Effect of the level of task abstraction on the transfer of knowledge from virtual environments in cognitive and motor tasks.

Introduction: Virtual environments are increasingly being used for training. It is not fully understood what elements of virtual environments have the most impact and how the virtual training is integrated by the brain on the sought-after skill transference to the real environment. In virtual training, we analyzed how the task level of abstraction modulates the brain activity and the subsequent ability to execute it in the real environment and how this learning generalizes to other tasks. The training of a task under a low level of abstraction should lead to a higher transfer of skills in similar tasks, but the generalization of learning would be compromised, whereas a higher level of abstraction facilitates generalization of learning to different tasks but compromising specific effectiveness. Methods: A total of 25 participants were trained and subsequently evaluated on a cognitive and a motor task following four training regimes, considering real vs. virtual training and low vs. high task abstraction. Performance scores, cognitive load, and electroencephalography signals were recorded. Transfer of knowledge was assessed by comparing performance scores in the virtual vs. real environment. Results: The performance to transfer the trained skills showed higher scores in the same task under low abstraction, but the ability to generalize the trained skills was manifested by higher scores under high level of abstraction in agreement with our hypothesis. Spatiotemporal analysis of the electroencephalography revealed higher initial demands of brain resources which decreased as skills were acquired. Discussion: Our results suggest that task abstraction during virtual training influences how skills are assimilated at the brain level and modulates its manifestation at the behavioral level. We expect this research to provide supporting evidence to improve the design of virtual training tasks.

An internet-based self-applied rat phobia treatment using a Virtual Therapy Assistant: Study protocol for a randomized controlled trial.

Specific phobias are a common anxiety disorder that deteriorates the lives of people who suffer from them. To reduce the symptoms produced by this mental disorder exposure therapies have been used. However, low- and middle-income countries, including Mexico, have the lowest rate of treatment due to multiple barriers that prevent addressing mental health problems. Self-applied treatments have been explored in previous studies, nevertheless, high dropout rates are a common problem in this kind of treatment. An alternative is using immersive self-applied treatments that could help increase adherence to the treatment. This article aims to present a study protocol to explore the feasibility of an Internet self-applied exposure treatment for rat phobias, using four types of immersive multimedia elements: images, videos, video games, and 360° videos. Also, the satisfaction and perception of a Virtual Therapy Assistant (VTA) that provides information and support to the user are described. The study protocol will compare two groups of participants, one on the waiting list, and the other will receive the self-applied treatment for rat phobia supported by the VTA. For this study, 45 participants will be recruited and the evaluation measures will be taken at four different times: baseline, post-treatment, and follow-ups at 3 and 6 months. The levels of anxiety and avoidance of the user manifested during the exposure to the multimedia elements, the improvement of the user's clinical symptoms, the level of satisfaction, the perception of effectiveness, and ease of use of the self-applied system will be evaluated. This study is expected to support the viability of self-applied treatment for rat phobias and the use of a VTA, showing the impact on treatment adherence. To the best of our knowledge, this is the first study to explore an exposure treatment for rats using different multimedia elements with the support of a VTA. The work will serve as a basis for the development of new virtual assistants that help in the treatment of other types of specific phobias. This research has been registered in Clinical Trials NCT (NCT05081323).

COVID-19 and Neurologic Manifestations: An Experience at Major New York City Hospitals.

