bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous concentrations of ouabain act as a cofactor to stimulate fluid secretion and cyst growth of in vitro ADPKD models via cAMP and EGFR-Src-MEK pathways
Authors: Jansson Kyle , Nguyen Anh-Nguyet T. , Magenheimer Brenda S. , Reif Gail A. , Aramadhaka Lavakumar Reddy , Bello-Reuss Elsa , Wallace Darren P. , Calvet James P. , Blanco Gustavo
Published: August 2012

In autosomal-dominant polycystic kidney disease (ADPKD), renal cysts develop by aberrant epithelial cell proliferation and transepithelial fluid secretion. We previously showed that ouabain increases proliferation of cultured human ADPKD cells via stimulation of the EGF receptor (EGFR)-Src-MEK/ERK signaling pathway. We examined whether ouabain affects fluid secretion and in vitro cyst growth of human ADPKD cell monolayers, ADPKD cell microcysts cultured in a three-dimensional collagen matrix, and metanephric organ cultures from Pkd1m1Beimice. Physiological concentrations of ouabain alone did not affect net transepithelial basal-to-apical fluid transport in ADPKD monolayers or growth of cultured ADPKD microcysts. In contrast, in the presence of forskolin or 8-bromo-cAMP, ouabain significantly enhanced ADPKD fluid secretion and microcyst expansion. Ouabain exerted this effect by enhancing cAMP-dependent Cl−secretion via the CFTR. Similarly, ouabain accelerated cAMP-dependent cyst enlargement in Pkd1m1Beimice metanephroi, with a more prominent response in homozygous than heterozygous mice. Ouabain had no effect on fluid secretion and cystogenesis of normal human kidney cells and caused only slight cystic dilations in wild-type mouse kidneys. The effects of ouabain in ADPKD cells and Pkd1m1Beimetanephroi were prevented by inhibitors of EGFR (AG1478), Src (PP2), and MEK (U0126). Together, our results show that ouabain, used in physiological concentrations, has synergistic effects on cAMP-mediated fluid secretion and cyst growth, via activation of the EGFR-Src-MEK pathway. These data provide important evidence for the role of ouabain as an endogenous hormone that exacerbates ADPKD cyst progression.
5-Hydroxytryptamine 2C receptors tonically augment synaptic currents in the nucleus tractus solitarii
Authors: Austgen James R. , Dantzler Heather A. , Barger Brenna K. , Kline David D.
Published: August 2012

The nucleus tractus solitarii (nTS) is the primary termination and integration point for visceral afferents in the brain stem. Afferent glutamate release and its efficacy on postsynaptic activity within this nucleus are modulated by additional neuromodulators and transmitters, including serotonin (5-HT) acting through its receptors. The 5-HT2receptors in the medulla modulate the cardiorespiratory system and autonomic reflexes, but the distribution of the 5-HT2Creceptor and the role of these receptors during synaptic transmission in the nTS remain largely unknown. In the present study, we examined the distribution of 5-HT2Creceptors in the nTS and their role in modulating excitatory postsynaptic currents (EPSCs) in monosynaptic nTS neurons in the horizontal brain stem slice. Real-time RT-PCR and immunohistochemistry identified 5-HT2Creceptor message and protein in the nTS and suggested postsynaptic localization. In nTS neurons innervated by general visceral afferents, 5-HT2Creceptor activation increased solitary tract (TS)-EPSC amplitude and input resistance and depolarized membrane potential. Conversely, 5-HT2Creceptor blockade reduced TS-EPSC and miniature EPSC amplitude, as well as input resistance, and hyperpolarized membrane potential. Synaptic parameters in nTS neurons that receive sensory input from carotid body chemoafferents were also attenuated by 5-HT2Creceptor blockade. Taken together, these data suggest that 5-HT2Creceptors in the nTS are located postsynaptically and augment excitatory neurotransmission.
Transcranial electrical stimulation over visual cortex evokes phosphenes with a retinal origin
Authors: Kar Kohitij , Krekelberg Bart
Published: August 2012

Transcranial electrical stimulation (tES) is a promising therapeutic tool for a range of neurological diseases. Understanding how the small currents used in tES spread across the scalp and penetrate the brain will be important for the rational design of tES therapies. Alternating currents applied transcranially above visual cortex induce the perception of flashes of light (phosphenes). This makes the visual system a useful model to study tES. One hypothesis is that tES generates phosphenes by direct stimulation of the cortex underneath the transcranial electrode. Here, we provide evidence for the alternative hypothesis that phosphenes are generated in the retina by current spread from the occipital electrode. Building on the existing literature, we first confirm that phosphenes are induced at lower currents when electrodes are placed farther away from visual cortex and closer to the eye. Second, we explain the temporal frequency tuning of phosphenes based on the well-known response properties of primate retinal ganglion cells. Third, we show that there is no difference in the time it takes to evoke phosphenes in the retina or by stimulation above visual cortex. Together, these findings suggest that phosphenes induced by tES over visual cortex originate in the retina. From this, we infer that tES currents spread well beyond the area of stimulation and are unlikely to lead to focal neural activation. Novel stimulation protocols that optimize current distributions are needed to overcome these limitations of tES.
Green Tea Extract Ameliorates Learning and Memory Deficits in Ischemic Rats via Its Active Component Polyphenol Epigallocatechin-3-gallate by Modulation of Oxidative Stress and Neuroinflammation
Authors: Wu Kuo-Jen , Hsieh Ming-Tsuen , Wu Chi-Rei , Wood W. Gibson , Chen Yuh-Fung
Published: August 2012

