Cross-cultural adaptation and validation of the “spinal cord injury-falls concern scale” in the Italian population

Study design: Psychometrics study. Objective: The objective of this study was to develop an Italian version of the Spinal Cord Injury-Falls Concern Scale (SCI-FCS) and examine its reliability and validity. Setting: Multicenter study in spinal units in Northern and Southern Italy. The scale also was administered to non-hospitalized outpatient clinic patients. Methods: The original scale was translated from English to Italian using the “Translation and Cultural Adaptation of Patient-Reported Outcomes Measures” guidelines. The reliability and validity of the culturally adapted scale were assessed following the “Consensus-Based Standards for the Selection of Health Status Measurement Instruments” checklist. The SCI-FCS-I internal consistency, inter-rater, and intra-rater reliability were examined using Cronbach’s alpha coefficient and the intraclass correlation coefficient, respectively. Concurrent validity was evaluated using Pearson’s correlation coefficient with the Italian version of the short form of the Wheelchair Use Confidence Scale for Manual Wheelchair Users (WheelCon-M-I-short form). Results: The Italian version of the SCI-FCS-I was administered to 124 participants from 1 June to 30 September 2017. The mean ± SD of the SCI-FCS-I score was 16.73 ± 5.88. All SCI-FCS items were either identical or similar in meaning to the original version’s items. Cronbach’s α was 0.827 (p < 0.01), the inter-rater reliability was 0.972 (p < 0.01), and the intra-rater reliability was 0.973 (p < 0.01). Pearson’s correlation coefficient of the SCI-FCS-I scores with the WheelCon-M-I-short form was 0.56 (p < 0.01). Conclusions: The SCI-FCS-I was found to be reliable and a valid outcome measure for assessing manual wheelchair concerns about falling in the Italian population

Extension of Yeast Chronological Lifespan by Methylamine

Background: Chronological aging of yeast cells is commonly used as a model for aging of human post-mitotic cells. The yeast Saccharomyces cerevisiae grown on glucose in the presence of ammonium sulphate is mainly used in yeast aging research. We have analyzed chronological aging of the yeast Hansenula polymorpha grown at conditions that require primary peroxisome metabolism for growth. Methodology/Principal Findings: The chronological lifespan of H. polymorpha is strongly enhanced when cells are grown on methanol or ethanol, metabolized by peroxisome enzymes, relative to growth on glucose that does not require peroxisomes. The short lifespan of H. polymorpha on glucose is mainly due to medium acidification, whereas most likely ROS do not play an important role. Growth of cells on methanol/methylamine instead of methanol/ammonium sulphate resulted in further lifespan enhancement. This was unrelated to medium acidification. We show that oxidation of methylamine by peroxisomal amine oxidase at carbon starvation conditions is responsible for lifespan extension. The methylamine oxidation product formaldehyde is further oxidized resulting in NADH generation, which contributes to increased ATP generation and reduction of ROS levels in the stationary phase. Conclusion/Significance: We conclude that primary peroxisome metabolism enhanced chronological lifespan of H. polymorpha. Moreover, the possibility to generate NADH at carbon starvation conditions by an organic nitrogen source supports further extension of the lifespan of the cell. Consequently, the interpretation of CLS analyses in yeast should include possible effects on the energy status of the cell.

Quantum Scalar Field on the Massless (2+1)-Dimensional Black Hole Background

The behavior of a quantum scalar field is studied in the metric ground state of the (2+1)-dimensional black hole of Ba\~nados, Teitelboim and Zanelli which contains a naked singularity. The one-loop BTZ partition function and the associate black hole effective entropy, the expectation value of the quantum fluctuation as well as the renormalized expectation value of the stress tensor are explicitly computed in the framework of the $\zeta$-function procedure. This is done for all values of the coupling with the curvature, the mass of the field and the temperature of the quantum state. In the massless conformally coupled case, the found stress tensor is used for determining the quantum back reaction on the metric due to the scalar field in the quantum vacuum state, by solving the semiclassical Einstein equations. It is finally argued that, within the framework of the 1/N expansion, the Cosmic Censorship Hypothesis is implemented since the naked singularity of the ground state metric is shielded by an event horizon created by the back reaction.Comment: 18 pages, RevTeX, no figures, minor changes, final version accepted for publication in Phys. Rev.

Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription

Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 is a known cytosolic immune antagonist, but how NS1 modulates host responses remains poorly defined. Here, we observe NS1 partitioning into the nucleus of RSV-infected cells, including the human airway epithelium. Nuclear NS1 coimmunoprecipitates with Mediator complex and is chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment of NS1 that overlaps Mediator and transcription factor binding within the promoters and enhancers of differentially expressed genes during RSV infection. Mutation of the NS1 C-terminal helix reduces NS1 impact on host gene expression. These data suggest that nuclear NS1 alters host responses to RSV infection by binding at regulatory elements of immune response genes and modulating host gene transcription. Our study identifies another layer of regulation by virally encoded proteins that shapes host response and impacts immunity to RSV

Novel highly potent CD4bs bNAb with restricted pathway to HIV-1 escape

Purpose: Broadly HIV-1 neutralizing antibodies (bNAbs) can suppress viremia in humans and represent a novel approach for effective immunotherapy. However, bNAb monotherapy selects for antibody-resistant viral variants. Thus, we focused on the identification of new antibody combinations and/or novel bNAbs that restrict pathways of HIV-1 escape. Methods: We screened HIV-1 positive patients for their neutralizing capacities. Following, we performed single cell sorting and PCR of HIV-1 Env-reactive mature B cells of identified elite neutralizers. Found antibodies were tested for neutralization and binding capacities in vitro. Further, their antiviral activity was tested in an HIV-1 infected humanized mouse model. Results: Here we report the isolation of antibody 1–18, a VH1–46-encoded CD4 binding site (CD4bs) bNAb identified in an individual ranking among the top 1% neutralizers of 2,274 HIV-1-infected subjects. Tested on a 119-virus panel, 1–18 showed to be exceptionally broad and potent with a coverage of 97% and a mean IC50 of 0.048 lg/mL, exceeding the activity of most potent CD4bs bNAbs described to-date. A 2.4 Å cryo-EM structure of 1–18 bound to a native-like Env trimer revealed that it interacts with HIV-1 env similar to other CD4bs bNAbs, but includes additional contacts to the V3 loop of the adjacent protomer. Notably, in vitro, 1–18 maintained activity against viruses carrying mutations associated with escape from VRC01-class bNAbs. Further, its HIV-1 env wide escape profile differed critically from other CD4bs bNAbs. In humanized mice, monotherapy with 1–18 was sufficient to prevent the development of viral escape variants that rapidly emerged during treatment with other CD4bs bNAbs. Finally, 1–18 overcame classical HIV-1 mutations that are driven by VRC01-like bNAbs in vivo. Conclusion: 1–18 is a highly potent and broad bNAb that restricts escape and overcomes frequent CD4bs escape pathways, providing new options for bNAb combinations to prevent and treat HIV-1 infection

Isolation and characterization of resident endogenous c-Kit⁺ cardiac stem cells from the adult mouse and rat heart

This protocol describes the isolation of endogenous c-Kit (also known as CD117)-positive (c-Kit⁺), CD45-negative (CD45⁻) cardiac stem cells (eCSCs) from whole adult mouse and rat hearts. The heart is enzymatically digested via retrograde perfusion of the coronary circulation, resulting in rapid and extensive breakdown of the whole heart. Next, the tissue is mechanically dissociated further and cell fractions are separated by centrifugation. The c-Kit⁺ CD45⁻ eCSC population is isolated by magnetic-activated cell sorting technology and purity and cell numbers are assessed by flow cytometry. This process takes ∼4 h for mouse eCSCs or 4.5 h for rat eCSCs. We also describe how to characterize c-Kit⁺ CD45⁻ eCSCs. The c-Kit⁺ CD45⁻eCSCs exhibit the defining characteristics of stem cells: they are self-renewing, clonogenic and multipotent. This protocol also describes how to differentiate eCSCs into three main cardiac lineages: functional, beating cardiomyocytes, smooth muscle, and endothelial cells. These processes take 17-20 d

The Brazilian Developments on the Regional Atmospheric Modeling System (BRAMS 5.2): An Integrated Environmental Model Tuned for Tropical Areas

We present a new version of the Brazilian developments on the Regional Atmospheric Modeling System where different previous versions for weather, chemistry and carbon cycle were unified in a single integrated software system. The new version also has a new set of state-of-the-art physical parameterizations and greater computational parallel and memory usage efficiency. Together with the description of the main features are examples of the quality of the transport scheme for scalars, radiative fluxes on surface and model simulation of rainfall systems over South America in different spatial resolutions using a scale-aware convective parameterization. Besides, the simulation of the diurnal cycle of the convection and carbon dioxide concentration over the Amazon Basin, as well as carbon dioxide fluxes from biogenic processes over a large portion of South America are shown. Atmospheric chemistry examples present model performance in simulating near-surface carbon monoxide and ozone in Amazon Basin and Rio de Janeiro megacity. For tracer transport and dispersion, it is demonstrated the model capabilities to simulate the volcanic ash 3-d redistribution associated with the eruption of a Chilean volcano. Then, the gain of computational efficiency is described with some details. BRAMS has been applied for research and operational forecasting mainly in South America. Model results from the operational weather forecast of BRAMS on 5 km grid spacing in the Center for Weather Forecasting and Climate Studies, INPE/Brazil, since 2013 are used to quantify the model skill of near surface variables and rainfall. The scores show the reliability of BRAMS for the tropical and subtropical areas of South America. Requirements for keeping this modeling system competitive regarding on its functionalities and skills are discussed. At last, we highlight the relevant contribution of this work on the building up of a South American community of model developers

Visual field loss and vision-related quality of life in the Italian Primary Open Angle Glaucoma Study

