Diseases transmissible by transfusion of blood components

La complejidad de la medicina transfusional actual, está dada por los avances en el conocimiento de la inmunohematología de cada uno de los componentes sanguíneos, y de sus indicaciones. Igualmente se debe garantizar la transfusión de unidades seguras para el resepto. Cada unidad de sangre debe ser obtenida de un donante seleccionado, ser sometida a una tipificación de grupo sanguíneo, a la separación en sus componentes, y una serie de estudios serológicos que garanticen el mínimo riesgo de transmisión de una enfermedad infecciosa por esta vía.The complexity of current transfusion medicine is given by advances in knowledge of the immunohematology of each of the blood components, and their indications. Likewise, the transfusion of safe units for resept must be guaranteed. Each unit of blood must be obtained from a selected donor, be subjected to blood group typing, separation into its components, and a series of serological studies that guarantee the minimum risk of transmission of an infectious disease through this rout

Inhibidores contra los factores de la coagulación adquiridos espontáneamente: Hemofilia B adquirida

ResumenLos inhibidores adquiridos  del factor IX son extremadamente raros. Un hombre de 70 años presentó sangrado profundo continuo luego de una cirugía ortopédica. Su PTT activado inicial fue 77.4 segundos (intervalo normal, 25-36) y su PT fue normal. La corrección del PTT activado expandido, resulta a favor del déficit del factor IX, confirmando el nivel de dicho factor 52%, con niveles normales de factor VIII. Esto fue realizado con plasma fresco congelado. Se presenta una revición exhaustiva del tema.[Sossa CI, Jiménez SI, Rodríguez P. Inhibidores contra los factores de la coagulación adquiridos espontáneamente: Hemofilia B adquirida. MedUNAB 2003; 6(16):36-38.]Palabras clave: Hemofilia B adquirida, factor IX, tiempo de tromboplastina parcial activado prolongado, tiempo de tromboplastina parcial cruzado

MYH10 activation rescues contractile defects in arrhythmogenic cardiomyopathy (ACM).

The most prevalent genetic form of inherited arrhythmogenic cardiomyopathy (ACM) is caused by mutations in desmosomal plakophilin-2 (PKP2). By studying pathogenic deletion mutations in the desmosomal protein PKP2, here we identify a general mechanism by which PKP2 delocalization restricts actomyosin network organization and cardiac sarcomeric contraction in this untreatable disease. Computational modeling of PKP2 variants reveals that the carboxy-terminal (CT) domain is required for N-terminal domain stabilization, which determines PKP2 cortical localization and function. In mutant PKP2 cells the expression of the interacting protein MYH10 rescues actomyosin disorganization. Conversely, dominant-negative MYH10 mutant expression mimics the pathogenic CT-deletion PKP2 mutant causing actin network abnormalities and right ventricle systolic dysfunction. A chemical activator of non-muscle myosins, 4-hydroxyacetophenone (4-HAP), also restores normal contractility. Our findings demonstrate that activation of MYH10 corrects the deleterious effect of PKP2 mutant over systolic cardiac contraction, with potential implications for ACM therapy.This study was supported by MCIU grant BFU2016-75144-R and PID2020- 116935RB-I00, and by a “la Caixa” Banking Foundation grant under the project code HR18-00304” to J.A.B.; The study was also supported by the “Ayudas a la Investigación Cátedra Real Madrid-Universidad Europea” (2017/RM01). C.M.-L. and S.S. hold MCIU predoctoral contracts BES-2017-079715, and BES-2017-079707 respectively. R.G. acknowledges funding from the European Research Council under grant ERCAG-340177 (3DNanoMech) and from the MCIU under grant MAT2016- 76507-R. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence, grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033. The microscopy experiments were carried out at the Dynamic Microscopy and Image Unit, CNIC, ICTS-ReDib, co-financed by MCIN/AEI /10.13039/ 501100011033 and FEDER “A way of making Europe” (#ICTS-2018-04- CNIC-16). Imaris full analysis were carried out at the Microscopy & Dynamic Imaging, CNIC, ICTS-ReDib, co-funded by MCIN/AEI /10.13039/501100011033. Biomedical Imaging has been conducted at the Advanced Imaging Unit of the CNIC (Centro Nacional de Investigaciones Cardiovasculares Carlos III), Madrid, Spain. This project used the ReDIB ICTS infrastructure TRIMA@CNIC, Ministerio de Ciencia e Innovación (MCIN).S

