bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Engineering Applications of Dynamic Transfer Processes Possessing the Self-Organized Fractal Interfaces
Authors: Alevanau Aliaksandr Yurievich , Kuznechik Olgerd Pavlovich , Vyhoniailo Oleksandr Ivanovych
Published: May 2013

General formulation of practically applicable fundamental approach for development of engineering applications in systems with dynamically appearing and disappearing fractal structures is proposed. The approach is illustrated on the low-temperature pyrolysis of butane/propane mixture being pumped via the liquid tin and bismuth alloy preserved at the temperature 200 ± 20°C in the U-shaped test glass. Other prospective engineering applications of the approach are proposed on the base of analysis of selected experiments described in literature.
RANKL Cytokine: From Pioneer of the Osteoimmunology Era to Cure for a Rare Disease
Authors: Lo Iacono Nadia , Pangrazio Alessandra , Abinun Mario , Bredius Robbert , Zecca Marco , Blair Harry C. , Vezzoni Paolo , Villa Anna , Sobacchi Cristina
Published: May 2013

Since its identification, the RANKL cytokine has been demonstrated to play a crucial role in bone homeostasis and lymphoid tissue organization. Genetic defects impairing its function lead to a peculiar form of autosomal recessive osteopetrosis (ARO), a rare genetic bone disease presenting early in life and characterized by increased bone density due to failure in bone resorption by the osteoclasts. Hematopoietic stem cell transplantation (HSCT) is the only option for the majority of patients affected by this life-threatening disease. However, the RANKL-dependent ARO does not gain any benefit from this approach, because the genetic defect is not intrinsic to the hematopoietic osteoclast lineage but rather to the mesenchymal one. Of note, we recently provided proof of concept of the efficacy of a pharmacological RANKL-based therapy to cure this form of the disease. Here we provide an overview of the diverse roles of RANKL in the bone and immune systems and review the clinical features of RANKL-deficient ARO patients and the results of our preclinical studies. We emphasize that these patients present a continuous worsening of the disease in the absence of a cure and strongly wish that the therapy we propose will be further developed.
Amyloidosis in Alzheimer’s Disease: The Toxicity of Amyloid Beta (Aβ), Mechanisms of Its Accumulation and Implications of Medicinal Plants for Therapy
Authors: Prasansuklab Anchalee , Tencomnao Tewin
Published: May 2013

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to memory deficits and death. While the number of individuals with AD is rising each year due to the longer life expectancy worldwide, current therapy can only somewhat relieve the symptoms of AD. There is no proven medication to cure or prevent the disease, possibly due to a lack of knowledge regarding the molecular mechanisms underlying disease pathogenesis. Most previous studies have accepted the “amyloid hypothesis,” in which the neuropathogenesis of AD is believed to be triggered by the accumulation of the toxic amyloid beta (Aβ) protein in the central nervous system (CNS). Lately, knowledge that may be critical to unraveling the hidden pathogenic pathway of AD has been revealed. This review concentrates on the toxicity of Aβand the mechanism of accumulation of this toxic protein in the brain of individuals with AD and also summarizes recent advances in the study of these accumulation mechanisms together with the role of herbal medicines that could facilitate the development of more effective therapeutic and preventive strategies.
Antidiabetic and Hypolipidemic Activities ofCurculigo latifoliaFruit:Root Extract in High Fat Fed Diet and Low Dose STZ Induced Diabetic Rats
Authors: Ishak Nur Akmal , Ismail Maznah , Hamid Muhajir , Ahmad Zalinah , Abd Ghafar Siti Aisyah
Published: May 2013

Curculigo latifoliafruit is used as alternative sweetener while root is used as alternative treatment for diuretic and urinary problems. The antidiabetic and hypolipidemic activities ofC. latifoliafruit:root aqueous extract in high fat diet (HFD) and 40 mg streptozotocin (STZ) induced diabetic rats through expression of genes involved in glucose and lipid metabolisms were investigated. Diabetic rats were treated withC. latifoliafruit:root extract for 4 weeks. Plasma glucose, insulin, adiponectin, lipid profiles, alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), urea, and creatinine levels were measured before and after treatments. Regulations of selected genes involved in glucose and lipid metabolisms were determined. Results showed the significant (P<0.05) increase in body weight, high density lipoprotein (HDL), insulin, and adiponectin levels and decreased glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), urea, creatinine, ALT, and GGT levels in diabetic rats after 4 weeks treatment. Furthermore,C. latifoliafruit:root extract significantly increased the expression ofIRS-1,IGF-1,GLUT4,PPARα,PPARγ,AdipoR1,AdipoR2,leptin,LPL, andlipasegenes in adipose and muscle tissues in diabetic rats. These results suggest thatC. latifoliafruit:root extract exerts antidiabetic and hypolipidemic effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats.
DNS Study of the Turbulent Taylor-Vortex Flow on a Ribbed Inner Cylinder
Authors: Tsukahara Takahiro , Ishikawa Manabu , Kawaguchi Yasuo
Published: May 2013

