Field experience with the 8-HPV-type oncoprotein test for cervical cancer screening among HPV-positive women living with and without HIV in LMICs.

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted.

BCL7A is silenced by hypermethylation to promote acute myeloid leukemia.

BACKGROUND: Recent massive sequencing studies have revealed that SWI/SNF complexes are among the most frequently altered functional entities in solid tumors. However, the role of SWI/SNF in acute myeloid leukemia is poorly understood. To date, SWI/SNF complexes are thought to be oncogenic in AML or, at least, necessary to support leukemogenesis. However, mutation patterns in SWI/SNF genes in AML are consistent with a tumor suppressor role. Here, we study the SWI/SNF subunit BCL7A, which has been found to be recurrently mutated in lymphomas, but whose role in acute myeloid malignancies is currently unknown. METHODS: Data mining and bioinformatic approaches were used to study the mutational status of BCL7A and the correlation between BCL7A expression and promoter hypermethylation. Methylation-specific PCR, bisulfite sequencing, and 5-aza-2'-deoxycytidine treatment assays were used to determine if BCL7A expression was silenced due to promoter hypermethylation. Cell competition assays after BCL7A expression restoration were used to assess the role of BCL7A in AML cell line models. Differential expression analysis was performed to determine pathways and genes altered after BCL7A expression restoration. To establish the role of BCL7A in tumor development in vivo, tumor growth was compared between BCL7A-expressing and non-expressing mouse xenografts using in vivo fluorescence imaging. RESULTS: BCL7A expression was inversely correlated with promoter methylation in three external cohorts: TCGA-LAML (N = 160), TARGET-AML (N = 188), and Glass et al. (2017) (N = 111). The AML-derived cell line NB4 silenced the BCL7A expression via promoter hypermethylation. Ectopic BCL7A expression in AML cells decreased their competitive ability compared to control cells. Additionally, restoration of BCL7A expression reduced tumor growth in an NB4 mouse xenograft model. Also, differential expression analysis found that BCL7A restoration altered cell cycle pathways and modified significantly the expression of genes like HMGCS1, H1-0, and IRF7 which can help to explain its tumor suppressor role in AML. CONCLUSIONS: BCL7A expression is silenced in AML by promoter methylation. In addition, restoration of BCL7A expression exerts tumor suppressor activity in AML cell lines and xenograft models.

Síndrome de cascanueces y agenesia renal derecha. Una rara asociación

Introducción: El síndrome de cascanueces se considera una anomalía infrecuente y poco pensada en la práctica médica; su incidencia no está bien establecida debido a su sintomatología variada. La agenesia renal unilateral se estima entre 1/2500 y 1/4000 nacidos vivos. Objetivos: Describir una paciente de 18 años con sospecha prenatal de agenesia renal derecha confirmada por imágenes después del nacimiento, que ingresó por proteinuria. Presentación del caso: Paciente de 18 años con agenesia renal derecha conocida, en la que un examen de orina detectó proteinuria desde los 13 años. En su estudio se clasificó como proteinuria ortostática y evolutivamente refirió dolor lumbar izquierdo ligero y transitorio. En el ultrasonido renal, realizado para valorar crecimiento del riñón único, se detectó dilatación de la vena renal izquierda. Se repitió el estudio ecográfico para precisar ángulo aorto-mesentérico y dilatación de vena renal izquierda, y se confirmó el síndrome de cascanueces. Conclusiones: La asociación entre agenesia renal derecha y síndrome de cascanueces, resulta extremadamente rara, y, cuando se presenta con proteinuria ortostática y dolor lumbar ocasional, debe seguirse en forma expectante, pero no se necesita tratamiento quirúrgico en la mayoría de los casos.

