Identification of Amino Acids within Nonstructural Proteins 10 and 14 of the Avian Coronavirus Infectious Bronchitis Virus That Result in Attenuation In Vivo and In Ovo

The Gammacoronavirus infectious bronchitis virus (IBV) is a highly contagious global pathogen prevalent in all types of poultry flocks. IBV is responsible for economic losses and welfare issues in domestic poultry, resulting in a significant risk to food security. IBV vaccines are currently generated by serial passage of virulent IBV field isolates through embryonated hens' eggs. The different patterns of genomic variation accumulated during this process means that the exact mechanism of attenuation is unknown and presents a risk of reversion to virulence. Additionally, the passaging process adapts the virus to replicate in chicken embryos, increasing embryo lethality. Vaccines produced in this manner are therefore unsuitable for in ovo application. We have developed a reverse genetics system, based on the pathogenic IBV strain M41, to identify genes which can be targeted for rational attenuation. During the development of this reverse genetics system, we identified four amino acids, located in nonstructural proteins (nsps) 10, 14, 15, and 16, which resulted in attenuation both in vivo and in ovo. Further investigation highlighted a role of amino acid changes, Pro85Leu in nsp 10 and Val393Leu in nsp 14, in the attenuated in vivo phenotype observed. This study provides evidence that mutations in nsps offer a promising mechanism for the development of rationally attenuated live vaccines against IBV, which have the potential for in ovo application. IMPORTANCE The Gammacoronavirus infectious bronchitis virus (IBV) is the etiological agent of infectious bronchitis, an acute, highly contagious, economically important disease of poultry. Vaccination is achieved using a mixture of live attenuated vaccines for young chicks and inactivated vaccines as boosters for laying hens. Live attenuated vaccines are generated through serial passage in embryonated hens' eggs, an empirical process which achieves attenuation but retains immunogenicity. However, these vaccines have a risk of reversion to virulence, and they are lethal to the embryo. In this study, we identified amino acids in the replicase gene which attenuated IBV strain M41, both in vivo and in ovo. Stability assays indicate that the attenuating amino acids are stable and unlikely to revert. The data in this study provide evidence that specific modifications in the replicase gene offer a promising direction for IBV live attenuated vaccine development, with the potential for in ovo application

Experiencias y conclusiones en el desarrollo y validación de instrumentos de evaluación enfocados a la adquisición de la competencia transversal ‘CT13 Instrumental Específica’ en asignaturas de Ingeniería Mecánica

[EN] This paper presents the results of the experience carried out in the lab-sessions of several subjects of Mechanical Engineering. The aim of this work is to find a common methodology focused on the acquisition and evaluation of the Specific Instrumental Transversal Competence (CT13 in the UPV institutional project). The work has been applied in two types of lab-sessions: computer lab and laboratory. The instrumentation used in each of them has a different nature, while the former is focused on the use and comprehension of a numerical calculation software, in the latter the students must understand the management and purpose of some experimental measurement equipments. In the computer sessions, after an accompanied learning, the students must carry out and justify the steps followed in solving a numerical problem. The evaluation takes into account the level of adequacy of the steps followed throughout the process. In the laboratory practices, the students must demonstrate the ability to correctly select the proper equipment based on the parameter to be measured as well as to define the sequence of treatments in the measurement process. The measurement of the level of acquisition of the CT13 is done through an individual questionnaire.[ES] En este trabajo se presentan los resultados de la experiencia llevada a cabo en las prácticas de diversas asignaturas de Ingeniería Mecánica. El objetivo final es encontrar una metodología unificada enfocada a la adquisición y evaluación de la Competencia Transversal Instrumental Específica (CT13 en el proyecto institucional de la UPV).Se ha trabajado con dos tipos de prácticas: informáticas y de laboratorio. La instrumentación empleada en cada una de ellas tiene distinta naturaleza, mientras las primeras están enfocadas al manejo de un programa de cálculo numérico, en las segundas los estudiantes deben comprender el manejo y la finalidad de diversos equipos de medida experimental.En las prácticas informáticas los alumnos, tras un aprendizaje acompañado, deben ser capaces de realizar y justificar los pasos seguidos en la resolución de un problema numérico. En la evaluación se tiene en cuenta el nivel de adecuación de los pasos seguidos a lo largo del proceso. En las prácticas de laboratorio los alumnos deben demostrar la capacidad de seleccionar correctamente el equipo adecuado en función del parámetro a medir, así como definir la secuencia de tratamientos en el proceso experimental. La medida del nivel de adquisición de la CT13 se realiza con un cuestionario individual.Los autores agradecen la financiación recibida del Vicerrectorado de Estudios, Calidad y Acreditación, el Vicerrectorado de Recursos Digitales y Documentación (proyecto PIME B/19-20/165) y el Instituto de Ciencias de la Educación de la Universitat Politècnica de València (EICE INTEGRAL).Pedrosa Sanchez, AM.; Besa Gonzálvez, AJ.; Rupérez Moreno, MJ.; Sánchez Orgaz, EM.; Giner Navarro, J.; Martinez Sanchis, S.; Vila Tortosa, MP.... (2021). Experiencias y conclusiones en el desarrollo y validación de instrumentos de evaluación enfocados a la adquisición de la competencia transversal ‘CT13 Instrumental Específica’ en asignaturas de Ingeniería Mecánica. En IN-RED 2021: VII Congreso de Innovación Edicativa y Docencia en Red. Editorial Universitat Politècnica de València. 1521-1532. https://doi.org/10.4995/INRED2021.2021.13771OCS1521153

