AIB1 is a novel target of the high-risk HPV E6 protein and a biomarker of cervical cancer progression.

The high-risk human papillomaviruses (HPV-16, -18) are critical etiologic agents in human malignancy, most importantly in cervical cancer. These oncogenic viruses encode the E6 and E7 proteins that are uniformly retained and expressed in cervical cancers and required for maintenance of the tumorigenic phenotype. The E6 and E7 proteins were first identified as targeting the p53 and pRB tumor suppressor pathways, respectively, in host cells, thereby leading to disruption of cell cycle controls. In addition to p53 degradation, a number of other functions and critical targets for E6 have been described, including telomerase, Myc, PDZ-containing proteins, Akt, Wnt, mTORC1, as well as others. In this study, we identified Amplified in Breast Cancer 1 (AIB1) as a new E6 target. We first found that E6 and hTERT altered similar profiling of gene expression in human foreskin keratinocytes (HFK), independent of telomerase activity. Importantly, AIB1 was a common transcriptional target of both E6 and hTERT. We then verified that high-risk E6 but not low-risk E6 expression led to increases in AIB1 transcript levels by real-time RT-PCR, suggesting that AIB1 upregulation may play an important role in cancer development. Western blots demonstrated that AIB1 expression increased in HPV-16 E6 and E7 expressing (E6E7) immortalized foreskin and cervical keratinocytes, and in three of four common cervical cancer cell lines as well. Then, we evaluated the expression of AIB1 in human cervical lesions and invasive carcinoma using immunohistochemical staining. Strikingly, AIB1 showed positivity in the nucleus of cells in the immediate suprabasal epithelium, while nuclei of the basal epithelium were negative, as evident in the Cervical Intraepithelial Neoplasia 1 (CIN1) samples. As the pathological grading of cervical lesions increased from CIN1, CIN2, CIN3 carcinoma in situ and invasive carcinoma, AIB1 staining increased progressively, suggesting that AIB1 may serve as a novel histological biomarker for cervical cancer development. For cases of invasive cervical carcinoma, AIB1 staining was specific to cancerous lesions. Increased expression of AIB1 was also observed in transgenic mouse cervical neoplasia and cancer models induced by E6E7 and estrogen. Knockdown of AIB1 expression in E6E7 immortalized human cervical cells significantly abolished cell proliferation. Taken together, these data support AIB1 as a novel target of HPV E6 and a biomarker of cervical cancer progression.

Loss of the NKX3.1 tumorsuppressor promotes the TMPRSS2-ERG fusion gene expression in prostate cancer.

BACKGROUND: In normal prostate epithelium the TMPRSS2 gene encoding a type II serine protease is directly regulated by male hormones through the androgen receptor. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. Although, the androgenic activation of TMPRSS2 gene has been established, little is known about other elements that may interact with TMPRSS2 promoter sequences to modulate ERG expression in TMPRSS2-ERG gene fusion context. METHODS: Comparative genomic analyses of the TMPRSS2 promoter upstream sequences and pathway analyses were performed by the Genomatix Software. NKX3.1 and ERG genes expressions were evaluated by immunoblot or by quantitative Real-Time PCR (qRT-PCR) assays in response to siRNA knockdown or heterologous expression. QRT-PCR assay was used for monitoring the gene expression levels of NKX3.1-regulated genes. Transcriptional regulatory function of NKX3.1 was assessed by luciferase assay. Recruitment of NKX3.1 to its cognate elements was monitored by Chromatin Immunoprecipitation assay. RESULTS: Comparative analysis of the TMPRSS2 promoter upstream sequences among different species revealed the conservation of binding sites for the androgen inducible NKX3.1 tumor suppressor. Defects of NKX3.1, such as, allelic loss, haploinsufficiency, attenuated expression or decreased protein stability represent established pathways in prostate tumorigenesis. We found that NKX3.1 directly binds to TMPRSS2 upstream sequences and negatively regulates the expression of the ERG protooncogene through the TMPRSS2-ERG gene fusion. CONCLUSIONS: These observations imply that the frequently noted loss-of-function of NKX3.1 cooperates with the activation of TMPRSS2-ERG fusions in prostate tumorigenesis.

