Breast cancer risk associated with gene expression and genotype polymorphisms of the folate-metabolizing MTHFR gene: a case-control study in a high altitude Ecuadorian mestizo population.

Breast cancer (BC) is the leading cause of cancer-related death among women in 2014. Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and MTR reductase (MTRR) are enzymes that play an important role in folate metabolism. The single nucleotide polymorphisms, MTHFR C677T, A1298C, MTR A2756G, and MTRR A66G, alter plasmatic folate and homocysteine concentrations, causing problems during the repairment, synthesis, and methylation of the genetic material. Therefore, it is essential to know how BC risk is associated with histopathological and immunohistochemical characteristics, genotype polymorphisms, and gene expression in a high altitude Ecuadorian mestizo population. DNA was extracted from 195 healthy and 114 affected women. Genotypes were determined by restriction enzymes and genomic sequencing. mRNA was extracted from 26 glandular breast tissue samples, both from cancerous tissue and healthy tissue adjacent to the tumor. Relative gene expression was determined with the comparative Livak method (2(-ΔΔCT)). We found significant association between the rs1801133 (A222V) genotypes and an increased risk of BC development: C/T (odds ratio [OR] = 1.8; 95 % confidence interval [CI] = 1.1-3.2; P = 0.039), T/T (OR = 2.9; 95 % CI = 1.2-7.2; P = 0.025), and C/T + T/T (OR = 1.9; 95 % CI = 1.1-3.3; P = 0.019). Regarding relative gene expression, we found significant mRNA subexpression between the combined genotypes C/T + T/T (rs1801133) and triple negative breast cancer (TNBC) (P = 0.034). In brief, the MTHFR gene and its protein could act as potential predictive biomarkers of BC, especially TNBC among the high altitude Ecuadorian mestizo population.

Incidence of Citrus leprosis virus C and Orchid fleck dichorhavirus Citrus Strain in Mites of the Genus Brevipalpus in Mexico.

The incidences of Citrus leprosis virus C (CiLV-C) and Orchid fleck dichorhavirus Citrus strain (OFV-citrus) were determined in field populations of Brevipalpus mites from 15 citrus-producing states in Mexico. Mites were collected from orange, grapefruit, mandarin, lime, and sweet lime orchards. Brevipalpus yothersi (Baker) (Trombidiformes: Tenuipalpidae) was the most abundant species followed by Brevipalpus californicus (Banks) (Trombidiformes: Tenuipalpidae), which confirmed previous reports. The viruses CiLV-C and OFV-citrus were found in both mite species. The incidence of CiLV-C, OFV-citrus and both viruses simultaneously (CiLV-C and OFV-citrus) was 17.2, 10.3, and 3.4% (n = 116) for B. yothersi, and 12.5, 20.8, and 4.1% (n = 24) for B. californicus, respectively. No significant difference was found when the incidence of these viruses was compared between both mite species. The importance of our results in relation to the epidemiology of leprosis is discussed.

Mutational Analysis of Oncogenic AKT1 Gene Associated with Breast Cancer Risk in the High Altitude Ecuadorian Mestizo Population.

Breast cancer is the leading cause of cancer-related death among women worldwide. AKT1 encodes the kinase B alpha protein. The rs121434592, rs12881616, rs11555432, rs11555431, rs2494732, and rs3803304 single nucleotide polymorphisms have been identified in the AKT1 kinase gene. Activated AKT1 phosphorylates downstream substrates regulating cell growth, metabolism, apoptosis, angiogenesis, and drug responses. It is essential to know how breast cancer risk is associated with histopathological and immunohistochemical characteristics and genotype polymorphisms in a high altitude Ecuadorian mestizo population. This is a retrospective case-control study. DNA was extracted from 185 healthy and 91 affected women who live 2,800 meters above sea level. Genotypes were determined by genomic sequencing. We found a possible association between the noncoding intronic variant rs3803304 and breast cancer risk development: GG (odds ratio [OR] = 5.2; 95% confidence interval [CI] = 1.3-20.9; P ≤ 0.05; Q > 0.05). Regarding pathologic characteristics, we found significant risk between estrogen receptor, progesterone receptor, and HER2 status and molecular subtypes (P ≤ 0.001; Q ≤ 0.05). On the other hand, we did not find risk between variants and histopathological characteristics. Despite the small sample size, we found that the intronic variant, AKT1 rs3803304, may act as a predictive biomarker in the risk of developing breast cancer in the high altitude Ecuadorian mestizo population.

