SLESIS-R: an improved score for prediction of serious infection in patients with systemic lupus erythematosus based on the RELESSER prospective cohort.

OBJECTIVE: To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort. METHODS: We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance. RESULTS: A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777-0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48. CONCLUSIONS: SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures.

Use of Fibula Nails With Proximal and Distal Fixation.

Background: Ankle fractures are a frequent injury in the adult population and a quarter of all ankle fractures are classified as unstable, requiring surgical intervention. Plate-and-screw construct is the traditionally used fixation method for fibula fractures. The use of an intramedullary nail is an alternative fixation method, with current literature supporting very low complication rates and hardware removal surgeries. The purpose of this study was to evaluate the outcomes, including complication rates and implant removal rates, using a fibula nail with both proximal and distal fixation capabilities by an experienced surgeon. Methods: We retrospectively reviewed 203 consecutive fibula nail cases from a single surgeon using a mini-open technique for anatomic reduction. Demographic, operative, clinical, and radiographic outcome data were analyzed, specifically examining complication rates and need for implant removal. Results: The average follow-up was 18.8 months (6-54 months). All fractures healed. We identified 2 cases of superficial wound infection, 1 superficial peroneal nerve irritation, and 1 case of implant removal. In the first 110 cases, 2 fractures were converted to a plate intraoperatively prior to a technique modification which has prevented this occurrence. No deep infection, delayed union, or nonunion occurred. Conclusion: Our data support that fibula nails with proximal and distal locking capabilities offer an alternative to plating with the potential for lower complication rates and lower need for implant removal. Level of evidence: Level IV, case series.

Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia.

BACKGROUND: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs. METHODS: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG). RESULTS: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16). CONCLUSION: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence.

Sexual behaviour of young rams is improved and less stressful after intranasal administration of oxytocin.

The aim of this study was to determine if intranasal administration of oxytocin modifies sexual behaviour and the stress response in young rams during sexual tests with ewes in oestrus. Ten rams were used in a cross-over design. At Day 0, the control group (CG, n = 5) received isotonic saline spray intranasally, and the treated group (OTG, n = 5) received oxytocin (24 IU) intranasally, 40 min before the sexual test. At Day 15, the groups were reversed. In each sexual test (20 min) with an oestrous-induced ewe, the sexual behaviour of the young rams was recorded. Serum cortisol concentrations were determined before and after the test. Less flehmen was observed in the OTG, but mounts with ejaculation were increased. The OTG presented lower serum cortisol concentration than the CG. In conclusion, intranasal administration of oxytocin modified the sexual behaviour of rams, evidenced by a decrease in flehmen behaviour and an increase in mounts with ejaculation, making sexual activity more efficacious. In addition, the treatment decreased the stress response of the rams in the sexual tests. Therefore, intranasal administration of oxytocin could be used to increase sexual activity in rams, and with less stress, providing better welfare conditions.

Aprendizaje autónomo en la educación a distancia en estudiantes de Psicopedagogía durante la COVID-19: una revisión sistemática

Introducción: Durante la COVID-19, la educación a distancia fue una oportunidad para el ejercicio del autoaprendizaje en salud mediante el uso de recursos electrónicos, con el dinamismo e impulso del aprendizaje autodidacta mediante el uso de las TIC. Objetivo: Valorar a través de una revisión sistemática el comportamiento del aprendizaje autónomo en estudiantes de Psicopedagogía durante la pandemia por la COVID-19. Método: Se realizó una revisión sistemática en publicaciones entre los años 2020-2022, donde se identificaron 767 artículos en Scopus, 64 registros en SciELO y 759 en Google Scholar, luego de su procesamiento quedó una muestra de 52 artículos. Fueron recopilados: título, año, tipo de artículo, contexto, revista, indexación, tema, comentario, posible uso en el artículo, referencia bibliográfica y DOI. Las referencias bibliográficas se procesaron mediante el gestor bibliográfico Mendeley. Resultados: Se destacó el creciente acto investigativo acerca de las estrategias metodológicas de la autonomía en los aprendizajes en educación básica y con aspiraciones a efectuar estudios en salud, durante la pandemia por la COVID-19. El país con más producciones académicas sobre aprendizaje autónomo en educación básica fue Perú con cuatro, seguido de Ecuador con tres producciones científicas vinculadas a salud; también se encontraron investigaciones de otras latitudes. Conclusiones: El aprendizaje autónomo es una prioridad de vigencia actual, indispensable para responder a las demandas de una sociedad cambiante y compleja. En los países de Latinoamérica hubo creciente interés investigativo sobre aprendizaje autónomo en educación básica y que aspiraron a efectuar estudios en salud durante la pandemia por la COVID-19.

