Bone marrow mesenchymal/fibroblastic stromal cells induce a distinctive EMT-like phenotype in AML cells.

The development of epithelial-to-mesenchymal transition (EMT) like features is emerging as a critical factor involved in the pathogenesis of acute myeloid leukaemia (AML). However, the extracellular signals and the signalling pathways in AML that may regulate EMT remain largely unstudied. We found that the bone marrow (BM) mesenchymal/fibroblastic cell line HS5 induces an EMT-like migratory phenotype in AML cells. AML cells underwent a strong increase of vimentin (VIM) levels that was not mirrored to the same extent by changes of expression of the other EMT core proteins SNAI1 and SNAI2. We validated these particular pattern of co-expression of core-EMT markers in AML cells by performing an in silico analysis using datasets of human tumours. Our data showed that in AML the expression levels of VIM does not completely correlate with the co-expression of core EMT markers observed in epithelial tumours. We also found that vs epithelial tumours, AML cells display a distinct patterns of co-expression of VIM and the actin binding and adhesion regulatory proteins that regulate F-actin dynamics and integrin-mediated adhesions involved in the invasive migration in cells undergoing EMT. We conclude that the BM stroma induces an EMT related pattern of migration in AML cells in a process involving a distinctive regulation of EMT markers and of regulators of cell adhesion and actin dynamics that should be further investigated. Understanding the tumour specific signalling pathways associated with the EMT process may contribute to the development of new tailored therapies for AML as well as in different types of cancers.

Effect of treatment with paliperidone palmitate versus oral antipsychotics on frontal lobe intracortical myelin volume in participants with recent-onset schizophrenia: Magnetic resonance imaging results from the DREaM study.

OBJECTIVE: We investigated changes in brain intracortical myelin (ICM) volume in the frontal lobe after 9 months of treatment with paliperidone palmitate (PP) compared with 9 months of treatment with oral antipsychotics (OAP) in participants with recent-onset schizophrenia or schizophreniform disorder from the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial. METHODS: DREaM included 3 phases: Part I, a 2-month oral run-in; Part II, a 9-month disease progression phase (PP or OAP); and Part III, 9 months of additional treatment (participants receiving PP continued PP [PP/PP] and participants receiving OAP were rerandomized to receive either PP [OAP/PP] or OAP [OAP/OAP]). In Part II, magnetic resonance imaging (MRI) and functional and symptomatic assessment was performed at baseline, day 92, and day 260. ICM volume as a fraction of the entire brain volume was quantified by subtraction of a proton density image from an inversion recovery image. Within-treatment-group changes from baseline were assessed by paired t-tests. Analysis of covariance was used to analyze ICM volume changes between treatment groups, adjusting for country. RESULTS: The MRI analysis sample size included 71 DREaM participants (PP, 23; OAP, 48) and 64 healthy controls. At baseline, mean adjusted ICM fraction values did not differ between groups (PP, 0.057; OAP, 0.058, p = 0.79). By day 92, the adjusted ICM fraction in the OAP group had decreased significantly (change from baseline, -0.002; p = 0.001), whereas the adjusted ICM fraction remained unchanged from baseline in the PP group (0.000; p = 0.80). At day 260, the change from baseline in adjusted ICM fraction was -0.004 (p = 0.004) in the OAP group and -0.001 (p = 0.728) in the PP group. The difference between treatment groups did not reach statistical significance (p = 0.147). CONCLUSIONS: In participants with recent-onset schizophrenia or schizophreniform disorder, frontal ICM volume was preserved at baseline levels in those treated with PP over 9 months. However, a decrease of frontal ICM volume was observed among participants treated with OAPs. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT02431702.

Experiencia en el tratamiento de la enfermedad de Dupuytren con ondas de choque radiales: estudio de caso / Experience in the treatment of Dupuytren's disease with radial extracorporeal shockwave therapy: A case report

