Cataract surgery in cancer patients and its impact on quality of life as measured by the National Eye Institute Visual Functioning Questionnaire - 25 (NEI-VFQ-25)

Purpose. The measurement of quality of life has become an important topic in healthcare and in the allocation of limited healthcare resources. Improving the quality of life (QOL) in cancer patients is paramount. Cataract removal and lens implantation appears to improve patient well-being of cancer patients, though a formal measurement has never been published in the US literature. In this current study, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), a validated vision quality of life metric, was used to study the change in vision-related quality of life in cancer patients who underwent cataract extraction with intraocular lens implantation. ^ Methods. Under an IRB approved protocol, cancer patients who underwent cataract surgery with intraocular lens implantation (by a single surgeon) from December 2008 to March 2011, and who had completed a pre- and postoperative NEI-VFQ-25 were retrospectively reviewed. Post-operative data was collected at their routine 4-6 week post-op visit. Patients' demographics, cancer history, their pre and postoperative ocular examinations, visual acuities, and NEI-VFQ-25 with twelve components were included in the evaluation. The responses were evaluated using the Student t test, Spearman correlation and Wilcoxon signed rank test. ^ Results. 63 cases of cataract surgery (from 54 patients) from the MD Anderson Cancer Center were included in the study. Cancer patients had a significant improvement in the visual acuity (P<0.0001) postoperatively, along with a significant increase in vision-related quality of life (P<0.0001). Patients also had a statistically significant improvement in ten of the twelve subcategories which are addressed in the NEI-VFQ-25. ^ Conclusions. In our study, cataract extraction and intraocular implantation showed a significant impact on the vision-related quality of life in cancer patients. Although this study includes a small sample size, it serves as a positive pilot study to evaluate and quantify the impact of a surgical intervention on QOL in cancer patients and may help to design a larger study to measure vision related QOL per dollar spent for health care cost in cancer patients.^

Expression of p53, {\it * ras\/} and PCNA in human colonic neoplasms: Possible biomarkers of malignant potential

Colorectal cancer is a leading cause of cancer mortality and early detection can significantly improve the clinical outcome. Most colorectal cancers arise from benign neoplastic lesions recognized as adenomas. Only a small percentage of all adenomas will become malignant. Thus, there is a need to identify specific markers of malignant potential. Studies at the molecular level have demonstrated an accumulation of genetic alterations, some hereditary but for the most occurring in somatic cells. The most common are the activation of ras, an oncogene involved in signal transduction, and the inactivation of p53, a tumor suppressor gene implicated in cell cycle regulation. In this study, 38 carcinomas, 95 adenomas and 20 benign polyps were analyzed by immunohistochemistry for the abnormal expression of p53 and ras proteins. An index of cellular proliferation was also measured by labeling with PCNA. A general overexpression of p53 was immunodetected in 66% of the carcinomas, while 26% of adenomas displayed scattered individual positive cells or a focal high concentration of positive cells. This later was more associated with severe dysplasia. Ras protein was detected in 37% of carcinomas and 32% of adenomas mostly throughout the tissue. p53 immunodetection was more frequent in adenomas originating in colons with synchronous carcinomas, particularly in patients with familial adenomatous polyposis and it may be a useful marker in these cases. Difference in the frequency of p53 and ras alterationbs was related to the location of the neoplasm. Immunodetection of p53 protein was correlated to the presence of a mutation in p53 gene at exon 7 and 5 in 4/6 carcinomas studied and 2 villous adenomas. Thus, we characterized in adenomas the abnormal expression of two proteins encoded by the most commonly altered genes in colorectal cancer. p53 alteration appears to be more specifically associated with transition to malignancy than ras. By using immunohistochemistry, a technique that keeps the architecture of the tissue intact, it was possible to correlate these alterations to histopathological characteristics that were associated with higher risks for transformation: villous content, dysplasia and size of adenoma. ^

The role of p53 in skin cancer induction by UV radiation and as a potential tumor antigen in UV-induced murine skin tumors