Introduction: During COVID-19, distance education was an opportunity to practice self-learning in health through the use of electronic resources, with the dynamism and promotion of self-taught learning through the use of ICT. Objective: To assess, through a systematic review, the behavior of autonomous learning in Psychopedagogy students during the COVID-19 pandemic. Method: A systematic review was carried out on publications between the years 2020-2022, where 767 articles were identified in Scopus, 64 records in SciELO and 759 in Google Scholar, after processing a sample of 52 articles remained. The following were collected: title, year, type of article, context, journal, indexing, topic, comment, possible use in the article, bibliographic reference and DOI. Bibliographic references were processed using the Mendeley bibliographic manager. Results: The growing research act was highlighted about the methodological strategies of autonomy in learning in basic education and with aspirations to carry out health studies, during the COVID-19 pandemic. The country with the most academic productions on autonomous learning in basic education was Peru with four, followed by Ecuador with three scientific productions linked to health; Research from other latitudes was also found. Conclusions: Autonomous learning is a current priority, essential to respond to the demands of a changing and complex society. In Latin American countries, there was growing research interest in autonomous learning in basic education and they aspired to carry out health studies during the COVID-19 pandemic.

Introdução: Durante a COVID-19, a educação a distância foi uma oportunidade para praticar a autoaprendizagem em saúde através do uso de recursos eletrônicos, com a dinamização e promoção da aprendizagem autodidata através do uso das TIC. Objetivo: Avaliar, por meio de uma revisão sistemática, o comportamento da aprendizagem autônoma em estudantes de Psicopedagogia durante a pandemia da COVID-19. Método: Foi realizada uma revisão sistemática sobre publicações entre os anos de 2020 a 2022, onde foram identificados 767 artigos na Scopus, 64 registros na SciELO e 759 no Google Acadêmico, após processamento permaneceu uma amostra de 52 artigos. Foram coletados: título, ano, tipo de artigo, contexto, periódico, indexação, tema, comentário, possível uso no artigo, referência bibliográfica e DOI. As referências bibliográficas foram processadas utilizando o gerenciador bibliográfico Mendeley. Resultados: Destacou-se a crescente atuação de pesquisa sobre as estratégias metodológicas de autonomia na aprendizagem na educação básica e com aspirações à realização de estudos em saúde, durante a pandemia de COVID-19. O país com mais produções acadêmicas sobre aprendizagem autônoma na educação básica foi o Peru com quatro, seguido pelo Equador com três produções científicas ligadas à saúde; Pesquisas de outras latitudes também foram encontradas. Conclusões: A aprendizagem autónoma é uma prioridade atual, essencial para responder às exigências de uma sociedade complexa e em mudança. Nos países latino-americanos, havia um crescente interesse de investigação na aprendizagem autónoma no ensino básico e aspiravam a realizar estudos de saúde durante a pandemia da COVID-19.

La evaluación de los logros del aprendizaje de la Educación Física, en época de pandemia

La Educación Física, en la actualidad, presta cada vez más atención al desarrollo de estrategias pedagógicas, con la finalidad de perfeccionar los logros del aprendizaje y que este sea sostenible y enfrenta muchos retos de cómo acceder y mantener, en cualquier edad de la vida, la participación de experiencias de aprendizaje estimulantes. El objetivo de este trabajo fue desarrollar un estudio comparativo entre dos grupos de estudiantes para evaluar la calidad del proceso de enseñanza-aprendizaje, de la Educación Física, basado en la diferencia entre la clase presencial y la clase a distancia, demostrado en los resultados académicos. La investigación fue desarrollada con enfoque cuantitativo y diseño cuasiexperimental con prestest y postest, participaron estudiantes de educación básica regular del cuarto grado, en el año 2020 y de quinto grado durante el año 2021. La prueba de hipótesis determinó que la diferencia de los promedios fue significativa, durante el año 2020 fue de 14,5 y en el año 2021, de 13,5 para 0,05. Se obtuvo el rechazo de la hipótesis nula (Sig<0,05) y se aprobó la hipótesis alterna; lo que evidenció que en el periodo de confinamiento por la pandemia del COVID-19, los promedios en el área de Educación Física disminuyeron.

A Educação Física, atualmente, dá cada vez mais atenção ao desenvolvimento de estratégias pedagógicas, com o objetivo de aperfeiçoar as conquistas da aprendizagem e torná-la sustentável e enfrenta muitos desafios de como acessar e manter, em qualquer idade da vida, o envolvimento em experiências de aprendizagem estimulantes. . O objetivo deste trabalho foi desenvolver um estudo comparativo entre dois grupos de alunos para avaliar a qualidade do processo de ensino-aprendizagem da Educação Física, a partir da diferença entre a aula presencial e a aula a distância, demonstrada no resultados acadêmicos. . A pesquisa foi desenvolvida com abordagem quantitativa e delineamento quase-experimental com pré-teste e pós-teste, participaram alunos do ensino fundamental regular da quarta série no ano de 2020 e da quinta série durante o ano de 2021. O teste de hipótese determinou que a diferença na médias foi significativa, durante o ano de 2020 foi de 14,5 e em 2021, de 13,5 para 0,05. A hipótese nula foi rejeitada (Sig<0,05) e a hipótese alternativa foi aprovada; que mostrou que no período de confinamento devido à pandemia de COVID-19, as médias na área da Educação Física diminuíram.

