Protocol of a multisite randomized controlled trial of Bright IDEAS-Young Adults: Problem-solving skills training to reduce distress among young adults with Cancer.

BACKGROUND: Young adults with cancer diagnosed between the ages of 18 to 39 are recognized as a vulnerable group with unique emotional, social, and practical needs that put them at risk of poor psychosocial outcomes and impaired health-related quality of life (HRQOL). This study describes the protocol of a randomized controlled trial to evaluate the efficacy of Bright IDEAS-Young Adults (Bright IDEAS-YA), a problem-solving skills training intervention, on psychosocial outcomes of young adults newly diagnosed with cancer. METHODS: Bright IDEAS-YA is a two-arm, parallel, randomized controlled trial. Young adults are eligible if they are 18-39 years of age, within four months of a first cancer diagnosis, and receiving systemic therapy with life expectancy of at least six months. Participants are randomized 1:1 to Bright IDEAS-YA or enhanced usual care. Survey measures are completed at enrollment and 3, 6, 12, and 24 months. The primary endpoint will be the estimated change from baseline to 6 months in symptoms of depression, anxiety, and psychosocial HRQOL. The other time points are secondary endpoints. Mediators and moderators will be examined. CONCLUSIONS: This randomized trial will determine the efficacy of Bright IDEAS-YA on psychosocial outcomes for young adults newly diagnosed with cancer. Analyses will also examine mechanisms of action and potentially identify subgroups for whom the intervention is particularly useful. TRIAL REGISTRATION: clinicaltrials.gov #NCT04585269.

Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients.

BACKGROUND: In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted. RESULTS: We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure. CONCLUSION: This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.

Functional Analysis of BRCA1 3'UTR Variants Predisposing to Breast Cancer.

Purpose: Breast Cancer (BC) is the main female cancer diagnosed worldwide, and it has been described that few genes, such as BRCA1, have a high penetrance for this type of cancer. In this manuscript, we were interested in evaluating the effect of 3'UTR variants on BRCA1 expression. Patients and Methods: To accomplish this objective, Whole Exome Sequencing (WES) data of 400 patients with unselected BC was used to filter variants located in the region of interest of BRCA1 gene, finding two of them (c.*36C>G and c.*369_373del). miRGate and miRanda in silico tools were used to predict microRNA (miRNA) interaction. Results: The two variants (c.*36C>G, c.*369_373del) were predicted to affect miRNA interaction. After cloning of BRCA1 3'UTR into pMIR-Report vector, the construct was transfected into two BC cell lines (MDA-MB-231 and MCF-7), and the variant c.*36C>G evidenced overexpression of reporter gene luciferase, showing that the transcript was not being degraded by the miRNA in MDA-MB-231 cells. Conclusion: The variant seems to protect against Triple Negative BC probably due to the expression level of miRNA in this particular cell line (MDA-MB-231). This is consistent with the clinical history of the patients who harbor BC Hormone Receptors positive (HR+).

Wnt/ß-catenin signaling is a therapeutic target in anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy that has consistently shown Wnt/ß-catenin (canonical) signaling activation in various study populations. There are currently no targetable treatments for BRAF-wildtype ATC and a lack of effective treatment for BRAFV600EATC. Our aim is to identify whether Wnt inhibitors could be potential therapeutic agents for ATC patients with limited treatment options. METHODS: In this Institutional Review Board-approved study, we utilize a cohort of 32 ATCs and 20 non-neoplastic multinodular goiters (MNG). We also use 4 ATC spheroid cell lines (THJ-16T, THJ-21T, THJ-29T, and THJ-11T) and two primary patient-derived ATC organoid cultures (VWL-T5 and VWL-T60). Finally, we use a murine xenograft mouse model of ATC for in vivo treatment studies. RESULTS: Using a large patient cohort, we demonstrate that this near-universal Wnt signaling activation is associated with ligand expression- rather than being mutationally-driven. We show that pyrvinium pamoate, a potent Wnt inhibitor, exhibits in vitro efficacy against both ATC cell lines and primary patient-derived ATC organoids VWL-T5 (p < 0.05) and VWL-T60 (p < 0.01) Finally, using a murine xenograft model of ATC, we show that pyrvinium significantly delays the growth of ATC tumors in THJ-16T (p < 0.005) and THJ-21T (p < 0.001). CONCLUSIONS: We tested Wnt inhibitor treatment, both in vitro and in vivo, as a potential novel therapy for this highly lethal disease. Future large-scale studies utilizing multiple Wnt inhibitors will lay the foundation for the development of these novel therapies for patients with ATC.

AAV-mediated expression of mouse or human GLDC normalises metabolic biomarkers in a GLDC-deficient mouse model of Non-Ketotic Hyperglycinemia.