Turbulent Taylor-vortex flows over regularly spaced square ribs mounted on a rotating inner cylinder surface were investigated using direct numerical simulations (DNSs) for a Reynolds number of 3200 (based on the inner-wall velocity and the gap width between two cylinders) in an apparatus with an inner-to-outer radius ratio of 0.617, while varying the streamwise interval of the ribs. We examined the flow and pressure fields around each rib, focusing on the recirculation zone, the frictional drag coefficient, and the pressure (form) drag. Our results for the Taylor-Couette flows were compared to DNS for plane Poiseuille flows over ribbed surfaces performed by Leonardi et al. (2003). We determined the qualitative consistency between them with respect to the roughness effect, which depends significantly on the rib interval, but the rate of increase in the flow resistance was remarkably dampened by roughness in the present flows. Taylor vortices remaining over roughened cylinder surfaces were found to induce quick pressure recovery behind each rib, leading to less pressure drag and an enhanced backflow in the recirculation zone.
Balloon Occlusion of the Contralateral Iliac Artery to Assist Recanalization of the Ipsilateral Iliac Artery in Total Aortoiliac Occlusion: A Technical Note
Authors: Jaffan Abdel Aziz A.
Published: May 2013

Endovascular recanalization of chronic total aortoiliac occlusion is technically challenging. Inability to reenter the true aortic lumen, following retrograde iliac recanalization, is one of the most common causes of failure. We describe a case of a total aortoiliac occlusion where balloon occlusion of the right common iliac artery, following its recanalization from a brachial approach, was used to facilitate antegrade recanalization of the occluded contralateral left common iliac artery.
Fault Detection for Linear Discrete Time-Varying Systems with Measurement Packet Dropping
Authors: Li Yueyang , Liu Shuai , Wang Zhonghua
Published: May 2013

The fault detection (FD) problem for linear discrete time-varying (LDTV) systems with measurement packet dropouts is considered. The objective is to design a new observer-based fault detection filter (FDF) as a residual generator through employing packet dropout information on the measurement sequence. Based on some new defined input-to-output operators, the FD problem is formulated in a framework of maximizing stochasticH−/H∞orH∞/H∞performance index. By introducing an adjoint-operator-based optimization method, the analytical optimal solution can be derived in terms of solving a modified Riccati equation. A numerical example is provided to demonstrate the effectiveness of the proposed approach.
A Method to Determine Structural Patterns of Mechanical Systems with Impacts
Authors: Blazejczyk-Okolewska Barbara , Serweta Wioleta
Published: May 2013

A structural classification of vibroimpact systems based on the principles given by Blazejczyk-Okolewska et al. (2004) has been proposed for an arbitrary finite number of degrees-of-freedom. A new matrix representation to formulate the notation of the relations occurring in the system has been introduced. The developed identification and elimination procedures of equivalent systems and identification procedures of connected systems enable the determination of a set of structural patterns of systems with impacts.
n-Butane Isomerization over Silica-Supported Heteropolyacids: Study of Some Parameters
Authors: Grinenval Eva , Garron Anthony , Lefebvre Frédéric
Published: May 2013

Isomerization of n-butane was studied on silica-supported heteropolyacids. The activity depends strongly on the solvent used for the preparation and on the polyoxometalate loading. This behavior was explained by different proportions of isolated and bulk heteropolyacids. Silicotungstic acid is inherently more selective than phosphotungstic acid. In presence of platinum and hydrogen the catalysts are stable and highly selective (more than 97%) to isobutane. A study as a function of temperature shows that there is an optimal temperature for performing the reaction.
Stability Study of Darunavir Ethanolate Tablets Applying a New Stability-Indicating HPLC Method
Authors: Corrêa Josilene Chaves Ruela , Serra Cristina Helena dos Reis , Salgado Hérida Regina Nunes
Published: May 2013

Chemical and physical degradation of drugs may result in altered therapeutic efficacy and even toxic effects. Therefore, the aim of this work was to study the stability of darunavir and to develop and validate a liquid chromatography (LC) method to determine darunavir in raw material and tablets in the presence of degradation products. The novel method showed to be linear from 6.0 to 21.0 μg/mL, with high precision (CV < 2%) and accuracy (recuperation of 99.64%). It is simple and reliable, free of placebo interferences. The robustness of the method was evaluated by a factorial design using seven different parameters. Forced degradation study was done under alkaline, acidic, and oxidative stress at ambient temperature and by heating. The LC method was able to quantify and separate darunavir and its degradation products. Darunavir showed to be unstable under alkaline, acid, and oxidative conditions. The novelty of this study is understanding the factors that affect darunavir ethanolate stability in tablets, which is the first step to unravel the path to know the degradation products. The novel stability-indicating method can be used to monitor the drug and the main degradation products in low concentrations in which there is linearity.
Visceral Nociceptive Afferent Facilitates Reaction of Subnucleus Reticularis Dorsalis to Acupoint Stimulation in Rats
Authors: Li Liang , Yu Lingling , Rong Peijing , Ben Hui , Li Xia , Zhu Bing , Chen Rixin
Published: May 2013

Objective. To explore the area and sensitization variance of acupoint when internal organs are under pathological condition. To observe quantity-effect variance of subnucleus reticularis dorsalis (SRD) to electroacupuncture under both physiological and pathological conditions. To explain medulla oblongata mechanism of acupoint sensitization.Method. Mustard oil was imported into colon and rectum of 20 male SD rats in order to observe its influence on acupoint sensitization. SRD neuron activity was recorded. Visceral nociceptive stimulus was generated by colorectal distension (CRD). Quantity-effect variance of neuron activity to electroacupuncture to “Zusanli-Shangjuxu” area both before and after CRD was observed. Pairedt-test is used for cross-group comparison;P<0.05is deemed as of statistical differences.Result. Visceral inflammation could facilitate SRD neuron activity to acupoint stimulation. Visceral nociceptive afference could enhance neuron activity to acupoint acupuncture. Wide dynamic range (WDR) neuron activity caused by electroacupuncture increased when visceral nociception increased.Conclusion. The size and function of the acupoints comply with the functionality of the internal organs. The sensitive degree of acupoints changed according to malfunction of internal organs.
Hearing Loss due to Carbon Monoxide Poisoning
Authors: Mehrparvar Amir Houshang , Davari Mohammad Hossein , Mollasadeghi Abolfazl , Vahidi Mohammad Reza , Mostaghaci Mehrdad , Bahaloo Maryam , Shokouh Pedram
Published: May 2013

