Virtual Reality as a Vehicle to Empower Motor-Cognitive Neurorehabilitation

In this paper, we advocate the combination of four key ingredients that we believe are necessary to design long-lasting effective treatments for neurorehabilitation: (i) motor-cognitive training, (ii) evidence-based neuroscience principles, in particular those related to body perception, (iii) motivational games, and (iv) empowerment techniques. Then, we propose virtual reality (VR) as the appropriate medium to encompass all the requirements mentioned above. VR is arguably one of the most suitable technologies for neurorehabilitation able to integrate evidence-based neurorehabilitation techniques and neuroscience principles into motivating training approaches that promote self-management by empowering patients to own their recovery process. We discuss the advantages and challenges of such an approach on several exemplary applications and outline directions for future developments. We strongly believe that the combination of positive psychology and positive technology mediated by VR-based interventions can heavily impact the rehabilitation outcomes of motor-cognitive functions along all the stages of the rehabilitation path

Integrin Alpha 8 Recessive Mutations Are Responsible for Bilateral Renal Agenesis in Humans

Renal hypodysplasia (RHD) is a heterogeneous condition encompassing a spectrum of kidney development defects including renal agenesis, hypoplasia, and (cystic) dysplasia. Heterozygous mutations of several genes have been identified as genetic causes of RHD with various severity. However, these genes and mutations are not associated with bilateral renal agenesis, except for RET mutations, which could be involved in a few cases. The pathophysiological mechanisms leading to total absence of kidney development thus remain largely elusive. By using a whole-exome sequencing approach in families with several fetuses with bilateral renal agenesis, we identified recessive mutations in the integrin α8-encoding gene ITGA8 in two families. Itga8 homozygous knockout in mice is known to result in absence of kidney development. We provide evidence of a damaging effect of the human ITGA8 mutations. These results demonstrate that mutations of ITGA8 are a genetic cause of bilateral renal agenesis and that, at least in some cases, bilateral renal agenesis is an autosomal-recessive disease

CARMA1- and MyD88-dependent activation of Jun/ATF-type AP-1 complexes is a hallmark of ABC diffuse large B-cell lymphomas.

A hallmark of the diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) type, a molecular subtype characterized by adverse outcome, is constitutive activation of the transcription factor nuclear factor-κB (NF-κB), which controls expression of genes promoting cellular survival and proliferation. Much less, however, is known about the role of the transcription factor activator protein-1 (AP-1) in ABC DLBCL. Here, we show that AP-1, like NF-κB, was controlled by constitutive activation of the B-cell receptor signaling component caspase recruitment domain-containing membrane-associated guanylate kinase 1 (CARMA1) and/or the Toll-like receptor signaling component myeloid differentiation primary response gene 88 (MyD88) in ABC DLBCL cell lines. In contrast to germinal center (GC) B-cell (GCB) DLBCL, ABC DLBCL cell lines expressed high levels of the AP-1 family members c-Jun, JunB, and JunD, which formed heterodimeric complexes with the AP-1 family members activating transcription factor (ATF) 2, ATF3, and ATF7. Inhibition of these complexes by a dominant-negative approach led to impaired growth of a majority of ABC DLBCL cell lines. Individual silencing of c-Jun, ATF2, or ATF3 decreased cellular survival and revealed c-Jun/ATF2-dependent control of ATF3 expression. As a consequence, ATF3 expression was much higher in ABC vs GCB DLBCL cell lines. Samples derived from DLBCL patients showed a clear trend toward high and nuclear ATF3 expression in nodal DLBCL of the non-GC or ABC subtype. These findings identify the activation of AP-1 complexes of the Jun/ATF-type as an important element controlling the growth of ABC DLBCL

Integrating hydrological features and genetically validated occurrence data in occupancy modeling of an endemic and endangered semi-aquatic mammal species, Galemys pyrenaicus, in a Pyrenean catchment

