Biomarker candidates for progression and clinical management of COVID-19 associated pneumonia at time of admission.

COVID-19 pathophysiology is currently not fully understood, reliable prognostic factors remain elusive, and few specific therapeutic strategies have been proposed. In this scenario, availability of biomarkers is a priority. MS-based Proteomics techniques were used to profile the proteome of 81 plasma samples extracted in four consecutive days from 23 hospitalized COVID-19 associated pneumonia patients. Samples from 10 subjects that reached a critical condition during their hospital stay and 10 matched non-severe controls were drawn before the administration of any COVID-19 specific treatment and used to identify potential biomarkers of COVID-19 prognosis. Additionally, we compared the proteome of five patients before and after glucocorticoids and tocilizumab treatment, to assess the changes induced by the therapy on our selected candidates. Forty-two proteins were differentially expressed between patients' evolution groups at 10% FDR. Twelve proteins showed lower levels in critical patients (fold-changes 1.20-3.58), of which OAS3 and COG5 found their expression increased after COVID-19 specific therapy. Most of the 30 proteins over-expressed in critical patients (fold-changes 1.17-4.43) were linked to inflammation, coagulation, lipids metabolism, complement or immunoglobulins, and a third of them decreased their expression after treatment. We propose a set of candidate proteins for biomarkers of COVID-19 prognosis at the time of hospital admission. The study design employed is distinctive from previous works and aimed to optimize the chances of the candidates to be validated in confirmatory studies and, eventually, to play a useful role in the clinical practice.

Assessing treatment tolerability for rheumatoid arthritis. Validation and practical applications of the 'TOL-AR-18 questionnaire' / Evaluación de la tolerabilidad al tratamiento de la artritis reumatoide. Validación y aplicaciones prácticas del «cuestionario TOL-AR-18»

INTRODUCTION: Given the lack of standardized tools to assess tolerability from patient's perspective, we carried out the validation of a questionnaire to asses treatment tolerability for rheumatoid arthritis (RA): TOL-AR-18. METHODS: The TOL-AR-18 was validated in the cross-sectional observational study in adult patients with RA. Socio-demographic and clinical variables were collected. Patients completed the TOL-AR-18 and ARTS questionnaires and a question about their general health status. RESULTS: Data of 66 patients with a mean age (standard deviation; SD) of 56.71 (10.50) years were analyzed; 66.7% were women. Mean (SD) time to disease progression was 10.76 (8.23) years, and time from first treatment initiation was 9.24 (7.70) years. Patients did not report other adverse events rather than those included in the TOL-AR-18. The questionnaire was feasible with high internal consistency (Cronbach's Alpha >0.90). Discriminant validity was moderate, with significant differences between patients in remission and all other, and between patients who did not report adverse events and the rest (P<.05). Convergent validity was moderate-low when correlated with the ARTS questionnaire. CONCLUSION: The TOL-AR-18 is valid for use in a clinical setting and useful as an additional tool for all professionals to manage and assess tolerability in RA

INTRODUCCIÓN: La ausencia de herramientas estandarizadas para evaluar la tolerabilidad desde la perspectiva del paciente, planteó la posibilidad de validar el cuestionario TOL-AR-18 de tolerabilidad al tratamiento de la artritis reumatoide (AR) y evaluar su aplicación en la práctica clínica. MÉTODOS: El desarrollo del cuestionario se realizó siguiendo la metodología estandarizada y posteriormente se validó mediante un estudio observacional y transversal con pacientes >18 años diagnosticados de AR, en tratamiento durante al menos 3 meses. Se recogieron variables socio-demográficas y clínicas. Los pacientes completaron los cuestionarios TOL-AR-18, ARTS, y el cuestionario sobre el estado de salud percibida. RESULTADOS: Se analizaron datos de 66 pacientes de edad media (desviación estándar [DE]) de 56,71 (10,50) años; un 66,7% eran mujeres y el 65,1% presentaba remisión/baja actividad por DAS28. La media (DE) del tiempo de evolución y del inicio del primer tratamiento fue de 11,34 (9,41) y 9,24 (7,7) años, respectivamente. Los pacientes no reportaron reacciones adversas adicionales a las incluidas en el TOL-AR-18. El cuestionario resultó factible con una consistencia interna elevada (alfa de Cronbach>0,9). La validez discriminante fue moderada, con diferencias estadísticamente significativas entre pacientes en remisión y el resto, y entre quienes no reportaban reacciones adversas y el resto (p < 0,05). La validez convergente fue moderada-baja al correlacionarse con el cuestionario ARTS. CONCLUSIONES: El cuestionario TOLAR-18 es válido para su uso en la práctica clínica y útil como herramienta complementaria para el manejo y valoración de la tolerabilidad en la AR por parte de todos los profesionales implicados

Assessing treatment tolerability for rheumatoid arthritis. Validation and practical applications of the 'TOL-AR-18 questionnaire'.