Carbon monoxide poisoning is one of the rare causes of hearing loss which may cause reversible or irreversible, unilateral or bilateral hearing loss after acute or chronic exposure. In this report, we present a case of bilateral sensorineural hearing loss in a secondary smelting workshop worker after an acute exposure to carbon monoxide. This complication was diagnosed by pure-tone audiometry and confirmed by transient evoked otoacoustic emissions. Hearing loss has not improved after 3 months of followup.
Extraction of Affine Invariant Features Using Fractal
Authors: Yang Jianwei , Cheng Guosheng , Li Ming
Published: May 2013

An approach based on fractal is presented for extracting affine invariant features. Central projection transformation is employed to reduce the dimensionality of the original input pattern, and general contour (GC) of the pattern is derived. Affine invariant features cannot be extracted from GC directly due to shearing. To address this problem, a group of curves (which are called shift curves) are constructed from the obtained GC. Fractal dimensions of these curves can readily be computed and constitute a new feature vector for the original pattern. The derived feature vector is used in question for pattern recognition. Several experiments have been conducted to evaluate the performance of the proposed method. Experimental results show that the proposed method can be used for object classification.
First Autologous Cell Therapy of Cerebral Palsy Caused by Hypoxic-Ischemic Brain Damage in a Child after Cardiac Arrest—Individual Treatment with Cord Blood
Authors: Jensen A. , Hamelmann E.
Published: May 2013

Each year, thousands of children incur brain damage that results in lifelong sequelae. Therefore, based on experimental evidence, we explored the therapeutic potential of human cord blood, known to contain stem cells, to examine the functional neuroregeneration in a child with cerebral palsy after cardiac arrest. The boy, whose cord blood was stored at birth, was 2.5 years old and normally developed when global ischemic brain damage occurred resulting in a persistent vegetative state. Nine weeks later, he received autologous cord blood (91.7 mL, cryopreserved,5.75×10e8mononuclear cells) intravenously. Active rehabilitation (physio- and ergotherapy) was provided daily, follow-up at 2, 5, 12, 24, 30, and 40 months. At 2-months follow-up the boy’s motor control improved, spastic paresis was largely reduced, and eyesight was recovered, as did the electroencephalogram. He smiled when played with, was able to sit and to speak simple words. At 40 months, independent eating, walking in gait trainer, crawling, and moving from prone position to free sitting were possible, and there was significantly improved receptive and expressive speech competence (four-word sentences, 200 words). This remarkable functional neuroregeneration is difficult to explain by intense active rehabilitation alone and suggests that autologous cord blood transplantation may be an additional and causative treatment of pediatric cerebral palsy after brain damage.
Measurement of the Quasi-Two-BodyBDecays
Authors: Mehraban Hossein , Mohammadi Behnam
Published: May 2013

We study the contributions of theB→ψ(3770)K[ψ(3770)→DD̅],B→K*(1410)π[K*(1410)→Kπ], andB→X(3872)K[X(3872)→J/ψγ,ψ(2S)γ,DD-π,J/ψω,J/ψππ, andDD-*π]quasi-two-body decays. There are no existing previous measurements of the three-body branching fractions for three final states of theX(3872)→J/ψγ,ψ(2S)γ, andDD̅π, but several quasi-two-body modes that can decay to this final state have been seen.
Therapeutic Enhancement of ER Stress by Insulin-Like Growth Factor I Sensitizes Myeloma Cells to Proteasomal Inhibitors
Authors: Tagoug Inès , Jordheim Lars Petter , Herveau Stéphanie , Matera Eva-Laure , Huber Anne-Laure , Chettab Kamel , Manié Serge , Dumontet Charles
Published: May 2013

Purpose: Multiple myeloma is a clonal plasma cell disorder in which growth and proliferation are linked to a variety of growth factors, including insulin-like growth factor type I (IGF-I). Bortezomib, the first-in-class proteasome inhibitor, has displayed significant antitumor activity in multiple myeloma.

Experimental Design: We analyzed the impact of IGF-I combined with proteasome inhibitors on multiple myeloma cell lines in vivo and in vitro as well as on fresh human myeloma cells.

Results: Our study shows that IGF-I enhances the cytotoxic effect of proteasome inhibitors against myeloma cells. The effect of bortezomib on the content of proapoptotic proteins such as Bax, Bad, Bak, and BimS and antiapoptotic proteins such as Bcl-2, Bcl-XL, XIAP, Bfl-1, and survivin was enhanced by IGF-I. The addition of IGF-I to bortezomib had a minor effect on NF-κB signaling in MM.1S cells while strongly enhancing reticulum stress. This resulted in an unfolded protein response (UPR), which was required for the potentiating effect of IGF-I on bortezomib cytotoxicity as shown by siRNA-mediated inhibition of GADD153 expression.