INTRODUCTION: The exact incidence of neurologic manifestations in coronavirus disease 2019 (COVID-19) patients is not clear. The New York City Hospital system has been severely affected by the COVID-19 pandemic between December 2019 and 202. A large number of patients were treated at these centers. This study aims to investigate the incidence of such neurologic manifestations. Secondly, we wanted to find out if there is a correlation between comorbidities and neurologic manifestations in patients with COVID-19. METHODOLOGY: A retrospective analysis of 5,455 Electronic Medical Records of patients with a positive polymerase chain reaction (PCR) result admitted to Elmhurst Hospital, Queens Hospital Center, Jacobi Medical Center, and North Central Bronx Hospitals, four of the 11 teaching hospitals in the NYCHH (New York Health + Hospitals) between 3-1-2020 to 8-31-2020 was carried out. Comprehensive data were collected using medical documentation in five categories: demographic details, comorbidities, symptoms, laboratory findings, and radiologic examinations. All neurologic manifestation keywords were provided to the statisticians by two trained and board-certified physiatrists. Neurologic manifestations were categorized into central nervous system (CNS) manifestations and peripheral nervous system (PNS) manifestations. Results; Out of the 5,455 patients, 285 patients (5.2%) had central nervous system manifestations, a prevalence in people older than 50, and had a high incidence of comorbidities. We found increased D-dimer and high C reactive protein levels. Our findings agree with two of the three authors with significant case volume.

Frecuencia de Lesiones y Condiciones Orales en Pacientes Mayores de 18 Años en una Clínica de Atención Primaria en México / Frequency of Lesions and Oral Conditions in Patients Older than 18 Years in a Primary Care Clinic in Mexico

RESUMEN: La patología oral es el área de la odontología que se especializa en el diagnóstico y tratamiento de enfermedades orales. Se realizó un estudio transversal, en el cual fueron incluidos pacientes mayores de 18 años que acudieron a una clínica de atención primaria del departamento de estomatología de la universidad Autónoma de Ciudad Juárez, en México y a los cuales independientemente del motivo de consulta se les realizo historia clínica y exploración intraoral detallada. Fueron examinados 650 pacientes (424 mujeres y 226 hombres) con un rango de edad de 18 a 89 años (media=42.27). Las lesiones más frecuentes fueron la queratosis friccional (30,46 %) e hiperplasia fibrosa (6,92 %), la melanosis fisiológica (42,92 %) y los gránulos de Fordyce (36,46 %) fueron las condiciones más identificadas. En las lesiones de la mucosa oral que identificamos estuvo presente el factor traumático de manera crónica, es importante que el odontólogo este familiarizado con las lesiones más frecuentes, con su etiología, características clínicas y tratamiento de cada una de ellas.

ABSTRACT: Oral pathology it's the branch of medicine that focuses on the diagnosis and treatment of oral diseases. A cross-sectional study was carried out in which patients older than 18 years was included, that were attended in the primary care clinic at the stomatology department of the Autonomous University of Ciudad Juárez, in Mexico, and regardless of the reason for consultation the clinical history and intraoral examination was done We examined 650 patients (424 women and 226 men) with an age range of 18 to 89 years (mean=42.27). The most frequent oral lesion was the frictional keratosis (30.46 %), fibrous hyperplasia (6.92 %), physiological melanosis (42.92 %), and fordyce granules (36.46 %). In the oral mucosal lesions identified was present a chronic traumatic factor, it is important that the dental staff knows about the most frequent injuries, their etiology, clinical characteristics and treatment of each one.

Evaluation Results of an Ontology-based Design Model of Virtual Environments for Upper Limb Motor Rehabilitation of Stroke Patients.

OBJECTIVES: 1) To enhance the content of an ontology for designing virtual environments (VEs) for upper limb motor rehabilitation of stroke patients according to the suggestions and comments of rehabilitation specialists and software developers, 2) to characterize the perceived importance level of the ontology, 3) to determine the perceived usefulness of the ontology, and 4) to identify the safety characteristics of the ontology for VEs design according to the rehabilitation specialists. METHODS: Using two semi-structured Web questionnaires, we asked six rehabilitation specialists and six software developers to provide us with their perception regarding the level of importance and the usability of the ontology. From their responses we have identified themes related to perceived and required safety characteristics of the ontology. RESULTS: Significant differences in the importance level were obtained for the Stroke Disability, VE Configuration, Outcome Measures, and Safety Calibration classes, which were perceived as highly important by rehabilitation specialists. Regarding usability, the ontology was perceived by both groups with high usefulness, ease of use, learnability and intention of use. Concerning the thematic analysis of recommendations, eight topics for safety characteristics of the ontology were identified: adjustment of therapy strategies; selection and delimitation of movements; selection and proper calibration of the interaction device; proper selection of measuring instruments; gradual modification of the difficulty of the exercise; adaptability and variability of therapy exercises; feedback according to the capabilities of the patient; and real-time support for exercise training. CONCLUSIONS: The rehabilitation specialists and software developers confirmed the importance of the information contained in the ontology regarding motor rehabilitation of the upper limb. Their recommendations highlight the safety features and the advantages of the ontology as a guide for the effective design of VEs.

