Ensemble Models Based on QuBiLS-MAS Features and Shallow Learning for the Prediction of Drug-Induced Liver Toxicity: Improving Deep Learning and Traditional Approaches.

Drug-induced liver injury (DILI) is a key safety issue in the drug discovery pipeline and a regulatory concern. Thus, many in silico tools have been proposed to improve the hepatotoxicity prediction of organic-type chemicals. Here, classifiers for the prediction of DILI were developed by using QuBiLS-MAS 0-2.5D molecular descriptors and shallow machine learning techniques, on a training set composed of 1075 molecules. The best ensemble model build, E13, was obtained with good statistical parameters for the learning series, namely, the following: accuracy = 0.840, sensibility = 0.890, specificity = 0.761, Matthew's correlation coefficient = 0.660, and area under the ROC curve = 0.904. The model was also satisfactorily evaluated with Y-scrambling test, and repeated k-fold cross-validation and repeated k-holdout validation. In addition, an exhaustive external validation was also carried out by using two test sets and five external test sets, with an average accuracy value equal to 0.854 (±0.062) and a coverage equal to 98.4% according to its applicability domain. A statistical comparison of the performance of the E13 model, with regard to results and tools (e.g., Padel DDPredictor Software, Deep Learning DILIserver, and Vslead) reported in the literature, was also performed. In general, E13 presented the best global performance in all experiments. The sum of the ranking differences procedure provided a very similar grouping pattern to that of the M-ANOVA statistical analysis, where E13 was identified as the best model for DILI predictions. A noncommercial and fully cross-platform software for the DILI prediction was also developed, which is freely available at http://tomocomd.com/apps/ptoxra. This software was used for the screening of seven data sets, containing natural products, leads, toxic materials, and FDA approved drugs, to assess the usefulness of the QSAR models in the DILI labeling of organic substances; it was found that 50-92% of the evaluated molecules are positive-DILI compounds. All in all, it can be stated that the E13 model is a relevant method for the prediction of DILI risk in humans, as it shows the best results among all of the methods analyzed.

High OCT4 Expression Might Be Associated with an Aggressive Phenotype in Rectal Cancer.

Rectal cancer (RC) is one of the most common malignant neoplasms, and cancer stem cells (CSCs) of the intestinal tract have been implicated in its origin. The oncofetal protein OCT4 has been linked to neoplastic processes, but its role and clinical significance in RC are unknown. This study investigates the expression of the stem cell marker OCT4 related to clinical-pathological characteristics and its clinical significance in RC patients. The expression level of stem cell marker OCT4 was analyzed in 22 primary rectal tumors by western blot. The association between OCT4 protein expression and the clinical-pathological features of tumors was evaluated by χ2 test and Fisher's exact test. We demonstrated that the expression of the stem cell marker OCT4 was observed in tumor tissue but not adjacent non-tumor tissue. High expression of the stem cell marker OCT4 was significantly associated with histological differentiation grade (p = 0.039), tumor invasion level (p = 0.004), lymph node involvement (p = 0.044), tumor-node-metastasis (TNM) stage (p = 0.002), and clinical stage (p = 0.021). These findings suggest that high OCT4 expression is associated with a more aggressive RC phenotype, with a greater likelihood of progression and metastasis. These results shed light on the importance of targeting this CSC marker to attenuate RC progression.

CEA-delta could be a biomarker of tumor phenotype, clinical stage, and chemotherapeutic response in rectal cancer with OCT4-positive cancer stem cells.

Background: There is very limited evidence on biomarkers for evaluating the clinical behavior and therapeutic response in rectal cancer (RC) with positive expression of cancer stem cells (CSCs). Methods: An exploratory prospective study was conducted, which included fresh samples of tumor tissue from 109 patients diagnosed with primary RC. Sociodemographic, pathological and clinical characteristics were collected from medical records and survey. The OCT4 protein was isolated using the Western Blot technique. It was calculated the ΔCEA, ΔOCT4, and ΔOCT4/GUSB values by assessing the changes before and after chemotherapy, aiming to evaluate the therapeutic response. Results: Patients had an average age of 69.9 years, with 55% (n=60) being male. Approximately 63.3% of the tumors were undifferentiated, and the most frequent staging classification was pathological stage III (n=64; 58.7%). Initial positive expression was observed in 77.1% of the patients (n=84), and the median ΔCEA was -1.03 (-3.82 - 0.84) ng/ml, with elevated levels (< -0.94 ng/ml) found in 51.4% of the subjects (n=56). Being OCT4 positive and having an elevated ΔCEA value were significantly associated with undifferentiated tumor phenotype (p=0.002), advanced tumor progression stage (p <0.001), and negative values of ΔOCT4 (p <0.001) (suggestive of poor therapeutic response) compared to those without this status. Conclusion: This study identified a significant and directly proportional association among the values of ΔCEA, ΔOCT4, and ΔOCT4/GUSB. These findings suggest that ΔCEA holds potential as a clinical biomarker for determining the undifferentiated tumor phenotype, advanced clinical stage, and poor therapeutic response in RC with CSCs positive expression.

Condiciones de vida, violencia sexual y sintomatología psiquiátrica de mujeres afrocolombianas víctimas del conflicto armado colombiano: estudio de corte transversal en Cartagena, Colombia

Objetivo: Evaluar el fenómeno de violencia sexual y condición de vida de mujeres afrocolombianas víctimas del conflicto armado, asentadas en la ciudad de Cartagena, Colombia. Materiales y métodos: Estudio prospectivo de corte transversal, tipo encuesta poblacional, realizado entre septiembre de 2019 y marzo del 2020, en la ciudad de Cartagena, Colombia. Se evaluaron variables sociodemográficas, tipo de delitos sufridos en el conflicto armado y factores relacionados, además de antecedentes o presencia de sintomatología psiquiátrica asociada a los eventos traumáticos. A través de análisis descriptivo, se caracterizó las condiciones de vida actuales de las participantes y se exploraron asociaciones entre la condición de violencia sexual y sintomatología psiquiátrica, por medio de Odds Ratio (OR). Resultados: Participaron 215 mujeres, con una mediana de edad de 40 años y desplazadas principalmente del departamento de Bolívar (55%). El 85% eran amas de casa y solo el 60% tiene vivienda propia, encontrándose más del 65% del total de las viviendas en zonas de riesgo por inundación. Por lo menos el 35% habían sufrido discriminación de género, racial o habían sido víctima de violencia sexual. Aproximadamente la mitad de la muestra declaró padecer insomnio, ansiedad y depresión. El 40% mencionó haber tenido pensamientos suicidas y solo 1 de cada 5 mujeres recibió apoyo psicológico. Haber sido secuestrada (OR 4,71; IC 95%, 1,05-21,07), perseguida (OR 3,33; IC 95%, 1,61-6,89) y abusada sexualmente (OR 3,09; IC 95%, 1,60-5,96), son hechos que se asociaron de forma sostenida y significativa con sintomatología psiquiátrica. Conclusión: Las mujeres afrocolombianas víctimas del conflicto armado colombiano asentadas en Cartagena, presentan condiciones de vida inestables, no han recibido la ayuda adecuada de redes de apoyo, han sido discriminadas por su etnia, género y condición de víctima, y tienen una prevalencia elevada de sintomatología psiquiátrica asociada a los hechos traumáticos vividos.

