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BackgroundTinnitus presents a major public health challenge, impacting quality of life. With conventional therapies being often time-consuming and costly, interest in Internet-based treatments, such as auditory treatments and Internet-based cognitive behavioral therapy, has grown due to their improved patient adherence. This meta-analysis aims to review existing scientific literature to assess the effectiveness of Internet-based therapies (IBTs) in treating tinnitus.MethodsStudies up to February 2024 using the Tinnitus Functional Index (TFI), Tinnitus Handicap Inventory (THI), or Tinnitus Reactions Questionnaire (TRQ) to monitor tinnitus before and after IBTs were searched in PubMed, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials. Variation of the score with time was analyzed and a comparison was made with non-IBT studies. Treatment effects were analyzed using Cohen's d model.ResultsA total of 14 articles were considered, with a total of 1574 patients. Significant improvements in questionnaire scores were noted post-treatment. In the IBT group, THI and TFI decreased by 17.97 and 24.56 points, respectively (Cohen's d THI: 0.85; TFI: 0.80). In the control group, THI and TFI decreased by 13.7 and 4.25 points, respectively (Cohen's d THI: 0.55; TFI: 0.10).ConclusionsInternet-based therapies showed reliable effectiveness, possibly due to improved patient compliance, accessibility, cost-effectiveness, and customization.

Abstract Background Fever in children represents one of the most common causes of medical evaluation. Infants younger than 90 days of age are at higher risk of severe and invasive bacterial infections (SBI and IBI). However, clinical signs and symptoms of viral and bacterial infections in young infants are frequently similar, and several studies have shown that the risk of SBIs remains non-negligible even in the presence of a positive point-of-care viral test. Our study aims to evaluate whether the proportion of SBIs and IBIs in febrile infants younger than 90 days during the COVID-19 pandemic was higher than that in the pre-pandemic period, and to describe the proportion of SBIs and IBIs in infants with and without SARS-CoV-2 infection. Methods This was a retrospective single-center cohort study conducted at the Children's Hospital of the University of Padua in Italy, involving febrile young infants evaluated in the Pediatric Emergency Department (PED) and admitted to Pediatric Acute Care Unit (PACU) between March 2017 to December 2022. Infants admitted before the COVID-19 pandemic were compared to infants admitted during the pandemic period and SARS-CoV-2 positive patients to the negative ones. Results 442 febrile infants younger than 90 days were evaluated in Padua PED and admitted to the wards. The proportion of SBIs and IBIS did not significantly change over the study periods, ranging between 10.8% and 32.6% (p = 0.117) and between 0% and 7.6%, respectively (p = 0.367). The proportion of infants with a diagnosis of SBIs and IBIs was higher in the SARS-CoV-2 negative group (30.3% and 8.2%, respectively) compared to the positive group (8.5% and 2.8%, respectively) (p

Abstract Immune cell-derived extracellular vesicles (EV) affect tumor progression and hold promise for therapeutic applications. Eosinophils are major effectors in Th2-related pathologies recently implied in cancer. Here, we evaluated the anti-tumor activities of eosinophil-derived EV following activation with the alarmin IL-33. We demonstrate that IL-33-activated mouse and human eosinophils produce higher quantities of EV with respect to eosinophils stimulated with IL-5. Following incorporation of EV from IL-33-activated eosinophils (Eo33-EV), but not EV from IL-5-treated eosinophils (Eo5-EV), mouse and human tumor cells increased the expression of cyclin-dependent kinase inhibitor (CDKI)-related genes resulting in cell cycle arrest in G0/G1, reduced proliferation and inhibited tumor spheroid formation. Moreover, tumor cells incorporating Eo33-EV acquired an epithelial-like phenotype characterized by E-Cadherin up-regulation, N-Cadherin downregulation, reduced cell elongation and migratory extent in vitro, and impaired capacity to metastasize to lungs when injected in syngeneic mice. RNA sequencing revealed distinct mRNA signatures in Eo33-EV and Eo5-EV with increased presence of tumor suppressor genes and enrichment in pathways related to epithelial phenotypes and negative regulation of cellular processes in Eo33-EV compared to Eo5-EV. Our studies underscore novel IL-33-stimulated anticancer activities of eosinophils through EV-mediated reprogramming of tumor cells opening perspectives on the use of eosinophil-derived EV in cancer therapy.

