La perdita di peso volontaria e controllata può ridurre i sintomi ed il dosaggio degli inibitori di pompa protonica nei pazienti con malattia da reflusso gastroesofageo: studio comparativo.

STUDIO CLINICO Scopo dello studio: Numerosi studi hanno evidenziato che l'obesità è associata con un significativamente aumentato rischio di sviluppare i sintomi e le complicanze da malattia da reflusso gastroesofageo (MRGE). Lo scopo dello studio è quello di valutare gli effetti della perdita di peso sui sintomi in pazienti sovrappeso od obesi affetti da MRGE Pazienti e metodi: Abbiamo arruolato tra Giugno 2012 e Giugno 2013 un campione di pazienti sovrappeso/obesi con i sintomi tipici da MRGE ed esofagite erosiva. All'inizio dello studio i pazienti si sono sottoposti a dettagliate valutazioni sulla sintomatologia da reflusso ed antropometriche e vengono suddivisi in due gruppi con differenti terapie. Nel gruppo A si somministrano inibitori di pompa protonica (PPI) ed una dieta ipocalorica personalizzata ed esercizio aerobico, il gruppo B riceve PPI ed una dieta standard. La terapia dietetica viene considerata efficace se si ottiene una perdita di peso di almeno il 10% entro 6 mesi. Inoltre tutti i pazienti sono valutati per quanto riguarda i parametri antropometrici, sintomi da MRGE ed uso dei PPI. Risultati: Nel gruppo A l'indice di massa corporea (BMI) medio è calato da 30±4,1 a 25,7±3,1 (P<0,05) ed il peso medio è calato da 82,1±16,9 kg a 69,9±14,4 kg (P<0,05). Nel gruppo B invece non ci sono state variazioni in BMI e peso corporeo. La percezione dei sintomi si è ridotta (P<0,05) in entrambi i gruppi durante la terapia con PPI, ma si è registrato un miglioramento maggiore nel gruppo A. Nel gruppo A la terapia con PPI è stata completamente interrotta in 27/50 pazienti e dimezzata in 16/50. Solo 7/50 hanno continuato lo stesso dosaggio di PPI. Nel gruppo B 22/51 hanno dimezzato la terapia e 29/51 hanno mantenuto la terapia a dosaggio pieno, a causa della ricorrenza dei sintomi nessuno ha interrotto la terapia. Conclusioni: La perdita di peso di almeno il 10% è raccomandata in tutti i pazienti con MRGE con il fine di aumentare gli effetti dei PPI sui sintomi da reflusso e per ridurre l'utilizzo cronico di farmaci. Parole chiave: MRGE, obesità, esofagite erosiva, perdita di peso

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Efficacy of Convalescent Plasma to Treat Long-Standing COVID-19 in Patients with B-Cell Depletion

The use of antivirals, corticosteroids, and IL-6 inhibitors has been recommended by the WHO to treat COVID-19. CP has also been considered for severe and critical cases. Clinical trials on CP have shown contradictory results, but an increasing number of patients, including immunocompromised ones, have shown benefits from this treatment. We reported two clinical cases of patients with prolonged COVID-19 infection and B-cell depletion who showed rapid clinical and virological recovery after the administration of CP. The first patient in this study was a 73-year-old female with a history of follicular non-Hodgkin lymphoma previously treated with bendamustine followed by maintenance therapy with rituximab. The second patient was a 68-year-old male with chronic obstructive pulmonary disease, bipolar disorder, alcoholic liver disease, and a history of mantellar non-Hodgkin lymphoma treated with rituximab and radiotherapy. After the administration of CP, both patients showed a resolution of symptoms, improvement of their clinical conditions, and a negative result of the nasopharyngeal swab test. The administration of CP might be effective in resolving symptoms and improving clinical and virological outcomes in patients with B-cell depletion and prolonged SARS-CoV2 infections