Assessing the user experience of older adults using a neural network trained to recognize emotions from brain signals.

The use of Ambient Assisted Living (AAL) technologies as a means to cope with problems that arise due to an increasing and aging population is becoming usual. AAL technologies are used to prevent, cure and improve the wellness and health conditions of the elderly. However, their adoption and use by older adults is still a major challenge. User Experience (UX) evaluations aim at aiding on this task, by identifying the experience that a user has while interacting with an AAL technology under particular conditions. This may help designing better products and improve user engagement and adoption of AAL solutions. However, evaluating the UX of AAL technologies is a difficult task, due to the inherent limitations of their subjects and of the evaluation methods. In this study, we validated the feasibility of assessing the UX of older adults while they use a cognitive stimulation application using a neural network trained to recognize pleasant and unpleasant emotions from electroencephalography (EEG) signals by contrasting our results with those of additional self-report and qualitative analysis UX evaluations. Our study results provide evidence about the feasibility of assessing the UX of older adults using a neural network that take as input the EEG signals; the classification accuracy of our neural network ranges from 60.87% to 82.61%. As future work we will conduct additional UX evaluation studies using the three different methods, in order to appropriately validate these results.

Hermangioma intraóseo: reto diagnóstico. Presentación de un caso y revisión de la literatura / Intraosseous hemangioma: a diagnostic challenge. Report of a case and review of the literature

Los hemangiomas son neoplasias benignas de origen endotelial, formadoras de vasos. Los hemangiomas intraóseos son condiciones raras que comprenden del 0.5 a 1% de todos los tumores intraóseos. Su localización más común es la columna vertebral y los huesos del cráneo. Aquéllos que se presentan en los maxilares son tumores muy raros. Dos tercios de éstos se localizan en la mandíbula, con una proporción de mujer a hombre de 2:1. El objetivo de este artículo es reportar un caso signifi cativo de un hemangioma central de grandes dimensiones de la rama de la mandíbula del lado derecho, el cual fuetratado exitosamente con resección quirúrgica y ligadura de vasos nutricionales. Caso clínico: Paciente de 14 años que presenta un área radiolúcida unilocular en la rama mandibular del lado derecho. Clínicamente se observa aumento de la cara difuso, que causa asimetría facialasintomática de tres años de evolución. Conclusiones: La importancia del hemangioma intraóseo de los maxilares radica en su proximidad con los dientes, lo que representa un alto riesgo de sangrado debido a cualquier traumatismo por intento de extracción. El diagnóstico de hemangioma intraóseo, debido a su baja incidencia e inusual manera de presentación, es un reto diagnóstico...

On the Effect of Previous Technological Experience on the Usability of a Virtual Rehabilitation Tool for the Physical Activation and Cognitive Stimulation of Elders.