Introduction: Nutcracker syndrome is considered an infrequent and poorly thought out anomaly in medical practice; its incidence is not well established due to its varied symptomatology. Unilateral renal agenesis is estimated to be between 1/2500 and 1/4000 live births. Objectives: To describe an 18-year-old female patient with suspected pre-natal imaging-confirmed right renal agenesis after birth, who was admitted due to proteinuria. Case presentation: An 18-year-old female patient with known right renal agenesis, in whom a urine test detected proteinuria from the age of 13. In the study it was classified as orthostatic proteinuria and evolutionarily she referred mild and transient left low back pain. Renal ultrasound, performed to assess single kidney growth, showed dilation of the left renal vein. The ultrasound study was repeated to specify aorto-mesenteric angle and left renal vein dilation, and nutcracker syndrome was confirmed. Conclusions: The association between right renal agenesis and nutcracker syndrome is extremely rare, and, when it presents with orthostatic proteinuria and occasional low back pain, it should be followed expectantly, but surgical treatment is not needed in most cases.

Redundancy Analysis to Reduce the High-Dimensional Near-Infrared Spectral Information to Improve the Authentication of Olive Oil.

The high price of marketing of extra virgin olive oil (EVOO) requires the introduction of cost-effective and sustainable procedures that facilitate its authentication, avoiding fraud in the sector. Contrary to classical techniques (such as chromatography), near-infrared (NIR) spectroscopy does not need derivatization of the sample with proper integration of separated peaks and is more reliable, rapid, and cost-effective. In this work, principal component analysis (PCA) and then redundancy analysis (RDA)─which can be seen as a constrained version of PCA─are used to summarize the high-dimensional NIR spectral information. Then PCA and RDA factors are contemplated as explanatory variables in models to authenticate oils from qualitative or quantitative analysis, in particular, in the prediction of the percentage of EVOO in blended oils or in the classification of EVOO or other vegetable oils (sunflower, hazelnut, corn, or linseed oil) by the use of some machine learning algorithms. As a conclusion, the results highlight the potential of RDA factors in prediction and classification because they appreciably improve the results obtained from PCA factors in calibration and validation.

Multi-omic alterations of the SWI/SNF complex define a clinical subgroup in lung adenocarcinoma.

SWI/SNF complexes are major targets of mutations in cancer. Here, we combined multiple "-omics" methods to assess SWI/SNF composition and aberrations in LUAD. Mutations in lung SWI/SNF subunits were highly recurrent in our LUAD cohort (41.4%), and over 70% of the mutations were predicted to have functional impact. Furthermore, SWI/SNF expression in LUAD suffered an overall repression that could not be explained exclusively by genetic alterations. Finally, SWI/SNF mutations were associated with poorer overall survival in TCGA-LUAD. We propose SWI/SNF-mutant LUAD as a separate clinical subgroup with practical implications.

PKP1 and MYC create a feedforward loop linking transcription and translation in squamous cell lung cancer.

PURPOSE: Plakophilin 1 (PKP1) is well-known as an important component of the desmosome, a cell structure specialized in spot-like cell-to-cell adhesion. Although desmosomes have generally been associated with tumor suppressor functions, we recently found that PKP1 is recurrently overexpressed in squamous cell lung cancer (SqCLC) to exert an oncogenic role by enhancing the translation of MYC (c-Myc), a major oncogene. In this study, we aim to further characterize the functional relationship between PKP1 and MYC. METHODS: To determine the functional relationship between PKP1 and MYC, we performed correlation analyses between PKP1 and MYC mRNA expression levels, gain/loss of function models, chromatin immunoprecipitation (ChIP) and promoter mutagenesis followed by luciferase assays. RESULTS: We found a significant correlation between the mRNA levels of MYC and PKP1 in SqCLC primary tumor samples. In addition, we found that MYC is a direct transcription factor of PKP1 and binds to specific sequences within its promoter. In agreement with this, we found that MYC knockdown reduced PKP1 protein expression in different SqCLC models, which may explain the PKP1-MYC correlation that we found. Conversely, we found that PKP1 knockdown reduced MYC protein expression, while PKP1 overexpression enhanced MYC expression in these models. CONCLUSIONS: Based on these results, we propose a feedforward functional relationship in which PKP1 enhances MYC translation in conjunction with the translation initiation complex by binding to the 5'-UTR of MYC mRNA, whereas MYC promotes PKP1 transcription by binding to its promoter. These results suggest that PKP1 may serve as a therapeutic target for SqCLC.