Non-Ketotic Hyperglycinemia (NKH) is a rare inborn error of metabolism caused by impaired function of the glycine cleavage system (GCS) and characterised by accumulation of glycine in body fluids and tissues. NKH is an autosomal recessive condition and the majority of affected individuals carry mutations in GLDC (glycine decarboxylase). Current treatments for NKH have limited effect and are not curative. As a monogenic condition with known genetic causation, NKH is potentially amenable to gene therapy. An AAV9-based expression vector was designed to target sites of GCS activity. Using a ubiquitous promoter to drive expression of a GFP reporter, transduction of liver and brain was confirmed following intra-venous and/or intra-cerebroventricular administration to neonatal mice. Using the same capsid and promoter with transgenes to express mouse or human GLDC, vectors were then tested in GLDC-deficient mice that provide a model of NKH. GLDC-deficient mice exhibited elevated plasma glycine concentration and accumulation of glycine in liver and brain tissues as previously observed. Moreover, the folate profile indicated suppression of folate one­carbon metabolism (FOCM) in brain tissue, as found at embryonic stages, and reduced abundance of FOCM metabolites including betaine and choline. Neonatal administration of vector achieved reinstatement of GLDC mRNA and protein expression in GLDC-deficient mice. Treated GLDC-deficient mice showed significant lowering of plasma glycine, confirming functionality of vector expressed protein. AAV9-GLDC treatment also led to lowering of brain tissue glycine, and normalisation of the folate profile indicating restoration of glycine-derived one­carbon supply. These findings support the hypothesis that AAV-mediated gene therapy may offer potential in treatment of NKH.

Spectrum of somatic mutational features of colorectal tumors in ancestrally diverse populations.

Ancestrally diverse and admixed populations, including the Hispanic/Latino/a/x/e community, are underrepresented in cancer genetic and genomic studies. Leveraging the Latino Colorectal Cancer Consortium, we analyzed whole exome sequencing data on tumor/normal pairs from 718 individuals with colorectal cancer (128 Latino, 469 non-Latino) to map somatic mutational features by ethnicity and genetic ancestry. Global proportions of African, East Asian, European, and Native American ancestries were estimated using ADMIXTURE. Associations between global genetic ancestry and somatic mutational features across genes were examined using logistic regression. TP53 , APC , and KRAS were the most recurrently mutated genes. Compared to non-Latino individuals, tumors from Latino individuals had fewer KRAS (OR=0.64, 95%CI=0.41-0.97, p=0.037) and PIK3CA mutations (OR=0.55, 95%CI=0.31-0.98, p=0.043). Genetic ancestry was associated with presence of somatic mutations in 39 genes (FDR-adjusted LRT p<0.05). Among these genes, a 10% increase in African ancestry was associated with significantly higher odds of mutation in KNCN (OR=1.34, 95%CI=1.09-1.66, p=5.74×10 -3 ) and TMEM184B (OR=1.53, 95%CI=1.10-2.12, p=0.011). Among RMGs, we found evidence of association between genetic ancestry and mutation status in CDC27 (LRT p=0.0084) and between SMAD2 mutation status and AFR ancestry (OR=1.14, 95%CI=1.00-1.30, p=0.046). Ancestry was not associated with tumor mutational burden. Individuals with above-average Native American ancestry had a lower frequency of microsatellite instable (MSI-H) vs microsatellite stable tumors (OR=0.45, 95%CI=0.21-0.99, p=0.048). Our findings provide new knowledge about the relationship between ancestral haplotypes and somatic mutational profiles that may be useful in developing precision medicine approaches and provide additional insight into genomic contributions to cancer disparities. Significance: Our data in ancestrally diverse populations adds essential information to characterize mutational features in the colorectal cancer genome. These results will help enhance equity in the development of precision medicine strategies.

[Baseline characterization of a cohort of colombian patients with chronic rhinosinusitis with nasal polyps]. / Caracterización clínica y demográfica de pacientes colombianos con rinosinusitis crónica con poliposis nasal.

OBJECTIVE: To present the baseline clinical and demographic characteristics of CRSwNP patients over the age of 18 enrolled in a Patient Support Program (PSP) prior to biologic treatment. METHODS: Descriptive, cross-sectional study performed in a Colombian CRSwNP asthma PSP sponsored by Sanofi from Aug-2021 to Jul-2022. Data was collected from CRSwNP patients, prior to the start of Dupilumab treatment, who consented to the use of their data. The following information was reported: Age, reporting city, treating medical specialty, comorbidities, and persistence of treatment. RESULTS: 339 patients were included, 171 (50,4%) were women and 168 (49,6%) were men. The mean age at Dupilumab treatment initiation was 52,4 years. 62,8% began treatment during adulthood (26-59y), while 34.1% started at elderly (+60y) and 3.1% were young adults (18-25y). Most cases (29,7%) were included in Bogotá, followed by Antioquia (19%), Valle del Cauca (7,3%) and the remaining 44% nationwide. Comorbidities were present in 67,1% of the patients, with diagnosis of allergic rhinitis, atopic dermatitis, asthma, and other non-type 2 inflammatory diseases. Nasal surgical history was present in 89,6% of the patients, most of them with one to three previous surgeries. Continuous treatment was observed in 70,3% of patients for 6 to 12 months, in 21,3% for more than 12 months and in 8,4% for less than six months. The most frequently treating medical specialty was otorhinolaryngology (79,6%), followed by allergology (16%) and other medical professionals (4,4%). CONCLUSIONS: There is concordance with the literature on a higher presentation of the disease in women than in men. There is a large proportion of patients with nasal surgical history and type 2 inflammatory comorbidities by the moment of biologic treatment initiation. The care and identification of CRSwNP colombian patients is mainly provided by otorhinolaryngologists, followed by allergologists.

