant Enterobacterales. Methods: A total of 459 carbapenem-resistant KP isolates collected from patients hospitalised with bloodstream infections were tested using a commercial multiplex real-time polymerase chain reaction to identify carbapenemase genes. A subset of 27 isolates was subjected to whole-genome sequencing. Core-genome multilocus sequence typing was performed by analysing a panel of 4884 genes. Results: Molecular testing revealed that 104 (22.6%) isolates carried the carbapenemase NDM gene. Phylogenetic analysis of the 27 isolates subjected to whole-genome sequencing revealed high genetic relatedness among strains. All isolates were resistant to all first-line antibiotics. Virulome analysis identified the ybt locus, the two well-recognised virulence factors iucABCDiutA and rmpA, and the genes encoding the type 3 pilus virulence factor. Plasmids IncFIB(pkPHS1), IncFIB(pNDM-Mar), IncFIB(pQil), IncHI1B(pNDM-MAR), IncR, and Col(pHAD28) were identified in all isolates. Moreover, further analysis identified the IncFIB-type plasmid carrying the NDM-1 genes. Conclusion: The increasing circulation of extensively drug-resistant NDM-1 ST147 KP strains in Southern Italy in recent years is worrisome, because these clones pose a real risk, particularly in hospital settings. Genomic surveillance is a crucial tool for early identification of emerging threats such as the spread of high-risk pathogens. Rapid infection control measures and antimicrobial stewardship are key to preventing further spread of hypervirulent KP strains.

Resumen Los procesos de segregación educativa tienen una importancia crucial y su abordaje constituye un factor relevante en relación a la diferenciación en el acceso y la permanencia en los circuitos educativos así como en la reproducción del propio sistema. El presente estudio coloca el foco en la segregación educativa en el Nivel Secundario de la ciudad de Bahía Blanca (Buenos Aires- Argentina) entre los años 2016 y 2019, específicamente sobre cinco casos de estudio que permiten caracterizar las trayectorias estudiantiles, las políticas educativas y los procesos socioeconómicos y espaciales de ese contexto en particular. Los instrumentos metodológicos utilizados fueron el análisis de datos estadísticos, el relevamiento critico de documentos legales y una serie de entrevistas semiestructuradas a diversos actores de las comunidades educativas, seleccionados como informantes claves del periodo Entre las conclusiones obtenidas se observa que la implementación de distintos programas y políticas públicas educativas incidieron levemente en la acentuación de la segregación educativa. A su vez, se observa una fuerte vinculación con la segregación socio-residencial y las acciones que pueden o no llevar adelante las distintas autoridades intermedias del Sistema Educativo de la provincia de Buenos Aires. Abstract The processes of educational segregation are of crucial importance and their approach constitutes a relevant factor in relation to the differentiation in access and permanence in the educational circuits as well as in the reproduction of the system itself. This study focuses on educational segregation at the secondary level in the city of Bahía Blanca (Buenos Aires, Argentina) between 2016 and 2019, specifically on five case studies that allow characterizing student trajectories, educational policies and socioeconomic and spatial processes in this particular context. The methodological tools used were the analysis of statistical data, the critical survey of legal documents and a series of semi-structured interviews with various actors of the educational communities, selected as key informants of the period.Among the conclusions obtained, it can be observed that the implementation of different educational programs and public policies had a slight influence on the accentuation of educational segregation. In turn, these seem to be strongly linked to socio-residential segregation and the actions that may or may not be carried out by the different intermediate authorities of the Educational System of the province of Buenos Aires.

Candida auris is an emerging yeast considered a serious threat to global health. We report the first case of C. auris candidemia in Southern Italy, characterized using whole genome sequencing (WGS), and compared with a second strain isolated from a patient who presented as C. auris-colonized following screening. The C. auris strain was isolated from clinical samples, identified via MALDI-TOF, and subjected to WGS. Antifungal susceptibility testing was performed using commercial broth microdilution plates, and resistance protein sequences were evaluated with TBLASTN-2.15.0. Following the initial C. auris isolation from patient A, active surveillance and environmental investigations were implemented for all ICU patients. Of the 26 ICU surfaces sampled, 46.1% tested positive for C. auris via real-time PCR. Screening identified a second patient (patient B) as C. auris-colonized. The phylogenetic characterization of strains from patients A and B, based on the D1/D2 region of the 28s rDNA and the internal transcribed spacer (ITS) region, showed high similarity with strains from Lebanon. SNP analysis revealed high clonality, assigning both strains to clade I, indicating a significant similarity with Lebanese strains. This case confirms the alarming spread of C. auris infections and highlights the need for stringent infection control measures to manage outbreaks.

