Mechanical Properties of Solidifying Assemblies of Nanoparticle Surfactants at the Oil-Water Interface.

The effect of polymer surfactant structure and concentration on the self-assembly, mechanical properties, and solidification of nanoparticle surfactants (NPSs) at the oil-water interface was studied. The surface tension of the oil-water interface was found to depend strongly on the choice of the polymer surfactant used to assemble the NPSs, with polymer surfactants bearing multiple polar groups being the most effective at reducing interfacial tension and driving the NPS assembly. By contrast, only small variations in the shear modulus of the system were observed, suggesting that it is determined largely by particle density. In the presence of polymer surfactants bearing multiple functional groups, NPS assemblies on pendant drop surfaces were observed to spontaneously solidify above a critical polymer surfactant concentration. Interfacial solidification accelerated rapidly as polymer surfactant concentration was increased. On long timescales after solidification, pendant drop interfaces were observed to spontaneously wrinkle at sufficiently low surface tensions (approximately 5 mN m-1). Interfacial shear rheology of the NPS assemblies was elastic-dominated, with the shear modulus ranging from 0.1 to 1 N m-1, comparable to values obtained for nanoparticle monolayers elsewhere. Our work paves the way for the development of designer, multicomponent oil-water interfaces with well-defined mechanical, structural, and functional properties.

Microwave Ablation in Intermediate Hepatocellular Carcinoma in Cirrhosis: An Italian Multicenter Prospective Study.

Background and Aims: To report long-term results in treatment of intermediate hepatocellular carcinoma (HCC) in cirrhotics using new high-powered microwaves (MWS) ablation alone. Methods: This multicenter study included 215 cirrhotics (age range: 67-84 years; 137 males; 149 Child A, 66 Child B) who underwent percutaneous ultrasound-guided high-powered MWS ablation instead of transarterial chemoembolization. Among the patient population, 109 had a single nodule (Ø 5.3-8 cm) [group A], 70 had 2 nodules (Ø 3-6 cm) [group B] and 36 had 3-5 nodules (Ø 1.5-6.8 cm) [group C]. MWS ablation efficacy was evaluated using enhanced-computed tomography and/or magnetic resonance imaging. Primary end-point was 5-year cumulative overall survival (OS). Results: On enhanced-computed tomography and/or magnetic resonance imaging, complete ablation rates were 100% for 1.5-3.5 cm nodules. In nodules >3.5-5 cm, it was 89% for the first ablation and 100% for the second. For lesions >5-8 cm, ablation was up to 92%. Overall, 1-, 3- and 5-year survival rates were 89, 60, and 21%, respectively. The cumulative OS rate of group A was 89%, 66% and 34% at 1, 3 and 5 years. The cumulative OS rate of group B was 88%, 60% and 11% at 1, 3 and 5 years. The cumulative OS rate of group C was 86%, 55% and 0%. The 5-year survival rate was significantly different among the groups (p <0.001). One patient died from rupture of HCC. Upon multivariate analysis, preablation total bilirubin >1.5 mg/dL was an independent factor for predicting lower survival. Conclusions: Percutaneous MWS ablation of intermediate HCC is safe and effective in inducing large volume of necrosis in intermediate HCC nodules, providing long-term survival rates similar to transarterial chemoembolization. Preablation total bilirubin >1.5 mg/dL as expression of liver function reserve is the main factor predicting a worse outcome.

Droplet Coalescence and Spontaneous Emulsification in the Presence of Asphaltene Adsorption.

In a refinery, undesired high levels of salt concentration in crude oils are reduced by the contact of water with crude oils, where an emulsion is formed. Later, the separation of the water from the desalted oil is essential for the quality of both wastewater discharge and refined oil. However, complex components of crude oils such as asphaltenes may stabilize these emulsions, causing difficulties in efficient separation. Here, we show the coalescence inhibition caused by asphaltene adsorption for both water-in-oil and oil-in-water emulsions, where the oil phase consists of a simple model of asphaltenes dissolved in toluene. We find that oil-in-water emulsions are less stable than water-in-oil emulsions by using a newly developed instrument where controlled experiments can be performed to measure the coalescence time of a single droplet against an oil/water interface as a function of asphaltene aging (associated with the adsorption process of asphaltene molecules onto the interfaces) and asphaltene concentration. Furthermore, we find that the coalescence time for water droplets exhibits a maximum because of a spontaneous emulsification at the oil/water interface that produces droplets consisting of asphaltene-laden water droplets.

Percutaneous radiofrequency ablation of hepatocellular carcinoma in cirrhosis: analysis of complications in a single centre over 20 years.

OBJECTIVE: To report on our 20 years' experience on complications after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS: From 1994 to 2014, 1787 RFA procedures were performed percutaneously in 1162 patients with cirrhosis (852 Child A and 310 Child B) with HCC nodules (1.2-7 cm), prothrombin time >50%, platelet count of 50.000 mm3 and total bilirubin ranging from 0.80 to 4.5 mg dl-1. In 67 patients, RFA was performed on both intraparenchymal HCC nodule and tumour thrombus extended in the main portal vein and/or its branches. RESULTS: Four patients (0.3%) died after RFA. 39 patients (3.2%) changed in Child's class: 26 out of 28 Child A patients with cirrhosis changed to Child B and 2 changed to Child C class; 11 Child B patients changed to Child C class. On multivariate analysis, the total bilirubin pre-RFA was the only independent risk factor for impairment of liver function and death. Complications were hemoperitoneum, abscess and intrahepatic haematoma. CONCLUSION: RFA of HCC in patients with cirrhosis is safe, even in case of invasion of the portal venous system. Functional liver reserve should be strictly monitored, mainly when pre-RFA total bilirubin value is >2.5 mg dl-1. The study was approved by our institutional review board. Advances in knowledge: The total bilirubin value >2.5 mg dl-1 represents the main marker of functional liver reserve that predicts decompensation of liver cirrhosis in patients undergoing RFA for HCC.

Dysmorphic patterns are associated with cytoskeletal alterations in human oocytes.

Study question: Are specific morphological anomalies in human mature oocytes, as revealed by transmitted light microscopy, associated with intrinsic damage to the meiotic spindle and actin cytoskeleton? Summary answer: Aggregates of smooth endoplasmic reticulum (SER) and domains of centrally localized granular cytoplasm (GC) reflect intrinsic damage to the oocyte cytoskeleton, namely alterations in spindle size, chromosome misalignment and cortical actin disorganization. What is known already: In preparation for ICSI, oocytes are often selected for use in treatment by morphological criteria, but the rationale and implications of this practice are controversial. Very little information is available on the relationship between oocyte morphology and intrinsic cellular characteristics, such as the actin cytoskeleton, meiotic spindle and chromosome alignment. Study design, size, duration: A total of 170 metaphase II (MII) oocytes were donated by consenting IVF patients and analysed; 62 were classified as morphologically normal (control), 54 had SER clusters and 54 had centrally localized GC. Participants/materials, setting, methods: Supernumerary oocytes were fixed within 3 h from recovery and stained for tubulin, chromatin and actin. Spindles were analysed for 1D and 2D characteristics by high-performance confocal microscopy. Chromosomes were classified as scattered or aligned and the conformation and intensity of cortical actin was evaluated. Main results and the role of chance: In comparison with control oocytes, both SER and GC oocytes showed greater spindle length (P = 0.033 and 0.003, respectively) and GC oocytes also showed greater spindle width (P= 0.049) and area (P= 0.036). Control and SER oocytes had statistically comparable rates of chromosome displacement from the metaphase plate, unlike GC oocytes where chromosome displacement occurred at higher rate (P = 0.013). In situations where a complete Z-stack was reconstructed from a polar angle, chromosome disposition was classified as being normal when two sets of concentric arrays were visible. Based on these parameters, the proportions of oocytes with normal chromosomal arrangement or partial/total disarrangement was not statistically different between control and SER oocytes. Conversely, in GC oocytes, chromosome disarrangement was higher (P = 0.002). All control oocytes displayed a continuous meshwork of suboolemmal actin, which appeared as an uninterrupted ring in thin optical sections. In contrast, in SER and  GC groups, integrity of suboolemmal actin was observed in only 66.7 and 42.9% of oocytes, respectively (P = 0.0001). Large scale data: N/A. Limitations reason for caution: Only two of several known oocyte dysmorphisms were investigated, while oocyte quality was assessed only by cytoskeletal criteria. Wider implications of the findings: This study represents a significant step toward a more objective assessment of oocyte morphology, offering information that can assist embryologists to make a more aware and rationally founded decision on whether, and with what possible implications, oocytes with certain dysmorphic characters should be used for treatment or discarded. More generally, it also demonstrates that morphometric parameters of the cytoskeleton and chromosome organization can be used as biomarkers of oocyte quality. Study funding and competing interest(s): This study was funded by Biogenesi Reproductive Medicine Centre (Monza, Italy). All authors declare no conflict of interests.

Sorafenib Combined with Radio-frequency Ablation Compared with Sorafenib Alone in Treatment of Hepatocellular Carcinoma Invading Portal Vein: A Western Randomized Controlled Trial.

