Emricasan (IDN-6556) Lowers Portal Pressure in Patients with Compensated Cirrhosis and Severe Portal Hypertension

Caspases play a central role in apoptosis, inflammation and fibrosis. They produce hemodynamically-active, pro-inflammatory microparticles that cause intrahepatic inflammation, vasoconstriction and extrahepatic splanchnic vasodilation. Emricasan is a pan-caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open-label study enrolled 23 subjects with compensated cirrhosis and PH (HVPG >5 mmHg). Emricasan 25 mg BID was given for 28 days. HVPG measurements were standardized and performed before and after emricasan. A single expert read all HVPG tracings.Median age was 59 (range 49-80); 70% were male. Cirrhosis etiologies were NASH and HCV. Subjects were Child class A (87%) with median MELD score of 8 (range 6-15). Twelve had severe PH (HVPG?12mmHg). Overall, there was no significant change in HVPG after emricasan (mean [SD] -1.1[4.57] mmHg). HVPG decreased significantly (mean [SD] -3.7[4.05] mmHg; p=0.003) in those with severe PH. 4/12 had a ?20% decrease; 8/12 had a ?10% decrease; and 2/12 HVPG decreased below 12mmHg. There were no significant changes in blood pressure or heart rate. AST/ALT decreased significantly in the entire group and in severe PH. Serum cCK18 and caspase-3/7 decreased significantly. Emricasan was well-tolerated. One subject discontinued for non-serious adverse events.Emricasan administered for 28 days decreased HVPG in patients with compensated cirrhosis and severe PH. An effect upon portal venous inflow is likely and concomitant decreases in AST/ALT suggest an intrahepatic anti-inflammatory effect

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed

SIVA UAV: A Case Study for the EMC Analysis of Composite Air Vehicles

[EN] The increased use of carbon-fiber composites in unmanned aerial vehicles is a challenge for their EMC assessment by numerical solvers. For accurate and reliable simulations, numerical procedures should be tested not only for individual components, but also within the framework of complete systems. With this aim, this paper presents a benchmark test case based on experimental measurements coming from direct-current injection tests in the SIVA unmanned air vehicle, reproduced by a numerical finite-difference-time-domain solver that employs a new subgridding scheme to treat lossy composite thin panels. Validation was undertaken by applying the feature selective validation method, which quantifies the agreement between experimental and numerical data.This work was supported by the Projects TEC2013-48414C3-{ 1,2,3}-R, TEC2016-79214-C3-{1,2,3}-R, and TEC2015-68766-REDC (Spanish MINECO, EU FEDER), P12-TIC-1442 (J. de Andalucia, Spain), Alhambra-UGRFDTD (AIRBUS DS), and by the CSIRC alhambra.ugr.es supercomputing center.Cabello, MR.; Fernández, S.; Pous, M.; Pascual-Gil, E.; Angulo, LD.; López, P.; Riu, PJ.... (2017). SIVA UAV: A Case Study for the EMC Analysis of Composite Air Vehicles. IEEE Transactions on Electromagnetic Compatibility. 59(4):1103-1113. https://doi.org/10.1109/TEMC.2017.2648507S1103111359

