Children with extended oligoarticular and polyarticular juvenile idiopathic arthritis have alterations in B and T follicular cell subsets in peripheral blood and a cytokine profile sustaining B cell activation.

OBJECTIVES: The main goal of this study was to characterise the frequency and phenotype of B, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in peripheral blood and the cytokine environment present in circulation in children with extended oligoarticular juvenile idiopathic arthritis (extended oligo JIA) and polyarticular JIA (poly JIA) when compared with healthy controls, children with persistent oligoarticular JIA (persistent oligo JIA) and adult JIA patients. METHODS: Blood samples were collected from 105 JIA patients (children and adults) and 50 age-matched healthy individuals. The frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry. Serum levels of APRIL, BAFF, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, IL-22, IFN-γ, PD-1, PD-L1, sCD40L, CXCL13 and TNF were measured by multiplex bead-based immunoassay and/or ELISA in all groups included. RESULTS: The frequency of B, Tfh and Tfr cells was similar between JIA patients and controls. Children with extended oligo JIA and poly JIA, but not persistent oligo JIA, had significantly lower frequencies of plasmablasts, regulatory T cells and higher levels of Th17-like Tfh cells in circulation when compared with controls. Furthermore, APRIL, BAFF, IL-6 and IL-17A serum levels were significantly higher in paediatric extended oligo JIA and poly JIA patients when compared with controls. These immunological alterations were not found in adult JIA patients in comparison to controls. CONCLUSIONS: Our results suggest a potential role and/or activation profile of B and Th17-like Tfh cells in the pathogenesis of extended oligo JIA and poly JIA, but not persistent oligo JIA.

Thromboaspiration of Abdominal Aortic Mural Thrombus: A New Endovascular Approach.

Primary aortic mural thrombus (PAMT) is defined as a thrombus attached to the aortic wall in the absence of any atherosclerotic or aneurysmal disease in the aorta and a cardiac source of embolus. There is no consensus on the ideal treatment of PAMT. There are a few reports of thromboaspiration of aortic thrombus in literature. The objective of this article is to report a new endovascular approach of abdominal aortic mural thrombus. The use of Penumbra Thromboaspiration System is a feasible procedure to treat abdominal aortic thrombus and may be an option for patients unsuitable for open repair or conservative treatment.

Elastic and Thermoreversible Iongels by Supramolecular PVA/Phenol Interactions.

Iongels have attracted much attention over the years as ion-conducting soft materials for applications in several technologies including stimuli-responsive drug release and flexible (bio)electronics. Nowadays, iongels with additional functionalities such as electronic conductivity, self-healing, thermo-responsiveness, or biocompatibility are actively being searched for high demanding applications. In this work, a simple and rapid synthetic pathway to prepare elastic and thermoreversible iongels is presented. These iongels are prepared by supramolecular crosslinking between polyphenols biomolecules with a hydroxyl-rich biocompatible polymer such as poly(vinyl alcohol) (PVA) in the presence of ionic liquids. Using this strategy, a variety of iongels are obtained by combining different plant-derived polyphenol compounds (PhC) such as gallic acid, pyrogallol, and tannic acid with imidazolium-based ionic liquids, namely 1-ethyl-3-methylimidazolium dicyanamide and 1-ethyl-3-methylimidazolium bromide. A suite of characterization tools is used to study the structural, morphological, mechanical, rheological, and thermal properties of the supramolecular iongels. These iongels can withstand large deformations (40% under compression) with full recovery, revealing reversible transitions from solid to liquid state between 87 and 125 °C. Finally, the polyphenol-based thermoreversible iongels show appropriated properties for their potential application as printable electrolytes for bioelectronics.

Influence of Anion Structure on Thermal, Mechanical and CO2 Solubility Properties of UV-Cross-Linked Poly(ethylene glycol) Diacrylate Iongels.

Iongel-based CO2 separation membranes were prepared by fast (< 1 min) UV-initiated polymerization of poly(ethylene glycol) diacrylate (PEGDA) in the presence of different ionic liquids (ILs) with the [C2mim]+ cation and anions such as [TFSI]-, [FSI]-, [C(CN)3]- and [B(CN)4]-. The four ILs were completely miscible with the non-ionic PEGDA network. Transparent and free-standing iongels containing between 60 and 90 %wt of IL were obtained and characterized by diverse techniques (FTIR, TGA, DSC, DMTA, SEM, CO2 solubility and pure gas permeability). The thermal and mechanical stability of the iongels, as well as CO2 solubility, were found to be strictly dependent on the IL content and the anion's nature. The TGA results indicated that the iongels mostly follow the thermal profile of the respective neat ILs. The DMTA analysis revealed that the iongels based on fluorinated anions have higher storage modulus than those of cyano-functionalized anions. Conversely, the PEGDA-C(CN)3 iongels presented the highest CO2 solubility values ranging from 72 to 80 mmol/g. Single CO2 permeabilities of 583 ± 29 Barrer and ideal CO2/N2 selectivities of 66 ± 3 were obtained with the PEGDA-70 C(CN)3 iongel membrane. This work demonstrates that the combination of PEGDA with high contents of the best performing ILs is a promising and simple strategy, opening up new possibilities in the design of high-performance iongel membranes for CO2 separation.