Carcinoma of the skin is the most common type of human cancer in the United States. Ultraviolet radiation (UVR) present in the sunlight is thought to be the major carcinogen responsible for induction of skin cancer. In UV-associated skin carcinogenesis, mutations in p53 are not only present with very high frequency, but occur early in the course of tumor development. In addition, UV-induced skin tumors in mice exhibit unique immunological characteristics. They are highly antigenic and express both individually-specific tumor transplantation antigens recognized by effector T cells and the UV-associated common antigen recognized by UV-induced suppressor T cells. ^ To examine the hypothesis that p53 plays a critical role in preventing skin cancer induction by UVR, mice constitutively lacking one or two functional p53 alleles were compared to wild-type mice for their susceptibility to UV carcinogenesis. Both p53 +/– and –/– mice showed greater susceptibility to skin cancer induction than wild-type mice, and –/– mice were the most susceptible, Accelerated tumor development in the p53 +/– mice was not associated with loss of the remaining wild-type allele of p53 , but in many cases was associated with UV-induced mutations in p53. Our studies clearly demonstrate the essential role of p53 in protection against UV carcinogenesis, particularly in the eye and epidermis. ^ The role of p53 in the antigenicity of UV-induced murine skin tumors was also addressed. Primary UV-induced tumors from p53 –/–, +/– and +/+ mice were transplanted into both normal and immunosuppressed mice, and rates of tumor rejection were compared. Tumors from mice with only one or no functional p53 alleles were less antigenic than those from mice with two functional p53 alleles. Moreover, tumors with no functional p53 also failed to grow well in chronically UV-irradiated mice. These results indicate that p53 contributes to the strong antigenicity of UV-induced murine skin tumors, and suggest that it may play a critical role in expression of the UV-associated common antigen recognized by suppressor T cells. ^ In this study we also monitored the effect of UVR on the development of lymphoid malignancies in p53 deficient mice. The incidence of lymphoid malignancies in UV-irradiated p53 +/– mice was drastically enhanced compared to that in unirradiated counterparts. The immune responses of the mice were identical and were suppressed to the same extent by UV irradiation regardless of the p53 genotype. These data provide the first experimental evidence that exposure to UVR can contribute to the development of lymphoid neoplasms in genetically susceptible hosts. ^

Síndrome MAPE, heavy eye y esclerodermia

Paciente de 60 años de edad y sexo femenino con esclerodermia y miopía alta bilateral que consulta por estrabismo y ptosis palpebral. El estrabismo consiste en esotropía progresiva con hipotropía de ojo derecho (OD) asociado a miopía alta axial con gran tamaño del globo ocular medido por ecometría ultrasónica que conjuntamente con imágenes de Resonancia Magnética Nuclear (RMN) llevan al diagnóstico de Síndrome MAPE (Miopic Acquired Progressive Esotropia). La hipotropía se diagnostica como heavy eye (ojo pesado). El tratamiento del estrabismo mediante cirugía de retroceso de recto medio derecho con técnica de suturas ajustables corrigió la esotropía mientras que la normalización del trayecto del recto lateral descendido no mejoró la hipotropía en esta paciente. Ésta se compensó parcialmente con el plegamiento ajustable del recto superior. Persiste la ptosis palpebral causada por la esclerodermia.

Integración de tecnologías eye-tracking con vídeos interactivos para neurorrehabilitación cognitiva

La integración de las nuevas tecnologías en el proceso de rehabilitación permite la generación de terapias personalizadas, ubicuas y basadas en la evidencia. Tecnologías como el vídeo interactivo son propicias para el desarrollo de entornos virtuales en los que el paciente se ve inmerso dentro de actividades de la vida diaria en los que tiene que lograr un objetivo ecológico en un contexto seguro, controlado y adaptado a su perfil disfuncional. Dentro de este marco de rehabilitación la interacción visual paciente-entorno virtual se entiende como el mecanismo de comunicación principal, siendo además la atención visual un reflejo del estado cognitivo del paciente. El trabajo presentado en este artículo permite la integración de un sistema de eye-tracking con un entorno de neurorrehabilitación basado en vídeo interactivo. El objetivo último del sistema es la monitorización en tiempo real de la atención visual del usuario durante el proceso de neurorrehabilitación. Esta monitorización permite no sólo reproducir la ejecución de la actividad junto con el foco de la mirada, sino también detectar faltas de atención por parte del usuario, que permiten al vídeo interactivo reaccionar y adaptar la presentación de estímulos para ayudar a centrar su atención y así completar el objetivo de la actividad.

