bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of Gene Amplification via Yeast Autonomously Replicating Sequences
Authors: Sehgal Shelly , Kaul Sanjana , Dhar M. K.
Published: January 2015

The present investigation was aimed at understanding the molecular mechanism of gene amplification. Interplay of fragile sites in promoting gene amplification was also elucidated. The amplification promoting sequences were chosen from the Saccharomyces cerevisiae ARS, 5S rRNA regions of Plantago ovata and P. lagopus, proposed sites of replication pausing at Ste20 gene locus of S. cerevisiae, and the bend DNA sequences within fragile site FRA11A in humans. The gene amplification assays showed that plasmid bearing APS from yeast and human beings led to enhanced protein concentration as compared to the wild type. Both the in silico and in vitro analyses were pointed out at the strong bending potential of these APS. In addition, high mitotic stability and presence of TTTT repeats and SAR amongst these sequences encourage gene amplification. Phylogenetic analysis of S. cerevisiae ARS was also conducted. The combinatorial power of different aspects of APS analyzed in the present investigation was harnessed to reach a consensus about the factors which stimulate gene expression, in presence of these sequences. It was concluded that the mechanism of gene amplification was that AT rich tracts present in fragile sites of yeast serve as binding sites for MAR/SAR and DNA unwinding elements. The DNA protein interactions necessary for ORC activation are facilitated by DNA bending. These specific bindings at ORC promote repeated rounds of DNA replication leading to gene amplification.
Phase Transitions of Binary Lipid Mixtures: A Combined Study by Adiabatic Scanning Calorimetry and Quartz Crystal Microbalance with Dissipation Monitoring
Authors: Losada-Pérez P. , Mertens N. , de Medio-Vasconcelos B. , Slenders E. , Leys J. , Peeters M. , van Grinsven B. , Gruber J. , Glorieux C. , Pfeiffer H. , Wagner P. , Thoen J.
Published: January 2015

The phase transitions of binary lipid mixtures are studied by a combination of Peltier-element-based adiabatic scanning calorimetry (pASC) and quartz crystal microbalance with dissipation monitoring (QCM-D). pASC, a novel type of calorimeter, provides valuable and unambiguous information on the heat capacity and the enthalpy, whereas QCM-D is proposed as a genuine way of determining phase diagrams by analysing the temperature dependence of the viscosity. Two binary mixtures of phospholipids with the same polar head and differing in the alkyl chain length, DMPC + DPPC and DMPC + DSPC, are discussed. Both techniques give consistent phase diagrams, which compare well with literature results, showing their capability to map the phase behaviour of pure lipids as well as lipid mixtures. This work can be considered as a departure point for further investigations on more complex lipid mixtures displaying relevant phases such as the liquid-ordered phase and solid-lipid interfaces with biologically functional importance.
Successful Desensitization of a Patient with Rituximab Hypersensitivity
Authors: Ataca Pinar , Atilla Erden , Kendir Resat , Bavbek Sevim , Ozcan Muhit
Published: January 2015

Rituximab is a monoclonal antibody which targets CD20 in B cells that is used for the treatment of CD20 positive oncologic and hematologic malignancies. Rituximab causes hypersensitivity reactions during infusions. The delay of treatment or loss of a highly efficient drug can be prevented by rapid drug desensitization method in patients who are allergic to rituximab. We report a low grade B cell non-Hodgkin lymphoma patient with rituximab hypersensitivity successfully treated with rapid drug desensitization. In experienced centers, drug desensitization is a novel modality to break through in case of hypersensitivity that should be considered.
Human Leucocyte Antigen‐G (HLA‐G) and Its Murine Functional Homolog Qa2 in the Trypanosoma cruzi Infection
Authors: Dias Fabrício C. , Mendes-Junior Celso T. , Silva Maria C. , Tristão Fabrine S. M. , Dellalibera-Joviliano Renata , Moreau Philippe , Soares Edson G. , Menezes Jean G. , Schmidt André , Dantas Roberto O. , Marin-Neto José A. , Silva João S. , Donadi Eduardo A.
Published: January 2015

Genetic susceptibility factors, parasite strain, and an adequate modulation of the immune system seem to be crucial for disease progression after Trypanosoma cruzi infection. HLA‐G and its murine functional homolog Qa2 have well‐recognized immunomodulatory properties. We evaluated the HLA-G 3′ untranslated region (3′UTR) polymorphic sites (associated with mRNA stability and target for microRNA binding) and HLA‐G tissue expression (heart, colon, and esophagus) in patients presenting Chagas disease, stratified according to the major clinical variants. Further, we investigated the transcriptional levels of Qa2 and other pro‐ and anti‐inflammatory genes in affected mouse tissues during T. cruzi experimental acute and early chronic infection induced by the CL strain. Chagas disease patients exhibited differential HLA-G 3′UTR susceptibility allele/genotype/haplotype patterns, according to the major clinical variant (digestive/cardiac/mixed/indeterminate). HLA‐G constitutive expression on cardiac muscle and colonic cells was decreased in Chagasic tissues; however, no difference was observed for Chagasic and non‐Chagasic esophagus tissues. The transcriptional levels of Qa2 and other anti and proinflammatory (CTLA-4, PDCD1, IL-10, INF-γ, and NOS-2) genes were induced only during the acute T. cruzi infection in BALB/c and C57BL/6 mice. We present several lines of evidence indicating the role of immunomodulatory genes and molecules in human and experimental T. cruzi infection.
Zeaxanthin Inhibits Hypoxia-Induced VEGF Secretion by RPE Cells through Decreased Protein Levels of Hypoxia-Inducible Factors-1α
Authors: Rosen Richard , Vagaggini Tommaso , Chen Yueqin , Hu Dan-Ning
Published: January 2015

