SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

Peptaibols as naturally-based fungicides against grapevine pathogens

Fungi belonging to the genus Trichoderma are widespread and have been used successfully in protection against many crop pathogens. Among the secondary metabolites secreted against dangerous plant pathogens, Trichoderma species produce peptaibols, a peculiar family of peptides that significantly contribute to their attack arsenal against other microorganisms. Such secondary metabolites are known for their plant-protection properties: they (i) possess antimicrobial activity, (ii) act as stimulants of plant defences and growth (iii) elicit plant production of volatiles to attract natural enemies of herbivorous insects. Moreover, peptides are ecofriendly compounds that can be degraded by enzymes to nontoxic amino acids. We present our progress towards the exploitation of analogs of the peptaibols family as fungicides. These peptides have been screened against Plasmopara viticola and Botrytis cinerea, two of the most important grapevine pathogens in the temperate regions including Italy. We found that treatments with selected peptaibols on grapevine leaves inhibit sporangia production by the downy mildew pathogen P. viticola and decrease the incidence of leaf rot by the grey mould fungus B. cinerea. Experiments are in progress to assay the effectiveness of peptaibols against Colletotrichum gleosporioides and C. acutatum, two of the most dangerous ripe rot fungi in sub-tropical climate including the south regions of Brazil. Additional experiments showed a low level of toxicity against the yeast Saccharomyces cerevisiae. Such compounds can match the demand of environmental safe fungicides and circumvent the unreliable effectiveness of antagonistic microorganisms used as biological control agents in open field

Trattamento integrato della disfagia: proposta di un percorso valutativo-riabilitativo condiviso.

Per disfagia s\u2019intende la difficolt\ue0 o impossibilit\ue0 di masticare il cibo, preparare il bolo e deglutirlo. Il gruppo regionale Veneto SIMFER per la disfagia si \ue8 riunito nei primi mesi del 2008 per concordare un protocollo che preveda l\u2019applicazione di procedure d\u2019intervento condivise sui pazienti affetti da disturbi della deglutizione allo scopo di ottimizzare le risorse terapeutiche dei diversi Centri afferenti ad un determinato territorio e, conseguentemente, migliorare l\u2019efficacia dei trattamenti impiegati. Dalla discussione tra le diverse figure professionali che si occupano della gestione dei pazienti affetti da disfagia in diverse strutture riabilitative del territorio Veneto \ue8 emersa la necessit\ue0 di un confronto tra le metodiche di valutazione e di trattamento applicate. Tra queste sono state individuate quelle di maggiore riscontro, efficacia ed utilit\ue0 clinica al fine di ottimizzare ed uniformare le procedure in vigore

Trattamento integrato della disfagia: proposta di un percorso valutativo-riabilitativo condiviso

L\u2019attuazione di strategie mirate all\u2019individuazione precoce dei disturbi della deglutizione ed al loro recupero funzionale \ue8 tra i principali obiettivi del Riabilitatore. In particolare, l\u2019individuazione di un percorso valutativo-riabilitativo per il paziente disfagico, condiviso da pi\uf9 strutture afferenti ad un territorio comune ha il fine di ottimizzare le risorse impiegate, migliorando l\u2019efficacia dei trattamenti impiegati e una gestione clinica del paziente attraverso l\u2019impiego di un linguaggio comune basato non solo sull\u2019esperienza ma anche su evidenze bibliografiche aggiornate. L\u2019impiego di un protocollo diagnostico-terapeutico condiviso ha, inoltre, l\u2019obiettivo di migliorare l\u2019outcome del paziente, diminuendo il tempo di ospedalizzazione, la durata di nutrizione enterale artificiale tramite SNG e possibili complicanze, quali: ulcerazioni o perforazioni delle mucose, reflusso gastroesofageo, polmonite ab ingestis, rottura, dislocazione o ostruzione del SNG

Spread of botulinum neurotoxin type a at standard doses is inherent to the successful treatment of spastic equinus foot in cerebral palsy: short-term neurophysiological and clinical study.