Objective: To evaluate the phenomenon of sexual violence and the living conditions of Afro-Colombian women victims of the armed conflict, who lives in city of Cartagena, Colombia. Materials and methods: Prospective cross-sectional study, population-based survey type, conducted between September 2019 and March 2020, in the city of Cartagena, Colombia. Sociodemographic variables, type of crimes suffered in the armed conflict and related factors were evaluated, as well as history or presence of psychiatric symptoms associated with traumatic events. Through descriptive analysis, it was characterized the current living conditions of the participants; and also explored associations between the condition of sexual violence and psychiatric symptomatology, through Odds Ratio (OR). Results: 215 women participated, with a median age of 40 years and displaced mainly from the department of Bolívar (55%). 85% percent were housewives and only 60% have their own house, with more than 65% of the total number of houses located in flood risk areas. 35% had suffered gender or racial discrimination or had been victims of sexual violence. Approximately half of the sample reported suffering from insomnia, anxiety and depression. 40% mentioned having had suicidal thoughts and only 1 in 5 women received psychological support. Having been kidnapped (OR 4.71; 95% CI, 1.05-21.07), persecuted (OR 3.33; 95% CI, 1.61-6.89) and sexually abused (OR 3.09; 95% CI, 1.60-5.96), are events that were consistently and significantly associated with psychiatric symptomatology. Conclusion: The Afro-Colombian women victims of the Colombian armed conflict who lives in Cartagena, present unstable living conditions, have not received adequate help from support networks, have been discriminated against because of their ethnicity, gender and victim status, and have a high prevalence of psychiatric symptoms associated with the traumatic events experienced.

Prevalencia de sarcopenia en adultos mayores de dos hogares geriátricos de Pereira, Colombia Prevalence of sarcopenia in older adults in t / Prevalence of sarcopenia in older adults in two retirement homes in Pereira, Colombia

Introducción: La sarcopenia es un factor de riesgo para morbilidad, mortalidad y discapacidad en adultos mayores, por lo que su manejo es prioridad en geriatría. El objetivo de este artículo, consiste en caracterizar una población de adultos mayores de dos hogares geriátricos y establecer la prevalencia de sarcopenia y el grado de dependencia. Métodos: Estudio de corte transversal desarrollado en la ciudad de Pereira-Colombia. Se incluyó a una población de 72 adultos desde los 65 hasta los 98 años, usando muestreo probabilístico. Se determinó la sarcopenia por medio de los Criterios del Consenso Europeo sobre Definición y Diagnóstico de Sarcopenia; evaluándose la fuerza de prensión, índice de masa muscular esquelética, en caso de presentarse sarcopenia, la severidad de esta junto a la velocidad de marcha, y el grado de dependencia según la escala de Barthel. Resultados: Participaron finalmente 57 personas. El 68,4% (n=39) eran mujeres. La mediana de la edad fue de 83 años. El 2% no presentó sarcopenia, 9% presentaban sospecha de sarcopenia, 28% tenían sarcopenia confirmada y 61% sarcopenia grave. Según la escala de Barthel, el 31,5% eran independientes, 45,6% tenían dependencia leve, 15,8% moderada, 5,3% severa y 1,8% total. Conclusiones: La prevalencia de sarcopenia en los hogares geriátricos de Pereira es mayor en comparación a la reportada en la literatura. Del mismo modo, encontrarse en un hogar geriátrico privado no garantiza una mejor condición física y/o calidad de vida.

Introduction: Is a risk factor for morbidity, mortality and disability in older adults, so its management is a priority in geriatrics. The aim of this article is to characterize a population of older adults from two geriatric homes and to establish the prevalence of sarcopenia and the degree of dependence. Methods: Cross-sectional study developed in the city of Pereira-Colombia. A population of 72 adults from 65 to 98 years of age was included, using probability sampling. Sarcopenia was determined by means of the Criteria of the European Consensus on Definition and Diagnosis of Sarcopenia, evaluating grip strength, skeletal muscle mass index, in case of sarcopenia, the severity of sarcopenia together with walking speed, and the degree of dependence according to the Barthel scale. Results: 57 people participated. A total of 68.4% (n=39) were women. The median age was 83 years. Two percent had no sarcopenia, 9% had suspected sarcopenia, 28% had confirmed sarcopenia and 61% had severe sarcopenia. According to the Barthel scale, 31.5% were independent, 45.6% had mild, 15.8% moderate, 5.3% severe and 1.8% total dependence. Conclusions: The prevalence of sarcopenia in nursing homes in Pereira is higher compared to that reported in the literature. Similarly, being in a private nursing home does not guarantee a better physical condition and/or quality of life

Factores socioeconómicos, clínicos y quirúrgicos relacionados al manejo de trauma abdominal penetrante en un hospital de alto nivel de complejidad del caribe colombiano: experiencia de 3 años / Socio-economic, clinical, and surgical factors related to the management of penetrating abdominal trauma in a high-complexity institution in the Colombian Caribbean: 3-year experience