Breast Cancer Risk Associated with Genotype Polymorphisms of the Aurora Kinase a Gene (AURKA): a Case-Control Study in a High Altitude Ecuadorian Mestizo Population.

Breast cancer (BC) is the leading cause of cancer related death among women in 2014. The AURKA gene that encodes the protein called Aurora kinase A plays an important role in the progression of the cell cycle, by controlling and promoting the entry into the phase of mitosis. The single nucleotide polymorphism AURKA T91A (rs2273535) (Phe21Ile) has been identified as functional alternator of this kinase, the Ile allele is associated with the occurrence of chromosome segregation errors and tumor progression. Therefore, it is essential to know how BC risk is associated with histopathological characteristics, immunohistochemical characteristics, and genotype polymorphism in a high altitude Ecuadorian mestizo population. In this retrospective case-control study 200 individuals were analyzed. DNA was extracted from 100 healthy and 100 affected women. Genotypes were determined by genomic sequencing. We found significant association between the AURKA T91A (rs2273535) (Phe21Ile) genotype and an increased risk of BC development: Phe/Ile (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.4-4.9; P = 0.004), Ile/Ile (OR = 3.8; 95% CI = 1.6-9.0; P = 0.002), and Phe/Ile + Ile/Ile (OR = 2.9; 95% CI = 1.6-5.2; P = 0.001). Additionally, the rs2273535 variant was associated with the tumor grade SBR III (OR = 9.6; 95% CI = 1.0-91.9; P = 0.048) and the Ki-67 ≥ 20 (OR = 16.5; 95% CI = 2.7-101.3; P = 0.002). In brief, this study provides the first evidence where the Ile allele of the AURKA gene could act as potentially predictive biomarker of BC in the high altitude Ecuadorian mestizo population that lives at 2800 m above sea level (masl).

Manejo de la presión del cuff en usuarios adultos con vía aérea artificial por profesionales de salud en Chile / Management of the cuff pressure in patients with an artificial airway by health professionals in Chile

Existen diferentes recomendaciones internacionales sobre el rango de presión delcuff para utilizar en usuarios adultos con vía aérea artificial. Algunas instituciones de salud chilenas han creado sus protocolos de vía aérea basadas en dichas recomendaciones, ya que no existe una guía nacional. Se desarrolló una revisiónbibliográficaen la Universidad de Southampton, Reino Unido,para determinar el rango adecuado de presión delcuff siendo entre 20-30 cmH2O. Posteriormente, se creó un cuestionario online válido y confiable en español en la Universidad de Southampton, Reino Unido,para ser aplicado en Chile. El objetivo de este estudio es analizar las respuestas emanadas de los profesionales de salud en Chile sobre el manejo de la presión delcuff en pacientes adultos con vía aérea artificial. Es un estudio analítico, observacional y transversal. Consistió en analizar las respuestas de enfermeros, kinesiólogos y fonoaudiólogos con experiencia en pacientes con vía aérea artificialtras aplicar el cuestionario. Los resultados muestran que la técnica objetiva fue ampliamente utilizada de forma aislada (58%) en comparación al uso exclusivo de subjetivas (7%). La presión mínima fue de 25 cmH2O mientras que la máxima fue de 34 cmH2O, rango mayor a lo reportado por la evidencia. Solo un 38% declaró la existencia de protocolo en su trabajo. Hubo diferencia estadísticamente significativa entre las presiones máximas usadas y las recomendadas en dichos protocolos (p=0,029). Se concluye que los participantes en Chile mostraron un manejo poco seguro de la presión delcuff en pacientes adultos con vía aérea artificial que puede generar riesgos asociados a cuffssobre o sub insuflados. Se sugiere desarrollar una guía Ministerial.