Hypoxia is the most important stimulus leading to upregulation of VEGF in the retina and this is caused by accumulation of hypoxia-inducible factors-1α(HIF-1α) protein. The effects of zeaxanthin, a natural phytochemical, on the VEGF and HIF-1αexpression in the primary culture of human retinal pigment epithelial (RPE) cells were studied. An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2) to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without zeaxanthin under normoxic and hypoxic conditions. VEGF and HIF-1αprotein and RNA levels were measured by ELISA kits and RT-PCR, respectively. Hypoxia caused a significant increase of VEGF expression and accumulation of HIF-1αin RPE cells. Zeaxanthin at 50–150 μM significantly inhibited the expression of VEGF and accumulation of HIF-1αprotein caused by hypoxia but did not affect expression of VEGF and HIF-1αunder normoxic conditions. This is the first report on the effect of zeaxanthin on VEGF and HIF-1αlevels in cultured RPE cells and suggests that zeaxanthin may have potential value in the prevention and treatment of various retinal diseases associated with vascular leakage and neovascularization.
Optimized Design of an ECAP Die Using the Finite Element Method for Obtaining Nanostructured Materials
Authors: Ponce-Peña Patricia , López-Chipres Edgar , García-Sánchez Edgar , Escobedo-Bretado Miguel Angel , Ochoa-Salazar Brenda Xiomara , González-Lozano María Azucena
Published: January 2015

An alloy type A16060 was exposed to severe plastic deformation to study its reaction using the finite element method (FEM). To perform this, six different configurations were used in the design of the die’s channel for ECAP (equal channel angular pressing) to obtain nanostructure materials and to optimize the process. Thanks to simulation performed with FEM, it is possible to study the homogeneity in the deformation due to the variation of conditions affecting directly the material being processed using the ECAP technique, such as the friction coefficient, extrusion speed, and mainly the die’s channel geometry being utilized in the ECAP process. Due to the tensile strain area being located mainly in the upper part of the deformed test cylinder (plastic deformation area) which increases the fracture and cracking tendency preventing the processing through ECAP the die being utilized was modified to eliminate the tensile strain area favoring the appearance of compressive stress which reduces the cracking tendency and the fracture of the sample being processed. The FEM analysis demonstrated that the strain state changed significantly from tension to compression when the modified die was used, facilitating the processing of the piece by ECAP.
Measurement of Capsaicinoids in Chiltepin Hot Pepper: A Comparison Study between Spectrophotometric Method and High Performance Liquid Chromatography Analysis
Authors: González-Zamora Alberto , Sierra-Campos Erick , Pérez-Morales Rebeca , Vázquez-Vázquez Cirilo , Gallegos-Robles Miguel A. , López-Martínez José D. , García-Hernández José L.
Published: January 2015

Direct spectrophotometric determination of capsaicinoids content in Chiltepin pepper was investigated as a possible alternative to HPLC analysis. Capsaicinoids were extracted from Chiltepin in red ripe and green fruit with acetonitrile and evaluated quantitatively using the HPLC method with capsaicin and dihydrocapsaicin standards. Three samples of different treatment were analyzed for their capsaicinoids content successfully by these methods. HPLC-DAD revealed that capsaicin, dihydrocapsaicin, and nordihydrocapsaicin comprised up to 98% of total capsaicinoids detected. The absorbance of the diluted samples was read on a spectrophotometer at 215–300 nm and monitored at 280 nm. We report herein the comparison between traditional UV assays and HPLC-DAD methods for the determination of the molar absorptivity coefficient of capsaicin (ε280=3,410andε280=3,720 M−1 cm−1) and dihydrocapsaicin (ε280=4,175andε280=4,350 M−1 cm−1), respectively. Statistical comparisons were performed using the regression analyses (ordinary linear regression and Deming regression) and Bland-Altman analysis. Comparative data for pungency was determined spectrophotometrically and by HPLC on samples ranging from 29.55 to 129 mg/g with a correlation of 0.91. These results indicate that the two methods significantly agree. The described spectrophotometric method can be routinely used for total capsaicinoids analysis and quality control in agricultural and pharmaceutical analysis.
Radiographic and MR Imaging Findings of the Spine after Bisphosphonate Treatment, in a Child with Idiopathic Juvenile Osteoporosis
Authors: Papakonstantinou Olympia , Sakalidou Maria , Atsali Erato , Bizimi Vasiliki , Mendrinou Maria , Alexopoulou Efthymia
Published: January 2015

Bisphosphonates are employed with increasing frequency in various pediatric disorders, mainly associated with osteoporosis. After cessation of bisphosphonate treatment in children, skeletal radiologic changes have been documented including dense metaphyseal lines of the long bones and “bone in bone” appearance of the vertebrae. However, the evolution of these radiographic changes has not been fully explored. We describe the MR imaging appearance of the spine that, to our knowledge, has not been previously addressed in a child with idiopathic juvenile osteoporosis who had received bisphosphonates and emphasize the evolution of the radiographic findings of the spine and pelvis over a four-year period.
The “Gender Factor” in Wearing‐Off among Patients with Parkinson’s Disease: A Post Hoc Analysis of DEEP Study
Authors: Colombo Delia , Abbruzzese Giovanni , Antonini Angelo , Barone Paolo , Bellia Gilberto , Franconi Flavia , Simoni Lucia , Attar Mahmood , Zagni Emanuela , Haggiag Shalom , Stocchi Fabrizio
Published: January 2015