Effect of rowing on mobility, functionality, and quality of life in women with and without breast cancer: a 4-month intervention.

PURPOSE: Of the different modalities of rowing, dragon boat training is the most analyzed in breast cancer (BC). However, other types of boats, such as the felucca, use different biomechanical techniques, which have not been studied in the scientific literature. Consequently, in this study, we sought to determine the benefits of felucca rowing on the physical, psychological, and emotional well-being of patients with BC and healthy persons. METHODS: A pre- and post-intervention, single-arm study without a control group with a 4-month intervention was carried out in Spain in 2019. The study sample included six women with BC and 15 healthy women. The following questionnaires were administered before and after the intervention: Disabilities of the Arm, Shoulder, and Hand (DASH), Constant-Murley score (CMS), and the European Quality of Life 5 Dimensions (EQ-5D, rate your health today). Differences were determined before and after the intervention using the paired t test. RESULTS: Significant differences (p < 0.05) were found in the results of all the questionnaires for the women with BC and for the healthy women: DASH (- 13.8 BC and - 6.7 healthy), CMS (+ 12.0 BC and 9.2 healthy), and EQ-5D (+ 8.5 BC and 10.5 healthy). CONCLUSION: Felucca rowing showed benefits in health and quality of life in both women with BC and healthy women. In future studies with controlled design, values regarding clinical relevance, such as effect sizes/confidence intervals, are needed to corroborate our results.

Infecciones neonatales tardías

Introducción: La infección neonatal constituye una de las enfermedades más comunes debido a la susceptibilidad de estos pacientes. Esta infección puede llegar a la sepsis neonatal e incrementar la mortalidad. Objetivo: Determinar las características clínicas y epidemiológicas de la infección neonatal tardía. Métodos: Estudio descriptivo retrospectivo y transversal de registros de neonatos ingresados en el servicio de neonatología del Hospital "William Soler Ledea" entre los años 2017-2019 con diagnóstico de infección. Se excluyeron aquellos registros de neonatos infectados intervenidos quirúrgicamente. Las variables estudiadas fueron: epidemiológicas, factores de riesgo, clínicas y paraclínicas. Se emplearon técnicas de estadísticas descriptivas como porcentajes, razón, media o promedio. Resultados: La muestra estuvo conformada por 1078 registros de pacientes para una tasa de infección de 59,4 × 100 ingresos. Los factores de riesgo prenatales y connatales obtuvieron razón de prevalencia < 1. Los factores de riesgo posnatales con mayor prevalencia fueron el sexo masculino (57,6 %) y el cateterismo venoso central (53,6 %). De 83 a 88 % de los neonatos infectados presentaron alteraciones del perfil hematopoyético. Las infecciones respiratorias, de piel y de partes blandas se presentaron en 36 % de los neonatos y fueron las bacterias grampositivas los principales microorganismos aislados. Hubo 11 pacientes fallecidos para una tasa de mortalidad del 22,9 %. Conclusiones: La morbilidad por infección tardía es notable, predominan los factores de riesgo posnatales y el sexo masculino; la prematuridad y el bajo peso tuvieron la mayor representación en los fallecidos.

Introduction: Neonatal infection is one of the most common diseases due to the sensitivity of these patients. This infection can lead to neonatal sepsis and increase mortality. Objective: Determine the clinical and epidemiological characteristics of late neonatal infection. Methods: Retrospective and cross-sectional descriptive study of records on neonates admitted to the neonatology service of "William Soler Ledea" Hospital in the period 2017-2019 with a diagnosis of infection. Records of infected infants undergoing surgery were excluded. The variables studied were: epidemiological, risk factors, clinical and paraclinical. Descriptive statistical techniques such as percentages, ratio, mean or average were used. Results: The sample consisted of 1078 patient´s records, with an infection rate of 59.4 × 100 admissions. Prenatal and conatal risk factors obtained prevalence ratio < 1. The postnatal risk factors with the highest prevalence were male sex (57.6%) and central venous catheterization (53.6%). From 83 to 88% of infected neonates had alterations in the hematopoietic profile. Respiratory, skin and soft tissue infections occurred in 36% of the neonates and gram-positive bacteria were the main isolated microorganisms. There were 11 patients who died representing a mortality rate of 22.9%. Conclusions: Morbidity due to late infection is remarkable, postnatal risk factors predominate and male sex; prematurity and low weight had the highest representation in the deceased ones.

Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models.

Mammalian SWI/SNF (SWitch/Sucrose Non-Fermentable) complexes are ATP-dependent chromatin remodelers whose subunits have emerged among the most frequently mutated genes in cancer. Studying SWI/SNF function in cancer cell line models has unveiled vulnerabilities in SWI/SNF-mutant tumors that can lead to the discovery of new therapeutic drugs. However, choosing an appropriate cancer cell line model for SWI/SNF functional studies can be challenging because SWI/SNF subunits are frequently altered in cancer by various mechanisms, including genetic alterations and post-transcriptional mechanisms. In this work, we combined genomic, transcriptomic, and proteomic approaches to study the mutational status and the expression levels of the SWI/SNF subunits in a panel of 38 lung adenocarcinoma (LUAD) cell lines. We found that the SWI/SNF complex was mutated in more than 76% of our LUAD cell lines and there was a high variability in the expression of the different SWI/SNF subunits. These results underline the importance of the SWI/SNF complex as a tumor suppressor in LUAD and the difficulties in defining altered and unaltered cell models for the SWI/SNF complex. These findings will assist researchers in choosing the most suitable cellular models for their studies of SWI/SNF to bring all of its potential to the development of novel therapeutic applications.

LncRNA DLG2-AS1 as a Novel Biomarker in Lung Adenocarcinoma.

Long non-coding RNAs (lncRNAs) are a heterogeneous class of non-coding RNAs whose biological roles are still poorly understood. LncRNAs serve as gene expression regulators, frequently interacting with epigenetic factors to shape the outcomes of crucial biological processes, and playing roles in different pathologies including cancer. Over the last years, growing scientific evidence supports the key role of some lncRNAs in tumor development and proposes them as valuable biomarkers for the clinic. In this study, we aimed to characterize lncRNAs whose expression is altered in tumor samples from patients with lung adenocarcinoma (LUAD) compared to adjacent normal tissue samples. On an RT-qPCR survey of 90 cancer-related lncRNAs, we found one lncRNA, DLG2-AS1, which was consistently downregulated in 70 LUAD patients. To gain insight into its biological function, DLG2-AS1 was cloned and successfully re-expressed in LUAD cancer cell lines. We determined that DLG2-AS1 is not a cis-regulatory element of its overlapping gene DLG2, as their transcription levels were not correlated, nor did DLG2-AS1 restoration modify the expression of DLG2 protein. Furthermore, after generating a receiver operating curve (ROC) and calculating the area under curve (AUC), we found that DLG2-AS1 expression showed high sensitivity and specificity (AUC = 0.726) for the classification of LUAD and normal samples, determining its value as a potential lung cancer biomarker.

PCR multiplex en tiempo real para sepsis (Film array): caracterización como método diagnóstico en un centro pediátrico en Cali

