bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated with Placenta Praevia in Primigravidas and Its Pregnancy Outcome
Authors: Nur Azurah Abdul Ghani , Wan Zainol Zakaria , Lim Pei Shan , Shafiee Mohd Nasir , Kampan Nirmala , Mohsin Wan Syahirah , Mokhtar Norfilza Mohd , Muhammad Yassin Muhammad Abdul Jamil
Published: November 2014

Aim.To examine the factors associated with placenta praevia in primigravidas and also compare the pregnancy outcomes between primigravidas and nonprimigravidas.Method.A retrospective cohort study was conducted in women who underwent caesarean section for major placenta praevia in a tertiary university hospital from January 2007 till December 2013. Medical records were reviewed.Result.Among 243 with major placenta praevia, 56 (23.0%) were primigravidas and 187 (77.0%) were nonprimigravidas. Factors associated with placenta praevia in the primigravidas were history of assisted conception (P=0.02) and history of endometriosis (P=0.01). For maternal outcomes, the nonprimigravidas required earlier delivery than primigravidas (35.76 ± 2.54 weeks versus 36.52 ± 1.95 weeks,P=0.03) and had greater blood loss (P=0.04). A vast majority of the primigravidas had either posterior type II or type III placenta praevia. As for neonatal outcomes, the Apgar score at 1 minute was significantly lower for the nonprimigravidas (7.89 ± 1.72 versus 8.39 ± 1.288.39 ± 1.28,P=0.02).Conclusion.This study highlighted that endometriosis and assisted conception were highly associated with placenta praevia in primigravida. Understanding the pregnancy outcomes of women with placenta praevia can assist clinicians in identifying patients who are at higher risk of mortality and morbidity. Identifying potential risk factors in primigravida may assist in counseling and management of such patients.
Research on Improvement of Spectrum Efficiency of Spread Spectrum OFDM Communication Scheme for Cruising Sensor Network
Authors: Wang Yuan , Zeng Zhoumo , Li Yibo , Zhang Wen , Feng Hao , Jin Shijiu
Published: November 2014

Cruising sensor nodes have an attractive application in monitoring liquid-based industrial environments. A cruising sensor node, equipped with various sensors, is self-propelled so that they can “cruise” to specified area to gather scientific data. The cruising sensor network consists of an array of such cruising nodes to perform collaborative monitoring task over a given area. A reliable and high-speed underwater acoustic (UWA) communication scheme is necessary for node-to-node communication. Most of the industrial liquid reservoirs are confined spaces, including large oil tanks and nuclear storage ponds. The communication in confined underwater space will suffer more severe multipath interference caused by numerous reflections from boundaries. Conventional orthogonal frequency-division multiplexing (OFDM) technique has poor performance in this channel. Instead, spread spectrum orthogonal frequency-division multiplexing (SS-OFDM), which applies spread spectrum technique into OFDM, has better performance in such severely multipath fading underwater channels. However, the spread spectrum process causes a huge waste in the spectrum efficiency. In order to enhance the transmission efficiency, a mapping sequence spread spectrum OFDM (MSSS-OFDM) method is proposed in this paper. The simulation and experimental results show that our scheme is a robust and spectrum efficient communication method for confined underwater space.
Effect of Zishenpingchan Granule on Neurobehavioral Manifestations and the Activity and Gene Expression of Striatal Dopamine D1 and D2 Receptors of Rats with Levodopa‐Induced Dyskinesias
Authors: Ye Qing , Yuan Xiao-Lei , Zhou Jie , Yuan Can-xing , Yang Xu-ming
Published: November 2014

This study was performed to observe the effects of Zishenpingchan granule on neurobehavioral manifestations and the activity and gene expression of striatal dopamine D1 and D2 receptors of rats with levodopa‐induced dyskinesias (LID). We established normal control group, LID model group, and TCM intervention group. Each group received treatment for 4 weeks. Artificial neural network (ANN) was applied to excavate the main factor influencing variation in neurobehavioral manifestations of rats with LID. The results showed that overactivation in direct pathway mediated by dopamine D1 receptor and overinhibition in indirect pathway mediated by dopamine D2 receptor may be the main mechanism of LID. TCM increased the efficacy time of LD to ameliorate LID symptoms effectively mainly by upregulating dopamine D2 receptor gene expression.
Effects of Combined Anisodamine and Neostigmine Treatment on the Inflammatory Response and Liver Regeneration of Obstructive Jaundice Rats after Hepatectomy
Authors: Li Chong-Hui , Zhang Xuan , Ge Xin-Lan , Huang Xin , Zhang Ai-Qun , Gu Wan-Qing
Published: November 2014

Background. Cholestasis is associated with high rates of morbidity and mortality in patients undergoing major liver resection. This study aimed to evaluate the effects of a combined anisodamine and neostigmine (Ani+Neo) treatment on the inflammatory response and liver regeneration in rats with obstructive jaundice (OJ) after partial hepatectomy.Materials and Methods. OJ was induced in the rats by bile duct ligation. After 7 days biliary drainage and partial hepatectomy were performed. These rats were assigned to a saline group or an Ani+Neo treatment group. The expressions of inflammatory mediators, liver regeneration, and liver damage were assessed at 48 h after hepatectomy.Results. The mRNA levels of TNF-α, IL-1β, IL-6, MCP-1, and MIP-1α, in the remnant livers, and the serum levels of TNF-αand IL-1βwere substantially reduced in the Ani+Neo group compared with saline group(P<0.05). The Ani+Neo treatment obviously promoted liver regeneration as indicated by the liver weights and Ki-67 labeling index(P<0.05). The serum albumin andγ-GT levels and liver neutrophil infiltration also significantly improved in the Ani+Neo group(P<0.05)compared with the saline group.Conclusions. These results demonstrate that the combined anisodamine and neostigmine treatment is able to improve the liver regeneration in rats with OJ by substantially alleviating the inflammatory response.
An Improved Fuzzyc-Means Clustering Algorithm Based on Shadowed Sets and PSO
Authors: Zhang Jian , Shen Ling
Published: November 2014