Background. The early detection of wearing‐off in Parkinson disease (DEEP) observational study demonstrated that women with Parkinson’s disease (PD) carry an increased risk (80.1%) for wearing‐off (WO). This post hoc analysis of DEEP study evaluates gender differences on WO and associated phenomena. Methods. Patients on dopaminergic treatment for ≥1 year were included in this multicenter observational cross‐sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as the use of the 19‐item wearing‐off questionnaire (WOQ‐19); WO was defined for scores ≥2. Post hoc analyses were conducted to investigate gender difference for demographic and clinical features with respect to WO. Results. Of 617 patients enrolled, 236 were women and 381 were men. Prevalence of WO was higher among women, according to both neurologists’ judgment (61.9% versus 53.8%, P = 0.045) and the WOQ‐19 analysis (72.5% versus 64.0%, P = 0.034). In patients with WO (WOQ‐19), women experienced ≥1 motor symptom in 72.5% versus 64.0% in men and ≥1 nonmotor symptom in 44.5% versus 36.7%, in men. Conclusions. Our results suggest WO as more common among women, for both motor and nonmotor symptoms. Prospective studies are warranted to investigate this potential gender‐effect.
Hesitant Fuzzy Soft Sets with Application in Multicriteria Group Decision Making Problems
Authors: Wang Jian-qiang , Li Xin-E , Chen Xiao-hong
Published: January 2015

Soft sets have been regarded as a useful mathematical tool to deal with uncertainty. In recent years, many scholars have shown an intense interest in soft sets and extended standard soft sets to intuitionistic fuzzy soft sets, interval‐valued fuzzy soft sets, and generalized fuzzy soft sets. In this paper, hesitant fuzzy soft sets are defined by combining fuzzy soft sets with hesitant fuzzy sets. And some operations on hesitant fuzzy soft sets based on Archimedean t‐norm and Archimedean t‐conorm are defined. Besides, four aggregation operations, such as the HFSWA, HFSWG, GHFSWA, and GHFSWG operators, are given. Based on these operators, a multicriteria group decision making approach with hesitant fuzzy soft sets is also proposed. To demonstrate its accuracy and applicability, this approach is finally employed to calculate a numerical example.
Alleviation of Kainic Acid-Induced Brain Barrier Dysfunction by 4-O-Methylhonokiol inIn VitroandIn VivoModels
Authors: Han Jin-Yi , Ahn Sun-Young , Yoo Jae Hyeon , Nam Sang-Yoon , Hong Jin Tae , Oh Ki-Wan
Published: January 2015

This experiment was designed to investigate whether 4-O-methylhonokiol (MH), a principal ingredient ofMagnolia (M.) officinalisbark, alleviated acute intraperitoneal (i.p.) kainic acid- (KA-) induced brain blood barrier dysfunction (BBBD)viapathological examination and cytological analyses of the brain tissues of mice. KA (10–30 mg/kg) time- and dose-dependently increased the water content of brain tissues and induced edema and encephalopathy. However, pretreatment with MH (5 and 20 mg/kg, i.p.) significantly reduced the water content of the brain compared to that observed in the KA control group. Furthermore, MH significantly and dose-dependently reversed the remarkable variations in evan’s blue dye (EBD) staining and malondialdehyde (MDA) levels that were induced by KA (10 mg/kg, i.p.). MH also decreased the elevated seizure scores that were induced by KA (10 mg/kg, i.p.) in mice in a manner similar to scavengers such as DMTU and trolox. Additionally, MH significantly scavenged intracellular ROS and Ca2+within hippocampal cells. The tight junction seals mediated by claudin (Cld-5) were also found to be modulated by MH. MH efficiently reduced 1,1-diphenyl-2-picrylhydrazyl (DPPH) (IC50, 52.4 mM) and•OH with an electron spin resonance (ESR) signal rate constant of4×109 M-1·S-1, which is close to the reactivity of the vitamin E analog trolox. Taken together, these results suggest that MH may enhance radical scavenging in lipid and hydrophobic environments, which may be important for the physiological activity of the barrier.
Icariin Intervenes in Cardiac Inflammaging through Upregulation of SIRT6 Enzyme Activity and Inhibition of the NF-Kappa B Pathway
Authors: Chen Yang , Sun Tao , Wu Junzhen , Kalionis Bill , Zhang Changcheng , Yuan Ding , Huang Jianhua , Cai Waijiao , Fang Hong , Xia Shijin
Published: January 2015

The aim of the study was to investigate the effect of icariin (ICA) on cardiac aging through its effects on the SIRT6 enzyme and on the NF-κB pathway. Investigating the effect of ICA on the enzymatic activity of histone deacetylase SIRT6 revealed a concentration of 10−8 mol/L ICA had a maximum activating effect on histone deacetylase SIRT6 enzymatic activity. Western analysis showed that ICA upregulated SIRT6 protein expression and downregulated NF-κB (p65) protein expression in animal tissues and cell models. ICA upregulated the expression of SIRT6 and had an inhibitory effect on NF-κB inflammatory signaling pathways as shown by decreasing mRNA levels of the NF-κB downstream target genes TNF-α, ICAM-1, IL-2, and IL-6. Those effects were mediated directly or indirectly by SIRT6. We provided evidence that inflammaging may involve a novel link between the effects of ICA on SIRT6 (a regulator of aging) and NF-κB (a regulator of inflammation).
Weyl-Invariant Extension of the Metric-Affine Gravity
Authors: Vazirian R. , Tanhayi M. R. , Motahar Z. A.
Published: January 2015