RESUMEN Introducción: La sepsis es una condición que genera alta morbilidad y mortalidad en donde la detección temprana de los microorganismos causantes es esencial para un manejo oportuno. Objetivo: determinar la frecuencia de detección y tipificación de los microorganismos por el PCR multiplex (Film Array) en pacientes pediátricos (menores de 18 años) ingresados al servicio de urgencias con el diagnóstico confirmado de sepsis. Materiales y Métodos: Se realizó un estudio observacional descriptivo retrospectivo. Fueron analizados los paneles positivos de hemocutivos de pacientes menores de 18 años, con diagnóstico de sepsis, por medio de la tecnología PCR multiplex (Film Array) en el Hospital Clínica Infantil Club Noel. Los resultados fueron comparados. Los datos fueron analizados con Microsof Excel, empleando estadísticas descriptivas. Resultados: De 101 hemocultivos positivos, el panel molecular Film Array detecto el 92 (91%). Hubo predominio de sepsis con puerta de entrada respiratoria y menores de 3 años de edad. Los gérmenes más frecuentemente detectados fueron los gram negativos tanto en el hemocultivo como en el panel molecular. Conclusiones: los hallazgos en cuanto a detección de bacteriemia, en nuestra población por PCR multiplex en tiempo real demuestran su capacidad de detección y su importancia en el diagnóstico temprano y tratamiento oportuno.

ABSTRACT Introduction: Sepsis is a condition that generates high morbidity and mortality: The early detection of the causative microorganisms is essential for timely management. Objective: to determine the frequency of detection and typing of microorganisms by multiplex PCR (Film Array) in pediatric patients (under 18 years of age) admitted to the emergency department with a confirmed diagnosis of sepsis. Materials and Methods: This was a retrospective, descriptive and observational study, Positive blood culture panels of patients under 18 years of age, diagnosed with sepsis, were analyzed using multiplex PCR technology (Film Array) at the Hospital Clínica Infantil Club Noel. The results were compared. The data was analyzed with Microsoft Excel, using descriptive statistics. Results: Of 101 positive blood cultures, the Film Array molecular panel detected 92 (91%). There was a predominance of sepsis from a respiratory source and children under 3 years of age. The most frequently detected germs were gram-negative organisms, both in the blood culture and in the molecular panel. Conclusions: the findings regarding the detection of bacteremia in our population, using multiplex real-time PCR, demonstrate its detection ability and its importance in early diagnosis and timely treatment.

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol.

INTRODUCTION: Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. METHODS AND ANALYSIS: Women aged 30-64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT01881659.

The value of lncRNA FENDRR and FOXF1 as a prognostic factor for survival of lung adenocarcinoma.

It is increasingly evident that non-coding RNAs play a significant role in tumour development. However, we still have a limited knowledge of the clinical significance of long non-coding RNAs (lncRNAs) in lung cancer. The FENDRR is a long coding RNA (also named FOXF1-AS1) located in the vicinity of the protein-coding gene FOXF1 at 16q24.1 chromosomal region. The present study aimed to define the clinic pathological significance of the long-non-coding RNA FENDRR in lung adenocarcinomas. FENDRR expression measured by quantitative PCR was found significantly downregulated (p<0.001) in lung adenocarcinoma samples in comparison with their normal adjacent tissues (n=70). RNA in situ hybridization (RNA-FISH) corroborated independently the down-regulation of FENDRR. Interestingly, the expression of FENDRR correlated positively (p<0.001) with the expression of its protein-coding neighbor gene FOXF1. Additionally, FOXF1 expression was also found downregulated in adenocarcinomas compared to normal samples (p<0.001) and its expression was significantly correlated with overall survival alone (p=0.003) or in combination with FENDRR expression (p=0.01). In conclusion, our data support that FENDRR and FOXF1 expression is decreased in lung adenocarcinoma and should be considered as new potential diagnostic/prognosis biomarkers.

Functional approach and agro-climatic information to improve the estimation of olive oil fatty acid content from near-infrared data.

Extra virgin olive oil (EVOO) is very appreciated by its taste, flavor, and benefits for health, and so, it has a high price of commercialization. This fact makes it necessary to provide reliable and cost-effective analytical procedures, such as near-infrared (NIR) spectroscopy, to analyze its traceability and purity, in combination with chemometrics. Fatty acids profile of EVOO, considered as a quality parameter, is estimated, firstly, from NIR data and, secondly, by adding agro-climatic information. NIR and agro-climatic data sets are summarized by using principal component analysis (PCA) and treated by both scalar and functional approaches. The corresponding PCA and FPCA are progressively introduced in regression models, whose goodness of fit is evaluated by the dimensionless root-mean-square error. In general, SFAs, MUFAs, and PUFAs (and disaggregated fatty acids) estimations are improved by adding agro-climatic besides NIR information (mainly, temperature or evapotranspiration) and considering a functional point of view for both NIR and agro-climatic data.

Correction: Plakophilin 1 enhances MYC translation, promoting squamous cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Plakophilin 1 enhances MYC translation, promoting squamous cell lung cancer.

Plakophilin 1 (PKP1) is a member of the arm-repeat (armadillo) and plakophilin gene families and it is an essential component of the desmosomes. Although desmosomes have generally been associated with tumor suppressor functions, we have consistently observed that PKP1 is among the top overexpressed proteins in squamous cell lung cancer. To explore this paradox, we developed in vivo and in vitro functional models of PKP1 gain/loss in squamous cell lung cancer. CRISPR-Cas9 PKP1 knockout severely impaired cell proliferation, but it increased cell dissemination. In addition, PKP1 overexpression increased cell proliferation, cell survival, and in vivo xenograft engraftment. We further investigated the molecular mechanism of the mainly oncogenic function of PKP1 by combining transcriptomics, proteomics, and protein-nucleic acid interaction assays. Interestingly, we found that PKP1 enhances MYC translation in collaboration with the translation initiation complex by binding to the 5'-UTR of MYC mRNA. We propose PKP1 as an oncogene in SqCLC and a novel posttranscriptional regulator of MYC. PKP1 may be a valuable diagnostic biomarker and potential therapeutic target for SqCLC. Importantly, PKP1 inhibition may indirectly target MYC, a primary anticancer target.

VE-cadherin promotes vasculogenic mimicry by modulating kaiso-dependent gene expression.

Aberrant extra-vascular expression of VE-cadherin (VEC) has been observed in metastasis associated with vasculogenic mimicry (VM); however, the ultimate reason why non-endothelial VEC favors the acquisition of this phenotype is not established. In this study, we show that human malignant melanoma cells have a constitutively high expression of phoshoVEC (pVEC) at Y658; pVEC is a target of focal adhesion kinase (FAK) and forms a complex with p120-catenin and the transcriptional repressor kaiso in the nucleus. FAK inhibition enabled kaiso to suppress the expression of its target genes and enhanced kaiso recruitment to KBS-containing promoters. Finally we have found that ablation of kaiso-repressed genes WNT11 and CCDN1 abolished VM. Thus, identification of pVEC as a component of the kaiso transcriptional complex establishes a molecular paradigm that links FAK-dependent phosphorylation of VEC as a major mechanism by which ectopical VEC expression exerts its function in VM.

El estado periodontal de los pacientes diabéticos en Caroní, Venezuela / Diabetic patients´ periodontal state at Caroni, Venezuela

Introducción: las afecciones periodontales están catalogadas entre las más comunes del género humano, y como la causa más frecuente de la morbilidad y mortalidad dentarias. Objetivo: caracterizar las enfermedades periodontales crónicas en pacientes diabéticos. Métodos: se realizó un estudio transversal sobre la epidemiología de las enfermedades periodontales crónicas en pacientes diabéticos, del Consultorio Médico Popular Colinas, del Área de Salud Integral Comunitaria (ASIC) La Unidad, municipio de Caroní, estado de Bolívar, Venezuela, entre septiembre del 2014 a diciembre del 2015. El universo lo integraron 61 pacientes diabéticos de 19 a 60 años, y la muestra quedó constituida por 52 pacientes que cumplieron con los criterios de inclusión. Se utilizó el Índice Periodontal de Russell, conforme a la Organización Mundial de la Salud (OMS); revisado para determinar la prevalencia y gravedad de la enfermedad periodontal. Resultados: en el grupo de 41 a 60 años predominó 40,4% de pacientes con periodontitis. El sexo masculino fue el más afectado por la enfermedad periodontal crónica, con 51,9%. Tanto la gingivitis como la periodontitis se presentaron en su forma leve con mayor frecuencia, con el 57,9%. Conclusiones: elevada prevalencia de enfermedades periodontales crónicas, según la edad y el sexo, con mayor intensidad y frecuencia en las periodontitis en su forma leve, donde el sexo masculino resultó ser el más afectado.