OBJETIVO: Presentar las características clínicas y demográficas iniciales de los pacientes con RSCcPN, mayores de 18 años, inscritos en un Programa de Soporte al Paciente (PSP), antes del inicio de tratamiento biológico. MÉTODOS: Estudio descriptivo y transversal realizado en un PSP para RSCcPN en Colombia, entre agosto de 2021 y julio de 2022, patrocinado por Sanofi. Los datos se recopilaron de pacientes con RSCcPN, antes de comenzar el tratamiento con Dupilumab, quienes dieron su consentimiento para el uso de sus datos. Se reportó la siguiente información: edad, ciudad de origen, especialidad médica tratante, comorbilidades y persistencia del tratamiento. RESULTADOS: Se incluyeron 339 pacientes, 171 mujeres (50,4%), y 168 hombres (49,6%). La edad promedio al inicio del tratamiento con Dupilumab, fue de 52,4 años. El 62,8% inició tratamiento durante la edad adulta (entre 26 y 59 años), mientras que el 34,1% comenzó en la vejez (+60 años), y el 3,1% entre los 18 y 25 años. La mayoría de los casos (29,7%) se incluyeron en Bogotá, seguidos por Antioquia (19%), Valle del Cauca (7,3%) y el 44% restante en todo el país. Las comorbilidades estuvieron presentes en el 67,1% de los pacientes, con diagnóstico de rinitis alérgica, dermatitis atópica, asma y otras enfermedades no inflamatorias tipo 2. El 89,6% de los pacientes tenía antecedentes de cirugía nasal, la mayoría de ellos con entre una y tres cirugías previas. Se observó tratamiento continuo en el 70,3% de los pacientes durante 6 y 12 meses, en el 21,3%, durante más de 12 meses, y en el 8,4% durante menos de 6 meses. La especialidad médica que trató a los pacientes con más frecuencia fue la otorrinolaringología (79,6%), seguida por la alergología (16%) y otros profesionales médicos (4,4%). CONCLUSIONES: Existe concordancia con la literatura con una mayor presentación de la enfermedad en mujeres que en hombres. Hay una gran proporción de pacientes con antecedentes de cirugía nasal y comorbilidades inflamatorias tipo 2, al inicio del tratamiento biológico. La atención e identificación de los pacientes colombianos con RSCcPN es proporcionada principalmente por otorrinolaringólogos, seguidos por alergólogos.

Stop and Think: A Case Study Illustrating the Implementation of Bright IDEAS-YA Being Delivered via Telehealth to a Young Adult Cancer Patient.

Bright IDEAS-Young Adults (Bright IDEAS-YA) is a problem-solving skills training intervention that has been adapted for young adults with cancer. Presently, a multisite randomized control trial is being conducted to determine Bright IDEAS-YA's efficacy in supporting a young adult population. This case study demonstrates the young adult adaptation of Bright IDEAS - Bright IDEAS-YA - being delivered to a young adult cancer patient via telehealth. Telehealth is a novel delivery method for Bright IDEAS and Bright IDEAS-YA that was established due to COVID-19 safety precautions. The patient, who reported challenges in several life domains, was taught how to apply the Bright IDEAS-YA framework over six telehealth sessions. After completing the Bright IDEAS-YA framework, the patient reported increased feelings of confidence in managing new stressors, which was corroborated through outcome measures delivered during and following intervention. This case illustrates how early psychosocial intervention following a cancer diagnosis, delivered via telehealth, can help patients develop and implement personal strategies to reduce stress levels.

Atypical Hemolytic Uremic Syndrome: A Nationwide Colombian Pediatric Series.

Objectives. Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease with genetic predisposition and represents up to 10% of pediatric hemolytic uremic syndrome (HUS) cases. Few studies have evaluated aHUS in Latin American population. We studied a Colombian pediatric cohort to delineate disease presentation and outcomes. Methods. A multicenter cohort of 27 Colombian children with aHUS were included. Patients were grouped by age at onset. Clinical features were compared using analysis of variance (ANOVA) and Fisher exact tests. Renal biopsy was performed on 6 patients who were suspected of having other renal diseases before aHUS diagnosis. Results. Most patients were male (70%). The onset of aHUS occurred frequently before age 4 years (60%) and followed gastroenteritis as the main triggering event (52%). Age groups showed comparable clinical presentation, disease severity, treatment, and outcomes. Pulmonary involvement (67%) was the main extrarenal manifestation, particularly in the 1 to 7 age group (P = .01). Renal biopsies were as follows: 3 had membranoproliferative glomerulonephritis (MPGN) type I, one MPGN type III, one C3-glomerulonephritis, and one rapidly progressive GN. Genetic screening was available in 6 patients and identified 2xCFHR5, 2xMCP, 1xADAMTS13/THBD, and 1xDGKE mutations. A total of 15 relapses were seen, of which 8 (72%) occurred in the 1 to 7 age group. The renal outcome was not significantly different regardless of age group. Conclusion. In our cohort, we observed a relatively high frequency of extrarenal involvement at first presentation represented by pulmonary manifestations. The renal prognosis at initial presentation was worse than in previous reports.

