First Case of Multiple Resistance to EPSPS and PSI in Eleusine indica (L.) Gaertn. Collected in Rice and Herbicide-Resistant Crops in Colombia

Eleusine indica is a highly competitive and difficult-to-control plant in annual and perennial crops. In Colombia, broad-spectrum herbicides, such as paraquat and glyphosate, have begun to present poor levels of control for this weed. The multiple resistance to glyphosate and paraquat, the increase in herbicide performance with adjuvants (Retenol® and Trend® 90), and alternative herbicides were evaluated in a resistant (R) population of E. indica collected in rice fields, which is rotated with herbicide-resistant (HR) crops. Based on plant mortality, the R population was 9.8 and 7.2 times more resistant than susceptible (S) plants to glyphosate and paraquat, respectively. R plants accumulated 4.2 less shikimic acid and had at least 70% less electrolyte leakage than S plants when they were exposed to glyphosate and paraquat, respectively. Both adjuvants increased the foliar retention of herbicides. In addition, adjuvants also increased the performance of glyphosate effectiveness between 22% and 58% and that of paraquat from 61% to 100%. Alternative herbicides (atrazine, clethodim, imazamox, diuron, flazasulfuron, glufosinate, oxyfluorfen, quizalofop, and tembotrione) provided high levels of control in both populations of E. indica. This is the first case of multiple resistant E. indica confirmed in Colombia. Adjuvants improved the leaf retention and efficacy of glyphosate and paraquat. In summary, the alternative herbicides evaluated in this study should be adopted by Colombian farmers and provide additional herbicide modes-of-action to combat future resistance

Infancia y flexibilidad laboral en la agricultura de exportación mexicana

Desde mediados de los ochenta del siglo pasado, la reducción del gasto público destinado al campo y la eliminación de barreras comerciales pusieron en juego la competitividad del sector agrícola mexicano. Las empresas adoptaron cambios tecnológicos y de organización laboral a partir de una combinación de mano de obra calificada con fuerza de trabajo desvalorizada por razones de género, edad o etnia; esta última opera en condiciones de amplia flexibilidad laboral. El presente artículo analiza las formas de inserción del trabajo infantil migrante en la agricultura de exportación mexicana. Los datos fueron levantados en un campo de jornaleros de una de las empresas más importantes del ramo. Se aplicó una encuesta a 66 familias y se hicieron 41 entrevistas semi-estructuradas, 3 talleres con infantes y una matriz de riesgos laborales. El 94% de los niños y niñas trabajan en el corte de pepino y jitomate y el 6% restante (chicas mayores de 14 años) en labores de empaque. Las niñas presentan una doble jornada de trabajo debido a sus responsabilidades domésticas. El ingreso promedio diario es de 97 pesos mexicanos (alrededor de $9.40 dólares de los EE. UU.), que contribuye a cerca de la mitad del ingreso global de la familia. Se concluye que el derecho a la educación y a la salud de la población infantil jornalera son los más afectados, ya que dos tercios de los niños y niñas encuestados no asisten a la escuela y sus condiciones de trabajo conllevan considerables riesgos para la salud.-1. Introducción. -2. Diseño metodológico. -3. Marco conceptual: flexibilidad laboral y trabajo infantil. -4. Flexibilidad laboral y trabajo infantil jornalero. -4.1. Eventualidad en el empleo. -4.2. Jornada laboral.-4.3. Forma de contratación y pago. -4.4. Riesgos para la salud. -5. Conclusiones. -Bibliografí

Estudio de la viabilidad de la integración de un Sistema de Posicionamiento Óptico en el entorno de la radioterapia intraoperatoria