Ischemic stroke results in brain damage and behavioral deficits including memory impairment. Protective effects of green tea extract (GTex) and its major functional polyphenol (−)-epigallocatechin gallate (EGCG) on memory were examined in cerebral ischemic rats. GTex and EGCG were administered 1 hr before middle cerebral artery ligation in rats. GTex, EGCG, and pentoxifylline (PTX) significantly improved ishemic-induced memory impairment in a Morris water maze test. Malondialdehyde (MDA) levels, glutathione (GSH), and superoxide dismutase (SOD) activity in the cerebral cortex and hippocampus were increased by long-term treatment with GTex and EGCG. Both compounds were also associated with reduced cerebral infraction breakdown of MDA and GSH in the hippocampus. Inin vitroexperiments, EGCG had anti-inflammatory effects in BV-2 microglia cells. EGCG inhibited lipopolysaccharide- (LPS-) induced nitric oxide production and reduced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV-2 cells. GTex and its active polyphenol EGCG improved learning and memory deficits in a cerebral ischemia animal model and such protection may be due to the reduction of oxidative stress and neuroinflammation.
Cellular Automata-Based Parallel Random Number Generators Using FPGAs
Authors: Hoe David H. K. , Comer Jonathan M. , Cerda Juan C. , Martinez Chris D. , Shirvaikar Mukul V.
Published: August 2012

Cellular computing represents a new paradigm for implementing high-speed massively parallel machines. Cellular automata (CA), which consist of an array of locally connected processing elements, are a basic form of a cellular-based architecture. The use of field programmable gate arrays (FPGAs) for implementing CA accelerators has shown promising results. This paper investigates the design of CA-based pseudo-random number generators (PRNGs) using an FPGA platform. To improve the quality of the random numbers that are generated, the basic CA structure is enhanced in two ways. First, the addition of a superrule to each CA cell is considered. The resulting self-programmable CA (SPCA) uses the superrule to determine when to make a dynamic rule change in each CA cell. The superrule takes its inputs from neighboring cells and can be considered itself a second CA working in parallel with the main CA. When implemented on an FPGA, the use of lookup tables in each logic cell removes any restrictions on how the super-rules should be defined. Second, a hybrid configuration is formed by combining a CA with a linear feedback shift register (LFSR). This is advantageous for FPGA designs due to the compactness of the LFSR implementations. A standard software package for statistically evaluating the quality of random number sequences known as Diehardis used to validate the results. Both the SPCA and the hybrid CA/LFSR were found to pass all the Diehardtests.
Depression Treatment with Duloxetine and Reduction of Inability to Work
Authors: Happich Michael , Schneider Edith , Wilhelm Stefan , Zimmermann Thomas , Schacht Alexander
Published: August 2012

Data on inability to work from an observational study in patients treated with duloxetine for major depressive disorder in clinical practice in Germany were collected. Ability to work was compared between baseline and up to 6 months after initiation of duloxetine. All patients with a working status at baseline other than retired or retired early were included. 2,825 patients were analyzed, 54.8% were able to work at baseline increasing to 83.8% at 6 months. Of those patients unable to work at baseline, 72.7% were able to work after 6 months. A relevant reduction of inability to work was also found for patient subgroups with moderate to severe pain at baseline and those with and without MDD pretreatment. As inability to work is one of the main cost drivers for depressive patients in Germany, the reduction of inability to work could potentially result in considerable cost savings for health insurance companies and society.
The Interaction between Pesticide Use and Genetic Variants Involved in Lipid Metabolism on Prostate Cancer Risk
Authors: Andreotti Gabriella , Koutros Stella , Berndt Sonja I. , Hughes Barry Kathryn , Hou Lifang , Hoppin Jane A. , Sandler Dale P. , Lubin Jay H. , Burdette Laurie A. , Yuenger Jeffrey , Yeager Meredith , Beane Freeman Laura E. , Alavanja Michael C. R.
Published: August 2012

Background. Lipid metabolism processes have been implicated in prostate carcinogenesis. Since several pesticides are lipophilic or are metabolized via lipid-related mechanisms, they may interact with variants of genes in the lipid metabolism pathway.Methods. In a nested case-control study of 776 cases and 1444 controls from the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators, we examined the interactions between 39 pesticides (none, low, and high exposure) and 220 single nucleotide polymorphisms (SNPs) in 59 genes. The false discovery rate (FDR) was used to account for multiple comparisons.Results. We found 17 interactions that displayed a significant monotonic increase in prostate cancer risk with pesticide exposure in one genotype and no significant association in the other genotype. The most noteworthy association was forALOXE3rs3027208 and terbufos, such that men carrying the T allele who were low users had an OR of 1.86 (95% CI = 1.16–2.99) and high users an OR of 2.00 (95% CI = 1.28–3.15) compared to those with no use of terbufos, while men carrying the CC genotype did not exhibit a significant association.Conclusion. Genetic variation in lipid metabolism genes may modify pesticide associations with prostate cancer; however our results require replication.
Ventricular Septal Defect in an Octogenarian: A Case Report of VSD Surgical Repair Concomitant with Coronary Artery Bypass and Valvular Surgery
Authors: Tayama Eiki , Fujita Satoshi , Ueda Tomohiro , Imasaka Ken-ich , Enomoto Naofumi , Onitsuka Hirofumi , Tomita Yukihiro
Published: August 2012