Alimentación a conciencia. Experiencia de práctica sociocomunitaria

En el 2014 se incorporaron las Prácticas Socio Comunitarias a la Facultad de Ingeniería de la Universidad Nacional de Mar del Plata. Mediante el “Aprendizaje-Servicio”, los y las estudiantes contextualizan los contenidos en los que se están formando al interactuar con la sociedad y su realidad. Se realizó un taller integrando docencia y extensión. Por un lado, participaron docentes e investigadoras/es y alumnos/as y por otro lado, la Cooperativa de Cuidadores Domiciliarios Mar del Plata e instituciones educativas. Se analizaron las deficiencias que poseen los actores de la comunidad respecto al “consumo seguro e informado” de los alimentos. A partir de ello es que las y los estudiantes, con la orientación de sus docentes tutores, recopilaron, analizaron y compararon con la legislación vigente información sobre alimentos light, apto celíaco, bajo en sodio, ultraprocesados y funcionales. Se generaron recursos audiovisuales logrando una comunidad de aprendizaje consciente de los criterios para seleccionar un alimento.In 2014, the Socio-Community Practices were incorporated into the Faculty of Engineering of the National University of Mar del Plata. Through “Service-Learning”, the students contextualize the contents in which they are being trained by interacting with society and its reality. A workshop was held integrating teaching and extension. On the one hand, teachers and researchers and students participated, and on the other hand, the Mar del Plata Home Caregiver Cooperative and educational institutions. The deficiencies that the community actors have regarding the “safe and informed consumption” of food were analyzed. Based on this, the students, with the guidance of their tutors, collected, analyzed and compared information on light foods, celiac-friendly, low-sodium, ultra-processed and functional foods with current legislation. Audiovisual resources were generated, achieving a learning community aware of the criteria to select a food.Fil: Agustinelli, Silvina Paola. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Grupo de Investigación en Preservación y Calidad de Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Benitez, Carmen. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Cátedra de Química General I; ArgentinaFil: Goñi, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Cátedra de Química General I; ArgentinaFil: Olaizola, Lourdes. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Pellegrini, María Celeste. Universidad Nacional de Mar del Plata. Facultad de Ingenieria. Instituto en Ciencia y Tecnología de Alimentos y Ambiente; . Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wasswrman, Cecilia. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Vázquez, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Schroeder, Carolina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Puglia, Iara Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Pages, Iara. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Lasaga, L. I.. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Garcia Machin, T.. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: De Pascuale, Sofia. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Coppa Legarreta, J. F.. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Cyras, Viviana Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ponce, Alejandra Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Manfredi, Lorena. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; Argentin

Seropositivity rates for agents of canine vector-borne diseases in Spain : a multicentre study

Background: Controlling canine vector-borne diseases (CVBD) is a major concern, since some of these diseases are serious zoonoses. This study was designed to determine seropositivity rates in Spain for agents causing the following five CVBD: leishmaniosis (Leishmania infantum: Li), heartworm (Dirofilaria immitis: Di), ehrlichiosis (Ehrlichia canis: Ec), anaplasmosis (Anaplasma phagocytophilum/Anaplasma platys: An) and Lyme disease (Borrelia burgdorferi: Bb). Methods: Anti-An, -Bb, and -Ec antibodies and the Di antigen were determined using the 4DX SNAP® Test (IDEXX Laboratories) and anti-L. infantum (Li) antibodies using the Leishmania SNAP® Test (IDEXX Laboratories) in blood and/or serum samples. Results: Among 1100 dogs examined, overall seropositivity rates were: Li (15.7%), Ec (5%), An (3.1%), Di (1.25%) and Bb (0.4%). While seropositivity towards Bb and Di was similar in all geographic regions, rates were significantly higher in the east of Spain (8.3%) for An, significantly higher in the north (20%) for Ec, and significantly higher in the Southeast (46.6%) and South (27.4%), and significantly lower in the north (0%) for Li. No statistical associations were observed between sex and the CVBD analyzed (p ≥ 0.05) while the following associations with other variables were detected: a higher seropositivity to Ec (40%) and Bb (6.7%) in dogs under one year of age compared with adults (p < 0.05); and a higher seropositivity to An and Li in dogs that lived outdoors versus indoors (p = 0.01; p < 0.001, respectively). Seropositivity rates of 2.1%, 0%, 1.7%, 0.5% and 4.2% were recorded respectively for An, Bb, Ec, Di and Li in dogs with no clinical signs (n = 556) versus 3.8%, 0.6%, 7.5%, 1.8% and 25.9% for those with signs (n = 507) suggestive of a CVBD. Conclusion: The data obtained indicate a risk for dogs in Spain of acquiring any of the five CVBD examined. Veterinarians in the different regions should include these diseases in their differential diagnoses and recommend the use of repellents and other prophylactic measures to prevent disease transmission by arthropod vectors. Public health authorities also need to become more involved in the problem, since some of the CVBD examined here also affect humans

Magnitude and Complexity of Rectal Mucosa HIV-1-Specific CD8+ T-Cell Responses during Chronic Infection Reflect Clinical Status