Resumen Introducción: El trauma es una importante causa de mortalidad a nivel mundial y la cuarta causa de muerte en Colombia. Esta condición genera morbilidad y discapacidad, impactando sustancialmente sobre los años de vida potencialmente perdidos, sobre todo, en las edades más tempranas donde es más prevalente. Objetivo: Caracterizar epidemiológica y clínicamente pacientes con trauma abdominal penetrante manejados quirúrgicamente. Materiales y métodos: Estudio observacional de corte transversal y linealidad retrospectiva de pacientes con trauma abdominal penetrante, manejados quirúrgicamente en un hospital de alto nivel de complejidad entre 2016 y 2018, que incluye variables sociodemográficas y clínicas relacionadas con el trauma, el tipo de intervención quirúrgica y complicaciones asociadas. Resultados: Se identificaron 115 pacientes, el 94,8% de sexo masculino. El mecanismo de lesión predominante fue por arma corto-punzante con 67,8%. Se encontró consumo de drogas y sustancias embriagantes relacionado en el 43,7% de los casos. Los principales órganos lesionados fueron el intestino delgado 39.1%, pequeños vasos con 20% e hígado con 16.5%. Los tipos de reparo realizados más frecuentemente fueron la rafia de intestino delgado (22,6 %), y la anastomosis de intestino delgado (20,9%). El Penetrating Abdominal Trauma Index >25 mostró mayor hiperlactatemia (80%) y sepsis (50%). La mortalidad fue del 3.4%, asociado a reintervención y sepsis. Conclusión: La mortalidad por trauma abdominal penetrante en la costa del caribe colombiano es baja. 9 de cada 10 casos son hombres, casi la mitad de los casos se relaciona a consumo de sustancias psicoactivas y las principales complicaciones son la hiperlactatemia y sepsis.

Abstract Introduction: Trauma is an important cause of mortality worldwide and the fourth cause of death in Colombia. This condition generates morbidity and disability, having a substantial impact on the years of life potentially lost, especially in the younger ages where it is more prevalent. Objective: To characterize epidemiologically and clinically patients with penetrating abdominal trauma managed surgically. Materials and methods: Observational cross-sectional retrospective study of patients with penetrating abdominal trauma, surgically managed in a high complexity level hospital between 2016 and 2018, including sociodemographic and clinical variables related to trauma, type of surgical intervention and associated complications. Results: A total of 115 patients were identified, 94.8% of whom were male. The predominant mechanism of injury was a short stabbing weapon (67.8%). Drug and intoxicant use were found in 43.7% of the cases. The main organs injured were the small intestine (39.1%), small vessels (20%) and liver (16.5%). The most frequent types of repair performed were small bowel raffia (22.6%) and small bowel anastomosis (20.9%). The Penetrating Abdominal Trauma Index >25 showed higher hyperlactatemia (80%) and sepsis (50%). Mortality was 3.4%, associated with reoperation and sepsis. Conclusion: Mortality due to penetrating abdominal trauma in the Colombian Caribbean coast is low. Nine out of ten cases are men, almost half of the cases are related to the consumption of psychoactive substances and the main complications are hyperlactatemia and sepsis.

Validación de los criterios predictivos de alto riesgo para coledocolitiasis de la Sociedad Americana de Endoscopia Gastrointestinal, 2010: Experiencia de un centro del caribe colombiano / Validation of the predictive criteria of high risk for choledocholithiasis of the american society for Gastrointestinal Endoscopy, 2010: experience of a Colombian Caribbean Center

Introducción: La colangiopancreatografía retrógrada endoscópica (CPRE) se ha convertido en el estándar de oro para el diagnóstico y tratamiento de la coledocolitiasis. La Sociedad Americana de Endoscopia Gastrointestinal (ASGE) propuso en 2010 estratificar a los pacientes en 3 niveles de riesgo; sin embargo, los estudios han encontrado resultados controvertidos sobre los parámetros predictivos de estos criterios diagnósticos. El objetivo de este estudio consiste en determinar el desempeño de los criterios predictivos de alto riesgo de la ASGE 2010 en el diagnóstico de coledocolitiasis en una población del Caribe colombiano. Métodos: Estudio transversal retrospectivo, en el que se incluyeron pacientes con sospecha de coledocolitiasis, y que fueron llevados a evaluación por CPRE, cumpliendo los criterios propuestos por la ASGE de alta probabilidad. El resultado obtenido se comparó con la presencia de coledocolitiasis en la CPRE, a partir de la cual se estimaron los valores y los intervalos de confianza del 95% para la sensibilidad, la especificidad, el valor predictivo positivo y negativo, y la razón de probabilidad positiva y negativa. Resultados: En este estudio se incluyeron los datos de 118 pacientes. La edad media de los pacientes era de 46 años (RIQ= 31; 17- 89); el 78% (n= 92) eran mujeres. El 65,3% (n= 77) eran mayores de 55 años. El resultado de la CPRE fue positivo en el 81,4% (n= 96) de los pacientes. La presencia de un perfil hepático alterado (90%) resultó ser la prueba más sensible, la colangitis clínica (86%) la más específica, la presencia de litiasis ductal por US (85%) fue la prueba con mayor valor predictivo positivo, y la presencia de litiasis ductal por US (35%) fue la prueba con mayor valor predictivo negativo. Conclusión: Los parámetros predictivos de los criterios de la ASGE 2010 para el diagnóstico de coledocolitiasis muestran variabilidad con respecto al rendimiento propuesto en las guías.

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) has become the gold standard for diagnosis and treatment of choledocholithiasis. The American Society for Gastrointestinal Endoscopy (ASGE) in 2010 proposed stratifying patients into 3 risk levels; however, studies have found controversial results about the predictive parameters of these diagnostic criteria. The objective of this study is to determine the performance of the high-risk predictive criteria of the ASGE 2010 in the diagnosis of choledocholithiasis in a Colombian Caribbean population. Methods: Retrospective cross-sectional study, which included patients with suspected choledocholithiasis, and who were taken for evaluation by ERCP, meeting the criteria proposed by the ASGE of high probability. The result obtained was compared with the presence of choledocholithiasis on ERCP, from which values and 95% confidence intervals were estimated for sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio. Results: A total of 118 patient data were included in this study. The median age of the patients was 46 years (IQR= 31; 17- 89); 78% (n= 92) were female. 65.3% (n= 77) were older than 55 years. The ERCP result was positive in 81.4% (n= 96) of the patients. The presence of an altered liver profile (90%) was found to be the most sensitive test, clinical cholangitis (86%) the most specific, the presence of duct lithiasis by US (85%) was the test with the highest positive predictive value, and the presence of duct lithiasis by US (35%) was the test with the highest negative predictive value. Conclusions: The predictive parameters of the ASGE 2010 criteria for the diagnosis of choledocholithiasis show variability with respect to the performance proposed in the guidelines.

