Influence of Quaternary Benzophenantridine and Protopine Alkaloids on Growth Performance, Dietary Energy, Carcass Traits, Visceral Mass, and Rumen Health in Finishing Ewes under Conditions of Severe Temperature-humidity Index.

Twenty Pelibuey×Katahdin ewes (35±2.3 kg) were used to determine the effects of the consumption of standardized plant extract containing a mixture of quaternary benzophenanthridine alkaloids and protopine alkaloids (QBA+PA) on growth performance, dietary energetics, visceral mass, and ruminal epithelial health in heat-stressed ewes fed with a high-energy corn-based diet. The basal diet (13.9% crude protein and 2.09 Mcal of net energy [NE] of maintenance/kg of dry matter) contained 49.7% starch and 15.3% neutral detergent fiber. Source of QBA+PA was Sangrovit RS (SANG) which contains 3 g of quaternary benzophenathridine and protopine alkaloids per kg of product. Treatments consisted of a daily consumption of 0 or 0.5 g SANG/ewe. Ewes were grouped by weight and assigned to 10 pens (5 pens/treatment), with two ewes per pen. The experimental period lasted 70 days. The mean temperature humidity index during the course of this experiment was 81.7±1.0 (severe heat stress). There were no treatment effects on water intake. Dry matter intake was not affected (p = 0.70) by treatments, but the group fed SANG had a numerically (11.2%) higher gain in comparison to the control group, SANG improved gain efficiency (8.3%, p = 0.04), dietary NE (5.2%, p<0.01) and the observed-to-expected NE (5.9%, p<0.01). Supplemental SANG did not affect (p≥0.12) carcass characteristics, chemical composition of shoulder, and organ weights (g/kg empty body weight) of stomach complex, intestines, and heart/lung. Supplemental SANG decreased liver weight (10.3%, p = 0.02) and increased visceral fat (16.9%, p = 0.02). Rumen epithelium of ewes fed SANG had lower scores for cellular dropsical degeneration (2.08 vs 2.34, p = 0.02), parakeratosis (1.30 vs 1.82, p = 0.03) and neutrophil infiltration (2.08 vs 2.86, p = 0.05) than controls. It is concluded that SANG supplementation helped ameliorate the negative effects of severe heat on growth performance of feedlot ewes fed high-energy corn-based diets. Improvement in energetic efficiency may have been mediated, in part, by anti-inflammatory effects of supplemental SANG and corresponding enhancement of nutrient uptake

Importance of twitching and surface-associated motility in the virulence of Acinetobacter baumannii

Acinetobacter baumannii is a pathogen of increasing clinical importance worldwide, especially given its ability to readily acquire resistance determinants. Motile strains of this bacterium can move by either or both of two types of motility: (i) twitching, driven by type IV pili, and (ii) surface-associated motility, an appendage-independent form of movement. A. baumannii strain MAR002 possesses both twitching and surface-associated motility. In this study, we isolated spontaneous rifampin-resistant mutants of strain MAR002 in which point mutations in the rpoB gene were identified that resulted in an altered motility pattern. Transcriptomic analysis of mutants lacking twitching, surface-associated motility, or both led to the identification of deregulated genes within each motility phenotype, based on their level of expression and their biological function. Investigations of the corresponding knockout mutants revealed several genes involved in the motility of A. baumannii strain MAR002, including two involved in twitching (encoding a minor pilin subunit and an RND [resistance nodulation division] component), one in surface-associated motility (encoding an amino acid permease), and eight in both (encoding RND and ABC components, the energy transducer TonB, the porin OprD, the T6SS component TagF, an IclR transcriptional regulator, a PQQ-dependent sugar dehydrogenase, and a putative pectate lyase). Virulence assays showed the reduced pathogenicity of mutants with impairments in both types of motility or in surface-associated motility alone. By contrast, the virulence of twitching-affected mutants was not affected. These results shed light on the key role of surface-associated motility and the limited role of twitching in the pathogenicity of A. baumannii

