Combined Endoscopic and Laparoscopic Approach to a Gastroesophageal Tumor

Minimally invasive techniques may be used in combination to manage difficult problems in general surgery leading to shorter hospital stays and improved patient satisfaction

Manipulation of the follicular phase: Uterodomes and pregnancy - is there a correlation?

BACKGROUND: Manipulation of the follicular phase uterine epithelium in women undergoing infertility treatment, has not generally shown differing morphological effects on uterine epithelial characteristics using Scanning Electron Microscopy (SEM) and resultant pregnancy rates have remained suboptimal utilising these manipulations. The present study observed manipulation of the proliferative epithelium, with either 7 or 14 days of sequential oestrogen (E) therapy followed by progesterone (P) and assessed the appearance of pinopods (now called uterodomes) for their usefulness as potential implantation markers in seven women who subsequently became pregnant. Three endometrial biopsies per patient were taken during consecutive cycles: day 19 of a natural cycle - (group 1), days 11/12 of a second cycle after 7 days E then P - (group 2), and days 19/22 of a third cycle after 14 days E then P - (group 3). Embryo transfer (ET) was performed in a subsequent long treatment cycle (as per Group 3). RESULTS: Seven pregnancies resulted in seven viable births including one twins and one miscarriage. Analysis of the individual regimes showed 5 days of P treatment to have a higher correlation for uterodomes in all 3 cycles observed individually. It was also observed that all 7 women demonstrated the appearance of uterodomes in at least one of their cycles. CONCLUSIONS: We conclude that manipulation of the follicular phase by shortening the period of E exposure to 7 days, does not compromise uterine epithelial morphology and we add weight to the conclusion that uterodomes indicate a receptive endometrium for implantation

The Pathophysiology of Farnesoid X Receptor (FXR) in the GI Tract: Inflammation, Barrier Function and Innate Immunity

The Farnesoid-X Receptor, FXR, is a nuclear bile acid receptor. Its originally described function is in bile acid synthesis and regulation within the liver. More recently, however, FXR has been increasingly appreciated for its breadth of function and expression across multiple organ systems, including the intestine. While FXR’s role within the liver continues to be investigated, increasing literature indicates that FXR has important roles in responding to inflammation, maintaining intestinal epithelial barrier function, and regulating immunity within the gastrointestinal (GI) tract. Given the complicated and multi-factorial nature of intestinal barrier dysfunction, it is not surprising that FXR’s role appears equally complicated and not without conflicting data in different model systems. Recent work has suggested translational applications of FXR modulation in GI pathology; however, a better understanding of FXR physiology is necessary for these treatments to gain widespread use in human disease. This review aims to discuss current scientific work on the role of FXR within the GI tract, specifically in its role in intestinal inflammation, barrier function, and immune response, while also exploring areas of controversy

The C-terminal non-catalytic domain of Mkp-1 phosphatase harbors a complex signal for rapid proteasome degradation in enterocytes

Mitogen-activated kinase phosphatase Mkp-1 is an essential negative regulator of innate immune responses. In enterocytes, Mkp-1, which is transiently expressed in response to Toll-like receptor (TLR) ligands, plays a role as an initial step in establishing tolerance to bacteria and their pro-inflammatory molecules. Mkp-1 has a very short half-life (about 30 min) in IEC-6 enterocytes. Here we examined the mechanism of Mkp-1 rapid degradation in IEC-6 cells. Immunoprecipitation and proteolysis inhibitor analysis indicated that Mkp-1 is monoubiquitinated and degraded by proteasome. Dominant negative ubiquitin increased Mkp-1 half-life, indicating involvement of ubiquitination in Mkp-1 degradation. Stability of Mkp-1 is not affected by LPS treatment, consistent with constitutive degradation. U0126, a potent and selective inhibitor of extracellular response kinase (ERK) had negligible effect on the stability of both intrinsic and ectopically expressed Mkp-1, therefore enterocytes, unlike other cell types, do not regulate Mkp-1 degradation via ERK-dependent phosphorylation. C-Truncations of the C-terminal non-catalytic domain (at amino acids 306, 331, and 357), the 306-330 deletion obliterating the potential PEST domains, as well as S296A mutation, but not S323A, S358A, or S363A mutations in potential ERK phosphorylation sites dramatically stabilized Mkp-1. C-terminal fusion of the non-catalytic C-terminal domain of Mkp-1 conferred accelerated degradation on the intrinsically stable green fluorescent protein. According to these results, rapid degradation of Mkp-1 in IEC-6 enterocytes is ubiquitin-proteasome-dependent and ERK-independent. Multiple elements of the C-terminal non-catalytic domain play essential roles in the formation of the complex rapid degradation signal

Neonatal sepsis

This chapter examines the definition, epidemiology, pathophysiology, diagnosis, management, and outcome of neonatal sepsis. Sepsis was classically described in the adult patient with a Gram-negative infection who subsequently developed fever, hypotension with poor tissue perfusion, and ultimately multiple organ failure. Until recently, sepsis was defined as the presence of a systemic inflammatory response syndrome (SIRS) response coupled with a causative infection. Risk factors for neonatal sepsis can be divided into maternal and neonatal factors. Maternal contributors are more likely to be involved in early onset sepsis (EOS) than late onset sepsis (LOS) and have been divided into three categories: infection, colonization, and risk factors. Acute phase reactants and biomarkers can be measured in the evaluation of neonatal sepsis. Given the profound morbidity and mortality associated with neonatal sepsis, management should begin with prevention. The most significant prevention strategy has been the implementation of prenatal screening and administration of intrapartum antibiotics for group B Streptococcus (GBS) infection