Especies reactivas de oxígeno, estrés oxidativo y su relación con la destrucción tisular en periodontitis / Reactive species of oxygen, oxidative stress and its relationship with tissular destruction in periodontitis / Espécies reativas de oxigênio, estresse oxidativo e sua relação com destruição tecidual na periodontite

Resumen Durante la periodontitis se liberan mediadores inflamatorios y especies reactivas de oxígeno (ROS), cuando se incrementan producen estrés oxidativo. Este artículo de revisión describe el papel que desempeñan las ROS y el estrés oxidativo en el desarrollo y evolución de la inflamación y lesión tisular durante la periodontitis. Para ello, se realizó una revisión de la literatura en bases de datos como PubMed, ScienceDirect, Wiley Online Library, Springer, Plos one, Nature, Sage journals, Hindawi y Taylor & Francis Online, mostrando los siguientes resultados: las ROS producen daño directo e indirecto a los tejidos periodontales. Los daños directos in- cluyen peroxidación de lípidos, oxidación de proteínas y del ADN. Los daños indirectos involucran la regulación de las vías de señalización del factor de trans- cripción nuclear kappa B (NF-κB), la vía de la quinasa c-Jun N-terminal (JNK), las vías del inflamasoma y autofagia provocando la destrucción tisular y creación de un estado proinflamatorio en la periodontitis.

Abstract During periodontitis inflammatory mediators and reactive oxygen species (ROS) are released, when they increase they produce oxidative stress. This review article describes the role played by ROS and oxidative stress in the development and evolution of inflammation and tissue injury during periodontitis. For this, a review of the literature was carried out in databases such as PubMed, ScienceDirect, Wiley Online Library, Springer, Plos one, Nature, Sage journals, Hindawi and Taylor & Francis Online, showing the following results: ROS produce direct damage and indirect to periodontal tissues. Direct damages include lipid peroxidation, protein and DNA oxidation. Indirect damage involves the regulation of signaling pathways of the nuclear transcription factor kappa B (NF-κB), the c-Jun N-terminal kinase pathway (JNK), the pathways of inflammasome and autophagy causing tis- sue destruction and creation of a pro-inflammatory state in periodontitis.

Resumo Durante a periodontite, são liberados mediadores inflamatórios e espécies reati- vas de oxigênio (EROs), no momento em que eles incrementam produzem estresse oxidativo. Este artigo de revisão descreve o papel que desempenham as EROS e o estresse oxidativo no desenvolvimento e na evolução da inflamação e lesão tecidual durante a periodontite. Por isso, uma revisão da literatura foi realizada em bancos de dados como PubMed, ScienceDirect, Wiley Online Library, Springer, Plos one, Nature, Sage, Hindawi e Taylor & Francis Online, mostrando os seguintes resultados: as EROS produzem dano direto e indireto para os tecidos periodontais. O dano direto inclui peroxidação lipídica, oxidação de proteínas e DNA. O dano indireto involucra a regulação das vias de sinalização do fator de transcrição nuclear kappa B (NF-κB), da via c-Jun N-terminal kinase (JNK), das vias inflamassoma e autofagia, causando destruição tecidual e criação de um estado pró-inflamatório na periodontite.

Epidemiología de la interrelación cáncer colorrectal y diabetes mellitus tipo 2. Revisión sistemática / Epidemiology of the interrelationship between colorectal cancer and diabetes mellitus type 2. Systematic review / Epidemiologia da inter-relação câncer colorretal e Diabetes Mellitus tipo 2 - Revisão sistemática

Resumen Objetivos: Describir el estado del arte sobre estudios epidemiológicos que evalúen asociaciones de riesgo entre el cáncer colorrectal y la diabetes tipo 2, y las políticas de salud pública internacionales y colombianas encaminadas a reducir tales patologías. Metodología: Revisión sistemática cualitativa sobre estudios epidemiológicos que evalúen asociaciones de riesgo entre el cáncer colorrectal y la diabetes tipo 2, publicados en idioma español e inglés en PubMed®, United States National Library of Medicine (u.s nlm®), Embase®, Literatura Latinoamericana y del Caribe en Ciencias de la Salud (Lilacs®) y Scientific Electronic Library Online (SciELO®), antes del 30 de junio de 2019. Adicionalmente, se describen las políticas internacionales y nacionales para el control de la diabetes y el cáncer colorrectal. Resultados: De 251 estudios evaluados para elegibilidad, se incluyeron 32 investigaciones originales tipo casos y controles, cohorte prospectivo y retrospectivo, retrospectivos con enfoque de casos y controles, retrospectivos con enfoque casos-cohorte, al mostrar asociaciones de riesgo de padecer cáncer de colon o recto en individuos diabéticos tipo 2. Existen cinco normatividades internacionales para el control de diabetes y cáncer, y dos normatividades colombianas de control de ambas patologías. Conclusiones: La evidencia epidemiológica a nivel mundial señala que individuos con diabetes tipo 2 poseen mayor riesgo de padecer cáncer de colón o recto, en comparación con los no diabéticos, en una forma dependiente de la etnicidad y el sexo. Las políticas de salud pública internacionales y colombianas no han logrado reducir significativamente la carga de ambas patologías, ni los factores de riesgo comunes entre ambas condiciones, y tampoco reconocen los nexos epidemiológicos y biológicos entre la diabetes tipo 2 y el cáncer colorrectal.

Abstract Objective: Describe the state of the art on epidemiological studies that assess risk associations between colorectal cancer and type 2 diabetes, and Colombian and international public health policies to reduce these pathologies. Methodology: Qualitative systematic review on epidemiological studies that assess risk associations between colorectal cancer and type 2 diabetes, published in Spanish and English in PubMed®, United States National Library of Medicine (U.S NLM®), Embase®, Literatura Latinoamericana y del Caribe en Ciencias de la Salud (Lilacs®) and Scientific Electronic Library Online (SciELO®), before 30 June 2019. Furthermore, we describe the international and national policies for the control of diabetes and colorectal cancer. Results: Of 251 studies assessed for eligibility, we included 32 original case-control studies, prospective and retrospective cohort studies, retrospective studies with a case-control approach and retrospective studies with a case-cohort approach as they showed risk associations for colon or rectal cancer in type 2 diabetic individuals. There are five international regulations for the control of diabetes and cancer, and two Colombian regulations for the control of both pathologies. Conclusions: The global epidemiological evidence indicates that individuals with type 2 diabetes have an increased risk of cancer of the colon or rectum, compared with non-diabetics, dependent on ethnicity and sex. International and Colombian public health policies have not been able to significantly reduce the burden of both pathologies, nor the common risk factors between both conditions, nor recognize the epidemiological and biological links between type 2 diabetes and colorectal cancer.