Introducción y objetivos La enfermedad de Dupuytren (ED) es un trastorno proliferativo benigno que afecta a la aponeurosis palmar y dedos en la mano. Los tratamientos propuestos son en su mayoría invasivos y presentan recurrencias. Se ha postulado la utilización de ondas de choque para el manejo de esta enfermedad dado su bajo costo, además de ser una técnica no invasiva. El objetivo de este trabajo es describir una experiencia terapéutica en el manejo de la ED utilizando ondas de choque radiales (OCr). Material y métod Mujer de 72 años, presenta tejido fibroso retráctil en la palma de ambas manos asociado al dedo meñique, manifestando dolor a la presión y limitación severa de la movilidad en extensión. Se evaluó la intensidad de dolor al reposo y al movimiento, umbral de dolor a la presión, movilidad, fuerza prensil, discapacidad y severidad de la ED. Se realizaron 6 sesiones de OCr distribuidas en 4 semanas, utilizando 2000 pulsos a 14Hz y 1,4bar, para luego seguir con 2000 pulsos a 6Hz y 3,4bar. Resultados: Se evidenciaron mínimas mejorías en todas las variables evaluadas. Estas no generaron una diferencia mínima clínicamente importante. Conclusión Basado en esta experiencia, las OCr no produjeron un cambio clínico relevante en el tratamiento de la ED en estadio avanzado. Es necesario profundizar en la eficacia de esta técnica considerando el tipo de ondas de choque que se utiliza, así como una estadificación variada que permita evidenciar los efectos según la severidad de la ED (AU)

Background and objectives Dupuytren's disease (DD) is a benign proliferative disorder that affects the palmar aponeurosis and fingers. Current treatments are mostly invasive and have recurrences. Extracorporeal shockwave therapy has been proposed for the management of this disease, given its low cost, in addition to being a non-invasive technique. The aim of this study is present a therapeutic experience in DD using radial extracorporeal shockwave therapy (rESWT). Material and method A 72-year-old woman presented in both hands a band of palmar fibrous tissue associated with the little finger, manifesting pain on pressure and severe limitation of extension. Pain intensity at rest and movement, pressure pain threshold, mobility, grip strength, disability, and severity of DD were evaluated. Six sessions of rESWT were performed distributed over 4 weeks using 2000 pulses at 14Hz and 1.4bar followed by 2000 pulses at 6Hz and 3.4bar. Results Minimal improvements were evidenced in all the variables evaluated. The effect of the intervention was not sufficient to generate a minimal clinically important difference. Conclusion Based on this experience, rESWT did not generate a relevant clinical change in the treatment of advanced-stage DD. It is necessary to inquire into the efficacy of this technique considering the type of extracorporeal shockwave used, as well as a varied staging that allows evidence the effects of radial shockwaves according to the severity of disease (AU)

Instrucciones con foco atencional durante el ejercicio terapéutico en personas con trastornos musculoesqueléticos. Una revisión de alcance / Attentional focus instructions for therapeutic exercise in people with musculoskeletal disorders. A scoping review

Las instrucciones con foco atencional son estrategias verbales que podrían maximizar los efectos del ejercicio. El objetivo de esta revisión fue explorar y sintetizar la evidencia sobre la incorporación de instrucciones con foco atencional al ejercicio terapéutico de personas con trastornos musculoesqueléticos. Se realizó una búsqueda en 11 bases de datos hasta octubre de 2020. De 4.227 estudios identificados en las búsquedas, 15 fueron incluidos. Los estudios presentaron deficiencia en la conceptualización y definición de instrucciones con foco atencional. La evidencia disponible indica que el foco externo es efectivo para mejorar el aprendizaje motor y la función. Sin embargo, limitaciones metodológicas, la heterogeneidad clínica, el reducido número de artículos incluidos y los nuevos estudios experimentales desafían las conclusiones de las revisiones sistemáticas disponibles a la fecha. Las instrucciones con foco atencional en los trastornos musculoesqueléticos es un campo emergente y requiere más investigación. Esta revisión es una guía para futuros estudios.(AU)

Attentional focus instructions are verbal strategies that could maximize the effects of exercise. The objective of this review was to explore and synthesize the available evidence on the incorporation of attentional focus instruction in the exercise of people with musculoskeletal disorders. A search of 11 databases was carried out until October 2020. Of 4,227 studies identified in the searches, 15 were included. The studies showed deficiencies in the conceptualization and definition of attentional focus instructions. The available evidence indicates that external focus is effective in improving motor learning and function. However, methodological limitations, clinical heterogeneity, the small number of articles included, and new experimental studies challenge the conclusions of the systematic reviews available to date. Attentional focus instructions in musculoskeletal disorders is an emerging field and requires further research. This review is a guide for future studies.(AU)

[Attentional focus instructions for therapeutic exercise in people with musculoskeletal disorders. A scoping review]. / Instrucciones con foco atencional durante el ejercicio terapéutico en personas con trastornos musculoesqueléticos. Una revisión de alcance.

