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BACKGROUND: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19. METHODS: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728). FINDINGS: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group. INTERPRETATION: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19. FUNDING: Biophytis.

Integrating remote Internet of Things (IoT) laboratories into project-based learning (PBL) in higher education institutions (HEIs) while exploiting the approach of technology-enhanced learning (TEL) is a challenging yet pivotal endeavor. Our proposed approach enables students to interact with an IoT-equipped lab locally and remotely, thereby bridging theoretical knowledge with practical application, creating a more immersive, adaptable, and effective learning experience. This study underscores the significance of combining hardware, software, and coding skills in PBL, emphasizing how IoTRemoteLab (the remote lab we developed) supports a customized educational experience that promotes innovation and safety. Moreover, we explore the potential of IoTRemoteLab as a TEL, facilitating and supporting the understanding and definition of the requirements of remote learning. Furthermore, we demonstrate how we incorporate generative artificial intelligence into IoTRemoteLab’s settings, enabling personalized recommendations for students leveraging the lab locally or remotely. Our approach serves as a model for educators and researchers aiming to equip students with essential skills for the digital age while addressing broader issues related to access, engagement, and sustainability in HEIs. The practical findings following an in-class experiment reinforce the value of IoTRemoteLab and its features in preparing students for future technological demands and fostering a more inclusive, safe, and effective educational environment.

Innovation models are key to fostering technology-focused entrepreneurship in higher education institutions (HEIs). These models create dynamic environments that encourage collaboration, creativity, and problem-solving skills among students and faculty. HEIs face several challenges in fostering entrepreneurship, including allocating sufficient financial and human resources, integrating entrepreneurship education across disciplines, and managing intellectual property. Overcoming these challenges requires HEIs to cultivate an entrepreneurial culture and establish strong partnerships with industry stakeholders. To achieve these goals, HEIs must adopt successful innovation models proven to work. This article presents an international case study highlighting such models and the factors contributing to their success. This study explores the implementation and impact of innovation models, specifically IDEATION and DEETECHTIVE, within HEIs to foster technology-focused entrepreneurship. By implementing numerous actions focusing on online education integration and the Quintuple Helix Innovation Model, these models support shifting engineering students’ mindsets toward entrepreneurship. This research highlights the importance of academia–industry collaboration, international partnerships, and the integration of entrepreneurship education in technology-focused disciplines. This study presents two models. The first, IDEATION, focuses on open innovation and sharing economy aspects. This model underwent rigorous testing and refinement, evolving into the second model, DEETECHTIVE, which is more comprehensive and deep tech-focused. These models have been validated as effective frameworks for fostering entrepreneurship and innovation within HEIs. This study’s findings underscore the potential of these models to enhance innovation capacity, foster an entrepreneurial culture, and create ecosystems rich in creativity and advancement. Practical implications include the establishment of open innovation-oriented structures and mechanisms, the development of specialized curriculum components, and the creation of enhanced collaboration platforms.

Unhealthy behaviors (UBs) can affect mental health. The most impactful of these are alcohol abuse, sedentary behavior, and sleep disturbances. Since these UBs are not well explored in medical residents, this study aims to overcome this gap, focusing on outcomes such as depression and anxiety. The Public Health Residents’ Anonymous Survey in Italy (PHRASI) is a nationwide cross-sectional study based on an 88-item questionnaire. UBs were explored through validated questionnaires: the Alcohol Use Disorders Identification Test-c (AUDIT-C), the International Physical Activity Questionnaire (IPAQ), and the Insomnia Severity Index (ISI). Depressive symptoms and anxiety were detected by Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Hierarchical cluster analysis described clusters using responses from the AUDIT-C, IPAQ, and ISI. A total of 375 participants were included in this study. Three distinct clusters (CL) were identified: CL1 was characterized by a moderate risk for alcohol abuse and high insomnia dissatisfaction, with a significantly higher frequency of depressive symptoms (46%, p < 0.001) and anxiety (53%, p < 0.001); CL2 had no risk for alcohol abuse, high sleep satisfaction, and better mental health profile, with the lowest prevalence of depressive symptoms (15%, p < 0.001); CL3 had the highest risk of alcohol abuse, the highest rate of physical activity (40%, p = 0.013), and the lowest prevalence of anxiety (27%, p < 0.001). Subjects belonging to CL1 required much more attention to prevent the worsening of mental outcomes. Interventions for promoting mental health should be addressed in all Public Health schools to create more sustainable working conditions.