Validación clínica de la prueba RT-LAMP para el diagnóstico rápido del SARS-CoV-2 / Clinical validation of the isothermal RT-LAMP test for rapid diagnosis of SARS-CoV-2

Introducción. Desde el primer reporte en la provincia de Wuhan (China) en el año 2019, el SARS-CoV-2 se ha diseminado por todo el mundo, provocando un enorme impacto en la salud pública. Para su diagnóstico, la Organización Mundial de la Salud ha incentivado el desarrollo de pruebas rápidas, de simple ejecución, sensibles y específicas, que complementan la RT-qPCR como prueba de referencia. La prueba RT-LAMP ha mostrado ser una excelente alternativa para la detección del SARS-CoV-2 en diferentes biofluidos. Objetivo. Validar la técnica RT-LAMP colorimétrica en muestras de hisopado nasofaríngeo previamente confirmadas por RT-qPCR, usando el protocolo Charité, Berlín, Alemania. Materiales y métodos. Un total de 153 muestras de hisopado nasofaríngeo de individuos con sospecha de COVID-19 se sometieron a RT-qPCR y RT-LAMP, usando un estuche comercial colorimétrico (NEB, Germany). La RT-LAMP se practicó con las muestras de ARN extraídas del hisopado nasofaríngeo y con muestras crudas sin previa extracción de ARN. El resultado fue evaluado por un simple cambio de color en la reacción. Resultados. La sensibilidad y especificidad de la técnica RT-LAMP para detectar el gen N del SARS-CoV-2 mediante un set de cebadores previamente reportados (set de Broughton), arrojó valores de 0,97 (0,85-1,00) y 0,81 (0,65-0,92), respectivamente, con un intervalo de confianza del 95%. Otro set de cebadores dirigidos contra otra región del mismo gen (set de Lalli) arrojó valores de sensibilidad y especificidad de 0,96 (0,78-1,00) y 0,77 (0,55-0,92), respectivamente. Sin previa extracción de ARN, se encontró que la sensibilidad fue del 0,95 (0,74-1,00) y la especificidad del 0,88 (0,64-0,99). Conclusiones. Estos resultados evidencian que la técnica RT-LAMP podría considerarse una prueba diagnóstica rápida, de fácil ejecución, libre de equipos sofisticados, sensible y específica, para el diagnóstico del SARS-CoV-2 en muestras de hisopados nasofaríngeos.

Introduction: Since the first report in Wuhan (China) in 2019, the SARS-CoV-2 virus has spread throughout the world, with a significant impact in public health. To contain its transmission, the WHO has encouraged the development of rapid, simple, sensitive and specific tests that complement qRT-PCR, as the gold standard. RT-LAMP has shown to be a good alternative to detect SARS-CoV-2 in different fluid samples. Objective: To validate the colorimetric RT-LAMP technique using two sets of primers targeting N gene of SARS-CoV-2 in 117 nasopharyngeal swab samples previously confirmed by RT-qPCR, using the Charité/Berlin protocol. Material and methods: A total of 153 nasopharyngeal swab samples from individuals with suspected COVID-19 were subjected to qRT-PCR and RT-LAMP using a commercial colorimetric kit (NEB, Germany). RT-LAMP was performed using both extracted RNA samples and raw samples without prior RNA extraction, and the result was assessed by a simple color change in the reaction. Results: Sensitivity and specificity for the previously reported RT-LAMP primers (Broughton set) targeting N gene of SARS-CoV-2 were 0.97 (0.85-1.00) and 0.81 (0.65-0.92) respectively, with CI95%. The Lalli primers targeting another region of the N gene used showed a sensitivity value of 0.96 (0.78-1.00) and a specificity of 0.77 (0.55-0.92). Without RNA extraction we found a sensitivity value of 0.95 (0.74, 1.00) and a specificity of 0.88 (0.64, 0.99). A sensitivity value of 0.95 (0.74-1.00) and a specificity 0.88 (0.64-0.99) were found without prior RNA extraction. Conclusion: Taking together, the results showed that RT-LAMP technique could be considered as a rapid diagnostic test, easy to perform, free of sophisticated equipment, sensitive and specific to diagnose SARS-CoV-2 in nasopharyngeal swabs with and without prior RNA extraction, allowing its implementation in places with scarce resources.

Prácticas espaciales de infancias en edificio de gran altura y densidad habitacional / Spatial practices of childhood in a high-rise and high-density building / Práticas espaciais da infância em um prédio alto e densamente povoado

Resumen (analítico) El objetivo del artículo es analizar las prácticas y representaciones espaciales de niños/as residentes de un edificio de gran altura y densidad habitacional del centro de la capital chilena. Con un diseño cualitativo, crítico-etnográfico, y un modelo colaborativo, se contó con la participación de 5 niños/as de 10 a 13 años, y 6 adultos/as de 25 a 55 años, de diversas nacionalidades y tiempos de residencia. El análisis de contenido constató que la composición física y dinámicas relacionales en el edificio, han restringido severamente las posibilidades de despliegue espacial de niños/as residentes en este, contribuyendo a su histórica invisibilización y encierro. A pesar de esto, se encontraron prácticas de resistencia y resignificación del espacio por parte de los niños/as, que crean comunidad en un marco urbano que no la favorece.

Abstract (analytical) The objective of this article is to analyze the spatial practices and representations of children living in a high-rise building in the center of the Chilean capital. With a qualitative, critical-ethnographic design and a collaborative model, 5 children from 10 to 13 years old and 6 adults from 25 to 55 years old, of different nationalities and residence times, participated in both studies. The content analysis found that the physical composition and relational dynamics in the building have severely restricted the possibilities of spatial deployment of children residing in the building, contributing to their historical invisibility and confinement. In spite of this, practices of resistance and resignification of space were found on the part of the children, who create community in an urban framework that does not favor it.

