Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests.

PURPOSE: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies. METHODS: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. RESULTS: Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%. CONCLUSION: The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies-positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.

Detección de anticuerpos contra el virus de la hepatitis C en donantes de sangre voluntarios / Detection of antibodies against hepatitis C virus in volunteer blood donors

Introducción: las pruebas de detección de anticuerpos contra el virus de la hepatitis C en donantes de sangre han servido para la identificación de enfermos y son un elemento importante para interrumpir la transmisión por esta vía. Objetivo: describir el comportamiento de la detección de anti-HVC en el municipio de Artemisa entre los años 2006-2010 e identificar las principales alteraciones clínicas en los pacientes con prueba de detección de ARN positiva. Métodos: se realizó un estudio ecológico de series temporales. El universo estuvo conformado por los 162 pacientes pertenecientes al municipio Artemisa a los cuales, en las donaciones de sangre, se les detectó positividad para en anti-VHC según método de ELISA (UMELISA). La información se obtuvo a través de la base de datos del Banco de Sangre Territorial de San Antonio de los Baños entre el 1º de enero de 2006 y el 31 de diciembre de 2010. Resultados: de las 8 057 donaciones de sangre realizadas en el período; el 2,01 por ciento resultaron positivas. Se demostró el comportamiento estacional, la variación cíclica de la serie cronológica y una tendencia creciente. Se identificaron los meses de septiembre, junio y noviembre como los de mayor incidencia. La relación hombre/mujer fue de 13:1, predominando el sexo masculino entre los donantes anti-HVC positivos con el 94,7 por ciento. Se detectó el ácido nucleico del virus C por biopsia hepática en 41 casos comprendidos entre los 41 y 45 años predominantemente. El 95,1 por ciento de los enfermos presentaron transaminasas normales, antecedentes de instrumentaciones percutáneas y cambios histológicos compatibles con una hepatitis crónica en el momento del diagnóstico. Conclusiones: se confirma la utilidad del pesquisaje del anti-HVC para la planificación de los recursos de salud en el territorio y para la identificación de enfermos con distintos grados de lesión hepática, a pesar de estar asintomáticos y con transaminasas normales(AU)

Introduction: Tests for antibodies to the hepatitis C virus in blood donors have been used to identify patients and it is an important element in disrupting transmission by this route. Objective: The objective of the present investigation was to describe the behavior of the detection of anti-HVC in Artemisa municipality between 2006-2010 years and to identify the main clinical alterations in the patients with positive RNA detection test. Methods: An ecological study of time series was carried out. The universe was 162 patients resident in Artemisa municipality, to whom, in blood donations, they were detected positivity for anti-HCV according to the ELISA method (UMELISA). The information was obtained through the database of the Territorial Blood Bank of San Antonio de los Baños between January 1, 2006 and December 31, 2010. Results: In this period 8057 blood donations were made; 2.01 percent were positive. The seasonal behavior, the cyclical variation of the chronological series and an increasing tendency were demonstrated. The months of September, June and November were identified as months with highest incidence. The male-to-female ratio was 13: 1, with male sex predominating among anti-HVC positive donors with 94.7 percent. Nucleic acid of C virus was detected by liver biopsy in 41 cases between 41 and 45 years old predominantly. The 95.1 percent of the patients presented normal transaminases, a history of percutaneous instrumentation and histological changes compatible with chronic hepatitis at the time of diagnosis. Conclusions: The usefulness of anti-HVC screening for the planning of health resources in the territory and for the identification of patients with different degrees of liver injury, despite being asymptomatic and with normal transaminases, is confirmed(AU)

Polµ deficiency induces moderate shortening of P53-/- mouse lifespan and modifies tumor spectrum.

Non-homologous end joining (NHEJ) is the main mechanism for double strand break (DSB) DNA repair. The error-prone DNA polymerase mu (Polµ) is involved in immunoglobulin variable region rearrangement and in general, NHEJ in non-lymphoid cells. Deletion of NHEJ factors in P53-/- mice, which are highly prone to development of T cell lymphoma, generally increases cancer incidence and shifts the tumor spectrum towards aggressive pro-B lymphoma. In contrast, Polµ deletion increased sarcoma incidence, proportionally reducing pro-B lymphoma development on the P53-deficient background. Array comparative genomic hybridization (aCGH) analyses showed DNA copy number alterations in both P53-/- and Polµ-/-P53-/- lymphomas. Our results also indicate that the increase in sarcoma incidence in Polµ-/-P53-/- mice could be associated with Cdk4 and Kub3 amplification and overexpression. These results identify a role for Polµ in the prevention of sarcomagenesis on a murine P53-deficient background, in contrast to most other NHEJ factors.

Targeted gene therapy and cell reprogramming in Fanconi anemia.

Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies.

Evaluación de la vigilancia microbiológica del cólera / Evaluation of cholera microbiological surveillance

Introducción: el cólera constituye una enfermedad infecciosa, por lo que desde hace más de 40 años ha sido objeto de vigilancia en Cuba. La razón de ser de la vigilancia es la obtención de información, su procesamiento, análisis y elaboración de recomendaciones para la acción oportuna. Objetivo: evaluar la vigilancia microbiológica del cólera en el Centro Provincial de Higiene y Epidemiología de La Habana. Método: se realizó un estudio descriptivo transversal de evaluación táctica en el período del I de octubre al I8 de noviembre del año 20I2. El universo lo constituyeron la Vicedirección de Higiene y Epidemiología y la Vicedirección de Microbiología con sus 22 laboratorios. Se seleccionó una muestra no aleatoria, por conveniencia, que quedó integrada por el jefe de departamento de la unidad de análisis y tendencias de salud, el jefe del programa de control de enfermedades de transmisión digestiva, el vicedirector de microbiología y el personal que se encontraba presente en los laboratorios de agua y de enterobacterias. Se aplicó la metodología de la evaluación rápida propuesta por la Dra. Fariñas, visitándose en un período de 2 días, el laboratorio provincial de microbiología. Resultados: se identificaron brechas existente entre lo que estaba orientado para realizar ante todo paciente sospechosos o confirmado de cólera por parte del laboratorio de microbiología y lo que en realidad se estaba realizando. Conclusiones: las acciones de vigilancia microbiológica del cólera en el Centro Provincial de Higiene y Epidemiología fueron evaluadas de medianamente útil. Estructura medianamente suficiente. Proceso aceptable e impacto satisfactorio...

Background: cholera is an infectious disease, so for more than 40 years it has been under surveillance in Cuba. The reason for monitoring cholera in Cuba is to obtain information, processing, analysis, and development of recommendations for appropriate action. Objective: to evaluate cholera microbiological surveillance in Havana Center of Hygiene and Epidemiology. Method: a descriptive cross-sectional study of tactical assessment was conducted from October to 1st November I8th, 20I2. The universe was formed by vice-direction of Hygiene and Epidemiology and vice-direction of Microbiology with its 22 laboratories. A non-random sample of convenience was chosen. it was composed of the head of the department of the unit for analysis and health trends, the program chief for controlling digestive transmission disease, the deputy director of microbiology and the staff who was present in water laboratories and Enterobacteriaceae. A rapid assessment methodology proposed by Dr. Farinas was applied, visiting the provincial microbiology laboratory over a period of 2 days. Results: existing gaps were identified between what was primarily instructed for a suspected or confirmed case of cholera by the microbiology laboratory and what actually was taking place. Conclusions: cholera microbiological surveillance actions were evaluated fairly useful in Havana Center of Hygiene and Epidemiology, as reasonably sufficient structure, good enough process, and satisfactory impact...

Evaluación de la vigilancia del cólera en el policlínico Héroes del Moncada / Evaluation of cholera surveillance at Heroes of Moncada polyclinic

Introducción: la evaluación está concebida como la actividad que permite emitir un juicio de valor. El cólera constituye una enfermedad infecciosa conocida desde tiempos inmemoriales, por lo que desde hace más de 40 años ha sido objeto de vigilancia en Cuba. Múltiples y complejas variables han sido las responsables de la entrada del Vibrio cholerae en el país, condicionando la aparición en el territorio nacional de diversos brotes. Objetivo: evaluar la vigilancia del cólera en el policlínico Héroes del Moncada del municipio Plaza de la Revolución, en el período de octubre-noviembre de 2012. Método: se realizó un estudio descriptivo, transversal, de evaluación táctica. El universo estuvo conformado por: 26 médicos de consultorios de médico de familia, un vicedirector de Higiene y Epidemiología, 3 técnicas de laboratorios, dos de estadísticas y 3 técnicos de Higiene del área. Se seleccionó una muestra por conveniencia que representó el 20 por ciento del universo. Se aplicó la metodología de la evaluación rápida propuesta por la Dra. Teresa Fariñas, visitándose en un período de 2 días un total de 5 consultorios del policlínico. Además se recogió información retrospectiva del mes de octubre y primera quincena de noviembre. Resultados: se identificaron brechas entre lo que estaba orientado vigilar por los médicos y enfermeras de la familia ante todo caso que solicitara atención médica por padecer de una enfermedad diarreica aguda y lo que en realidad se estaba realizando. Conclusiones: la valoración de la vigilancia del cólera en nuestro estudio fue evaluada de medianamente satisfactoria, al calificarse como no útil, con una calidad medianamente aceptable y unos resultados satisfactorios...