Conjunctival Inflammation and Panuveitis as Manifestations of Ig-G4-Related Disease: A Case Report.

PURPOSE: To report a case of isolated conjunctival inflammation as initial manifestation of IgG4-related disease and subsequent development of panuveitis. CASE REPORT: A 75-year-old female presented with a diffuse mass lesion in the temporal area of the left eye, involving the conjunctiva, and an abscessed corneal ulcer. An incisional biopsy was diagnostic of IgG4-related disease with an elevated IgG4/IgG ratio (>40%) and the presence of >10 cells that tested positive for IgG4/CGA. No other ocular, orbital or systemic manifestations were noted at the time of diagnosis. After a year of treatment with topical dexamethasone, oral prednisone, and methotrexate, the patient developed panuveitis, which was controlled by increasing steroids and switching to rituximab. CONCLUSION: IgG4-related disease is a rare entity that can be particularly challenging to diagnose if it manifests in an atypical manner. Continuous follow-up of patients is crucial as relapses and worsening of symptoms can occur despite treatment.

Unusual radiological finding in foreign bodies ingestion: three esophageal coins.

Case description: A 5-year-old girl presented to the emergency department with a history of foreign body ingestion. A cervico-thoracoabdominal radiograph demonstrate a foreign body in the esophagus, which seemed to show a double rim sign suspecting a button battery. After an emetic episode and expelling a coin, the child became asymptomatic. Close inspection of the X-ray demonstrated that the image was formed by superimposition of 3 circumferential objects of different sizes. Another X-ray observed the persistence of two superimposed objects. Clinical findings: The girl presented with sialorrhea, odynophagia, and nausea. Vital signs and physical examination were normal. There was no significant medical history. Treatment and Outcome: With the suspicion of multiple impacted esophageal objects, the patient was then taken to the operating room. During the flexible esophagoscopy 2 coins were found in the esophagus, both were removed without difficulty. The patient had an uneventful postoperative recovery and there have been no long-term complications. Clinical relevance: Unusual radiographic findings regarding esophageal foreign bodies have been reported, however, we describe the first case of a child with 3 coins impacted in the esophagus and a new radiological finding in foreign bodies ingestions that allow to avoid misdiagnosis and improve outcomes.

Descripción del caso: Una niña de 5 años es llevada a urgencias tras la ingesta de un cuerpo extraño. La radiografía cérvico-toraco-abdominal evidenció un cuerpo extraño esofágico con signo de doble halo, lo que hizo sospechar una pila de botón. Tras un vómito con expulsión de una moneda los síntomas desaparecieron. Una inspección minuciosa de la radiografía demostró que la imagen estaba formada por la superposición de 3 objetos circunferenciales de diferentes tamaños. Una nueva radiografía mostró persistencia de dos objetos superpuestos. Hallazgos clínicos: La niña refería odinofagia, náuseas y tenía sialorrea. Los signos vitales y el examen físico eran normales. No tenía antecedentes médicos relevantes. Tratamiento y desenlace: Con la sospecha de impactación esofágica múltiple, la paciente fue llevada al quirófano. Durante la esofagoscopia se encontraron 2 monedas en el esófago que fueron extraídas sin dificultad. La evolución postoperatoria fue favorable y no hubo complicaciones a largo plazo. Relevancia clínica: Aunque se han reportado hallazgos radiográficos inusuales en cuerpos extraños esofágicos, describimos el primer caso de un niño con 3 monedas impactadas en el esófago y un nuevo hallazgo radiológico en la ingesta de cuerpos extraños que permite evitar diagnósticos erróneos y mejorar los desenlaces.

Larval stages of trematodes in gastropods from Lake Chicnahuapan, State of Mexico, Mexico.

During the period from January to December (2007), 1,095 freshwater molluscs of four species were captured (Lymnaea stagnalis, Stagnicola elodes, Physella cubensis and Physa acuta) in Lake Chicnahuapan, State of Mexico, Mexico. Two hundred seventy-two (24.84% prevalence) of these molluscs were parasitised by 11 trematode species (from which two were not identified at the species level) having six cercariae species and five metacercariae species represented in five families. The cercariae Telorchis corti (Plagiorchiidae) and the metacercariae Cotylurus cornutus (Strigeidae) were the species with the highest prevalence among the examined snails. The highest percentage of infection was observed in L. stagnalis (27.45% of prevalence, n = 572) and P. cubensis (23.96%, n = 455). Twenty-one of the examined snails had multiple infections with up to three trematode species.