Resumo (analítico) O objetivo do artigo é analisar as práticas e representações espaciais das crianças que vivem em um prédio alto e densamente povoado no centro da capital chilena. Com um desenho qualitativo, crítico etnográfico e um modelo colaborativo, 5 crianças de 10 a 13 anos e 6 adultos de 25 a 55 anos, de diferentes nacionalidades e durações de residência, participaram dos estudos. A análise de conteúdo constatou que a composição física e a dinâmica relacional no edifício restringiram severamente as possibilidades de implantação espacial das crianças que vivem no edifício, contribuindo para sua invisibilidade e confinamento histórico. Apesar disso, foram encontradas práticas de resistência e resignificação do espaço por parte das crianças, que criam comunidade em uma estrutura urbana que não a favorece.

Delayed onset muscle soreness intensity affects muscular performance / El Dolor muscular de aparición tardía afecta el desempeño muscular

Abstract Background: The study of functional impact of delayed onset muscle soreness has been limited to describe the decline on maximal isometric contraction, but muscular work and time to peak torque has not been examined yet. Purpose: To describe the changes induced by a session of lengthening contractions on muscle performance and delayed onset muscle soreness (DOMS). Methods: A quasi-experimental study was conducted in the Institutional laboratory; Twenty healthy men; mean age 21 SD 0.34 were recruited, all subjects performed 200 lengthening contractions of the quadriceps at 120°/s. Isometric and isokinetic peak torque, muscular work, time to peak torque, DOMS and creatine kinase activity were assessed at baseline, 48 h and 96 h post-exercise. The muscle performance was assessed with an isokinetic dynamometer and DOMS with a visual analog scale (VAS). Results: Relative to baseline, isometric and isokinetic peak torque and muscular work decreased in ~30% at 48 h post-exercise; delayed onset muscle soreness increased ~300%, which remained at 96 h post-exercise. Conclusions: These reflect that the decline in muscular performance is due to the changes in peak torque and muscular work, which has greater implications on muscle function. No changes were detected in time to peak torque. The alterations in muscular performance variables are accompanied by delayed onset muscle soreness which has also a negative impact on force production (29% of the drop on peak torque is explain by soreness intensity).

Resumen Introducción: Los estudios de impacto funcional del dolor muscular de aparición tardía (DMAT) se han limitado a describir la disminución de la contracción isométrica máxima, pero aún no se ha examinado el trabajo muscular y el tiempo del torque máximo. Objetivo: Describir los cambios inducidos por una sesión de ejercicio excéntrico sobre el rendimiento muscular y DMAT. Método: se realizó un estudio cuasi-experimental, los participantes fueron veinte hombres sanos; edad media 21 DE 0,34, todos los sujetos realizaron 200 contracciones excéntricas del cuádriceps a 120°/s. Se evaluó el torque pico isométrico e isocinético, el trabajo muscular, el tiempo hasta el torque máximo, DMAT y la actividad de la creatina quinasa al inicio, 48 h y 96 h después del ejercicio, el rendimiento muscular se evaluó con un dinamómetro isocinético y DOMS con una escala análoga visual (EAV). Resultados: en relación con la línea de base, el torque pico isométrico e isocinético y el trabajo muscular disminuyeron en ~ 30 % a las 48 h post-ejercicio; El dolor muscular de aparición tardía aumentó ~300 %, que permaneció 96 h después del ejercicio. Conclusiones: los resultados reflejan que la disminución del rendimiento muscular se debe a los cambios en el torque pico y trabajo muscular, lo que tiene mayores implicaciones en la función muscular. No se detectaron cambios en el tiempo hasta el torque máximo. Las alteraciones en las variables de rendimiento muscular se acompañan de DMAT que también tiene un impacto negativo en la producción de fuerza (el 29 % de la caída en el torque máximo se explica por la intensidad del dolor).

Impact on Mechanical Properties of 10 versus 20 Minute Treatment of Human Pericardium with Glutaraldehyde in OZAKI Procedure.

PURPOSE: The aim of this study was to analyze the effects of 10-minute (standard term) versus 20-minute treatment with glutaraldehyde (GA) on mechanical stability and physical strength of human pericardium in the setting of the OZAKI procedure. METHODS: Leftover pericardium (6 patients) was bisected directly after the operation, and one-half was further fixed for 10 additional minutes. Uniaxial tensile tests were performed and ultimate tensile strength (UTS), ultimate tensile strain (uts), and collagen elastic modulus were evaluated. RESULTS: Both treatments resulted in similar values of uniaxial stretching-generated elongations at rupture (10 minutes 25 ± 7 % vs. 20 minutes: 22 ± 5 %; p = 0.05), UTS (5.16 ± 2 MPa vs. 6.54 ± 3 MPa; p = 0.59), and collagen fiber stiffness (elastic modulus: 31.80 ± 15.05 MPa vs. 37.35 ± 15.78 MPa; p = 0.25). CONCLUSION: Prolongation of the fixation time of autologous pericardium has no significant effect on its mechanical stability; thus, extending the intraoperative treatment cannot be recommended.

Decellularization and In Vivo Recellularization of Abdominal Porcine Fascial Tissue.