Finding an untreated or asymptomatic large ventricular septal defect (VSD) in an elderly patient is uncommon. The present case was an 81-year-old man who suffered from acute myocardial infarction due to three-vessel coronary disease, mitral and tricuspid valve insufficiency, and high-flow perimembranous VSD (Qp/Qs 2.3). Although the patient was elderly and the VSD had been asymptomatic for a long time, we considered that high-flow VSD and valve diseases should be repaired simultaneously with coronary disease. Then, he underwent elective surgery, namely, VSD patch repair concomitant with coronary artery bypass grafting, and mitral and tricuspid annuloplasty. His postoperative course was uneventful. We conclude that, even for an octogenarian, surgical repair of VSD is recommendable, if surgical indications are appropriate.
Emerging Stem Cell Therapies: Treatment, Safety, and Biology
Authors: Sng Joel , Lufkin Thomas
Published: August 2012

Stem cells are the fundamental building blocks of life and contribute to the genesis and development of all higher organisms. The discovery of adult stem cells has led to an ongoing revolution of therapeutic and regenerative medicine and the proposal of novel therapies for previously terminal conditions. Hematopoietic stem cell transplantation was the first example of a successful stem cell therapy and is widely utilized for treating various diseases including adult T-cell leukemia-lymphoma and multiple myeloma. The autologous transplantation of mesenchymal stem cells is increasingly employed to catalyze the repair of mesenchymal tissue and others, including the lung and heart, and utilized in treating various conditions such as stroke, multiple sclerosis, and diabetes. There is also increasing interest in the therapeutic potential of other adult stem cells such as neural, mammary, intestinal, inner ear, and testicular stem cells. The discovery of induced pluripotent stem cells has led to an improved understanding of the underlying epigenetic keys of pluripotency and carcinogenesis. More in-depth studies of these epigenetic differences and the physiological changes that they effect will lead to the design of safer and more targeted therapies.
Direct Synthesis of Dual-Parameter Concentric Ring RA with Enhanced Bandwidth
Authors: Ha Bui Van , Pirinoli Paola , Zich Riccardo E. , Mussetta Marco
Published: August 2012

Reflectarray antennas (RAs) are nowadays a quite popular technology, used in several applications, due to a significant number of attractive properties, such as low cost, low weight, conformal deployment, and the possibility of introducing suitable reconfigurable capabilities. Unfortunately, they present also some intrinsic limitations and drawbacks compared with other solutions and, in particular, a relatively narrow bandwidth; that of course could be enlarged, but generally with a drastic increase of the structure complexity. The objective of this work is the design of a single-layer passive reflectarray, in which the reradiated elements have no conventional shape and enough degrees of freedom to compensate both the spatial and frequency phase variation of the reradiated field. In particular, here we focus on a reradiating element consisting in two concentric square rings in which two different and quite independent geometric parameters are varied.
Encountering Anger in the Emergency Department: Identification, Evaluations and Responses of Staff Members to Anger Displays
Authors: Arik Cheshin , Anat Rafaeli , Arie Eisenman
Published: August 2012

Background. Anger manifestations in emergency departments (EDs) occur daily, interrupting workflow and exposing staff to risk.Objectives. How staff assess and recognize patients’ angry outbursts in EDs and elucidate responses to anger expressions, while considering effects of institution guidelines.Methods. Observations of staff patient interaction in EDs and personal interviews of staff (n=38) were conducted. Two questionnaires were administered (n=80&n=144). Assessment was based mainly on regression statistic tests.Results. Staff recognizes two types of anger displays. Magnitude of anger expressions were correlated with staff’s fear level. Staff’s responses ranged from ignoring incidents, giving in to patients’ requests or immediately calling security. When staff felt fear and became angry they tended to call security. Staff was more likely to ignore anger when incident responsibility was assigned to patients.Discussion. Anger encounters are differentiated according to intensity level, which influences interpretations and response. Organizational policy has an effect on staff’s response.Conclusions. Staff recognizes anger at varying levels and responds accordingly. The level of danger staff feels is a catalyst in giving in or calling security. Call security is influenced by fear, and anger. Permanent guidelines can help staff in responding to anger encounters.
Multiobjective Interaction Programming Problem with Interaction Constraint for Two Players
Authors: Jiang Min , Meng Zhiqing , Xu Xinsheng , Shen Rui , Zhou Gengui
Published: August 2012

This paper extends an existing cooperative multi‐objective interaction programming problem with interaction constraint for two players (or two agents). First, we define an s‐optimal joint solution with weight vector to multi‐objective interaction programming problem with interaction constraint for two players and get some properties of it. It is proved that the s‐optimal joint solution with weight vector to the multi‐objective interaction programming problem can be obtained by solving a corresponding mathematical programming problem. Then, we define another s‐optimal joint solution with weight value to multi‐objective interaction programming problem with interaction constraint for two players and get some of its properties. It is proved that the s‐optimal joint solution with weight vector to multi‐objective interaction programming problem can be obtained by solving a corresponding mathematical programming problem. Finally, we build a pricing multi‐objective interaction programming model for a bi‐level supply chain. Numerical results show that the interaction programming pricing model is better than Stackelberg pricing model and the joint pricing model.
Inverse Estimation of Open Boundary Conditions in the Bohai Sea
Authors: Guo Zheng , Cao Anzhou , Lv Xianqing
Published: August 2012