There are different international recommendations on the cuff pressure range for the management of adult patients with an artificial airway. Some Chilean health institutions have developed their own airway management protocols based on these recommendations due to the lack of a national guide. A literature review wasundertaken at the University of Southampton, U.K., to determine the appropriate cuff pressure range. Results found that this is between 20-30 cmH2O. Afterwards, a valid and reliable online questionnaire was developed in Spanish at the University of Southampton for application in Chile. The aim of this study is to analyse the cuff pressure management of adult patients with an artificial airway performed by non-medical health professionals in Chile. An analytical, observational and cross-sectional study was performed. A database which contained the responses of nurses, physiotherapists and speech therapists with experience attending adult patients with an artificial airway in Chile was analysed. Results show that 58% of the participants used exclusively the objective technique whilst 7% only used subjective techniques. The minimum and maximum pressures used were 25 and 34 cmH2O respectively, which were higher than the recommended range. 38% of the participants declared that there was an existing protocol at their workplace. There was a significant difference between the maximum pressures used by the clinicians and the pressures recommended on the protocols (p=.029). In conclusion, the participants showed a poor manage of the cuff pressure which could create risks linked with over-inflated or under-inflated cuffs. It is suggested to develop a national guide.

Dotación fonoaudiológica para la atención de pacientes adultos en hospitales de alta complejidad en Chile / Speech and language therapists for attending adult patients in high-complexity hospitals in Chile

A nivel internacional se propone un mínimo de un profesional fonoaudiólogo por cada diez camas críticas o más, dependiendo de la complejidad de cada institución. En Chile no existen lineamientos similares, no obstante, el Ministerio de Salud ha generado recomendaciones para el cálculo de la brecha profesional según número y complejidad de las camas hospitalarias. El objetivo de este estudio es estimar el número de fonoaudiólogos y horas de contratación teóricas requeridas para la atención de pacientes adultos hospitalizados en instituciones públicas de alta complejidad en Chile. Para ello se realizó un estudio descriptivo, observacional, transversal. Se incluyeron todos los hospitales públicos de alta complejidad del país, excluyendo aquellos pediátricos y psiquiátricos. Como instrumentos se utilizaron el documento "Modelo de Gestión Red de Rehabilitación" del Ministerio de Salud, la base de datos actualizada del total de camas de la red hospitalaria y el software Microsoft Excel. El estudio fue aprobado por Comité Ético Científico del Hospital San Juan de Dios. En total 59 de 188 hospitales existentes en Chile fueron incluidos. De acuerdo con el análisis realizado basado en el número de camas en Chile, se requieren aproximadamente 269 fonoaudiólogos contratados 44 horas semanales para la atención de pacientes adultos en hospitales de alta complejidad. De ellos 104 se ubican en la Región Metropolitana; alrededor de 31 en la Región del BíoBío y cerca de 24 en la Región de Valparaíso. Se sugiere la revisión de las orientaciones ministeriales y la realización de un segundo estudio sobre la brecha profesional existente en Chile con los datos obtenidos.

International institutions have suggested one Speech and Language Therapist per ten critical beds, and possibly even more forhigh-complexity institutions. However, there are no similar recommendations in Chile, although the Ministry of Health has developed recommendations to calculate the number of professionals required according to the number and type of clinical bed. The aim of this study is to describe the number of Speech and Language Therapists along with the number of theorical working hours per week required for the attention of hospitalised adult patients in high-complexity hospitals in Chile, for which a descriptive, observational and transversal study was performed. High-complexity hospitals were included, excluding psychiatric and paediatric institutions. Microsoft Excel, the "Modelo de Gestión Red de Rehabilitación" guideline from the Ministry of Health, and the updated database of the clinical network beds were also used. This study was previously approved by a Research Ethics Committee from Hospital San Juan de Dios, and a total of 59 out of 188 hospitals were included. According to the analysis based on features of the clinical beds, 269 Speech and Language Therapists are required for 44 hours per week to attend adult patients in high-complexity hospitals across the country. Of the 269 professionals, 104 are needed in the Metropolitan region, approximately 31 in the Bío-Bío region and circa 24 in the Valparaíso region. According to these results, it is suggested the Ministry review its guidelines and undertake a further project in order to identify the current professional gap in Chile.

