The correlation between immune subtypes and consensus molecular subtypes in colorectal cancer identifies novel tumour microenvironment profiles, with prognostic and therapeutic implications.

BACKGROUND: Solid tumour growth is the consequence of a complex interplay between cancer cells and their microenvironment. Recently, a new global transcriptomic immune classification of solid tumours has identified six immune subtypes (ISs) (C1-C6). Our aim was to specifically characterise ISs in colorectal cancer (CRC) and assess their interplay with the consensus molecular subtypes (CMSs). METHODS: Clinical and molecular information, including CMSs and ISs, were obtained from The Cancer Genome Atlas (TCGA) (N = 625). Immune cell populations, differential gene expression and gene set enrichment analysis were performed to characterise ISs in the global CRC population by using CMSs. RESULTS: Only 5 ISs were identified in CRC, predominantly C1 wound healing (77%) and C2 IFN-γ dominant (17%). CMS1 showed the highest proportion of C2 (53%), whereas C1 was particularly dominant in CMS2 (91%). CMS3 had the highest representation of C3 inflammatory (7%) and C4 lymphocyte depleted ISs (4%), whereas all C6 TGF-ß dominant cases belonged to CMS4 (2.3%). Prognostic relevance of ISs in CRC substantially differed from that reported for the global TCGA, and ISs had a greater ability to stratify the prognosis of CRC patients than CMS classification. C2 had higher densities of CD8, CD4 activated, follicular helper T cells, regulatory T cells and neutrophils and the highest M1/M2 polarisation. C2 had a heightened activation of pathways related to the immune system, apoptosis and DNA repair, mTOR signalling and oxidative phosphorylation, whereas C1 was more dependent of metabolic pathways. CONCLUSIONS: The correlation of IS and CMS allows a more precise categorisation of patients with relevant clinical and biological implications, which may be valuable tools to improve tailored therapeutic interventions in CRC patients.

Determinación de la documentación del bioterio del Instituto Nacional de Higiene "Rafael Rangel" basado en la norma ISO 9001: 2015 / Determination of the documentation of the biotery National Institute of Hygiene "Rafael Rangel" by norm ISO 9001:2015

Un sistema de gestión de la calidad (SGC) según norma ISO 9001:2015, requiere un soporte documental de sus procesos, que permita a la organización demostrar la eficacia de planificación, operación, control, implantación y mejora continúa de su SGC. La producción de animales de laboratorio (AL) requiere además otros documentos que garanticen las buenas prácticas de producción (BPP). Objetivo: Describir y analizar los procesos del Bioterio definiendo su documentación según la ISO 9001:2015, para apoyar la operatividad, lograr mejoras y recomendar acciones que garanticen la trazabilidad y la satisfacción del cliente. Materiales y métodos: Se hace la descripción del SGC y de BPP diseñado e implantado en la producción de AL bajo condiciones convencionales con barreras. Norma ISO 9001:2015; Mapas y diagramas de procesos, interacciones y documentación nueva y existente. Resultados: Se toma como soporte el enfoque de procesos de la ISO 9001:2015; Levantamiento e Identificación de los procesos claves, clientes y partes interesadas; expectativas y requisitos; Definición de las especificaciones del AL a producir; Descripción de diagramas de flujo asociados en recepción, producción, control y entrega; Mantenimiento de la documentación asociada a la gestión de procesos; planes de control, procedimientos, instructivos y registros. Conclusiones: Producción de AL con la documentación especializada que agrega valor al proceso y al SGC. .La documentación coadyuva la valoración, eficacia y adecuación del SGC. Identifican y controla los procesos claves garantizando su función a satisfacción. Estimula la actitud de mejora en la Institución necesaria para el cambio en la cultura de trabajo

A quality management system (QMS) according to ISO 9001: 2015 standard requires documentary support of this processes, which allows the organization to demonstrate the efficiency of planning, operation, control, implementation and continuous improvement of its QMS. The production of Laboratory Animals (AL) also requires other documents that guarantee good production practices (BPP). Objective: the aim of this study was to describe and analyze the processes of the biotery defining its documentation according to ISO 9001: 2015, to support the operation, achieve improvements and recommend actions that guarantee traceability and customer satisfaction. Materials and methods: The description of the SGC and BPP is designed and implemented in the production of AL under conventional conditions with barriers. The ISO 9001: 2015 standard; Maps and diagrams of processes, interactions and new and existing documentation. Results: The process approach of ISO 9001: 2015 is taken as support; survey and identification of key processes, clients and interested parties; expectations and requirements; definition of the LA specifications to be produced; description of associated flow diagrams in reception, production, control and delivery; maintenance of documentation associated with process management; control plans, procedures, instructions and records. Conclusions: The production of AL with specialized documentation that adds value to the process and the QMS. The documentation contributes to the assessment, effectiveness and adequacy of the QMS. They identify and control the key processes guaranteeing their function to satisfaction and stimulate the attitude of improvement in the Institution necessary for the change in the work culture.

