All-carbon microporous graphitic photocatalyst-promoted reduction of CO2 to CO in the absence of metals or dopant elements

[EN] Microporous graphitic carbon (mp-C) derived from the pyrolysis of alpha-, beta-, and gamma-cyclodextrins exhibited photocatalytic activity in CO2-saturated acetonitrile-water upon irradiation with UV-Vis light and in the presence of triethanolamine, forming H-2 (19 mu mol h(-1)) and CO (23 mu mol h(-1)) accompanied by a lesser proportion of CH4 (4 mu mol h(-1)). The most efficient was the mp-C material derived from alpha-cyclodextrin (mp-C-alpha) and having a pore dimension of 0.68 nm. The process also occured, although to a much lesser extent, under simulated sunlight or with UV-Vis irradiation in the absence of a sacrificial agent, with H2O being the electron donor. The origin of the CO was proved by isotopic C-13 labelling experiments. Photocurrent measurements proved the occurrence of charge separation and the increase in photocurrent intensity in the presence of CO2. Transient absorption spectroscopy was used to detect the charge separate state decay in the microsecond time scale and proved that a fraction of the photogenerated electrons were able to react with CO2.Financial support by the Spanish Ministry of Science and Innovation (Severo Ochoa, PID-2021-12607OB-C21 and RTI2018-89237-CO2-1) and Generalitat Valenciana (Prometeo 2021/083) are gratefully acknowledged. A. G.-M. thanks the Spanish Ministry of Science and Innovation for a postgraduate scholarship.Garcia-Mulero, A.; Asiri, AM.; Albero-Sancho, J.; Primo Arnau, AM.; García Gómez, H. (2022). All-carbon microporous graphitic photocatalyst-promoted reduction of CO2 to CO in the absence of metals or dopant elements. Nanoscale. 14(32):11575-11582. https://doi.org/10.1039/d2nr02655d1157511582143

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Microporous 3D graphitic carbons obtained by soft templating as carbocatalysts for aerobic oxidation

[EN] Herein it is reported that chitosan, a natural filmogenic biopolymer, can undergo soft-templating in liquid phase under hydrothermal conditions by two typical structure directing agents, namely hexamethyleneimine (HMI) and tetraethylammonium (TEA) employed in the synthesis of zeolites MCM-22 and Beta, respectively. After templation, pyrolysis of chitosan under inert atmosphere renders 3D graphitic sponges with defined ultra- and microporous channels. These porous structured graphitic carbons exhibit much enhanced activity as metal-free catalyst in the aerobic oxidation of benzylamine compared to other analogous 2D graphene oxide and reduced graphene oxide, as well as large area active carbons. It is proposed that this superior activity of these 3D structured microporous carbons derives from confinement effects activating molecular oxygen and benzylamine within the micropores. Quenching studies indicate that the reactive oxygen species are mostly adsorbed within the pores of the 3D graphitic carbonsFinancial support by the Spanish Ministry of Science and Innovation (RTI2018-098237-CO2-R1 and Severo Ochoa) and Generalitat Valenciana (Prometeo 2017/083) is gratefully acknowledged. H.G.B. and A.P. thank the Generalitat Valenciana and Spanish Ministry of Science and Innovation for their research associate contracts. A.G.M. thanks the Spanish Ministry of Science and Innovation for the scholarship FPU18/02706. A.D. thanks University Grants Commission for awarding Assistant Professorship under the Faculty recharge programGarcia-Mulero, A.; Garcia-Baldovi, H.; Dhakshinamoorthy, A.; Primo Arnau, AM.; Corma Canós, A.; García Gómez, H. (2021). Microporous 3D graphitic carbons obtained by soft templating as carbocatalysts for aerobic oxidation. Applied Catalysis A General. 612:1-8. https://doi.org/10.1016/j.apcata.2021.118014S1861

Band Engineering of Semiconducting Microporous Graphitic Carbons by Phosphorous Doping: Enhancing of Photocatalytic Overall Water Splitting

[EN] Carbon-based solar photocatalysts for overall water splitting could provide H2 as an energy vector in a clean and sustainable way. Band engineering to align energy levels can be achieved, among other ways, by doping. Herein, it is shown that phosphorous doping of microporous graphitic carbons derived from pyrolysis of ¿-, ß-, and ¿-cyclodextrin increases the valence band edge energy of the material, and the energy value of the conduction band decreases with the P content. In this way, P doping increases the activity of these metal-free materials in photocatalytic overall water splitting under simulated sunlight and visible-light illumination. The optimal P-doped photocatalyst in the absence of any metal as a cocatalyst affords, after 4 h of irradiation with simulated sunlight, a H2 production of 2.5 mmol of H2 × gcatalyst¿1 in the presence of methanol as the sacrificial agent or 225 ¿mol of H2 × gcatalyst¿1 from pure H2O.Financial support by the Spanish Ministry of Science and Innovation (Severo Ochoa and RTI-2018-98237-CO2-R1) and Generalitat Valenciana (Prometeo 2021/038) is gratefully acknowledged. A.G.M. and A. P. also thank the Spanish Ministry of Science and Innovation by a postgraduate scholarship and a Ramon y Cajal research associate contract, respectively.Garcia-Mulero, A.; Rendón-Patiño, A.; Asiri, AM.; Primo Arnau, AM.; García Gómez, H. (2021). Band Engineering of Semiconducting Microporous Graphitic Carbons by Phosphorous Doping: Enhancing of Photocatalytic Overall Water Splitting. ACS Applied Materials & Interfaces. 13(41):48753-48763. https://doi.org/10.1021/acsami.1c14357S4875348763134

