bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Orai1-mediated Ca2+ entry is a key mechanism of the antiproliferative action of sirolimus in human arterial smooth muscle
Authors: König Sarah , Browne Sara , Doleschal Bernhard , Schernthaner Michaela , Poteser Michael , Mächler Heinrich , Wittchow Eric , Braune Marlen , Muik Martin , Romanin Christoph , Groschner Klaus
Published: September 2013

Sirolimus (rapamycin) is used in drug-eluting stent strategies and proved clearly superior in this application compared with other immunomodulators such as pimecrolimus. The molecular basis of this action of sirolimus in the vascular system is still incompletely understood. Measurements of cell proliferation in human coronary artery smooth muscle cells (hCASM) demonstrated a higher antiproliferative activity of sirolimus compared with pimecrolimus. Although sirolimus lacks inhibitory effects on calcineurin, nuclear factor of activated T-cell activation in hCASM was suppressed to a similar extent by both drugs at 10 μM. Sirolimus, but not pimecrolimus, inhibited agonist-induced and store-operated Ca2+ entry as well as cAMP response element binding protein (CREB) phosphorylation in human arterial smooth muscle, suggesting the existence of an as-yet unrecognized inhibitory effect of sirolimus on Ca2+ signaling and Ca2+-dependent gene transcription. Electrophysiological experiments revealed that only sirolimus but not pimecrolimus significantly blocked the classical stromal interaction molecule/Orai-mediated, store-operated Ca2+ current reconstituted in human embryonic kidney cells (HEK293). A link between Orai function and proliferation was confirmed by dominant-negative knockout of Orai in hCASM. Analysis of the effects of sirolimus on cell proliferation and CREB activation in an in vitro model of arterial intervention using human aorta corroborated the ability of sirolimus to suppress stent implantation-induced CREB activation in human arteries. We suggest inhibition of store-operated Ca2+ entry based on Orai channels and the resulting suppression of Ca2+ transcription coupling as a key mechanism underlying the antiproliferative activity of sirolimus in human arteries. This mechanism of action is specific for sirolimus and not a general feature of drugs interacting with FK506-binding proteins.
Metabolic shift in lung alveolar cell mitochondria following acrolein exposure
Authors: Agarwal Amit R. , Yin Fei , Cadenas Enrique
Published: September 2013

Acrolein, an α,β unsaturated electrophile, is an environmental pollutant released in ambient air from diesel exhausts and cooking oils. This study examines the role of acrolein in altering mitochondrial function and metabolism in lung-specific cells. RLE-6TN, H441, and primary alveolar type II (pAT2) cells were exposed to acrolein for 4 h, and its effect on mitochondrial oxygen consumption rates was studied by XF Extracellular Flux analysis. Low-dose acrolein exposure decreased mitochondrial respiration in a dose-dependent manner because of alteration in the metabolism of glucose in all the three cell types. Acrolein inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, leading to decreased substrate availability for mitochondrial respiration in RLE-6TN, H441, and pAT2 cells; the reduced GAPDH activity was compensated in pAT2 cells by an increase in the activity of glucose-6-phosphate dehydrogenase, the regulatory control of the pentose phosphate pathway. The decrease in pyruvate from glucose metabolism resulted in utilization of alternative sources to support mitochondrial energy production: palmitate-BSA complex increased mitochondrial respiration in RLE-6TN and pAT2 cells. The presence of palmitate in alveolar cells for surfactant biosynthesis may prove to be the alternative fuel source for mitochondrial respiration. Accordingly, a decrease in phosphatidylcholine levels and an increase in phospholipase A2activity were found in the alveolar cells after acrolein exposure. These findings have implications for understanding the decrease in surfactant levels frequently observed in pathophysiological situations with altered lung function following exposure to environmental toxicants.
Effects of MRP8, LPS, and Lenalidomide on the Expressions of TNF‐α, Brain‐Enriched, and Inflammation‐Related MicroRNAs in the Primary Astrocyte Culture
Authors: Omran Ahmed , Ashhab Muhammad Usman , Gan Na , Kong Huimin , Peng Jing , Yin Fei
Published: September 2013

Astrocytes are now recognized as a heterogeneous class of cells with many important and diverse functions in healthy and diseased central nervous system (CNS). MicroRNAs (miRNAs) are small, noncoding RNAs which may have key roles in astrocytes activation in response to various stimuli. We performed quantitative real‐time PCR (qPCR) to detect changes in the expressions of brain‐enriched miRNAs (124, 134, 9, 132, and 138), inflammation‐related miRNAs (146a, 21, 181a, 221, and 222), and tumor necrosis factor alpha (TNF‐α) in the rat primary astrocyte cultures after stimulation with myeloid‐related protein 8 (MRP8) and lipopolysaccharides (LPS). Further, we inhibited the expression of TNF‐α in the astrocytes by using TNF‐α inhibitor (lenalidomide) and tested for the first time the effect of this inhibition on the expressions of the same tested miRNAs. Stimulation of the astrocytes with MRP8 or LPS leads to significant upregulation of miRNAs (124, 134, 9, 132, 146a, 21, 181a, 221, and 222), while miRNA‐138 was downregulated. TNF‐α inhibition with lenalidomide leads to opposite expressions of the tested miRNAs. These miRNAs may play an important role in activation of the astrocytes and may be a novel target for cell‐specific therapeutic interventions in multiple CNS diseases.
Environmental Kuznets Curve Analysis of the Economic Development and Nonpoint Source Pollution in the Ningxia Yellow River Irrigation Districts in China
Authors: Mao Chunlan , Zhai Ningning , Yang Jingchao , Feng Yongzhong , Cao Yanchun , Han Xinhui , Ren Guangxin , Yang Gaihe , Meng Qing-xiang
Published: September 2013

