Space-based and object-centered gaze cuing of attention in right hemisphere-damaged patients

Gaze cuing of attention is a well established phenomenon consisting of the tendency to shift attention to the location signaled by the averted gaze of other individuals. Evidence suggests that such phenomenon might follow intrinsic object-centered features of the head containing the gaze cue. In the present exploratory study, we aimed to investigate whether such object-centered component is present in neuropsychological patients with a lesion involving the right hemisphere, which is known to play a critical role both in orienting of attention and in face processing. To this purpose, we used a modified gaze-cuing paradigm in which a centrally placed head with averted gaze was presented either in the standard upright position or rotated 90° clockwise or anti-clockwise. Afterward, a to-be-detected target was presented either in the right or in the left hemifield. The results showed that gaze cuing of attention was present only when the target appeared in the left visual hemifield and was not modulated by head orientation. This suggests that gaze cuing of attention in right hemisphere-damaged patients can operate within different frames of reference

Virtual reality telerehabilitation for postural instability in Parkinson's Disease: a multicenter, single-blind, randomized, controlled trial

Introduction: Telerehabilitation enables patients to access remote rehabilitation services for patient-physiotherapist videoconferencing in their own homes. Home-based virtual reality (VR) balance training has been shown to reduce postural instability in patients with Parkinson's disease (PD). The primary aim was to compare improvements in postural stability after remotely supervised in-home VR balance training and in-clinic sensory integration balance training (SIBT). Methods: In this multicenter study, 76 PD patients (modified Hoehn and Yahr stages 2.5-3) were randomly assigned to receive either in-home VR telerehabilitation (n = 38) or in-clinic SIBT (n = 38) in 21 sessions of 50 minutes each, 3 days/week for 7 consecutive weeks. VR telerehabilitation consisted of graded exergames using the Nintendo Wii Fit system; SIBT included exercises to improve postural stability. Patients were evaluated before treatment, after treatment, and at 1-month follow-up. Results: Analysis revealed significant between-group differences in improvement on the Berg Balance Scale for the VR telerehabilitation group (p = 0.04) and significant Time 7 Group interactions in the Dynamic Gait Index (p = 0.04) for the in-clinic group. Both groups showed differences in all outcome measures over time, except for fall frequency. Cost comparison yielded between-group differences in treatment and equipment costs. Conclusions: VR is a feasible alternative to in-clinic SIBT for reducing postural instability in PD patients having a caregiver

Virtual Reality Telerehabilitation for Postural Instability in Parkinson’s Disease: A Multicenter, Single-Blind, Randomized, Controlled Trial

Introduction. Telerehabilitation enables patients to access remote rehabilitation services for patient-physiotherapist videoconferencing in their own homes. Home-based virtual reality (VR) balance training has been shown to reduce postural instability in patients with Parkinson’s disease (PD). The primary aim was to compare improvements in postural stability after remotely supervised in-home VR balance training and in-clinic sensory integration balance training (SIBT). Methods. In this multicenter study, 76 PD patients (modified Hoehn and Yahr stages 2.5–3) were randomly assigned to receive either in-home VR telerehabilitation (n=38) or in-clinic SIBT (n=38) in 21 sessions of 50 minutes each, 3 days/week for 7 consecutive weeks. VR telerehabilitation consisted of graded exergames using the Nintendo Wii Fit system; SIBT included exercises to improve postural stability. Patients were evaluated before treatment, after treatment, and at 1-month follow-up. Results. Analysis revealed significant between-group differences in improvement on the Berg Balance Scale for the VR telerehabilitation group (p=0.04) and significant Time × Group interactions in the Dynamic Gait Index (p=0.04) for the in-clinic group. Both groups showed differences in all outcome measures over time, except for fall frequency. Cost comparison yielded between-group differences in treatment and equipment costs. Conclusions. VR is a feasible alternative to in-clinic SIBT for reducing postural instability in PD patients having a caregiver

PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease

International audienceSevere COVID-19 is associated with hyperinflammation and weak T cell responses against SARS-CoV-2. However, the links between those processes remain partially characterized. Moreover, whether and how therapeutically manipulating T cells may benefit patients are unknown. Our genetic and pharmacological evidence demonstrates that the ion channel TMEM176B inhibited inflammasome activation triggered by SARS-CoV-2 and SARS-CoV-2–related murine β-coronavirus. Tmem176b −/− mice infected with murine β-coronavirus developed inflammasome-dependent T cell dysfunction and critical disease, which was controlled by modulating dysfunctional T cells with PD-1 blockers. In critical COVID-19, inflammasome activation correlated with dysfunctional T cells and low monocytic TMEM176B expression, whereas PD-L1 blockade rescued T cell functionality. Here, we mechanistically link T cell dysfunction and inflammation, supporting a cancer immunotherapy to reinforce T cell immunity in critical β-coronavirus disease

PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease

Severe COVID-19 is associated with hyperinflammation and weak T cell responses against SARS-CoV-2. However, the links between those processes remain partially characterized. Moreover, whether and how therapeutically manipulating T cells may benefit patients are unknown. Our genetic and pharmacological evidence demonstrates that the ion channel TMEM176B inhibited inflammasome activation triggered by SARS-CoV-2 and SARS-CoV-2- related murine β-coronavirus. Tmem176b-/- mice infected with murine β-coronavirus developed inflammasome-dependent T cell dysfunction and critical disease, which was controlled by modulating dysfunctional T cells with PD-1 blockers. In critical COVID-19, inflammasome activation correlated with dysfunctional T cells and low monocytic TMEM176B expression, whereas PD-L1 blockade rescued T cell functionality. Here, we mechanistically link T cell dysfunction and inflammation, supporting a cancer immunotherapy to reinforce T cell immunity in critical β-coronavirus disease.Fil: Duhalde Vega, Maite. Institut Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Olivera, Daniela. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Davanzo, Gustavo Gastão. Universidade Estadual de Campinas; BrasilFil: Bertullo, Mauricio. Immunoregulation And Inflammation Lab; UruguayFil: Noya, Verónica. Sanatorio Americano; UruguayFil: de Souza, Gabriela Fabiano. Universidade Estadual de Campinas; BrasilFil: Muraro, Stéfanie Primon. Universidade Estadual de Campinas; BrasilFil: Castro, Icaro. Hospital Israelita Albert Einstein; BrasilFil: Arévalo, Ana Paula. Institut Pasteur de Montevideo; UruguayFil: Crispo, Martina. Institut Pasteur de Montevideo; UruguayFil: Galliussi, Germán. Institut Pasteur de Montevideo; UruguayFil: Russo, Sofía. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Charbonnier, David. Institut Pasteur de Montevideo; UruguayFil: Rammauro, Florencia. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Jeldres, Mathías. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Alamón, Catalina. Institut Pasteur de Montevideo; UruguayFil: Varela, Valentina. Institut Pasteur de Montevideo; UruguayFil: Batthyany, Carlos. Institut Pasteur de Montevideo; UruguayFil: Bollati Fogolín, Mariela. Institut Pasteur de Montevideo; UruguayFil: Oppezzo, Pablo. Institut Pasteur de Montevideo; UruguayFil: Pritsch, Otto. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Proença Módena, José Luiz. Universidade Estadual de Campinas; BrasilFil: Nakaya, Helder I.. Hospital Israelita Albert Einstein; BrasilFil: Trias, Emiliano. Institut Pasteur de Montevideo; UruguayFil: Barbeito, Luis. Institut Pasteur de Montevideo; UruguayFil: Anegon, Ignacio. Center For Research In Transplantation And Immunology; FranciaFil: Cuturi, María Cristina. Center For Research In Transplantation And Immunology; FranciaFil: Moraes Vieira, Pedro. Universidade Estadual de Campinas; BrasilFil: Segovia, Mercedes. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Hill, Marcelo. Universidad de la República; Uruguay. Institut Pasteur de Montevideo; Urugua

Bortezomib-thalidomide-dexamethasone is superior to thalidomide- dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma

In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484. \ua9 2012 by The American Society of Hematology