Resumo Objetivo: Descrever o estado da arte relacionado aos estudos epidemiológicos que avaliam associações de risco entre o câncer colorretal e o diabetes tipo 2, e as políticas de saúde pública colombianas e internacionais encaminhadas à redução de tais patologias. Metodologia: Revisão sistemática qualitativa sobre estudos epidemiológicos que avaliem associações de risco entre o câncer colorretal e o diabetes tipo 2, publicados nos idiomas espanhol e inglês em PubMed®, United States National Library of Medicine (U.S NLM®), Embase®, Literatura Latinoamericana y del Caribe em Ciencias de la Salud (Lilacs®) e Scientific Electronic Library Online (SciELO®), antes de 30 de junho de 2019. Adicionalmente são descritas as políticas nacionais e internacionais para o controle do diabetes e o câncer colorretal. Resultados: Dos 251 estudos avaliados para elegibilidade foram incluídas 32 pesquisas originais tipo casos e controles, coorte prospectivo e retrospectivo, retrospectivos com foco de casos e controles, retrospectivos com foco casos-coorte, ao mostrar associações de risco de sofrer câncer de cólon ou reto em pacientes diabéticos tipo 2. Existem cinco regulamentos internacionais para o controle de diabetes e câncer e dois regulamentos colombianos de controle para ambas as patologias. Conclusões: A evidencia epidemiológica a nível mundial mostra que pacientes com diabetes tipo 2 possuem um risco maior de sofrer câncer de cólon ou reto, em comparação com os não-diabéticos, numa forma dependendo da etnia e do sexo. As políticas de saúde pública colombianas e internacionais ainda não conseguiram diminuir significativamente a carga de ambas as patologias, nem os fatores de risco comuns entre ambas as condições, além de não reconhecerem os nexos epidemiológicos e biológicos entre o diabetes tipo 2 e o câncer colorretal.

Consideraciones clínicas de la abetalipoproteinemia: revisión de la literatura / Clinical considerations of abetalipoproteinemia: literature review

La abetalipoproteinemia es una enfermedad rara que se suele presentarse en la primera década de la vida; sus principales manifestaciones son esteatorrea, alteración en el desarrollo y niveles plasmáticos lipídicos onsiderablemente disminuidos. Sin embargo, este cuadro suele ser confuso, puesto que existe un grupo de desórdenes genéticos que conllevan a mala absorción lipídica, que requieren un exhaustivo diagnóstico diferencial desde el punto de vista clínico, bioquímico y molecular. Este artículo expone una revisión actualizada sobre la abetalipoproteinemia, enfocándose en su fisiopatología, manifestaciones sistémicas, diagnóstico y abordaje en general, para facilitar su comprensión integral. La estrategia de búsqueda y los métodos de selección de estudios se realizó con base en elementos de la declaración prisma y guías Cochrane, utilizando términos de búsqueda tales como "abetalipoproteinemia" ,"bioquímica" y sinónimos, los cuales fueron combinados con los operadores "and" y "or", en las bases de datos PubMed, Science Direct, Clinical Key y Ebsco. No existe mucha literatura específica sobre esta condición, lo cual explica que sea una entidad subvalorada y poco conocida. Es fundamental realizar más investigaciones en torno al tema, pues en caso de no establecerse un diagnóstico y manejo adecuado, las complicaciones serán muchas y severas..Au

Abetalipoproteinemia is a rare disease that occurs predominantly in the first decade of life, having as main manifestations, steatorrhea, alteration in development and considerably decreased lipid plasma levels. However, this clinical presentation is often confusing, since there is a group of genetic disorders that lead to poor lipid absorption, requiring the need to make a comprehensive differential diagnosis from a clinical, biochemical and molecular point of view. This article will provide an updated review on Abetalipoproteinemia, focusing on its pathophysiology, systemic manifestations, diagnosis and general approach, allowing easy access to an integral knowledge. The search strategy and study selection methods were based on elements of the prisma statement and Cochrane guidelines, using search terms such as "Abetalipoproteinemia" and "Biochemistry", in addition to synonyms, which were combined with "and" and "or" operators, in the PubMed, Science Direct, Clinical Key and Ebsco databases. It is necessary to highlight that there is not much specific literature on this condition, which would support the fact that it is an undervalued and little-known entity, it is essential to carry out more research on the subject, taking into account that if a diagnosis is not established proper management, the complications are many and severe..Au

Hernia inguinoescrotal reincidente con megauréter: presentación de caso / Recurrent inguinoscrotal hernia with megaureter: a case report

RESUMEN La frecuencia de la enfermedad herniaria es una de las más altas dentro de los cuadros quirúrgicos. Sin embargo, su asociación al megauréter en el saco herniario o contenido es extremadamente rara y existen pocos reportes en la literatura internacional. El diagnóstico es incidental, ya sea por hallazgo transoperatorio o por estudios contrastados de imagen. Se presenta el caso clínico de un paciente con antecedente de hernia inguinal que fue sometido a una herniorrafia hace veinte años y que se presenta a un servicio de urgencias con un aparente defecto herniario. Además, padece diabetes mellitus que está mal controlada. Durante la estancia hospitalaria se confirma la reaparición de la hernia con un saco que contiene megauréter y adherencias visceroparietales con ciego en posición subhepática.

ABSTRACT Herniation is one of the most frequent surgical conditions. However, the presence of a megaureter in the hernia sac or content is extremely rare. Little has been reported on this topic in the world literature, and its diagnosis has been incidentally reached either as an intraoperative finding or during different contrast imaging studies. This is the clinical case of a patient with a history of inguinal hernia who underwent a herniorrhaphy 20 years ago and presented to the emergency department with a diagnostic impression of a relapsed hernial defect. He also had poorly-controlled diabetes mellitus. During his hospital stay, a diagnosis of relapsed hernia sac containing a megaureter was confirmed, and visceral-parietal adhesions and a subhepatic cecum were found.