Introduction: periodontal affections are, among most common mankind jaws´ morbility and mortality causes. Objective: to characterize diabetic patients´chronic periodontal diseases. Methods: a traverse study on diabetic patients´ chronic periodontal diseases epidemiology, was carried out at Colinas doctor's office, from the Community Integral Health Area (CIHA) La Unidad, Caroni municipality, Bolivar state, Venezuela; from September 2014 to December 2015. The universe was composed by 61 from 19 to 60 years old diabetic patients, and the sample was formed by 52 patients which fulfill inclusion expectatations. Periodontal Russell index was used by the World Health Organization (WHO), in order to find periodontal diseases´graveness and prevalence. Results: the 40.4 % of the 41 to 60 year-old periodontitis patients, prevailed. The 51.9% of males were the most affected by periodontal chronic diseases. Gingivitis and periodontitis showed in their light form, up to 57.9%. Conclusions: the elevated chronic periodontal diseases prevalence. Light periodontitis intensity and frequency, according to age and sex, showed males as the most affected group.

Necesidad real y sentida de prótesis estomatológica en pacientes mayores de 15 años / Real and Perceived Need for Dental Prosthesis in Patients Older than 15 Years

Introducción: la rehabilitación protésica se extiende más allá del diente individual o del área desdentada única, comprende la restauración de la normalidad de las relaciones de los músculos y dientes, de modo que se devuelva la salud bucal, tiene como objetivo la sustitución de los dientes, cuando se encuentran perdidos o ausentes, por medios artificiales capaces de restablecer la función masticatoria, estética y fonética. Objetivos: identificar la necesidad real y sentida de prótesis estomatológica en pacientes mayores de 15 años del Policlínico Universitario III René Vallejo Ortiz. Métodos: se realizó un estudio descriptivo transversal donde del universo de 19 760 personas se examinaron 500 personas que representaron la muestra la cual se escogió de forma aleatoria; se realizó el examen bucal y formulario, se contó con el consentimiento de todos los pacientes seleccionados. Resultados: el sexo femenino representó el 60% de los examinados y el grupo de 35-59 años el 45%. El 56% de los examinados necesitó tratamiento, las prótesis parciales fueron las más necesitadas con 62,5%, el sexo femenino mostró una necesidad real del 64,3% y la necesidad sentida de prótesis estomatológica fue del 51,8%, mayor en el sexo femenino con el 68,9% y en el grupo de edad de 35-59 años con el 56,7%. Conclusiones: más de la mitad de la población examinada necesitó tratamiento protésico de tipo parcial, la necesidad real y sentida de tratamiento fue más notoria en el sexo femenino y en el grupo de edad de 35 a 59 años.

Introduction: prosthetic rehabilitation extends beyond the individual tooth or the single area without teeth, which includes restoring the normality of the relations of muscles and teeth, as well as the proper oral health, substituting the teeth absent by artificial means and achieving the masticatory, aesthetics and phonetics function. Objective: to identify the real need for stomatology prosthesis in patients older than 15 years of René Vallejo Ortiz University Polyclinic III Method: a cross-sectional descriptive study was done. Of a total of 19.760 individuals, 500 of them were randomly selected, representing the sample. The oral examination was performed considering the informed consent of all patients. Results: the female sex represented 60% and the group of 35-59 years 45%; 56% of the patients needed treatment, partial dentures were the most needed with 62.5%, the female sex showed a real need of 64.3% and the felt need for the prosthesis represented 51.8%, higher in the female sex with 68.9% and in the age group between 35-59 (56.7%). Conclusions: more than half of the population required partial-type prosthetic treatment, the real and felt need for treatment was more evident in the female sex and in the age group between 35-59.