Physical Education, currently, pays more and more attention to the development of pedagogical strategies, with the aim of perfecting learning achievements and making it sustainable and faces many challenges of how to access and maintain, at any age of life, engaging in stimulating learning experiences. The objective of this work was to carry out a comparative study between two groups of students to evaluate the quality of the teaching-learning process of Physical Education, based on the difference between the face-to-face class and the distance class, demonstrated in the academic results. The research was developed with a quantitative approach and quasi-experimental design with pretest and posttest, regular basic education students from the fourth grade in the year 2020 and from the fifth grade during the year 2021 participated. The hypothesis test determined that the difference in the averages was significant, during the year 2020 it was 14.5 and in 2021, from 13.5 to 0.05. The null hypothesis was rejected (Sig <0.05) and the alternative hypothesis was approved; which showed that in the period of confinement due to the COVID-19 pandemic, the averages in the area of Physical Education decreased.

Revisión documental sobre el software GeoGebra aplicado a la Cultura Física y el deporte

El software GeoGebra es muy útil en las simulaciones de movimientos físicos porque con la ayuda de este el profesional del deporte es capaz de interpretar con valores matemáticos y geométricos la realización de un lanzamiento, una acción que a simple vista es muy difícil descifrar. Sin embargo, a pesar de ser este recurso una vía recurrente para contribuir al desarrollo de la cultura física y el deporte, no ha sido muy generalizado su uso en esta área del conocimiento. Es por ello que los autores de esta investigación se proponen como objetivo: realizar una sistematización documental sobre el software Geogebra enfocado en la cultura Física para que se convierta en un referente a tener en cuenta para futuras innovaciones e investigaciones referente al tema. Con vistas a lograr esta meta consultaron un grupo de artículos en bases de datos de Scopus y Google Académico y publicados en los últimos cinco años referente al uso del Software GeoGebra y se visualizaron las características de este medio y los diversos beneficios que ha ofrecido a través del tiempo. Los artículos hallados se sistematizaron considerando la matriz de análisis, conteniendo aspectos preponderantes en cantidad de publicaciones durante el año 2021 con 12 publicaciones y menor cantidad de publicaciones durante el 2022. Se estudió un prototipo de 29 artículos, en los últimos cinco años referente al uso del Softwares educativos que implican al GeoGebra.

O software GeoGebra é muito útil na simulação de movimentos físicos porque com a ajuda dele o profissional do esporte consegue interpretar com valores matemáticos e geométricos a execução de um arremesso, ação muito difícil de decifrar a olho nu. Contudo, apesar deste recurso ser uma forma recorrente de contribuir para o desenvolvimento da cultura física e do desporto, a sua utilização nesta área do conhecimento não tem sido muito difundida. É por isso que os autores desta pesquisa propõem como objetivo: realizar uma sistematização documental sobre o software Geogebra voltado para a Cultura Física para que ele se torne uma referência a ser levada em conta para futuras inovações e pesquisas sobre o tema. do tempo. Os artigos encontrados foram sistematizados considerando a matriz de análise, contendo aspectos predominantes no número de publicações durante o ano de 2021 com 12 publicações e um menor número de publicações durante 2022. Foi estudado um protótipo de 29 artigos, nos últimos cinco anos quanto ao uso de software educacional que envolve o GeoGebra.

The GeoGebra software is very useful in simulating physical movements because with the help of it the sports professional is able to interpret with mathematical and geometric values the execution of a throw, an action that is very difficult to decipher with the naked eye. However, although this resource is a recurring way to contribute to the development of physical culture and sports, its use in this area of knowledge has not been very widespread. That is why the authors of this research propose as an objective: to carry out a documentary systematization on the Geogebra software focused on Physical culture so that it becomes a reference to be taken into account for future innovations and research on the topic. With a view to achieving this goal, they consulted a group of articles in Scopus and Google Scholar databases and published in the last five years regarding the use of GeoGebra Software and the characteristics of this medium, as well as the various benefits it has offered to users through time were visualized. The articles found were systematized considering the analysis matrix, containing predominant aspects in the number of publications during the year 2021 with 12 publications and a smaller number of publications during 2022. A prototype of 29 articles was studied, in the last five years regarding the use of Educational software that involves GeoGebra.

In vitro and in vivo studies on a group of chalcones find promising results as potential drugs against fascioliasis.