We present and discuss our findings on the identified causes for the differences of the results of two usability studies on the borrowed use of Gesture Therapy, a virtual rehabilitation tool for the cognitive stimulation and physical activation of elders. The studies focused on usability aspects including perceived usefulness, ease of use, intention of use and user experience. In the first study, we used self-report techniques to gather data, and found that previous technological experience had a significant effect on the perceived anxiety of elders; while on the second study, we used indirect observation techniques to gather data, and found that previous technological experience had a significant effect on the perceived enjoyment of elders. After a further analysis of the video recordings of the playing sessions, we identified that elders developed two different approaches to their using the application (explore-and-learn and score-and-compete), which could be related to their previous technological experience, and explain the identified differences. We observed that in the presence of problems, the response of participants was different depending on the adopted behavior. Based on this evidence, we distilled a set of preliminary guidelines to foster or inhibit certain behaviors and outcomes related to the effect of previous experience that were observed during our evaluation studies of virtual tools for the cognitive stimulation and physical activation of the elderly.

CANoE: a context-aware notification model to support the care of older adults in a nursing home.

Taking care of elders in a nursing home is not an easy task. Caregivers face two major problems: a lack of awareness of the situations surrounding the elderly care and the lack of information regarding the availability and the activities of other caregivers to support their coordination process. Various efforts have proposed solutions to cope with these problems, but they do it without considering all the requirements imposed by the criticality of this type of environment. In this paper we propose CANoE, a model for the design of context-aware notifications in critical environments, such as a nursing home. The main feature of this model is that it considers three sources of context (the environment, and the issuer and the receiver of the notification) for adapting the content, the terms of delivery and the presentation of the notification message. Based on the CANoE model we developed the CANoE-Aw and CU-IDA systems, which were evaluated through two case studies in a nursing home. The results of these evaluations provide evidence that caregivers achieved an increased awareness of the situations of care of the elderly and perceived the systems as adequate tools to support their coordination while attending a situation of care.

Differential expression of senescence and cell death factors in non-small cell lung and colorectal tumors showing telomere attrition.

OBJECTIVE: The main aim of this work is to investigate the expression of factors related to senescence and cell death pathways in non-small cell lung cancers (NSCLCs) and colorectal cancers (CRCs) in relation to telomere status. METHODS: We analyzed 158 tissue samples, 36 NSCLCs, 43 CRCs, and their corresponding control tissues obtained from patients submitted to surgery. Telomere function was evaluated by determining telomerase activity and telomere length. Expression of factors related to senescence, cell death pathways, transformation and tumorigenesis was investigated using arrays. Results were validated by real-time quantitative PCR. RESULTS: Considering tumors with telomere shortening, expression for BNIP3, DAPK1, NDRG1, EGFR, and CDKN2A was significantly higher in NSCLC than in CRC, whereas TP53 was overexpressed in CRC with respect to NSCLC. Moreover, compared to nontumor samples, DAPK1, GADD45A, SHC1, and TP53 were downregulated in the group of NSCLCs with telomere shortening, and no significant differences were found in CRC. CONCLUSIONS: In NSCLC, the failure of pathways which involve factors such as DAPK1, GADD45A, SHC1, and TP53, in response to short telomeres, could promote tumor progression. In CRC, the viability of these pathways in response to short telomeres could contribute to limiting tumorigenesis.

Methylation profiling in non-small cell lung cancer: clinical implications.

The aim of this study was to identify a panel of methylation markers that distinguish non-small cell lung cancers (NSCLCs) from normal lung tissues. We also studied the relation of the methylation profile to clinicopathological factors in NSCLC. We collected a series of 46 NSCLC samples and their corresponding control tissues and analyzed them to determine gene methylation status using the Illumina GoldenGate Methylation bead array, which screens up to 1505 CpG sites from 803 different genes. We found that 120 CpG sites, corresponding to 88 genes were hypermethylated in tumor samples and only 17 CpG sites (16 genes) were hypomethylated when compared with controls. Clustering analysis of these 104 genes discriminates almost perfectly between tumors and normal samples. Global hypermethylation was significantly associated with a worse prognosis in stage IIIA NSCLC patients (P=0.012). Moreover, hypermethylation of the CALCA and MMP-2 genes were statistically associated to a poor clinical evolution of patients, independently of TNM tumor stage (P=0.06, RR=2.64; P=0.04, RR=2.96, respectively). However, hypermethylation of RASSF1 turned out to be a protective variable (P=0.02; RR=0.53). In conclusion, our results could be useful for establishing a gene methylation pattern for the detection and prognosis of NSCLC.