Arranjos político-jurídico-sanitários na Espanha e no Brasil sobre requisição de leitos de UTI na pandemia: um estudo comparado / Political-legal-sanitary arrangements in Spain and in Brazil regarding the request for ICU beds duringthe pandemic: a comparative study / Acuerdos político-jurídico-sanitarios en España y Brasil sobre requisición de camas de UCI en la pandemia: un estudio comparado

Objetivo: fazer um estudo comparado entre a Espanha e o Brasil sobre os arranjos político-jurídico-sanitários para a requisição de leitos de UTI pelos sistemas de saúde espanhol e brasileiro durante a pandemia de COVID-19. Metodologia: foi realizado estudo descritivo-comparativo com base em variantes pré-selecionadas e analisadas mediante o método funcionalista. Resultados: embora os países tenham muitas semelhanças no perfil organizativo dos sistemas de saúde, há possibilidades legais na Espanha que não se verificam no arco normativo brasileiro que permitam decisões centralizadoras em saúde. Conclusão: diante de uma emergência de saúde, sob a declaração de estado de alarme, o quadro constitucional espanhol permite que as autoridades de saúde dos entes subnacionais (Comunidades Autônomas)permaneçam sob as ordens diretas do Ministro da Saúde, o que não ocorreno sistema federativo brasileiro.

Objective: to carry out a comparative study between Spain and Brazil on the political-legal-sanitary arrangements for the requisition of ICU beds by the Spanish and Brazilian health systems during the COVID-19 pandemic. Methodology: a descriptive-comparative study was carried out based on pre-selected variants and analyzed using the functionalist method. Results:although the countries have many similarities in the organizational profile of the health system, there are legal possibilities in Spain that are not found inthe Brazilian regulatory frameworkthat allowcentralizing decisions in health. Conclusion: in the eventof a health emergency, under the declaration of a state of alarm, the Spanish constitutional framework enables the health authorities of the subnational entities (Autonomous Communities) to remainunder the direct orders of the Minister of Health, which is not the case in the Brazilian federative system.

Objetivo: realizar un estudio comparativo entre España y Brasil sobre los acuerdos político-jurídico-sanitarios para la requisición de camas de UCI por parte de los sistemas sanitarios español y brasileño durante la pandemia de COVID-19. Metodología: se realizó un estudio descriptivo-comparado basado envariantes preseleccionadas y analizadas mediante el método funcionalista. Resultados: aunque los países tienen muchas similitudes en el perfil organizativo del sistema de salud, existen posibilidades legales en España que no se encuentran en el marco normativo brasileño, y que permiten decisiones centralizadas en salud. Conclusión:ante una emergencia sanitaria, bajo la declaración de un estado de alarma, el marco constitucional español permite que las autoridades sanitarias de las entidades subnacionales (Comunidades Autónomas) queden bajo las órdenes directas del Ministro de Salud, lo que no ocurre en el sistema federativo brasileño.

Genomic comparison of early-passage conditionally reprogrammed breast cancer cells to their corresponding primary tumors.

Conditionally reprogrammed cells (CRCs) are epithelial cells that are directly isolated from patients' specimens and propagated in vitro with feeder cells and a Rho kinase inhibitor. A number of these cells have been generated from biopsies of breast cancer patients, including ductal carcinoma in situ and invasive carcinomas. The characterization of their genomic signatures is essential to determine their ability to reflect the natural biology of their tumors of origin. In this study, we performed the genomic characterization of six newly established invasive breast cancer CRC cultures in comparison to the original patients' primary breast tumors (PBT) from which they derived. The CRCs and corresponding PBTs were simultaneously profiled by genome-wide array-CGH, targeted next generation sequencing and global miRNA expression to determine their molecular similarities in the patterns of copy number alterations (CNAs), gene mutations and miRNA expression levels, respectively. The CRCs' epithelial cells content and ploidy levels were also evaluated by flow cytometry. A similar level of CNAs was observed in the pairs of CRCs/PBTs analyzed by array-CGH, with >95% of overlap for the most frequently affected cytobands. Consistently, targeted next generation sequencing analysis showed the retention of specific somatic variants in the CRCs as present in their original PBTs. Global miRNA profiling closely clustered the CRCs with their PBTs (Pearson Correlation, ANOVA paired test, P<0.05), indicating also similarity at the miRNA expression level; the retention of tumor-specific alterations in a subset of miRNAs in the CRCs was further confirmed by qRT-PCR. These data demonstrated that the human breast cancer CRCs of this study maintained at early passages the overall copy number, gene mutations and miRNA expression patterns of their original tumors. The further characterization of these cells by other molecular and cellular phenotypes at late cell passages, are required to further expand their use as a unique and representative ex-vivo tumor model for basic science and translational breast cancer studies.