This study applies the environmental Kuznets curve to test the relationship between the regional economic growth and the different types of agricultural nonpoint source pollution loads in the Ningxia Yellow River irrigation area by using the Johnes export coefficient method. Results show that the pollution load generated by crop cultivation and livestock-breeding industries in the Ningxia Yellow River irrigation area shows an inverted U-shaped feature; however, this feature is absent in living-sewage pollution load. Crop pollution has shown a decreasing trend since 1997 because of the increased per capita income of farmers. Livestock-breeding pollution load reached its turning point when the per capita income of farmers reached 8386.74 RMB. Therefore, an increase in the per capita income of farmers corresponds to an increase in the livestock-breeding pollution load in the Ningxia Yellow River irrigation area.
Ameloblastoma of the Nasal Septum Origin: A Case Report
Authors: Temporale Hanna , Zatoński Tomasz , Roszkowska Anna , Kręcicki Tomasz
Published: September 2013

Background. Ameloblastoma is the most common odontogenic tumor. It represents about 1% of all tumors of the jaw. Extragnathic location of the ameloblastoma is typical and extremely rare.Case Report. We report a case of ameloblastoma of the nasal septum origin, causing nasal obstruction. According to our information, this is the first reported case of ameloblastoma coming from the nasal septum as a primary tumor without maxillary sinus involvement.Conclusions. Ameloblastoma can not only locate in the maxilla and mandible, but also in other regions of the craniofacial. Ameloblastoma should be considered in the differential diagnosis of tumors causing nasal obstruction. Nonspecific clinical features of sinonasal ameloblastoma make it extremely important to perform accurate diagnostic imaging and histopathological examination.
Familial Aggregation of Metabolic Syndrome Indicators in Portuguese Families
Authors: Santos D. M. , Katzmarzyk P. T. , Trégouet D.-A. , Gomes T. N. , Santos F. K. , Maia J. A.
Published: September 2013

Background and Aims. Family studies are well suited to investigate the genetic architecture underlying the metabolic syndrome (MetS). The purposes of this paper were (i) to estimate heritabilities for each of the MetS indicators, and (ii) to test the significance of familial intratrait and cross-trait correlations in MetS markers.Methods and Results. This study included 1,363 individuals from 515 Portuguese families in which five MetS components, including waist circumference (WC), blood pressure (BP), HDL-cholesterol, triglycerides (TG), and glucose (GLU), were measured. Intratrait and cross-trait familial correlations of these five components were estimated using Generalized Estimating Equations. Each MetS component was significantly heritable (h2ranged from 0.12 to 0.60) and exhibited strong familial resemblance with correlations between biological relatives of similar magnitude to those observed between spouses. With respect to cross-trait correlations, familial resemblance was very weak except for the HDL-TG pair.Conclusions. The present findings confirm the idea of familial aggregation in MetS traits. Spousal correlations were, in general, of the same magnitude as the biological relatives' correlations suggesting that most of the phenotypic variance in MetS traits could be explained by shared environment.
A Collaborative Neighbor Representation Based Face Recognition Algorithm
Authors: Li Zhengming , Zhu Qi , Xie Binglei , Cao Jian , Zhang Jin
Published: September 2013

We propose a new collaborative neighbor representation algorithm for face recognition based on a revised regularized reconstruction error (RRRE), called the two-phase collaborative neighbor representation algorithm (TCNR). Specifically, the RRRE is the division of  l2-norm of reconstruction error of each class into a linear combination of  l2-norm of reconstruction coefficients of each class, which can be used to increase the discrimination information for classification. The algorithm is as follows: in the first phase, the test sample is represented as a linear combination of all the training samples by incorporating the neighbor information into the objective function. In the second phase, we use thekclasses to represent the test sample and calculate the collaborative neighbor representation coefficients. TCNR not only can preserve locality and similarity information of sparse coding but also can eliminate the side effect on the classification decision of the class that is far from the test sample. Moreover, the rationale and alternative scheme of TCNR are given. The experimental results show that TCNR algorithm achieves better performance than seven previous algorithms.
Behavior-Based Fuzzy Control for Mobile Robot Navigation
Authors: Mo Hongwei , Tang Qirong , Meng Longlong
Published: September 2013

A new behavior-based fuzzy control method for mobile robot navigation is presented. It is based on behavioral architecture which can deal with uncertainties in unknown environments and has the ability to accommodate different behaviors. Basic behaviors are controlled by specific fuzzy logic controllers, respectively. The proposed approach qualifies for driving a robot to reach a target while avoiding obstacles in the environment. Simulation and experiments are performed to verify the correctness and feasibility of the proposed method.
Modeling of the Radiation Doses during Dismantling of RBMK-1500 Reactor Pressurized Tanks from Emergency Core Cooling System
Authors: Simonis A. , Poskas P. , Sirvydas A. , Grigaliuniene D.
Published: September 2013