The Grapevine Uncharacterized Intrinsic Protein 1 (VvXIP1) Is Regulated by Drought Stress and Transports Glycerol, Hydrogen Peroxide, Heavy Metals but Not Water.

A MIP (Major Intrinsic Protein) subfamily called Uncharacterized Intrinsic Proteins (XIP) was recently described in several fungi and eudicot plants. In this work, we cloned a XIP from grapevine, VvXIP1, and agrobacterium-mediated transformation studies in Nicotiana benthamiana revealed that the encoded aquaporin shows a preferential localization at the endoplasmic reticulum membrane. Stopped-flow spectrometry in vesicles from the aqy-null yeast strain YSH1172 overexpressing VvXIP1 showed that VvXIP1 is unable to transport water but is permeable to glycerol. Functional studies with the ROS sensitive probe CM-H2DCFDA in intact transformed yeasts showed that VvXIP1 is also able to permeate hydrogen peroxide (H2O2). Drop test growth assays showed that besides glycerol and H2O2, VvXIP1 also transports boric acid, copper, arsenic and nickel. Furthermore, we found that VvXIP1 transcripts were abundant in grapevine leaves from field grown plants and strongly repressed after the imposition of severe water-deficit conditions in potted vines. The observed downregulation of VvXIP1 expression in cultured grape cells in response to ABA and salt, together with the increased sensitivity to osmotic stress displayed by the aqy-null yeast overexpressing VvXIP1, corroborates the role of VvXIP1 in osmotic regulation besides its involvement in H2O2 transport and metal homeostasis.

Diosgenin: Recent Highlights on Pharmacology and Analytical Methodology.

Diosgenin, a steroidal sapogenin, occurs abundantly in plants such as Dioscorea alata, Smilax China, and Trigonella foenum graecum. This bioactive phytochemical not only is used as an important starting material for the preparation of several steroidal drugs in the pharmaceutical industry, but has revealed also high potential and interest in the treatment of various types of disorders such as cancer, hypercholesterolemia, inflammation, and several types of infections. Due to its pharmacological and industrial importance, several extraction and analytical procedures have been developed and applied over the years to isolate, detect, and quantify diosgenin, not only in its natural sources and pharmaceutical compositions, but also in animal matrices for pharmacodynamic, pharmacokinetic, and toxicological studies. Within these, HPLC technique coupled to different detectors is the most commonly analytical procedure described for this compound. However, other alternative methods were also published. Thus, the present review aims to provide collective information on the most recent pharmacological data on diosgenin and on the most relevant analytical techniques used to isolate, detect, and quantify this compound as well.

Independent predictors and a prognostic model for surgical outcome in refractory frontal lobe epilepsy.

PURPOSE: Refractory frontal lobe epilepsy (FLE) remains one of the most challenging surgically remediable epilepsy syndromes. Nevertheless, definition of independent predictors and predictive models of postsurgical seizure outcome remains poorly explored in FLE. METHODS: We retrospectively analyzed data from 70 consecutive patients with refractory FLE submitted to surgical treatment at our center from July 1994 to December 2006. Univariate results were submitted to logistic regression models and Cox proportional hazards regression to identify isolated risk factors for poor surgical results and to construct predictive models for surgical outcome in FLE. RESULTS: From 70 patients submitted to surgery, 45 patients (64%) had favorable outcome and 37 (47%) became seizure free. Isolated risk factors for poor surgical outcome are expressed in hazard ratio (H.R.) and were time of epilepsy (H.R.=4.2; 95% C.I.=1.5-11.7; p=0.006), ictal EEG recruiting rhythm (H.R.=2.9; 95% C.I.=1.1-7.7; p=0.033); normal MRI (H.R.=4.8; 95% C.I.=1.4-16.6; p=0.012), and MRI with lesion involving eloquent cortex (H.R.=3.8; 95% C.I.=1.2-12.0; p=0.021). Based on these variables and using a logistic regression model we constructed a model that correctly predicted long-term surgical outcome in up to 80% of patients. CONCLUSION: Among independent risk factors for postsurgical seizure outcome, epilepsy duration is a potentially modifiable factor that could impact surgical outcome in FLE. Early diagnosis, presence of an MRI lesion not involving eloquent cortex, and ictal EEG without recruited rhythm independently predicted favorable outcome in this series.

DMBT1 is frequently downregulated in well-differentiated gastric carcinoma but more frequently upregulated across various gastric cancer types.

Well-differentiated gastric carcinomas are considered to represent a distinct entity emerging via specific molecular changes different from those found in other gastric carcinoma types. The gene deleted in malignant brain tumours 1 (DMBT1) at 10q25.3-q26.1 codes for a protein presumably involved in cell differentiation and protection and has been proposed as a candidate tumour suppressor for brain and epithelial cancer. One study reported a loss of DMBT1 expression in 12.5% (5/40) of gastric cancer samples. Here, we examined in more detail DMBT1 protein and mRNA expression in 78 primary gastric tumour samples and corresponding normal gastric mucosa. DMBT1 was expressed in all non-tumour gastric mucosa tissues. Eleven out of 71 (15%) gastric tumours were negative for the DMBT1 protein in immunohistochemical analyses. Lack of DMBT1 expression was significantly more frequently found in well-differentiated gastric tumours (6/18 well-differentiated tumours vs. 5/53 other subtypes; P=0.025). Quantitative RT-PCR revealed a downregulation of the DMBT1 mRNA for 8/21 (38%) cases, while the remaining 13 cases (62%) displayed a substantial upregulation. Our data suggest that a loss of DMBT1 expression may preferentially take place in well-differentiated gastric carcinoma. However, an upregulation of DMBT1 expression is more frequently found across all gastric cancer types.

Atrial ablation for the surgical treatment of atrial fibrillation: principles and limitations.

This article reviews the development of procedures designed to eradicate atrial fibrillation by creating nonincisional lesions in the atria. Percutaneous interventional and surgical data are reviewed and analyzed. A major limitation of the surgical approaches, which utilize a variety of energy sources, appears to be the difficulty in achieving transmurality in all patients. A second limitation is related to a poor understanding of the underlying mechanisms of atrial fibrillation, and the consequent uncertainty as to the ideal lesion configurations necessary to counter these mechanisms. The article also discusses the various types of clinical atrial fibrillation, and discusses the differences between endocardial and epicardial application of thermal energy sources. Finally, atrial contractility is addressed, and the authors conclude that the ideal procedure will achieve a balance between conversion to normal sinus rhythm and the preservation of atrial contractility.

Epicardial radiofrequency applications: in vitro and in vivo studies on human atrial myocardium.

OBJECTIVES: To obtain a better understanding of tissue damage induced in human atria by epicardial radiofrequency ablation and its correlation with intra-tissue temperatures measured sub-epicardially and sub-endocardially. METHODS: Radiofrequency (RF) currents were delivered to human atrial tissues using experimental set-ups to simulate surgical RF epicardial ablation at 80, 85 and 90 degrees C. Sub-endocardial and sub-epicardial temperatures were measured with thermocouples during the ablations. Twelve samples from in vitro epicardial ablations were histologically assessed. Localized RF epicardial ablations at same temperatures were performed on 38 mitral patients with concomitant atrial fibrillation (AF) before full cardiopulmonary bypass and samples histologically assessed. All patients had endocardial RF ablation at 70 degrees C to treat AF. RESULTS: In vitro Sub-endocardial temperatures were lower than 50 degrees C except on thin atria (approximately 2-3 mm) in ablations at 80 and 85 degrees C and on thicker atria (approximately 5 mm) in ablations at 90 degrees C. Lesions measured 0.85-1.98 mm, all showed epicardial and myocardial damage but none were transmural. Mitral patients: Lesions measured 0.38-3.25 mm and 13/25 induced at 70 degrees C, 2/8 at 80 degrees C, 1/4 at 85 degrees C and 0/1 at 90 degrees C were confined to the epicardium leaving the myocardium undamaged. The remaining had damage of the epicardium and of variable portions of the myocardium, and three were transmural. CONCLUSIONS: The application temperature and the intra-tissue temperature are not the sole factors that determine lesion depth. The thickness and the composition of the epicardium and of the myocardium are major determinants in the formation of the lesion.

Intra-atrial temperatures in radiofrequency endocardial ablation: histologic evaluation of lesions.

BACKGROUND: Because of the limited information on the effects of ablation in human tissues, we studied intra-atrial temperatures during endocardial radiofrequency applications. We correlated the intra-tissue temperatures with the tissue thickness and with the histologic appearance of the lesions. METHODS: Radiofrequency currents were delivered to human atrial tissue, simulating conditions in endocardial ablation during surgery at set temperature of 70 degrees and 80 degrees C, and intra-tissue temperatures were measured with thermocouples. Radiofrequency applications at 70 degrees C were performed in patients undergoing mitral valve surgery and biopsy specimens were obtained. Samples from in vitro studies and from patients were assessed histologically. RESULTS: The subepicardial temperatures were usually over 60 degrees C in applications in vitro at 70 degrees C and over 70 degrees C in applications at 80 degrees C. Values were higher when the interior of the tissue was warmer than its surface as a result of consecutive radiofrequency applications over the same area. Histologic examination of 12 in vitro samples showed that 10 had transmural lesions. Five of 10 samples from patients with mitral valve surgery had lesions confined to the endocardium, 3 had damaged variable portions of the myocardium, and 2 had transmural lesions. CONCLUSIONS: Although it is possible to obtain transmural lesions in vitro and in vivo with endocardial applications at 70 degrees C, it is significantly more difficult to achieve transmural lesions in patients with mitral valve disease than in normal atrial tissue in vitro. Consecutive applications can raise the intra-tissue temperatures to values significantly higher than those used for application. Our findings suggest that the composition of the endocardium and of the myocardium is a major determinant in lesion formation.