Gene expression of collagen type I alpha 2 and its relationship with dental fluorosis

Objective: to compare the gene expression levels of collagen type I alpha 2 (COL1A2) in children with and without dental fluorosis. methods: cross-sectional study involving 92 children between 5 and 12 years of age. socio-demographic characteristics, the presence of dental fluorosis by means of the Thylstrup-Fejerskov index, and gene expression analysis of COL1A2 in peripheral blood samples by reverse transcription polymerase chain reaction (RT-PCR) assays, were described. for the descriptive analysis, measures of central tendency, dispersion and proportions were used. differences between the groups (p<0.05) were established by the student t-test. results: mean age was 8.6 (SD=1.9) years, 51.1 percent were female; 54 children were diagnosed with fluorosis and 38 without fluorosis; prevalence of dental fluorosis was 58.7 percent (95 percent CI: 48.4 percent -68.9 percent). gene expression of COL1A2 was statistically significantly lower (p<0.05) in the participants with dental fluorosis. conclusion: there are differences in the expression levels of the COL1A2 gene among the population under study. therefore, COL1A2 may be potentially involved in the development of dental fluorosis.

Mouse hepatic oval cells require Met-dependent PI3K to impair TGF-ß-induced oxidative stress and apoptosis.

We have previously shown that oval cells harboring a genetically inactivated Met tyrosine kinase (Met(-/-) oval cells) are more sensitive to TGF-ß-induced apoptosis than cells expressing a functional Met (Met(flx/flx)), demonstrating that the HGF/Met axis plays a pivotal role in oval cell survival. Here, we have examined the mechanism behind this effect and have found that TGF-ß induced a mitochondria-dependent apoptotic cell death in Met(flx/flx) and Met(-/-) oval cells, associated with a marked increase in levels of the BH3-only proteins Bim and Bmf. Bmf plays a key role during TGF-ß-mediated apoptosis since knocking down of BMF significantly diminished the apoptotic response in Met(-/-) oval cells. TGF-ß also induced oxidative stress accompanied by NADPH oxidase 4 (Nox4) mRNA up-regulation and decreased protein levels of antioxidant enzymes. Antioxidants inhibit both TGF-ß-induced caspase 3 activity and Bmf up-regulation, revealing an oxidative stress-dependent Bmf regulation by TGF-ß. Notably, oxidative stress-related events were strongly amplified in Met(-/-) oval cells, emphasizing the critical role of Met in promoting survival. Pharmacological inhibition of PI3K did impair HGF-driven protection from TGF-ß-induced apoptosis and increased sensitivity of Met(flx/flx) oval cells to TGF-ß by enhancing oxidative stress, reaching apoptotic indices similar to those obtained in Met(-/-) oval cells. Interestingly, both PI3K inhibition and/or knockdown itself resulted in caspase-3 activation and loss of viability in Met(flx/flx) oval cells, whereas no effect was observed in Met(-/-) oval cells. Altogether, results presented here provide solid evidences that both paracrine and autocrine HGF/Met signaling requires PI3K to promote mouse hepatic oval cell survival against TGF-ß-induced oxidative stress and apoptosis.

Plan Control del cáncer en Colombia 2012-2021. Un análisis formal / Cancer Control Plan in Colombia 2012-2021. A Formal Analysis / Plano Controle do cancro na Colômbia 2012-2021. Análise formal

Resumen En Colombia el cáncer es un problema de salud pública. Su incidencia y mortalidad afectan tanto a la población adulta como a la población pediátrica. Desde el año 2010 el país se viene preparando para afrontar este problema. El Instituto Nacional de Cancerología (INC) ha realizado investigaciones para caracterizar epidemiológicamente el cáncer, así como otros factores que inciden en su letalidad. Las leyes 1384 y 1388 de 2010 fijaron las bases para el control integral del cáncer y designaron al INC para asesorar al Ministerio de Salud y Protección Social en esta tarea. Se analizó el contenido del plan, con base en una guía elaborada por la Facultad de Salud Pública de la Universidad de Antioquia. Debido a la importancia del problema y la complejidad de la política, se concluye: solo con un sistema estricto de monitoreo, una evaluación permanente de las actividades del plan y la aplicación de correctivos oportunos, Colombia podría alcanzar las metas en el control del cáncer.

Abstract In Colombia, cancer is a public health problem. Its incidence and mortality affects both adult and pediatric population. Since 2010 the country has been preparing to address this problem. The National Cancer Institute (NCI) has conducted research to characterize epidemiologically cancer as well as other factors that influence their lethality. 1384 and 1388 laws of 2010 laid the foundation for comprehensive cancer control and designated the INC to advise the Ministry of Health and Social Protection in this task. We analyzed the contents of the plan, based on a guide developed by the School of Public Health at the University of Antioquia. Because of the importance of the problem and the complexity of the policy concludes: Only a strict monitoring system, continuous evaluation and timely corrective plan of activities, Colombia could reach targets in cancer control.

Resumo Na Colômbia, o câncer é um problema de saúde pública. A incidência e a mortalidade afectar ambos os adultos e a população pediátrica. Desde 2010 o país tem vindo a preparar para resolver este problema. O Instituto Nacional do Câncer (INC) realizou uma pesquisa para caracterizar epidemiologicamente câncer, bem como outros fatores que influenciam sua letalidade. 1384 e 1388 leis de 2010 lançou as bases para o controle integral de câncer eo INC nomeado para assessorar o Ministério da Saúde e Protecção Social nesta tarefa. o conteúdo do plano foi analisado, com base em um guia desenvolvido pela Escola de Saúde Pública da Universidade de Antioquia. Devido à importância do problema e da complexidade da política, ele conclui: Colômbia poderia atingir as metas para o controle do câncer se aplicado rigoroso sistema de monitorização, uma avaliação contínua das actividades do plano ea implementação de medidas corretivas adequadas.

