bluuebunny/crossref_metadata_2025 huggingface dataset:
GDNF Increases the Density of Cells Containing Calbindin but Not of Cells Containing Calretinin in Cultured Rat and Human Fetal Nigral Tissue
Authors: Meyer Morten , Zimmer Jens , Seiler Rolf W. , Widmer Hans R.
Published: June 2017

Among the dopaminergic neurons in substantia nigra pars compacta and in the ventral tegmental area, subpopulations express the calcium-binding proteins calbindin (CB) and calretinin (CR), and the CB-containing neurons are supposed to be less prone to degeneration in Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for nigrostriatal dopaminergic neurons. Using free-floating roller-tube (FFRT) cultures derived from fetal rat (E14) ventral mesencephalon we found that GDNF (10 ng/ml) significantly increased the number of surviving tyrosine hydroxylase (TH)-immunoreactive neurons. The possible effects of GDNF treatment on CB-immunoreactive (CB-ir) and CR-ir neurons in such cultures were examined in the present study. The neuronal cell densities were measured by quantifying the numbers of CB-ir and CR-ir neurons in areas of sections through the most extensive parts of the spherical cultures. In 4-day-old and 8-day-old cultures GDNF treatment increased the density of CB-ir neurons by 50% and 59%, respectively. Partial co-existence of TH and CB was shown using the method of double immunolabeling. The density of CR-containing neurons was unaffected by GDNF treatment as confirmed by Western blotting for CR. Parallel effects of GDNF treatment were obtained for cultures of human fetal ventral mesencephalon (8 weeks postconception). In conclusion, our findings identify GDNF as a potent factor for fetal rat and human nigral CB-ir neurons able to promote their survival in culture. Referring to a suggested neuroprotective role of CB, the results may be of relevance in the context of neuronal transplantation of patients suffering from severe Parkinson's disease.
In Vivo Evaluation of Glucose Permeability of an Immunoisolation Device Intended for Islet Transplantation: A Novel Application of the Microdialysis Technique
Authors: Rafael E. , Wernerson A. , Arner P. , Wu G. S. , Tibell A.
Published: June 2017

Immunoisolation devices consist of semipermeable membranes chosen to protect the islets from the immune system but still allow sufficient passage of nutrients, oxygen, and the therapeutic products, insulin. The exchange between the device and the microcirculation will influence the survival of the graft as well as the metabolic efficacy of the islet implant. Glucose is the important trigger factor for insulin secretion. In this study, we evaluate the in vivo glucose permeability of the Theracyte™ immunoisolation device at various times after implantation. Empty devices were implanted SC in rats. The glucose kinetics in the device was compared to that in the SC tissue during IV glucose tolerance tests (IVGTTs), using the microdialysis technique. In rats studied on day 1, or 1, 2, and 4 weeks after implantation, the peak glucose levels (Cmax) were significantly lower, the times-to-peak (TTP) were significantly longer, and the areas under the curve during the first 40 min (AUC0–40) were significantly smaller in the device than in the SC fat. However, at 3 months all parameters improved and Cmax, TTP, and AUC0–40 in the device did not differ significantly from those measured in the SC fat. Thus, during the first 4 weeks the device constitutes a significant diffusion barrier, but at 3 months the exchange between the lumen of devices and the blood stream improves. Our data indicate that implantation of the device several months before transplantation of the cellular graft would improve the exchange across the membrane during the early posttransplant period. This should have positive effects on graft survival and function. We also suggest that microdialysis is a useful tool for evaluating the in vivo performance of macroencapsulation devices.
Studies on Smaller (~315 μM) Microcapsules: IV. Feasibility and Safety of Intrahepatic Implantations of Small Alginate Poly-L-Lysine Microcapsules
Authors: Leblond François A. , Simard Ginette , Henley Nathalie , Rocheleau Bernard , Huet P.-Michel , Hallé Jean-Pierre
Published: June 2017

The most successful transplantation site of nonencapsulated islets of Langerhans is the liver. Because usual alginate poly-L-lysine microcapsules were too large (700–1200 μm diameter) for intravascular implantations and were almost exclusively implanted intraperitoneally, the question of the preferred implantation site of microencapsulated islets has received little attention. The feasibility of implanting smaller (~315 μm) alginate poly-L-lysine microcapsules into the liver and the effect of such implantations on portal pressure and liver histology was evaluated in Wistar rats. A bolus of 10,000 microcapsules of 315 μm diameter was injected intraportally (group 1; n = 22). The portal pressure increased from 6.4 ± 1.8 mmHg to a maximum of 19 mmHg, returned to basal levels within 2 h, and remained normal after 2 months. In group 2 (n = 3), following the injection of 10,000 larger microcapsules (420 μm), the portal pressure increased to > 60 mmHg and two out of the three rats died within 3 h. When 5,000 microcapsules of 420-μm diameter were injected (group 3; n = 5), the portal pressure peaked to 30 ± 8 mmHg and remained elevated after 4 h (12 ± 3 mmHg), but returned to normal (8 ± 1 mmHg) after 2 weeks. Histological studies showed normal hepatic architecture without collagen deposition into portal tracts occupied by microcapsules. Conclusion: intrahepatic implantations of ~315-μm alginate poly-L-lysine microcapsules are feasible and safe. These results justify further investigation of this potential implantation site for microencapsulated islets.
Enhanced Cytochrome P450 IA1 Activity of Self-Assembled Rat Hepatocyte Spheroids
Authors: Wu Florence J. , Friend Julie R. , Remmel Rory P. , Cerra Frank B. , Hu Wei-Shou
Published: June 2017