Abstract Pharmacogenetics investigates sequence of genes that affect drug response, enabling personalized medication. This approach reduces drug-induced adverse reactions and improves clinical effectiveness, making it a crucial consideration for personalized medical care. Numerous guidelines, drawn by global consortia and scientific organizations, codify genotype-driven administration for over 120 active substances. As the scientific community acknowledges the benefits of genotype-tailored therapy over traditionally agnostic drug administration, the push for its implementation into Italian healthcare system is gaining momentum. This evolution is influenced by several factors, including the improved access to patient genotypes, the sequencing costs decrease, the growing of large-scale genetic studies, the rising popularity of direct-to-consumer pharmacogenetic tests, and the continuous improvement of pharmacogenetic guidelines. Since EMA (European Medicines Agency) and AIFA (Italian Medicines Agency) provide genotype information on drug leaflet without clear and explicit clinical indications for gene testing, the regulation of pharmacogenetic testing is a pressing matter in Italy. In this manuscript, we have reviewed how to overcome the obstacles in implementing pharmacogenetic testing in the clinical practice of the Italian healthcare system. Our particular emphasis has been on germline testing, given the absence of well-defined national directives in contrast to somatic pharmacogenetics.

Introdução: De acordo com as diretrizes da Política Nacional de Atenção Integral à Saúde da Mulher (PNAISM), o Sistema Único de Saúde (SUS) deve estar apto a promover atenção integral à saúde da mulher, incluindo garantia de acesso a um planejamento reprodutivo adequado. No Brasil, mais de 55% das gestações não são planejadas ou são não intencionais, sobretudo em regiões de maior vulnerabilidade, resultando em prejuízo em índices de saúde materno-fetal, altas taxas de abortamento, prematuridade, óbito fetal intrauterino e mortalidade infantil. A Atenção Primária à Saúde (APS) é o equipamento de saúde com maior inserção e contato com a população, principalmente as mais vulneráveis, contribuindo para a melhoria das condições de vida e saúde da população brasileira. É incumbência da APS a prescrição e a oferta do método contraceptivo escolhido. Nesse contexto, conta-se com os contraceptivos reversíveis de longa ação, denominados LARC (Long Acting Reversible Contraceptive), com destaque para o implante subdérmico de etonogestrel (IMPLANON NXT®), aprovado pelo SUS para mulheres em situação de vulnerabilidade e que se sobressai por sua eficácia, independentemente da motivação e da adesão da usuária. Objetivo: Sensibilizar os leitores das potencialidades da inserção do IMPLANON NXT® na APS a fim de aprimorar o planejamento reprodutivo no SUS. Métodos: Estudo qualitativo analítico baseado no Arco de Maguerez. A quinta etapa do método (aplicação à realidade) não foi realizada. Resultados: Identificou-se que a proximidade geográfica, o vínculo com a comunidade e a capacidade de inserção no tempo hábil necessário são elementos de destaque das potencialidades da APS. Percebeu-se também que a APS pode contribuir a superar barreiras como reduzir o gasto com transporte e facilitar a remoção do dispositivo. Ademais, a capacitação de profissionais da APS também se mostra como ferramenta para ampliação da oferta do procedimento. Conclusões: Os achados deste estudo sugerem que a APS, considerando suas práticas e atributos específicos, deve ser incorporada nos protocolos de inserção do IMPLANON NXT® no SUS, visando ao aprimoramento do planejamento reprodutivo do país e à garantia de cuidado integral à saúde das pessoas que podem gestar.

Background The COVID-19 pandemic had an important psychological impact on children and their families. This study aims to explore paediatric health services users’ perceptions of quality of care (QOC) and COVID-19-related fears, and their evolution over time in relation to COVID-19 pandemic.Methods In a multicentre cross-sectional study involving 11 public hospitals providing paediatric care across the Italian territory, we collected data from services users through a validated questionnaire. We analysed four indicators—(1) QOC perceived in relation to COVID-19; (2) overall QOC perceived; (3) fear of accessing health services due to COVID-19; (4) fear of contracting COVID-19 in hospital—and calculated Spearman’s correlation indexes (ρ) with the number of COVID-19 new cases over time. Subgroup analyses were conducted by macroregions and single facility.Results Data from 956 services users were analysed. QOC indicators were stable over time at values close to the maximum (range 77–100 and median 100 for COVID-19 QOC, range 74–98 and median 80 for overall QOC), and no correlations were found with the COVID-19 new cases (ρ=−0.073 and −0.016, respectively). Fear of accessing care and fear of contracting the infection varied over time in between 0%–52% and 0%–53%, respectively, but did not correlate directly with number of COVID-19 new cases (ρ=0.101, 0.107 and 0.233, 0.046, respectively). At subgroup analyses, significantly higher frequencies of fear (p values