Actas de: XXIX Congreso Anual de la Sociedad Espñaola de Ingeniería Biomédica (CASEIB 2011). Cáceres, 16-18 Noviembre 2011.La radioterapia intraoperatoria (RIO) es una técnica que combina cirugía y radioterapia, que se aplica en pacientes con tumores para los que se ha indicado su resección y con alto riesgo recidivante. El oncólogo radioterapeuta planifica esta intervención sobre una imagen TAC del paciente. Sin embargo, los datos del escenario real encontrado en la sala de tratamiento (posición y orientación del aplicador respecto del paciente y energía del haz) se deben recoger de forma manual para actualizar la planificación. Esta información es muy valiosa para la documentación y posterior seguimiento del procedimiento realizado. En este trabajo se evalúa la viabilidad de la integración de un sistema de posicionamiento óptico en el entorno RIO, y su precisión para localizar el aplicador sobre la imagen de planificación.Este trabajo ha sido financiado por el Minsiterio de Ciencia e Innovación (PI09/90568 IPT-3000000-2010-3, TEC2010-21619-C04-01), la Comunidad de Madrid (ARTEMIS S2009/DPI-1802) y fondos FEDER.Publicad

Intraoperative computed tomography imaging for dose calculation in intraoperative electron radiation therapy: Initial clinical observations

In intraoperative electron radiation therapy (IOERT) the energy of the electron beam is selected under the conventional assumption of water-equivalent tissues at the applicator end. However, the treatment field can deviate from the theoretic flat irradiation surface, thus altering dose profiles. This patient-based study explored the feasibility of acquiring intraoperative computed tomography (CT) studies for calculating three-dimensional dose distributions with two factors not included in the conventional assumption, namely the air gap from the applicator end to the irradiation surface and tissue heterogeneity. In addition, dose distributions under the conventional assumption and from preoperative CT studies (both also updated with intraoperative data) were calculated to explore whether there are other alternatives to intraoperative CT studies that can provide similar dose distributions. The IOERT protocol was modified to incorporate the acquisition of intraoperative CT studies before radiation delivery in six patients.This study was supported by Ministerio de Ciencia, Innovación y Universidades (http://www.ciencia.gob.es) [grant number TEC2013–48251-C2 to JP, VG-V and MJL-C], co-funded by European Regional Development Fund (ERDF), “A way of making Europe” (https://ec.europa.eu/regional_policy/en/funding/erdf); by Ministerio de Ciencia, Innovación y Universidades (http://www.ciencia.gob.es), Instituto de Salud Carlos III (https://www.isciii.es) [grant numbers DTS14/00192 to JP, VG-V and FAC; PI15/02121 to FAC and JC-H; PI18/01625 to JP], co-funded by European Regional Development Fund (ERDF), “A way of making Europe” (https://ec.europa.eu/regional_policy/en/funding/erdf); and by Comunidad de Madrid (http://www.comunidad.madrid) [grant number TOPUS-CM S2013/MIT3024 to JP], co-funded by European Structural and Investment Fund (https://ec.europa.eu/info/funding-tenders/funding-opportunities/funding-programmes/overview-funding-programmes_en). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades (http://www.ciencia.gob.es) and the Pro CNIC Foundation (https://www.fundacionprocnic.es) [to MD], and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Teladorsagia circumcincta beta tubulin: the presence of the E198L polymorphism on its own is associated with benzimidazole resistance.