About a third of the world population is infected by helminth parasites implicated in foodborne trematodiasis. Fascioliasis is a worldwide disease caused by trematodes of the genus Fasciola spp. It generates huge economic losses to the agri-food industry and is currently considered an emerging zoonosis by the World Health Organization (WHO). The only available treatment relies on anthelmintic drugs, being triclabendazole (TCBZ) the drug of choice to control human infections. The emergence of TCBZ resistance in several countries and the lack of an effective vaccine to prevent infection highlights the need to develop new drugs to control this parasitosis. We have previously identified a group of benzochalcones as inhibitors of cathepsins, which have fasciolicidal activity in vitro and are potential new drugs for the control of fascioliasis. We selected the four most active compounds of this group to perform further preclinical studies. The compound's stability was determined against a liver microsomal enzyme fraction, obtaining half-lives of 34-169 min and low intrinsic clearance values (<13 µL/min/mg), as desirable for potential new drugs. None of the compounds were mutagenic or genotoxic and no in vitro cytotoxic effects were seen. Compounds C31 and C34 showed the highest selectivity index against liver fluke cathepsins when compared to human cathepsin L. They were selected for in vivo efficacy studies observing a protective effect, similar to TCBZ, in a mouse model of infection. Our findings strongly encourage us to continue the drug development pipeline for these molecules.

Automatic detection of Cryptosporidium in optical microscopy images using YOLOv5x: a comparative study.

Here, a machine learning tool (YOLOv5) enables the detection of Cryptosporidium microorganisms using optical and phase contrast microscope images. The two databases were processed using 520 images (optical microscopy) and 1200 images (phase contrast microscopy). It used Python libraries to label, standardize the size, and crop the images to generate the input tensors to the YOLOv5 network (s, m, and l). It implemented two experiments using randomly initialized weights in optical and phase contrast microscope images. The other two experiments used the parameters for the best training time obtained before and after retraining the models. Metrics used to assess model accuracy were mean average accuracy, confusion matrix, and the F1 scores. All three metrics confirmed that the optimal model used the best epoch of optical imaging training and retraining with phase contrast imaging. Experiments with randomly initialized weights with optical imaging showed the lowest precision for Cryptosporidium detection. The most stable model was YOLOv5m, with the best results in all categories. However, the differences between all models are lower than 2%, and YOLOv5s is the best option for Cryptosporidium detection considering the differences in computational costs of the models.

Disposición de espacios públicos y áreas verdes para aprender a convivir y fomentar las prácticas deportivas

El estudio es importante porque permitió conocer la disposición de espacios públicos y áreas verdes para aprender a convivir y fomentar las prácticas deportivas, y ha permitido determinar que el 90% de los 45 directivos concuerdan de que la municipalidad deberá asignar un presupuesto para habilitar de más espacios con algunos mecanismos propios de los gobiernos municipales, debido a que, a la fecha se ha observado que por cada loza deportiva pavimentada publica, aproximadamente existen 3 campos deportivos con gras artificial con administración privada; el objetivo de esta investigación es determinar la relación que existe entre los tipos de comunicación al interior de los barrios de la liga provincial de futbol; el estudio fue descriptivo de alcance correlacional, con diseño no experimental, transversal. Los sujetos de la muestra fueron seleccionados por conveniencia, es decir, muestra no probabilística, estaba conformada por la totalidad de 45 representantes de 15 equipos deportivos, que incluyeron 3 representantes por cada equipo deportivo de futbol. Los participantes en las competencias deportivas organizadas por la Subgerencia de deporte Pearson 2 de las 3 correlaciones son altas, por ser mayores de 0,50, a excepción de la correlación entre las dimensiones: ascendente, y horizontal es una baja correlación de Pearson de 0,36; eso explica las ligeras dificultades en la convivencia. En consecuencia, la comunicación para superar la carencia de espacios habilitados para las prácticas deportivas es viable, tal como se aprecia en la mayoría de correlaciones.

O estudo é importante porque permitiu conhecer a disposição de espaços públicos e áreas verdes para aprender a conviver e promover práticas esportivas, e permitiu determinar que 90% dos 45 diretores concordam que o município deve alocar um orçamento para permitir mais espaços com alguns mecanismos dos governos municipais, porque, até o momento, observou-se que, para cada campo esportivo público pavimentado, existem aproximadamente 3 campos esportivos com grama artificial com administração privada; O objetivo desta pesquisa é determinar a relação existente entre os tipos de comunicação nos bairros da liga provincial de futebol; o estudo foi descritivo e correlacional, com um desenho não experimental e transversal. Os sujeitos da amostra foram selecionados por conveniência, ou seja, uma amostra não probabilística, e consistiram em 45 representantes de 15 times esportivos, incluindo 3 representantes de cada time de futebol. Os participantes das competições esportivas organizadas pelo gerente adjunto de esporte Pearson 2 das 3 correlações são altas, sendo maiores que 0,50, exceto pela correlação entre as dimensões: ascendente e horizontal, que é uma correlação de Pearson baixa, de 0,36; isso explica as pequenas dificuldades de convivência. Consequentemente, a comunicação para superar a falta de espaços para atividades esportivas é viável, como pode ser visto na maioria das correlações.

