Notch activation results in phenotypic and functional changes consistent with endothelial-to-mesenchymal transformation

Various studies have identified a critical role for Notch signaling in cardiovascular development. In this and other systems, Notch receptors and ligands are expressed in regions that undergo epithelial-to-mesenchymal transformation. However, there is no direct evidence that Notch activation can induce mesenchymal transdifferentiation. In this study we show that Notch activation in endothelial cells results in morphological, phenotypic, and functional changes consistent with mesenchymal transformation. These changes include downregulation of endothelial markers (vascular endothelial [VE]-cadherin, Tie1, Tie2, platelet-endothelial cell adhesion molecule-1, and endothelial NO synthase), upregulation of mesenchymal markers (alpha-smooth muscle actin, fibronectin, and platelet-derived growth factor receptors), and migration toward platelet-derived growth factor-BB. Notch-induced endothelial-to-mesenchymal transformation does not seem to require external regulation and is restricted to cells expressing activated Notch. Jagged1 stimulation of endothelial cells induces a similar mesenchymal transformation, and Jagged1, Notch1, and Notch4 are expressed in the ventricular outflow tract during stages of endocardial cushion formation. This is the first evidence that Jagged1-Notch interactions induce endothelial-to-mesenchymal transformation, and our findings suggest that Notch signaling may be required for proper endocardial cushion differentiation and/or vascular smooth muscle cell development.     

Fluoride bioactive glass paste improves bond durability and remineralizes tooth structure prior to adhesive restoration

ObjectiveThe current study aimed at examining a fluoride containing bioactive glass (BiominF®) paste as a temporary filling material capable of remineralizing the demineralized enamel or dentin, and its ability to decrease a simulated dentinal fluids pressure on the resin/dentin interface, without affecting the shear bond strength of a universal bonding agent to enamel and dentin.Methods60 premolars were utilized for the acid resistance, trans-microradiography (TMR) and shear bond strength (SBS) experiments. Enamel and dentin discs were demineralized for 4 days to create a subsurface demineralized zone followed by applying BiominF® paste, 1.23% acidulated phosphate fluoride, or a temporary filling material for 24 h.30 extracted human non-carious third molars were utilized for the pulpal pressure experiment in which direct communication to the pulp chamber was created by cutting at a level approximately 1 mm below the cemento-enamel junction while the coronal enamel was ground to expose mid coronal dentin. The dentin surface was exposed to a simulated pulpal pressure. The dentin surfaces had BiominF® paste, an oxalate desensitizing agent, or temporary filling material followed by application of a universal adhesive system.ResultsOne way ANOVA showed that BiominF® paste remineralized effectively the demineralized enamel or dentin, did not affect the bond strength of the enamel and dentin surfaces to the tested adhesive system p < 0.05, and improved the acid resistance of the demineralized enamel and dentin against a secondary erosive challenge. Moreover, BiominF® paste decreased the nanoleakage expression in the dentin/adhesive interface exposed to a simulated pulpal pressure.SignificanceBiominF® paste may serve as a temporary filling material that may improve the longevity of adhesive restorations and help to conserve tooth structures by preserving the demineralized enamel and dentin form cutting during cavity preparation.     

The gene for the alpha 4 subunit of the VLA-4 integrin maps to chromosome 2Q31-32

The VLA-4 integrin (CD49d/CD29), initially discovered on lymphoid cells, is actually known to be highly expressed on T cells, B cells, monocytes, and derived cell lines. Unlike other VLA integrins, mainly involved in cell-matrix adhesive interactions, VLA-4 has also been implicated in several cellular interactions. Based on the published alpha 4 cDNA sequence, a 1,142-bp alpha 4 cDNA fragment was amplified using the polymerase chain reaction. This fragment was used to isolate three overlapping genomic clones from a phage library. By Southern analysis with the cDNA probe, and using the polymerase chain reaction on DNA isolated from a panel of human/mouse somatic cell hybrids, the alpha 4 gene was mapped to chromosome 2. Fluorescence in situ hybridization confirmed this assignment and allowed a more precise mapping to chromosome 2q31-32.     

Robotic colorectal surgery: summary of the current evidence

Background

Several studies have confirmed that laparoscopic colorectal surgery results in improved early post-operative outcomes. Nevertheless, conventional laparoscopic approach and instruments have several limitations. Robotic approach could potentially address of many of these limitations.

Objectives

This review aims to present a summary of the current evidence on the role of robotic colorectal surgery.

Methods

A comprehensive search of electronic databases (Pubmed, Science Direct and Google scholar) using the key words “rectal surgery”, “laparoscopic”, “colonic” and “robotic.” Evidence from these data was critically analysed and summarised to produce this article.