Asociación entre tiroiditis linfocítica crónica y carcinoma papilar de tiroides: Revisión sistemática y metaanálisis de estudios en especímenes quirúrgicos / Association between chronic lymphocityc thyroiditis and papillary thyroid carcinoma: Systematic review and meta-analysis of studieson surgical specimens

Introducción. Existen resultados inconsistentes con relación al planteamiento de la hipótesis que sugiere una mayor probabilidad de documentar un carcinoma papilar de tiroides en especímenes quirúrgicos con cambios compatibles con tiroiditis linfocítica crónica. En los metaanálisis existentes se han incluido estudios no comparables metodológicamente y no se proponen claras fuentes de sesgo, justificación para la realización del presente metaanálisis. Métodos. Se realizó una búsqueda bibliográfica en Pubmed y Embase. Fueron obtenidos estudios retrospectivos donde se comparaba la prevalencia de carcinoma papilar de tiroides en especímenes con y sin cambios por tiroiditis linfocítica crónica. La evidencia recolectada fue sintetizada estadísticamente. Resultados. Un total de 22 artículos fueron incluidos. La población estuvo conformada por 63.548 especímenes. El OR combinado fue 1,81 (IC95%: 1,51-2,21). Hubo heterogeneidad entre la distribución de las razones de oportunidad entre los estudios (I2= 91 %; p>0,00001). La forma del gráfico en embudo de los estudios incluidos en el análisis parece estar simétrica, lo que indica la ausencia del sesgo atribuible a los estudios pequeños. Conclusiones. La literatura actual sugiere que existe un mayor riesgo de documentar un carcinoma papilar de tiroides en especímenes quirúrgicos en los que se observan cambios compatibles con tiroiditis linfocítica crónica; sin embargo, existen fuentes de sesgo que no será posible controlar en estudios retrospectivos, por lo que recomendamos estudiar la hipótesis que sugiere una mayor probabilidad de diagnosticar un carcinoma papilar de tiroides en especímenes con cambios compatibles con tiroiditis linfocítica crónica mediante metodologías prospectivas

Introduction. Inconsistent results exist in the literature regarding the hypothesis statement suggesting an increased likelihood of documenting papillary thyroid carcinoma (PTC) in surgical specimens with changes compatible with chronic lymphocytic thyroiditis. Existing meta-analyses have included studies that are not methodologically comparable and do not propose clear sources of bias, thus, this is justification for the present meta-analysis. Methods. A literature search in Pubmed and Embase was performed from January 1, 1950 to December 31, 2020. Retrospective studies comparing the prevalence of papillary thyroid carcinoma in specimens with and without chronic lymphocytic thyroiditis changes were obtained. The collected evidence was statistically analyzed. Results. A total of 22 articles were included. The study population consisted of 63,548 surgical specimens. The pooled OR, based on the studies, was 1.81 (95% CI: 1.51-2.21). There was heterogeneity between the distribution of prevalence ratios and opportunity ratios across studies (I²= 91%; p>0.00001). The funnel plot shape of the studies included in the analysis appears to be symmetrical, indicating the absence of bias attributable to small studies. Conclusions. The current literature suggests that there is an increased risk of documenting papillary thyroid carcinoma in surgical specimens in which chronic lymphocytic thyroiditis-compatible changes are observed; however, there are sources of bias that will not be possible to control for in retrospective studies, so we recommend studying the hypothesis suggesting an increased likelihood of diagnosing PTC in specimens with chronic lymphocytic thyroiditis-compatible changes using prospective methodologies

[Topical corticosteroids as a therapeutic alternative in linear immunoglobulin A bullous dermatosis in childhood: case report]. / Corticoides tópicos como alternativa terapéutica en la dermatosis ampollosa por inmunoglobulina A lineal de la infancia: caso clínico.