Conclusions: These results suggest that the high baseline level of protein synthesis in myeloma can be exploited therapeutically by combining proteasome inhibitors with IGF-I, which possesses a “priming” effect on myeloma cells for this family of compounds. Clin Cancer Res; 19(13); 3556–66. ©2013 AACR.
PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated Malignancies
Authors: Chen Benjamin J. , Chapuy Bjoern , Ouyang Jing , Sun Heather H. , Roemer Margaretha G.M. , Xu Mina L. , Yu Hongbo , Fletcher Christopher D.M. , Freeman Gordon J. , Shipp Margaret A. , Rodig Scott J.
Published: May 2013

Purpose: Programmed cell death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells and select tumors that engages receptors on T cells to inhibit T-cell immunity. Immunotherapies targeting the PD-1/PD-L1 pathway have shown durable antitumor effects in a subset of patients with solid tumors. PD-L1 can be expressed by Reed–Sternberg cells comprising classical Hodgkin lymphoma (CHL) and by malignant B cells comprising EBV-positive posttransplant lymphoproliferative disorders (PTLD). We sought to determine whether the expression of PD-L1 represents a general strategy of immune evasion among aggressive B-cell lymphomas and virus- and immunodeficiency-associated tumors.

Experimental Design: Using novel antibodies and formalin-fixed, paraffin-embedded (FFPE) tissue biopsies, we examined 237 primary tumors for expression of PD-L1.

Results: Robust PD-L1 protein expression was found in the majority of nodular sclerosis and mixed cellularity CHL, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich B-cell lymphoma, EBV-positive and -negative PTLD, and EBV-associated diffuse large B-cell lymphoma (DLBCL), plasmablastic lymphoma, extranodal NK/T-cell lymphoma, nasopharyngeal carcinoma, and HHV8-associated primary effusion lymphoma. Within these tumors, PD-L1 was highly expressed by malignant cells and tumor-infiltrating macrophages. In contrast, neither the malignant nor the nonmalignant cells comprising nodular lymphocyte-predominant Hodgkin lymphoma, DLBCL-not otherwise specified, Burkitt lymphoma, and HHV8-associated Kaposi sarcoma expressed detectable PD-L1.

Conclusion: Certain aggressive B-cell lymphomas and virus- and immunodeficiency-associated malignancies associated with an ineffective T-cell immune response express PD-L1 on tumor cells and infiltrating macrophages. These results identify a group of neoplasms that should be considered for PD-1/PD-L1-directed therapies, and validate methods to detect PD-L1 in FFPE tissue biopsies. Clin Cancer Res; 19(13); 3462–73. ©2013 AACR.
Targeting 6-Phosphofructo-2-Kinase (PFKFB3) as a Therapeutic Strategy against Cancer
Authors: Clem Brian F. , O'Neal Julie , Tapolsky Gilles , Clem Amy L. , Imbert-Fernandez Yoannis , Kerr Daniel A. , Klarer Alden C. , Redman Rebecca , Miller Donald M. , Trent John O. , Telang Sucheta , Chesney Jason
Published: May 2013

In human cancers, loss of PTEN, stabilization of hypoxia inducible factor-1α, and activation of Ras and AKT converge to increase the activity of a key regulator of glycolysis, 6-phosphofructo-2-kinase (PFKFB3). This enzyme synthesizes fructose 2,6-bisphosphate (F26BP), which is an activator of 6-phosphofructo-1-kinase, a key step of glycolysis. Previously, a weak competitive inhibitor of PFKFB3, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), was found to reduce the glucose metabolism and proliferation of cancer cells. We have synthesized 73 derivatives of 3PO and screened each compound for activity against recombinant PFKFB3. One small molecule, 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15), was selected for further preclinical evaluation of its pharmacokinetic, antimetabolic, and antineoplastic properties in vitro and in vivo. We found that PFK15 causes a rapid induction of apoptosis in transformed cells, has adequate pharmacokinetic properties, suppresses the glucose uptake and growth of Lewis lung carcinomas in syngeneic mice, and yields antitumor effects in three human xenograft models of cancer in athymic mice that are comparable to U.S. Food and Drug Administration–approved chemotherapeutic agents. As a result of this study, a synthetic derivative and formulation of PFK15 has undergone investigational new drug (IND)-enabling toxicology and safety studies. A phase I clinical trial of its efficacy in advanced cancer patients will initiate in 2013 and we anticipate that this new class of antimetabolic agents will yield acceptable therapeutic indices and prove to be synergistic with agents that disrupt neoplastic signaling. Mol Cancer Ther; 12(8); 1461–70. ©2013 AACR.
Concurrent Chemoradiotherapy with a Novel Fluoropyrimidine, S-1, and Cisplatin for Locally Advanced Esophageal Cancer: Long-Term Results of a Phase II Trial
Authors: Iwase Hiroaki , Shimada Masaaki , Tsuzuki Tomoyuki , Hirashima Noboru , Okeya Masayuki , Hibino Yusuke , Ryuge Nobumitsu , Yokoi Misaki , Kida Yuichi , Kuno Takeshi , Tanaka Yusaku , Kato Bunichiro , Esaki Masaya , Urata Noboru , Kato Eriko
Published: May 2013

Objectives: A phase II study was performed to investigate the safety and efficacy of concurrent chemoradiotherapy (CCRT) combined with an orally active fluoropyrimidine, S-1, plus cisplatin for locally advanced esophageal cancer (LAEC). Methods: CCRT comprised 2 courses, a 30-Gy radiotherapy over 3 weeks plus daily oral S-1 (80 mg/m2/day) for 2 weeks and a 24-hour cisplatin infusion (70 mg/m2) on day 8, and an identical course administered after a 2-week break. Results: One hundred and sixteen patients, 12 with stage II, 71 with stage III, and 33 with stage IVa LAEC participated, and 106 of them (91.4%) completed the CCRT course. The most serious toxicity was myelosuppression: grade 3 and 4 neutropenia occurred in 28.4 and 9.5% of patients, respectively. Nonhematologic toxicity was moderate. Complete response rates in patients with stage II, III, and IVa LAEC were 91.7, 67.6, and 36.4%, respectively. The overall median survival time  was 2.3 years and that of patients with stage II, III, and IVa cancer was 7.0, 2.6, and 1.3 years, respectively. Conclusions: CCRT combined with S-1 plus cisplatin showed promising safety and efficacy. Potentially, this combination therapy could become a baseline medication for patients with LAEC.
Intracellular ATP-Binding Cassette Transporter A3 is Expressed in Lung Cancer Cells and Modulates Susceptibility to Cisplatin and Paclitaxel
Authors: Overbeck Tobias R. , Hupfeld Timo , Krause Doris , Waldmann-Beushausen Regina , Chapuy Bjoern , Güldenzoph Bjoern , Aung Thiha , Inagaki Nobuya , Schöndube Friedrich A. , Danner Bernhard C. , Truemper Lorenz , Wulf Gerald G.
Published: May 2013

Patients with advanced-stage bronchial cancer benefit from systemic cytostatic therapy, in particular from regimens integrating cisplatin and taxanes. However, eventual disease progression leads to a fatal outcome in most cases, originating from tumor cells resisting chemotherapy. We here show that the intracellular ATP-binding cassette transporter A3 (ABCA3), previously recognized as critical for the secretion of surfactant components from type 2 pneumocytes, is expressed in non-small-cell lung cancer (NSCLC) cells. With some heterogeneity in a given specimen, expression levels detected immunohistochemically in primary cancer tissue were highest in adenocarcinomas and lowest in small cell lung cancers. Genetic silencing of ABCA3 in the NSCLC cell line models A549, NCI-H1650 and NCI-H1975 significantly increased tumor cell susceptibility to the cytostatic effects of both cisplatin (in all cell lines) and paclitaxel (in two of three cell lines). Taken together, ABCA3 emerges as a modulator of NSCLC cell susceptibility to cytostatic therapy.
Oral Activated Charcoal Adsorbent (AST-120) Ameliorates Chronic Kidney Disease-Induced Intestinal Epithelial Barrier Disruption
Authors: Vaziri Nosratola D. , Yuan Jun , Khazaeli Mahyar , Masuda Yuichi , Ichii Hirohito , Liu Shuman
Published: May 2013

Background: Chronic kidney disease (CKD) impairs intestinal barrier function which by allowing influx of noxious products causes systemic inflammation. We have recently shown that intestinal barrier dysfunction in CKD is due to degradation of epithelial tight junction (TJ) which is, in part, mediated by influx of urea and its conversion to ammonia by microbial urease. We hypothesized that by adsorbing urea and urea-derived ammonia, oral activated charcoal (AST-120) may ameliorate CKD-induced intestinal epithelial barrier disruption and systemic inflammation. Methods: Rats were randomized to the CKD or control groups. The CKD group was fed a chow containing 0.7% adenine for 2 weeks. They were then randomized to receive a chow with or without AST-120 (4 g/kg/day) for 2 weeks. Rats consuming regular diet served as controls. Animals were then euthanized, colons were removed and processed for Western blot and immunohistology, and plasma was used to measure endotoxin and oxidative and inflammatory markers. Results: Compared with the controls, the untreated CKD rats showed elevated plasma endotoxin, IL-6, TNF-α, MCP-1, CINC-3, L-selectin, ICAM-1, and malondialdehyde, and depletions of colonic epithelial TJ proteins, claudin-1, occludin, and ZO1. Administration of AST-120 resulted in partial restoration of the epithelial TJ proteins and reduction in plasma endotoxin and markers of oxidative stress and inflammation. Conclusions: CKD animals exhibited depletion of the key protein constituents of the colonic epithelial TJ which was associated with systemic inflammation, oxidative stress and endotoxemia. Administration of AST-120 attenuated uremia-induced disruption of colonic epithelial TJ and the associated endotoxemia, oxidative stress and inflammation.
Individual and Community Determinants of Calling 911 for Stroke Among African Americans in an Urban Community
Authors: Skolarus Lesli E. , Murphy Jillian B. , Zimmerman Marc A. , Bailey Sarah , Fowlkes Sophronia , Brown Devin L. , Lisabeth Lynda D. , Greenberg Emily , Morgenstern Lewis B.
Published: May 2013

Background—

African Americans receive acute stroke treatment less often than non-Hispanic whites. Interventions to increase stroke preparedness (recognizing stroke warning signs and calling 911) may decrease the devastating effects of stroke by allowing more patients to be candidates for acute stroke therapy. In preparation for such an intervention, we used a community-based participatory research approach to conduct a qualitative study exploring perceptions of emergency medical care and stroke among urban African American youth and adults.

Methods and Results—

Community partners, church health teams, and church leaders identified and recruited focus group participants from 3 black churches in Flint, MI. We conducted 5 youth (11–16 years) and 4 adult focus groups from November 2011 to March 2012. A content analysis approach was taken for analysis. Thirty-nine youth and 38 adults participated. Women comprised 64% of youth and 90% of adult focus group participants. All participants were black. Three themes emerged from the adult and youth data: (1) recognition that stroke is a medical emergency; (2) perceptions of difficulties within the medical system in an under-resourced community, and; (3) need for greater stroke education in the community.

Conclusions—

Black adults and youth have a strong interest in stroke preparedness. Designs of behavioral interventions to increase stroke preparedness should be sensitive to both individual and community factors contributing to the likelihood of seeking emergency care for stroke.
Mortality in Medicare Patients Undergoing Elective Percutaneous Coronary Intervention With or Without Antecedent Stress Testing
Authors: Lin Grace A. , Lucas F. Lee , Malenka David J. , Skinner Jonathan , Redberg Rita F.
Published: May 2013

Background—

Guidelines advise testing for ischemia, such as with stress testing, before elective percutaneous coronary intervention (PCI). However, pre-PCI stress testing is not always done; the implications of this practice are not known. Our objective was to evaluate whether receipt of stress testing before elective PCI predicts mortality.

Methods and Results—

Using claims data from a 20% random sample of Medicare beneficiaries, we identified patients who had elective PCI in 2004 and followed them for a median of 3.4 years (n=23 887). Cox proportional hazards models were used to test the relationship of pre-PCI stress testing to survival. Population-based rates of elective PCI and stress testing were calculated for 306 hospital referral regions and categorized into 4 groups: high stress test/high PCI, low stress test/low PCI, low stress test/high PCI, and high stress/low PCI regions. Cox modeling was used to test whether category of hospital referral regions is related to survival. Patients who underwent pre-PCI stress testing had a 13% lower risk of mortality than those who did not (adjusted hazard ratio, 0.87; 95% confidence interval, 0.81–0.92) after median follow-up of 3.4 years. Patients in low stress test/high PCI regions had a 14% higher risk of mortality than those in high stress test/high PCI regions (adjusted hazard ratio, 1.14; 95% confidence interval, 1.03–1.26).

Conclusions—

Pre-PCI stress testing is associated with lower mortality in patients undergoing elective PCI. Greater adherence to guidelines with respect to documenting ischemia before elective PCI may result in improved outcomes for patients.
High-Dose Statin Therapy in Patients With Stable Coronary Artery Disease
Authors: Dorresteijn Johannes A.N. , Boekholdt S. Matthijs , van der Graaf Yolanda , Kastelein John J.P. , LaRosa John C. , Pedersen Terje R. , DeMicco David A. , Ridker Paul M , Cook Nancy R. , Visseren Frank L.J.
Published: May 2013

Background—

Clinicians need to identify coronary artery disease patients for whom the benefits of high-dose versus usual-dose statin therapy outweigh potential harm. We therefore aimed to develop and validate a model for prediction of the incremental treatment effect of high-dose statins for individual patients in terms of reduction of 5-year absolute risk for myocardial infarction, stroke, coronary death, or cardiac resuscitation.

Methods and Results—

Based on data from the Treating to New Targets trial (TNT; n=10 001), a Cox proportional hazards model was developed comprising 13 easy-to-measure clinical predictors: age, sex, smoking, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, history of myocardial infarction, coronary artery bypass grafting, congestive heart failure or abdominal aortic aneurysm, glomerular filtration rate, and treatment status (ie, atorvastatin 80 mg or 10 mg). External validation in the Incremental Decrease in End Points Through Aggressive Lipid Lowering trial (IDEAL; n=8888) confirmed adequate goodness-of-fit and calibration, but moderate discrimination (C-statistic, 0.63; 95% confidence interval, 0.62–0.65). Still, among participants of both trials combined, the model identified a group of 11.7% whose predicted 5-year number needed to treat was ≤25 and a group of 41.9% whose predicted needed to treat was ≥50. A decision curve shows that making treatment decisions on the basis of predictions using our model may improve net benefit.

Conclusions—

Estimation of the incremental treatment effect of high-dose versus usual-dose statin therapy in individual coronary artery disease patients enables selection of high-risk patients that benefit most from more aggressive therapy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00327691 and NCT00159835.
Low Serum Calcium Levels Contribute to Larger Hematoma Volume in Acute Intracerebral Hemorrhage
Authors: Inoue Yasuteru , Miyashita Fumio , Toyoda Kazunori , Minematsu Kazuo
Published: May 2013

Background and Purpose—

We investigate whether admission serum calcium levels are associated with hematoma volume, stroke severity, and outcomes in patients with acute intracerebral hemorrhage.

Methods—

A total of 273 patients admitted within 24 hours after intracerebral hemorrhage onset was divided into quartiles based on admission serum calcium levels (Q1 [≤9.0], Q2 [9.1–9.3], Q3 [9.4–9.7], Q4 [≥9.8] mg/dL).