NAMPT-derived NAD(+) fuels PARP1 to promote skin inflammation through parthanatos cell death

Several studies have revealed a correlation between chronic inflammation and nicotinamide adenine dinucleotide (NAD(+)) metabolism, but the precise mechanism involved is unknown. Here, we report that the genetic and pharmacological inhibition of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the salvage pathway of NAD(+) biosynthesis, reduced oxidative stress, inflammation, and keratinocyte DNA damage, hyperproliferation, and cell death in zebrafish models of chronic skin inflammation, while all these effects were reversed by NAD(+) supplementation. Similarly, genetic and pharmacological inhibition of poly(ADP-ribose) (PAR) polymerase 1 (Parp1), overexpression of PAR glycohydrolase, inhibition of apoptosis-inducing factor 1, inhibition of NADPH oxidases, and reactive oxygen species (ROS) scavenging all phenocopied the effects of Nampt inhibition. Pharmacological inhibition of NADPH oxidases/NAMPT/PARP/AIFM1 axis decreased the expression of pathology-associated genes in human organotypic 3D skin models of psoriasis. Consistently, an aberrant induction of NAMPT and PARP activity, together with AIFM1 nuclear translocation, was observed in lesional skin from psoriasis patients. In conclusion, hyperactivation of PARP1 in response to ROS-induced DNA damage, fueled by NAMPT-derived NAD(+), mediates skin inflammation through parthanatos cell death

New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from 0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopath

New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab

none60siOverview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from &lt;1/3,300 in patients with anti-John Cunninghan virus antibody indices &lt;0.9 and relapse rate &gt;0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from &lt;1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices &lt;0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.mixedToboso, Inmaculada; Tejeda-Velarde, Amalia; Alvarez-Lafuente, Roberto; Arroyo, Rafael; Hegen, Harald; Deisenhammer, Florian; Sainz de la Maza, Susana; Alvarez-Cermeño, José C; Izquierdo, Guillermo; Paramo, Dolores; Oliva, Pedro; Casanova, Bonaventura; Agüera-Morales, Eduardo; Franciotta, Diego; Gastaldi, Matteo; Fernández, Oscar; Urbaneja, Patricia; Garcia-Dominguez, José M; Romero, Fernando; Laroni, Alice; Uccelli, Antonio; Perez-Sempere, Angel; Saiz, Albert; Blanco, Yolanda; Galimberti, Daniela; Scarpini, Elio; Espejo, Carmen; Montalban, Xavier; Rasche, Ludwig; Paul, Friedemann; González, Inés; Álvarez, Elena; Ramo, Cristina; Caminero, Ana B; Aladro, Yolanda; Calles, Carmen; Eguía, Pablo; Belenguer-Benavides, Antonio; Ramió-Torrentà, Lluis; Quintana, Ester; Martínez-Rodríguez, José E; Oterino, Agustín; López de Silanes, Carlos; Casanova, Luis I; Landete, Lamberto; Frederiksen, Jette; Bsteh, Gabriel; Mulero, Patricia; Comabella, Manuel; Hernández, Miguel A; Espiño, Mercedes; Prieto, José M; Pérez, Domingo; Otano, María; Padilla, Francisco; García-Merino, Juan A; Navarro, Laura; Muriel, Alfonso; Frossard, Lucienne Costa; Villar, Luisa MToboso, Inmaculada; Tejeda-Velarde, Amalia; Alvarez-Lafuente, Roberto; Arroyo, Rafael; Hegen, Harald; Deisenhammer, Florian; Sainz de la Maza, Susana; Alvarez-Cermeño, José C; Izquierdo, Guillermo; Paramo, Dolores; Oliva, Pedro; Casanova, Bonaventura; Agüera-Morales, Eduardo; Franciotta, Diego; Gastaldi, Matteo; Fernández, Oscar; Urbaneja, Patricia; Garcia-Dominguez, José M; Romero, Fernando; Laroni, Alice; Uccelli, Antonio; Perez-Sempere, Angel; Saiz, Albert; Blanco, Yolanda; Galimberti, Daniela; Scarpini, Elio; Espejo, Carmen; Montalban, Xavier; Rasche, Ludwig; Paul, Friedemann; González, Inés; Álvarez, Elena; Ramo, Cristina; Caminero, Ana B; Aladro, Yolanda; Calles, Carmen; Eguía, Pablo; Belenguer-Benavides, Antonio; Ramió-Torrentà, Lluis; Quintana, Ester; Martínez-Rodríguez, José E; Oterino, Agustín; López de Silanes, Carlos; Casanova, Luis I; Landete, Lamberto; Frederiksen, Jette; Bsteh, Gabriel; Mulero, Patricia; Comabella, Manuel; Hernández, Miguel A; Espiño, Mercedes; Prieto, José M; Pérez, Domingo; Otano, María; Padilla, Francisco; García-Merino, Juan A; Navarro, Laura; Muriel, Alfonso; Frossard, Lucienne Costa; Villar, Luisa

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I 2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None