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IntroductionBluetongue (BT), caused by bluetongue virus (BTV), is an important arthropod-borne livestock disease listed by the World Organization for Animal Health. Live-attenuated and inactivated vaccines have permitted to control BT but they do not simultaneously protect against the myriad of BTV serotypes. Recently, we identified the highly conserved BTV nonstructural protein NS1 and the N-terminal region of NS2 as antigens capable of conferring multiserotype protection against BTV. MethodsHere, we designed Modified Vaccinia Ankara (MVA) viral vectors that expressed BTV-4 proteins VP2 or VP7 along with NS1 and NS2-Nt as well as MVAs that expressed proteins VP2, VP7 or NS1 and NS2-Nt. ResultsImmunization of IFNAR(-/-) mice with two doses of MVA-NS1-2A-NS2-Nt protected mice from BTV-4M infection by the induction of an antigen-specific T cell immune response. Despite rMVA expressing VP7 alone were not protective in the IFNAR(-/-) mouse model, inclusion of VP7 in the vaccine formulation amplified the cell-mediated response induced by NS1 and NS2-Nt. Expression of VP2 elicited protective non-cross-reactive neutralizing antibodies (nAbs) in immunized animals and improved the protection observed in the MVA-NS1-2A-NS2-Nt immunized mice when these three BTV antigens were co-expressed. Moreover, vaccines candidates co-expressing VP2 or VP7 along with NS1 and NS2-Nt provided multiserotype protection. We assessed protective efficacy of both vaccine candidates in sheep against virulent challenge with BTV-4M.DiscussionImmunization with MVA-VP7-NS1-2A-NS2-Nt partially dumped viral replication and clinical disease whereas administration of MVA-VP2-NS1-2A-NS2-Nt promoted a complete protection, preventing viraemia and the pathology produced by BTV infection.

Summary: The Aedes aegypti midgut is crucial for blood digestion, nutrition, reproduction, and pathogen interaction. Using single-cell RNA sequencing, we explored virus infection and transcriptomic changes at the cellular level. We identified 12 distinct cell clusters in the Ae. aegypti midgut post-Zika virus infection, including intestinal stem cells, enteroblasts, enteroendocrine cells (EE), and enterocytes (ECs). The virus was found mainly in specific subsets of ECs and EE. Infection altered transcriptional profiles related to metabolism, signaling, and immune responses. Functional studies highlighted three significantly differentially expressed genes in infected cells. Notably, silencing apolipophorin III reduced virus RNA copy number in the midgut, emphasizing the role of specific genes in viral infection. These findings enhance our understanding of mosquito midgut cell processes during Zika virus infection and suggest potential targets for vector control.

La hepatitis autoinmune (HAI) es una enfermedad inflamatoria inmunomediada la cual requiere para su diagnóstico la integración de anomalías histológicas, hallazgos de laboratorio característicos, positividad de autoanticuerpos y exclusión de otras enfermedades hepáticas. Se presenta el caso de una paciente femenina de 28 años con un cuadro de ictericia generalizada de una semana de evolución asociado a dolor abdominal difuso e intermitente. Las pruebas hepáticas revelaron lesión hepatocelular (factor R= 17,6) con transaminasemia grave (aspartato-aminotransferasa [AST]: 1,502 UI/L, alanina-aminotransferasa [ALT]: 2,029 UI/L) e hiperbilirrubinemia conjugada (bilirrubina sérica total: 10,9 mg/dL, bilirrubina directa: 8,50 mg/dL). Las pruebas serológicas para virus hepatotropos fueron negativas, así como los autoanticuerpos para hepatitis autoinmune. La biopsia hepática percutánea reveló hallazgos compatibles de hepatitis autoinmune. Se calculó el puntaje revisado del Grupo Internacional de Hepatitis Autoinmune (IAIHG) de 1999 pretratamiento, en el que se obtuvo un puntaje de 16, por lo que se diagnosticó como HAI grave definitiva. La paciente fue manejada con esteroides orales y se obtuvo una mejoría clínica y bioquímica, por lo que fue egresada a los siete días de hospitalización, sin eventualidades. Mantener un alto índice de sospecha de HAI, a pesar de la negatividad inicial de los autoanticuerpos, y complementar el abordaje diagnóstico con biopsia hepática percutánea permite el diagnóstico y tratamiento oportuno de este grupo de pacientes, de modo que se previene la progresión a cirrosis avanzada y sus complicaciones.