Cuestionario sobre el uso de técnicas y manejo de presión del cuff en usuarios adultos con vía aérea artificial por parte de profesionales de la salud en Chile / Questionnaire on the techniques and cuff pressure management in artificial airway patients performed by Chilean health professionals

La evidencia internacional recomienda diferente presión de 'cuff' a utilizar en usuarios con vía aérea artificial. En Chile,algunas instituciones sanitarias han creado protocolos internos referenciando dicha evidencia. Sin embargo, no existe una guía nacional, por lo que distintos profesionales utilizan diferentes criterios. El objetivo de este trabajo fue crear un cuestionario válido y confiable sobre el uso de técnicas y manejo de la presión del 'cuff' en usuarios adultos con vía aérea artificial por parte de profesionales de salud en Chile. Para ello, se utilizó un diseño cualitativo-cuantitativo, descriptivo y longitudinal. El proceso fue dividido en tres fases. En la fase A sedesarrolló un cuestionario en inglés que fue traducido al español con ayuda de tres hablantes hispanos nativos. En la fase B diez expertos chilenos en el manejo de usuarios con vía aérea artificial analizaron la herramienta y recomendaron modificaciones de algunos componentes del cuestionario. Después dedichos cambios, la herramienta fue validada a través de un Índice de Validez de Contenido. En la fase C treinta y tres profesionales de la salud chilenos respondieron voluntariamente el cuestionario en dos ocasiones con un lapso de treinta días entre respuestas, con el fin de medir la confiabilidad a través de 'test-retest'. El cuestionario desarrollado tuvo una validez de 0,93 mientras que 72,73% y 27,27% de sus ítems tuvieron excelente y buena confiabilidad respectivamente. Lo anterior permite concluir que este cuestionario cumple con su objetivo y servirá para conocer las técnicas y presiones del 'cuff' que profesionales de la salud en Chile utilizan para el manejo de usuarios adultos con vía aérea artificial.

International evidence recommends different cuff pressure to use with patients with an artificial airway. In Chile, some health institutions have created internal protocols referencing this evidence. However, there is no national guidelines, thus different health professionals use different criteria to manage these patients. The present researched aimed at creating a valid and reliable questionnaire on the use and management of the cuff pressure in adult patients with an artificial airway for health professionals in Chile. A qualitative-quantitative, descriptive and longitudinal design was implemented. This process was divided in three phases. In phase A, a draft of the questionnaire was developed in English and then translated to Spanish by three native Spanish speakers. In phase B, ten Chilean, ten clinical experts in the management of users with artificial airway analysed the tool and recommended modifications of some of the questionnaire. After the modifications, the tool was validated through a Content Validity Index form. In phase C, thirty-three Chilean health professional voluntarily responded the questionnaire twice, with a period of thirty days between responses, to measure the reliability of the tool through 'test-retest'. The questionnaire had a validity of .93, while 72.73% and 27.27% of the items had an excellent reliability and good reliability, respectively. This allows us to conclude that this questionnaire meets its objectives and will serve to know the techniques and pressure of the cuff that health professionals in Chile use for the management of adult patients with an artificial airway.

Genetic polymorphisms in MTHFR (C677T, A1298C), MTR (A2756G) and MTRR (A66G) genes associated with pathological characteristics of prostate cancer in the Ecuadorian population.

INTRODUCTION: The methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and MTR reductase (MTRR) enzymes act in the folate metabolism, which is essential in methylation and synthesis of nucleic acids. The single nucleotide polymorphisms, MTHFR C677T, A1298C, MTR A2756G and MTRR A66G, cause alteration in the homocysteine levels and reduced enzymatic activity that generates deficiency in the assimilation of folates associated with DNA damage; that is, why it is important to know if the single nucleotide polymorphisms are associated with the pathological characteristics and development of prostate cancer, through a case-control retrospective study. METHODS: DNA was extracted from 110 healthy and 104 affected men. The genotypes were determined by means of the polymerase chain reaction-restriction fragment length polymorphism and confirmed with genomic sequencing. RESULTS: We found significant association between the genotypes of the MTHFR C677T polymorphism: C/T (odds ratio [OR] = 2.2; 95% confidence interval [CI] = 1.3-3.9; P = 0.008) and C/T + T/T (OR = 2.2; 95% CI = 1.3-3.9; P = 0.009) with the risk of prostate cancer development, and a slight association with MTRR A66G. Regarding pathological characteristics, we found significant risk between the C/T + T/T genotypes and the Gleason score (7-10) of poorly differentiated carcinoma (OR = 5.2; 95% CI = 1.7-16.2; P = 0.007). On the other hand, a significant association between A1298C, A66G, and A2756G with the pathological characteristics was not found (P > 0.05). CONCLUSIONS: The MTHFR C677T polymorphism has significant effects on susceptibility to prostate cancer in Ecuadorian population, especially with the Gleason grade.