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Evolució dels resultats en competència matemàtica de l’alumnat de les Illes Balears

En l’estudi següent es presenta una anàlisi de l’evolució dels resultats en matemàtiques obtinguts pels alumnes de les Illes Balears, tant en les avaluacions internes com externes, en els darrers cursos escolars de les etapes d’ensenyament obligatori. Es posa especial atenció en el darrer nivell de l’educació primària i educació secundària obligatòria, i en les avaluacions externes, els resultats de les quals es desagreguen per illa, titularitat del centre i gènere de l’alumnat. Finalment, es comparen entre si per tal de mostrar una fotografia de la situació actual dels alumnes de les Illes Balears pel que fa a la competència matemàtica.En el siguiente estudio se presenta un análisis de la evolución de los resultados en matemáticas obtenidos por los alumnos de las Islas Baleares, tanto en las evaluaciones internas como externas, en los últimos cursos escolares de las etapas de enseñanza obligatoria. Se pone especial atención en el último nivel de la educación primaria y educación secundaria, y en las evaluaciones externas, cuyos resultados se desagregan por isla, titu-laridad del centro y género del alumnado. Finalmente, se comparan entre si para mostrar una fotografía de la actual situación de los alumnos de las Islas Baleares con respecto a la competencia matemática

The oscillatory profile induced by the anxiogenic drug fg-7142 in the amygdala-hippocampal network is reversed by infralimbic deep brain stimulation: Relevance for mood disorders

Anxiety and depression exhibit high comorbidity and share the alteration of the amygdala-hippocampal-prefrontal network, playing different roles in the ventral and dorsal hippocampi. Deep brain stimulation of the infralimbic cortex in rodents or the human equivalent-the subgenual cingulate cortex-constitutes a fast antidepressant treatment. The aim of this work was: (1) to describe the oscillatory profile in a rodent model of anxiety, and (2) to deepen the therapeutic basis of infralimbic deep brain stimulation in mood disorders. First, the anxiogenic drug FG-7142 was administered to anaesthetized rats to characterize neural oscillations within the amygdala and the dorsoventral axis of the hippocampus. Next, deep brain stimulation was applied. FG-7142 administration drastically reduced the slow waves, increasing delta, low theta, and beta oscillations in the network. Moreover, FG-7142 altered communication in these bands in selective subnetworks. Deep brain stimulation of the infralimbic cortex reversed most of these FG-7142 effects. Cross-frequency coupling was also inversely modified by FG-7142 and by deep brain stimulation. Our study demonstrates that the hyperactivated amygdala-hippocampal network associated with the anxiogenic drug exhibits an oscillatory fingerprint. The study contributes to comprehending the neurobiological basis of anxiety and the effects of infralimbic deep brain stimulation.This work was funded by the Fondo de Investigaciones Sanitarias FIS—Instituto de Salud Carlos Tercero and FEDER funds of the EU (Reference FIS-ISCIII PI16/00287). Hanna Vila-Merkle’s PhD studies are funded by the Valencian Ministry of Education (Generalitat Valenciana; grant reference ACIF/2017/394)

Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial

BACKGROUND: The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation. METHODS: BELIEF was an international, multicentre, single-arm, phase 2 trial done at 29 centres in eight European countries. Eligible patients were aged 18 years or older and had treatment-naive, pathologically confirmed stage IIIB or stage IV lung adenocarcinoma with a confirmed, activating EGFR mutation (exon 19 deletion or L858R mutation). Patients received oral erlotinib 150 mg per day and intravenous bevacizumab 15 mg/kg every 21 days and were tested centrally for the pretreatment T790M resistance mutation with a peptide nucleic acid probe-based real-time PCR. The primary endpoint was progression-free survival. The primary efficacy analysis was done in the intention-to-treat population and was stratified into two parallel substudies according to the centrally confirmed pretreatment T790M mutation status of enrolled patients (T790M positive or negative). The safety analysis was done in all patients that have received at least one dose of trial treatment. This trial was registered with ClinicalTrials.gov, number NCT01562028. FINDINGS: Between June 11, 2012, and Oct 28, 2014, 109 patients were enrolled and included in the efficacy analysis. 37 patients were T790M mutation positive and 72 negative. The overall median progression-free survival was 13·2 months (95% CI 10·3-15·5), with a 12 month progression-free survival of 55% (95% CI 45-64). The primary endpoint was met only in substudy one (T790M-positive patients). In the T790M-positive group, median progression-free survival was 16·0 months (12·7 to not estimable), with a 12 month progression-free survival of 68% (50-81), whereas in the T790M-negative group, median progression-free survival was 10·5 months (9·4-14·2), with a 12 month progression-free survival of 48% (36-59). Of 106 patients included in the safety analysis, five had grade 4 adverse events (one acute coronary syndrome, one biliary tract infection, one other neoplasms, and two colonic perforations) and one died due to sepsis. INTERPRETATION: The BELIEF trial provides further evidence of benefit for the combined use of erlotinib and bevacizumab in patients with NSCLC harbouring activating EGFR mutations. FUNDING: European Thoracic Oncology Platform, Roche

The association between SARS-CoV-2 infection and preterm delivery: a prospective study with a multivariable analysis.

To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19 disease) exposure in pregnancy, compared to non-exposure, is associated with infection-related obstetric morbidity. We conducted a multicentre prospective study in pregnancy based on a universal antenatal screening program for SARS-CoV-2 infection. Throughout Spain 45 hospitals tested all women at admission on delivery ward using polymerase-chain-reaction (PCR) for COVID-19 since late March 2020. The cohort of positive mothers and the concurrent sample of negative mothers was followed up until 6-weeks post-partum. Multivariable logistic regression analysis, adjusting for known confounding variables, determined the adjusted odds ratio (aOR) with 95% confidence intervals (95% CI) of the association of SARS-CoV-2 infection and obstetric outcomes. Preterm delivery (primary), premature rupture of membranes and neonatal intensive care unit admissions. Among 1009 screened pregnancies, 246 were SARS-CoV-2 positive. Compared to negative mothers (763 cases), SARS-CoV-2 infection increased the odds of preterm birth (34 vs 51, 13.8% vs 6.7%, aOR 2.12, 95% CI 1.32-3.36, p = 0.002); iatrogenic preterm delivery was more frequent in infected women (4.9% vs 1.3%, p = 0.001), while the occurrence of spontaneous preterm deliveries was statistically similar (6.1% vs 4.7%). An increased risk of premature rupture of membranes at term (39 vs 75, 15.8% vs 9.8%, aOR 1.70, 95% CI 1.11-2.57, p = 0.013) and neonatal intensive care unit admissions (23 vs 18, 9.3% vs 2.4%, aOR 4.62, 95% CI 2.43-8.94, p  This prospective multicentre study demonstrated that pregnant women infected with SARS-CoV-2 have more infection-related obstetric morbidity. This hypothesis merits evaluation of a causal association in further research

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present