ABSTRACTBluetongue virus (BTV) is the causative agent of the important livestock disease bluetongue (BT), which is transmitted via Culicoides bites. BT causes severe economic losses associated with its considerable impact on health and trade of animals. By reverse genetics, we have designed and rescued reporter-expressing recombinant (r)BTV expressing NanoLuc luciferase (NLuc) or Venus fluorescent protein. To generate these viruses, we custom synthesized a modified viral segment 5 encoding NS1 protein with the reporter genes located downstream and linked by the Porcine teschovirus-1 (PTV-1) 2A autoproteolytic cleavage site. Therefore, fluorescent signal or luciferase activity is only detected after virus replication and expression of non-structural proteins. Fluorescence or luminescence signals were detected in cells infected with rBTV/Venus or rBTV/NLuc, respectively. Moreover, the marking of NS2 protein confirmed that reporter genes were only expressed in BTV-infected cells. Growth kinetics of rBTV/NLuc and rBTV/Venus in Vero cells showed replication rates similar to those of wild-type and rBTV. Infectivity studies of these recombinant viruses in IFNAR(−/−) mice showed a higher lethal dose for rBTV/NLuc and rBTV/Venus than for rBTV indicating that viruses expressing the reporter genes are attenuated in vivo. Interestingly, luciferase activity was detected in the plasma of viraemic mice infected with rBTV/NLuc. Furthermore, luciferase activity quantitatively correlated with RNAemia levels of infected mice throughout the infection. In addition, we have investigated the in vivo replication and dissemination of BTV in IFNAR (−/−) mice using BTV/NLuc and non-invasive in vivo imaging systems.IMPORTANCEThe use of replication-competent viruses that encode a traceable fluorescent or luciferase reporter protein has significantly contributed to the in vitro and in vivo study of viral infections and the development of novel therapeutic approaches. In this work, we have generated rBTV that express fluorescent or luminescence proteins to track BTV infection both in vitro and in vivo. Despite the availability of vaccines, BTV and other related orbivirus are still associated with a significant impact on animal health and have important economic consequences worldwide. Our studies may contribute to the advance in orbivirus research and pave the way for the rapid development of new treatments, including vaccines.

At the end of the eighteenth century took place the discovery and the consequent colonization of Australia under the charge of the British Crown. The purpose of our investigation is to study the causes and the effects of this process that took place in the last years of the Modern Age. For that, we studied the phases of the process of the discovery that would be followed by the colonization of the territory. We contextualized it in the context of “Colonial Empires Era” where we analyzed the different major powers and the types of colonies they developed to obtain a great number of economic profits. Finally, we studied the economic advances and the process of construction of the australian nation at the arrival of the colonists. While, we highlighted the consequences of the colonization and the construction of this identity to the aborigine population.

Este artículo plantea el reto de escribir un nuevo relato en torno al estudio de las músicas coloniales latinoamericanas desde el paradigma de la “historia conectada”. A partir de un estudio de caso concreto, el de las conexiones musicales entre los actuales territorios de México y Colombia durante los siglos XVI y XVII, se reflexiona sobre el modo en que este enfoque puede enriquecer la visión del periodo colonial, superando la rigidez de otros modelos teóricos. El texto se divide en cuatro secciones. En la primera se discute el marco cronológico y geográfico. La segunda parte se aproxima al proceso paralelo de institucionalización de la tradición musical occidental en Nueva España y Nueva Granada. La tercera sección analiza las analogías entre el universo musical aborigen colombo-mexicano desde la particular visión que transmitieron los primeros pobladores europeos. La cuarta parte se centra en el ámbito catedralicio y en los nexos musicales entre las catedrales de ambas regiones. Para ello, se conjuga la revisión de bibliografía previa con la documentación de archivo. Además de ampliar nuestro conocimiento sobre las conexiones entre dos espacios geográficos específicos, las conclusiones de este trabajo –entre ellas la existencia de conexiones musicales entre virreinatos– pueden resultar aplicables a otros territorios del continente más allá del marco cronológico y geográfico estudiado en este artículo.