OBJECTIVES:. In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient’s respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN:. Retrospective observational cohort study. SETTING:. Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS:. Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION:. The transition period from CMV to PSV was evaluated. We defined it as “failure of assisted breathing” if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS:. Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99–1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42–3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS:. Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.

Questo articolo mira a indagare la ricezione di Edgar Allan Poe (1809-1849) in Germania, concentrandosi – in particolare – sulla POEtica di uno dei maggiori esponenti del Gruppe 47, lo scrittore tedesco sperimentale e avanguardistico Arno Schmidt (1914-1979). Sebbene l’influenza di Poe nei Paesi di lingua tedesca non sia stata così intensa come in Francia, la sua importanza per la Germanistica risiede nel fatto che ha proposto idee moderne e innovative, legate principalmente alla sfera del soprannaturale e dell’irrazionale. Partendo da una breve panoramica della ricezione di Poe nella letteratura tedesca – soprattutto nei primi anni del ventesimo secolo – il saggio esplorerà più da vicino il caso specifico di “Arno Schmidt,” che ha aperto le porte a una comprensione raffinata, curiosa e moderna del genio introspettivo di Poe. Verrà infatti dimostrato come la monumentale opera di Schmidt, intitolata Zettel’s Traum (1970), non solo costituisca una ricchissima raccolta di fonti sulla vita e l’opera di Poe – utile per gli studiosi e gli esperti di letteratura e storia americana – ma offra anche un’interpretazione originale e senza pari dello scrittore americano, che può portare a studi interessanti e approfonditi sulla vita e l’opera di Poe in Germania. Attraverso esempi concreti, si mostrerà infine come il labile confine tra ambientazione fantastica e realistica nelle opere di Schmidt, a partire da Zettel’s Traum, sembri essere un tema direttamente suggerito da Poe, i cui tratti sono straordinariamente reinterpretati da Schmidt in una moderna prospettiva psicoanalitica. La profonda riflessione di Schmidt sullo scrittore americano ha infine contribuito allo sviluppo di una teoria di tipo linguistico-esistenziale – l’Etymtheorie – che, una volta applicata, porta a risultati tanto interessanti quanto sorprendenti.

Medical residents constitute a vulnerable population susceptible to mental health disorders. In Italy, this was evident during the COVID-19 pandemic, when medical residents served on the front line and provided significant support to healthcare services. Therefore, the working group on “Public Mental Health” of the Medical Residents’ Council of the Italian Society of Hygiene, Preventive Medicine, and Public Health (S.It.I.) designed the “Residents’ mental health investigation, a dynamic longitudinal study in Italy” (ReMInDIt). This longitudinal study aims to assess the mental status of medical residents and to explore potential cause–effect relationships between risk/protective factors (identified among sociodemographic, residency program, and lifestyle characteristics) and mental health outcomes (anxiety and depressive symptoms). Data will be collected from a study population of 3615 residents enrolled in Italian residency programs in public health, occupational medicine, and forensic medicine through an online questionnaire that includes validated tools, requires 10 min for completion, and is disseminated by the residents’ Councils. It will be followed by a follow-up administration after 12 months. The ReMInDIt study will play a significant role in generating evidence crucial for enhancing mental health services and promoting protective factors for the mental well-being of this important segment of healthcare professionals.