This paper presents an algorithm for the estimation of open boundary conditions (OBCs) which force tides in the interior region by an adjoint data assimilation approach. Assuming that OBCs are position dependent, OBCs can be approximated by linear interpolation among values at certain independent points (IPs). Twin experiments are performed to examine the sensitivity of the model to the IP distribution and interpolation radius. It is proved that the prescribed OBCs can be well recovered with appropriate number of IP and interpolation radius. In the Bohai Sea model domain with horizontal resolution of 10’×10’, the appropriate number of IP is 3 and the interpolation radius is 60′. In the practical experiment, the M2 constituent in the Bohai Sea is simulated by assimilating the T/P data and tidal gauge data. The mean absolute errors in amplitude and phase are 5.0 cm and 5.7°, respectively, and the cochart obtained shows the character of M2 constituent in the Bohai Sea.
Review of Minimally Invasive Esophagectomy and Current Controversies
Authors: Kim T. , Hochwald S. N. , Sarosi G. A. , Caban A. M. , Rossidis G. , Ben-David K.
Published: August 2012

Esophagectomy is a complex operation with significant morbidity and mortality. Minimally invasive esophagectomy (MIE) was described in the 1990s in an effort to reduce operative morbidity. Since then many institutions have adopted and described their series with this technique. This paper reviews the literature on the variety of MIE techniques, clinical and quality of life outcomes with open versus MIE, and controversies surrounding MIE—such as prone positioning, stapling techniques, size of the gastric conduit, and robotic techniques.
Thyroid Peroxidase Gene Mutation in Patients with Congenital Hypothyroidism in Isfahan, Iran
Authors: Hashemipour Mahin , Soheilipour Fahimeh , Karimizare Sakineh , Khanahmad Hossein , Karimipour Morteza , Aminzadeh Sepideh , Kokabee Leila , Amini Massoud , Hovsepian Silva , Hadian Rezvaneh
Published: August 2012

Background. Thyroid peroxidase gene (TPO) mutations are one of the most common causes of thyroid dyshormonogenesis in patients with congenital hypothyroidism (CH). In this study, the prevalence of TPO gene mutations in patients with thyroid dyshormonogenesis in Isfahan was investigated.Methods. In this cross-sectional study, genomic DNA of 41 patients with permanent CH due to thyroid dyshormonogenesis was extracted using the salting out method. The 17 exonic regions of the TPO gene were amplified. SSCP technique was performed for scanning of the exonic regions of the TPO gene, except exon 8. DNA sequencing was performed for those with different migration patterns in SSCP by chain termination method. Exon 8 was sequenced directly in all patients. In 4 patients, all fragments were also sequenced.Results. One missense mutationc.2669G>A(NM_000547.5) at exon 15 (14th coding exon) in one patient in homozygous form and seven different single nucleotide polymorphisms (SNPs) in exons 1, 7, 8, 11, and 15 of TPO gene.Conclusion. The TPO gene mutations among CH patients with dyshormonogenesis in Isfahan were less frequent in comparison with other similar studies. It may be due to the presence of other unknown gene mutations which could not be detected by SSCP and sequencing methods.
Comparison Study of Resource Allocation Strategies for OFDM Multimedia Networks
Authors: Guéguen Cédric , Baey Sébastien
Published: August 2012

Advanced MAC scheduling schemes provide efficient support of multimedia services in multiuser OFDM wireless networks. Designed in a cross layer approach, they opportunistically consider the channel state and are well adapted to the wireless multipath fading environment. These schedulers take advantage of time, frequency, and multiuser diversity. Thereby they maximize the global system throughput while ensuring the highest possible level of fairness. However their performances heavily depend on the bandwidth granularity (i.e., the number of elementary resource units) that is used in the resource allocation process. This paper presents and compares the main OFDM scheduling techniques. In particular it studies the influence of bandwidth granularity on the resource allocation strategies performances. The paper reveals that though bandwidth granularity has never been considered in former studies, it is of major importance for determining the application range of advanced OFDM scheduling techniques.
Numerical Solution of Stochastic Hyperbolic Equations
Authors: Aggez Necmettin , Ashyralyyewa Maral
Published: August 2012

A two‐step difference scheme for the numerical solution of the initial‐boundary value problem for stochastic hyperbolic equations is presented. The convergence
estimate for the solution of the difference scheme is established. In applications, the convergence estimates for the solution of the difference scheme are obtained for different initialboundary value problems. The theoretical statements for the solution of this difference
scheme are supported by numerical examples.
Investigating Properties of the Cardiovascular System Using Innovative Analysis Algorithms Based on Ensemble Empirical Mode Decomposition
Authors: Yeh Jia-Rong , Lin Tzu-Yu , Chen Yun , Sun Wei-Zen , Abbod Maysam F. , Shieh Jiann-Shing
Published: August 2012

Cardiovascular system is known to be nonlinear and nonstationary. Traditional linear assessments algorithms of arterial stiffness and systemic resistance of cardiac system accompany the problem of nonstationary or inconvenience in practical applications. In this pilot study, two new assessment methods were developed: the first is ensemble empirical mode decomposition based reflection index (EEMD-RI) while the second is based on the phase shift between ECG and BP on cardiac oscillation. Both methods utilise the EEMD algorithm which is suitable for nonlinear and nonstationary systems. These methods were used to investigate the properties of arterial stiffness and systemic resistance for a pig’s cardiovascular system via ECG and blood pressure (BP). This experiment simulated a sequence of continuous changes of blood pressure arising from steady condition to high blood pressure by clamping the artery and an inverse by relaxing the artery. As a hypothesis, the arterial stiffness and systemic resistance should vary with the blood pressure due to clamping and relaxing the artery. The results show statistically significant correlations between BP, EEMD-based RI, and the phase shift between ECG and BP on cardiac oscillation. The two assessments results demonstrate the merits of the EEMD for signal analysis.
The Relationship Between Homologous Recombination Repair and the Sensitivity of Human Epidermis to the Size of Daily Doses Over a 5-Week Course of Breast Radiotherapy
Authors: Somaiah Navita , Yarnold John , Daley Frances , Pearson Ann , Gothard Lone , Rothkamm Kai , Helleday Thomas
Published: August 2012

Purpose: A molecular understanding of tissue sensitivity to radiotherapy fraction size is missing. Here, we test the hypothesis that sensitivity to fraction size is influenced by the DNA repair system activated in response to DNA double-strand breaks (DSB). Human epidermis was used as a model in which proliferation and DNA repair were correlated over 5 weeks of radiotherapy.