The aim of this study was to examine the relationship between visual field (VF) loss, vision-related quality of life (QoL) and glaucoma-related symptoms in a large cohort of primary open angle glaucoma (POAG) patients. POAG patients with or without VF defects or "glaucoma suspect" patients were considered eligible. QoL was assessed using the validated versions of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and glaucoma-related symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were classified as having VF damage in one eye (VFD-1), both eyes (VFD-2), or neither eye (VFD-0). 3227 patients were enrolled and 2940 were eligible for the analysis. 13.4% of patients were classified in the VFD-0, 23.7% in the VFD-1, and 62.9% in the VFD-2 group. GSS visual symptoms domain (Func-4) and GSS non-visual symptoms domain (Symp-6) scores were similar for the VFD-0 and VFD-1 groups (p = 0.133 and p = 0.834 for Func-4 and Symp-6, respectively). VFD-0 group had higher scores than VFD-2 both in Func-4 (p < 0.001) and Symp-6 domains (p = 0.035). Regarding the NEI-VFQ-25, our data demonstrated that bilateral VF defects are associated with vision-related QoL deterioration, irrespective of visual acuity

The Brazilian developments on the Regional Atmospheric Modeling System (BRAMS 5.2): an integrated environmental model tuned for tropical areas

We present a new version of the Brazilian developments on the Regional Atmospheric Modeling System (BRAMS), in which different previous versions for weather, chemistry, and carbon cycle were unified in a single integrated modeling system software. This new version also has a new set of state-of-the-art physical parameterizations and greater computational parallel and memory usage efficiency. The description of the main model features includes several examples illustrating the quality of the transport scheme for scalars, radiative fluxes on surface, and model simulation of rainfall systems over South America at different spatial resolutions using a scale aware convective parameterization. Additionally, the simulation of the diurnal cycle of the convection and carbon dioxide concentration over the Amazon Basin, as well as carbon dioxide fluxes from biogenic processes over a large portion of South America, are shown. Atmospheric chemistry examples show the model performance in simulating near-surface carbon monoxide and ozone in the Amazon Basin and the megacity of Rio de Janeiro. For tracer transport and dispersion, the model capabilities to simulate the volcanic ash 3-D redistribution associated with the eruption of a Chilean volcano are demonstrated. The gain of computational efficiency is described in some detail. BRAMS has been applied for research and operational forecasting mainly in South America. Model results from the operational weather forecast of BRAMS on 5 km grid spacing in the Center for Weather Forecasting and Climate Studies, INPE/Brazil, since 2013 are used to quantify the model skill of near-surface variables and rainfall. The scores show the reliability of BRAMS for the tropical and subtropical areas of South America. Requirements for keeping this modeling system competitive regarding both its functionalities and skills are discussed. Finally, we highlight the relevant contribution of this work to building a South American community of model developers.CNPqFAPESPEarth System Research Laboratory at the National Oceanic and Atmospheric Administration (ESRL/NOAA), Boulder, USAInst Nacl Pesquisas Espaciais, Ctr Previsao Tempo & Estudos Climat, Cachoeira Paulista, SP, BrazilDiv Ciência da Computação, Instituto Tecnológico de Aeronáutica, São José dos Campos, SP, BrazilUniv Estadual Paulista Unesp, Fac Ciencias, Bauru, SP, BrazilCtr Meteorol Bauru IPMet, Bauru, SP, BrazilUniv Fed Sao Paulo, Dept Ciencias Ambientais, Diadema, SP, BrazilUniv Sao Paulo, Inst Astron Geofis & Ciencias Atmosfer, Sao Paulo, SP, BrazilUniv Fed Campina Grande, Dept Ciencias Atmosfer, Campina Grande, PB, BrazilEmbrapa Informat Agr, Campinas, SP, BrazilUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilUniv Fed Rio Grande do Norte, Dept Ciencias Atmosfer & Climat, Programa Pos Grad Ciencias Climat, Natal, RN, BrazilInst Nacl Pesquisas Espaciais, Ctr Ciencias Sistema, Sao Jose Dos Campos, SP, BrazilUniv Fed Sao Joao Del Rei, Dept Geociencias, Sao Joao Del Rei, MG, BrazilInst Nacl Pesquisas Espaciais, Lab Associado Computacao & Matemat Aplica, Sao Jose Dos Campos, BrazilUniv Evora, Inst Ciencias Agr & Ambientais Mediterr, Evora, PortugalUniv Lusofona Humanidades & Tecnol, Ctr Interdisciplinar Desenvolvimento Ambient Gest, Lisbon, PortugalUniv Fed Pelotas, Fac Meteorol, Pelotas, RS, BrazilUnive Tecnol Fed Parana, Londrina, PR, BrazilNASA, Goddard Space Flight Ctr, Univ Space Res Assoc, Goddard Earth Sci Technol & Res Global Modeling &, Greenbelt, MD USAUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilCNPq: 306340/2011-9FAPESP: 2014/01563-1FAPESP: 2015/10206-0FAPESP: 2014/01564-8Web of Scienc