Attentional focus instructions are verbal strategies that could maximize the effects of exercise. The objective of this review was to explore and synthesize the available evidence on the incorporation of attentional focus instruction in the exercise of people with musculoskeletal disorders. A search of 11 databases was carried out until October 2020. Of 4,227 studies identified in the searches, 15 were included. The studies showed deficiencies in the conceptualization and definition of attentional focus instructions. The available evidence indicates that external focus is effective in improving motor learning and function. However, methodological limitations, clinical heterogeneity, the small number of articles included, and new experimental studies challenge the conclusions of the systematic reviews available to date. Attentional focus instructions in musculoskeletal disorders is an emerging field and requires further research. This review is a guide for future studies.

Asociación entre la dependencia funcional, capacidad funcional y dolor, en personas mayores con artrosis severa de cadera / Association between functional dependence, functional capacity, and pain in older people with severe osteoarthritis of the hip

Antecedentes y objetivo: Determinar si existe asociación entre dependencia funcional, capacidad funcional e intensidad del dolor en personas mayores con artrosis de cadera. Materiales y métodos: Estudio transversal-analítico con reclutamiento consecutivo de 85 individuos. Se evaluó dependencia funcional (índice de Barthel), capacidad funcional (WOMAC) y dolor (escala numérica del dolor). Se determinaron diferencias en capacidad funcional y dolor, según la condición de dependencia funcional. Además, se analizó la correlación entre estas variables. Todos los análisis consideraron un nivel de significación de p<0,05. Resultados: Ochenta y cinco participantes (72,26±5,69 años de edad; 54,12% mujeres) fueron incluidos en el estudio. Los promedios para el índice de Barthel, WOMAC e intensidad del dolor fueron 94,00±9,35; 44,49±17,08 y 6,09±3,12 respectivamente. Del total de participantes 46 fueron clasificados como independientes. El análisis demostró que los participantes clasificados como dependientes presentaron un mayor puntaje en WOMAC-total (p=0,001), WOMAC-dolor (p=0,037), WOMAC-función (p<0,001) y dolor (p=0,010), con tamaños de efecto entre medio y grande. No se encontró diferencias en WOMAC-rigidez (p=0,184). Se encontró una correlación inversa, moderada y significativa entre los puntajes de WOMAC-total (p<0,001), WOMAC-dolor (p=0,007), WOMAC-función (p<0,001) e intensidad del dolor (p=0,002) con el puntaje de dependencia funcional de Barthel, pero no con WOMAC-rigidez (p=0,141). Conclusiones: Los individuos con artrosis de cadera avanzada dependientes funcionalmente tienen una capacidad funcional menor y una intensidad del dolor mayor que los clasificados como independientes. Esta información provee un insumo valioso para clínicos y para la planificación de estrategias de salud.

Background and aim: To determine the association between functional dependence, functional capacity, and pain intensity in older adults with hip osteoarthritis. Methods: Cross-sectional study with a consecutive sampling of 85 participants. Functional dependence (Barthel Index), functional capacity (WOMAC questionnaire), and pain (Numerical Rating Scale) were measured. Differences between functional capacity and pain, depending on functional dependence status were determined. Moreover, correlation analyses were performed between these outcomes. All analyses considered a significance level of p<.05. Results: 85 participants (72.26±5.69 years old; 54.12% women) were included. Mean values for Barthel Index, WOMAC, and pain intensity were 94.00±9.35; 44.49±17.08 and 6.09±3.12, respectively. Of the total participants, 46 were classified as independent. The analysis showed that participants classified as dependent exhibited a higher score in WOMAC-total (p=.001), WOMAC-pain (p=.037), WOMAC-function (p<.001), and pain intensity (p=.01), with medium to high effect sizes. No differences were seen in WOMAC-stiffness (p=.184). An inversed, moderate correlation between the Barthel Index and WOMAC-total (p<.001), WOMAC-pain (p=.007), WOMAC-function (p<.001) and pain intensity (p=.002) were seen, but not in WOMAC-stiffness (p = .141). Conclusion: Functionally dependent older adults with advanced hip osteoarthritis have lower functional capacity and higher pain intensity than those classified as functionally independent. This information provides a valuable insight for clinicians to plan future health strategies.

Axonal quantification of the white matter association fasciculi in cerebral hemispheres of cow (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus).