BACKGROUND: Tissue decellularization has evolved as a promising approach for tissue engineering applications. METHODS: In this study, we harvested fascial tissue from porcine anterior abdominal wall and the samples were decellularized with a combination of agents such as Triton X-100, trypsin and DNAase. Afterwards, we evaluated cell removal by histological analysis and DNA quantification. Mechanical functionality was evaluated by applying a range of hydrostatic pressures. A sample of decellularized fascia was transplanted into a rabbit and after 15 days a biopsy of this tissue was examined; the animal was observed during 6 months after surgery. RESULTS: The extracellular matrix was retained with a complete decellularization as evidenced by histologic examination. The DNA content was significantly reduced. The scaffold preserved its tensile mechanical properties. The graft was incorporated into a full thickness defect made in the rabbit abdominal wall. This tissue was infiltrated by granulation and inflammatory cells and the histologic structure was preserved 15 days after surgery. The animal did not develop hernias, infections or other complications, after a 6-months of follow up. CONCLUSIONS: The protocol of decellularization of fascial tissue employed in this study proved to be efficient. The mechanical test demonstrated that the samples were not damaged and maintained its physical characteristics; clinical evolution of the rabbit, recipient of the decellularized fascia, demonstrated that the graft was effective as a replacement of native tissue.In conclusion, a biological scaffold derived from porcine fascial tissue may be a suitable candidate for tissue engineering applications.

Impairment, disability, and handicap associated with hearing problems and voice disorders among Colombian teachers / Deficiencia, discapacidad y minusvalía asociadas a los problemas de voz y audición en profesores colombianos

Objectives: 1. define the occurrence of work-related hearing problems and voice disorders among teachers that have contacted the Colombian National Board of Disability Assessment (NBDA) for follow-up; 2. identify individual associated factors of hearing problems and voice disorders among teachers; 3. assess the limitations and restrictions due to hearing problems and voice disorders among these participants. Methods: Retrospective study. The National Database of the Colombian NBDA was reviewed. Information on distributions of occupation, individual characteristics, and diagnosis code (ICD-10) was analyzed. Results: Communication disorders among teachers that have contacted the Colom-bian NBDA for follow-up included voice disorders, with a prevalence of 51%, and hearing problems, with a prevalence of 7%. Female teachers who have contacted the Colombian NBDA for follow-up were 4 times more likely to be identified as having voice disorders compared with their male colleagues. Conclusions: While teachers that have contacted the Colombian NBDA for fol-low-up have a high occurrence of voice disorders, hearing problems are more likely to be stated as a debilitating condition. One possible explanation is that teachers who contacted the Colombian NBDA for follow-up continued working even when many voice symptoms were evident, while hearing problems would prevent a teacher from interacting with students, thereby affecting the teaching-learning process soon-er. Nevertheless, with both voice and hearing problems, work performance and social interaction is affected, and, therefore, quality of life is reduced.

Objetivos: 1. definir la ocurrencia de problemas de audición y de voz relacionados con el trabajo de docentes que contactaron la Junta Nacional de Evaluación de la Discapacidad de Colombia (NBDA) para su seguimiento; 2. identificar los factores individuales asociados a los problemas de audición y voz entre los profesores; 3. eva-luar las limitaciones y restricciones debidas a problemas de audición y voz asociados al trabajo entre los participantes.Métodos: estudio retrospectivo. Se revisó la Base de Datos Nacional de la NBDA colombiana. Se analizó información sobre distribuciones de ocupación, característi-cas individuales y código de diagnóstico (CIE-10).Resultados: Los trastornos de comunicación entre los docentes que han contacta-do a la NBDA colombiana para seguimiento incluyeron problemas de la voz, con una prevalencia del 51%, y problemas de audición, con una prevalencia del 7%. Las pro-fesoras que se han puesto en contacto con la NBDA colombiana para el seguimiento tenían 4 veces más probabilidades de ser identificadas con trastornos de la voz en comparación con sus colegas masculinos.Conclusiones: Si bien los maestros que contactaron a la NBDA colombiana para el seguimiento tienen una alta incidencia de trastornos de la voz, es más probable que los problemas de audición se consideren una condición debilitante. Una posible ex-plicación es que los maestros que se comunicaron con la NBDA colombiana para el seguimiento continuaron trabajando incluso cuando muchos síntomas vocales eran evidentes, mientras que los problemas de audición evitarían que un maestro inte-ractuara con los estudiantes, afectando así el proceso de enseñanza-aprendizaje. Sin embargo, tanto con los problemas de voz como de audición, el desempeño laboral y la interacción social se ven afectados y, por lo tanto, la calidad de vida se reduce.

Manifestaciones dermatológicas de la diabetes: clasificación y diagnóstico / Diabetes mellitus and the skin

RESUMEN Se estima que en Colombia hay 2.836.500 adultos con diabetes, una enfermedad con una prevalencia del 8,4 %. La exposición a niveles elevados de glucosa afecta los procesos de proliferación y diferenciación en las células de todos los órganos y tejidos, así mismo en los queratinocitos, fibroblastos y demás células presentes en la piel, alteraciones que ocurren en más de un tercio de los diabéticos y que pueden ser la manifestación inicial de la enfermedad. La frecuencia y presentación de estas dermatosis varía según la población estudiada. La dermopatía diabética, la acantosis nigricans, los fibromas laxos, el prurito y la xerosis son las formas más comunes y se consideran marcadores cutáneos de la diabetes. La presente revisión se enfoca en las manifestaciones dermatológicas específicas y no específicas de la diabetes, así como en las relacionadas con su tratamiento. Estas pueden ser un reflejo del estado metabólico actual o previo del paciente diabético y su oportuna identificación permite orientar el diagnóstico primario, sospechar un estado prediabético u optimizar el tratamiento de la enfermedad en los individuos ya diagnosticados.