Implementation and Performance of the tau trigger in the ATLAS experiment

Triggering on hadronic taus at the LHC is a difficult task due to the high rate and occupancy of the events. On the other hand, the tau trigger increases the discovery potential of ATLAS in many physics channels, among others the Standard Model or SuperSymmetric Higgs (charged or neutrals) production. In order to cope with the rate and optimize the efficiency on important physics channels, the results of the current simulation studies indicate that the ATLAS tau trigger should be used either with relatively high transverse momentum thresholds alone, or with more relaxed threshold requirements in combination with other triggers, like the missing transverse energy trigger or a leptonic or jet trigger. In this contribution we describe the ATLAS tau trigger, and we present some of the current results from the simulation studies, focusing both on early physics and on physics at high luminosity

Efficacy of current treatments against hepatitis C virus

It is estimated that currently, in the world, approximately 3% of the population has chronic hepatitis, the hepatitis C virus is the etiological agent most related to the development of this pathology. The diversity of genotypes (7) and quasi-species of HCV, due to its high mutation rate, interferes with an effective humoral immunity. The aim of this work is precisely to evoke those usual drugs used in HCV therapy, as well as cutting-edge drugs. The goal of treatment is the eradication of HCV infection. One strategy offered by the WHO is to eradicate the virus in at-risk populations. Alternatives to the previously used treatment with interferon and ribavirin are shown in this paper; protease inhibitors and other targets have now been developed to make eradication of the virus more effective

Tumor testicular de saco vitelino con metástasis a pleura: primer caso reportado en la literatura

ResumenEl cáncer testicular es el tumor urológico maligno más común en hombres jóvenes. Más del 90% corresponden a tumores de células germinales. El objetivo del estudio es el reporte del primer caso de cáncer testicular de tumores de células germinales con metástasis a pleura.Paciente masculino de 21 años, inicia su padecimiento con dolor en hemitórax derecho; la radiografía de tórax presenta una radioopacidad en lóbulo medio de pulmón derecho y la tomografía de tórax detecta una masa intratorácica y extrapulmonar. La biopsia torácica guiada por ultrasonido muestra una masa sólida adosada a la pared torácica, con efecto de desplazamiento sobre la pleura, conocido como «efecto en cola de cometa». La biopsia fue positiva para lesión neoplásica maligna poco diferenciada de la pleura. A la exploración encontramos testículo derecho con tumoración en polo inferior el cual se corrobora por ultrasonido. Los marcadores tumorales solo con elevación de alfa-fetoproteína 295.87ng/dL y deshidrogenasa láctica en 2,380UI/L. En la tomografía de abdomen se identificó actividad ganglionar interaortocava. Realizamos orquiectomía radical derecha. Reporte patológico: tumor testicular de saco vitelino, pT1N2M1S2.En este caso se pudo comprobar que las metástasis fueron a nivel pleural, que lo ubica como una forma de diseminación excepcional.AbstractTesticular cancer is the most common malignant urologic tumor in young men. More than 90% are germ cell tumors. The aim of this study was to report the first case of germ cell tumor testicular cancer with metastasis to the pleura.A 21-year-old man had disease onset with pain in the right hemithorax. The chest x-ray showed radio-opacity in the middle lobe of the right lung. A chest tomography scan detected an intrathoracic and extrapulmonary mass. Ultrasound-guided thoracic biopsy revealed a solid mass attached to the thoracic wall, displaced over the pleura, known as the “comet tail effect”. The biopsy was positive for a poorly differentiated malignant neoplastic lesion of the pleura. Upon physical examination we encountered a right testis with a tumor at the lower pole; this was corroborated through ultrasound. In relation to tumor markers, only alpha-fetoprotein was elevated at 295.87ng/dl and lactate dehydrogenase at 2,380 IU/l. An abdominal tomography scan identified interaortocaval lymph node activity. We performed a right radical orchiectomy and the pathology report was testicular yolk sac tumor, pT1N2M1S2.In our patient, metastasis at the level of the pleura was confirmed, making this a case with an exceptional form of spread

Simultaneous co-delivery of neuroprotective drugs from multiloaded PLGA microspheres for the treatment of glaucoma