Metric-affine geometry provides a nontrivial extension of the general relativity where the metric and connection are treated as the two independent fundamental quantities in constructing the spacetime (with nonvanishing torsion and nonmetricity). In this paper, we study the generic form of action in this formalism and then construct the Weyl-invariant version of this theory. It is shown that, in Weitzenböck space, the obtained Weyl-invariant action can cover the conformally invariant teleparallel action. Finally, the related field equations are obtained in the general case.
Fiber-Optic Temperature and Pressure Sensors Applied to Radiofrequency Thermal Ablation in Liver Phantom: Methodology and Experimental Measurements
Authors: Tosi Daniele , Macchi Edoardo Gino , Cigada Alfredo
Published: January 2015

Radiofrequency thermal ablation (RFA) is a procedure aimed at interventional cancer care and is applied to the treatment of small- and midsize tumors in lung, kidney, liver, and other tissues. RFA generates a selective high-temperature field in the tissue; temperature values and their persistency are directly related to the mortality rate of tumor cells. Temperature measurement in up to 3–5 points, using electrical thermocouples, belongs to the present clinical practice of RFA and is the foundation of a physical model of the ablation process. Fiber-optic sensors allow extending the detection of biophysical parameters to a vast plurality of sensing points, using miniature and noninvasive technologies that do not alter the RFA pattern. This work addresses the methodology for optical measurement of temperature distribution and pressure using four different fiber-optic technologies: fiber Bragg gratings (FBGs), linearly chirped FBGs (LCFBGs), Rayleigh scattering-based distributed temperature system (DTS), and extrinsic Fabry-Perot interferometry (EFPI). For each instrument, methodology forex vivosensing, as well as experimental results, is reported, leading to the application of fiber-optic technologiesin vivo. The possibility of using a fiber-optic sensor network, in conjunction with a suitable ablation device, can enable smart ablation procedure whereas ablation parameters are dynamically changed.
Acute Obstructive Suppurative Pancreatic Ductitis in an Asymptomatic Patient
Authors: Wali Eisha , Koo Patrick , Packer Clifford D.
Published: January 2015

Acute obstructive suppurative pancreatic ductitis (AOSPD), defined as suppuration from the pancreatic duct without associated pseudocyst, abscess, or necrosis, is a rare complication of chronic pancreatitis. We present the first case of AOSPD in an asymptomatic patient with a polymicrobial infection and review the literature on this rare clinical entity.
High Performance Indium‐Doped ZnO Gas Sensor
Authors: Qi Junjie , Zhang Hong , Lu Shengnan , Li Xin , Xu Minxuan , Zhang Yue
Published: January 2015

Gas sensors for ethanol and acetone based on ZnO nanobelts with doping element indium were fabricated. Excellent sensitivity accompanied with short response time (10 s) and recovery time (23 s) to 150 ppm ethanol is obtained. For In‐doped sensors, a minimum concentration of 37.5 ppm at 275°C in acetone was observed with an average sensitivity of 714.4, which is 7 times larger than that of the pure sensors and much larger than that reported response (16) of Co‐doped ZnO nanofibers to acetone. These results indicate that doping elements can improve gas sensitivity, which is associated with oxygen space and valence ions. In‐doped ZnO nanobelts exhibit higher sensitivity to acetone than that to ethanol. These results indicate that doped ZnO nanobelts can successfully distinguish acetone and ethanol, which can be put into various practical applications.
Enhanced Efficiency of Dye‐Sensitized Solar Cells by Trace Amount Ca‐Doping in TiO2 Photoelectrodes
Authors: Pan Mengmei , Liu Hanjun , Yao Zhongyu , Zhong Xiaoli
Published: January 2015

Trace amount Ca‐doped TiO2 films were synthesized by the hydrothermal method and applied as photoanodes of dye‐sensitized solar cells (DSSCs). To prepare Ca‐doped TiO2 film electrodes, several milliliters of Ca(NO3)2 solution was added in TiO2 solution during the hydrolysis process. The improvements of DSSCs were confirmed by photocurrent density‐voltage (J-V) characteristics, electrochemical impedance spectroscopy (EIS) measurements. Owing to the doping effect of Ca, the Ca‐doped TiO2 thin film shows power conversion efficiency of 7.45% for 50 ppm Ca‐doped TiO2 electrode, which is higher than that of the undoped TiO2 film (6.78%) and the short‐circuit photocurrent density (Jsc) increases from 13.68 to 15.42 mA·cm−2. The energy conversion efficiency and short‐circuit current density (Jsc) of DSSCs were increased due to the faster electron transport in the Ca‐doped TiO2 film. When Ca was incorporated into TiO2 films, the electrons transport faster and the charge collection efficiency ηcc is higher than that in the undoped TiO2 films.
Fine-tuning Tumor Immunity with Integrin Trans-regulation
Authors: Cantor Joseph M. , Rose David M. , Slepak Marina , Ginsberg Mark H.
Published: January 2015

Inefficient T-cell homing to tissues limits adoptive T-cell immunotherapy of solid tumors. αLβ2 and α4β1 integrins mediate trafficking of T cells into tissues via engagement of ICAM-1 and VCAM-1, respectively. Inhibiting protein kinase A (PKA)–mediated phosphorylation of α4 integrin in cells results in an increase in αLβ2-mediated migration on mixed ICAM-1–VCAM-1 substrates in vitro, a phenomenon termed “integrin trans-regulation.” Here, we created an α4(S988A)-bearing mouse, which precludes PKA-mediated α4 phosphorylation, to examine the effect of integrin trans-regulation in vivo. The α4(S988A) mouse exhibited a dramatic and selective increase in migration of lymphocytes, but not myeloid cells, to sites of inflammation. Importantly, we found that the α4(S988A) mice exhibited a marked increase in T-cell entry into and reduced growth of B16 melanomas, consistent with antitumor roles of infiltrating T cells and progrowth functions of tumor-associated macrophages. Thus, increased α4 trans-regulation of αLβ2 integrin function biases leukocyte emigration toward lymphocytes relative to myeloid cells and enhances tumor immunity. Cancer Immunol Res; 3(6); 661–7. ©2015 AACR.
Genetic Evidence That Intratumoral T-cell Proliferation and Activation Are Associated with Recurrence and Survival in Patients with Resected Colorectal Liver Metastases
Authors: Maker Ajay V. , Ito Hiromichi , Mo Qianxing , Weisenberg Elliot , Qin Li-Xuan , Turcotte Simon , Maithel Shishir , Shia Jinru , Blumgart Leslie , Fong Yuman , Jarnagin William R. , DeMatteo Ronald P. , D'Angelica Michael I.
Published: January 2015

Though immune responses correlate with prognosis in primary colorectal cancer, the role of tumor immunity in metastatic disease is less clear. We hypothesized that patient survival and tumor recurrence correlate with transcriptional evidence of lymphocyte proliferation/activation in resected colorectal cancer liver metastases (CRLM). Microarray gene analysis was performed on liver tumor specimens from 96 patients who underwent resection for CRLM. A Cox proportional hazards model identified genes associated with overall survival (OS) and recurrence-free survival (RFS). Conventional gene ontology (GO) enrichment analysis ranked biologically relevant processes. Survival probabilities of prioritized processes were assessed. Protein expression was validated with immunohistochemistry in an independent set of patients. GO analysis identified and ranked unique biologic processes that correlated with survival. Genes that specifically functioned in the biologic process of “T-cell proliferation” were significant predictors of OS (P = 0.01), and both “T-cell proliferation” and “activation” were highly associated with RFS (P ≤ 0.01). Analysis of genes in these GO categories identified increased TNFSF14/LIGHT expression to be most associated with improved OS and RFS (P ≤ 0.0006). Immunohistochemistry of an independent validation set of CRLM confirmed that both increased tumor-infiltrating lymphocytes (TIL) and higher LIGHT expression on TILs were associated with improved OS and RFS. Differential expression of genes involved in T-cell proliferation/activation was associated with survival outcomes in a large number of surgical patients who underwent resection of CRLM. These biologic functions determined by GO analysis of the tumor microenvironment have identified specific immune-related genes that may be involved in an antitumor immune response. Cancer Immunol Res; 3(4); 380–8. ©2015 AACR.
Successful Fetoscopic Surgery to Release a Complete Obstruction of the Urethral Meatus in a Case of Congenital Megalourethra
Authors: Migliorelli Federico , Martínez José María , Gómez Olga , Bennasar M. , Crispi Fatima , García Luis , Castañón Montserrat , Gratacós Eduard
Published: January 2015

We report the successful use of fetoscopy to treat a case of severe low urinary tract obstruction (LUTO) secondary to a congenital megalourethra. A second trimester male fetus presented at 21 weeks of gestation with massive dilatation of the penile urethra. In addition, bilateral hydronephrosis, an enlarged and hypertrophic bladder, with progressive oligohydramnios were found, suggesting poor prognosis. Extensive counselling was performed and, after the approval from the local ethics committee and informed consent, patients accepted fetal therapy by fetoscopy. The procedure consisted in fetoscopic identification of the tip of the penis and confirmation of the complete absence of the urethral meatus. Thereafter, under combined endoscopic and ultrasound guidance a perforation of the tip of the penis was performed with contact diode laser, until an opening into the urethra was achieved. After the operation, resolution of the cystic penile dilation, with reduction of the penile size, and normalization of the amniotic fluid volume were observed. The pregnancy continued uneventfully and a normal male infant was born at term at the local hospital. The baby was developing normally with normal renal function at 6 months of age. Our report demonstrates that fetoscopic decompression of a distal urethra obstruction can achieve neonatal survival in the rare event of congenital megalourethra.
Is Prolonged Operation Time a Predictor for the Occurrence of Complications in Ureteroscopy?
Authors: Knipper Sophie , Tiburtius Christian , Gross Andreas J. , Netsch Christopher
Published: January 2015

Objective: To determine the impact of duration of ureteroscopy for urolithiasis on complication rates (CRs) of the procedure. Methods: A retrospective analysis of 2,010 patients, treated between 2006 and 2011, was done. The operation time (OT) and the occurrence of complications were compared. Results: The overall CR was 14.3% [298 complications, minor complications (Clavien I-II) 91.7%]. The median OT was 35 min [interquartile range (IQR) 20-61]. The OT differed significantly between those without complications [34 min (IQR 20-60)] and those with complications [45 min (IQR 25-76)] (p < 0.0001). The correlation between the OT and the occurrence of complications (r = -0.009648, p < 0.0001) was very weak and passed the level of significance (r = 0.2). The effect size was of minor relevance (Cohen's d = 0.27972). Conclusions: Longer OT correlates significantly with a higher CR. The effect is however shown to be minor and the overall rate of complications, especially severe ones, is low.
Impact of the Use of Bowel for Urinary Diversion on Perioperative Complications and 90-Day Mortality in Patients Aged 75 Years or Older
Authors: Berger Ingrid , Wehrberger Clemens , Ponholzer Anton , Wolfgang Martina , Martini Thomas , Breinl Eckart , Dunzinger Michael , Hofbauer Johann , Höltl Wolfgang , Jeschke Klaus , Krause Steffen F. , Kugler Walter , Rauchenwald Michael , Pauer Walter , Pycha Armin , Madersbacher Stephan
Published: January 2015

Objective: A potential strategy to decrease the high complication rate of radical cystectomy (RC) in the elderly is to avoid the use of bowel for urinary diversion. The aim of this study was to address this issue in a multicentre study of patients aged ≥75 years. Patients and Methods: We performed a retrospective, multicentre study of a consecutive series of patients aged ≥75 years who underwent RC for muscle-invasive bladder cancer between 2006 and 2010. Medical, surgical and wound complications were graded according to the modified Clavien-Dindo classification. Results: A total of 256 patients (68% men, mean age 79.6 years) were analysed. 204 (80%) patients received a urinary diversion with use of bowel and 52 (20%) a ureterocutaneostomy (UC). Patients with UC were older (82.0 vs. 78.9 years, p < 0.001) and had a higher ASA score (2.6 vs. 2.3, p = 0.007), while the mean Charlson score was lower (4.2 vs. 5.6, p < 0.001). Patients with UC had a shorter operating time (279 vs. 311 min, p = 0.002) and a shorter period in the intensive care unit (0.9 vs. 2.2 days). The overall rate of severe complications graded as Clavien III-V was significantly lower in the UC group (11.5%) as compared to patients receiving bowel for urinary diversion (25.0%) (p = 0.003). Severe (Clavien grade III-V) medical (3.9 vs. 10.3%) and surgical (2.1 vs. 14.1%) complications were all less frequent in the UC group. Inpatient, 30- and 90-day mortality was 5.8, 7.7 and 17.3% in the UC group as compared to 3.9, 5.9 and 6.9% in the bowel cohort, respectively. Conclusion: UC following RC is associated with a lower complication rate in geriatric patients. The constantly increasing cohort of geriatric, multimorbid patients requiring cystectomy might justify reconsideration of this form of diversion.
Changes of Dopamine Transporter Availability in Depressed Patients with and without Anhedonia: A 123I-N-ω-Fluoropropyl-Carbomethoxy-3β- (4-Iodophenyl)tropane SPECT Study
Authors: Camardese Giovanni , De Risio Luisa , Di Nicola Marco , Pucci Lorella , Cocciolillo Fabrizio , Bria Pietro , Giordano Alessandro , Janiri Luigi , Di Giuda Daniela
Published: January 2015

Background/Aims: Dopamine is an important neurotransmitter involved in the pathophysiology of depression and anhedonia. Dopamine transporters (DAT) may play a crucial role in the pathophysiology of dopaminergic transmission. We investigated the relationship between striatal DAT availability and depression, pointing out possible correlations with anhedonia and treatment outcomes. Methods: Ten depressed patients with anhedonia, 10 depressed patients without anhedonia and 20 healthy controls underwent single photon emission computed tomography using 123I-FP-CIT [123I-N-ω-fluoropropyl-carbomethoxy-3β-(4-iodophenyl)tropane]. Psychometric measures included the Snaith-Hamilton Pleasure Scale and the Hamilton Depression Rating Scale. A further assessment of DAT availability was performed in the 10 patients with marked anhedonia after a 3-month pharmacological treatment. Results: Depressed patients with and without anhedonia showed significantly lower 123I-FP-CIT binding ratios in the bilateral striatum, caudate and putamen. No significant changes were detected after treatment in the 10 patients with marked anhedonia. When considering clinical outcomes, subjects with remission of depression showed a significant reduction of 123I-FP-CIT binding ratios in all regions at baseline, but after treatment no differences were found any longer. Conclusions: We suppose that a hypofunction of the striatal dopaminergic system may be a ‘state' feature of a depressive condition as a whole rather than anhedonia itself. On the other hand, some anhedonic features mainly represent an enduring trait that persists independently of mood state.
Pseudoamniotic Band Syndrome after In Utero Intervention for Twin-to-Twin Transfusion Syndrome: Case Reports and Literature Review
Authors: Ting Yuen Ha , Lao Terence T. , Law Kwok Ming , Cheng Yvonne Kwun Yue , Lau Tze Kin , Leung Tak Yeung
Published: January 2015

Pseudoamniotic band syndrome (PABS) is a rare iatrogenic complication that arises after invasive procedures in monochorionic twins. We report 3 cases of PABS, 2 after fetoscopic laser photocoagulation and 1 after bipolar cord coagulation. Two cases were detected antenatally by ultrasound; out of the two, one underwent successful fetoscopic release of amniotic band, which is the first report in twin pregnancy to our knowledge. In our centre, the incidence of PABS was found to be 2%. There were 25 cases of PABS reported previously, of which 12 cases with clinical details were reviewed together with our 3 cases. The fetal limbs were involved in all 15 cases, leading to constriction or amputation. The umbilical cord was involved in 2 cases, resulting in fetal death in one and pregnancy termination in the other. Antenatal detection of PABS is rare (27%; 4/15) as this requires a high index of suspicion. Serial postoperative targeted ultrasound surveillance of the fetal limbs and umbilical cord is necessary, particularly when features of septostomy or chorioamniotic membrane separation are found. Colour Doppler examination for the perfusion of the affected limb should be performed when PABS is detected. Fetoscopic release of amniotic band could salvage the fetal limb from amputation when impaired blood flow is detected.
WT1 Deletion Leading to Severe 46,XY Gonadal Dysgenesis, Wilms Tumor and Gonadoblastoma: Case Report
Authors: Finken Martijn J.J. , Hendriks Yvonne M.C. , van der Voorn J. Patrick , Veening Margreet A. , Lombardi M. Paola , Rotteveel Joost
Published: January 2015

Background: Heterozygous missense mutations in the WT1 gene that affect the function of the wild-type allele have been identified in Denys-Drash syndrome, which is characterized by severe gonadal dysgenesis, early-onset nephropathy and a predisposition to renal and gonadal cancer. Intron 9 splice-site mutations that influence the balance between WT1 isoforms cause a nearly similar phenotype, known as Frasier syndrome. Nonsense mutations and deletions only lead to WT1 haploinsufficiency and, hence, to less severe gonadal dysgenesis and late-onset nephropathy. WT1 analysis is mandatory in 46,XY gonadal dysgenesis with renal abnormality. Patient: We describe a newborn with 46,XY severe partial gonadal dysgenesis, in whom structural renal anomalies and proteinuria were excluded. Gonadectomy was performed at the age of 1 month and the microscopy was thought to be suggestive for a gonadoblastoma. At the age of 9 months, the patient presented with a bilateral Wilms tumor. Results: We found a heterozygous WT1 whole-gene deletion but no other gene defects. Conclusions: This case description illustrates that a WT1 deletion might be associated with a more severe phenotype than previously thought. It also illustrates that, even in the absence of renal abnormality, it is recommended to test promptly for WT1 defects in 46,XY gonadal dysgenesis.
Unique Roles of TLR9- and MyD88-Dependent and -Independent Pathways in Adaptive Immune Responses to AAV-Mediated Gene Transfer
Authors: Rogers Geoffrey L. , Suzuki Masataka , Zolotukhin Irene , Markusic David M. , Morel Laurence M. , Lee Brendan , Ertl Hildegund C.J. , Herzog Roland W.
Published: January 2015

The immune system represents a significant barrier to successful gene therapy with adeno-associated viral (AAV) vectors. In particular, adaptive immune responses to the viral capsid or the transgene product are of concern. The sensing of AAV by toll-like receptors (TLRs) TLR2 and TLR9 has been suggested to play a role in innate immunity to the virus and may also shape subsequent adaptive immune responses. Here, we investigated the functions of TLR2, TLR9 and the downstream signaling adaptor MyD88 in antibody and CD8+ T-cell responses. Antibody formation against the transgene product occurred largely independently of TLR signaling following gene transfer with AAV1 or AAV2 vectors, whereas loss of signaling through the TLR9-MyD88 pathway substantially reduced CD8+ T-cell responses. In contrast, MyD88 (but neither of the TLRs) regulated antibody responses to capsid. B cell-intrinsic MyD88 was required for the formation of anti-capsid IgG2c independently of vector serotype or route of administration. However, MyD88-/- mice instead produced anti-capsid IgG1 that emerged with delayed kinetics but nonetheless completely prevented in vivo readministration. We conclude that there are distinct roles for TLR9 and MyD88 in promoting adaptive immune responses to AAV-mediated gene transfer and that there are redundant MyD88-dependent and MyD88-independent mechanisms that stimulate neutralizing antibody formation against AAV.
Electronic Cigarettes and Cannabis: An Exploratory Study
Authors: Etter Jean-Francois
Published: January 2015

Aims: To describe cannabis ‘vaping' with electronic cigarettes (e-cigarettes) or electronic vaporizers (e-vaporizers). Methods: Internet survey in 2013-2014. Participants were 11 people who ‘vaped' cannabis with e-cigarettes and 44 people who vaped cannabis with e-vaporizers, enrolled online. Results: Most participants were men (78%). They had used e-cigarettes for 6 days and e-vaporizers for 50 days on average to vape cannabis. Current users of e-cigarettes vaped cannabis on 2 days/week versus 6 days/week for users of e-vaporizers. In these devices, they mostly inserted cannabis buds and oil rather than hashish or wax/butane honey oil. Dual users, who both smoked and vaped cannabis, currently smoked 5 joints/week compared to 14 joints/week before they started to vape cannabis (p = 0.004). Half the participants (45%) reported that vaping cannabis helped them stop or reduce their total cannabis use, 37% that it had no impact on their cannabis use, and 6% that it increased it. Vaping cannabis was perceived as healthier and more discrete than smoking it (less odor). Disadvantages included dry mouth and fewer positive cannabis effects. Conclusions: Cannabis vaping via e-cigarettes or e-vaporizers is an infrequent behavior that was previously almost undocumented. E-cigarettes do not appear to be a very appealing way to use cannabis.
A Continuous Metabolic Syndrome Score Is Associated with Specific Biomarkers of Inflammation and CVD Risk in Prepubertal Children
Authors: Olza Josune , Aguilera Concepción M. , Gil-Campos Mercedes , Leis Rosaura , Bueno Gloria , Valle Miguel , Cañete Ramón , Tojo Rafael , Moreno Luis A. , Gil Ángel
Published: January 2015

Background/Aims: We aimed to evaluate the use of a continuous metabolic syndrome (MetS) score and to assess the associations of this score with risk biomarkers of inflammation, endothelial damage and cardiovascular disease (CVD) in prepubertal children. Methods: A total of 677 prepubertal children (295 obese, 146 overweight, and 236 normal-weight) were recruited. MetS traits, markers of inflammation, endothelial damage and CVD risk were measured, and a continuous MetS score was calculated, consisting of the sum/5 of the standardised scores of the MetS components. Results: The continuous MetS score was significantly associated with active plasminogen activator inhibitor-1 (r = 0.406, p < 0.001), adiponectin (r = -0.212, p < 0.001), resistin (r = 0.263, p < 0.001), C-reactive protein (r = 0.254, p < 0.001), tumour necrosis factor alpha (r = 0.120, p = 0.003), myeloperoxidase (r = 0.188, p < 0.001) and sE-selectin (r = 0.278, p < 0.001). Children in the normal-weight, overweight and obese groups with MetS totalled 0 (0%), 1 (0.7%) and 24 (8.7%), respectively, whereas the at-risk children identified using the continuous MetS score in each group totalled 2 (0.85%), 17 (11.6%) and 167 (56.6%), respectively. Conclusions: The association of the continuous MetS score with specific risk biomarkers of inflammation, endothelial damage and CVD supports its use in the early identification of children at increased risk of metabolic dysfunction.
Accuracy of Reporting the Hyperdense Middle Cerebral Artery Sign as a Function of Clinical Experience
Authors: Aouad Patrick , Hughes Andrew , Neeman Terry , Lueck Christian J.
Published: January 2015