To organize the wide variety of data sets automatically and acquire accurate classification, this paper presents a modified fuzzyc-means algorithm (SP-FCM) based on particle swarm optimization (PSO) and shadowed sets to perform feature clustering. SP-FCM introduces the global search property of PSO to deal with the problem of premature convergence of conventional fuzzy clustering, utilizes vagueness balance property of shadowed sets to handle overlapping among clusters, and models uncertainty in class boundaries. This new method uses Xie-Beni index as cluster validity and automatically finds the optimal cluster number within a specific range with cluster partitions that provide compact and well-separated clusters. Experiments show that the proposed approach significantly improves the clustering effect.
Differentially Expressed MicroRNAs in Maternal Plasma for the Noninvasive Prenatal Diagnosis of Down Syndrome (Trisomy 21)
Authors: Kamhieh-Milz Julian , Moftah Reham Fadl Hassan , Bal Gürkan , Futschik Matthias , Sterzer Viktor , Khorramshahi Omid , Burow Martin , Thiel Gundula , Stuke-Sontheimer Annegret , Chaoui Rabih , Kamhieh-Milz Sundrela , Salama Abdulgabar
Published: November 2014

Objectives. Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies.Methods. Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls.Results. Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially expressed mature miRNAs were identified as potential biomarkers. Hierarchical cluster analysis of these miRNAs resulted in the clear discrimination of DS from euploid pregnancies. Gene targets of the differentially expressed miRNAs were enriched in signaling pathways such as mucin type-O-glycans, ECM-receptor interactions, TGF-beta, and endocytosis, which have been previously associated with DS.Conclusions. miRNAs are promising and stable biomarkers for a broad range of diseases and may allow a reliable, cost-efficient diagnostic tool for the noninvasive prenatal diagnosis of DS.
Tolerance and Nature of Residual Refraction in Symmetric Power Space as Principal Lens Powers and Meridians Change
Authors: Abelman Herven , Abelman Shirley
Published: November 2014

Unacceptable principal powers in well-centred lenses may require a toric over-refraction which differs in nature from the one where correct powers have misplaced meridians. This paper calculates residual (over) refractions and their natures. The magnitude of the power of the over-refraction serves as a general, reliable, real scalar criterion for acceptance or tolerance of lenses whose surface relative curvatures change or whose meridians are rotated and cause powers to differ. Principal powers and meridians of lenses are analogous to eigenvalues and eigenvectors of symmetric matrices, which facilitates the calculation of powers and their residuals. Geometric paths in symmetric power space link intended refractive correction and these carefully chosen, undue refractive corrections. Principal meridians alone vary along an arc of a circle centred at the origin and corresponding powers vary autonomously along select diameters of that circle in symmetric power space. Depending on the path of the power change, residual lenses different from their prescription in principal powers and meridians are pure cross-cylindrical or spherocylindrical in nature. The location of residual power in symmetric dioptric power space and its optical cross-representation characterize the lens that must be added to the compensation to attain the power in the prescription.
A Case of Femoral Fracture in Klippel Trenaunay Syndrome
Authors: Nahas Sam , Wong Fabian , Back Diane
Published: November 2014

We present a case of Klippel Trenaunay syndrome (KTS) who presented with severe bilateral knee osteoarthritis (OA). Preoperative planning was commenced for a total knee replacement (TKR). Whilst on the waiting list the patient suffered a fall and sustained a complete femoral diaphysis fracture. Conservative management in the form of skin traction was initially chosen as significant extra- and intramedullary vascular malformations posed an increased risk of perioperative bleeding. This failed to progress to union, and so open reduction and internal fixation was performed. This subsequently resulted in on-going delayed union, which was subsequently managed with low intensity pulsed ultrasound (LIPUS, otherwise known as Exogen (Bioventus. exogen. Secondary exogen, 2012)). There are only two previous documented cases of femoral fracture in KTS. This is the first report of a patient with this rare syndrome receiving this treatment. We discuss the management of fracture in this challenging group of patients.
Significance of Algal Polymer in Designing Amphotericin B Nanoparticles
Authors: Bhatia Saurabh , Kumar Vikash , Sharma Kiran , Nagpal Kalpana , Bera Tanmoy
Published: November 2014