BACKGROUND NlmCategory: BACKGROUND content: "Benzimidazole resistance is associated with isotype-1 \xCE\xB2-tubulin gene F200Y, E198A and F167Y SNPs. In this study, the recently described polymorphism E198L was reported and analysed in Teladorsagia circumcincta." - Label: METHODS NlmCategory: METHODS content: "The benzimidazole phenotypic resistance was measured by the faecal egg count reduction test (FECRT) and the egg hatch test (EHT) using a discriminating dose (DD) in 39 sheep flocks. Around 1000 larvae collected before and after treatment were used for DNA extraction. The resistant species identified in all flocks was T. circumcincta. The resistance alleles frequencies were measured for F200Y and E198A. A 371-bp fragment of the isotype-1 \xCE\xB2-tubulin gene was analysed, including the three codons of interest, and a new pyrosequencing assay was designed for testing E198L." - Label: RESULTS NlmCategory: RESULTS content: "The percentage of resistant flocks was 35% by FECRT or 26% by EHT; however, F200Y and E198A SNPs were absent in T. circumcincta. The amplification of a 371-bp fragment confirmed the absence of F167Y and F200Y in 6 resistant flocks. Regarding codon 198, all samples after treatment carried a leucine (CTA). A pyrosequencing assay analysed the allele frequencies for the first two bases at codon 198 independently, G/C and A/T. The correlation between C and T frequencies was almost 1 (r\xE2\x80\x89=\xE2\x80\x890.929, P\xE2\x80\x89<\xE2\x80\x890.0001) and the mean value of both was calculated to measure the leucine frequency; this value ranged between 10.4-80.7% before treatment, and 82.3-92.8% after treatment. High and similar correlations were reported between the genotypic variables (C frequency, T frequency or mean of both frequencies) and phenotypic resistance (r\xE2\x80\x89>\xE2\x80\x890.720, P\xE2\x80\x89<\xE2\x80\x890.0001), although negatively associated with the FECRT and positively with the EHT. According to multivariate linear regression analysis, the T frequency was the most significant variable influencing the phenotypic resistance (FECRT or EHT; P\xE2\x80\x89<\xE2\x80\x890.0001). In the EHT, 67.1% of the phenotypic variability is associated with the T frequency but in the FECRT only 33.4%; therefore, the EHT using a DD seems to detect the genotypic resistance more accurately than the FECRT." - Label: CONCLUSIONS NlmCategory: CONCLUSIONS content: The E198L polymorphism can confer BZ resistance on its own in T. circumcincta

ANGPTL-4 is Associated with Obesity and Lipid Profile in Children and Adolescents

Angiopoietin-like protein 4 (ANGPTL-4) regulates lipidic metabolism and affects energy homeostasis. However, its function in children with obesity remains unknown. We investigated plasma ANGPTL-4 levels in children and its relationship with body mass index (BMI) and different lipidic parameters such as free fatty acids (FFA). Plasma ANGPTL-4 levels were analyzed in two different cohorts. In the first cohort (n = 150, age 3–17 years), which included children with normal weight or obesity, we performed a cross-sectional study. In the second cohort, which included only children with obesity (n = 20, age 5–18 years) followed up for two years after an intervention for weight loss, in which we performed a longitudinal study measuring ANGPTL-4 before and after BMI-loss. In the cross-sectional study, circulating ANGPTL-4 levels were lower in children with obesity than in those with normal weight. Moreover, ANGPTL-4 presented a negative correlation with BMI, waist circumference, weight, insulin, homeostasis model assessment of insulin resistance index (HOMA index), triglycerides, and leptin, and a positive correlation with FFA and vitamin-D. In the longitudinal study, the percent change in plasma ANGPTL-4 was correlated with the percent change in FFA, total-cholesterol and high-density lipoprotein cholesterol. This study reveals a significant association of ANGPTL-4 with pediatric obesity and plasma lipid profileThis research was funded by INSTITUTO DE SALUD CARLOS III cofounded by FEDER, grants number PI18/00998, PI15/01272, PI11/02042, PI16/01301, and PI16/00871, and FUNDACIÓN MUTUA MADRILEÑAS

Specialized proresolving mediators protect against experimental autoimmune myocarditis by modulating Ca2+ handling and NRF2 activation