Modelling and Analysis of Central Metabolism Operating Regulatory Interactions in Salt Stress Conditions in a L-Carnitine Overproducing E. coli Strain

Based on experimental data from E. coli cultures, we have devised a mathematical model in the GMA-power law formalism that describes the central and L-carnitine metabolism in and between two steady states, non-osmotic and hyperosmotic (0.3 M NaCl). A key feature of this model is the introduction of type of kinetic order, the osmotic stress kinetic orders (gOSn), derived from the power law general formalism, which represent the effect of osmotic stress in each metabolic process of the model

The general fault in our fault lines

Pervading global narratives suggest that political polarization is increasing, yet the accuracy of such group meta-perceptions has been drawn into question. A recent US study suggests that these beliefs are inaccurate and drive polarized beliefs about out-groups. However, it also found that informing people of inaccuracies reduces those negative beliefs. In this work, we explore whether these results generalize to other countries. To achieve this, we replicate two of the original experiments with 10,207 participants across 26 countries. We focus on local group divisions, which we refer to as fault lines. We find broad generalizability for both inaccurate meta-perceptions and reduced negative motive attribution through a simple disclosure intervention. We conclude that inaccurate and negative group meta-perceptions are exhibited in myriad contexts and that informing individuals of their misperceptions can yield positive benefits for intergroup relations. Such generalizability highlights a robust phenomenon with implications for political discourse worldwide

RLIP76, a Glutathione-Conjugate Transporter, Plays a Major Role in the Pathogenesis of Metabolic Syndrome

PURPOSE: Characteristic hypoglycemia, hypotriglyceridemia, hypocholesterolemia, lower body mass, and fat as well as pronounced insulin-sensitivity of RLIP76⁻/⁻ mice suggested to us the possibility that elevation of RLIP76 in response to stress could itself elicit metabolic syndrome (MSy). Indeed, if it were required for MSy, drugs used to treat MSy should have no effect on RLIP76⁻/⁻ mice. RESEARCH DESIGN AND METHODS: Blood glucose (BG) and lipid measurements were performed in RLIP76⁺/⁺ and RLIP76⁻/⁻ mice, using Ascensia Elite Glucometer® for glucose and ID Labs kits for cholesterol and triglycerides assays. The ultimate effectors of gluconeogenesis are the three enzymes: PEPCK, F-1,6-BPase, and G6Pase, and their expression is regulated by PPARγ and AMPK. The activity of these enzymes was tested by protocols standardized by us. Expressions of RLIP76, PPARα, PPARγ, HMGCR, pJNK, pAkt, and AMPK were performed by Western-blot and tissue staining. RESULTS: The concomitant activation of AMPK and PPARγ by inhibiting transport activity of RLIP76, despite inhibited activity of key glucocorticoid-regulated hepatic gluconeogenic enzymes like PEPCK, G6Pase and F-1,6-BP in RLIP76⁻/⁻ mice, is a salient finding of our studies. The decrease in RLIP76 protein expression by rosiglitazone and metformin is associated with an up-regulation of PPARγ and AMPK. CONCLUSIONS/SIGNIFICANCE: All four drugs, rosiglitazone, metformin, gemfibrozil and atorvastatin failed to affect glucose and lipid metabolism in RLIP76⁻/⁻ mice. Studies confirmed a model in which RLIP76 plays a central role in the pathogenesis of MSy and RLIP76 loss causes profound and global alterations of MSy signaling functions. RLIP76 is a novel target for single-molecule therapeutics for metabolic syndrome

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams