Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women

Endometriosis is a disorder that affects 5% of the normal population but is present in up to 40% of women with pelvic pain and/or infertility. Recent evidence suggests that the endometrium of women with endometriosis exhibits progesterone insensitivity. One endometrial protein that fluctuates in response to progesterone is the estrogen receptor-alpha (ER alpha), being down-regulated at the time of peak progesterone secretion during the window of implantation. Here we demonstrate that the biomarker of uterine receptivity, beta 3 integrin subunit, is reduced or absent in some women with endometriosis and that such defects are accompanied by inappropriate over-expression of ER alpha during the mid-secretory phase. Using a well-differentiated endometrial cell line we showed that the beta 3 integrin protein is negatively regulated by estrogen and positively regulated by epidermal growth factor (EGF). By competing against estrogen with various selective estrogen receptor modulators (SERMs) and estrogen receptor agonists and antagonists, inhibition of expression of the beta 3 integrin by estrogen can be mitigated. In conclusion, we hypothesize that certain types of uterine receptivity defects may be caused by the loss of appropriate ER alpha down-regulation in the mid-secretory phase, leading to defects in uterine receptivity. Such changes might be effectively treated by timely administration of the appropriate anti-estrogens to artificially block ER alpha and restore normal patterns of gene expression. Such treatments will require further clinical studies

Syndromics: A Bioinformatics Approach for Neurotrauma Research

Substantial scientific progress has been made in the past 50 years in delineating many of the biological mechanisms involved in the primary and secondary injuries following trauma to the spinal cord and brain. These advances have highlighted numerous potential therapeutic approaches that may help restore function after injury. Despite these advances, bench-to-bedside translation has remained elusive. Translational testing of novel therapies requires standardized measures of function for comparison across different laboratories, paradigms, and species. Although numerous functional assessments have been developed in animal models, it remains unclear how to best integrate this information to describe the complete translational “syndrome” produced by neurotrauma. The present paper describes a multivariate statistical framework for integrating diverse neurotrauma data and reviews the few papers to date that have taken an information-intensive approach for basic neurotrauma research. We argue that these papers can be described as the seminal works of a new field that we call “syndromics”, which aim to apply informatics tools to disease models to characterize the full set of mechanistic inter-relationships from multi-scale data. In the future, centralized databases of raw neurotrauma data will enable better syndromic approaches and aid future translational research, leading to more efficient testing regimens and more clinically relevant findings

"How I Do It"-Radical Right Colectomy with Side-to-Side Stapled Ileo-Colonic Anastomosis.

BACKGROUND AND OBJECTIVE: Standardization of surgical technique helps to reproduce excellent clinical outcomes, especially in teaching institutions. We aim to describe in detail our established approach for oncological right colectomy. TECHNIQUE: The right colon is mobilized in a five-step latero-inferior approach starting off with (1) the terminal ileum, visualizing the duodenum and the head of pancreas. (2) The ascending colon is dissected from the retroperitoneum, and takedown of the hepatic flexure is completed coming retrograde from the transverse colon (3). (4) Transection of the remaining retroperitoneal attachments completes exposure of the duodenum and mobilization of the right colon. (5) Ileocolic vessels are dissected out and divided close to their origin, and the mesocolon is divided. We then establish intestinal continuity by use of a side-to-side stapled technique. (1) The arms of a linear cutting stapler are inserted via transverse incisions at the anti-mesenteric sides of the terminal ileum and the transverse colon (tenia) and fired. (2) The enterotomy site is closed by removal of the specimen using a second transverse firing of the linear cutting stapler. An important final step is the (3) reinforcement of the anastomotic ends and the crossing of the staple lines; an omental patch and closure of the mesenteric window are optional. CONCLUSION: The suggested standardized five-step lateral-to-medial dissection of the right colon and the three-step side-to-side stapled technique for ileo-colonic anastomosis are easy to learn and to reproduce. Careful adherence to pivotal technical details will help to obtain an optimal oncological outcome and a consistently low leak rate around 2 %