Primary rat hepatocytes can self-assemble to form multicellular spheroids when plated onto Primaria petri dishes. Spheroids have been observed to exhibit enhanced liver-specific functions and differentiated ultrastructure compared to monolayer cultures on dry collagen. With confocal scanning laser microscopy, CYP1A1 activity was evaluated in situ by detecting resorufin. This highly fluorescent molecule is the P450-mediated product of 7-ethoxyresorufin O-dealkylation (EROD). Significantly higher P450 activity was observed in spheroids compared to monolayers on collagen upon induction with 50 μM β-naphthoflavone (BNF), a CYP1A inducer. This was confirmed by measuring microsomal EROD activity. The distribution of CYP1A1 activity within spheroids was heterogeneous, with higher activity localized to the hepatocytes in the interior. During the process of spheroid formation, cells were initially seen to attach and spread out as a monolayer. This stage was associated with relatively low CYP1A1 activity. As cells formed multicellular structures and aggregated into spheroids, the level of CYP1A1 activity increased over time. At least a fivefold higher fluorescence intensity was observed in spheroids compared to that of monolayers maintained on collagen. The higher P450 activity within spheroids may be associated with their ability to maintain a greater degree of differentiation compared to monolayers. These studies demonstrate the potential of hepatocyte spheroids as a model system for investigating drug metabolism, tissue engineering, and tissue self-assembly.
Intraductal Collagenase Delivery into the Human Pancreas Using Syringe Loading or Controlled Perfusion
Authors: Lakey Jonathan R. T. , Warnock Garth L. , Shapiro A. M. James , Korbutt Gregory S. , Ao Ziliang , Kneteman Norman M. , Rajotte Ray V.
Published: June 2017

Effective intraductal delivery of the enzyme collagenase into the pancreas is crucial to the subsequent ability to isolate viable islets. Most clinical islet transplant centers load the enzyme into the pancreas by retrograde injection using a syringe following cannulation of the pancreatic duct. An alternative approach is to perfuse the pancreas via the pancreatic duct with collagenase solution using a recirculating perfusion device system. This provides control over perfusion pressures and collagenase temperature. This study reports on our evaluation of the delivery of Liberase™-HI into the pancreas of 14 consecutive adult multiorgan cadaveric donors. Alternate glands were procured and processed using an identical protocol with the exception of collagenase delivery. The first group of pancreases was loaded using the perfusion technique where cold (4°C) Liberase™-HI was perfused at 80 mmHg for 5 min after which the pressure was increased to 180 mmHg. The collagenase solution was then slowly warmed to 35°C, transferred to the dissociation chamber and mechanically dissociated, and then purified using discontinuous gradients of Ficoll. Pancreases in the second group were loaded with collagenase (28–32°C) using the syringe technique before mechanical dissociation and purification. There were no significant differences in pancreas cold ischemia, donor age, body mass index, maximum blood glucose, or serum amylase of the donors between the two groups. Mean collagenase digestion time in the digestion chamber was not different between the two groups; however, the amount of undigested tissue remaining after dissociation was significantly higher in the syringe-loaded group (15.3 ± 2.6 g vs. 4.6 ±2.1 g, mean ± SEM, p < 0.05). Postdigestion recovery of islets was 471 ± 83 × 103 IE in the perfusion group compared with 391 ± 57 × 103 IE for the syringe-loaded group. Postpurification recovery was higher in the perfused group (379 ± 45 vs. 251 ± 28 × 103 IE, p < 0.05, two-tailed paired t-test). No difference in in vitro islet viability was observed between the two groups following glucose perifusion with the calculated stimulation index of 4.6 ± 0.6 for the perfusion group and 4.2 ± 0.7 for the syringe-loaded group. Controlled perfusion via the pancreatic duct allows the effective delivery of the enzyme achieving maximal distension to all regions of the pancreas leading to an increased recovery of the islets with no detrimental effect on subsequent in vitro islet function.
Evaluation of Reaction of Primate Brain to Grafted PC12 Cells
Authors: Yoshida Hideyuki , Date Isao , Shingo Tetsuro , Fujiwara Kenjiro , Miyoshi Yasuyuki , Furuta Tomohisa , Ohmoto Takashi
Published: June 2017

Intrastriatal implantation of polymer-encapsulated PC12 cells, which constitute a dopaminergic cell line derived from rat pheochromocytoma, has proved useful for ameliorating parkinsonian symptoms in several kinds of animals. In considering the clinical application of this technique, we should make sure that PC12 cells are rejected completely by the host immune system in case the capsule breaks. In the present study, unencapsulated PC12 cells were injected into the brain of Japanese monkeys (Macaca fuscata). Histological [hematoxylin-eosin (H&E), Nissl] and immunocytochemical [tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP)] analyses were performed 1, 2, 4, and 8 weeks after transplantation. Also, encapsulated PC12 cells were transplanted into the brain of another group of Japanese monkeys to investigate the host reaction to the capsule and to confirm that the encapsulated PC12 cells continue to survive in the host brain. H&E and GFAP staining were performed 2, 4, and 8 weeks after transplantation. L-DOPA and dopamine release from the explanted capsules was measured by high performance liquid chromatography. Magnetic resonance imaging was performed in both unencapsulated and encapsulated PC12 cell grafted groups. Although the xenografted unencapsulated cells formed a small cluster at 1 and 2 weeks after implantation, very few and no viable PC12 cells remained at 4 and 8 weeks, respectively. The reaction of the host towards the xenograft gradually decreased. Encapsulated PC12 cells retrieved from the host brain were found to release L-DOPA and dopamine continuously even 8 weeks after implantation. The host reaction to the PC12-loaded capsule was much weaker than that to the unencapsulated PC12 cells, and decreased with time. These results indicate that encapsulated PC12 cell transplantation is an effective and safe strategy for the treatment of Parkinson's disease.
Increased Myogenic Potential and Fusion of Matrilysin-Expressing Myoblasts Transplanted in Mice
Authors: Caron Nicolas J. , Asselin Isabelle , Morel Guy , Tremblay Jacques P.
Published: June 2017

The success of myoblast transplantation in clinical trials has been limited in part by the low dispersion of grafted cells outside the injection site. Our research group previously reported that the culture of myoblasts with concanavalin A, a stimulator of metalloproteinase production, increased their migration. Several lines of evidence also suggested that muscle cell fusion involves metalloproteinase-sensitive mechanisms. To determine whether the increased expression of metalloproteinases had an influence on myoblast fusion and dispersion through the muscle following transplantation, we generated a myoblast cell line expressing human matrilysin (MMP-7). The MMP-7-expressing myoblasts were obtained by the stable transfection of a matrilysin expression vector in a TnILacZ immortomouse myoblast clone. Matrilysin-expressing myoblasts showed a highly increased in vitro fusion index, forming seven times (p < 0.001) more myotubes than the control cell line and three times (p < 0.001) more myotubes than the Immortomyoblast parental clone. Single-site transplantation of matrilysin-expressing myoblasts generated more fibers (p < 0.001), over a greater surface (p < 0.001) than the control cell line. The cotransplantation of matrilysin-expressing myoblasts and of normal human myoblasts in SCID mice increased the number of human dystrophin-positive fibers and myotubes by sixfold. Although no significant increased migration of myoblasts outside the injection sites was observed, our results show that the metalloproteinase activity can improve the myogenic potential of myoblasts in vitro and the fusion of myoblasts with host fibers in vivo. MMP-7 expression may be useful in increasing myoblast transplantation success.
Lack of Effect of Short-Term Depletion of Plasma Complement C3 on the Survival of Syngeneic Dopaminergic Neurons following Grafting into the Intact Rat Striatum
Authors: Khorooshi M. H. , Meyer M. , Pedersen E. B. , Finsen B.
Published: June 2017

Metabolically compromised cells may be subject to complement-mediated cytotoxicity. The aim of this study was to clarify to what extent plasma complement C3 might contribute to the low survival (5–20%) of grafted dopaminergic neurons. The survival of intrastriatal cell suspension grafts of syngeneic dopaminergic, tyrosine hydroxylase (TH)-containing neurons was compared in rats subjected to short-term IV treatment with 1) cobra venom factor (CVF), or 2) placebo treatment. Depletion of plasma complement C3 by CVF was confirmed by crossed immunoelectrophoresis. With 159 ± 37 (mean ± SEM) TH-immunoreactive and 154 ± 40 TH mRNA-expressing neurons in the CVF-treated rats (n = 9), and 117 ± 34 TH-immunoreactive and 160 ± 49 TH mRNA-expressing neurons in placebo rats (n = 6), the CVF treatment did not increase the survival of the grafted dopaminergic neurons. Similarly, CVF had no apparent effect on the astroglial, microglial, or oligodendroglial cell response within and around the graft. The data indicate that depletion of plasma complement C3 at the time of grafting has no effect on the long-term survival of syngeneic ventral mesencephalic dopaminergic neuronal grafts.
Immunosuppression and Rejection of Cartilage Formed by Allogeneic Chondrocytes in Rats
Authors: Osiecka-Iwan Anna , Hyc Anna , Moskalewski Stanislaw
Published: June 2017

Rat syngeneic and allogeneic chondrocytes were transplanted intramuscularly or into defects prepared in articular cartilage (intracartilaginous transplants). Recipients of allogeneic transplants received cyclosporin A (CsA), cladribine (2-chlorodeoxyadenosine, 2-CdA), or both drugs in combination. Transplants were taken for examination after 5 weeks. Cartilage formed intramuscularly by syngeneic chondrocytes was ossified. Allogeneic cartilage was resorbed by infiltrating cells. CsA or 2-CdA partially suppressed, and both these agents in combination strongly suppressed, formation of infiltrations. Both syngeneic and allogeneic chondrocytes formed cartilage in joint surface defects but only allogeneic cartilage was attacked by infiltrating cells. CsA + 2-CdA treatment slightly decreased intensity of infiltrations but did not prevent cartilage resorption. Antichondrocyte response was studied by evaluation of spleen mononuclear cells (SMC) stimulation in mixed splenocyte–chondrocyte cultures and by detection of antichondrocyte cytotoxic antibodies. SMC stimulation index (SI) was calculated separately for syngeneic and allogeneic chondrocytes. Comparison of SMC SI for syngeneic and allogeneic chondrocytes indicated lack of stimulation of SMC from control or syngeneic transplant recipients and significant stimulation of SMC from recipients of allogeneic transplants. SMC from animals treated with CsA + 2-CdA were not stimulated. Additional experiments aiming at an explanation of the lack of stimulation of SMC from intact animals by syngeneic chondrocytes reported in this work and contrary to other findings disclosed that it was caused by the use of collagenase solution containing Nα-p-tosyl-l-lysine chloromethyl ketone for chondrocyte isolation. Spontaneous antichondrocyte cytotoxic antibody activity was found in intact rats raised only in sera from recipients of allogeneic intramuscular transplants without immunosuppression. Thus, strong immunosuppressive treatment of rats with allogeneic chondrocyte transplants was more effective in relation to the general immunological response than to the local reaction.
Pretreatment with Glucocorticoids Enhances T-Cell Effector Function: Possible Implication for Immune Rebound Accompanying Glucocorticoid Withdrawal
Authors: Almawi Wassim Y. , Hess David A. , Assi Joumana W. , Chudzik Dagmara M. , Rieder Michael J.
Published: June 2017

Glucocorticoids (GCs) exert their immunosuppressive/antiproliferative effects largely through inhibition of cytokine expression, and paradoxically upregulate the expression of (proinflammatory) cytokine receptors on select nonlymphoid cells. Clinically, withdrawal of GCs was frequently associated with worsening of the outcome of heightened immunity disorders, thereby implicating enhanced cytokine and cytokine receptor expression as a possible consequence of acute/short-term GCs withdrawal. In view of the significance of this complication of GC therapy, we addressed the effect of GC withdrawal on cytokine receptor expression and subsequent T-cell effector function, using the proliferation of human T cells as biological readout. To mimic GC withdrawal, T cells were treated with GCs or controls, stimulated, and incubated for 16–20 h at 37°C, washed, and reactivated for a further 4–48 h. Surface marker expression was assessed by FACS analysis, and proliferation was determined by measuring the cellular uptake of tritiated thymidine. Dexamethasone (DEX) and prednisolone (PRED), in a concentration-dependent manner, inhibited T-cell proliferation induced by anti-CD28 Ab + PMA. However, pretreatment of T cells activated with mitogens, cross-linking antibodies, or PMA + ionomycin (“CD3-bypass” stimulation regimen), but not resting T cells, with DEX or PRED resulted in a marked increase in IL-1R, IL-2Rα, and IL-6R expression, which was accompanied by a significant enhancement in T-cell proliferation. This effect of GCs was neither stimulus specific nor did it result from alteration in cell viability, and was paralleled by augmentation in cytokine (rIL-2) effects on DEX-pretreated and preactivated T cells. Taken together, our results underline the dual effects of GCs in regulating T-cell activation and cytokine expression. In essence, GCs directly inhibited T-cell proliferation by suppressing cytokine production, and, by enhancing cytokine receptor expression, pretreatment with GCs augmented T-cell proliferation.
Xenogeneic Transplantation of Porcine Hepatocytes into the CCl4 Cirrhotic Rat Model
Authors: Stefan Andreas M. , Coulter Sarah , Gray Brian , Lamorte Wayne , Nikelaeson Sigfus , Edge Albert S. B. , Afdhal Nezam H.
Published: June 2017

Liver support using extracorporeal devices and hepatocyte transplantation has received renewed interest for the management of acute and chronic liver failure. The aim of this study was to determine whether xenogeneic porcine hepatocytes could integrate into the liver parenchyma of cirrhotic Lewis rats when administered by an intrasplenic route. Cirrhosis was induced by carbon tetrachloride (CCl4) inhalation and confirmed histologically. Freshly isolated porcine hepatocytes were infused directly into the splenic pulp at laparotomy over a 5–15-min interval. Using 111In-labeled hepatocytes, the degree of localization of porcine hepatocytes to the spleen and liver was found to be greater than 60% in both control and cirrhotic rats. Integration of porcine hepatocytes into the rat liver parenchyma was determined by immunohistochemical staining for porcine albumin in rat liver sections. Further confirmation was provided by in situ hybridization using a porcine-specific probe that binds to a distinct repetitive element (PRE) in porcine DNA. Evidence of integrated porcine hepatocytes was seen for over 50 days in animals under cyclosporine immunosuppression. These data demonstrate the integration of xenogeneic porcine hepatocytes into the liver of the cirrhotic rat and their ability to produce porcine albumin for up to 50 days.
Users on Social Network Sites—Flight from Reality and Its Effects on Acceptance of Social Network Advertising: A Gratification Perspective
Authors: Mir Imran Anwar
Published: June 2017

Social network sites (SNSs) have emerged as a common place for social interactivity and communication in cyberspace. They have rapidly grown in fame and user acceptance globally. The business model of many of these SNS firms is based on advertising. Therefore, it is crucial that users accept social network advertising (SNA). Literature shows that users accept the advertising which is congruent with their motivations for using media. Many people participate in SNSs to forget the problems and worries of everyday life. Yet, empirical evidence is lacking which shows the effects of social escapism motivation on user acceptance of SNA. Grounded on the uses and gratifications theory, the present study proposes and tests a model which shows the effects of social escapism motivation on user attitudes toward SNA as well as on their SNS banner ad-clicking behaviour.
Ethanol-induced symptoms in patients receiving gemcitabine diluted from a concentrate for solution for infusion containing ethanol
Authors: Diez-Fernández Raúl , Vázquez-Sánchez Rocío , López-Esteban Laura , Enrech-Frances Santos , Sánchez-Peña Ana María , Díaz-Paniagua Laura , Soria-Tristán Miguel , Martín Martínez José Miguel , Molina-García Teresa
Published: June 2017

Purpose

Ethanol as an excipient is used to enhance the solubility of gemcitabine, but, sometimes, the dose of ethanol a patient may be given is much higher than the dose considered to be toxic. We aimed to assess ethanol-related symptoms and signs in patients receiving two formulations of gemcitabine, with and without ethanol.

Methods

A randomized double blind cross-over study was conducted. All patients being treated with gemcitabine received two consecutive doses of the drug, one diluted from a concentrate for solution for infusion (CSI) containing ethanol and the other from a lyophilized powder, without ethanol, which was used as control group. After each administration, patients were surveyed in order to assess the appearance of any alcohol consumption symptoms (dizziness, difficulty speaking, unsteady walking, impaired balance, mood swings and slower reactions). Widmark formula and the amount of alcohol measured on the breath (breathalyzer) were used to estimate blood alcohol concentration.

Results

Twenty-four patients received both formulations and were included in the analysis. Mean administered ethanol dose when prepared from CSI was 15.81 ± 2.25 g (mean ± SD). When using CSI gemcitabine, estimated blood ethanol concentration was 0.033 g/dl according to Widmark formula and 0.02 g/dl according to breathalyzer results. Although overall incidence of symptoms was higher in the study group, the difference was not statistically significant (33% vs. 25%; p = 0.53).

Conclusions

These findings prove there is no difference in the onset of ethanol related symptoms when using CSI instead of lyophilized powder on the reconstitution of gemcitabine.
A third-order shear deformation theory for nonlinear vibration analysis of stiffened functionally graded material sandwich doubly curved shallow shells with four material models
Authors: Dong Dang T , Van Dung Dao
Published: June 2017

This study presents a nonlinear vibration analysis of function graded sandwich doubly curved shallow shells, which reinforced by functionally graded material stiffeners and rested on the Pasternak foundation. The shells are subjected to the combination of mechanical, thermal, and damping loading. Four models of the sandwich shells with general sigmoid and power laws distribution are considered. The governing equations are established based on the third-order shear deformation theory. Von Kármán-type nonlinearity and smeared stiffener technique are taken into account. The explicit expressions for determining natural frequencies, nonlinear frequency–amplitude relation, and time–deflection curves are obtained by employing the Galerkin method. Finally, the fourth-order Runge–Kutta method is applied to investigate the influences of functionally graded material stiffeners, the boundary conditions, the models of the shells, thermal environment, foundation and geometrical parameters on the natural frequencies and dynamic nonlinear responses of the sandwich shells.
A Quantitative Systems Pharmacology Platform to Investigate the Impact of Alirocumab and Cholesterol-Lowering Therapies on Lipid Profiles and Plaque Characteristics
Authors: Ming Jeffrey E , Abrams Ruth E , Bartlett Derek W , Tao Mengdi , Nguyen Tu , Surks Howard , Kudrycki Katherine , Kadambi Ananth , Friedrich Christina M , Djebli Nassim , Goebel Britta , Koszycki Alex , Varshnaya Meera , Elassal Joseph , Banerjee Poulabi , Sasiela William J , Reed Michael J , Barrett Jeffrey S , Azer Karim
Published: June 2017

Reduction in low-density lipoprotein cholesterol (LDL-C) is associated with decreased risk for cardiovascular disease. Alirocumab, an antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduces LDL-C. Here, we report development of a quantitative systems pharmacology (QSP) model integrating peripheral and liver cholesterol metabolism, as well as PCSK9 function, to examine the mechanisms of action of alirocumab and other lipid-lowering therapies, including statins. The model predicts changes in LDL-C and other lipids that are consistent with effects observed in clinical trials of single or combined treatments of alirocumab and other treatments. An exploratory model to examine the effects of lipid levels on plaque dynamics was also developed. The QSP platform, on further development and qualification, may support dose optimization and clinical trial design for PCSK9 inhibitors and lipid-modulating drugs. It may also improve our understanding of factors affecting therapeutic responses in different phenotypes of dyslipidemia and cardiovascular disease.
Driveline Infection in Ventricular Assist Devices and Its Implication in the Present Era of Destination Therapy
Authors: Hernandez Gabriel A , Nunez Breton Jonatan D , Chaparro Sandra V
Published: June 2017

Advances in mechanical circulatory support devices provided the technology to develop long-term, implantable left ventricular assist devices as bridge to transplant, destination therapy, and in a lesser group of patients, as bridge to recovery. Despite the benefits from this innovative therapy, with their increased use, many complications have been encountered, one of the most common being infections. With the driveline acting as a portal to the exterior environment, an infection involving this structure is the most frequent one. Because patients with destination therapy are expected to receive circulatory support for a longer period of time, we will focus this review on the risk factors, prevention, and treatment options for driveline infections.
Effect of Chronic Hepatitis C Virus Treatment by Combination Therapy on Cardiovascular System
Authors: Biomy Reda , Abdelshafy Mohamed , Abdelmonem Ahmed , Abu-Elenin Hesham , Ghaly George
Published: June 2017

Background:

The prevalence of hepatitis C virus (HCV) in Egypt is quite high, and the combined oral direct-acting antiviral agents (DAAs) may have impressive results.