Metástasis de neuroblastoma de glándula suprarrenal en mandíbula / Metastases of adrenal glands’ neuroblastoma in mandible

Los neuroblastomas son tumores que se originan a partir de una alteración en las células del sistema nervioso simpático. La mayoría de estas variaciones ocurren en la infancia, con foco primario usual en glándulas suprarrenales y metástasis a nódulos linfáticos cercanos o médula ósea; su diseminación a mandíbula es bastante infrecuente. La detección temprana de las metástasis es uno de los elementos más importantes para mejorar la rehabilitación, funcionamiento y calidad de vida del paciente, ya que produce deformidades faciales y afecta la autopercepción, además dado que el tratamiento en estos casos es por lo general agresivo. Se presenta un caso de neuroblastoma de origen suprarrenal con metástasis a región mandibular, que a pesar del adecuado tratamiento primario, ocasionó el fallecimiento del paciente a causa de la sepsis generada al intentar realizar un trasplante preventivo de medula ósea, posterior a la hemimandibulectomía realizada para la exéresis de lesión metastásica mandibular...

The neuroblastomas are caused by an alteration of sympathetic nerve system formation. These tumors are more usual in childhood. Most of the neuroblastomas are found at the adrenal glands and their metastases are usually found in nearby lymphatic nodes or the bone marrow. Mandibular metastases are extremely rare. Detecting early stage metastases is one of the essential factors for improving treatment, rehabilitation and functionality of the patient of mandibular neuroblastoma’s patients. A young age patient is reported with adrenal glands’ neuroblastoma and metastases to mandibular angle. Regarding primary adequate treatment, the patient died due to sepsis while a bone marrow transplant was made, as a preventive measure to stop new spreads after hemimandibulectomy made for mandibular metastasic excision...

Differential colorectal carcinogenesis: Molecular basis and clinical relevance.

Colorectal cancer (CCR) is one of the most frequent cancers in developed countries. It poses a major public health problem and there is renewed interest in understanding the basic principles of the molecular biology of colorectal cancer. It has been established that sporadic CCRs can arise from at least two different carcinogenic pathways. The traditional pathway, also called the suppressor or chromosomal instability pathway, follows the Fearon and Vogelstein model and shows mutation in classical oncogenes and tumour suppressor genes, such as K-ras, adenomatous polyposis coli, deleted in colorectal cancer, or p53. Alterations in the Wnt pathway are also very common in this type of tumour. The second main colorectal carcinogenesis pathway is the mutator pathway. This pathway is present in nearly 15% of all cases of sporadic colorectal cancer. It is characterized by the presence of mutations in the microsatellite sequences caused by a defect in the DNA mismatch repair genes, mostly in hMLH1 or hMSH2. These two pathways have clear molecular differences, which will be reviewed in this article, but they also present distinct histopathological features. More strikingly, their clinical behaviours are completely different, having the "mutator" tumours a better outcome than the "suppressor" tumours.

MMP-7 and SGCE as distinctive molecular factors in sporadic colorectal cancers from the mutator phenotype pathway.