Development of oral amphotericin B (AmB) loaded nanoparticles (NPs) demands a novel technique which reduces its toxicity and other associated problems. Packing of AmB in between two oppositely charged ions by polyelectrolyte complexation technique proved to be a successful strategy. We have developed a novel carrier system in form of polyelectrolyte complex of AmB by using chitosan (CS) and porphyran (POR) as two oppositely charged polymers with TPP as a crosslinking agent. Initially POR was isolated fromPorphyra vietnamensisfollowed by the fact that its alkali induced safe reduction in molecular weight was achieved. Formulation was optimized using three-factor three-level (33) central composite design. High concentration of POR in NPs was confirmed by sulfated polysaccharide (SP) assay. Degradation and dissolution studies suggested the stability of NPs over wide pH range. Hemolytic toxicity data suggested the safety of prepared formulation.In vivoandin vitroantifungal activity demonstrated the high antifungal potential of optimized formulation when compared with standard drug and marketed formulations. Throughout the study TPP addition did not cause any significant changes. Therefore, these experimental oral NPs may represent an interesting carrier system for the delivery of AmB.
Urinary Iodine Clearance following Iodinated Contrast Administration: A Comparison of Euthyroid and Postthyroidectomy Subjects
Authors: Ho Janice D. , Tsang James F. , Scoggan Kylie A. , Leslie William D.
Published: November 2014

Purpose.To compare iodine clearance following iodinated contrast administration in thyroidectomised thyroid cancer patients and euthyroid individuals.Methods.A convenience population (6 thyroidectomised thyroid cancer patients and 7 euthyroid controls) was drawn from patients referred for iodinated contrast-enhanced computed tomography (CT) studies. Subjects had sequential urine samples collected up to 6 months (50 samples from the thyroidectomised and 63 samples from the euthyroid groups).t-tests and generalised estimating equations (GEE) were used to test for group differences in urinary iodine creatinine ratios.Results.Groups had similar urinary iodine creatinine ratios at baseline, with a large increase 2 weeks following iodinated contrast (P=0.005). Both groups had a return of urinary iodine creatinine ratios to baseline by 4 weeks, with no significant group differences overall or at any time point.Conclusions.Thyroidectomised patients did not have a significantly different urinary iodine clearance than euthyroid individuals following administration of iodinated contrast. Both had a return of urinary iodine creatinine ratios to baseline within 4 weeks.
Age-Related Macular Degeneration: Insights into Inflammatory Genes
Authors: Cascella Raffaella , Ragazzo Michele , Strafella Claudia , Missiroli Filippo , Borgiani Paola , Angelucci Francesco , Marsella Luigi Tonino , Cusumano Andrea , Novelli Giuseppe , Ricci Federico , Giardina Emiliano
Published: November 2014

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old). AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension). In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species) have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8,andARMS2) that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines), immune cells (macrophages), and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression.
Unified Registration Model for Both Stationary and Mobile 3D Radar Alignment
Authors: Chen Lei , Wang G. H. , Progri Ilir F.
Published: November 2014

For mobile radar, offset biases and attitude biases influence radar measurements simultaneously. Attitude biases generated from the errors of the inertial navigation system (INS) of the platform can be converted into equivalent radar measurement errors by three analytical expressions (range, azimuth, and elevation, resp.). These expressions are unique and embody the dependences between the offset and attitude biases. The dependences indicate that all the attitude biases can be viewed as and merged into some kind of offset biases. Based on this, a unified registration model (URM) is proposed which only contains radar “offset biases” in the form of system variables in the registration equations, where, in fact, the “offset biases” contain the influences of the attitude biases. URM has the same form as the registration model of stationary radar network where no attitude biases exist. URM can compensate radar offset and attitude biases simultaneously and has minor computation burden compared with other registration models for mobile radar network.
An Improved Differential Evolution Algorithm for Maritime Collision Avoidance Route Planning
Authors: Zhao Yu-xin , Li Wang , Feng Shaojun , Ochieng Washington Y. , Schuster Wolfgang
Published: November 2014

High accuracy navigation and surveillance systems are pivotal to ensure efficient ship route planning and marine safety. Based on existing ship navigation and maritime collision prevention rules, an improved approach for collision avoidance route planning using a differential evolution algorithm was developed. Simulation results show that the algorithm is capable of significantly enhancing the optimized route over current methods. It has the potential to be used as a tool to generate optimal vessel routing in the presence of conflicts.
Constraint Analysis and Redundancy of Planar Closed Loop Double Chain Linkages
Authors: Cai Jianguo , Deng Xiaowei , Xu Yixiang , Feng Jian
Published: November 2014

This paper studies the kinematics of planar closed double chain linkages using the natural coordinate method. Different constraints including the rigid bar, pin joint, generalized angulated element (GAE) joint, and the boundary conditions of linkages were firstly used to form the system constraint equations. Then the degree of freedom of the linkages was calculated from the dimension of null space of the Jacobian matrix, which is the derivative of the constraint equations with respect to time. Furthermore, the redundant constraints can also be given by this method. Many types of planar linkages, such as the Hoberman linkage, Types I and II GAEs, nonintersecting GAEs, and linkages with the loop parallelogram condition, were investigated in this paper. It is found that when three boundary conditions are added to the system, the global motion of the system is lost. The results show that these linkages have only one degree of freedom. Moreover, the last two GAE constraints of the numerical examples given in this paper are redundant.
Recurrence of Pelvic Chondrosarcoma through Fascial Defect into Abdominal Cavity
Authors: Gökkuş Kemal , Akin Tolgay , Sagtas Ergin , Saylik Murat , Aydın Ahmet Turan
Published: November 2014

Our patient was a 76-year-old female who has been operated on 2 times in 8 years for pelvic chondrosarcoma. The patient came to our clinic with a large mass in left iliac region which extended into the paravertebral area. Physical examination and preoperative imagining studies revealed a mass at the left iliac area that infiltrated sciatic notch and extended from posterior iliac region towards the anterior side of iliac bone through the sciatic notch and an incisional hernia including descending colon. The mass was also penetrating the abdominal cavity through the hernia. Surgical intervention was planned. Since the tumor infiltrated the sciatic nerve, hemipelvectomy was indicated. Patient refused hemipelvectomy. Therefore, palliative debulking surgery was considered. We treated the case with marginal excision and abdominal wall reconstruction employing prolene and vicryl suture materials in order to prevent a postoperative visceral herniation and local invasion. At the latest follow-up appointment in 2 years, the patient still had no signs of tumor recurrence. This case showed us that an incisional hernia can serve as a pathway for the recurrence invasion of the chondrosarcoma.
On the Compactness of the Commutator of the Parabolic Marcinkiewicz Integral with Variable Kernel
Authors: Chen Yanping , Zhu Kai , Ding Yong
Published: November 2014

The authors prove that the commutator of the parabolic Marcinkiewicz integralgΩwith variable kernel is a compact operator onLp(Rn)  (1<p<∞)if and only ifb∈CMO (Rn,ρ). The result is substantial improvement and extension of some known results.
Deleterious Effects of Increased Intra-Abdominal Pressure on Kidney Function
Authors: Armaly Zaher , Abassi Zaid
Published: November 2014

Elevated intra-abdominal pressure (IAP) occurs in many clinical settings, including sepsis, severe acute pancreatitis, acute decompensated heart failure, hepatorenal syndrome, resuscitation with large volume, mechanical ventilation with high intrathoracic pressure, major burns, and acidosis. Although increased IAP affects several vital organs, the kidney is very susceptible to the adverse effects of elevated IAP. Kidney dysfunction is among the earliest physiological consequences of increased IAP. In the last two decades, laparoscopic surgery is rapidly replacing the open approach in many areas of surgery. Although it is superior at many aspects, laparoscopic surgery involves elevation of IAP, due to abdominal insufflation with carbonic dioxide (pneumoperitoneum). The latter has been shown to cause several deleterious effects where the most recognized one is impairment of kidney function as expressed by oliguria and reduced glomerular filtration rate (GFR) and renal blood flow (RBF). Despite much research in this field, the systemic physiologic consequences of elevated IAP of various etiologies and the mechanisms underlying its adverse effects on kidney excretory function and renal hemodynamics are not fully understood. The current review summarizes the reported adverse renal effects of increased IAP in edematous clinical settings and during laparoscopic surgery. In addition, it provides new insights into potential mechanisms underlying this phenomenon and therapeutic approaches to encounter renal complications of elevated IAP.
On Continuity of Functions between Vector Metric Spaces
Authors: Çevik Cüneyt
Published: November 2014

We introduce vectorial and topological continuities for functions defined on vector metric spaces and illustrate spaces of such functions. Also, we describe some fundamental classes of vector valued functions and extension theorems.
Ordering Cost Reduction in Inventory Model with Defective Items and Backorder Price Discount
Authors: Annadurai Karuppuchamy , Uthayakumar Ramasamy
Published: November 2014

In the real market, as unsatisfied demands occur, the longer the length of lead time is, the smaller the proportion of backorder would be. In order to make up for the inconvenience and even the losses of royal and patient customers, the supplier may offer a backorder price discount to secure orders during the shortage period. Also, ordering policies determined by conventional inventory models may be inappropriate for the situation in which an arrival lot contains some defective items. To compensate for the inconvenience of backordering and to secure orders, the supplier may offer a price discount on the stockout item. The purpose of this study is to explore a coordinated inventory model including defective arrivals by allowing the backorder price discount and ordering cost as decision variables. There are two inventory models proposed in this paper, one with normally distributed demand and another with distribution free demand. A computer code using the software Matlab 7.0 is developed to find the optimal solution and present numerical examples to illustrate the models. The results in the numerical examples indicate that the savings of the total cost are realized through ordering cost reduction and backorder price discount.
Epidemic Spread Modeling with Time Variant Infective Population Using Pushdown Cellular Automata
Authors: Athithan Senthil , Shukla Vidya Prasad , Biradar Sangappa Ramachandra
Published: November 2014

The world without a disease is a dream of any human being. The disease spread if not controlled could cause an epidemic situation to spread and lead to pandemic. To control an epidemic we need to understand the nature of its spread and the epidemic spread model helps us in achieving this. Here we propose an epidemic spread model which considers not only the current infective population around the population but also the infective population which remain from the previous generations for computing the next generation infected individuals. A pushdown cellular automata model which is an enhanced version of cellular automata by adding a stack component is being used to model the epidemic spread and the model is validated by the real time data of H1N1 epidemic in Abu Dhabi.
Does Preoperative Radio(chemo)therapy Increase Anastomotic Leakage in Rectal Cancer Surgery? A Meta-Analysis of Randomized Controlled Trials
Authors: Qin Changjiang , Ren Xuequn , Xu Kaiwu , Chen Zhihui , He Yulong , Song Xinming
Published: November 2014

Objective. Preoperative radio(chemo)therapy (pR(C)T) appears to increase postoperative complications of rectal cancer resection, but clinical trials have reported conflicting results. The objective of this meta-analysis was performed to assess the effects of pR(C)T on anastomotic leak after rectal cancer resection.Methods. PubMed, Embase, and the Cochrane Library were searched from January 1980 to January 2014. Randomized controlled trials included all original articles reporting anastomotic leak in patients with rectal cancer, among whom some received preoperative radiotherapy or chemoradiotherapy while others did not. The analysed end-points were the anastomotic leak.Result. Seven randomized controlled trials with 3375 patients were included in the meta-analysis. 1660 forming the group undergoing preoperative radiotherapy or chemoradiotherapy versus 1715 patients undergoing without preoperative radiotherapy or chemoradiotherapy. The meta-analyses found that pR(C)T was not an independent risk factor for anastomotic leakage (OR 1.02, 95% CI 0.80–1.30;P=0.88). Subgroups analysis was performed and the result was not altered.Conclusions. Current evidence demonstrates that pR(C)T did not increase the risk of postoperative anastomotic leak after rectal cancer resection in patients.
Doppler Velocity Estimation of Overlapping Linear-Period-Modulated Ultrasonic Waves Based on an Expectation-Maximization Algorithm
Authors: Thong-un Natee , Kurosawa Minoru K.
Published: November 2014

The occurrence of an overlapping signal is a significant problem in performing multiple objects localization. Doppler velocity is sensitive to the echo shape and is also able to be connected to the physical properties of moving objects, especially for a pulse compression ultrasonic signal. The expectation-maximization (EM) algorithm has the ability to achieve signal separation. Thus, applying the EM algorithm to the overlapping pulse compression signals is of interest. This paper describes a proposed method, based on the EM algorithm, of Doppler velocity estimation for overlapping linear-period-modulated (LPM) ultrasonic signals. Simulations are used to validate the proposed method.
Hermitian Self-Orthogonal Constacyclic Codes over Finite Fields
Authors: Sahni Amita , Sehgal Poonam Trama
Published: November 2014

Necessary and sufficient conditions for the existence of Hermitian self-orthogonal constacyclic codes of length n over a finite field Fq2, n coprime to q, are found. The defining sets and corresponding generator polynomials of these codes are also characterised. A formula for the number of Hermitian self-orthogonal constacyclic codes of length n over a finite field Fq2 is obtained. Conditions for the existence of numerous MDS Hermitian self-orthogonal constacyclic codes are obtained. The defining set and the number of such MDS codes are also found.
NOTCH Decoys That Selectively Block DLL/NOTCH or JAG/NOTCH Disrupt Angiogenesis by Unique Mechanisms to Inhibit Tumor Growth
Authors: Kangsamaksin Thaned , Murtomaki Aino , Kofler Natalie M. , Cuervo Henar , Chaudhri Reyhaan A. , Tattersall Ian W. , Rosenstiel Paul E. , Shawber Carrie J. , Kitajewski Jan
Published: November 2014

A proangiogenic role for Jagged (JAG)-dependent activation of NOTCH signaling in the endothelium has yet to be described. Using proteins that encoded different NOTCH1 EGF-like repeats, we identified unique regions of Delta-like ligand (DLL)–class and JAG-class ligand–receptor interactions, and developed NOTCH decoys that function as ligand-specific NOTCH inhibitors. N110–24 decoy blocked JAG1/JAG2–mediated NOTCH1 signaling, angiogenic sprouting in vitro, and retinal angiogenesis, demonstrating that JAG-dependent NOTCH signal activation promotes angiogenesis. In tumors, N110–24 decoy reduced angiogenic sprouting, vessel perfusion, pericyte coverage, and tumor growth. JAG–NOTCH signaling uniquely inhibited expression of antiangiogenic soluble (s) VEGFR1/sFLT1. N11–13 decoy interfered with DLL1–DLL4-mediated NOTCH1 signaling and caused endothelial hypersprouting in vitro, in retinal angiogenesis, and in tumors. Thus, blockade of JAG- or DLL-mediated NOTCH signaling inhibits angiogenesis by distinct mechanisms. JAG–NOTCH signaling positively regulates angiogenesis by suppressing sVEGFR1–sFLT1 and promoting mural–endothelial cell interactions. Blockade of JAG-class ligands represents a novel, viable therapeutic approach to block tumor angiogenesis and growth.

Significance: This is the first report identifying unique regions of the NOTCH1 extracellular domain that interact with JAG-class and DLL-class ligands. Using this knowledge, we developed therapeutic agents that block JAG-dependent NOTCH signaling and demonstrate for the first time that JAG blockade inhibits experimental tumor growth by targeting tumor angiogenesis. Cancer Discov; 5(2); 182–97. ©2014 AACR.

See related commentary by Briot and Iruela-Arispe, p. 112

This article is highlighted in the In This Issue feature, p. 97
Short-Term Risk of Falling after Cochlear Implantation
Authors: Stevens Madelyn N. , Baudhuin Jacqueline E. , Hullar Timothy E. ,   Washington University Cochlear Implant Study Group
Published: November 2014