Glaucoma is a multifactorial neurodegenerative disorder and one of the leading causes of irreversible blindness globally and for which intraocular pressure is the only modifiable risk factor. Although neuroprotective therapies have been suggested to have therapeutic potential, drug delivery for the treatment of ocular disorders such as glaucoma remains an unmet clinical need, further complicated by poor patient compliance with topically applied treatments. In the present study we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating three recognised neuroprotective agents (dexamethasone (DX), melatonin (MEL) and coenzyme Q10 (CoQ10)) in a single formulation (DMQ-MSs) to create a novel sustained-release intraocular drug delivery system (IODDS) for the treatment of glaucoma. MSs were spherical, with a mean particle size of 29.04 ± 1.89 μm rendering them suitable for intravitreal injection using conventional 25G-32G needles. Greater than 62% incorporation efficiency was achieved for the three drug cargo and MSs were able to co-deliver the encapsulated active compounds in a sustained manner over 30-days with low burst release. In vitro studies showed DMQ-MSs to be neuroprotective in a glutamate-induced cytotoxicity model (IC50 10.00±0.94 mM versus 6.89±0.82 mM in absence of DMQ-MSs) in R28 cell line. In vivo efficacy studies were performed using a well-established rodent model of chronic ocular hypertension (OHT), comparing single intravitreal injections of microspheres of DMQ-MSs to their equivalent individual single drug loaded MSs mixture (MSsmix), empty MSs, no-treatment OHT only and naïve groups. Twenty one days after OHT induction, DMQ-MSs showed a significantly neuroprotective effect on RGCs compared to OHT only controls. No such protective effect was observed in empty MSs and single-drug MSs treated groups. This work suggests that multi-loaded PLGA MSs present a novel therapeutic approach in the management of retinal neurodegeneration conditions such as glaucoma

Bacteria-instructed B cells cross-prime naïve CD8+ T cells triggering effective cytotoxic responses.

In addition to triggering humoral responses, conventional B cells have been described in vitro to cross-present exogenous antigens activating naïve CD8+ T cells. Nevertheless, the way B cells capture these exogenous antigens and the physiological roles of B cell-mediated cross-presentation remain poorly explored. Here, we show that B cells capture bacteria by trans-phagocytosis from previously infected dendritic cells (DC) when they are in close contact. Bacterial encounter "instructs" the B cells to acquire antigen cross-presentation abilities, in a process that involves autophagy. Bacteria-instructed B cells, henceforth referred to as BacB cells, rapidly degrade phagocytosed bacteria, process bacterial antigens and cross-prime naïve CD8+ T cells which differentiate into specific cytotoxic cells that efficiently control bacterial infections. Moreover, a proof-of-concept experiment shows that BacB cells that have captured bacteria expressing tumor antigens could be useful as novel cellular immunotherapies against cancer.We are grateful to advanced light microscopy and cytometry facilities of CNB for technical supporting. The research is supported by grants: SAF2017-84091- R, and PID2020-116393RB-I00/AEI/10.13039/501100011033, financed by MCIN, BFERO2020.04, financed by FERO foundation and PI20/0036 from ISCIII. RGF is supported by BES-2016-076526 from the Spanish Ministry of Economy Industry and Competitiveness, JOP is supported by fellowship LCF/BQ/SO16/ 52270012 from La Caixa, BHF is supported by FPU18/00895 and AMP by FPU18/03199 from Ministry of Science, Innovation and Universities. LdC has been supported by Juan de la Cierva grant IJC2018-035386-I and a contract associated to SEV-2017-0712. EVC, AMP, AMAM, and NMM belong to the Spanish National Research Council (CSIC)’s Cancer Hub. Synopsis image made with biorender.com by Eduardo Roman Camacho and Esteban Veiga. We thanks Prof. Dan Portnoy who kindly provided bacterial strains.S

Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response

Malignant pleural effusion (MPE) is a common severe complication of advanced lung adenocarcinoma (LAC). Neutrophils, an essential component of tumor infiltrates, contribute to tumor progression and their counts in MPE have been associated with worse outcome in LAC. This study aimed to evaluate phenotypical and functional changes of neutrophils induced by MPE to determine the influence of MPE immunomodulatory factors in neutrophil response and to find a possible association between neutrophil functions and clinical outcomes. Pleural fluid samples were collected from 47 LAC and 25 heart failure (HF) patients. We measured neutrophil degranulation products by ELISA, oxidative burst capacity and apoptosis by flow cytometry, and NETosis by fluorescence. The concentration of degranulation products was higher in MPE-LAC than in PE-HF. Functionally, neutrophils cultured with MPE-LAC had enhanced survival and neutrophil extracellular trap (NET) formation but had reduced oxidative burst capacity. In MPE, NETosis was positively associated with MMP-9, P-selectin, and sPD-L1 and clinically related to a worse outcome. This is the first study associating NETs with a worse outcome in MPE. Neutrophils likely contribute to tumor progression through the release of NETs, suggesting that they are a potential therapeutic target in LAC