The study is important because it allowed to know the existence of public spaces and green areas to learn to coexist and promote sports practices, and it has allowed to determine that 90% of the 45 managers agree that the municipality should allocate a budget to enable more spaces with some own mechanisms of municipal governments, due to the fact that, to date, it has been observed that for each public paved sports ground, there are approximately 3 sports fields with artificial grass with private administration; the objective of this research is to determine the relationship that exists between the types of communication within the neighborhoods of the provincial soccer league; the study was descriptive with a correlational scope, with a non-experimental, cross-sectional design. The subjects of the sample were selected for convenience, that is, a non-probabilistic sample, it was made up of a total of 45 representatives of 15 sports teams, which included 3 representatives for each soccer sports team. The participants in the sports competitions organized by the Sports Department Pearson 2 of the 3 correlations are high, being greater than 0.50, with the exception of the correlation between the dimensions: ascending, and horizontal is a low Pearson correlation of 0 .36; that explains the slight difficulties in coexistence. Consequently, communication to overcome the lack of spaces set up for sports practice is viable, as can be seen in most correlations.

The impact of disease activity on health-related quality of life in patients with systemic lupus erythematosus / Impacto de la actividad clínica en la calidad de vida relacionada con la salud de pacientes con lupus eritematoso sistémico

Background and objective The aim of this research was to investigate the relationship between disease activity and health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) considering the increased interest in the management of this disease. Materials and methods HRQoL was measured at clinic visits during a 12-month follow-up period using questionnaires on fatigue (FACIT-FATIGUE); quality of life, EuroQol 5-dimension (EQ-5D-5L) health questionnaire with 5 levels; disability, Health Assessment Questionnaire (HAQ), and a Global Health Status (GHS) scale. Disease activity, organ damage and other clinical factors that could affect HRQoL were recorded. The association between disease activity and HRQoL was assessed using Bayesian linear regression models with monotonic effects. Results Data from 70 patients at the baseline visit and 42 patients with 1 year of follow-up were analyzed. At baseline, 28.57% of patients presented Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)>6. In the 70 baseline patients, disease activity was associated with HRQoL in all four parameters. In the 42 patients with 12 months of follow-up, the positive association of disease activity with GHS, FACIT-FATIGUE and EQ-5D-5L and the negative association with HAQ was maintained.Patients who are smokers and those receiving immunosuppressant therapy presented low GHS and FACIT-FATIGUE scores. Moreover, older age at inclusion was significantly associated to low GHS, while low leucocyte and 25-OH-vitamin D levels were associated to fatigue perception in SLE patients. Conclusion Our results showed a statistically significant association between disease activity and HRQoL parameters. (AU)

Objetivo El objetivo del estudio fue analizar la relación entre la actividad clínica y la calidad de vida relacionada con la salud (CVRS) en pacientes con lupus eritematoso sistémico (LES).Material y métodos La CVRS se evaluó en la visita basal y durante 12 meses de seguimiento mediante un cuestionario de fatiga (FACIT-FATIGUE), calidad de vida (EQ-5D-5L), discapacidad (HAQ) y una escala analógica visual de estado general de salud (EVA). La actividad clínica, el daño acumulado y otros factores clínicos que pudieran afectar a la CVRS se analizaron mediante un modelo de regresión lineal bayesiano con efectos monotónicos. Resultados Se analizaron los datos de 70 pacientes incluidos en la visita basal y los 42 con 12 meses de seguimiento seleccionados aleatoriamente. En la visita basal el 28,57% de los pacientes presentaban un índice SLEDAI>6. La actividad clínica medida mediante el índice SLEDAI se asociaba de forma estadísticamente significativa a los 4 parámetros de CVRS. En los 42 pacientes con un año de seguimiento la relación directa entre la actividad clínica y el FACIT-FATIGUE, EVA y EQ-5D-5L, así como la relación indirecta con el HAQ, se mantuvieron. Los pacientes fumadores y aquellos bajo tratamiento inmunosupresor presentaban valores disminuidos de EVA y FACIT-FATIGUE. Además, los pacientes con edades más avanzadas presentaban valores disminuidos de EVA, y aquellos con niveles bajos de vitamina D o leucopenia presentaban mayor percepción de fatiga. Conclusión La actividad clínica se asocia a diferentes dominios de la CVRS, apoyando la evaluación de la CVRS como complemento en el manejo del LES. (AU)

The impact of disease activity on health-related quality of life in patients with systemic lupus erythematosus.

BACKGROUND AND OBJECTIVE: The aim of this research was to investigate the relationship between disease activity and health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) considering the increased interest in the management of this disease. MATERIALS AND METHODS: HRQoL was measured at clinic visits during a 12-month follow-up period using questionnaires on fatigue (FACIT-FATIGUE); quality of life, EuroQol 5-dimension (EQ-5D-5L) health questionnaire with 5 levels; disability, Health Assessment Questionnaire (HAQ), and a Global Health Status (GHS) scale. Disease activity, organ damage and other clinical factors that could affect HRQoL were recorded. The association between disease activity and HRQoL was assessed using Bayesian linear regression models with monotonic effects. RESULTS: Data from 70 patients at the baseline visit and 42 patients with 1 year of follow-up were analyzed. At baseline, 28.57% of patients presented Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)>6. In the 70 baseline patients, disease activity was associated with HRQoL in all four parameters. In the 42 patients with 12 months of follow-up, the positive association of disease activity with GHS, FACIT-FATIGUE and EQ-5D-5L and the negative association with HAQ was maintained. Patients who are smokers and those receiving immunosuppressant therapy presented low GHS and FACIT-FATIGUE scores. Moreover, older age at inclusion was significantly associated to low GHS, while low leucocyte and 25-OH-vitamin D levels were associated to fatigue perception in SLE patients. CONCLUSION: Our results showed a statistically significant association between disease activity and HRQoL parameters.

