Correspondence: Strongly-driven Re + CO2 redox reaction at high-pressure and high-temperature

Santamaría-Perez, D.; Mcguire, C.; Makhluf, A.; Kavner, A.; Chulia-Jordan, R.; Jorda Moret, JL.; Rey Garcia, F.... (2016). Correspondence: Strongly-driven Re + CO2 redox reaction at high-pressure and high-temperature. Nature Communications. 7:1-3. doi:10.1038/ncomms13647S137Yoo, C. S. et al. Crystal structure of carbon dioxide at high pressure: “superhard” polymeric carbon dioxide. Phys. Rev. Lett. 83, 5527–5530 (1999).Santoro, M. et al. Partially collapsed cristobalite structure in the non molecular phase V in CO2 . Proc. Natl Acad. Sci. 109, 5176–5179 (2012).Datchi, F., Mallick, B., Salamat, A. & Ninet, S. Structure of polymeric carbon dioxide CO2-V. Phys. Rev. Lett. 108, 125701 (2012).Santoro, M. et al. Silicon carbonate phase formed from carbon dioxide and silica under pressure. Proc. Natl Acad. Sci. 108, 7689–7692 (2011).Santoro, M. et al. Carbon enters silica forming a cristobalite-type CO2.SiO2 solid solution. Nat. Commun. 5, 3761 (2014).Corma, A., Rey, F., Rius, J., Sabater, M. J. & Valencia, S. Supramolecular self-assembled molecules as organic directing agent for synthesis of zeolites. Nature 431, 287–290 (2004).Guth, J.-L., Kessler, H. & Wey, R. in Studies in Surface Science and Catalysis Vol. 28 (eds Murakami, Y., Iijima, A. & Ward, J. W.) 121 (Kodansha-Elsevier, 1986).Santamaria-Perez, D. et al. Exploring the chemical reactivity between carbon dioxide and three transition metals (Au, Pt, and Re) at high-pressure high-temperature conditions. Inorg. Chem. 55, 10793–10799 (2016).Magneli, A. Studies on rhenium oxides. Acta Chem. Scand. 11, 28–33 (1957)

The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent.

BACKGROUND AND AIMS Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. APPROACH AND RESULTS C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD + /NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. CONCLUSIONS Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.This work was supported by grants from Ministerio de Ciencia e Innovación, Programa Retos-Colaboración RTC2019-007125-1 (for Jorge Simon and Maria Luz Martinez-Chantar); Ministerio de Economía, Industria y Competitividad, Retos a la Sociedad AGL2017- 86927R (for F.M.); Instituto de Salud Carlos III, Proyectos de Investigación en Salud DTS20/00138 and DTS21/00094 (for Jorge Simon and Maria Luz Martinez-Chantar, and Asis Palazon. respectively); Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias co-founded by European Regional Development Fund/European Social Fund, “Investing in your future” PI19/00819, “Una manera de hacer Europa” FIS PI20/00765, and PI21/01067 (for Jose J. G. Marin., Pau Sancho-Bru,. and Mario F. Fraga respectively); Departamento de Industria del Gobierno Vasco (for Maria Luz Martinez-Chantar); Asturias Government (PCTI) co-funding 2018-2023/ FEDER IDI/2021/000077 (for Mario F. Fraga.); Ministerio de Ciencia, Innovación y Universidades MICINN: PID2020-117116RB-I00, CEX2021-001136-S PID2020-117941RB-I00, PID2020-11827RB-I00 and PID2019-107956RA-100 integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER (for Maria Luz Martinez-Chantar, Francisco J Cubero., Yulia A Nevzorova and Asis Palazon); Ayudas Ramón y Cajal de la Agencia Estatal de Investigación RY2013-13666 and RYC2018- 024183-I (for Leticia Abecia and Asis Palazon); European Research Council Starting Grant 804236 NEXTGEN-IO (for Asis Palazon); The German Research Foundation SFB/TRR57/P04, SFB1382-403224013/ A02 and DFG NE 2128/2-1 (for Francisco J Cubero and Yulia A Nevzorova); National Institute of Health (NIH)/National Institute of Alcohol Abuse and Alcoholism (NIAAA) 1U01AA026972-01 (For Pau Sancho-Bru); Junta de Castilla y León SA074P20 (for Jose J. G. Marin); Junta de Andalucía, Grupo PAIDI BIO311 (for Franz Martin); CIBERER Acciones Cooperativas y Complementarias Intramurales ACCI20-35 (for Mario F. Fraga); Ministerio de Educación, Cultura y Deporte FPU17/04992 (for Silvia Ariño); Fundació Marato TV3 201916-31 (for Jose J. G. Marin.); Ainize Pena-Cearra is a fellow of the University of the Basque Country (UPV/ EHU); BIOEF (Basque Foundation for Innovation and Health Research); Asociación Española contra el Cáncer (Maria Luz Martinez-Chantar and Teresa C. Delgado.); Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (for Maria Luz Martinez-Chantar); La Caixa Foundation Program (for Maria Luz Martinez-Chantar); Proyecto Desarrollo Tecnologico CIBERehd (for Maria Luz Martinez-Chantar); Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III.S