Deterioro cognitivo posquirúrgico a largo plaza tras cirugía cardiaca

Objetivos: Evaluar de forma longitudinal el Deterioro Cognitivo Postquirúrgico (DCP) a largo plazo en pacientes tras cirugía cardíaca, analizar el perfil cognitivo obtenido e identificar los factores de riesgo involucrados. Material y Métodos: Estudio prospectivo de 70 pacientes sometidos a cirugía cardíaca (36 con……..). Se recogieron los datos sociodemográficos y clínicos y se realizó evaluación longitudinal neuropsicológica (pre y postquirúrgica a los 1, 6 y 12 meses) para caracterizar el DCP (Proyecto Neuronorma). Se evaluaron las funciones ejecutivas (Test del Trazo, Test de Stroop), memoria (Test de Recuerdo libre y selectivamente facilitado), fluidez verbal (Semántica y Fonológica) y función visuoespacial (Orientación de Líneas. Se valoró también depresión y ansiedad (escalas de Hamilton). Resultados: Se comprobó la presencia de DCP en los dos grupos de pacientes (p>0.05-p>0.001, mayor en el grupo con CEC), que fue máximo a los 6 meses de la intervención, pero aún significativo a los 12 meses. El deterioro cognitivo se asoció con variables intraoperatorias (baja saturación de oxígeno intraoperatoria y tiempo de bypass cardiopulmonar prolongado) y con factores de riesgo cardiovasculares (tabaquismo, insuficiencia cardíaca, hipertrofia ventricular izquierda, diabetes mellitus, enfermedad coronaria de 3 vasos y arteriopatía periférica) como factores predictivos. Conclusión: Los resultados indican la prevalencia del deterioro cognitivo postquirúrgico (DCP) al año de la intervención en ambos grupos, siendo mayor en el grupo con CEC. El DCP se caracteriza por un deterioro multidominio significativo en atención, funciones ejecutivas y fluencia verbal. Se describen los factores intraoperatorios y cardiovasculares significativos en el DCP, planteando la necesidad de establecer protocolos para su detección así como su prevención.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Randomized clinical trial of the safety and immunogenicity of the Tdap vaccine in pregnant Mexican women

ABSTRACT Immunization with the tetanus, diphtheria, and pertussis (Tdap) vaccine raises controversies on immunogenicity and possible antibody interference. We performed an experimental, double-blind, parallel group controlled clinical trial to evaluate the safety and immunogenicity of the Tdap vaccine in 204 pregnant women and their children and to determine its interference in antibody production. Pregnant women 18 to 38 y of age with 12 to 24 weeks gestation, a low obstetric risk, and without serious disease were randomly selected. The experimental group received 0.5 mL IM of Tdap and the control group normal saline. Six blood samples were drawn before and after solution application, and from the umbilical cord of the infants and at 2, 4, and 6 months of age. Pertactin and Pertussis toxin antibodies and possible interference of maternal antibodies with the vaccine were determined. In the experimental group, antibodies against Bordetella pertussis pertactin (anti-PRN) (112 E/mL 95% CI 89.9–139.9) and antibodies against pertussis toxin (anti-PT) (24.0 E/mL, 95% CI 18.3–31.4) were elevated in the mother before vaccination. These were higher in the umbilical cord and descended in the infant at 2 months (71.4 (95% CI 56.8–89.7 and 10.9; 95% CI 8.7–13.7, respectively). Anti-PT showed a delay in production. Tdap safety was confirmed with only mild local pain at 24 and 48 hours. Anti-PRN and anti-PT antibodies in the infant descend at 2 months of age. There is a delay in anti-PT in children of immunized mothers. Further studies are needed to elucidate its clinical significance