Isolation of entomopathogenic nematodes and control of Phyllophaga vetula Horn in Oaxaca, Mexico

This study aimed to isolate native entomopathogenic nematodes (EPN) in the Central Valleys of Oaxaca and to determine their potential for control of white grub (Phyllophaga vetula Horn). Fifty-five (55) soil samples were collected in 13 communities in the period August to October 2008 and 29.1% of these were found positive for EPN. Five isolates were selected for their apparent pathogenicity to third instar Galleria mellonella; two of the genus Steinernema and three Heterorhabditis. After evaluating these five isolates for control of white grubs, the Heterorhabditidae EPN presented the lowest values for both lethal dosages and lethal times. Using  polymerase chain reaction (PCR) procedures, the species Heterorhabditis mexicana, Steinernema  carpocapsae and Steinernema feltiae were identified. We concluded that H. mexicana was the most effective isolate for control of P. vetula larvae.Key words: Entomopathogenic nematodes, Steinernema, Heterorhabditis, bioassays, lethal dosages

Tracking changes on soil structure and organic carbon sequestration after 30 years of different tillage and management practices

Long-term field trials are essential for monitoring the effects of sustainable land management strategies for adaptation and mitigation to climate change. The influence of more than thirty years of different management is analyzed on extensive crops under three tillage systems, conventional tillage (CT), minimum tillage (MT), and no-tillage (NT), and with two crop rotations, monoculture winter-wheat (Triticum aestivum L.) and wheat-vetch (Triticum aestivum L.-Vicia sativa L.), widely present in the center of Spain. The soil under NT experienced the largest change in organic carbon (SOC) sequestration, macroaggregate stability, and bulk density. In the MT and NT treatments, SOC content was still increasing after 32 years, being 26.5 and 32.2 Mg ha−1, respectively, compared to 20.8 Mg ha−1 in CT. The SOC stratification (ratio of SOC at the topsoil/SOC at the layer underneath), an indicator of soil conservation, increased with decreasing tillage intensity (2.32, 1.36, and 1.01 for NT, MT, and CT respectively). Tillage intensity affected the majority of soil parameters, except the water stable aggregates, infiltration, and porosity. The NT treatment increased available water, but only in monocropping. More water was retained at the permanent wilting point in NT treatments, which can be a disadvantage in dry periods of these edaphoclimatic conditions

Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer's disease

Designing drugs with a specific multi-target profile is a promising approach against multifactorial illnesses as Alzheimer's disease. In this work, new indazole ethers that possess dual activity as both cannabinoid agonists CB2 and inhibitors of BuChE have been designed by computational methods. On the basis of this knowledge, the synthesis, pharmacological evaluation and docking studies of a new class of indazoles has been performed. Pharmacological evaluation includes radioligand binding assays with [3H]-CP55940 for CB1R and CB2R and functional activity for cannabinoid receptors on isolated tissue. Additionally, in vitro inhibitory assays of AChE/BuChE and the corresponding competition studies have been carried out. The results of pharmacological tests have revealed that three of these derivatives behave as CB2 cannabinoid agonists and simultaneously show BuChE inhibition. In particular, compounds 3 and 24 have emerged as promising candidates as novel cannabinoids that inhibit BuChE by a non-competitive or mixed mechanism, respectively. On the other hand, both molecules show antioxidant properties. © 2013 Elsevier Masson SAS. All rights reserved.Peer Reviewe

Diversidad de artrópodos y sus enemigos naturales asociados al café (Coffea arabica L.) en El Salvador

El presente libro pretende dar un aporte en tal sentido, ofreciendo al lector una muestra de la diversidad de fauna invertebrada que se pueden encontrar en los cafetales bajo variados niveles de tecnificación y que en la mayoría de casos se ha logrado comprobar su cría a expensas del cultivo. Sin duda alguna que el esfuerzo no es del todo exhaustivo ya que existe mucha más diversidad por descubrir; pero es una muestra representativa del reto que representa el estudio de la fauna de artrópodos de este cultivo. En consecuencia se espera que motive al lector y a otros interesados en la temática, para profundizar en estos estudios de los cafetales y aumentar así el conocimiento de la entomología nacional. Por tanto, el presente libro ilustra los insectos, arañas y caracoles que están en poblaciones no dañinas que comprende 60 fotografías de arañas depredadoras y 350 fotografías de insectos entre fitófagos y benéficos (depredadores y parasitoides), con más de 200 especies de artrópodos asociados a los cafetales de El Salvador

Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization

Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3 treatment-related adverse events observed (hypersensitivity and diarrhea). The discharge rates by Days 8 and 15 were 56.8% and 81.8%, respectively, with data sustaining dose-effect. A mean 4.2 log10 viral load reduction was attained by Day 15. Improvement in inflammation markers was also noted in a seemingly dose-dependent manner. These results suggest that plitidepsin impacts the outcome of patients with COVID-19.This study has been funded by Pharmamar, S.A. (Madrid, Spain). This work was supported by grants from the Government of Spain (PIE_INTRAMURAL_ LINEA 1 - 202020E079; PIE_INTRAMURAL_CSIC-202020E043). The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. We also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). N.I.U. has non-restrictive funding from PharmaMar to study the antiviral effect of Plitidepsin. N.J.K. was funded by grants from the National Institutes of Health (P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, and P01AI063302); by the Excellence in Research Award (ERA) from the Laboratory for Genomics Research (LGR), a collaboration between UCSF, UCB, and GSK (#133122P); by the Roddenberry Foundation, and gifts from QCRG philanthropic donors. This work was supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement #HR0011-19-2-0020. The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. This research was partly funded by CRIP (Center for Research for Influenza Pathogenesis), a NIAID supported Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), by DARPA grant HR0011-19-2-0020, by supplements to NIAID grants U19AI142733, U19AI135972 and DoD grant W81XWH-20-1-0270, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)), and anonymous donors to AG-S. S.Y. received funding from a Swiss National Foundation (SNF) Early Postdoc Mobility fellowship (P2GEP3_184202).N

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.This work was supported by grants from the Government of Spain (PIE_INTRAMURAL_ LINEA 1 - 202020E079; PIE_INTRAMURAL_CSIC-202020E043). The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. We also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). N Izquierdo-Useros has nonrestrictive funding from PharmaMar to study the antiviral effect of Plitidepsin. NJ Krogan was funded by grants from the National Institutes of Health (P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, and P01AI063302); by the Excellence in Research Award (ERA) from the Laboratory for Genomics Research (LGR), a collaboration between the University of California, San Francisco (UCSF), University of California, Berkley (UCB), and GlaxoSmithKline (GSK) (#133122P); by the Roddenberry Foundation, and gifts from QCRG philanthropic donors. This work was supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement #HR0011-19-2-0020. The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. This research was partly funded by Center for Research for Influenza Pathogenesis and Transmission (CRIPT), a National Institute of Allergy and Infectious Diseases (NIAID) supported Center of Excellence for Influenza Research and Response (CEIRS, contract # 75N93021C00014), by DARPA grant HR0011-19-2-0020, by supplements to NIAID grants U19AI142733, U19AI135972, and DoD grant W81XWH-20-1-0270, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)), and anonymous donors to A García-Sastre. S Yildiz received funding from a Swiss National Foundation Early Postdoc Mobility fellowship (P2GEP3_184202).Peer reviewe

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Evolución posquirúrgica de 7 sarcomas pulmonares primitivos

Los sarcomas primitivos pulmonares son muy raros, pero no los metastásicos. Se analizaron 7 sarcomas primarios operados en nuestro servicio entre 1985 y 2001. El diagnóstico histológico preoperatorio fue correcto en 2 pacientes. Se realizó cirugía en todos. En uno se amplió la resección a aurícula izquierda, en otro a pared torácica y en otros 2 se extirpó pleura parietal. Se consideró cirugía completa en 6 casos. En el estudio histológico 4 fueron fibrohistiocitomas malignos, uno angiosarcoma, uno sarcoma osteogénico y uno sarcoma indiferenciado. Las adenopatías extirpadas estaban libres de tumor. Se hizo tratamiento complementario en 3 pacientes. En los 3 de mayor supervivencia se realizó sólo cirugía, con un seguimiento de 16, 9 y 4 años, respectivamente. Uno tiene actualmente una recidiva tumoral nodular en pulmón único. En cuanto a los fallecidos, 3 murieron antes de un año y otro después de 24 meses de evolución. En conclusión, la cirugía en los sarcomas pulmonares primitivos puede conseguir una elevada supervivenci

Experiencia de 25 años en tumores vasculares de la pared torácica

En el período de 1978 a 2003 realizamos 73 intervenciones en tumores de la pared del tórax, de los cuales 6 eran tumores vasculares, un 8,2%. Cuatro eran tumores de partes blandas y 2 tenían afectación ósea. El diagnóstico histológico fue de 4 hemangiomas, un hemangioendotelioma y un angiosarcoma de bajo grado. En todos el diagnóstico se estableció tras la cirugía, excepto en un caso que había sido diagnosticado previamente en un intento de resección antes de llegar a nuestro servicio. A 4 enfermos se les realizó una punción-aspiración con aguja fina, que no fue concluyente en ningún caso. Se practicó resección completa del tumor en todos los pacientes, con un margen superior a 3 cm. En un enfermo con fístula arteriovenosa y angiomatosis difusa se practicó embolización con posterior ligadura quirúrgica de los vasos intercostales antes de la resección tumoral. La reconstrucción parietal del defecto tras la extirpación del tumor se llevó a cabo con tejidos propios, excepto en un caso en que utilizamos placa de Marlex y prótesis metálica para evitar la deformidad de la arcada costal inferior. Hemos realizado seguimiento de todos los enfermos, que en la actualidad están vivos y sin signos de recidiva, entre 2 y 25 años tras la cirugía