Colorectal cancers (CRCs) from the suppressor and the mutator carcinogenic pathways display distinctive pathological and clinical features that remain not completely understood. In this context, the aim of this work was to study the differential expression of metalloproteinases and adhesion molecules related to cancer invasiveness in both groups of tumours. We analyzed 84 tissue specimens, 42 primary sporadic CRCs obtained from patients who underwent radical surgery, and its corresponding control tissues. According to microsatellite instability, 31 cancers showed low or null microsatellite instability (MSI-L/MSS) and 11 tumours displayed high microsatellite instability (MSI-H). Expression assays were established using the Oligo GEArray(R) human extracellular matrix and adhesion molecules microarray containing 114 genes. Real-time quantitative PCR (RT-qPCR) confirmed expression data from arrays, using TaqMan probes. Results from oligoarray expression analyses indicated that ITGA3, ITGA9, ITGB4, ITGB7 and MMP15 had significantly higher expression levels in MSI-H tumours versus MSS/MSI-L cancers, whereas COL12A1, CSPG2, FN1, MMP-7 and SGCE were down-regulated in tumours with high microsatellite instability when compared to the stable group. After RT-qPCR validation, two of these genes, MMP-7 and SGCE, were confirmed to have statistical differences between the two groups of tumours studied. In both cases, MSI-H tumours displayed significant lower expression levels than MSI-L/MSS tumours. In conclusion, these two distinctive molecular markers could be related to a diminished invasion in colorectal tumours from the mutator pathway, this may contribute to the understanding of the better patient prognosis conferred by this type of tumours.

Expression of Human MDGA1 Increases Cell Motility and Cell-Cell Adhesion and Reduces Adhesion to Extracellular Matrix Proteins in MDCK Cells.

Characterization of the novel human protein MDGA1 (MAM Domain containing Glycosylphosphatidylinositol Anchor-1) has been reported in our laboratory in the past few years. hMDGA1 is a glycoprotein containing 955 aminoacids (137 kDa) attached to the eukaryotic cell membrane by a GPI (Glycosylphosphatidylinositol) anchor and localized specifically into membrane microdomains known as lipid rafts. Moreover, MDGA1 protein contains structural features found in different types of cell adhesion molecules (CAMs) such as the presence of immunoglobulin domains and a MAM domain (Meprin, A5 protein, receptor protein-tyrosine phosphatase µ), suggesting a role of MDGA1 in cell migration and/or adhesion. In order to investigate this aim, stable MDCK cell lines expressing MDGA1 or the truncated proteins IgGPI (lacking the MAM domain) and MAMGPI (lacking Ig domains) were generated. Our results reveal that MDGA1 increases the ability of MDCK cells to migrate, as it contains both Ig and MAM domains which have been implicated in cell motility. In addition, cell adhesion to extracellular matrix proteins, mainly to collagen IV, is reduced by MDGA1 and the IgGPI and MAMGPI truncated proteins. Accordingly, silencing MDGA1 by siRNA revealed a significant increase in adhesion to collagen IV. Furthermore, MDGA1 expression, through the intrinsic properties of the MAM domain, increases cell-cell adhesion independently of the cell monolayer used, suggesting that MDGA1 mediates cell-cell adhesiveness in a heterophilic manner.

Understanding and supporting lightweight communication in hospital work.

Informal communication is an essential resource in hospital work; it is used as a means to collaborate and coordinate the way in which work is performed, as well as to locate and gather the artifacts and human resources required for patient care. The need of physical proximity to establish and hold informal communications has motivated the development of tools that support remote informal interaction. However, this kind of technology has not been widely adopted in hospitals, where workers experience intense mobility. In this paper, we present the results of an observational study in a hospital aimed at understanding how local mobility changes the rules in the provision of support for informal communication, and how technology could improve this form of communication. We found that local mobility fosters opportunities for colocated communication; however, it faces some inconveniences related to the affordances of the physical environment. We address these issues through the design of SOLAR, a collaborative application that supports colocated interactions in hospital work through the implementation and integration of five services that form a ubicomp infrastructure. Additionally, we present a discussion about the perception of users related to the usefulness of this tool.

Telomere function in colorectal cancer.

Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world. Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process. Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length. It is achieved mainly, by telomerase activation. Thus, the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized. Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours. Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis. Taking into account all the results achieved by different groups, quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma.