External validation is crucial in developing reliable machine learning models. This study aimed to validate three novel indices—Thermographic Joint Inflammation Score (ThermoJIS), Thermographic Disease Activity Index (ThermoDAI), and Thermographic Disease Activity Index-C-reactive protein (ThermoDAI-CRP)—based on hand thermography and machine learning to assess joint inflammation and disease activity in rheumatoid arthritis (RA) patients. A 12-week prospective observational study was conducted with 77 RA patients recruited from rheumatology departments of three hospitals. During routine care visits, indices were obtained at baseline and week 12 visits using a pre-trained machine learning model. The performance of these indices was assessed cross-sectionally and longitudinally using correlation coefficients, the area under the receiver operating curve (AUROC), sensitivity, specificity, and positive and negative predictive values. ThermoDAI and ThermoDAI-CRP correlated with CDAI, SDAI, and DAS28-CRP cross-sectionally (ρ = 0.81; ρ = 0.83; ρ = 0.78) and longitudinally (ρ = 0.55; ρ = 0.61; ρ = 0.60), all p < 0.001. ThermoDAI and ThermoDAI-CRP also outperformed Patient Global Assessment (PGA) and PGA + C-reactive protein (CRP) in detecting changes in 28-swollen joint counts (SJC28). ThermoJIS had an AUROC of 0.67 (95% CI, 0.58 to 0.76) for detecting patients with swollen joints and effectively identified patients transitioning from SJC28 > 1 at baseline visit to SJC28 ≤ 1 at week 12 visit. These results support the effectiveness of ThermoJIS in assessing joint inflammation, as well as ThermoDAI and ThermoDAI-CRP in evaluating disease activity in RA patients.

In the 1960s-1970s, Jumilla, like other cities in the Region of Murcia, lost a large part of its population, around 20% as a consequence of the emigration produced during these decades. The purpose of our investigation is to know in more detail the emigration that took place during the 1960s-1970s in this municipality. The main objective set to carry out our research is to determine the profile of the Jumillan emigrant at that time and analyze the effects of emigration on the living standards and quality of life of these people. For the methodology of our project, a survey was designed with the Google Forms platform. This survey would be carried out in the form of a personal interview with people from Jumilla that emigrated during the aforementioned decades, both inside and outside of Spain. Once the interviews with the Jumillan emigrants were carried out, we went on to analyze the results, from which we were able to establish our conclusions about the research project: first, we highlight that the emigrant in Jumilla in the 60’s and 70’s was mainly a young man and that he was emigrating for economic or labor reasons; secondly, most emigrants claim to have improved their economic situation with emigration; and finally, all migrants currently living in a different place claim to maintain ties to Jumilla, whether family, economic or cultural.

Bullying and cyberbullying have been intensively studied in many countries, and research on the topic has been fruitful. Nevertheless, it is still necessary to advance knowledge on bullying and cyberbullying in many geographical areas and to discover their risk and protective factors. The objective of this study was to describe and compare the involvement in different bullying and cyberbullying roles in Spain and Poland, identifying risk and protective factors such as moral disengagement, social and emotional competencies, moral emotions and empathy. This study was carried out with a sample of 2535 primary and secondary school students from Spain and Poland. More bullying and cyberbullying involvement were found in Poland in comparison with Spain. Different moral disengagement mechanisms were found to be risk factors for involvement in bullying and cyberbullying in both countries. Low moral emotions were a risk factor for bullying and cyberbullying perpetration in Spain and Poland. Different social and emotional competencies were protective against bullying and cyberbullying in both countries. These results suggest the need to design and implement more programs to promote social, emotional and moral competencies in Spain and Poland to protect children against bullying and cyberbullying.

Background and objective: The present study aims to analyze the levels of health-related quality of life (HRQoL) in patients with end-stage kidney disease (ESKD) in haemodialysis, and to explore what demographic, medical and psychological variables are associated with HRQL and contribute to its prediction. Materials and methods: Cross-sectional study with 302 patients with ACKD on haemodialysis. They were assessed: (1) HRQoL (Shorter Form Health Survey Questionnaire); (2) Anxiety and depression (Goldberg Anxiety and Depression Scale); (3) Sociodemographic data and (4) Medical data. Correlational analyses, means comparison and a path analyses with latent variables (PALV) were conducted. Results: The PALV showed that 42% of the variance in the HRQL could be explained by the variables evaluated (χ2/df = 2.10; GFI = .938; IFI = .920; CFI = .918; RMSEA = .062; SRMR = .056). Depression was the strongest predictor of HRQL (−.71; p =.002), followed by physical activity (−.19; p = .044). Age (−.122; p = .034) and comorbidity (−.206; p = .001) were weakly associated with physical HRQL. The practice of regular physical activity is related to the physical HRQoL (r = .21; p = .00) and mental (r = .12; p = .028). Conclusions: A high percentage of the variance in HRQoL is explained by the levels of depression and physical activity. Interventions to promote HRQoL in patients with ESKD should focus in promoting physical activity and taking care of patient’s mental health. Resumen: Antecedentes y objetivo: El presente estudio tiene como objetivo analizar los niveles de calidad de vida relacionada con la salud (CVRS) de los pacientes con enfermedad renal crónica avanzada (ERCA) en hemodiálisis y conocer qué variables demográficas, médicas y psicológicas se asocian con la CVRS y contribuyen a predecirla. Materiales y métodos: Estudio transversal con 302 pacientes con ERCA en tratamiento de hemodiálisis. Se evaluaron las siguientes variables: 1) CVRS (cuestionario Shorter Form Health Survey Questionnaire); 2) Ansiedad y depresión (Escala de ansiedad y depresión de Goldberg) 3) Datos sociodemográficos y 4) Datos médicos. Se realizaron análisis correlacionales, comparación de medias y análisis de vías con variables latentes (PALV). Resultados: El PALV mostró que el 42% de la varianza en la CVRS podría explicarse por las variables evaluadas (χ2/df = 2,10; GFI = ,938; IFI = ,920; CFI = ,918; RMSEA = ,062; SRMR = ,056). La depresión fue el predictor más fuerte de la CVRS (−,71; p = ,002), seguida de la actividad física (−,19; p = ,044). La edad (−,122; p = ,034) y la comorbilidad (−,206; p = ,001) se asociaron débilmente con la CVRS física. La práctica de una actividad física regular está relacionado con la CVRS física (r = ,21; p = ,00) y mental (r = ,12; p = ,028). Conclusiones: Un alto porcentaje de la varianza en CVRS se explica por los niveles de depresión y actividad física. Las intervenciones para promover la CVRS en pacientes con ERCA deben centrarse en promover la actividad física y cuidar la salud mental del paciente.

