Transcriptional changes through menstrual cycle reveal a global transcriptional derepression underlying the molecular mechanism involved in the window of implantation.

The human endometrium is a dynamic tissue that only is receptive to host the embryo during a brief time in the middle secretory phase, called the window of implantation (WOI). Despite its importance, regulation of the menstrual cycle remains incompletely understood. The aim of this study was to characterize the gene cooperation and regulation of menstrual cycle progression, to dissect the molecular complexity underlying acquisition of endometrial receptivity for a successful pregnancy, and to provide the scientific community with detailed gene co-expression information throughout the menstrual cycle on a user-friendly web-tool database. A retrospective gene co-expression analysis was performed based on the endometrial receptivity array (ERarray) gene signature from 523 human endometrial samples collected across the menstrual cycle, including during the WOI. Gene co-expression analysis revealed the WOI as having the significantly smallest proportion of negative correlations for transcriptional profiles associated with successful pregnancies compared to other cycle stages, pointing to a global transcriptional derepression being involved in acquisition of endometrial receptivity. Regulation was greatest during the transition between proliferative and secretory endometrial phases. Further, we prioritized nuclear hormone receptors as major regulators of this derepression and proved that some genes and transcription factors involved in this process were dysregulated in patients with recurrent implantation failure. We also compiled the wealth of gene co-expression data to stimulate hypothesis-driven single-molecule endometrial studies in a user-friendly database: Menstrual Cycle Gene Co-expression Network (www.menstrualcyclegcn.com). This study revealed a global transcriptional repression across the menstrual cycle, which relaxes when the WOI opens for transcriptional profiles associated with successful pregnancies. These findings suggest that a global transcriptional derepression is needed for embryo implantation and early development.

[Social health evolution in Vall d'Uixó. Application of multivariate analysis as a new health status indicator method]. / Evolución sociosanitaria de la Vall d'Uixó. Aplicación del análisis multivariado como una forma nueva de diagnóstico de salud.

OBJECTIVES: This study evaluated the relative position of Vall d'Uixó within the province of Castellón, the Valencian Community and Spain. DESIGN: The study covers the period from 1981 to 1993. A multivariate analysis of the main components was performed. This compared the interrelationship of these indicators in the different zones analysed. PATIENTS AND OTHER PARTICIPANTS: Our study focused on an area of 27,387 population, geographically within the province of Castellón in the south-west of La Plana county. RESULTS: The analysis showed that Vall d'Uixó had a low level of development and little economic activity. It had a relatively young population. CONCLUSIONS: The health problems were linked to the social and economic situation. Apart from the re-creation of industrial jobs, it would be desirable to improve programmes to monitor TB and cardiovascular diseases.

Reproducibility of digital image analysis for measuring corneal haze after myopic photorefractive keratectomy.

PURPOSE: To evaluate the usefulness of digital image analysis for quantifying corneal haze by determining the reproducibility of its measurements at the corneal plane. METHODS: In a prospective study, 20 randomly selected eyes that had undergone myopic photorefractive keratectomy were photographed focusing the slit beam on their anterior corneal surface. Each photograph was examined using computer image analysis techniques that detect the edge of the reticular pattern of the image. Quantification of the difference between two areas, treated and adjacent untreated cornea, each containing 3,750 pixels with a resolution of 256 gray levels, was performed. Intra-analyzer variation was determined by evaluating the photographs obtained by two analyzers under standard conditions on four separate visits. Interanalyzer variation was calculated using one measurement and the mean of the four measurements. RESULTS: The pooled standard deviation of the measurements for the analyzers was 0.63 and 0.62 gray levels (coefficient of variation, 4.1% and 3.3%). An association between less severe haze measurements and higher reproducibility scores was found (r = .42; P = .007). The mean interanalyzer variation was smaller for the average of four measurements, 0.55 +/- 0.37 gray levels, than for one measurement, 0.94 +/- 0.73 gray levels (P = .014). CONCLUSIONS: Good reproducibility for haze measurements by digital image analysis of the differences between the treated and adjacent untreated corneal areas was obtained. When the average of four measurements was used instead of a single measurement, interanalyzer reproducibility increased significantly. This new technique may be used to quantify and analyze corneal haze after myopic photorefractive keratectomy.

Direct objective quantification of corneal haze after excimer laser photorefractive keratectomy for high myopia.

PURPOSE: The purpose of the study is to measure regional distribution differences in corneal haze after excimer laser photorefractive keratectomy for high myopia. METHODS: The authors developed computerized gradient edge detectors with which were analyzed digitized anterior slit-lamp photographs of 40 eyes, an average of 21.0 plus or minus 14.5 weeks after photorefractive keratectomy for high myopia (-6 to -22 diopters). A treated area an adjacent untreated area on the anterior corneal surface, each containing six regions, were quantified, and the difference was correlated with various parameters. RESULTS: Mean differences between scarred and clear areas for haze grade 0.5, 1.0, 2.0, 3.0, and 4.0 were 16.9, 26.6, 42.6, 60.4, and 76.4 gray levels, respectively (rs = 0.96; P = 0.0001). A low but statistically significant correlation between the intended correction and postoperative corneal haze was found (r = 0.33; P = 0.037). The mean coefficient of variation of the amount of opacification within each treated area was 9.4%. This coefficient of variation increased with a longer follow-up time (r = 0.88; P = 0.0001). The difference in the intensity of haze between the center and more peripheral regions over the entrance pupil did not correlate with the attempted correction. However, a strong association between a relatively less severe central corneal haze with respect to more peripheral haze and longer follow-up time was found (r = -0.96; P = 0.0001). CONCLUSION: The amount of corneal haze showed a weak positive association with the attempted correction in excimer laser photorefractive keratectomy for high myopia. Corneal haze appeared fairly uniformly distributed within the ablation zone, but a more heterogeneous distribution was found with a longer follow-up time. Furthermore, later postoperative examinations disclosed a clear trend toward diminishing central opacification relative to peripheral regions over the entrance pupil.