To evaluate whether botulinum toxin type A at standard doses spreads to antagonist leg muscles in dynamic equinus foot, we studied 18 ambulatory children with hemiplegic cerebral palsy. The gastrocnemius muscle on the affected side was injected with botulinum toxin type A (Dysport) (mean \ub1 standard deviation, 14.3 \ub1 0.9 U/kg). Compound muscle action potential areas were assessed in the lateral gastrocnemius and tibialis anterior muscles on the treated and untreated sides before botulinum toxin type A injections and on days 10 and 30 after injections. In all patients, compound muscle action potential areas recorded from both the muscles on the treated side decreased from preinjection values at day 10 (P < .05) and 30 (P < .002). After injection, ankle spasticity had diminished (P < .05), equinus foot excursion increased (P < .05), and functional gait improved (P < .05). This study shows that botulinum toxin type A spreads from foot flexors to antagonist extensors and suggests that spread may be partly responsible for improving gait in children with cerebral palsy

Realt\ue0 virtuale in tele-riabilitazione vs. esercizi di integrazione sensoriale nella riabilitazione dell\u2019instabilit\ue0 posturale nei pazienti affetti da malattia di parkinson: uno studio randomizzato controllato.

Introduzione: Nintendo Wii \ue8 stato dimostrato essere un valido dispositivo per la riabilitazione dell\u2019instabilit\ue0 posturale nei pazienti affetti da Malattia di Parkinson (Pompeu et al, 2012, dos Santos Mendes 2012, Escluder et al. 2012). Tuttavia, la sua fattibilit\ue0 ed efficacia in tele-riabilitazione non \ue8 stata ancora valutata. Inoltre non \ue8 chiaro se tale approccio pu\uf2 avere la stessa efficacia di un trattamento d\u2019integrazione sensoriale svolto presso la struttura ospedaliera. Obiettivo: Valutare la fattibilit\ue0, efficacia e i costi di un trattamento riabilitativo con Nintendo Wii in tele-riabilitazione per ridurre l\u2019instabilit\ue0 posturale in pazienti affetti da Malattia di Parkinson. Materiali e Metodi: Settantasei pazienti affetti da Malattia di Parkinson (H&amp;Y-stage 2.5-3) sono stati randomizzati e assegnati a due gruppi. Tutti i pazienti sono stati sottoposti ad un trattamento di 21 sedute, della durata di 45 minuti, 3 giorni a settimana, per 7 settimane consecutive. Il gruppo sperimentale (n=38) \ue8 stato sottoposto a un trattamento con Nintendo Wii in tele-riabilitazione (TeleWii), mentre il gruppo di controllo (n=38) \ue8 stato sottoposto ad un trattamento dell\u2019equilibrio con esercizi di integrazione sensoriale (SIBT). Prima del trattamento, subito dopo, e con un mese di follow-up dopo il trattamento, i pazienti sono stati valutati con la misura di outcome primaria Berg Balance Scale (BBS). Le misura di outcome secondarie erano: Activity Balance Confidence Scale(ABC), 10-Meter Walking Test(10MWT), Dynamic Gait Index(DGI), UPDRS, Numero di cadute, PD Quality of Life 8, Questionario, e analisi dei costi. Risultati: Sono state individuate differenze statisticamente significative nella BBS tra il gruppo in TeleWii e il SIBT. Un miglioramento significativo \ue8 stato trovato dopo il trattamento nel DGI in favore del gruppo SIBT (pre-DGI: 17.66\ub14.39; post-DGI: 20.82\ub13.07) (TeleWii group, pre-DGI: 19.60\ub14.10; post-DGI: 21.47\ub12.62). Un miglioramento significativo \ue8 stato trovato per entrambi i gruppi dopo il trattamento e al follow-up per la the BBS, ABC, DGI, and PDQ8. Il 10MWT \ue8 migliorato dopo il trattamento e al follow-up solo il gruppo SIBT. I costi del TeleWii sono inferiori a quelli riportati nel SIBT . Conclusione: Il trattamento in TeleWii \ue8 fattibile e rappresenta una valida alternativa al SIBT per ridurre l\u2019instabilit\ue0 posturale in pazienti affetti da Malattia di Parkinson e che vivono in luoghi rurali dove vi \ue8 difficolt\ue0 ad accedere alle cure riabilitative. I pazienti che possono beneficiare del trattamento sono quelli aventi una scala H&amp;Y modificata allo stadio 2.5-3, e l\u2019assistenza domiciliare di un caregiver

Results of a multicenter, controlled, randomized clinical trial evaluating the combination of piperacillin/tazobactam and tigecycline in high-risk hematologic patients with cancer with febrile neutropenia.

Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria. In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment. Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups. The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies