A Meta-Analysis on the Effects of Hydroxychloroquine on COVID-19.

Introduction Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread throughout the world with a large medical and economic impact. On March 12, 2020, the World Health Organization (WHO) classified SARS-CoV-2 as a pandemic. As a result of this worldwide public health crisis, politicians, elected officials, and healthcare professionals emergently began trialing hydroxychloroquine (HCQ) in efforts to treat and prevent the transmission of the virus. This meta-analysis was performed to assess the effects of HCQ on patients with COVID-19. Methods This meta-analysis adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMA) guidelines. Selected articles published between December 2019 and July 2020 were found utilizing the following search engines: PubMed, Google Scholar, Cochrane Library, DisasterLit, Clinicaltrials.gov, Medrxiv, and Embase. Two independent physician reviewers screened eligible articles that met the inclusion and exclusion criteria of the analysis. The outcome measures analyzed were mortality rate, rate of disease progression/improvement, rate of disease severity, and adverse effects of treatment. Six out of 14 studies that met the study\u27s eligibility criteria were selected and further analyzed, with a total of 381 participants (n= 381). Conclusion From the studies analyzed, it was found that groups treated with HCQ had an overall mortality rate that was 2.5 times greater than that of the control group. HCQ treated patients had higher rates of adverse clinical outcomes and side effects compared with the control populations. Lastly, there was a 1.2 times higher rate of improvement in the group of HCQ treated patients with mild to moderate symptoms as compared to the control group

Influencia de la fertilización nitrogenada, sistema de riego, tipo de plantación y variedad en la productividad, calidad y composición nutritiva de las hojas de fresón

En 2 ensayos de campo realizados con fresón se estudié la influencia de 3 niveles de fertigación nitrogenada en la productividad, calidad de los frutos y contenido nutritivo en plantas frigo y frescas bajo dos sistemas: goteo e inundación. Los datos de producción obtenidos con las variedades Douglas y Chandler indican ausencia de respuesta a la fertilización nitrogenada a dosis superiores a 150 y 75 Kg N/ha en plantación de verano y otoño, respectivamente. Las plantas frigo resultaron mucho mas productivas que las frescas, y el riego por goteo produjo, con respecto al de inundación, considerables aumentos de rendimiento. Las dosis más altas de N provocaron una disminución en el tamaño y en la resistencia a la deformación por compresión. Los contenidos de NO3, en pecíolos y de N en hojas presentaron una ligera tendencia a aumentar con las sucesivas dosis de fertilización nitrogenada; y la variedad Chandler produjo niveles de N alrededor de 0,20% mas bajos que la Douglas

Recombinant human erythropoietin in the treatment of chemotherapy-induced anemia and prevention of transfusion requirement associated with solid tumors: A randomized, controlled study

Background: Anemia is a common side effect of anticancer chemotherapy. Blood transfusion, previously the only available treatment for chemotherapy-induced anemia, may result insome clinical or subclinical adverse effects in the recipients. Recombinant human erythropoietin (rhEPO) provides a new treatment modality for chemotherapy-induced anemia. Patients and methods: To evaluate the effect of rhEPO onthe need for blood transfusions and on hemoglobin (Hb)concentrations, 227 patients with solid tumors and chemotherapy-induced anemia were enrolled in a randomized, controlled, clinical trial. Of 189 patients evaluable for efficacy, 101 received 5000 IU rhEPO daily s.c, while 88 patients received no treatment during the 12-week controlled phase of the study. Results: The results demonstrate a statistically significant reduction in the need for blood transfusions (28% vs. 42%, P = 0.028) and in the mean volume of packed red blood cells transfused (152 ml vs. 190 ml, p = 0.044) in patients treated with rhEPO compared to untreated controls. This effect was even more pronounced in patients receiving platinum-based chemotherapy (26% vs. 45%, % 0.038). During the controlled treatment phase, the median Hb values increased in the rhEPO patients while remaining unchanged in the control group. The response was seen in all tumor types. Conclusions: RhEPO administration at a dose of 5000 IU daily s.c. increases hemoglobin levels and reduces transfusionrequirements in chemotherapy-induced anemia, especially during platinum-based chemotherap

Métodos y progreso de la conservación de los recursos genéticos de los olmos en Europa

The progress made in the conservation of European elm genetic resources since the 1st International Elm Conference is reviewed, and the complementarity of in situ and ex situ methods is discussed. The financial support of the European Union to RESGEN project CT96-78 has permitted to co-ordinate and rationalize the ex situ conservation of elms. The project, which involved 17 partner institutes in nine west European countries, aimed at a better evaluation, conservation and utilisation of the existing collections of native elm clones. Main achievements are: establishing a common database of about 2,000 clones; characterizing over 500 clones through RAPDs and chloroplast DNA PCR-RFLPs molecular markers; completing and rationalizing the existing collections; establishing a long-term core collection of 850 clones; cryo-preserving a subset of 444 clones; and identifying clones of interest for breeding and prudent use in the reconstruction of countryside hedges. The «Noble Hardwoods» network of the pan-European programme EUFORGEN groups members representative of 31 countries, and promotes the dynamic conservation of the genetic resources of several genera of broadleaf forest trees, including Ulmus spp. Strategies for the conservation of the adaptive potential of elm resources were defined and will be disseminated among foresters and conservationists through «Guidelines» leaflets. Some countries have already started implementing conservation measures for U. laevis, associating in situ preservation and the establishment of seed orchards. Others are undertaking inventories, or acquiring genetic knowledge on target populations.Se discute el progreso realizado en la conservación de los olmos europeos desde la primera conferencia Internacional del Olmo y los métodos complementarios de conservación in situ y ex situ. El apoyo financiero de la Unión Europea al proyecto RESGEN CT96-78 ha permitido coordinar y racionalizar la conservación ex situ de los olmos. El proyecto, en el cual están involucrados 17 instituciones participantes en nueve países de Europa Occidental, tiene por objetivo una mejor evaluación, conservación y utilización de las colecciones actualmente existentes de clones nativos de olmo. Los principales logros son: el establecimiento de una base de datos común de aproximadamente 2.000 clones; la caracterización de más de 500 clones usando RAPD y marcadores moleculares PCR-RFLP de ADN cloroplástico; la finalización y racionalización de las colecciones existentes; el establecimiento a largo plazo de una colección central con 850 clones; la criopreservación de un conjunto de 444 clones; y la identificación de clones de interés para la mejora y para su uso en la restauración de setos en campo. La red «Noble Hardwoods» del programa pan-europeo EUFORGEN agrupa a miembros representantes de 31 países, y promueve la conservación dinámica de los recursos genéticos de varios géneros de árboles planifolios, incluido Ulmus spp.. Las estrategias para la conservación del potencial adaptativo de los recursos de los olmos se definieron y se dieron a conocer entre forestales y conservacionistas a través de folletos guía. Algunos países han comenzado ya a implementar medidas de conservación para U. laevis mediante el uso de la preservación in situ y el establecimiento de huertos semilleros. Otros están elaborando inventarios, o adquiriendo información genética de poblaciones de interés

Overview of resource and turbine modelling in the Tidal Stream Industry Energiser Project: TIGER

This is the author accepted manuscript. The final version is available from EWTEC via the DOI in this recordTidal energy projects require numerical modelling for the assessment of tidal site conditions and turbine/array performance. The Interreg TIGER project has offered a unique opportunity to implement a wide range of numerical models. This paper provides an overview and comparison of the different numerical models developed by academic partners in the TIGER project. The models cover a variety of spatial and temporal scales. The largest scale models provide long-term climatic studies covering the entire English Channel region, at relatively low resolution, whilst the highest-resolution models provide detailed information about short-term and small-scale turbulent flow and its interaction with tidal turbines. The models are used for various purposes. At one end of the scale, the models have been used to inform the large-scale techno-economic assessment of tidal energy and its impact on the energy mix in the UK and France. At the other end of the scale, the numerical models provide information that feeds into detailed engineering design of tidal turbines at particular sites, and assessment of the energy yield. The models showcase the range of computational tools available to aid the development of the tidal energy industry. This paper will be useful for investors, technology developers and project stakeholders to help identify suitable numerical models to support and develop ongoing and future tidal stream projects.European Regional Development Fund (ERDF

Novel lines of Pax6-/- embryonic stem cells exhibit reduced neurogenic capacity without loss of viability

<p>Abstract</p> <p>Background</p> <p>Embryonic stem (ES) cells can differentiate into all cell types and have been used extensively to study factors affecting neuronal differentiation. ES cells containing mutations in known genes have the potential to provide useful in vitro models for the study of gene function during neuronal differentiation. Recently, mouse ES cell lines lacking the neurogenic transcription factor Pax6 were reported; neurons derived from these <it>Pax6</it>^-/-ES cells died rapidly after neuronal differentiation in vitro.</p> <p>Results</p> <p>Here we report the derivation of new lines of <it>Pax6</it>^-/-ES cells and the assessment of their ability to survive and differentiate both in vitro and in vivo. Neurons derived from our new <it>Pax6</it>^-/-lines were viable and continued to elaborate processes in culture under conditions that resulted in the death of neurons derived from previously reported <it>Pax6</it>^-/-ES cell lines. The new lines of <it>Pax6</it>^-/-ES cells showed reduced neurogenic potential, mimicking the effects of loss of Pax6 in vivo. We used our new lines to generate <it>Pax6</it>^-/-↔ <it>Pax6</it>^+/+chimeras in which the mutant cells survived and displayed the same phenotypes as <it>Pax6</it>^-/-cells in <it>Pax6</it>^-/-↔ <it>Pax6</it>^+/+chimeras made by embryo aggregation.</p> <p>Conclusions</p> <p>We suggest that loss of Pax6 from ES cells reduces their neurogenic capacity but does not necessarily result in the death of derived neurons. We offer these new lines as additional tools for those interested in the generation of chimeras and the analysis of in vitro ES cell models of Pax6 function during neuronal differentiation, embryonic and postnatal development.</p

The Rho-Family GTPase Rac1 Regulates Integrin Localization in Drosophila Immunosurveillance Cells

BACKGROUND: When the parasitoid wasp Leptopilina boulardi lays an egg in a Drosophila larva, phagocytic cells called plasmatocytes and specialized cells known as lamellocytes encapsulate the egg. The Drosophila β-integrin Myospheroid (Mys) is necessary for lamellocytes to adhere to the cellular capsule surrounding L. boulardi eggs. Integrins are heterodimeric adhesion receptors consisting of α and β subunits, and similar to other plasma membrane receptors undergo ligand-dependent endocytosis. In mammalian cells it is known that integrin binding to the extracellular matrix induces the activation of Rac GTPases, and we have previously shown that Rac1 and Rac2 are necessary for a proper encapsulation response in Drosophila larvae. We wanted to test the possibility that Myospheroid and Rac GTPases interact during the Drosophila anti-parasitoid immune response. RESULTS: In the current study we demonstrate that Rac1 is required for the proper localization of Myospheroid to the cell periphery of haemocytes after parasitization. Interestingly, the mislocalization of Myospheroid in Rac1 mutants is rescued by hyperthermia, involving the heat shock protein Hsp83. From these results we conclude that Rac1 and Hsp83 are required for the proper localization of Mys after parasitization. SIGNIFICANCE: We show for the first time that the small GTPase Rac1 is required for Mysopheroid localization. Interestingly, the necessity of Rac1 in Mys localization was negated by hyperthermia. This presents a problem, in Drosophila we quite often raise larvae at 29°C when using the GAL4/UAS misexpression system. If hyperthermia rescues receptor endosomal recycling defects, raising larvae in hyperthermic conditions may mask potentially interesting phenotypes

Combined loss of the BH3-only proteins Bim and Bmf restores B-cell development and function in TACI-Ig transgenic mice.

Terminal differentiation of B cells depends on two interconnected survival pathways, elicited by the B-cell receptor (BCR) and the BAFF receptor (BAFF-R), respectively. Loss of either signaling pathway arrests B-cell development. Although BCR-dependent survival depends mainly on the activation of the v-AKT murine thymoma viral oncogene homolog 1 (AKT)/PI3-kinase network, BAFF/BAFF-R-mediated survival engages non-canonical NF-κB signaling as well as MAPK/extracellular-signal regulated kinase and AKT/PI3-kinase modules to allow proper B-cell development. Plasma cell survival, however, is independent of BAFF-R and regulated by APRIL that signals NF-κB activation via alternative receptors, that is, transmembrane activator and CAML interactor (TACI) or B-cell maturation (BCMA). All these complex signaling events are believed to secure survival by increased expression of anti-apoptotic B-cell lymphoma 2 (Bcl2) family proteins in developing and mature B cells. Curiously, how lack of BAFF- or APRIL-mediated signaling triggers B-cell apoptosis remains largely unexplored. Here, we show that two pro-apoptotic members of the 'Bcl2 homology domain 3-only' subgroup of the Bcl2 family, Bcl2 interacting mediator of cell death (Bim) and Bcl2 modifying factor (Bmf), mediate apoptosis in the context of TACI-Ig overexpression that effectively neutralizes BAFF as well as APRIL. Surprisingly, although Bcl2 overexpression triggers B-cell hyperplasia exceeding the one observed in Bim(-/-)Bmf(-/-) mice, Bcl2 transgenic B cells remain susceptible to the effects of TACI-Ig expression in vivo, leading to ameliorated pathology in Vav-Bcl2 transgenic mice. Together, our findings shed new light on the molecular machinery restricting B-cell survival during development, normal homeostasis and under pathological conditions. Our data further suggest that Bcl2 antagonists might improve the potency of BAFF/APRIL-depletion strategies in B-cell-driven pathologies