Anafilaxia após a vacinação é rara, ocorrendo a uma taxa de 1,31 episódios por 1 milhão de vacinas, podendo ocorrer entre pessoas sem história de hipersensibilidade prévia. A raiva é uma doença fatal com quase 100% de mortalidade se a profilaxia pós exposição não for eficaz oportuna e adequada. Paciente feminina, 51 anos, mordedura canina múltipla em mão e antebraço direito no dia 17 de setembro de 2022. Realizou lavagem local com água e sabão. Negava história pessoal de alergia, contato com equinos ou uso prévio de soro heterólogo. Cão não observável. 2 dias após o acidente iniciada a profilaxia com vacina antirrábica purificada de células VERO intramuscular e, programado esquema 0-3-7-14. Na 3a dose da vacina, administrado concomitantemente imunoglobulina antirrábica equina (ERIG) na dose de 40 UI/kg totalizando 12,4 mL, em 3 aplicações intramusculares em nádegas. Logo após iniciou prurido e vermelhidão nos locais das aplicações. Após 15 minutos, tosse seca e sensação de pigarro. Paciente foi liberada após cerca de 1 hora e logo que chegou em casa notou início de edema em lábios, prurido e hiperemia no rosto. Admitida no hospital afônica e com placas eritematosas e pruriginosas disseminadas pelo corpo. Feito adrenalina intramuscular, corticoide e anti-histamínico. Permaneceu internada em unidade de terapia intensiva por 4 dias e não necessitou de ventilação mecânica. Encaminhada para avaliação no ambulatório de eventos adversos pós vacina do Instituto de Infectologia Emílio Ribas em 20 de outubro. Coletada sorologia antirrábica no dia 24 de outubro – 4 semanas após administração da ERIG, cujo resultado foi um titulo de 2,0 UI/mL. Repetida em 14 de dezembro e 15 de fevereiro de 2023 com titulo de 1,5 e 0,67 UI/mL respectivamente. Avaliada pela equipe da imunologia do Hospital das Clinicas da Universidade de São Paulo em 5 de abril de 2023, realizado prick test com amostras da vacina, imunoglobulina antirrábica humana e ERIG, cujo resultado foi positivo para ERIG. Realizado teste cutâneo intradérmico na diluição 1:100 também positivo para ERIG, sem manifestações sistêmicas. Coletada sorologia em 19 de abril de 2023 com resultado de 5,33 UI/mL. No controle sorológico após realização dos testes intradérmicos foi evidenciado um titulo alto de anticorpos neutralizantes, o que pode ser explicado pelo fato desses testes terem funcionado como uma “dose booster” de vacina e ativado a imunidade de memória gerada pelo esquema de vacinação prévio.

Rivers serve many societal functions and are one of the most intensively human influenced ecosystems worldwide, and, due to their importance, are included under the monitoring programs of the Water Framework Directive across Europe. Macroinvertebrates play an important role when monitoring running waters for the assessment of their environmental quality due to their reliability as bioindicators and utility in long-term studies. Macroinvertebrates do not constitute a systematic unit but they are formed by a set of different taxa, grouped according to taxonomic ranks, size and habitat preferences. They represent the base of the aquatic food chain, serving as a food source for amphibians, birds, reptiles, fish and humans, and contributing in the organic matter processing. Despite the large amount of data collected on Italian river macroinvertebrates and the increased interest in the study of this group, only few data are available for research scientist and managers. In this paper, we collected and homogenized knowledge on the presence, distribution and abundances of macroinvertebrates taxa inhabiting the River Po catchment (Northern Italy) in the last decade. The data set includes 130,727 records collected between 2007 and 2018 including 143 taxa of macroinvertebrates, mostly identified at family rank level. Moreover, the data set provides information on the geographic distribution of these families and their abundance by sub-catchment, altitude, meso- and micro-habitat.

Tight-junctions (TJs) are multi-protein complexes between adjacent endothelial or epithelial cells. In the blood-brain-barrier (BBB), they seal the paracellular space and the Claudin-5 (Cldn5) protein forms their backbone. Despite the fundamental role in brain homeostasis, little is known on Cldn5-based TJ assemblies. Different structural models were suggested, with Cldn5 protomers generating paracellular pores that restrict the passage of ions and small molecules. Recently, the first Cldn5 pathogenic mutation, G60R, was identified and shown to induce Cl−-selective channels and Na+ barriers in BBB TJs, providing an excellent opportunity to validate the structural models. Here, we used molecular dynamics to study the permeation of ions and water through two distinct G60R-Cldn5 paracellular architectures. Only the so-called Pore I reproduces the functional modification observed in experiments, displaying a free energy (FE) minimum for Cl− and a barrier for Na+ consistent with anionic selectivity. We also studied the artificial Q57D and Q63D mutations in the constriction region, Q57 being conserved in Cldns except for cation permeable homologs. In both cases, we obtain FE profiles consistent with facilitated passage of cations. Our calculations provide the first in-silico description of a Cldn5 pathogenic mutation, further assessing the TJ Pore I model and yielding new insight on BBB’s paracellular selectivity.