INTRODUCTION: Given the lack of standardized tools to assess tolerability from patient's perspective, we carried out the validation of a questionnaire to asses treatment tolerability for rheumatoid arthritis (RA): TOL-AR-18. METHODS: The TOL-AR-18 was validated in the cross-sectional observational study in adult patients with RA. Socio-demographic and clinical variables were collected. Patients completed the TOL-AR-18 and ARTS questionnaires and a question about their general health status. RESULTS: Data of 66 patients with a mean age (standard deviation; SD) of 56.71 (10.50) years were analyzed; 66.7% were women. Mean (SD) time to disease progression was 10.76 (8.23) years, and time from first treatment initiation was 9.24 (7.70) years. Patients did not report other adverse events rather than those included in the TOL-AR-18. The questionnaire was feasible with high internal consistency (Cronbach's α >0.90). Discriminant validity was moderate, with significant differences between patients in remission and all other, and between patients who did not report adverse events and the rest (P<.05). Convergent validity was moderate-low when correlated with the ARTS questionnaire. CONCLUSION: The TOL-AR-18 is valid for use in a clinical setting and useful as an additional tool for all professionals to manage and assess tolerability in RA.

Clima motivacional, satisfacción, compromiso y éxito académico en estudiantes angoleños y dominicanos / Clima motivacional, satisfação, engajamento e sucesso acadêmico em estudantes angolanos e dominicanos / Motivational climate, satisfaction, engagement, and academic success in Angolan and Dominican students

El objetivo fue triple: validar las versiones portuguesa y española de la Escala de Orientación y Clima Motivacional (MOC), evaluar la invarianza métrica en muestras de estudiantes dominicanos y angoleños, y estudiar las relaciones de las orientaciones y climas motivacionales con aspectos educativos relevantes. Participaron 2302 estudiantes dominicanos y 2028 angoleños de 14 a 18 años. Mediante Análisis Factorial Confirmatorio se comprobó que las cuatro dimensiones hipotetizadas del MOC se ajustaban bien a los datos de ambas muestras. Los resultados más relevantes mostraron que las percepciones de los estudiantes sobre el clima de maestría se relacionaron positivamente con el compromiso escolar y el éxito académico en ambas muestras, mientras que las percepciones del clima de ejecución se relacionaron negativamente con estas variables escolares. Los resultados se discuten en el marco de la teoría de las metas de logro (TML) y en relación con las implicaciones para la práctica educativa.

O objetivo do estudo foi triplo: validar as versões em português e espanhol da Escala de Orientação e Clima Motivacional (MOC); avaliar a sua invariância métrica em amostras de estudantes dominicanos e angolanos; e estudar as relações das orientações e climas motivacionais com os aspectos educacionais relevantes. Participaram 2.302 estudantes dominicanos e 2.028 angolanos, de 14 a 18 anos. A Análise Fatorial Confirmatória mostrou que as quatro dimensões da hipótese do MOC se ajustaram bem aos dados de ambas as amostras. Os resultados mais relevantes mostraram que as percepções dos alunos sobre o clima de ensino estavam positivamente relacionadas ao engajamento escolar e ao sucesso acadêmico em ambas as amostras, enquanto as percepções do clima de desempenho estavam negativamente relacionadas com ditas variáveis. Os resultados são discutidos no âmbito da teoria das metas de realização e com relação às implicações para a prática educacional.

The aim was threefold: to validate the Portuguese and Spanish versions of the Motivational Orientation and Climate Scale (MOC), to test for measurement invariance across large Dominican and Angolan students' samples, and to study the relationships of motivational orientations and climates with relevant educational outcomes. Participants were 2302 Dominican and 2028 Angolan students from 14 to 18 years old. Confirmatory Factor Analyses were used to study factorial structure of the MOC. Main results showed that the hypothesized four dimensions fitted the data from both samples well. Regarding the relationships analyzed, the most relevant results shown that students' perceptions of mastery class climate was positively related with school engagement and academic success in both Dominican and Angolan samples, while perceptions of performance class climate was negatively related to these school variables. Results are discussed within the achievement goal framework and in regard to the implications for educational practices.

A 76-kb duplicon maps close to the BCR gene on chromosome 22 and the ABL gene on chromosome 9: possible involvement in the genesis of the Philadelphia chromosome translocation.

A patient with a typical form of chronic myeloid leukemia was found to carry a large deletion on the derivative chromosome 9q+ and an unusual BCR-ABL transcript characterized by the insertion, between BCR exon 14 and ABL exon 2, of 126 bp derived from a region located on chromosome 9, 1.4 Mb 5' to ABL. This sequence was contained in the bacterial artificial chromosome RP11-65J3, which in fluorescence in situ hybridization experiments on normal metaphases was found to detect, in addition to the predicted clear signal at 9q34, a faint but distinct signal at 22q11.2, where the BCR gene is located, suggesting the presence of a large region of homology between the two chromosomal regions. Indeed, blast analysis of the RP11-65J3 sequence against the entire human genome revealed the presence of a stretch of homology, about 76 kb long, located approximately 150 kb 3' to the BCR gene, and containing the 126-bp insertion sequence. Evolutionary studies using fluorescence in situ hybridization identified the region as a duplicon, which transposed from the region orthologous to human 9q34 to chromosome 22 after the divergence of orangutan from the human-chimpanzee-gorilla common ancestor about 14 million years ago. Recent sequence analyses have disclosed an unpredicted extensive segmental duplication of our genome, and the impact of duplicons in triggering genomic disorders is becoming more and more apparent. The discovery of a large duplicon relatively close to the ABL and BCR genes and the finding that the 126-bp insertion is very close to the duplicon at 9q34 open the question of the possible involvement of the duplicon in the formation of the Philadelphia chromosome translocation.