Resumen: Antecedentes y objetivo: El presente estudio tiene como objetivo analizar los niveles de calidad de vida relacionada con la salud (CVRS) de los pacientes con enfermedad renal crónica avanzada (ERCA) en hemodiálisis y conocer las variables demográficas, médicas y psicológicas que se asocian con la CVRS y contribuyen a predecirla. Materiales y métodos: Estudio transversal con 302 pacientes con ERCA en tratamiento de hemodiálisis. Se evaluaron las siguientes variables: 1) CVRS (cuestionario Shorter Form Health Survey Questionnaire); 2) Ansiedad y depresión (Escala de ansiedad y depresión de Goldberg); 3) Datos sociodemográficos, y 4) Datos médicos. Se realizaron análisis correlacionales, comparación de medias y análisis de vías con variables latentes (PALV). Resultados: El PALV mostró que el 42% de la varianza en la CVRS podría explicarse por las variables evaluadas (χ2 / df = 2,10; GFI = 0,938; IFI = 0,920; CFI = 0,918; RMSEA = 0,062; SRMR = 0,056). La depresión fue el predictor más fuerte de la CVRS (-,71; p = 0,002), seguida de la actividad física (-,19; p = 0,044). La edad (-,122; p = 0,034) y la comorbilidad (-,206; p = 0,001) se asociaron débilmente con la CVRS física. La práctica de una actividad física regular está relacionado con la CVRS física (r = 0,21; p = 0,00) y mental (r = 0,12; p = 0,028). Conclusiones: Un alto porcentaje de la varianza en CVRS se explica por los niveles de depresión y actividad física. Las intervenciones para promover la CVRS en pacientes con ERCA deben centrarse en promover la actividad física y cuidar la salud mental del paciente. Abstract: Background and objective: The present study aims to analyze the levels of health-related quality of life (HRQL) in patients with end-stage kidney disease (ESKD) in haemodialysis, and to explore what demographic, medical and psychological variables are associated with HRQL and contribute to its prediction. Matrials and methods: Cross-sectional study with 302 patients with advanced chronic kidney disease (ACKD) on haemodialysis. They were assessed: (1) HRQoL (Shorter Form Health Survey Questionnaire); (2) Anxiety and depression (Goldberg Anxiety and Depression Scale); (3) Sociodemographic data and (4) Medical data. Correlational analyses, means comparison and path analyses with latent variables (PALV) were conducted. Results: The PALV showed that 42% of the variance in the HRQL could be explained by the variables evaluated (χ2/df = 2.10; GFI = .938; IFI = .920; CFI = .918; RMSEA = .062; SRMR = .056). Depression was the strongest predictor of HRQL (−.71; p = .002), followed by physical activity (−.19; p = .044). Age (−.122; p = .034) and comorbidity (−.206; p = .001) were weakly associated with physical HRQL. The practice of regular physical activity is related to the physical HRQoL (r = .21; p = .00) and mental (r = .12; p = .028). Conclusions: A high percentage of the variance in HRQoL is explained by the levels of depression and physical activity. Interventions to promote HRQoL in patients with ESKD should focus in promoting physical activity and taking care of patient's mental health.