Autoimmune hemolytic anemia in systemic lupus erythematosus at diagnosis: differences between pediatric and adult patients.

Objective To determine the overall prevalence of autoimmune hemolytic anemia (AIHA), and to compare clinical and laboratory features in a large population of children and adult lupus patients at diagnosis. Methods This retrospective study evaluated the medical charts of 336 childhood-onset systemic lupus erythematosus (cSLE) and 1830 adult SLE (aSLE) patients followed in the same tertiary hospital. Demographic data, clinical features and disease activity were recorded. AIHA was defined according to the presence of anemia (hemoglobin <10 g/dL) and evidence of hemolysis (reticulocytosis and positive direct antiglobulin test (DAT)/Coombs test) at SLE diagnosis. Evans syndrome (ES) was defined by the combination of immune thrombocytopenia (platelet count <100,000/mm3) and AIHA. Results The frequency of AIHA at diagnosis was significantly higher in cSLE patients compared to aSLE (49/336 (14%) vs 49/1830 (3%), p = 0.0001), with similar frequency of ES (3/336 (0.9%) vs 10/1830 (0.5%), p = 0.438). The median of hemoglobin levels was reduced in cSLE vs aSLE patients (8.3 (2.2-10) vs 9.5 (6.6-10) g/dL, p = 0.002) with a higher frequency of multiple hemorrhagic manifestations (41% vs 7%, p = 0.041) and erythrocyte transfusion due to bleeding (24% vs 5%, p = 0.025). cSLE patients also had more often constitutional involvement (84% vs 31%, p < 0.001), fever (65% vs 26%, p < 0.001), weight loss > 2 kg (39% vs 6%, p < 0.001), reticuloendothelial manifestations (48% vs 8%, p < 0.001), hepatomegaly (25% vs 2%, p < 0.001) and splenomegaly (21% vs 2%, p = 0.004). Other major organ involvements were common but with similar frequencies in cSLE and aSLE ( p > 0.05). Median systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) was comparable in cSLE and aSLE (p = 0.161). Conclusions We identified that AIHA was not a common condition in cSLE and aSLE, with distinct features characterized by a higher prevalence/severity in children and concomitant constitutional symptoms in the majority of them.

Premature ovarian failure and FMR1 premutation co-segregation in a large Brazilian family.

Fragile X syndrome is the most common form of inherited mental retardation in men. The molecular mechanism underlying the disease is an amplification of a polymorphic trinucleotide repeat (CGG)n located at 5' end of FMR1 which promotes transcriptional silencing of the gene. Four different classes of alleles could be distinguished in the population based on the size of the repeat, however only large amplifications over 200 CGG are associated with the disease. In the past decade several authors have associated premutated alleles, which harbor expansions from 61 to 200 repeats, with the occurrence of premature ovarian failure (POF). In this work we describe a large Brazilian family in which a POF/premutated woman has transmitted to five out of seven daughters a FMR1 premutated allele. From these five women with premutations, three have experienced premature ovarian failure. Our data clearly indicate a co-segregation pattern of inheritance between POF and fragile X premutation.

Nd:YAG laser effects on the microleakage of composite resin restorations.

OBJECTIVE: This study evaluated microleakage of composite restorations submitted to marginal treatment with Nd:YAG laser and surface sealant. BACKGROUND DATA: Previous studies have demonstrated that Nd:YAG-lased enamel melted and became recrystallized with a morphologic appearance similar to lava, and has been used clinically in the sealing of enamel pits and fissures. METHODS: Class V cavities in enamel of human premolars were restored with composite resin (Z100, 3M) and randomly divided in six groups: G1, control; G2, surface sealant marginal treatment; G3 to G6, were treated with pulsed Nd:YAG laser (1.064 microm) marginal treatment, contact fiberoptic (300 microm), air cooling, for 30 seconds, powers of 1.2-2 W, repetition rates of 20-30 Hz, energies of 40-100 mJ. Teeth were impermeabilized, immersed in a rhodamine dye, sectioned, and evaluated under stereomicroscope microscopy with scores. RESULTS: There were significant differences between marginal treatments; there were no differences between groups 1, 2, and 4, and 3,5, and 6; lower values of microleakage were at groups 3, 5, and 6 (Kruskal-Wallis,p = 0.05). CONCLUSION: Nd:YAG laser showed improved marginal sealing and decreased microleakage of composite resins restorations.