BACKGROUND: Cerebral white matter consists mainly of axons surrounded by myelin sheaths, which are grouped to form association, commissural, and projection fasciculi. The aim of our work was to quantify and compare under the microscope the axons of the white matter association fasciculi in the cerebral hemispheres of cow (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus) indirectly by identification of their myelin sheaths. MATERIALS AND METHODS: The samples were taken from 30 cerebral hemispheres: 10 cow, 10 pig and 10 rabbit (15 right and 15 left). They were obtained following a protocol based on the Talairach-Tournoux coordinate system for human and primate brains. The slides were stained with Luxol Fast Blue, observed by optical microscopy, and photographed at 600×. Samples were also prepared for observation in scanning transmission electron microscopy with osmium tetroxide. The myelin sheaths/axons were counted with the ImageJ software. RESULTS: Statistically significant differences in the number of myelin sheaths per 410 µm² were found in the inferior and superior longitudinal fasciculi between the left and right hemispheres of cows, with predominance of the right hemisphere; and in the inferior occipitofrontal fasciculus of the rabbit with predominance of the left hemisphere. CONCLUSIONS: The use of animal models for experiments in the cerebral fasciculi, especially pig, could give us a greater understanding of the behaviour of demyelinating and neurodegenerative diseases in humans.

[Antimicrobials in neonatology. Part II: Recommendations for the dilution and administration of antimicrobials in the newborn]. / Antimicrobianos en neonatología. Parte II: Recomendaciones para la dilución y administración de antimicrobianos utilizados en el recién nacido.

Antimicrobials are among the most commonly prescribed classes of medications in Neonatal Intensive Care Units; however, its use has been constantly associated with a number of medication errors in clinical practice. In contrast to this situation, there is no common agreement when it comes to determining the right dosing, administration, or handling of antibiotics in this population. In order to help improve the use of antibiotics, decrease the rate of medication errors and optimize clinical results in the newborn, this review aims to provide recommendations to support and guide the correct preparation of some of the most relevant antibiotics used in neonatal wards.

Antimicrobianos en neonatología. Parte II: Recomendaciones para la dilución y administración de antimicrobianos utilizados en el recién nacido / Antimicrobials in neonatology. Part II: Recommendations for the dilution and administration of antimicrobials in the newborn

Resumen Los antimicrobianos corresponden al grupo de medicamentos más utilizados en Unidades de Cuidados Intensivos Neonatales; no obstante, su uso ha sido asociado a constantes errores de medicación en la práctica clínica. Paradojalmente, aún no existe consenso en torno a la administración adecuada de estos medicamentos y existen importantes brechas de conocimiento en torno a los procesos de dosificación, administración y manipulación de antimicrobianos en esta población. Con el fin de mejorar el uso de antimicrobianos, disminuir errores y optimizar los resultados clínicos en el recién nacido, la presente revisión tiene por objetivo entregar recomendaciones y servir de guía para la correcta preparación de aquellos antimicrobianos de mayor relevancia en neonatología.

Abstract Antimicrobials are among the most commonly prescribed classes of medications in Neonatal Intensive Care Units; however, its use has been constantly associated with a number of medication errors in clinical practice. In contrast to this situation, there is no common agreement when it comes to determining the right dosing, administration, or handling of antibiotics in this population. In order to help improve the use of antibiotics, decrease the rate of medication errors and optimize clinical results in the newborn, this review aims to provide recommendations to support and guide the correct preparation of some of the most relevant antibiotics used in neonatal wards.

Prognostic value of molecular biomarkers in patients with metastatic colorectal cancer: a real-world study

Purpose Outcomes for patients with metastatic colorectal cancer (mCRC) have been improved by the identification of biomarkers predictive and prognostic of clinical outcome. The present retrospective analysis was undertaken to assess the utility of key biomarkers and clinical parameters in predicting outcomes in Spanish patients with mCRC. Methods We retrospectively analyzed tumor samples from a series of patients aged > 18 years with mCRC who were treated at the Hospital General Universitario Gregorio Marañón Spain. Real-time polymerase chain reaction was used to detect KRAS, NRAS, BRAF, and PIK3CA mutations. The key outcome of interest was overall survival (OS). Survival curves were estimated using the Kaplan–Meier method and stratified by the variables of greatest clinical interest. Differences were tested using the log-rank test. Results Median OS in the overall population was 24.4 months. Triple WT patients (WT KRAS, NRAS, and BRAF) and quadruple WT patients (WT KRAS, NRAS, BRAF, and PIK3CA) had significantly better OS than those who did not have triple or quadruple WT tumors. OS was significantly better in patients with left- vs. right-sided tumors, patients with resected primary tumors and metastases vs. those without resection, and patients with isolated hepatic and isolated pulmonary metastases. Conclusions This retrospective, observational study has confirmed the prognostic value of the location and resection status of the primary tumor and metastases in Spanish patients with mCRC. Triple WT status, in particular, was prognostic in this patient population, with PIK3CA adding to the prognostic value in the quadruple WT population (AU)