Abstract Background Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effects of CER-001, an engineered HDL-mimetic, in a swine model of LPS-induced acute kidney injury (AKI) and a Phase 2a clinical trial, aiming to better understand its molecular basis in systemic inflammation and renal function. Methods We carried out a translational approach to study the effects of HDL administration on sepsis. Sterile systemic inflammation was induced in pigs by LPS infusion. Animals were randomized into LPS (n = 6), CER20 (single dose of CER-001 20 mg/kg; n = 6), and CER20 × 2 (two doses of CER-001 20 mg/kg; n = 6) groups. Survival rate, endothelial dysfunction biomarkers, pro-inflammatory mediators, LPS, and apolipoprotein A-I (ApoA-I) levels were assessed. Renal and liver histology and biochemistry were analyzed. Subsequently, we performed an open-label, randomized, dose-ranging (Phase 2a) study included 20 patients with sepsis due to intra-abdominal infection or urosepsis, randomized into Group A (conventional treatment, n = 5), Group B (CER-001 5 mg/kg BID, n = 5), Group C (CER-001 10 mg/kg BID, n = 5), and Group D (CER-001 20 mg/kg BID, n = 5). Primary outcomes were safety and efficacy in preventing AKI onset and severity; secondary outcomes include changes in inflammatory and endothelial dysfunction markers. Results CER-001 increased median survival, reduced inflammatory mediators, complement activation, and endothelial dysfunction in endotoxemic pigs. It enhanced LPS elimination through the bile and preserved liver and renal parenchyma. In the clinical study, CER-001 was well-tolerated with no serious adverse events related to study treatment. Rapid ApoA-I normalization was associated with enhanced LPS removal and immunomodulation with improvement of clinical outcomes, independently of the type and gravity of the sepsis. CER-001-treated patients had reduced risk for the onset and progression to severe AKI (stage 2 or 3) and, in a subset of critically ill patients, a reduced need for organ support and shorter ICU length of stay. Conclusions CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage. Trial registration The study was approved by the Agenzia Italiana del Farmaco (AIFA) and by the Local Ethic Committee (N° EUDRACT 2020–004202-60, Protocol CER-001- SEP_AKI_01) and was added to the EU Clinical Trials Register on January 13, 2021.

S’intéresser aux rapports que les individus entretiennent à l’égard du futur et à la façon dont ceux-ci façonnent des états émotionnels (individuels ou collectifs) est utile pour mieux comprendre ce qui motive les pratiques sociales. Cet article propose de s’intéresser aux théories de l’effondrement qui nourrissent l’imaginaire de certains protagonistes du phénomène du « retour à la terre ». Sur la base d’un travail de terrain de longue durée au sein d’une dizaine de collectifs néopaysans dans le Massif central, je mobiliserai le paradigme des temporalités multiples pour nuancer les effets des théories de l’effondrement sur le quotidien des individus. J’argumenterai que les projets visant le repli en monde rural et l’autonomie alimentaire s’inscrivent dans une temporalité présentiste paradoxale qui fait coexister des horizons temporels antinomiques, à la fois pessimistes et optimistes, vis-à-vis de l’avenir et de la lutte sociale. Le refus des acteurs d’adhérer aux grands récits linéaires et d’un mode de lutte organisé et cohérent à visée universelle me permettra ici d’alimenter les réflexions 1) sur l’action humaine dans son rapport à la crise environnementale et sociale et 2) sur des fondements épistémologiques plus généraux, relatifs à la manière d’appréhender les temporalités en sciences sociales.

Stem and progenitor cells have been observed to contribute to regenerative processes in acute renal failure and chronic kidney disease. Recent research has delved into the intricate mechanisms by which stem and progenitor cells exert their influence on kidney diseases. Understanding how these cells integrate with the existing renal architecture and their response to injury could pave the way for innovative treatment strategies aimed at promoting kidney repair and regeneration. Overall, the role of stem and progenitor cells in kidney diseases is multifaceted, with their ability to contribute to tissue regeneration, immune modulation, and the maintenance of renal homeostasis. Here, we review the studies that we have available today about the involvement of stem and progenitor cells both in regenerative therapies and in the causes of renal diseases, as well as in natural healing mechanisms, taking into account the main kidney disorders, such as IgA nephropathy, lupus nephritis, diabetic nephropathy, C3 glomerulopathy, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and ANCA-associated crescentic glomerulonephritis. Moreover, based on the comprehensive data available in the framework of the specific kidney diseases on stem cells and renal progenitors, we hypothesize a possible role of adult renal progenitors in exacerbating or recovering the illness.