Results

Robotic colorectal surgery is both safe and feasible. However, it has no clear advantages over standard laparoscopic colorectal surgery in terms of early postoperative outcomes or complications profile. It has shorter learning curve but increased operative time and cost. It could offer potential advantage in resection of rectal cancer as it has a lower conversion rates even in obese individuals, distal rectal tumours and patients who had preoperative chemoradiotherpy. There is also a trend towards better outcome in anastomotic leak rates, circumferential margin positivity and perseveration of autonomic function, but there was no clear statistical significance to support this from the currently available data.

Conclusion

The use of robotic approach seems to be capable of addressing most of the shortcomings of the standard laparoscopic surgery. The technique has proved its safety profile in both colonic and rectal surgery. However, the cost involved may restrict its use to patients with challenging rectal cancer and in specialist centres.     

Role of peritoneal ultrasonography and ultrasound-guided fine needle aspiration cytology/biopsy of extravisceral masses in the diagnosis of ascites of undetermined origin

Background and study aimsAscites may be of undetermined origin despite comprehensive study. This study aimed to assess the accuracy and safety of conventional and interventional high-frequency peritoneal ultrasound in the diagnosis of patients with ascites of unclear origin.Patients and methodsA total of 62 patients were prospectively enrolled; they underwent conventional (3.5–5 MHz) and high-frequency (6–8 MHz) transabdominal peritoneal ultrasound to suggest the nature of ascites supplemented by fine needle aspiration cytology (FNAC) of ascites and/or core biopsy of the omentum or other extra-visceral masses for final histopathologic diagnosis. Laparoscopy or laparotomy was needed if biopsy was inconclusive.ResultsUltrasound-guided procedures were diagnostic in 55 (87.7%) patients. Thirty-six (58.1%) were benign, of whom 86% had tuberculous peritonitis, 26 (41.9%) were malignant, of whom 76.9% had peritoneal metastasis. High-frequency ultrasound was able to propose ultrasonographic criteria in a trial to diagnose the nature of ascites. Our proposed ultrasonographic criteria were based on the amount and texture of ascites in addition to the omental and mesenteric features. These were able to suggest the diagnosis with 80.7% sensitivity for malignant ascites and 75% specificity for benign ascites. Moreover, histopathological examination of tissues obtained by ultrasound-guided procedures increased the sensitivity to 88.5% and the specificity to 88.9% in diagnosing malignant and benign disease, respectively, with an overall diagnostic accuracy of 88.6%. These procedures were considered to be safe as only one major (haemoperitoneum) and two minor complications (temporary ascitic fistula) were reported.ConclusionHigh-frequency peritoneal ultrasound together with the minimally invasive ultrasound-guided FNAC/biopsy of extra-visceral lesions may be considered an effective and safe tool in the diagnosis of ascites of undetermined origin.     

Validation of the RHL30 digital gene expression assay as a prognostic biomarker for relapsed Hodgkin lymphoma

Despite continuing improvements in the management of classical Hodgkin lymphoma (cHL), relapse remains associated with a risk of lymphoma-related mortality. The biological composition of relapse tumour biopsies shows interpatient variability, which can be leveraged to design prognostic biomarkers. Here, we validated the RHL30 assay, a previously reported gene expression model in an independent cohort of 41 patients with relapsed cHL. Patients classified as high-risk by the RHL30 assay had inferior failure-free survival (FFS) after autologous stem cell transplantation (2-year FFS 41% vs. 92%, P = 0·035). The RHL30 model is a robust biomarker that risk-stratifies patients considered for autologous stem cell transplantation.     

Distal splenorenal shunt for management of variceal bleeding in patients with schistosomal hepatic fibrosis.

The distal splenorenal shunt was performed in 60 patients with schistosomal hepatic fibrosis in whom no evidence of cirrhosis was documented by preoperative needle and operative wedge biopsy. No patients have been lost to follow-up with a median of 37 months (range: 17-86). The results showed low operative mortality (1.7%), high patency rate (92.5%), and low recurrent variceal hemorrhage (6.7%). Thrombosed shunts were treated either by refashioning the shunt (1 patient) or splenectomy and gastric devascularization (2 patients). Initial hyperbilirubinemia and reduction in serum albumin were found in the early postoperative period, with persistent hyperbilirubinemia in 32% of the patients. The 5-year survival was 88%, with liver disease related mortality in only three patients. Clinical encephalopathy was detected in three patients (5.1%); only one of them was incapacitated. These data showed that: selective shunt (distal splenorenal shunt, DSRS) is an effective surgical procedure in the treatment of schistosomal variceal bleeding, shunt thrombosis is rare and can possible be corrected if detected early, schistosomal patients have a better survival and a lower incidence of encephalopathy after DSRS than that reported in cirrhotics, and liver biopsy should be performed for proper assessment of the schistosomal population especially in the geographic areas where the schistosoma parasite and viral hepatitis are endemic.