Experimental design: Radiotherapy (25 fractions of 2 Gy) was prescribed to the breast in 30 women with early breast cancer. Breast skin biopsies were collected 2 hours after the 1st and 25th fractions. Samples of contralateral breast skin served as controls. Sections were coimmunostained for Ki67, cyclin A, p21, RAD51, 53BP1, and β1-integrin.

Results: After 5 weeks of radiotherapy, the mean basal Ki67 density increased from 5.72 to 15.46 cells per millimeter of basement membrane (P = 0.002), of which the majority were in S/G2 phase, as judged by cyclin A staining (P < 0.0003). The p21 index rose from 2.8% to 87.4% (P < 0.0001) after 25 fractions, indicating cell cycle arrest. By week 5, there was a 4-fold increase (P = 0.0003) in the proportion of Ki67-positive cells showing RAD51 foci, suggesting increasing activation of homologous recombination.

Conclusions: Cell cycle arrest in S/G2 phase in the basal epidermis after a 5-week course of radiotherapy is associated with greater use of homologous recombination for repairing DSB. The high fidelity of homologous recombination, which is independent of DNA damage levels, may explain the low-fractionation sensitivity of tissues with high-proliferative indices, including self-renewing normal tissues and many cancers. Clin Cancer Res; 18(19); 5479–88. ©2012 AACR.
First Identification of Culex flavivirus (Flaviviridae) in Brazil
Authors: Machado Daiane Cristina , Mondini Adriano , Santana Vinicius dos Santos , Yonamine Patrícia Tiemi Kamiya , Chiaravalloti Neto Francisco , Zanotto Paolo Marinho de Andrade , Nogueira Mauricio Lacerda
Published: August 2012

Introduction:Culex flavivirus (CxFV) was first isolated in 2007 from Culex pipiens in Japan and then identified in several other countries. Characterization of the CxFV showed that all strains are related to the cell fusing agent virus. In this manuscript we report the first identification of CxFV in South America. Material and Methods: We have collected Culex sp. mosquitoes using BG-Sentinel traps and manual aspirators. They were pooled according to genus, species, sex and location. Viral RNA was extracted and multiplex nested PCR was performed to test the presence of Flavivirus. The positive samples were isolated in C6/36 cells and sequenced for phylogenetic analyses. Results: 265 female Culex mosquitoes pooled in 83 pools were tested with specific CxFV, Saint Louis encephalitis virus (SLEV) and West Nile virus (WNV) primers. Our sequence data indicated maximum sequence similarity of 97% with CxFV. Discussion: In this study we report the circulation of CxFV in an urban setting where SLEV had previously caused an outbreak. In terms of public health, this is an important finding due to the assumption that the previous exposition of mosquitoes to CxFV might lessen the susceptibility of these mosquitoes to other flaviviruses.
Updated Reference Ranges for the Ductus Venosus Pulsatility Index at 11–13 Weeks
Authors: Sabria Joan , Comas Carmina , Barceló-Vidal Carles , Garcia-Posada Raul , Echevarria Monica , Gomez-Roig Maria Dolors , Borrell Antoni
Published: August 2012

Objective: To update the reference ranges for the ductus venosus pulsatility index (DVPI) at 11+0 to 13+6 gestational weeks. Methods: DVPI was calculated in 14,444 singleton fetuses at 11+0 to 13+6 weeks in two Fetal Medicine Centers, during a 4-year period. Using previously described medians, DVPI evolution was assessed both over the study period on a yearly basis and over gestation, grouping fetuses according to 5-mm crown-rump length (CRL) ranges. Weighted DVPI medians, the 5th and 95th percentiles and distribution parameters for unaffected and trisomy 21 fetuses were newly calculated. Results: A significant DVPI multiple of the median decrease was observed over both the study period (p < 0.01) and over gestation (p < 0.01) using previous medians, in the two centers. Newly calculated weighted medians were lower than those previously described, decreasing with CRL. Distribution parameters calculated using the new medians were different from those previously described. Conclusion: DVPI reference ranges were lower than those previously reported and decreased with CRL. Updated medians and distribution parameters should be considered to include the DVPI as a Gaussian marker in trisomy 21 screening and for quality control purposes.
Pseudorabies Virus and Herpes Simplex Virus Type 1 Utilize Different Tegument-Glycoprotein Interactions to Mediate the Process of Envelopment
Authors: Omar Omar S. , Simmons Alicia J. , Andre Nicole M. , Wilson Duncan W. , Gross Sarah T.
Published: August 2012