Cochlear implantation is a highly effective intervention for hearing loss, but insertion of an implant into the cochlea is often accompanied by loss of residual hearing function. Sometimes, postoperative testing also shows loss of function in the semicircular canals or otolith organs. The effect of this loss on equilibrium, particularly in the short term following surgery, and the risk of falling due to this loss is unknown. We prospectively measured balance in 16 consecutive adult cochlear implant patients before and 2 weeks after surgery. Subjects stood on a foam pad with eyes closed, feet together and arms at the side. The length of time over which this posture could be maintained was recorded up to a maximum value of 30 s indicating normal performance. Ten of 16 subjects reached a maximal time on preoperative testing. Nine of 16 subjects lost balance function after surgery. Four of the 10 subjects with normal preoperative balance function lost function. Subjects older than the age of 60 were more likely to lose balance function than younger subjects. We used previously published values relating balance performance on foam to risk of falling to calculate the fall risk among our subjects. The relative risk of falling increased after surgery by more than threefold in some patients. Imbalance after cochlear implantation may be much more common, particularly in the short term, than previously appreciated. This imbalance is accompanied by an increased risk of falling in many patients. Careful preoperative counseling before implantation and postoperative therapeutic intervention to improve comfort and reduce the chance of falling may be warranted, particularly in patients at a risk for injuries from falls (level of evidence: 2b). i 2014 S. Karger AG, Basel
Small Biparietal Diameter and Head Circumference Are Part of the Phenotype instead of Independent Prognostic Markers in Fetuses with Spinal Dysraphism
Authors: Cuppen Inge , de Bruijn Dagmar , Geerdink Niels , Rotteveel Jan J. , Willemsen Michèl A.A.P. , van Vugt John M.G. , Pasman Jaco W. , Roeleveld Nel
Published: November 2014

Objective: The aim of this retrospective study was to assess the fetal biparietal diameter (BPD) and head circumference (HC) in the second trimester of pregnancy in fetuses with open spinal dysraphism. Methods: BPD and HC were measured at 16-26 weeks in 74 fetuses with open spinal dysraphism and compared with reference values. Results: BPD was smaller in fetuses with open spinal dysraphism. Of all cases with open spinal dysraphism, 62.2% had a BPD <3rd percentile and 79.7% had a BPD <10th percentile. Of all patients, 54.1% had an HC <3rd percentile and 74.3% had an HC <10th percentile. Conclusion: Almost all fetuses with open neural tube defects have a smaller BPD and HC at 16-26 weeks compared with reference values, which implicates that this is part of the phenotype of children with open spinal dysraphism instead of an independent prognostic marker for a poor cognitive outcome.
Vaccines for the Elderly
Authors: Del Giudice Giuseppe , Weinberger Birgit , Grubeck-Loebenstein Beatrix
Published: November 2014

The aging of the human population is posing serious challenges to research and to public health authorities in order to prevent diseases that more frequently affect the elderly, a portion of the population that will increase more and more in the coming years. While some vaccines exist and are used in the elderly to effectively fight against some infections (e.g. influenza, pneumococci, varicella-zoster virus, diphtheria, and tetanus), still a lot of work remains to be done to better adapt these vaccines and to develop new ones for this age group. The prevention of infectious diseases affecting the elderly can be successful only through a holistic approach. This approach will aim at the following: (1) a deeper understanding of the mechanisms leading to the senescence of the immune system, (2) a better and broader use of vaccines recommended for the elderly, (3) the use of vaccines currently considered only for other age groups and (4) actively priming the population when they are immunological competent, before the physiological waning of immune responsiveness may affect the beneficial effects of vaccination.
Acute Severe Methotrexate Toxicity in Patients with Psoriasis: A Case Series and Discussion
Authors: Yélamos Oriol , Català Alba , Vilarrasa Eva , Roé Esther , Puig Lluís
Published: November 2014

Background: Methotrexate (MTX) is considered a relatively safe drug when prescribed at low-dose regimens not exceeding 25 mg/week. Severe acute toxicity is rare and presents with mucositis, cutaneous ulceration and pancytopenia. Most cases occur as the result of inadvertent overdosing due to erroneously taking the drug daily. However, concomitant factors such as older age, co-medication and renal failure may increase the drug's toxicity. Case Reports: We report four consecutive cases of acute MTX toxicity in patients with psoriasis vulgaris. In three patients, MTX was erroneously taken daily for 2-4 weeks. All three patients recovered following MTX withdrawal and intensive treatment. The fourth patient was taking 7.5 mg weekly MTX as prescribed, but had concomitant factors and died. Conclusion: Although low-dose MTX appears to be a safe medication, acute MTX toxicity can be a life-threatening emergency. Greater awareness of possible MTX toxicity is still needed for its prevention, early diagnosis and management.
Pericardial Endoscopy–Guided Left Atrial Appendage Ligation
Authors: Kimura Takehiro , Takatsuki Seiji , Miyoshi Shunichiro , Katsumata Yoshinori , Nishiyama Takahiko , Nishiyama Nobuhiro , Tanimoto Yoko , Aizawa Yoshiyasu , Jinzaki Masahiro , Fukuda Keiichi
Published: November 2014

Background—

Approaches for closing the left atrial appendage (LAA) have been developed for stroke prevention. However, the prevailing maneuvers require an open-chest surgery, intravascular access, or transseptal puncture. We evaluated the feasibility and safety of pericardial endoscopy-guided LAA ligation in a canine model.