Results—

Median hematoma volumes for each quartile (Q1 to Q4) were 18, 9, 10, and 9 mL (
P
=0.005), and median National Institutes of Health Stroke Scale scores were 16, 11, 11, and 9 (
P
=0.010), respectively. On multivariate analysis, Q1 had larger hematoma volume (
P
=0.025) and higher National Institutes of Health Stroke Scale score (
P
=0.020) than Q4. There were fewer patients with modified Rankin Scale scores 0 to 2 in Q1 than Q4 after adjustment for risk factors and comorbidities (odds ratio, 0.31; 95% confidence interval, 0.11–0.84) but not after additional adjustment for hematoma volume and National Institutes of Health Stroke Scale score. There were more patients with modified Rankin Scale scores 5 to 6 (
P
=0.016) and with fatal outcomes (
P
=0.048) in Q1 than Q4 as crude values, but not after adjustment.

Conclusions—

Low admission serum calcium levels were associated with larger hematoma volume and higher National Institutes of Health Stroke Scale score among patients with acute intracerebral hemorrhage.
Insertable Cardiac Event Recorder in Detection of Atrial Fibrillation After Cryptogenic Stroke
Authors: Etgen Thorleif , Hochreiter Manfred , Mundel Markus , Freudenberger Thomas
Published: May 2013

Background and Purpose—

Atrial fibrillation (AF) is the most frequent risk factor in ischemic stroke but often remains undetected. We analyzed the value of insertable cardiac event recorder in detection of AF in a 1-year cohort of patients with cryptogenic ischemic stroke.

Methods—

All patients with cryptogenic stroke and eligibility for oral anticoagulation were offered the insertion of a cardiac event recorder. Regular follow-up for 1 year recorded the incidence of AF.

Results—

Of the 393 patients with ischemic stroke, 65 (16.5%) had a cryptogenic stroke, and in 22 eligible patients, an event recorder was inserted. After 1 year, in 6 of 22 patients (27.3%), AF was detected.

Conclusions—

These preliminary data show that insertion of cardiac event recorder was eligible in approximately one third of patients with cryptogenic stroke and detected in approximately one quarter of these patients new AF.
Transient Receptor Potential Canonical 3 Inhibitor Pyr3 Improves Outcomes and Attenuates Astrogliosis After Intracerebral Hemorrhage in Mice
Authors: Munakata Masaya , Shirakawa Hisashi , Nagayasu Kazuki , Miyanohara Jun , Miyake Takahito , Nakagawa Takayuki , Katsuki Hiroshi , Kaneko Shuji
Published: May 2013

Background and Purpose—

Intracerebral hemorrhage (ICH) stems from the rupture of blood vessels in the brain, with the subsequent accumulation of blood in the parenchyma. Increasing evidence suggests that blood-derived factors induce excessive inflammatory responses that are involved in the progression of ICH-induced brain injury. Thrombin, a major blood-derived factor, leaks into the brain parenchyma on blood–brain barrier disruption and induces brain injury and astrogliosis. Furthermore, thrombin dynamically upregulates transient receptor potential canonical 3 channel, which contributes to pathological astrogliosis through a feed-forward upregulation of its own expression. The present study investigated whether Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3), a specific transient receptor potential canonical 3 inhibitor, can improve functional outcomes and attenuate astrogliosis after ICH in mice.

Methods—

Male C57BL6 mice received an intracerebral infusion of collagenase or autologous blood to induce ICH. Pyr3 was given both intracerebroventricularly and intraperitoneally after ICH induction. ICH-induced brain injury was evaluated by quantitative assessment of neurological deficits, brain swelling, and injury volume after ICH. Astrocyte activation was evaluated by immunohistochemical assessment of changes in S100 protein expression.

Results—

Neurological deficits, neuronal injury, brain edema, and astrocyte activation were all significantly improved by administration of Pyr3. Moreover, delayed administration of Pyr3 at 6 hours or 1 day after blood or collagenase infusion, respectively, also improved the symptoms.

Conclusions—

Pyr3, a specific inhibitor of transient receptor potential canonical 3, reduced the perihematomal accumulation of astrocytes and ameliorated ICH–induced brain injury. Therefore, transient receptor potential canonical 3 provides a new therapeutic target for the treatment of hemorrhagic brain injury.
17q25 Locus Is Associated With White Matter Hyperintensity Volume in Ischemic Stroke, But Not With Lacunar Stroke Status
Authors: Adib-Samii Poneh , Rost Natalia , Traylor Matthew , Devan William , Biffi Alessandro , Lanfranconi Silvia , Fitzpatrick Kaitlin , Bevan Steve , Kanakis Allison , Valant Valerie , Gschwendtner Andreas , Malik Rainer , Richie Alexa , Gamble Dale , Segal Helen , Parati Eugenio A. , Ciusani Emilio , Holliday Elizabeth G. , Maguire Jane , Wardlaw Joanna , Worrall Bradford , Bis Joshua , Wiggins Kerri L. , Longstreth Will , Kittner Steve J. , Cheng Yu-Ching , Mosley Thomas , Falcone Guido J. , Furie Karen L. , Leiva-Salinas Carlos , Lau Benison C. , Saleem Khan Muhammed ,   Australian Stroke Genetics Collaborative,   Wellcome Trust Case-Control Consortium-2 (WTCCC2),   METASTROKE, Sharma Pankaj , Fornage Myriam , Mitchell Braxton D. , Psaty Bruce M. , Sudlow Cathie , Levi Christopher , Boncoraglio Giorgio B. , Rothwell Peter M. , Meschia James , Dichgans Martin , Rosand Jonathan , Markus Hugh S.
Published: May 2013

Background and Purpose—

Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke.

Methods—

We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke.

Results—

Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (
P
=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke.