Manejo del dolor postoperatorio en pacientes de cirugía cardiotorácica / Management of postoperative pain in patients with cardio surgery

El efecto beneficioso principal de un control eficaz del dolor es la satisfacción del paciente. La importancia de una correcta analgesia perioperatoria obliga a un profundo conocimiento de las características del dolor, de las armas terapeúticas de las que se dispone y de la técnica utilizada. Si bien la analgesia intravenosa pautada es la forma más extendida de control del dolor postoperatorio, el desarrollo de técnicas de analgesia controlada por el paciente (PCA) y las ventajas que ofrece la analgesia epidural obliga a plantear cuál sería el tratamiento ideal. Por tanto, las ventajas que ofrece un estricto control del dolor postoperatorio tras la cirugía cardiotorácica obliga a tenerlo cada vez más en cuenta y perseguirlo como uno de los objetivos primordiales del período postoperatorio.

Differential Wnt pathway gene expression and E-cadherin truncation in sporadic colorectal cancers with and without microsatellite instability.

PURPOSE: Alterations in the Wnt pathway play a major role in colorectal cancer with high (MSI-H) or low microsatellite instability (MSS/MSI-L). However, the differential impact of the Wnt pathway components on these tumors is poorly understood. MMP-3 (stromelysin-1) promoter is a target of the mutator phenotype in sporadic colorectal cancer. Among MMP-3 targets, we investigated E-cadherin integrity status in both groups of tumors. Because beta-catenin is the main effector of the Wnt pathway, we have also investigated the differential cellular status of beta-catenin. EXPERIMENTAL DESIGN: Expression profiles of 114 genes related to the Wnt pathway were analyzed by oligo microarrays in 48 tumors classified by their MSI status. In addition, we analyzed 48 sporadic colorectal cancers for E-cadherin integrity status. We performed investigation of beta-catenin and cyclin D1 by immunohistochemistry using tissue arrays containing 96 tumors. RESULTS: Our data show that a group of genes that negatively regulate Wnt signaling are downregulated in MSS/MSI-L as compared with MSI-H colorectal tumors. E-cadherin truncation was significantly higher in MSS/MSI-L as compared with MSI-H tumors. Moreover, MSI-H tumors showed low or null beta-catenin nuclear presence, whereas the group of tumors classified as MSS or MSI-L displayed a high content of the nuclear beta-catenin location. CONCLUSIONS: Our results suggest that the differential expression of genes that negatively regulate the Wnt pathway, as well as the status of E-cadherin and beta-catenin in MSI-H or MSS/MSI-L colorectal tumors, shed some light on the different clinical behavior showed by the two groups.

Telomere shortening is associated with poor prognosis and telomerase activity correlates with DNA repair impairment in non-small cell lung cancer.

BACKGROUND AND PURPOSE: Telomere function and DNA damage response pathways are frequently inactivated in cancer. Moreover, some telomere-binding proteins have been implicated in DNA repair. The purpose of this work consists of evaluating the prognostic impact of telomere dysfunction and its relationship with DNA repair systems in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We analysed 83 NSCLCs and their corresponding control samples obtained from patients submitted to surgery. Telomere function was evaluated by determining telomerase activity and telomere length. DNA repair expression assays were established by using cDNA arrays containing 96 DNA-repair genes and by Real Time Quantitative PCR. RESULTS: Our data indicated that telomere attrition was significantly associated with poor clinical outcome of patients (P=0.02), being this parameter a significant prognostic factor independent of tumour stage (P=0.012; relative risk=1.887; 95% CI: 1.147-3.102). DNA-repair gene expression studies showed down regulation of DCLRE1C and GTF2H1 and a clear FLJ10858 up regulation in tumour tissues, as compared to controls. In addition, a number of genes related to DNA-repair were significantly down regulated in tumours that reactivated telomerase (DCLRE1C, GTF2H1, PARP-3, MLH1, and TRF2). CONCLUSIONS: Telomere shortening emerged as a poor clinical evolution parameter in NSCLC. Moreover, results from this work suggest a relationship between the loss of several DNA repair genes and telomerase activity, which may be of relevance in the pathogenesis of non-small lung cancer.