Methods and Results—

We used a total of 8 canines and computed tomography was performed before the procedures. After a double percutaneous pericardiocentesis, a transurethral rigid endoscope was inserted into the pericardial space. The ENDOLOOP ligature was advanced to the ostium of the LAA by counter pulling the tip of the LAA with forceps. After confirming the positioning guided by transesophageal echocardiography, the ligature was securely tightened. Acute success was evaluated by transesophageal echocardiography and chronic success was evaluated by blood testing, computed tomography, and transesophageal echocardiography. The LAA ligation was safely achieved in all canines without major complications. One month after the ligation, the ligated LAA was replaced by fibrotic tissue, and both the transesophageal echocardiography and computed tomographic images revealed no residual shunt. There was only a localized adhesion of the pericardium, where the original LAA was located, without the need for antibiotic or steroid administration. The postprocedural internal surface of the ligated LAA was smooth by virtue of intimal growth. Blood tests showed a slight elevation of the inflammatory markers, but this normalized spontaneously.

Conclusions—

Pericardial endoscopy-guided LAA ligation could provide an alternative, minimally invasive, and feasible solution for LAA closure that does not require vascular access or a transseptal puncture.
Long-Term Effects of 4 Popular Diets on Weight Loss and Cardiovascular Risk Factors
Authors: Atallah Renée , Filion Kristian B. , Wakil Susan M. , Genest Jacques , Joseph Lawrence , Poirier Paul , Rinfret Stéphane , Schiffrin Ernesto L. , Eisenberg Mark J.
Published: November 2014

Background—

We conducted a systematic review to examine the efficacy of the Atkins, South Beach, Weight Watchers (WW), and Zone diets, with a particular focus on sustained weight loss at ≥12 months.

Methods and Results—

We systematically searched MEDLINE, EMBASE, and the Cochrane Library of Clinical Trials to identify randomized controlled trials (RCTs) published in English with follow-up ≥4 weeks that examined the effects of these 4 popular diets on weight loss and cardiovascular risk factors. We identified 12 RCTs (n=2559) with follow-up ≥12 months: 10 versus usual care (5 Atkins, 4 WW, and 1 South Beach) and 2 head-to-head (1 of Atkins, WW, and Zone, and 1 of Atkins, Zone, and control). At 12 months, the 10 RCTs comparing popular diets to usual care revealed that only WW was consistently more efficacious at reducing weight (range of mean changes: −3.5 to −6.0 kg versus −0.8 to −5.4 kg;
P
<0.05 for 3/4 RCTs). However, the 2 head-to-head RCTs suggest that Atkins (range: −2.1 to −4.7 kg), WW (−3.0 kg), Zone (−1.6 to −3.2 kg), and control (−2.2 kg) all achieved modest long-term weight loss. Twenty-four-month data suggest that weight lost with Atkins or WW is partially regained over time.

Conclusions—

Head-to-head RCTs, providing the most robust evidence available, demonstrated that Atkins, WW, and Zone achieved modest and similar long-term weight loss. Despite millions of dollars spent on popular commercial diets, data are conflicting and insufficient to identify one popular diet as being more beneficial than the others.
GPIHBP1
Missense Mutations Often Cause Multimerization of GPIHBP1 and Thereby Prevent Lipoprotein Lipase Binding
Authors: Beigneux Anne P. , Fong Loren G. , Bensadoun André , Davies Brandon S.J. , Oberer Monika , Gårdsvoll Henrik , Ploug Michael , Young Stephen G.
Published: November 2014

Rationale:

GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the subendothelial spaces and shuttles it to the capillary lumen.
GPIHBP1
missense mutations that interfere with LPL binding cause familial chylomicronemia.

Objective:

We sought to understand mechanisms by which
GPIHBP1
mutations prevent LPL binding and lead to chylomicronemia.

Methods and Results:

We expressed mutant forms of GPIHBP1 in Chinese hamster ovary cells, rat and human endothelial cells, and
Drosophila
S2 cells. In each expression system, mutation of cysteines in GPIHBP1’s Ly6 domain (including mutants identified in patients with chylomicronemia) led to the formation of disulfide-linked dimers and multimers. GPIHBP1 dimerization/multimerization was not unique to cysteine mutations; mutations in other amino acid residues, including several associated with chylomicronemia, also led to protein dimerization/multimerization. The loss of GPIHBP1 monomers is relevant to the pathogenesis of chylomicronemia because only GPIHBP1 monomers—and not dimers or multimers—are capable of binding LPL. One GPIHBP1 mutant, GPIHBP1-W109S, had distinctive properties. GPIHBP1-W109S lacked the ability to bind LPL but had a reduced propensity for forming dimers or multimers, suggesting that W109 might play a more direct role in binding LPL. In support of that idea, replacing W109 with any of 8 other amino acids abolished LPL binding—and often did so without promoting the formation of dimers and multimers.

Conclusions:

Many amino acid substitutions in GPIHBP1’s Ly6 domain that abolish LPL binding lead to protein dimerization/multimerization. Dimerization/multimerization is relevant to disease pathogenesis, given that only GPIHBP1 monomers are capable of binding LPL.
Functional Disability and Cognitive Impairment After Hospitalization for Myocardial Infarction and Stroke
Authors: Levine Deborah A. , Davydow Dimitry S. , Hough Catherine L. , Langa Kenneth M. , Rogers Mary A.M. , Iwashyna Theodore J.
Published: November 2014

Background—

We assessed the acute and long-term effect of myocardial infarction (MI) and stroke on postevent functional disability and cognition while controlling for survivors’ changes in functioning over the years before the event.