A Characterization System for the Monitoring of ELI-NP Gamma Beam

The ELI-NP (Extreme Light Infrastructure-Nuclear Physics) facility, currently under construction near Bucharest (Romania), is the pillar of the project ELI dedicated to the generation of high-brilliance gamma beams and high-power laser pulses that will be used for frontier research in nuclear physics. To develop an experimental program at the frontiers of the present-day knowledge, two pieces of equipment will be deployed at ELI-NP: a high power laser system consisting of two 10 PW lasers and a high brilliance gamma beam system. The ELI-NP Gamma beam system will deliver an intense gamma beam with unprecedented specifications in terms of photon flux, brilliance and energy bandwidth in an energy range from 0.2 to 20 MeV. Such a gamma beam requires special devices and techniques to measure and monitor the beam parameters during the commissioning and the operational phase. To accomplish this task, the Gamma Beam Characterization System, equipped with four elements, was developed: a Compton spectrometer (CSPEC), to measure and monitor the photon energy spectrum; a nuclear resonant scattering system (NRSS), for absolute beam energy calibration and inter-calibration of the other detectors; a beam profile imager (GPI) to be used for alignment and diagnostics purposes; and finally a sampling calorimeter (GCAL), for a fast combined measurement of the beam average energy and intensity. The combination of the measurements performed by GCAL and CSPEC allows fully characterizing the gamma beam energy distribution and intensity with a precision at the level of few per mill, enough to demonstrate the fulfillment of the required parameters. This article presents an overview of the gamma beam characterization system with focus on these two detectors, which were designed, assembled and are currently under test at INFN-Firenze. The layout and the working principle of the four devices is described, as well as some of the main results of detector test

Sì canta l’empia…: Rinascimento e Opera. Seminari « L’Opéra narrateur » 2013-2014 (Saint-Denis, Université Paris 8-Paris, Institut National d’Histoire de l’Art)

International audienceCe volume inclut vingt-deux essais sur les sources Renaissance dans le livret d'opéra. Structuré en quatre parties, il recueille des études sur les adaptations opératiques du Roland Furieux («L’Arioste et le Furieux»), de La Jérusalem Délivrée («Le Tasso et Armide») et de leurs «Epigones» (Cervantès, Métastase), en plus d'une section consacrée à la réception lyrique des personnages de la Renaissance (Mona Lisa, les Médicis, Christophe Colomb, Pier Luigi Farnese, Beatrice Cenci, Torquato Tasso lui-même). Il rend publics les résultats de la troisième phase des séminaires consacrés à «L’Opéra narrateur», Renaissance et Opéra (2013–2014) qui se sont tenus dans le cadre du Laboratoire d’Études Romanes de l’Université Paris 8. Il analyse la manière dont la scène musicale a su intégrer à ses propres fins les poèmes chevaleresques et privilégie le lien entre modèle littéraire et écriture pour le théâtre en musique, sans toutefois négliger les questions de mise en scène, de scénographie et de chorégraphie.Il presente volume include ventidue saggi sulle fonti rinascimentali nella librettistica. Strutturato in quattro parti, raccoglie studi sugli adattamenti operistici dell’Orlando furioso («L’Ariosto e il Furioso»), de La Gerusalemme liberata («Il Tasso e Armida») e dei loro «Epigoni» (Cervantes, Metastasio), oltre a una sezione dedicata alle recezione lirica dei personaggi del Rinascimento (Monna Lisa, i Medici, Cristoforo Colombo, Pier Luigi Farnese, Beatrice Cenci, lo stesso Torquato Tasso). Rende pubblici i risultati della terza fase dei seminari dedicati a «L’Opéra narrateur», Rinascimento e Opera (2013–2014), tenutisi nell’ambito del Laboratoire d’Études Romanes dell’Università Paris 8. Analizza il modo in cui la scena musicale ha saputo interpretare ai propri fini i poemi cavallereschi, privilegiando il nesso tra modello letterario e scrittura per il teatro in musica, pur senza trascurare le questioni inerenti alla messinscena, alla scenografia e alla coreografia