Phenotypic and Target-Directed Screening Yields New Acaricidal Alternatives for the Control of Ticks.

Rhipicephalus microplus, the "common cattle tick", is the most important ectoparasite in livestock worldwide due to the economic and health losses it produces. This tick is a vector for pathogens of several tick-borne diseases. In Latin American countries, damages reach approximately USD 500 million annually due to tick infections, as well as tick-borne diseases. Currently, resistant populations for every chemical group of acaricides have been reported, posing a serious problem for tick control. This study aims to find new alternatives for controlling resistant ticks with compounds derived from small synthetic organic molecules and natural origins. Using BME26 embryonic cells, we performed phenotypic screening of 44 natural extracts from 10 Mexican plants used in traditional medicine, and 33 compounds selected from our chemical collection. We found 10 extracts and 13 compounds that inhibited cell growth by 50% at 50 µg/mL and 100 µM, respectively; the dose-response profile of two of them was characterized, and these compounds were assayed in vitro against different life stages of Rhipicephalus microplus. We also performed a target-directed screening of the activity of triosephosphate isomerase, using 86 compounds selected from our chemical collection. In this collection, we found the most potent and selective inhibitor of tick triosephosphate isomerase reported until now. Two other compounds had a potent acaricidal effect in vitro using adults and larvae when compared with other acaricides such as ivermectin and Amitraz. Those compounds were also selective to the ticks compared with the cytotoxicity in mammalian cells like macrophages or bovine spermatozoids. They also had a good toxicological profile, resulting in promising acaricidal compounds for tick control in cattle raising.

Current clinical spectrum of common variable immunodeficiency in Spain: The multicentric nationwide GTEM-SEMI-CVID registry.

Common variable immunodeficiency (CVID) constitutes a heterogenic group of primary immunodeficiency disorders with a wide-ranging clinical spectrum. CVID-associated non-infectious morbidity constitutes a major challenge requiring a full understanding of its pathophysiology and its clinical importance and global variability, especially considering the broad clinical, genetic, and regional heterogeneity of CVID disorders. This work aimed to develop a nationwide, multicenter, retrospective study over a 3-year period describing epidemiological, clinical, laboratory, therapeutic, and prognostic features of 250 CVID patients in Spain. The mean diagnostic delay was around 10 years and most patients initially presented with infectious complications followed by non-infectious immune disorders. However, infectious diseases were not the main cause of morbimortality. Non-infectious lung disease was extraordinarily frequent in our registry affecting approximately 60% of the patients. More than one-third of the patients in our cohort showed lymphadenopathies and splenomegaly in their follow-up, and more than 33% presented immune cytopenias, especially Evans' syndrome. Gastrointestinal disease was observed in more than 40% of the patients. Among biopsied organs in our cohort, benign lymphoproliferation was the principal histopathological alteration. Reaching 15.26%, the global prevalence of cancer in our registry was one of the highest reported to date, with non-Hodgkin B lymphoma being the most frequent. These data emphasize the importance of basic and translational research delving into the pathophysiological pathways involved in immune dysregulation and diffuse lymphocytic infiltration. This would reveal new tailored strategies to reduce immune complications, and the associated healthcare burden, and ensure a better quality of life for CVID patients.

Real-world Effectiveness and Safety of JAK Inhibitors in Rheumatoid Arthritis: A Single-centre Study / Efectividad y seguridad en el mundo real de los inhibidores de JAK en la artritis reumatoide: Estudio unicéntrico

Background/objective: To assess the effectiveness and safety of Baricitinib and Tofacitinib in rheumatoid arthritis (RA) patients in “real world” conditions. Methods: A single centre retrospective study was performed including RA patients who had initiated treatment with Baricitinib or Tofacitinib from September-2017 to January-2020. Demographic, clinical, laboratory, efficacy and safety variables were collected from baseline and at months 1, 3, 6, 12, 18 and 24. Effectiveness was evaluated by changes from the baseline in DAS28, SDAI, HAQ and acute phase reactants. Safety analysis included adverse events due to any cause, including infection or intolerance. Infection was considered severe if it implied hospitalization. Statistical analysis consisted in Bayesian mixed ordinal regression models including the monotonic effect of each visit and Kaplan–Meier survival curves. Results: Overall, 98 patients were included. A significant reduction of disease activity scores was noted in both groups. No difference between either treatment was detected in terms of effectiveness even in first line, after bDMARD failure, in monotherapy nor combined therapy. A total of 54 adverse events were recorded of which 18 were considered relevant. The incidence of infection, including Herpes Zoster, was similar in both groups. No patients in either group suffered any tuberculosis, thromboembolic event, malignancy, death or cardiovascular adverse events. Survival analysis did not show any difference between groups. Conclusion: Baricitinib and Tofacitinib are both comparable in terms of effectiveness and safety in real world conditions.(AU)