Background and Objective: During herpesvirus envelopment capsids, tegument polypeptides and membrane proteins assemble at the site of budding, and a cellular lipid bilayer becomes refashioned into a spherical envelope. A web of interactions between tegument proteins and the cytoplasmic tails of viral glycoproteins play a critical role in this process. We have previously demonstrated that for herpes simplex virus (HSV)-1 the cytoplasmic tail of glycoprotein H (gH) binds the tegument protein VP16. The HSV and pseudorabies virus (PRV) genomes are essentially collinear, and individual gene products show significant sequence homology. However, the demarcation of function often differs between PRV and HSV proteins. The goal of this study was to determine whether PRV gH and VP16 interact in a manner similar to their homologs in HSV. Methods: A fusion protein pull-down assay was performed in which a PRV gH cytoplasmic tail-glutathione S-transferase fusion protein, bound to glutathione-Sepharose beads, was incubated with PRV-infected cell cytosol, washed and subjected to Western blot analysis using anti-PRV VP16 antisera. Results: Western blots indicate that PRV VP16 does not specifically bind to the PRV gH tail. Conclusion: Our results highlight that, despite the relatively close evolutionary relationship between HSV and PRV, there are significant differences in their protein interactions that drive envelopment.
Local Hemodynamics at the Rupture Point of Cerebral Aneurysms Determined by Computational Fluid Dynamics Analysis
Authors: Omodaka Shunsuke , Sugiyama Shin-ichirou , Inoue Takashi , Funamoto Kenichi , Fujimura Miki , Shimizu Hiroaki , Hayase Toshiyuki , Takahashi Akira , Tominaga Teiji
Published: August 2012

Background: Cerebral aneurysms carry a high risk of rupture and so present a major threat to the patient’s life. Accurate criteria for predicting aneurysm rupture are important for therapeutic decision-making, and some clinical and morphological factors may help to predict the risk for rupture of unruptured aneurysms, such as sex, size and location. Hemodynamic forces are considered to be key in the natural history of cerebral aneurysms, but the effect on aneurysm rupture is uncertain, and whether low or high wall shear stress (WSS) is the most critical in promoting rupture remains extremely controversial. This study investigated the local hemodynamic features at the aneurysm rupture point. Methods: Computational models of 6 ruptured middle cerebral artery aneurysms with intraoperative confirmation of rupture point were constructed from 3-dimensional rotational angiography images. Computational fluid dynamics (CFD) simulations were performed under pulsatile flows using patient-specific inlet flow conditions. Time-averaged WSS (TAWSS) and oscillatory shear index (OSI) were calculated, and compared at the rupture point and at the aneurysm wall without the rupture point. We performed an additional CFD simulation of a bleb-removed model for a peculiar case in which bleb formation could be confirmed by magnetic resonance angiography. Results: All rupture points were located at the body or dome of the aneurysm. The TAWSS at the rupture point was significantly lower than that at the aneurysm wall without the rupture point (1.10 vs. 4.96 Pa, p = 0.031). The OSI at the rupture point tended to be higher than at the aneurysm wall without the rupture point, although the difference was not significant (0.0148 vs. 0.0059, p = 0.156). In a bleb-removed simulation, the TAWSS at the bleb-removed area was 6.31 Pa, which was relatively higher than at the aneurysm wall (1.94 Pa). Conclusion: The hemodynamics of 6 ruptured cerebral aneurysms of the middle cerebral artery were examined using retrospective CFD analysis. We could confirm the rupture points in all cases. With those findings, local hemodynamics of ruptured aneurysms were quanti-tatively investigated. The rupture point is located in a low WSS region of the aneurysm wall. Bleb-removed simulation showed increased WSS of the bleb-removed area, associated with the flow impaction area. Although the number of subjects in this study was relatively small, our findings suggest that the location of the rupture point is related to a low WSS at the aneurysm wall. Further investigations will elucidate the detailed hemodynamic effects on aneurysm rupture.
Ictal Intracranial Recording from a ‘Burned-Out Hippocampus’
Authors: Gatzonis Stylianos , Siatouni Anna , Georgaculias Nikos , Korfias Stefanos , Sakas Damianos E.
Published: August 2012

Objective: To present a case involving a discrepancy in the presurgical data of a patient suffering from pharmacoresistant mesial temporal lobe epilepsy. Clinical Presentation and Intervention: A 47-year-old, female patient with complex partial seizures since her twenties came to be evaluated in the Epilepsy Surgery Unit. The ictal electroencephalogram suggested a left temporal epileptogenic zone and the magnetic resonance image showed an abnormality in the right mesial temporal lobe. Intracranial monitoring revealed a pacemaker zone in the right hippocampus that discharged fast spreading to the left mesial temporal lobe, a phenomenon known as ‘burned-out hippocampus’. Conclusion: The intracranial recording, even though it is an invasive procedure, was necessary for the presurgical evaluation of our patient. This case demonstrates the risks of using surface electroencephalography to determine localization of epileptogenic zones.
Is PCA3 Score Useful in Preoperative Staging of a Single Microfocus of Prostate Cancer Diagnosed at Saturation Biopsy
Authors: Pepe Pietro , Fraggetta Filippo , Galia Antonio , Aragona Francesco
Published: August 2012