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure

Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Diseño de un Dispositivo de Rehabilitación para la Articulación de Muñeca desde el Enfoque de la Ingeniería Concurrente

International audienceEn esta investigación se desarrolló el diseño de un dispositivo de rehabilitación automatizado para la articulación de la muñeca, el cualpuede ser empleado especialmente para los cuadros de tendinitis, sinovitis, artritis reumatoidea y procesos de terapia pre y postoperatoriapara dicha articulación. Durante la etapa de diseño se hicieron numerosas investigaciones relacionadas con los equipos que han sido utilizados parala rehabilitación en dichas patologías, así como un estudio antropométrico en el que se definen las dimensiones y ángulos de movimiento dela articulación de la muñeca en la población venezolana. A partir de la información recolectada se elaboraron diferentes propuestas deconceptos de diseño, las cuales fueron evaluadas mediante la aplicación del Proceso Analítico de Jerarquía a través de la definición de criteriosy atributos de diseño relacionados con su funcionalidad. Luego de la evaluación y selección de las propuestas se utilizaron programasCAD para la definición de las formas, geometrías y materiales de los diferentes componentes del dispositivo, y estos componentes se analizaron posteriormente a través de la utilización de programas CAE, con los cuales se logró determinar el estado tensional de esfuerzos ydeformación de las diferentes piezas que componen el dispositivo. Adicionalmente se desarrolló un software para la adquisición y registro de los diferentes movimientos producidos durante la ejecución de la terapia de rehabilitación, así como una aplicación computarizada parala reproducción y ejecución de los ejercicios terapéuticos. Finalmente, mediante la investigación desarrollada se logró diseñar un dispositivo queayudara a la rehabilitación de la articulación de la muñeca permitiendo hacer la combinación de movimientos de flexión dorsal-palmar y cubital-radial y contribuyendo así a la recuperación de la funcionalidad de la articulación con diversas patologías presentadas en la población venezolana. Otras de las características resaltantes del diseño propuesto fue su facilidad de manufactura

Diseño de un Dispositivo de Rehabilitación para la Articulación de Muñeca desde el Enfoque de la Ingeniería Concurrente

International audienceEn esta investigación se desarrolló el diseño de un dispositivo de rehabilitación automatizado para la articulación de la muñeca, el cualpuede ser empleado especialmente para los cuadros de tendinitis, sinovitis, artritis reumatoidea y procesos de terapia pre y postoperatoriapara dicha articulación. Durante la etapa de diseño se hicieron numerosas investigaciones relacionadas con los equipos que han sido utilizados parala rehabilitación en dichas patologías, así como un estudio antropométrico en el que se definen las dimensiones y ángulos de movimiento dela articulación de la muñeca en la población venezolana. A partir de la información recolectada se elaboraron diferentes propuestas deconceptos de diseño, las cuales fueron evaluadas mediante la aplicación del Proceso Analítico de Jerarquía a través de la definición de criteriosy atributos de diseño relacionados con su funcionalidad. Luego de la evaluación y selección de las propuestas se utilizaron programasCAD para la definición de las formas, geometrías y materiales de los diferentes componentes del dispositivo, y estos componentes se analizaron posteriormente a través de la utilización de programas CAE, con los cuales se logró determinar el estado tensional de esfuerzos ydeformación de las diferentes piezas que componen el dispositivo. Adicionalmente se desarrolló un software para la adquisición y registro de los diferentes movimientos producidos durante la ejecución de la terapia de rehabilitación, así como una aplicación computarizada parala reproducción y ejecución de los ejercicios terapéuticos. Finalmente, mediante la investigación desarrollada se logró diseñar un dispositivo queayudara a la rehabilitación de la articulación de la muñeca permitiendo hacer la combinación de movimientos de flexión dorsal-palmar y cubital-radial y contribuyendo así a la recuperación de la funcionalidad de la articulación con diversas patologías presentadas en la población venezolana. Otras de las características resaltantes del diseño propuesto fue su facilidad de manufactura