Influence of salt concentration on the formation of Pickering emulsions.

Here we study emulsification in a model experimental system comprised of water, an oil and colloidal particles. The particles are charge-stabilised colloidal silica; unsurprisingly, by varying the concentration of salt the degree of flocculation of the particles can be modified. The influence of salt on the formation of particle-stabilised oil droplets goes well beyond considerations of the colloidal stability of the particles. Our results demonstrate that the influence of salt on the particle-particle interaction is less important for emulsion formation than the influence of salt on both the particle wettability and the particle-interface interaction.

The secret life of Pickering emulsions: particle exchange revealed using two colours of particle.

Emulsion droplets stabilised by colloidal particles (Pickering emulsions) can be highly stable, so it is unsurprising that they are beginning to be exploited industrially. The individual colloidal particles have interfacial attachment energies that are vastly larger than the thermal energy, hence they are usually thought of as being irreversibly adsorbed. Here we show, for the first time, particles being exchanged between droplets in a Pickering emulsion. This occurs when the emulsion contains droplets that share particles, often called bridging. By starting with two emulsions showing bridging, each stabilised by a different colour of particle, the dynamics can be studied as they are gently mixed together on a roller bank. We find that particle exchange occurs by two routes: firstly, during a period of unbridging and rebridging whose duration can be tuned by varying the wettability of the particles, and secondly, during very rare events when particles are ejected from one droplet and re-adsorbed onto another.

Making and breaking bridges in a Pickering emulsion.

HYPOTHESIS: Particle bridges form in Pickering emulsions when the oil-water interfacial area generated by an applied shear is greater than that which can be stabilised by the available particles and the particles have a slight preference for the continuous phase. They can subsequently be broken by low shear or by modifying the particle wettability. EXPERIMENTS: We have developed a model oil-in-water system for studying particle bridging in Pickering emulsions stabilised by fluorescent Stöber silica. A mixture of dodecane and isopropyl myristate was used as the oil phase. We have used light scattering and microscopy to study the degree to which emulsions are bridged, and how this is affected by parameters including particle volume fraction, particle wettability and shear rate. We have looked for direct evidence of droplets sharing particles using freeze fracture scanning electron microscopy. FINDINGS: We have created strongly aggregating Pickering emulsions using our model system. This aggregating state can be accessed by varying several different parameters, including particle wettability and particle volume fraction. Particles with a slight preference for the continuous phase are required for bridging to occur, and the degree of bridging increases with increasing shear rate but decreases with increasing particle volume fraction. Particle bridges can subsequently be removed by applying low shear or by modifying the particle wettability.

Major bleeding during HeartMate II support.

OBJECTIVES: The aim of this study was to characterize a single-center experience of major bleeding complications during HeartMate II (HMII) (Thoratec Corp., Pleasanton, California) left ventricular assist device support, with focus on the subtypes and temporal patterns of post-operative bleeding. BACKGROUND: Bleeding complications are the most common post-operative adverse events after HMII implantation. The timing of bleeding events, relationship to coagulation status, and effect on post-operative survival are incompletely understood. METHODS: From October 2004 to June 2010, 139 HMII recipients at the Cleveland Clinic received 145 devices as a bridge to transplant or destination therapy for advanced heart failure. Major bleeding was defined using Interagency Registry for Mechanically Assisted Circulatory Support criteria, with an additional category created to maximize sensitivity for events. Pre-operative variables, coagulation status, and bleeding recurrence were assessed for correlation to primary events using modulated renewal within a multivariable analysis. RESULTS: The cumulative occurrence of major bleeding was 58% during 171 patient-years of follow-up. There were 1.14 major bleeds per patient-year, with 44% occurring as repeat bleeding events. A first bleed did not predict subsequent bleeding. The greatest risk of bleeding was noted within 2 weeks post-implantation. The international normalized ratio profile correlated poorly with the risk of bleeding. Bleeding early after surgery was associated with reduced survival while on HMII support. CONCLUSIONS: The risk of bleeding peaks early after HMII implantation. Bleeding of thoracic and gastrointestinal sources dominates these events, although many patients undergo transfusions for anemia without an apparent source of hemolysis or bleeding.

Overexpression of folate binding protein is associated with shortened progression-free survival in uterine adenocarcinomas.