Serie de casos: Tumores del Golfo de la yugular / Case series: Glomus jugulare tumors

Introducción: Los tumores del foramen yugular son lesiones de la base del cráneo poco frecuentes, que presentan dificultades tanto para el diagnóstico como para el manejo. El objetivo del presente reporte es presentar una serie de casos y el manejo que se dio a estos pacientes. Métodos: El presente estudio descriptivo incluye pacientes con tumores del foramen yugular manejados quirúrgicamente desde el 2002 hasta 2006 en el Hospital Oncológico "Solón Espinosa Ayala", donde se revisó la técnica quirúrgica y el pronóstico. Los tumores fueron abordados por un mismo equipo multidisciplinario, neurocirujano, cirujano otorrinolaringólogo y radio-oncólogo. Resultados: Se presentan 10 casos. El nervio facial fue reconstruido con injertos del nervio auricular mayor o con anastomosis en cinco casos. Los paragangliomas fueron las lesiones más frecuentes seguidas por Schwannomas y meningiomas. La escisión completa fue posible en 8 casos de tumores benignos y en 4 paragangliomas. Los nervios craneales bajos fueron los más frecuentemente comprometidos con lesiones transitorias en cuatro pacientes. Y la función del nervio facial se recobró espontáneamente en 3 casos. Dos casos desarrollaron fístula de líquido céfalo raquídeo. Un paciente falleció después de la cirugía. Conclusión: Los paragangliomas con extensión intracraneal deben ser radicalmente resecados a través de abordajes multidisciplinarios con preservación de los nervios. La embolización preoperatoria debería considerarse. La extubación precoz, traqueotomía en casos seleccionados y temprana rehabilitación son muy importantes en el manejo postoperatorio.

Introduction: Jugular foramen tumors are rare lesions of the base of the skull, which present difficulties for both diagnosis and management. The objective of this report is to present a series of cases and the management that was given to these patients. Methods: The present descriptive study includes patients with jugular foramen tumors managed surgically from 2002 to 2006 in the "Solón Espinosa Ayala" Oncological Hospital, where the surgical technique and prognosis were reviewed. The tumors were treated by the same multidisciplinary team, neurosurgeon, otolaryngologist and radiation oncologist. Results: 10 cases are presented. The facial nerve was reconstructed with grafts of the greater auricular nerve or with anastomosis in five cases. Paragangliomas were the most frequent lesions followed by Schwannomas and meningiomas. Complete excision was possible in 8 cases of benign tumors and in 4 paragangliomas. Low cranial nerves were the most frequently compromised with transient lesions in four patients. And the function of the facial nerve recovered spontaneously in 3 cases. Two cases developed cerebrospinal fluid fistula. One patient died after surgery. Conclusion: Paragangliomas with intracranial extension must be radically resected through multidisciplinary approaches with preservation of the nerves. Preoperative embolization should be considered. Early extubation, tracheotomy in selected cases and early rehabilitation are very important in postoperative management.

Rol de los genes metabolizadores de folatos MTR A2756G y MTRR A66G en las mujeres ecuatorianas afectadas de cáncer mamario / Role of folate metabolizing genes MTR A2756G and MTRR A66G in the Ecuadorian women affected by breast cancer

El cáncer de mama es la segunda causa de muerte a nivel mundial seguido del cáncer de ovario. La incidencia en el Ecuador es 35.8 / 100.000 individuos. Los genes MTR y MTRR están involucrados en la alteración del metabolismo de los folatos en varias poblaciones mundiales.Se analizaron 114 individuos afectados del Hospital Oncológico Solón Espinosa Ayala y 195 individuos sanos del Hospital de Machachi, durante el período 2012-2013. Los genotipos MTR A2756G y MTRR A66G no se relacionaron significativamente con el riesgo dea desarrollar cáncer de mama. MTR G/G (OR = 0.29; IC = 0.06-1.38; p = 0.186); MTRR G/G (OR = 0.93; IC = 0.2-4.9; p = 1). No hubo r iesgo significativo de cáncer de mama en los polimorfismos MTR A2756G y MTRR A66G de la población ecuatoriana.(AU)