Linear immunoglobulin A dermatosis of childhood is a rare autoimmune disorder. Its etiology remains unknown, although it has been linked to drugs, infections, immunological diseases and lymphoproliferative processes. We report the case of a 6 year old girl who consulted for perioral bullous lesions without other symptoms. Neither treatment with mupirocin nor methylprednisolone therapy achieved remission of cutaneous lesions. Skin biopsy showed a linear immunoglobulin A dermatosis. It was not possible to start treatment with dapsone because of a partial glucose-6-phosphate dehydrogenase deficiency, so topical treatment was maintained with good evolution of lesions. Linear immunoglobulin A dermatosis is a rare disease whose differential diagnosis includes other bullous diseases. Pathology is essential for diagnosis. When treatment with dapsone is not possible, topical corticosteroids may be an alternative, either alone or associated with other treatments.

La dermatosis por inmunoglobulina A lineal de la infancia es un trastorno autoinmunitario poco frecuente. Su etiología es desconocida, aunque se ha relacionado con fármacos, infecciones, enfermedades inmunológicas y procesos linfoproliferativos. Presentamos el caso de una niña de 6 años que consultaba por lesiones ampollosas periorales, sin otra sintomatología. Se pautó un tratamiento con mupirocina tópica primero y luego con metilprednisolona tópica, sin resolución del cuadro. Se realizó una biopsia cutánea, compatible con dermatosis por inmunoglobulina A lineal. No fue posible iniciar el tratamiento con dapsona por déficit parcial de glucosa-6-fosfato deshidrogenasa, por lo que se mantuvo el tratamiento tópico, con buena evolución de las lesiones. La dermatosis por inmunoglobulina A lineal es una enfermedad poco frecuente, cuyo diagnóstico diferencial incluye otras enfermedades ampollosas. La anatomía patológica es esencial para el diagnóstico. Si no es posible el tratamiento con dapsona, los corticoides tópicos pueden ser una alternativa, tanto en monoterapia como asociados a otros tratamientos.

Unusual radiological finding in foreign bodies ingestion: three esophageal coins / Hallazgo radiológico inusual en ingesta de cuerpos extraños: tres monedas esofágicas

Abstract Case description: A 5-year-old girl presented to the emergency department with a history of foreign body ingestion. A cervico-thoracoabdominal radiograph demonstrate a foreign body in the esophagus, which seemed to show a double rim sign suspecting a button battery. After an emetic episode and expelling a coin, the child became asymptomatic. Close inspection of the X-ray demonstrated that the image was formed by superimposition of 3 circumferential objects of different sizes. Another X-ray observed the persistence of two superimposed objects. Clinical findings: The girl presented with sialorrhea, odynophagia, and nausea. Vital signs and physical examination were normal. There was no significant medical history. Treatment and Outcome: With the suspicion of multiple impacted esophageal objects, the patient was then taken to the operating room. During the flexible esophagoscopy 2 coins were found in the esophagus, both were removed without difficulty. The patient had an uneventful postoperative recovery and there have been no long-term complications. Clinical relevance: Unusual radiographic findings regarding esophageal foreign bodies have been reported, however, we describe the first case of a child with 3 coins impacted in the esophagus and a new radiological finding in foreign bodies ingestions that allow to avoid misdiagnosis and improve outcomes.