Relación entre el factor de crecimiento hepático y el estadio de la cirrosis / Relationship between Hepatocyte Growth Factor (Hgf) and Stage of Cirrosis

Introducción: en el hígado, el factor de crecimiento hepático (FCH) es conocido por ser un potente agente mitogénico tanto in vivo como in vitro. Sin embargo, el papel del FCH en la cirrosis no está completamente claro y algunos estudios lo señalan como un marcador de severidad en la cirrosis, en la insuficiencia hepática aguda y en la hepatitis crónica. Objetivos: determinar la relación entre el FCH y el estadio de la cirrosis hepática e identificar los factores asociados con los niveles de FCH en esta población. Metodología: se evaluaron todos los pacientes con cirrosis hepática atendidos desde enero a marzo de 2014. La elastografía transitoria (ET), la recopilación de la información clínica y la extracción de la muestra para la determinación del FCH se realizó de forma simultánea en el momento de la inclusión. Resultados: no se encontró relación entre los niveles de FCH y la clasificación de Child-Pugh; sin embargo, se observaron niveles más elevados en pacientes con enfermedad descompensada. Se determinó una asociación lineal positiva entre el FCH y la dureza hepática estimada por elastografía (b = 0,53; r2 = 0,26; p = 0,002) y una asociación lineal negativa con la albúmina (b = -0,62; r2 = 0,39; p <0,001). Únicamente la albúmina conservó esta asociación en el análisis multivariante. Conclusión: el FCH es un marcador de severidad en la cirrosis hepática. La albúmina y el grado de fibrosis determinada por ET se asociaron con niveles de FCH

Introduction: Hepatocyte growth factor (HGF) is known to be a potent mitogenic agent both in vivo and in vitro. The role of HGF in cirrhosis is not completely clear, but some studies point to it as a marker of severity in cirrhosis, acute liver failure and chronic hepatitis. Objective: The objective of this study was to determine the relationship between HGF and the stage of hepatic cirrhosis and to identify factors associated with HGF levels in this population. Methodology: All patients with hepatic cirrhosis treated from January to March 2014 were evaluated. At the time patients were enrolled in the study their clinical histories were taken and they underwent transient elastography and extraction of samples for measurement of HGF. Results: No relationships were found between HGF levels and Child-Pugh classifications, however, higher levels of HGF were observed in patients with decompensated disease. A positive linear relations was found between HGF and hepatic hardness estimated by elastography (b = 0.53, r2 = 0.26, p = 0.002) and a negative linear relation was found between HGF and albumin (b = -0.62, r2 = 0.39, p <0.001). Only albumin retained this association in the multivariate analysis. Conclusion: HGF is a marker of severity in liver cirrhosis. Albumin and the degree of fibrosis determined by transient elastography were associated with HGF levels.

Evaluación de dos métodos para extracción de ARN en saliva en niños / Evaluation of two RNA extraction methods in children's saliva

Resumen Objetivo: Estandarizar un protocolo de extracción de ARN en muestras de saliva de niños. Material y métodos: A partir de muestras de saliva provenientes de 60 niños que participaron previa autorización de sus padres. Se compararon dos métodos para extracción de ARN, evaluando concentración, calidad y rendimiento; además se realizó la expresión génica del gen G USB a través de la técnica RT-PCR (transcriptase reversa-reacción en cadena de la polimerasa). Los datos fueron analizados mediante medidas de tendencia central y dispersión, frecuencias y porcentajes, para establecer diferencias se utilizaron las pruebas t-Student y χ2 (ρ < 0.05). Resultados: Al analizar la cantidad de células por mL de saliva se encontró una media de 564,977.8 (DE = 246,678.6); se logró estandarizar un método de extracción de ARN en saliva de niños, específicamente el que utilizó RNeasy® Protect Saliva Mini Kit-Qiagen mostró mejores características de concentración de ARN (p = 0.0000) y rendimiento (p = 0.0000) al compararlo con el que uso QlAzol®; no existieron diferencias en la calidad del ARN (p = 0.146). Conclusión: El ARN pudo extraerse de muestras salivales de niños, por lo cual se sugiere el uso de la saliva para análisis molecular de diferentes enfermedades sistémicas y de la cavidad bucal.

Abstract Objective: To standardize an RNA (ribonucleic acid) extraction protocol in children's saliva specimens. Methods: The study was conducted on saliva specimens from 60 children who participated in the study with their parents' authorization. Comparison of two RNA extraction methods was established; methods assessed concentration, quality and yield. Moreover, genie expression of GUSB gene was achieved with RT-PCR (reverse transcriptase-polymerase chain reaction). Data were analyzed through measurements of central tendency and dispersion, frequencies and percentages. Т-Student and χ2 tests were used in order to differentiate between both methods (p < 0.05). Results: Analysis of cell amounts per saliva ml revealed a mean of 564,977.8 (SD = 246,678.6); a RNA in children's saliva extraction method was standardized, specifically the method using RNeasy® Protect Saliva Mini Kit Qiagen exhibited better characteristics of RNA concentration (p = 0.0000) and yield (p = 0.0000) when compared to the method using QIAzór®; no RNA (p = 0.146) quality differences were found. Conclusions: RNA could be extracted from children's saliva specimens, therefore, it is suggested to use saliva for the molecular analysis of different oral and systemic diseases.

Expresión génica del factor de crecimiento transformante beta en niños con fisura labio palatina no sindrómica / Gene expression of transforming growth factor bet in children with non-syndromic cleft lip and palate

El objetivo fue determinar la expresión génica del factor de crecimiento transformante beta (TGF-ß) y posibles factores de riesgo en niños con y sin fisuras labio palatina no sindrómicas (FLPNS). Diseño de casos (Niños con fisuras orales; n= 20) y controles (niños no afectados; n= 40). A partir de muestras de saliva se realizó la extracción de mRNA utilizando el RNeasy® Protect Saliva Mini Kit-QIAgen y la expresión génica del TGF-ß mediante la reacción en cadena de la polimerasa en transcriptasa reversa, además se aplicó un cuestionario para registrar características sociodemográficas y posibles factores de riesgo durante el periodo de concepción (medicamentos, enfermedades, alcohol, cigarrillo y edad de los padres).Los datos fueron analizados mediante medidas de tendencia central y dispersión, frecuencias y porcentajes, para establecer asociaciones se utilizaron las prueba T-Student, Chi-cuadrado y Odds ratio, asumiendo un límite de confianza de 0,05. El promedio de edad de los participantes fue de 6,8 (DE= 4,6) años y el 63,3 % eran de sexo masculino. Al evaluar los posibles factores asociados con el desarrollo de FLPNS no se encontraron diferencias significativas, sin embargo el 11,7 % de las madres habían ingerido algún tipo de medicamentos durante el embarazo, el 1,7 % habían fumado algún cigarrillo y el 13,3 % ingerido alcohol. Existieron diferencias significativas en la expresión génica del TGF-ß entre los grupos (p= 0,0205), siendo menor en grupo de casos. Los factores de riesgo evaluados mostraron poca evidencia de asociación con la presencia de FLAPNS, los niños con esta alteración tienen menor expresión génica del TGF-ß, sugiriendo que alteraciones moleculares en la vía de señalización del TGF-ß posiblemente están involucradas en el desarrollo de las fisuras labio palatinas, ya que se pueden afectar procesos de diferenciación, crecimiento y proliferación celular, en donde participan varios genes incluyendo el TGF-ß.