The development of innovative products for restoring skin integrity and promoting wound healing is still a challenge. The aim of this work was to evaluate an innovative Spanish broom wound dressing impregnated with Glycyrrhiza glabra extract-loaded ufasomes to improve wound healing. Ufasomes were characterized in terms of size, polydispersity index, entrapment efficiency, zeta potential, and stability. In addition, in vitro release studies and biocompatibility, biosafety, and scratch tests on WS1 fibroblasts were performed. The loaded ufasomes showed a nanometric size (

IgA Nephropathy (IgAN) is the most common form of primary glomerulonephritis and is one of the most common causes of end-stage kidney disease (ESKD) worldwide. The immunopathogenic mechanism underlying IgAN is poorly identified. Currently, the mainstay treatment of IgAN is centered on the optimization of blood pressure and a reduction in proteinuria, using an angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARBs). According to KDIGO, patients who persistently remain at a high risk of progressive ESKD, despite maximal supportive care, are candidates for glucocorticoid therapy. Recent discoveries regarding the pathogenesis of this disease have led to the testing of new therapeutic drugs targeting, in particular, the excessive mucosal immune reaction and the resulting systemic response as well as the complement activation and the following kidney damage and fibrosis. In this review, we examine the various therapeutic approaches to this intriguing disease.

Abstract Background Raw seafood consumption was identified as the major risk factor for hepatitis A during the large epidemic of 1996 and 1997 in Puglia (South Italy). In Puglia, vaccination for toddlers and preadolescents has been recommended since 1998. The aim of the study was to evaluate the incidence, seroprevalence, molecular epidemiology, and environmental circulation of hepatitis A virus (HAV) in Puglia more than ten years after the introduction of anti-HAV vaccination in the regional immunization program. Methods Data on the incidence of acute hepatitis A in Puglia were analyzed. Characteristics and risk factors of 97 acute hepatitis A cases occurring in 2008–2009 were analyzed. Serum samples from 868 individuals aged 0 to 40 years were tested for anti-HAV antibodies. Fecal samples from 49 hepatitis A cases were analyzed by sequence analysis in the VP1/P2A region. In 2008, 203 mussel samples and 202 water samples from artesian wells were tested for HAV-RNA. Results Between 1998 and 2009, the incidence of acute hepatitis A declined from 14.8 to 0.8 per 100,000. The most frequent risk factors reported by cases in 2008–2009 were shellfish consumption (85%) and travel outside of Puglia or Italy (26%). Seroepidemiologic survey revealed high susceptibility to HAV in children and adults up to age 30 (65%-70%). None of the mussel or water samples were HAV-positive. Phylogenetic analysis revealed co-circulation of subtypes IA (74%) and IB (26%) and clustering of strains with strains from Germany and France, and those previously circulating in Puglia. Conclusion Vaccination and improved sanitation reduced the incidence of hepatitis A. Strict monitoring and improved vaccination coverage are needed to prevent disease resurgence.

Abstract Background The combination of Programmed Cell Death 1 (PD-1) and Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) blockade has dramatically improved the overall survival rate for malignant melanoma. Immune checkpoint blockers (ICBs) limit the tumor’s immune escape yet only for approximately a third of all tumors and, in most cases, for a limited amount of time. Several approaches to overcome resistance to ICBs are being investigated among which the addition of epigenetic drugs that are expected to act on both immune and tumor cells. Guadecitabine, a dinucleotide prodrug of a decitabine linked via phosphodiester bond to a guanosine, showed promising results in the phase-1 clinical trial, NIBIT-M4 (NCT02608437). Methods We used the syngeneic B16F10 murine melanoma model to study the effects of immune checkpoint blocking antibodies against CTLA-4 and PD-1 in combination, with and without the addition of Guadecitabine. We comprehensively characterized the tumor’s and the host’s responses under different treatments by flow cytometry, multiplex immunofluorescence and methylation analysis. Results In combination with ICBs, Guadecitabine significantly reduced subcutaneous tumor growth as well as metastases formation compared to ICBs and Guadecitabine treatment. In particular, Guadecitabine greatly enhanced the efficacy of combined ICBs by increasing effector memory CD8+ T cells, inducing effector NK cells in the spleen and reducing tumor infiltrating regulatory T cells and myeloid derived suppressor cells (MDSC), in the tumor microenvironment (TME). Guadecitabine in association with ICBs increased serum levels of IFN-γ and IFN-γ-induced chemokines with anti-angiogenic activity. Guadecitabine led to a general DNA-demethylation, in particular of sites of intermediate methylation levels. Conclusions These results indicate Guadecitabine as a promising epigenetic drug to be added to ICBs therapy.

Abstract The genetic characterization of wild-type measles strains isolated during an epidemic cluster of measles occurred in Puglia (South Italy), between November 2006 and January 2007, was performed. Measles virus (MV) detection was carried out by a nested RT-PCR on 8 of 18 total cases. The viruses were analyzed using the standard genotyping protocols. The N gene sequences of the strains from outbreak were identical to each other, and sequence analysis revealed that the viruses belonged to genotype B3, subgroup B3.1, never identified before in Italy. An importation of measles B3.1 strains from Africa was hypothesized. Molecular surveillance will help to monitor the progress in measles elimination.

IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin–angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.