Resumen Descripción del caso: Una niña de 5 años es llevada a urgencias tras la ingesta de un cuerpo extraño. La radiografía cérvico-toraco-abdominal evidenció un cuerpo extraño esofágico con signo de doble halo, lo que hizo sospechar una pila de botón. Tras un vómito con expulsión de una moneda los síntomas desaparecieron. Una inspección minuciosa de la radiografía demostró que la imagen estaba formada por la superposición de 3 objetos circunferenciales de diferentes tamaños. Una nueva radiografía mostró persistencia de dos objetos superpuestos. Hallazgos clínicos: La niña refería odinofagia, náuseas y tenía sialorrea. Los signos vitales y el examen físico eran normales. No tenía antecedentes médicos relevantes. Tratamiento y desenlace: Con la sospecha de impactación esofágica múltiple, la paciente fue llevada al quirófano. Durante la esofagoscopia se encontraron 2 monedas en el esófago que fueron extraídas sin dificultad. La evolución postoperatoria fue favorable y no hubo complicaciones a largo plazo. Relevancia clínica: Aunque se han reportado hallazgos radiográficos inusuales en cuerpos extraños esofágicos, describimos el primer caso de un niño con 3 monedas impactadas en el esófago y un nuevo hallazgo radiológico en la ingesta de cuerpos extraños que permite evitar diagnósticos erróneos y mejorar los desenlaces.

Régimen jurídico de las recetas médicas en España e Iberoamérica / Legal regime of medical prescriptions in Spain and Iberoamerica

RESUMEN Esta contribución se ocupa de uno de los ejes sobre los que se articula la prestación farmacéutica en nuestro sistema sanitario : la receta médica. En este artículo se abordan las notas más relevantes que caracterizan el régimen jurídico de la receta médica en España y en Latinoamérica: concepto, tipos, reconocimiento por otros estados, identificación de fármacos por la denominación común internacional, objeción de conciencia del farmacéutico, receta médica electrónica o atención farmacéutica.

SUMMARY This paper deals with one of the axes on which the pharmaceutical provision in our health system is articulated: the medical prescription. Here you will find some of the most relevant notes that characterize the legal regime of the medical prescription in Spain and Latin America: concept, types, recognition by other States, identification of medications by the international common name, conscientious objection of the pharmacist, electronic medical prescription or pharmaceutical care.

[Imperforate hymen as a cause of abdominal pain in adolescents: a case report]. / Himen imperforado como causa de dolor abdominal en la adolescencia: A propósito de un caso.

The imperforate hymen is a congenital anomaly of the female genital development. This is a rare pathology with an estimated incidence of 0.1% in female newborns. In many cases, the diagnosis goes unnoticed until puberty, debuting with cyclical abdominal pain in adolescents who have not submitted menarche. Diagnosis is based on history and physical examination, although additional tests, especially the ultrasound that allows to confirm clinical diagnosis and to exclude other genital malformations. We report a case of a 13-year-old that was diagnosed after consulting several times for recurrent abdominal pain.

Conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell-like phenotype.

Mammary epithelial (ME) cells cultured under conventional conditions senesce after several passages. Here, we demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV)-Neu-induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (CRCs) on irradiated fibroblasts in the presence of the Rho kinase inhibitor Y-27632. Cell surface progenitor-associated markers are rapidly induced in normal mouse ME-CRCs relative to ME cells. However, the expression of certain mammary progenitor subpopulations, such as CD49f+ ESA+ CD44+, drops significantly in later passages. Nevertheless, mouse ME-CRCs grown in a three-dimensional extracellular matrix gave rise to mammary acinar structures. ME-CRCs isolated from MMTV-Neu transgenic mouse mammary tumors express high levels of HER2/neu, as well as tumor-initiating cell markers, such as CD44+, CD49f+, and ESA+ (EpCam). These patterns of expression are sustained in later CRC passages. Early and late passage ME-CRCs from MMTV-Neu tumors that were implanted in the mammary fat pads of syngeneic or nude mice developed vascular tumors that metastasized within 6 weeks of transplantation. Importantly, the histopathology of these tumors was indistinguishable from that of the parental tumors that develop in the MMTV-Neu mice. Application of the CRC system to mouse mammary epithelial cells provides an attractive model system to study the genetics and phenotype of normal and transformed mouse epithelium in a defined culture environment and in vivo transplant studies.