Label-free biosensing for dry eye by Means of BICELLS

The use of Biophotonic Sensing Cells (BICELLs) based on micro-nano pattemed photonic architectures has been recently proven as an efficient methodology for label-free biosensing by using Optical Interrogation [1]. According to this, we have studied the different optical response for a specific typology of BICELL, consisting of structures of SU -8. This material is biocompatible with different types of biomolecules and can be immobilized on its sensing surface. In particular, we have measured the optical response for a biomarker in clinic diagnostic of dry eye. Although different proteins can be enstudied such as: PRDX5, ANXA 1, ANXA 11, CST 4, PLAA Y S 1 OOA6 related with ocular surface (dry eye), for this work PLAA (phospholipase A2) is studied by means of label free biosensing based on BICELLs for analyzing the performance and specificity according with means values of concentration in ROC curves.

Evaluación de un entorno de rehabilitación cognitiva basado en tecnologías de Vídeo Interactivo y Eye-Tracking

El Daño Cerebral Adquirido (DCA) se ha convertido en una de las principales causas de discapacidad neurológica de las sociedades desarrolladas. La alteración de las funciones cognitivas como consecuencia del DCA, limita no sólo la calidad de vida del paciente sino también la de las persona de su entorno. Aunque la neurorrehabilitación permite recuperar algunas de las funciones alteradas aprovechando la naturaleza plástica del sistema nervioso, su práctica siguiendo procesos tradicionales no permiten en muchos casos ajustarse a las necesidades de cada individuo ni, en general, cubrir todos los aspectos necesarios que conviertan al proceso rehabilitador en un tratamiento realmente efectivo. La incorporación al proceso de rehabilitación de las nuevas tecnologías ha permitido aumentar la intensidad del tratamiento, personalizando y prolongándolo en el tiempo de forma sostenible. Los entornos virtuales (EV) apoyados en esta tendencia permiten reproducir Actividades de Vida Diaria (AVD) controladas que incrementan el valor ecológico de las terapias. Este Trabajo Fin de Grado aborda el uso pionero de la tecnología de Vídeo Interactivo (VI) para el desarrollo de dichos entornos en el campo de la rehabilitación cognitiva. En concreto, el objetivo del TFG es la evaluación de un EV de rehabilitación desarrollado mediante tecnología de VI e integrado con un sistema de Eye-Tracking, capaz de capturar y analizar la información referente al comportamiento visual del paciente. Para este fin, se realiza el diseño, implementación y evaluación de un estudio experimental que registre el comportamiento de diferentes sujetos ante dos modalidades de AVD.

Dynamic characteristics and adaptability of mouse vestibulo-ocular and optokinetic response eye movements and the role of the flocculo-olivary system revealed by chemical lesions

The dynamic characteristics of reflex eye movements were measured in two strains of chronically prepared mice by using an infrared television camera system. The horizontal vestibulo-ocular reflex (HVOR) and horizontal optokinetic response (HOKR) were induced by sinusoidal oscillations of a turntable, in darkness, by 10° (peak to peak) at 0.11–0.50 Hz and of a checked-pattern screen, in light, by 5–20°at 0.11–0.17 Hz, respectively. The gains and phases of the HVOR and HOKR of the C57BL/6 mice were nearly equivalent to those of rabbits and rats, whereas the 129/Sv mice exhibited very low gains in the HVOR and moderate phase lags in the HOKR, suggesting an inherent sensory-motor anomaly. Adaptability of the HOKR was examined in C57BL/6 mice by sustained screen oscillation. When the screen was oscillated by 10° at 0.17 Hz, which induced sufficient retinal slips, the gain of the HOKR increased by 0.08 in 1 h on average, whereas the stimuli that induced relatively small or no retinal slips affected the gain very little. Lesions of the flocculi induced by local applications of 0.1% ibotenic acid and lesions of the inferior olivary nuclei induced by i.p. injection of 3-acetylpyridine in C57BL/6 mice little affected the dynamic characteristics of the HVOR and HOKR, but abolished the adaptation of the HOKR. These results indicate that the olivo-floccular system plays an essential role in the adaptive control of the ocular reflex in mice, as suggested in other animal species. The data presented provide the basis for analyzing the reflex eye movements of genetically engineered mice.