Objective:

To assess the cardiovascular effects of DAAs in patients with HCV.

Methods:

A total of 170 patients with HCV were divided into 2 groups: first group (100 patients) received triple combination therapy (pegylated interferon alfa, sofosbuvir, and ribavirin, whereas the second group (70 patients) received dual combination therapy (sofosbuvir and simeprevir). Group 1 patients were followed up for 1 year more than 3 visits, whereas group 2 patients were followed up for 6 months more than 2 visits; and the end point of the study was the development of a major cardiovascular event (eg, congestive heart failure, echocardiographic evidence of left ventricular dysfunction, occurrence of significant arrhythmias, or acute coronary syndrome). The following parameters were accomplished: medical history and clinical examination, electrocardiogram, echo-Doppler study, and laboratory investigations.

Results:

No significant differences were found between the 2 study groups regarding demographic criteria. None of the both group patients had developed any major cardiac event. No significant changes were observed regarding ST-T wave abnormalities, arrhythmias, or QT interval. None of the both group patients developed echocardiographic regional wall motion abnormalities at baseline or at study end. Systolic function parameters showed minute nonsignificant changes over study visits. Diastolic function parameters showed nonsignificant changes between baseline and 6-month and 12-month visits.

Conclusions:

The DAAs used in combination regimen with interferon or used orally in combination do not significantly affect the cardiovascular system.
Atypical Primary Cutaneous Rosai Dorfman Disease: A Case Report
Authors: Kinio Anna E. , Sawchuk Michael A. , Pratt Melanie
Published: June 2017

Background:

Rosai Dorfman disease (RDD) is a rare disorder that typically presents with bilateral cervical lymphadenopathy and follows a benign course.

Objective:

We present a case of late-onset atypical primary cutaneous RDD that is resistant to treatment modalities described in the literature.

Methods:

Case report.

Results:

An 84-year-old woman presented with a 7-year history of cutaneous lesions histologically consistent with RDD. She later failed initial treatments of acitretin and thalidomide.

Conclusion:

Physicians must be aware of unusual presentations of RDD. Also, further treatment options must be explored for patients resistant to classical management of RDD.
Experimental and numerical study of the influence of loading direction on the lubrication and cooling of self-circulating oil bearing system applied in internal gear pumps
Authors: Mo Jintao , Gu Chaohua , Pan Xiaohong , Zheng Shuiying , Ying Guangyao
Published: June 2017

For middle-pressure and high pressure gear pumps, the temperature failure problem of bearings is now of considerable concern due to their heavy loads. A self-circulating oil bearing system has been developed for gear pumps in this paper to solve this problem. A test rig has been designed and built to carry out a series of tests for variable loading directions and rotational speeds. An experimental investigation and numerical model development to predict the behaviour of the self-circulating bearing subjected to different loading directions is described. The experimental and numerical results agree well. It was found that the variation of loading directions has a strong effect on the oil flow rates of the system. The maximum oil flow rate can be achieved when the loading direction is along the hole axis direction and a considerable part of the friction heat can be carried away by the oil. The lubrication of the bearing will also be improved.
Experiences of stigma over the lifetime of people with xeroderma pigmentosum: A qualitative interview study in the United Kingdom
Authors: Anderson Rebecca , Walburn Jessica , Morgan Myfanwy
Published: June 2017

This study explored experiences of stigma in 25 adults with xeroderma pigmentosum. Analysis of semi-structured interviews revealed the changing nature of stigma over the lifetime. Bullying occurred in childhood, whereas adults were questioned about both their photoprotection and skin damage, often resulting in internalised feelings of stigma. Resilience and rejection of feelings of stigma increased with age and experiences of stigma differed across cultures. Findings indicate a need to develop social skills training to help people reject feelings of stigma. Future research should explore perspectives of families, friends and formal institutions and their potential to cause or reduce feelings of stigma.
HIV symptom management self-efficacy mediates the relationship of internalized stigma and quality of life among people living with HIV in China
Authors: Zhou Guangyu , Li Xiaoming , Qiao Shan , Shen Zhiyong , Zhou Yuejiao
Published: June 2017

HIV-related stigma negatively influences quality of life among people living with HIV. Little is known about psychological protective factors that mitigate negative impacts. This study aims to examine the role of self-efficacy in reducing effects of stigma on quality of life. A total of 2987 people living with HIV (age: M = 42.46 years, SD = 12.83; time since diagnosis: M = 3.23 years, SD = 2.39) provided data on internalized stigma, HIV symptom management self-efficacy, and health-related quality of life, as well as covariates. Using structural equation modeling, we found that self-efficacy mediated the relationship of stigma and quality of life. Future interventions to promote quality of life in people living with HIV need to focus on increasing HIV symptom management self-efficacy.
Biodiversity protection under the habitats directive
Authors: Kleining Bettina
Published: June 2017