The aim of this study was to determine gene expression of transforming growth factor beta (TGF-ß) and possible risk factors in children with and without non-syndromic oral clefts. Cases (Children with cleft lip and palate; n= 20) and controls (unaffected children; n= 40) study, from saliva samples mRNA extraction was performed using the RNeasy® Protect Saliva Mini Kit-QIAgen and gene expression of TGF-ß by reverse transcriptase polymerase chain reaction, a questionnaire was also applied to record sociodemographic characteristics and possible risk factors. Data were analyzed using measures of central tendency and dispersion, frequencies and percentages. Odds ratio, Chi-square and T-Student tests were used to determine association (p<0.05). The average age of participants was 6.8 (SD= 4.6) years and 63.3 % were male. No statistically significant association was found between any of the possible risk factors examined with the development of oral clefts (p> 0.05), however it was reported that 11.7 % of mothers had ingested some type of drug during pregnancy, 1.7 % reported maternal smoking and 13.3 % reported alcohol consumption. There were significant differences in gene expression levels of TGF-ß between groups (p= 0.0205), being lower in children with oral clefts. Most environmental risk factors evaluated here gave little evidence of association with the presence of oral clefts. Children with oral clefts have lower gene expression of TGF-ß, suggesting that molecular alterations in the signaling pathway of TGF-ß are possibly involved in the development of cleft lip and palate, as they can affect processes of differentiation, growth and proliferation cell, where several genes are involved including TGF-ß.

Caracterización clínica del dengue en un hospital infantil de Cartagena (Colombia) / Clinical characterization of dengue in a children's hospital of Cartagena (Colombia)

Objetivo: Caracterizar las manifestaciones clínicas del dengue en pacientes pediátricos en una institución de salud de tercer nivel de Cartagena (Colombia). Materiales y métodos: Estudio descriptivo por revisión de historias clínicas de pacientes hospitalizados por dengue en el Hospital Infantil Napoleón Franco Pareja de la ciudad de Cartagena. Se evaluaron 136 niños con cuadros febriles agudos de etiología inaparente. Se utilizaron pruebas serológicas para confirmar la infección por el virus del dengue. Resultados: Se analizaron 98 casos de niños hospitalizados con diagnóstico de dengue. La edad osciló entre menores de 6 meses a 16 años, siendo el rango de edades con mayor frecuencia de la enfermedad de 10 a 16 años (33,7 %). Los signos y síntomas más frecuentes fueron: exantema (49,0 %), mialgia (35,7 %), cefalea (33,7 %), artralgia (33,7 %), anorexia (24,5 %), torniquete (19,4%), prurito (11,2 %), escalofrío (8,2 %), eritema facial (7,1 %) y dolor retroocular (6,1 %). Conclusiones: La edad continúa siendo el factor predominante en la gravedad intrahos-pitalaria del dengue. Por lo tanto, se necesitan con urgencia medidas preventivas en la población pediátrica.

Objective: To characterize the clinical manifestations of dengue in pediatric patients in a health institution tertiary Cartagena (Colombia). Materials and methods: Descriptive study by review of medical records of patients hospitalized for dengue at Children's Hospital Napoleon Franco Pareja of Cartagena. We evaluated 136 children with acute fever unapparent etiology. Serology to confirm infection by dengue virus tests was used. Results: 98 cases of children hospitalized with dengue diagnosis were analyzed. Age ranged from under 6 months to 16 years, with the age range with the highest frequency of the disease 10 to 16 years (33.7 %). The most common signs and symptoms were rash (49.0 %), myalgia (35.7 %), headache (33.7 %), arthralgia (33.7 %), anorexia (24.5 %), tourniquet (19.4 %), pruritus (11.2 %), chills (8.2 %), facial erythema (7.1 %) and ocular retro pain (6.1 %). Conclusions: Age remains the predominant factor in the severity of dengue. Therefore urgently needed preventive measures in the pediatric population.

Encefalopatía epiléptica por fenilcetonuria / Epileptic encephalopathy by phenylcetonuria

La fenilcetonuria es un error innato del metabolismo con graves repercusiones neurológicas y sistémicas, si no se detecta antes del primer mes de vida. La implementación de pruebas de tamizaje metabólico en la etapa neonatal, constituye una herramienta económica, sencilla y no invasiva, que permite por lo menos sospechar si un niño nace con esta patología. El presente artículo muestra evidencia del daño neurológico de un niño con diagnóstico tardío de fenilcetonuria (PKU) en la Fundación Instituto de Habilitación “El Rosario” de Cartagena - Colombia, para niños con retardo mental. Este niño, tuvo un neurodesarrollo acorde a su edad hasta los siete meses, época en la que aparecieron crisis epilépticas, instalándose una encefalopatía epiléptica progresiva y con pobre respuesta a fármacos antiepilépticos. Se le practicó una tomografía axial computarizada (TAC), la cual no mostró daño estructural. Las crisis cesaron a los cuatro años, sin embargo, el paciente quedó con secuelas motoras y psíquicas. Sólo hasta los ocho años, después de una resonancia magnética nuclear (RM), se decidió practicar un tamizaje metabólico en suero y orina, cuyos resultados orientaron a solicitar pruebas más específicas, que permitieron cuantificar el aumento en plasma del aminoácido fenilalanina y confirmar el diagnóstico. Es de resaltar que la realización de un tamizaje metabólico en la etapa neonatal o al momento de la aparición de los espasmos, hubiera permitido incidir favorablemente en el curso de esta enfermedad, evitando el daño neurológico por medio de la instauración de una dieta libre de fenilalanina en etapas tempranas del desarrollo