Vitamin E succinate inhibits survivin and induces apoptosis in pancreatic cancer cells.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Identifying novel chemotherapeutic and chemopreventive approaches is critical in the prevention and treatment of cancers such as pancreatic cancer. Vitamin E succinate (VES) is a redox-silent analog of the fat-soluble vitamin alpha-tocopherol. In the present study, we explored the antiproliferative action of VES and its effects on inhibitor of apoptosis proteins in pancreatic cancer cells. We show that VES inhibits cell proliferation and induces apoptosis in pancreatic cancer cells. Further, we demonstrate that VES downregulates the expression of survivin and X-linked inhibitor of apoptosis proteins. The apoptosis induced by VES was augmented by siRNA-mediated inhibition of survivin in PANC-1 cells. In summary, our results suggest that VES targets survivin signaling and induces apoptosis in pancreatic cancer cells.

Gamma-tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells.

Gamma-tocotrienol (γ-T3) is a member of the vitamin E family. Tocotrienols (T3s) are powerful antioxidants and possess anticancer, neuroprotective and cholesterol-lowering properties. Tocotrienols inhibit the growth of various cancer cell lines without affecting normal cells. Less is known about the exact mechanisms of action of T3s on cell death and other growth inhibitory pathways. In the present study, we demonstrate that γ-T3 induces apoptosis in MDA-MB 231 and MCF-7 breast cancer cells as evident by PARP cleavage and caspase-7 activation. Gene expression analysis of MCF-7 cells treated with γ-T3 revealed alterations in the expression of multiple genes involved in cell growth and proliferation, cell death, cell cycle, cellular development, cellular movement and gene expression. Further analysis of differentially modulated genes using Ingenuity Pathway Analysis software suggested modulation of canonical signal transduction or metabolic pathways such as NRF-2-mediated oxidative stress response, TGF-ß signaling and endoplasmic reticulum (ER) stress response. Analysis of ER-stress-related proteins in MCF-7 and MDA-MB 231 cells treated with γ-T3 demonstrated activation of PERK and pIRE1α pathway to induce ER stress. Activating transcription factor 3 (ATF3) was identified as the most up-regulated gene (16.8-fold) in response to γ-T3. Activating transcription factor 3 knockdown using siRNA suggested an essential role of ATF3 in γ-T3-induced apoptosis. In summary, we demonstrate that γ-T3 modulates ER stress signaling and have identified ATF3 as a molecular target for γ-T3 in breast cancer cells.

Himen imperforado como causa de dolor abdominal en la adolescencia: A propósito de un caso / Imperforate hymen as a cause of abdominal pain in adolescents: a case report

El himen imperforado es una anomalía congénita del desarrollo genital femenino. Es una patología poco frecuente, con una incidencia estimada del 0,1% de los recién nacidos del sexo femenino. En muchas ocasiones, el diagnóstico pasa inadvertido hasta la pubertad y debuta con dolor abdominal cíclico en adolescentes que no han presentado la menarquia. El diagnóstico se basa en la anamnesis y la exploración física, aunque las pruebas complementarias, en especial la ecografía, permiten la comprobación del diagnóstico clínico y la exclusión de otras malformaciones genitales. Se presenta el caso clínico de una paciente de 13 años que fue diagnosticada tras consultar en varias ocasiones por dolor abdominal recurrente.

The imperforate hymen is a congenital anomaly of the female genital development. This is a rare pathology with an estimated incidence of 0.1% in female newborns. In many cases, the diagnosis goes unnoticed until puberty, debuting with cyclical abdominal pain in adolescents who have not submitted menarche. Diagnosis is based on history and physical examination, although additional tests, especially the ultrasound that allows to confrm clinical diagnosis and to exclude other genital malformations. We report a case of a 13-year-old that was diagnosed after consulting several times for recurrent abdominal pain.

Hospital infantil universitario "Lorencita Villegas de Santos". Atención hospitalaria de pacientes pediátricos procedentes de Armero / University Children Hospital \"Lorencita Villegas de Santos\". Hospitalary care of pediatric patients from Armero

El hospital infantil "Lorencita Villegas de Santos" atendió a 64 niños procedentes de la catástrofe de Armero. Cuarenta y ocho fueron hospitalizados y evolucionaron satisfactoriamente. No se presentaron fallecimientos. El manejo inicial de limpieza de las lesiones cutáneas en tinas de inmersión fue acertado. El uso racional de antibióticos fue fundamental para evitar resistencias microbianas. El apoyo psicológico y psiquiátrico temprano es de gran utilidad como complemtno de la atención de víctimas de desastres