As freshwater habitats are among the most endangered, there is an urgent need to identify critical areas for conservation, especially those that are home to endangered species. The Pyrenean desman (Galemys pyrenaicus) is a semi-aquatic mammal whose basic ecological requirements are largely unknown, hindering adequate conservation planning even though it is considered as a threatened species. Species distribution modelling is challenging for freshwater species. Indeed, the complexity of aquatic ecosystems (e.g., linear and hierarchical ordering) must be taken into account as well as imperfect sampling. High-quality and relevant hydrological descriptors should also be used. To understand the influence of environmental covariates on the occupancy and detection of the Pyrenean desman, we combine both a robust sign-survey data set (i.e. with genetic validation ensuring true presence information) and a hydrological model to simulate the flow regime across a whole catchment. Markovian site-occupancy analysis, taking into account sign detection and based on spatially adjacent replicates, indicated a positive influence of heterogeneity of substrate and shelters, and a negative influence of flow variability on Pyrenean desman detection. This valuable information should help to improve monitoring programs for this endangered species. Our results also highlighted a spatially clustered distribution and a positive influence of stream flow and number of tributaries on occupancy. Hence, modifications of flow regime (e.g. hydropower production, irrigation, climate change) and habitat fragmentation appear to be major threats for this species, altering the connectivity between tributaries and the mainstream river as well as between adjacent sub-catchments

Seal bypass at the Giant Gjallar Vent (Norwegian Sea): indications for a new phase of fluid venting at a 56-Ma-old fluid migration system

Highlights: • The Giant Gjallar Vent is still active in terms of fluid migration and faulting. • The Base Pleistocene Unconformity acts as a seal to upward fluid migration. • Seal bypass in at least one location leads to a new phase of fluid venting. The Giant Gjallar Vent (GGV), located in the Vøring Basin off mid-Norway, is one of the largest (~ 5 × 3 km) vent systems in the North Atlantic. The vent represents a reactivated former hydrothermal system that formed at about 56 Ma. It is fed by two pipes of 440 m and 480 m diameter that extend from the Lower Eocene section up to the Base Pleistocene Unconformity (BPU). Previous studies based on 3D seismic data differ in their interpretations of the present activity of the GGV, describing the system as buried and as reactivated in the Upper Pliocene. We present a new interpretation of the GGV’s reactivation, using high-resolution 2D seismic and Parasound data. Despite the absence of geochemical and hydroacoustic indications for fluid escape into the water column, the GGV appears to be active because of various seismic anomalies which we interpret to indicate the presence of free gas in the subsurface. The anomalies are confined to the Kai Formation beneath the BPU and the overlying Naust Formation, which are interpreted to act as a seal to upward fluid migration. The seal is breached by focused fluid migration at one location where an up to 100 m wide chimney-like anomaly extends from the BPU up to the seafloor. We propose that further overpressure build-up in response to sediment loading and continued gas ascent beneath the BPU will eventually lead to large-scale seal bypass, starting a new phase of venting at the GGV

Review of the current published evidence on single-dose HPV vaccination 3rd Edition

Prophylactic human papillomavirus (HPV) vaccines have been licensed for over ten years. They were initially administered as a three-dose regimen over a six-month period. In 2014, following a review of the evidence for dose reduction by the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) on Immunization, a two-dose regimen for individuals aged younger than 15 years was recommended. Since that time, evidence from observational studies suggests that a single-dose HPV vaccine may also provide protection against HPVinfectionand its sequelae. The primary objective of this paperis to summarize and assess the current evidence fora single-dose HPV vaccination schedule. We also identify gaps that remain in determining whether a single dose could be sufficiently protective to have a major impact against HPV infection and its sequelae within the context of immunization programs.The evidence has been compiled by a working group of the Single-Dose HPV Vaccine Evaluation Consortium, whose members representtechnical depth, a wide global reach, and extensive expertise in immunization programs, HPV vaccine introductions, and vaccine policy. Coordinated by PATH, the Consortium includes the London School of Hygiene & Tropical Medicine, the US Centers for Disease Control and Prevention, Harvard University, the US National Cancer Institute, Université Laval, the University of British Columbia, and the Wits Reproductive Health and HIV Institute at the University of Witwatersrand. The Consortium leverages the experience of expert groups working in HPV vaccine and other vaccine introductions. Members represent groups that have actively generated evidence for HPV vaccine safety and efficacy,as well as post-licensure effectiveness and delivery.They have implemented HPV vaccine delivery programs in numerous countries, comprehensively evaluated the delivery and impact of HPV vaccine

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2