Objective: To evaluate prostate cancer gene 3 (PCA3) score accuracy in preoperative staging of cases of single microfocus of prostate cancer (PCa; less than 5% with Gleason score ≤6) diagnosed after repeat saturation biopsy (median 30 cores). Methods: From January 2009 to March 2012, 38 patients (median 64 years) with a microfocus of PCa, median PSA of 9.1 ng/ml and T1c clinical stage underwent radical retropubic prostatectomy. PCA3 score (cut-off of 20 vs. 35) was evaluated in predicting insignificant PCa (pIPCa: cancer volume <0.5 ml and Gleason score ≤6) versus organ-confined (OC) versus non-OC PCa. Results: Median PCA3 score results were equal to 10 versus 53 (p < 0.05) versus 108 (p < 0.05) in the presence of pIPCa (13.2%), versus OC (65.8%) versus non-OC PCa (21%), respectively. PCA3 scores were significantly correlated with tumor volume. Conclusions: A PCA3 score cut-off >20 in the presence of a microfocus of PCa is highly predictive of significant PCa (diagnostic accuracy equal to 86.8%) at definitive specimen.
Surgical Management of Intractable Chyluria: A Comparison of Retroperitoneoscopy with Open Surgery
Authors: Zhang Yao , Zeng Jiayuan , Zhang Keqin , Jin Fengshuo , Ye Jin , Wu Gang , Wang Gang , Nie Zhilin
Published: August 2012

Background: Retroperitoneoscopic renal pedicle lymphatic disconnection has been described in the management of intractable chyluria. Methods: We retrospectively reviewed the clinical outcomes of 76 patients with intractable chyluria undergoing renal pedicle lymphatic disconnection via a retroperitoneoscopic (n = 59) or conventional open approach (n = 17). Operative time, intraoperative blood loss, volume of postoperative drainage, postoperative draining time, postoperative intestinal recovery, intraoperative and postoperative complications, and postoperative hospital stay were evaluated. Results: Compared with open surgery, retroperitoneoscopy was superior in terms of operative time, intraoperative blood loss, postoperative drainage, postoperative draining time, postoperative intestinal recovery time, and postoperative hospital stay. Recurrence developed in 2 patients due to the contralateral chylous efflux confirmed by cystoscopy during the period of 9–85 months of follow-up. Conclusions: With minimal invasion, sparing operative time, less blood loss, and rapid recovery, retroperitoneoscopic renal pedicle lymphatic disconnection can achieve at least the same clinical efficacy as open surgery.
Endothelial communication. State of the art lecture.
Authors: Davies P F , Olesen S P , Clapham D E , Morrel E M , Schoen F J
Published: August 2012

By virtue of its location at the interface of flowing blood and vascular tissue, the endothelial cell monolayer is in a unique position for interactions with soluble and cellular elements of the blood on one side and with component cells of the vascular tissue on the other. This brief review outlines humoral and contact-mediated endothelial communication with other cells, particularly the resident cells of the vessel wall. Evidence for gap junctional communication channels between endothelium and vascular cells is summarized and discussed in relation to endothelial ion channel activity. Myoendothelial gap junctional communication is proposed as a mechanism involved in vasorelaxation, either independent of or in concert with secreted endothelium-derived relaxing factor(s).
Effect of antihypertensive treatment on progression of incipient diabetic nephropathy.
Authors: Christensen C K , Mogensen C E
Published: August 2012

The aim of the study was to clarify whether antihypertensive treatment with a selective beta blocker would have an effect on the progression rate of kidney disease in patients with incipient diabetic nephropathy. Six male patients with juvenile-onset diabetes with incipient nephropathy (urinary albumin excretion above 15 micrograms/min and total protein excretion below 0.5 g/24 hr) were treated with metoprolol (200 mg daily). At the start of the antihypertensive treatment the mean age was 32 years +/- 4.2 (SD). The patients were followed a mean 5.4 years +/- 3.1 (SD) with repeated measurements of urinary albumin excretion before and during 2.6 years +/- 1.0 (SD) of treatment. The blood pressure was depressed by the treatment (systolic blood pressure from 135 mm Hg +/- 8.6 to 124 mm Hg +/- 6.2, NS; mean blood pressure from 107 mm Hg +/- 7.6 to 97 mm Hg +/- 3.4, 2p less than 0.05; diastolic blood pressure from 93 mm Hg +/- 9.1 to 84 mm Hg +/- 3.6, 2p less than 0.05. Albumin excretion decreased (131.0 micrograms/min X/divided by 2.9 [geometric mean X/divided by tolerance factor] to 56.1 micrograms/min X/divided by 3.7, 2p less than 0.02). The mean yearly increase in urinary albumin excretion before treatment was 18 +/- 17 (mean +/- SD). Albumin excretion decreased during treatment: 17% +/- 15 per year (mean +/- SD, 2p less than 0.02). No changes were seen in glomerular filtration rate or renal plasma flow (149 ml/min +/- 5.8 vs 144 ml/min +/- 11.1, and 516 ml/min +/- 31.0 vs 541 ml/min +/- 68.5 respectively [n = 5]).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of long-term antihypertensive treatment on kidney function in diabetic nephropathy.
Authors: Parving H H , Andersen A R , Hommel E , Smidt U
Published: August 2012