Breast cancer is a cell alteration of the mammary tissue, becoming the second cause of death worldwide followed by ovarian cancer. Ecuador has an incidence of 35.8 / 100,000 individuals. MTR and MTRR genes have involved in alterations of folate metabolism in some populations worldwide. The MTR A2756G and MTRR A66G genotypes were not significantly related with the risk of breast cancer development. MTR G/G (OR = 0.29; CI = 0.06-1.38; P = 0.186); MTRR G/G (OR = 0.93; CI = 0.2-4.9; P = 1). It was not found significantly risk of breast cancer development under presence of the MTR A2756G and MTRR A66G polymorphisms in the Ecuadorian population.(AU)

Tumor neuroendocrinó de vulva: presentación de caso clínico / Neuroendocrine tumor vulva: clinical case presentation

La tasa estandarizada del tumor de vulva más elevada esta en Australia 4,9 por cien mil habitantes, la tasa cruda nacional de Ecuador (2005) es de 0.8 y la tasa estandarizada es 0,8 por cien mil habitantes; el carcinoma neuroendocrino es una entidad rara menor al 0,5% (0,3% FIGO), con pocos casos reportados, el 70% se localizan en los labios mayores o menores. Este tumor se presenta como uno o varios nódulos intradémicos con eritema en la piel circundante, con afectación ganglionar, linfovascular y diseminación hematógena, recurrencia tumoral posterior y sobrevida menor de 35% a 5 años, aunque en tumores con resección total sin compromiso linfático la sobrevida es mayor, o se conoce completamente el comportamiento biológico e historia natural de estos tumores. El tumor de células de Merkel clínicamente es muy agresivo con metástasis en ganglios regionales generalmente luego de un año del diagnóstico. Histológicamente la lesión se encuentra localizada en la derrnis y tejido celular subcutáneo usualmente no presenta conexión con la epidermis. Es necesario el análisis por inmunohistoquimica para definir claramente el diagnóstico.

Rinorrea de líquido cefalorraquídeo post-traumática y hematoma epidural: presentación de un caso y revisión de la literatura / Rhinorrhea of cephalorrhachidaean fluid post-traumaytic: presentation of a case and review of the literature

Se describe el caso de un escolar que presentó traumatismo craneoencefálico y posteriormente rinorrea de líquido cefalorraquídeo así como hematoma epidural frontal, se le practicó craneotomía y cierre de la fístula, se hace incapié en el diagnóstico clínico, en la gran ayuda de las tomografías computadas y finalmente se manifiesta el manejo interdisciplinario en este tipo de casos.

Tecoma luteinizado de ovario: a propósito de un caso / Luteinizado Tecoma of ovary: with regard to a case

Se describe el caso clínico de una paciente de 32 años, que acudió a Solca de Quito presentando mal estado general, dolor pélvico y baja de peso, en la valoración ginecológica se encuentra una tumoración pélvica por lo que se programa una laparotomía exploratoria y el estudio histopatológico definitivo fue un tecoma luteinizado de ovario. Dentro de los tumores de los cordones sexuales y células del estroma ovárico, se encuentran los tecomas luteinizados. Se presentan en pacientes jóvenes en un 30 por ciento por ser un caso raro y poco frecuente describimos su anatomía patológica y una revisión actualizada del tema. (AU)

Tecoma luteinizado de ovario: a propósito de un caso / Luteinizado Tecoma of ovary: with regard to a case

Se describe el caso clínico de una paciente de 32 años, que acudió a Solca de Quito presentando mal estado general, dolor pélvico y baja de peso, en la valoración ginecológica se encuentra una tumoración pélvica por lo que se programa una laparotomía exploratoria y el estudio histopatológico definitivo fue un tecoma luteinizado de ovario. Dentro de los tumores de los cordones sexuales y células del estroma ovárico, se encuentran los tecomas luteinizados. Se presentan en pacientes jóvenes en un 30 por ciento por ser un caso raro y poco frecuente describimos su anatomía patológica y una revisión actualizada del tema.