The intestinal mucosa displays robust virus replication and pronounced CD4+ T-cell loss during acute human immunodeficiency virus type 1 (HIV-1) infection. The ability of HIV-specific CD8+ T-cells to modulate disease course has prompted intensive study, yet the significance of virus-specific CD8+ T-cells in mucosal sites remains unclear.We evaluated five distinct effector functions of HIVgag-specific CD8+ T-cells in rectal mucosa and blood, individually and in combination, in relationship to clinical status and antiretroviral therapy (ART). In subjects not on ART, the percentage of rectal Gag-specific CD8+ T-cells capable of 3, 4 or 5 simultaneous effector functions was significantly related to blood CD4 count and inversely related to plasma viral load (PVL) (p<0.05). Polyfunctional rectal CD8+ T-cells expressed higher levels of MIP-1beta and CD107a on a per cell basis than mono- or bifunctional cells. The production of TNFalpha, IFN-gamma, and CD107a by Gag-specific rectal CD8+ T-cells each correlated inversely (p<0.05) with PVL, and MIP-1beta expression revealed a similar trend. CD107a and IFN-gamma production were positively related to blood CD4 count (p<0.05), with MIP-1beta showing a similar trend. IL-2 production by rectal CD8+ T-cells was highly variable and generally low, and showed no relationship to viral load or blood CD4 count.The polyfunctionality of rectal Gag-specific CD8+ T-cells appears to be related to blood CD4 count and inversely related to PVL. The extent to which these associations reflect causality remains to be determined; nevertheless, our data suggest a potentially important role for mucosal T-cells in limiting virus replication during chronic infection

Alimentación a conciencia. Experiencia de práctica sociocomunitaria

En el 2014 se incorporaron las Prácticas Socio Comunitarias a la Facultad de Ingeniería de la Universidad Nacional de Mar del Plata. Mediante el “Aprendizaje-Servicio”, los y las estudiantes contextualizan los contenidos en los que se están formando al interactuar con la sociedad y su realidad. Se realizó un taller integrando docencia y extensión. Por un lado, participaron docentes e investigadoras/es y alumnos/as y por otro lado, la Cooperativa de Cuidadores Domiciliarios Mar del Plata e instituciones educativas. Se analizaron las deficiencias que poseen los actores de la comunidad respecto al “consumo seguro e informado” de los alimentos. A partir de ello es que las y los estudiantes, con la orientación de sus docentes tutores, recopilaron, analizaron y compararon con la legislación vigente información sobre alimentos light, apto celíaco, bajo en sodio, ultraprocesados y funcionales. Se generaron recursos audiovisuales logrando una comunidad de aprendizaje consciente de los criterios para seleccionar un alimento.In 2014, the Socio-Community Practices were incorporated into the Faculty of Engineering of the National University of Mar del Plata. Through “Service-Learning”, the students contextualize the contents in which they are being trained by interacting with society and its reality. A workshop was held integrating teaching and extension. On the one hand, teachers and researchers and students participated, and on the other hand, the Mar del Plata Home Caregiver Cooperative and educational institutions. The deficiencies that the community actors have regarding the “safe and informed consumption” of food were analyzed. Based on this, the students, with the guidance of their tutors, collected, analyzed and compared information on light foods, celiac-friendly, low-sodium, ultra-processed and functional foods with current legislation. Audiovisual resources were generated, achieving a learning community aware of the criteria to select a food.Fil: Agustinelli, Silvina Paola. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Grupo de Investigación en Preservación y Calidad de Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Benitez, Carmen. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Cátedra de Química General I; ArgentinaFil: Goñi, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Cátedra de Química General I; ArgentinaFil: Olaizola, Lourdes. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Pellegrini, María Celeste. Universidad Nacional de Mar del Plata. Facultad de Ingenieria. Instituto en Ciencia y Tecnología de Alimentos y Ambiente; . Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wasswrman, Cecilia. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Vázquez, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Schroeder, Carolina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Puglia, Iara Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Pages, Iara. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Lasaga, L. I.. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Garcia Machin, T.. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: De Pascuale, Sofia. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Coppa Legarreta, J. F.. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Cyras, Viviana Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ponce, Alejandra Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Manfredi, Lorena. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; Argentin

LeishVet guidelines for the practical management of canine leishmaniosis

The LeishVet group has formed recommendations designed primarily to help the veterinary clinician in the management of canine leishmaniosis. The complexity of this zoonotic infection and the wide range of its clinical manifestations, from inapparent infection to severe disease, make the management of canine leishmaniosis challenging. The recommendations were constructed by combining a comprehensive review of evidence-based studies, extensive clinical experience and critical consensus opinion discussions. The guidelines presented here in a short version with graphical topic displays suggest standardized and rational approaches to the diagnosis, treatment, follow-up, control and prevention of canine leishmaniosis. A staging system that divides the disease into four stages is aimed at assisting the clinician in determining the appropriate therapy, forecasting prognosis, and implementing follow-up steps required for the management of the leishmaniosis patient