SUMMARY It is estimated that in Colombia there are 2,836,500 adults with diabetes, and that the disease has a prevalence of 8.4%. Exposure to elevated glucose levels affects the processes of cell proliferation and cell differentiation in all organs and tissues, as well as keratinocytes, fibroblasts, melanocytes and other cells present in the skin, alterations that occur in more than one third of diabetics and which may be the initial manifestation of the disease. The frequency and presentation of these dermatoses varies according to the population studied, with a pre-dominance of fungal and bacterial infections. Diabetic dermopathy, acanthosis nigricans, lax fibroids, pruritus and xerosis are also very frequent and are considered cutaneous markers of diabetes. This review focuses on the specific and non-specific dermatological manifestations of diabetes, as well as those related to its treatment. These manifestations can be a reflectionof the current or previous metabolic state of the diabetic patient and its timely identification allows guiding the primary diagnosis, to suspect a prediabetic state or to optimize the treatment of the disease in already diagnosed individuals.

DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation.

In humans, pathogenic variants in the DHH gene underlie cases of 46,XY gonadal dysgenesis. DHH is part of the Hedgehog family of proteins, which require extensive processing, including self-cleavage of the precursor for efficient signalling. In our work, we have assessed the effect of several human DHH pathogenic variants involved in recessive complete or partial gonadal dysgenesis, on protein processing and sub-cellular localization. We found that a subset of variants was unable to perform self-cleavage, which correlated albeit not perfectly with an altered subcellular localization of the resulting proteins. For the processing-proficient variants, we used structural modelling tools and molecular dynamic (MD) simulations to predict the potential impact of the variants on protein conformation and/or interaction with partners. Our study contributes to a better understanding of the molecular mechanisms involved in DHH dysfunction leading to 46,XY disorders of sex development.

Quality of life in patients with multiple sclerosis and their caregivers in Colombia: One-year follow-up. / Calidad de vida en pacientes con esclerosis múltiple y sus cuidadores en Colombia: un año de seguimiento

INTRODUCTION: Multiple sclerosis is a chronic inflammatory demyelinating disease associated with neurological disability. Clinical features include motor, cerebellar, visual, and sensory function alterations, as well as psychiatric comorbidities, such as depression, anxiety, and irritability. There is little literature available on the quality of life of patients and their caregivers. OBJECTIVE: To assess the quality of life of patients with multiple sclerosis and their caregivers in Colombia given that there is no information on the subject in this particular population to establish comprehensive management plans. MATERIALS AND METHODS: We used the MusiQol and CareQol questionnaires and the Beck Depression Inventory. A prospective analytical observational protocol was designed to include patients aged 18 to 65 years with a diagnosis of relapsing-remitting multiple sclerosis between October, 2014, and October, 2015, at the Hospital Universitario San Ignacio. We evaluated quantitative variables and Spearman correlations. The data analysis was carried out with Student t and Mann-Whitney U tests. RESULTS: A total of 55 patients with relapsing-remitting multiple sclerosis participated in the study. Chronic fatigue was the most common comorbidity in 27%. The MusiQol questionnaire revealed a good basal quality of life, which remained at similar levels in the follow-ups at six and 12 months. Quality of life was good during the study since there were no statistically significant differences between baseline and follow-up MusiQol scores. Good quality of life was also observed in caregivers. CONCLUSIONS: The quality of life of several Colombian patients diagnosed with multiple sclerosis was very good. This positive result was also observed in caregivers as evidenced by the results of the CareQol questionnaire. We also observed and indicated an inversely proportional correlation between the Expanded Disability Status Scale and the quality of life indexes.

Introducción. La esclerosis múltiple es una enfermedad desmielinizante inflamatoria crónica asociada con discapacidad neurológica que afecta la función motora, cerebelosa, visual y sensorial, y se presenta con comorbilidades psiquiátricas como depresión, ansiedad e irritabilidad. Hay escasa literatura disponible sobre la calidad de vida de los pacientes y sus cuidadores. Objetivo. Evaluar la calidad de vida de los pacientes con esclerosis múltiple y sus cuidadores en Colombia dado que no hay información sobre el tema en esta población en particular para establecer planes de manejo integral. Materiales y métodos. Se utilizaron los cuestionarios MusiQol, CareQol y el inventario de depresión de Beck. Se diseñó un protocolo observacional analítico prospectivo para pacientes de 18 a 65 años con diagnóstico de esclerosis múltiple remitente recurrente entre octubre de 2014 y octubre de 2015 en el Hospital Universitario San Ignacio. Se evaluaron variables cuantitativas y las correlaciones de Spearman. El análisis de datos se hizo mediante la prueba t de Student y la U de Mann-Whitney. Resultados. Participaron 55 pacientes diagnosticados con esclerosis múltiple remitente recurrente. En el 27 % de ellos la fatiga crónica fue la comorbilidad más frecuente. El cuestionario MusiQol reveló una buena calidad de vida de base, que se mantuvo en niveles similares en los seguimientos a los seis y los 12 meses. La calidad de vida fue buena durante el estudio y sin diferencias estadísticamente significativas entre las puntuaciones de base del cuestionario MusiQol y las de seguimiento. Se observó una buena calidad de vida en los cuidadores. Conclusiones. La calidad de vida de los pacientes colombianos participantes en el estudio con diagnóstico de esclerosis múltiple fue muy buena, así como la de los cuidadores según los resultados del cuestionario CareQol. Se observó una correlación inversamente proporcional entre la Expanded Disability Status Scale y los índices de calidad de vida.