Background: Urinary tract infections (UTIs) are the most common bacterial infections in children. The high variability in pathogen susceptibility rates leads to the lack of clear guidelines for empiric and targeted therapies. In this view, local microbiological surveillance and locally adapted stewardship interventions need to be implemented. Objective: The study aims to describe the results of a pediatric antimicrobial stewardship program on antibiotic prescriptions for UTIs over 8 years in a pediatric general ward of a tertiary center. Design: This quasi-experimental study was conducted between 2015 and 2022, with two different implementations, one in 2018 and one in 2021. Methods: Demographic, clinical, microbiological, and therapeutic data were retrieved from the electronic clinical records of included patients. The primary outcomes were adherence to local guidelines for empiric therapies and the adequacy of targeted therapy. Secondary outcomes were evaluating antibiotic prescription patterns stratified by antibiotics during hospital stay and at discharge, and assessing the microbiological characteristics of UTI episodes. Results: During the study period, 7038 patients were admitted to the pediatric acute care unit (PACU), and 264 (3.7%) were included in this study. Adherence to local guidelines was highest immediately after the interventions, and it slightly decreased thereafter. Use of cephalosporins remained high throughout the 8 years but the changing microbiological scenario observed led to changing recommendations within the study period. An increase in E. coli strains resistant to co-amoxiclav was observed in the last years. Oral second-line agent consumption remained high but was adequate considering the prevalence of resistant bacteria. Conclusion: The variability of antimicrobial consumption reflects the changing resistance patterns for UTIs pathogens, underlying the importance of locally adapted, persevering antimicrobial stewardship interventions.

Patent foramen ovale (PFO) is a congenital heart abnormality consisting of the persistence of a tunnel between the right and left atrium; it is associated with a higher prevalence of strokes. A 52-year-old man was admitted to the emergency room for confusion and deep vein thrombosis with signs of pulmonary embolism; he started treatment with fondaparinux. After admission, there was an ischemic stroke. Blood tests, thrombogenic screening, and infectious diseases showed no alterations. Holter-electrocardiogram, echocardiography, and positron emission tomography-computed tomography were negative except for the presence of PFO. Apixaban and cardioaspirin were started. The surgical treatment was planned, but despite the therapy, there was a new ischemic stroke, so the treatment with mechanical thrombectomy was attempted but failed. The patient was continuing therapy until a new cerebral ischemic episode caused his death; the etiopathogenesis of brain events appears to be associated with the presence of PFO; association with deep venous thrombosis is described in the literature.

High-density polyethylene (HDPE) geomembranes are commonly used as an environmental protection liner due to their good chemical and mechanical resistances and low cost. Ultraviolet (UV) radiation is an essential issue in durability studies for pond applications. This study evaluated a 1.5-mm thick HDPE geomembrane exposed to ultraviolet fluorescent radiation for 8760 h in a laboratory and thermoanalytical and physical analyses were conducted towards the understanding of its performance after exposure. According to the results, although the geomembrane maintained the ductile behavior, it showed a 52.48% final decrease in stress crack resistance (SCR) compared to virgin SCR. Moreover, a considerable antioxidant depletion occurred after 8760 h exposure shown by the Std. OIT (standard oxidative-induction time) results, demonstrating a Std. OIT value decrease of 89.19% compared to the virgin Std. OIT. Such a behavior contributed to the susceptibility of thermal effects in the DSC (differential scanning calorimetry) curves and the losses observed in the SCR values, attesting the geomembrane’s oxidative degradation mechanism occurred and changed the polymer’s structure.

Introduction: Obstructive Sleep Apnea (OSA) in children is characterized by repeated episodes of partial or complete obstruction of the upper airways that impair normal ventilation and cause hypoxia and sleep disruption. These episodes activate innate and adaptive immunity resulting in the production of proinflammatory cytokines: IL-1β, IL-6, TNF-α, and reactive oxygen species. The hypothalamic–pituitary–adrenal (HPT) axis is also activated with alteration of the circadian rhythm of cortisol synthesis. OSA in children, and even more in adults, induces a systemic inflammatory condition that contributes to the genesis of clinical complications: poor growth, learning disabilities, cardiovascular changes, insulin resistance, and metabolic syndrome. Methods: A total of 42 non-obese children (age 1–15 years) were enrolled among those sent to our sleep center to perform full polysomnography (PSG). After PSG, 6 children did not show OSA (controls), 20 had mild OSA (m OSA), and 16 had medium-severe OSA (MS OSA). In vitro IL-1β, TNF-α, and serum cortisol levels were measured at 2 and 8 am in the analyzed groups. Results: Cortisol levels did not differ between controls and OSA children. At 2 am, there were no differences between controls and OSA in TNF-α production, whereas at 8 am, TNF-α was reduced in MS-OSA. IL-1β production showed no differences between OSA and controls. Conclusions: In our population, only TNF-α production is suppressed in MS-OSA: this might indicate a role of OSA severity in inducing inflammation. In adults, the phenomenon is more pronounced due to the habitual greater severity/duration of OSA, presence of comorbidities (cardiovascular and metabolic), and different immune system function.