evaluation is conceived as the activity that allows a judgment of value. Cholera is an infectious disease known since ancient times, so for more than 40 years it has been under surveillance in Cuba. Multiple and complex variables have been responsible for the entry of Vibrio cholerae in Cuba, conditioning the emergence of several outbreaks on the national territory. Objective: to assess cholera surveillance at Heroes of Moncada polyclinic in Plaza Township, Havana from October to November 2012. Method: a tactical, descriptive, cross-sectional study assessment was performed. The universe consisted of 26 medical practices, a principal assistant of Hygiene and Epidemiology, 3 laboratory technicians, 2 of statistics technicians, and 3 hygiene technicians from this area. A convenience sample was selected representing 20 percent of the universe. The rapid assessment methodology proposed by Dr. Teresa Fariñas was applied, visiting 5 medical practices of this area over a total period of two days. Further background information from October and first half of November was collected. Results: gaps were identified between what was primarily instructed to control by family physicians and nurses in case of health care due to acute diarrheal disease and what actually was taking place. Conclusions: the evaluation of cholera surveillance in our study was assessed fairly satisfactory, by being scored as unuseful, with a fairly acceptable quality and satisfactory results...

Brief report: impaired cell reprogramming in nonhomologous end joining deficient cells.

Although there is an increasing interest in defining the role of DNA damage response mechanisms in cell reprogramming, the relevance of proteins participating in nonhomologous end joining (NHEJ), a major mechanism of DNA double-strand breaks repair, in this process remains to be investigated. Herein, we present data related to the reprogramming of primary mouse embryonic fibroblasts (MEF) from severe combined immunodeficient (Scid) mice defective in DNA-PKcs, a key protein for NHEJ. Reduced numbers of induced pluripotent stem cell (iPSC) colonies were generated from Scid cells using reprogramming lentiviral vectors (LV), being the reprogramming efficiency fourfold to sevenfold lower than that observed in wt cells. Moreover, these Scid iPSC-like clones were prematurely lost or differentiated spontaneously. While the Scid mutation neither reduce the proliferation rate nor the transduction efficacy of fibroblasts transduced with reprogramming LV, both the expression of SA-ß-Gal and of P16/INK(4a) senescence markers were highly increased in Scid versus wt MEFs during the reprogramming process, accounting for the reduced reprogramming efficacy of Scid MEFs. The use of improved Sleeping Beauty transposon/transposase systems allowed us, however, to isolate DNA-PKcs-deficient iPSCs which preserved their parental genotype and hypersensitivity to ionizing radiation. This new disease-specific iPSC model would be useful to understand the physiological consequences of the DNA-PKcs mutation during development and would help to improve current cell and gene therapy strategies for the disease.

Increased learning and brain long-term potentiation in aged mice lacking DNA polymerase µ.

A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in DNA repair mechanisms mostly result in accelerated aging and reduced brain function. DNA polymerase µ is a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, and its deficiency causes reduced DNA repair. Using associative learning and long-term potentiation experiments, we demonstrate that Polµ(-/-) mice, however, maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polµ(-/-) mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. This is the first example in which the genetic ablation of a DNA-repair function results in a substantially better maintenance of learning abilities, together with fewer signs of brain aging, in old mice.

Caracterización de cepas de candida albicans aisladas de la cavidad oral de pacientes de sida / Characterization of Candida Albicans cultures isolated of the oral cavity of AIDS patients

La candidiasis oral es la micosis oportunista más frecuente en individuos portadores del virus de inmunodeficiencia humana (VIH) y pacientes con el síndrome de inmunodeficiencia adquirida (SIDA).En este estudio se realizó la caracterización fenotípica y genotípica a cepas de C. albicans aisladas de la cavidad oral de pacientes con SIDA.Se estudiaron 52 cepas de C. Albicans aisladas de 47 pacientes con SIDA con lesión sugestiva de candidiasis oral y se les realizó tipificación morfológica, en el medioagar Sabouraud trifeniltetrazolio (AST). Además se empleó la Reacción en Cadena de la Polimerasa con cebadores arbitrarios (AP-PCR) con tres cebadores (OPA-3, (GACA)4yM13) para la caracterización de 11 de las 52 cepas mencionadas anteriormente.Se determinaron ocho morfotipos diferentes, siendo los más frecuentes: LD1N (28, 9 por cento), LD2N (28, 9 por ciento) y LD2S (19, 2 por ciento). Se encontraron diferentes patrones de amplificación con cada cebador: con el OPA-3 se obtuvieron 3 patrones, con el M13 se observaron 5 y sólo 2 con(GACA)4