Specialized proresolving mediators and, in particular, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester (BML-111) emerge as new therapeutic tools to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis progression. The cardioprotective role of BML-111 is mainly caused by the prevention of increased oxidative stress and nuclear factor erythroid-derived 2-like 2 (NRF2) down-regulation induced by myocarditis. At the molecular level, BML-111 activates NRF2 signaling, which prevents sarcoplasmic reticulum–adenosine triphosphatase 2A down-regulation and Ca2+ mishandling, and attenuates the cardiac dysfunction and tissue damage induced by myocarditis.This work was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (SAF-2017-84777R), Instituto de Salud Carlos III (ISCIII) (PI17/01093, PI17/01344, and PI20/01482), Sociedad Española de Cardiología, Proyecto Traslacional 2019 and Asociación del Ritmo Cardiaco (SEC, España), Proyecto Asociación Insuficiencia Cardiaca (Trasplante Cardiaco) 2020, Fondo Europeo de Desarrollo Regional, Fondo Social Europeo, and CIBERCV, a network funded by ISCIII, Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00), Ministerio de Economía, Industria y Competitividad/Agencia Estatal de Investigación 10.13039/501100011033 PID2020-113238RB-I00, PID2019-105600RB-I00, the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3 [PT17/0019/0003-ISCIII-SGEFI/ERDF, ProteoRed]), and “la Caixa” Foundation (project code HR17-00247). The Centro Nacional de Investigaciones Cardiovasculares is supported by the ISCIII, the Ministerio de Ciencia, Innovación y Universidades. Dr Ruiz-Hurtado is Miguel Servet I researcher of ISCIII (CP15/00129 Carlos III Health Institute). Dr Tamayo and R.I. Jaén, and M. Gil-Fernández were or currently are PhD students funded by the Formación de Profesorado Universitario program of the Spanish Ministry of Science, Innovation and Universities (FPU17/06135; FPU16/00827, FPU1901973)

Anthelmintic activity of aminoalcohol and diamine derivatives against the gastrointestinal nematode Teladorsagia circumcincta

11 páginas, 5 figuras, 4 tablas.Gastrointestinal nematodes (GIN) infections are a serious problem in livestock production due to the great economic losses they cause. Their control is increasingly difficult because of the rapid development of drug resistance and the limited number of available drugs. Therefore, this study evaluated 18 aminoalcohol and 16 diamine derivatives against eggs, first and third stage larvae from a susceptible and a resistant isolate of Tela-dorsagia circumcincta collected from sheep. The effectiveness of the in vitro anthelmintic activity of the com-pounds was evaluated using three different procedures: Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT). Those compounds with activities higher than 90 % in the initial screening at 50 μM were selected to determine their half maximal effective concentration (EC50). In parallel, cytotoxicity assays were conducted on Caco2 and HepG2 cell lines to calculate Selectivity Indexes (SI) for each compound. The diamine 30 presented the best results in preventing egg hatching, displaying the lowest EC50 value (1.01 ±0.04 μM) of all compounds tested and the highest SI (21.21 vs. Caco-2 cells). For the LMIT, the diamine 34 showed the highest efficacy, with EC50 values of 2.67 ±0.08 and 3.02 ±0.09 μM on the susceptible and resistant isolate of the parasite, respectively.We are grateful to Dave Bartley, from Moredun Research Institute for providing the triple-resistant isolate of T. circumcincta. RE thank the RICET contract (E07D401988BR) EC Programs. Financial support came from MINECO: RETOS (AGL2016-79813-C2-1R/2R) and Junta de Castilla y León (JCyL) co-financed by FEDER, UE (LE020P17). EVG was funded by FPU16/03536; JV, VCGA and MAB are recipients of Junta de Castilla y Leon and European Social Found (ESF)’s Fellowships Scheme for Doctoral Training Programs. (JCYL-USAL35B, LE082-18, LE051-18, respectively) and MMV by the Spanish “Ramon y Cajal” Programme (Ministerio de Economía y Competitividad; RYC-2015-18368).Peer reviewe

Anti-IL-6 Receptor Tocilizumab in Refractory Graves? Orbitopathy: National Multicenter Observational Study of 48 Patients

Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the e cacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age standard deviation 51 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 0.25 vs. 0.9 0.16; p = 0.0001), CAS (4.64 1.5 vs. 1.05 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 4.1 vs. 16.73 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 2.1 months, low disease activity (CAS 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or ine cacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain)

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). Methods: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (b-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. Results: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with b-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. Conclusion: In patients with PCa and bone metastases treated with ZA, b-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially importantThis study was supported by Novartis Oncology Spai