Although the Habitats Directive has enhanced nature conservation in Europe, it has failed to stop deterioration in its biodiversity. A significant contribution to this failure is the weak provision on compensatory measures under Article 6(4) of the directive in the event that Member States decide to authorise activities which harm protected areas. As the directive’s Natura 2000 network fails to include sufficient private land, it forms a patchwork of conservation areas which do not thrive. This article investigates the extent to which this weakness could be effectively addressed via habitats banking, a system in which developers purchase credits from private landowners to offset adverse impacts of developments on protected sites. While habitats banking does not prevent developments as such, it ensures the maintenance of a certain biodiversity level on the participating sites. A draft proposal will show how such a banking scheme could work in practice, critically bearing in mind the dangers of a fully privatised system. The article draws the conclusion that a European system of habitats banking with a sensible amount of public administration would improve the overall effectiveness of compensatory measures under the Habitats Directive.
What would Wittgenstein say about social media?
Authors: Brooker Phillip , Dutton William , Greiffenhagen Christian
Published: June 2017

Much of the excitement in social media analytics revolves around, a) capturing large-scale collections of naturally-occurring talk, b) repurposing them as data, and, c) finding ways to speak sociologically about them. Researchers have raised concerns over the use of social media data in research (for example, boyd and Crawford, 2012; Housley et al, 2014; Tinati et al, 2014), exploring the ontological and epistemological grounding of the emerging field. We contribute to this debate by drawing on Wittgensteinian philosophy to elucidate hitherto neglected aspects; namely that it is not just social scientists who are in the business of analysing social media, but users themselves. We explore how mainstream social media analytics research (1) overinflates the importance of sociological theories, concepts and methodologies (which do not typically feature in the accounts of social media users), (2) downplays the extent to which social media platforms already exhibit order prior to any sociological accounting of them, and, (3) thereby produces findings which explain social scientific perspectives rather than the phenomena themselves. We reformulate the ontological and epistemological basis of social media analytics research from a Wittgensteinian perspective concerned with what it makes sense to say about social media, as members of society and as researchers studying those members. Such a project aims to explore social media users’ language as a practice embedded within the context of social life and online communication. This reflects the everyday use of language as an evolving toolkit for undertaking social interaction, pointing towards an alternative conception of social media analytics.
Effects of a heedful interrelating intervention on collaborative teams
Authors: Daniel Sarah R , Jordan Michelle E
Published: June 2017

Working in collaborative groups has been shown to have beneficial outcomes; however, these benefits are linked to the quality of group member interactions. Heedful interrelating, which entails interacting with sensitivity to the task at hand while paying attention to how one’s actions affect overall team functioning, is theorized to be useful in assessing the quality of these interactions. This mixed-methods intervention study examined whether learning about heedful interrelating influenced students’ heedful interrelating, quiz performance, its perceived usefulness, and their perceptions of positive interdependence and metacognition. Quantitative outcomes were analyzed using analysis of variance and Pearson’s correlations, while the open-ended items were examined using open coding. No statistically significant difference in perceived heedful interrelating was found between the intervention and control conditions. However, significant positive relationships were found between heedful interrelating and quiz performance, positive interdependence, and metacognition. The majority of students in the intervention found the heedfulness training to be beneficial in prompting positive, effective collaborative experiences. Implications for practice are discussed.
Evidence-Based Clinical Recommendations for the Administration of the Sequential Motion Rates Task
Authors: Icht Michal , Ben-David Boaz M.
Published: June 2017

The sequential motion rates (SMR) task, that involves rapid and accurate repetitions of a syllable sequence, /pataka/, is a commonly used evaluation tool for oro-motor abilities. Although the SMR is a well-known tool, some aspects of its administration protocol are unspecified. We address the following factors and their role in the SMR protocol: (a) selecting the appropriate stimulus for the client—nonword, real word or both, (b) the necessity of a practice round, (c) using visual feedback, (d) using language-specific performance rate norms, and (e) the implications for using different measurements (time-based, rate-based). We also provide rate norms for Hebrew-speaking clients and a pair of simple equations for transforming data from time-based units (seconds) to rate-based units (syllables/s). These recommendations can be considered in the clinical assessment process and may be integrated into the speech-language pathologists’ practice, allowing for a more accurate and cost-effective evaluation procedure.
Modifying the surface of poly(ethylene terephthalate) nanofibrous materials by alkaline treatment and TiO2 nanoparticles
Authors: Karimi Ali , Izadan Hossein , Khoddami Akbar , Hosseini Seyed A
Published: June 2017

The mutual effects of nano-TiO2 and alkaline hydrolysis on the morphology, chemical structure, water absorption, and the dyeing behavior of poly(ethylene terephthalate) nanofibers were investigated via employing scanning electron microscope, Fourier Transform Infra Red Spectroscopy (FTIR) and X-ray diffraction, and measuring water contact angle, 3M repellency, and dye absorption. A direct relation between the alkaline hydrolysis rate and nanofibers hydrophilicity was observed, while the addition of the nano-TiO2 led to more hydrophobicity. However, the alkaline hydrolysis had the prominent effect. FTIR spectra illustrated no chemical interaction between the nanoparticles and nanofibers. It was also shown that the dye absorption at dyeing equilibrium and the rate of dyeing were increased by the presence of the nano-TiO2 and these effects were intensified by the alkaline hydrolysis. These observations were related to the reduction in the nanofibers diameter and the increase in the surface roughness, as evidenced in the scanning electron microscope, and the increase in the amorphous regions of the nanofibers, as shown by the X-ray diffraction diffractograms.
Detection Test for Language Impairments in Adults and the Aged—A New Screening Test for Language Impairment Associated With Neurodegenerative Diseases: Validation and Normative Data
Authors: Macoir Joël , Fossard Marion , Lefebvre Laurent , Monetta Laura , Renard Antoine , Tran Thi Mai , Wilson Maximiliano A.
Published: June 2017