Conclusions—

This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.
Estimation of Random-Coefficient Demand Models: Two Empiricists' Perspective
Authors: Knittel Christopher R. , Metaxoglou Konstantinos
Published: May 2013

We document the numerical challenges we experienced estimating random-coefficient demand models as in Berry, Levinsohn, and Pakes (1995) using two well-known data sets and a thorough optimization design. The optimization algorithms often converge at points where the first- and second-order optimality conditions fail. There are also cases of convergence at local optima. On convergence, the variation in the values of the parameter estimates translates into variation in the models' economic predictions. Price elasticities and changes in consumer and producer welfare following hypothetical merger exercises vary at least by a factor of 2 and up to a factor of 5.
Object use in childhood: development and possible functions
Authors: Pellegrini Anthony D.
Published: May 2013

The ways in which children use objects is central to many theories of development, yet we lack systematic descriptions of the various ways in which objects are used across childhood. In this paper, I first describe the different forms of object use (i.e., exploration, construction, play, tool use and tool making) for males and females in childhood, then establish time budgets for each type of object use. Second, I make functional inferences about each form of object use and the social contexts in which each is embedded. I suggest that putative functions of object play, specifically, may be related to children’s discovery of novel uses for objects, as well as peer group centrality in abundant niches. These dynamics produce a connected social network in which object play and group structure might interact to spread novel ideas.
“May You Live in Interesting Times”: Moral Philosophy and Empirical Psychology
Authors: Snow Nancy E.
Published: May 2013

The Moral Psychology Handbook is a contribution to a relatively new genre of philosophical writing, the “handbook.” In the first section, I comment on an expectation about handbooks, namely that handbooks contain works representative of a field, and raise concerns about The Moral Psychology Handbook in this regard. In the rest of the article I comment in detail on two Handbook articles, “Moral Motivation” by Timothy Schroeder, Adina Roskies, and Shaun Nichols, and “Character” by Maria W. Merritt, John M. Doris, and Gilbert Harman. Both articles illustrate the perils as well as the promise of reliance on empirical studies for philosophers who work in moral psychology.
‘Phoenix from the Ashes’: Religious Communities Arising from Globalization
Authors: Kippenberg Hans G.
Published: May 2013

When in the 1960s religious congregations were suffering from diminishing membership, the sociology of religion turned away from the study of organized religion in order to study private religiosity, even though new social forms of religion were emerging. The article addresses first the impact of globalization on the place of religious communities in the fabric of national and transnational society. Labor migration severs the individual from his or her transmitted loyalties and places him or her amid the risks of the labor market. Parallel to this, the nation state conveys public tasks into private hands in the realms of education, health care, social welfare, and sometimes security. Both changes open up new opportunities for religious communities. Second, the paper addresses the subjective side of the shift, focusing on the Abrahamic religions. They claim the promise given to Abraham—that he and his descendants will be blessed and become a great nation—for their communities. When the factual history contradicts that expectation, prophetic and apocalyptic visions of a bright future keep alive that faith. They summon the believers to fight for the well being of their community, to assist and support each other, and to claim public recognition for their community, since it is beneficial to the entire society. The article argues that this model of religious communality enabled believers in the past to appropriate official legal and social forms for their community. Max Weber in his Economy and Society also argued that religious communality remains a powerful social order in modern society. According to him its strength derives from the subjective religious expectations of social actors and the positive or negative impact their practices exercise on other social orders such as economy, family, state, and law.
Agents, Armies, Allies: Semantics of Public-Private Partnerships in US Welfare Reform
Authors: Nagel Alexander-Kenneth
Published: May 2013

Global competition and demographic change have put modern welfare states under pressure. To ensure budget consolidation without too harsh a retrenchment of benefits, privatization and competition have become white hopes in the social-political debate. As states are courting civil society to take over responsibility in the realm of social welfare, they create opportunity structures for religious communities to re-enter the public sphere. While it has become fashionable to announce the resurgence of religion in heroic diagnoses of the world order, little attention has been given to what is going on below on the meso-level of public-private collaboration between religious and non-religious organizations. In this article I will examine US welfare reform as a strong case of privatization and communalization of welfare responsibility, which involves an explicit invitation to religious communities to join in as public social service providers. I will argue for a religious studies perspective to religion and social politics that focuses on the semantic patterns of the political discourse and explore the guiding semantics of public-private partnerships from the initial Charitable Choice legislation under the Clinton government to George W. Bush’s Faith-based Initiative and finally to the New Era of Partnerships announced by Barack Obama.
Role of India’s and China’s FDI, Trade and ODA in the Development of African Region
Authors: Alam Iqbal Badar , Rawat Bhawana
Published: May 2013

In the present global scenario, many emerging countries are showing an increasing interest in the growth and development of African region. This is because of the existing potential and opportunities and a rising trend in GDP of African region i.e. at the rate of 5.1 per cent which is well above the global growth rate of GDP that stood at 2.9 per cent. These trends have been resulted into an appreciable growth in African global exports which witnessed a rise of 12.9 per cent as compared to increase in global exports rate of 8.9 per cent. Keeping these rising trends, the two most vital emerging economic powers namely- China (3rd biggest economy) and India (11th largest economy) have come forward to enhance their economic partnership/economic relations with African region in the form of trade, investment and official development assistance. The paper attempts to carve out the role of the two “Asian Economic Giants” within the continent with respect to Foreign Direct Investment (FDI), Trade and Official Development Assistance (ODA) in the process of development of African region.