Identification of genes required for Drosophila eye development using a phenotypic enhancer-trap

A novel method of P-element mutagenesis is described for the isolation of mutants affecting the development of the Drosophila compound eye. It exploits the interaction between the Bride of Sevenless (Boss) ligand and the Sevenless (Sev) receptor tyrosine kinase that triggers the formation of the UV-sensitive photoreceptor neuron, R7. Transposition of a boss cDNA transgene, in an otherwise boss mutant background, was used as a “phenotypic trap” in live flies to identify enhancers expressed during a narrow time window in eye development. Using a rapid behavioral screen, more than 400,000 flies were tested for restoration of R7. Some 1,800 R7-containing flies were identified. Among these, 21 independent insertions with expression of the boss reporter gene in the R8 cell were identified by a external eye morphology and staining with an antibody against Boss. Among 900 lines with expression of the boss reporter gene in multiple cells assessed for homozygous mutant phenotypes, insertions in the marbles, glass, gap1, and fasciclin II genes were isolated. This phenotypic enhancer-trap facilitates (i) the isolation of enhancer-traps with a specific expression pattern, and (ii) the recovery of mutants disrupting development of specific tissues. Because the temporal and tissue specificity of the phenotypic trap is dependent on the choice of the marker used, this approach can be extended to other tissues and developmental stages.

P element insertion-dependent gene activation in the Drosophila eye

Insights into the function of a gene can be gained in multiple ways, including loss-of-function phenotype, sequence similarity, expression pattern, and by the consequences of its misexpression. Analysis of the phenotypes produced by expression of a gene at an abnormal time, place, or level may provide clues to a gene’s function when other approaches are not illuminating. Here we report that an eye-specific, enhancer–promoter present in the P element expression vector pGMR is able to drive high level expression in the eye of genes near the site of P element insertion. Cell fate determination, differentiation, proliferation, and death are essential for normal eye development. Thus the ability to carry out eye-specific misexpression of a significant fraction of genes in the genome, given the dispensability of the eye for viability and fertility of the adult, should provide a powerful approach for identifying regulators of these processes. To test this idea we carried out two overexpression screens for genes that function to regulate cell death. We screened for insertion-dependent dominant phenotypes in a wild-type background, and for dominant modifiers of a reaper overexpression-induced small eye phenotype. Multiple chromosomal loci were identified, including an insertion 5′ to hid, a potent inducer of apoptosis, and insertions 5′ to DIAP1, a cell death suppressor. To facilitate the cloning of genes near the P element insertion new misexpression vectors were created. A screen with one of these vectors identified eagle as a suppressor of a rough eye phenotype associated with overexpression of an activated Ras1 gene.

AP-2-null cells disrupt morphogenesis of the eye, face, and limbs in chimeric mice

The homozygous disruption of the mouse AP-2 gene yields a complex and lethal phenotype that results from defective development of the neural tube, head, and body wall. The severe and pleiotropic developmental abnormalities observed in the knockout mouse suggested that AP-2 may regulate several morphogenic pathways. To uncouple the individual developmental mechanisms that are dependent on AP-2, we have now analyzed chimeric mice composed of both wild-type and AP-2-null cells. The phenotypes obtained from these chimeras indicate that there is an independent requirement for AP-2 in the formation of the neural tube, body wall, and craniofacial skeleton. In addition, these studies reveal that AP-2 exerts a major influence on eye formation, which is a critical new role for AP-2 that was masked previously in the knockout mice. Furthermore, we also have uncovered an unexpected influence of AP-2 on limb pattern formation; this influence is typified by major limb duplications. The range of phenotypes observed in the chimeras displays a significant overlap with those caused by teratogenic levels of retinoic acid, strongly suggesting that AP-2 is an important component of the mechanism of action of this morphogen.