Decommissioning of the Ignalina Nuclear Power Plant involves multiple problems. One of them is personnel radiation safety during the performance of dismantling activities. In this paper, modeling results of radiation doses during the dismantling of the pressurized tank from the emergency core cooling system (ECCS PT) of RBMK-1500 reactor are presented. The radiological surveys indicate that the inner surface of the ECCS PT is contaminated with radioactive products of corrosion and sediments due to the radioactive water. The effective doses to the workers have been modeled for different strategies of ECCS PT dismantling. In order to select the optimal personnel radiation safety, the modeling has been performed by the means of computer code “VISIPLAN 3D ALARA Planning tool” developed by SCK CEN (Belgium). The impacts of dismantling tools, shielding types, and extract ventilation flow rate on effective doses during the dismantling of ECCS PT have been analyzed. The total effective personnel doses have been obtained by summarizing the effective personnel doses from various sources of exposure, that is, direct radiation from radioactive equipment, internal radiation due to inhalation of radioactive aerosols, and direct radiation from radioactive aerosols arising during hot cutting in premises. The uncertainty of the collective doses is also presented in this paper.
Tapered Fiber Coated with Hydroxyethyl Cellulose/Polyvinylidene Fluoride Composite for Relative Humidity Sensor
Authors: Muhammad M. Z. , Lokman A. , Batumalay M. , Arof H. , Ahmad H. , Harun S. W.
Published: September 2013

A simple relative humidity (RH) sensor is demonstrated using a tapered fiber coated with hydroxyethyl cellulose/polyvinylidene fluoride (HEC/PVDF) composite as a probe. This coating acts as an inner cladding whose refractive index decreases with the rise in humidity and thus allows more light to be transmitted in humid state. A difference of up to 0.89 dB of the transmitted optical power is observed when RH changes from 50% to 80% in case of the silica fiber probe. The proposed sensor has a sensitivity of about 0.0228 dB/%RH with a slope linearity of more than 99.91%. In case of the plastic optical fiber (POF) probe, the output voltage of the sensor increases linearly with a sensitivity of 0.0231 mV/%RH and a linearity of more than 99.65% as the relative humidity increases from 55% to 80%.
Sequential MR Images and Radiographs of Epiphyseal Osteomyelitis in the Distal Femur of an Infant
Authors: Hara Hitomi , Akisue Toshihiro , Kawamoto Teruya , Kurosaka Masahiro
Published: September 2013

Magnetic resonance imaging (MRI) plays an important role in the diagnosis of osteomyelitis, especially during the early phase of the disease. The findings of sequential MRIs during the course of treatment in acute osteomyelitis in children have not yet been reported in the literature. We present a case of acute epiphyseal osteomyelitis in the distal femur of an infant. We monitored imaging changes by sequential MRIs and radiographs. MRI was more useful than radiograph for early diagnosis and evaluation of therapeutic response.
The use of Multidimensional Data to Identify the Molecular Biomarker for Pancreatic Ductal Adenocarcinoma
Authors: Zhuang Liwei , Qi Yue , Wu Yun , Liu Nannan , Fu Yili
Published: September 2013

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and the patient has an extremely poor overall survival with a less than 5% 5-year survival rate. Development of potential biomarkers provides a critical foundation for the diagnosis of PDAC. In this project, we have adopted an integrative approach to simultaneously identify biomarker and generate testable hypothesis from multidimensional omics data. We first examine genes for which expression levels are correlated with survival data. The gene list was screened with TF regulation, predicted miRNA targets information, and KEGG pathways. We identified that 273 candidate genes are correlated with patient survival data. 12 TF regulation gene sets, 11 miRNAs targets gene sets, and 15 KEGG pathways are enriched with these survival genes. Notably, CEBPA/miRNA32/PER2 signaling to the clock rhythm qualifies this pathway as a suitable target for therapeutic intervention in PDAC. PER2 expression was highly associated with survival data, thus representing a novel biomarker for earlier detection of PDAC.
Factorial Validity and Invariance of Four Psychosocial Constructs of Colorectal Cancer Screening: Does Screening Experience Matter?
Authors: Murphy Caitlin C. , McQueen Amy , Bartholomew L. Kay , del Junco Deborah J. , Coan Sharon P. , Vernon Sally W.
Published: September 2013

Background: Few studies have examined the psychometric properties and invariance of scales measuring constructs relevant to colorectal cancer screening (CRCS). We sought to: (i) evaluate the factorial validity of four core constructs associated with CRCS (benefits, barriers, self-efficacy, and optimism); and (ii) examine measurement invariance by screening status (currently screened, overdue, never screened).

Methods: We used baseline survey data from a longitudinal behavioral intervention trial to increase CRCS among U.S. veterans. Respondents were classified as currently screened (n = 3,498), overdue (n = 418), and never screened (n = 1,277). The measurement model was developed using a random half of the sample and then validated with the second half of the sample and the full baseline sample (n = 5,193). Single- and multi-group confirmatory factor analysis was used to examine measurement invariance by screening status.

Results: The four-factor measurement model demonstrated good fit. Factor loadings, item intercepts, and residual item variance and covariance were invariant when comparing participants never screened and overdue for CRCS, indicating strict measurement invariance. All factor loadings were invariant among the currently screened and overdue groups. Only the benefits scale was invariant across current screeners and never screeners. Non-invariant items were primarily from the barriers scale.

Conclusion: Our findings provide additional support for the construct validity of scales of CRCS benefits, barriers, self-efficacy, and optimism. A greater understanding of the differences between current and never screeners may improve measurement invariance.

Impact: Measures of benefits, barriers, self-efficacy, and optimism may be used to specify intervention targets and effectively assess change pre- and post-intervention across screening groups. Cancer Epidemiol Biomarkers Prev; 22(12); 2295–302. ©2013 AACR.
DNA Demethylating Agents Synergize with Oncolytic HSV1 against Malignant Gliomas
Authors: Okemoto Kazuo , Kasai Kazue , Wagner Benjamin , Haseley Amy , Meisen Hans , Bolyard Chelsea , Mo Xiaokui , Wehr Allison , Lehman Amy , Fernandez Soledad , Kaur Balveen , Chiocca E. Antonio
Published: September 2013

Purpose: Oncolytic viruses (OV) based on herpes simplex virus type 1 (HSV1) are being used in clinical trials for a variety of cancers. The OV, rQNestin34.5, uses a nestin promoter/enhancer to selectively drive robust viral replication in malignant glioma cells. We have discovered that this promoter becomes extensively methylated in infected glioma cells, reducing OV efficacy.

Experimental Design: We used demethylating drugs [5-azacytidine (5-Aza)], decitabine, or valproic acid (VPA) in both in vitro and in vivo malignant glioma models to determine if they improved the efficacy of rQNestin34.5 therapy.

Results: The use of demethylating agents, such as 5-Aza, improved OV replication and tumor cell lysis in vitro and, in fact, synergized pharmacologically on Chou–Talalay analysis. In vivo, the combination of the demethylating agents, 5-Aza or decitabine, with rQNestin34.5 significantly prolonged the survivorship of athymic mice harboring intracranial human glioma xenografts over single agent alone.

Conclusion: These results, thus, provide further justification for the exploration of demethylating agents when combined with the OV, rQNestin34.5, in preclinical therapeutics and, possibly, clinical trials for malignant glioma. Clin Cancer Res; 19(21); 5952–9. ©2013 AACR.
A Negative Feedback of the HIF-1α Pathway via Interferon-Stimulated Gene 15 and ISGylation
Authors: Yeh Yen-Hsiu , Yang Yu-Chen , Hsieh Mei-Yi , Yeh Yen-Cheng , Li Tsai-Kun
Published: September 2013

Purpose: The IFN-stimulated gene 15 (ISG15)- and ubiquitin-conjugation pathways play roles in mediating hypoxic and inflammatory responses. To identify interaction(s) between these two tumor microenvironments, we investigated the effect of ISG15 on the activity of the master hypoxic transcription factor HIF-1α.

Experimental Design: IFN and desferoxamine treatments were used to induce the expression of ISGs and HIF-1α, respectively. Interactions between HIF-1α and the ISG15 and ISGylation system were studied using knockdown of mRNA expression, immunoblotting, coimmunoprecipitation, and pull-down analyses. Effects of the ISG15 and ISGylation system on the HIF-1α–directed processes were examined using reporter, reverse transcription polymerase chain reaction (RT-PCR), and tumorigenic growth assays.

Results: We found that the level of the free form of HIF-1α is differentially regulated by IFN treatment, and that the free ISG15 level is lower under hypoxia. Mechanism-directed studies have shown that HIF-1α not only interacts physically with ISG15, but is also ISGylated in multiple domains. ISG15 expression disrupts the functional dimerization of HIF-1α and -1β. Subsequently, expression of the ISG15 and/or ISGylation system attenuates HIF-1α–mediated gene expression and tumorigenic growth.

Conclusion: In summary, our results revealed cross-talk between inflammatory and hypoxic pathways through the ISGylation of HIF-1α. On the basis of these results, we propose a novel negative feedback loop for the HIF-1α–mediated pathway involving the regulation of HIF-1α via IFN-induced ISGylation. Clin Cancer Res; 19(21); 5927–39. ©2013 AACR.
Evaluation of Utility of Pharmacokinetic Studies in Phase I Trials of Two Oncology Drugs
Authors: Wu Kehua , House Larry , Ramírez Jacqueline , Seminerio Michael J. , Ratain Mark J.
Published: September 2013

Purpose: There are many phase I trials of oncology drug combinations, very few of which report clinically significant pharmacokinetic interactions. We hypothesized that the utility of such pharmacokinetic drug–drug interaction (DDI) studies is low in the absence of a mechanistic hypothesis.

Experimental Design: We retrospectively reviewed 152 phase I (two drug) combination studies published between 2007 and 2011.

Results: Only 28 (18%) studies had an implicit or explicit rationale, either inhibition/induction of a drug-metabolizing enzyme or transporter, cosubstrates for the same enzyme or transporter, potential for end-organ toxicity, or protein binding. Only 12 (8%) studies demonstrated a statistically significant DDI, on the basis of change in clearance (or area under the curve) of parent drug and/or active metabolite. There was a strong association between a rationale and a demonstrable drug interaction, as only 2% of studies without a rationale demonstrated a DDI, compared with 32% of studies with a rationale (Fisher exact test; P < 10−6).

Conclusion: DDI studies should not be routinely performed as part of phase I trials of oncology combinations. Clin Cancer Res; 19(21); 6039–43. ©2013 AACR.
Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia
Authors: Pemovska Tea , Kontro Mika , Yadav Bhagwan , Edgren Henrik , Eldfors Samuli , Szwajda Agnieszka , Almusa Henrikki , Bespalov Maxim M. , Ellonen Pekka , Elonen Erkki , Gjertsen Bjørn T. , Karjalainen Riikka , Kulesskiy Evgeny , Lagström Sonja , Lehto Anna , Lepistö Maija , Lundán Tuija , Majumder Muntasir Mamun , Marti Jesus M. Lopez , Mattila Pirkko , Murumägi Astrid , Mustjoki Satu , Palva Aino , Parsons Alun , Pirttinen Tero , Rämet Maria E. , Suvela Minna , Turunen Laura , Västrik Imre , Wolf Maija , Knowles Jonathan , Aittokallio Tero , Heckman Caroline A. , Porkka Kimmo , Kallioniemi Olli , Wennerberg Krister
Published: September 2013

We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profiling and ex vivo drug sensitivity and resistance testing (DSRT) of patients' cancer cells to 187 oncology drugs, (ii) clinical implementation of therapies predicted to be effective, and (iii) studying consecutive samples from the treated patients to understand the basis of resistance. Here, application of ISM to 28 samples from patients with acute myeloid leukemia (AML) uncovered five major taxonomic drug-response subtypes based on DSRT profiles, some with distinct genomic features (e.g., MLL gene fusions in subgroup IV and FLT3-ITD mutations in subgroup V). Therapy based on DSRT resulted in several clinical responses. After progression under DSRT-guided therapies, AML cells displayed significant clonal evolution and novel genomic changes potentially explaining resistance, whereas ex vivo DSRT data showed resistance to the clinically applied drugs and new vulnerabilities to previously ineffective drugs.

Significance: Here, we demonstrate an ISM strategy to optimize safe and effective personalized cancer therapies for individual patients as well as to understand and predict disease evolution and the next line of therapy. This approach could facilitate systematic drug repositioning of approved targeted drugs as well as help to prioritize and de-risk emerging drugs for clinical testing. Cancer Discov; 3(12); 1416–29. ©2013 AACR.

See related commentary by Hourigan and Karp, p. 1336

This article is highlighted in the In This Issue feature, p. 1317
CD8+ T-cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate
Authors: Bak S. Peter , Barnkob Mike Stein , Wittrup K. Dane , Chen Jianzhu
Published: September 2013

Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined to understand and achieve long-term therapeutic effects. In this study, we have investigated the expression of a tumor-specific antigen in situ after treatment with tumor-specific CD8+ T cells in an autochthonous mouse model of prostate cancer. After T-cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of the prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continued to grow in T-cell–treated mice. Interestingly, the remaining tumor cells were antigen negative and downregulated MHC class I expression. These results show that CD8+ T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate that not only induces potent immune responses but also avoids selection and outgrowth of antigen-negative tumor cells. Cancer Immunol Res; 1(6); 393–401. ©2013 AACR.
Hemodynamic Stabilizing Effects of L-Carnitine in Chronic Hemodialysis Patients
Authors: Kudoh Y. , Aoyama S. , Torii T. , Chen Q. , Nagahara D. , Sakata H. , Nozawa A.
Published: September 2013

Background: The effects of L-carnitine on the hemodynamic state of chronic hemodialysis patients have been debated. In order to clarify the effect of administered L-carnitine on cardiac function and hypotensive episodes during the hemodialysis procedure, a randomized double-blind placebo-controlled study was performed for 3 months. Methods and Results: Twenty stable outpatients undergoing hemodialysis treatment were divided into two groups: controls (placebo) and treated patients (L-carnitine 900 mg p.o. daily). After 3 months, cardiac function was reevaluated by echocardiography, and hypotensive episodes during hemodialysis were assessed. Free and acyl carnitine levels increased significantly from 22.3 ± 7.1 to 140.3 ± 57.5 μmol/l and from 15.8 ± 2.8 to 94.8 ± 50.4 μmol/l, respectively, in the treated group. The ejection fraction significantly increased from 61.8 ± 16.0 to 64.4 ± 13.8% (p < 0.05) in the treated group. However, there was no difference in other echocardiographic parameters between the two groups. Hypotensive episodes significantly decreased from 4.0 ± 1.7 to 1.3 ± 0.9 times per month (p < 0.05), although patients' body weight did not change significantly. Conclusions: Beneficial effects of L-carnitine on the hemodynamic state of chronic hemodialysis patients were observed. L-Carnitine supplementation might be considered especially for chronic hemodialysis patients with unstable hemodynamic conditions.
Lipoprotein Apheresis in Patients With Maximally Tolerated Lipid-Lowering Therapy, Lipoprotein(a)-Hyperlipoproteinemia, and Progressive Cardiovascular Disease
Authors: Leebmann Josef , Roeseler Eberhard , Julius Ulrich , Heigl Franz , Spitthoever Ralf , Heutling Dennis , Breitenberger Paul , Maerz Winfried , Lehmacher Walter , Heibges Andreas , Klingel Reinhard
Published: September 2013

Background—

Lipoprotein(a) (Lp(a)) hyperlipoproteinemia is a major risk factor for cardiovascular disease, which is not affected by treatment of other cardiovascular risk factors. This study sought to assess the effect of chronic lipoprotein apheresis (LA) on the incidence of cardiovascular events in patients with progressive cardiovascular disease receiving maximally tolerated lipid-lowering treatment.