AIM: To compare in a randomized controlled trial (RCT) 3-year survival of cirrhotic patients with hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombus (PVTT) treated with sorafenib plus percutaneous radiofrequency ablation (RFA) of both intraparenchymal HCC and PVTT (combination Group) or sorafenib alone (sorafenib-alone Group). PATIENTS AND METHODS: Ninety-nine consecutive Child A cirrhotics were randomized to receive RFA of both HCC and main portal vein tumor thrombus (MPVTT) plus sorafenib (n=49) or sorafenib alone (n=50). RESULTS: One-, 2- and 3-year survival rates were 60%, 35% and 26%, respectively, in the combination group and 37% and 0 % at 1- and 2-year, respectively, in the sorafenib alone group. At multivariate analysis, the combination of RFA of both HCC and MPVTT was the only factor predicting survival. CONCLUSION: Use of RFA of both HCC and MPVTT plus sorafenib significantly increases 3-year survival compared to sorafenib alone.

Contrast-Enhanced Ultrasound: a Simple and Effective Tool in Defining a Rapid Diagnostic Work-up for Small Nodules Detected in Cirrhotic Patients during Surveillance.

BACKGROUND AND AIMS: Disappearance of portal blood flow and arterial vascularization is the hallmark of hepatocarcinogenesis. The capability of a dynamic imaging modality detecting arterial hypervascularization of small nodules is crucial to promote a rapid diagnostic and therapeutic work-up improving survival. We aimed to evaluate the capability of CEUS to detect arterial vascularization of ≤ 2 cm HCC nodules arising during surveillance so as to shorten the diagnostic and therapeutic work-up. METHODS: From October 2009 to September 2014, among 1757 consecutive cirrhotic patients under surveillance with ultrasound (US), 243 patients had new single nodules 7-20 mm; 229/243 had a conclusive histologic diagnosis and comprised the study group. All patients underwent CEUS followed by enhanced MRI and US guided percutaneous 18G needle core biopsy of the nodules. Of the 229 nodules, 27 were hyperechoic, 171 hypoechoic and 31 isoechoic lesions. RESULTS: The histology results revealed that 199/229 nodules were HCC and 30 were benign. Of 199 HCC, CEUS evidenced arterial hypervascularity in 190 nodules (95.5%) (sensitivity 94.48 %, specificity 100%, PPV 100%, NPV 76.92 %). Of the 39 CEUS arterial-unenhanced nodules, 30 were benign and 9 (23%) were well-differentiated HCC. eMRI showed arterial hypervascularity in 199 nodules (86,9%). Of these, only 193 (97%) were histologically HCCs while 6 were benign (sensitivity: 97%, specificity: 80%, PPV: 97%, NPV: 80%). CONCLUSIONS: CEUS has a great capability to detect arterial hypervascularity of small HCC. Because only 4.5% of new nodules escape the demonstration of arterial hyervascularity, CEUS must be performed immediately after conventional US to contrast the malignant fate of small lesions arising in a cirrhotic liver.

Depletion, melting and reentrant solidification in mixtures of soft and hard colloids.

We present extensive experimental and theoretical investigations on the structure, phase behavior, dynamics and rheology of model soft-hard colloidal mixtures realized with large, multiarm star polymers as the soft component and smaller, compact stars as the hard one. The number and length of the arms in star polymers control their softness, whereas the size ratio, the overall density and the composition are additional parameters varied for the mixtures. A coarse-grained theoretical strategy is employed to predict the structure of the systems as well as their ergodicity properties on the basis of mode coupling theory, for comparison with rheological measurements on the samples. We discovered that dynamically arrested star-polymer solutions recover their ergodicity upon addition of colloidal additives. At the same time the system displays demixing instability, and the binodal of the latter meets the glass line in a way that leads, upon addition of a sufficient amount of colloidal particles, to an arrested phase separation and reentrant solidification. We present evidence for a subsequent solid-to-solid transition well within the region of arrested phase separation, attributed to a hard-sphere-mixture type of glass, due to osmotic shrinkage of the stars at high colloidal particle concentrations. We systematically investigated the interplay of star functionality and size ratio with glass melting and demixing, and rationalized our findings by the depletion of the big stars due to the smaller colloids. This new depletion potential in which, contrary to the classic colloid-polymer case, the hard component depletes the soft one, has unique and novel characteristics and allows the calculation of phase diagrams for such mixtures. This work covers a broad range of soft-hard colloidal mixture compositions in which the soft component exceeds the hard one in size and provides general guidelines for controlling the properties of such complex mixtures.

Double-strand DNA breaks and repair response in human immature oocytes and their relevance to meiotic resumption.