Quality of life in patients with multiple sclerosis and their caregivers in Colombia: One-year follow-up / Calidad de vida en pacientes con esclerosis múltiple y sus cuidadores en Colombia: un año de seguimiento

Introduction: Multiple sclerosis is a chronic inflammatory demyelinating disease associated with neurological disability. Clinical features include motor, cerebellar, visual, and sensory function alterations, as well as psychiatric comorbidities, such as depression, anxiety, and irritability. There is little literature available on the quality of life of patients and their caregivers. Objective: To assess the quality of life of patients with multiple sclerosis and their caregivers in Colombia given that there is no information on the subject in this particular population to establish comprehensive management plans. Materials and methods: We used the MusiQol and CareQol questionnaires and the Beck Depression Inventory. A prospective analytical observational protocol was designed to include patients aged 18 to 65 years with a diagnosis of relapsing-remitting multiple sclerosis between October, 2014, and October, 2015, at the Hospital Universitario San Ignacio. We evaluated quantitative variables and Spearman correlations. The data analysis was carried out with Student t and Mann-Whitney U tests. Results: A total of 55 patients with relapsing-remitting multiple sclerosis participated in the study. Chronic fatigue was the most common comorbidity in 27%. The MusiQol questionnaire revealed a good basal quality of life, which remained at similar levels in the follow-ups at six and 12 months. Quality of life was good during the study since there were no statistically significant differences between baseline and follow-up MusiQol scores. Good quality of life was also observed in caregivers. Conclusions: The quality of life of several Colombian patients diagnosed with multiple sclerosis was very good. This positive result was also observed in caregivers as evidenced by the results of the CareQol questionnaire. We also observed and indicated an inversely proportional correlation between the Expanded Disability Status Scale and the quality of life indexes.

Introducción. La esclerosis múltiple es una enfermedad desmielinizante inflamatoria crónica asociada con discapacidad neurológica que afecta la función motora, cerebelosa, visual y sensorial, y se presenta con comorbilidades psiquiátricas como depresión, ansiedad e irritabilidad. Hay escasa literatura disponible sobre la calidad de vida de los pacientes y sus cuidadores. Objetivo. Evaluar la calidad de vida de los pacientes con esclerosis múltiple y sus cuidadores en Colombia dado que no hay información sobre el tema en esta población en particular para establecer planes de manejo integral. Materiales y métodos. Se utilizaron los cuestionarios MusiQol, CareQol y el inventario de depresión de Beck. Se diseñó un protocolo observacional analítico prospectivo para pacientes de 18 a 65 años con diagnóstico de esclerosis múltiple remitente recurrente entre octubre de 2014 y octubre de 2015 en el Hospital Universitario San Ignacio. Se evaluaron variables cuantitativas y las correlaciones de Spearman. El análisis de datos se hizo mediante la prueba t de Student y la U de Mann-Whitney. Resultados. Participaron 55 pacientes diagnosticados con esclerosis múltiple remitente recurrente. En el 27 % de ellos la fatiga crónica fue la comorbilidad más frecuente. El cuestionario MusiQol reveló una buena calidad de vida de base, que se mantuvo en niveles similares en los seguimientos a los seis y los 12 meses. La calidad de vida fue buena durante el estudio y sin diferencias estadísticamente significativas entre las puntuaciones de base del cuestionario MusiQol y las de seguimiento. Se observó una buena calidad de vida en los cuidadores. Conclusiones. La calidad de vida de los pacientes colombianos participantes en el estudio con diagnóstico de esclerosis múltiple fue muy buena, así como la de los cuidadores según los resultados del cuestionario CareQol. Se observó una correlación inversamente proporcional entre la Expanded Disability Status Scale y los índices de calidad de vida.

Clinical Practice Guidelines and Consensus Statements About Pain Management in Critically Ill End-of-Life Patients: A Systematic Review.

OBJECTIVES: To identify and synthesize available recommendations from scientific societies and experts on pain management at the end-of-life in the ICU. DATA SOURCES: We conducted a systematic review of PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and Biblioteca Virtual en Salud from their inception until March 28, 2019. STUDY SELECTION: We included all clinical practice guidelines, consensus statements, and benchmarks for quality. DATA EXTRACTION: Study selection, methodological quality, and data extraction were performed independently by two investigators. A quality assessment was performed by four investigators using the Appraisal of Guidelines for Research and Evaluation II instrument. The recommendations were then synthesized and categorized. DATA SYNTHESIS: Ten publications were included. The Appraisal of Guidelines for Research and Evaluation II statement showed low scores in various quality domains, especially in the applicability and rigor of development. Most documents were in agreement on five topics: 1) using a quantitative tool for pain assessment; 2) administering narcotics for pain relief and benzodiazepines for anxiety relief; 3) against prescribing neuromuscular blockers during withdrawal of life support to assess pain; 4) endorsing the use of high doses of opioids and sedatives for pain control, regardless of the risk that they will hasten death; and 5) using quality indicators to improve pain management during end-of-life in the ICU. CONCLUSIONS: In spite of the lack of high-quality evidence, recommendations for pain management at the end-of-life in the ICU are homogeneous and are justified by ethical principles and agreement among experts. Considering the growing demand for the involvement of palliative care teams in the management of the dying patients in the ICU, there is a need to clearly define their early involvement and to further develop comprehensive evidence-based pain management strategies. Based on the study findings, we propose a management algorithm to improve the overall care of dying critically ill patients.