Methods and Results—

In a prospective observational multicenter study, 170 patients were investigated who commenced LA because of Lp(a)-hyperlipoproteinemia and progressive cardiovascular disease. Patients were characterized regarding plasma lipid status, lipid-lowering drug treatment, and variants at the LPA gene locus. The incidence rates of cardiovascular events 2 years before (y-2 and y-1) and prospectively 2 years during LA treatment (y+1, y+2) were compared. The mean age of patients was 51 years at the first cardiovascular event and 57 years at the first LA. Before LA, mean low-density lipoprotein cholesterol and Lp(a) were 2.56±1.04 mmol·L
−1
(99.0±40.1 mg·dL
−1
) and Lp(a) 3.74±1.63 µmol·L
−1
(104.9±45.7 mg·dL
−1
), respectively. Mean annual rates for major adverse coronary events declined from 0.41 for 2 years before LA to 0.09 for 2 years during LA (
P
<0.0001). Event rates including all vascular beds declined from 0.61 to 0.16 (
P
<0.0001). Analysis of single years revealed increasing major adverse coronary event rates from 0.30 to 0.54 (
P
=0.001) for y-2 to y-1 before LA, decline to 0.14 from y-1 to y+1 (
P
<0.0001) and to 0.05 from y+1 to y+2 (
P
=0.014).

Conclusions—

In patients with Lp(a)-hyperlipoproteinemia, progressive cardiovascular disease, and maximally tolerated lipid-lowering medication, LA effectively lowered the incidence rate of cardiovascular events.

Clinical Trial Registration—

URL:
https://drks-neu.uniklinik-freiburg.de
. Unique identifier: DRKS00003119.
Redefining Islamic Tradition
Authors: Terem Etty
Published: September 2013

In 1910, as the possibility that Morocco would fall to French control threatened to overwhelm the Muslim community, al-Mahdī al-Wazzānī, a distinguished Moroccan Islamic scholar, penned the conclusion of his massive compilation of Mālikī fatwās and named it theNew Mi‘yār. This essay explores the nature and meaning of theNew Mi‘yār. I argue that al-Wazzānī did notmerelyassemble a collection of fatwās, but deliberately formulated a text that was firmly rooted in the specific challenges and changes generated by Moroccan modernity and was designed to redefine Mālikī legal tradition to make it relevant to his time. For al-Wazzānī, redefining Mālikī tradition and thought as an effective regulator of contemporary social relations and Islamic morality was necessary to reinforce the authority of Mālikī scholarship and to ensure the moral survival of the Muslim community in the context of the dramatic transformations that characterized Moroccan modernity.
Migration Background and Subjective Well-Being A Multilevel Analysis Based on the European Social Survey
Authors: Hadjar Andreas , Backes Susanne
Published: September 2013

Abstract

Contributing to the debate on the integration of migrants in Europe, this study focuses on Subjective Well-Being (SWB) of people with migration backgrounds compared to people without a migration background – specifying SWB in terms of successful integration. The analyses employ a multilevel perspective (data base: European Social Survey). On the macro level, gross domestic product (GDP), welfare regime, xenophobia and the migrant integration policy index (MIPEX) are considered; on the micro level, social origin, education, unemployment, income deprivation, relationship status, health status and controls. Findings indicate a disadvantage in SWB of first-generation migrants that goes beyond deficits regarding well-studied SWB determinants. The SWB gap between migrants and non-migrants is larger in countries with a high GDP and smaller in countries with a high MIPEX score.
The Specters of Marx in Edward Said’s Orientalism
Authors: Sing Manfred , Younes Miriam
Published: September 2013

Edward Said’s Orientalism was not only an attack on Western scholarship and impe­rialism, but also on Marxism. Said depicted Karl Marx as yet another Orientalist, Marxism as a form of Western domination and Arab Marxism as an expression of Self-Orientalization. Said claimed to have surpassed Marxism and Marxists who were “blinded to the fact of imperialism”. Said’s ambivalent relation to Marxism has not been thoroughly studied until now although it forms an important cornerstone in his argumentation and self-representation. This lacuna is surprising since many early Arab critics of Orientalism came from a Marxist background. Said either ignored them or rebuffed their interventions as “dogmatist”. The following article analyzes the nature of the conflict between the two sides and their underlying differences and reflects on the conditions affecting the Arab reception of Orientalism.
Do Excellent Surgeons Make Miserable Exegetes?
Authors: Fuchs Simon Wolfgang
Published: September 2013

This article is an attempt to explore how ǧihādī authors make use of the Sunni tradition to bolster their case. Islamicists have rarely embarked on such a discussion, given the tendency to a priori chastise extremist authors for their untenable misrepresentation of Islam. Similarly, ǧihādī arguments are frequently tossed aside as an already familiar rehashing of an insignificant, isolated stream of thought that stretches directly from Ibn Taimīya via Muḥammad b. ʿAbd al-Wahhāb to Saiyid Quṭb. In revisiting this claim, I employ a close reading of the crucial ǧihādī manual al-ʿUmda fī iʿdād al-ʿudda li-l-ǧihād fī sabīl Allāh (The Essential Guide of Preparation for ǧihād on the Path of God), written in the mid-1980s in the context of Afghanistan by an influential ideologue who is widely known as Dr. Faḍl. After presenting and evaluating a selection of the religious sources and authorities on which the author draws, the article enters into a discussion of his political thought. I argue that Dr. Faḍl makes a convincing case for a political project in the camps that is deeply embedded within the Sunni tradition. Reading Ibn Taimīya faithfully, Dr. Fadl does not turn him in into a proponent of violence against the ruler. Rather, the author sticks to the profound quietism the Damascene scholar is known for, thereby questioning supposedly established, clear-cut paths of reception.
The South African Women’s Theological Project: Practices of Solidarity and Degrees of Separation in the Context of the HIV Epidemic
Authors: Haddad Beverley
Published: September 2013