Background/Aim: The hyperdense middle cerebral artery sign (HMCAS) is a useful clinical sign in the management of acute stroke and may alter time-critical decisions within an emergency setting. Though gold standards have been published, these are rarely used in clinical practice and scans tend to be reported subjectively. It is therefore possible that the level of experience of the doctor reporting the scan may impact on the accuracy of the reporting and hence patient management. This study was designed to evaluate the accuracy in detecting HMCAS across doctors with varying levels of experience. Methods: Forty doctors were recruited into four categories of experience. Each subject received a brief computer-based tutorial on how to identify an HMCAS and was then asked to report on the presence or absence of an HMCAS in 19 pre-prepared CT scans using a standardised viewing template. Results: The mean (±SE) percentage correct scores increased with experience from 76.8 ± 3.69 among interns and residents to 90.1 ± 2.23 (neurologists and radiologists; p < 0.01). Sensitivity and specificity as well as positive and negative predictive values all increased with experience. In addition, more experienced clinicians were better able to distinguish scans which met the radiological criteria for HMCAS from those which only just failed to do so. Conclusions: Experienced neurologists and radiologists consistently and accurately reported the presence or absence of HMCAS, whereas less experienced clinicians tended to over-report the presence of HMCAS. This may have implications for the acute management of thromboembolic stroke.
Iron Intake and Status of Children Aged 6-36 Months in Europe: A Systematic Review
Authors: Eussen Simone , Alles Martine , Uijterschout Lieke , Brus Frank , van der Horst-Graat Judith
Published: January 2015

Background: Iron deficiency is the most common nutritional disorder in the world. Young children are particularly vulnerable to the consequences of iron deficiency because of their rapidly developing brain. This review evaluates the prevalence of inadequate iron intake and iron deficiency (anaemia) in European children aged 6-36 months. Summary: Computerized searches for relevant articles were performed in November 2013. A total of 7,297 citations were screened and 44 studies conducted in 19 European countries were included in this review. In both infants (6-12 months) and young children (12-36 months), the mean value of iron intakes in most countries was close to the RDA. Nevertheless, proportions of inadequate intakes were considerable, ranging from about 10% in the Netherlands up to 50% in Austria, Finland and the United Kingdom. The prevalence of iron deficiency varied between studies and was influenced by children's characteristics. Two to 25% of infants aged 6-12 months were found to be iron deficient, with a higher prevalence in those who were socially vulnerable and those who were drinking cow's milk as a main type of drink in their first year of life. In children aged 12-36 months, prevalence rates of iron deficiency varied between 3 and 48%. Prevalence of iron deficiency anaemia in both age groups was high in Eastern Europe, as high as 50%, whereas the prevalence in Western Europe was generally below 5%. Key Messages: In most European countries, mean iron intakes of infants and children aged 6 to 36 months were found to be close to the RDA. Nevertheless, high proportions of inadequate intakes and high prevalence rates of iron deficiency were observed. Health programs should (keep) focus(ing) on iron malnutrition by educating parents on food choices for their children with iron-rich and iron-fortified foods, and encourage iron supplementation programmes where iron intakes are the lowest.
Using a Cardiac Arrest Registry to Measure the Quality of Emergency Medical Service Care
Authors: Nehme Ziad , Bernard Stephen , Cameron Peter , Bray Janet E. , Meredith Ian T. , Lijovic Marijana , Smith Karen
Published: January 2015

Background—

Although the value of clinical registries has been well recognized in developed countries, their use for measuring the quality of emergency medical service care remains relatively unknown. We report the methodology and findings of a statewide emergency medical service surveillance initiative, which is used to measure the quality of systems of care for patients with out-of-hospital cardiac arrest.

Methods and Results—

Between July 1, 2002, and June 30, 2012, data for adult out-of-hospital cardiac arrest cases of presumed cardiac cause occurring in the Australian Southeastern state of Victoria were extracted from the Victorian Ambulance Cardiac Arrest Registry. Regional and temporal trends in bystander cardiopulmonary resuscitation, event survival, and survival to hospital discharge were analyzed using logistic regression and multilevel modeling. A total of 32 097 out-of-hospital cardiac arrest cases were identified, of whom 14 083 (43.9%) received treatment by the emergency medical service. The risk-adjusted odds of receiving bystander cardiopulmonary resuscitation (odds ratio [OR], 2.96; 95% confidence interval, 2.62–3.33), event survival (OR, 1.55; 95% confidence interval, 1.30–1.85), and survival to hospital discharge (OR, 2.81; 95% confidence interval, 2.07–3.82) were significantly improved by 2011 to 2012 compared with baseline. Significant variation in rates of bystander cardiopulmonary resuscitation and survival were observed across regions, with arrests in rural regions less likely to survive to hospital discharge. The median OR for interhospital variability in survival to hospital discharge outcome was 70% (median OR, 1.70).

Conclusions—

Between 2002 and 2012, there have been significant improvements in bystander cardiopulmonary resuscitation and survival outcome for out-of-hospital cardiac arrest patients in Victoria, Australia. However, regional survival disparities and interhospital variability in outcomes pose significant challenges for future improvements in care.