Antecedentes/objetivo: Evaluar la efectividad y seguridad de baricitinib y tofacitinib en los pacientes con artritis reumatoide (AR) en condiciones del «mundo real». Métodos: Se realizó un estudio retrospectivo unicéntrico que incluyó a los pacientes de AR que habían iniciado tratamiento con baricitinib o tofacitinib de septiembre de 2017 a enero de 2020. Se recopilaron las variables demográficas, clínicas, de laboratorio, de eficacia y seguridad a nivel basal, y transcurridos uno, 3, 6, 12, 18 y 24 meses. La efectividad se evaluó mediante los cambios desde el punto basal en cuanto a DAS28, SDAI, HAQ y los reactantes de fase aguda. El análisis de seguridad incluyó los episodios adversos debido a cualquier causa, incluyendo infección o intolerancia. Se consideró infección grave cuando se produjo hospitalización. El análisis estadístico consistió en modelos mixtos de regresión ordinaria de Bayes incluyendo el efecto monotónico de cada visita y las curvas de supervivencia de Kaplan-Meier. Resultados: En total se incluyeron 98 pacientes. Se observó una reducción significativa de la actividad de la enfermedad en ambos grupos. No se detectó diferencia alguna entre ninguno de los tratamientos en términos de efectividad incluso en primera línea, tras el fallo de bDMARD, en monoterapia ni en terapia combinada. Se registró un total de 54 episodios adversos, de los cuales se consideraron relevantes 18. La incidencia de la infección, incluyendo herpes zoster, fue similar en ambos grupos. Ningún paciente de cualquiera de los grupos padeció episodios adversos tales como tuberculosis, episodio tromboembólico, malignidad, muerte ni episodios adversos de tipo cardiovascular. El análisis de supervivencia no reflejó diferencia alguna entre los grupos. Conclusión: Baricitinib y tofacitinib son comparables en términos de efectividad y seguridad en condiciones del mundo real.(AU)

Cardiovascular risk assessment with carotid ultrasound in rheumatoid arthritis

Background/Objective: To assess the Cardiovascular Risk (CV) in Rheumatoid Arthritis (RA) patients using carotid ultrasound additionally to the traditional CV risk factors.MethodsA cross-sectional case control study was performed including RA patients and matched controls. This study was performed from July-2019 to January-2020. Population over 75 years old, established CV disease and/or chronic kidney disease (from III Stage) were excluded. Statistical analysis included a multivariate variance analysis (Manova) and a negative binomial regression adjusted by confounding factors.ResultsOverall, a total of 200 cases and 111 controls were included in the study. Demographical and clinical variables were comparable between groups. A relationship between age, BMI and high blood pressure was detected in both groups. RA patients showed higher intima-media thickness and higher plaque account compared to controls and it was related to the disease duration and DAS28 score.ConclusionRA leads to a higher intima-media thickness, and this is related to the disease duration and DAS28 score. These findings support that RA acts as an independent cardiovascular risk factor. (AU)

Objetivo: Evaluar el riesgo cardiovascular (RCV) en pacientes con artritis reumatoide (AR) mediante el empleo de la ecografía de carótidas en adición a los factores de riesgo cardiovascular clásicos.MétodosSe realizó un estudio de casos y controles transversal incluyendo pacientes con AR y controles voluntarios sin historia de eventos cardiovasculares. El estudio se llevó a cabo entre julio de 2019 y enero de 2020. Se excluyeron individuos con edad por encima de los 75 años, enfermedad cardiovascular establecida y/o enfermedad renal crónica.ResultadosEn total, se incluyeron 200 pacientes con AR y 111 controles. Las variables demográficas y clínicas fueron comparables entre los grupos de estudio. Se halló correlación entre la edad, el IMC y la presencia de hipertensión arterial en ambos grupos. Los pacientes con AR evidenciaron un mayor grosor íntima-media y una mayor presencia de placas en el estudio de ecografía carotídea respecto a los controles y además demostró guardar relación con una mayor duración de la enfermedad.ConclusionesLa AR conlleva el desarrollo de un mayor grosor íntima-media y ello correlaciona con la duración y la actividad de la enfermedad, lo cual apoya que la AR actúa como un factor de riesgo cardiovascular independiente. (AU)

Real-world Effectiveness and Safety of JAK Inhibitors in Rheumatoid Arthritis: A Single-centre Study.