Abstract

It has previously been argued that the HIV epidemic is the new kairos in South Africa. The Circle of African Women Theologians has been at the forefront of theologising this crisis, particularly as it affects women. This article seeks to analyse the HIV work of six South African Circle writers namely, Denise Ackermann, Christina Landman, Madipoane Masenya, Sarojini Nadar, Miranda Pillay and Beverley Haddad. The focus of this analysis revolves around the “degrees of separation and practices of solidarity” inherent in their work. The first part of the article deals with each theologian in turn. It then identifies common threads and differences in their work employing the methodological framework of African women’s theology as outlined by Sarojini Nadar and Isabel Phiri. The article concludes with a discussion of the particularities of the South African women’s theological project and argues that the work of these six women does not deal sufficiently with “difference” or “solidarity” thus limiting their influence on the political HIV project.
Mapping Dissent: The Responsibility to Protect and Its State Critics
Authors: Quinton-Brown Patrick
Published: September 2013

Addressing dissent, also known as ‘rejectionism’, will broaden and deepen the global consensus on the Responsibility to Protect (R2P) principle. However, how should scholars understand the objections raised by state critics? To answer this question, I analyse R2P opposition as presented in official UN transcripts, voting records, and resolutions. The article reveals that six related themes of dissent exist with varying degrees of emphasis amongst opponents. Conventional depictions of R2P opposition, such as the absolute sovereignty or North vs. South explanations, are therefore inadequate representations of the diverse range of arguments employed by dissenters. Ultimately, I conclude that in order to build consensus at the expense of dissent, the principle should be further developed around four key notions: 1) non-coercive prevention and domestic capacity building, 2) enhanced prudential criteria for intervention, 3) global norm entrepreneurship from the Global South, and 4) veto restraint in R2P scenarios.
From Sudan to Syria: Locating ‘Regime Change’ in R2P and the ICC
Authors: McMillan Nesam , Mickler David
Published: September 2013

Recently, R2P and the ICC have been mobilised in different forms to respond to state-directed mass atrocities in Sudan, Libya and Syria. Notably, this has generated debate over the capacity and legitimacy of using R2P and the ICC to facilitate ‘regime change’ in those cases and beyond. This article critically examines where regime change, as an aim and outcome, sits within R2P and ICC doctrine and practice. We demonstrate the ambiguous position of regime change in R2P and ICC doctrine, where it is not explicitly endorsed as an objective but actions that may lead to it are permitted. In practice, R2P and the ICC have been used to starkly different ends in the three cases. Such ambiguity—about what regime change is, and about how far international intervention can legitimately go—and inconsistency in application, can undermine global support for R2P and the ICC as tools for preventing and responding to atrocities.
Gaddafi and Grotius: Some Historical Roots of the Libyan Intervention
Authors: Glanville Luke
Published: September 2013

It is increasingly well understood that concepts of ‘humanitarian intervention’ and the ‘responsibility to protect’ enjoy a long and rich history. Nevertheless, it is surprising how plainly the arguments offered by states seeking to justify intervention in Libya in 2011 echo those used by theologians, jurists, and philosophers to justify intervention in the sixteenth, seventeenth, and eighteenth centuries. Those advocating intervention in Libya drew not just on the language of ‘human rights,’ that emerged relatively recently, but on a wider and much older range of idioms and ideas to make their case. In this article, I identify three key arguments that were employed by states in support of the intervention and I demonstrate their parallels with three principal arguments that have been advanced to justify intervention in response to tyranny since the sixteenth century. The three arguments are: the need to protect ‘innocents’; the need to hold ‘tyrants’ to account; and the need to defend the will of a sovereign people. After exploring each argument, I conclude by noting that the claim often heard today, that intervention is under certain circumstances a responsibility rather than merely a right, also has deep roots in early modern thought.
One Bed and Two Dreams? Contentious Public Religion in the Discourses of Ayatollah Khomeini and Ali Shariati
Authors: Mahdavi Mojtaba
Published: September 2013

Ayatollah Khomeini and Ali Shariati are seen as twin pillars of revolutionary Islam in contemporary Iran. This article contextualizes and compares these radical discourses in three sections. It first problematizes the transformation of Khomeini as a quietist cleric into a revolutionary ayatollah. While Khomeini’s theory of velayat-e faqih was a radical departure from the dominant Shiite tradition, its practice has contributed to a new era of post-Khomeinism. Second, it examines Shariati’s discourse and a new reading of his thought in the post-revolutionary context. Third, it demonstrates that these discourses differ radically on the three concepts of radicalism, public religion, and state. The conclusion sheds some light on the conditions of Khomeinism after Khomeini, and Shariati’s discourse three decades after the revolution. It suggests that Iran has gradually entered into a new era of post-Islamism.
Efficacy of Immunity-to-Change Coaching for Leadership Development
Authors: Markus Inna
Published: September 2013