Methods and Results—

Among participants in the nationally representative Health and Retirement Study with linked Medicare data (1998–2010), we determined within-person changes in functional limitations (basic and instrumental activities of daily living) and cognitive impairment after hospitalization for stroke (n=432) and MI (n=450), controlling for premorbid functioning using fixed-effects regression. In persons without baseline impairments, an acute MI yielded a mean acute increase of 0.41 functional limitations (95% confidence interval [CI], 0.18–0.63) with a linear increase of 0.14 limitations/year in the following decade. These increases were 0.65 limitations (95% CI, 0.07–1.23) and 0.27 limitations/year afterward for those with mild-to-moderate impairment at baseline. Stroke resulted in an acute increase of 2.07 (95% CI, 1.51–2.63) limitations because of the acute event and an increase of 0.15 limitations/year afterward for those unimpaired at baseline. There were 2.65 new limitations (95% CI, 1.86–3.44) and 0.19/year afterward for those with baseline mild-to-moderate impairment. Stroke hospitalization was associated with greater odds of moderate-to-severe cognitive impairment (odds ratio, 3.86; 95% CI, 2.10–7.11) at the time of the event, after adjustment for premorbid cognition but MI hospitalization was not.

Conclusions—

In this population-based cohort, most MI and stroke hospitalizations were associated with significant increases in functional disability at the time of the event and in the decade afterward. Survivors of MI and stroke warrant screening for functional disability over the long-term.
Reducing Door‐to‐Puncture Times for Intra‐Arterial Stroke Therapy: A Pilot Quality Improvement Project
Authors: Mehta Brijesh P. , Leslie‐Mazwi Thabele M. , Chandra Ronil V. , Bell Donnie L. , Sun Chung‐Huan J. , Hirsch Joshua A. , Rabinov James D. , Rost Natalia S. , Schwamm Lee H. , Goldstein Joshua N. , Levine Wilton C. , Gupta Rishi , Yoo Albert J.
Published: November 2014

Background

Delays to intra‐arterial therapy (IAT) lead to worse outcomes in stroke patients with proximal occlusions. Little is known regarding the magnitude of, and reasons for, these delays. In a pilot quality improvement (QI) project, we sought to examine and improve our door‐puncture times.

Methods and Results

For anterior‐circulation stroke patients who underwent IAT, we retrospectively calculated in‐hospital time delays associated with various phases from patient arrival to groin puncture. We formulated and then implemented a process change targeted to the phase with the greatest delay. We examined the impact on time to treatment by comparing the pre‐ and post‐QI cohorts. One hundred forty‐six patients (93 pre‐ vs. 51 post‐QI) were analyzed. In the pre‐QI cohort (ie, sequential process), the greatest delay occurred from imaging to the neurointerventional (NI) suite (“picture‐suite”: median, 62 minutes; interquartile range [IQR], 40 to 82). A QI measure was instituted so that the NI team and anesthesiologist were assembled and the suite set up in parallel with completion of imaging and decision making. The post‐QI (ie, parallel process) median picture‐to‐suite time was 29 minutes (IQR, 21 to 41;
P
<0.0001). There was a 36‐minute reduction in median door‐to‐puncture time (143 vs. 107 minutes;
P
<0.0001). Parallel workflow and presentation during work hours were independent predictors of shorter door‐puncture times.

Conclusions

In‐hospital delays are a major obstacle to timely IAT. A simple approach for achieving substantial time savings is to mobilize the NI and anesthesia teams during patient evaluation and treatment decision making. This parallel workflow resulted in a >30‐minute (25%) reduction in median door‐to‐puncture times.
Synergistic Effect of Gestational Hypertension and Postpartum Incident Hypertension on Cardiovascular Health: A Nationwide Population Study
Authors: Yeh Jong Shiuan , Cheng Hao‐Min , Hsu Pai‐Feng , Sung Shih‐Hsien , Liu Wen‐Ling , Fang Hsin‐Ling , Chuang Shao‐Yuan
Published: November 2014

Background

Gestational hypertension (
GH
) is a common complication of pregnancy and is associated with increased risk of incident hypertension in later life (
IH
) and cardiovascular events. However, the interactive effect of
GH
and
IH
on postpartum cardiovascular health remains unclear.

Methods and Results

A nationwide population‐based study was conducted using 1 million individuals from the Taiwan National Health Insurance database. Records from 1998 to 2009 were used to identify 1260 pregnant women with
GH
and without previous cardiovascular disease. The control group comprised 5040 pregnant women without
GH
, matched for age and date of delivery. During the follow‐up period (median duration, 5.8 years), 182 cardiovascular events developed. Women with
GH
had significantly higher risk of cardiovascular events (hazard ratio [95%
CI
], 2.44 [1.80 to 3.31]) and
IH
(8.29 [6.30 to 10.91]) than controls. Compared with women without
GH
and
IH
, there was a significantly higher risk of cardiovascular events for women without
GH
but with
IH
(relative risk [95%
CI
], 2.89 [1.27–6.58]), women with
GH
but without
IH
(1.66 [1.16–2.39]), and women with
GH
and
IH
(8.11 [5.36–12.30]). The synergy index was 2.91 (95%
CI
1.11 to 7.59), suggesting a positive interaction between
GH
and
IH
.

Conclusions

GH
increased the risk of subsequent
IH
. Women with both
GH
and
IH
were at a substantially higher cardiovascular risk than were women with either
GH
or
IH
. The synergistic adverse effect of
GH
and
IH
on postpartum cardiovascular health indicates that more attention should be paid to this special population.