The purpose of our prospective study was to evaluate the long-term effect of aggressive antihypertensive treatment on glomerular filtration rate and albuminuria in young female and male patients with insulin-dependent diabetes mellitus with diabetic nephropathy and blood pressure greater than 90 mm Hg. Eight patients received treatment with metoprolol (200-400 mg/day), hydralazine (100-200 mg/day), and furosemide (80-500 mg/day). The untreated control group consisted of eight patients matched for age (mean 32 years), diabetes duration (mean 17 years), and sex (two female and six male patients). All patients except one had diabetic retinopathy. Glomerular filtration rate was measured after a single intravenous injection of 51Cr-labeled ethylenediaminetetraacetic acid. Urinary albumin concentration was determined with a radial immunodiffusion method. The investigations were performed two to four times per year in each patient. The mean observation period was 59 and 27 months in the treated and untreated groups respectively. Due to a considerable rise in arterial blood pressure, it was considered unethical to prolong the observation in the untreated group. Arterial blood pressure rose from 140/96 +/- 4/1 to 150/100 +/- 3/2 mm Hg; albuminuria increased from 1517 +/- 502 to 1911 +/- 120 micrograms/min; and glomerular filtration rate decreased by a mean of 0.84 +/- 0.17 ml/min/mo in the untreated group. Antihypertensive treatment induced blood pressure reduction 151/100 +/- 3/2 to 131/87 +/- 2/1 mm Hg; diminished albuminuria 1467 +/- 515 to 729 +/- 65 micrograms/min; and caused a slow rate of decline in GFR, mean 0.37 +/- 0.08 ml/min/mo.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of indapamide on blood pressure and glucose tolerance in non-insulin-dependent diabetes.
Authors: Harrower A D , McFarlane G , Donnelly T , Gray C E
Published: August 2012

Ten hypertensive non-insulin-dependent diabetic patients were treated with the antihypertensive drug indapamide to assess its effect on glucose tolerance over 1 year. Both systolic and diastolic blood pressures fell significantly (p less than 0.001) over the first month of treatment, and no change in plasma glucose or plasma insulin levels during an oral glucose tolerance test occurred at any time. Indapamide is an effective antihypertensive drug and, in contrast to thiazide diuretics, has no adverse effect on glucose tolerance in non-insulin-dependent diabetic patients.
Hypertension as related to renal function in diabetes mellitus.
Authors: Reubi F C , Franz K A , Horber F
Published: August 2012

The relationships between blood pressure and renal function were investigated in 78 hypertensive patients with diabetes mellitus type I or II. Renal function was assessed by determining the glomerular filtration rate and the para-aminohippurate clearance in 32 and serum creatinine in 46 subjects. In the latter, the reciprocal serum creatinine, corrected for age and changing creatinine/insulin clearance ratio, was used as an estimate of glomerular filtration rate. In the 54 patients with serial determinations, the duration of follow-up averaged 10.5 years. In older patients with type II diabetes without clinical proteinuria, hypertension developed either before or after the onset of diabetes. When it appeared, renal function was only slightly reduced. During follow-up, the decline in reciprocal serum creatinine averaged 2.7% per year, a figure very similar to that found in nondiabetic patients with benign essential hypertension. It did not correlate with the blood pressure. In patients with a proteinuria greater than 2.5 g per day and histologic and/or clinical evidence of diabetic glomerulosclerosis, the severity of hypertension correlated inversely with the level of renal function. The rate of decline in function averaged 11% per year but varied widely. It was not significantly related to the blood pressure. These data suggest that different types of hypertension (essential, diabetic, and nephrogenic) may be associated with diabetes mellitus. The rate of decline in renal function is closely related to the presence or absence of clinical proteinuria but not to the level of blood pressure.
Epidemiology of hypertension associated with diabetes mellitus.
Authors: Fuller J H
Published: August 2012

The clinical impression of an association between hypertension and diabetes mellitus has not been consistently confirmed by epidemiological studies. The variety of methodological problems in this area of research includes the choice of appropriate patient and control groups, the measurement techniques used, and consideration of many possible confounding variables. Several prospective studies have shown that hypertension may be a potent risk factor for diabetic macrovascular and microvascular disease. This relationship may have important preventive implications, and raises the question of the optimal antihypertensive therapy in diabetic patients.
Pressor factors and responsiveness in hypertension accompanying diabetes mellitus.
Authors: Weidmann P , Beretta-Piccoli C , Trost B N
Published: August 2012

Hypertension accompanying diabetes mellitus may involve abnormalities in at least two major blood pressure-regulating systems: the body sodium-fluid volume state and cardiovascular reactivity. In metabolically stable nonazotemic diabetes, exchangeable sodium is increased by 10% on average, regardless of age, insulin dependence or nondependence, or the presence or absence of diabetic retinopathy or clinical nephropathy (proteinuria greater than or equal to 0.3 g/24 hr). Possible contributing mechanisms include renal sodium retention and an extravascular shift of fluid and sodium; intracellular accumulation is not excluded. Circulatory volume is normal or low and the total exchangeable sodium/blood volume ratio increased. In hypertensive diabetes, the latter abnormality is particularly pronounced; systolic pressure tended to correlate with exchangeable sodium (r = 0.47, p less than 0.001) and diastolic pressure with the plasma sodium/potassium ratio (r = 0.25, p less than 0.05). Plasma aldosterone, renin, epinephrine, and norepinephrine levels are generally normal or sometimes low in metabolically stable nonazotemic diabetic patients with normal or high blood pressure; the plasma clearance of norepinephrine also appears to be unaltered. The cardiovascular pressor responsiveness to norepinephrine is often exaggerated relative to concomitant plasma concentrations, regardless of age, type of antidiabetic treatment, or presence or absence of diabetic retinopathy, peripheral neuropathy, or high blood pressure. Pressor responsiveness to angiotensin II also may sometimes be increased relative to plasma renin levels. Sodium retention and diabetic vasculopathy of resistance vessels could be important complementary mechanisms of hyperreactivity. In diabetes with mild hypertension, diuretic treatment restored exchangeable sodium, norepinephrine pressor responsiveness, and blood pressure toward normal. Thus sodium retention and cardiovascular hyperreactivity tend to occur even at the normotensive, nonazotemic stage of diabetes and may concomitantly predispose for the frequent development of hypertension in the diabetic population.