BACKGROUND/OBJECTIVE: To assess the effectiveness and safety of Baricitinib and Tofacitinib in rheumatoid arthritis (RA) patients in "real world" conditions. METHODS: A single centre retrospective study was performed including RA patients who had initiated treatment with Baricitinib or Tofacitinib from September-2017 to January-2020. Demographic, clinical, laboratory, efficacy and safety variables were collected from baseline and at months 1, 3, 6, 12, 18 and 24. Effectiveness was evaluated by changes from the baseline in DAS28, SDAI, HAQ and acute phase reactants. Safety analysis included adverse events due to any cause, including infection or intolerance. Infection was considered severe if it implied hospitalization. Statistical analysis consisted in Bayesian mixed ordinal regression models including the monotonic effect of each visit and Kaplan-Meier survival curves. RESULTS: Overall, 98 patients were included. A significant reduction of disease activity scores was noted in both groups. No difference between either treatment was detected in terms of effectiveness even in first line, after bDMARD failure, in monotherapy nor combined therapy. A total of 54 adverse events were recorded of which 18 were considered relevant. The incidence of infection, including Herpes Zoster, was similar in both groups. No patients in either group suffered any tuberculosis, thromboembolic event, malignancy, death or cardiovascular adverse events. Survival analysis did not show any difference between groups. CONCLUSION: Baricitinib and Tofacitinib are both comparable in terms of effectiveness and safety in real world conditions.

Polygenic risk scores for prediction of breast cancer risk in women of African ancestry: a cross-ancestry approach.

Polygenic risk scores (PRSs) are useful for predicting breast cancer risk, but the prediction accuracy of existing PRSs in women of African ancestry (AA) remains relatively low. We aim to develop optimal PRSs for the prediction of overall and estrogen receptor (ER) subtype-specific breast cancer risk in AA women. The AA dataset comprised 9235 cases and 10 184 controls from four genome-wide association study (GWAS) consortia and a GWAS study in Ghana. We randomly divided samples into training and validation sets. We built PRSs using individual-level AA data by a forward stepwise logistic regression and then developed joint PRSs that combined (1) the PRSs built in the AA training dataset and (2) a 313-variant PRS previously developed in women of European ancestry. PRSs were evaluated in the AA validation set. For overall breast cancer, the odds ratio per standard deviation of the joint PRS in the validation set was 1.34 [95% confidence interval (CI): 1.27-1.42] with the area under receiver operating characteristic curve (AUC) of 0.581. Compared with women with average risk (40th-60th PRS percentile), women in the top decile of the PRS had a 1.98-fold increased risk (95% CI: 1.63-2.39). For PRSs of ER-positive and ER-negative breast cancer, the AUCs were 0.608 and 0.576, respectively. Compared with existing methods, the proposed joint PRSs can improve prediction of breast cancer risk in AA women.

Semirigid Fiberglass Casting for the Early Management of Clubfoot: A Single-Center Experience.

Background Semirigid fiberglass (SRF) is an alternative material to plaster of Paris (POP) for idiopathic clubfoot casting in the Ponseti method. The purpose of this study was to evaluate early clinical outcomes in a series of idiopathic clubfoot patients treated with SRF at a single institution and to compare these findings to historical norms with POP casting present in the literature. Methods A series of idiopathic clubfoot patients managed exclusively with SRF in the Ponseti method was identified. Treatment efficacy was evaluated by number of casts, change in Pirani score, frequency of treatment-related complications, and frequency of surgery other than tenotomy. A comprehensive literature review was used for comparative historical norms. Results The study included 34 feet in 26 patients. Pirani score was 4.7±1.3 at presentation and 1.9±1.4 at the end of casting, representing a score change of 2.8±1.3 with SRF. Initial correction was obtained with 6.9±1.4 casts. Treatment-related complications occurred in six treated feet (17.6%) including 13 cast slippages in five feet and one cast-related thigh abrasion. A total of 25 (73.5%) feet underwent tenotomy. Two feet required an additional surgical procedure. Conclusion Clubfoot patients treated with SRF demonstrated acceptable deformity correction following Ponseti-style casting. The quantitative clinical outcomes evaluated appeared similar to norms using POP present in the literature. The findings of this study support SRF as a viable alternative to plaster casting for clubfoot correction utilizing the Ponseti method. As such, further investigation for rigorous comparative assessment is warranted.

Cardiovascular risk assessment with carotid ultrasound in rheumatoid arthritis.

BACKGROUND/OBJECTIVE: To assess the Cardiovascular Risk (CV) in Rheumatoid Arthritis (RA) patients using carotid ultrasound additionally to the traditional CV risk factors. METHODS: A cross-sectional case control study was performed including RA patients and matched controls. This study was performed from July-2019 to January-2020. Population over 75 years old, established CV disease and/or chronic kidney disease (from III Stage) were excluded. Statistical analysis included a multivariate variance analysis (Manova) and a negative binomial regression adjusted by confounding factors. RESULTS: Overall, a total of 200 cases and 111 controls were included in the study. Demographical and clinical variables were comparable between groups. A relationship between age, BMI and high blood pressure was detected in both groups. RA patients showed higher intima-media thickness and higher plaque account compared to controls and it was related to the disease duration and DAS28 score. CONCLUSION: RA leads to a higher intima-media thickness, and this is related to the disease duration and DAS28 score. These findings support that RA acts as an independent cardiovascular risk factor.