OBJECTIVES: Oligonucleotide array and tissue microarray analysis (TMA) by our group has revealed that folate binding protein (FOLR1) is overexpressed in some types of uterine cancer, particularly tumors with serous histology. Since FOLR1 overexpression is a frequent event in some types of endometrial carcinoma, we examined the relationship between FOLR1 overexpression and clinical and pathologic features to determine its prognostic relevance. METHODS: A tissue microarray (TMA) comprised of primary tumor specimens from 485 patients diagnosed with endometrial adenocarcinoma was used to identify cases characterized by FOLR1 overexpression. A proportional hazards model was used to evaluate the association of FOLR1 overexpression with progression-free survival while accounting for confounding influences. RESULTS: Overexpression of FOLR1 was observed in 50/292 (17%) cases and was seen more often in poorly differentiated cancers (22/90 [24%], p=0.051) and tumors with serous histology (16/32 [50%], p<0.001). A shorter progression-free survival was noted in patients with FOLR1 overexpression (log-rank p=0.016) that persisted when the data were limited to patients with stage III/IV disease (log-rank p=0.021) or serous tumors (log-rank p=0.020). Multivariate Cox regression analysis revealed that patients with FOLR1 overexpression had a shorter progression-free survival (H.R. 2.14; 95% CI 1.07-4.28) even when controlling for stage, grade, myometrial invasion and adjuvant chemotherapy. CONCLUSIONS: Our data show that FOLR1 overexpression is not only a biomarker associated with endometrial cancer, but it also appears to be a prognostic factor associated with adverse outcome. These findings suggest that FOLR1 may be an appealing target for biological therapies in some types of endometrial carcinomas.

Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma.

PURPOSE: Folate receptor alpha (FOLR1) is a membrane bound receptor involved in the transport of folate as well as other regulatory cellular processes. The purpose of this study was to examine the expression of FOLR1 in uterine cancers and to identify changes in gene expression that are associated with overexpression of FOLR1. EXPERIMENTAL DESIGN: Fifty-eight frozen uterine cancer specimens were stained for FOLR1 using immunohistochemistry and results were correlated with transcript expression noted on quantitative PCR. Total RNA from 16 cases of uterine serous carcinoma (USC) was analyzed for gene expression using the Affymetrix HG-U133A and HG-U133B GeneChip set. USCs overexpressing FOLR1 were compared to cancers with an absence of FOLR1 using binary comparison and template matching of data was used to identify genes that correlate with FOLR1 expression. Selected targets from this analysis were evaluated by quantitative PCR as well as in an independent set of USC represented in quadruplicate on a tissue microarray (TMA). RESULTS: Overexpression of FOLR1 was observed in 11/16 (69%) of USC and 0/10 normal endometrium cases using frozen tissue specimens. Binary comparison between FOLR1 positive and negative cases identified 121 genes altered by 2-fold at p<0.01 of which 45 are well correlated with FOLR1 expression pattern. Using quantitative PCR, both mesothelin (MSLN) and PTGS1 (COX1) were significantly increased in FOLR1 overexpressing tumors (p=0.014 and p=0.006 respectively). TMA confirmed that overexpression of FOLR1 and MSLN respectively occurred in 23/48 (48%) and 17/54 (32%) of pure USC. CONCLUSION: Both FOLR1 and MSLN are cell surface targets that are co-expressed at high levels in USC and are appealing targets for biologic therapy.

A new prognostic model for FIGO stage 1 epithelial ovarian cancer.

BACKGROUND: No consensus exists which patients with surgical stage 1 epithelial ovarian should receive postoperative chemotherapy. The purpose of this study was to evaluate the prognostic impact of preoperative CA-125 and to establish a prognostic index to identify patients in different risk categories. METHODS: Data of 600 surgically staged patients with FIGO stage 1 EOC treated in eleven gynecological cancer centers in Australia, the USA and Europe were analyzed. Eligible patients include those with invasive EOC where a preoperative CA-125 was obtained and standard surgical staging performed. Overall survival (OS) was chosen as study endpoint. Preoperative CA-125 values were compared with other prognostic factors, and univariate and multivariate Cox models were calculated. RESULTS: Two hundred and one patients (33.5%) had preoperative CA-125 < or =30 U/ml and CA-125 levels < or =30 U/ml were associated with lower grade, sub-stage 1A and mucinous histologic cell type. Patients with elevated CA-125 levels were more likely to receive chemotherapy. OS probability was 95% and 85% for patients with pretreatment CA-125 < or =30 U/ml and >30 U/ml, respectively (p 0.003). Multivariate analysis confirmed preoperative serum CA-125 >30 U/ml (OR 2.7) and age at diagnosis >70 years (OR 2.6) as the only independent predictors for overall survival. CONCLUSION: Pretreatment of CA-125 < or =30 U/ml dominates over histologic cell type, sub-stage and grade to identify a subgroup of FIGO stage 1 patients with a genuinely good prognosis with extremely good survival and who could possibly be spared with adjuvant chemotherapy.