PURPOSE: Only 50-60 % of immature human oocytes attain the mature stage in vitro. Such a deficiency may be a reflection of inadequate conditions of in vitro maturation (IVM) or a manifestation of intrinsic oocyte defects. In the present study, we explored the possibility that the DNA of immature oocytes may be damaged and that such a condition, or inability to trigger a repair action, is associated to germinal vesicle (GV) arrest. METHODS: Immature oocytes (GV-stage oocytes) were obtained from women undergoing stimulated (Stim-C) or IVM (IVM-C) cycles. GV oocytes obtained from stimulated cycles were fixed for successive analysis either after recovery (T0) or following 30 h (T30) of culture if still arrested at the GV stage. Oocytes retrieved in IVM cycles were used only if they were found arrested at the GV stage after 30 h (T30) of culture. All oocytes were fixed and stained to detect chromatin and actin. They were also assessed for positivity to γH2AX and Rad51, markers revealing the presence of double-strand DNA breaks and the activation of a DNA repair response, respectively. Labelled oocytes were analysed using a Leica TCS SP2 laser scanning confocal microscope. RESULTS: In Stim-C oocytes, γH2AX positivity was 47.5 and 81.5 % in the T0 and T30 groups, respectively (P = 0.003), while γH2AX-positive oocytes were 58.3 % in the IVM-C T30 group (Stim-C T0 vs. IVM-C T30, P = 0.178; Stim-C T30 vs. IVM-C T30, P = 0.035). Positivity for nuclear staining to Rad51 occurred in 42.1 and 74.1 % of Stim-C in the T0 and T30 subgroups, respectively (T = 0.006), while 66.7 % of IVM-C T30 oocytes resulted positive for a DNA repair response (Stim-C T0 vs. IVM-C T30, P = 0.010; Stim-C T30 vs. IVM-C T30, P = 0.345). CONCLUSIONS: The present data document the existence of double-strand DNA breaks (DSBs) in human immature oocytes. Also, they are consistent with the hypothesis that insults to DNA integrity may be an important factor affecting meiotic resumption.

Pulmonary artery intramural hematoma associated with Stanford type B aortic dissection.

Pulmonary artery intramural hematoma is a very rare condition that can occur isolated or in patients with aortic dissection, usually of Stanford type A. We present a rare case of pulmonary artery intramural hematoma associated with a Stanford type B aortic dissection in an 85-year-old man.

Cumulus cell-oocyte complexes retrieved from antral follicles in IVM cycles: relationship between COCs morphology, gonadotropin priming and clinical outcome.

PURPOSE: To assess retrospectively the developmental potential of different types of cumulus cell-oocyte complexes (COCs) derived from IVM cycles. METHODS: IVM cycles were performed in natural cycles or after HCG, FSH, or FSH/HCG priming. COCs recovered were morphologically characterized in different types: compact (CC) or expanded (EC) cumulus mass but including an immature oocyte, and expanded cumulus mass enclosing a mature oocyte (EC-MII). Embryo developmental competence was investigated analysing exclusively cycles in which all transferred embryos derived from the same COC category. RESULTS: Fertilization rates did not differ significantly. Significant differences in pregnancy rates (14.5%, 10.0% and 27.6 % in the CC, EC, and EC-MII categories, respectively) were observed. Likewise, significant differences in implantation rates (8.9%, 6.3% and 19.1% in the CC, EC, and EC-MII categories, respectively) were found. Overall, priming with FSH/HCG had a beneficial effect on pregnancy and implantation rates, while no priming or HCG alone generated oocytes with poor competence. CONCLUSIONS: In IVM cycles, morphological evaluation at the time of collection can predict the developmental ability of different COCs. FSH/HGC priming has a positive effect on oocyte competence.

Efficacy of rituximab in gastric diffuse large B cell lymphoma patients.

AIM: To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma (DLBCL). METHODS: Sixty patients (median age: 58 years) with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007, were included in this analysis. Patients were selected by stage (I-IV, Lugano staging system), European Cooperative Oncology Group performance status (0-2) and treatment strategies. Treatment strategies were chemotherapy alone (group A, n = 30) [scheduled as cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) and CHOP-like], and chemotherapy combined with rituximab (group B, n = 30). The primary end point of the study was complete response (CR) rate; the secondary end points were disease-free survival (DFS) at 5 years and overall survival (OS). RESULTS: Median follow-up was 62 mo (range: 31-102 mo). We observed a significant difference between the two groups (A vs B) in terms of CR [76.6% (23/30) vs 100%, P = 0.04) and DFS at 5 years [73.3% (22/30) vs 100%, P = 0.03). To date, 19 group A (63.3%) patients are alive and 11 have died, while all group B patients are alive. No significant differences in toxicity were observed between the two groups. CONCLUSION: Rituximab in combination with chemotherapy improves CR rate, DFS and OS. Further prospective trials are needed to confirm our results.