This study is the first formal, quantitative investigation of the effectiveness of Immunity-to-Change coaching for leadership development. Forty-five supervisors who engaged in Immunity-to-Change coaching were compared with a comparison group of 25 supervisors from the same company to determine whether coached participants reported more progress on their leadership development goals than did comparisons. Coached participants indicated their likelihood of using Immunity-to-Change tools to pursue further goals and identified the coaching components they found most useful. Extensive analyses revealed that the coached group reported significantly more progress toward their leadership development goals than their comparison group counterparts. Accordingly, a vast majority of coached participants indicated intent to use Immunity-to-Change coaching tools again in the future, especially the four-column map. These findings suggest that Immunity-to-Change coaching may be an effective intervention for corporate employees seeking to make progress on their leadership development goals.
Calcium-phosphate-coated Oral Implants Promote Osseointegration in Osteoporosis
Authors: Alghamdi H.S. , Cuijpers V.M.J.I. , Wolke J.G.C. , van den Beucken J.J.J.P. , Jansen J.A.
Published: September 2013

Osteoporotic conditions are anticipated to affect the osseointegration of dental implants. This study aimed to evaluate the effect of a radiofrequent magnetron-sputtered calcium phosphate (CaP) coating on dental implant integration upon installment in the femoral condyles of both healthy and osteoporotic rats. At 8 weeks post-implantation, bone volume and histomorphometric bone area were lower around non-coated implants in osteoporotic rats compared with healthy rats. Interestingly, push-out tests revealed significantly enhanced implant fixation for CaP-coated compared with non-coated implants in both osteoporotic ( i.e., 2.9-fold) and healthy rats ( i.e., 1.5-fold), with similar implant fixation for CaP-coated implants in osteoporotic conditions compared with that of non-coated implants in healthy conditions. Further, the presence of a CaP coating significantly increased bone-to-implant contact compared with that in non-coated implants in both osteoporotic ( i.e., 1.3-fold) and healthy rats ( i.e., 1.4-fold). Sequential administration of fluorochrome labels showed significantly increased bone dynamics close to CaP-coated implants at 3 weeks of implantation in osteoporotic conditions and significantly decreased bone dynamics in osteoporotic compared with healthy conditions. In conclusion, analysis of the data obtained demonstrated that dental implant modification with a thin CaP coating effectively improves osseointegration in both healthy and osteoporotic conditions.
GABA Heteroreceptors Modulate Noradrenaline Release in Human Dental Pulp
Authors: Parker D.A.S. , Marino V.
Published: September 2013

γ-aminobutyric-acid-containing neurons and GABAB receptors have been identified in human dental pulp; however, their significance in pulpal physiology is unclear. The purpose of this study was to determine whether pre-synaptic GABAergic heteroreceptors influence the release of noradrenaline (NA). Segments of vital pulp were incubated in [3H]NA (0.6 μM) and superfused with Krebs solution. GABA, a GABAB receptor agonist (baclofen), GABAA and B receptor antagonists [bicuculline and (+)-(S)-5, 5-dimethylmorpholinyl-2-acetic acid (Sch 50911), respectively], and a GABAA receptor-mediated Cl- channel inhibitor (picrotoxin) were added to the superfusion medium at least 10 min prior to the second period of stimulation (S2). Sympathetic nerves were stimulated electrically after 70 (S1) and 115 (S2) min. We determined the effects of agonists/antagonists by comparing the overflow of [3H]NA at S2 with that at S1 in the presence and absence of the compound. Baclofen (3 µM) inhibited the release of [3H]NA (IC50 = 2 µM), an action reversed by Sch 50911 (10 µM). GABA (100 µM) inhibited the release of [3H]NA (IC50 = 75 µM), an effect reversed by Sch 50911 (10 µM) but not by bicuculline (10 µM). However, picrotoxin (100 µM) prevented the inhibitory action of GABA. GABAB and GABAA heteroceptors mediate the release of NA from sympathetic nerves in human dental pulp in vitro.
Political Gardening in a Post-disaster City: Lessons from New Orleans
Authors: Kato Yuki , Passidomo Catarina , Harvey Daina
Published: September 2013

The study examines the emergence of urban gardening activities in New Orleans in the wake of Hurricane Katrina. Drawing on ethnographic and qualitative research conducted throughout the city between 2009 and 2012, it examines the ways in which various gardening projects in New Orleans exhibit different levels and scopes of political engagement, with a particular focus on how they manifest (sometimes in contradictory ways) in the projects’ missions and practices. On the basis of these findings, it is argued that current conceptualisations of political gardening are too limiting and do not account for the nuances of how politics shape, challenge and materialise in urban gardening activities. By highlighting the ever-shifting social, economic, and political context of the post-disaster recovery, the study illustrates how urban gardening is inherently political, but cautions that the extent to which gardening can subvert social injustice in the city may be limited.
Rediscovering the lost art of internal podalic version: two case reports
Authors: Zhao Peng , Yang Xiaofu
Published: September 2013

Internal podalic version was once widely used for the management of placenta praevia. In modern obstetrics, it has been replaced by caesarean section which can lead to uterine rupture in a subsequent pregnancy. However, if the foetus is dead or very small, internal podalic version still may be carried out without major complication to avoid unnecessary caesarean section in developing countries where follow up is not satisfactory and the foetal prognosis is poor.