To date, there is no quick screening test that could be used during routine office visits to accurately assess language disorders in neurodegenerative diseases. To fill this important gap, we developed the Detection Test for Language impairments in Adults and the Aged (DTLA), a quick, sensitive, standardized screening test designed to assess language disorders in adults and the elderly individuals. In Study 1, we describe the development of the DTLA. In Study 2, we report data on the DTLA’s validity and reliability. Finally, in Study 3, we establish normative data for the test. The DTLA has good convergent and discriminant validity as well as good internal consistency and test–retest reliability. Norms for the DTLA obtained from a sample of 545 healthy, community-dwelling, French-speaking adults from 4 French-speaking countries (Belgium, Canada (Quebec), France, and Switzerland) are provided. The development, validation, and standardization of the DTLA constitute a significant effort to meet the need for a language screening test adapted to neurodegenerative diseases.
Midterm Analysis of Survival and Cause of Death Following Endovascular Abdominal Aortic Aneurysm Repair
Authors: Healy Gerard M. , Redmond Ciaran E. , Gray Sam , Iacob Lucian , Sheehan Stephen , Dowdall Joseph F. , Barry Mary , Cantwell Colin P. , Brophy David P.
Published: June 2017

Purpose:

To assess rates of complications, secondary interventions, survival, and cause of death following endovascular abdominal aortic aneurysm (AAA) repair over a 10-year period.

Materials and Methods:

Single-institution retrospective cohort study of all patients undergoing primary endovascular aortic aneurysm repair (EVAR) between July 2006 and June 2015. The population constituted 175 patients with 163 fusiform and 12 saccular AAAs. Of these, 149 (85%) were male, with mean age 75.4 (±7.1) years. Patients were followed up until June 30, 2016. Cause of death was determined from the national death register.

Results:

Mean follow-up was 34.4 (±24.4) months. The secondary intervention rate was 9.7%, and there were 4 aneurysm ruptures (0.8% annual incidence). Thirty-day mortality was 0.6%. Survival at 1, 3, and 5 years was 93.1%, 84%, and 64.9%, respectively. Forty-eight patients died during follow-up, 3 secondary to rupture, leading to overall and aneurysm-related death rates of 9.7 and 0.6 per 100 person-years. All other deaths were due to nonaneurysm causes, most commonly cardiovascular (n = 15), pulmonary (n = 13), and malignancy (n = 9). Baseline renal impairment ( P < .001), ischemic heart disease ( P < .05), age greater than 75 years ( P < .05), and urgent/emergency EVAR were associated with inferior long-term survival. Type II endoleak negatively influenced fusiform aneurysm sac regression ( P = .02), but there was no association between survival and occurrence of any complication or secondary intervention.

Conclusion:

The majority of deaths during medium-term follow-up post-EVAR are due to nonaneurysm-related causes. Survival is determined by the following baseline factors: renal impairment, ischemic heart disease, advanced age, and the presence of a symptomatic/ruptured aneurysm.
Intraoperative Correction of Femoral Rotational Deformity Using a Conventional Navigation System and a Smartphone: A Novel Technique
Authors: Cao Jia-Qing , Huang Jing-Huan , Yuan Ting , Jia Wei-Tao , Gao Hong
Published: June 2017

The intraoperatively rotational control of femoral shaft fractures treated with a closed intramedullary interlocking nailing is a challenging problem. A novel surgical technique that includes respective insertions of guidewires into the proximal and distal femur under the guidance of a 2-dimensional fluoroscopy-based navigation system and the measurements of the intersection angle subtended by the proximal and distal guidewires with the smartphone positional software has been designed to provide intraoperatively quantitative parameters of femoral rotation deformation. The comparison of these parameters with preoperative measurement values of the contralateral intact femur on computed tomography images was used to align the proximal and distal femur fragments based on periaxial rotation. The purpose of this study was to evaluate its clinical suitability. Ten adult patients with femoral shaft fractures were attempted to correct intraoperatively femoral rotational deformity using this novel technique. The additional operation time was 20.04 ± 3.27 minutes. The angle of femoral anteversion was 20.85° ± 4.22°, 38.14° ± 19.07°, and 22.77° ± 3.38° in the contralateral intact and preoperatively and postoperatively injured femur, respectively. The mean absolute difference between both limbs was preoperatively 21.55° ± 10.14° with a statistically significant difference ( P = .005) and postoperatively 3.24° ± 1.69° with no statistically significant difference ( P = .092). Our results showed this novel technique could become an effective tool to correct intraoperatively rotational malalignment of femoral fractures.
Active and passive labour market policies in Austria and Hungary
Authors: Risak Martin , Kovács Erika
Published: June 2017

This article analyses the benefits/assistance and activation initiatives for the unemployed provided by Austria and Hungary, highlighting recent changes and trends in the regulation.

These two European states, which represent the Continental and the Eastern European systems, differ significantly in their history and approaches: Austria’s labour market and social security system remained quite stable in recent decades but underwent some changes that reflect a stricter and more activating approach. Hungary, on the other hand, is a post-socialist state that only had to establish an unemployment system in the 1990s and which recently limited the benefits and increased activation.